Miracle-dz/UniFAR-FTUs huggingface dataset:
Cystic Fibrosis Transmembrane Conductance Regulator: Using Differential Reactivity toward Channel-Permeant and Channel-Impermeant Thiol-Reactive Probes To Test a Molecular Model for the Pore†

The sixth transmembrane segment (TM6) of the CFTR chloride channel has been intensively investigated. The effects of amino acid substitutions and chemical modification of engineered cysteines (cysteine scanning) on channel properties strongly suggest that TM6 is a key component of the anion-conducting pore, but previous cysteine-scanning studies of TM6 have produced conflicting results. Our aim was to resolve these conflicts by combining a screening strategy based on multiple, thiol-directed probes with molecular modeling of the pore. CFTR constructs were screened for reactivity toward both channel-permeant and channel-impermeant thiol-directed reagents, and patterns of reactivity in TM6 were mapped onto two new, molecular models of the CFTR pore: one based on homology modeling using Sav1866 as the template and a second derived from the first by molecular dynamics simulation. Comparison of the pattern of cysteine reactivity with model predictions suggests that nonreactive sites are those where the TM6 side chains are occluded by other TMs. Reactive sites, in contrast, are generally situated such that the respective amino acid side chains either project into the predicted pore or lie within a predicted extracellular loop. Sites where engineered cysteines react with both channel-permeant and channel-impermeant probes occupy the outermost extent of TM6 or the predicted TM5−6 loop. Sites where cysteine reactivity is limited to channel-permeant probes occupy more cytoplasmic locations. The results provide an initial validation of two, new molecular models for CFTR and suggest that molecular dynamics simulation will be a useful tool for unraveling the structural basis of anion conduction by CFTR.
Human papillomavirus and survival of patients with oropharyngeal cancer.

BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. RESULTS The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)
Indirect Dark Matter Detection from Dwarf Satellites: Joint Expectations from Astrophysics and Supersymmetry

We present a general methodology for determining the gamma-ray flux from annihilation of dark matter particles in Milky Way satellite galaxies, focusing on two promising satellites as examples: Segue 1 and Draco. We use the SuperBayeS code to explore the best-fitting regions of the Constrained Minimal Supersymmetric Standard Model (CMSSM) parameter space, and an independent MCMC analysis of the dark matter halo properties of the satellites using published radial velocities. We present a formalism for determining the boost from halo substructure in these galaxies and show that its value depends strongly on the extrapolation of the concentration-mass (c(M)) relation for CDM subhalos down to the minimum possible mass. We show that the preferred region for this minimum halo mass within the CMSSM with neutralino dark matter is ~ 10−9–10−6 M⊙. For the boost model where the observed power-law c(M) relation is extrapolated down to the minimum halo mass we find average boosts of about 20, while the Bullock et al (2001) c(M) model results in boosts of order unity. We estimate that for the power-law c(M) boost model and photon energies greater than a GeV, the Fermi space-telescope has about 20% chance of detecting a dark matter annihilation signal from Draco with signal-to-noise greater than 3 after about 5 years of observation.
Disparities in Early Transitions to Obesity in Contemporary Multi-Ethnic U.S. Populations

Background Few studies have examined weight transitions in contemporary multi-ethnic populations spanning early childhood through adulthood despite the ability of such research to inform obesity prevention, control, and disparities reduction. Methods and Results We characterized the ages at which African American, Caucasian, and Mexican American populations transitioned to overweight and obesity using contemporary and nationally representative cross-sectional National Health and Nutrition Examination Survey data (n = 21,220; aged 2–80 years). Age-, sex-, and race/ethnic-specific one-year net transition probabilities between body mass index-classified normal weight, overweight, and obesity were estimated using calibrated and validated Markov-type models that accommodated complex sampling. At age two, the obesity prevalence ranged from 7.3% in Caucasian males to 16.1% in Mexican American males. For all populations, estimated one-year overweight to obesity net transition probabilities peaked at age two and were highest for Mexican American males and African American females, for whom a net 12.3% (95% CI: 7.6%-17.0%) and 11.9% (95% CI: 8.5%-15.3%) of the overweight populations transitioned to obesity by age three, respectively. However, extrapolation to the 2010 U.S. population demonstrated that Mexican American males were the only population for whom net increases in obesity peaked during early childhood; age-specific net increases in obesity were approximately constant through the second decade of life for African Americans and Mexican American females and peaked at age 20 for Caucasians. Conclusions African American and Mexican American populations shoulder elevated rates of many obesity-associated chronic diseases and disparities in early transitions to obesity could further increase these inequalities if left unaddressed.
Aspects of learning within networks of spiking neurons

