Miracle-dz/UniFAR-FTUs huggingface dataset:
The expression kinetics of CD137 in chronic hepatitis C patients treated with pegylated-interferon and ribavirin

Abstract Objective. CD137, a member of the tumor necrosis factor receptor family, generates co-stimulatory signals leading to T-cell activation and proliferation for viral eradication. We examined the expression kinetics of CD137 to validate whether it can affect treatment outcomes of chronic hepatitis C (CHC) patients. Methods. The expression of CD137 on peripheral blood mononuclear cells (PBMC) from 50 CHC patients and 20 healthy controls was analyzed by flow cytometry. CD137 expression levels were examined before treatment, and every 4 weeks during treatment until week 24 or 48, and at the 24-week follow-up. Results. CD137 expression on PBMC was significantly lower in CHC patients than controls (15.5 ± 7.8% vs 23.4 ± 5.2%; p < 0.05). Patients with sustained virological response (SVR) showed higher level of CD137 expression on PBMC than treatment failures at week 4 (20.11% vs 10.97%; p < 0.05) and week 12 (15.48% vs 5.74%; p < 0.01). CD137 expression on CD4 T cells was also higher in patients with SVR at week 8 (7.75% vs 3.29%; p < 0.05). CD137 expression on PBMC from patients with SVR recovered to the control level at the 24-week follow-up. In multivariate analysis, the increased expression of CD137 at week 4 and genotype non-1 were significantly associated with SVR. Conclusions. The increased expression of CD137 within 12 weeks after the initiation of interferon therapy might be associated with a successful treatment outcome. Modulation to improve expression of CD137 might improve efficacy of CHC treatment.
Low-loss liquid-core optical fiber for low-refractive-index liquids: fabrication, characterization, and application in Raman spectroscopy.

We describe a liquid-core optical fiber based on capillary tubing of Teflon AF 2400, which is a clear, amorphous fluoropolymer having a refractive index of 1.29. When filled with virtually any transparent liquid, the fiber is capable of transmitting light by total internal reflection. Loss below 3 dB/microm is demonstrated throughout much of the visible region for a 250-microm-i.d. fiber filled with water. The utility of this device in enhancing the intensity of Raman spectra of core liquids is demonstrated.
Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes

It has been shown that a subset of human cancers, notably, melanoma and hepatocellular carcinoma (HCC) are auxotrophic for arginine (Arg), because they do not express argininosuccinate synthetase (ASS), the rate-limiting enzyme for the biosynthesis of arginine from citrulline. These ASS-negative cancer cells require Arg from extracellular sources for survival. When they are exposed to recombinant Arg-degrading enzymes, e.g. arginine deiminase (ADI) or arginase, they die because of Arg starvation; whereas normal cells which express ASS are able to survive. A pegylated ADI (ADI-PEG20) has been developed for clinical trials for advanced melanoma and HCC; and favorable results have been obtained. ADI-PEG20 treatment induces autophagy in auxotrophic cancer cells leading to cell death. Clinical studies in melanoma patients show that re-expression of ASS is associated with ADI-PEG20 resistance. ADI-PEG20 treatment down-regulates the expression of HIF-1α but up-regulates c-Myc in culture melanoma cells. Induction of ASS by ADI-PEG20 involves positive regulators c-Myc and Sp4 and negative regulator HIF1α. Since both HIF-1α and c-Myc play important roles in cancer cell energy metabolism, together these results suggest that targeted cancer cell metabolism through modulation of HIF-1α and c-Myc expression may improve the efficacy of ADI-PEG20 in treating Arg auxotrophic tumors.
Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera

Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
High-Throughput Modeling of Human G-Protein Coupled Receptors: Amino Acid Sequence Alignment, Three-Dimensional Model Building, and Receptor Library Screening

The current study describes the development of a computer package (GPCRmod) aimed at the high-throughput modeling of the therapeutically important family of human G-protein coupled receptors (GPCRs). GPCRmod first proposes a reliable alignment of the seven transmembrane domains (7 TMs) of most druggable human GPCRs based on pattern/motif recognition for each of the 7 TMs that are considered independently. It then converts the alignment into knowledge-based three-dimensional (3-D) models starting from a set of 3-D backbone templates and two separate rotamer libraries for side chain positioning. The 7 TMs of 277 human GPCRs have been accurately aligned, unambiguously clustered in three different classes (rhodopsin-like, secretin-like, metabotropic glutamate-like), and converted into high-quality 3-D models at a remarkable throughput (ca. 3s/model). A 3-D GPCR target library of 277 receptors has consequently been setup. Its utility for "in silico" inverse screening purpose has been demonstrated by recovering among top scorers the receptor of a selective GPCR antagonist as well as the receptors of a promiscuous antagonist. The current GPCR target library thus constitutes a 3-D database of choice to address as soon as possible the "virtual selectivity" profile of any GPCR antagonist or inverse agonist in an early hit optimization process.
Twelve testable hypotheses on the geobiology of weathering

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth’s surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar‐to‐chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant‐microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term. (4) In eroding landscapes, weathering‐front advance at depth is coupled to surface denudation via biotic processes. (5) Biology shapes the topography of the Critical Zone. (6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws. (7) Rising global temperatures will increase carbon losses from the Critical Zone. (8) Rising atmospheric PCO2 will increase rates and extents of mineral weathering in soils. (9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering. (10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales. (12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur.
Novel Rateless Coded Selection Cooperation in Dual-Hop Relaying Systems

Selection cooperation is proposed for rateless coded relaying by developing a novel low-complexity protocol that exploits all source-destination, source-relay, and relay-destination link qualities for relay selection. The source or any decoding relay having a link to the destination with a gain greater than a preset threshold is a candidate for collaboration. When the number of candidates reaches a preset value, the best of them is selected for passing the source data to the destination. The source and relays are informed of the selected node by a broadcast feedback from the destination. Limited feedback is required only between the destination and the other nodes and merely for declaring success in decoding or selecting the next transmitting node. The system power and complexity are independent of the system parameters. Also, the system dispenses with internode synchronization at carrier or symbol levels, multireception combining, multiaccess interference, and multiuser detection. Assuming independent fading on different links, a general performance analysis of the new system is presented valid for any individual link fading model. It is shown through numerical results that the novel scheme is considerably more energy efficient, for diverse input conditions, than a more complex commensurate scheme previously proposed. Also, the energy efficiency is enhanced as the number of relays increases, such that despite an increase in the capacity, the energy expenditure diminishes.
Edge-connectivity augmentation preserving simplicity

Given a simple graph G=(V, E), the goal is to find a smallest set F of new edges such that G=(V, E/spl cup/F) is /spl kappa/ edge connected and simple. Very recently this problem was shown to be NP hard by T. Jordan (1997). We prove that if OPT/sub P//sup /spl kappa// is high enough-depending on /spl kappa/ only-then OPT/sub S//sup /spl kappa//=OPT/sub P//sup /spl kappa// holds, where OPT/sub S//sup /spl kappa// (OPT/sub P//sup /spl kappa//) is the size of an optimal solution of the augmentation problem with (without) the simplicity preserving requirement, respectively. Furthermore, OPT/sub S//sup /spl kappa//-OPT/sub P//sup /spl kappa///spl les/g(/spl kappa/) holds for a certain (quadratic) function of /spl kappa/. Based on these results an algorithm is given which computes an optimal solution in time O(n/sup 4/) for any fixed /spl kappa/. Most of these results are extended to the case of non-uniform demands, as well.
The Effects of Individual-Level Culture on Mobile Commerce Adoption: An Empirical Study

As mobile commerce spreads across the globe, the effect of culture on user’ adoption has become an important issue. To date, however, little research has been conducted on the role of cultural factors play in the adoption of m-commerce services. This study defines culture on individual level and attains three roles (network members, technology users and consumers) out of m-commerce users with different adoption decisions. Therefore, a m-commerce adoption model based on individual-level cultural characteristics has been proposed. The four cultural dimensions representing individual-level culture (uncertainty avoidance, individualism/collectivism, context and time perception) are integrated into adoption model as moderators or independent variables in this study. A survey instrument is also developed for collecting data and empirically testing the proposed model.
Haptic u-Table: A Believable Feedback System with a Quasi-tangible Tabletop Interface

A haptic tabletop interface is developed to provide its users with a shared digital space and its believable feedbacks in multimodal interactions. The shared digital space means a table where the users can join and enjoy digital content such as games, pictures, etc. The believable feedback can be defined as a consistent notification mechanism to recognize actions of users and notify them of the corresponding results with various feedbacks. It can help users recognize errors and mistakes. It also improves performance of error recovery. Since the users of the tabletop interfaces are not necessarily computer experts, their performances and error recovery functions are important. The proposed haptic tabletop interface was evaluated in terms of its performances, errors and error recovery times. The results showed that the proposed tabletop interface demonstrated better performance in dragging operations.
How phrase sense disambiguation outperforms word sense disambiguation for statistical machine translation

We present comparative empirical evidence arguing that a generalized phrase sense disambiguation approach better improves statistical machine translation than ordinary word sense disambiguation, along with a data analysis suggesting the reasons for this. Standalone word sense disambiguation, as exemplified by the Senseval series of evaluations, typically defines the target of disambiguation as a single word. But in order to be useful in statistical machine translation, our studies indicate that word sense disambiguation should be redefined to move beyond the particular case of single word targets, and instead to generalize to multi-word phrase targets. We investigate how and why the phrase sense disambiguation approach—in contrast to recent efforts to apply traditional word sense disambiguation to SMT—is able to yield statistically significant yimprovements in translation quality even under large data conditions, and consistently improve SMT across both IWSLT and NIST Chinese-English text translation tasks. We discuss architectural issues raised by this change of perspective, and consider the new model architecture necessitated by the phrase sense disambiguation approach. This material is based upon work supported in part by
Ten Simple Rules for Getting Grants

This piece follows an earlier Editorial, ‘‘Ten Simple Rules for Getting Published’’ [1], which has generated significant interest, is well read, and continues to generate a variety of positive comments. That Editorial was aimed at students in the early stages of a life of scientific paper writing. This interest has prompted us to try to help scientists in making the next academic career step—becoming a young principal investigator. Leo Chalupa has joined us in putting together ten simple rules for getting grants, based on our many collective years of writing both successful and unsuccessful grants. While our grant writing efforts have been aimed mainly at United States government funding agencies, we believe the rules presented here are generic, transcending funding institutions and national boundaries. At the present time, US funding is frequently below 10% for a given grant program. Today, more than ever, we need all the help we can get in writing successful grant proposals. We hope you find these rules useful in reaching your research career goals.
Concurrence et régulation : mise en oeuvre et effets de politiques publiques en France

La these porte sur l’effet de politiques publiques visant a agir sur le fonctionnement concurrentiel des marches, en traitant une question de politique de la concurrence et une question de regulation sectorielle. La premiere partie de la these porte sur le controle des concentrations : elle examine tout d'abord les effets des concentrations sur les prix des biens produits, avant de rendre endogene la decision de l'autorite de concurrence. Un premier article examine si l'un des objectifs justifiant l'existence d'un controle de la concurrence – l'amelioration du surplus des consommateurs – est bien atteint en pratique dans le cas du controle des concentrations, par l’estimation empirique de l'effet des concentrations sur les prix des biens et services vendus dans les secteurs concernes, a partir de donnees francaises multisectorielles. Dans un deuxieme article, la prise de decision d'une autorite de concurrence est examinee, par une analyse empirique des determinants des avis du Conseil de la concurrence en matiere de concentration. La seconde partie de la these porte sur un probleme de regulation : comment les restrictions a la libre entree sont valorisees par les acteurs presents sur le marche, du fait des profits anticipes, et quels sont les determinants de cette valeur. Cette question est examinee dans deux situations : tout d’abord, la valorisation des frequences du « dividende numerique », qui sont liberees par l'extinction de la diffusion analogique de la television ; ensuite, la valeur d’une licence de taxi, dont l'elasticite au nombre de licences attribuees est estimee.
Human Immunoglobulin G Recognizing Fibrinogen-Binding Surface Proteins Is Protective against both Staphylococcus aureus and Staphylococcus epidermidis Infections In Vivo

ABSTRACT A human donor-selected immunoglobulin G for intravenous injection (IGIV) product with elevated titers against the staphylococcal fibrinogen-binding MSCRAMM proteins ClfA and SdrG (INH-A21) was tested in vitro and in vivo. INH-A21 contained a significantly increased ability to inhibit the fibrinogen-binding activity of recombinant forms of both ClfA and SdrG. Evaluation of the opsonizing potential of INH-A21 was evaluated using fluorescently labeled bacteria; this assay indicated an increase in phagocytic activity compared to normal IGIV. The prophylactic efficacy of INH-A21 against an intraperitoneal challenge of methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a neonatal rat model. INH-A21 was also evaluated for prophylactic and therapeutic efficacy in a rabbit model of catheter-induced aortic valve infective endocarditis caused by either MRSE or methicillin-resistant Staphylococcus aureus (MRSA). Results from the in vivo models demonstrated potent prophylactic and therapeutic efficacy against both MRSE and MRSA. These data suggest that INH-A21 may be an important tool for the prevention and treatment of staphylococcal infections, especially in high-risk populations.
Ubisco and CDC: Analysis of a Failure

The Union Bank of Switzerland (UBS) and Control Data Corporation (CDC) started the Ubisco project in the early 1970s. The project should have automated all the bank's operations with a single CDC computer system, but Ubisco failed four years later. Unraveling the reasons behind the project's failure might help researchers and historians learn why such large computer projects are so often unsuccessful.
Defining and generating axial lines from street center lines for better understanding of urban morphologies

Axial lines are defined as the longest visibility lines for representing individual linear spaces in urban environments. The least set of axial lines that cover the free space of an urban environment or the space between buildings constitute what is often called an axial map. This is a fundamental tool in space syntax, a theory developed by Bill Hillier and his colleagues for characterizing the underlying urban morphologies. For a long time, generating axial lines with the help of some graphic software has been a tedious manual process that is criticized for being time consuming, subjective, or even arbitrary. In this article, we redefine axial lines as the least set of individual straight line segments mutually intersected along natural streets that are generated from street center lines using the Gestalt principle of good continuity. Based on this new definition, we develop an automatic solution for generating the newly defined axial lines from street center lines. We apply this solution to six typical street networks (three from North America and three from Europe) and generate a new set of axial lines for analyzing the urban morphologies. Through a comparison study between the new axial lines and the conventional or old axial lines and between the new axial lines and natural streets, we demonstrate with empirical evidence that the newly defined axial lines are a better alternative for capturing the underlying urban structure.
Family living sets the stage for cooperative breeding and ecological resilience in birds

Cooperative breeding is an extreme form of cooperation that evolved in a range of lineages, including arthropods, fish, birds, and mammals. Although cooperative breeding in birds is widespread and well-studied, the conditions that favored its evolution are still unclear. Based on phylogenetic comparative analyses on 3,005 bird species, we demonstrate here that family living acted as an essential stepping stone in the evolution of cooperative breeding in the vast majority of species. First, families formed by prolonging parent–offspring associations beyond nutritional independency, and second, retained offspring began helping at the nest. These findings suggest that assessment of the conditions that favor the evolution of cooperative breeding can be confounded if this process is not considered to include 2 steps. Specifically, phylogenetic linear mixed models show that the formation of families was associated with more productive and seasonal environments, where prolonged parent–offspring associations are likely to be less costly. However, our data show that the subsequent evolution of cooperative breeding was instead linked to environments with variable productivity, where helpers at the nest can buffer reproductive failure in harsh years. The proposed 2-step framework helps resolve current disagreements about the role of environmental forces in the evolution of cooperative breeding and better explains the geographic distribution of this trait. Many geographic hotspots of cooperative breeding have experienced a historical decline in productivity, suggesting that a higher proportion of family-living species could have been able to avoid extinction under harshening conditions through the evolution of cooperative breeding. These findings underscore the importance of considering the potentially different factors that drive different steps in the evolution of complex adaptations.
Distributed database design using evolutionary algorithms

The performance of a distributed database system depends particularly on the site-allocation of the fragments. Queries access different fragments among the sites, and an originating site exists for each query. A data allocation algorithm should distribute the fragments to minimize the transfer and settlement costs of executing the query plans. The primary cost for a data allocation algorithm is the cost of the data transmission across the network. The data allocation problem in a distributed database is NP-complete, and scalable evolutionary algorithms were developed to minimize the execution costs of the query plans. In this paper, quadratic assignment problem heuristics were designed and implemented for the data allocation problem. The proposed algorithms find near-optimal solutions for the data allocation problem. In addition to the fast ant colony, robust tabu search, and genetic algorithm solutions to this problem, we propose a fast and scalable hybrid genetic multi-start tabu search algorithm that outperforms the other well-known heuristics in terms of execution time and solution quality.