ALBERT

Description: Presents corrections to the paper, "Estimation of forest biomass from two-level model inversion of single-pass InSAR data" (Soja, M.J., et al.,Trans. Geosci. Remote Sens., vol. 53, no. 9, pp. 5083???5099, Sep. 2015).

Description: by Cheng-Jui Lin, Tai-Cherng Liou, Chi-Feng Pan, Pei-Chen Wu, Fang-Ju Sun, Hsuan-Liang Liu, Han-Hsiang Chen, Chih-Jen Wu Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A–C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1–4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without ( p

Description: by Guangde Zhang, Hongbo Shi, Lin Wang, Meng Zhou, Zhenzhen Wang, Xiaoxia Liu, Liang Cheng, Weimin Li, Xueqi Li Myocardial infarction (MI) is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs) and known human transcription factors (TFs), and we then identified 1,232 feed-forward loops (FFLs) among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p) and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

Description: by Dominik Eichin, Juha P. Laurila, Sirpa Jalkanen, Marko Salmi The ectoenzyme CD73 catalyzes the hydrolysis of AMP, and is one of the most important producers of extracellular adenosine. On regulatory T cells, CD73 is necessary for immunosuppressive functions, and on Th17 cells CD73-generated adenosine exerts anti-inflammatory effects. However, the expression and function of CD73 in pro-inflammatory M1 and in immunosuppressive M2 macrophages is largely unknown. Here we show that CD73 expression and enzyme activity were induced in in vitro polarized pro-inflammatory human M(LPS+TNF) monocytes/macrophages, while CD73 was absent from immunosuppressive M(IL-4+M-CSF)-polarized macrophages. Inhibition of CD73 activity with the inhibitor AMPCP did not affect the polarization of human monocytes. In mice, CD73 was present on resident peritoneal macrophages. In striking contrast, elicited peritoneal macrophages remained CD73 negative regardless of their polarization towards either a pro-inflammatory M(LPS) or anti-inflammatory M(IL-4c) direction. Finally, the ability of peritoneal macrophages to polarize to pro- and anti-inflammatory cells was perfectly normal in CD73-deficient mice in vivo . These data indicate that, in contrast to other major leukocyte subpopulations, CD73 activity on macrophages does not play a major role in their polarization and that in mice host CD73 on any cell type is not required in vivo for peritoneal macrophage polarization towards either a pro- or an anti-inflammatory direction.

Description: by Hui San Ong, Mohd Syafiq Rahim, Mohd Firdaus-Raih, Effirul Ikhwan Ramlan The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures. By utilising evolutionary programming in the design stage, DNA blocks are subjected to processes such as sequence insertion, deletion and base shifting in order to enrich the diversity of the resulting shapes based on a set of cascading filters. The optimisation algorithm allows mutation to be exerted indefinitely on the candidate sequences until these sequences complied with all the four fitness criteria. Generated candidates from the protocol are in agreement with the filter cascades and thermodynamic simulation. Further validation using gel electrophoresis indicated the formation of the designed shapes. Thus, supporting the plausibility of constructing DNA nanostructures in a more hierarchical, modular, and interchangeable manner.

Description: by Nima Toosizadeh, Jane Mohler, David G. Armstrong, Talal K. Talal, Bijan Najafi Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m 2 ) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m 2 ) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-control slope = 1.23±1.06×10 -2 cm 2 /sec, P

Description: by Raphael H. Heiberger Today´s connected world allows people to gather information in shorter intervals than ever before, widely monitored by massive online data sources. As a dramatic economic event, recent financial crisis increased public interest for large companies considerably. In this paper, we exploit this change in information gathering behavior by utilizing Google query volumes as a "bad news" indicator for each corporation listed in the Standard and Poor´s 100 index. Our results provide not only an investment strategy that gains particularly in times of financial turmoil and extensive losses by other market participants, but reveal new sectoral patterns between mass online behavior and (bearish) stock market movements. Based on collective attention shifts in search queries for individual companies, hence, these findings can help to identify early warning signs of financial systemic risk. However, our disaggregated data also illustrate the need for further efforts to understand the influence of collective attention shifts on financial behavior in times of regular market activities with less tremendous changes in search volumes.

Description: by Sea H. Kim, Birendra Babu Adhikari, Siobanth Cruz, Michael P. Schramm, Joe A. Vinson, Vasanthy Narayanaswami The objective of this study is to transport and deliver resveratrol to intracellular sites using apolipoprotein E3 (apoE3). Reconstituted high-density lipoprotein (rHDL) bearing resveratrol (rHDL/res) was prepared using phospholipids and the low-density lipoprotein receptor (LDLr)-binding domain of apoE3. Biophysical characterization revealed that resveratrol was partitioned into the phospholipid bilayer of discoidal rHDL/res particles (~19 nm diameter). Co-immunoprecipitation studies indicated that the LDLr-binding ability of apoE3 was retained. Cellular uptake of resveratrol to intracellular sites was evaluated in glioblastoma A-172 cells by direct fluorescence using chemically synthesized NBD-labeled resveratrol (res/NBD) embedded in rHDL/res. Competition and inhibition studies indicate that the uptake is by receptor mediated endocytosis via the LDLr, with co-localization of apoE3 and res/NBD in late endosomes/lysosomes. We propose that rHDL provides an ideal hydrophobic milieu to sequester resveratrol and that rHDL containing apoE3 serves as an effective “nanovehicle” to transport and deliver resveratrol to targeted intracellular sites.

Description: by JunLi Liu, YiHu Wang, ShuJun Song, XiJie Wang, YaYa Qin, ShaoYan Si, YanChuan Guo Purpose Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Methods Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups ( n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. Results OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Conclusions Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Description: by Jennifer Choe Bush, Peter Christopher Pantelis, Xavier Morin Duchesne, Sebastian Alexander Kagemann, Daniel Patrick Kennedy We present a novel “Gaze-Replay” paradigm that allows the experimenter to directly test how particular patterns of visual input—generated from people’s actual gaze patterns—influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze “donor.” This was intended to simulate the donor’s visual selection, such that a participant could effectively view scenes “through the eyes” of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition.

Description: by David G. Warnock, Daniel G. Bichet, Myrl Holida, Ozlem Goker-Alpan, Kathy Nicholls, Mark Thomas, Francois Eyskens, Suma Shankar, Mathews Adera, Sheela Sitaraman, Richie Khanna, John J. Flanagan, Brandon A. Wustman, Jay Barth, Carrolee Barlow, Kenneth J. Valenzano, David J. Lockhart, Pol Boudes, Franklin K. Johnson Trial Registration ClinicalTrials.gov NCT01196871

Description: by Clementine Menz, Mahroo K. Parsi, Julian R. J. Adams, Mohamed A. Sideek, Zlatko Kopecki, Allison J. Cowin, Mark A. Gibson Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the fibrillin-LTBP superfamily of extracellular matrix proteins. LTBPs and fibrillins are involved in the sequestration and storage of latent growth factors, particularly transforming growth factor β (TGF-β), in tissues. Unlike other LTBPs, LTBP-2 does not covalently bind TGF-β, and its molecular functions remain unclear. We are screening LTBP-2 for binding to other growth factors and have found very strong saturable binding to fibroblast growth factor-2 (FGF-2) (Kd = 1.1 nM). Using a series of recombinant LTBP-2 fragments a single binding site for FGF-2 was identified in a central region of LTBP-2 consisting of six tandem epidermal growth factor-like (EGF-like) motifs (EGFs 9–14). This region was also shown to contain a heparin/heparan sulphate-binding site. FGF-2 stimulation of fibroblast proliferation was completely negated by the addition of 5-fold molar excess of LTBP-2 to the assay. Confocal microscopy showed strong co-localisation of LTBP-2 and FGF-2 in fibrotic keloid tissue suggesting that the two proteins may interact in vivo. Overall the study indicates that LTBP-2 is a potent inhibitor of FGF-2 that may influence FGF-2 bioactivity during wound repair particularly in fibrotic tissues.

Description: by Xinwei Shi, Hao Liu, Jing Cao, Qing Liu, Guiju Tang, Wanlu Liu, Haiyi Liu, Dongrui Deng, Fuyuan Qiao, Yuanyuan Wu Objective Extravillous trophoblast (EVT) cells invade the endometrium and the maternal spiral arterioles during the first trimester. Mammary Serine Protease Inhibitor (Maspin, SERPINB5) plays a putative role in regulating the invasive activity of cytotrophoblasts. The maspin gene is silenced in various cancers by an epigenetic mechanism that involves aberrant cytosine methylation. We investigated the effect of the methylation status of the maspin promoter on the maspin expression and the aggressiveness of EVT cells. Methods Western blotting was used to detect the maspin protein expression in EVT cells upon hypoxia. The proliferative ability, the apoptosis rate and the migration and invasiveness were measured with Cell Counting Kit-8 assay, Flow Cytometry technology and Transwell methods. Subsequently, we treated cells with recombinant maspin protein. The methylation degree of maspin promoter region upon hypoxia/ decitabine was detected by bisulfite sequencing PCR and methylation-specific PCR. Finally, we explored the effects of decitabine on maspin protein expression and the aggressiveness of EVT cells. Results Hypoxia effectively increased maspin protein expression in EVT cells and significantly inhibited their aggressiveness. The addition of recombinant maspin protein inhibited this aggressiveness. Decitabine reduced the methylation in the maspin promoter region and effectively increased the maspin protein expression, which significantly weakened the migration and invasiveness of EVT cells. Discussion The methylation status of the maspin promoter is an important factor that affects the migration and invasion of EVT cells during early pregnancy. A decrease in the methylation status can inhibit the migration and invasion of EVT cells to affect placentation and can result in the ischemia and hypoxia of placenta.

