Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular analysis of the differential hepatic expression of rat kininogen family genes

Serum concentration of rat T1 kininogen increases 20- to 30-fold in response to acute inflammation, an induced hepatic synthesis regulated primarily at the transcriptional level. We have demonstrated by transient transfection analyses that rat T1 kininogen gene/chloramphenicol acetyltransferase (T1K/CAT) constructs are highly responsive to interleukin-6 and dexamethasone. In these studies we examined the regulation of a highly homologous K kininogen gene promoter and showed that it is minimally induced under identical conditions. The basal expression of the KK/CAT construct was, however, five- to sevenfold higher than that of the analogous T1K/CAT construct. Promoter-swapping experiments to examine the molecular basis of this differentially regulated basal expression showed that at least two K kininogen promoter regions are important for conferring its high basal expression: a distal 19-bp region (C box) constituted a binding site for C/EBP family proteins, and a proximal 66-bp region contained two adjacent binding sites for hepatocyte nuclear factor 3 (HNF-3). While the C box in the K kininogen promoter was able to interact with C/EBP transcription factors, the T1 kininogen promoter C box could not. In addition, HNF-3 binding sites of the K kininogen promoter demonstrated stronger affinities than those of the T1 kininogen promoter. Since C/EBP and HNF-3 are highly enriched in the liver and are known to enhance transcription of liver-specific genes, these differences in their binding activities thus accounted for the K kininogen gene's higher basal expression. Our studies demonstrated that evolutionary divergence of a few critical nucleotides may lead to subtle changes in the binding affinities of a transcription factor to its recognition site, profoundly altering expression of the downstream gene.
Harm reduction for alcohol-use-related problems among college students.

Traditionally, the college Spring Break in the U.S. is used by a significant number of university students as an opportunity for excessive alcohol use. Thus, this fairly discreet time period lends itself to the introduction of a harm reduction intervention for problems related to alcohol use. During the week prior to the Spring Break, university students completed a diary for the eight days of the break (Saturday to Saturday). Students were asked to predict their alcohol consumption and the frequency and type of alcohol problems they would experience during the Spring Break. These same students were then asked to complete the diary one week after the Spring Break reporting their actual consumption and alcohol problems. A control group also completed the diary after Spring Break. Although consumption rates for beer, wine and liquor did not differ between groups, students who completed the diary before Spring Break reported a significantly lower frequency of alcohol problems for the eight day period. Results are discussed in terms of harm reduction strategies for high risk periods and targeting alcohol problems.
Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma.

BACKGROUND & AIMS Interleukin (IL)-1 gene cluster proinflammatory polymorphisms have been associated with development of gastric atrophy and with increased risk of gastric carcinoma. We aimed to determine the association between IL-1 loci polymorphisms and increased risk of gastric carcinoma in samples from a Portuguese population, and to find whether there was any relationship with the histologic types of gastric carcinoma. METHODS In a case-control study including 220 controls and 152 patients with gastric carcinoma (intestinal, 76; diffuse, 37; and atypical, 39), both the IL-1B-511 biallelic polymorphism and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. RESULTS We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma. A trend towards an increased risk of tumor development was also observed in patients with diffuse-type gastric carcinoma. No significant relationship was observed in patients with atypical carcinoma. Carriers of IL-1B-511T and IL-1RN*2 homozygotes had increased risk for developing intestinal-type gastric carcinoma with odds ratios of 2.7 (95% confidence interval [CI], 1.5-4.9) and 3.1 (95% CI, 1.5-6.5), respectively. Statistical analysis showed an interaction between the 2 loci with the risk conferred by the IL-1B-511T allele substantially increased (odds ratio, 9.0; 95% CI, 3.5-23.0) in individuals homozygous for the IL-1RN*2 allele. CONCLUSIONS Our results provide further support to the association between IL-1 gene cluster proinflammatory polymorphisms and increased risk of gastric carcinoma. Furthermore, we found evidence pointing to the existence of a synergistic interaction between the IL-1B and IL-1RN polymorphisms.
A superpositional model applied to F0 parameterization using DCT for text-to-speech synthesis

This paper addresses the idea of the superpositional model based on the DCT (Discrete Cosine Transform) parameterization of the F0 contours. We examine the capacity of the DCT coefficients to estimate the fast variations in the F0 contour at syllable level and also the overall trend of the phrase level. The method determines the coefficients at syllable level, based on the subtraction of the estimated phrase level contour from the original one; thus considering that the syllable has an additive prosodic effect over the phrase level. We also compare the use of 3 different decision and regression tree algorithms for DCT coefficients clustering and prediction. Additional features are selected based on a greedy stepwise without backtracking feature selection method. The results support the proposed method through low average square errors and little or no perceivable errors in the synthesized speech.
Erythropoietin Protects against Local Anesthetic Myotoxicity during Continuous Regional Analgesia

Background:Local anesthetics offer the benefits of extended analgesia with greater patient satisfaction and faster rehabilitation compared with intravenous morphine. These benefits, however, can be offset by adverse iatrogenic muscle pain caused by bupivacaine. Here, the authors describe the mechanisms of local anesthetic–induced myotoxicity and a partial protective effect of recombinant human erythropoietin (rhEPO). Methods:The authors developed a rat analgesia model with femoral nerve catheter and a cell culture model of human skeletal muscle myoblasts to study local anesthetic effects. Rats were randomly assigned to four different groups: daily intraperitoneal injection with 5,000 U/kg rhEPO or saline coupled to a perineural catheter injection with 1 ml/kg bupivacaine, 0.25%, or saline. In psoas rat muscle, oxygen consumption rates were measured using a Clark-type electrode in saponin-skinned fibers. Mitochondrial adenosine triphosphate synthesis rates were determined by bioluminescence. Enzymatic activity of mitochondrial respiratory chain complexes was measured on tissue homogenates using spectrophotometric procedures, and mitochondrial morphology was analyzed by transmission electron microscopy. In addition, the interaction between bupivacaine and rhEPO was investigated on human skeletal muscle myoblasts by fluorescence microscopy using mitotracker green and using the lipophilic cation JC-1. Results:Bupivacaine caused impairment of mitochondrial structure and bioenergetics in rats. Human myoblasts treated with bupivacaine showed a dose-dependent decrease in mitochondrial membrane potential associated with unusual morphologies. Impairment of mitochondrial bioenergetics was prevented partially by the use of rhEPO coadministered with bupivacaine. Conclusions:The authors demonstrated a dose- and time-dependent protective effect of rhEPO against bupivacaine-induced myotoxicity in regional analgesia.
Synchrophasor-Based Islanding Detection for Distributed Generation Systems Using Systematic Principal Component Analysis Approaches

Systematic principal component analysis (PCA) methods are presented in this paper for reliable islanding detection for power systems with significant penetration of distributed generations (DGs), where synchrophasors, recorded by phasor measurement units, are used for system monitoring. Existing islanding detection methods, such as rate-of-change-of-frequency and vector shift are fast for processing local information; however, with the growth in installed capacity of DGs, they suffer from several drawbacks. Incumbent genset islanding detection cannot distinguish a system-wide disturbance from an islanding event, leading to maloperation. The problem is even more significant when the grid does not have sufficient inertia to limit frequency divergences in the system fault/stress due to the high penetration of DGs. To tackle such problems, this paper introduces PCA methods for islanding detection. A simple control chart is established for intuitive visualization of the transients. A recursive PCA scheme is proposed as a reliable extension of the PCA method to reduce the false alarms for time-varying process. To further reduce the computational burden, the approximate linear dependence condition errors are calculated to update the associated PCA model. The proposed PCA and RPCA methods are verified by detecting abnormal transients occurring in the U.K. utility network.
ABLIM1 splicing is abnormal in skeletal muscle of patients with DM1 and regulated by MBNL, CELF and PTBP1

