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

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

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

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

Local Food Systems: Concepts, Impacts, and Issues

This comprehensive overview of local food systems explores alternative definitions of local food, estimates market size and reach, describes the characteristics of local consumers and producers, and examines early indications of the economic and health impacts of local food systems. There is no consensus on a definition of “local” or “local food systems” in terms of the geographic distance between production and consumption. But defining “local” based on marketing arrangements, such as farmers selling directly to consumers at regional farmers’ markets or to schools, is well recognized. Statistics suggest that local food markets account for a small, but growing, share of U.S. agricultural production. For smaller farms, direct marketing to consumers accounts for a higher percentage of their sales than for larger farms. Findings are mixed on the impact of local food systems on local economic development and better nutrition levels among consumers, and sparse literature is so far inconclusive about whether localization reduces energy use or greenhouse gas emissions.local food systems, farmers’ markets, direct-to-consumer marketing, direct-to-retail/ foodservice marketing, community supported agriculture, farm to school programs, Farmers’ Market Promotion Program, food miles, Community/Rural/Urban Development,

Cipher, A Polarimeter Telescope Concept for Hard X-Ray Astronomy

Abstract The polarisation of astrophysical source emission in the energy range from a few tens of keV up to the MeV region is an almost unexplored field of high-energy astrophysics. Till date, polarimetry in astrophysics–in the energy domain from hard X-rays up to soft ?-rays–has not been pursued due to the difficulties involved in obtaining sufficient sensitivity. Indeed for those few instruments that are capable of performing this type of measurement (e.g. the COMPTEL instrument on the Compton Gamma-ray Observatory and the IBIS instrument on INTEGRAL), polarimetry itself plays a secondary role in the mission objectives, as the efficiencies (0.5% and 10% maximum, respectively) and polarimetric Q factors (0.1 and 0.3, respectively) are relatively limited. In order to perform efficient polarimetric measurements for hard X-ray and soft gamma-ray sources, with an instrument of relatively robust and simple design, a CdTe based telescope (CIPHER: Coded Imager and Polarimeter for High Energy Radiation) is under study. This instrument is based on a thick (10 mm) CdTe position-sensitive spectrometer comprising four modules of 32 32 individual pixels, each with a surface area of 2 2 mm2 (about 160 cm2 total detection area). The polarimetric performance and design optimisation of the CIPHER detection surface have been studied by use of a Monte Carlo code. This detector, due to its intrinsic geometry, can allow efficient polarimetric measurements to be made between 100 keV and 1 MeV. In order to predict the polarimetric performance and to optimise the design and concept of the CIPHER detection plane, a Monte Carlo code based on GEANT4 library modules was developed to simulate the detector behaviour under a polarised photon flux. The Compton double event efficiency, as well bi-dimensional double event distribution maps and the corresponding polarimetric modulation factor will be presented and discussed. Modulation Q factors better than 0.50 and double event total efficiencies greater than 10% were calculated in the energy range between 100 keV and 1 MeV. Herein we will present and discuss the general problems that affect polarimetric measurements in space, such as the inclination of the source with respect to the telescope optical axis and background radiation. Q factor calculations for several beam inclinations as well as for background together with simulated astronomical sources will be presented and discussed

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P&lt; 0.02) with a large number of outliers (&gt;25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized