Resistive switching in ZrO2 films: physical mechanism for filament formation and dissolution

Resistive switching devices, also called memristors, have attracted much attention due to their potential memory, logic and even neuromorphic applications. Multiple physical mechanisms underpin the non-volatile switching process and are ultimately believed to give rise to the formation and dissolution of a discrete conductive filament within the active layer. However, a detailed nanoscopic analysis that fully explains all the contributory events remains to be presented. Here, we present aspects of the switching events that are correlated back to tunable details of the device fabrication process. Transmission electron microscopy and atomically resolved electron energy loss spectroscopy (EELS) studies of electrically stressed devices will then be presented, with a view to understanding the driving forces behind filament formation and dissolution

The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses

open access articlePolyphenols are secondary metabolites involved in a myriad of critical processes in plants. Over recent decades, special attention has been paid to the anti-oxidative role of fruit-derived polyphenols in the human diet, with evidence supporting the contribution of polyphenols in the prevention of numerous non-communicable disease outcomes. However, due to the low concentration in biological fluids in vivo, the antioxidant properties of polyphenols seem to be related to an enhanced endogenous antioxidant capacity induced via signaling through the nuclear respiratory factor 2 pathway. Polyphenols also seem to possess anti-inflammatory and antioxidant properties and have been shown to enhance vascular function via nitric oxide mediated mechanisms. Consequently, there is rationale to support fruit-derived polyphenol supplementation to enhance exercise performance, possibly via improved muscle perfusion. Fruit-derived polyphenol supplementation in exercise studies have included a variety of fruits, e.g., New Zealand blackcurrant, pomegranate, and cherry, in the form of extracts (multicomponent or purified), juices and infusions to varying degrees of benefit. For example, research has yet to link the health-related benefits of black elderberry (Sambucus nigra L.) ingestion to exercise performance in spite of the purported health benefits associated with black elderberry provision in vitro and in vivo models, which has been attributed to their high antioxidant capacity and polyphenol content. This review summarizes the existing evidence supporting a beneficial effect of fruit-derived polyphenols on various biological processes and outlines the potential for black elderberry ingestion to improve nitric oxide production, exercise performance, and the associated physiological responses before-, during- and post-exercise

Polarisation measurements with a CdTe pixel array detector for Laue hard X-ray focusing telescopes

Polarimetry is an area of high energy astrophysics which is still relatively unexplored, even though it is recognized that this type of measurement could drastically increase our knowledge of the physics and geometry of high energy sources. For this reason, in the context of the design of a Gamma-Ray Imager based on new hard-X and soft gamma ray focusing optics for the next ESA Cosmic Vision call for proposals (Cosmic Vision 2015-2025), it is important that this capability should be implemented in the principal on-board instrumentation. For the particular case of wide band-pass Laue optics we propose a focal plane based on a thick pixelated CdTe detector operating with high efficiency between 60-600 keV. The high segmentation of this type of detector (1-2 mm pixel size) and the good energy resolution (a few keV FWHM at 500 keV) will allow high sensitivity polarisation measurements (a few % for a 10 mCrab source in 106s) to be performed. We have evaluated the modulation Q factors and minimum detectable polarisation through the use of Monte Carlo simulations (based on the GEANT 4 toolkit) for on and off-axis sources with power law emission spectra using the point spread function of a Laue lens in a feasible configuration.Comment: 10 pages, 6 pages. Accepted for publication in Experimental Astronom