Description: by Jun-Ha Hwang, Mi Ran Byun, A. Rum Kim, Kyung Min Kim, Hang Jun Cho, Yo Han Lee, Juwon Kim, Mi Gyeong Jeong, Eun Sook Hwang, Jeong-Ho Hong Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

Description: by Maria Cecilia P. Moura, Steven J. Smith, David B. Belzer Residential buildings are a key driver of energy consumption and also impact transportation and land-use. Energy consumption in the residential sector accounts for one-fifth of total U.S. energy consumption and energy-related CO 2 emissions, with floor space a major driver of building energy demands. In this work a consistent, vintage-disaggregated, annual long-term series of U.S. housing stock and residential floor space for 1891–2010 is presented. An attempt was made to minimize the effects of the incompleteness and inconsistencies present in the national housing survey data. Over the 1891–2010 period, floor space increased almost tenfold, from approximately 24,700 to 235,150 million square feet, corresponding to a doubling of floor space per capita from approximately 400 to 800 square feet. While population increased five times over the period, a 50% decrease in household size contributed towards a tenfold increase in the number of housing units and floor space, while average floor space per unit remains surprisingly constant, as a result of housing retirement dynamics. In the last 30 years, however, these trends appear to be changing, as household size shows signs of leveling off, or even increasing again, while average floor space per unit has been increasing. GDP and total floor space show a remarkably constant growth trend over the period and total residential sector primary energy consumption and floor space show a similar growth trend over the last 60 years, decoupling only within the last decade.

Description: by Yi-Ling Chen, Shiun Chang, Ting-Ting Chen, Chien-Kuo Lee Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are critical for initiating and controlling the immune response. However, study of DC, particularly pDC, function is hampered by their low frequency in lymphoid organs, and existing methods for in vitro DC generation preferentially favor the production of cDCs over pDCs. Here, we demonstrated that pDCs could be efficiently generated in vitro from common lymphoid progenitors (CLPs) using Flt3 ligand (FL) in three different culture systems, namely feeder-free, BM-feeder and AC-6-feeder. This was in stark contrast to common DC progenitors (CDPs), in which cDCs were prominently generated under the same conditions. Moreover, the efficiency and function of pDCs generated from these three systems varied. While AC-6 system showed the greatest ability to support pDC development from CLPs, BM-feeder system was able to develop pDCs with better functionality. pDCs could also be expanded in vivo using hydrodynamic gene transfer of FL, which was further enhanced by the combined treatment of FL and IFN-α. Interestingly, IFN-α selectively promoted the proliferation of CLPs and not CDPs, which might contribute to enhanced pDC development. Together, we have defined conditions for in vitro and in vivo generation of pDCs, which may be useful for investigating the biology of pDCs.

Description: by Andrew Erwin, Frank C. Sup In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper limb amputees might be created.

Description: by Aparajita Chatterjee, Daniel M. Ratner, Christopher M. Ryan, Patricia J. Johnson, Barry R. O’Keefe, W. Evan Secor, Deborah J. Anderson, Phillips W. Robbins, John Samuelson Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans ( N -glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N -glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N -glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas . Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N -glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas .

Description: by Suzan J. W. Robroek, Anne Rongen, Coos H. Arts, Ferdy W. H. Otten, Alex Burdorf, Merel Schuring Background Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment. Methods 14,708 Dutch employees participated in a ten-year follow-up study during 1999–2008. At baseline, education, self-perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work-characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach. Results Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84), unemployment (SHR:1.74), and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92). Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle-related factors. Conclusions There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work characteristics, particularly for disability benefits. Health promotion and improving working conditions seem important measures to maintain a productive workforce, particularly among workers with a low education.

Description: by SK Hafizul Islam, Muhammad Khurram Khan, Xiong Li Over the past few years, secure and privacy-preserving user authentication scheme has become an integral part of the applications of the healthcare systems. Recently, Wen has designed an improved user authentication system over the Lee et al.’s scheme for integrated electronic patient record (EPR) information system, which has been analyzed in this study. We have found that Wen’s scheme still has the following inefficiencies: (1) the correctness of identity and password are not verified during the login and password change phases; (2) it is vulnerable to impersonation attack and privileged-insider attack; (3) it is designed without the revocation of lost/stolen smart card; (4) the explicit key confirmation and the no key control properties are absent, and (5) user cannot update his/her password without the help of server and secure channel. Then we aimed to propose an enhanced two-factor user authentication system based on the intractable assumption of the quadratic residue problem (QRP) in the multiplicative group. Our scheme bears more securities and functionalities than other schemes found in the literature.

Description: by Sherif H. Elmeligy Abdelhamid, Chris J. Kuhlman, Madhav V. Marathe, Henning S. Mortveit, S. S. Ravi Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools.

Description: by Lisa Kellman, Amy Myette, Hugo Beltrami Forest harvesting induces a step change in the climatic variables (temperature and moisture), that control carbon dioxide ( CO 2 ) production arising from soil organic matter decomposition within soils. Efforts to examine these vertically complex relationships in situ within soil profiles are lacking. In this study we examined how the climatic controls on CO 2 production change within vertically distinct layers of the soil profile in intact and clearcut forest soils of a humid temperate forest system of Atlantic Canada. We measured mineral soil temperature (0, 5, 10, 20, 50 and 100 cm depth) and moisture (0–15 cm and 30–60 cm depth), along with CO 2 surface efflux and subsurface concentrations (0, 2.5, 5, 10, 20, 35, 50, 75 and 100 cm depth) in 1 m deep soil pits at 4 sites represented by two forest-clearcut pairs over a complete annual cycle. We examined relationships between surface efflux at each site, and soil heat, moisture, and mineral soil CO 2 production. Following clearcut harvesting we observed increases in temperature through depth (1–2°C annually; often in excess of 4°C in summer and spring), alongside increases in soil moisture (30%). We observed a systematic breakdown in the expected exponential relationship between CO 2 production and heat with mineral soil depth, consistent with an increase in the role moisture plays in constraining CO 2 production. These findings should be considered in efforts to model and characterize mineral soil organic matter decomposition in harvested forest soils.

Description: by Peng Yu, Jing Zhang, Shuchun Yu, Zhenzhong Luo, Fuzhou Hua, Linhui Yuan, Zhidong Zhou, Qin Liu, Xiaohong Du, Sisi Chen, Lieliang Zhang, Guohai Xu Background and Purpose Myocardial infarction leads to heart failure. Autophagy is excessively activated in myocardial ischemia/reperfusion (I/R) in rats. The aim of this study is to investigate whether the protection of sevoflurane postconditioning (SPC) in myocardial I/R is through restored impaired autophagic flux. Methods Except for the sham control (SHAM) group, each rat underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by hemodynamics and echocardiography. The activation of autophagy was evaluated by autophagosome accumulation, LC3 conversion and p62 degradation. Potential molecular mechanisms were investigated by immunoblotting, real-time PCR and immunofluorescence staining. Results SPC improved the hemodynamic parameters, cardiac dysfunction, histopathological and ultrastructural damages, and decreased myocardial infarction size after myocardial I/R injury ( P 〈 0.05 vs. I/R group). Compared with the cases in I/R group, myocardial ATP and NAD + content, mitochondrial function related genes and proteins, and the expressions of SOD2 and HO-1 were increased, while the expressions of ROS and Vimentin were decreased in the SPC group ( P 〈 0.05 vs. I/R group). SPC significantly activated Akt/mTOR signaling, and inhibited the formation of Vps34/Beclin1 complex via increasing expression of Bcl2 protein ( P 〈 0.05 vs. I/R group). SPC suppressed elevated expressions of LC3 II/I ratio, Beclin1, Atg5 and Atg7 in I/R rat, which indicated that SPC inhibited over-activation of autophagy, and promoted autophagosome clearance. Meanwhile, SPC significantly suppressed the decline of Opa1 and increases of Drp1 and Parkin induced by I/R injury ( P 〈 0.05 vs. I/R group). Moreover, SPC maintained the contents of ATP by reducing impaired mitochondria. Conclusion SPC protects rat hearts against I/R injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance.

Description: by Lisa Müller, Erich Müller, Carolin Hildebrandt, Elmar Kornexl, Christian Raschner The relative age effect (RAE), which refers to an over-representation of selected athletes born early in the selection year, was proven to be present in alpine ski racing in all age categories at both national and international levels. However, the influential factors on, or the causal mechanisms of, the RAE are still unknown. Therefore, the aim of the present study was to examine three possible influential factors on the relative age effect in alpine skiing: physical performance, anthropometric characteristics and biological maturational status. The study included the investigation of 282 elite Austrian youth ski racers and 413 non-athletes (comparison group) of the same age (10–13 years) and region. Six physical performance tests were performed, body mass and height were assessed, and the age at peak height velocity (APHV) was calculated. A significant RAE was present in the ski racers. No differences were shown in the physical performance characteristics or in the calculated APHV between the relative age quarters. These results suggest that ski racers born in the last quarter can counteract the relative age disadvantages if they already present the same level of physical performance and maturational status as those born at the beginning of the year. The height and weight of ski racers born at the beginning of the year were significantly higher compared to the non-athletes, and ski racers born in relative age quarter 1 were taller and heavier compared to the ski racers of the other quarters. This indicates that the anthropometric characteristics influence the selection process in alpine ski racing, and that relatively older athletes are more likely to be selected if they exhibit advanced anthropometric characteristics.

Description: by Andrea Pelletier-Baldelli, Jessica A. Bernard, Vijay A. Mittal Social processes are key to navigating the world, and investigating their underlying mechanisms and cognitive architecture can aid in understanding disease states such as schizophrenia, where social processes are highly impacted. Evidence suggests that social processes are impaired in individuals at ultra high-risk for the development of psychosis (UHR). Understanding these phenomena in UHR youth may clarify disease etiology and social processes in a period that is characterized by significantly fewer confounds than schizophrenia. Furthermore, understanding social processing deficits in this population will help explain these processes in healthy individuals. The current study examined resting state connectivity of the salience (SN) and default mode networks (DMN) in association with facial emotion recognition (FER), an integral aspect of social processes, as well as broader social functioning (SF) in UHR individuals and healthy controls. Consistent with the existing literature, UHR youth were impaired in FER and SF when compared with controls. In the UHR group, we found increased connectivity between the SN and the medial prefrontal cortex, an area of the DMN relative to controls. In UHR youth, the DMN exhibited both positive and negative correlations with the somatosensory cortex/cerebellum and precuneus, respectively, which was linked with better FER performance. For SF, results showed that sensory processing links with the SN might be important in allowing for better SF for both groups, but especially in controls where sensory processing is likely to be unimpaired. These findings clarify how social processing deficits may manifest in psychosis, and underscore the importance of SN and DMN connectivity for social processing more generally.

Description: by Marc O. Nadon, Jerald S. Ault, Ivor D. Williams, Steven G. Smith, Gerard T. DiNardo The coral reef fish community of Hawaii is composed of hundreds of species, supports a multimillion dollar fishing and tourism industry, and is of great cultural importance to the local population. However, a major stock assessment of Hawaiian coral reef fish populations has not yet been conducted. Here we used the robust indicator variable “average length in the exploited phase of the population (L¯)”, estimated from size composition data from commercial fisheries trip reports and fishery-independent diver surveys, to evaluate exploitation rates for 19 Hawaiian reef fishes. By and large, the average lengths obtained from diver surveys agreed well with those from commercial data. We used the estimated exploitation rates coupled with life history parameters synthesized from the literature to parameterize a numerical population model and generate stock sustainability metrics such as spawning potential ratios (SPR). We found good agreement between predicted average lengths in an unfished population (from our population model) and those observed from diver surveys in the largely unexploited Northwestern Hawaiian Islands. Of 19 exploited reef fish species assessed in the main Hawaiian Islands, 9 had SPRs close to or below the 30% overfishing threshold. In general, longer-lived species such as surgeonfishes, the redlip parrotfish ( Scarus rubroviolaceus ), and the gray snapper ( Aprion virescens ) had the lowest SPRs, while short-lived species such as goatfishes and jacks, as well as two invasive species ( Lutjanus kasmira and Cephalopholis argus ), had SPRs above the 30% threshold.

Description: by Leonie J. P. Steenis, Marjolein Verhoeven, Dave J. Hessen, Anneloes L. van Baar Background The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. Methods Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring 〈 1-SD and 〈 -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms. Results Scaled scores based on Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p 〈 .01) with small to large effect sizes ( η p 2 ) ranging from .03 to .26). Using the US instead of Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills. Conclusions The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data.

Description: by Xiao-Dan Wang, Hui Lu, Zhihong Shi, Li Cai, Shuai Liu, Shuling Liu, Tong Han, Ying Wang, Yuying Zhou, Xinping Wang, Shuo Gao, Yong Ji Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11 C-PIB PET scan and 18 F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11 C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11 C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18 F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings.

Description: by Q. Wang, M. Li, Edmond H. M. Lou, M. S. Wong Background Non-ionizing radiation imaging assessment has been advocated for the patients with adolescent idiopathic scoliosis (AIS). As one of the radiation-free methods, ultrasound imaging has gained growing attention in scoliosis assessment over the past decade. The center of laminae (COL) method has been proposed to measure the spinal curvature in the coronal plane of ultrasound image. However, the reliability and validity of this ultrasound method have not been validated in the clinical setting. Objectives To evaluate the reliability and validity of clinical ultrasound imaging on lateral curvature measurements of AIS with their corresponding magnetic resonance imaging (MRI) measurements. Methods Thirty curves (ranged 10.2°–68.2°) from sixteen patients with AIS were eligible for this study. The ultrasound scan was performed using a 3-D ultrasound unit within the same morning of MRI examination. Two researchers were involved in data collection of these two examinations. The COL method was used to measure the coronal curvature in ultrasound image, compared with the Cobb method in MRI. The intra- and inter-rater reliability of the COL method was evaluated by intra-class correlation coefficient (ICC). The validity of this method was analyzed by paired Student’s t -test, Bland–Altman statistics and Pearson correlation coefficient. The level of significance was set as 0.05. Results The COL method showed high intra- and inter-rater reliabilities (both with ICC (2, K) 〉0.9, p

Description: by Yongkang Kim, Taesung Park Genome-wide association studies (GWAS) have successfully discovered hundreds of associations between genetic variants and complex traits. Most GWAS have focused on the identification of single variants. It has been shown that most of the variants that were discovered by GWAS could only partially explain disease heritability. The explanation for this missing heritability is generally believed to be gene-gene (GG) or gene-environment (GE) interactions and other structural variants. Generalized multifactor dimensionality reduction (GMDR) has been proven to be reasonably powerful in detecting GG and GE interactions; however, its performance has been found to decline when outlying quantitative traits are present. This paper proposes a robust GMDR estimation method (based on the L-estimator and M-estimator estimation methods) in an attempt to reduce the effects caused by outlying traits. A comparison of robust GMDR with the original MDR based on simulation studies showed the former method to outperform the latter. The performance of robust GMDR is illustrated through a real GWA example consisting of 8,577 samples from the Korean population using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) level as a phenotype. Robust GMDR identified the KCNH1 gene to have strong interaction effects with other genes on the function of insulin secretion.

Description: by Min Gao, Renli Tian, Junhao Wen, Qingyu Xiong, Bin Ling, Linda Yang In recent years, recommender systems have become an effective method to process information overload. However, recommendation technology still suffers from many problems. One of the problems is shilling attacks-attackers inject spam user profiles to disturb the list of recommendation items. There are two characteristics of all types of shilling attacks: 1) Item abnormality: The rating of target items is always maximum or minimum; and 2) Attack promptness: It takes only a very short period time to inject attack profiles. Some papers have proposed item anomaly detection methods based on these two characteristics, but their detection rate, false alarm rate, and universality need to be further improved. To solve these problems, this paper proposes an item anomaly detection method based on dynamic partitioning for time series. This method first dynamically partitions item-rating time series based on important points. Then, we use chi square distribution (χ 2 ) to detect abnormal intervals. The experimental results on MovieLens 100K and 1M indicate that this approach has a high detection rate and a low false alarm rate and is stable toward different attack models and filler sizes.

Description: by Morgan Kruse, Rebecca Wildner, Gisoo Barnes, Monique Martin, Udo Mueller, Francesco Lo-Coco, Ashutosh Pathak The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all- trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared to the current first-line standard of care in APL.

Description: by Antonella Agodi, Martina Barchitta, Annalisa Quattrocchi, Andrea Maugeri, Manlio Vinciguerra Objective The Death-Associated Protein Kinase 1 ( DAPK1 ) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. Methods A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. Results A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14–40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83–36.78). The association was also confirmed in all the subgroups analyses. Conclusions A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus.

Description: The temporal variations (diurnal and annual) in arboreal $(varepsilon_mathrm{Tree})$ and bare soil $(varepsilon_mathrm{Soil})$ dielectric constants and their correlation with precipitation were examined for several trees in Japan. A significant (1 $sigma$ (standard deviation) and 2 $sigma$ ) $varepsilon_mathrm{Tree}$ increase is observed after rainfall at 89.8% and 90.5% probability. However, rainfall does not always induce significant $varepsilon_mathrm{Tree}$ increases. Rainfall of more than 5 mm/day can induce 1 $sigma$ $varepsilon_mathrm{Tree}$ Tree increase at a 59.6% probability. In order to examine whether the increase in $varepsilon_mathrm{Tree}$ affects the L-band $sigma^{0}$ variation in a forest, the four-year temporal variation of the L-band backscattering coefficient $(sigma^{0})$ was estimated from observations by the Advanced Land Observing Satellite Phased Array type L-band Synthetic Aperture Radar. Observed maximum absolute deviations from the mean over the forest area were 1.0 and 1.2 dB for $sigma_{mathrm{HH}}^{0}$ and $sigma_mathrm{HV}^{0}$ , respectively, and 4.0 and 3.0 dB over open land. $sigma^{0}$ and rainfall correlations show that $varepsilon_mathrm{Tree}$ and $sigma_mathrm{Forest}^{0}$ are proportional to precipitation integrated over seven or eight days; $varepsilon_mathrm{Soil}$ and $sigma_mathrm{Open land}^{0}$ are proportional to precipitation integrated over three days. This finding indicates that $varepsilon_mathrm{Tree}$ variations influence $sigma_{mathrm{Forest areas}}^{0}$ . A stronger correlation between $sigma_mathrm{HV}^{0}$ and precipitation is observed in several sites with low $sigma_mathrm{HV}^{0}$ , where less biomass is expected, and several sites with high $sigma_mathrm{HV}^{0}$ , where more biomass is expected. A weaker correlation between $sigma_mathrm{HV}^{0}$ and precipitation is observed for several sites with high $sigma_mathrm{HV}^{0}$ . These differences may be explained by the different contributions of double bounce scattering and potential transpiration, which is a measure of the ability of the atmosphere to remove water from the surface th

Description: The spectral and radiometric quality of airborne imaging spectrometer data is affected by the anisotropic reflectance behavior of the imaged surface. Illumination and observation angle-dependent patterns of surface reflected radiation propagate into products, hinder quantitative assessment of biophysical/biochemical parameters, and decrease the comparability of data from multiple flight lines. The Ross–Li model, originally developed for multiangular observations, can be inverted to estimate and correct for surface anisotropy effects. This requires land cover be stratified into distinct types of scattering behavior. When the observations subsumed in these classes cover a range of view angles, a pseudo multiangular view on the surface can be employed to invert the Ross–Li model. A discrete land cover classification, however, bears the risk of inappropriate scattering correction resulting in spatial artifacts in the corrected data, predominantly in transition regions of two land cover types (e.g., soil and sparse vegetation with varying fractions). We invert the Ross–Li model on continuous land cover fraction layers. We decompose land cover in dominating structural types using linear spectral unmixing. Ross–Li kernel weights and formulations are estimated for each type independently; the correction is then applied pixel-wise according to the fractional distribution. The corrected Airborne Prism EXperiment imaging spectrometer data show significant reduction of anisotropic reflectance effects of up to 90% (average 60% to 75%, $p=0.05$ ), measured in the overlapping regions of adjacent flight lines. No spatial artifacts or spectral irregularities are observed after correction.

Description: Most spaceborne sensors have a tradeoff between high spatial and high temporal resolutions. This tradeoff limits the use of remote sensing data in various applications that require images in both the high spatial and high temporal resolutions. In this paper, we propose a novel technique to create a fine spatial and high temporal resolution images at a ground-based data processing system. Resourcesat-2 is one of the Indian Space Research Organization missions, and it carries the Linear Imaging Self-Scanning sensors (LISS III and LISS IV) and an Advanced Wide-Field Sensor (AWiFS) onboard. The spatial resolution of LISS III is 23.5 m, and that of AWiFS is 56 m. The temporal resolution of LISS III is 24 days, and that of AWiFS is five days. The proposed method creates a synthetic LISS-III image at 23.5-m spatial and five-day temporal resolutions. It is based on the subpixel relationship between a single AWiFS–LISS-III image pair, which is acquired before or after the prediction date. In temporal data composition, spurious spatial discontinuities are inevitable for land-cover type changes. These discontinuities were identified with temporal edge primitives and were smoothed with a spatial-profile-averaging method. A synthetic LISS-III image for time $t_{k}$ is predicted from an AWiFS image at time $t_{k}$ and a single AWiFS–LISS-III image pair at time $t_{0}$ , where $t_{0}ne t_{k}$ . Experimental results demonstrated that the proposed method is superior in terms of the computational efficiency and prediction accuracy with the other existing methods.

