Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of HIV integrase resistance mutations

Purpose of review Integrase strand transfer inhibitors (INSTIs) have become a key component of antiretroviral therapy since the approval of twice-daily raltegravir in 2007 and the more recent approval of elvitegravir in 2012. At the same time, a third compound, dolutegravir, is in late-phase clinical trials, being tested as part of a multidrug once-daily formulation comprising this INSTI and two other antiretroviral (ARV) drugs. This review focuses on the factors leading to the development of drug resistance mutations (DRMs) against INSTIs, evidence of cross-resistance among them, and the results of regimen simplification in regard to this topic. Recent findings Sequencing data show that DRMs are highly dynamic in patients failing INSTI therapy. Considerations of viral fitness and drug resistance can together determine the evolution of drug resistance mutations, and in this regard the Y143 and Q148 pathways are superior to the N155 pathway in the promotion of resistance. Preventing the emergence of DRMs requires that effective reverse transcriptase or other inhibitors be used together with INSTIs and that high-level adherence to treatment be maintained. Summary Because of the susceptibility to drug resistance, INSTIs should always be used together with other effective ARV drugs.
Analogue of the Total Variation Denoising Model in the Context of Geometry Processing

We propose a new variational model for surface processing. It is the natural analogue, in the context of geometry processing, of the total variation based image denoising model of Rudin, Osher, and Fatemi. In particular, it admits as solutions surfaces that may have discontinuities in their normals and can reconstruct shapes with sharp ridges and corners. As the analogue of a perfectly well-posed image model, the proposed surface model differs from those based on ill-posed equations of image processing. Since the proposed geometry regularization is variational, it can be incorporated into a variety of applications, such as surface fairing, three-dimensional object reconstruction from multiple viewpoints, or shape optimization. Drawing on important previous work of geometers who were interested in extending certain classical theorems from smooth to polyhedral manifolds, we describe in detail the appropriate numerical implementation of the proposed model in the case of triangulated surfaces. We then demonst.
Intrinsic transverse momentum and the polarized Drell-Yan process.

In this paper we study the cross section at leading order in 1/Q for polarized Drell-Yan scattering at measured lepton-pair transverse momentum QT. We find that for a hadron with spin 1/2 the quark content at leading order is described by six distribution functions for each flavor, which depend on both the lightcone momentum fraction x, and the quark transverse momentum k 2 . These functions are illustrated for a free-quark ensemble. The cross sections for both longitudinal and transverse polarizations are expressed in terms of convolution integrals over the distribution functions.
Gene Expression Divergence is Coupled to Evolution of DNA Structure in Coding Regions

Sequence changes in coding region and regulatory region of the gene itself (cis) determine most of gene expression divergence between closely related species. But gene expression divergence between yeast species is not correlated with evolution of primary nucleotide sequence. This indicates that other factors in cis direct gene expression divergence. Here, we studied the contribution of DNA three-dimensional structural evolution as cis to gene expression divergence. We found that the evolution of DNA structure in coding regions and gene expression divergence are correlated in yeast. Similar result was also observed between Drosophila species. DNA structure is associated with the binding of chromatin remodelers and histone modifiers to DNA sequences in coding regions, which influence RNA polymerase II occupancy that controls gene expression level. We also found that genes with similar DNA structures are involved in the same biological process and function. These results reveal the previously unappreciated roles of DNA structure as cis-effects in gene expression.
Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors

Naturally occurring variations in maternal licking/grooming influence neural development and are transmitted from mother to female offspring. We found that the induction of maternal behavior in virgin females through constant exposure to pups (pup sensitization) was significantly shorter in the offspring of High compared with Low licking/grooming mothers, suggesting differences in maternal responsivity. In randomly selected females screened for individual differences in maternal responsivity and subsequently mated, there was a significant and negative correlation (r = −0.73) between the latency to exhibit maternal behavior in the pup sensitization paradigm and the frequency of pup licking/grooming during lactation. Females that were more maternally responsive to pups and that showed increased levels of pup licking/grooming also showed significantly higher oxytocin receptor levels in the medial preoptic area, the lateral septum, the central nucleus (n.) of the amygdala, the paraventricular n. of the hypothalamus, and the bed n. of the stria terminalis. Intracerebroventricular administration of an oxytocin receptor antagonist to mothers on postpartum day 3 completely eliminated the differences in pup licking/grooming, suggesting that differences in oxytocin receptor levels are functionally related to maternal behavior. Finally, estrogen treatment of virgin females significantly increased oxytocin receptor binding in the medial preoptic area and lateral septum of female offspring of High, but not Low, licking/grooming mothers. These findings suggest that maternal licking/grooming influences the development of estrogen sensitivity in brain regions that regulate maternal behavior, providing a potential mechanism for the intergenerational transmission of individual differences in maternal behavior.
Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2 through an PI3K/Akt‐dependent pathway in rats

Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha‐naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT‐induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma‐glutamyl transpeptidase (γ‐GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT‐administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate‐cysteine ligase catalytic subunit (GCLc) and glutamate‐cysteine ligase modifier subunit (GCLm) in ANIT‐treated group. In addition, the RNA and protein expression of Akt and nuclear factor‐E2‐related factor‐2 (Nrf2) were also activated by paeoniflorin in ANIT‐induced rats. These findings indicated that paeoniflorin protected ANIT‐induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt‐dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanical and Water Vapor Barrier Properties of Bagasse Hemicellulose-based Films

The film-forming ability of bagasse hemicellulose and its potential for packaging were investigated in terms of its mechanical and water vapor barrier properties. The films were prepared under various hemicellulose concentrations, chitosan/glycerol amounts (based on the amount of hemicellulose), and temperatures. These were subsequently evaluated by measurement of their mechanical and water vapor barrier properties. Bagasse hemicellulose-based films with higher tensile strengths were obtained at higher hemicellulose concentrations. Scanning electron microscope images showed that the bagasse hemicellulose-based films did not have pores less than one micron in size, suggesting compatibility between the hemicelluloses and the other components present in the films. Moreover, the tensile strength, elongation, and water vapor barrier of the film increased by approximately 124%, 115%, and 48%, respectively, when the drying temperature increased from 25 to 55 °C. These results indicate that the bagasse hemicellulose can be used as part of the raw material for films with good barrier and mechanical properties.
K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension

Potassium channel mutations drive both cell growth and hormone production in an adrenal tumor that causes severe hypertension. Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K+) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na+) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca2+) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited KCNJ5 mutation that produces increased Na+ conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive cell proliferation and hormone production.
Trends in adaptive MISO system identification for multichannel audio reproduction and speech communication

Online identification of multiple-input/single-output (MISO) acoustic systems is one of the long-standing and continuing challenges in multichannel speech and audio applications. Fast and robust estimation of the impulse response of an acoustic system is a key requirement for several adaptive solutions in time-varying scenarios, such as stereophonic acoustic echo cancellation, room equalization, or crosstalk cancellation. The inevitable presence of cross-correlated loudspeaker signals that is implied by multichannel applications, however, entails the well-known non-uniqueness problem of MISO system identification. Apart from this fundamental issue, a more practical problem already consists in the lack of techniques to evaluate the estimated impulse responses properly. Since well-established measures are often not capable of accounting for all aspects of online MISO system identification, we revert to the recently proposed spectral-importance weighted misalignment (SIWM) to assess MISO identification. In this contribution, we review SIWM and its relation to well-established evaluation tools. On this basis, we provide an insight into the problem of MISO system identification in applications driven by real stereo data. We also analyze and compare a traditional and a very recent approach to deal with the non-uniqueness problem.
RT-notification: A novel real-time notification protocol for wireless control in fog computing

Fog computing is an emerging paradigm that has broad applications including storage, measurement and control. In this paper, we propose a novel real-time notification protocol called RT-Notification for wireless control in fog computing. RT-Notification provides low-latency TDMA communication between an access point in Fog and a large number of portable monitoring devices equipped with sensor and actuator. RT-Notification differentiates two types of controls: urgent downlink actuator-oriented control and normal uplink access & scheduling control. Different from existing protocols, RT-Notification has two salient features: (i) support real-time notification of control frames, while not interrupting ongoing other transmissions, and (ii) support on-demand channel allocation for normal uplink access & scheduling control. RT-Notification can be implemented based on the commercial off-the-shelf 802.11 hardware. Our extensive simulations verify that RT-Notification is very effective in supporting the above two features.
Temporal and spatial coordination of chromosome movement, spindle formation, and nuclear envelope breakdown during prometaphase in Drosophila melanogaster embryos

