Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation of Patched1 in Murine Chondrocytes Causes Spinal Fusion Without Inflammation

During development of the vertebrate skeleton, chondrocytes form a cartilage template that is gradually replaced by bone. Hormones of the Hedgehog (HH) family have been implicated in the ossification process, but their exact relationship to normal or pathogenic bone formation is unclear. This study was undertaken to establish a genetic tool that allows the discrete inactivation of genes in spinal chondrocytes, and to investigate in vivo how chondrocyte‐specific ablation of the inhibitory HH receptor Patched 1 (Ptch1) affects skeleton integrity.
Named entity recognition for Chinese telecommunications field based on Char2Vec and Bi-LSTMs

Named Entity Recognition (NER) is a basic task in Natural Language Processing (NLP), which extracts the meaningful named entities from the text. Compared with the English NER, the Chinese NER is more challenge, since there is no tense in the Chinese language. Moreover, the omissions and the Internet catchwords in the Chinese corpus make the NER task more difficult. Traditional machine learning methods (e.g., CRFs) cannot address the Chinese NER effectively because they are hard to learn the complicated context in the Chinese language. To overcome the aforementioned problem, we propose a deep learning model Char2Vec+Bi-LSTMs for Chinese NER. We use the Chinese character instead of the Chinese word as the embedding unit, and the Bi-LSTMs is used to learn the complicated semantic dependency. To evaluate our proposed model, we construct the corpus from the China TELECOM FAQs. Experimental results show that our model achieves better performance than other baseline methods and the character embedding is more appropriate than the word embedding in the Chinese language.
Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters

Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC–metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]–PC2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)–PC2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs.
Incorporating Genotype Uncertainties Into the Genotypic TDT for Main Effects and Gene‐Environment Interactions

Genotype imputation has become a standard option for researchers to expand their genotype datasets to improve signal precision and power in tests of genetic association with disease. In imputations for family‐based studies however, subjects are often treated as unrelated individuals: currently, only BEAGLE allows for simultaneous imputation for trios of parents and offspring; however, only the most likely genotype calls are returned, not estimated genotype probabilities. For population‐based SNP association studies, it has been shown that incorporating genotype uncertainty can be more powerful than using hard genotype calls. We here investigate this issue in the context of case‐parent family data. We present the statistical framework for the genotypic transmission‐disequilibrium test (gTDT) using observed genotype calls and imputed genotype probabilities, derive an extension to assess gene‐environment interactions for binary environmental variables, and illustrate the performance of our method on a set of trios from the International Cleft Consortium. In contrast to population‐based studies, however, utilizing the genotype probabilities in this framework (derived by treating the family members as unrelated) can result in biases of the test statistics toward protectiveness for the minor allele, particularly for markers with lower minor allele frequencies and lower imputation quality. We further compare the results between ignoring relatedness in the imputation and taking family structure into account, based on hard genotype calls. We find that by far the least biased results are obtained when family structure is taken into account and currently recommend this approach in spite of its intense computational requirements.
Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension

Background L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertension, perhaps due to adverse effects on autonomic nervous system (ANS) function. Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects. Objective and design This double-blind, parallel group study compared the effect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) versus mibefradil (T-type CCB) on ANS function in patients with mild–moderate essential hypertension. Methods Sixteen patients (10 male, 6 female; age 57.2 ± 2.3 years), diastolic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg daily or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibefradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) was assessed using norepinephrine kinetics. Parasympathetic nervous system activity (PSNA) was assessed from 24 h Holter recordings of heart rate variability (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS. Results Patient groups were well matched at baseline. Achieved DBP was lower in patients treated with mibefradil compared with nifedipine, (83.4 ± 1.7 versus 95.25 ± 3.3 mmHg). There were no significant differences in SNSA and BRS between groups, however the root mean square of successive differences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 ± 1.6 versus −3.36 ± 1.2 ms, P < 0.05) and (+ 0.28 ± 0.1 versus −0.23 ± 0.1 ms2, P < 0.01), respectively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group, (0.71 ± 0.02 versus 0.74 ± 0.03, P = 0.046). Conclusion No differences existed between effect of L- and T-type CCBs on SNSA and BRS. However, T-type CCBs increased PSNA, independent of achieved changes in heart rate.
Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

