Miracle-dz/UniFAR-FTUs huggingface dataset:
Unusual Effects of a QT-Prolonging Drug, Arsenic Trioxide, on Cardiac Potassium Currents

Background—Cases of QT prolongation, torsades de pointes, and sudden death have been reported with arsenic trioxide (As2O3), a highly effective agent for acute promyelocytic leukemia. In this study, we evaluated the effects of As2O3 on repolarizing cardiac ion currents. Methods and Results—In HERG- or KCNQ1+KCNE1-transfected CHO cells (n=32; total), As2O3 caused concentration-dependent block of both IKr and IKs, with an IC50 for tail current block of 0.14±0.01 &mgr;mol/L for IKr and 1.13±0.06 &mgr;mol/L for IKs. In contrast to other QT-prolonging drugs, As2O3 also activated a time-independent current that additional experiments identified as IK-ATP. Conclusions—As2O3 blocks both IKr and IKs at clinically relevant concentrations. On the other hand, it also activates IK-ATP, which maintains normal repolarization. We infer that variability in the extent of QT interval prolongation and onset of ventricular arrhythmias during arsenic therapy represents competing effects to block and activate multiple repolarizing potassium currents.
A neural approach to adaptive behavior and multi-sensor action selection in a mobile device

Sampling multisensory information and taking the appropriate motor action is critical for a biological organism's survival, but a difficult task for robots. We present a Neurally Organized Mobile Adaptive Device (NOMAD), whose behavior is controlled by a simulated nervous system based on the anatomy and physiology of the vertebrate brain, that is capable of action selection in a real world environment. NOMAD's nervous system consists of an auditory system, a visual system, a taste system, sets of motor neurons capable of triggering behavior, a tracking system driven by visual stimuli, and a value system. The device itself, which moves autonomously, has a CCD camera for vision, microphones for hearing, and a gripper manipulator to pick up and taste objects by measuring the object's conductivity. Similar to a biological organism, NOMAD learns to categorize sensory information from its environment with no prior instruction, associate positive and negative value with this sensory information, and then learn to select the appropriate motor actions. We suggest that this neurobiological approach to action selection may be generalized to other robot systems.
Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval (8 months vs. ≤ 8 months) from initial diagnosis to first recurrence and reponse to chemotherapy had a tendency for a longer survival duration after relapse by univariate analysis. Multivariate analysis revealed that progressive response to chemotherapy (P = 0.002, HR = 4.6) and recurrence within the previously irradiated field (P = 0.04, HR = 2.7) were significant independent prognostic factors for a shorter time to progression after recurrence. Furthermore, advanced stage at presentation (P = 0.001, HR = 3.0) and a short disease-free interval after primary treatment (<8 months, P = 0.003, HR = 3.4) were determined as independent prognostic factors with a significant negative influence on progression-free survival and overall survival from initial diagnosis, respectively. The use of toxic and expensive combinations for the treatment of recurrent cervical cancer patients should be well balanced against potential hazards. Based on our data, less toxic regimens would be more feasible in patients who present with advanced disease at initial diagnosis, or those that experience recurrence within the previously irradiated field after a progression-free interval of less than 8 months.
Deviant sex ratio associated with segregation distortion in Drosophila melanogaster.

