Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Modified‐release (MR) zolpidem was developed to maintain effective plasma concentrations during the 3‐ to 6‐hour post‐dosage interval, corresponding to the middle portion of the typical sleep interval. Modified‐release zolpidem (12.5 mg), standard immediate‐release (IR) zolpidem (10 mg), and placebo were compared in a double‐blind, single‐dose, 3‐way crossover daytime study of healthy volunteers (n = 70 completers). Effect areas for electroencephalographic β amplitude during 0 to 8 hours and 3 to 6 hours after dosage were greater for MR compared to IR (P <.001). The digit‐symbol substitution test and sedation rating scales behaved similarly. MR and IR did not differ in effects at 8 hours post‐dosage nor in half‐life or clearance. Time of peak plasma concentration (tmax) was significantly longer for MR (2.4 vs 2.0 hours, P <.004), and dose‐normalized peak plasma concentration (Cmax) was lower (12.2 vs 14.0 ng/mL/mg, P <.001). MR zolpidem also had greater area under the plasma concentration curve (AUC) during the 3‐ to 6‐hour interval (P <.001). Thus, MR zolpidem produces sustained plasma levels compared to IR, with resulting enhancement of pharmacodynamic effects in the 3‐ to 6‐hour post‐dosage interval.
Using radioligand‐binding assays to measure tissue transglutaminase autoantibodies in young children

Aim: To measure autoantibodies against tissue transglutaminase (tTG) in young children prospectively screened for coeliac disease (CD). Methods: In total, 652 children aged 2.9 (2.5–4.2) y were analysed for IgA‐tTG and IgG‐tTG with radioligand‐binding assays and IgA endomysial antibodies (EMA) by indirect immunofluorescence. Antibody‐positive children were retested after 1.2 (range 0.2–1.9) y. Intestinal biopsy was performed on children with persistently high antibody levels. Results: In total, 3.2% (95% CI: 1.9–4.6%) of the 652 children were positive for at least one antibody at baseline: 2.5% (95% CI: 1.3–3.7%) for IgA‐tTG, 1.7% (95% CI: 0.7–2.7%) for IgG‐tTG and 2.9% (95% CI: 1.6–4.2%) for IgA‐EMA, respectively. Ten children were positive for all three antibodies, five for both IgA‐tTG and EMA, four for EMA only, one for IgA‐tTG and another for IgG‐tTG. IgA‐EMA titres correlated with IgA‐tTG levels (r= 0.73, p= 0.0003). At follow‐up, seven of 20 children remained positive for all three antibodies, three for IgA‐tTG only, one for both IgA‐tTG and EMA, one for IgA‐tTG and IgG‐tTG, and the remaining child refused further participation. Three biopsies showed villous atrophy, two increased intraepithelial lymphocytes and two normal findings. Biopsy was not performed in four children with low or declining tTG antibody levels at follow‐up and in one child who declined. CD was evident in 0.5% (95% CI: 0.0–1.0%) (3/652).
On nonnegative garrote estimator in a linear regression model

In a bit line driver for MOS memory units of a microcomputer, which is connected between a pair of complementary bit lines and provided with an equalizing MOS transistor, a pair of active-load MOS transistors and a pair of clamping MOS transistors are connected separately to the complementary bit lines, and further the area of the clamping MOS transistors is determined to be about three times greater than that of the active-load transistors. An increase in the area of the clamping MOS transistors serves to decrease the internal resistance thereof, so that the clamping operation can be improved. A decrease in area of the active-load MOS transistor serves to increase the internal resistance, so that the access time can be improved. In addition, the driver can operate stably in response to a low power clock pulse.
Structures and distributions in morphology learning

One of the great challenges in linguistics and cognitive science is to understand the nature of the mental representation of language. The precise mechanisms of the mind are unknown, but can be modeled through observation and experimentation. By viewing the mind as a computational device that receives input (primary linguistic data) and produces output (the development of grammatical speech) during language acquisition, one can reason about what representations and algorithms must be internal to the learner. In this thesis, I investigate the acquisition of morphology. The principal challenges are how to learn a theory in the presence of sparse data, and in a manner that can provide explanations for the developmental processes in child language acquisition. The main idea underlying this work is that a consideration of the different aspects of language acquisition places strong constraints on cognitively plausible representations and algorithms that are internal to the learner. To develop a model of morphology acquisition, I pursue three lines of work: First, I formulate a cognitively-oriented computational framework for studying language acquisition that consists of four components: the linguistic representation, the statistical distribution of the input data, the observed behavior of the human learner, and the performance of the learning algorithm. All four components and their interactions are important for understanding language acquisition. Second, I examine the statistical distributions of morphology in naturally occurring corpora and discuss their implications for acquisition and theories of morphology. The Zipfian distribution of morphological inflections favors a rule-based model of morphology, where rules are learned one at a time by relating them to the morphological base. This provides an explanation of children's incremental acquisition of morphology. Third, to provide empirical support for this theory of acquisition, I implement unsupervised algorithms for the induction of morphology and lexical categories from text corpora. A rule-based model of morphology called the base-and-transforms model is learned, which consists of lexical categories, morphological base forms, and rules that convert base forms to other inflections. Morphological base forms play an important role in bootstrapping the acquisition of morphological relations, and simplify lexical category induction through distributional analysis.
Sedimentation of Bacillus sphaericus in tap water and sewage water.

Formulations of Bacillus sphaericus products were applied in 1-m columns of clean water and sewage water in tubes. Samples taken through valves attached to the walls of the tubes showed that spores settled as a function of application method, droplet size, particle size, and water characteristics. In a mixture of deionized and tap water, the slowest sedimentation rate was obtained with a primary powder sonicated in water with 0.1% detergent. This product and a commercial fluid product settled faster in sewage water than in clean water and after 4 weeks, most spores were found in the sediment. In clean water, most spores remained suspended during the 4 weeks but the density was highest at the bottom. Calculation of total spore numbers in the columns after 4 weeks indicated that about 90% of spores disappeared in clean water, and 95-97% disappeared in sewage water. Bioassays showed that toxicity declined in parallel with the sedimentation, but at a higher rate, indicating a loss of toxicity from the residual spores.
Light‐activated nanofibre textiles exert antibacterial effects in the setting of chronic wound healing

The maintenance of an aseptic environment for chronic wounds is one of the most challenging tasks in the wound‐healing process. Furthermore, the emergence of antibiotic‐resistant bacterial strains is on the rise, rendering conventional treatments less effective. A new antibacterial material consisting of a polyurethane Tecophilic™ nanofibre textile (NT) that was prepared by electrospinning and doped by a tetraphenylporphyrin (TPP) photosensitizer activated by visible light was tested for use in wound beds and bandages. In vitro experiments were performed to assess the antibacterial activity of the textile against three bacterial strains. Furthermore, the new textile was tested in 162 patients with chronic leg ulcers. A complete inhibition of in vitro growth of the three tested bacterial strains was observed on the surface of NTs that had been illuminated with visible light and was clinically demonstrated in 89 patients with leg ulcers. The application of the textiles resulted in a 35% decrease in wound size, as assessed via computer‐aided wound tracing. Wound‐related pain, which was estimated using a visual analogue scale, was reduced by 71%. The results of this trial reveal that the photoinactivation of bacteria through the photosensitized generation of short‐lived, highly reactive singlet oxygen O2(1Δg) results in relatively superficial antibacterial effects in comparison with standard antiseptic treatment options. Thus, such treatment does not interfere with the normal healing process. This method therefore represents a suitable alternative to the use of topical antibiotics and antiseptics and demonstrates potentially broad applications in medicine.
A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice

Peptidic mimics of the gut hormone glucagon-like peptide (GLP) 1, exemplified by the recently approved drug exenatide, show promise as therapies for type 2 diabetes. Such “incretin mimetics” regulate glucose appearance in the plasma and can restore glucose-stimulated insulin secretion without excess risk of hypoglycemia. The need for injection, which may limit the use of peptidic GLP-1 receptor (GLP-1R) agonists, has driven largely unsuccessful efforts to find smaller molecules. The failure to identify orally effective agonists has instead promoted the indirect approach of inhibiting the GLP-1-degrading enzyme dipeptidyl peptidase IV. Here we report a nonpeptidic GLP-1R agonist with sufficient activity to evoke effects in whole animals, including antidiabetic efficacy in db/db mice. Two substituted cyclobutanes (S4P and Boc5) were developed after screening a compound library against a cell line stably cotransfected with GLP-1R and a cAMP-responsive reporter. Each bound to GLP-1R and increased intracellular cAMP. Agonist effects were blocked by the GLP-1R antagonist exendin(9–39). Boc5 amplified glucose-stimulated insulin secretion in isolated rat islets. Both i.p. and oral administration of Boc5 dose-dependently inhibited food intake in mice, an effect that could be blocked by pretreatment with exendin(9–39). Daily injections of Boc5 into db/db mice reduced HbA1c to nondiabetic values, an effect not observed in ad libitum-fed or pair-fed diabetic controls. Thus, Boc5 behaved as a full GLP-1 mimetic in vitro and in vivo. The chemical genus represented by Boc5 may prompt the exploration of orally available GLP-1R agonists with potential utility in diabetes and obesity.
The Relation between Personality Traits, Social Support and Traumatic Stress

This study examines the relationship between the Big Five personality traits, social support and traumatic stress symptoms in the context of secondary exposure to traumatic life events. Moreover, we examine if emotional and informational social support moderate the relation between personality traits and all the three dimensions of traumatic stress – intrusions, avoidance, and arousal. A sample of 162 nurses and physicians participated in this study and completed self-reports measuring neuroticism, extraversion, agreeability, openness, conscientiousness, social support, and symptoms of secondary traumatic stress. The results revealed positive associations between neuroticism and all the symptoms of traumatic stress, while extraversion, agreeability, openness, and conscientiousness negatively correlated with intrusions, avoidance, and arousal. Moreover, emotional and informational social support moderates the relation between extraversion, openness and traumatic stress symptoms. These findings are discussed from the perspective of the resilient value of personality traits and the importance of perceiving support in promoting emotional adjustment, for persons indirectly exposed to traumatic events.
Chymotrypsin effects on the determination of sperm parameters and seminal biochemistry markers

Abstract Background: Few reports of the effects of treatment with chymotrypsin on the determination of sperm parameters and seminal biochemistry markers are documented. Methods: Sperm parameters of 63 liquefied and 27 non-liquefied samples, untreated or treated with chymotrypsin, were evaluated using computer-assisted semen analysis. In addition, biochemistry markers such as γ-glutamyltranspeptidase, α-glucosidase and fructose in 50 liquefied and 39 non-liquefied samples, untreated or treated with chymotrypsin, were determined. Results: Treatment with chymotrypsin had no effect on sperm concentration, motility, motility a and b, straightness, curvilinear velocity, straight line velocity, average path velocity and beat cross frequency in both liquefied and non-liquefied semen. However, linearity (p=0.025) decreased and the amplitude of the lateral head (p=0.029) increased significantly in non-liquefied semen after treatment with chymotrypsin. The levels of γ-glutamyltranspeptidase, α-glucosidase and fructose in seminal plasma were unaffected by chymotrypsin, regardless of liquefaction status. Conclusions: Chymotrypsin had no effects on the detection of sperm parameters and biochemistry markers, and could be used to treat non-liquefied samples before semen analysis in the andrology laboratory. Clin Chem Lab Med 2006;44:1335–9.
Closing the Gap Between Strategy and Execution

Many markets are affected by the complex interactions of multiple variables: geopolitics, technical innovation, capital market swings, competitive dynamics, shifting consumer preferences and so on. These volatile markets throw out a steady stream of opportunities and threats, and managers can neither predict nor control the form, magnitude or timing of future events with accuracy. In such environments, the traditional linear view of strategy ? plan then execute ? is woefully inadequate because it hinders people from incorporating new information into action. But instead of thinking of strategy as a linear process, why not consider it as inherently iterative ? a loop instead of a line? According to this view, every strategy is a work in progress that is subject to revision in light of ongoing interactions between the organization and its shifting environment. To accommodate those interactions, the strategy loop consists of four major steps: making sense of a situation, making choices on what to do (and what not to do), making those things happen and making revisions based on new information. Reconceptualizing strategy as an iterative loop is simple enough, but putting that new mindset into practice is not. Here, the crucial thing to remember is that discussions ? formal and informal, short and long, one-on-one and in groups ? are the key mechanism for coordinating activity inside a company. Thus, to put the strategy loop into practice, managers at every level in the organization must be proficient at leading discussions that reflect the four major steps (making sense, making choices, making things happen and making revisions). Companies such as Diageo Ireland, All America Latina Logistica and Onset Venture Services demonstrate that each of the four types of discussions has a different objective that requires a specific tone, supporting information, leadership traits and accompanying tactics.
Sensitive and Specific Detection of Staphylococcal Epidermolysins A and B in Broth Cultures by Flow Cytometry-Assisted Multiplex Immunoassay

ABSTRACT Two of the most common bacterial skin infections of young infants and children are bullous impetigo due to Staphylococcus aureus and its more acute form, staphylococcal scalded skin syndrome. Epidermolysin A (ETA), ETB and, possibly, ETD are responsible for these diseases, which may appear as epidemics in pediatric patients. We tested the reliability of a flow cytometry-assisted multiplex immunoassay (Bio-Plex system) for the detection of ETA and ETB. The Bio-Plex system was found to be highly specific and highly sensitive for toxin concentrations of between 2 and 80,000 pg/ml. The results of this assay were 100% identical to the results of a PCR-based method. We demonstrated that this test did not generate any cross-reactions with ETD-producing isolates. The level of detection of ETB by this test differed according to culture conditions and from isolate to isolate; these results must be taken into account for diagnostic purposes.
S-Palmitoylation of Junctional Adhesion Molecule C Regulates Its Tight Junction Localization and Cell Migration*

Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. JAM-C has been implicated in leukocyte transendothelial migration, angiogenesis, cell adhesion, cell polarity, spermatogenesis, and metastasis. Here, we show that JAM-C undergoes S-palmitoylation on two juxtamembrane cysteine residues, Cys-264 and Cys-265. We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmitoyltransferases (DHHCs). Ectopic expression of DHHC7, but not a DHHC7 catalytic mutant, enhances JAM-C S-palmitoylation. Moreover, DHHC7 knockdown decreases the S-palmitoylation level of JAM-C. Palmitoylation of JAM-C promotes its localization to tight junctions and inhibits transwell migration of A549 lung cancer cells. These results suggest that S-palmitoylation of JAM-C can be potentially targeted to control cancer metastasis.
Musculocontractural Ehlers‐Danlos Syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan‐4‐sulfotransferase 1 encoding CHST14 gene

We present clinical and molecular findings of three patients with an EDS VIB phenotype from two consanguineous families. The clinical findings of EDS kyphoscoliotic type (EDS type VIA and B) comprise kyphoscoliosis, muscular hypotonia, hyperextensible, thin and bruisable skin, atrophic scarring, joint hypermobility and variable ocular involvement. Distinct craniofacial abnormalities, joint contractures, wrinkled palms, and normal urinary pyridinoline ratios distinguish EDS VIB from EDS VIA. A genome‐wide SNP scan and sequence analyses identified a homozygous frameshift mutation (NM_130468.2:c.145delG, NP_569735.1:p.Val49*) in CHST14, encoding dermatan‐4‐sulfotransferase 1 (D4ST‐1), in two Turkish siblings. Subsequent sequence analysis of CHST14 identified a homozygous 20‐bp duplication (NM_130468.2:c.981_1000dup, NP_569735.1:p.Glu334Glyfs*107) in an Indian patient. Loss‐of‐function mutations in CHST14 were recently reported in adducted thumb–clubfoot syndrome (ATCS). Patients with ATCS present similar craniofacial and musculoskeletal features as the EDS VIB patients reported here, but lack the severe skin manifestations. By identifying an identical mutation in patients with EDS VIB and ATCS, we show that both conditions form a phenotypic continuum. Our findings confirm that the EDS‐variant associated with CHST14 mutations forms a clinical spectrum, which we propose to coin as “musculocontractural EDS” and which results from a defect in dermatan sulfate biosynthesis, perturbing collagen assembly.
Optimization in High Dimensions via Accelerated, Parallel, and Proximal Coordinate Descent

We propose a new randomized coordinate descent method for minimizing the sum of convex functions, each of which depends on a small number of coordinates only. Our method (APPROX) is simultaneously Accelerated, Parallel, and PROXimal; this is the first time such a method has been proposed. In the special case when the number of processors is equal to the number of coordinates, the method converges at the rate $2\bar{\omega}\bar{L} R^2/(k+1)^2 $, where $k$ is the iteration counter, $\bar{\omega}$ is a data-weighted average degree of separability of the loss function, $\bar{L}$ is the average of Lipschitz constants associated with the coordinates and individual functions in the sum, and $R$ is the distance of the initial point from the minimizer. We show that the method can be implemented without the need to perform full-dimensional vector operations, which is the major bottleneck of accelerated coordinate descent, rendering it impractical. The fact that the method depends on the average degree of separabili.
Membrane-associated prostaglandin E synthase-1 is required for neuropathic pain

It is widely accepted that prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid and plays an important role in inflammatory pain. However whether PGE2 is involved in neuropathic pain remains unknown. PGE2 is produced from arachidonic acid via PGH2 by at least three PGE synthases (PGES), cytosolic PGES (cPGES), and membrane-associated PGES (mPGES)-1 and -2. In the present study, to clarify the involvement of PGE2 and identify PGES mediating neuropathic pain, we applied a neuropathic pain model prepared by L5 spinal nerve transection to mPGES-1 knockout (mPGES-1−/−) mice. Whereas they retained normal nociceptive responses, mPGES-1−/− mice did not exhibit mechanical allodynia and thermal hyperalgesia over a week. These results demonstrate that PGE2 produced by mPGES-1 is involved in neuropathic pain.
Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative

BACKGROUND Public Law 102-321 established a block grant for adults with "serious mental illness" (SMI) and required the Substance Abuse and Mental Health Services Administration (SAMHSA) to develop a method to estimate the prevalence of SMI. METHODS Three SMI screening scales were developed for possible use in the SAMHSA National Household Survey on Drug Abuse: the Composite International Diagnostic Interview Short-Form (CIDI-SF) scale, the K10/K6 nonspecific distress scales, and the World Health Organization Disability Assessment Schedule (WHO-DAS). An enriched convenience sample of 155 respondents was administered all screening scales followed by the 12-month Structured Clinical Interview for DSM-IV and the Global Assessment of Functioning (GAF). We defined SMI as any 12-month DSM-IV disorder, other than a substance use disorder, with a GAF score of less than 60. RESULTS All screening scales were significantly related to SMI. However, neither the CIDI-SF nor the WHO-DAS improved prediction significantly over the K10 or K6 scales. The area under the receiver operating characteristic curve of SMI was 0.854 for K10 and 0.865 for K6. The most efficient screening scale, K6, had a sensitivity (SE) of 0.36 (0.08) and a specificity of 0.96 (0.02) in predicting SMI. CONCLUSIONS The brevity and accuracy of the K6 and K10 scales make them attractive screens for SMI. Routine inclusion of either scale in clinical studies would create an important, and heretofore missing, crosswalk between community and clinical epidemiology.