ALBERT

Description: Compelling evidences indicate a key role for regulatory T cells (Tregs) on the host response to cancer and recent studies indicated that the generation of effective WT1-specific cytotoxic T cells can be largely affected by the presence of Tregs. This is the first study to describe human Tregs generated specifically against the WT1 antigen which is overexpressed in several human leukemias and provide the mechanism by which these anti-WT1 Tregs inhibit the immune response in leukemia patients. We have generated T cell lines and clones that specifically recognized a WT1-84 peptide in an HLA DRB1*0402/TCR-Vb8-restricted manner. Importantly, they recognized HLADRB1* 04-matched fresh leukemic cells expressing the WT1 antigen. These clones exerted a Th2 cytokine profile, had a CD4+CD25+Foxp3+GITR+CD127− Tregs phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell-contact. Priming of allo-reactive T cells in the presence of Tregs strongly inhibited the expansion of NK; NK-T and CD8+ T cells, had an inhibitory effect on NK/NK-T cytotoxic activity but not on CD8+ T cells. Furthermore, priming of T cells with the WT1- 126 HLA-A0201-restricted peptide in the presence of Tregs strongly inhibited the induction of anti-WT1-126 CD8+ CTL responses as evidenced by both very low cytotoxic activity and IFN-g production. Moreover, these Tregs clones specifically produced Granzyme-B and selectively induced apoptosis in WT1-84 pulsed-autologous APCs but not in apoptoticresistant DR4-matched leukemic cells. Importantly, we have also detected anti-WT1-84 IL-5+/Granzyme-B+/Foxp3+ CD4+ Tregs in 5 out of 8 HLA-DR4+ AML patients. These findings suggest a critical role for anti-WT1 Tregs in the inhibition of T cell responses against leukemia. This study may have important implications for the clinical manipulation of Tregs such as immuno-targeting of TCR-Vb-8 with mAbs to eliminate anti-WT1 Tregs in leukemia patients in order to enhance GVL before vaccination with the WT1 antigen. On the other hand, leukemia patients with GVHD should be clinically-tried for vaccination with the current WT1-84 peptide or adoptively-treated with ex-vivo anti-WT1 Treg cells to specifically enhance their frequency, which is known to be very low in these patients.

Description: Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myeloid and megakaryocytic bone marrow production. MDS patients are classified according to the WHO classification of myeloid neoplasms. During the past 15 years management of MDS patients has been stratified according to the International Prognostic Scoring System (IPSS) risk score. Recently a revised version of IPSS has been introduced (IPSS-R). One quarter of LR-MDS in this new IPSS-R were reclassified as having a higher risk and a substantial subset of high risk-MDS (HR-MDS) were reclassified as lower risk. In LR-MDS a differentiation block is observed in the erythroid lineage. The diagnosis and follow up of cytopenias in particular anemia must be the main objective (1). The soluble transferrin receptor (sTfR) directly reflects the erythropoietic activity in individuals without iron defiency and may appreciate ineffective dysplastic erythropoiesis in LR-MDS. In LR-MDS there is also an inverse relationship between EPO level and the degree of anemia but a wide range of EPO levels is found in patients with similar Hb concentrations. Thus the highest EPO levels are found in patients with erythroid hypoplasia in bone marrow. Aims The combination of several biomarkers: Hb, ferritin, EPO and sTfR may be useful in LR-MDS for diagnosis and follow up. Methods A total of 192 patients with LR-MDS were investigated. Median age of the 192 patients was 71 years (21-92) with 56% males, median survival: 54 months, median follow up: 102 months. The stratification according to the WHO criteria and IPSS risk score was realized. Bone marrows were studied and cytogenetic assessment was realized in the same time. Serum concentrations of ferritin, EPO and sTfR has been analyzed by immuno-assays. Hb level was determined on Beckman Coulter apparatus. The follow up of Hb, ferritin, EPO and sTfR was realized every 2 months in patients with supportive care only until the first specific treatment. A multivariate logistic regression analysis to ascertain the correlations between disease progression and studied biological parameters was realized. Results The logistic regression analysis of our results is significant to define a biological evolutive profile of LR-MDS patients with these biomarkers. The combination of these routine parameters may represent a functional erythropoietic follow up in LR-MDS patients (table 1). This biological tool is an easy method to observe the red cell lineage of LR-MDS patients. This combination informs about the progressive ineffective and dysplatic erythropoiesis in LR-MDS patients. The measurement of ferritin which is a correlated parameter in LR-MDS shows the level of iron overload. A normal or high level without inflammation condition excludes an iron deficiency. The EPO level can give a predictive information about the future efficacy of ESA (endogenous EPO 〈 500 U/l). Conclusion With our results and a correlative logistic regression analysis, we can propose a biological scoring system to appreciate the evolutive anemia of LR-MDS progression in patients. In LR-MDS the management of patients may be based on personalized medicine according a risk assessment with IPSS-R, cytogenetics, mutations and HLA typing (2). But an additional biological and functional predictive scoring system informs about the important independent role of dysplasias particularly anemia in LR-MDS patients before to choose a suitable therapy: transfusions, iron chelation, ESA, TGF-ï¢ pathway inhibitors, G-CSF, immun suppressive treatment, lenalidomide, azacytidine, allogeneic HSCT Table 1. Hb ± EPO ±  sTfRDysplastic erythropoiesis without anemia Hb ±  EPO  sTfRStabilized dysplastic erythropoiesis Hb  EPO  sTfRUnstabilized dysplactic erythropoiesis Hb  EPO  sTfRIneffective dysplastic erythropoiesis EPO 〈 500 U/l : ESA may be efficient〉 500 U/l : ESA will be inefficientFerritin level : iron overload References Giagounidis A Management of low-risk myelodysplastic syndromes Hematology Education, 2015, 9 (1), 219-225 Platzbecker U et al Personalized medicine in myelodysplastic syndromes: wishful thinking or already clinical reality? Hematologica, 2015, 100 (5), 568-571 Disclosures No relevant conflicts of interest to declare.

