Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials

ABSTRACT The influence of AS03A, a tocopherol oil-in-water emulsion-based adjuvant system, on humoral and cell-mediated responses to A/California/7/2009 H1N1 pandemic vaccine was investigated. In two observer-blind studies, a total of 261 healthy adults aged 18 to 60 years were randomized to receive either AS03A-adjuvanted H1N1 vaccine containing 3.75 μg hemagglutinin (HA) or nonadjuvanted H1N1 vaccine containing 15 or 3.75 μg HA on days 0 and 21. Hemagglutination inhibition (HI) antibody and T-cell responses were analyzed up to day 42. A first dose of AS03A-adjuvanted vaccine (3.75 μg HA) or nonadjuvanted vaccine (15 μg HA) induced HI responses of similar magnitudes that exceeded licensure criteria (e.g., 94 to 100% with titers of ≥40). A lower response following 3.75 μg HA without adjuvant was observed (73% with titers of ≥40). Following a second dose, geometric mean HI titers at day 42 were higher for AS03A-adjuvanted vaccine (636 and 637) relative to nonadjuvanted vaccine (341 for 15 μg HA and 150 for 3.75 μg HA). Over the 42-day period, the increase in frequency of A/H1N1/2009-specific CD4+ T cells was significantly higher in the adjuvanted group than in the nonadjuvanted group. There was no evidence of correlation between baseline CD4+ T-cell frequencies and day 21 HI antibody titers, while there was some correlation (R = 0.35) between day 21 CD4+ T-cell frequencies and day 42 HI titers. AS03A adjuvant enhanced the humoral and CD4+ T-cell-mediated responses to A/H1N1/2009 vaccine. Baseline A/H1N1/2009-specific CD4+ T-cell frequencies did not predict post-dose 1 antibody responses, but there was some correlation between post-dose 1 CD4+ T-cell frequencies and post-dose 2 antibody responses.
Connections: heart disease, cellular electrophysiology, and ion channels

Our purpose in this article is to examine the hypothesis that both myocardial disease and ischemia can alter the electrophysiologic function of the ion channels responsible for the cellular electrical activity of the heart. Changes in the intracellular and extracellular milieus occur during ischemia and can alter the electrophysiology of several species of ionic channels and the cellular electrophysiologic activity of cardiac myocytes. Included are 1) changes in extracellular [K+] and pH and in intracellular [Na+], [Ca2+], and pH; 2) accumulation of noxious metabolic products such as lysophosphatidylcholine; and 3) depletion of intracellular ATP. Finally, ischemia or disease (e.g., hypertrophy) can alter the electrophysiology of at least two types of K+ channels, the A‐like channels underlying the transient outward current and the inward rectifier, by mechanisms that apparently do not involve alteration of either the intra‐ or extracellular milieus. Findings suggest that the expression of cardiac A‐like channel function can be altered by hypertrophy and that at least one intrinsic conductance property of the inward rectifier can be altered by ischemia. We speculate that the control of expression, function, and regulation of cardiac ion channels can be affected at the molecular level by heart disease and myocardial ischemia. —Ten Eick, R. E. ; Whalley, D. W. ; Rasmussen, H. H. Connections: heart disease, cellular electrophysiology, and ion channels. FASEB J. 6: 2568‐2580; 1992.
Genome Scan for Blood Pressure in Dutch Dyslipidemic Families Reveals Linkage to a Locus on Chromosome 4p

Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, &agr;-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic &agr;-adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.
Implementation and Analysis of Homomorphic Encryption Schemes

An encryption scheme is “homomorphic” if it is possible to perform implicit operation on the plaintext by processing the ciphertext only. The scheme is said to be “fully homomorphic’’ when we can perform (a sequence of operations) both addition and multiplication, whereas, it is “somewhat homomorphic’’ if it supports a limited number of operations. We describe how Gentry’s transformation can be applied on bootstrappable Somewhat Homomorphic Encryption (SHE) scheme to make it a fully homomorphic scheme (FHE) by squashing the decryption circuit i.e. evaluating with a low-degree polynomial. The security of the above scheme is based on the hardness of Approximate Integer Common Divisor Problem (ACDP) which was introduced in 2001 by Howgrave–Graham. Among the two versions of ACDP, the general version (GACDP) is apparently more secure than its partial version (PACDP). We have implemented and analyzed Gentry’s scheme and have suggested some improvements to make it more secure by selecting the Keys parameter in the permissible range.
Bile Acids Specifically Increase Hepatitis C Virus RNA-Replication

Background Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication. Methods We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine infection of Con1 particles. Results BAs increased RNA-replication of GT1b replicons up to 10-fold but had no effect on subgenomic GT2a replicons both in Huh-7 and HuH6 cells. They did not increase viral RNA translation, virus assembly and release or cell entry. Lowering replication efficiency of GT2a replicons rendered them susceptible to stimulation by BAs. Moreover, replication of full length GT1b with or without replication enhancing mutations and GT2a genomes were also stimulated by BAs. Conclusions Bile acids specifically enhance RNA-replication. This is not limited to GT1, but also holds true for GT2a full length genomes and subgenomic replicons with low replication capacity. The increase of HCV replication by BAs may influence the efficacy of antiviral treatment in vivo and may improve replication of primary HCV genomes in cell culture.
Production and partial characterization of a Vibrio fluvialis cytotoxin

Conditions are described for the production of an extracellular cytotoxin or CHO cell-killing factor by Vibrio fluvialis, a recently recognized enteric pathogen. The cell-killing factor was ammonium sulfate precipitable, heat labile, and inactivated by proteases, and had an isoelectric point (estimated by sucrose density gradient electrofocusing) and an apparent molecular weight (estimated by gel filtration) of ca. 4.8 and 12,200, respectively. The culture supernatant fluids also possessed hemolytic and phospholipase A2 activities; however, they were separable from cell-killing factor activity by gel filtration. The substance(s) possessing the hemolytic and phospholipase activities coeluted when fractionated by gel filtration with Sephacryl S-200 (apparent molecular weight of ca. 34,500) and had isoelectric points of ca. 4.4 and 4.5, respectively.
Current and emerging therapies for metastatic colorectal cancer: applying research findings to clinical practice.

PURPOSE The results of clinical trials that led to modern first- and second-line chemotherapeutic regimens for metastatic colorectal cancer, including studies of recently introduced monoclonal antibody products that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), are described, as well as new therapeutic targets being studied and challenges in research to identify and evaluate new therapies. SUMMARY Modern chemotherapy regimens for first-line treatment of metastatic colorectal cancer contain fluorouracil, leucovorin, either oxaliplatin or irinotecan, and the VEGF inhibitor bevacizumab. The EGFR inhibitors cetuximab and panitumumab currently are reserved for second- or third-line therapy, but their role could change as the results of clinical research become available. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway, src kinases, and insulin-like growth factor-1 receptor are among the targets of current research. Identifying the subset of patients with metastatic colorectal cancer who stand to benefit from a particular therapy presents a challenge in conducting clinical research. CONCLUSION Modern chemotherapeutic and monoclonal antibody regimens have improved survival in patients with meta-static colorectal cancer. The optimal combinations, timing, and sequence of agents remain to be determined.
Towards test-driven software defined networking

To configure, troubleshoot and operate their networks, operators often have no alternatives than relying on error-prone manual procedures. The emerging Software Defined Networking paradigm opens new possibilities for more structured networking methodologies.We argue that provably-effective practices can be borrowed from more developed engineering fields, especially software engineering. In this paper, we propose an adaptation of test-driven software development methodologies to software defined networks (SDNs). To support our methodological guidelines, we propose an expressive requirement formalization language. Further, we describe a prototype tool able to check the compliance of an SDN controller with requirements expressed in the proposed language. Our evaluation of the prototype shows promising results on the practical viability of our approach.
MINIMAX SPARSE PRINCIPAL SUBSPACE ESTIMATION IN HIGH DIMENSIONS

