798 research outputs found

    Can hydrodynamic contact line paradox be solved by evaporation--condensation?

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    We investigate a possibility to regularize the hydrodynamic contact line singularity in the configuration of partial wetting (liquid wedge on a solid substrate) via evaporation-condensation, when an inert gas is present in the atmosphere above the liquid. The no-slip condition is imposed at the solid-liquid interface and the system is assumed to be isothermal. The mass exchange dynamics is controlled by vapor diffusion in the inert gas and interfacial kinetic resistance. The coupling between the liquid meniscus curvature and mass exchange is provided by the Kelvin effect. The atmosphere is saturated and the substrate moves at a steady velocity with respect to the liquid wedge. A multi-scale analysis is performed. The liquid dynamics description in the phase-change-controlled microregion and visco-capillary intermediate region is based on the lubrication equations. The vapor diffusion is considered in the gas phase. It is shown that from the mathematical point of view, the phase exchange relieves the contact line singularity. The liquid mass is conserved: evaporation existing on a part of the meniscus and condensation occurring over another part compensate exactly each other. However, numerical estimations carried out for three common fluids (ethanol, water and glycerol) at the ambient conditions show that the characteristic length scales are tiny

    A Longitudinal Examination of the Hopelessness Theory of Depression in People Who Have Multiple Sclerosis.

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    PURPOSE: Hopelessness theory predicts that negative attributional style will interact with negative life events over time to predict depression. The intention of this study was to test this in a population who are at greater risk of negative life events, people with Multiple Sclerosis (MS). METHOD: Data, including measures of attributional style, negative life events, and depressive symptoms, were collected via postal survey in 3 phases, each one a year apart. RESULTS: Responses were received from over 380 participants at each study phase. Negative attributional style was consistently able to predict future depressive symptoms at low to moderate levels of association; however, this ability was not sustained when depressive symptoms at Phase 1 were controlled for. No substantial evidence to support the hypothesised interaction of negative attributional style and negative life events was found. CONCLUSIONS: Findings were not supportive of the causal interaction proposed by the hopelessness theory of depression. Further work considering other time frames, using methods to prime attributional style before assessment and specifically assessing the hopelessness subtype of depression, may prove to be more fruitful. Intervention directly to address attributional style should also be considered

    Didactic Situations and Didactical Engineering in university mathematics: cases from the study of Calculus and proof

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    This paper discusses the use of the Theory of Didactic Situations (TDS) at university level, paying special attention to the constraints and specificities of its use at this level. We begin by presenting the origins and main tenets of this approach, and discuss how these tenets are used towards the design of Didactical Engineering (DE), particularly adapted at the tertiary level. We then illustrate the potency of the TDS-DE approach in three university level Research Cases, two related to Calculus, and one related to proof. These studies deploy constructs such as didactic contract, milieu, didactic variables, and epistemological analyses, among others, to design Situations at university level. We conclude with a few thoughts on how the TDS-DE approach relates to other approaches, most notably the Anthropological Theory of the Didactic

    A Longitudinal Examination of the Hopelessness Theory of Depression in People Who Have Multiple Sclerosis.

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    PURPOSE: Hopelessness theory predicts that negative attributional style will interact with negative life events over time to predict depression. The intention of this study was to test this in a population who are at greater risk of negative life events, people with Multiple Sclerosis (MS). METHOD: Data, including measures of attributional style, negative life events, and depressive symptoms, were collected via postal survey in 3 phases, each one a year apart. RESULTS: Responses were received from over 380 participants at each study phase. Negative attributional style was consistently able to predict future depressive symptoms at low to moderate levels of association; however, this ability was not sustained when depressive symptoms at Phase 1 were controlled for. No substantial evidence to support the hypothesised interaction of negative attributional style and negative life events was found. CONCLUSIONS: Findings were not supportive of the causal interaction proposed by the hopelessness theory of depression. Further work considering other time frames, using methods to prime attributional style before assessment and specifically assessing the hopelessness subtype of depression, may prove to be more fruitful. Intervention directly to address attributional style should also be considered

