Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene transfer in humans using a conditionally replicating lentiviral vector

We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21–36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.
Axonal injury or loss in the internal capsule and motor impairment in multiple sclerosis.

OBJECTIVE To test the hypothesis that axonal damage extending into primarily normal-appearing white matter is clinically important by comparing the concentrations of N-acetylaspartate (NAA) bilaterally within the internal capsule with lateralization of motor impairment in patients with multiple sclerosis (MS) and persistent asymmetrical motor deficit. DESIGN We performed magnetic resonance spectroscopy and T2-weighted imaging of the internal capsule, calculated central motor conduction times, and related these results to measures of motor function asymmetry in 12 patients with MS. RESULTS Levels of NAA from normal-appearing white matter of the internal capsule in patients with MS were significantly lower than those in control subjects (P = .05). Side-to-side differences in NAA levels were also significantly greater in patients with MS than in controls (P = .01). There was a correlation between asymmetry in motor function for the left and right limbs and asymmetry of internal capsule NAA concentrations (r = 0.60; P = .04). This correlation seemed slightly stronger when tests specifically of arm and hand motor asymmetry were considered alone. Central motor conduction times were abnormal in most patients with MS and showed a side-to-side difference that also correlated with asymmetry in motor function. CONCLUSION Our demonstration of a graded association between NAA concentrations within primarily normal-appearing white matter of a specific tract and functional impairments referable to that tract suggests that axonal pathology distant from macroscopic lesions might be an important determinant of disability in MS.
On Stability Region and Delay Performance of Linear-Memory Randomized Scheduling for Time-Varying Networks

Throughput optimal scheduling policies in general require the solution of a complex and often NP-hard optimization problem. Related literature has shown that in the context of time-varying channels, randomized scheduling policies can be employed to reduce the complexity of the optimization problem but at the expense of a memory requirement that is exponential in the number of data flows. In this paper, we consider a linear-memory randomized scheduling policy (LM-RSP) that is based on a pick-and-compare principle in a time-varying network with N one-hop data flows. For general ergodic channel processes, we study the performance of LM-RSP in terms of its stability region and average delay. Specifically, we show that LM-RSP can stabilize a fraction of the capacity region. Our analysis characterizes this fraction as well as the average delay as a function of channel variations and the efficiency of LM-RSP in choosing an appropriate schedule vector. Applying these results to a class of Markovian channels, we provide explicit results on the stability region and delay performance of LM-RSP.
Uptake in Incidental Focus on Form in Meaning‐Focused ESL Lessons

Uptake is a term used to describe learners’ responses to the provision of feedback after either an erroneous utterance or a query about a linguistic item within the context of meaning-focused Language activities. Some researchers argue that uptake may contribute to second Language acquisition by facilitating noticing and pushing learners to produce more accurate linguistic forms. This study investigated the occurrence of uptake in 32 hr of meaning-focused lessons in 12 English as a second Language classes in Auckland, New Zealand. It also examined which characteristics of incidental focus on form predicted uptake and successful uptake. The results indicated that uptake occurred in these classes and that characteristics such as complexity, timing, and type of feedback influenced both the production of uptake and the successfulness of it.
The interplay between risk and protective factors in the prediction of self-harm or suicidal behaviour within a prison environment

Self-harm and suicide is more prevalent within the prison environment than in community samples, with those in the first weeks of imprisonment at greatest risk. Descriptions and evaluations of static risk factors (e.g. mental health diagnosis) dominate the empirical literature with few dynamic (e.g. defeat) and protective factors (e.g. resilience) evaluated. Additionally, current research is largely atheoretical and the integration of existing knowledge into a unifying model may improve the predictability of assessment. In the current research Williams and Pollock’s cry of pain model provided the template for assessing predictors of self-harm or suicide. For three months, all new arrivals at a local prison were invited to complete baseline questionnaires to assess factors derived from the cry of pain model. It was hypothesised that the factors derived from the model (perceived stress, defeat, entrapment and absence of rescue factors) would be predictive of self-harm and suicide risk and would distinguish prior self-harmers from non self-harmers. Two hundred and seventy prisoners participated in the study. Prisoners with active psychosis and non-English speakers were excluded. All participants were followed up for four months for instances of self-harm. Eighteen participants engaged in self-harm during this period. The hypotheses derived from the model were supported in the prediction of future engagement in self-harm in prison and had some support in identifying those who engaged in previous self-harm and those at risk of suicide. Additional research is needed to confirm the factor structure of defeat and entrapment and the presence of ‘scripts’ as relevant factors in the cry of pain model. The
An automatic method for discovering rational heuristics for risky choice

What is the optimal way to make a decision given that your time is limited and your cognitive resources are bounded? To answer this question, we formalized the bounded optimal decision process as the solution to a meta-level Markov decision process whose actions are costly computations. We approximated the optimal solution and evaluated its predictions against human choice behavior in the Mouselab paradigm, which is widely used to study decision strategies. Our computational method rediscovered well-known heuristic strategies and the conditions under which they are used, as well as novel heuristics. A Mouselab experiment conﬁrmed our model’s main predictions. These ﬁndings are a proof-of-concept that optimal cognitive strategies can be automatically derived as the rational use of ﬁnite time and bounded cognitive resources.
Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise

Noise-induced hearing loss (NIHL) is the most significant occupational health issue worldwide. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with hearing threshold shift in young males undergoing their first encounter with occupational impulse noise. We report a significant association of SNP rs7598759 (p < 5 x 10-7; p = 0.01 after permutation and correction; Odds Ratio = 12.75) in the gene coding for nucleolin, a multifunctional phosphoprotein involved in the control of senescence and protection against apoptosis. Interestingly, nucleolin has been shown to mediate the anti-apoptotic effect of HSP70, a protein found to prevent ototoxicity and whose polymorphisms have been associated with susceptibility to NIHL. Increase in nucleolin expression has also been associated with the prevention of apoptosis in cells undergoing oxidative stress, a well-known metabolic sequela of noise exposure. To assess the potential role of nucleolin in hearing loss, we tested down-regulation of nucleolin in cochlear sensory cells HEI-OC1 under oxidative stress conditions and report increased sensitivity to cisplatin, a chemotherapeutic drug with ototoxic side effects. Additional SNPs were found with suggestive association (p < 5 x 10-4), of which 7 SNPs were located in genes previously reported to be related to NIHL and 43 of them were observed in 36 other genes previously not reported to be associated with NIHL. Taken together, our GWAS data and in vitro studies reported herein suggest that nucleolin is a potential candidate associated with NIHL in this population.
A Method for Rapid Demineralization of Teeth and Bones

Tooth and bone specimen require extensive demineralization for careful analysis of cell morphology, as well as gene and protein expression levels. The LacZ gene, which encodes the ß-galactosidase enzyme, is often used as a reporter gene to study gene-structure function, tissue-specific expression by a promoter, cell lineage and fate. This reporter gene is particularly useful for analyzing the spatial and temporal gene expression pattern, by expressing the LacZ gene under the control of a promoter of interest. To analyze LacZ activity, and the expression of other genes and their protein products in teeth and bones, it is necessary to carry out a complete demineralization of the specimen before cutting sections. However, strong acids, such as formic acid used for tooth demineralization, destroy the activities of enzymes including those of ß-galactosidase. Therefore, most protocols currently use mild acids such as 0.1 M ethylene diamine tetra-acetic acid (EDTA) for demineralization of tooth and bone specimen, which require a longer period of treatment for complete demineralization. A method by which hard tissue specimens such as teeth and bones can be rapidly, but gently, decalcified is necessary to save time and effort. Here, we report a suitable method for rapid demineralization of mouse teeth in 0.1M EDTA at 42˚C without any loss of ß-galactosidase activity.
Bounded Variation Singular Stochastic Control and Dynkin Game

We consider a bounded variation singular stochastic control problem with value V in a general situation with control of a diffusion and nonlinear cost functional defined as solution to a backward stochastic differential equation (BSDE). Associated with this is a Dynkin game with value u. We establish the well-known relation $\frac{\partial}{\partial x}V=u$ for this general situation. A saddle point for the Dynkin game is given by the pair of first action times of an optimal control. The methods are from stochastic analysis and include a priori estimates, pathwise construction, and comparison theorems for forward stochastic differential equations (FSDE) and BSDE.
Understanding the Failure of CD8+ T-Cell Vaccination against Simian/Human Immunodeficiency Virus

ABSTRACT Although CD8+ T cells play an important role in controlling viral infections, boosting specific CD8+ T cells by prophylactic vaccination with simian immunodeficiency virus (SIV) epitopes fails to provide sterilizing immunity. Viral replication rates and viral contraction rates after the peak viremia hardly depend on the presence of memory CD8+ T cells. To study these paradoxical findings, we parameterize novel mathematical models for acute SIV and human immunodeficiency virus infection. These models explain that failure of vaccination is due to the fact that effector/target ratios are too low during the viral expansion phase. Because CD8+ T cells require cell-to-cell contacts, immune protection requires high effector/target ratios at the primary site of infection. Effector/target ratios become favorable for immune control at the time of the peak in the viral load when the virus becomes limited by other factors, such as the availability of uninfected target cells. At the viral set point, effector/target ratios are much higher, and perturbations of the number of CD8+ effector cells have a large impact on the viral load. Such protective effector/target ratios are difficult to achieve with nucleic acid- or protein-based vaccines.
Superchunk-Based Proficient Explore in P2P-VoD System

In this project, we seek to provide reliable and fast substance discovery in peer-to-peer (P2P) video-on- demand(VoD) format to smooth the progress of user interactivity under peer dynamics. We first be acquainted with two characteristics of substance detection in P2P-VoD: real-time constraints and inadequate local cache. Tapping on these properties, we suggest a hybrid substance discovery mechanism: Super chunk-based proficient explore Network (SURF Net). SURF Net divides movies into super chunks and chunks. Unwavering peers that are likely to have longer duration in the system are used to assemble an AVL tree to provide super chunk-level data availability information. Peers storing the equivalent superchunk are grouped into a holder-chain, which is then fond of to a swelling in the AVL tree. This structured superimpose is further extensive by a gossip-based formless network for chunk-level information exchange and data communication. Since the AVL tree consists of only unwavering peers, it provides a trustworthy backbone even in highly dynamic surroundings. Our scrutiny and simulation results show that SURF Net supports nearly-constant and logarithmic look for time for seeking inside a video and jumping to a different video, correspondingly.
Structural Biology and Crystallization Communications Expression, Purification, Crystallization and Preliminary X-ray Analysis of the Dna-binding Domain of a Chlamydia Trachomatis Ompr/phob- Subfamily Response Regulator Homolog, Chxr

Two-component signal transduction systems in bacteria are a primary mechanism for responding to environmental stimuli and adjusting gene expression accordingly. Generally in these systems a sensor kinase phosphorylates a response regulator that regulates transcription. Response regulators contain two domains: a receiver domain and an effector domain. The receiver domain is typically phosphorylated and as a result facilitates the DNA-binding and transcriptional activity of the effector domain. The OmpR/PhoB subfamily is the largest of the response-regulator subfamilies and is primarily defined by the winged helix–turn–helix DNA-binding motif within the effector domain. The overall structure of effector domains is highly conserved and contains three defined elements that are critical for transcriptional regulation: a DNA major-groove binding helix, a DNA minor-groove binding wing and a transcriptional activation loop. These functional elements are often diverse in sequence and conformation and reflect the functional differences observed between individual subfamily members. ChxR from Chlamydia trachomatis is an atypical OmpR/ PhoB response regulator homolog that has transcriptional activity in the absence of phosphorylation. To facilitate the precise identification of the functional elements of the ChxR effector domain, this protein was cloned, expressed, purified and crystallized. Crystals were obtained from two separate mother liquors, producing two morphologically distinct crystals. The space group of both crystals was P4 3 2 1 2 (or its enantiomorph P4 1 2 1 2) with isomorphous unit-cell parameters; the crystals diffracted to 2.2–2.5 A ˚ resolution.
PIANA: protein interactions and network analysis

UNLABELLED We present a software framework and tool called Protein Interactions And Network Analysis (PIANA) that facilitates working with protein interaction networks by (1) integrating data from multiple sources, (2) providing a library that handles graph-related tasks and (3) automating the analysis of protein-protein interaction networks. PIANA can also be used as a stand-alone application to create protein interaction networks and perform tasks such as predicting protein interactions and helping to identify spots in a 2D electrophoresis gel. AVAILABILITY PIANA is under the GNU GPL. Source code, database and detailed documentation may be freely downloaded from http://sbi.imim. es/piana.
Contracting for the transfer of technology within multinational corporations: Empirical evidence from Spain

This article analyzes a sample of contracts that includes transfers of technology to Spanish subsidiaries in 1991. First, know-how is more likely transmitted within multinationals than between unrelated firms, highlighting the key role of multinationals in the diffusion of tacit knowledge. The determinants of scheduled payments are also studied to find, among other things, that multinationals adjust scheduled payments depending on differences in taxes between the source and host countries.
Exploring Multiple Feature Spaces for Novel Entity Discovery

Continuously discovering novel entities in news and Web data is important for Knowledge Base (KB) maintenance. One of the key challenges is to decide whether an entity mention refers to an in-KB or out-of-KB entity. We propose a principled approach that learns a novel entity classifier by modeling mention and entity representation into multiple feature spaces, including contextual, topical, lexical, neural embedding and query spaces. Different from most previous studies that address novel entity discovery as a submodule of entity linking systems, our model is more a generalized approach and can be applied as a pre-filtering step of novel entities for any entity linking systems. Experiments on three real-world datasets show that our method significantly outperforms existing methods on identifying novel entities.
The Aging Heart, Myocardial Fibrosis, and its Relationship to Circulating C-Type Natriuretic Peptide

Myocardial aging is characterized by left ventricular (LV) fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent antifibrotic and antiproliferative properties of C-type natriuretic peptide (CNP); however, the relationship between circulating CNP, LV fibrosis, and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2-, 11-, and 20-month–old male Fischer rats. Further in vitro, we established the antiproliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis that precedes impairment of diastolic and systolic function. Additionally, we demonstrate in cultured adult human cardiac fibroblasts that the direct antiproliferative actions of high-dose CNP may involve a non-cGMP pathway via the clearance receptor. Together, these studies provide new insights into myocardial aging and the relationship to the antifibrotic and antiproliferative peptide CNP.
Development of non-weak link bulk YBCO grain boundaries for high magnetic field engineering applications

A non-weak link joining technique has been developed for YBCO pseudo-crystals fabricated by seeded peritectic solidification based on the formation of a liquid phase which segregates from the platelet boundaries at temperatures above /spl ap/920/spl deg/C. Electrical and magnetic measurements on these boundaries suggest that their irreversibility field can be as high as 7 T at 77 K in fully oxygenated pseudo-crystals joined along their crystallographic ab-planes which is comparable to the irreversibility behaviour of the adjacent YBCO grains.
Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

BACKGROUND: We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. METHODS: We performed a randomized, masked, multicenter study comparing Darbe (10 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks’ postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months’ corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. RESULTS: Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks’ gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment. CONCLUSIONS: Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants.
Biomechanics feedback for rowing

Factors that affect boat speed are important determinants of rowing performance and should form the basis of feedback to rowers and their coaches. Biomechanical analysis of rowing has led to variables that are causally linked to boat speed. With modern technology, these variables can be measured and feedback can be presented instantaneously on-water, or be presented simultaneously with video after the event. This paper demonstrates the links between the criterion of success in rowing, the time for completing 2000 m and the forces acting on the boat, and describes an instrumentation system for providing feedback of these variables to rowers and coaches. These feedback techniques have been used with rowers from national to Olympic competition standard. Aspects of technique have been linked to the determinants of boat speed and several examples are presented here. The motor learning literature supports the effectiveness of kinetic information feedback for the improvement of motor skill and provides a relevant conceptual framework for the improvement of rowing performance. However, although rowers and their coaches value this feedback, further research must be undertaken to establish a sound basis for comparing the effectiveness of such feedback compared with traditional styles, such as verbal feedback of performance.
Physiologic findings in children previously ventilator dependent at home due to bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is the primary respiratory complication of premature birth. Some preterm newborns develop chronic respiratory failure, requiring home ventilator support. While physiologic measures have been described for prematurely born children, little is known about spirometric indices in patients with severe BPD who were previously ventilator dependent at home.