Description: Glacier avalanches are natural hazards that could damage infrastructures and threaten lives in high-altitude mountainous terrains. On April 7, 2012, a massive ice avalanche struck a Pakistani base at Gayari sector, Saltoro Valley, and buried/killed 148 soldiers and civilians. Keeping in view the catastrophe, a study was designed with the objectives to: 1) model and simulate the Gayari sector glacier avalanche incident in terms of height, extent, velocity, pressure, and momentum; 2) generate hazard risk assessment of possible other glacier avalanches in the Saltoro Valley through modeling and simulation; and 3) suitability analysis of current camp sites and recommendation of new safe camps sites locations in the Saltoro valley. To simulate the Gayari sector glacier event and other Glacier possible avalanches, a physical process-based rapid mass movements (RAMMS) was used. The RAMMS has two main components, i.e., Voellmy–Salm (VS) model and random kinetic energy, which deals with variables such as avalanche height and the mean avalanche velocity during the course of simulation. The suitability analysis of current camp sites were achieved using weighted overlay analysis with different constraints in ArcGIS Spatial Analyst. The RAMMS model simulation of the Gayari avalanche event predicted a maximum velocity of 74 ms -1 , generating a pressure of 5074 kPa and attaining a height of 45 m, whereas the predicted debris volume on the ground was 3.8145 million m 3 . A good agreement was found between actual debris height and extent, as compared with the RAMMS model output. The RAMMS model simulated all the potential tributary glacier avalanches of Saltoro valley very well. The weighted overlay analyses in ArcGIS Spatial Analyst revealed that the existing camp sites are safe and were not threatened by the glacier avalanche hazard. However, it was recommended that the Gayari camp should not be constructed at the same location and should be relocated- to the proposed safe camp sites identified in this research study. The proposed methodology developed in the current study could be applied in the Siachen conflict zone for avalanche hazard/risk analysis of all the camp sites located in the valley.

Description: Object-oriented remote sensing image classification is becoming more and more popular because it can integrate spatial information from neighboring regions of different shapes and sizes into the classification procedure to improve the mapping accuracy. However, object identification itself is difficult and challenging. Superpixels, which are groups of spatially connected similar pixels, have the scale between the pixel level and the object level and can be generated from oversegmentation. In this paper, we establish a new classification framework using a superpixel-based graphical model. Superpixels instead of pixels are applied as the basic unit to the graphical model to capture the contextual information and the spatial dependence between the superpixels. The advantage of this treatment is that it makes the classification less sensitive to noise and segmentation scale. The contribution of this paper is the application of a graphical model to remote sensing image semantic segmentation. It is threefold. 1) Gradient fusion is applied to multispectral images before the watershed segmentation algorithm is used for superpixel generation. 2) A probabilistic fusion method is designed to derive node potential in the superpixel-based graphical model to address the problem of insufficient training samples at the superpixel level. 3) A boundary penalty between the superpixels is introduced in the edge potential evaluation. Experiments on three real data sets were conducted. The results show that the proposed method performs better than the related state-of-the-art methods tested.

Description: We introduce a practical and accurate model, referred to as “GO4,” to describe near-nadir microwave scattering from the sea surface, and at the same time, we address the issue of the filtered mean square slope (mss) conventionally used in the geometrical optics model. GO4 is a simple correction of this last model, taking into account the diffraction correction induced by the rough surface through what we call an effective mean square curvature (msc). We evaluate the effective msc as a function of the surface wavenumber spectrum and the radar frequency and show that GO4 reaches the same accuracy as the physical optics model in a wide range of incidence and frequency bands with the sole knowledge of the mss and msc parameters. The key point is that the mss entering in GO4 is not the filtered but the total slope. We provide estimation of the effective msc on the basis of classical sea spectrum models. We also evaluate the effective msc from near-nadir satellite data in various bands and show that it is consistent with model predictions. Non-Gaussian effects are discussed and shown to be incorporated in the effective msc. We give some applications of the method, namely, the estimation of the total sea surface mss and the recalibration of relative radar cross sections.

Description: This paper evaluates the radiometric accuracy of observations from the Advanced Technology Microwave Sounder (ATMS) onboard Suomi National Polar-orbiting Partnership and Sondeur Atmospherique du Profil d' Humidité Intropicale par Radiométrie (SAPHIR) onboard Megha-Tropiques through intercalibration and validation versus in situ radiosonde and Global Positioning System Radio Occultation (GPS-RO) observations. SAPHIR and ATMS water vapor channels operate at slightly different frequencies. We calculated the bias due to radiometric errors as the difference between the observed and simulated differences between the two instruments. This difference, which is often referred to as double difference, ranges between 0.3 and 0.7 K, which shows good consistency between the instruments. We used a radiative transfer model to simulate the satellite brightness temperatures (Tbs) using radiosonde and GPS-RO profiles and then compared simulated and observed Tbs. The difference between radiosonde and ATMS Tbs for the middle and upper tropospheric temperature sounding channels was less than 0.5 K at most stations, but the difference between radiosonde and ATMS/SAPHIR Tbs for water vapor channels was between 0.5 and 2.0 K. The larger bias for the water vapor channels is mainly due to several errors in radiosonde humidity observations. The mean differences between the ATMS observations and the Tbs simulated using GPS-RO profiles were 0.2, 0.3, 0.4, 0.2, and −0.2 K for channels 10–14, respectively; and the uncertainty increases from 0.02 K for channel 10 to 0.07 K for channel 14.

Description: This paper presents a completely automatic processing chain for orthorectification of optical pushbroom sensors. The procedure is robust and works without manual intervention from raw satellite image to orthoimage. It is modularly divided in four main steps: metadata extraction, automatic ground control point (GCP) extraction, geometric modeling, and orthorectification. The GCP extraction step uses georeferenced vector roads as a reference and produces a file with a list of points and their accuracy estimation. The physical geometric model is based on collinearity equations and works with sensor-corrected (level 1) optical satellite images. It models the sensor position and attitude with second-order piecewise polynomials depending on the acquisition time. The exterior orientation parameters are estimated in a least squares adjustment, employing random sample consensus and robust estimation algorithms for the removal of erroneous points and fine-tuning of the results. The images are finally orthorectified using a digital elevation model and positioned in a national coordinate system. The usability of the method is presented by testing three RapidEye images of regions with different terrain configurations. Several tests were carried out to verify the efficiency of the procedure and to make it more robust. Using the geometric model, subpixel accuracy on independent check points was achieved, and positional accuracy of orthoimages was around one pixel. The proposed procedure is general and can be easily adapted to various sensors.

Description: This paper presents a new ground moving target imaging (GMTIm) algorithm for airborne synthetic aperture radar (SAR) based on a novel time-frequency representation (TFR), Lv's distribution (LVD). We first analyze generic moving target signatures for a multichannel SAR and then derive the analytical spectrum of a point target moving at a constant velocity by a polar format algorithm for SAR image formation. SAR motion deviation from a predetermined flight track is considered to facilitate airborne SAR applications. LVD, as a recently developed TFR for the analysis of multicomponent linear-frequency-modulated signal, is adopted to represent the target kinematic spectrum in the Doppler centroid frequency and chirp rate domain. As a result, the proposed SAR-GMTIm algorithm is capable of imaging multiple moving targets even when they are located at the same range resolution cell. Some practical issues such as imaging maneuvering targets and small/weak targets are discussed to enhance the applicability of the proposed algorithm. Simulation results with isotropic point moving targets are presented to validate the effectiveness and superiority of the proposed algorithm. Raw data collected by an airborne multichannel SAR are also used to verify the performance improvement made by the proposed algorithm.

Description: Satellite soil moisture estimates have received increasing attention over the past decade. This paper examines the applicability of estimating soil moisture states and soil hydraulic parameters through two particle filter (PF) methods: The PF with commonly used sampling importance resampling (PF-SIR) and the PF with recently developed Markov chain Monte Carlo sampling (PF-MCMC) methods. In a synthetic experiment, the potential of assimilating remotely sensed near-surface soil moisture measurements into a 1-D mechanistic soil water model (HYDRUS-1D) using both the PF-SIR and PF-MCMC algorithms is analyzed. The effects of satellite temporal resolution and accuracy, soil type, and ensemble size on the assimilation of soil moisture are analyzed. In a real data experiment, we first validate the Advanced Microwave Scanning Radiometer--Earth Observing System (AMSR-E) soil moisture products in the Oklahoma Little Washita Watershed. Aside from rescaling the remotely sensed soil moisture, a bias correction algorithm is implemented to correct the deep soil moisture estimate. Both the ascending and descending AMSR-E soil moisture data are assimilated into the HYDRUS-1D model. The synthetic assimilation results indicated that, whereas both updating schemes showed the ability to correct the soil moisture state and estimate hydraulic parameters, the PF-MCMC scheme is consistently more accurate than PR-SIR. For real data case, the quality of remotely sensed soil moisture impacts the benefits of their assimilation into the model. The PF-MCMC scheme brought marginal gains than the open-loop simulation in RMSE at both surface and root-zone soil layer, whereas the PF-SIR scheme degraded the open-loop simulation.

Description: We propose a new deterministic approach for remote sensing retrieval, called modified total least squares (MTLS), built upon the total least squares (TLS) technique. MTLS implicitly determines the optimal regularization strength to be applied to the normal equation first-order Newtonian retrieval using all of the noise terms embedded in the residual vector. The TLS technique does not include any constraint to prevent noise enhancement in the state space parameters from the existing noise in measurement space for an inversion with an ill-conditioned Jacobian. To stabilize the noise propagation into parameter space, we introduce an additional empirically derived regularization proportional to the logarithm of the condition number of the Jacobian and inversely proportional to the L2-norm of the residual vector. The derivation, operational advantages and use of the MTLS method are demonstrated by retrieving sea surface temperature from GOES-13 satellite measurements. An analytic equation is derived for the total retrieval error, and is shown to agree well with the observed error. This can also serve as a quality indicator for pixel-level retrievals. We also introduce additional tests from the MTLS solutions to identify contaminated pixels due to residual clouds, error in the water vapor profile and aerosols. Comparison of the performances of our new and other methods, namely, optimal estimation and regression-based retrieval, is performed to understand the relative prospects and problems associated with these methods. This was done using operational match-ups for 42 months of data, and demonstrates a relatively superior temporally consistent performance of the MTLS technique.