S I N C E segregation distorter (symbolized SD) was discovered in a natural population of Drosophila melanogater, extensive studies on this element were carried out at the University of Wisconsin, and the results were reported in a series of studies under a general title of “Meiotic drive in natural populations of Drosophila melanogaster” ( SANDLER, HIRAIZUMI and SANDLER 1959; SANDLER and HIRAIZUMI 1959, 1960a, b; HIRAIZUMI, SANDLER and CROW 1960; SANDLER and HIRAIZUMI 1961a, b; MANGE 1961; SANDLER 1962; CROW, THOMAS and SANDLER 1962). For the convenience of the readers, the main conclusions from these studies relevant to the present study will be briefly given below. 1. SD is a locus located on the right arm of chromosome 2, close to the centromere. When SD/SD+ heterozygous males are mated to the standard, normal females, SD is recovered, in the F, generation of this mating, in a great excess over its theoretical frequency of 50%; often 90% or more SD are recovered. Throughout the present study, the value of k is defined as the proportion of recovery of SD in the F, generation of the above mating. Thus, when the segregation is normal, k = 0.5 and if distortion is complete, k = 1. 2. Segregation distortion occurs only in the SD heterozygous males, but not in the SD homozygous males nor in females, 3. Segregation distortion is due to some sort of misreplication (formally equivalent to a chromosome breakage) of the SD+-bearing chromosome, conditioned by SD. 4. At. or near, the tip of the right arm of chromosome 2, there is a stabilizer of SD [symbolized St(SD) 1. In the presence of St(SD), the SD action is stable and the segregation ratio is constantly high (often the k value is 0.95 or more) ; in the absence of St(SD), the distorting effect of SD becomes somewhat variable resulting in a reduced value of k (usually 0.80 or more). 5. The SD region consists of at least two elements. One of these is the SD locus itself which causes the “misreplication” of SD+. Closely linked to, and to the right of SD, there is an activator of SD [symbolized Ac(SD)] , which, in coupling with SD. is necessary for SD to operate. Both SD and Ac(SD) are located within a small chromosomal aberration, presumably duplication o r insertion, which itself is immune to, or unbreakable by, SD. Later on, however, several studies were carried out in other laboratories and,
Prognostic Implication of Adrenocortical Response during the Course of Critical Illness

Background Critical illness-related corticosteroid insufficiency (CIRCI) and adrenocorticotropic hormone (ACTH)-cortisol dissociation are hormonal conditions frequently observed in patients in the intensive care unit (ICU). The aim of this study was to evaluate the association between ACTH-cortisol dissociation and clinical outcomes of critically ill patients. Methods We retrospectively reviewed the medical records of 94 ICU patients who underwent two rapid cosyntropin tests during hospital admission and compared the clinical aspects of patients with and without ACTH-cortisol dissociation. ACTH-cortisol dissociation was defined as plasma ACTH and serum cortisol concentrations of <22 pmol/L and >600 nmol/L, respectively. Results Dissociation was present in 30 of the 94 patients (31.9%). Patients with ACTH-cortisol dissociation in the initial test had significantly higher hospital mortality rate than those in the control group (55% vs. 25.7%, P=0.013) There was no difference in hospital mortality between patients classified as having CIRCI and those who were not. In multivariate adjusted Cox regression analysis, the mortality risk was higher in the group with ACTH-cortisol dissociation (hazard ratio, 2.98; 95% confidence interval, 1.34 to 6.63; P=0.007). Patients with dissociation in two consecutive stimulation tests showed the highest hospital mortality rate among groups classified according to stimulation test results (100% vs. 31.3%). Conclusions The hospital mortality was higher in ICU patients diagnosed with ACTH-cortisol dissociation. It is clinically feasible to evaluate the presence of ACTH-cortisol dissociation by analyzing rapid ACTH stimulation test results in critically ill patients.
University of North Carolina caries risk assessment study. III. Multiple factors in caries prevalence.

The baseline caries experienced of approximately 5,000 children in South Carolina and Maine was used as the dependent variable in caries risk assessment analyses. Clinical, microbiologic, and demographic factors served as independent variables in a multivariate relationship to caries through regression and discriminant function analyses. Four factors--number of dental visits by the child in the past year, presence of white spot lesions, and both the urgency of need for restorative care and the future caries increment predicted by the examiner--associated significantly and consistently with caries prevalence in primary and permanent teeth of first and fifth graders at both study sites. Several factors associated significantly with caries prevalence at only one site or grade within a site, suggesting that wide applicability of a specific caries risk assessment model may be limited. In these analyses, sensitivity ranged from . 60 to . 72 and specificity varied from . 86 to . 91 in the four grade-site groups. The ultimate goal of this longitudinal study is to identify highly caries-prone children in time to prevent the occurrence of a future caries increment. Although the lack of consistent association of many variables, including microbiologic factors, with baseline caries prevalence was unexpected, it is expected that some of these variables will contribute predictive power in the prospective study.
Unique Expression Patterns of Cell Fate Molecules Delineate Sequential Stages of Dentate Gyrus Development