    The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm

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    The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration ([Ca2+]i) and plays an essential role in sperm function. It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput screening (HTS) assay to measure changes in [Ca2+]i in human sperm and screened 1,280 approved and off-patent drugs including 90 steroids from the Prestwick chemical library. More than half of the steroids tested (53%) induced an increase in [Ca2+]i and reduced the P4-induced Ca2+ influx in human sperm in a dose-dependent manner. Ten of the most potent steroids (activating and P4-inhibiting) were selected for a detailed analysis of their action on CatSper and their ability to act on sperm acrosome reaction (AR) and penetration in viscous media. We found that these steroids show an inhibitory effect on P4 but not on prostaglandin E1-induced CatSper activation, suggesting that they compete for the same binding site as P4. Pregnenolone, dydrogesterone, epiandrosterone, nandrolone, and dehydroepiandrosterone acetate (DHEA) were found to activate CatSper at physiologically relevant concentrations within the nanomolar range. Like P4, most tested steroids did not significantly affect the AR while stanozolol and estropipate slightly increased sperm penetration into viscous medium. Furthermore, using a hybrid approach integrating pharmacophore analysis and statistical modelling, we were able to screen in silico for steroids that can activate the channel and define the physicochemical and structural properties required for a steroid to exhibit agonist activity against CatSper. Overall, our results indicate that not only physiological but also synthetic steroids can modulate the activity of CatSper with varying potency and if bound to CatSper prior to P4, could impair the timely CatSper activation necessary for proper fertilization to occur

    Identification of Pigment Epithelium-Derived Factor Protein Forms with Distinct Activities on Tumor Cell Lines

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    Purpose. Pigment epithelium-derived factor (PEDF) is a multifunctional serpin. The purpose of this study is to identify PEDF protein forms and investigate their biological activities on tumor cell lines. Methods. Recombinant human PEDF proteins were purified by cation- and anion-exchange column chromatography. They were subjected to SDS-PAGE, IEF, deglycosylation, heparin affinity chromatography, and limited proteolysis. Cell viability, real-time electrical impedance of cells, and wound healing assays were performed using bladder and breast cancer cell lines, rat retinal R28, and human ARPE-19 cells. Results. Two PEDF protein peaks were identified after anion-exchange column chromatography: PEDF-1 eluting with lower ionic strength than PEDF-2. PEDF-1 had higher pI value and lower apparent molecular weight than PEDF-2. Both PEDF forms were glycosylated, bound to heparin, and had identical patterns by limited proteolysis. However, PEDF-2 emerged as being highly potent in lowering cell viability in all tumor cell lines tested, and in inhibiting tumor and ARPE-19 cell migration. In contrast, PEDF-1 minimally affected tumor cell viability and cell migration but protected R28 cells against death caused by serum starvation. Conclusion. Two distinct biochemical forms of PEDF varying in overall charge have distinct biological effects on tumor cell viability and migration. The existence of PEDF forms may explain the multifunctional modality of PEDF

    A New Type of Electron Nuclear-Spin Interaction from Resistively Detected NMR in the Fractional Quantum Hall Effect Regime

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    Two dimensional electron gases in narrow GaAs quantum wells show huge longitudinal resistance (HLR) values at certain fractional filling factors. Applying an RF field with frequencies corresponding to the nuclear spin splittings of {69}Ga, {71}Ga and {75}As leads to a substantial decreases of the HLR establishing a novel type of resistively detected NMR. These resonances are split into four sub lines each. Neither the number of sub lines nor the size of the splitting can be explained by established interaction mechanisms.Comment: 4 pages, 3 figure

    Inhibition of Expression in Escherichia coli of a Virulence Regulator MglB of Francisella tularensis Using External Guide Sequence Technology

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    External guide sequences (EGSs) have successfully been used to inhibit expression of target genes at the post-transcriptional level in both prokaryotes and eukaryotes. We previously reported that EGS accessible and cleavable sites in the target RNAs can rapidly be identified by screening random EGS (rEGS) libraries. Here the method of screening rEGS libraries and a partial RNase T1 digestion assay were used to identify sites accessible to EGSs in the mRNA of a global virulence regulator MglB from Francisella tularensis, a Gram-negative pathogenic bacterium. Specific EGSs were subsequently designed and their activities in terms of the cleavage of mglB mRNA by RNase P were tested in vitro and in vivo. EGS73, EGS148, and EGS155 in both stem and M1 EGS constructs induced mglB mRNA cleavage in vitro. Expression of stem EGS73 and EGS155 in Escherichia coli resulted in significant reduction of the mglB mRNA level coded for the F. tularensis mglB gene inserted in those cells

    Novel associations in disorders of sex development: findings from the I-DSD registry

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    Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt
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