Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Genetic Screening for Alpha1-Antitrypsin Deficiency in a High-Prevalence Area

Background: Current guidelines for α1-antitrypsin deficiency (AATD) state that adult population screening should only be done in high-risk areas. Up-to-date genetic methods are always recommended. Objectives: To determine the prevalence of AATD in a suspected high-risk area by population screening, applying new genetic analyses and comparing the prevalence of liver and lung abnormalities in subjects with or without AATD. Methods: Adult residents of Pezzaze, a village in an Italian alpine valley, voluntarily participated in the screening, and were examined for: nephelometric α1-antitrypsin (AAT) serum level, DNA analysis (mutagenic polymerase chain reaction and restriction fragment length polymorphism tests for Z and S AATD causative mutations, and denaturing high-performance liquid chromatography and/or direct gene sequencing if needed), serum aspartate and alanine transaminases, a respiratory questionnaire and the Medical Research Council dyspnea index scale. The prevalence of AATD was compared with that expected in Italy (Hardy-Weinberg equilibrium), and transaminases and the prevalence of respiratory symptoms were compared between study groups. Results: Of 1,353 residents, 817 (60.4%) participated; 67 (8.2%) had low AAT serum levels (<90 mg/dl); 118 were carriers of AATD-associated alleles, 4 (0.5%) homozygotes or compound heterozygotes (1 Z, 1 S, 2 ZPbrescia), 114 (14%) heterozygotes (46 Z, 52 S, 9 Pbrescia, 4 Mwurzburg, 2 I, 1 Plowell). The prevalence and frequency of all AATD-related alleles was higher than expected for Italy (p < 0.001). There were no differences in symptoms of respiratory disease and transaminases between individuals with normal and low serum AAT. Conclusion: The screening design is one of the main strengths of this study. The large number of mostly asymptomatic individuals with AATD identified suggests that in high-risk areas adult population screening programs employing the latest genetic methods are feasible. Early recognition of individuals at risk means primary or secondary prevention measures can be taken.
Hypoxic stress suppresses RNA polymerase III recruitment and tRNA gene transcription in cardiomyocytes

RNA polymerase (pol) III transcription decreases when primary cultures of rat neonatal cardiomyocytes are exposed to low oxygen tension. Previous studies in fibroblasts have shown that the pol III-specific transcription factor IIIB (TFIIIB) is bound and regulated by the proto-oncogene product c-Myc, the mitogen-activated protein kinase ERK and the retinoblastoma tumour suppressor protein, RB. The principal function of TFIIIB is to recruit pol III to its cognate gene template, an activity that is known to be inhibited by RB and stimulated by ERK. We demonstrate by chromatin immunoprecipitation (ChIP) that c-Myc also stimulates pol III recruitment by TFIIIB. However, hypoxic conditions cause TFIIIB dissociation from c-Myc and ERK, at the same time as increasing its interaction with RB. Consistent with this, ChIP assays indicate that the occupancy of tRNA genes by pol III is significantly reduced, whereas promoter binding by TFIIIB is undiminished. The data suggest that hypoxia can inhibit pol III transcription by altering the interactions between TFIIIB and its regulators and thus compromising its ability to recruit the polymerase. These effects are independent of cell cycle changes.
The Cost-Effectiveness of Directly Observed Highly-Active Antiretroviral Therapy in the Third Trimester in HIV-Infected Pregnant Women

Background In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. Methods and Findings A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. Conclusions Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.
Current-induced domain nucleation in ferromagnet

A key mechanism of the current-induced magnetization dynamics is the spin torque from a spin polarized current (spin current), which couples to spatial gradient of magnetization. Recently, it was pointed out that a large spin current applied to a uniform ferromagnet leads to a spin-wave instability. In this paper, we show that such instability is absent in a state containing a domain wall. This may indicate that nucleation of magnetic domains occurs above a certain critical spin current. This scenario is supported by an explicit energy comparison between the uniformly magnetized state and the domain-wall state under spin current.
Multifactorial analysis of p53 alteration in human cancer: A review

