Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans

Paramyotonia congenita (PC) is a dominantly inherited skeletal muscle disorder caused by missense mutations in the SCN4A gene encoding the pore‐forming α subunit (hSkM1) of the skeletal muscle Na+ channel. Muscle stiffness is the predominant clinical symptom. It is usually induced by exposure to cold and is aggravated by exercise. The most prevalent PC mutations occur at T1313 on DIII–DIV linker, and at R1448 on DIV–S4 of the α subunit. Only one substitution has been described at T1313 (T1313M), whereas four distinct amino‐acid substitutions were found at R1448 (R1448C/H/P/S). We report herein a novel mutation at position 1313 (T1313A) associated with a typical phenotype of PC. We stably expressed T1313A or wild‐type (hSkM1) channels in HEK293 cells, and performed a detailed study on mutant channel gating defects using the whole‐cell configuration of the patch‐clamp technique. T1313A mutation impaired Na+ channel fast inactivation: it slowed and reduced the voltage sensitivity of the kinetics, accelerated the recovery, and decreased the voltage‐dependence of the steady state. Slow inactivation was slightly enhanced by the T1313A mutation: the voltage dependence was shifted toward hyperpolarization and its steepness was reduced compared to wild‐type. Deactivation from the open state assessed by the tail current decay was only slowed at positive potentials. This may be an indirect consequence of disrupted fast inactivation. Deactivation from the inactivation state was hastened. The T1313A mutation did not modify the temperature sensitivity of the Na+ channel per se. However, gating kinetics of the mutant channels were further slowed with cooling, and reached levels that may represent the threshold for myotonia. In conclusion, our results confirm the role of T1313 residue in Na+ channel fast inactivation, and unveil subtle changes in other gating processes that may influence the clinical phenotype.
Non-magnetic doping induced a high spin-filter efficiency and large spin Seebeck effect in zigzag graphene nanoribbons

Based on nonequilibrium Green's functions (NGF) and density-functional theory (DFT), we investigate the magnetotransport properties and magnetothermoelectric effects in zigzag graphene nanoribbons (ZGNRs) with non-magnetic doping on the double ribbon edges. One of the carbon atoms without hydrogen saturation in each ribbon edge is replaced by one boron (B) or one nitrogen (N) atom. Compared with boron–boron (BB) and nitrogen–nitrogen (NN) double-edge doping, the boron–nitrogen (BN) double-edge doping induces a perfect spin-filter effect with 100% negative spin polarization at the Fermi level. Moreover, we find that the thermoelectric effect can be enhanced by the double-edge doping. Interestingly, the spin Seebeck effect in NN- and BN-doped ZGNRs becomes comparable with the charge Seebeck effect and even larger than it. These results originate from the spin-dependent transmission node near the Fermi level induced by the non-magnetic doping. These findings strongly suggest that the double-edge-doped ZGNRs are promising materials for spintronics and thermo-spintronics.
Computational Intelligence and Game Design for Effective At-Home Stroke Rehabilitation.

OBJECTIVE The aim of this article is to describe a game engine that has all the characteristics needed to support rehabilitation at home. The low-cost tracking devices recently introduced in the entertainment market allow measuring reliably at home, in real time, players' motion with a hands-free approach. Such systems have also become a source of inspiration for researchers working in rehabilitation. Computer games appear suited to guide rehabilitation because of their ability to engage the users. However, commercial videogames and game engines lack the peculiar functionalities required in rehabilitation: Games should be adapted to each patient's functional status, and monitoring the patient's motion is mandatory to avoid maladaptation. Feedback on performance and progression of the exercises should be provided. Lastly, several tracking devices should be considered, according to the patient's pathology and rehabilitation aims. SUBJECTS AND METHODS We have analyzed the needs of the clinicians and of the patients associated in performing rehabilitation at home, identifying the characteristics that the game engine should have. RESULTS The result of this analysis has led us to develop the Intelligent Game Engine for Rehabilitation (IGER) system, which combines the principles upon which commercial games are designed with the needs of rehabilitation. IGER is heavily based on computational intelligence: Adaptation of the difficulty level of the exercise is carried out through a Bayesian framework from the observation of the patient's success rate. Monitoring is implemented in fuzzy systems and based on rules defined for the exercises by clinicians. Several devices can be attached to IGER through an input abstraction layer, like the Nintendo® (Kyoto, Japan) Wii™ Balance Board™, the Microsoft® (Redmond, WA) Kinect, the Falcon from Novint Technologies (Albuquerque, NM), or the Tyromotion (Graz, Austria) Timo® plate balance board. IGER is complemented with videogames embedded in a specific taxonomy developed to support rehabilitation progression through time. CONCLUSIONS A few games aimed at postural rehabilitation have been designed and developed to test the functionalities of the IGER system. The preliminary results of tests on normal elderly people and patients with the supervision of clinicians have shown that the IGER system indeed does feature the characteristics required to support rehabilitation at home and that it is ready for clinical pilot testing at patients' homes.
Study protocol for a randomised controlled trial to test the effectiveness of providing information on childbirth and postnatal period to partners of pregnant women

Introduction The objective of this study is to investigate the effect of the distribution of a booklet providing information to fathers during their partners' pregnancies on fathers' and mothers' postpartum mental health and quality of life (QOL), as well as on fathers' childcare participation and living situations. Methods and analysis This randomised controlled trial will comprise 554 couples consisting of pregnant women due to give birth at an obstetric institution in Aichi Prefecture, Japan and their partners. Participants will be recruited during prenatal check-ups in the third trimester, and those who provide written consent will be allocated randomly to an intervention and a control group. The pregnant women's partners allocated to the intervention group will be given a booklet written for men containing information on childbirth and postnatal period. Its content will include matters such as what preparations the partner should make before birth and tips for housework and childcare as well as how to prevent unintentional injury to the baby. The control group will not receive any intervention. A baseline survey in the third trimester and follow-up surveys at 1 and 3 months post partum will be carried out using self-administered questionnaires. The primary outcome is the proportion of new mothers' partners at risk for paternal depression (Edinburgh Postnatal Depression Scale score ≥8). Secondary outcomes include the risk of postnatal depression in new mothers, QOL of new mothers and their partners, partners' knowledge of and engagement in housework and childcare, marital relations and parenting stress on the part of new mothers. Ethics and dissemination This study has been approved by the Ethical Committee at the National Center for Child Health and Development, Tokyo, Japan. The results of the study will be widely disseminated as peer-reviewed papers and at international conferences, with the aim of improving public health services in Japan. Trial registration number UMIN000021475; Pre-results.
The angular momentum distribution within haloes in different dark matter models

We study the angular momentum profile of dark matter haloes for a statistical sample drawn from a set of high-resolution cosmological simulations of 256(3) particles. Two typical cold dark matter (CDM) models have been analysed, and the haloes are selected to have at least 3 x 10(4) particles in order to measure the angular momentumprofile reliably. In contrast with the recent claims of Bullock et al., we find that the degree of misalignment of angular momentum within a halo is very high. Approximately 50 per cent of haloes have more than 10 per cent of the halo mass in the mass of negative angular momentum j. After the mass of negative j is excluded, the cumulative mass function M(
Design of waveguiding photonic bandgap devices by using the resonant PBG device Bloch-Floquet theorem

The design of some 1D waveguiding photonic bandgap (PBG) devices has been carried out by a model based on the Bloch-Floquet theorem. A low loss, very narrow passband GaAs PBG filter for the operating wavelength of 1.55 /spl mu/m, having an air bridge configuration, was designed and simulated. Moreover, a resonant Si on glass PBG device has been designed to obtain the resonance condition at 1.55 /spl mu/m.
Genetics and Genomics of Core Short Tandem Repeat Loci Used in Human Identity Testing

ABSTRACT: Over the past decade, the human identity testing community has settled on a set of core short tandem repeat (STR) loci that are widely used for DNA typing applications. A variety of commercial kits enable robust amplification of these core STR loci. A brief history is presented regarding the selection of core autosomal and Y‐chromosomal STR markers. The physical location of each STR locus in the human genome is delineated and allele ranges and variants observed in human populations are summarized as are mutation rates observed from parentage testing. Internet resources for additional information on core STR loci are reviewed. Additional topics are also discussed, including potential linkage of STR loci to genetic disease‐causing genes, probabilistic predictions of sample ethnicity, and desirable characteristics for additional STR loci that may be added in the future to the current core loci. These core STR loci, which form the basis for DNA databases worldwide, will continue to play an important role in forensic science for many years to come.
Hybrid plasmonic magnetic nanoparticles as molecular specific agents for MRI/optical imaging and photothermal therapy of cancer cells

Nanoparticles which consist of a plasmonic layer and an iron oxide moiety could provide a promising platform for development of multimodal imaging and therapy approaches in future medicine. However, the feasibility of this platform has yet to be fully explored. In this study we demonstrated the use of gold-coated iron oxide hybrid nanoparticles for combined molecular specific MRI/optical imaging and photothermal therapy of cancer cells. The gold layer exhibits a surface plasmon resonance that provides optical contrast due to light scattering in the visible region and also presents a convenient surface for conjugating targeting moieties, while the iron oxide cores give strong T2 (spin–spin relaxation time) contrast. The strong optical absorption of the plasmonic gold layer also makes these nanoparticles a promising agent for photothermal therapy. We synthesized hybrid nanoparticles which specifically target epidermal growth factor receptor (EGFR), a common biomarker for many epithelial cancers. We demonstrated molecular specific MRI and optical imaging in MDA-MB-468 breast cancer cells. Furthermore, we showed that receptor-mediated aggregation of anti-EGFR hybrid nanoparticles allows selective destruction of highly proliferative cancer cells using a nanosecond pulsed laser at 700 nm wavelength, a significant shift from the peak absorbance of isolated hybrid nanoparticles at 532 nm.
They talk the talk: surveying attitudes and judging behavior about living anonymous kidney donation1

Background. Over the past 30 years, numerous studies have reported that some individuals are willing to donate a kidney anonymously to a stranger; however, intentions are poor predictors of behavior. We surveyed individuals interested in being living anonymous donors (LADs), exposed them to an interview paralleling live-donor assessment, and measured their LAD commitment. Personality and donation decision factors were examined to corroborate cases of attitudinal and behavioral congruency. Methods. A telephone survey of 1,002 randomly selected adults living in Vancouver, British Columbia, asked respondents how willing they were to donate a kidney, while alive, to particular individuals including a stranger. A subsample participated in a follow-up, which involved completing a mailed questionnaire and taking part in an in-depth interview. Expert raters judged respondents’ commitment to being a LAD on the basis of the interviews. Results. Two hundred fifty-eight (26%) of those surveyed stated they would probably or definitely be willing to donate a kidney to a stranger. Fifty-two completed the follow-up. Sixteen of the 52 (31%) were judged to be “committed LADs. ” No demographic differences were found between the committed LADs and the 33 remaining “noncommitted participants. ” The committed LADs differed significantly from the noncommitted participants on personality measures and donation decision factors. These differences underscore the latter group’s anonymous donation commitment. Conclusions. This study brings into focus the potential for a significant number of individuals coming forward as potential LAD candidates if they are informed about the need and given unbiased information about the procedure. We believe there is ethical latitude in allowing the promotion of LAD donation by interested third parties such as patient advocacy groups and professional bodies. We advocate public awareness of LAD programs as a first step followed thereafter by more provocative measures to engage the public in this endeavor.
The 54-kD protein of signal recognition particle contains a methionine- rich RNA binding domain

Signal recognition particle (SRP) plays the key role in targeting secretory proteins to the membrane of the endoplasmic reticulum (Walter, P., and V. R. Lingappa. 1986. Annu. Rev. Cell Biol. 2:499- 516). It consists of SRP7S RNA and six proteins. The 54-kD protein of SRP (SRP54) recognizes the signal sequence of nascent polypeptides. The 19-kD protein of SRP (SRP19) binds to SRP7S RNA directly and is required for the binding of SRP54 to the particle. We used deletion mutants of SRP19 and SRP54 and an in vitro assembly assay in the presence of SRP7S RNA to define the regions in both proteins which are required to form a ribonucleoprotein particle. Deletion of the 21 COOH- terminal amino acids of SRP19 does not interfere with its binding to SRP7S RNA. Further deletions abolish SRP19 binding to SRP7S RNA. The COOH-terminal 207 amino acids of SRP54 (M domain) were found to be necessary and sufficient for binding to the SRP19/7S RNA complex in vitro. Limited protease digestion of purified SRP confirmed our results for SRP54 from the in vitro binding assay. The SRP54M domain could also bind to Escherichia coli 4.5S RNA that is homologous to part of SRP7S RNA. We suggest that the methionine-rich COOH terminus of SRP54 is a RNA binding domain and that SRP19 serves to establish a binding site for SRP54 on the SRP7S RNA.
Heat shock protein 90 targets a chaperoned peptide to the static early endosome for efficient cross-presentation by human dendritic cells

The presentation of an exogenous antigen in a major histocompatibility complex class‐I‐ restricted fashion to CD8+ T cells is called cross‐presentation. Heat shock proteins (HSPs) such as Hsp70, gp96, and Hsp90 have been shown to elicit efficient CTL responses by cross‐presentation through an as‐yet entirely unknown mechanism. Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We have shown that a tumor antigen peptide complexed with Hsp90 could be cross‐presented by dendritic cells (DCs) through an endosomal pathway in a murine system. However, it has not been determined whether human DCs also cross‐present an Hsp90–peptide complex and induce peptide‐specific CTLs. In this study, we found that an Hsp90–cancer antigen peptide complex was efficiently cross‐presented by human monocyte‐derived DCs and induced peptide‐specific CTLs. Furthermore, we observed that the internalized Hsp90–peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90‐chaperoned peptide was processed and bound to MHC class I molecules through an endosome‐recycling pathway. Our data indicate that targeting of the antigen to a “static” early endosome by Hsp90 is essential for efficient cross‐presentation.
Directional hybrid channel model for ultra-wideband MIMO systems

In this paper a hybrid ray tracing/statistical channel model for the ultra-wideband (UWB) frequency range is proposed. The conventional ray tracing model is complemented with randomly distributed point scatterers placed on the surface of objects in the scenario model. The wave propagation in such scenario is calculated in a deterministic way and preserves the directional properties of the channel. Thus, it is suitable for simulation of MIMO channels. The scatterers parameters are derived from the measurements. The proposed model reflects the channel impulse response and the channel parameter better than the conventional ray tracing simulation.
Cerebral cortical lesions in multiple sclerosis detected by MR imaging at 8 Tesla.

BACKGROUND AND PURPOSE Conventional imaging of ex-vivo brain at 1.5T in multiple sclerosis (MS) detects only a small fraction of the gray matter cerebral cortical lesions that can be detected by pathology. Our purpose was to examine if imaging at 8T can detect plaques in cortical gray matter (CGM) not evident at 1.5T. METHODS An ex-vivo brain obtained at autopsy from a patient with MS was formalin fixed and 1 cm coronal slices were examined using MR imaging at 8T. RESULTS Numerous cerebral cortical lesions not evident at 1.5T were seen at 8T. Lesions were easily identified using gradient-echo and spin-echo (SE) as well as diffusion images. MR imaging at 8T identified many of the types of plaques previously evident only by pathology. The magnitude of the cortical involvement in this 1 patient was severe. Lesions in the gray matter readily visible by high-field MR imaging were sometimes barely visible by pathology. MR imaging at 8T often facilitated the detection of such plaques by pathology. CONCLUSION This study establishes the utility of high-field imaging at 8T in the delineation of plaques in the cerebral CGM in MS.
Anytime Coalition Structure Generation with Worst Case Guarantees

Coalition formation is a key topic in multiagent systems. One would prefer a coalition structure that maximizes the sum of the values of the coalitions, but often the number of coalition structures is too large to allow exhaustive search for the optimal one. But then, can the coalition structure found via a partial search be guaranteed to be within a bound from optimum? We show that none of the previous coalition structure generation algorithms can establish any bound because they search fewer nodes than a threshold that we show necessary for establishing a bound. We present an algorithm that establishes a tight bound within this minimal amount of search, and show that any other algorithm would have to search strictly more. The fraction of nodes needed to be searched approaches zero as the number of agents grows.If additional time remains, our anytime algorithm searches further, and establishes a progressively lower tight bound. Surprisingly, just searching one more node drops the bound in half. As desired, our algorithm lowers the bound rapidly early on, and exhibits diminishing returns to computation. It also drastically outperforms its obvious contenders. Finally, we show how to distribute the desired search across self-interested manipulative agents.
Comparative Anti-Tumor Activity Study of Tartary Buckwheat Flavonoids and Amphibian Peptides

In China, many kinds of natural products extracted from plant and animal were used to treat cancer. Flavonoids extracted from tartary buckwheat and skin peptide purified from rufous-spotted torrent frog had respectively been proved to have anti-tumor activity. In present study, both tartary buckwheat flavonoids and amphibian frog peptides were applied for cell proliferation inhibitory activity against human gastric cancer MGC 80-3 cells using MTT assay. According to the data, the buckwheat flavonoids exhibited much stronger anti-tumor activity than amphibian peptides, and the complex mixture of this two kinds of bioactive compounds still possess anti-tumor activity.
Prevalence of Human Papillomavirus Antibodies in Males and Females in England

Background: Most studies of human papillomavirus (HPV) epidemiology have employed DNA testing, which measures current infections. Serum antibodies offer a longer-term marker of infection in individuals who seroconvert and can therefore provide additional information about the exposure of populations to HPV. Methods: Sera from a population-based sample of males and females aged 10 to 49 years, in England, were tested for type-specific HPV antibodies using a multiplexed competitive Luminex assay and previously defined cutoffs of 20, 16, 20, and 24 mMU mL−1 for HPV 6, 11, 16, and 18, respectively. Seropositivity and geometric mean titers of seropositives were analyzed by HPV type, gender, and age. Catalytic models were developed to explore potential effects of antibody waning over time and changing risk of infection by age-cohort. Results: Seroprevalence for HPV 6, 11, 16, and 18 was 16.4%, 5.7%, 14.7%, and 6.3%, respectively, among females and 7.6%, 2.2%, 5.0%, and 2.0%, respectively, among males. Seroprevalence in females was significantly higher than males (P < 0.001 for all types) and showed a decline in older ages that was not seen in males. There was no evidence of declining antibody titers with increasing age. Model results suggest that cohort effects mediated through changes in sexual behavior better explain the observed trend in seroprevalence than waning antibodies over time. Conclusions: Preimmunization HPV seroprevalence in England shows similar trends to reports from other developed countries. We find the lower seroprevalence in older females probably reflects changes in sexual behavior over the last few decades. This study provides baseline data to monitor the impact of the immunization programme.
Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network

microRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. It is anticipated that, in combination with transcription factors (TFs), they span a regulatory network that controls thousands of mammalian genes. Here we set out to uncover local and global architectural features of the mammalian miR regulatory network. Using evolutionarily conserved potential binding sites of miRs in human targets, and conserved binding sites of TFs in promoters, we uncovered two regulation networks. The first depicts combinatorial interactions between pairs of miRs with many shared targets. The network reveals several levels of hierarchy, whereby a few miRs interact with many other lowly connected miR partners. We revealed hundreds of “target hubs” genes, each potentially subject to massive regulation by dozens of miRs. Interestingly, many of these target hub genes are transcription regulators and they are often related to various developmental processes. The second network consists of miR–TF pairs that coregulate large sets of common targets. We discovered that the network consists of several recurring motifs. Most notably, in a significant fraction of the miR–TF coregulators the TF appears to regulate the miR, or to be regulated by the miR, forming a diversity of feed-forward loops. Together these findings provide new insights on the architecture of the combined transcriptional–post transcriptional regulatory network.