Crystal cleaving machine

A machine is disclosed for cleaving hard crystals. A typical example of which is lithium fluoride, with prcision and uniformity and includes vertical axis positioning control means for an adjustable spring tension guided hammer mechanism employed to strike an anvil. A crystal cleaving shock wave transmitted to a cleaving blade is generated having an angulated cleaving edge in contact with one corner of the crystal. Connection between the anvil and the blade is by means of a pair of vertical shafts held in substantially friction free engagement by two pairs of adjustable linear bearings. An underlying crystal holding fixture with horizontal position control means includes a zero reference stop face for the crystal and opposing spring-loaded clamping and vertical positioning elements which are precisely guided

Method and apparatus for slicing crystals

The crystal slicing method is described as follows. A crystal is sliced in a plane parallel to flat, opposed parallel end faces of the crystal. The end faces of the crystal are gripped by a pair of opposed, perforated platens of a pair of vacuum chambers, one of which is translatable relative to the other. A blade cuts the crystal through the desired plane. A spring biases one of the vacuum chambers away from the other vacuum chamber while both of the faces are gripped by the vacuum chambers and the blade is cleaving the crystal. A sliced portion of the crystal gripped by one of the vacuum chambers is pulled away from the remainder of the crystal gripped by the second vacuum chamber when the crystal was cleaved by the blade through the plane

Lumbosacral plexus in Brazilian Common Opossum

The opossum has been suggested as an animal model for biomedical studies due to its adaptability to captivity and number of births per year. Despite many studies on morphology and experimental neurology using this opossum model, the literature does not offer details of the nerves of the lumbosacral plexus in this species. Ten lumbosacral plexus were dissected to describe the peripheral innervations of the Brazilian Common Opossum (Didelphis aurita) and compare the results with Eutheria clade species. The tensor fasciae latae muscle was absent and there was only one sartorius muscle for each limb. The distribution of the nerves were similar to other mammals, except for the caudal gluteal nerve, sartorius muscle innervations and the position of the pudendal nerve which arose from the major ischiatic foramen together with the ischiatic nerve, the cranial gluteal nerve and the caudal gluteal nerve. No anatomical variation was found. The special position of the pudendal nerve suggested that the Brazilian Common Opossum is a better model than rats or rabbits in surgical procedures with that specific nerve. In addition, the study revealed that the pelvic limb nerves are not an invariable structure of reference for muscle homology and homonym as reported previously. New investigation using other species of opossums are necessary to best comprehend the lumbosacral plexus distribution in the Methatheria clade and to confirm that other opossum species is eligible as a good model for pudendal nerve studies

Multi-technique characterisation of MOVPE-grown GaAs on Si

The heterogeneous integration of III-V materials on a Si CMOS platform offers tremendous prospects for future high speed and low power logic applications. That said this integration generates immense scientific and technological challenges. In this work multi-technique characterisation is used to investigate properties of GaAs layers grown by Metal-Organic Vapour Phase Epitaxy (MOVPE) on Si substrates - (100) with 4⁰ offset towards - under various growth conditions. This being a crucial first step towards the production of III-V template layers with a relatively lower density of defects for selective epitaxial overgrowth of device quality material. The optical and structural properties of heteroepitaxial GaAs are first investigated by micro-Raman spectroscopy and photoluminescence and reflectance measurements. High-resolution X-ray diffraction (HR-XRD) is used to investigate structural properties. Advanced XRD techniques, including double-axis diffraction and X-ray crystallographic mapping are used to evaluate degrees of relaxation and distribution of the grain orientations in the epilayers, respectively. Results obtained from the different methodologies are compared in an attempt to understand growth kinetics of the materials system. The GaAs overlayer grown with annealing at 735⁰C following As predeposition at 500⁰C shows the best crystallinity. Close inspection confirms the growth of epitaxial GaAs preferentially oriented along (100) embedded in a highly-textured polycrystalline structure