For some time, studies of the molecular biology of cancer have emphasized the importance of a number of proto-oncogenes in human cancer. These studies were initiated by identification of these genes as DNA sequences which could be transduced by oncogenic retroviruses. The isolation and characterization of their cellular counterparts led to intense investigation, with the description of dominant alterations found in a wide variety of human tumors (Bishop, 1991). Nevertheless, several lines of investigation have lent support to the hypothesis that neoplastic transformation may also involve alterations in genes whose products negatively regulate cell proliferation. Studies of the suppression of malignant phenotypes in cell hybrids produced by fusing a tumorigenic cell with a non-tumorigenic cell have led to the proposal that recessive mutations could also contribute to cell transformation. This observation was reinforced by the identification of tumor-suppressor genes during the study of familial cancer. Such inactivation (through deletion or mutation) is generally linked to the loss of the other allele viavarious mechanisms (Sager, 1985; Stanbridge, 1990). Using colorectal carcinoma as a model of tumor progression, Vogelstein et al. (1988) showed that loss of heterozygosity (LOH) of the short arm of chromosome 17 (17p) was a frequent event (75%) in this type of cancer. Using the new development of PCR technology, they were able to show that point mutations in thep53 gene were present in DNA from 2 tumors examined, one at position 143 and the second at position 175 (Baker et al., 1989). In another report, Takahashi et al. (1989) demonstrated the presence of point mutations in thep53 gene from lung carcinoma, in which 17p LOH was also a frequent event. Finally, Nigro et a1. (
Memory registration caching correctness

Fast and powerful networks are becoming more popular on clusters to support applications including message passing, file systems, and databases. These networks require special treatment by the operating system to obtain high throughput and low latency. In particular, application memory must be pinned and registered in advance of use. However, popular communication libraries such as MPI have interfaces that do not require explicit registration calls from the user, thus the libraries must manage this aspect themselves. Registration caching is a necessary and effective tool to reuse memory registrations and avoid the overheads of pinning and unpinning pages around every send or receive. Current memory registration caching schemes do not take into account the fact that the user has access to a variety of operating system calls that can alter memory layout and destroy earlier cached registrations. The work presented in this paper fixes that problem by providing a mechanism for the operating system to notify the communication library of changes in the memory layout of a process while preserving existing application semantics. This permits the safe and accurate use of memory registration caching.
Organization of chromosome ends in the rice blast fungus, Magnaporthe oryzae

Eukaryotic pathogens of humans often evade the immune system by switching the expression of surface proteins encoded by subtelomeric gene families. To determine if plant pathogenic fungi use a similar mechanism to avoid host defenses, we sequenced the 14 chromosome ends of the rice blast pathogen, Magnaporthe oryzae. One telomere is directly joined to ribosomal RNA-encoding genes, at the end of the ∼2 Mb rDNA array. Two are attached to chromosome-unique sequences, and the remainder adjoin a distinct subtelomere region, consisting of a telomere-linked RecQ-helicase (TLH) gene flanked by several blocks of tandem repeats. Unlike other microbes, M.oryzae exhibits very little gene amplification in the subtelomere regions—out of 261 predicted genes found within 100 kb of the telomeres, only four were present at more than one chromosome end. Therefore, it seems unlikely that M.oryzae uses switching mechanisms to evade host defenses. Instead, the M.oryzae telomeres have undergone frequent terminal truncation, and there is evidence of extensive ectopic recombination among transposons in these regions. We propose that the M.oryzae chromosome termini play more subtle roles in host adaptation by promoting the loss of terminally-positioned genes that tend to trigger host defenses.
A secure delegation scheme of large polynomial computation in multi-party cloud

Cloud computing is becoming widely used both in academia and industry and one of the most important applications is delegating computation. A computationally weak client delegates tasks to one or more workers in cloud, and this is called delegation computation. Delegation computation has high security requirements, and it needs to ensure that the information of the client would not be leaked and the computation will be computed correctly. What's more, the clients can verify the result after computation. This paper presents a delegation protocol and it allows the client to delegate a large polynomial to more than one worker while keeping privacy and correctness. In this paper, the workers make computations directly on the shares from the client, and keep the threshold unchanged. This protocol has these advantages: the protocol keeps privacy of the original input; the workers have no interaction with each other during the execution; the protocol keeps the threshold unchanged.
Factor V Is an Anticoagulant Cofactor for Activated Protein C during Inactivation of Factor Va

Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FVLeiden. However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/protein S also readily inactivates activated FV (FVa). We therefore hypothesized that FV can function as an anticoagulant cofactor for APC/protein S in the inactivation of FVa. FV was titrated into FV-deficient plasma, and the APC sensitivity ratio (APCsr; a measure of APC activity) was measured in a clotting assay that was not sensitive to FVIII. Our results showed an increase in APCsr as the FV concentration increased, suggesting an anticoagulant function for FV in this assay. FVLeiden showed APC resistance with an APCsr of 1.0. Therefore, under our experimental conditions, FV acted as an anticoagulant cofactor for APC in the inactivation of FVa.
Outage Minimization via Power Adaptation and Allocation for Truncated Hybrid ARQ

