Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine Learning to Interrogate High-throughput Genomic Data: Theory and Applications

The missing heritability in genome-wide association studies (GWAS) is an intriguing open scientific problem which has attracted great recent interest. The interaction effects among risk factors, both genetic and environmental, are hypothesized to be one of the main missing heritability sources. Moreover, detection of multilocus interaction effect may also have great implications for revealing disease/biological mechanisms, for accurate risk prediction, personalized clinical management, and targeted drug design. However, current analysis of GWAS largely ignores interaction effects, partly due to the lack of tools that meet the statistical and computational challenges posed by taking into account interaction effects. Here, we propose a novel statistically-based framework (Significant Conditional Association) for systematically exploring, assessing significance, and detecting interaction effect. Further, our SCA work has also revealed new theoretical results and insights on interaction detection, as well as theoretical performance bounds. Using in silico data, we show that the new approach has detection power significantly better than that of peer methods, while controlling the running time within a permissible range. More importantly, we applied our methods on several real data sets, confirming well-validated interactions with more convincing evidence (generating smaller pvalues and requiring fewer samples) than those obtained through conventional methods, eliminating inconsistent results in the original reports, and observing novel discoveries that are
Experimental Induction of Cerebral Aneurysms by Developmental Low Copper Diet

Optimal models are needed to understand the pathophysiology of human cerebral aneurysms (CA). We investigated the development of experimental CA by decreasing the activity of lysyl oxidases by dietary copper deficiency from the time of gestation and then augmenting vascular stress by angiotensin II infusion in adulthood. Rats were fed copper-free, low-copper, or normal diets at different time periods from gestation to adulthood. The incidences of CAs were evaluated and autopsies performed to determine the coexistence of cardiovascular diseases. A copper-free diet from gestation was associated with high mortality rates (79.1%) resulting from rupture of ascending aorta aneurysms; a low-copper diet led to acceptable mortality rates (13.6%) and produced CAs and subarachnoid hemorrhage in 46.4% and 3.6% of animals, respectively. Higher proportions of CAs (up to 33.3%) in the rats primed for copper deficiency from gestation ruptured following angiotensin II infusion from adulthood. Gene expression array analyses of the CAs indicated that genes involving extracellular matrix and vascular remodeling were altered in this model. This model enables future research to understand the entire pathogenetic basis of CA development and rupture in association with systemic vasculopathies.
Exercise Tolerance in a Hot and Humid Climate in Heat-Acclimatized Girls and Women

This study compared physiological responses associated with exercise tolerance in girls (G) and women (W) of similar fitness and heat acclimatization level during exercise in a hot and humid outdoor environment (33.4 degrees C and 55.1 % RH; WBGT = 29.9 +/- 0.2 degrees C). Nine pre-menarcheal G (age = 11.3 yr) and nine W (age = 26.8 yr), matched for aerobic capacity and heat acclimatization level, performed a cycling session at 60 % VO2max until fatigue. A sports drink was provided periodically to prevent dehydration. Tolerance time was not different between the groups (G = 56.9 +/- 6.3, W = 76.5 +/- 9.9 min, p > 0.05). During exercise, sweat rate (G = 9.1 +/- 1.1, W = 12.0 +/- 1.1 ml.m(-2). min(-1)), the increase in rectal temperature [T(re)] (G = 0.9 +/- 0.1, W = 1.1 +/- 0.1 degrees C), and heat storage (G = 10.6 +/- 5.3, W = 20.5 +/- 4.5 W.m(-2)) did not differ between the groups. At fatigue, T(re) (G = 38.2 +/- 0.1, W = 38.4 +/- 0.1 degrees C), heart rate (G = 167.3 +/- 7.3, W = 171 +/- 3.3 beats.min(-1)), stroke index (G = 48.3 +/- 1.5, W = 52.4 +/- 1.8 ml.m(-2)), and forearm skin blood flow (G = 9.5 +/- 1.3, W = 11.7 +/- 1.5 ml.100 ml(- 1). min(-1)) did not differ between the groups. Similar to women, the main reasons reported by girls to stop exercising in the heat were localized leg fatigue and gluteus muscle discomfort. We conclude that heat-acclimatized girls exhibit an adequate cardiovascular and thermoregulatory adjustment while exercising in a hot and humid outdoor environment when hypohydration is prevented.
Constrained versus unconstrained intensive language therapy in two individuals with chronic, moderate-to-severe aphasia and apraxia of speech: behavioral and fMRI outcomes.