Description: Radar-based remote sensing for measurement of ocean surface waves presents advantages over conventional point sensors such as wave buoys. As its use becomes more widespread, it is important to understand the sensitivity of the extracted wave parameters to the characteristics of the radar and the scatterers. To examine such issues, experiments were performed offshore of the Scripps Institution of Oceanography pier in July 2010. Radar measurements in low wind speeds were performed with a dual-polarized high-resolution X-band pulse-Doppler radar at low grazing angles along with two independent measurements of the surface waves using conventional sensors, a GPS-based buoy, and an ultrasonic array. Comparison between radar cross section (RCS) and Doppler modulations shows peak values occurring nearly in-phase, in contrast with tilt modulation theory. Spectral comparisons between Doppler-based and RCS-based spectra show that Doppler-based spectra demonstrate greater sensitivity to swell-induced modulations, whereas RCS-based spectra show greater sensitivity to small-scale modulations (or generally have more noise at high frequency), and they equally capture energy at the wind wave peak. Doppler estimates of peak period were consistent with the conventional sensors, whereas the RCS differed in assignment of peak period to wind seas rather than swell in a couple of cases. Higher order period statistics of both RCS and Doppler were consistent with the conventional sensors. Radar-based significant wave heights are lower than buoy-based values and contain nontrivial variability of ∼33%. Comparisons between HH and VV polarization data show that VV data more accurately represent the wave field, particularly as the wind speeds decrease.

Description: Polarimetric synthetic aperture radar satellite and ground-based Ku- and X-band scatterometer measurements are used to explore the scattering mechanism for ice in shallow Arctic lakes, wherein strong radiometric responses are seen for floating ice, and low returns are evident where the ice has grounded. Scatterometer measurements confirm that high backscatter is from the ice/water interface, whereas polarimetric decomposition suggests that the dominant scattering mechanism from that interface is single bounce. Using Fresnel equations, a simple model for surface bounce from the ice/water interface is proposed, and its predictions are supported by experimental parameters such as co-pol phase difference, co-pol ratio, and the results of rigorous numerical modeling. Despite early research suggesting double-bounce scattering from columnar air bubbles and the ice/water interface as the dominant scattering mechanism in shallow lakes, this paper strongly supports a single-bounce model.

Description: The on-orbit radiometric calibration of the reflective solar bands (RSBs) of the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership satellite is carried out primarily through observations of a fully illuminated solar diffuser (SD) panel. Accurate knowledge of the solar spectral radiance scattered from the SD is available. The sensor aperture spectral radiance is assumed to be a quadratic polynomial function of a VIIRS detector's background-subtracted response in digital number. The coefficients of the polynomial were initially determined prelaunch. Once on orbit, we assume that these coefficients change uniformly by a common calibration factor, which is referred to as the $F$ -factor. The known solar spectral radiance scattered from a fully illuminated SD allows for the determination of these $F$ -factors. We describe the methodology and the associated algorithms used in the calculation of the RSB $F$ -factors. Our results show that the $F$ -factors change over time, with the largest change occurring at a wavelength of 862 nm (with a value of about 1.55 on day 950 after the satellite launch, relative to its value at the beginning of the launch) . In addition, we estimate the relative error standard deviations of the computed top-of-the-atmosphere reflectance at the detector pixel level. On day 950 of the mission, the relative error standard deviations are all less or equal to 0.016, except for the M11 band (band central wavelength of 2257 nm) , which has a relative error standard deviation of about 0.049 due to a very low signal-to-noise ratio.

Description: by Shu-I Wu, Su-Chiu Chen, Shen-Ing Liu, Fang-Ju Sun, Jimmy J. M. Juang, Hsin-Chien Lee, Kai-Liang Kao, Michael E. Dewey, Martin Prince, Robert Stewart Objective Despite high mortality associated with serious mental illness, risk of acute myocardial infarction (AMI) remains unclear, especially for patients with bipolar disorder. The main objective was to investigate the relative risk of AMI associated with schizophrenia and bipolar disorders in a national sample. Method Using nationwide administrative data, an 11-year historic cohort study was assembled, comprised of cases aged 18 and above who had received a diagnosis of schizophrenia or bipolar disorder, compared to a random sample of all other adults excluding those with diagnoses of serious mental illness. Incident AMI as a primary diagnosis was ascertained. Hazard ratios stratified by age and gender were calculated and Cox regression models were used to adjust for other covariates. Results A total of 70,225 people with schizophrenia or bipolar disorder and 207,592 people without serious mental illness were compared. Hazard ratios in men adjusted for age, income and urbanization were 1.15 (95% CI 1.01~1.32) for schizophrenia and 1.37 (1.08~1.73)for bipolar disorder, and in women, 1.85 (1.58~2.18) and 1.88(1.47~2.41) respectively. Further adjustment for treated hypertension, diabetes and hyperlipidaemia attenuated the hazard ratio for men with schizophrenia but not the other comparison groups. Hazard ratios were significantly stronger in women than men and were stronger in younger compared to older age groups for both disorders; however, gender modification was only significant in people with schizophrenia, and age modification only significant in people with bipolar disorder. Conclusions In this large national sample, schizophrenia and bipolar disorder were associated with raised risk of AMI in women and in the younger age groups although showed differences in potential confounding and modifying factors.

Description: by Kwi Young Kang, In Je Kim, Min A Yoon, Yeon Sik Hong, Sung-Hwan Park, Ji Hyeon Ju Objective To study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA). Methods One hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression. Results Among the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p

Description: by Andrew J. Massey High-content imaging is a powerful tool for determining cell phenotypes at the single cell level. Characterising the effect of small molecules on cell cycle distribution is important for understanding their mechanism of action especially in oncology drug discovery but also for understanding potential toxicology liabilities. Here, a high-throughput phenotypic assay utilising the PerkinElmer Operetta high-content imager and Harmony software to determine cell cycle distribution is described. PhenoLOGIC, a machine learning algorithm within Harmony software was employed to robustly separate single cells from cell clumps. DNA content, EdU incorporation and pHH3 (S10) expression levels were subsequently utilised to separate cells into the various phases of the cell cycle. The assay is amenable to multiplexing with an additional pharmacodynamic marker to assess cell cycle changes within a specific cellular sub-population. Using this approach, the cell cycle distribution of γH2AX positive nuclei was determined following treatment with DNA damaging agents. Likewise, the assay can be multiplexed with Ki67 to determine the fraction of quiescent cells and with BrdU dual labelling to determine S-phase duration. This methodology therefore provides a relatively cheap, quick and high-throughput phenotypic method for determining accurate cell cycle distribution for small molecule mechanism of action and drug toxicity studies.

Description: by Stéphane J. Montuelle, Susan H. Williams Cranial kinesis refers to movements of skeletal sub-units relative to one another at mobile sutures within the skull. The presence and functional significance of cranial kinesis has been investigated in various vertebrates, with much of our understanding coming from comparative studies and manipulation of ligamentous specimens. Drawing on these studies, cranial kinesis in lizards has been modeled as a four-bar linkage system involving streptostyly (rotation of the quadrate), hypokinesis (dorsoventral flexion and extension of the palato-maxillary sub-unit), mesokinesis (dorsoventral flexion and extension of the snout at the fronto-parietal suture) and metakinesis (sliding movements between parietal and supraocciptal bones). In vivo studies, although limited, suggest that cranial kinesis serves an important role during routine behaviors such as feeding. Here, we use X-ray Reconstruction Of Moving Morphology to further quantify mesokinesis in vivo in Gekko gecko during three routine behaviors: gape display, biting and post-ingestion feeding. During gape display, the snout rotates dorsally above rest position, with mesokinesis accounting for a 10% increase in maximum gape over that achieved solely by the depression of the lower jaw. During defensive biting, the snout rotates ventrally below rest position to participate in gape closure. Finally, ventroflexion of the snout also occurs during post-ingestion feeding, accounting for 42% of gape closure during intra-oral transport, 86% during puncture-crushing, and 61% during pharyngeal packing. Mesokinesis thus appears to facilitate prey puncturing by allowing the snout to rotate ventrally so that the upper teeth pierce the prey item, thus limiting the need for large movements of the lower jaw. This is suggested to maintain a firm grip on the prey and reduce the possibility of prey escape. More generally, this study demonstrates that mesokinesis is a key component of defensive biting and gape display behaviors, as well as post-ingestion feeding, all of which are linked to organismal fitness.

Description: by Xianqiong Gong, Jiaen Yang, Jinmo Tang, Chong Gu, Lijian Huang, Ying Zheng, Huiqing Liang, Min Wang, Chuncheng Wu, Yue Chen, Manying Zhang, Zhijian Yu, Qianguo Mao To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.

Description: by Seungcheol Kang, Han-Soo Kim, Ilkyu Han Unplanned excision of extremity soft tissue sarcoma (STS) is common and has detrimental effects not only on patients’ oncologic outcomes but also on functional and economic issues. However, no study has analyzed a nationwide population-based database. To estimate the incidence and treatment pattern of unplanned excision in extremity STS in the Korean population, a nationwide epidemiologic study was performed using the Korean Health Insurance Review and Assessment Service database, a centralized nationwide healthcare claims registry of Korea that covers the entire Korean population. Among 1,517 patients with extremity STS in the 4-year study period, 553 (36.5%) underwent unplanned excision (unplanned group). About 80% of unplanned excisions were performed in tertiary or general hospitals. Of the unplanned group, 240 (43.4%) underwent re-excision with or without radiation therapy and/or chemotherapy, and 51 (9.2%) did not undergo re-excision but were treated with radiation therapy and/or chemotherapy; whereas, 262 (47.4%) did not undergo any further treatment following unplanned excision. This study is the first nationwide population-based study on the unplanned excision of extremity STS. The results may have implications in establishing preventive or therapeutic measures to reduce the burden of unplanned excision of extremity STS.

