Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptosis: A review of pro‐apoptotic and anti‐apoptotic pathways and dysregulation in disease

Abstract Objective – To review the human and veterinary literature on the biology of apoptosis in health and disease. Data Sources – Data were examined from the human and veterinary literature identified through Pubmed and references listed in appropriate articles pertaining to apoptosis. Human Data Synthesis – The role of apoptosis in health and disease is a rapidly growing area of research in human medicine. Apoptosis has been identified as a component of human autoimmune diseases, Alzheimer's disease, cancer, and sepsis. Veterinary Data Synthesis – Research data available from the veterinary literature pertaining to apoptosis and its role in diseases of small animal species is still in its infancy. The majority of veterinary studies focus on oncologic therapy. Most of the basic science and human clinical research studies use human blood and tissue samples and murine models. The results from these studies may be applicable to small animal species. Conclusions – Apoptosis is the complex physiologic process of programmed cell death. The pathophysiology of apoptosis and disease is only now being closely evaluated in human medicine. Knowledge of the physiologic mechanisms by which tissues regulate their size and composition is leading researchers to investigate the role of apoptosis in human diseases such as cancer, autoimmune disease and sepsis. Because it is a multifaceted process, apoptosis is difficult to target or manipulate therapeutically. Future studies may reveal methods to regulate or manipulate apoptosis and improve patient outcome.
Engineering chitinolytic activity into a cellulose-active lytic polysaccharide monooxygenase provides insights into substrate specificity

Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of recalcitrant polysaccharides such as cellulose and chitin and play an important role in the enzymatic degradation of biomass. Although it is clear that these monocopper enzymes have extended substrate-binding surfaces for interacting with their fibrous substrates, the structural determinants of LPMO substrate specificity remain largely unknown. To gain additional insight into substrate specificity in LPMOs, here we generated a mutant library of a cellulose-active family AA10 LPMO from Streptomyces coelicolor A3(2) (ScLPMO10C, also known as CelS2) having multiple substitutions at five positions on the substrate-binding surface that we identified by sequence comparisons. Screening of this library using a newly-developed MS-based high-throughput assay helped identify multiple enzyme variants that contained four substitutions and exhibited significant chitinolytic activity and a concomitant decrease in cellulolytic activity. The chitin-active variants became more rapidly inactivated during catalysis than a natural chitin-active AA10 LPMO, an observation likely indicative of suboptimal substrate binding leading to autocatalytic oxidative damage of these variants. These results reveal several structural determinants of LPMO substrate specificity and underpin the notion that productive substrate binding by these enzymes is complex, depending on a multitude of amino acids located on the substrate-binding surface.
Diffusion of effects of the ASSIST school‐based smoking prevention intervention to non‐participating family members: a secondary analysis of a randomized controlled trial

Abstract Aims To investigate whether effects of the ASSIST (A Stop Smoking In Schools Trial) school‐based smoking prevention intervention diffused from students to the people they lived with. Design Secondary analysis of a cluster‐randomized control trial (cRCT). Setting England and Wales. Participants A total of 10 730 students aged 12–13 years in 59 schools assigned using stratified block randomization to the control (29 schools, 5372 students) or intervention (30 schools, 5358 students) condition. Intervention and comparator The ASSIST intervention involves 2 days of off‐site training of influential students to encourage their peers not to smoke during a 10‐week period. The control group continued with their usual education. Measurements The outcomes were the proportion of students who self‐reported living with a smoker and the smoking status of each resident family member/caregiver. Follow‐up assessments were immediately after the intervention and at 1 and 2 years post‐intervention. Findings The odds ratio (OR) for living with a smoker in the intervention compared with the control groups was 0.86 [95% confidence interval (CI) = 0.72, 1.03] immediately after the intervention, OR = 0.84 (95% CI = 0.72, 0.97) at a 1‐year follow‐up and OR = 0.86 (95% CI = 0.75, 0.99) at 2‐year follow‐up. In a three‐tier multi‐level model with data from all three follow‐ups, student‐reported smoking by fathers (OR = 0.90, 95% CI = 0.80, 1.00), brothers (OR = 0.78, 95% CI = 0.67, 0.92) and sisters (OR = 0.80, 95% CI = 0.69, 0.92) was lower in the intervention compared with control group. Subgroup analyses by baseline smoking status suggested that these effects were more consistent with prevention of uptake than prompting cessation. Conclusions A Stop Smoking In Schools Trial (ASSIST) school‐based smoking prevention intervention may have reduced the prevalence of smoking in people who lived with ASSIST‐trained students. This indirect transmission is consistent with the predictions of diffusion of innovations theory which underpins the design of ASSIST.
Mechanisms of virus dissemination in bone marrow of HIV-1–infected humanized BLT mice

