Streak camera recording of shock wave transit times at large distances using laser illumination

A pulsed laser illumination system for streak camera recording of impact-induced shock wave transit times (~1 µs) during impact experiments is described. Laser illumination of centimeter-sized subjects offers many advantages over diffuse illumination techniques for streak photography. Source-to-sample and sample-to-camera distances of ~10^0 to 10^1 m can be employed. Light filtering, and simultaneous recording of both the impact event and the camera streak rate calibration, can be carried out easily. For use in such a system we describe a Pockels cell controller in which the reference 10-MHz oscillator signal is synchronously divided down to 38 Hz to provide a trigger signal for laser and streak camera testing

A Prospective Study of Predictors and Consequences of Hooking Up for Sexual Minority Women

Hooking up, which refers to a sexual encounter (ranging from kissing to penetrative sex) between individuals who are not in a committed relationship, is an increasingly normative form of sexual exploration among emerging adults. Past research has focused on hookups within a heteronormative context, and some of this work has examined hookups as a way to cope with distress. Building on this work, we examined the role of hookups as a means for lesbian and bisexual women to cope with minority stress through increasing connection and engagement with the LGBTQ (lesbian/gay/bisexual/transgender/queer or questioning) community. A nationally recruited sample of 520 lesbian and bisexual women ages 18 to 25 completed questionnaires regarding their hookup behaviors as part of a longitudinal study. Childhood sexual abuse, posttraumatic stress symptoms, alcohol use, minority stress, and involvement and connectedness with the LGBTQ community were also assessed. First, regression analyses were used to examine baseline predictors of hookup behaviors reported at a 12-month follow-up. Findings revealed that alcohol use was associated with a greater likelihood of any subsequent hookups, and individuals reporting more minority stress subsequently hooked up with more partners. Second, hookup behaviors at 12 months were examined as predictors of outcomes at a 24-month follow-up, after controlling for baseline variables. Findings revealed that hookup behaviors were associated with reduced minority stress as well as increased involvement with and connectedness to the LGBTQ community, suggesting hookups may serve a protective function. Overall, findings support the notion that for sexual minority women, hookups may operate as a means of coping and connection

Friends-Based Protective Strategies and Unwanted Sexual Experiences: A Daily Diary Examination of First Year College Women

Risk for unwanted sexual experiences can emerge in social contexts—the same contexts that early college women navigate with their friends. Though friends naturally engage in prevention strategies, less is known about how capable guardianship influences risk. Using multilevel structural equation modeling, the present study examined guardianship at the person and situation levels. First-year college women (N = 132) completed eight weekends of daily surveys. We examined whether guardianship (e.g., more friends present, greater proportion of female friends, no intoxicated friends) would reduce unwanted sexual experience risk and if this relation was mediated by friends-based strategy use. An alternative model was also tested with the same predictors, but with unwanted sexual experiences as the mediator and friends-based strategy use as the outcome. Over half (58%) of extended weekend nights with friends involved drinking or using drugs. Friends-based strategies were used on 29% of nights. Across models, being with one or more intoxicated friends was associated with friends-based strategy use and an unwanted sexual experience, but only at the situation level. Parents, educators, and policy makers can encourage college women to draw on their social networks to enhance safety. Interventions could incorporate more universal strategies for responding to risk in social contexts

An Event-Level Evaluation of Women’s Self-Medicated Drinking: The Role of Sexual Assault Severity, Affect, and Drinking Motives

Objective.—Women with sexual assault (SA) histories report heavier and more frequent drinking. Consistent with the motivational model of alcohol use, women with SA histories may consume alcohol to both down-regulate negative emotions and up-regulate positive ones. The present event-level study used a Bayesian multilevel moderated mediation approach to examine the extent to which women’s alcohol use and intoxication was influenced by coping and enhancement drinking motives to down-regulate or up-regulate affect, respectively. Method.—Women ages 21–30 were recruited from the community to participate in a larger study that included a 32-day daily diary assessment of affect, drinking motives, and alcohol use. Results.—We found consistent support for women’s tendencies to be motivated to drink to cope or enhance negative or positive affect, respectively, and those drinking motives were associated with indicators of increased drinking. Becoming intoxicated to down-regulate negative emotion was common and this pathway was particularly strong for women who reported more severe SA histories. Although women with more severe SA histories were generally more likely to drink more, they were not likely to do so as a way to enhance positive experiences. Conclusions.—Alcohol interventions that provide adaptive regulatory strategies are needed for women who experience increased negative or positive affect, with a particular focus on self-medication for young women with more severe SA histories