Myotonic dystrophy type 1 (DM1) is an RNA‐mediated disorder characterized by muscle weakness, cardiac defects and multiple symptoms and is caused by expanded CTG repeats within the 3′ untranslated region of the DMPK gene. In this study, we found abnormal splicing of actin‐binding LIM protein 1 (ABLIM1) in skeletal muscles of patients with DM1 and a DM1 mouse model (HSALR). An exon 11 inclusion isoform is expressed in skeletal muscle and heart of non‐DM1 individuals, but not in skeletal muscle of patients with DM1 or other adult human tissues. Moreover, we determined that ABLIM1 splicing is regulated by several splice factors, including MBNL family proteins, CELF1, 2 and 6, and PTBP1, using a cellular splicing assay. MBNL proteins promoted the inclusion of ABLIM1 exon 11, but other proteins and expanded CUG repeats repressed exon 11 of ABLIM1. This result is consistent with the hypothesis that MBNL proteins are trapped by expanded CUG repeats and inactivated in DM1 and that CELF1 is activated in DM1. However, activation of PTBP1 has not been reported in DM1. Our results suggest that the exon 11 inclusion isoform of ABLIM1 may have a muscle‐specific function, and its abnormal splicing could be related to muscle symptoms of DM1.
Effects of resistance versus endurance training on serum adiponectin and insulin resistance index.

PURPOSE The purpose of the present study was to investigate the effects of resistance and endurance training on serum adiponectin and insulin resistance index (SI) in healthy men. METHODS Twenty-four healthy males (age, 35-48 years) participated in the study. The subjects were randomly assigned to one of three groups: endurance training group (n=8), resistance training group (n=8) and control group (n=8). Blood samples were taken in fasting state from all subjects. The experimental groups performed either endurance or resistance training 3 days a week for 12 weeks. The endurance training programme included continuous running at an intensity corresponding to 75-85% of maximal heart rate, while resistance training consisted of four sets of circuit weight training for 11 stations and at an intensity corresponding to 50-60% of one-repetition maximum. The maximum numbers of repetitions in each station was 12. RESULTS There were significant negative correlations between serum adiponectin and body fat percentage, waist-to-hip ratio, body mass index and the insulin resistance index at baseline, whereas changes in response to training were not significantly correlated. Both endurance and resistance training resulted in a significant decrease in the SI in comparison with the control group. However, serum adiponectin did not change significantly in response to resistance and endurance training. CONCLUSION Endurance and resistance training caused an improvement in insulin resistance in healthy men, but this improvement was not accompanied by increased adiponectin levels.
Core Loss Estimation of Various Materials Magnetized With the Symmetrical/Asymmetrical Rectangular Voltage

Core losses were estimated for various magnetic core materials magnetized with a duty-cycle-changed symmetrical and asymmetrical rectangular voltage. Each voltage waveform is applied to a transformer and a dc reactor in a dc/dc converter, respectively. Core losses were measured for the four typical magnetic core materials often used in power electronics: 3% grain-oriented silicon steel sheet, 6.5% silicon steel sheet, amorphous material, and nanocrystalline material. Measurement results were evaluated by the loss separation model. An approximation method was proposed for the core loss magnetized with asymmetrical rectangular voltage that divides the total core loss into the core loss of the magnetization from -Bm to Bm and that of the magnetization from Bm to -Bm. This method was confirmed to approximate the core loss accurately except for silicon steel sheet in an extreme duty cycle condition. However, it was demonstrated experimentally that dc component of the magnetic field strength caused this error.
Probabilistic Obstacle Detection Using 2 1/2 D Terrain Maps

Navigating unstructured environments requires reliable perception that generates an appropriate world representation. This representation must encompass all types of impediments to traversal, whether they be insurmountable obstacles, or mobility inhibitors such as soft soil. Traditionally, traversability and obstacle avoidance have represented separate capabilities with individual rangefinders dedicated to each task. This paper presents a statistical technique that, through the analysis of the underlying 21/2 D terrain map, determines the probability of an obstacle. This integrated approach eliminates the need for multiple data sources and is applicable to range data from various sources, including laser rangefinders and stereo vision. The proposed obstacle detection technique has been tested in simulated environments and under real world conditions, and these experiments revealed that it accurately identifies obstacles.
WNK1-related Familial Hyperkalemic Hypertension results from an increased expression of L-WNK1 specifically in the distal nephron