Immune progenitor cells differentiate in bone marrow (BM) and then migrate to tissues. HIV-1 infects multiple BM cell types, but virus dissemination within BM has been poorly understood. We used light microscopy and electron tomography to elucidate mechanisms of HIV-1 dissemination within BM of HIV-1–infected BM/liver/thymus (BLT) mice. Tissue clearing combined with confocal and light sheet fluorescence microscopy revealed distinct populations of HIV-1 p24-producing cells in BM early after infection, and quantification of these populations identified macrophages as the principal subset of virus-producing cells in BM over time. Electron tomography demonstrated three modes of HIV-1 dissemination in BM: (i) semi-synchronous budding from T-cell and macrophage membranes, (ii) mature virus association with virus-producing T-cell uropods contacting putative target cells, and (iii) macrophages engulfing HIV-1–producing T-cells and producing virus within enclosed intracellular compartments that fused to invaginations with access to the extracellular space. These results illustrate mechanisms by which the specialized environment of the BM can promote virus spread locally and to distant lymphoid tissues.
Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology

Mice with the C3H background show greater behavioral propensity for schizophrenia, including lower prepulse inhibition (PPI), than C57BL/6 (B6) mice. To characterize as‐yet‐unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H2S)/polysulfide‐producing enzyme, and greater sulfide deposition in C3H than B6 mice. Mpst‐deficient mice exhibited improved PPI with reduced storage sulfide levels, while Mpst‐transgenic (Tg) mice showed deteriorated PPI, suggesting that “sulfide stress” may be linked to PPI impairment. Analysis of human samples demonstrated that the H2S/polysulfides production system is upregulated in schizophrenia. Mechanistically, the Mpst‐Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H2S/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory/oxidative insults in early brain development result in upregulated H2S/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H2S/polysulfides production.
Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus‐1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub‐study A5334s

AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight‐based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults. The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized.
Protein and thiamin intakes are not related to cognitive function in well-nourished community-living older adults

Aim Some studies have suggested that thiamin (vitamin B1) may have a protective effect on the maintenance of cognitive function in older people. The aim of this exploratory study was to investigate the association between dietary intakes, specifically protein and thiamin with cognitive function. Methods A cross-sectional analysis was conducted on community-living older adults aged ≥60 years in the Illawarra region of New South Wales. Dietary intakes were collected using a three-day food record and various domains of cognition were tested. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Correlations and regressions were conducted to investigate the association between dietary intakes and areas of cognitive function. Results Forty-eight volunteers participated (mean age: 78.2 ± 6.1 years; BMI: 28.8 ± 5.4 kg/m2; MNA Score: 26.8 ± 2.4; 35% men). Men had higher intakes of energy (kJ), carbohydrate, saturated fat and sodium than women. No significant association was found between protein or thiamin and the tested domains of cognition. Associations were found between vitamin D intake and the Letter Fluency Test (r = −0.302, P < 0.05) and Rey Auditory Verbal Learning Test (r = −0.400, P < 0.001), and between both carbohydrate (r = 0.383, P = < 0.05) and iron intake (r = 0.333, P < 0.05) and the GDS. Conclusions In a sample of generally healthy, well-nourished older adults, no associations were found between protein or thiamin intakes and the tested components of cognition. Further investigation is required to determine if an increase in these nutrients through the provision of food sources has benefits to improve cognitive function.
Room‐Temperature‐Formed PEDOT:PSS Hydrogels Enable Injectable, Soft, and Healable Organic Bioelectronics

There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe‐injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room‐temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large‐scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room‐temperature‐formed PEDOT:PSS hydrogels (RT‐PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self‐healable hydrogel bioelectronic devices.
Implications of the circular RNAs in localized prostate cancer.

Stochastic and contingent events in molecular biology tune the advent of new molecular entities, most recent being the circular RNAs (circRNAs) which bestowed new avenues in cancer research. The circRNAs are stable, single-stranded covalently closed transcripts resulting from the back-splicing events of RNA (1). circRNAs are present in the plasma, cell-free saliva and urine of cancer patients and healthy individuals, either in the free forms or bound to the proteins or associated with exosomes highlighting their importance as non-invasive biomarkers (2).
Universal scaling of three-dimensional bosonic gases in a trapping potential

We investigate some aspects of the Bose-Einstein condensation (BEC) of quantum gases in the presence of inhomogeneous conditions. We consider three-dimensional (3D) quantum gases trapped by an external potential when the temperature is sufficiently low to show a BEC phase region around the center of the trap. If the trap is sufficiently large, different phases may coexist in different space regions, when moving from the center of the trap. We show that the quantum gas develops a peculiar critical behavior at the boundary of the BEC region, whose scaling behavior is controlled by the universality class of the homogenous BEC transition. We provide numerical evidence of this phenomenon, for lattice atomic gases modeled by the 3D Bose-Hubbard Hamiltonian.
Structure‐Activity Relationships Analysis of Monomeric and Polymeric Polyphenols (Quercetin, Rutin and Catechin) Obtained by Various Polymerization Methods