Description: by Dong-He Li, Wei Shi, Thomas A. Munroe, Li Gong, Xiao-Yu Kong Mitogenomes of flatfishes (Pleuronectiformes) exhibit the greatest diversity of gene rear-rangements in teleostean fishes. Duplicate control regions (CRs) have been found in the mito-genomes of two flatfishes, Samariscus latus (Samaridae) and Laeops lanceolata (Bothidae), which is rare in teleosts. It has been reported that duplicate CRs have evolved in a concerted fashion in fishes and other animals, however, whether concerted evo-lution exists in flatfishes remains unknown. In this study, based on five newly sequenced and six previously reported mitogenomes of lefteye flounders in the Bothidae, we explored whether duplicate CRs and concerted evolution exist in these species. Results based on the present study and previous reports show that four out of eleven bothid species examined have duplicate CRs of their mitogenomes. The core regions of the duplicate CRs of mitogenomes in the same species have identical, or nearly identical, sequences when compared to each other. This pattern fits the typical characteristics of concerted evolution. Additionally, phylogenetic and ancestral state reconstruction analysis also provided evidence to support the hypothesis that duplicate CRs evolved concertedly. The core region of concerted evolution is situated at the conserved domains of the CR of the mitogenome from the termination associated sequences (TASs) to the conserved sequence blocks (CSBs). Commonly, this region is con-sidered to regulate mitochondrial replication and transcription. Thus, we hypothesize that the cause of concerted evolution of the duplicate CRs in the mtDNAs of these four bothids may be related to some function of the conserved sequences of the CRs during mitochondrial rep-lication and transcription. We hope our results will provide fresh insight into the molecular mechanisms related to replication and evolution of mitogenomes.

Description: by David Knight, Konstantin G. Iliadi, Natalia Iliadi, Ronit Wilk, Jack Hu, Henry M. Krause, Paul Taylor, Michael F. Moran, Gabrielle L. Boulianne Synaptic transmission is highly plastic and subject to regulation by a wide variety of neuromodulators and neuropeptides. In the present study, we have examined the role of isoforms of the cytochrome b561 homologue called no extended memory ( nemy ) in regulation of synaptic strength and plasticity at the neuromuscular junction (NMJ) of third instar larvae in Drosophila . Specifically, we generated two independent excisions of nemy that differentially affect the expression of nemy isoforms. We show that the nemy 45 excision, which specifically reduces the expression of the longest splice form of nemy , leads to an increase in stimulus evoked transmitter release and altered synaptic plasticity at the NMJ. Conversely, the nemy 26.2 excision, which appears to reduce the expression of all splice forms except the longest splice isoform, shows a reduction in stimulus evoked transmitter release, and enhanced synaptic plasticity. We further show that nemy 45 mutants have reduced levels of amidated peptides similar to that observed in peptidyl-glycine hydryoxylating mono-oxygenase (PHM) mutants. In contrast, nemy 26.2 mutants show no defects in peptide amidation but rather display a decrease in Tyramine β hydroxylase activity (TβH). Taken together, these results show non-redundant roles for the different nemy isoforms and shed light on the complex regulation of neuromodulators.

Description: by Davide Bolignano, Graziella D’Arrigo, Anna Pisano, Giuseppe Coppolino Background Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia management also in CKD patients is still object of debate. Study Design Systematic review and meta-analysis. Population Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb

Description: by Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Nan Zhang, Ali Maawy, Takashi Murakami, Sumiyuki Mii, Fuminari Uehara, Mako Yamamoto, Shinji Miwa, Shuya Yano, Masashi Momiyama, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M. Hoffman A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 10 7 CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S . typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S . typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S . typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.

Description: by Fangqun OuYang, Jian-Feng Mao, Junhui Wang, Shougong Zhang, Yue Li The mechanisms by which different light spectra regulate plant shoot elongation vary, and phytohormones respond differently to such spectrum-associated regulatory effects. Light supplementation can effectively control seedling growth in Norway spruce. However, knowledge of the effective spectrum for promoting growth and phytohormone metabolism in this species is lacking. In this study, 3-year-old Norway spruce clones were illuminated for 12 h after sunset under blue or red light-emitting diode (LED) light for 90 d, and stem increments and other growth traits were determined. Endogenous hormone levels and transcriptome differences in the current needles were assessed to identify genes related to the red and blue light regulatory responses. The results showed that the stem increment and gibberellin (GA) levels of the seedlings illuminated by red light were 8.6% and 29.0% higher, respectively, than those of the seedlings illuminated by blue light. The indoleacetic acid (IAA) level of the seedlings illuminated by red light was 54.6% lower than that of the seedlings illuminated by blue light, and there were no significant differences in abscisic acid (ABA) or zeatin riboside [ZR] between the two groups of seedlings. The transcriptome results revealed 58,736,166 and 60,555,192 clean reads for the blue-light- and red-light-illuminated samples, respectively. Illumina sequencing revealed 21,923 unigenes, and 2744 (approximately 93.8%) out of 2926 differentially expressed genes (DEGs) were found to be upregulated under blue light. The main KEGG classifications of the DEGs were metabolic pathway (29%), biosynthesis of secondary metabolites (20.49%) and hormone signal transduction (8.39%). With regard to hormone signal transduction, AUXIN-RESISTANT1 ( AUX1 ), AUX/IAA genes, auxin-inducible genes, and early auxin-responsive genes [( auxin response factor ( ARF ) and small auxin-up RNA ( SAUR )] were all upregulated under blue light compared with red light, which might have yielded the higher IAA level. DELLA and phytochrome-interacting factor 3 (PIF3), involved in negative GA signaling, were also upregulated under blue light, which may be related to the lower GA level. Light quality also affects endogenous hormones by influencing secondary metabolism. Blue light promoted phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis and flavone and flavonol biosynthesis, accompanied by upregulation of most of the genes in their pathways. In conclusion, red light may promote stem growth by regulating biosynthesis of GAs, and blue light may promote flavonoid, lignin, phenylpropanoid and some hormones (such as jasmonic acid) which were related to plant defense in Norway spruce, which might reduce the primary metabolites available for plant growth.

Description: by Xin Zhang, Shijiang Xiong, Yue Ma, Ting Han, Xinyu Chen, Fang Wan, Yating Lu, Songhe Yan, Yan Wang The purpose of this study was to conduct a cone-beam computed tomographic (CBCT) investigation on the root and canal configuration of the mandibular first molars, especially the morphology of the disto-lingual (DL) root, in a Chinese subpopulation. A total of 910 CBCT images of the mandibular first molars were collected from 455 patients who underwent CBCT examinations as a preoperative assessment for implants or orthodontic treatment. The following information was analyzed and evaluated: tooth position, gender, root and root canal number per tooth, root canal type of the mesial root(s) and distal root(s), angle of the DL root canal curvature, distance between two distal canal orifices in the teeth with DL root, and angle of disto-buccal canal orifice–disto-lingual canal orifice–mesio-lingual canal orifice (DB-DL-ML). Most of the mandibular first molars (64.9%, n = 591) had two roots with three root canals, and most of the mesial root canals (87.7%, n = 798) were type VI. The prevalence of the DL root was 22.1% (n = 201). The right side had a higher prevalence of DL root than the left side ( p

Description: by Hsin-Lun Wu, Wen-Kuei Chang, Ken-Hua Hu, Richard M. Langford, Mei-Yung Tsou, Kuang-Yi Chang Although procedure time analyses are important for operating room management, it is not easy to extract useful information from clinical procedure time data. A novel approach was proposed to analyze procedure time during anesthetic induction. A two-step regression analysis was performed to explore influential factors of anesthetic induction time (AIT). Linear regression with stepwise model selection was used to select significant correlates of AIT and then quantile regression was employed to illustrate the dynamic relationships between AIT and selected variables at distinct quantiles. A total of 1,060 patients were analyzed. The first and second-year residents (R1-R2) required longer AIT than the third and fourth-year residents and attending anesthesiologists ( p = 0.006). Factors prolonging AIT included American Society of Anesthesiologist physical status ≧ III, arterial, central venous and epidural catheterization, and use of bronchoscopy. Presence of surgeon before induction would decrease AIT ( p 〈 0.001). Types of surgery also had significant influence on AIT. Quantile regression satisfactorily estimated extra time needed to complete induction for each influential factor at distinct quantiles. Our analysis on AIT demonstrated the benefit of quantile regression analysis to provide more comprehensive view of the relationships between procedure time and related factors. This novel two-step regression approach has potential applications to procedure time analysis in operating room management.

Description: by Guifang Shao, Tiejun Li, Wangda Zuo, Shunxiang Wu, Tundong Liu Microarray technology plays an important role in drawing useful biological conclusions by analyzing thousands of gene expressions simultaneously. Especially, image analysis is a key step in microarray analysis and its accuracy strongly depends on segmentation. The pioneering works of clustering based segmentation have shown that k-means clustering algorithm and moving k-means clustering algorithm are two commonly used methods in microarray image processing. However, they usually face unsatisfactory results because the real microarray image contains noise, artifacts and spots that vary in size, shape and contrast. To improve the segmentation accuracy, in this article we present a combination clustering based segmentation approach that may be more reliable and able to segment spots automatically. First, this new method starts with a very simple but effective contrast enhancement operation to improve the image quality. Then, an automatic gridding based on the maximum between-class variance is applied to separate the spots into independent areas. Next, among each spot region, the moving k-means clustering is first conducted to separate the spot from background and then the k-means clustering algorithms are combined for those spots failing to obtain the entire boundary. Finally, a refinement step is used to replace the false segmentation and the inseparable ones of missing spots. In addition, quantitative comparisons between the improved method and the other four segmentation algorithms--edge detection, thresholding, k-means clustering and moving k-means clustering--are carried out on cDNA microarray images from six different data sets. Experiments on six different data sets, 1) Stanford Microarray Database (SMD), 2) Gene Expression Omnibus (GEO), 3) Baylor College of Medicine (BCM), 4) Swiss Institute of Bioinformatics (SIB), 5) Joe DeRisi’s individual tiff files (DeRisi), and 6) University of California, San Francisco (UCSF), indicate that the improved approach is more robust and sensitive to weak spots. More importantly, it can obtain higher segmentation accuracy in the presence of noise, artifacts and weakly expressed spots compared with the other four methods.