The dentate gyrus of the hippocampus is uniquely organized with a displaced proliferative zone that continues to generate dentate granule cells throughout life. We have analyzed the expression of Notch receptors, Notch ligands, and basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine whether the need to maintain a pool of undifferentiated precursors is reflected in the patterns of expression of these genes. Many of these genes are expressed diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in the rat, just preceding the migration of newly born granule cells and dentate precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells. Two days later, at the time of migration of the first granule cells and dentate precursor cells, cells expressing Mash1 are seen in the migratory route from the subventricular zone to the developing dentate gyrus. Newly born granule cells expressing NeuroD are also present in this migratory pathway. In the first postnatal week, precursor cells expressing Mash1 reside in the dentate hilus, and by the third postnatal week they have largely taken up their final position in the subgranular zone along the hilar side of the dentate granule cell layer. After terminal differentiation, granule cells born in the hilus or the subgranular zone begin to express NeuroD followed by NeuroD2. This study establishes that the expression patterns of bHLH mRNAs evolve during the formation of the dentate gyrus, and the precursor cells resident in the mature dentate gyrus share features with precursor cells found in development. Thus, many of the same mechanisms that are known to regulate cell fate and precursor pool size in other brain regions are likely to be operative in the dentate gyrus at all stages of development.
A New Phase Speciation Leaching Procedure for the Determination of Metals in Oxic and Anoxic Sediments

A NEW PHASE SPECIATION LEACHING PROCEDURE FOR THE DETERMINATION OF METALS IN OXIC AND ANOXIC SEDIMENTS Brandon R. Gipson Old Dominion University, 2012 Director: Dr. Gregory A. Cutter Toxic trace elements such as cadmium, lead, chromium, and arsenic released by human activities can accumulate in marine and estuarine sediments, where these metals are often sequestered until local environmental changes (e.g., redox, salinity, and/or pH) allow these elements to be reintroduced into the food web. In order to assess the extent of toxic trace element contamination in sediment, numerous leaching schemes have been developed that separate sediment-bound trace metals into operationally defined geochemical phases. These "phase speciation" leaching schemes are typically designed with the purpose of being used on either oxic or anoxic sediments. However, natural sediments often contain prominent redox boundaries; therefore, it is useful to develop a single phase speciation leaching scheme which can be used on both oxic and anoxic sediments. A six step leaching scheme was developed in order to separate sediment-bound trace elements into five operationally defined phases: exchangeable, oxide, acid volatile sulfide (AVS), organic, and pyrite. The efficacy of five of the six leaching steps (oxide, AVS, organic #1 and #2, and pyrite) was evaluated using standard reference sediments (NIST 2702 and BCR-701) and actual sediment samples. Overall, the results show that the six step leaching process compared well with other frequently utilized phase speciation leaching schemes ("Tessier" and "optimized BCR"). With the exception of some surface sediment oxides carrying over into the AVS phase, the leach AVS and pyrite results compared well with H2S generation sediment sulfide analysis methods. The organic phase extractions were about three times more effective (-60% removal efficiency) at removing labile organic material (e.g., proteins and humic and fulvic acids) in sediment than refractory organics (e.g., protokerogens) (~20% removal efficiency). The six step leach method was applied to bulk sediments obtained from three estuaries with differing geochemical environments (salinity and sediment C and S concentrations). The sediment phase speciation results for the major (Fe, Mn, and Ca) and trace metals (Cd, Pb, Cr, and As) of interest are similar to those reported by other workers for similar environments, with the majority of the trace metals being located in the oxide and organic
How a Firm's Competitive Environment and Digital Strategic Posture Influence Digital Business Strategy

