Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloroquine Blocks a Mutant Kir2.1 Channel Responsible for Short QT Syndrome and Normalizes Repolarization Properties in silico

Short QT Syndrome (SQTS) is a novel clinical entity characterized by markedly rapid cardiac repolarization and lethal arrhythmias. A mutation in the Kir2.1 inward rectifier K+ channel (D172N) causes one form of SQTS (SQT3). Pharmacologic block of Kir2.1 channels may hold promise as potential therapy for SQT3. We recently reported that the anti-malarial drug chloroquine blocks Kir2.1 channels by plugging the cytoplasmic pore domain. In this study, we tested whether chloroquine blocks D172N Kir2.1 channels in a heterologous expression system and if chloroquine normalizes repolarization properties using a mathematical model of a human ventricular myocyte. Chloroquine caused a dose- and voltage-dependent reduction in wild-type (WT), D172N and WT-D172N heteromeric Kir2.1 current. The potency and kinetics of chloroquine block of D172N and WT-D172N Kir2.1 current were similar to WT. In silico modeling of the heterozygous WT-D172N Kir2.1 condition predicted that 3 μM chloroquine normalized inward rectifier K+ current magnitude, action potential duration and effective refractory period. Our results suggest that therapeutic concentrations of chloroquine might lengthen cardiac repolarization in SQT3.
The accumulation channel driven bipolar transistor (ACBT)

A new three-terminal power switch called the Accumulation Channel driven Bipolar Transistor (ACBT) is proposed and experimentally demonstrated. In the on-state, the characteristics of the ACBT have been found to approach those of a P-I-N rectifier with a MOSFET in series for regulating its current, an equivalent circuit considered to be an ideal for MOS/Bipolar power devices. Unlike previous devices, the high off-state voltage is supported by the formation of a potential barrier to the flow of electrons from the N/sup +/ emitter into the N-drift region within a depletion region. The absence of the P-base region within the ACBT cells eliminates the parasitic four layer PNPN thyristor which had limited the performance of previous MOS/Bipolar transistor structures. Consequently, the ACBT structure has large maximum controllable and surge current densities in addition to low on-state voltage drop and high-voltage current saturation capability.
Linking data from the Multiethnic Cohort Study to Medicare data: linkage results and application to chronic disease research.

The Multiethnic Cohort Study of Diet and Cancer (MEC), a prospective study, was established between 1993 and 1996 to study risk factors for cancer by taking advantage of the ethnic and cultural diversity of Hawaii and California (1). The cohort included more than 215,000 men and women and was comprised of 5 racial/ethnic populations. At recruitment, the participants were aged 45–75 years. By 2013, more than 90% of surviving participants had become eligible for Medicare (aged ≥65 years). Given its ethnic diversity, the value of MEC for etiological research on cancer is widely recognized (2). To expand and identify health outcomes, we recently completed a study of linkage of MEC data to Centers for Medicare & Medicaid Services claim data. Medicare claims have been widely used as a population-based source of data for research (3–6). Here, we describe the success of linking MEC with Medicare data and use congestive heart failure (CHF) to illustrate its value for etiological research.
Multiple Bit Upset Tolerant Memory Using a Selective Cycle Avoidance Based SEC-DED-DAEC Code

Conventional error correcting code (ECC) schemes used in memories and caches cannot correct double bit errors caused by a single event upset (SEU). As memory density increases, multiple bit upsets in nearby cells become more frequent. A methodology is proposed here for deriving an error correcting code through heuristic search that can detect and correct the most likely double bit errors in a memory while minimizing the miscorrection probability of the unlikely double bit errors. A key feature of the proposed ECC is that it uses the same number of check bits as the conventional single error correcting/double error detecting (SEC-DED) codes commonly used, and has nearly identical syndrome generator/encoder area and timing overhead. Hence, there is very little additional cost to using the proposed ECC. The proposed ECC can be used instead of or in addition to bit interleaving to provide greater flexibility for optimizing a memory layout and/or provide better protection from multiple bit upsets. It is also useful for small memories, e.g., content addressable memory or register files, where interleaving is not possible
Imbalances between Matrix Metalloproteinases (MMPs) and Tissue Inhibitor of Metalloproteinases (TIMPs) in Maternal Serum during Preterm Labor

Background Matrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor. Methods A case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology. Results MMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor. Conclusions Serum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition.
The influence of complex distractors in the remote distractor effect paradigm

This thesis reports six experiments that examine the influence of complex distractors in the Remote Distractor Paradigm. Experiment 1 examined whether linguistic distractors modulated the RDE in any systematic way under bilateral target presentation. This was found not to be the case, but all types of linguistic distractors produced prolonged saccades for central versus peripheral distractor location. Non-linguistic distractors produced equivalent saccade onset latencies for central and peripheral presentation and these were significantly shorter than those produced for all types of linguistic distractors. This unexpected finding was investigated in Experiment 2, which showed that repeated presentation of a distractor resulted in shorter saccade latencies at central presentation, compared to those distractors that changed on every trial. This was termed the 'constancy' effect. Experiments 3 and 4 employed only repeated non-linguistic distractors under different target presentation conditions. Under bilateral target presentation peripheral distractors produced longer saccade latencies and greater RDE magnitudes compared to central distractors. Under unilateral target presentation RDE magnitudes for peripheral distractors were of a similar order to those produced by Walker et al, (1997). This replicated for linguistic and non-linguistic distractors, and for repeated and changing distractors in Experiment 5. Thus repeated distractors result in shorter saccade onset latencies compared to changing distractors at central presentation, and RDE magnitudes of a similar order to those obtained for central and peripheral distractors in the Walker et al., (1997) study only occur under unilateral target presentation, hi Experiment 6 a difference was obtained between two different types of linguistic distractors for saccade onset latencies and RDE magnitudes at an intermediate dish-actor location, and the 'constancy' effect was reproduced for same category repeated and changing distractors. Taken together the findings show that saccade onset latencies and RDE magnitudes can, under some circumstances be modulated by higher-level cognitive factors.
Regeneration of rabbit calvarial defects using biphasic calcium phosphate and a strontium hydroxyapatite-containing collagen membrane.

OBJECTIVES Biphasic calcium phosphate (BCP) composed of 10% hydroxyapatite (HA) and 90% beta-tricalcium phosphate has been developed. Recently, a strontium hydroxyapatite-containing collagen membrane (Sr) was shown to stimulate early bone formation in rat calvarial defects at 4 weeks postoperatively, as compared with a cross-linked collagen membrane, for guided bone regeneration (GBR). The objective of this study was to evaluate these novel biomaterials for GBR in relation to a non-cross-linked collagen membrane (BG) and deproteinized bovine bone mineral (BO). MATERIALS AND METHODS Twenty New Zealand rabbits were used in this study. Four defects of 7 mm in diameter were created in each rabbit, and three of the defects were treated with BG/BO, Sr/BO, and Sr/BCP. Ten rabbits were sacrificed at 12 and 24 weeks, respectively. Histological and histomorphometric analyses were conducted. Volumetric densities of mineralized new bone (MNB), bone marrow (BM), residual grafting material (RG), and non-mineralized connective tissue (NCT) were determined for each group. RESULTS After 12 weeks, Sr/BCP yielded more MNB than BG/BO and Sr/BO with no significant difference among the three groups. After 24 weeks, however, Sr/BCP demonstrated significantly more MNB than BG/BO and Sr/BO. Both after 12 and 24 weeks, Sr/BCP showed significantly less RG than BG/BO and Sr/BO. There was a significant increase in MNB in Sr/BCP from 12 to 24 weeks. CONCLUSIONS In defects grafted with BCP, more MNB was formed while less RG remained, than in defects grafted with BO. The Sr membrane was as effective as BG when comparing Sr/BO with BG/BO.
Regulation of NF‐κB by the CARD proteins

Summary: Scaffold proteins play pivotal roles in the regulation of signal transduction pathways by connecting upstream receptors to downstream effector molecules. During the last decade, many scaffold proteins that contain caspase‐recruitment domains (CARD) have been identified. Investigating the roles of CARD proteins has revealed that many of them play crucial roles in signaling cascades leading to activation of nuclear factor‐κB (NF‐κB). In this review, we discuss the contributions of CARD proteins to NF‐κB activation in various signaling cascades. In particular, we share some of our personal experiences during the initial investigation of the functions of the CARMA family of CARD proteins and then summarize the roles of these proteins in signaling pathways induced by antigen receptors, G protein‐coupled receptors, receptor tyrosine kinase, and C‐type lectin receptors in the context of recent progress in these field.
Designing for Humans in Autonomous Systems Military Applications

Abstract : The purpose of this report is to review U.S. Army Research Laboratory (ARL)-sponsored research on the human s role in future autonomous systems and to derive design guidelines to foster human/autonomy collaboration. The research was conducted as part of a larger Army program, Safe Operations for Unmanned systems for Reconnaissance in Complex Environments (SOURCE), that focused on developing safe autonomy for urban applications. The human-autonomy design research encompasses agent reliability, span of control, safety issues, individual differences, training, function allocation, and results from field experiments evaluating advanced interface solutions. The main sections of this report cover (1) autonomy and intelligent agents, (2) RoboLeader, (3) safety for autonomous systems, (4) naturalistic interfaces, and (5) situation understanding using unmanned vehicle imagery. After each section, implications of the results are summarized to develop design guidelines for incorporating humans into autonomous military systems.
Polymorphism in the Vesicular Monoamine Transporter 2 Gene Decreases the Risk of Parkinson's Disease in Han Chinese Men

Background. Polymorphisms rs363371 and rs363324 in the vesicular monoamine transporter 2 (VMAT2) gene have been associated with risk of PD in an Italian population, and our aim is to investigate the association between the two single-nucleotide polymorphisms and PD in Han Chinese. Methods. 561 Han Chinese PD patients and 491 healthy age- and gender-matched controls were genotyped using Ligase detection reaction (LDR) method. Result. Both of patient and control groups showed similar genotype frequencies between patients and controls at both rs363371 and rs363324, as well as similar minor A allele frequencies at rs363371 (P = 0.452) and rs363324 (P = 0.413). None of the observed haplotypes showed a significant association with PD. Subgroup analysis by gender and age at onset revealed a significant association between the A allele of rs363371 and PD in Han Chinese males relative to healthy controls (OR 0.799, 95% CI 0.665 to 0.959, P = 0.016), and this association remained significant after adjusting for age (OR 0.785, 95% CI 0.652 to 0.945, P = 0.011). Conclusion. These results suggest that polymorphism of VMAT2 locus is associated with risk of PD in Han Chinese overall but that the A allele at rs363371 may protect against PD in Han Chinese males.
Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

Topical treatment of mouse and human skin with small-molecule inhibitors of the JAK-STAT pathway results in hair growth. Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.
Features Extraction of ECG signal for Detection of Cardiac Arrhythmias

Electrocardiogram (ECG) is the record of the heart muscle electric impulses. Received and processed ECG signal could be analyzed, and results could be used for detection and diagnostics of cardiovascular diseases (CVD). One of the important cardiovascular diseases is arrhythmia.This paper deals with improved ECG signal features Extraction using Wavelet Transform Techniques which may be employed for Arrhythmia detection. This improvement is
Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.

As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.
Flux-averaging Analysis of Type Ia Supernova Data

Because of flux conservation, flux-averaging justifies the use of the distance-redshift relation for a smooth universe in the analysis of Type Ia supernova (SN Ia) data. We have combined the SN Ia data from the High-z SN Search and the Supernova Cosmology Project and binned the combined data by flux-averaging in redshift intervals of Δz = 0.05 and Δz = 0.1. We find that the unbinned data yield a Hubble constant of H0 = 65 ± 1 km s-1 Mpc-1 (statistical error only), a matter density fraction of Ωm = 0.7 ± 0.4, and a vacuum energy density fraction of ΩΛ = 1.2 ± 0.5. The binned data for Δz = 0.1 yield H0 = 65 ± 1 km s-1 Mpc-1 (statistical error only), Ωm = 0.3 ± 0.6, and ΩΛ = 0.7 ± 0.7. Our results are not sensitive to the redshift bin size. Flux-averaging leads to less biased estimates of the cosmological parameters by reducing the bias due to systematic effects such as weak lensing. Comparison of the data of 18 SNe Ia published by both groups yields a mean SN Ia peak absolute magnitude of MB = -19.33 ± 0.25. The internal dispersion of each data set is about 0.20 mag in the calibrated SN Ia peak absolute magnitudes. The difference in analysis techniques introduces an additional uncertainty of about 0.15 mag. If the SNe Ia peak absolute luminosity changes with redshift due to evolution, our ability to measure the cosmological parameters from SN Ia data will be significantly diminished. Assuming power-law evolution in the peak absolute luminosity, (1 + z)β, we find a strong degeneracy between the evolution power-law index β and the matter density fraction Ωm. For Ωm = 0.3, we find that the unbinned data yield H0 = 65 ± 1 km s-1 Mpc-1 (statistical error only), ΩΛ = 1.4 ± 1.1, and β = 0.5 ± 1.6, and the binned data (with Δz = 0.1) yield H0 = 65 ± 1 km s-1 Mpc-1 (statistical error only), ΩΛ = 0.6 ± 1.4, and β = 0.0 ± 1.0.
Reconfigurable liquid crystal reflectarray with extended tunable phase range

A coupled microstrip structure is investigated consisting of three fingerlike patches which are designed for liquid crystal technology. A unit cell based on the coupled structure is realized and characterized with a waveguide simulator. The proposed structure has a measured tunable phase range of 582°. It is used as an antenna element to design a reconfigurable reflectarray. The realized antenna is composed of 16×16 elements, and a slotted substrate integrated waveguide is used to illuminate it. Antenna patterns for desired main beam directions are synthesized at W-band with a developed Particle Swarm Optimization algorithm. Beam steering capability of the reflectarray is presented by steering the main beam to various angles applying the bias voltages obtained from the optimization algorithm.
Approaching the MIMO capacity with Superposition Coded Modulation

We present an optimization method for Superposition Coded Modulation (SCM) systems to approach the capacity limits of ergodic MIMO channels. The proposed method, based on EXtrinsic Information Transfer (EXIT) analysis, aims to optimize the constituent channel codes and their corresponding power coefficients in a jointly manner. Simulation results show that optimized SCM systems with throughputs of up to 48 bits per channel use perform at less than 2 dB from the MIMO capacity limits with affordable complexity.
Risk and protective factors for drug use among rural American youth.

Rural and urban America differ in many ways, but drug use is a common phenomenon throughout the country. There may be differences in the extent, social contexts, and consequences of use, but, in general, drugs are as much a problem in rural America as they are in cities. Commonality between urban and rural areas also appears when the personal and social risk factors for drug use are examined: Many of the same characteristics relate to drug use among both urban or rural adolescents.
What regularized auto-encoders learn from the data-generating distribution

What do auto-encoders learn about the underlying data generating distribution? Recent work suggests that some auto-encoder variants do a good job of capturing the local manifold structure of data. This paper clarifies some of these previous observations by showing that minimizing a particular form of regularized reconstruction error yields a reconstruction function that locally characterizes the shape of the data generating density. We show that the auto-encoder captures the score (derivative of the log-density with respect to the input). It contradicts previous interpretations of reconstruction error as an energy function. Unlike previous results, the theorems provided here are completely generic and do not depend on the parametrization of the auto-encoder: they show what the auto-encoder would tend to if given enough capacity and examples. These results are for a contractive training criterion we show to be similar to the denoising auto-encoder training criterion with small corruption noise, but with contraction applied on the whole reconstruction function rather than just encoder. Similarly to score matching, one can consider the proposed training criterion as a convenient alternative to maximum likelihood because it does not involve a partition function. Finally, we show how an approximate Metropolis-Hastings MCMC can be setup to recover samples from the estimated distribution, and this is confirmed in sampling experiments.