Plant polyphenols, especially flavonoids, are active and pro‐health substances found in fruits and vegetables. Quercetin and its glycoside rutin are representatives of flavonoids, commonly found in plant products. Catechins found in large quantities in tea are also a well‐known group of natural polyphenols. These compounds are based on the structure of flavan‐3‐ol, which is why the number, positions and types of substitutions affect the scavenging of radicals and other properties. Despite some inconsistent evidence, several structure−activity relationships of monomeric flavonoids are well established in vitro. However, the relationships between the activity and other properties of the polymeric forms of flavonoids and their structures are poorly understood so far. The aim of this article is to compare the data on polymerization of quercetin, rutin and catechin, as well as to systematize knowledge about the structure−activity relationship of the polymeric forms of these compounds.
Transfer RNA-Derived Small Non-Coding RNA: Dual Regulator of Protein Synthesis

Transfer RNA-derived small RNAs (tsRNAs) play a role in various cellular processes. Accumulating evidence has revealed that tsRNAs are deeply implicated in human diseases, such as various cancers and neurological disorders, suggesting that tsRNAs should be investigated to develop novel therapeutic intervention. tsRNAs provide more complexity to the physiological role of transfer RNAs by repressing or activating protein synthesis with distinct mechanisms. Here, we highlight the detailed mechanism of tsRNA-mediated dual regulation in protein synthesis and discuss the necessity of novel sequencing technology to learn more about tsRNAs.
Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats

Disruption of the tightly regulated mitochondrial dynamics and energy homeostasis leads to oxidative stress and apoptotic cell death, as observed in neurodegenerative disorders such as Parkinson's disease (PD). Polyphenolic plant derivatives have been shown to alleviate such pathological features and have been used in models of neurodegenerative disorders in previous reports. In the current study, we utilized a 6‐hydroxydopamine (6‐OHDA) lesioned rat model of PD to explore the protective efficacy of polyphenolic phytochemical ferulic acid (FA) against mitochondrial dysfunction and explored its effect on gene and protein expression of mitochondrial dynamics regulators dynamin‐related protein 1 (Drp1)/mitofusin 2 (Mfn2) in lesioned animals. We also evaluated its effect on expression of mitochondrial biogenesis regulator PGC1α and apoptotic regulators BAX, cyt c, p53, and cleaved PARP. We found that oral FA supplementation alleviated 6‐OHDA induced oxidative stress, DNA fragmentation, morphological changes, and blocked apoptotic cascade. FA also reduced mitochondrial Drp1 expression and increased gene and protein expression of PGC1α, thereby regulating expression of its downstream target Mfn2 and restoring mitochondrial dynamics in lesioned animals. Our data suggest that targeting mitochondrial dynamics through modulation of PGC1α can prove to be a potent preventive strategy against PD pathology.
Cholesterol accessibility at the ciliary membrane controls hedgehog signaling

Previously we proposed that transmission of the hedgehog signal across the plasma membrane by Smoothened is triggered by its interaction with cholesterol (Luchetti et al., 2016). But how is cholesterol, an abundant lipid, regulated tightly enough to control a signaling system that can cause birth defects and cancer? Using toxin-based sensors that distinguish between distinct pools of cholesterol, we find that Smoothened activation and hedgehog signaling are driven by a biochemically-defined, small fraction of membrane cholesterol, termed accessible cholesterol. Increasing cholesterol accessibility by depletion of sphingomyelin, which sequesters cholesterol in complexes, amplifies hedgehog signaling. Hedgehog ligands increase cholesterol accessibility in the membrane of the primary cilium by inactivating the transporter-like protein Patched 1. Trapping this accessible cholesterol blocks hedgehog signal transmission across the membrane. Our work shows that the organization of cholesterol in the ciliary membrane can be modified by extracellular ligands to control the activity of cilia-localized signaling proteins.
M ar 2 00 9 DAMTP-2008-82 IFUP-TH / 2008-22 TIT / HEP 589 September , 2008 SO and USp Kähler and Hyper-Kähler Quotients and Lumps

