Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein

Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self-assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by folding into the RNA-binding cleft. Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals. DOI: http://dx.doi. org/10.7554/eLife.12627. 001
Homebound patients’ perspectives on technology and telemedicine: A qualitative analysis

ABSTRACT Telemedicine holds promise in bridging the gap between homebound patients and high quality health care, but uptake of such technology remains limited. Qualitative interviews conducted with 17 homebound patients found two major barriers to telemedicine. First, participants who lack familiarity with technology are hesitant about telemedicine, as baseline use of technology in the home is limited, participants did not feel capable of learning, and the advantages of telemedicine were unclear. Second, homebound patients place a high value on in-office visits due to therapeutic benefit, face-to-face communication, and the social aspect of medical appointments.
An empirical investigation into factors influencing the adoption of an e-learning system

Purpose – The purpose of this research is to investigate the factors affecting the adoption of the e‐learning system (ELS) in mandatory and voluntary settings, through an extension of the technology acceptance model (TAM). Design/methodology/approach – Regression analysis was used to observe the associations of proposed constructs.Findings – The results of the study confirm the original TAM findings. In mandatory settings, students would only intend to use the ELS. Computer self‐efficacy demonstrated significant influence on perceived ease of use. Effects of course attributes on perceived usefulness were negatively significant. Effects of content quality on perceived usefulness were significant. This study found that the effects of subjective norm significantly influenced perceived usefulness in both settings. Also, perceived network externality exerts a significant direct effect on usage intentions, perceived usefulness, and perceived ease of use. This research implied that, first of all, mandatory usage .
Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial.

IMPORTANCE No highly effective interventions to prevent delirium have been identified. OBJECTIVE To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium. DESIGN, SETTING, AND PARTICIPANTS A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital. Eligible patients were 65 to 89 years old, newly admitted due to serious medical problems, and able to take medicine orally. Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours. INTERVENTIONS Sixty-seven patients were randomly assigned using the sealed envelope method to receive ramelteon (8 mg/d; 33 patients) or placebo (34 patients) every night for 7 days. MAIN OUTCOMES AND MEASURES Incidence of delirium, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). RESULTS Ramelteon was associated with a lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09 (95% CI, 0.01-0.69). Even after risk factors were controlled for, ramelteon was still associated with a lower incidence of delirium (P = .01; odds ratio, 0.07 [95% CI, 0.008-0.54]). The Kaplan-Meier estimates of time to development of delirium were 6.94 (95% CI, 6.82-7.06) days for ramelteon and 5.74 (5.05-6.42) days for placebo. Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon than in those taking placebo (χ(2) = 9.83; P = . 002). CONCLUSIONS AND RELEVANCE Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium. TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000005591.
Riccati Equation and EM Algorithm Convergence for Inertial Navigation Alignment

This correspondence investigates the convergence of a Kalman filter-based expectation-maximization (EM) algorithm for estimating variances. It is shown that if the variance estimates and the error covariances are initialized appropriately, the underlying Riccati equation solution and the sequence of iterations will be monotonically nonincreasing. Further, the process noise variance estimates converge to the actual values when the measurement noise becomes negligibly small. Conversely, when the process noise variance becomes negligible, the measurement noise variance estimates asymptotically approach the true values. An inertial navigation application is discussed in which performance depends on accurately estimating the process variances.
A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.

OBJECTIVE To describe a large, multicenter prospective cohort study of first-degree relatives (FDRs) of probands with rheumatoid arthritis (RA), and outline the use of such a study in investigating the natural history of RA development. METHODS A total of 1,058 FDRs, none of whom met the American College of Rheumatology criteria for RA, were enrolled in a prospective study investigating genetic and environmental influences on the development of RA-related autoimmunity. Demographic, epidemiologic, genetic, autoantibody, and physical examination data from the initial study enrollment visit were described for these FDRs, and the relationship was examined between genetic factors, autoantibodies, inflammation, and joint disease. RESULTS Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody. IgM-RF positivity is associated with > or =1 tender joint on examination (odds ratio [OR] 2.50, 95% confidence interval [95% CI] 1.27-4.89; P < 0.01) and elevated C-reactive protein (CRP) levels (OR 5.31, 95% CI 1.45-19.52; P = 0.01). CONCLUSION FDRs without RA demonstrate high prevalences of genetic risk factors and RA-related autoantibodies. Additionally, an RF association with tender joints and elevated CRP levels suggests that autoantibodies are a valid intermediate marker of RA-related autoimmunity in this cohort. This prospective FDR cohort will be a valuable resource for evaluating the relationship between genetic and epidemiologic factors and the development of RA-related autoimmunity.
The MOS capacitor amplifier