Background The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora. Methods In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs from 1278 patients were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia. Results In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 perce.
Extreme High-altitude Asian and Andean Pierid Butterflies Are Not Each Others' Closest Relatives

ABSTRACT Some of the world's highest-altitude butterflies belong to the tribe Pierini of the family Pieridae. Two nominal species of Baltia occur in arid-semiarid oreal environments in Central Asia, the Himalaya, and Pamir to over 5500 m. At least 13 species currently placed in four genera (Phulia, Infraphulia, Pierphulia, Piercolias) occur in similar environments at similar altitudes in the high Andes. These genera all share numerous morphospecializations whose functional relation to the oreal environment is not understood. Their evolutionary and biogeographic relationships have been debated for over a century. We performed a phylogenetic analysis based on sequencing portions of the mitochondrial cytochrome oxidase subunit I and subunit II regions (COI and COII), incorporating all the genera but Piercolias and a variety of suspected relatives. The results from analyses of COI and COII were compared to relationships inferred from morphological and ecological characters. We conclude that Baltia is not the sister-group of the Andean genera, which are clearly nested within a Neotropical clade. The “Camelid scenario” deriving all the genera from a common ancestor no longer appears viable.
Sorafenib suppresses growth and survival of hepatoma cells by accelerating degradation of enhancer of zeste homolog 2

Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes that regulate cancer cell growth and survival. It is overexpressed in hepatocellular carcinoma (HCC) with a clinical significance that remains obscure. Sorafenib, a multikinase inhibitor, has been used as a first‐line therapeutic drug and shown clinical efficiency for advanced‐stage HCC patients. In the present study, we found that sorafenib lowered the protein level of EZH2 through accelerating proteasome‐mediated EZH2 degradation in hepatoma cells. Overexpression of EZH2 reversed sorafenib‐induced cell growth arrest, cell cycle arrest, and cell apoptosis dependent on histone methyltransferase activity in hepatoma cells. More importantly, shRNA‐mediated EZH2 knockdown or EZH2 inhibition with 3‐deazaneplanocin A treatment promoted sorafenib‐induced hepatoma cell growth arrest and apoptosis. Sorafenib altered the hepatoma epigenome by reducing EZH2 and H3K27 trimethylation. These results revealed a novel therapeutic mechanism underlying sorafenib treatment in suppressing hepatoma growth and survival by accelerating EZH2 degradation. Genetic deletion or pharmacological ablation of EZH2 made hepatoma cells more sensitive to sorafenib, which helps provide a strong framework for exploring innovative combined therapies for advanced‐stage HCC patients.
Changes in Patient Drawings of the Heart Identify Slow Recovery After Myocardial Infarction

Objective: The objective of this study was to investigate how changes in heart attack patients’ drawings of their heart over the recovery period relate to psychological and functional recovery. Methods: Sixty-nine inpatients admitted for acute myocardial infarction at the coronary care unit at a metropolitan hospital completed questionnaires at discharge, including a drawing of what they thought had happened to their heart after their heart attack. Fifty-six patients returned follow-up questionnaires at 3 and 6 months, including heart drawings, cardiac anxiety, time to return to work, changes in exercise frequency, and healthcare use. Results: Increases in the size of the heart drawn at the 3-month follow-up relative to discharge were related to slower return to work (r = 0.48, p < .01), higher cardiac anxiety (r = 0.35, p < .05), and more phone calls to health services (r = 0.37, p < .05) as well as increases in worry about another myocardial infarction (r = 0.39, p < .01), increased activity restriction (r = 0.34, p < .05), higher use of alternative medicines (r = 0.40, p < .05), and less frequent exercise (r = −0.39, p < .05) relative to before the myocardial infarction. Conclusions: Drawings of the heart may be useful in identifying patients who have experienced heart attacks who are likely to develop greater heart-focused anxiety, complaints of ill health, and higher use of health care. Increases in the size of the patient’s drawing of the heart may reflect increases in the extent to which their heart condition plays on their mind and directs their daily activities. MI = myocardial infarction; CAQ = Cardiac Anxiety Questionnaire.
Robust Nonlinear Control for Direct Torque Control of Induction Motor Drive Using Space Vector Modulation

To solve the problems of torque ripple and inconstant switch frequency of inverter in the conventional direct torque control (DTC), a novel DTC method using space vector modulation (SVM) is proposed based on input– output feedback linearization technique, where hysteresis controller is substituted by input–output feedback linearization and switch table is substituted by SVM. In order to preserve the system robustness with respect to rotor resistances variations and uncertainties. IM drive simulation model with novel SVM-DTC is created and studied using MATLAB. Simulation results demonstrate the feasibility and validity of the proposed DTC system by effectively accelerating system response, reducing torque and flux ripple and a very satisfactory performance has been achieved.
A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies.