We study sparse principal components analysis in high dimensions, where p (the number of variables) can be much larger than n (the number of observations), and analyze the problem of estimating the subspace spanned by the principal eigenvectors of the population covariance matrix. We prove optimal, non-asymptotic lower and upper bounds on the minimax subspace estimation error under two different, but related notions of lq subspace sparsity for 0 � q � 1. Our upper bounds apply to general classes of covariance matrices, and they show that lq constrained estimates can achieve optimal minimax rates without restrictive spiked covariance conditions. 1. Introduction. Principal components analysis (PCA) was introduced in the early 20th century (Pearson, 1901; Hotelling, 1933) and is arguably the most well known and widely used technique for dimension reduction. It is part of the mainstream statistical repertoire and is routinely used in numerous and diverse areas of application. However, contemporary applications often involve much higher-dimensional data than envisioned by the early developers of PCA. In such high-dimensional situations, where the number of variables p is of the same order or much larger than the number of observations n, serious difficulties emerge: standard PCA can produce inconsistent estimates of the principal directions of variation and lead to unreliable conclusions (Johnstone and Lu, 2009; Paul, 2007; Nadler, 2008). The principal directions of variation correspond to the eigenvectors of the covariance matrix, and in high-dimensions consistent estimation of the eigenvectors is generally not possible without additional assumptions about the covariance matrix or its eigenstructure. Much of the recent development in PCA has focused on methodology that applies the concept of sparsity to eigenvector estimation (some examples include Jolliffe, Trendafilov and Uddin,
Telomere erosion in NF1 tumorigenesis

Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant cause of morbidity and mortality in NF1 and currently there is no treatment or definite prognostic biomarkers for these tumors. Telomere shortening has been documented in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it is considered that the ensuing genomic instability may facilitate clonal evolution and the progression to malignancy. To evaluate the potential role of telomere dysfunction in NF1-associated tumors, we undertook a comparative analysis of telomere length in samples derived from 10 cutaneous and 10 diffused plexiform neurofibromas, and 19 MPNSTs. Telomere length was determined using high-resolution Single Telomere Length Analysis (STELA). The mean Xp/Yp telomere length detected in MPNSTs, at 3.282 kb, was significantly shorter than that observed in both plexiform neurofibromas (5.793 kb; [p = 0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The telomere length distributions of MPNSTs were within the length-ranges in which telomere fusion is detected and that confer a poor prognosis in other tumor types. These data indicate that telomere length may play a role in driving genomic instability and clonal progression in NF1-associated MPNSTs.
Bridging Clinical Investigators and Statisticians

Clinical investigators often find the thought of writing the statistical analysis plan daunting. Early collaboration between the clinical investigator and statistician can improve the study design and validity of the results by developing the statistical methodology that specifically addresses the research hypothesis. With the clinical investigator, a statistician often writes the statistical methods section that includes sample size and power analyses, randomization and blinding procedures, interim analysis, and data monitoring plans, in addition to the statistical analysis plan. To make this process less mysterious, we describe how the statistical methods section is developed in collaboration with a statistician.
Senescence: An Age-Based Character Simulation Framework

The paper presents the development and initial validation of the Senescence character framework, a simulation tool that can be used for rigging muscle deformer-based humanoid characters, with support for age. The senescence framework allows the user to rig any bipedal 3D character and manipulate skeleton and muscle parameters in order to render the age of the character realistically. The framework was developed using Python, Maya Embedded Language and PyQt. A study with 100 subjects was conducted to determine whether participants were able to perceive the age of the characters simulated with the Senescence framework. Findings show that while subjects were able to perceive age differences, they were not able to identify the age of the simulated characters with high level of accuracy. Results also show that subjects with animation expertise were able to identify the age of the characters more accurately than subjects without animation experience.
Traffic steering of middlebox policy chain based on SDN

The delivery of services typically requires packets to be steered through a sequence of middleboxes to improve network security and performance. One constraint on the deployment of services is that middleboxes are tightly coupled to the physical network topology. As a result, ensuring successful deployment requires error-prone and complex low-level configurations. Software-Defined Networking (SDN) can eliminate the need to configure network devices manually to deploy services. However, in terms of steering middlebox-specific traffic in data plane, applying the existing capabilities supported by OpenFlow protocol may lead to incorrect forwarding decisions when there is a loop in the route used to steer traffic. In this paper, we present an implementation using tagging to discriminate different instances of the same packet arriving at the same ingress port on the same switch (i.e. the existence of the loop). Moreover, we propose an algorithm to judge the existence of the loop in a physical sequence of switches and decide which switches are responsible for adding tags. The experimental result demonstrates that our implementation can properly steer traffic through a specific sequence of middleboxes even when there are loops in forwarding path.
Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium.

Tumor growth is dependent in part on "neoangiogenesis. " Functional involvement of bone marrow (BM)-derived cells in this process has been demonstrated. However, it remains controversial as to whether tumor endothelium itself is BM derived. Here we sought to address this issue with an endothelial-specific, inducible transgenic model. We generated Cretransgenic mice (endothelial-SCL-Cre-ER(T)) using the tamoxifen-inducible Cre-ER(T) recombinase driven by the 5' endothelial enhancer of the stem cell leukemia (SCL) locus. These mice were intercrossed with Cre reporter strains in which beta-galactosidase (LacZ) or enhanced yellow fluorescent protein (EYFP) are expressed upon Cre-mediated recombination. After tamoxifen administration, endothelial LacZ staining was observed in embryonic and adult tissues. Cre-mediated recombination was also observed in newly generated tumor endothelium. In adult BM cells we could only detect trace amounts of recombination by flow cytometry. Subsequently, BM from endothelial-SCL-Cre-ER(T);R26R mice was transplanted into irradiated recipients. When tumors were grown in recipient mice, which received tamoxifen, no tumor LacZ staining was detected. However, when tumors were grown in endothelial-SCL-Cre-ER(T);R26R mice 3 weeks after the cessation of tamoxifen treatment, there was widespread endothelial LacZ staining present. Thus, this genetic model strongly suggests that BM cells do not contribute to tumor endothelium and demonstrates the lineage relation between pre-existing endothelium and newly generated tumor endothelial cells.
A direct comparison of methods used to measure oxidized glutathione in biological samples: 2-vinylpyridine and N-ethylmaleimide

Abstract The ratio of glutathione disulfide (GSSG) to reduced glutathione (GSH) in biological samples is a frequently used parameter of oxidative stress. As a result, many methods are developed to measure GSSG. The most popular and convenient of these relies on enzymatic cycling following the chemical masking of GSH in the sample using 2-vinylpyridine (2VP). However, 2VP is a slow reactant and its use may result in artificially high GSSG values due to oxidation of the sample over time. Fast-reacting reagents such as N-ethylmaleimide (NEM) may provide more accurate results. We performed a direct comparison of methods using 2VP and NEM. With 2VP, the percentage of total glutathione (GSH + GSSG) in the oxidized form was significantly higher in all tested tissues (kidney, lung and liver) compared to the same procedure performed using NEM. We conclude that NEM, when coupled with a simple solid-phase extraction procedure, is more accurate for the determination of GSSG. We also tested the effects of various handling and storage conditions on GSSG. A detailed description and a discussion of other methods are also included.
Computing Normalizing Constants for Finite Mixture Models via Incremental Mixture Importance Sampling (IMIS)

This article proposes a method for approximating integrated likelihoods in finite mixture models. We formulate the model in terms of the unobserved group memberships, z, and make them the variables of integration. The integral is then evaluated using importance sampling over the z. We propose an adaptive importance sampling function which is itself a mixture, with two types of component distributions, one concentrated and one diffuse. The more concentrated type of component serves the usual purpose of an importance sampling function, sampling mostly group assignments of high posterior probability. The less concentrated type of component allows for the importance sampling function to explore the space in a controlled way to find other, unvisited assignments with high posterior probability. Components are added adaptively, one at a time, to cover areas of high posterior probability not well covered by the current importance sampling function. The method is called incremental mixture importance sampling (IMIS). IMIS is easy to implement and to monitor for convergence. It scales easily for higher dimensional mixture distributions when a conjugate prior is specified for the mixture parameters. The simulated values on which the estimate is based are independent, which allows for straightforward estimation of standard errors. The self-monitoring aspects of the method make it easier to adjust tuning parameters in the course of estimation than standard Markov chain Monte Carlo algorithms. With only small modifications to the code, one can use the method for a wide variety of mixture distributions of different dimensions. The method performed well in simulations and in mixture problems in astronomy and medical research.
Discriminating capabilities of syllable-based features and approaches of utilizing them for voice retrieval of speech information in Mandarin Chinese

With the rapidly growing use of the audio and multimedia information over the Internet, the technology for retrieving speech information using voice queries is becoming more and more important. In this paper, considering the monosyllabic structure of the Chinese language, a whole class of syllable-based indexing features, including overlapping segments of syllables and syllable pairs separated by a few syllables, is extensively investigated based on a Mandarin broadcast news database. The strong discriminating capabilities of such syllable-based features were verified by comparing with the word- or character-based features. Good approaches for better utilizing such capabilities, including fusion with the word- and character-level information and improved approaches to obtain better syllable-based features and query expressions, were extensively investigated. Very encouraging experimental results were obtained.