Heterogeneous Transfer Learning for Building High-Dimensional Generalized Linear Models with Disparate Datasets

Development of comprehensive prediction models are often of great interest in many disciplines of science, but datasets with information on all desired features typically have small sample sizes. In this article, we describe a transfer learning approach for building high-dimensional generalized linear models using data from a main study that has detailed information on all predictors, and from one or more external studies that have ascertained a more limited set of predictors. We propose using the external dataset(s) to build reduced model(s) and then transfer the information on underlying parameters for the analysis of the main study through a set of calibration equations, while accounting for the study-specific effects of certain design variables. We then use a generalized method of moment (GMM) with penalization for parameter estimation and develop highly scalable algorithms for fitting models taking advantage of the popular glmnet package. We further show that the use of adaptive-Lasso penalty leads to the oracle property of underlying parameter estimates and thus leads to convenient post-selection inference procedures. We conduct extensive simulation studies to investigate both predictive performance and post-selection inference properties of the proposed method. Finally, we illustrate a timely application of the proposed method for the development of risk prediction models for five common diseases using the UK Biobank study, combining baseline information from all study participants (500K) and recently released high-throughout proteomic data (# protein = 1500) on a subset (50K) of the participants.Comment: 46 pages, 8 figures, 3 table

CHEMOTHERAPEUTIC POTENTIAL OF NOVEL XANTHONE SOURCED FROM SWERTIA CHIRATA AGAINST SKIN CARCINOGENESIS

Objective: Swertia chirata forms a rich source of bio-active compounds, among which xanthones form an important part. Among the xanthones present in it, 1,5,8 Tri-hydroxy-3-methoxy xanthone (TMX) was found to be the most active. The present study aims to evaluate the chemotherapeutic potential of it against metastatic skin cancer cell lines. Methods: In this study, the antitumor activity of TMX (the active component of chirata plant) was evaluated in A431, SKMEL-5, and A375 cell line by using in-vitro assays such as cell viability assay, cell cycle analysis, caspase 3 activity assay, intracellular reactive oxygen species (ROS) level determination by dichlorofluorescein diacetate, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: In vitro studies showed that TMX from S. chirata exhibited significant antitumor activity by inducing apoptosis and restricting proliferation in both melanoma and non-melanoma skin cancer cell lines, but no such activity was seen in normal skin cancer cell line WS1. The qRT-PCR analysis revealed that in both the melanoma ad non-melanoma cell lines, TMX could exert its antitumor activity by downregulating c-Myc, cyclin-D1, and β-catenin and up-regulating Wnt antagonist gsk-3β, thereby suppressing wnt self-renewal pathway, but such regulation was absent in normal cell line. Conclusions: TMX from chirata could effectively inhibit the proliferation of metastatic skin cancer (both melanoma and non-melanoma) cell lines while being non-toxic to normal cell lines. The chemotherapeutic potential of TMX against metastatic skin cancer cell lines was achieved by downregulating several key regulatory genes enabling the suppression of the self-renewal pathway, the chief reason behind the invasiveness of cancer cells

Haitian Variant Vibrio cholerae O1 Strains Manifest Higher Virulence in Animal Models

Vibrio cholerae causes fatal diarrheal disease cholera in humans due to consumption of contaminated water and food. To instigate the disease, the bacterium must evade the host intestinal innate immune system; penetrate the mucus layer of the small intestine, adhere and multiply on the surface of microvilli and produce toxin(s) through the action of virulence associated genes. V. cholerae O1 that has caused a major cholera outbreak in Haiti contained several unique genetic signatures. These novel traits are used to differentiate them from the canonical El Tor strains. Several studies reported the spread of these Haitian variant strains in different parts of the world including Asia and Africa, but there is a paucity of information on the clinical consequence of these genetic changes. To understand the impact of these changes, we undertook a study involving mice and rabbit models to evaluate the pathogenesis. The colonization ability of Haitian variant strain in comparison to canonical El Tor strain was found to be significantly more in both suckling mice and rabbit model. Adult mice also displayed the same results. Besides that, infection patterns of Haitian variant strains showed a completely different picture. Increased mucosal damaging, colonization, and inflammatory changes were observed through hematoxylin-eosin staining and transmission electron microscopy. Fluid accumulation ability was also significantly higher in rabbit model. Our study indicated that these virulence features of the Haitian variant strain may have some association with the severe clinical outcome of the cholera patients in different parts of the world

