ALBERT

Description: In this paper, we present a methodology to evaluate the feasibility, effectiveness and complexity of a class of cache-based side-channel attacks. The methodology provides estimates on the lower bound of the required number of observations on the side channel and the number of trials for a successful attack. As a case study, a weak implementation of the Advanced Encryption Standard algorithm is selected to apply the proposed methodology to three different categories of cache-based attacks; namely, access-driven, trace-driven and time-driven attacks. The approach, however, is generic in the sense that it can be utilized in other algorithms that are subject to the micro-architectural side-channel attacks. The adopted approach bases its analysis method partially on the conditional entropy of secret keys given the observations of the intermediate variables in software implementations of cryptographic algorithms via the side channel and explores the extent to which the observations can be exploited in a successful attack. Provided that the intermediate variables are relatively simple functions of the key material and the known inputs or outputs of cryptographic algorithms, a successful attack is theoretically feasible. Our methodology emphasizes the need for an analysis of this leakage through such intermediate variables and demonstrates a systematic way to measure it. The method allows us to explore every attack possibility, estimate the feasibility of an attack, and compare the efficiency and the costs of different attack strategies to determine an optimal level of effective countermeasures.

Description: In Cramer et al. (2007, Bounded CCA2-Secure Encryption. In Kurosawa, K. (ed.), Advances in Cryptology – ASIACRYPT 2007 , Kuching, Malaysia, December 2–6, Lecture Notes in Computer Science, Vol. 4833, pp. 502–518. Springer, Berlin, Germany) proposed a public-key encryption scheme secure against adversaries with a bounded number of decryption queries based on the decisional Diffie–Hellman problem. In this paper, we show that the same result can be obtained based on weaker computational assumptions, namely: the computational Diffie–Hellman and the hashed Diffie–Hellman assumptions.

Description: Certificateless public key encryption (CLE) and certificate-based encryption (CBE) are motivated to simultaneously solve the heavy certificate management problem inherent in the traditional public key encryption (PKE) and the key escrow problem inherent in the identity-based encryption (IBE). Al-Riyami and Paterson proposed a general conversion from CLE to CBE, which is neat and natural. Kang and Park pointed out a flaw in their security proof. Wu et al. proposed another generic conversion from CLE to CBE which additionally involves collision resistant hash functions. It remains an open problem whether the generic conversion due to Al-Riyami and Paterson is provably secure or not. We are motivated to solve this open problem. Our basic idea is to enhance Type II adversary's power a little by allowing it to conditionally replace a user's public key. We first formalize a new security model of CLE in this way. Then, we succeed in proving that the Al-Riyami–Paterson generic conversion from CLE to CBE is secure, if the CLE scheme is secure in our new security model. Finally, a concrete provably secure CBE scheme is presented to demonstrate the applicability of our result.

Description: Human recognition with heartbeat signal is useful for different applications such as information security, user identification and remote patient monitoring. In this paper, we propose a model-based method for the alignment of heartbeat morphology to enhance the recognition capability. The scale change of different heartbeats of the same individual due to heart rate variability is estimated and inversed to yield better alignment. Recognition capabilities of different alignment methods are analyzed and measured by intra-individual and inter-individual distances of aligned heartbeats. A framework for heartbeat recognition incorporating the model-based alignment method is also presented. We tested the recognition capability of heartbeat morphology by using two different databases. It was found that model-based alignment method was useful to boost the recognition capability of heartbeat morphology. A statistical t -test revealed that the improvement was significant with respect to recognition capabilities of other existing alignment methods. We also used the aligned morphology as a feature, tested the recognition accuracy on both databases and compared the recognition performance to those of four other state-of-the-art features. A large increase in recognition accuracy was obtained especially for a multisession database of heartbeat signals captured from fingers using a handheld ECG device.

Description: Malicious code attacks pose a serious threat to the security of information systems, as malware evolved from innocuous conceptual software to advanced and destructive cyber weapons. However, there is still the lack of a comprehensive and useful taxonomy to classify malware according to their behavior, since commonly used names are obsolete and unable to handle the complex and multipurpose currently observed samples. In this article, we present a brief survey on available malware taxonomies, discuss about issues on existing naming schemes and introduce an extensible taxonomy consisting of an initial set of behaviors usually exhibited by malware during an infection. The main goal of our proposed taxonomy is to address the menace of potentially malicious programs based on their observed behaviors, thus aiding in incident response procedures. Finally, we present a case study to evaluate our behavior-centric taxonomy, in which we apply identification patterns extracted from the proposed taxonomy to over 12 thousand known malware samples. The leveraged results show that it is possible to screen malicious programs that exhibit suspicious behaviors, even when they remain undetected by antivirus tools.

Description: Metamorphism is a technique that mutates the binary code using different obfuscations and never keeps the same sequence of opcodes in the memory. This stealth technique provides the capability to a malware for evading detection by simple signature-based (such as instruction sequences, byte sequences and string signatures) anti-malware programs. In this paper, we present a new scheme named Annotated Control Flow Graph (ACFG) to efficiently detect such kinds of malware. ACFG is built by annotating CFG of a binary program and is used for graph and pattern matching to analyse and detect metamorphic malware. We also optimize the runtime of malware detection through parallelization and ACFG reduction, maintaining the same accuracy (without ACFG reduction) for malware detection. ACFG proposed in this paper: (i) captures the control flow semantics of a program; (ii) provides a faster matching of ACFGs and can handle malware with smaller CFGs, compared with other such techniques, without compromising the accuracy; (iii) contains more information and hence provides more accuracy than a CFG. Experimental evaluation of the proposed scheme using an existing dataset yields malware detection rate of 98.9% and false positive rate of 4.5%.

Description: The success of location-based services is growing together with the diffusion of GPS-equipped smart devices. As a consequence, privacy concerns are raising year by year. Location privacy is becoming a major interest in research and industry world, and many solutions have been proposed for it. One of the simplest and most flexible approaches is obfuscation, in which the precision of location data is artificially degraded before disclosing it. In this paper, we present an obfuscation approach capable of dealing with measurement imprecision, multiple levels of privacy, untrusted servers and adversarial knowledge of the map. We estimate its resistance against statistical-based deobfuscation attacks, and we improve it by means of three techniques, namely extreme vectors , enlarge-and-scale and hybrid vectors .

Description: We consider the problem of access privilege management in a classical protection environment featuring subjects attempting to access the protected objects. We express an access privilege in terms of an access right and a privilege level. The privilege level and a protection diagram associated with each given object determine whether a nominal access privilege for this object corresponds to an effective, possibly weaker access privilege, or is revoked. We associate a password system with each object; the password system takes the form of a hierarchical bidimensional one-way chain. A subject possesses a nominal access privilege for a given object if it holds a key that matches one of the passwords in the password system of this object; the protection diagram determines the extent of the corresponding effective access privilege. The resulting protection environment has several interesting properties. A key reduction mechanism allows a subject that holds a key for a given object to distribute keys for weaker access rights at lower privilege levels. A subject that owns a given object can review or revoke the passwords for this object by simply modifying the protection diagram. The memory requirements to represent a protection diagram are negligible; as far as password storage is concerned, space–time trade-offs are possible.

Description: A proxy re-encryption (PRE) allows a data owner to delegate the decryption rights of some encrypted data stored on the cloud without revealing the data to an honest-but-curious cloud service provider (i.e. the PRE proxy). Furthermore, the data owner can offload most of the computational operations to the cloud service provider and hence, using PRE for encrypted cloud data sharing can be very effective even for data owners using limited resource devices (e.g. mobile devices). However, PRE schemes only enables data owners to delegate the decryption rights of all their encrypted data. A more practical notion is a conditional PRE (CPRE) that allows us to specify under what condition the decryption of an encrypted data can be delegated, for example, only sharing all the encrypted files under a directory called ‘public’. In this paper, we provide an affirmative result on the long-standing question of building a full chosen-ciphertext attacks (CCA)-secure CPRE system in the standard model and for the first time, we show that a class of Hierarchical Identity-Based Encryption (HIBE) schemes can be transferred to building a CCA-secure CPRE in the standard model. We also list out some concrete HIBE schemes which fall into this class, e.g., Lewko-Waters HIBE. All existing CCA-secure PRE schemes in the standard model are not conditional while all existing CPRE schemes are either not CCA secure or not in the standard model. By instantiating our generic HIBE-based transformation, we show that an efficient and concrete CPRE scheme which is both CCA secure in the standard model and conditional can be built.

Description: Ferritins and other cage proteins have been utilized as models to understand the fundamentals of protein folding and self-assembly. The bacterioferritin (BFR) from Escherichia coli, a maxi-ferritin made up of 24 subunits, was chosen as the basis for a mutagenesis study to investigate the role of electrostatic intermolecular interactions mediated through charged amino acids. Through structural and computational analyses, three charged amino acids R30, D56 and E60 which involved in an electrostatic interaction network were mutated to the opposite charge. Four mutants, R30D, D56R, E60H and D56R-E60H, were expressed, purified and characterized. All of the mutants fold into α-helical structures. Consistent with the computational prediction, they all show a lowered thermostability; double mutant D56R-E60H was found to be 16°C less stable than the wild type. Except for the mutant E60H, all the other mutations completely shut down the formation of protein cages to favour the dimer state in solution. The mutants, however, retain their ability to form cage-like nanostructures in the dried, surface immobilized conditions of transmission electron microscopy. Our findings confirm that even a single charge-inversion mutation at the 2-fold interface of BFR can affect the quaternary structure of its dimers and their ability to self-assemble into cage structures.

Description: Most of bacteria can swim by rotating flagella bidirectionally. The C ring, located at the bottom of the flagellum and in the cytoplasmic space, consists of FliG, FliM and FliN, and has an important function in flagellar protein secretion, torque generation and rotational switch of the motor. FliG is the most important part of the C ring that interacts directly with a stator subunit. Here, we introduced a three-amino acids in-frame deletion mutation (PSA) into FliG from Vibrio alginolyticus , whose corresponding mutation in Salmonella confers a switch-locked phenotype, and examined its phenotype. We found that this FliG mutant could not produce flagellar filaments in a fliG null strain but the FliG(PSA) protein could localize at the cell pole as does the wild-type protein. Unexpectedly, when this mutant was expressed in a wild-type strain, cells formed flagella efficiently but the motor could not rotate. We propose that this different phenotype in Vibrio and Salmonella might be due to distinct interactions between FliG mutant and FliM in the C ring between the bacterial species.

Description: Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo . This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported.

Description: In this study, the physicochemical and enzymatic properties of recombinant human ubiquitin (Ub)-specific protease (USP) 47, a novel member of the C19 family of de-ubiquitinating enzymes (DUB), were characterized for the first time. Recombinant human USP47 was expressed in a baculovirus expression system and purified to homogeneity. The purified protein was shown to be a monomeric protein with a molecular mass of ~146 kDa on sodium dodecyl sulphate—polyacrylamide gel electrophoresis. USP47 released Ub from Ub-aminoacyl-4-metheylcoumaryl-7-amide and Ub-tagged granzyme B. The substitution of the potential nucleophile Cys109 with Ser severely abrogated the Ub-releasing activity of USP47, indicating that USP47 is indeed a cysteine DUB. An assay using Ub dimer substrates showed that the enzyme cleaved a variety of isopeptide bonds between 2 Ub molecules, including the Lys48- and Lys63-linked isopeptide bonds. USP47 also released a Ub moiety from Lys48- and Lys63-linked polyUb chains. Of the inhibitors tested, N -ethylmaleimide, Zn ion and Ub aldehyde revealed a dose-dependent inhibition of USP47. In this study, clear differences in the enzymatic properties between USP47 and USP7 (the most closely related proteins among DUBs) were also found. Therefore, our results suggest that USP47 may play distinct roles in Ub-mediated cellular processes via DUB activity.

Description: P24 antigen is the main structural protein of HIV-1, its detection provide a means to aid the early diagnosis of HIV-1 infection. The aim of this study was to improve the selectivity and sensitivity of the HIV P24 diagnostic assay by developing a cohort of 9E8 affinity-matured antibodies through in vitro phage affinity maturation which was performed by complementarity determining region (CDR)-hot spot mutagenesis strategy. Antibody 9E8-491 had an affinity constant of 5.64 x 10 –11 M, which was 5.7-fold higher than that of the parent antibody (9E8). Furthermore, the affinity, sensitivity and specificity of 9E8-491 were higher than those of 9E8, which indicate that 9E8-491 is a good candidate detection antibody for HIV P24 assay. Structure analysis of matured variants revealed that most hydrogen bonds resided in HCDR3. Among the antibody–antigen predicted binding residues, Tyr 100A/100B was the original conserved residue that was commonly present in HCDR3 of 9E8 and variants. Arg 100 /Asp 100C was the major variant substitution that most likely influenced the binding differences among variants and 9E8 monoclonal antibody. Both efficient library panning and predicted structural data were in agreement that the binding residues were mostly located in HCDR3 and enabled identification of key residues that influence antibody affinity.

Description: Many skeletal diseases have common pathological phenotype of defective osteogenesis of bone marrow stromal cells (BMSCs), in which histone modifications play an important role. However, few studies have examined the dynamics of distinct histone modifications during osteogenesis. In this study, we examined the dynamics of H3K9/K14 and H4K12 acetylation; H3K4 mono-, di- and tri-methylation; H3K9 di-methylation and H3K27 tri-methylation in osteogenic genes, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase, bone sialoprotein and osteocalcin, during C3H10T1/2 osteogenesis. H3 and H4 acetylation and H3K4 di-methylation were elevated, and H3K9 di-methylation and H3K27 tri-methylation were reduced in osteogenic genes during C3H10T1/2 osteogenesis. C3H10T1/2 osteogenesis could be modulated by altering the patterns of H3 and H4 acetylation and H3K27 tri-methylation. In a glucocorticoid-induced osteoporosis mouse model, we observed the attenuation of osteogenic potential of osteoporotic BMSCs in parallel with H3 and H4 hypo-acetylation and H3K27 hyper-tri-methylation in Runx2 and Osx genes. When H3 and H4 acetylation was elevated, and H3K27 tri-methylation was reduced, the attenuated osteogenic potential of osteoporotic BMSCs was rescued effectively. These observations provide a deeper insight into the mechanisms of osteogenic differentiation and the pathophysiology of osteoporosis and can be used to design new drugs and develop new therapeutic methods to treat skeletal diseases.

Description: Dihydrouridine (D) is formed by tRNA dihydrouridine synthases (Dus). In mesophiles, multiple Dus enzymes bring about D modifications at several positions in tRNA. The extreme-thermophilic eubacterium Thermus thermophilus , in contrast, has only one dus gene in its genome and only two D modifications (D20 and D20a) in tRNA have been identified. Until now, an in vitro assay system for eubacterial Dus has not been reported. In this study, therefore, we constructed an in vitro assay system using purified Dus. Recombinant T. thermophilus Dus lacking bound tRNA was successfully purified. The in vitro assay revealed that no other factors in living cells were required for D formation. A dus gene disruptant ( dus ) strain of T. thermophilus verified that the two D20 and D20a modifications in tRNA were derived from one Dus protein. The dus strain did not show growth retardation at any temperature. The assay system showed that Dus modified tRNA Phe transcript at 60°C, demonstrating that other modifications in tRNA are not essential for Dus activity. However, a comparison of the formation of D in native tRNA Phe purified from the dus strain and tRNA Phe transcript revealed that other tRNA modifications are required for D formation at high temperatures.

Description: Human lactate dehydrogenase (LDH) has attracted attention as a potential target for cancer therapy and contraception. In this study, we reconstituted human lactic acid fermentation in Saccharomyces cerevisiae , with the goal of constructing a yeast cell-based LDH assay system. pdc null mutant yeast (mutated in the endogenous pyruvate decarboxylase genes) are unable to perform alcoholic fermentation; when grown in the presence of an electron transport chain inhibitor, pdc null strains exhibit a growth defect. We found that introduction of the human gene encoding LDHA complemented the pdc growth defect; this complementation depended on LDHA catalytic activity. Similarly, introduction of the human LDHC complemented the pdc growth defect, even though LDHC did not generate lactate at the levels seen with LDHA. In contrast, the human LDHB did not complement the yeast pdc null mutant, although LDHB did generate lactate in yeast cells. Expression of LDHB as a red fluorescent protein (RFP) fusion yielded blebs in yeast, whereas LDHA-RFP and LDHC-RFP fusion proteins exhibited cytosolic distribution. Thus, LDHB exhibits several unique features when expressed in yeast cells. Because yeast cells are amenable to genetic analysis and cell-based high-throughput screening, our pdc /LDH strains are expected to be of use for versatile analyses of human LDH.

Description: RelB is activated by the non-canonical NF-B pathway, which is crucial for immunity by establishing lymphoid organogenesis and B-cell and dendritic cell (DC) maturation. To elucidate the mechanism of the RelB-mediated immune cell maturation, a precise understanding of the relationship between cell maturation and RelB expression and activation at the single-cell level is required. Therefore, we generated knock-in mice expressing a fusion protein between RelB and fluorescent protein (RelB-Venus) from the Relb locus. The Relb Venus / Venus mice developed without any abnormalities observed in the Relb –/– mice, allowing us to monitor RelB-Venus expression and nuclear localization as RelB expression and activation. Relb Venus / Venus DC analyses revealed that DCs consist of RelB – , RelB low and RelB high populations. The RelB high population, which included mature DCs with projections, displayed RelB nuclear localization, whereas RelB in the RelB low population was in the cytoplasm. Although both the RelB low and RelB – populations barely showed projections, MHC II and co-stimulatory molecule expression were higher in the RelB low than in the RelB – splenic conventional DCs. Taken together, our results identify the RelB low population as a possible novel intermediate maturation stage of cDCs and the Relb Venus / Venus mice as a useful tool to analyse the dynamic regulation of the non-canonical NF-B pathway.

Description: Hyperthermophilic bacteria Thermotoga maritima and Thermotoga hypogea produce ethanol as a metabolic end product, which is resulted from acetaldehyde reduction catalysed by an alcohol dehydrogenase (ADH). However, the enzyme that is involved in the production of acetaldehyde from pyruvate is not well characterized. An oxygen sensitive and coenzyme A-dependent pyruvate decarboxylase (PDC) activity was found to be present in cell free extracts of T. maritima and T. hypogea . Both enzymes were purified and found to have pyruvate ferredoxin oxidoreductase (POR) activity, indicating their bifunctionality. Both PDC and POR activities from each of the purified enzymes were characterized in regards to their optimal assay conditions including pH dependency, oxygen sensitivity, thermal stability, temperature dependency and kinetic parameters. The close relatedness of the PORs that was shown by sequence analysis could be an indication of the presence of such bifunctionality in other hyperthermophilic bacteria. This is the first report of a bifunctional PDC/POR enzyme in hyperthermophilic bacteria. The PDC and the previously reported ADHs are most likely the key enzymes catalysing the production of ethanol from pyruvate in bacterial hyperthermophiles.

Description: As people increasingly rely on road maps in the digital age, manually maintained maps cannot keep up with the demand for accuracy and freshness, evidenced by the recent iOS map incident and the bidding war for Waze. There are many research works on automatic map inference using GPS data, and some have suggested that Google and Waze automate their map update processes to some degree with user data. However, existing published work focuses on refining road geometry. In reality, connectivity issues at intersections, including missing connections and unmarked turn restrictions, are much more prevalent and also more difficult to infer. In this paper, we report our study on the connectivity issues in the OSM Shanghai map using 21 months of GPS data from over $10\,000$ taxis. We first adapt a robust map matching algorithm. Then, we propose simple algorithms for detecting missing intersections, turn restrictions and road closures. Empirical results show that our algorithms of connectivity refinement for road maps are effective.

Description: The degree distribution is an important characteristic of complex networks. In many data analysis applications, the networks should be represented as fixed-length feature vectors and therefore the feature extraction from the degree distribution is a necessary step. Moreover, many applications need a similarity function for comparison of complex networks based on their degree distributions. Such a similarity measure has many applications, including classification and clustering of network instances, evaluation of network sampling methods, anomaly detection and study of epidemic dynamics. The existing methods are unable to effectively capture the similarity of degree distributions, particularly when the corresponding networks have different sizes. In this paper, we propose a feature extraction method and a similarity function for the degree distributions in complex networks. We propose to calculate the feature values based on the mean and standard deviation of the node degrees in order to decrease the effect of the network size on the extracted features. Experiments on a wide range of real and artificial networks confirms the accuracy, stability and effectiveness of the proposed method.

Description: Given a query photo characterizing a location-aware landmark shot by a user, landmark retrieval is about returning a set of photos ranked in their similarities to the query. Existing studies on landmark retrieval focus on conducting a matching process between candidate photos and a query photo by exploiting location-aware visual features. Notwithstanding the good results achieved, these approaches are based on an assumption that a landmark of interest is well-captured and distinctive enough to be distinguished from others. In fact, distinctive landmarks may be badly selected, e.g. changes on viewpoints or angles. This will discourage the recognition results if a biased query photo is issued. In this paper, we present a novel technique that exploits user communities in social media networks. Given a biased query photo containing some landmarks taken by a user, we select multiple users to complement this user for retrieval. Multiple photos are then used to enrich the query photo, constituting a more representative yet robust multi-query set. A pattern mining method is developed to obtain a compact feature representation of photos from the multi-query set. Such a representation is utilized to efficiently query the database so as to improve retrieval results. Extensive experiments on real-world datasets demonstrate the effectiveness and efficiency of our approach.

Description: Social media have been used by some companies to support customer co-creation in recent years. However, few academic studies have been done to investigate the use of social media in customer co-creation. To understand the current state-of-the-art and future trends about the use of social media in customer co-creation, we conducted two studies to analyze relevant posts on blogs and social media-based online forums. This study reveals some interesting patterns, themes and future trends in this specific area. Recommendations are given to help managers engage in co-creation activities with customers.

Description: The scaffolding protein Salvador (Sav) plays a key role in the Hippo (Hpo) signalling pathway, which controls tissue growth by inhibiting cell proliferation and promoting apoptosis. Dysregulation of the Hippo pathway contributes to cancer development. Since the identification of the first Sav gene in 2002, very little is known regarding the molecular basis of Sav-SARAH mediating interactions due to its insolubility. In this study, refolding of the first Sav (known as WW45)-SARAH provided insight into the biochemical and biophysical properties, indicating that WW45-SARAH exhibits properties of a disordered protein, when the domain was refolded at a neutral pH. Interestingly, WW45-SARAH shows folded and rigid conformations relative to the decrease in pH. Further, diffracting crystals were obtained from protein refolded under acidic pH, suggesting that the refolded WW45 protein at low pH has a homogeneous and stable conformation. A comparative analysis of molecular properties found that the acidic-stable fold of WW45-SARAH enhances a heterotypic interaction with Mst2-SARAH. In addition, using an Mst2 mutation that disrupts homotypic dimerization, we showed that the monomeric Mst2-SARAH domain could form a stable complex of 1:1 stoichiometric ratio with WW45 refolded under acidic pH.

Description: Hypercholesterolemia is one of the factors contributing to cardiovascular problems. Erythrocytes are known to contribute its cholesterol to atherosclerotic plaque. Our earlier study showed that erythrocytes overexpress chondroitin sulphate/dermatan sulphate (CS/DS), a linear co-polymer, during diabetes which resulted in increased cytoadherence to extracellular matrix (ECM) components. This study was carried out to determine whether diet-induced hypercholesterolemia had any effect on erythrocyte CS/DS and impacted cytoadherence to ECM components. Unlike in diabetes, diet-induced hypercholesterolemia did not show quantitative changes in erythrocyte CS/DS but showed difference in proportion of un-sulphated and 4- O -sulphated disaccharides. Erythrocytes from hypercholesterolemic rats showed increased adhesion to ECM components which was abrogated to various extents when subjected to chondroitinase ABC digestion. However, isolated CS/DS chains showed a different pattern of binding to ECM components indicating that orientation of CS/DS chains could be playing a role in binding.