In this paper, we examine how the competitive industry environment shapes the way that digital strategic posture (defined as a focal firm's degree of engagement in a particular class of digital business practices relative to the industry norm) influences firms' realized digital business strategy. We focus on two forms of digital strategy: general IT investment and IT outsourcing investment. Drawing from prior literature on determinants of IT activity and competitive dynamics, we argue that three elements of the industry environment determine whether digital strategic posture has an increasingly convergent or divergent influence on digital business strategy. By divergent influence, we mean an influence that leads to spending substantially more or less on a particular strategic activity than industry norms. We predict that a digital strategic posture (difference from the industry mean) has an increasingly divergent effect on digital business strategy under higher industry turbulence, while having an increasingly convergent effect on digital business strategy under higher industry concentration and higher industry growth. The study uses archival data for 400 U.S.-based firms from 1999 to 2006. Our findings imply that digital business strategy is not solely a matter of optimizing firm operations internally or of responding to one or two focal competitors, but also arises strikingly from awareness and responsiveness to the digital business competitive environment. Collectively, the findings provide insights on how strategic posture and industry environment influence firms' digital business strategy.
Distribution and Antimicrobial Susceptibility Pattern of Bacterial Pathogens Causing Urinary Tract Infection in Urban Community of Meerut City, India

Urinary tract infection is one of the common infections in the Indian community. Distribution and susceptibility of UTI-causing pathogens change according to time and place. This study was conducted to determine the distribution and antimicrobial susceptibility of uropathogens in the Indian community as well as to determine the effect of gender and age on the etiology of bacterial uropathogens. Clean catch midstream urine samples were collected from 288 patients of the age ranging from 15 to ≥48 years. Antimicrobial susceptibility was performed on all isolated bacteria by Kirby Bauer's disc diffusion method. The multiple antibiotic resistance (MAR) index of each antibiotic was calculated. The UTI prevalence was 53.82% in patients; however, the prevalence was significantly higher in females than in males (females: 73.57%; males: 35.14%; P = 0.000). Females within the age group of 26–36 years and elderly males of ≥48 years showed higher prevalence of UTI. Gram negative bacteria (90.32%) were found in high prevalence than Gram positive (9.68%). Escherichia coli (42.58%) was the most prevalent gram negative isolate. Nitrofurantoin (78.71%) was found the most resistant drug among all uropathogens. Tested carbapenems were found the most susceptible drug against isolated uropathogens which showed 92.26% and 84.52% susceptibility, respectively.
Structural Alterations of Microvascular Smooth Muscle Cells in Reduced Renal Mass Hypertension

Loss of microvessels (anatomic rarefaction) occurs in chronic reduced renal mass (RRM) hypertension and is mediated via structural degeneration of vascular smooth muscle (VSM) and endothelial cells. The purpose of the present study was to determine if structural changes occur in VSM cells of the microvessels that remain in the tissue of rats with chronic RRM hypertension. Samples of cremaster muscles were taken from normotensive control rats and rats with acute (3-7 days) and chronic (14-28 days) RRM hypertension (75% reduction in kidney mass with 4% NaCl loading). The samples were fixed in situ and processed for light and electron microscopy. Ultrastnictural morphology of VSM cells in terminal artenoles of control animals was normal. Although VSM morphology in many microvessels of RRM hypertensive rats was also normal, some vessels exhibited structural changes that were not present in artenoles of the normotensive animals. The most striking change was the appearance of more extensive dense bodies anchoring the contractile filaments around the outer membrane of the cells. Extreme vasoconstriction was observed in some artenoles of RRM rats as long as 2 weeks after salt loading. Focal areas of VSM cell proliferation were evident Many of the changes occurring in RRM were detected as early as 1 week after the onset of hypertension. These observations suggest that renal mass reduction-salt loading hypertension is associated with early structural and functional changes in the VSM cells.
Coordinate interaction between ATP-sensitive K+ channel and Na+, K+-ATPase modulates ischemic preconditioning.

BACKGROUND We reported that digoxin abolishes the infarct size (IS)-limiting effect of ischemic preconditioning (IPC). Because ATP-sensitive K+ (KATP) channels are involved in IPC, we studied whether Na+,K+-ATPase and KATP channels functionally interact, thereby modulating IPC. METHODS AND RESULTS Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC was elicited by 5 minutes of occlusion followed by 10 minutes of reperfusion. The IS, expressed as a percentage of the area at risk, was 40.2+/-2.8% in control and 39.8+/-5.0% in digoxin pretreatment rabbits. Both IPC and pretreatment with cromakalim, a KATP channel opener, reduced IS to 11.8+/-1.8% and 13.4+/-2.6% (P<0. 05 versus control). Digoxin abolished the reduction in IS induced by IPC (33.5+/-3.3%), whereas it did not change that induced by cromakalim (18.8+/-3.0%). In patch-clamp experiments, digoxin was found to inhibit the opening of KATP channels in single ventricular myocytes in which ATP depletion had been induced by metabolic stress. In contrast, digoxin had little effect on the channel opening induced by cromakalim. Moreover, the inhibitory action of digoxin on channel activities was dependent on subsarcolemmal ATP concentration. CONCLUSIONS The IS-limiting effect of IPC is modulated by an interaction between KATP channels and Na+,K+-ATPase through subsarcolemmal ATP.
Antidepressant activity of Ceratonia siliqua L. fruit extract, a source of polyphenols

A previous study from our laboratory has shown the facilitatory effect of Ceratonia siliqua L. (Fabaceae) on the dopaminergic function. This study investigates the involvement of monoamines in the antidepressant activity of the total polyphenol content of Ceratonia siliqua extract (CS) in mice using a tail suspension test (TST) and forced swim test (FST). The immobility time in the TST and FST were significantly reduced by CS (25 and 50 mg kg−1, i.p.). The extract considerably attenuated the duration of immobility induced by prazosin (62.5 µg kg−1, i.p., an α-adrenoceptor antagonist) and eticlopride (0.1 µg kg−1, i.p., a classical D2-like dopamine receptor antagonist) in both TST and FST, whereas the extract could not modify the immobility in mice treated with p-chlorophenylalanine (100 mg kg−1, i.p., ×3 days; an inhibitor of serotonin synthesis) and baclofen (10 mg kg−1, i.p., GABAB agonist). This suggests that the antidepressant effect of CS is mediated by dopamine and noradrenaline.
FPGA Implementation of Boolean Neural Networks using UML

This paper suggests a new approach for modeling of Boolean neural networks on field-programmable gate arrays (FPGAs) using UML. The presented Boolean neural networks (BNN) allow a decreasing of the required number of configurable logic blocks (CLB) for the realizing of Boolean neuron. The element of BNN, called Boolean neuron, may be mapped directly to lookup table (LUT) and configurable logic block (CLB) of FPGAs. Our approach solves digital design problems especially with respect of the performance and gate count. In the examples through paper we describe the UML model of the BNN, its transformation, and the mapping to FPGAs.
Effects of 6-month, Multimodal Exercise Program on Clinical and Gait Parameters of Patients with Idiopathic Parkinson's Disease: A Pilot Study

This pilot study aimed to identify the effects of a 6-month, multimodal exercise program on clinical and gait parameters in patients with Parkinson's disease. Two groups of participants were enrolled in the study: Trained Group (TG) and Control Group (CG). Individuals in the TG exercised three times a week for 24 weeks (in a multimodal exercise program), while the CG participants maintained their regular activity level. Participants in both the TG and the CG were assessed at pre- and posttest by clinical rates and the spatiotemporal parameters of self-paced walking. The two groups were not significantly different in demographic, clinical, and gait data at baseline. There were no significant differences between groups for clinical data at posttest. The purposed multimodal exercise program has found improvement in some kinematic gait parameters for the TG. Further study in the form of randomized controlled trial would be required to establish effectiveness of the intervention.