The spatial and temporal dynamics of diploid chromosome organization, microtubule arrangement, and the state of the nuclear envelope have been analyzed in syncytial blastoderm embryos of Drosophila melanogaster during the transition from prophase to metaphase, by three- dimensional optical sectioning microscopy. Time-lapse, three- dimensional data recorded in living embryos revealed that congression of chromosomes (the process whereby chromosomes move to form the metaphase plate) at prometaphase occurs as a wave, starting at the top of the nucleus near the embryo surface and proceeding through the nucleus to the bottom. The time-lapse analysis was augmented by a high- resolution analysis of fixed embryos where it was possible to unambiguously trace the three-dimensional paths of individual chromosomes. In prophase, the centromeres were found to be clustered at the top of the nucleus while the telomeres were situated at the bottom of the nucleus or towards the embryo interior. This polarized centromere-telomere orientation, perpendicular to the embryo surface, was preserved during the process of prometaphase chromosome congression. Correspondingly, breakdown of the nuclear envelope started at the top of the nucleus with the mitotic spindle being formed at the positions of the partial breakdown of the nuclear envelope. Our observation provide an example in which nuclear structures are spatially organized and their functions are locally and coordinately controlled in three dimensions.
Hemicellulose from Plant Biomass in Medical and Pharmaceutical Application: A Critical Review.

Hemicellulose is the second most abundant plant polysaccharides after cellulose. Due to the non-toxicity, abundance and biodegradability, recently more and more attention has been focused on the exploration of hemicellulose as the potential substrate for the production of liquid fuels and other value-added chemicals and materials in different fields. Especially in the pharmaceutical and medical field, hemicellulose currently has aroused growing concern in immune regulation, bacteria inhibition, drug release, anti-caries, scaffold materials and anti-tumor because of its unique special physiological characteristics including biocompatibility, inhibiting cell mutation and anti-cancer effect, etc. In this paper, we introduce the application of nature hemicellulose, its degradation products, its derivatives and hemicellulose-based materials in the medical field. Their properties and use effects are also discussed in detail. Moreover, the extraction technologies of nature hemicelluloses, the preparation of hemicellulose-derived products are reviewed here briefly. The recent trends and perspectives of future development are highlighted.
Gene associations: true romance or chance meeting in a nuclear neighborhood?

Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene–gene interactions, communication, and even “romance. ” However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor–rich speckles (a.k.a., SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene–domain (or apparent gene–gene) associations within nuclei.
Extended dissipative filtering of fuzzy systems with time-varying delay under imperfect premise matching

ABSTRACT This paper investigates the extended dissipative filter design problems for continuous-time fuzzy systems with time-varying delays under imperfect premise variables based on a unified performance index−extended dissipative. Attention is focused on solving the H∞, L2 − L∞, passive and dissipative filtering problems for fuzzy systems with time-varying delays under this unified framework. Based on the unified performance index, a new delay-dependent filter design approach in terms of linear matrix inequalities is obtained by employing Lyapunov–Krasovskii functional method together with a novel efficient integral inequality. The designed filter can guarantee the filtering error system satisfy the prescribed H∞, L2 − L∞, passive and dissipative performance by tuning the weighting matrices in the conditions. Moreover, in this paper, the fuzzy filter does not need to share the same membership function with fuzzy model, which can enhance design flexibility and robust property of the fuzzy filter system. Finally, two examples are provided to illustrate the effectiveness and significant improvement of the method proposed in this paper.
Designing of Glass‐Free LTCC Microwave Ceramic‐ Ca1−x(Li0.5Nd0.5)xWO4 by Crystal Chemistry