In this work, we analyze hybrid ARQ (HARQ) protocols over the independent block fading channel. We assume that the transmitter is unaware of the channel state information (CSI) but has a knowledge about the channel statistics. We consider two scenarios with respect to the feedback received by the transmitter: i) ''conventional'', one-bit feedback about the decoding success/failure (ACK/NACK), and ii) the multi-bit feedback scheme when, on top of ACK/NACK, the receiver provides additional information about the state of the decoder to the transmitter. In both cases, the feedback is used to allocate (in the case of one-bit feedback) or adapt (in the case of multi-bit feedback) the power across the HARQ transmission attempts. The objective in both cases is the minimization of the outage probability under long-term average and peak power constraints. We cast the problems into the dynamic programming (DP) framework and solve them for Nakagami-m fading channels. A simplified solution for the high signal-to-noise ratio (SNR) regime is presented using a geometric programming (GP) approach. The obtained results quantify the advantage of the multi-bit feedback over the conventional approach, and show that the power optimization can provide significant gains over conventional power-constant HARQ transmissions even in the presence of peak-power constraints.
A soft-constrained unscented Kalman filter estimator for Li-ion cells electrochemical model

Li-ion batteries require advanced Battery Management Systems (BMSs). The estimation of the cells internal quantities (residual energy, temperature, ions concentrations) is paramount for the correct and safe operation of Li-ion batteries. Accurate estimation of these quantities is however a challenging task. This work addresses the internal state estimation of a Li-ion cell applying the Unscented Kalman Filter (UKF) approach to the complete P2D model. The use of the complete P2D model allows for the estimation of the spatial distribution of Li-ions concentrations, along with the estimate of the bulk State of Charge (SoC). The paper illustrates how the UKF can address the two main issues involved in using the P2D model in estimation: weak observability and computational load. The observability issue is addressed imposing a soft mass conservation constraint in the UFK particles computation, while a parallelized implementation softens the computational burden. Extensive simulations validate the approach with currents up to 50C.
Influence of genes and family environment on adult smoking behavior assessed in an adoption study

Twin studies suggest that genetic factors influence smoking behavior. However, in these studies, genetic and environmental influences may be confounded. We examined whether smoking behavior of adoptees is associated with smoking behavior in adoptive and biological relatives in a design in which this confounding is minimized. Data on smoking status were collected using a mailed questionnaire in a sample of 840 adoptive families from the Danish Adoption Register including all non‐familial adoptions from 1924 through 1947. Smoking data were available for 706 adoptees, 451 biological fathers, 580 biological mothers, 641 adoptive fathers, 693 adoptive mothers, 199 biological full‐siblings, 684 maternal half‐siblings, and 576 paternal half‐siblings. Adoptees’ status as ever, current, heavy, or former (ex‐)smokers was related to their relatives’ smoking status. Adoptees ever smoking was associated with their full‐siblings’ status as ever smokers (OR = 3.6 [1.5–8.7]). Adoptees’ current smoking was also associated with their full‐siblings’ ever (OR = 3.2 [1.5–7.7]) and current (OR = 2.6 [1.3–5.0]) smoking, whereas adoptees’ heavy smoking was associated with their full‐siblings ever (OR = 5.5 [2.1–14.3]), current (OR = 4.0[1.9–8.6]) and heavy (OR = 2.0[1.0–4.2]) smoking. Compared with current smokers, adoptee ex‐smokers had full‐siblings who were ex‐smokers more often (OR = 3.5 [1.0–11.6]), current (OR = 0.4 [0.2–0.8]), and heavy (OR = 0.3 [0.1–0.9]) smokers less often. Adoptees’ smoking behavior was not associated with adoptive or biological parents’ status as current smokers. This study of smoking behavior in adult adoptees and their biological and adoptee family supports the finding in twin studies of a genetic influence on smoking within the same generation. Genet. Epidemiol. 21:193–200, 2001. © 2001 Wiley‐Liss, Inc.
An Evaluation of Family-based Intervention with Schizophrenia Using Single-system Research

The purpose of this study was to determine the effects of a short-term model of intervention on schizophrenic out-patients and their relatives. The author implemented an in-home ten session educational and skills training programme adapted from existing models. The intervention's effects on patient's clinical status and social functioning, relative's attitudes, and family stress were evaluated using a multiple baseline across four cases, as well as pre, post, and follow-up data.
In utero Mycobacterium avium subspecies paratuberculosis infection of a pygmy goat

TRANSMISSION of Mycobacterium avium subspecies paratuberculosis (MAP) in utero has not previously been recorded in goats. This short communication documents the presence of MAP in fetal tissues of a heavily infected pregnant doe. A two-year-old female pygmy goat ( Capra hircus ) was evaluated for
Inducing domain theories

Inducing Domain Theories A thesis submitted to the Committee for Linguistics, Philology and Phonetics in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the University of Oxford. by Maria Liakata, St Edmund Hall, Trinity Term 2004 This thesis presents a method for learning a domain theory automatically from a corpus of parsed sentences. What is meant by a ‘domain theory’ is a collection of facts and generalisations or rules which capture what commonly happens (or does not happen) in some domain of interest. As language users we implicitly draw on such theories in various disambiguation tasks, such as anaphora resolution and prepositional phrase attachment, and formal encodings of domain theories can be used for this purpose in natural language processing. Domain theories may also be objects of interest in their own right, that is, as the output of a knowledge discovery process, providing previously unobserved information to aid with the understanding of the domain. The learning paradigm employed is Inductive Logic Programming (ILP), which generalises over examples from the domain to obtain more general patterns covering the majority of the input instances. ILP was preferred over other machine learning techniques due to the expressive power of the language specifications guiding the search for general patterns and the fact that it allows the inclusion of background knowledge. Different ILP algorithms were explored in conjunction with the domain of company succession events. The relational data mining algorithm WARMR gave the most satisfactory results as it was able to capture frequent patterns of complex structure, often encoding causal relations, consisting of two or more verbs and information about their respective arguments. Finite State Automata (FSA) minimisation techniques were employed to render the rules learnt into a more compact format. Thus, sets of rules were represented as weighted FSAs, which are easier for humans to visualise than a first order logic
RESEARCH ON SPOKEN LANGUAGE PROCESSING Progress Report No . 28 ( 2007 ) Indiana University Perceptual Learning Under a Cochlear Implant Simulation

Adaptation to the acoustic world following cochlear implantation does not typically include formal training or extensive audiological rehabilitation. Can cochlear implant (CI) users benefit from formal training, and if so, what type of training is best? This study used a pre/post-test design to evaluate the efficacy and generalization of training in normal hearing subjects listening to CI simulations (8-channel sinewave vocoder). Subjects were trained with words (simple or complex), sentences (meaningful or anomalous), or environmental stimuli, and then were tested using an open-set identification task. Subjects were trained on only one type of material but were tested on all materials. All groups showed significant improvement as a result of training, which successfully generalized to some, but not all stimulus materials. For easier tasks, all types of training generalized equally well. For more difficult tasks, training specificity was observed. Training on speech did not generalize to the recognition of environmental signals; however, training on environmental signals successfully generalized to speech. These data demonstrate that the perceptual learning of degraded speech is highly context-dependent and that the specific stimulus materials that a subject experiences during training have a substantial impact on generalization to new materials.
Fidelity and near-optimality of Elmore-based routing constructions

We address the efficient construction of interconnection trees with near-optimal delays. We study the accuracy and fidelity of easily-computed delay models with respect to detailed simulation (e.g., SPICE-computed delays). We show that Elmore delay minimization (W.C. Elmore, 1948) is a high-fidelity interconnect objective for IC interconnect technologies, and propose a greedy low delay tree (LDT) heuristic which for any monotone delay function can efficiently minimize maximum delay. For comparison, we also generate optimal routing trees (ORTs) with respect to Elmore delay, using branch-and-bound search. Experimental results show that the LDT heuristic approximates ORTs very accurately: for nets with up to seven pins, LDT trees have a maximum sink delay within 2.3% of optimum on average. Moreover, compared with minimum spanning tree constructions, the LDT achieves average reductions in delay of up to 35% depending on the net size. <<ETX>>
Multi-field inflation from holography

We initiate the study of multi-field inflation using holography. Bulk light scalar fields correspond to nearly marginal operators in the boundary theory and the dual quantum field theory is a deformation of a CFT by such operators. We compute the power spectra of adiabatic and entropy perturbations in a simple model and find that the adiabatic curvature perturbation is not conserved in the presence of entropy perturbations but becomes conserved when the entropy perturbations are set to zero or the model is effectively a single scalar model, in agreement with expectations from cosmological perturbation theory.