Decomposing labeled interval orders as pairs of permutations

We introduce ballot matrices, a signed combinatorial structure whose definition naturally follows from the generating function for labeled interval orders. A sign reversing involution on ballot matrices is defined. We show that matrices fixed under this involution are in bijection with labeled interval orders and that they decompose to a pair consisting of a permutation and an inversion table. To fully classify such pairs, results pertaining to the enumeration of permutations having a given set of ascent bottoms are given. This allows for a new formula for the number of labeled interval orders

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< 0.02) with a large number of outliers (>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

Development of a rapid, antimicrobial susceptibility test for E. coli based on low-cost, screen-printed electrodes

Antibiotic resistance has been cited by the World Health Organisation (WHO) as one of the greatest threats to public health. Mitigating the spread of antibiotic resistance requires a multipronged approach with possible interventions including faster diagnostic testing and enhanced antibiotic stewardship. This study employs a low-cost diagnostic sensor test to rapidly pinpoint the correct antibiotic for treatment of infection. The sensor comprises a screen-printed gold electrode, modified with an antibiotic-seeded hydrogel to monitor bacterial growth. Electrochemical growth profiles of the common microorganism, Escherichia coli (E. coli) (ATCC 25922) were measured in the presence and absence of the antibiotic streptomycin. Results show a clear distinction between the E. coli growth profiles depending on whether streptomycin is present, in a timeframe of ≈2.5 h (p < 0.05), significantly quicker than the current gold standard of culture-based antimicrobial susceptibility testing. These results demonstrate a clear pathway to a low cost, phenotypic and reproducible antibiotic susceptibility testing technology for the rapid detection of E. coli within clinically relevant concentration ranges for conditions such as urinary tract infections

Processing of alcohol-related health threat in at-risk drinkers: an online study of gender-related self-affirmation effects

Aims: Defensiveness in response to threatening health information related to excessive alcohol consumption prevents appropriate behaviour change. Alternatively, self-affirmation may improve cognitive-affective processing of threatening information, thus contributing to successful self-regulation. Methods: Effects of an online self-affirmation procedure were examined in at-risk university student drinkers. Participants were randomly assigned to a self-affirmation (writing about personally relevant values) or control task (writing about values relevant to another person) prior to presentation of alcohol-related threatening information. Assessment of prosocial feelings (e.g. ‘love’) after the task served as a manipulation check. Generic and personalized information regarding the link between alcohol use and cancer was presented, followed by assessment of perceived threat, message avoidance and derogation. Page dwell-times served as indirect indices of message engagement. Alcohol consumption and intention to drink less were assessed during the first online session and at 1-week and 1-month follow-up. Results: Although self-affirmation resulted in higher levels of prosocial feelings immediately after the task, there was no effect on behaviour in the self-affirmation group. Effects on intention were moderated by gender, such that men showed lower intention immediately after self-affirmation, but this increased at 1-week follow-up. Women's intention to reduce consumption in the self-affirmation group reduced over time. Trend-level effects on indices of derogation and message acceptance were in the predicted direction only in men. Conclusion: It is feasible to perform self-affirmation procedures in an online environment with at-risk drinkers. However, use of internet-based procedures with this population may give rise to (gender-dependent) effects that are substantially diluted compared with lab-based experiments

Cnih3 deletion dysregulates dorsal hippocampal transcription across the estrous cycle

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gen

Biologically modified microelectrode sensors provide enhanced sensitivity for detection of nucleic acid sequences from Mycobacterium tuberculosis

This paper describes improved sensitivity when using biosensors based on microfabricated microelectrodes to detect DNA, with the goal of progressing towards a low cost and mass manufacturable assay for antibiotic resistance in tuberculosis (TB). The microelectrodes gave a near 20 times improvement in sensitivity compared to polycrystalline macroelectrodes. In addition, experimental parameters such as redox mediator concentration and experimental technique were investigated and optimised. It was found that lower concentrations of redox mediator gave higher signal changes when measuring hybridisation events and, at these lower concentrations, square wave voltammetry was more sensitive and consistent than differential pulse voltammetry. Together, this paper presents a quantifiable comparison of macroelectrode and microelectrode DNA biosensors. The final assay demonstrates enhanced sensitivity through reduction of sensor size, reduction of redox mediator concentration and judicious choice of detection technique, therefore maintaining manufacturability for incorporation into point of care tests and lab-on-a-chip devices

DC magnetism of Niobium thin films

Niobium thin films were deposited onto a-plane sapphire with varying kinetic energy and varying substrate temperature. There were no consistent trends which related the particle energy or substrate temperature to RRR. The sample which displayed the largest RRR of 229 was then compared to both a thin film deposited with similar conditions onto copper substrate and to bulk niobium. DC magnetometry measurements suggest that the mechanism of flux entry into thin film niobium and bulk niobium may vary due to differences in the volumes of both defects and impurities located within the grains. Results also suggest that magnetic flux may penetrate thin films at small fields due to the sample geometry

Physical vapour deposition of thin films for use in superconducting RF cavities

The production of superconducting coatings for radio frequency cavities is a rapidly developing field that should ultimately lead to acceleration gradients greater than those obtained by bulk Nb RF cavities. Optimizing superconducting properties of Nb thin-films is therefore essential. Nb films were deposited by magnetron sputtering in pulsed DC mode onto Si (100) and MgO (100) substrates and also by high impulse magnetron sputtering (HiPIMS) onto Si (100), MgO (100) and polycrystalline Cu. The films were characterised using scanning electron microscopy, x-ray diffraction and DC SQUID magnetometry