Description: by Prachi R. Bapat, Ashish R. Satav, Aliabbas A. Husain, Seema D. Shekhawat, Anuja P. Kawle, Justin J. Chu, Hemant J. Purohit, Hatim F. Daginawala, Girdhar M. Taori, Rajpal S. Kashyap Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis ( M . tb ) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Description: by Amit Kumar Sinha, Hamada AbdElgawad, Gaurav Zinta, Antony Franklin Dasan, Rindra Rasoloniriana, Han Asard, Ronny Blust, Gudrun De Boeck Salinity fluctuation is one of the main factors affecting the overall fitness of marine fish. In addition, water borne ammonia may occur simultaneously with salinity stress. Additionally, under such stressful circumstances, fish may encounter food deprivation. The physiological and ion-osmo regulatory adaptive capacities to cope with all these stressors alone or in combination are extensively addressed in fish. To date, studies revealing the modulation of antioxidant potential as compensatory response to multiple stressors are rather lacking. Therefore, the present work evaluated the individual and combined effects of salinity challenge, ammonia toxicity and nutritional status on oxidative stress and antioxidant status in a marine teleost, European sea bass ( Dicentrarchus labrax ). Fish were acclimated to normal seawater (32 ppt), to brackish water (20 ppt and 10 ppt) and to hypo-saline water (2.5 ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20 mg/L representing 50% of 96h LC 50 value for ammonia) for 12 h, 48 h, 84 h and 180 h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Results show that in response to decreasing salinities, oxidative stress indices such as xanthine oxidase activity, levels of hydrogen peroxide (H 2 O 2 ) and lipid peroxidation (malondialdehyde, MDA) increased in the hepatic tissue of fasted fish but remained unaffected in fed fish. HEA exposure at normal salinity (32 ppt) and at reduced salinities (20 ppt and 10 ppt) increased ammonia accumulation significantly (84 h–180 h) in both feeding regimes which was associated with an increment of H 2 O 2 and MDA contents. Unlike in fasted fish, H 2 O 2 and MDA levels in fed fish were restored to control levels (84 h–180 h); with a concomitant increase in superoxide dismutase (SOD), catalase (CAT), components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase), ascorbate peroxidase (APX) activity and reduced ascorbate (ASC) content. On the contrary, fasted fish could not activate many of these protective systems and rely mainly on CAT and ASC dependent pathways as antioxidative sentinels. The present findings exemplify that in fed fish single factors and a combination of HEA exposure and reduced seawater salinities (upto 10 ppt) were insufficient to cause oxidative damage due to the highly competent antioxidant system compared to fasted fish. However, the impact of HEA exposure at a hypo-saline environment (2.5 ppt) also defied antioxidant defence system in fed fish, suggesting this combined factor is beyond the tolerance range for both feeding groups. Overall, our results indicate that the oxidative stress mediated by the experimental conditions were exacerbated during starvation, and also suggest that feed deprivation particularly at reduced seawater salinities can instigate fish more susceptible to ammonia toxicity.

Description: by Junjie Wu, Shuting Xiong, Jing Jing, Xin Chen, Weimin Wang, Jian-Fang Gui, Jie Mei YY super-males have rarely been detected in nature and only been artificially created in some fish species including tilapia and yellow catfish ( Pelteobagrusfulvidraco ), which provides a promising model for testis development and spermatogenesis. In our previous study, significant differences in morphology and miRNA expression were detected between XY and YY testis of yellow catfish. Here, solexa sequencing technology was further performed to compare mRNA expression between XY and YY testis. Compared with unigenes expressed in XY testis, 1146 and 1235 unigenes have significantly higher and lower expression in YY testis, respectively. 605 differentially expressed unigenes were annotated to 1604 GO terms with 319 and 286 genes having relative higher expression in XY and YY testis. KEGG analysis suggested different levels of PI3K-AKT and G protein-coupled receptor (GPCR) signaling pathways between XY and YY testis. Down-regulation of miR-141/429 in YY testis was speculated to promote testis development and maturation, and several factors in PI3K-AKT and GPCR signaling pathways were found as predicted targets of miR-141/429, several of which were confirmed by dual-luciferase reporter assays. Our study provides a comparative transcriptome analysis between XY and YY testis, and reveals interactions between miRNAs and their target genes that are possibly involved in regulating testis development and spermatogenesis.

Description: by Liu Yang, Guosheng Wang, Xinyi Zhao, Song Ye, Peng Shen, Weilin Wang, Shusen Zheng Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2 . Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.

Description: by You Luo, Dong-Li She, Hu Xiong, Li Yang, Sheng-Jun Fu Objective To evaluate the value of liquid-based cytology (LBC) in the diagnosis of urothelial carcinoma. Method Diagnostic studies were searched for the diagnostic value of LBC in urothelial carcinoma in PubMed, Embase, Cochrane Library, Web of Science, CBM and CNKI. The latest retrieval date was September 2014. The data were extracted and the quality of the included studies was independently assessed by 2 reviewers. Stata 13 software was used to perform the statistical analysis. The research was conducted in compliance with the PRISMA statement. Result Nineteen studies, which included 8293 patients, were evaluated. The results of the meta-analysis showed that the pooled sensitivity and specificity of LBC were 0.58 (0.51–0.65) and 0.96 (0.93–0.98), respectively. The diagnostic odds ratio (DOR) was 31 (18–56) and the area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.83 (0.80–0.86). The post-test probability was 80% when a positive diagnosis was made. Compared with high grade urothelial carcinoma (HGUC), the sensitivity of detecting low-grade urothelial carcinoma (LGUC) was significantly lower, risk ratio of sensitivity was 0.54 (0.43–0.66), P

Description: by Jaehyuk Choi, Hyunjung Chung, Gir-Won Lee, Sun-Ki Koh, Suhn-Kee Chae, Yong-Hwan Lee Rice blast fungus, Magnaporthe oryzae , is the most destructive pathogen in the rice-growing area. This fungus has a biotrophic phase early in infection and later switches to a necrotrophic lifestyle. During the biotrophic phase, the fungus competes with its host for nutrients and oxygen. Continuous uptake of oxygen is essential for successful establishment of blast disease of this pathogen. Here, we report transcriptional responses of the fungus to oxygen limitation. Transcriptome analysis using RNA-Seq identified that 1,047 genes were up-regulated in response to hypoxia. Those genes are involved in mycelial development, sterol biosynthesis, and metal ion transport based on hierarchical GO terms, and are well-conserved among three fungal species. In addition, null mutants of two hypoxia-responsive genes were generated and their roles in fungal development and pathogenicity tested. The mutant for the sterol regulatory element-binding protein gene, MoSRE1 , exhibited increased sensitivity to a hypoxia-mimicking agent, increased conidiation, and delayed invasive growth within host cells, which is suggestive of important roles in fungal development. However, such defects did not cause any significant decrease in disease severity. The other null mutant, for the alcohol dehydrogenase gene MoADH1 , showed no defect in the hypoxia-mimicking condition (using cobalt chloride) and fungal development. Taken together, this comprehensive transcriptional profiling in response to a hypoxic condition with experimental validations would provide new insights into fungal development and pathogenicity in plant pathogenic fungi.

Description: by Kornsorn Srikulnath, Yoshinobu Uno, Chizuko Nishida, Hidetoshi Ota, Yoichi Matsuda The Hokou gecko ( Gekko hokouensis : Gekkonidae, Gekkota, Squamata) has the chromosome number 2n = 38, with no microchromosomes. For molecular cytogenetic characterization of the gekkotan karyotype, we constructed a cytogenetic map for G . hokouensis , which retains the ancestral karyotype of Gekkota, with 86 functional genes, and compared it with cytogenetic maps for four Toxicofera species that have many microchromosomes ( Elaphe quadrivirgata , Varanus salvator macromaculatus , Leiolepis reevesii rubritaeniata , and Anolis carolinensis ) and that for a lacertid species ( Lacerta agilis ) with only one pair of autosomal microchromosomes. Ten pairs of G . hokouensis chromosomes [GHO1, 2, 3, Z(4), 6, 7, 8, 13, 14, and 15] showed highly conserved linkage homology with macrochromosomes and/or macrochromosome arms of the four Toxicofera species and corresponded to eight L . agilis macrochromosomes (LAG). However, GHO5, GHO9, GHO10, GHO11, and LAG6 were composed of chromosome segments that have a homology with Toxicofera microchromosomes, and no homology was found in the chromosomes between G . hokouensis and L . agilis . These results suggest that repeated fusions of microchromosomes may have occurred independently in each lineage of Gekkota and Lacertidae, leading to the disappearance of microchromosomes and appearance of small-sized macrochromosomes.

Description: by Xinguang Chen, Bin Yu, Dunjin Zhou, Wang Zhou, Jie Gong, Shiyue Li, Bonita Stanton Background Mobile populations and men who have sex with men (MSM) play an increasing role in the current HIV epidemic in China and across the globe. While considerable research has addressed both of these at-risk populations, more effective HIV control requires accurate data on the number of MSM at the population level, particularly MSM among migrant populations. Methods Survey data from a random sample of male rural-to-urban migrants (aged 18-45, n=572) in Wuhan, China were analyzed and compared with those of randomly selected non-migrant urban (n=566) and rural counterparts (580). The GIS/GPS technologies were used for sampling and the survey estimation method was used for data analysis. Results HIV-related risk behaviors among rural-to-urban migrants were similar to those among the two comparison groups. The estimated proportion of MSM among migrants [95% CI] was 5.8% [4.7, 6.8], higher than 2.8% [1.2, 4.5] for rural residents and 1.0% [0.0, 2.4] for urban residents, respectively. Among these migrants, the MSM were more likely than non-MSM to be older in age, married, and migrated to more cities. They were also more likely to co-habit with others in rental properties located in new town and neighborhoods with fewer old acquaintances and more entertainment establishments. In addition, they were more likely to engage in commercial sex and less likely to consistently use condoms. Conclusion Findings of this study indicate that compared to rural and urban populations, the migrant population in Wuhan consists of a higher proportion of MSM who also exhibit higher levels of HIV-related risk behaviors. More effective interventions should target this population with a focus on neighborhood factors, social capital and collective efficacy for risk reduction.

Description: by Gen Kanaya, Takao Suzuki, Eisuke Kikuchi A huge tsunami is one of the greatest disturbance events in coastal benthic communities, although the ecological consequences are not fully understood. Here we examined the tsunami-induced changes in the sediment environment and macrozoobenthic assemblage in a eutrophic brackish lagoon in eastern Japan. The 7.2-m-high tsunami completely replaced muddy sediment with drifting sea sand throughout the lagoon, leading to the drastic changes in quantity and quality of sedimental organic matters, sulfide contents, and sediment redox condition. Intensive physical stress devastated the benthic community, but the disappearance of sulfidic muddy bottoms significantly improved the habitat quality for macrozoobenthos. The re-established macrozoobenthic community after 5 months was characterized by (1) a 2-fold higher total density, but sharp declines in species richness, diversity, and evenness; (2) an increased density of opportunistic taxa (e.g., polychaete Pseudopolydora spp. and amphipod Monocorophium uenoi ) in newly created sandy bottoms; and (3) disappearance of several dominant taxa including bivalves and chironomid larvae. These findings indicate that the sensitivity and recovery potential of macrozoobenthos were highly taxa-specific, which was closely related to the taxa’s ecological characteristics, including tolerance to physical disturbance, life-history traits, and life form. Our data revealed the rapid recolonization of opportunistic macrozoobenthos after a huge tsunami, which would contribute to the functional recovery of estuarine soft-bottom habitats shortly after a disturbance event.

