Miracle-dz/UniFAR-FTUs huggingface dataset:
In utero alcohol exposure and prediction of alcohol disorders in early adulthood: a birth cohort study.

CONTEXT Little is known about the contribution of fetal alcohol exposure to the development of alcohol disorders in early adulthood. OBJECTIVE To examine the independent effect of maternal alcohol use during early vs late periods in pregnancy on the time of onset of alcohol disorders in offspring. DESIGN Follow-up study of the Mater-University of Queensland Study of Pregnancy and Its Outcomes (MUSP), a population-based birth cohort study commenced in Brisbane, Australia, in 1981 and designed to examine the association of maternal alcohol exposure with the onset of alcohol disorders. Mothers and children were followed up at birth, 6 months, and 5, 14, and 21 years after the initial interview. Maternal alcohol use was assessed before pregnancy, in early and late pregnancy, and at the 5- and 14-year follow-up visits. Alcohol disorders in early adulthood were assessed at age 21 years using the lifetime version of the Composite International Diagnostic Interview-computerized version. SETTING Population-based birth cohort study. PARTICIPANTS A subsample of 2138 participants for whom complete data were available at the 21-year follow-up. MAIN OUTCOME MEASURE Onset of alcohol disorder from adolescence to 21 years of age. RESULTS In utero alcohol exposure of 3 or more glasses was associated with alcohol disorders. The fully adjusted odds ratios (95% confidence intervals) of developing early-onset alcohol disorders at age 21 years were 2.95 (1.62-5.36) for those exposed to maternal drinking in early pregnancy and 1.35 (0.69-2.63) for those exposed in late pregnancy. There was also a strong association between alcohol exposure in early pregnancy and late-onset alcohol disorders (odds ratio, 3.29 [95% confidence interval, 1.74-6.24]). CONCLUSIONS Our results provide support for a biological origin of adult alcohol disorders and suggest that the association is not explained solely by maternal drinking or smoking during childhood and adolescence or other intervening factors. Further research is needed to understand the mechanisms underlying the association.
Identification of caspase‐10 in human neutrophils and its role in spontaneous apoptosis

In the present study, we investigated the molecular mechanisms of spontaneous and tumor necrosis factor α (TNF‐α)‐mediated apoptosis of human polymorphonuclear neutrophils (PMN). Whereas TNF‐α‐mediated apoptosis was almost absent in the presence of the caspase‐8 inhibitor Z‐Ac‐Ala‐Glu‐Val‐Asp‐7‐fluoromethyl ketone (Z‐AEVD‐FMK), the inhibitor had no effect on spontaneous apoptosis, sggesting that spontaneous apoptosis was independent of caspase‐8. Subsequently, we identified different isoforms of caspase‐10 in human PMN and found high expression of caspase‐10/b and/or ‐10/d and low expression of caspase‐10/a and ‐10/c at the mRNA level. At the protein level, freshly isolated PMN showed high expression of caspase‐10/b and ‐10/d as well as moderate expression of caspase‐10/a and ‐10/c. Upon spontaneous apoptosis, caspase‐10/b was down‐regulated, which was accompanied by the appearance of a specific 47‐kDa caspase‐10/b cleavage product and an increased caspase‐10 activity. In contrast, no down‐regulation of caspase‐10/a, ‐10/c, or ‐10/d was observed, suggesting that spontaneous apoptosis was associated with a differential activation of caspase‐10/b. This was confirmed by the finding that spontaneous apoptosis was inhibited in the presence of Z‐Ile‐Glu‐Thr‐Asp (Z‐IETD)‐FMK, which blocks caspase‐10. However, no down‐regulation of caspase‐10 isoforms was observed in the presence of TNF‐α, suggesting that caspase‐10 was not involved in TNF‐α‐induced apoptosis. Taken together, our study demonstrates that spontaneous and TNF‐α‐mediated apoptosis of PMN have different molecular requirements. Whereas TNF‐α‐mediated apoptosis depends on the activation of caspase‐8, spontaneous apoptosis requires the activation of caspase‐10/b. This finding may reveal that PMN apoptosis in different (patho‐) physiological settings results from distinct molecular mechanisms.
Impact of Transcranial Magnetic Stimulation on Functional Movement Disorders: Cortical Modulation or a Behavioral Effect?

Introduction Recent studies suggest that repeated transcranial magnetic stimulation (TMS) improves functional movement disorders (FMDs), but the underlying mechanisms are unclear. The objective was to determine whether the beneficial action of TMS in patients with FMDs is due to cortical neuromodulation or rather to a cognitive-behavioral effect. Method Consecutive patients with FMDs underwent repeated low-frequency (0.25 Hz) magnetic stimulation over the cortex contralateral to the symptoms or over the spinal roots [root magnetic stimulation (RMS)] homolateral to the symptoms. The patients were randomized into two groups: group 1 received RMS on day 1 and TMS on day 2, while group 2 received the same treatments in reverse order. We blindly assessed the severity of movement disorders before and after each stimulation session. Results We studied 33 patients with FMDs (dystonia, tremor, myoclonus, Parkinsonism, or stereotypies). The median symptom duration was 2.9 years. The magnetic stimulation sessions led to a significant improvement (>50%) in 22 patients (66%). We found no difference between TMS and RMS. Conclusion We suggest that the therapeutic benefit of TMS in patients with FMDs is due more to a cognitive-behavioral effect than to cortical neuromodulation.
Does tougher enforcement make drugs more expensive?

AIMS To review empirical research that seeks to relate marginal increases in enforcement against the supply of illicit drugs to changes in drug prices at the level of the drug supply system being targeted. METHOD Review of empirical studies. FINDINGS Although the fact of prohibition itself raises prices far above those likely to pertain in legal markets, there is little evidence that raising the risk of arrest, incarceration or seizure at different levels of the distribution system will raise prices at the targeted level, let alone retail prices. The number of studies available is small; they use a great variety of outcome and input measures and they all face substantial conceptual and empirical problems. CONCLUSION Given the high human and economic costs of stringent enforcement measures, particularly incarceration, the lack of evidence that tougher enforcement raises prices call into question the value, at the margin, of stringent supply-side enforcement policies in high-enforcement nations.
Perceived Spatial Frequency Shift after Adaptation to Compound Gratings of Two Sinusoidals in Phase or 180゜out of Phase

gratings composed of the fundamental and the third harmonic which were in phase or 180°out of phase. Six well trained subjects served the experiment. Perceptual frequency shift was found to occur as predicted but no phase effect was found. This was confirmed by multiple correlation solutions where the compound effects, the target variable, were explained by independent contributions of the effect of componental sinusoidals. It was concluded that the change in the sensitivity of some spatial-frequency-tuned mechanisms due to an adaptation to stimulus frequency caused the perceived spatial frequency shift and the hypothetical mechanisms are mutually independent with respect to frequency.
A Well-Conditioned and Sparse Estimation of Covariance and Inverse Covariance Matrices Using a Joint Penalty

We develop a method for estimating well-conditioned and sparse covariance and inverse covariance matrices from a sample of vectors drawn from a sub-gaussian distribution in high dimensional setting. The proposed estimators are obtained by minimizing the quadratic loss function and joint penalty of `1 norm and variance of its eigenvalues. In contrast to some of the existing methods of covariance and inverse covariance matrix estimation, where often the interest is to estimate a sparse matrix, the proposed method is flexible in estimating both a sparse and well-conditioned covariance matrix simultaneously. The proposed estimators are optimal in the sense that they achieve the minimax rate of estimation in operator norm for the underlying class of covariance and inverse covariance matrices. We give a very fast algorithm for computation of these covariance and inverse covariance matrices which is easily scalable to large scale data analysis problems. The simulation study for varying sample sizes and variables shows that the proposed estimators performs better than several other estimators for various choices of structured covariance and inverse covariance matrices. We also use our proposed estimator for tumor tissues classification using gene expression data and compare its performance with some other classification methods.
Multimodal and alternative perception for the visually impaired: a survey