BACKGROUND AT9283 is an inhibitor of aurora kinases A and B with antitumor activity in preclinical models. This a First in Human phase I study assessed the safety, tolerability, pharmacokinetic and pharmacodynamic properties and preliminary efficacy of AT9283. PATIENTS AND METHODS Patients with advanced tumors received AT9283 as a continuous central venous infusion over 3 days in cohorts of three to six patients starting at 1.5 mg/m(2)/day (equivalent to 4.5 mg/m(2)/72 h). The oral bioavailability of AT9283 was assessed in a cohort of seven patients. Pharmacodynamic analysis of biomarkers included phosphorylation of histone H3 on serine 10, proliferating cell nuclear antigen, Ki67, M30 and M65 in skin and plasma. RESULTS Forty patients were included in all analyses. AT9283 was generally well tolerated with main toxic effects of reversible dose-related myelosuppression, gastrointestinal disturbance, fatigue and alopecia. The dose-limiting toxicity of AT9283 was grade 3 febrile neutropenia in two patients at 36 mg/m(2)/72 h and the maximum tolerated dose (MTD) was established at 27 mg/m(2)/72 h. Systemic exposure was dose proportional. The mean oral bioavailability of a 0.9 mg/m(2) dose was 29.4% (range 11.2%-36.7%). Pharmacodynamic analyses indicated antiproliferative and apoptotic activity of AT9283. Four patients with esophageal, non-small-cell lung cancer (n = 2) and colorectal cancer demonstrated RECIST stable disease ≥ 6 months. CONCLUSION AT9283 was well tolerated up to the MTD of 27 mg/m(2)/72 h. AT9283 is currently assessed in phase II trials.
Simulation methods for signal integrity of automotive bus systems

Automotive bus systems like FlexRay or CAN have to provide correct functionality for safety critical applications under various circumstances. In addition many parameters can influence signal integrity. To ensure correct behaviour under all given conditions, simulation based analyses are performed. In this article it is presented how simulation models have been developed, automated workflow and signal analysis have been implemented and parameter search methodologies have been chosen and adapted to provide tools for validation of bus system topologies.
Longitudinal change in basal ganglia volume in patients with Huntington's disease

Article abstract-Cross-sectional MRI studies demonstrating an association between caudate atrophy and symptom severity and duration of symptoms in patients with Huntington's disease (HD) have been assumed to reflect longitudinal changes in basal ganglia, but such neuropathologic progression has never been directly demonstrated. Subjects in the current study were 23 HD patients at various stages of the disorder who had two MRI images at least 10 months apart (mean interimage interval = 20.8 months). We measured volumes of caudate, putamen, and globus pallidus blind to the order of the images. For each structure, we calculated a change score by subtracting the volume obtained on the follow-up imaging from that obtained on the initial imaging. Results indicated significant decreases over time in caudate, putamen, and total basal ganglia volume. Age at onset and length of trinucleotide repeat correlated significantly with amount of volume change in caudate and total basal ganglia, even after controlling for length of interimage interval, duration of disease, and measures of symptom severity. Amount of change in basal ganglia structures was not significantly correlated with neurologic symptom severity at the time of the initial imaging or duration of symptoms. This is the first longitudinal MRI study to document progressive basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with serial MRI may be useful in monitoring effectiveness of potential treatments. In addition, demonstration of greater rate of basal ganglia atrophy in patients with earlier symptom onset suggests that treatment effects may be more quickly observed in this subgroup of patients than in the general HD population. NEUROLOGY 1997;48: 394-399
Appearance-Based QR Code Beautifier