Description: The antigen-binding domain of camelid dimeric heavy chain antibodies, known as VHH or Nanobody, has much potential in pharmaceutical and industrial applications. To establish the isolation process of antigen-specific VHH, a VHH phage library was constructed with a diversity of 8.4 x 10 7 from cDNA of peripheral blood mononuclear cells of an alpaca ( Lama pacos ) immunized with a fragment of IZUMO1 (IZUMO1 PFF ) as a model antigen. By conventional biopanning, 13 antigen-specific VHHs were isolated. The amino acid sequences of these VHHs, designated as N-group VHHs, were very similar to each other (〉93% identity). To find more diverse antibodies, we performed high-throughput sequencing (HTS) of VHH genes. By comparing the frequencies of each sequence between before and after biopanning, we found the sequences whose frequencies were increased by biopanning. The top 100 sequences of them were supplied for phylogenic tree analysis. In total 75% of them belonged to N-group VHHs, but the other were phylogenically apart from N-group VHHs (Non N-group). Two of three VHHs selected from non N-group VHHs showed sufficient antigen binding ability. These results suggested that biopanning followed by HTS provided a useful method for finding minor and diverse antigen-specific clones that could not be identified by conventional biopanning.

Description: The autophosphorylation of specific tyrosine residues occurs in the cytoplasmic region of the insulin receptor (IR) upon insulin binding, and this in turn initiates signal transduction. The R3 subfamily (Ptprb, Ptprh, Ptprj and Ptpro) of receptor-like protein tyrosine phosphatases (RPTPs) is characterized by an extracellular region with 6–17 fibronectin type III-like repeats and a cytoplasmic region with a single phosphatase domain. We herein identified the IR as a substrate for R3 RPTPs by using the substrate-trapping mutants of R3 RPTPs. The co-expression of R3 RPTPs with the IR in HEK293T cells suppressed insulin-induced tyrosine phosphorylation of the IR. In vitro assays using synthetic phosphopeptides revealed that R3 RPTPs preferentially dephosphorylated a particular phosphorylation site of the IR: Y960 in the juxtamembrane region and Y1146 in the activation loop. Among four R3 members, only Ptprj was co-expressed with the IR in major insulin target tissues, such as the skeletal muscle, liver and adipose tissue. Importantly, the activation of IR and Akt by insulin was enhanced, and glucose and insulin tolerance was improved in Ptprj -deficient mice. These results demonstrated Ptprj as a physiological enzyme that attenuates insulin signalling in vivo , and indicate that an inhibitor of Ptprj may be an insulin-sensitizing agent.

Description: The diazotrophic cyanobacterium Anabaena sp. strain PCC 7120 (A.7120) differentiates into specialized heterocyst cells that fix nitrogen under nitrogen starvation conditions. Although reducing equivalents are essential for nitrogen fixation, little is known about redox systems in heterocyst cells. In this study, we investigated thioredoxin (Trx) networks in Anabaena using TrxM, and identified 16 and 38 candidate target proteins in heterocysts and vegetative cells, respectively, by Trx affinity chromatography (Motohashi et al. (Comprehensive survey of proteins targeted by chloroplast thioredoxin. Proc Natl Acad Sci USA , 2001; 98 , 11224–11229)). Among these, the Fe–S cluster scaffold protein NifU that facilitates functional expression of nitrogenase in heterocysts was found to be a potential TrxM target. Subsequently, we observed that the scaffold activity of N-terminal catalytic domain of NifU is enhanced in the presence of Trx-system, suggesting that TrxM is involved in the Fe–S cluster biogenesis.

Description: Mobile message push has become a ubiquitous technology in various applications such as online resource sharing, traffic surveillance, mobile health care and environmental monitoring. In mobile terminals, energy efficiency optimization is one of the most important issues due to battery power limitations, resource constraints and quality-of-service (QoS) requirements. Considering the timely delivery, network load and terminal diversity, this paper proposes an adaptive message push strategy (AMPS) for energy efficiency optimization in mobile terminals. In AMPS, running parameters including energy parameter, operating system (OS) version and connection/polling cost in mobile terminal are first acquired and sent to the server together with the requisition data, and then the dispatching module will automatically choose a message pushing mode between polling-based and connection-based ones. The AMPS was tested in real environments using mobile phones with different OSs. Experiment results show that AMPS can efficiently optimize energy exploitation with dynamic tradeoff between terminal using time and QoS performance in comparison with polling-based and connection-based message push strategies.

Description: Wireless sensor networks (WSNs) are vulnerable to the unfavorable funneling effect. The optimization of WSN clustering is a natural way to suppress the funneling effect. WSN clusters involve the edge effect that was undervalued in existing techniques. We propose an optimal clustering routing protocol GreenOCR to reduce the detrimental influence of the funnel effect and minimize the energy consumption in WSNs. Our work focuses on the approximate unequal optimal clustering and dropping energy consumption arising from the edge effect. First, according to the data repeat rate among overlapped clusters, we estimate the actual data compression ratio to offset the negative influence of the edge effect and save WSN energy. Secondly, we reduce the issue of minimizing the total energy consumption in a WSN to a nonlinear programming (NLP). We have proved that this NLP problem is NP complete. Third, we turn over to exploring an approximate optimal clustering and propose an approximate optimal clustering algorithm. A GreenOCR enabled WSN clustering minimizes the energy consumption in the whole network and extends the lifetime of the WSN. The simulation experiment shows that GreenOCR outperforms its rivals in alleviating the funnel effect.

Description: To improve the video semantic analysis for video surveillance, a new video semantic analysis method based on the kernel discriminative sparse representation (KSVD) and weighted K nearest neighbors (KNN) is proposed in this paper. A discriminative model is built by introducing a kernel discriminative function to the KSVD dictionary optimization algorithm, mapping the sparse representation features into a high-dimensional space. The optimal dictionary is then generated and applied to compute the sparse representations of video features. For video semantic analysis, a weighted KNN algorithm based on the optimal sparse representation is proposed. In the algorithm, a kernel function is introduced to establish discrimination about sparse representation features and the classification vote result is weighted, the purpose of which is to improve the accuracy and rationality for video semantic analysis. The experimental results show that the proposed method significantly improves the discrimination of sparse representation features when compared with the traditional KSVD-based support vector machine method. The method can effectively detect the concept and event, which can be potentially useful for improving the video surveillance.

Description: In cloud computing, companies usually use high-end storage systems to guarantee the I/O performance of virtual machines (VM). These storage systems cost a lot of energy for their high performance. In this paper, we propose an EEVS, a deduplication-based energy efficiency storage system for VM storage. We firstly investigate some VM image files with general operating systems. With the analysis result, we find there are many redundant data blocks that bring extra energy cost VM storage. Therefore, in the EEVS, we design an online-deduplication mechanism to reduce these redundant data without service interruption, while traditional deduplication technology is used for offline backup. Based on the system design, we implement an EEVS with the existing cloud platform. Since this mechanism needs considerable computing resources, we design a deduplication selection algorithm such that the storage energy consumption is minimized for a given set of VMs with limited resources for deduplication. Experiment results in a para-virtualization environments of the EEVS show that energy consumption is reduced by even up to 66% with negligible performance degradation.

Description: Smarter use of the renewable energy produced by solar panels reduces the return time of the investment necessary for their installation. This improvement consequently motivates more households to use solar panels so as to not only help protect the environment, but also better use the expensive energy. The difference in tariff prices at different hours of the day is one such opportunity for smarter use of solar electricity: we propose and implement a real-time strategy to more economically use the produced solar electrical energy by forecasting future demand of a few days ahead and by using that energy at the most economical time. Evaluation of the proposed technique in an educational building showed that this scheme improves financial advantage of solar panels by 41% compared with the direct connection of production of solar panels to the grid, or using the stored solar energy completely unawares, hence it can reduce the return time of investment by the same amount. Moreover, since our technique reduces power usage from the utility grid at peak tariff hours, it is one way to move toward a uniform consumption at the suppliers’ level that leads to better use and higher quality and stability.

Description: In vehicular networks, since reliable end-to-end paths between data source and destination seldom exist, replication-based routing protocols are widely used to increase the delivery ratio and reduce the transfer delay. However, after a data message is delivered, its replicas still exist and greatly waste network resources, such as transmission bandwidth and storage spaces. In mobile multimedia communications, the large size of multimedia data greatly aggravates this situation. In this paper, we propose a GPS-based replica deletion scheme with anti-packet distribution for vehicular networks, namely RAD. It utilizes vehicle-to-vehicle and vehicle-to-roadside-unit communications to remove redundant data replicas by a certain number of anti-packets. A roadside unit at each crossing distributes its collected anti-packets to nearby vehicles moving for different directions according to the geographical locations of the to-be-deleted targets. This distribution increases the delivery probability of these anti-packets. Experiment results in a real taxi network show that, compared with others, RAD accelerates replica deletion with less extra overhead

Description: The uncertainty and extreme large scale of cloud resources make task scheduling very difficult which affects the user quality of experience and probably result in a waste of cloud resources and energy consumption. Moreover, some resources stay in an unusable state for extended time. To take into account these problems a cloud resource evaluation model is proposed, termed Entropy Optimization Evaluation and ant colony clustering Model (EOEACCM). The model releases long-term unavailable resources to save energy. First, by mean of the entropy increasing minimum principle, the proposed model can maximize the system utilization and balance profits of both cloud resource providers and users. As a consequence, it can shorten task completion time. Secondly, the model narrows the task scheduling size and achieves optimal scheduling by clustering. To make the model more suitable for the dynamics of cloud resources, the model design improves pheromone update policies by fixing total path length in each function cycle when clustering by the ant colony algorithm. Evaluation of results using EOEACCM demonstrate that it may be applicable for resource management strategies for migration and release, an application which can effectively save energy. The proposed model was evaluated by simulation. Experiment results showed the positive effect of user satisfaction from entropy optimization, as well as scheduling time from clustering. Moreover, when the scale of tasks was large, this clustering algorithm performed much better than others. The clustering model also demonstrated better adaptability when some cloud resources were joined or terminated.

Description: To support the sustainable operation of wireless sensor networks using limited energy, duty cycling is a promising solution. However, it is a challenge to guarantee each node communicating with its neighbors under duty cycle when the network is asynchronous. The challenge becomes bigger when nodes’ duty cycles are required to be adjusted separately according to their demands to save energy and achieve high channel utilization. Existing low power listening- and contention-based protocols are not energy-efficient and cannot ensure high channel utility. Additionally, synchronization-based media access control (MAC) protocols suffer from extra energy consumption and low synchronization precision. This paper proposes a localized and on-demand (LOD) duty cycling scheme based on a specifically designed semi-quorum system. LOD can adjust duty cycle of each node adaptively according to its demand so as to avoid channel contention, consequently achieving high channel utilization. This allows the fairness for channel access within asynchronous sensor networks. Extensive experiments are conducted on a real test-bed of 100 TelosB nodes to evaluate the performance of LOD. As compared with B-MAC, LOD substantially reduces contention for channel access and the energy consumption, thus improving the network throughput significantly.