Structural investigation of MOVPE-Grown GaAs on Ge by X-ray techniques

The selection of appropriate characterisation methodologies is vital for analysing and comprehending the sources of defects and their influence on the properties of heteroepitaxially grown III-V layers. In this work we investigate the structural properties of GaAs layers grown by Metal-Organic Vapour Phase Epitaxy (MOVPE) on Ge substrates – (100) with 6⁰ offset towards – under various growth conditions. Synchrotron X-ray topography (SXRT) is employed to investigate the nature of extended linear defects formed in GaAs epilayers. Other X-ray techniques, such as reciprocal space mapping (RSM) and triple axis ω-scans of (00l)-reflections (l = 2, 4, 6) are used to quantify the degree of relaxation and presence of antiphase domains (APDs) in the GaAs crystals. The surface roughness is found to be closely related to the size of APDs formed at the GaAs/Ge heterointerface, as confirmed by X-ray diffraction (XRD), as well as atomic force microscopy (AFM), and transmission electron microscopy (TEM)

Structural investigation of MOVPE-Grown GaAs on Ge by X-ray techniques

The selection of appropriate characterisation methodologies is vital for analysing and comprehending the sources of defects and their influence on the properties of heteroepitaxially grown III-V layers. In this work we investigate the structural properties of GaAs layers grown by Metal-Organic Vapour Phase Epitaxy (MOVPE) on Ge substrates – (100) with 6⁰ offset towards – under various growth conditions. Synchrotron X-ray topography (SXRT) is employed to investigate the nature of extended linear defects formed in GaAs epilayers. Other X-ray techniques, such as reciprocal space mapping (RSM) and triple axis ω-scans of (00l)-reflections (l = 2, 4, 6) are used to quantify the degree of relaxation and presence of antiphase domains (APDs) in the GaAs crystals. The surface roughness is found to be closely related to the size of APDs formed at the GaAs/Ge heterointerface, as confirmed by X-ray diffraction (XRD), as well as atomic force microscopy (AFM), and transmission electron microscopy (TEM)

Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies

BACKGROUND: The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. METHODS/DESIGN: We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. DISCUSSION: Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016052762

The SR-BI Partner PDZK1 Facilitates Hepatitis C Virus Entry

Entry of hepatitis C virus (HCV) into hepatocytes is a multi-step process that involves a number of different host cell factors. Following initial engagement with glycosaminoglycans and the low-density lipoprotein receptor, it is thought that HCV entry proceeds via interactions with the tetraspanin CD81, scavenger receptor class B type I (SR-BI), and the tight-junction proteins claudin-1 (CLDN1) and occludin (OCLN), culminating in clathrin-dependent endocytosis of HCV particles and their pH-dependent fusion with endosomal membranes. Physiologically, SR-BI is the major receptor for high-density lipoproteins (HDL) in the liver, where its expression is primarily controlled at the post-transcriptional level by its interaction with the scaffold protein PDZK1. However, the importance of interaction with PDZK1 to the involvement of SR-BI in HCV entry is unclear. Here we demonstrate that stable shRNA-knockdown of PDZK1 expression in human hepatoma cells significantly reduces their susceptibility to HCV infection, and that this effect can be reversed by overexpression of full length PDZK1 but not the first PDZ domain of PDZK1 alone. Furthermore, we found that overexpression of a green fluorescent protein chimera of the cytoplasmic carboxy-terminus of SR-BI (amino acids 479–509) in Huh-7 cells resulted in its interaction with PDZK1 and a reduced susceptibility to HCV infection. In contrast a similar chimera lacking the final amino acid of SR-BI (amino acids 479–508) failed to interact with PDZK1 and did not inhibit HCV infection. Taken together these results indicate an indirect involvement of PDZK1 in HCV entry via its ability to interact with SR-BI and enhance its activity as an HCV entry factor

Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.This work was supported by the MQ Brighter Futures Award MQBFC/2 (LS, LC, LV, MRD, LvV, ALvH, HB) and the U.S. National Institute of Mental Health under Award Number R01MH117601 (LS, LvV, NJ). LvV received funding through the National Suicide Prevention Research Fund, managed by Suicide Prevention Australia. LS is supported by an NHMRC Career Development Fellowship (1140764). ALvH is funded through the Social Safety and Resilience program of Leiden University. SA, NB, FP, and GS acknowledge that data collected in IRCCS Santa Lucia Foundation, Rome, Italy was funded by a study funded by the Italian Ministry of Health grant RC17-18-19-20-21/A. ZB, KC, B K-D acknowledge data collected at the University of Minnesota was funded by the National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women’s Health Seed Grant, University of Minnesota. HB acknowledges data collected at the Yale School of Medicine, New Haven, CT, USA, was funded by: MQ Brighter Futures, R61MH111929RC1MH088366, R01MH070902, R01MH069747, American Foundation for Suicide Prevention, International Bipolar Foundation, Brain and Behavior Research Foundation, For the Love of Travis Foundation and Women’s Health Research at Yale. LC is supported by Interdisziplinäres Zentrum für Klinische Forschung, UKJ. BCD was funded by a CJ Martin Fellowship (NHMRC app 1161356). BCD research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06. CGD and BJH acknowledge that data collected in Melbourne, Australia, was supported by Australian National Health and Medical Research Council of Australia (NHMRC) Project Grants 1064643 (principal investigator, BJH) and 1024570 (principal investigator, CGD). BJH and CGD were supported by NHMRC Career Development Fellowships (1124472 and 1061757, respectively). UD and TH acknowledge data collected at the FOR2107-Münster was funded by the German Research Foundation (DFG, grant FOR2107-DA1151/5-1 and DA1151/5-2 to UD, and DFG grants HA7070/2-2, HA7070/3, HA7070/4 to TH). AJ and TK acknowledges data collected at the FOR2107-Marburg was funded by the German Research Foundation (DFG, grant FOR2107-JA 1890/7-1 and JA 1890/7-2 to AJ, and DFG, grant FOR2107-KI588/14-1 and FOR2107-KI588/14-2 to TK). KD acknowledges data collected for the Münster Neuroimaging Cohort was funded by the Medical Faculty Münster, Innovative Medizinische Forschung (Grant IMF KO 1218 06 to KD). JMF, PBM, BJO, and GR acknowledge that the “Kids and Sibs” Study was supported by the Australian National Medical and Health Research Council (Program Grant 1037196 and Investigator Grant 1177991 to PBM, Project Grant 1066177 to JMF), the Lansdowne Foundation, Good Talk and the Keith Pettigrew Family Bequest (PM). JMF gratefully acknowledges the Janette Mary O’Neil Research Fellowship. IHG is supported in part by R37MH101495. Support for TAD comes from the National Institute of Mental Health (K01MH106805). TH acknowledges support for TIGER includes the Klingenstein Third Generation Foundation, the National Institute of Mental Health (K01MH117442), the Stanford Maternal Child Health Research Institute, and the Stanford Center for Cognitive and Neurobiological Imaging. TCH receives partial support from the Ray and Dagmar Dolby Family Fund. KAM, ABM, MAS acknowledge data collected at Harvard University was funded by the National Institute of Mental Health (R01-MH103291). IN is supported by grants of the Deutsche Forschungsgemeinschaft (DFG grants NE2254/1-2, NE2254/3-1, NE2254/4-1).This study was supported by the NationalCenter for Complementary and Integrative Health (NCCIH) R21AT009173 and R61AT009864 to TTY; by the National Center for Advancing Translational Sciences(CTSI), National Institutes of Health, through UCSF-CTSI UL1TR001872 to TTY; bythe American Foundation for Suicide Prevention (AFSP) SRG-1-141-18 to TTY; byUCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fundto TTY; by the National Institute of Mental Health (NIMH) R01MH085734 and the Brain and Behavior Research Foundation (formerly NARSAD) to TTY. YC acknowledges the Medical Leader Foundation of Yunnan Province (L2019011) and FamousDoctors Project of Yunnan Province Plan (YNWR-MY-2018-041). DTG, BCF and RAAwish to thank all PAFIP patients and family members who participated in the studyas well as PAFIP´s research team and Instituto de Investigación Marqués deValdecilla. Work by the PAFIP group has been funded by Instituto de Salud Carlos III through the projects PI14/00639, PI14/00918 and PI17/01056 (Co-funded byEuropean Regional Development Fund/European Social Fund “Investing in yourfuture”) and Fundación Instituto de Investigación Marqués de Valdecilla(NCT0235832 and NCT02534363). MER received support from the AustralianNational Health and Medical Research Council (NHMRC) Centre for ResearchExcellence on Suicide Prevention (CRESP) [GNT1042580]. ETCL is supported bygrants from NIAAA (K01AA027573, R21AA027884) and the American Foundationfor Suicide Prevention. All authors thank the participants for volunteering theirtime and supporting our research. Open Access funding enabled and organized by CAUL and its Member Institutions

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)?three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions