3,528 research outputs found

    Size reconstructibility of graphs

    Get PDF
    The deck of a graph GG is given by the multiset of (unlabelled) subgraphs {Gv:vV(G)}\{G-v:v\in V(G)\}. The subgraphs GvG-v are referred to as the cards of GG. Brown and Fenner recently showed that, for n29n\geq29, the number of edges of a graph GG can be computed from any deck missing 2 cards. We show that, for sufficiently large nn, the number of edges can be computed from any deck missing at most 120n\frac1{20}\sqrt{n} cards.Comment: 15 page

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

    Get PDF
    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

    Implications of Simultaneity in a Physical Damage Function

    Get PDF
    A modeler must often rely on highly simplified representations of complex physical systems when analyzing associated economic issues. Herein, we consider a management problem in which a bioeconomic system exhibits simultaneity in processes governing productivity and damage. In this case, it may benefit the producer to sacrifice productivity to reduce the costs associated with increased damage. We specify empirically a structural damage relationship that explains the biological process by which an invasive species damages a host and estimate the structural model and its reduced form with an exceptional dataset on infestation of olives by the olive fruit fly. We contrast the results of these models with the approach typically taken in the economic literature, which expresses damage as a function of pest density. The population-based approach introduces significantly greater bias into the individual grower\u27s choice of damage-control inputs than estimates based on the structural model

    Pion and Kaon Vector Form Factors

    Get PDF
    We develop a unitarity approach to consider the final state interaction corrections to the tree level graphs calculated from Chiral Perturbation Theory (χPT\chi PT) allowing the inclusion of explicit resonance fields. The method is discussed considering the coupled channel pion and kaon vector form factors. These form factors are then matched with the one loop χPT\chi PT results. A very good description of experimental data is accomplished for the vector form factors and for the ππ\pi\pi P-wave phase shifts up to s1.2\sqrt{s}\lesssim 1.2 GeV, beyond which multiparticle states play a non negligible role. In particular the low and resonance energy regions are discussed in detail and for the former a comparison with one and two loop χPT\chi PT is made showing a remarkable coincidence with the two loop χPT\chi PT results.Comment: 20 pages, 7 figs, to appear in Phys. Rev.

    Photocarrier lifetime and transport in silicon supersaturated with sulfur

    No full text
    Doping of silicon-on-insulator layers with sulfur to concentrations far above equilibrium by ion implantation and pulsed laser melting can result in large concentration gradients. Photocarriers generated in and near the impurity gradient can separate into different coplanar transport layers, leading to enhanced photocarrier lifetimes in thin silicon-on-insulator films. The depth from which holes escape the heavily doped region places a lower limit on the minority carrier mobility-lifetime product of 10⁻⁸ cm²/V for heavily sulfur dopedsilicon. We conclude that the cross-section for recombination through S impurities at this concentration is significantly reduced relative to isolated impurities.Research at Rensselaer was supported by the Army Research Office under Contract No. W911NF0910470 and by the NSF REU program at Rensselaer. Research at Harvard was supported by US Army ARDEC under Contract No. W15QKN-07-P-0092. D.R. was supported in part by a National Defense Science and Engineering Graduate fellowship

    Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa

    Get PDF
    STUDY QUESTION Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success?SUMMARY ANSWER Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF.WHAT IS KNOWN ALREADY In human spermatozoa, Ca2+ influx induced by progesterone is mediated by CatSper, a sperm-specific Ca2+ channel. A suboptimal Ca2+ influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca2+]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception.STUDY DESIGN, SIZE, DURATION Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study.PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were primarily screened using the Ca2+ influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca2+ response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca2+ response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis.MAIN RESULTS AND THE ROLE OF CHANCE A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca2+ response. The mean (±SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca2+ response. Three men were initially identified with a defective Ca2+ influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF.LIMITATIONS, REASONS FOR CAUTION A key limitation relates to working with a specific functional parameter (Ca2+ influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼22% of IVF patients) could not be screened. As such the incidence of significant Ca2+ abnormalities induced by progesterone may be higher than the ∼1% observed here. Additionally, we used a strict definition of a defective Ca2+ influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca2+ influx.WIDER IMPLICATIONS OF THE FINDINGS These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception

    Prying into the intimate secrets of animal lives; software beyond hardware for comprehensive annotation in ‘Daily Diary’ tags

    Get PDF
    BACKGROUND: Smart tags attached to freely-roaming animals recording multiple parameters at infra-second rates are becoming commonplace, and are transforming our understanding of the way wild animals behave. Interpretation of such data is complex and currently limits the ability of biologists to realise the value of their recorded information.DESCRIPTION: This work presents Framework4, an all-encompassing software suite which operates on smart sensor data to determine the 4 key elements considered pivotal for movement analysis from such tags (Endangered Species Res 4: 123-37, 2008). These are; animal trajectory, behaviour, energy expenditure and quantification of the environment in which the animal moves. The program transforms smart sensor data into dead-reckoned movements, template-matched behaviours, dynamic body acceleration-derived energetics and position-linked environmental data before outputting it all into a single file. Biologists are thus left with a single data set where animal actions and environmental conditions can be linked across time and space.CONCLUSIONS: Framework4 is a user-friendly software that assists biologists in elucidating 4 key aspects of wild animal ecology using data derived from tags with multiple sensors recording at high rates. Its use should enhance the ability of biologists to derive meaningful data rapidly from complex data.</p

    Bypass of mutagenic O 6 -Carboxymethylguanine DNA Adducts by Human Y- and B-Family Polymerases

    Get PDF
    The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O6-carboxymethylguanine (O6-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O6-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O6-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described. Herein, we characterize the ability of the four human TLS Pols η, ι, κ, and ζ and the replicative Pol δ to bypass O6-CMG in a prevalent mutational hot-spot for colon cancer. The results indicate that Pol η replicates past O6-CMG, incorporating dCMP or dAMP, whereas Pol κ incorporates dCMP only, and Pol ι incorporates primarily dTMP. Additionally, the subsequent extension step was carried out with high efficiency by TLS Pols η, κ, and ζ, while Pol ι was unable to extend from a terminal mismatch. These results provide a first basis of O6-CMG-promoted base misincorporation by Y- and B-family polymerases potentially leading to mutational signatures associated with colon cancer
    corecore