Globally maximizing, locally minimizing : unsupervised discriminant projection with applications to face and palm biometrics

2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Differing Requirements for RAD51 and DMC1 in Meiotic Pairing of Centromeres and Chromosome Arms in Arabidopsis thaliana

During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains

Significance of the Balance between Regulatory T (Treg) and T Helper 17 (Th17) Cells during Hepatitis B Virus Related Liver Fibrosis

<div><h3>Background</h3><p>Hepatitis B virus-related liver fibrosis (HBV-LF) always progresses from inflammation to fibrosis. However, the relationship between these two pathological conditions is not fully understood. Here, it is postulated that the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells as an indicator of inflammation may predict fibrosis progression of HBV-LF.</p> <h3>Methodology/Principal Findings</h3><p>The frequencies and phenotypes of peripheral Treg and Th17 cells of seventy-seven HBeAg-positive chronic hepatitis B (CHB) patients who underwent liver biopsies and thirty healthy controls were determined by flow cytometry. In the periphery of CHB patients, both Treg and Th17 frequencies were significantly increased and correlated, and a lower Treg/Th17 ratio always indicated more liver injury and fibrosis progression. To investigate exact effects of Treg and Th17 cells during HBV-LF, a series of <em>in vitro</em> experiments were performed using purified CD4⁺, CD4⁺CD25⁺, or CD4⁺CD25⁻ cells from the periphery, primary human hepatic stellate cells (HSCs) isolated from healthy liver specimens, human recombinant interleukin (IL)-17 cytokine, anti-IL-17 antibody and HBcAg. In response to HBcAg, CD4⁺CD25⁺ cells significantly inhibited cell proliferation and cytokine production (especially IL-17 and IL-22) by CD4⁺CD25⁻ cells in cell-contact and dose-dependent manners. In addition, CD4⁺ cells from CHB patients, compared to those from HC subjects, dramatically promoted proliferation and activation of human HSCs. Moreover, in a dramatically dose-dependent manner, CD4⁺CD25⁺ cells from CHB patients inhibited, whereas recombinant IL-17 response promoted the proliferation and activation of HSCs. Finally, <em>in vivo</em> evidence about effects of Treg/Th17 balance during liver fibrosis was obtained in concanavalin A-induced mouse fibrosis models via depletion of CD25⁺ or IL-17⁺ cells, and it’s observed that CD25 depletion promoted, whereas IL-17 depletion, alleviated liver injury and fibrosis progression.</p> <h3>Conclusions/Significance</h3><p>The Treg/Th17 balance might influence fibrosis progression in HBV-LF via increase of liver injury and promotion of HSCs activation.</p> </div

Haplotype-based quantitative trait mapping using a clustering algorithm

BACKGROUND: With the availability of large-scale, high-density single-nucleotide polymorphism (SNP) markers, substantial effort has been made in identifying disease-causing genes using linkage disequilibrium (LD) mapping by haplotype analysis of unrelated individuals. In addition to complex diseases, many continuously distributed quantitative traits are of primary clinical and health significance. However the development of association mapping methods using unrelated individuals for quantitative traits has received relatively less attention. RESULTS: We recently developed an association mapping method for complex diseases by mining the sharing of haplotype segments (i.e., phased genotype pairs) in affected individuals that are rarely present in normal individuals. In this paper, we extend our previous work to address the problem of quantitative trait mapping from unrelated individuals. The method is non-parametric in nature, and statistical significance can be obtained by a permutation test. It can also be incorporated into the one-way ANCOVA (analysis of covariance) framework so that other factors and covariates can be easily incorporated. The effectiveness of the approach is demonstrated by extensive experimental studies using both simulated and real data sets. The results show that our haplotype-based approach is more robust than two statistical methods based on single markers: a single SNP association test (SSA) and the Mann-Whitney U-test (MWU). The algorithm has been incorporated into our existing software package called HapMiner, which is available from our website at . CONCLUSION: For QTL (quantitative trait loci) fine mapping, to identify QTNs (quantitative trait nucleotides) with realistic effects (the contribution of each QTN less than 10% of total variance of the trait), large samples sizes (≥ 500) are needed for all the methods. The overall performance of HapMiner is better than that of the other two methods. Its effectiveness further depends on other factors such as recombination rates and the density of typed SNPs. Haplotype-based methods might provide higher power than methods based on a single SNP when using tag SNPs selected from a small number of samples or some other sources (such as HapMap data). Rank-based statistics usually have much lower power, as shown in our study

Directed Self-Assembly: Expectations and Achievements

Nanotechnology has been a revolutionary thrust in recent years of development of science and technology for its broad appeal for employing a novel idea for relevant technological applications in particular and for mass-scale production and marketing as common man commodity in general. An interesting aspect of this emergent technology is that it involves scientific research community and relevant industries alike. Top–down and bottom–up approaches are two broad division of production of nanoscale materials in general. However, both the approaches have their own limits as far as large-scale production and cost involved are concerned. Therefore, novel new techniques are desired to be developed to optimize production and cost. Directed self-assembly seems to be a promising technique in this regard; which can work as a bridge between the top–down and bottom–up approaches. This article reviews how directed self-assembly as a technique has grown up and outlines its future prospects

GA-based multi-objective optimization of active nonlinear quarter car suspension system—PID and fuzzy logic control

Background The primary function of a suspension system is to isolate the vehicle body from road irregularities thus providing the ride comfort and to support the vehicle and provide stability. The suspension system has to perform conflicting requirements; hence, a passive suspension system is replaced by the active suspension system which can supply force to the system. Active suspension supplies energy to respond dynamically and achieve relative motion between body and wheel and thus improves the performance of suspension system. Methods This study presents modelling and control optimization of a nonlinear quarter car suspension system. A mathematical model of nonlinear quarter car is developed and simulated for control and optimization in Matlab/Simulink® environment. Class C road is selected as input road condition with the vehicle traveling at 80 kmph. Active control of the suspension system is achieved using FLC and PID control actions. Instead of guessing and or trial and error method, genetic algorithm (GA)-based optimization algorithm is implemented to tune PID parameters and FLC membership functions’ range and scaling factors. The optimization function is modeled as a multi-objective problem comprising of frequency weighted RMS seat acceleration, Vibration dose value (VDV), RMS suspension space, and RMS tyre deflection. ISO 2631-1 standard is adopted to assess the ride and health criterion. Results The nonlinear quarter model along with the controller is modeled and simulated and optimized in a Matlab/Simulink environment. It is observed that GA-optimized FLC gives better control as compared to PID and passive suspension system. Further simulations are validated on suspension system with seat and human model. Parameters under observation are frequency-weighted RMS head acceleration, VDV at the head, crest factor, and amplitude ratios at the head and upper torso (AR_h and AR_ut). Simulation results are presented in time and frequency domain. Conclusion Simulation results show that GA-based FLC and PID controller gives better ride comfort and health criterion by reducing RMS head acceleration, VDV at the head, CF, and AR_h and AR_ut over passive suspension system

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation