Miracle-dz/UniFAR-FTUs huggingface dataset:
EMD638683, a Novel SGK Inhibitor with Antihypertensive Potency

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is transcriptionally upregulated by mineralocorticoids and activated by insulin. The kinase enhances renal tubular Na+-reabsorption and accounts for blood pressure increase following high salt diet in mice made hyperinsulinemic by dietary fructose or fat. The present study describes the in vitro and in vivo efficacy of a novel SGK1 inhibitor (EMD638683). EMD638683 was tested in vitro by determination of SGK1-dependent phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1) in human cervical carcinoma HeLa-cells. In vivo EMD638683 (4460 ppm in chow, i.e. approx. 600 mg/kg/day) was administered to mice drinking tap water or isotonic saline containing 10% fructose. Blood pressure was determined by the tail cuff method, and urinary electrolyte (flame photometry) concentrations determined in metabolic cages. In vitro testing disclosed EMD638683 as a SGK1 inhibitor with an IC50 of 3 µM. Within 24 hours in vivo EMD638683 treatment significantly decreased blood pressure in fructose/saline-treated mice but not in control animals or in SGK1 knockout mice. EMD638683 failed to alter the blood pressure in SGK1 knockout mice. Following chronic (4 weeks) fructose/high salt treatment, additional EMD638683 treatment again decreased blood pressure. EMD638683 thus abrogates the salt sensitivity of blood pressure in hyperinsulinism without appreciably affecting blood pressure in the absence of hyperinsulinism. EMD638683 tended to increase fluid intake and urinary excretion of Na+, significantly increased urinary flow rate and significantly decreased body weight. Conclusion: EMD638683 could serve as a template for drugs counteracting hypertension in individuals with type II diabetes and metabolic syndrome.
Fatty acid patterns of film‐forming yeasts and new evidence for the heterogeneity of Pichia membranaefaciens

P. NORONHA‐DA‐COSTA, C. RODRIGUES, I. SPENCER‐MARTINS AND V. LOUREIRO. 1996. Total fatty acids (C14 : 0 to C18 : 3) of 50 strains assigned by classical identification methods to Pichia membranaefaciens (28), P. anomala (15), Dekkera anomala (2), D. bruxellensis (2) and Candida vini (3) were determined and data analysed by multivariate statistical procedures. Principal components cluster analysis defined six groups of strains. Thirteen strains of P. anomala formed a well‐defined cluster, whereas P. membranaefaciens was split into three groups. The taxonomic status of the P. membranaefaciens strains was evaluated by determination of the G+C content and DNA‐DNA hybridization. The results provided evidence in support of P. membranaefaciens encompassing distinct species. Only eight strains were certified as P. membranaefaciens and six were included in the same cluster, indicating that numerical analysis of fatty acid profiles points to genetic differences which remain undetectable by conventional phenotypic tests.
Evaluating and Improving the Depth Accuracy of Kinect for Windows v2

Microsoft Kinect sensor has been widely used in many applications since the launch of its first version. Recently, Microsoft released a new version of Kinect sensor with improved hardware. However, the accuracy assessment of the sensor remains to be answered. In this paper, we measure the depth accuracy of the newly released Kinect v2 depth sensor, and obtain a cone model to illustrate its accuracy distribution. We then evaluate the variance of the captured depth values by depth entropy. In addition, we propose a trilateration method to improve the depth accuracy with multiple Kinects simultaneously. The experimental results are provided to ascertain the proposed model and method.
Generalized multi-stage connection networks

This paper develops multi-stage connection networks in which each input terminal can be connected to any number of output terminals. Conditions are given such that these networks are strictly nonblocking or are rearrangeable. Rearrangement algorithms and upper bounds on the required number of moves are developed and it is shown that such networks have fewer cross-points than the product of input and output terminals for a sufficiently large number of input and output terminals.
Effect of transportation on lower respiratory tract contamination and peripheral blood neutrophil function.

OBJECTIVE To evaluate the effect of transportation on lower respiratory tract contamination and peripheral blood neutrophil function in horses and to compare results from transported horses with those obtained in earlier experiments from horses confined with heads elevated. DESIGN A prospective study. PROCEDURE Six horses were transported by road for 12 h. Clinical and haematological examination, transtracheal aspiration and cell function studies were conducted before and after transportation. Results obtained after transportation were compared to pre-transportation values. RESULTS After transportation, peripheral blood leucocyte and neutrophil numbers were increased and rectal temperatures were evaluated. Transtracheal aspirates showed an accumulation of purulent respiratory tract secretions with increased numbers of bacteria, particularly beta-haemolytic Streptococcus spp and members of the Pasteurellaceae family. Three horses also had increased numbers of bacteria from the Enterobacteriaceae family relative to corresponding samples from earlier studies. Phagocytosis by peripheral blood neutrophils was significantly reduced, while the oxidative burst activity of peripheral blood leucocytes was either unchanged or enhanced. CLINICAL IMPLICATIONS Bacterial contamination of the lower respiratory tract occurs as a routine consequence of transportation of horses and is likely to be an important determinant in the development of transport-associated respiratory disease. Inflammatory airway secretions and increased numbers of bacteria were rapidly cleared, without clinical evidence of significant pulmonary disease and without additional treatment, in normal horses that were allowed to lower their heads after transportation. Peripheral blood neutrophilia and a reduction in neutrophil phagocytic function were evident for at least 36 h after transportation, suggesting that horses may require a number of days to recover from the stress of transportation. As the potential role of bacteria from the Enterobacteriaceae family in the development of transport-associated respiratory disease has not been elucidated, horses which develop clinical disease following transportation should undergo thorough bacteriological investigation to ensure appropriate treatment.
A survey of larval digeneans in the commonest intertidal snails from Northern Patagonian coast, Argentina

Over a two-years period, a survey was carried out in order to increase the knowledge of digeneans parasitising the commonest intertidal gastropods on the Patagonian coast, Southwestern Atlantic Ocean. A total of 4,725 gastropods were examined. Six species of digenean parasitising four snail species were found; four of them were registered for first time: Maritrema sp. 1 (Microphallidae) in Crepidula dilatata (Calyptraeidae), Parorchis sp. (Philophtalmidae) and sporocyst of Renicolidae in Trophon geversianus (Muricidae), and Diphterostomum sp. (Zoogonidae) in Buccinanops globulosus (Nassariidae). Two other species were found in Siphonaria lessoni (Siphonariidae): Maritrema sp. 2 and Hemiuridae. One snail species, Tegula patagonica (Trochidae) was not parasitised. These gastropods act as first intermediate host, and C. dilatata, S. lessoni and B. globulosus also frequently host metacercariae within the sporocyst. Overall prevalences varied from 0.16% of Diphterostomum in the intertidal population of B. globulosus to 33.45% of Maritrema sp. 1 in C. dilatata.
Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome.

The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients.
Coupled-Wave Theory for Square-Lattice Photonic Crystal Lasers With TE Polarization

We present a coupled-wave analysis for square-lattice photonic crystal lasers with transverse electric polarization. A model consisting of eight plane waves coupled by Bragg diffraction is used to describe two-dimensional optical coupling. The resonant frequencies and threshold criteria for the modes of oscillation have been determined for the case of index periodicity with a lattice of circular holes. The spatial intensity distributions of these resonant modes have also been calculated. For the fundamental modes, we have investigated how the intensity distribution varies as a function of coupling strength. The dependence of the threshold gain of these modes on hole size has also been elucidated. This semianalytical approach provides a comprehensive understanding of square-lattice photonic crystal lasers and allows more effective optimization of their cavity design.
ATTENTIONAL BIAS FOR ALCOHOL CUES IN SOCIAL DRINKERS WHO DRINK TO COPE MATT FIELD

Aims: To investigate the effects of stress on alcohol craving and attentional bias for alcohol-related cues in a group of heavy social drinkers. Method: Forty-four heavy social drinkers were exposed to either a laboratory stressor task or a control manipulation before completing a questionnaire measure of alcohol craving and a visual probe task which measured attentional bias for alcohol-related cues. Participants were subdivided into those with high and low levels of coping motives for drinking. Results: Compared to a control manipulation, the laboratory stressor task produced increases in alcohol craving (P < 0.01). The laboratory stressor task also produced a significant attentional bias for alcohol-related cues, but only among participants who had high levels of coping motives (P < 0.05). Conclusions: Findings are broadly consistent with contemporary negative reinforcement models of substance abuse, and with models of subjective craving and attentional biases for substance-related cues.
Sex determination and gender expression: Reproductive investment in snails

Sex determination is generally seen as an issue of importance for separate‐sexed organisms; however, when considering other sexual systems, such as hermaphroditism, sex allocation is a less‐binary form of sex determination. As illustrated here, with examples from molluscs, this different vantage point can offer important evolutionary insights. After all, males and females produce only one type of gamete, whereas hermaphrodites produce both. In addition, sperm and accessory gland products are donated bidirectionally. For reciprocal mating, this is obvious since sperm are exchanged within one mating interaction; but even unilaterally mating species end up mating in both sexual roles, albeit not simultaneously. With this in mind, I highlight two factors that play an important role in how reproductive investment is divided in snails: First, the individual's motivation to preferentially donate rather than receive sperm (or vice versa) leads to flexible behavioral performance, and thereby investment, of either sex. Second, due to the presence of both sexual roles within the same individual, partners are potentially able to influence investment in both sexual functions of their partner to their own benefit. The latter has already led to novel insights into how accessory gland products may evolve. Moreover, the current evidence points towards different ways in which allocation to reproduction can be changed in simultaneous hermaphrodites. These often differ from the separate‐sexed situation, highlighting that comparison across different sexual systems may help identify commonalities and differences in physiological, and molecular mechanisms as well as evolutionary patterns. Mol. Reprod. Dev. 84: 132–143, 2017. © 2016 Wiley Periodicals, Inc.
Families of children with Down syndrome: What we know and what we need to know

This paper provides a brief overview of what is currently known about families of children with Down syndrome. In addition, it highlights a number of issues that require further research if we are to have a thorough understanding of the impact of a child with Down syndrome on families as a system and on the individuals who make up that system. Some of these issues include the need for: 1) a more balanced perspective – one that acknowledges both positive and negative aspects of the experience, 2) greater attention to the experiences of fathers, 3) more cross-cultural research and studies focused on cultural perspectives, 4) increased attention to the change in demands for families as the individual with Down syndrome ages, 5) more longitudinal studies, 6) greater variety in methodological approaches, for example greater use of qualitative approaches and observational methods, and 7) an increase in the use of statistical approaches that model change and test hypotheses about predictors of change in both parents and children.
Performance of the LAI-2000 plant canopy analyzer in estimating leaf area index of some Scots pine stands.

The LAI-2000 plant canopy analyzer (Li-Cor, Inc., Lincoln, NE) was tested at six experimental plots of Scots pine (Pinus sylvestris L.) in central Sweden at peak leaf area in August and after litterfall in October 1990. An independent estimate of leaf area index for August 1990 was obtained based on an empirically derived regression of needle area on stem sapwood area, and the decrease in leaf area between the two measurements was estimated from measurements of litterfall. A strong linear relationship was found between estimates by the LAI-2000 (L(Li-Cor)) and the indirect estimates of leaf area index (taken as half of total surface area) (L). The finding that L(Li-Cor) was considerably smaller than L was explained theoretically. It was shown that if shoots, instead of individual needles, are randomly distributed in the canopy, L(Li-Cor) corresponds to L multiplied by a factor (beta) characterizing the mutual shading of needles on the shoot. The shading factor, beta, was equal to the ratio of spherically projected shoot area to spherically projected needle area, where the spherically projected area is defined as the average projection (silhouette) area taken over all directions in space. The quantity betaL was defined as the shoot silhouette area index (SSAI), and an equation for the relationship between SSAI and the mean silhouette to total area ratio (mean STAR) of shoots was derived. Measured values of mean STAR for Scots pine indicated that L(Li-Cor) corresponds to SSAI rather than L. However, the decrease in leaf area index due to litterfall occurring between August and October was only partly detected by the LAI-2000, possibly because SSAI did not change to the same degree as L, i.e., there was an increase in the factor beta. This hypothesis is supported by data showing a large increase in mean STAR with shoot age.
An impact based frequency up-conversion mechanism for low frequency vibration energy harvesting

This paper presents a new mechanism for achieving frequency up-conversion in low frequency vibrational energy harvesting device, utilising the contact interaction between an end-stop and a cantilever beam. A mechanical model of the mechanism has been developed for simulation and a prototype device was fabricated to demonstrate the effect experimentally. Simulation showed an increase in the oscillation frequency of the cantilever mass by a factor of 12.5 from an excitation of 4Hz, while the peak-peak displacement was limited to 2.2mm. Frequency was increased by a factor 10 using the prototype device under similar conditions.
A Review of Innovation Diffusion Theories and Mechanisms

Many innovation studies focus on adoption behaviors at the individual and organizational level, while studies examine innovation adoption at the community and population level is relatively limited. These studies, focusing on the diffusion of an innovation across organizations, are important as they illustrate the dynamics of adoption behaviors in a broader context of socio-political factors. In this review study, we examine three prominent diffusion theories: classic diffusion theory, institutional diffusion theory, and cognitive-institutional diffusion theory. We identify the underlying diffusion mechanism in each theory. Future research is needed to show how these diffusion mechanisms interact in creating various diffusion patterns.
Tyrosine Phosphorylation of Cortactin Associated with Syk Accompanies Thromboxane Analogue-induced Platelet Shape Change*

Thromboxane A2(TxA2) is a potent vasoconstrictor and platelet agonist. Pharmacological studies have defined two classes of thromboxane receptors (TPs) in human platelets; sites that bind the agonist 1S-(1,2(5Z),3-(1E,3S),4)-7- 3-(3-hydroxy-4-(4′-iodophenoxy)-1-butenyl)-7-oxabicyclo-2.2. 1-heptan-2-yl-5-heptenoic acid (I-BOP) with high affinity support platelet shape change, whereas low affinity sites that bind irreversibly the antagonist GR 32191 transduce platelet aggregation. As the mechanisms of signal transduction involved in platelet aggregation begin to be elucidated, few results concern those involved in platelet shape change, which is independent of the engagement of GPIIb/IIIa. To elucidate the respective role of the two classes of pharmacological binding sites of TPs in shape change, platelets were incubated with I-BOP at low concentrations or stimulated by I-BOP at high concentrations after pretreatment with GR 32191 or activated with low concentrations of 8-epi-prostaglandin F2α. Under these three conditions, there is a rapid stimulation of protein tyrosine phosphorylation of the 80/85-kDa doublet identified as the cytoskeletal protein cortactin. Tyrosine phosphorylation of cortactin is kinetically correlated with the occurrence of shape change. These biochemical and morphological events are both inhibited by SQ 29548, a TP antagonist, indicating the specificity of the signal. Since tyrosine kinase Syk was activated early during platelet activation, we examined the possibility that cortactin is a potential substrate of Syk in TxA2-induced platelet shape change. p72 Syk phosphorylation and kinase activity took place during the period when platelets were changing shape upon low concentrations of I-BOP stimulation. Furthermore, cortactin was associated with Syk, and this association increases along with the level of phosphorylation. These data suggest a novel pathway for a G protein-coupled TxA2high affinity receptor to the protein-tyrosine kinase Syk, which is associated with cortactin in the very early steps of platelet activation.
Children's Protective Services and Law Enforcement: Fostering Partnerships in Investigations of Child Abuse

ABSTRACT Although collaboration in child abuse investigations has been emphasized since 1974, barriers, including role conflicts and organizational differences, have often been reported. This study describes the process of collaboration based on the perceptions of investigators working with a Child Advocacy Center. Telephone interviews were conducted with 290 child protective service workers and law enforcement officers from 28 child advocacy centers in 20 different states. Respondents identified barriers to the process of collaboration such as conflicts over case control and facilitators including co-housing and cross-training. Conditions that should contribute to successful collaboration are discussed.
Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer.

PURPOSE The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. PATIENTS AND METHODS We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. RESULTS Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P = .0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm. CONCLUSION TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.