Description: by Philippa Borrill, Brendan Fahy, Alison M. Smith, Cristobal Uauy It has been proposed that delayed leaf senescence can extend grain filling duration and thus increase yields in cereal crops. We found that wheat ( Triticum aestivum ) NAM RNAi plants with delayed senescence carried out 40% more flag leaf photosynthesis after anthesis than control plants, but had the same rate and duration of starch accumulation during grain filling and the same final grain weight. The additional photosynthate available in NAM RNAi plants was in part stored as fructans in the stems, whereas stem fructans were remobilised during grain filling in control plants. In both genotypes, activity of starch synthase was limiting for starch synthesis in the later stages of grain filling. We suggest that in order to realise the potential yield gains offered by delayed leaf senescence, this trait should be combined with increased grain filling capacity.

Description: by Chandler Sours, Jiachen Zhuo, Steven Roys, Kathirkamanthan Shanmuganathan, Rao P. Gullapalli Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.

Description: by Mário Angelo Claudino, Luiz Osório Silveira Leiria, Fábio Henrique da Silva, Eduardo Costa Alexandre, Andre Renno, Fabiola Zakia Mónica, Gilberto de Nucci, Kleber Yotsumoto Fertrin, Edson Antunes, Fernando Ferreira Costa, Carla Fernanda Franco-Penteado Background Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking. Objective Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo , in the Berkeley SCD murine model (SS). Methods Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl 2 (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder. Results SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying ( ex vivo ), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca 2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration. Conclusions Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients.

Description: by Leona Dold, Golo Ahlenstiel, Eva Althausen, Carolin Luda, Carolynne Schwarze-Zander, Christoph Boesecke, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Ulrich Spengler Background and aims HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART. Methods In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis. Results At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients. Conclusion Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.

Description: by Ho-Shiang Huang, Ming-Chieh Ma Enhanced sodium excretion is associated with intrarenal oxidative stress. The present study evaluated whether oxidative stress caused by high sodium (HS) may be involved in calcium oxalate crystal formation. Male rats were fed a sodium-depleted diet. Normal-sodium and HS diets were achieved by providing drinking water containing 0.3% and 3% NaCl, respectively. Rats were fed a sodium-depleted diet with 5% hydroxyl-L-proline (HP) for 7 and 42 days to induce hyperoxaluria and/or calcium oxalate deposition. Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance. HS did not affect the hyperoxaluria, hypocalciuria or supersaturation caused by HP; however, it increased calcium oxalate crystal deposition soon after 7 days of co-treatment. Massive calcium oxalate formation and calcium crystal excretion in HS+HP rats were seen after 42 days of treatment. HP-mediated hypocitraturia was further exacerbated by HS. Moreover, HS aggravated HP-induced renal injury and tubular damage via increased apoptosis and oxidative stress. Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress. Interestingly, this redox imbalance was associated with reduced renal osteopontin and Tamm-Horsfall protein expression (via increased excretion) and sodium-dependent dicarboxylate cotransporter NaDC-1 upregulation. Collectively, our results demonstrate that a HS diet induces massive crystal formation in the hyperoxaluric kidney; this is not due to increased urinary calcium excretion but is related to oxidative injury and loss of anticrystallization defense.

Description: by Kristen P. Lindgren, Reinout W. Wiers, Bethany A. Teachman, Melissa L. Gasser, Erin C. Westgate, Janna Cousijn, Matthew C. Enkema, Clayton Neighbors There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes. We sought to replicate and extend those findings in US undergraduate social drinkers (Study 1) and at-risk drinkers (Study 2). Three adaptations of the approach avoid task (AAT) were tested. The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations. The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations, which are robust predictors of hazardous drinking in US undergraduates. Study 1 included 300 undergraduate social drinkers. They were randomly assigned to real or sham training conditions for one of the three training adaptations, and completed two training sessions, spaced one week apart. Study 2 included 288 undergraduates at risk for alcohol use disorders. The same training procedures were used, but the two training sessions occurred within a single week. Results were not as expected. Across both studies, the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy. Finally, across both studies, the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. Despite having relatively large samples and using a well-validated training task, study results indicated all three training adaptations were ineffective at this dose in US undergraduates. These findings are important because training studies are costly and labor-intensive. Future research may benefit from focusing on more severe populations, pairing training with other interventions, increasing training dose, and increasing gamification of training tasks.

Description: by Laëtitia Kernaléguen, Yves Cherel, Travis C. Knox, Alastair M. M. Baylis, John P. Y. Arnould While sexual segregation is expected in highly dimorphic species, the local environment is a major factor driving the degree of resource partitioning within a population. Sexual and individual niche segregation was investigated in the Australian fur seal ( Arctocephalus pusillus doriferus ), which is a benthic foraging species restricted to the shallow continental shelf region of south-eastern Australia. Tracking data and the isotopic values of plasma, red blood cells and whiskers were combined to document spatial and dietary niche segregation throughout the year. Tracking data indicated that, in winter, males and females overlapped in their foraging habitat. All individuals stayed within central Bass Strait, relatively close ( 〈 220 km) to the breeding colony. Accordingly, both genders exhibited similar plasma and red cell δ 13 C values. However, males exhibited greater δ 13 C intra-individual variation along the length of their whisker than females. This suggests that males exploited a greater diversity of foraging habitats throughout the year than their female counterparts, which are restricted in their foraging grounds by the need to regularly return to the breeding colony to suckle their pup. The degree of dietary sexual segregation was also surprisingly low, both sexes exhibiting a great overlap in their δ 15 N values. Yet, males displayed higher δ 15 N values than females, suggesting they fed upon a higher proportion of higher trophic level prey. Given that males and females exploit different resources (mainly foraging habitats), the degree of individual specialisation might differ between the sexes. Higher degrees of individual specialisation would be expected in males which exploit a greater range of resources. However, comparable levels of inter-individual variation in δ 15 N whisker values were found in the sampled males and females, and, surprisingly, all males exhibited similar seasonal and inter-annual variation in their δ 13 C whisker values, suggesting they all followed the same general dispersion pattern throughout the year.

Description: by Martin K. K. Choo, Nabila El-Bassel, Philippe C. G. Adam, Louisa Gilbert, Elwin Wu, Brooke S. West, Alexander R. Bazazi, John B. F. De Wit, Rusli Ismail, Adeeba Kamarulzaman Fishermen in Southeast Asia have been found to be highly vulnerable to HIV, with research evidence highlighting the role of sexual risk behaviors. This study aims to estimate the rate of HIV as well as hepatitis C virus (HCV) infections among Malaysian fishermen, and the risky sexual and injection drug use behaviors that may contribute to these infections. The study also includes an assessment of socio-demographic, occupational and behavioral correlates of testing positive for HIV or HCV, and socio-demographic and occupational correlates of risk behaviors. The study had a cross-sectional design and recruited 406 fishermen through respondent-driven sampling (RDS). Participants self-completed a questionnaire and provided biological specimens for HIV and HCV testing. We conducted and compared results of analyses of both unweighted data and data weighted with the Respondent-Driven Sampling Analysis Tool (RDSAT). Of the participating fishermen, 12.4% were HIV positive and 48.6% had HCV infection. Contrary to expectations and findings from previous research, most fishermen (77.1%) were not sexually active. More than a third had a history of injection drug use, which often occurred during fishing trips on commercial vessels and during longer stays at sea. Of the fishermen who injected drugs, 42.5% reported unsafe injection practices in the past month. Reporting a history of injection drug use increased the odds of testing HIV positive by more than 6 times (AOR = 6.22, 95% CIs [2.74, 14.13]). Most fishermen who injected drugs tested positive for HCV. HCV infection was significantly associated with injection drug use, being older than 25 years, working on a commercial vessel and spending four or more days at sea per fishing trip. There is an urgent need to strengthen current harm reduction and drug treatment programs for Malaysian fishermen who inject drugs, especially among fishermen who work on commercial vessels and engage in deep-sea fishing.

Description: by Bruce E. Markham, Stace Kernodle, Jean Nemzek, John E. Wilkinson, Robert Sigler Poloxamer 188 NF (national formulary (NF) grade of P-188) improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin -/- (dko) muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c.) injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg) for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg) significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone’s effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.

Description: by Richard Schwameis, Christoph Grimm, Edgar Petru, Camilla Natter, Christine Staudigl, Wolfgang Lamm, Heinz Koelbl, Michael Krainer, Thomas Brodowicz, Alexander Reinthaller, Stephan Polterauer Objective C-reactive protein (CRP) has previously been shown to serve as a prognostic parameter in women with gynecologic malignancies. Due to the lack of valid prognostic markers for uterine leiomyosarcoma (ULMS) this study set out to investigate the value of pre-treatment CRP serum levels as prognostic parameter. Methods Data of women with ULMS were extracted from databases of three Austrian centres for gynaecologic oncology. Pre-treatment CRP serum levels were measured and correlated with clinico-pathological parameters. Univariate and multivariable survival analyses were performed. Results In total, 53 patients with ULMS were included into the analysis. Mean (SD) CRP serum level was 3.46 mg/dL (3.96). Solely, an association between pre-treatment CRP serum levels and tumor size ( p = 0.04) but no other clinic-pathologic parameter such as tumor stage ( p = 0.16), or histological grade ( p = 0.07), was observed. Univariate and multivariable survival analyses revealed that CRP serum levels ( HR 2 . 7 [1 . 1–7 . 2] , p = 0.037) and tumor stage ( HR 6 . 1 [1 . 9–19 . 5] , p = 0.002) were the only independent prognostic factors for overall survival (OS) in patients with ULMS. Patients with high pre-treatment CRP serum levels showed impaired OS compared to women with low levels (5-year-OS rates: 22.6% and 52.3%, p = 0.007). Conclusion High pre-treatment CRP serum levels were independently associated with impaired prognosis in women with ULMS and might serve as a prognostic parameter in these patients.