Significance Hypertension, one of the most common morbidity factors worldwide, is caused mostly by a deregulation of salt transport by the kidney, but underlying mechanisms remain elusive. The serine-threonine kinase With No lysine (K) 1 (WNK1) has been identified as a regulator of ion transport in the distal nephron, because its mutations cause Familial Hyperkalemic Hypertension (FHHt), a rare form of human hypertension. We generated a mouse model of WNK1-FHHt that fully recapitulates the disease and studied changes in expression of the Na+ and K+ transporters and channels involved in the maintenance of a correct blood pressure. Our study provides insights into the mechanisms underlying the pathogenesis of WNK1-FHHt and further corroborates the importance of WNK1 in ion homeostasis and blood pressure. Large deletions in the first intron of the With No lysine (K) 1 (WNK1) gene are responsible for Familial Hyperkalemic Hypertension (FHHt), a rare form of human hypertension associated with hyperkalemia and hyperchloremic metabolic acidosis. We generated a mouse model of WNK1-associated FHHt to explore the consequences of this intronic deletion. WNK1+/FHHt mice display all clinical and biological signs of FHHt. This phenotype results from increased expression of long WNK1 (L-WNK1), the ubiquitous kinase isoform of WNK1, in the distal convoluted tubule, which in turn, stimulates the activity of the Na–Cl cotransporter. We also show that the activity of the epithelial sodium channel is not altered in FHHt mice, suggesting that other mechanisms are responsible for the hyperkalemia and acidosis in this model. Finally, we observe a decreased expression of the renal outer medullary potassium channel in the late distal convoluted tubule of WNK1+/FHHt mice, which could contribute to the hyperkalemia. In summary, our study provides insights into the in vivo mechanisms underlying the pathogenesis of WNK1-mediated FHHt and further corroborates the importance of WNK1 in ion homeostasis and blood pressure.
Teaching evidence-based medicine: Impact on students’ literature use and inpatient clinical documentation

Background: Effective teaching of evidence-based medicine (EBM) to medical students is important for lifelong self-directed learning. Aims: We implemented a brief workshop designed to teach literature searching skills to third-year medical students. We assessed its impact on students’ utilization of EBM resources during their clinical rotation and the quality of EBM integration in inpatient notes. Methods: We developed a physician-led, hands-on workshop to introduce EBM resources to all internal medicine clerks. Pre- and post-workshop measures included student's attitudes to EBM, citations of EBM resources in their clinical notes, and quality of the EBM component of the discussion in the note. Computer log analysis recorded students’ online search attempts. Results: After the workshop, students reported improved comfort using EBM and increased utilization of EBM resources. EBM integration into the discussion component of the notes also showed significant improvement. Computer log analysis of students’ searches demonstrated increased utilization of EBM resources following the workshop. Conclusions: We describe the successful implementation of a workshop designed to teach third-year medical students how to perform an efficient EBM literature search. We demonstrated improvements in students’ confidence regarding EBM, increased utilization of EBM resources, and improved integration of EBM into inpatient notes.
Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib

Lapatinib, a dual tyrosine kinase inhibitor of ErbB1 and ErbB2, shows a clinical benefit in a subset of patients with advanced urothelial bladder cancer (UBC). We hypothesized that the corresponding gene, ERBB2, is affected by mutations in a subset of UBC and that these mutations impact ErbB2 function, signaling, UBC proliferation, gene expression, and predict response to lapatinib. We found ERBB2 mutations in 5 of 33 UBC cell lines (15%), all of which were derived from invasive or high grade tumors. Phosphorylation and activation of ErbB2 and its downstream pathways were markedly enhanced in mutated cell lines compared with the ERBB2 wild-type. In addition, the gene expression profile was distinct, specifically for genes encoding for proteins of the extracellular matrix. RT112 cells infected with ERBB2 mutants showed a particular growth pattern (“mini-foci”). Upon treatment with lapatinib, 93% of these “mini-foci” were reversed. The sensitivity to lapatinib was greatest among cell lines with ERBB2 mutations. In conclusion, ERBB2 mutations occur in a subset of UBC and impact proliferation, signaling, gene expression and predict a greater response to lapatinib. If confirmed in the clinical setting, this may lead the way toward personalized treatment of a subset of UBC.
A Mathematical Model for Stability Analysis of a DC Distribution System for Power System Integration of Plug-In Electric Vehicles