Multicomponent polymeric materials

The book offers an in-depth review of the materials design and manufacturing processes employed in the development of multi-component or multiphase polymer material systems. This field has seen rapid growth in both academic and industrial research, as multiphase materials are increasingly replacing traditional single-component materials in commercial applications. Many obstacles can be overcome by processing and using multiphase materials in automobile, construction, aerospace, food processing, and other chemical industry applications. The comprehensive description of the processing, characterization, and application of multiphase materials presented in this book offers a world of new ideas and potential technological advantages for academics, researchers, students, and industrial manufacturers from diverse fields including rubber engineering, polymer chemistry, materials processing and chemical science. From the commercial point of view it will be of great value to those involved in processing, optimizing and manufacturing new materials for novel end-use applications. The book takes a detailed approach to the description of process parameters, process optimization, mold design, and other core manufacturing information. Details of injection, extrusion, and compression molding processes have been provided based on the most recent advances in the field. Over two comprehensive sections the book covers the entire field of multiphase polymer materials, from a detailed description of material design and processing to the cutting-edge applications of such multiphase materials. It provides both precise guidelines and general concepts for the present and future leaders in academic and industrial sectors

Phylogeny and synonymous codon usage pattern of

Sub-Himalayan West Bengal is favorable for production of several fruits and vegetables. Papaya is one of the common plants cultivated in the area. Most of the papaya plants of the area are susceptible to PRSV. Coat protein genes of six Papaya ringspot virus (PRSV) isolates of the area have been sequenced following RT-PCR. Phylogenetic study of the PRSV isolates showed about 80-90% similarity with Cuban isolates also. The codon usage pattern of our isolates has also been analyzed along with several other isolates. PRSV isolates of our study showed more preference to 8 putative optimal codons. Correspondence analysis of the genes of different isolates along the first two major axes were done, as the first two axes contributed more in shaping codon usage pattern. In the phylogenetic tree, constructed by neighbour joining method our isolates clustered together with the east Indian, north Indian and Bangladeshi isolates. The diversity and codon usage pattern of the PRSV isolates of different regions were studied, where it has been observed that the codon usage pattern of PRSV isolates is influenced probably by translational selection along with mutational bias.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Tobacco-induced carcinogenesis and chemoprevention by some natural products

Tobacco habit is one of the main etiological factors responsible for cancer in body's multiple organs due to the presence of numerous carcinogens. In different animal models, it was evident that the carcinogens could induce carcinogenesis in multiple organs depending on its route of exposure site (e.g., skin, oral cavity, and lung), metabolism (e.g., liver and lung), and excretion (e.g., lung and kidney). It was evident that the active carcinogen metabolites could induce cellular reactive oxygen species (ROS) level, bind to DNA/RNA/proteins, thereby transforming the stem cell of the specific organs toward neoplasm. Different epidemiological studies including our own showed few natural compounds might reduce the risk of tobacco-induced carcinogenesis. The anticarcinogenic roles of crude extract as well as active compounds of such natural dietary ingredients were also evaluated by several in vivo animal models. Most of the active components have potential antioxidative, anti-inflammatory, and anticarcinogenic roles. For better understanding, the roles of three different types of compounds were selected for this review 1. Tea polyphenols from Camellia sinensis: epigallocatechin gallate and theaflavin; 2. amarogentin from Swertia chirata; and 3. Eugenol from Syzygium aromaticum. Studies showed that three types of compounds could restrict the carcinogenesis in different organs at premalignant stages. This might be due to antioxidation and activation of detoxification system, inhibition of cancer initiating stem cell population, modulation of multiple cellular pathways associated with cell cycle, cell proliferation, and survival which ultimately lead to restrict tumor development at initiation/promotion stage