Human sperm ion channel (dys)function:implications for fertilization

BACKGROUND: Intensive research on sperm ion channels has identified members of several ion channel families in both mouse and human sperm. Gene knock-out studies have unequivocally demonstrated the importance of the calcium and potassium conductances in sperm for fertility. In both species, the calcium current is carried by the highly complex cation channel of sperm (CatSper). In mouse sperm, the potassium current has been conclusively shown to be carried by a channel consisting of the pore forming subunit SLO3 and auxiliary subunit leucine-rich repeat-containing 52 (LRRC52). However, in human sperm it is controversial whether the pore forming subunit of the channel is composed of SLO3 and/or SLO1. Deciphering the role of the proton-specific Hv1 channel is more challenging as it is only expressed in human sperm. However, definitive evidence for a role in, and importance for, human fertility can only be determined through studies using clinical samples.OBJECTIVE AND RATIONALE: This review aims to provide insight into the role of sperm ion channels in human fertilization as evidenced from recent studies of sperm from infertile men. We also summarize the key discoveries from mouse ion channel knock-out models and contrast the properties of mouse and human CatSper and potassium currents. We detail the evidence for, and consequences of, defective ion channels in human sperm and discuss hypotheses to explain how defects arise and why affected sperm have impaired fertilization potential.SEARCH METHODS: Relevant studies were identified using PubMed and were limited to ion channels that have been characterized in mouse and human sperm. Additional notable examples from other species are included as appropriate.OUTCOMES: There are now well-documented fundamental differences between the properties of CatSper and potassium channel currents in mouse and human sperm. However, in both species, sperm lacking either channel cannot fertilize in vivo and CatSper-null sperm also fail to fertilize at IVF. Sperm-lacking potassium currents are capable of fertilizing at IVF, albeit at a much lower rate. However, additional complex and heterogeneous ion channel dysfunction has been reported in sperm from infertile men, the causes of which are unknown. Similarly, the nature of the functional impairment of affected patient sperm remains elusive. There are no reports of studies of Hv1 in human sperm from infertile men.WIDER IMPLICATIONS: Recent studies using sperm from infertile men have given new insight and critical evidence supporting the supposition that calcium and potassium conductances are essential for human fertility. However, it should be highlighted that many fundamental questions remain regarding the nature of molecular and functional defects in sperm with dysfunctional ion channels. The development and application of advanced technologies remains a necessity to progress basic and clinical research in this area, with the aim of providing effective screening methodologies to identify and develop treatments for affected men in order to help prevent failed ART cycles. Conversely, development of drugs that block calcium and/or potassium conductances in sperm is a plausible strategy for producing sperm-specific contraceptives.</p

Manufacturing and testing of a magnetically suspended composite flywheel energy storage system

This paper presents the work performed to develop a multiring composite material flywheel and improvements of a magnetically suspended energy storage system. The flywheel is constructed of filament would graphite/epoxy and is interference assembled for better stress distribution to obtain higher speeds. The stationary stack in the center of the disk supports the flywheel with two magnetic bearings and provides power transfer to the flywheel with a motor/generator. The system operates under a 10(exp -4) torr environment and has been demonstrated to 20,000 rpm with a total stored energy of 15.9 Wh. When this flywheel cycles between its design speeds (45,000 to 90,000 rpm), it will deliver 242 Wh and have a usable specific energy density of 42.6 Wh/kg

Complex CatSper-dependent and independent [Ca2⁺]i signalling in human spermatozoa induced by follicular fluid

STUDY QUESTION: Does progesterone in human follicular fluid (hFF) activate CatSper and do other components of hFF modulate this effect and/or contribute separately to hFF-induced Ca2+ signaling?SUMMARY ANSWER: hFF potently stimulates CatSper and increases [Ca2+]i, primarily due to high concentrations of progesterone, however,other components of hFF also contribute to [Ca2+]i signaling, including modulation of CatSper channel activity and inhibition of [Ca2+]i oscillations.WHAT IS KNOWN ALREADY: CatSper, the principal Ca2+ channel in spermatozoa, is progesterone-sensitive and essential for fertility. Both hFF and progesterone, which is present in hFF, influence sperm function and increase their [Ca2+]i.STUDY DESIGN, SIZE, DURATION: This basic medical research study used semen samples from &gt;40 donors and hFF from &gt;50 patients who were undergoing surgical oocyte retrieval for IVF/ICSI.PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service REC1. Activities of CatSper and KSper were assessed by patch clamp electrophysiology. Sperm [Ca2+]i responses were examined in sperm populations and single cells. Computer-assisted sperm analysis (CASA) parameters and penetration into viscous media were used to assess functional effects.MAIN RESULTS AND THE ROLE OF CHANCE: hFF and progesterone significantly potentiated CatSper currents. Under quasiphysiologicalconditions, hFF (up to 50%) failed to alter membrane K+ conductance or current reversal potential. hFF and progesterone (at an equivalent concentration) stimulated similar biphasic [Ca2+]i signals both in sperm populations and single cells. At a high hFF concentration (10%), the sustained (plateau) component of the [Ca2+]i signal was consistently greater than that induced by progesterone alone. In single cell recordings, 1% hFF-induced [Ca2+]i oscillations similarly to progesterone but with 10% hFF generation of [Ca2+]i oscillations was suppressed. After treatment to ‘strip’ lipid-derived mediators, hFF failed to significantly stimulate CatSper currents but induced small [Ca2+]i responsesthat were greater than those induced by the equivalent concentration of progesterone after stripping. Similar [Ca2+]i responses were observed when sperm pretreated with 3 μM progesterone (to desensitize progesterone responses) were stimulated with hFF or stripped hFF. hFF stimulated viscous media penetration and was more effective than the equivalent does of progesterone.LARGE SCALE DATA: N/A.LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study. Caution must be taken when extrapolating these results in vivo.WIDER IMPLICATIONS OF THE FINDINGS: This study directly demonstrates that hFF activates CatSper and establishes that the biologically important effects of hFF reflect, at least in part, action on this channel, primarily via progesterone. However, these experiments also demonstrate that other components of hFF both contribute to the [Ca2+]i signal and modulate the activation of CatSper. Simple in vitro experiments performed out of the context of the complex in vivo environment need to be interpreted with caution

Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity

STUDY QUESTIONDoes a man (patient 1) with a previously described deficiency in principle cation channel of sperm (CatSper) function have a mutation in the CatSper-epsilon (CATSPERE) and/or CatSper-zeta (CATSPERZ) gene?SUMMARY ANSWERPatient 1 has a homozygous in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE.WHAT IS KNOWN ALREADYCatSper is the principal calcium channel of mammalian spermatozoa. Spermatozoa from patient 1 had a specific loss of CatSper function and were unable to fertilize at IVF. Loss of CatSper function could not be attributed to genetic abnormalities in coding regions of seven CatSper subunits. Two additional subunits (CatSper-epsilon (CATPSERE) and CatSper-zeta (CATSPERZ)) were recently identified, and are now proposed to contribute to the formation of the mature channel complex.STUDY DESIGN, SIZE, DURATIONThis was a basic medical research study analysing genomic data from a single patient (patient 1) for defects in CATSPERE and CATSPERZ.PARTICIPANTS/MATERIALS, SETTING, METHODSThe original exome sequencing data for patient 1 were analysed for mutations in CATSPERE and CATSPERZ. Sanger sequencing was conducted to confirm the presence of a rare variant.MAIN RESULTS AND THE ROLE OF CHANCEPatient 1 is homozygous for an in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE that is predicted to be highly deleterious.LIMITATIONS, REASONS FOR CAUTIONThe nature of the molecular deficit caused by the rs761237686 variant and whether it is exclusively responsible for the loss of CatSper function remain to be elucidated.WIDER IMPLICATIONS OF THE FINDINGSPopulation genetics are available for a significant number of predicted deleterious variants of CatSper subunits. The consequence of homozygous and compound heterozygous forms on sperm fertilization potential could be significant. Selective targeting of CatSper subunit expression maybe a feasible strategy for the development of novel contraceptives.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by project grants from the MRC (MR/K013343/1 and MR/012492/1), Chief Scientist Office/NHS research Scotland. This work was also supported by NIH R01GM111802, Pew Biomedical Scholars Award 00028642 and Packer Wentz Endowment Will to P.V.L. C.L.R.B is the editor-in-chief of Molecular Human Reproduction, has received lecturing fees from Merck and Ferring, and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016)

Single-cell analysis of [Ca²⁺]i signalling in sub-fertile men:characteristics and relation to fertilization outcome