Description: Recently, wireless sensor networks (WSNs) have been widely used in many applications, such as Smart Grid. However, it is generally known that WSNs are energy limited, which makes WSNs vulnerable to malicious attacks. Among these malicious attacks, a sinkhole attack is the most destructive one, since only one sinkhole node can attract surrounding nodes with unfaithful routing information, and it executes severe malicious attacks, e.g. the selective forwarding attack. In addition, a sinkhole node can cause a large amount of energy wastes of surrounding nodes, which results in abnormal energy hole in WSNs. Thus, it is necessary to design an effective mechanism to detect the sinkhole attack. In this paper, we propose a novel Intrusion Detection Algorithm based on neighbor information against Sinkhole Attack (IDASA). Different from traditional intrusion detection algorithms, IDASA takes full advantage of neighbor information of sensor nodes to detect sinkhole nodes. In addition, we evaluate IDASA in terms of malicious node detection accuracy, packet loss rate, energy consumption and network throughput in MATLAB. Simulation results show that the performance of IDASA is better than that of other related algorithms.

Description: Loosely coupled and cross-platform features make Web services accessible and increasingly popular on the Internet. However, efficient service discovery and automated service composition are still challenges under the conventional practice where services are organized into categories. In this paper, we propose a graph-based method to organize Web services into a service ecosystem interlaced with service relationships at the semantic level. First, Web services are modelled as a set of interfaces, whose input and output parameters are annotated with well-defined ontologies. Secondly, semantic associations and interactions between Web services are mined, and services are constructed into a Web services network (SN), a variant of bipartite graph, by projecting the functional aspects of concrete Web services onto the abstract service layer. Thirdly, from the complex network perspective, the services relations are investigated and the structure of SN is analysed. To demonstrate the basic topological properties of SN, an empirical study is conducted on two data sets for comparative purposes, 10 000+ Web services collected from the Internet and 1231 Web services provided by Titan system of Zhejiang University. The experimental results reveal that SNs, which are built by different data sets on the semantic level, exhibit the same features such as small-world and scale-free. In addition, our results yield valuable insight for developing service discovery and automated composition algorithms, and characterizing the evolution of the entire Web service ecosystem.

Description: Mixed Polarity Reed-Muller (MPRM) logic draws more and more attention for its advantages over Boolean logic. This paper works on power optimization in logic synthesis for MPRM logic circuits. We present a power estimation model for MPRM logic circuits from a probabilistic point of view. A key feature of this technique is that it provides an accurate and efficient way to handle temporal signal correlations during estimation of average power by using lag-one Markov chains. Besides, an ordered binary decision diagrams-based procedure is used to propagate the temporal correlations from the primary inputs throughout the network. At last, this power estimation model is used in low power synthesis for MPRM logic circuits. This model has been evaluated in C language and a comparative analysis has been presented for many benchmark circuits. The results show that this model gives very good accuracy and does well in low power design for MPRM logic circuit.

Description: Energy demand in a smart grid is directly related to energy consumption, as defined by user needs and comfort experience. This article presents a multi-agent architecture for smart control of space heating and cooling processes, in an attempt to enable flexible ways of monitoring and adjusting energy supply and demand. In this proposed system, control agents are implemented in order to perform temperature set-point delegation for heating and cooling systems in a building, offering a means to observe and learn from both the environment and the occupant. Operation of the proposed algorithms is compared with traditional algorithms utilized for room heating, using a simulated model of a residential building and real data about user behaviour. The results show (i) the performance of machine learning for the occupancy forecasting problem and for the problem of calculating the time to heat or cool a room; and (ii) the performance of the control algorithms, with respect to energy consumption and occupant comfort. The proposed control agents make it possible to significantly improve an occupant comfort with a relatively small increase in energy consumption, compared with simple control strategies that always maintain predefined temperatures. The findings enable the smart grid to anticipate the energy needs of the building.

Description: Environment reconstruction is to rebuild the physical environment in the cyberspace using the sensory data collected by sensor networks, which is a fundamental method for human to understand the physical world in depth. A lot of basic scientific work such as nature discovery and organic evolution heavily relies on the environment reconstruction. However, gathering large amount of environmental data costs huge energy and storage space. The shortage of energy and storage resources has become a major problem in sensor networks for environment reconstruction applications. Motivated by exploiting the inherent feature of environmental data, in this paper, we design a novel data gathering protocol based on compressive sensing theory and time series analysis to further improve the resource efficiency. This protocol adapts the duty cycle and sensing probability of every sensor node according to the dynamic environment, which cannot only guarantee the reconstruction accuracy, but also save energy and storage resources. We implement the proposed protocol on a 51-node testbed and conduct the simulations based on three real datasets from Intel Indoor, GreenOrbs and Ocean Sense projects. Both the experiment and simulation performances demonstrate that our method significantly outperforms the conventional methods in terms of resource efficiency and reconstruction accuracy.

Description: Computing network paths under worst-case delay constraints has been the subject of abundant literature in the past two decades. Assuming weighted fair queueing scheduling at the nodes, this translates to computing paths and reserving rates at each link. The problem is NP -hard in general, even for a single path; hence polynomial-time heuristics have been proposed in the past that either assume equal rates at each node, or compute the path heuristically and then allocate the rates optimally on the given path. In this paper we show that the above heuristics, albeit finding optimal solutions quite often, can lead to failing of paths at very low loads, and that this could be avoided by solving the problem, i.e. path computation and rate allocation, jointly at optimality . This is possible by modeling the problem as a mixed-integer second-order cone program and solving it optimally in split-second times for relatively large networks on commodity hardware; this approach can also be easily turned into a heuristic one, trading a negligible increase in blocking probability for one order of magnitude of computation time. Extensive simulations show that these methods are feasible in today's Internet service provider networks and they significantly outperform the existing schemes in terms of blocking probability.

Description: There is considerable evidence that exposure to air pollution is harmful to health. In the USA, ambient air quality is monitored by Federal and State agencies for regulatory purposes. There are limited options, however, for people to access this data in real time, which hinders an individual's ability to manage their own risks. This paper describes a new software package that models environmental concentrations of fine particulate matter (PM 2.5 ), coarse particulate matter (PM 10 ) and ozone concentrations for the state of Oregon and calculates personal health risks at the smartphone's current location. Predicted air pollution risk levels can be displayed on mobile devices as interactive maps and graphs color-coded to coincide with Environmental Protection Agency air quality index categories. Users have the option of setting air quality warning levels via color-coded bars and are notified whenever warning levels are exceeded by predicted levels within 10 km. We validated the software using data from participants as well as from simulations, which showed that the application was capable of identifying spatial and temporal air quality trends. This unique application provides a potential low-cost technology for reducing personal exposure to air pollution which can improve quality of life, particularly for people with health conditions, such as asthma, that make them more susceptible to these hazards.

Description: IP address lookup modules for backbone routers should store 100Ks of entries, find the longest prefix match (LPM) for each incoming packet at 10s of Gbps line speed and support thousands of lookup table (LUT) updates each second. It is desired that these updates are non-blocking , that is without disrupting the ongoing lookups. Furthermore, considering the increasing line rates and table sizes, the scalability of the design is very important. Ternary content-addressable memory (TCAM) architectures are widely deployed for hardware IP lookup. In this paper, we propose a novel TCAM architecture, S-DIRECT-Scalable and Dynamically REConfigurable TCAM , that is custom designed for hardware IP lookup. S-DIRECT consists of hierarchically combined TCAM cells with inherent priority encoders (PEs) to support LPM. Hence, its design is scalable without any need for a separate PE or a redesign for different table size. Furthermore, S-DIRECT can perform constant time, non-blocking updates in hardware provided that certain write capabilities are present in the TCAM entries. S-DIRECT architecture is both independent of the hardware platform and the implementation of the TCAM cells. We demonstrate the generality and viability of S-DIRECT by implementing it both with prefix/mask register and LUT-based TCAM cells on FPGA.

Description: The IEEE 802.11 standard defines access categories (AC) and differentiated medium access control mechanisms for wireless local area networks. The preferential or deferral treatment of frames is achieved using configurable Arbitration Inter-Frame Spaces (AIFS) and customizable Contention Window (CW) sizes. In this paper, we address the problem of determining when a station, being a part of wireless communication, will access the medium. We present an algorithm calculating the probability of winning the contention by a given station, characterized by its AIFS and CW values. The probability of collision is calculated by similar means. The results were verified by simulations in Matlab and OPNET Modeler tools. We also introduce a web applet implementing and interactively demonstrating the results.

Description: Although the growth in the scale and complexity is the response of High Performance Computing (HPC) systems like computational grids to the ever-increasing demand for high processing capacity, it also makes these systems considerable energy consumers. In fact, high energy consumption is the new challenge in front of performance improvement of HPC systems and thus power management is now a necessity for them. One of the major components that can have a great role in the power-saving process is the scheduler. In this paper, a new power-aware scheduling algorithm is proposed by incorporating the characteristics of both job and resource into the job mapping and ordering, and frequency-setting decision steps. In addition to the analytical study, the proposed scheduler has been evaluated based on results obtained from experiments in different resources heterogeneity levels and workload conditions. The results show the greater capability of the proposed scheduling algorithm in comparison with other related approaches.

Description: Nowadays, green energy management is a fundamental perspective for supporting cyber-physical interactions and managing energy resources, and smart grid is emerging as the next generation energy management paradigm. Toward the green energy management and smart grid, there are several open issues to be explored. This special issue is to provide a platform for the last results in the related topics.

Description: With the energy and power costs increasing alongside the growth of the IT infrastructures, achieving workload concentration and high availability in cloud computing environments is becoming more and more complex. Virtual machine (VM) migration has become an important approach to address this issue, particularly; live migration of the VMs across the physical servers facilitates dynamic workload scheduling of the cloud services as per the energy management requirements, and also reduces the downtime by allowing the migration of the running instances. However, migration is a complex process affected by several factors such as bandwidth availability, application workload and operating system configurations, which in turn increases the complications in predicting the migration time in order to negotiate the service-level agreements in a real datacenter. In this paper, we propose an adaptive approach named improved MIGration (iMIG), in which we characterize some of the key metrics of the live migration performance, and conduct several experiments to study the impacts of the investigated metrics on the Kernel-based VM (KVM) functionalities, as well as the energy consumed by both the destination and the source hosts. Our results reveal the importance of the configured parameters: speed limit , TCP buffer size and max downtime , along with the VM properties and also their corresponding impacts on the migration process. Improper setting of these parameters may either incur migration failures or causes excess energy consumption. We witness a few bugs in the existing Quick EMUlator (QEMU)/KVM parameter computation framework, which is one of most widely used KVM frameworks based on QEMU. Based on our observations, we develop an analytical model aimed at better predictions of both the migration time and the downtime, during the process of VM deployment. Finally, we implement a suite of profiling tools in the adaptive mechanism based on the qemu-kvm-0.12.5 version, and our experiment results prove the efficiency of our approach in improving the live migration performance. In comparison with the default migration approach, our approach achieves a 40% reduction in the migration latency and a 45% reduction in the energy consumption.

Description: Community detection in social networks is one of the most active problems with lots of applications. Most of the existing works on the problem have focused on detecting the community considering only the closeness between community members. In the real world, however, it is also important to consider bad relationships between members. In this paper, we propose a new variant of the community detection problem, called friendly community search . In the proposed problem, for a given graph, we aim to not only find a densely connected subgraph that contains a given set of query nodes but also minimizes the number of nodes involved in bad relationships in the subgraph. We prove that is Non-deterministic Polynomial-time hard (NP-hard), and develop two novel algorithms, called G reedy and S teiner S wap that return the near optimal solutions. Experimental results show that two proposed algorithms outperform the algorithm adapted from an existing algorithm for the optimal quasi-clique problem.