Designing guidelines for glass-free low-temperature cofired ceramic (LTCC) materials were proposed from the point of view of crystal chemistry. As an example, Ca1−x(Nd0.5Li0.5)xWO4 was successfully designed as glass-free LTCC materials by crystal chemistry. The sintering behavior, microstructure, and microwave dielectric properties of Ca1−x(Nd0.5Li0.5)xWO4 ceramics were investigated in this study. The structure and microstructure of the compounds were investigated by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The microwave dielectric properties of the ceramics were studied with a network analyzer at the frequency of about 9–13 GHz. Continuous solid solutions Ca1−x(La0.5Na0.5)xWO4 (0.1 ≤ x≤0.5) were formed as expected in the experimented composition range. They could be sintered into dense ceramics (approximately 96%–98% theoretical density) at 825°C–875°C per 2 h. All samples exhibit Scheelite structure (I41/a) phase. Both of the sintering temperature and microwave dielectric properties, especially the temperature coefficient of resonant frequency (τf), could be tuned in a wide range. Combined excellent microwave dielectric properties with er = 11.7, Q × f = 36 700 GHz, and τf = 5.36 ppm/°C could be obtained for the x = 0.2 composition after sintering at 825°C/2 h. The chemical compatibility of Ca0.8(Nd0.5Li0.5)0.2WO4 ceramic with silver (Ag) powders was also investigated. No chemical reaction has taken place between the matrix phase and Ag after sintering at 850°C/2 h. Thus, it can be used as a promising glass-free microwave dielectric material for LTCC applications.
Learning to Rank Lexical Substitutions

The problem to replace a word with a synonym that fits well in its sentential context is known as the lexical substitution task. In this paper, we tackle this task as a supervised ranking problem. Given a dataset of target words, their sentential contexts and the potential substitutions for the target words, the goal is to train a model that accurately ranks the candidate substitutions based on their contextual fitness. As a key contribution, we customize and evaluate several learning-to-rank models to the lexical substitution task, including classification-based and regression-based approaches. On two datasets widely used for lexical substitution, our best models significantly advance the state-of-the-art.
Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant immunosuppressive drugs incompletely control GVHD and increase susceptibility to opportunistic infections. In this study, we used flagellin, a TLR5 agonist protein (∼50 kDa) extracted from bacterial flagella, as a novel experimental treatment strategy to reduce both acute and chronic GVHD in allogeneic HSCT recipients. On the basis of the radioprotective effects of flagellin, we hypothesized that flagellin could ameliorate GVHD in lethally irradiated murine models of allogeneic HSCT. Two doses of highly purified flagellin (administered 3 h before irradiation and 24 h after HSCT) reduced GVHD and led to better survival in both H-2 b → CB6F1 and H-2 K → B6 allogeneic HSCT models while preserving >99% donor T cell chimerism. Flagellin treatment preserved long-term posttransplant immune reconstitution characterized by more donor thymic-derived CD4 + CD25 + Foxp3 + regulatory T cells and significantly enhanced antiviral immunity after murine CMV infection. The proliferation index and activation status of donor spleen-derived T cells and serum concentration of proinflammatory cytokines in flagellin-treated recipients were reduced significantly within 4 d posttransplant compared with those of the PBS-treated control recipients. Allogeneic transplantation of radiation chimeras previously engrafted with TLR5 knockout hemato-poietic cells showed that interactions between flagellin and TLR5 expressed on both donor hematopoietic and host nonhemato-poietic cells were required to reduce GVHD. Thus, the peritransplant administration of flagellin is a novel therapeutic approach to control GVHD while preserving posttransplant donor immunity. T he major causes of mortality in cancer patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) are graft-versus-host disease (GVHD), relapse, and opportunistic infections (1, 2). GVHD is caused by allore-active activated donor T cells, in part, through the elaboration of inflammatory cytokines released by host tissues in response to pretransplant conditioning with radiation and/or high-dose che-motherapy (3). Recent data suggest that, beside the donor T cells, host epithelial cells also have a role in the initial presentation of the alloantigen to donor T cells during the initiation of GVHD (4– 6). Approximately 30–40% and 50–60% of long-term survivors of allogeneic HSCT develop acute GVHD and/or chronic GVHD, respectively, despite prophylactic administration of immunosup-pressive drugs (7). GVHD causes host tissue damage and suppresses the function of lymphoid organs, leading to increased susceptibility to opportunistic infections in human and in animal model systems (8, 9). Moreover, the long-term impairment …