Description: This study examined the effects of planting spacing on growth, yield, and wood properties of teak planted at square spacing regimes of 2 m, 3 m, and 4 m at Longuza Forest Plantation, Tanzania. To achieve this, tree, stand, and wood properties were studied at age of 14 years. Results showed that diameter at breast height and total height increased with increasing spacing. Mean annual increment increased significantly with increasing spacing while spacing did not have significant effect on total volume production and basal area. Basic density is also not affected by spacing while heartwood proportion increases as planting spacing increases. All studied wood properties (modulus of rupture, modulus of elasticity, compression strength tangential to grain, and shear tangential to the grain) except cleavage tangential to grain were not significantly affected by increasing spacing. It is recommended to use the spacing of 3 × 3 m, but if thinning can be done before onset of competition at 5 years, the currently used spacing of 2.5 × 2.5 m can still be used. However, the use of a spacing of 4 × 4 m can give at least 50% heartwood at shorter rotation age of 30 years.

Description: This paper presents an explicit, omnidirectional, analytical, and decoupled closed-form solution for the lower limb kinematics of the humanoid robot NAO. The paper starts by decoupling the position and orientation analysis from the overall Denavit-Hartenberg (DH) transformation matrices. Here, the joint activation sequence for the DH matrices is based on the geometry of a triangle. Furthermore, the implementation of a forward and a reversed kinematic analysis for the support and swing phase equations is developed to avoid matrix inversion. The allocation of constant transformations allows the position and orientation end-coordinate systems to be aligned with each other. Also, the redefinition of the DH transformations and the use of constraints allow decoupling the shared DOF between the legs and the torso. Finally, a geometric approach to avoid the singularities during the walking process is indicated. Numerical data is presented along with an experimental implementation to prove the validity of the analytical results.

Description: Carbapenem-resistant Gram-negative bacilli resulting from β-lactamases have been reported to be an important cause of nosocomial infections and are a critical therapeutic problem worldwide. This study aimed to describe the prevalence of imipenem-resistant Gram-negative bacilli isolates and detection of , , , , and genes in these clinical isolates in Egyptian hospitals. The isolates were collected from various clinical samples, identified by conventional methods and confirmed by API 20E. Antibiotic susceptibility testing was determined by Kirby-Bauer technique and interpreted according to CLSI. Production of , , , and genes was done by polymerase chain reaction (PCR). Direct sequencing from PCR products was subsequently carried out to identify and confirm these β-lactamases genes. Out of 65 isolates, (46.1%) Escherichia coli, (26.2%) Klebsiella pneumoniae, and (10.7%) Pseudomonas aeruginosa were identified as the commonest Gram-negative bacilli. 33(50.8%) were imipenem-resistant isolates. 22 isolates (66.7%) carried , 24(72.7%) had , and 5(15%) showed , while 12(36%), 6(18.2%), and 0(0.00%) harbored , , and , respectively. There is a high occurrence of β-lactamase genes in clinical isolates and sequence analysis of amplified genes showed differences between multiple SNPs (single nucleotide polymorphism) sites in the same gene among local isolates in relation to published sequences.

Description: This paper deals with asymptotic behavior of nonoscillatory solutions of certain forced integrodifferential equations of the form: From the obtained results, we derive a technique which can be applied to some related integrodifferential as well as integral equations.

Description: Wireless sensor networks have been the subject of intense research in recent years. Sensor nodes are used in wide range of applications such as security, military, and environmental monitoring. One of the most interesting applications in wireless sensor networks is target tracking, which mainly consists in detecting and monitoring the motion of mobile targets. In this paper, we present a comprehensive survey of target tracking approaches. We then analyze them according to several metrics. We also discuss some of the challenges that influence the performance of tracking schemes. In the end, we conduct detailed analysis and comparison between these algorithms and we conclude with some future directions.

Description: We will consider the higher order functional dynamic equations with mixed nonlinearities of the form , on an above-unbounded time scale , where , ,   with  , and . The function is a rd-continuous function such that for . The results extend and improve some known results in the literature on higher order nonlinear dynamic equations.

Description: This paper proposes a nonlinear Goal Programming Model (GPM) for solving the problem of admission capacity planning in academic universities. Many factors of university admission capacity planning have been taken into consideration among which are number of admitted students in the past years, total population in the country, number of graduates from secondary schools, desired ratios of specific specialties, faculty-to-students ratio, and the past number of graduates. The proposed model is general and has been tested at King Abdulaziz University (KAU) in the Kingdom of Saudi Arabia, where the work aims to achieve the key objectives of a five-year development plan in addition to a 25-year future plan (AAFAQ) for universities education in the Kingdom. Based on the results of this test, the proposed GPM with a modified differential evolution algorithm has approved an ability to solve general admission capacity planning problem in terms of high quality, rapid convergence speed, efficiency, and robustness.