This paper proposes a systematic method for developing a model of a dc distribution system, based on the configuration of the system. The dc distribution system is assumed to host electric vehicles and photovoltaic modules, using dc-dc converters, and to integrate them with an ac power grid. The developed model is of the matrix form and, therefore, can be readily expanded to represent a dc distribution system of any desired number of dc-dc converters. The model captures both the steady-state and dynamic characteristics of the system and includes port capacitors of the converters, as well as the interconnection cables. Thus, it can be used for identifying the condition for existence of a steady state, as well as for stability analysis. This paper further proposes an alternative set of characteristic equations that are less computationally intensive than the original matrix representation, for example, for online stability assessment tasks. The adequacy of the proposed model has been demonstrated through a number of case studies conducted and compared in the PSCAD/EMTDC and MATLAB software environments.
Space Robotics

In this second of three short papers, I introduce some of the basic concepts of space robotics with an emphasis on some specific challenging areas of research that are peculiar to the application of robotics to space infrastructure development. The style of these short papers is pedagogical and the concepts in this paper are developed from fundamental manipulator robotics. This second paper considers the application of space manipulators to on-orbit servicing (OOS), an application which has considerable commercial application. I provide some background to the notion of robotic on-orbit servicing and explore how manipulator control algorithms may be modified to accommodate space manipulators which operate in the micro-gravity of space.
Adverse Maternal and Birth Outcomes in Women Admitted to Hospital for Hyperemesis Gravidarum: a Population‐Based Cohort Study

BACKGROUND Evidence for risks of adverse maternal and birth outcomes in women with hyperemesis gravidarum (HG) is predominantly from small studies, unknown, or conflicting. METHODS A population-based cohort study using secondary health care records (Hospital Episode Statistics covering all of England from 1997 to 2012) was used to calculate odds ratios (OR) with 99% confidence intervals (CI) for the association between HG hospital admission and adverse outcomes, adjusting for maternal and pregnancy confounders. RESULTS Within 8 211 850 pregnancies ending in live births or stillbirths, women with HG had increased odds of anaemia (OR 1.28, 99% CI 1.23, 1.33), preeclampsia (OR 1.16, 99% CI 1.09, 1.22), eclampsia (OR 1.84, 99% CI 1.07, 3.18), venous thromboembolism antenatally (OR 1.94, 99% CI 1.57, 2.39 for deep vein thrombosis, and OR 2.54, 99% CI 1.89, 3.40 for pulmonary embolism) and post-partum. Odds of stillbirth (OR 0.77, 99% CI 0.66, 0.89) and post-term (OR 0.86, 99% CI 0.81, 0.92) delivery were decreased. Women were more likely to be induced (OR 1.20, 99% CI 1.16, 1.23), to deliver preterm (OR 1.11, 99% CI 1.05, 1.17), very preterm (OR 1.18, 99% CI 1.05, 1.32), or by caesarean section (OR 1.12, 99% CI 1.08, 1.16), to have low birthweight (OR 1.12, 99% CI 1.08, 1.17) or small for gestational age (OR 1.06, 99% CI 1.01, 1.11) babies and although absolute risks were small, their offspring were more likely to undergo resuscitation or neonatal intensive care. CONCLUSION HG may have important antenatal and postnatal consequences that should be considered in communications between health care professionals and women to best manage HG and prevent progression during pregnancy.