Description: In this study, we examined the role of aminopeptidases with reference to endoplasmic reticulum aminopeptidase 1 (ERAP1) in nitric oxide (NO) synthesis employing murine macrophage cell line RAW264.7 cells activated by lipopolysaccharide (LPS) and interferon (IFN)- and LPS-activated peritoneal macrophages derived from ERAP1 knockout mouse. When NO synthesis was measured in the presence of peptides having N-terminal Arg, comparative NO synthesis was seen with that measured in the presence of Arg. In the presence of an aminopeptidase inhibitor amastatin, NO synthesis in activated RAW264.7 cells was significantly decreased. These results suggest that aminopeptidases are involved in the NO synthesis in activated RAW264.7 cells. Subsequently, significant reduction of NO synthesis was observed in ERAP1 knockdown cells compared with wild-type cells. This reduction was rescued by exogenously added ERAP1. Furthermore, when peritoneal macrophages prepared from ERAP1 knockout mouse were employed, reduction of NO synthesis in knockout mouse macrophages was also attributable to ERAP1. In the presence of amastatin, further reduction was observed in knockout mouse-derived macrophages. Taken together, these results suggest that several aminopeptidases play important roles in the maximum synthesis of NO in activated macrophages in a substrate peptide-dependent manner and ERAP1 is one of the aminopeptidases involved in the NO synthesis.

Description: Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits. Each subunit has two distinct maltooligosaccharide binding sites: a storage site and a catalytic site. Our characterization of the properties of these sites suggested that GP activity consists of two activities: (i) binding to the glycogen molecule and (ii) phosphorolysis of the non-reducing-end glucose residues. Activity (i) is mainly due to the activities of the two storage sites, which depended on the ionic strength of the medium and were directly inhibited by cyclodextrins (CDs). Activity (i) is of benefit to GP because a high concentration of non-reducing-end glucose residues is localized on the surface of the glycogen molecule. Activity (ii), the total activity of the two catalytic sites, exhibited relatively little ionic strength dependence. Because the combined activity of (i) and (ii) is deduced using glycogen as an assay substrate, the sole activity of (ii) must be measured using small maltooligosyl-substrates. By using a very low concentration of pyridylaminated maltohexaose, we demonstrated that the GP catalytic sites are active even in the presence of CDs, and that the actions of the catalytic site and the storage site are independent of each other.

Description: O -GlcNAcylation is a ubiquitous, dynamic and reversible post-translational protein modification in metazoans, and it is catalysed and removed by O -GlcNAc transferase (OGT) and O -GlcNAcase, respectively. Prokaryotes lack endogenous OGT activity. It has been reported that coexpression of mammalian OGT with its target substrates in Escherichia coli produce O -GlcNAcylated recombinant proteins, but the plasmids used were not compatible, and the expression of both OGT and its target protein were induced by the same inducer. Here, we describe a compatible dual plasmid system for coexpression of OGT and its target substrate for O -GlcNAcylated protein production in E. coli . The approach was validated using the CKII and p53 protein as control. This compatible dual plasmid system contains an arabinose-inducible OGT expression vector with a pUC origin and an isopropyl β - d -thiogalactopyranoside-inducible OGT target substrate expression vector bearing a p15A origin. The dual plasmid system produces recombinant proteins with varying O -GlcNAcylation levels by altering the inducer concentration. More importantly, the O -GlcNAcylation efficiency was much higher than the previously reported system. Altogether, we established an adjustable compatible dual plasmid system that can effectively yield O -GlcNAcylated proteins in E. coli .

Description: Active equi-paritioning of the F plasmid is achieved by its sopABC gene. SopA binds to the sopAB promoter region and SopB binds to sopC . SopA also polymerizes in the presence of ATP and Mg(II), which is stimulated by SopB. Non-specific DNA is known to inhibit SopA polymerization and disassemble SopA polymer. This study followed kinetics of polymerization and de-polymerization of SopA by turbidity measurement and found new effects by DNA and SopB. Plasmid DNA, at low concentrations, shortened the lag (nucleation) phase of SopA polymerization and also caused an initial ‘burst’ of turbidity. Results with two non-specific 20-bp DNAs indicated sequence/length dependence of these effects. sopAB operator DNA only showed inhibition of SopA polymerization. Results of turbidity decrease of pre-formed SopA polymer in the presence of ethylenediaminetetraacetic acid showed that SopB also accelerates disassembly of the SopA polymer. The steady-state level of turbidity in the presence of SopB and plasmid DNA indicated synergy between SopB and DNA in the disassembly. SopB protein showed no effect on SopA polymerization, when SopB was specifically bound to DNA. This result and others with truncation mutants of SopB suggested that a proper configuration of the domains of SopB is important for SopA-SopB interactions.

Description: Influenza A virus (IAV) has been raising public health and safety concerns worldwide. Cyanovirin-N (CVN) is a prominent anti-IAV candidate, but both cytotoxicity and immunogenicity have hindered the development of this protein as a viable therapy. In this article, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli at a 〉15-l scale. PEGylation at the N-terminal α-amine of LCVN was also reformed as 20 kDa PEGylated linkered Cyanovirin-N (PEG 20k –LCVN). The 50% effective concentrations of PEG 20k –LCVN were 0.43 ± 0.11 µM for influenza A/HK/8/68 (H3N2) and 0.04 ± 0.02 µM for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88 ± 0.66 x 10 3 µM and 1.79 ± 0.62 x 10 3 µM, respectively). A total of 12.5 µM PEG 20k –LCVN effectively inactivate the propagation of H3N2 in chicken embryos. About 2.0 mg/kg/day PEG 20k –LCVN increased double the survival rate (66.67%, P = 0.0378) of H3N2 infected mice, prolonged the median survival period, downregulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG 20k –LCVN, exhibited potent and strain-dependent anti-IAV activity in nanomolar concentrations in vitro, as well as in micromolar concentration in vivo .

Description: The semi-filamentous multicellular cyanobacterium Limnothrix / Pseudanabaena sp. strain ABRG5-3 undergoes autolysis, which involves the accumulation of polyphosphate compounds and disintegration of thylakoid membranes in cells, as a unique feature that occurs due to growth conditions. In this study, the overexpression and easy recovery of alkane (a saturated hydrocarbon, C 17 H 36 ) as a biofuel were examined in recombinants of the cyanobacteria ABRG5-3 and Synechocystis sp. strain PCC6803. The results obtained indicated that the accumulated mass of alkane accounted for ~50 or 60% of the dry weight of ABRG5-3 or PCC6803 recombinant cells, respectively. Furthermore, cultivating cells in liquid medium BG11 in which the nitrogen resource had been depleted promoted the production of alkane and cell lysis, resulting in the easy recovery of target products from the supernatant.

Description: Leucine-rich repeat kinase 2 (LRRK2) has been identified as a causative gene for Parkinson’s disease (PD). LRRK2 contains a kinase and a GTPase domain, both of which provide critical intracellular signal-transduction functions. We showed previously that Rab5b, a small GTPase protein that regulates the motility and fusion of early endosomes, interacts with LRRK2 and co-regulates synaptic vesicle endocytosis. Using recombinant proteins, we show here that LRRK2 phosphorylates Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was confirmed by western analysis using cells stably expressing LRRK2 G2019S. The phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited GTPase activity stronger than that of the unphosphorylated Rab5b protein. Two assays testing Rab5’s activity, neurite outgrowth analysis and epidermal growth factor receptor degradation assays, showed that Rab5b T6D exhibited phenotypes that were expected to be observed in the inactive Rab5b, including longer neurite length and less degradation of EGFR. These results suggest that LRRK2 kinase activity functions as a Rab5b GTPase activating protein and thus, negatively regulates Rab5b signalling.

Description: The cellular Src (c-Src) tyrosine kinase is upregulated and believed to play a pivotal role in various human cancers. However, the molecular mechanism underlying c-Src-mediated tumour progression remains elusive. Recent studies have revealed that several microRNAs (miRNAs) function as tumour suppressors by regulating the malignant expression of signalling molecules. Aberrant expression of miRNAs is frequently observed in human cancers and should be exploited to seek related molecular targets. In this review, we focus on miRNAs found to be involved in Src signalling in various cancers. We summarize recent findings on Src-related miRNAs, their target genes, mechanisms behind their interplay and their implications for cancer therapeutics.

Description: Tail-anchored (TA) proteins, a class of membrane proteins having an N-terminal cytoplasmic region anchored to the membrane by a single C-terminal transmembrane domain, are posttranslationally inserted into the endoplasmic reticulum (ER) membrane. In yeasts, the posttranslational membrane insertion is mediated by the Guided Entry of TA Proteins (GET) complex. Get3, a cytosolic ATPase, targets newly synthesized TA proteins to the ER membrane, where Get2 and Get3 constitute the Get3 receptor driving the membrane insertion. While mammalian cells employ TRC40 and WRB, mammalian homologs of Get3 and Get1, respectively, they lack the gene homologous to Get2. We recently identified calcium-modulating cyclophilin ligand (CAML) as a TRC40 receptor, indicating that CAML was equivalent to Get2 in the context of the membrane insertion. On the other hand, CAML has been well characterized as a signaling molecule that regulates various biological processes, raising the question of how the two distinct actions of CAML, the membrane insertion and the signal transduction, are assembled. In this review, we summarize recent progress of the molecular mechanism of the membrane insertion of TA proteins and discuss the possibility that CAML could sense the various signals at the ER membrane, thereby controlling TA protein biogenesis.

Description: In bacterial organisms, the oriC -independent primosome plays an essential role in replication restart after dissociation of the replication DNA-protein complex following DNA damage. PriC is a key protein component in the oriC -independent replication restart primosome. Our previous study suggested that PriC was divided into an N-terminal domain and a C-terminal domain, with the latter domain being the major contributor to single-stranded DNA (ssDNA) binding capacity. In this study, we prepared several PriC mutants in which basic and aromatic amino acid residues were mutated to alanine. Five of these residues, Arg107, Lys111, Phe118, Arg121 and Lys165 in the C-terminal domain, were shown to be involved in ssDNA binding. Moreover, we evaluated the binding of the PriC mutants to the ssDNA-binding protein (SSB) complex. Five residues, Phe118, Arg121, Arg129, Tyr152 and Arg155 in the C-terminal domain of PriC, were shown to be involved in SSB binding in the presence of ssDNA. On the basis of these results, we propose a structural model of the C-terminal domain of PriC and discuss how the interactions of PriC with SSB and ssDNA may contribute to the regulation of PriC-dependent replication restart.

Description: L -Lysine α-oxidase (LysOX) from Trichoderma viride is a homodimeric 112 kDa flavoenzyme that catalyzes the oxidative deamination of L -lysine to form α-keto--aminocaproate. LysOX severely inhibited growth of cancer cells but showed relatively low cytotoxicity for normal cells. We have determined the cDNA nucleotide sequence encoding LysOX from T. viride. The full-length cDNA consists of 2,119 bp and encodes a possible signal peptide (Met1-Arg77) and the mature protein (Ala78-Ile617). The LysOX gene have been cloned and heterologously expressed in Streptomyces lividans TK24 with the enzyme activity up to 9.8 U/ml. The enzymatic properties of the purified recombinant LysOX, such as substrate specificity and thermal stability, are same as those of native LysOX. The crystal structure of LysOX at 1.9 Å resolution revealed that the overall structure is similar to that of snake venom L -amino acid oxidase (LAAO), and the residues involved in the interaction with the amino or carboxy group of the substrate are structurally conserved. However, the entrance and the inner surface structures of the funnel to the active site, as well as the residues involved in the substrate side-chain recognition, are distinct from LAAOs. These structural differences well explain the unique substrate specificity of LysOX.

Description: For a multistep pre-targeting method using antibodies, a streptavidin mutant with low immunogenicity, termed low immunogenic streptavidin mutant No. 314 (LISA-314), was produced previously as a drug delivery tool. However, endogenous biotins (BTNs) with high affinity ( K d 〈 10 –10 M) for the binding pocket of LISA-314 prevents access of exogenous BTN-labelled anticancer drugs. In this study, we improve the binding pocket of LISA-314 to abolish its affinity for endogenous BTN species, therefore ensuring that the newly designed LISA-314 binds only artificial BTN analogue. The replacement of three amino acid residues was performed in two steps to develop a mutant termed V212, which selectively binds to 6-(5-((3a S ,4 S ,6a R )-2-iminohexahydro-1 H -thieno[3,4- d ]imidazol-4-yl)pentanamido)hexanoic acid (iminobiotin long tail, IMNtail). Surface plasmon resonance results showed that V212 has a K d value of 5.9 x 10 –7 M towards IMNtail, but no binding affinity for endogenous BTN species. This V212/IMNtail system will be useful as a novel delivery tool for anticancer therapy.

Description: A number of gene mutations are detected in cells derived from human cancer tissues, but roles of these mutations in cancer cell development are largely unknown. We examined G364R mutation of MCM4 detected in human skin cancer cells. Formation of MCM4/6/7 complex is not affected by the mutation. Consistent with this notion, the binding to MCM6 is comparable between the mutant MCM4 and wild-type MCM4. Nuclear localization of this mutant MCM4 expressed in HeLa cells supports this conclusion. Purified MCM4/6/7 complex containing the G364R MCM4 exhibited similar levels of single-stranded DNA binding and ATPase activities to the complex containing wild-type MCM4. However, the mutant complex showed only 30–50% of DNA helicase activity of the wild-type complex. When G364R MCM4 was expressed in HeLa cells, it was fractionated into nuclease-sensitive chromatin fraction, similar to wild-type MCM4. These results suggest that this mutation does not affect assembly of MCM2-7 complex on replication origins but it interferes some step at function of MCM2-7 helicase. Thus, this mutation may contribute to cancer cell development by disturbing DNA replication.

Description: A conditional proxy re-encryption (CPRE) scheme enables the proxy to convert a ciphertext from Alice to Bob, if the ciphertext satisfies one condition set by Alice. To improve the issue of more fine-grained on the condition set, Fang, Wang, Ge and Ren proposed a new primitive named Interactive conditional PRE with fine grain policy (ICPRE-FG) in 2011, and left an open problem on how to construct CCA-secure ICPRE-FG without random oracles. In this paper, we answer this open problem affirmatively by presenting a new construction of CCA-secure key-policy attribute-based PRE (KP-ABPRE) without random oracles. In this paper, we enhance the security model of Fang's ICPRE-FG scheme by allowing the adversary to make some extra queries, which do not help them win the game trivially. Finally, we present a CCA-secure KP-ABPRE without random oracles under the 3-weak decisional bilinear Diffie–Hellman inversion(3-wDBDHI) assumption.

Description: The key-insulated signature scheme provides a good method to solve key exposure problem. The key-insulated mechanism has been extended to the identity-based cryptography (IBC) and certificateless cryptography. As a new cryptographic primitive, certificate-based cryptography has unique advantage without key escrow problem in IBC and the complex certificate management problem in traditional PKI. However, certificate-based signature operations are usually performed on insecure environments where the signature key exposure is inevitable. In order to solve this problem, we intro- duce key-insulated idea into certificate-based cryptography and propose the notion and security model of the certificate-based key-insulated signature (CBKIS). In addition, we present a CBKIS scheme that is provably secure in the standard model. Security of scheme is reduced to the hardness of Non Pairing-based Generalized Bilinear DH problem and Many Diffie–Hellman problem. The proposed scheme solves the key exposure problem and improves the security in certificate-based cryptography.

Description: In this paper, we propose a privacy-preserving reservation system for electric vehicles (EV) charging stations. Due to the short driving range of EV, frequent charging is necessary. A mechanism for charging station reservation for EV owners is desirable. Our proposed system allows the vehicle owner to reserve a number of charging stations along the intended route at different time-slots. Yet it is secure against misuse such that a user can only hold a limited number of reservations simultaneously. More importantly, our system can provide privacy for users. The charging station does not know the identity of the user who has reserved it. Thus location privacy can be protected. We demonstrate the practicality of our system with a prototype implementation on a smart phone. Finally, we also provide a security proof to show that our system is secure under well-known computational assumptions.

Description: A blackbox traceable Attribute-Based Encryption (ABE) can identify a malicious user called traitor, which created a decryption box with respect to an attribute set (respectively, access policy), out of all the users who share the same attribute set (respectively, access policy). However, none of the existing traceable ABE schemes can also support revocation and large attribute universe, that is, being able to revoke compromised keys, and can take an exponentially large number of attributes. In this paper, we formalize the definitions and security models, and propose constructions of both Ciphertext-Policy ABE and Key-Policy ABE that support (i) public and fully collusion-resistant blackbox traceability, (ii) revocation, (iii) large universe and (iv) any monotonic access structures as policies (i.e. high expressivity). We also show that the schemes are secure and blackbox traceable in the standard model against selective adversaries.

Description: White-box cryptography aims at implementing a cipher to protect its key from being extracted in an untrusted environment, where the attacker has full access to the execution of the cryptographic software. In 2002, Chow et al. proposed the original white-box implementation of AES. Afterwards, various white-box implementations were presented. However, they were all badly broken because of a weakness of the implemented cryptographic algorithms: every parameter of the cryptographic operations is fixed except the round keys. In this paper, we present an AES-like cipher based on key-dependent S-boxes. The new cipher is designed to meet the design criteria of AES and hence provides a security level comparable to AES to resist black-box attacks. Moreover, we present a white-box implementation for our AES-like cipher, which is sufficient to withstand existing white-box attacks.

Description: Identity-based encryption (IBE) has many appealing applications. However, some traditional IBE schemes may not be secure in the real world due to the side-channel attacks. Leakage-resilient cryptography can capture these attacks by modeling information leakage that adversary can access. In this paper, we apply a hash proof technique in the existing CCA-secure variant of the Gentry's IBE scheme to construct a new leakage-resilient IBE scheme in the bounded-leakage model. The proposed scheme is more computationally efficient than the original Alwen et al. 's leakage-resilient IBE scheme. It enjoys a shorter key (public/secret key) length, and a higher relative key leakage ratio. The new leakage-resilient scheme is proved semantically secure against adaptive chosen ciphertext attack in the standard model under the truncated augmented bilinear Diffie-Hellman exponent ( $q$ -TABDHE) assumption.

Description: Importin α performs the indispensable role of ferrying proteins from the cytoplasm into the nucleus with a transport carrier, importin β1. Mammalian cells from mouse or human contain either six or seven importin α subtypes, respectively, each with a tightly regulated expression. Therefore, the combination of subtype expression in a cell defines distinct signaling pathways to achieve progressive changes in gene expression essential for cellular events, such as differentiation. Recent studies reveal that, in addition to nucleocytoplasmic transport, importin αs also serve non-transport functions. In this review, we first discuss the physiological significance of importin α as a nuclear transport regulator, and then focus on the functional diversities of importin αs based on their specific subcellular and cellular localizations, such as the nucleus and plasma membrane. These findings enrich our knowledge of how importin αs actively contribute to various cellular events.

Description: The structure of the complex of maize sulfite reductase (SiR) and ferredoxin (Fd) has been determined by X-ray crystallography. Co-crystals of the two proteins prepared under different conditions were subjected to the diffraction analysis and three possible structures of the complex were solved. Although topological relationship of SiR and Fd varied in each of the structures, two characteristics common to all structures were found in the pattern of protein-protein interactions and positional arrangements of redox centres; (i) a few negative residues of Fd contact with a narrow area of SiR with positive electrostatic surface potential and (ii) [2Fe-2S] cluster of Fd and [4Fe-4S] cluster of SiR are in a close proximity with the shortest distance around 12 Å. Mutational analysis of a total of seven basic residues of SiR distributed widely at the interface of the complex showed their importance for supporting an efficient Fd-dependent activity and a strong physical binding to Fd. These combined results suggest that the productive electron transfer complex of SiR and Fd could be formed through multiple processes of the electrostatic intermolecular interaction and this implication is discussed in terms of the multi-functionality of Fd in various redox metabolisms.

Description: Analysis of replicating mammalian mitochondrial DNA (mtDNA) suggested that initiation of the replication occurs not only at the specific position, Ori-H but also across a broad zone in mtDNA. We investigated relationship of mitochondrial transcription initiation which takes place upstream of Ori-H and mtDNA replication initiation through analysing the effect of knockdown of mitochondrial transcription factor B2, TFB2M and mitochondrial RNA polymerase, POLRMT, components of the transcription initiation complexes in cultured human cells. Under the conditions where suppression of the transcription initiation complexes was achieved by simultaneous depletion of TFB2M and POLRMT, decrease of replication intermediates of mtDNA RITOLS replication mode accompanied reduction in mtDNA copy number. On the other hand, replication intermediates of coupled leading and lagging strand DNA replication, another proposed replication mode, appeared to be less affected. The findings support the view that the former mode involves transcription from the light strand promoter (LSP), and suggest that initiation of the latter mode is independent from the transcription and has distinct regulation. Further, knockdown of TFB2M alone caused significant decrease of 7S DNA, which implies that transcription initiation complexes formed at the LSP engage 7S DNA synthesis more frequently than the initiation of productive replication and transcription.

Description: Cycas revoluta leaf lectin (CRLL) of mannose-recognizing jacalin-related lectin (mJRL) has two tandem repeated carbohydrate recognition domains, and shows the characteristic sugar-binding specificity toward high mannose-glycans, compared with other mJRLs. We expressed the N-terminal domain and C-terminal domain (CRLL-N and CRLL-C) separately, to determine the fine sugar-binding specificity of each domain, using frontal affinity chromatography, glycan array and equilibrium dialysis. The specificity of CRLL toward high mannose was basically derived from CRLL-N, whereas CRLL-C had affinity for α1-6 extended mono-antennary complex-type glycans. Notably, the affinity of CRLL-N was most potent to one of three Man 8 glycans and Man 9 glycan, whereas the affinity of CRLL-C decreased with the increase in the number of extended α1-2 linked mannose residue. The recognition of the Man 8 glycans by CRLL-N has not been found for other mannose recognizing lectins. Glycan array reflected these specificities of the two domains. Furthermore, it was revealed by equilibrium dialysis method that the each domain had two sugar-binding sites, similar with Banlec, banana mannose-binding Jacalin-related lectin.

Description: The ciphertext retrieval is of paramount importance for data confidentiality and utilization in mobile cloud environment. The receiver, usually equipped with resource constrained devices, retrieves data stored in the cloud server by submitting a confidential request (or trapdoor) to the cloud. Previous schemes need at least one exponentiation operation in group $\mathbb {G}$ for each keyword to generate the trapdoor, which is quite burdensome for mobile devices to support such computational cost. The computational cost of trapdoor generation limits the application of ciphertext retrieval, especially in a wireless environment. In this paper, we propose the first online/offline ciphertext retrieval (OOCR) scheme, where the trapdoor generation is split into two phases: offline phase and online phase . Most of the computation of the trapdoor could be performed in the offline phase prior to knowing the keyword. The generation of the real trapdoor with keyword can be done efficiently in the online phase. The most challenging task is to resist the so-called insider attacks, which is about keyword guessing attacks from the untrusted cloud server. We also build a novel framework to resist insider attacks and propose an OOCR scheme against insider attacks. Our semantic security proof and performance analysis demonstrate that the proposal is practical for mobile cloud applications.

Description: In this paper, we point out some faulty instantiations of threshold ring signatures (TRS) based on the threshold proof-of-knowledge (TPoK) protocol. Although a TRS can be regarded as the non-interactive version of the TPoK, the computational domains of the variables should be carefully chosen. We show that by choosing some inappropriate domains, two such instantiations suffer from forgery and anonymity attacks. Our attacks rely on algebraic techniques which involve solving some particular instances of the well-known subset sum problem. While we focus our attacks on two particular instantiations of the TRS, they are generic and are applicable to other schemes with the same choice of domains or a similar structure. We believe this paper can act as an important security remark on the design of future TRS schemes.