Gene Expression Meta-Analysis Identifies VDAC1 as a Predictor of Poor Outcome in Early Stage Non-Small Cell Lung Cancer

The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival.High VDAC1 expression was associated with shorter overall survival with hazard ratio (HR) = 0.6639 (95% confidence interval (CI) 0.4528 to 0.9721), p = 0.035352 corresponding to 52 versus 101 months. VDAC1 predicted shorter time to recurrence and was shown to be an independent prognostic factor compared with histology, gender, age, nodal stage and tumour stage in a Cox multivariate analysis. Supervised analysis of all the datasets identified a 6-gene signature comprising HNRNPC, HSPA4, HSPA9, UBE2D2, CSNK1A1 and G3BP1 with overlapping functions involving regulation of protein turnover, RAS-RAF-MEK pathway and transcription. VDAC1 predicted survival in breast cancer and myeloma and an unsupervised analysis revealed enrichment of the VDAC1 signature in specific subsets.In summary, gene expression analysis identifies VDAC1 gene expression as a predictor of poor outcome in NSCLC and other cancers and is associated with dysregulation of a conserved set of biological pathways, which may be causally associated with aggressive tumour behaviour

Maternal ethnicity and socioeconomic deprivation: influence on adverse pregnancy outcomes.

OBJECTIVES: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and the percentage of composite adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO-S) METHODS: This is a single centre retrospective cohort study conducted in a tertiary maternity unit. Data regarding the ethnicity and socioeconomic deprivation were collected for 13,165 singleton pregnant women routinely screened in the first trimester for preeclampsia using the Fetal Medicine Foundation combined algorithm. RESULTS: The prevalence or risk of CAPO was 16.3% for White women, 29.3% for Black women and 29.3% for South Asian women. However, half of all CAPO cases (51.7%) occurred in White women. There is a strong interaction between ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation). Both influence the prevalence of CAPO and CAPO-S, with the contribution of ethnicity being strongest. CONCLUSIONS: Black and Asian ethnicity as well as socioeconomic deprivation influence the prevalence of placentally-mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in White women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placentally-mediated CAPO. This article is protected by copyright. All rights reserved

Modular Chemical Construction of IgG-like Mono- and Bispecific Synthetic Antibodies (SynAbs)

In recent years there has been rising interest in the field of protein−protein conjugation, especially related to bispecific antibodies (bsAbs) and their therapeutic applications. These constructs contain two paratopes capable of binding two distinct epitopes on target molecules and are thus able to perform complex biological functions (mechanisms of action) not available to monospecific mAbs. Traditionally these bsAbs have been constructed through protein engineering, but recently chemical methods for their construction have started to (re)emerge. While these have been shown to offer increased modularity, speed, and for some methods even the inherent capacity for further functionalization (e.g., with small molecule cargo), most of these approaches lacked the ability to include a fragment crystallizable (Fc) modality. The Fc component of IgG antibodies offers effector function and increased half-life. Here we report a first-in-class disulfide rebridging and click-chemistry-based method for the generation of Fc-containing, IgG-like mono- and bispecific antibodies. These are in the FcZ-(FabX)-FabY format, i.e., two distinct Fabs and an Fc, potentially all from different antibodies, attached in a homogeneous and covalent manner. We have dubbed these molecules synthetic antibodies (SynAbs). We have constructed a T cellengager (TCE) SynAb, FcCD20-(FabHER2)-FabCD3, and have confirmed that it exhibits the expected biological functions, including the ability to kill HER2+ target cells in a coculture assay with T cells

Parental genome unification is highly error-prone in mammalian embryos

Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development

Scalable in vitro production of defined mouse erythroblasts

Mouse embryonic stem cells (mESCs) can be manipulated in vitro to recapitulate the process of erythropoiesis, during which multipotent cells undergo lineage specification, differentiation and maturation to produce erythroid cells. Although useful for identifying specific progenitors and precursors, this system has not been fully exploited as a source of cells to analyse erythropoiesis. Here, we establish a protocol in which characterised erythroblasts can be isolated in a scalable manner from differentiated embryoid bodies (EBs). Using transcriptional and epigenetic analysis, we demonstrate that this system faithfully recapitulates normal primitive erythropoiesis and fully reproduces the effects of natural and engineered mutations seen in primary cells obtained from mouse models. We anticipate this system to be of great value in reducing the time and costs of generating and maintaining mouse lines in a number of research scenarios