It is well known that low noise amplification can be performed by using a capacitor whose capacitance can be controlled. In this paper, it is shown that changing the inversion level of a MOS transistor allows voltage amplification. The theoretical characterization of this amplifier in terms of gain and harmonic distortion is made, and comparisons with HSPICE results are performed. Finally, some practical considerations to improve the performance of the circuit are presented.
Topological considerations in the design of the ARPA computer network

The ARPA Network will provide store-and-forward communication paths between a set of computer centers distributed across the continental United States. The message handling tasks at each node in the network are performed by a special purpose Interface Message Processor (IMP) located at each computer center. The centers will be interconnected through the IMPs by fully duplex telephone lines, of typically 50 kilobit/sec capacity.
Making sense of neuroimaging in psychiatry

Objective: Neuroimaging of psychiatric disorders has increased exponentially in the last decade; however, much of the uptake thus far has been in the realm of research. We anticipate that clinical use of neuroimaging modalities in psychiatry will increase dramatically in the near future and suggest that clinicians need to be aware of the potential applications.
Fidelity of DNA replication by extracts of normal and malignantly transformed human cells.

To test the hypothesis that a mutator phenotype may be associated with carcinogenesis (L. A. Loeb, Cancer Res., 51: 3074-3079, 1991), we have compared the fidelity of double-stranded DNA replication and the efficiency of mismatch repair in extracts from normal diploid and malignantly transformed human cells. Included was a diploid fibroblast strain and its transformed derivative, as well as a second diploid fibroblast strain and HeLa cells. The fidelity of DNA replication by cytoplasmic extracts in the presence of simian virus 40 large tumor antigen (SV40 T-antigen) was measured using a forward mutagenesis assay. The replicated DNA consisted of double-stranded M13 mp2 DNA containing the SV40 origin of replication and the lacZ alpha complementation gene as a target sequence for scoring mutations. T-antigen-dependent replication was detected in all cell extracts, with those from transformed cells having the greatest activity. No differences in replication fidelity were detected between normal and transformed cell extracts. Using a heteroduplex containing a G.G mispair, we also detected mismatch repair activity in the cell extracts, including efficient repair in extracts from malignantly transformed cells. While these data do not eliminate the possibility that a mutator phenotype may be associated with carcinogenesis, they do suggest that genetic instability associated with transformation does not involve reduced fidelity of replication of undamaged DNA or reduced mismatch repair efficiency.
The Effect of Preoperative Occlusion Therapy on Long-term Outcome after Surgery for Early-onset Exotropia

Purpose To investigate the effect of preoperative part-time occlusion therapy on long-term surgical success in early-onset exotropia. Methods The medical records of patients who underwent surgery for exotropia with onset before the first year of age and who were followed for ≥3 years were reviewed. Patients were divided into two groups according to the degree of compliance with part-time occlusion therapy: the good compliance group (>50% adherence rate) and the poor compliance group (≤50% adherence rate). Surgical success was defined as orthophoria to exodeviation less than 10 prism diopters both at distance and near. The level of postoperative stereopsis was compared between the two study groups among total enrolled patients and among those with constant exotropia. Results Of the 51 patients, 26 were assigned to the good compliance group and the remaining 25 patients to the poor compliance group. The surgical success rate was significantly higher in the good compliance group than in the poor compliance group (80.8% vs. 52.0%, p = 0.040). Among 24 constant exotropia patients (12 patients for each group), the success rate was insignificantly higher in the good compliance group than in the poor compliance group (75.0% vs. 58.3%, p = 0.448). The good compliance group had a better level of stereopsis than the poor compliance group (p = 0.045 for all 44 patients, p = 0.020 for 19 patients with constant exotropia). Conclusions Preoperative part-time occlusion therapy was useful for improving the surgical outcome of early-onset exotropia and postoperative stereopsis.
Norovirus-Specific Memory T Cell Responses in Adult Human Donors

Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney), and GI.3, and IFN-γ production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539-amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-γ in response to the peptides and five subjects produced IFN-γ in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A∗02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.
The vertebrate ortholog of Aristaless is regulated by Dlx genes in the developing forebrain

The Dlx transcription factors have a central role in controlling the development of γ‐aminobutyric acid (GABA)‐ergic neurons in the forebrain. However, little is known about how they control the properties of GABAergic neurons. One candidate is the Aristaless (Arx) homeobox gene, which lies genetically downstream of the fly Dlx gene (Distal‐less, Dll). The expression of Arx in the mouse forebrain includes Dlx‐expressing territories, such us the ventral thalamus, parts of the hypothalamus, and the ganglionic eminences and their derivatives in the subpallial telencephalon, and is expressed, as with the Dlx genes, in cortical GABAergic neurons. By using gain‐of‐function and loss‐of‐function assays in mouse and chicken embryos, we show that the Dlx genes have a conserved role in regulating the expression of Arx in the forebrain of vertebrates. Ectopic expression of Dlx genes with electroporation in brain slices from mouse embryos and in the neural tube of chick embryos shows that Dlx genes are sufficient to induce Arx ectopically. Moreover, we provide evidence that the Dlx genes exert a functionally relevant role in regulating Arx in vivo, as shown by the severe reduction in the expression of Arx in Dlx1/2 double‐knockout mice. Therefore, our results suggest evolutionarily conserved functions of Dlx genes in regulating Arx expression between Drosophila and vertebrates. J. Comp. Neurol. 483:292–303, 2005. © 2005 Wiley‐Liss, Inc.
Missing Women and the Price of Tea in China: The Effect of Relative Female Income on Sex Imbalance

Economists long have argued that the severe sex imbalance that exists in many developing countries is caused by underlying economic conditions. This paper uses plausibly exogenous increases in sex-specific agricultural income caused by post-Mao reforms in China to estimate the effects of total income and sex-specific income on sex ratios of surviving children. The results show that increasing income alone has no effect on sex ratios. In contrast, increasing female income, holding male income constant, increases survival rates for girls; increasing male income, holding female income constant, decreases survival rates for girls. Moreover, increasing the mother's income increases educational attainment for all children, while increasing the father's income decreases educational attainment for girls and has no effect on boys' educational attainment.
Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates

ABSTRACT Rational dosing of antibiotics in neonates should be based on pharmacokinetic (PK) parameters assessed in specific populations. PK studies of neonates are hampered by the limited total plasma volume, which restricts the sample volume and sampling frequency. Available drug assay methods require large sample volumes and are labor-intensive or time-consuming. The objective of this study was to develop a rapid ultra-performance liquid chromatographic method with tandem mass spectrometry detection for simultaneous quantification of amoxicillin, meropenem, cefazolin, cefotaxime, deacetylcefotaxime, ceftriaxone, and vancomycin in 50 μl of plasma. Cleanup consisted of protein precipitation with cold acetonitrile (1:4) and solvent evaporation before reversed-phase chromatographic separation and detection using electrospray ionization tandem mass spectrometry. Standard curves were prepared over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 100% ± 15% and 15%, respectively, with acceptable matrix effects. Coefficients of variation for matrix effects and recovery were <10% over six batches of plasma. Stability in plasma and aqueous stocks was generally sufficient, but stability of meropenem and ceftriaxone in extracts could limit autosampler capacity. The instrument run time was approximately 3.50 min per sample. Method applicability was demonstrated with plasma samples from an extracorporeal membrane oxygenation-treated neonate. Different β-lactam antibiotics can be added to this method with additional ion transitions. Using ultra-performance liquid chromatography mass spectrometry, this method allows simple and reliable quantification of multiple antibiotics in 50 μl of plasma for PK studies of neonates.
An upper bound for limited rate feedback MIMO capacity

We develop a technique to upper bound the point-to-point MIMO limited rate feedback (LRF) capacity under a wide class of vector quantization schemes. The upper bound turns out to be tight and can also be used to obtain an absolute upper bound by using a bounding distribution for Grassmannian beamforming. The bounding technique can be applied to other problems requiring the exact evaluation of the expected value of matrix determinant.
Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose

The transcription of the yeast FBP1 and PCK1 genes, which encode the gluconeogenic enzymes fructose‐1,6‐bisphosphatase and phosphoenolpyruvate car‐boxykinase, is repressed by glucose. Here, we show that this repression is both very strong and exceptionally sensitive to glucose, being triggered by glucose at concentrations less than 0.005% (0.27 mM). This repression remains operative in yeast mutants carrying any one of the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 mutant. In addition, 2‐deoxyglucose can trigger the repression, but 6‐deoxy‐glucose cannot, suggesting that internalization and phosphorylation of the glucose is essential for repression to occur. While gluconeogenic gene transcription is subject to the Mig1p‐dependent pathway of glucose repression, the exquisite response to glucose is maintained in hxk2 and mig1 mutants, suggesting that this pathway is not essential for the response. The response can also be triggered by the addition of exogenous cAMP, suggesting that the Ras/cAMP pathway can mediate repression of the FPB1 and PCK1 mRNAs. However, the response is not dependent upon this pathway because it remains intact in Ras, adenyl cyclase and protein kinase A mutants. The data show that yeast cells can detect very low glucose concentrations in the environment, and suggest that several distinct signalling pathways operate to repress FPB1 and PCK1 transcription in the presence of glucose.
The age dependence of halo clustering

We use a very large simulation of the concordance Λ cold dark matter cosmogony to study the clustering of dark matter haloes. For haloes less massive than about 1013 h−1 M⊙ the amplitude of the two-point correlation function on large scales depends strongly on halo formation time. Haloes that assembled at high redshift are substantially more clustered than those that assembled more recently. The effect is a smooth function of halo formation time and its amplitude increases with decreasing halo mass. At 1011 h−1 M⊙ the ‘oldest’ 10 per cent of haloes are more than five times more strongly correlated than the ‘youngest’ 10 per cent. This unexpected result is incompatible with the standard excursion set theory for structure growth, and it contradicts a fundamental assumption of the halo occupation distribution models often used to study galaxy clustering, namely that the galaxy content of a halo of given mass is statistically independent of its larger scale environment.
Algorithms for Large Scale Markov Blanket Discovery

This paper presents a number of new algorithms for discovering the Markov Blanket of a target variable T from training data. The Markov Blanket can be used for variable selection for classification, for causal discovery, and for Bayesian Network learning. We introduce a low-order polynomial algorithm and several variants that soundly induce the Markov Blanket under certain broad conditions in datasets with thousands of variables and compare them to other state-of-the-art local and global methods with excellent results.
Expression of a Mutant SEMA3A Protein with Diminished Signalling Capacity Does Not Alter ALS-Related Motor Decline, or Confer Changes in NMJ Plasticity after BotoxA-Induced Paralysis of Male Gastrocnemic Muscle

Terminal Schwann cells (TSCs) are specialized cells that envelop the motor nerve terminal, and play a role in the maintenance and regeneration of neuromuscular junctions (NMJs). The chemorepulsive protein semaphorin 3A (SEMA3A) is selectively up-regulated in TSCs on fast-fatigable muscle fibers following experimental denervation of the muscle (BotoxA-induced paralysis or crush injury to the sciatic nerve) or in the motor neuron disease amyotrophic lateral sclerosis (ALS). Re-expression of SEMA3A in this subset of TSCs is thought to play a role in the selective plasticity of nerve terminals as observed in ALS and following BotoxA-induced paralysis. Using a mouse model expressing a mutant SEMA3A with diminished signaling capacity, we studied the influence of SEMA3A signaling at the NMJ with two denervation paradigms; a motor neuron disease model (the G93A-hSOD1 ALS mouse line) and an injury model (BotoxA-induced paralysis). ALS mice that either expressed 1 or 2 mutant SEMA3A alleles demonstrated no difference in ALS-induced decline in motor behavior. We also investigated the effects of BotoxA-induced paralysis on the sprouting capacity of NMJs in the K108N-SEMA3A mutant mouse, and observed no change in the differential neuronal plasticity found at NMJs on fast-fatigable or slow muscle fibers due to the presence of the SEMA3A mutant protein. Our data may be explained by the residual repulsive activity of the mutant SEMA3A, or it may imply that SEMA3A alone is not a key component of the molecular signature affecting NMJ plasticity in ALS or BotoxA-induced paralysis. Interestingly, we did observe a sex difference in motor neuron sprouting behavior after BotoxA-induced paralysis in WT mice which we speculate may be an important factor in the sex dimorphic differences seen in ALS.