Description: The typical Secure Document Management System (SDMS) uses cryptography or access control mechanisms to restrict illegal access by unauthorized users to digital documents. However, these techniques are insufficient when authorized users betray the trust of their organizations, distributing sensitive digital documents to unauthorized users. This paper presents a novel end-to-end approach to construct a robust SDMS able to guarantee not only the integrity and confidentiality of digital documents (data-centric security), but also providing robust insider threat tracing mechanisms (user-centric security). As far as the authors' knowledge extends, this is the first contribution that analyses security issues of SDMS considering data-centric (by means of encryption) and user-centric (based on fingerprinting) security services for the construction of an SDMS. Security requirements are identified from the modeling of a digital document's lifecycle. Then cryptographic techniques are carefully coupled with a fingerprinting technique at specific stages of the proposed document lifecycle. As a proof of concept, an SDMS was created, implemented and evaluated, demonstrating its feasibility for deployment in production environments. The robustness of the SDMS was proved, using standard cryptographic algorithms and secure key lengths. The created SDMS also resisted the collusion and retyping attacks commonly directed at fingerprinting applications.

Description: Nowadays, trust systems (TSs) are widely used for tackling dishonest entities in many modern environments. However, these systems are vulnerable to some kinds of attacks where attackers try to deceive the system using sequences of misleading behaviors and dishonest recommendations. A robust TS is expected to function properly even in the possibility of such attacks. To the best of our knowledge, simulation has been the main approach for evaluation of TSs so far, and there is no remarkable verification method for this aim. In this paper, a method for quantitative verification of TSs' robustness against malicious attackers is proposed. The proposed method consists of a formalism for specifying any given trust model named TS attack process that is cast into partially observable Markov decision process mathematical framework. The proposed method is capable of verifying TSs against both well-known attacks and the worst possible attack scenario. The method could also be used to help adjusting parameters of the given TS. Moreover, a quantitative robustness measure is introduced, which helps to compare the robustness of different TSs. To illustrate the applicability of the proposed method, a number of case studies for analysis and comparison of selected trust models (including Subjective Logic and REGRET) are presented.

Description: Multivariate cryptographic systems are one of the most popular public key cryptographic systems, since they have the potential to resist quantum computer attacks. Multivariate signatures have few applications where low area is more of a priority since they are much larger than rivest-shamir-adleman and elliptic curves cryptography. In this paper, we propose a very small cryptographic processor for multivariate signatures and enhance our design in three directions. First, we propose a Modular Arithmetic Logic Unit based on composite field representations. Second, we design a small instruction set. Third, we adapt register reuse and time sharing. Via further other minor optimizations and by integrating the major improvement above, our design is implemented on a small Xilinx field programmable logic array and utilizes only 47 flip flops, 155 look up tables and 92 slices. Its small area would present a significant saving, including fitting into a smaller device, e.g. radio frequency identification tag. Our design can generate multivariate signatures with a moderate speed, e.g. Unbalanced Oil–Vinegar Signature, Rainbow and extensions of Tame Transformation Signature, which is sufficient for numerous applications where area usage is more of a priority. Comparison results show that our design is 50% smaller than the smallest available public key cryptographic system.

Description: Inversions in small finite fields are playing a key role in many areas. We present techniques to exploit binary trees for fast inversions in $GF(2^n)$ and $GF(p)$ , where $n$ is a positive integer and $p$ is a prime number. The non-pipelined versions of our design in $GF(2^n)$ and $GF(p)$ have the execution time of $(n-1)(T_{AND}+T_{XOR})$ and $\lfloor \log _2p\rfloor (T_{AND}+T_{XOR})$ , where $T_{AND}$ and ${T_{XOR}}$ are delays of AND and XOR gates, respectively. The pipelined version of our design has a throughput rate of one result per $T_{AND}$ (or $T_{XOR}$ ). The latency is the greater value between $T_{AND}$ and $T_{XOR}$ . In other words, the time complexities of non-pipelined and pipelined versions are $O(n)$ (or $O(log_2p)$ ) and $O(1)$ , respectively. Experimental results and comparisons show that our design provides significant reductions in both the execution time and time–area product, e.g. the execution time of inversion in $GF(2^{12})$ is reduced by 73 $\%$ and time–area product of inversion in $GF(2^6)$ is reduced by 77 $\%$ .

Description: We proposed two multiparty quantum secret sharing schemes based on n -particle Greenberger–Horne–Zeilinger-states (GHZ states), which are transformed from Einstein–Podolsky–Rosen pairs by entanglement swapping. In our schemes, the dealer imposes messages by performing local unitary operations ( I, x, i y, z ) on the n -particle GHZ state she holds, and the agents collaborate to deduce the dealer's messages by performing local unitary operations on their own qubit. The amount of dealer's secret message is positively related with the number of agents. The need of qubits is one-third less than the former schemes and, also, they can be reused for the next new round. The scheme (II) does not have to pre-share the code table, which increases the security without the risk of being stolen.

Description: Automatic fare collection (AFC) systems calculate the fare that the users must pay depending on the time of service (time-based) or the points of entrance and exit of the system (distance-based). The progressive introduction of Information and Communication Technologies allows the use of electronic tickets, which helps us to reduce costs and improve the control of the infrastructures. Nevertheless, these systems must be secure against possible fraud and they must also preserve users’ privacy. Therefore, we have studied the security requirements for the time-based and distance-based systems and we have proposed a protocol for each of the AFC systems. 1 The protocols offer strong privacy for honest users, i.e. the service provider is not able to disclose the identity of its users and, moreover, different journeys of the same user are not linkable between them. However, anonymity for users could be revoked if they misbehave. The protocols have been implemented in Android and its performance has been evaluated in two Android smartphones. The results remark that protocols are suitable to be used on an AFC system with a medium class mobile device although they offer a better experience with a high-class smartphone. The appearance in the market of more powerful mobile devices suggests a better usability of our proposal in a near future.

Description: Accurately locating unknown nodes is a critical issue in the study of wireless sensor networks (WSNs). Many localization approaches have been proposed based on anchor nodes, which are assumed to know their locations by manual placement or additional equipments such as global positioning system. However, none of these approaches can work properly under the adversarial scenario. In this paper, we propose a novel scheme called two-step secure localization (TSSL) stand against many typical malicious attacks, e.g. wormhole attack and location spoofing attack. TSSL detects malicious nodes step by step. First, anchor nodes collaborate with each other to identify suspicious nodes by checking their coordinates, identities and time of sending information. Then, by using a modified mesh generation scheme, malicious nodes are isolated and the WSN is divided into areas with different trust grades. Finally, a novel localization algorithm based on the arrival time difference of localization information is adopted to calculate locations of unknown nodes. Simulation results show that the TSSL detects malicious nodes effectively and the localization algorithm accomplishes localization with high localization accuracy.

Description: Distance-bounding protocols form a family of challenge–response authentication protocols that have been introduced to thwart relay attacks. They enable a verifier to authenticate and to establish an upper bound on the physical distance to an untrusted prover. We provide a detailed security analysis of a family of such protocols. More precisely, we show that the secret key shared between the verifier and the prover can be leaked after a number of nonce repetitions. The leakage probability, while exponentially decreasing with the nonce length, is only weakly dependent on the key length. Our main contribution is a high probability bound on the number of sessions required for the attacker to discover the secret, and an experimental analysis of the attack under noisy conditions. Both of these show that the attack's success probability mainly depends on the length of the used nonces rather than the length of the shared secret key. The theoretical bound could be used by practitioners to appropriately select their security parameters. While longer nonces can guard against this type of attack, we provide a possible countermeasure which successfully combats these attacks even when short nonces are used.

Description: In threshold public-key encryption (TPKE), the decryption key is divided into n shares, each one of which is given to a different decryption user in order to avoid single points of failure. A robust TPKE is that if threshold decryption of a valid ciphertext fails, the combiner can identify the decryption users that supplied invalid partial decryption shares. In this paper, we propose a practical and efficient TPKE scheme which is robust and non-interactive. Security against chosen-ciphertext attacks (CCAs) can be proved in the standard model under the hashed Diffie–Hellman assumption in bilinear groups. The security reduction is tight and simple. We use an instantiation hash function of the Kiltz's key encapsulation mechanism and Lai et al. 's chosen-ciphertext secure technique to construct a TPKE scheme. Moreover, our scheme is more simple and shown to be more efficient than currently existing CCA-secure TPKE schemes.

Description: The advances in the digital world (e.g. the Internet, Communications, etc.) are closing the gap between consumers and providers, in both Business to Consumer and Business to Business environments. Through the Internet, providers can offer their products directly to consumers, which increase their choices and allow them to contract a set of different services/products from different providers. But sometimes the consumer needs an all-or-nothing exchange with these providers: an atomic exchange. The consumer has negotiated/obtained a set of conditions that are only met if she acquires all the services/products. Thus, we need an Atomic Multi-Two-Party contract signing protocol. Even though digital signature of contracts is a topic that has been widely studied, it lacks a solution when applied to Atomic Multi-Two-Party scenarios. Here, we propose the first solution to solve this problem.

Description: Key-evolving cryptography is intended to mitigate the damage in case of a secret key compromise, one of the severest security threats to actual cryptographic schemes. In the public-key setting, the essential idea of key-evolving lies in updating the private key with time, while maintaining the same public key. Key evolution in encryption and signing has been well studied, especially in the identity-based (ID-based) setting where an entity's public key can be derived from that entity's identity information. From a more practical standpoint, however, one would like to use the primitive signcryption in the hierarchical ID-based setting. In this paper, we propose the first key-evolving hierarchical ID-based signcryption scheme that is scalable and joining-time-oblivious and allows secret keys to be updated autonomously. The security proofs of our construction depend on the bilinear Diffie–Hellman assumption and the computational Diffie–Hellman assumption in the random oracle model. To be specific, our proposal not only achieves the fundamental goals of confidentiality and authenticity, but also enjoys desirable properties of non-repudiation, ciphertext anonymity and strong forward security. Compared with the conventional sign-then-encrypt approach, our construction provides better efficiency in terms of the computation cost and the communication overhead.

Description: Cooperative Intelligent Transportation Systems (ITS) will turn up to us with safer and more efficient driving environments as well as convenient and infotainment features for future ITS stations. ETSI and ISO are completing the standardization of the building blocks of a reference communication architecture for cooperative ITS. Future ITS stations complying with this set of standards deployed in vehicles, at the roadside infrastructures and within the Internet are expected to communicate with each other through a combination of ITS dedicated communication protocols and legacy Internet protocols. However, in spite of the wide adoption of IPv6 for cooperative ITS communications, relatively little attention has been paid to the security issues related to IPv6 signaling and IPv6 transport communications. In this paper, we present our position on the emerging and urgent IPv6-related security issues that occur in communications between ITS stations complying with the ITS station reference architecture under standardization within ETSI TC ITS and ISO TC204.

Description: A requirement for advancing antibody-based medicine is the development of proteins that can bind with high affinity to a specific epitope related to a critical protein activity site. As a part of generating such proteins, we have succeeded in creating a binding protein without changing epitope by complementarity-determining region 3 (CDR3) grafting (Inoue et al. , Affinity transfer to a human protein by CDR3 grafting of camelid VHH. Protein Sci. 20, 1971–1981). However, the affinity of the target-binding protein was low. In this manuscript, the affinity maturation of a target-binding protein was examined using CDR3-grafted camelid single domain antibody (VHH) as a model protein. Several amino acids in the CDR1 and CDR2 regions of VHH were mutated to tyrosines and/or serines and screened for affinity-matured proteins by using in silico analysis. The mutation of two amino acids in the CDR2 region to arginine and/or aspartic acid increased the affinity by decreasing the dissociation rate. The affinity of designed mutant increased by ~20-fold over that of the original protein. In the present study, candidate mutants were narrowed down using in silico screening and computational modelling, thus avoiding much in vitro analytical effort. Therefore, the method used in this study is expected to be one of the useful for promoting affinity maturation of antibodies.