Purpose – The purpose of this paper is to provide an overview of navigational assistive technologies with various sensor modalities and alternative perception approaches for visually impaired people. It also examines the input and output of each technology, and provides a comparison between systems. Design/methodology/approach – The contributing authors along with their students thoroughly read and reviewed the referenced papers while under the guidance of domain experts and users evaluating each paper/technology based on a set of metrics adapted from universal and system design. Findings – After analyzing 13 multimodal assistive technologies, the authors found that the most popular sensors are optical, infrared, and ultrasonic. Similarly, the most popular actuators are audio and haptic. Furthermore, most systems use a combination of these sensors and actuators. Some systems are niche, while others strive to be universal. Research limitations/implications – This paper serves as a starting point for furthe.
ANALISIS PENGARUH MOTIVASI INTRINSIK DAN EKSTRINSIK TERHADAP KINERJA KARYAWAN BORONGAN DENGAN KOMITMEN ORGANISASI SEBAGAI MEDIASI (Studi Kasus: Perusahaan Rokok Adi Bungsu Malang)

Abstrak Perusahaan Rokok Adi Bungsu yang terletak di Malang, Jawa Timur, merupakan salah satu perusahaan yang menggunakan sistem kontrak khususnya pada karyawan borongan proses produksi rokok sigaret kretek tangan (SKT). Berdasarkan hasil wawancara dengan bagian personalia, terdapat permasalahan kinerja individu yang berfluktuatif pada karyawan borongan proses produksi SKT. Selain itu, sistem kontrak yang digunakan oleh Perusahaan Rokok Adi Bungsu mengakibatkan adanya perbedaan komitmen organisasi yang dimiliki karyawan borongan dengan karyawan lain yang merupakan karyawan tetap. Penelitian ini menganalisis bagaimana pengaruh motivasi intrinsik dan ekstrinsik terhadap kinerja dengan komitmen organisasi sebagai faktor mediasi menggunakan teknik analisis regresi berganda dan sobel test. Langkah awal yang dilakukan dalam pengumpulan data adalah dengan menyebarkan kuesioner kepada 89 orang karyawan borongan. Berdasarkan hasil penelitian diketahui bahwa hanya motivasi intrinsik yang berpengaruh positif terhadap komitmen organisasi, Selanjutnya berdasarkan hasil RCA untuk motivasi intrinsik terhadap komitmen organisasi, maka rekomendasi perbaikan ditujukan kepada beberapa manajemen perusahaan. Salah satu rekomendasinya adalah merencanakan kebijakan mengenai job rotation. Kata Kunci : Motivasi Intrinsik, Motivasi Ekstrinsik, Komitmen Organisasi, Kinerja, Regresi Berganda, Sobel Test , Root Cause Analysis (RCA).
Evaluation of genetic diversity and population structure of five Chinese indigenous donkey breeds using microsatellite markers

Di R. , Liu Q.Y. , Xie F. , Hu W.P., Wang X. -Y. , Cao X. -H. , Pan Z. -Y. , Chen G. -H. , Chu M. -X. (2017): Evaluation of genetic diversity and population structure of five Chinese indigenous donkey breeds using microsatellite markers. Czech J. Anim. Sci., 62, 219–225. China had the largest population of raising donkeys in the world, however the number of Chinese indigenous donkey decreased dramatically due to the increase of agriculture mechanization in the last century. The species has still been important in China because of its edible and medical value, therefore the survey on its genetic diversity in China is necessary for its conservation and utilization. In this study, 15 microsatellite markers were used to evaluate genetic diversity and population structure of five Chinese indigenous donkey breeds. The mean values of expected heterozygosity, allelic richness, and total number of alleles for all the tested Chinese donkeys were 0.70, 6.04, and 6.28 respectively, suggesting that the genetic diversity of Chinese indigenous donkeys is rich. The Bayesian analysis and principal component analysis plot yielded the same clustering result, which revealed that Guanzhong donkey was the most differentiated breed in all detected samples, and Jinnan (JN) and Guangling (GL) were genetically closed together. Additionally, our results indicated that the heterozygote deficit was severe in two Chinese indigenous donkey breeds (GL and JN), and it warned us that animal conservation activities on this species should be considered carefully in near future.
Eukaryotic RNase P RNA mediates cleavage in the absence of protein

The universally conserved ribonucleoprotein RNase P is involved in the processing of tRNA precursor transcripts. RNase P consists of one RNA and, depending on its origin, a variable number of protein subunits. Catalytic activity of the RNA moiety so far has been demonstrated only for bacterial and some archaeal RNase P RNAs but not for their eukaryotic counterparts. Here, we show that RNase P RNAs from humans and the lower eukaryote Giardia lamblia mediate cleavage of four tRNA precursors and a model RNA hairpin loop substrate in the absence of protein. Compared with bacterial RNase P RNA, the rate of cleavage (kobs) was five to six orders of magnitude lower, whereas the affinity for the substrate (appKd) was reduced ≈20- to 50-fold. We conclude that the RNA-based catalytic activity of RNase P has been preserved during evolution. This finding opens previously undescribed ways to study the role of the different proteins subunits of eukaryotic RNase P.
Gating Properties of SCN5A Mutations and the Response to Mexiletine in Long-QT Syndrome Type 3 Patients

Background— Mexiletine (Mex) has been proposed as a gene-specific therapy for patients with long-QT syndrome type 3 (LQT3) caused by mutations in the cardiac sodium channel gene (SCN5A). The degree of QT shortening and the protection from arrhythmias vary among patients harboring different mutations. We tested whether the clinical response to Mex in LQT3 could be predicted by the biophysical properties of the different mutations. Methods and Results— We identified 4 SCN5A mutations in 5 symptomatic LQT3 patients with different responses to Mex (6 to 8 mg · kg−1 · d−1). We classified the mutations as sensitive to Mex (P1332L, R1626P; ≥10% of QTc shortening and QTc <500 ms or no arrhythmias) or insensitive to Mex (S941N, M1652R; negligible or no QTc shortening and sudden death). We measured Na+ current from HEK 293 cells transfected with wild-type (WT) or mutant Nav1.5. All mutations showed impaired inactivation of Na+ current, but the mutations identified in patient responders to Mex (P1332L, R1626P) showed a hyperpolarizing shift of V1/2 of steady-state inactivation. Furthermore, Mex produced use-dependent block with the order R1626P=P1332L>S941N=WT>M1652R, suggesting that Mex-sensitive mutants present prolonged recovery from Mex block. Conclusions— We propose that voltage dependence of channel availability and shifts of V1/2 of steady-state inactivation correlate with the clinical response observed in LQT3 patients. This supports the view that the response to Mex is mutation specific and that in vitro testing may help to predict the response to therapy in LQT3.
The Layered Fabric of Cerebral Artery Fenestrations

Intravascular bridges, resulting from developmental anomalies of brain arteries, are now better known as arterial fenestrations. Their tendency to develop aneurysms, similar to arterial bifurcations, makes their anatomy and microstructure important for study. Methods Six segments of artery, each including a fenestration (five from the vertebrobasilar junction and one from the middle cerebral artery), were pressure distended, fixed, and sectioned. We made three-dimensional orientation measurements of smooth muscle and collagen, stained to enhance their birefringence, using the polarized light microscope. Results The general contour of the fenestrations is streamlined, with a thickened layered subendothelium at the trailing or distal edge, structurally similar to the region of convergence of major brain arteries. Defects of the medial layer were found at both proximal and distal edges of all the fenestrations. Results included regional mean orientations of individual layers, with circular SDs. The medial layer was found to be coherently aligned perpendicular to the direction of blood flow, with a mean circular SD of 12°. The adventitia was less coherent (mean circular SD, 16°) with the same average orientation, and the multilayered subendothelium had layers of obliquely oriented fibers with a wide range of coherence for individual fiber groups. Layers of the side regions were analogous to those in segments of brain artery and differed significantly from the proximal and distal edges of the fenestration structure. Conclusions The plasticity of form of the fenestrations at both the proximal and distal edges is in response to hemodynamic forces and is analogous to branching regions of brain arteries. Medial defects, a common feature in both brain arteries and fenestrations, may predispose the arterial fenestration to aneurysm formation.
Total Instructional Time Exposure and Student Achievement: An Extreme Bounds Analysis Based on German State-Level Variation

Using pooled data on instructional time and student performance by subject, our study finds evidence for the school inputs-student achievement relationship for German states. This finding is robust both to the inclusion of state fixed effects and in an extensive extreme bounds analysis. It stands in contrast to the majority of related studies. We argue that this is due to an error-in-variables problem and implied misinterpretation of existing studies that disregard the fact of learning being a cumulative process by relying on rather poor proxies for instructional time. Highschool ninth graders from the OECD Programme of International Student Assessment (PISA-E) tests’ bottom percentiles bene.t most from extra-instructional time measured in cumulated form from first up to ninth grade. Besides total instructional time exposure, we identify eight further social environment and institutional variables with robust impact on student performance. In contrast to instructional time hardly any of these factors can be affected by policy in the short run.
The effect of network topology on the stability of discrete state models of genetic control

Boolean networks have been proposed as potentially useful models for genetic control. An important aspect of these networks is the stability of their dynamics in response to small perturbations. Previous approaches to stability have assumed uncorrelated random network structure. Real gene networks typically have nontrivial topology significantly different from the random network paradigm. To address such situations, we present a general method for determining the stability of large Boolean networks of any specified network topology and predicting their steady-state behavior in response to small perturbations. Additionally, we generalize to the case where individual genes have a distribution of “expression biases,” and we consider a nonsynchronous update, as well as extension of our method to non-Boolean models in which there are more than two possible gene states. We find that stability is governed by the maximum eigenvalue of a modified adjacency matrix, and we test this result by comparison with numerical simulations. We also discuss the possible application of our work to experimentally inferred gene networks.
Block Sparse Compressed Sensing of Electroencephalogram (EEG) Signals by Exploiting Linear and Non-Linear Dependencies

This paper proposes a compressive sensing (CS) method for multi-channel electroencephalogram (EEG) signals in Wireless Body Area Network (WBAN) applications, where the battery life of sensors is limited. For the single EEG channel case, known as the single measurement vector (SMV) problem, the Block Sparse Bayesian Learning-BO (BSBL-BO) method has been shown to yield good results. This method exploits the block sparsity and the intra-correlation (i.e., the linear dependency) within the measurement vector of a single channel. For the multichannel case, known as the multi-measurement vector (MMV) problem, the Spatio-Temporal Sparse Bayesian Learning (STSBL-EM) method has been proposed. This method learns the joint correlation structure in the multichannel signals by whitening the model in the temporal and the spatial domains. Our proposed method represents the multi-channels signal data as a vector that is constructed in a specific way, so that it has a better block sparsity structure than the conventional representation obtained by stacking the measurement vectors of the different channels. To reconstruct the multichannel EEG signals, we modify the parameters of the BSBL-BO algorithm, so that it can exploit not only the linear but also the non-linear dependency structures in a vector. The modified BSBL-BO is then applied on the vector with the better sparsity structure. The proposed method is shown to significantly outperform existing SMV and also MMV methods. It also shows significant lower compression errors even at high compression ratios such as 10:1 on three different datasets.
Populist Policies in the Transition to Democracy

This paper develops a political economy model that provides an explanation as for why ruling elites in oligarquic societies may rely on income redistribution to the poor (the masses) in order to prevent them from attempting a revolution. We refer to this kind of redistribution as populist redistribution because, first it does not increase the poor’s productive capacity (human capital), and second it seeks to “buy” political support (peace) to perpetuate the elite’s control of political power. We examine the conditions under which ruling elites choose to deter the poor (by means of military repression and/or populist redistribution), to engage in a dispute with the poor for the control of political power, or, alternatively, to extend democracy. According to the results of the model populist redistribution (or military repression), if any, increases with initial wealth inequality and with the amount of redistribution that the poor can undertake under democracy, and decreases with the relative importance of a human capital externality in production. The model explains why in some cases the use of an apparently ine cient policy of populist redistribution turns out to be optimal for both groups (the ruling elite and the poor class) when the alternative is to use of military repression or default to conflict.
How to Develop Children as Researchers: A Step by Step Guide to Teaching the Research Process

This book is based on two year's research piloting optimal ways to engage children with research process as a route to enhanced learning. Engaging in research enhances children's crticial thinking skills and encourages independent learning. Undertaking their own research empowers children to explore issues which interest or concern them and to have a voice. The book adopts a child-centred and interactive approach to teaching children how to engage with research.