PURPOSE This Phase I study investigated behavioral and functional MRI (fMRI) outcomes of 2 intensive treatment programs to improve naming in 2 participants with chronic moderate-to-severe aphasia with comorbid apraxia of speech (AOS). Constraint-induced aphasia therapy (CIAT; Pulvermüller et al., 2001) has demonstrated positive outcomes in some individuals with chronic aphasia. Whether constraint to the speech modality or treatment intensity is responsible for such gains is still under investigation. Moreover, it remains to be seen whether CIAT is effective in individuals with persistent severe nonfluent speech and/or AOS. METHOD A single-subject multiple-baseline approach was used. Both participants were treated simultaneously, first with Promoting Aphasics' Communicative Effectiveness (PACE; Davis & Wilcox, 1985) and then with CIAT. Pre-/posttreatment testing included an overt naming fMRI protocol. Treatment effect sizes were calculated for changes in probe accuracy from baseline to posttreatment phases and maintenance where available. RESULTS Both participants made more and faster gains in naming following CIAT. Treatment-induced changes in BOLD activation suggested that better naming was correlated with the recruitment of perilesional tissue. CONCLUSION Participants produced more target words accurately following CIAT than following PACE. Behavioral and fMRI results support the notion that the intense and repetitive nature of obligatory speech production in CIAT has a positive effect on word retrieval, even in participants with chronic moderate-to-severe aphasia with comorbid AOS.
Approximation of Geometric Structures with Growing Cell Structures and Growing Neural Gas - A Performance Comparison

We compare Growing Cell Structures and Growing Neural Gas, which were introduced by Bernd Fritzke and which are famous for their facilities in classification, clustering, dimensionality reduction, data visualization, and approximation tasks. We practically test and analyze their capabilities in geometric approximation and focusing on the application of surface reconstruction from 3D point-data. Our focus is to work out the differences of the algorithms that are especially relevant concerning approximation purposes. We address the issue of suitable input data, their applied graphs, their topological properties, their run time complexities and we present a summary of suggested alternations to both approaches and evaluate our results.
Signaling pathways in renal cell carcinoma

Renal cell carcinoma (RCC), the most lethal type of genitourinary cancer, is generally resistant to chemotherapy and radiation therapy. Surgical excision of the tumor at a localized stage remains the mainstay for curative therapy. A number of drugs developed in recent years have shown limited to significant efficacy in treating RCC. These drugs act by blocking critical signaling pathways associated with RCC tumor growth and survival, and angiogenesis. Beyond well-validated signaling targets such as VHL, VEGFR and mTOR, additional pathways including HGF/c-MET and Wnt/β-catenin have emerged as important to RCC pathogenesis. Mutations in one or more components of these signaling networks may affect tumor response to therapy. This review summarizes the state of knowledge about signaling pathways in RCC and discusses the known genetic and epigenetic alterations that underlie dysregulation of these pathways.
Modulated error voltages for the diagnosis of faults in matrix converters

This paper presents a new method for the diagnosis of faults in matrix converters. The method is based on the monitoring of nine modulated error signals, each one associated to a bidirectional power switch of the converter. Using the proposed technique, an open-circuit in a given switch is detected whenever the associated modulated error voltage signal rises above an established threshold limit. This new method allows a fast detection and location of the faulty switches, independently of the type of load of the converter or its working conditions, namely amplitude and frequency of the output voltages. Simulation and experimental results demonstrate the validity of the proposed technique to detect open-circuit faults in matrix converters, even with more than one faulty switch at the same time.
AC927, a σ Receptor Ligand, Blocks Methamphetamine-Induced Release of Dopamine and Generation of Reactive Oxygen Species in NG108-15 Cells

Methamphetamine is a highly addictive psychostimulant drug of abuse that causes neurotoxicity with high or repeated dosing. Earlier studies demonstrated the ability of the selective σ receptor ligand N-phenethylpiperidine oxalate (AC927) to attenuate the neurotoxic effects of methamphetamine in vivo. However, the precise mechanisms through which AC927 conveys its protective effects remain to be determined. With the use of differentiated NG108-15 cells as a model system, the effects of methamphetamine on neurotoxic endpoints and mediators such as apoptosis, necrosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and dopamine release were examined in the absence and presence of AC927. Methamphetamine at physiologically relevant micromolar concentrations caused apoptosis in NG108-15 cells. At higher concentrations of methamphetamine, necrotic cell death was observed. At earlier time points, methamphetamine caused ROS/RNS generation, which was detected with the fluorigenic substrate 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescin diacetate, acetyl ester, in a concentration- and time-dependent manner. N-Acetylcysteine, catalase, and l-NG-monomethyl arginine citrate inhibited the ROS/RNS fluorescence signal induced by methamphetamine, which suggests the formation of hydrogen peroxide and RNS. Exposure to methamphetamine also stimulated the release of dopamine from NG108-15 cells into the culture medium. AC927 attenuated methamphetamine-induced apoptosis, necrosis, ROS/RNS generation, and dopamine release in NG108-15 cells. Together, the data suggest that modulation of σ receptors can mitigate methamphetamine-induced cytotoxicity, ROS/RNS generation, and dopamine release in cultured cells.
Intussusception among infants given an oral rotavirus vaccine.