Spiking neural networks have, in recent years, become a popular tool for investigating the properties and computational performance of large massively connected networks of neurons. Equally as interesting is the investigation of the potential computational power of individual spiking neurons. An overview is provided of current and relevant research into the Liquid Sate Machine, biologically inspired artificial STDP learning mechanisms and the investigation of aspects of the computational power of artificial, recurrent networks of spiking neurons. First, it is shown that, using simple structures of spiking Leaky Integrate and Fire (LIF) neurons, a network n(P), can be built to perform any program P that can be performed by a general parallel programming language. Next, a form of STDP learning with normalisation is developed, referred to as STDP + N learning. The effects of applying this STDP + N learning within recurrently connected networks of neurons is then investigated. It is shown experimentally that, in very specific circumstances Anti-Hebbian and Hebbian STDP learning may be considered to be approximately equivalent processes. A metric is then developed that can be used to measure the distance between any two spike trains. The metric is then used, along with the STDP + N learning, in an experiment to examine the capacity of a single spiking neuron that receives multiple input spike trains, to simultaneously learn many temporally precise Input/Output spike train associations. The STDP +N learning is further modified for use in recurrent networks of spiking neurons, to give the STDP + NType2 learning methodology. An experiment is devised which demonstrates that the Type 2 method of applying learning to the synapses of a recurrent network — effectively a randomly shifting locality of learning — can enable the network to learn firing patterns that the typical application of learning is unable to learn. The resulting networks could, in theory, be used to create to simple structures discussed in the first chapter of original work.
Konrad-zuse-zentrum Für Informationstechnik Berlin Competitive Online Multicommodity Routing Competitive Online Multicommodity Routing

We study online multicommodity routing problems in networks , in which commodities have to be routed sequentially. The flow of each commodity can be split on several paths. Arcs are equipped with load dependent price functions defining routing costs, which have to be minimized. We discuss a greedy online algorithm that routes each commodity by minimizing a convex cost function that depends on the previously routed flow. We present a competitive analysis of this algorithm showing that for affine price functions this algorithm is 4K 2 (1+K) 2-competitive, where K is the number of commodities. For networks with two nodes and parallel arcs, this algorithm is optimal. Without restrictions on the price functions and network, no algorithm is competitive. We then investigate a variant in which the demands have to be routed unsplittably. In this case, it is NP-hard to compute the offline optimum. The variant of the greedy algorithm that produces unsplittable flows is (3 + 2 √ 2)-competitive, and we prove a lower bound of 2 for the competitive ratio of any deterministic online algorithm.
Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson’s Disease with Dementia and Dementia with Lewy Bodies

Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in “orientation to place” tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients’ lower average scores for “repetition” (MMSE), “recent memory” (HDS-R), and “lexical fluency” (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients’ poorer average subscale scores of “orientation to place” (MMSE) and “similarities”, “conflicting instructions”, and “go-no go” (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD.
The Effect of Prenatal and Childhood Development on Hearing, Vision and Cognition in Adulthood

It is unclear what the contribution of prenatal versus childhood development is for adult cognitive and sensory function and age-related decline in function. We examined hearing, vision and cognitive function in adulthood according to self-reported birth weight (an index of prenatal development) and adult height (an index of early childhood development). Subsets (N = 37,505 to 433,390) of the UK Biobank resource were analysed according to visual and hearing acuity, reaction time and fluid IQ. Sensory and cognitive performance was reassessed after ~4 years (N = 2,438 to 17,659). In statistical modelling including age, sex, socioeconomic status, educational level, smoking, maternal smoking and comorbid disease, adult height was positively associated with sensory and cognitive function (partial correlations; pr 0.05 to 0.12, p < 0.001). Within the normal range of birth weight (10th to 90th percentile), there was a positive association between birth weight and sensory and cognitive function (pr 0.06 to 0.14, p < 0.001). Neither adult height nor birth weight was associated with change in sensory or cognitive function. These results suggest that adverse prenatal and childhood experiences are a risk for poorer sensory and cognitive function and earlier development of sensory and cognitive impairment in adulthood. This finding could have significant implications for preventing sensory and cognitive impairment in older age.
Evaluation of atlas based mouse brain segmentation

Magentic Reasonance Imaging for mouse phenotype study is one of the important tools to understand human diseases. In this paper, we present a fully automatic pipeline for the process of morphometric mouse brain analysis. The method is based on atlas-based tissue and regional segmentation, which was originally developed for the human brain. To evaluate our method, we conduct a qualitative and quantitative validation study as well as compare of b-spline and fluid registration methods as components in the pipeline. The validation study includes visual inspection, shape and volumetric measurements and stability of the registration methods against various parameter settings in the processing pipeline. The result shows both fluid and b-spline registration methods work well in murine settings, but the fluid registration is more stable. Additionally, we evaluated our segmentation methods by comparing volume differences between Fmr1 FXS in FVB background vs C57BL/6J mouse strains.
Non-convex consensus ADMM for satellite precoder design

Owing to the rapidly increasing traffic demands on satellite connectivity, the current exclusive frequency allocation is becoming obsolete. Instead, aggressive frequency reuse and interference mitigation techniques are promising ideas that both industry and academia are investigating. This paper proposes an optimization precoding technique for dealing with the multibeam interference due to the aggressive frequency reuse. In contrast to general multiuser multiple input multiple output (MIMO) schemes, multibeam satellite precoding techniques call for frame-by-frame quadratically constrained quadratic optimization of a large number of variables. We focus on the multigroup multicast beamforming optimization problem, and we propose to adopt a consensus-based alternating direction method of multipliers (C-ADMM) approach, in order to mitigate complexity. The proposed C-ADMM approach is shown to exhibit comparable optimization performance at considerably lower complexity relative to the prior state-of-art for the formulation considered.
Risk of Gastric Cancer by Water Source: Evidence from the Golestan Case-Control Study

Background Gastric cancer (GC) is the world’s fifth most common cancer, and the third leading cause of cancer-related death. Over 70% of incident cases and deaths occur in developing countries. We explored whether disparities in access to improved drinking water sources were associated with GC risk in the Golestan Gastric Cancer Case Control Study. Methods and Findings 306 cases and 605 controls were matched on age, gender, and place of residence. We conducted unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusted for age, gender, ethnicity, marital status, education, head of household education, place of birth and residence, homeownership, home size, wealth score, vegetable consumption, and H. pylori seropositivity. Fully-adjusted ORs were 0.23 (95% CI: 0.05–1.04) for chlorinated well water, 4.58 (95% CI: 2.07–10.16) for unchlorinated well water, 4.26 (95% CI: 1.81–10.04) for surface water, 1.11 (95% CI: 0.61–2.03) for water from cisterns, and 1.79 (95% CI: 1.20–2.69) for all unpiped sources, compared to in-home piped water. Comparing unchlorinated water to chlorinated water, we found over a two-fold increased GC risk (OR 2.37, 95% CI: 1.56–3.61). Conclusions Unpiped and unchlorinated drinking water sources, particularly wells and surface water, were significantly associated with the risk of GC.
Detecting Cyberbullying Entries on Informal School Websites Based on Category Relevance Maximization

We propose a novel method to detect cyberbullying entries on the Internet. “Cyberbullying” is defined as humiliating and slandering behavior towards other people through Internet services, such as BBS, Twitter or e-mails. In Japan members of Parent-Teacher Association (PTA) perform manual Web site monitoring called “net-patrol” to stop such activities. Unfortunately, reading through the whole Web manually is an uphill task. We propose a method of automatic detection of cyberbullying entries. In the proposed method we first use seed words from three categories to calculate semantic orientation score PMI-IR and then maximize the relevance of categories. In the experiment we checked the cases where the test data contains 50% (laboratory condition) and 12% (real world condition) of cyberbullying entries. In both cases the proposed method outperformed baseline settings.
Comparing surgeon outcomes in endoscopic sinus surgery for chronic rhinosinusitis

The objective of this investigation was to evaluate endoscopic sinus surgery (ESS) outcomes for chronic rhinosinusitis (CRS) between medical centers to determine if differences in quality‐of‐life outcomes were detectable. In addition, we sought to identify significant, independent cofactors toward the development of an ESS‐specific risk‐adjustment model so that ESS outcomes may be appropriately compared between institutions and healthcare providers.
Molecularly engineered vaccine which expresses an immunodominant T-cell epitope induces cytotoxic T lymphocytes that confer protection from lethal virus infection

Identification of a single viral T-cell epitope, associated with greater than 95% of the virus-specific cytotoxic T-lymphocyte (CTL) activity in BALB/c (H-2d) mice (J. L. Whitton, A. Tishon, H. Lewicki, J. Gebhard, T. Cook, M. Salvato, E. Joly, and M. B. A. Oldstone, J. Virol. 63:4303-4310, 1989), permitted us to design a CTL vaccine and test its ability to protect against a lethal virus challenge. Here we show that a single immunization with a recombinant vaccinia virus-lymphocytic choriomeningitis virus (LCMV) vaccine (VVNPaa1-201) expressing the immunodominant epitope completely protected H-2d mice from lethal infection with LCMV but did not protect H-2b mice. Furthermore, we show that the success or failure of immunization was determined entirely by the host class I major histocompatibility glycoproteins. The difference in outcome between mice of these two haplotypes was consistent with the presence or absence in the immunizing sequences of an epitope for CTL recognition and is correlated with the induction of LCMV-specific H-2-restricted CTL in H-2d mice. Protection is not conferred by a humoral immune response, since LCMV-specific antibodies were not detectable in sera from VVNPaa1-201-immunized mice. In addition, passive transfer of sera from vaccinated mice did not confer protection upon naive recipients challenged with LCMV. Hence, the molecular dissection of viral proteins can uncover immunodominant CTL epitope(s) that can be engineered into vaccines that elicit CTL. A single CTL epitope can protect against a lethal virus infection, but the efficacy of the vaccine varies in a major histocompatibility complex-dependent manner.
Public key distribution through "cryptoIDs"

In this paper, we argue that person-to-person key distribution is best accomplished with a key-centric approach, instead of PKI: users should distribute public key fingerprints in the same way they distribute phone numbers, postal addresses, and the like. To make this work, fingerprints need to be small, so users can handle them easily; multipurpose, so only a single fingerprint is needed for each user; and long-lived, so fingerprints don't have to be frequently redistributed. We show how these qualities can be achieved with simple and well-understood techniques. The chief technique is for each user to store a root key in a highly secure environment and use it to certify subkeys for use in more convenient environments. Certificate formats like X.509, PGP, and SPKI could be used for this, but we argue that a format designed expressly for this could do a better job; thus we design the cryptoID certificate format.
Dictionary-based Equivalent Source Method for Near-Field Acoustic Holography

In this paper, we propose a modification of the standard Equivalent Source Method (ESM) for Near-Field Acoustic Holography (NAH). As in EMS, we aim at modeling the acoustic pressure radiated from a vibrating object, and its surface velocity, as the joint effect of a set of equivalent sources located within or close to the object itself. The estimation of the equivalent source strengths (weigths) comes from the solution of a highly ill-conditioned problem. Rather than solving this problem in the least-squares sense, we exploit the 3D model of the vibrating object, along with a rough estimate of its physical parameters, to restrict the space of the solutions. More specifically, we make use of Finite Element Analysis for populating a compressed dictionary of possible equivalent source weights. NAH is then approached by seeking a sparse linear combination of the entries of the dictionary. Experiments carried on a public database prove the effectiveness of the proposed technique, especially when the number of available microphones is limited, and in the presence of a significant level of measurement noise.
Fast, Lean, and Accurate: Modeling Password Guessability Using Neural Networks

Human-chosen text passwords, today's dominant form of authentication, are vulnerable to guessing attacks. Unfortunately, existing approaches for evaluating password strength by modeling adversarial password guessing are either inaccurate or orders of magnitude too large and too slow for real-time, client-side password checking. We propose using artificial neural networks to model text passwords' resistance to guessing attacks and explore how different architectures and training methods impact neural networks' guessing effectiveness. We show that neural networks can often guess passwords more effectively than state-of-the-art approaches, such as probabilistic context-free grammars and Markov models. We also show that our neural networks can be highly compressed-to as little as hundreds of kilobytes-without substantially worsening guessing effectiveness. Building on these results, we implement in JavaScript the first principled client-side model of password guessing, which analyzes a password's resistance to a guessing attack of arbitrary duration with sub-second latency. Together, our contributions enable more accurate and practical password checking than was previously possible.