Quick Response (QR) code is a widely used matrix bar code with the increasing population of smart phones. However, QR code usually consists of random textures which are not suitable for incorporating with other visual designs (e.g. name card and business advertisement poster). In order to overcome the shortcomings of noise-like looks of QR codes, we propose a systematic QR code beautification framework where the visual appearance of QR code is composed of visually meaningful patterns selected by users, and more importantly, the correctness of message decoding is kept intact. Our work makes QR code from machine decodable only (i.e. standardized random texture) to a personalized form with human visual pleasing appearance. We expect the proposed QR code beautifier can inspire more visual-pleasant mobile multimedia applications.
Query by Humming by Using Scaled Dynamic Time Warping

Query by Singing/Humming(QBSH) is to retrieve songs in the music database using user's singing or humming. Open-End Dynamic Time Warping (OEDTW) is one of the methods which are commonly used in QBSH studies. This paper proposes a method for improving OEDTW performance using optimal scaling factor taken from Linear scaling phase. The proposed method finds an optimal global scale of a query for each target song by linear scaling and key shifting of the query and target song over the obtained scale can complement DTW or OEDTW. The experimental results demonstrate that the proposed method can improve Top-1 hit rate by 32% compared with the original DTW.
The impact of spousal loss on parent–child relations in later life: Are effects contingent upon the quality of the late marriage?

We use data from the Changing Lives of Older Couples (CLOC) to examine (1) the effect of late-life widowhood on parent–child relations at 6- and 18-month follow-ups; (2) the extent to which effects are conditional upon three qualities of the late marriage (positive and negative interactions, and emotional dependence); and (3) pathways linking marital quality to parent–child relations. We focus on three aspects of parent–child relationships: support, criticism and dependence. Widowed persons report significantly less criticism from and more dependence upon children than do married controls, although effects are conditional upon characteristics of the late marriage. Among the bereaved, marital warmth is associated with high levels of support from children post-loss, whereas marital strains are associated with less emotional support from and dependence on children. Widow(er)s who were highly dependent on their late spouse report lower levels of criticism from children. We discuss implications for bereavement and intergenerational relations in later life.
Antigenic Competition Between and Endotoxic Adjuvant and a Protein Antigen

Antigenic competition between bovine gamma globulin (BGG) and endotoxin from a smooth strain (S-ET) and a rough (R-ET) heptoseless mutant strain of Salmonella minnesota was studied in mice. Both endotoxins acted as adjuvants for enhancing the antibody response to BGG. However, other work showed that the R-ET had minimal antigenicity, and it was used as a control for the competition studies. Antigenic competition between BGG and endotoxin as expressed by a suppression of the antibody response to BGG could not be demonstrated when varying adjuvant doses of S-ET or R-ET were injected simultaneously with a small constant dose of BGG into normal mice. However, mice presensitized with S-ET several weeks before immunization with the S-ET and BGG combination produced anti-BGG levels which were four to eightfold lower than in normal mice. Nearly complete suppression of the anti-BGG response could be obtained in presensitized mice by reducing the BGG dose 10-fold or by increasing the adjuvant dose of endotoxin. Mice pretreated with R-ET and challenged with BGG plus S-ET or R-ET showed no depression of the anti-BGG response. These and other experiments confirmed the immunological basis of the competitive effect.
A Unified Influence Maximization Processing Framework for Independent Cascade Model and Its Extensions ∗

The “word-of-mouth” effect on social networks – opinion propagation – nowadays plays an important role in marketing. The influence maximization problem aims at maximizing the word-ofmouth effect and formulates such goal as a combinatorial optimization problem. As an important process of the influence maximization problem, evaluating influence is #P-hard which cannot be affordable in a polynomial time. Accordingly, devising a fast influence evaluation/approximation algorithm is crucial. We propose a scalable influence approximation algorithm called IPA. The main idea of IPA is considering an influence path as an independent influence evaluation unit. Using that idea, IPA approximates influence an order of magnitude faster and more accurately, and uses much less memory than PMIA, the current state of the art approximation algorithm. In addition, IPA is applicable to independent cascading (IC) model and its extensions (IC-N, t-IC, t-IC-N models), whereas PMIA is only adaptable to IC and IC-N models. We implement and demonstrate a desktop application which finds the most influential nodes and visualizes influence paths. The application is accessible at http://dm.postech. ac.kr/ipa_demo.