STUDY QUESTIONWhat are the characteristics of progesterone-induced (CatSper-mediated) single cell [Ca2+]i signals in spermatozoa from sub-fertile men and how do they relate to fertilizing ability?SUMMARY ANSWERSingle cell analysis of progesterone-induced (CatSper-mediated) [Ca2+]i showed that reduced progesterone-sensitivity is a common feature of sperm from sub-fertile patients and is correlated with fertilization rate.WHAT IS KNOWN ALREADYStimulation with progesterone is a widely used method for assessing [Ca2+]i mobilization by activation of CatSper in human spermatozoa. Although data are limited, sperm population studies have indicated an association of poor [Ca2+]i response to progesterone with reduced fertilization ability.STUDY DESIGN, SIZE, DURATIONThis was a cohort study using semen samples from 21 donors and 101 patients attending the assisted conception unit at Ninewells Hospital Dundee who were undergoing ART treatment. Patients were recruited from January 2016 to June 2017.PARTICIPANTS/MATERIALS, SETTING, METHODSSemen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service (EoSRES) REC1. [Ca2+]i responses were examined by single cell imaging and motility parameters assessed by computer-assisted sperm analysis (CASA).MAIN RESULTS AND THE ROLE OF CHANCEFor analysis, patient samples were divided into three groups IVF(+ve) (successful fertilization; 62 samples), IVF-FF (failed fertilization; eight samples) and ICSI (21 samples). A further 10 IVF samples showed large, spontaneous [Ca2+]i oscillations and responses to progesterone could not be analysed. All patient samples loaded with the [Ca2+]i-indicator fluo4 responded to progesterone stimulation with a biphasic increase in fluorescence (transient followed by plateau) which resembled that seen in progesterone-stimulated donor samples. The mean normalized response (progesterone-induced increase in fluorescence normalized to resting level) was significantly smaller in IVF-FF and ICSI patient groups than in donors. All samples were further analysed by plotting, for each cell, the relationship between resting fluorescence intensity and the progesterone-induced fluorescence increment. In donor samples these plots overlaid closely and had a gradient of ≈ 2 and plots for most IVF(+ve) samples closely resembled the donor distribution. However, in a subset (≈ 10%) of IVF(+ve) samples, 3/8 IVF-FF samples and one-third of ICSI samples the gradient of the plot was significantly lower, indicating that the response to progesterone of the cells in these samples was abnormally small. Examination of the relationship between gradient (regression coefficient of the plot) in IVF samples and fertilization rate showed a positive correlation. In IVF-FF and ICSI groups, the proportion of cells in which a response to progesterone could be detected was significantly lower than in donors and IVF (+ve) patients. Approximately 20% of cells in donor, IVF(+ve) and ICSI samples generated [Ca2+]i oscillations when challenged with progesterone but in IVF-FF samples only ≈ 10% of cells generated oscillations and there was a significantly greater proportion of samples where no oscillations were observed. Levels of hyperactivated motility were lower in IVF(+ve) and IVF-FF groups compared to controls, IVF-FF also having lower levels than IVF(+ve).LIMITATIONS, REASONS FOR CAUTIONThis is an in vitro study and caution must be taken when extrapolating these results in vivo.WIDER IMPLICATIONS OF THE FINDINGSThis study reveals important details of impaired [Ca2+]i signalling in sperm from sub-fertile men that cannot be detected in population studies

The Measurement of Christian Workers’ Citizenship Behaviour in Contemporary Workplace in Kumasi, Ghana

The purpose of this study is to demonstrate an adaptation of organisational citizenship behaviour scale for measuring Christian workers’ behaviour. This study used self-reported questionnaire from 530 valid respondents for analysis. This technique is intended to improve organisational citizenship behaviour measurement and its extended practice among Christians whose faith requires them to do same. Two dimensions of organisational citizenship behaviour are important in the context of Christian workers in Kumasi. The Christian workers are found to exhibit citizenship behaviour in line with their faith. The research implication to this finding is that, other organisational citizenship behaviour scales should be applied on Christian workers to compare results. Also, same measurement method should be used on other faith workers and compare the results with this modified organisational citizenship behaviour measurement. Further research should be tested on other faith workers in abroad for in depth understanding of the construct. The practical implication of this study shows that, management of organisations can have better understanding of Christian workers’ behaviour at the work place, thereby improving the usefulness of the Christian faith at the work place. The current findings have provided valuable insights into organisational citizenship measurement in Ghana as given by Christian workers. Keywords: organisational citizenship behaviour, Christian workers, altruism, commitment, faith-work practice, measurement