Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems.

Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions

Learning Clothing and Pose Invariant 3D Shape Representation for Long-Term Person Re-Identification

Long-Term Person Re-Identification (LT-ReID) has become increasingly crucial in computer vision and biometrics. In this work, we aim to extend LT-ReID beyond pedestrian recognition to include a wider range of real-world human activities while still accounting for cloth-changing scenarios over large time gaps. This setting poses additional challenges due to the geometric misalignment and appearance ambiguity caused by the diversity of human pose and clothing. To address these challenges, we propose a new approach 3DInvarReID for (i) disentangling identity from non-identity components (pose, clothing shape, and texture) of 3D clothed humans, and (ii) reconstructing accurate 3D clothed body shapes and learning discriminative features of naked body shapes for person ReID in a joint manner. To better evaluate our study of LT-ReID, we collect a real-world dataset called CCDA, which contains a wide variety of human activities and clothing changes. Experimentally, we show the superior performance of our approach for person ReID.Comment: 10 pages, 7 figures, accepted by ICCV 202

FingerSlide: Investigating Passive Haptic Sliding As A Tacton Channel

The haptic sensation of sliding a surface under a probing finger can be used to convey surface information or coded data to the user. In this paper, we investigate users' ability to discern different sliding profiles based on the velocity and direction of sliding for use as haptic-tactons. We built FingerSlide, a novel haptic device which can position and control moving surfaces under a user's finger and used this to run two independent studies. The first study investigates if users can identify the direction of sliding at different velocities. The second study investigates if the users can distinguish a difference between two velocities. Our results show a faster response for higher velocities in the direction study and high error rates in identifying differences in the direction study. We discuss these results and infer design considerations for haptic devices that use the sliding effect to convey information

Environmental, social and economic growth indicators spur logistics performance: from the perspective of South Asian Association for regional cooperation countries.

This article examines the association between green logistics operations, social, environmental and economic indicators of SAARC (South Asian Association for Regional Cooperation) countries. The research used GMM (Generalized Method of Moments) and FGLS (Feasible Generalized Least Squares) two methods to tackle the problems of heterogeneity, serial correlation and heteroskedasticity. The findings show that fossil fuel consumption is at the heart of logistics operations; the more fossil fuel and non-green energy resources that are used, the more negative effects on society and environmental sustain-ability result from this. A lower quality of transport-related infrastructure and logistics services is negatively correlated with fossil fuel usage, carbon emissions, health expenditure, greenhouse gas emissions and political instability of SAARC countries. Conversely, efficient customs procedures and greater information sharing among supply chain partners increase trade opportunities and also improve environmental sustainability in terms of minimum carbon emissions due to the shorter waiting and queue times involved. Further, the application of green energy resources and green practices can mitigate negative effects on social and environmental sustainability due to better logistics operations while improving financial performance in terms of higher GDP per capita, trade openness and greater export opportunities around the globe. As there is very limited research using green practices relationship with macro-level indicators in current literature, this research will assist both practitioners and policy makers to understand the roles of green supply chain and green logistics in enhancing environmental sustain-ability, social improvement and economic growth for a better future.N/

A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes

Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30mg/d) or risperidone (1-6mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications

Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

Today, farmers in many regions of eastern Asia sow their barley grains in the spring and harvest them in the autumn of the same year (spring barley). However, when it was first domesticated in southwest Asia, barley was grown between the autumn and subsequent spring (winter barley), to complete their life cycles before the summer drought. The question of when the eastern barley shifted from the original winter habit to flexible growing schedules is of significance in terms of understanding its spread. This article investigates when barley cultivation dispersed from southwest Asia to regions of eastern Asia and how the eastern spring barley evolved in this context. We report 70 new radiocarbon measurements obtained directly from barley grains recovered from archaeological sites in eastern Eurasia. Our results indicate that the eastern dispersals of wheat and barley were distinct in both space and time. We infer that barley had been cultivated in a range of markedly contrasting environments by the second millennium BC. In this context, we consider the distribution of known haplotypes of a flowering-time gene in barley, Ppd-H1, and infer that the distributions of those haplotypes may reflect the early dispersal of barley. These patterns of dispersal resonate with the second and first millennia BC textual records documenting sowing and harvesting times for barley in central/eastern China

Random DNA fragmentation allows detection of single-copy, single-exon alterations of copy number by oligonucleotide array CGH in clinical FFPE samples

Genomic technologies, such as array comparative genomic hybridization (aCGH), increasingly offer definitive gene dosage profiles in clinical samples. Historically, copy number profiling was limited to large fresh-frozen tumors where intact DNA could be readily extracted. Genomic analyses of pre-neoplastic tumors and diagnostic biopsies are often limited to DNA processed by formalin-fixation and paraffin-embedding (FFPE). We present specialized protocols for DNA extraction and processing from FFPE tissues utilizing DNase processing to generate randomly fragmented DNA. The protocols are applied to FFPE clinical samples of varied tumor types, from multiple institutions and of varied block age. Direct comparative analyses with regression coefficient were calculated on split-sample (portion fresh/portion FFPE) of colorectal tumor samples. We show equal detection of a homozygous loss of SMAD4 at the exon-level in the SW480 cell line and gene-specific alterations in the split tumor samples. aCGH application to a set of archival FFPE samples of skin squamous cell carcinomas detected a novel hemizygous deletion in INPP5A on 10q26.3. Finally we present data on derivative of log ratio, a particular sensitive detector of measurement variance, for 216 sequential hybridizations to assess protocol reliability over a wide range of FFPE samples

Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair

The original publication is available at http:/www.plosone.orgBackground: The Beijing family is a successful group of M. tuberculosis strains, often associated with drug resistance and widely distributed throughout the world. Polymorphic genetic markers have been used to type particular M. tuberculosis strains. We recently identified a group of polymorphic DNA repair replication and recombination (3R) genes. It was shown that evolution of M. tuberculosis complex strains can be studied using 3R SNPs and a high-resolution tool for strain discrimination was developed. Here we investigated the genetic diversity and propose a phylogeny for Beijing strains by analyzing polymorphisms in 3R genes. Methodology/Principal Findings: A group of 3R genes was sequenced in a collection of Beijing strains from different geographic origins. Sequence analysis and comparison with the ones of non-Beijing strains identified several SNPs. These SNPs were used to type a larger collection of Beijing strains and allowed identification of 26 different sequence types for which a phylogeny was constructed. Phylogenetic relationships established by sequence types were in agreement with evolutionary pathways suggested by other genetic markers, such as Large Sequence Polymorphisms (LSPs). A recent Beijing genotype (Bmyc10), which included 60% of strains from distinct parts of the world, appeared to be predominant. Conclusions/Significance: We found SNPs in 3R genes associated with the Beijing family, which enabled discrimination of different groups and the proposal of a phylogeny. The Beijing family can be divided into different groups characterized by particular genetic polymorphisms that may reflect pathogenic features. These SNPs are new, potential genetic markers that may contribute to better understand the success of the Beijing family. © 2011 Mestre et al.Publishers' Versio