BACKGROUND Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV-TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.
Impact of the PROVAUR stewardship programme on linezolid resistance in a tertiary university hospital: a before-and-after interventional study.

BACKGROUND There is little evidence of the impact of antimicrobial stewardship programmes on antimicrobial resistance. OBJECTIVES To study the efficacy and safety of a package of educational and interventional measures to optimize linezolid use and its impact on bacterial resistance. METHODS A quasi-experimental study was designed and carried out before and after implementation of a stewardship programme in hospitalized patients with Gram-positive infections treated with linezolid. RESULTS The intervention reduced linezolid consumption by 76%. The risk of linezolid-resistant CoNS isolates (OR = 0.37; 95% CI = 0.27-0.49; P < 0.001) and Enterococcus faecalis (OR = 0.44; 95% CI = 0.21-0.90; P = 0.03) during the intervention period was lower than in the pre-intervention period. CONCLUSIONS A programme to optimize linezolid use can contribute to reducing the resistance rate of CoNS and E. faecalis to this antibiotic.
Differential regulation of the nerve growth factor and brain‐derived neurotrophic factor genes in L929 mouse fibroblasts

Nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are structurally related survival and differentiation factors for distinct sets of peripheral and central neurons. The regulation of NGF gene expression has been extensively studied in L929 mouse fibroblasts. L929 cells also express the BDNF gene. Northern blot hybridization analysis revealed 4 discrete BDNF mRNA species in L929 cells and rat hippocampus after induction of seizures with kainic acid. Serum as well as 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA) stimulated NGF and all 4 BDNF mRNAs in L929 cells. Treatment with both agents induced NGF mRNA to a much larger extent than the BDNF mRNAs. The induction of the BDNF mRNAs was rapid, with nearly maximal levels by 1 hr. In contrast, NGF mRNA induction occurred later and peaked at 4–6 hr. Both NGF and BDNF mRNA induction were inhibited by actinomycin D. Cycloheximide, on the other hand, inhibited only NGF but not BDNF mRNA induction. Corticosterone rapidly decreased NGF mRNA but not the BDNF mRNAs, and had no effect on seizure‐induced NGF or BDNF mRNAs. Forskolin did not stimulate NGF or BDNF mRNAs. In contrast to NGF mRNA, forskolin did not interfere with the serum induction of BDNF mRNAs. These results demonstrate that 2 genes which encode closely related neurotrophic factors are differentially regulated in L929 cells. The molecular mechanisms which bring about this differential regulation remain to be elucidated. © 1992 Wiley‐Liss, Inc.
Osteonecrosis of the Knee after Arthroscopic Meniscectomy and Chondroplasty

Ahlback et al. first described spontaneous osteonecrosis of the knee as a distinct clinical entity in 1968. It is characterized by well-localized tenderness over the femoral condyle, most commonly on the medial side. Osteonecrosis can be associated with a variety of medical conditions, such as hyperbarism, alcoholism, corticosteroid use, hyperuricemia, Gaucher’s disease, sickle cell disease, pancreatitis, familial hyperlipidemia, and Cushing’s disease. The etiologic basis of spontaneous osteonecrosis is unknown. Theories include vascular insufficiency or microfractures of the subchondral plate, with synovial fluid being forced from the synovial space into the bone. An association between meniscal tears and osteonecrosis has also been postulated. We report on a patient who underwent arthroscopic surgery for a medial meniscal tear and returned shortly after surgery with markedly increased pain and swelling. Subsequent MRI demonstrated findings consistent with classic osteonecrosis of the medial femoral condyle.
Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs

Low oxygen tension is thought to be an integral component of the human mesenchymal stem cell (hMSC) native bone marrow microenvironment. HMSC were cultured under physiologically relevant oxygen environments (2% O2) in three‐dimensional (3D) constructs for up to 1 month in order to investigate the combined effects of chronic hypoxia and 3D architecture on hMSC tissue‐development patterns. Hypoxic hMSC exhibited an extended lag phase in order to acclimatize to culture conditions. However, they subsequently proliferated continuously throughout the culture period, while maintaining significantly higher colony‐forming unit capabilities and expressing higher levels of stem cell genes than hMSC cultured at 20% O2 (normoxic) conditions. Upon induction, hypoxic hMSC also expressed higher levels of osteoblastic and adipocytic differentiation markers than normoxic controls. Hypoxia induced increased total protein levels in hMSC throughout the culture period, as well as significantly different fibronectin expression patterns suggesting that oxygen levels can significantly affect tissue‐development patterns. Importantly, hMSC maintained the ability to thrive in prolonged hypoxic conditions suggesting that hypoxia may be an essential element of the in vivo hMSC niche. Further studies are required to determine how variations in cellular characteristics and ECM expression impact on the physiological properties of the engineered tissue, yet these results strongly indicate that oxygen tension is a key parameter that influences the in vitro characteristics of hMSC and their development into tissues. J. Cell. Physiol. 207: 331–339, 2006. © 2005 Wiley‐Liss, Inc.
User based Collaborative Filtering with Temporal Information for Purchase Data