We study non-linear σ models whose target spaces are the Higgs phases of supersymmetric SO and USp gauge theories by using the Kähler and hyper-Kähler quotient constructions. We obtain the explicit Kähler potentials and develop an expansion formula to make use of the obtained potentials from which we also calculate the curvatures of the manifolds. The 1/2 BPS lumps in the U(1) × SO and U(1) × USp Kähler quotients and their effective descriptions are also studied. In this connection, a general relation between moduli spaces of vortices and lumps is discussed. We find a new singular limit of the lumps with non-vanishing sizes in addition to the ordinary small lump singularity. The former is due to the existence of singular submanifolds in the target spaces. e-mail address: minoru(at)df.unipi. it e-mail address: fujimori(at)th.phys.titech.ac.jp e-mail address: gudnason(at)df.unipi. it e-mail address: nitta(at)phys-h.keio. ac.jp e-mail address: K.Ohashi(at)damtp.cam. ac.uk
A Unified Framework for Trees, MDS and Planar Graphs

Least squares trees, multidimensional scaling and Neighbor Nets are all different and popular ways of visualizing multi-dimensional data. The method of flexi-Weighted Least Squares (fWLS) is a powerful method of fitting phylogenetic trees, when the exact form of errors is unknown. Here, both polynomial and exponential weights are used to model errors. The exact same models are implemented for Multi-Dimensional Scaling to yield flexi-Weighted MDS, including as special cases methods such as the Sammon Stress function. Here we apply all these methods to population genetic data looking at the relationships of “Abrahams Children” encompassing Arabs and now widely dispersed populations of Jews, in relation to an African outgroup and a variety of European populations. Trees, MDS and Neighbor Nets of this data are compared within a common likelihood framework and the strengths and weaknesses of each method are explored. Because the errors in this type of data can be complex, for example, due to unexpected genetic transfer, we use a residual resampling method to assess the robustness of trees and the Neighbor Net. Despite the Neighbor Net fitting best by all criteria except BIC, its structure is ill defined following residual resampling. In contrast, fWLS trees are favored by BIC and retain considerable strong internal structure following residual resampling. This structure clearly separates various European and Middle Eastern populations, yet it is clear all of the models have errors much larger than expected by sampling variance alone.
L G ] 2 2 M ay 2 01 7 S MART P ASTE : Learning to Adapt Source Code

Deep Neural Networks have been shown to succeed at a range of natural language tasks such as machine translation and text summarization. While tasks on source code (i.e., formal languages) have been considered recently, most work in this area does not attempt to capitalize on the unique opportunities offered by its known syntax and structure. In this work, we introduce SMARTPASTE, a first task that requires to use such information. The task is a variant of the program repair problem that requires to adapt a given (pasted) snippet of code to surrounding, existing source code. As first solutions, we design a set of deep neural models that learn to represent the context of each variable location and variable usage in a data flow-sensitive way. Our evaluation suggests that our models can learn to solve the SMARTPASTE task in many cases, achieving 58.6% accuracy, while learning meaningful representation of variable usages.
M N ] 2 8 M ay 2 01 3 Stochastic gene expression with delay by

The expression of genes usually follows a two-step procedure. First, a gene (encoded in the genome) is transcribed resulting in a strand of (messenger) RNA. Afterwards, the RNA is translated into protein. Classically, this gene expression is modeled using a Markov jump process including activation and deactivation of the gene, transcription and translation rates together with degradation of RNA and protein. We extend this model by adding delays (with arbitrary distributions) to transcription and translation. Such delays can e.g. mean that RNA has to be transported to a different part of a cell before translation can be initiated. Already in the classical model, production of RNA and protein come in bursts by activation and deactivation of the gene, resulting in a large variance of the number of RNA and proteins in equilibrium. We derive precise formulas for this second-order structure with the model including delay in equilibrium. As a general fact, the delay decreases the variance of the number of RNA and proteins.
A ug 2 00 8 IPM / P-2008 / 029 Central Charge for 2 D Gravity on AdS 2 and AdS 2 / CFT 1 Correspondence

We study 2D Maxwell-dilaton gravity on AdS2. We distinguish two distinctive cases depending on whether the AdS2 solution can be lifted to an AdS3 geometry. In both cases, in order to get a consistent boundary condition we need to work with a twisted energy momentum tensor which has non-zero central charge. With this central charge and the explicit form of the twisted Virasoro generators we compute the entropy of the system using the Cardy formula. The entropy is found to be the same as that obtained from gravity calculations for a specific value of the level of the U(1) current. The agreement is an indication of AdS2/CFT1 correspondence.
D ec 2 01 3 Are two given maps homotopic ? An algorithmic

This paper presents two algorithms. In their simplest form, the first algorithm decides the existence of a pointed homotopy between given simplicial maps f, g : X → Y and the second computes the group [ΣX, Y ]∗ of pointed homotopy classes of maps from a suspension; in both cases, the target Y is assumed simply connected and the algorithms run in polynomial time when the dimension of X is fixed. More generally, these algorithms work relative to A ⊆ X, fibrewise over a simply connected B and also equivariantly when all spaces are equipped with a free action of a fixed finite group G.