Description: A method was previously established for evaluating Asn deamidation by matrix-assisted laser desorption/ionization time of flight-mass spectrometry using endoproteinase Asp-N. In this study, we demonstrated that this method could be applied to the identification of the deamidation site of the humanized fragment antigen-binding (Fab). First, a system for expressing humanized Fab from methylotrophic yeast Pichia pastoris was constructed, resulting in the preparation of ~30 mg of the purified humanized Fab from 1 l culture. Analysis of the L-chain derived from recombinant humanized Fab that was heated at pH 7 and 100°C for 1 h showed the deamidation at Asn138 in the constant region. Then, we prepared L-N138D Fab and L-N138A Fab and examined their properties. The circular dichroism (CD) spectrum of the L-N138D Fab was partially different from that of the wild-type Fab. The measurement of the thermostability showed that L-N138D caused a significant decrease in the thermostability of Fab. On the other hand, the CD spectrum and thermostability of L-N138A Fab showed the same behaviour as the wild-type Fab. Thus, it was suggested that the introduction of a negative charge at position 138 in the L-chain by the deamidation significantly affected the stability of humanized Fab.

Description: The tripartite motif (TRIM) or RBCC proteins are characterized by the TRIM composed of a RING finger, B-box and coiled-coil domains. TRIM proteins often play roles in the post-translational protein modification, including ubiquitylation and other ubiquitin-like modifications. Evidence has accumulated in regard to the contribution of TRIM proteins to diverse cellular processes, including such as cell cycle progression, apoptosis, immunity and transcriptional regulation. In particular, some of the TRIM proteins have been characterized to exert oncogenic or tumour suppressor-like functions depending on the context. A recent report by Inoue and his colleagues has revealed that Terf/TRIM17 stimulates the degradation of a kinetochore protein ZWINT and regulates the proliferation of breast cancer cells. Terf has also been paid attention as a factor promoting neuronal apoptosis, by degrading a Bcl2-like anti-apoptotic protein Mcl-1. Like aircraft trim tabs, TRIM proteins trim the balance of homoeostasis by modulating various biological pathways through protein–protein interactions.

Description: Cyclin-dependent kinase (CDK) that plays a central role in preventing re-replication of DNA phosphorylates several replication proteins to inactivate them. MCM4 in MCM2-7 and RPA2 in RPA are phosphorylated with CDK in vivo . There are inversed correlations between the phosphorylation of these proteins and their chromatin binding. Here, we examined in vitro phosphorylation of human replication proteins of MCM2-7, RPA, TRESLIN, CDC45 and RECQL4 with CDK2/cyclinE, CDK2/cyclinA, CDK1/cyclinB, CHK1, CHK2 and CDC7/DBF4 kinases. MCM4, RPA2, TRESLIN and RECQL4 were phosphorylated with CDKs. Effect of the phosphorylation by CDK2/cyclinA on DNA-binding abilities of MCM2-7 and RPA was examined by gel-shift analysis. The phosphorylation of RPA did not affect its DNA-binding ability but that of MCM4 inhibited the ability of MCM2-7. Change of six amino acids of serine and threonine to alanines in the amino-terminal region of MCM4 rendered the mutant MCM2-7 insensitive to the inhibition with CDK. These biochemical data suggest that phosphorylation of MCM4 at these sites by CDK plays a direct role in dislodging MCM2-7 from chromatin and/or preventing re-loading of the complex to chromatin.

Description: To determine the effects of alcohols on the low-frequency local motions that control slow changes in structural dynamics of native-like compact states of proteins, we have studied the effects of alcohols on structural fluctuation of M80-containing -loop by measuring the rate of thermally driven CO dissociation from a natively folded carbonmonoxycytochrome c under varying concentrations of alcohols (methanol, ethanol, 1-propanol, 2-propanol, 3°-butanol, 2,2,2-trifluoroethanol). As alcohol is increased, the rate coefficient of CO dissociation ( k diss ) first decreases in subdenaturing region and then increases on going from subdenaturing to denaturing milieu. This decrease in k diss is more for 2,2,2-trifluroethanol and 1-propanol and least for methanol, indicating that the first phase of motional constraint is due to the hydrophobicity of alcohols and intramolecular protein cross-linking effect of alcohols, which results in conformational entropy loss of protein. The thermal denaturation midpoint for ferrocytochrome c decreases with increase in alcohol, indicating that alcohol decrease the global stability of protein. The stabilization free energy ( G ) in alcohols’ solution was calculated from the slope of the Wyman–Tanford plot and water activity. The m -values obtained from the slope of G versus alcohols plot were found to be more negative for longer and linear chain alcohols, indicating destabilization of proteins by alcohols through disturbance of hydrophobic interactions and hydrogen bonding.

Description: Ubiquitination is a post-translational modification involved in the regulation of a broad variety of cellular functions, such as protein degradation and signal transduction, including nuclear factor-B (NF-B) signalling. NF-B is crucial for inflammatory and immune responses, and aberrant NF-B signalling is implicated in multiple disorders. We found that linear ubiquitin chain assembly complex (LUBAC), composed of HOIL-1L, HOIP and SHARPIN, generates a novel type of Met1 (M1)-linked linear polyubiquitin chain and specifically regulates the canonical NF-B pathway. Moreover, specific deubiquitinases, such as CYLD, A20 (TNFAIP3) and OTULIN/gumby, inhibit LUBAC-induced NF-B activation by different molecular mechanisms, and several M1-linked ubiquitin-specific binding domains have been structurally defined. LUBAC and these linear ubiquitination-regulating factors contribute to immune and inflammatory processes and apoptosis. Functional impairments of these factors are correlated with multiple disorders, including autoinflammation, immunodeficiencies, dermatitis, B-cell lymphomas and Parkinson’s disease. This review summarizes the molecular basis and the pathophysiological implications of the linear ubiquitination-mediated NF-B activation pathway regulation by LUBAC.

Description: We screened circadian-regulated genes in rat cartilage by using a DNA microarray analysis. In rib growth-plate cartilage, numerous genes showed statistically significant circadian mRNA expression under both 12:12 h light–dark and constant darkness conditions. Type II collagen and aggrecan genes—along with several genes essential for post-translational modifications of collagen and aggrecan, including prolyl 4-hydroxylase 1, lysyl oxidase, lysyl oxidase-like 2 and 3'-phosphoadenosine 5'-phosphosulphate synthase 2—showed the same circadian phase. In addition, the mRNA level of SOX9, a master transcription factor for the synthesis of type II collagen and aggrecan, has a similar phase of circadian rhythms. The circadian expression of the matrix-related genes may be critical in the development and the growth of various cartilages, because similar circadian expression of the matrix-related genes was observed in hip joint cartilage. However, the circadian phase of the major matrix-related genes in the rib permanent cartilage was almost the converse of that in the rib growth-plate cartilage under light–dark conditions. We also found that half of the oscillating genes had conserved clock-regulatory elements, indicating contribution of the elements to the clock outputs. These findings suggest that the synthesis of the cartilage matrix macromolecules is controlled by cell-autonomous clocks depending upon the in vivo location of cartilage.

Description: Human chromosome 7 open reading frame 24 (C7orf24)/-glutamyl cyclotransferase has been suggested to be a potential diagnostic marker for several cancers, including carcinomas in the bladder urothelium, breast and endometrial epithelium. We here investigated the epigenetic regulation of the human C7orf24 promoter in normal diploid ARPE-19 and IMR-90 cells and in the MCF-7 and HeLa cancer cell lines to understand the transcriptional basis for the malignant-associated high expression of C7orf24. Chromatin immunoprecipitation analysis revealed that histone modifications associated with active chromatin were enriched in the proximal region but not in the distal region of the C7orf24 promoter in HeLa and MCF-7 cells. In contrast, elevated levels of histone modifications leading to transcriptional repression and accumulation of heterochromatin proteins in the C7orf24 promoter were observed in the ARPE-19 and IMR-90 cells, compared to the levels in HeLa and MCF-7 cancer cells. In parallel, the CpG island of the C7orf24 promoter was methylated to a greater extent in the normal cells than in the cancer cells. These results suggest that the transcriptional silencing of the C7orf24 gene in the non-malignant cells is elicited through heterochromatin formation in its promoter region; aberrant expression of C7orf24 associated with malignant alterations results from changes in chromatin dynamics.

Description: Abscisic acid (ABA) is a stress-inducible plant hormone comprising an inevitable component of the human diet. Recently, stress-induced accumulation of autocrine ABA was shown in humans, as well as ABA-mediated modulation of a number of disease-associated systems. Now, the application of a chemical proteomics approach to gain further insight into ABA mechanisms of action in mammalian cells is reported. An ABA mimetic photoaffinity probe was applied to intact mammalian insulinoma and embryonic cells, leading to the identification of heat shock protein 70 (HSP70) family members, (including GRP78 and HSP70-2) as putative human ABA-binding proteins. In vitro characterization of the ABA–HSP70 interactions yielded K d s in the 20–60 µM range, which decreased several fold in the presence of co-chaperone. However, ABA was found to have only variable- and co-chaperone-independent effects on the ATPase activity of these proteins. The potential implications of these ABA–HSP70 interactions are discussed with respect to the intracellular protein folding and extracellular receptor-like activities of these stress-inducible proteins. While mechanistic and functional relevance remain enigmatic, we conclude that ABA can bind to human HSP70 family members with physiologically relevant affinities and in a co-chaperone-dependent manner.

Description: The objectives of this special issue are advanced security technologies and services for future computing environments, including, but not limited to, security primitives, protocols and security applications and services. Recent advances in security technologies and services for future computing environments have created a new class of the following: (i) Wireless sensor networks and radio-frequency identification security and privacy; (ii) security architectures for distributed network systems, P2P systems, cloud and grid systems; and (iii) security in e-commerce, mobile and wireless networks, and finally, security standards and assurance methods. All papers are expected to focus on novel approaches for advanced security technologies and services for future computing environments and to present high-quality results for tackling problems arising from the ever-growing advanced security technologies and services for future computing environments.

Description: In this paper, we present a statistical analysis of six traffic features based on entropy and distinct feature number at the packet level, and we find that, although these traffic features are unstable and show seasonal patterns like traffic volume in a long-time period, they are stable and consistent with Gaussian distribution in a short-time period. However, this equilibrium property will be violated by some anomalies. Based on this observation, we propose a Multi-dimensional Box plot method for Short-time scale Traffic (MBST) to classify abnormal and normal traffic. We compare our new method with the MCST method proposed in our prior work and the well-known wavelet-based and A Short-Timescale Uncorrelated-Traffic Equilibrium (ASTUTE) techniques. The detection result on synthetic anomaly traffic shows that MBST can better detect the low-rate attacks than wavelet-based and MCST methods, and detection result on real traffic demonstrates that MBST can detect more anomalies with lower false alarm rate than the two methods. Especially compared with ASTUTE, MBST performs much better for detecting anomalies involving a few large flows despite a little poor for detecting anomalies involving large number of small flows.

Description: Given a text or database T , the circular pattern discovery (CPD) problem is to identify ‘interesting’ circular patterns in T . Here, no specific input pattern is provided, and what is interesting is typically defined in terms of constraints in the search. We propose two algorithms for the CPD problem. The first algorithm uses suffix trees and suffix links to solve the exact CPD problem in time, where m 2 is the maximum length of the circular patterns and N is the total length of the sequence database. The second algorithm uses suffix arrays to solve the more challenging approximate CPD (ACPD) problem in worst case, and on average, where k is the maximum allowed error(s). By exploiting the nature of the ACPD problem, the complexity is reduced to time in the worst case, and on average.

Description: We introduce a process algebra with processes able to migrate between different explicit locations of a distributed environment defined by a number of distinct locations. We use timing constraints over local clocks to control migration and communication, together with local maximal concurrency in the way actions are executed. Two processes may communicate if they are present at the same location and, in addition, they have appropriate access permissions to communicate over a shared channel. Access permissions can be acquired or lost while moving from one location to another. Timing constraints coordinate and control both communication between processes and migration between locations. We completely characterize the situations in which a process is guaranteed to possess safe access permissions in all possible environments. In this way, one can design systems in which processes are not blocked (deadlocked) due to the lack of dynamically changing access permissions.