User based collaborative filtering algorithms are widely used for generating recommendations for users. Standard user based collaborative filtering algorithms do not consider time as a factor while measuring the user similarities and building the recommendation list. However, users’ interests often shift with time. Recommender systems should therefore rely on recent purchases of the users to address this user dynamics . Items also have their own dynamics. Most of the items in a recommender system are widely popular just after their releases but do not sell that well afterwards. Giving more importance to the recent purchases of the xpertsmay capture the item dynamics and hence result in better recommendation accuracy. We study the performances of different time-aware user based collaborative filtering algorithms on several benchmark datasets. The proposed algorithms use the time-of-purchase information for calculating user similarities. The time information is also used while combining the purchase behaviors of theexpertsand generating the final recommendation.
Polarity, protrusion-retraction dynamics and their interplay during keratinocyte cell migration.

Keratinocyte migration on a two-dimensional substrate can be split into four distinct phases: cell extension, attachment, contraction, and detachment. It is preceded by polarization of the cell which leads to a functional asymmetry observable by the formation of a leading lamella. In this work variation of fibronectin coating concentrations and competitive inhibition with RGD peptides are used to investigate the dependency of polarization, migration, lamella dynamics, and ruffling on substrate adhesiveness. Looking at migrating human epidermal keratinocytes with a well-defined polarity we find that a fibronectin-coating concentration of 10 microg/cm(2) stimulates migration and ruffling speed twofold, whereas protrusion speed increases only by 20% (compared to 2.5 microg/cm(2) fibronectin). Nonpolar cells show a constant migration and ruffling speed independent of the amount of fibronectin. In contrast protrusion speeds of polar and nonpolar cells are equal. Treatment of cells on 10 microg/cm(2) fibronectin with 1 mg/ml GRGDS reduces the characteristic migration, protrusion, and ruffling speed of polar cells which corresponds to lowering the effective coating concentration to under 5 microg/cm(2). The probability of being polarized (quantified by a polarity index) increases with increasing fibronectin concentration. However, addition of soluble RGD on 10 microg/cm(2) fibronectin does not simply reduce the polarity index like one would expect from the corresponding changes in the other motility parameters, but it remains unchanged.
A Constant-on-Time Control DC–DC Buck Converter With the Pseudowave Tracking Technique for Regulation Accuracy and Load Transient Enhancement

Constant-on-time (COT) control with an additional current feedback path in conventional buck converters can remove the need of large equivalent series resistance (ESR) at the output capacitor but it induces degraded output voltage regulation accuracy and slow transient response owing to opposite reaction between the output voltage and the additional current feedback information. Therefore, this paper proposes the pseudowave tracking (PWT) technique to reduce the load-dependent dc offset voltage of output load regulation while keeping the fast transient response similar to conventional COT buck converter with large ESR. The PWT technique further improves the transient response instantly by extending on-time and off-time periods during light-to-heavy and heavy-to-light load changes, respectively. The test chip fabricated in 28 nm CMOS process has demonstrated the improvement of offset voltage from 42 to 4 mV, while the transient response can be improved to 4 and 5 μs with load changes from 0.3 to 1.7 A and vice versa, respectively.
Differential brain activation according to chronic social reward frustration

Neural correlates of reward frustration are increasingly studied in humans. In line with prediction error theory, omission of an expected reward is associated with relative decreases of cerebral activation in dopaminergic brain areas. We investigated whether a history of chronic work-related reward frustration influences this reward-dependent activation pattern by means of functional magnetic resonance imaging. Solving arithmetic tasks was followed by either monetary reward or omission of reward. Hyperactivations in the medial prefrontal, anterior cingulate and dorsolateral prefrontal cortex were observed in a group of healthy adults with high susceptibility to reward frustration as compared with a group with low susceptibility. Findings indicate a compromised ability of adapting brain activation among those suffering form chronic social reward frustration.
Erythropoietin administration alone or in combination with endurance training affects neither skeletal muscle morphology nor angiogenesis in healthy young men

What is the central question of this study? Is an erythropoiesis‐stimulating agent (ESA), alone or in combination with endurance training, able to induce changes in human skeletal muscle fibre and vascular morphology? What is the main finding and its importance? Human skeletal muscle morphology and angiogenetic effects did not exhibit sensitivity to ESA treatment alone. Endurance training stimulates angiogenesis and fibre type transition in the direction of a more oxidative fibre phenotype; however, addition of ESA had no further effect.