An Electrically Detonated Downhole Seismic Gun

An electrically detonated downhole seismic gun (EDG) that will fire blank 8-guage shells underwater has been constructed and tested to 80m depth (hydrostatic pressures of 130 psi or 8.9 x 105 Pa). Although other engineering seismic guns which fire blank or projectile sources are available, they are for near-surface shots and are not meant to be used for downhold seismic surveys in water-filled boreholes. The EDG was designed primarily for checkshot surveys (well travel-time surveys) and high-quality reflection/refraction tests, but potential applications include shallow vertical seismic profiling and borehole to borehole or borehole to surface tomography, as well as optimum offset and common midpoint seismic reflection surveys. The EDG consists off four steel subassemblies: (1) chamber; (2) breech; (3) pipe; and (4) hanger. A blank 8-gauge electrical shell is held by the chamber and is detonated by an electrode located inside the breech. O-ring seals prevent water from entering the breech and causing short circuits. The breech is screwed into a pipe which is also fitted with o-ring seals to keep the internal wiring dry. A hanger subassembly provides a convenient attaching point for the hoist cable. Arming of the EDG with an explosives blaster occurs only after lowering to operating depth. The EDG has been tested with various size black powder loads up to 750 grains. Frequency bandwidth and repeatability tests were carried out under saturated conditions in a fluvial and lacustrine sedimentary section. These preliminary tests show significant frequency content in the 25-200 Hz band (peak near 100 Hz) for reflections from depths of 150-300 m, and acceptable waveform repeatability for different shot records obtained with identical geometry and acquisition parameters

A Test of the Psychometric Characteristics of the BIS-Brief Among Three Groups of Youth

The current study empirically investigates the relationships between the Dark Triad personality traits and cyber-aggression among adolescents (14–18 year old). The sample consisted of 324 participants aged 14–18 (M = 16.05, SD = 1.31). Participants completed the Short Dark Triad (SD3) as a measure of the Dark Triad personality traits, the Facebook Intensity Scale and a scale to measure cyber-aggression. Structural equation modelling was applied to investigate the relationships. Results show that only Facebook intensity and psychopathy significantly predict cyber-aggression, when controlling for age and gender. Findings are discussed regarding the potential importance to further study Dark Triad traits, and psychopathy in particular, in the context of adolescent cyber-aggression

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

The Prognostic Value of 14-3-3 Isoforms in Vulvar Squamous Cell Carcinoma Cases: 14-3-3β and ε Are Independent Prognostic Factors for These Tumors

BACKGROUND: The 14-3-3 family is comprised of highly conserved proteins that are functionally important in the maintenance of homeostasis. Their involvement with the cell cycle, their association with proto-oncogenes and oncogenes, and their abnormal expression in various tumors has linked this family of proteins to the etiology of human cancer. Mounting evidence now indicates that 14-3-3σ is a cancer suppressor gene but the roles of the other 14-3-3 isoforms and their interactions in tumorigenesis have not yet been elucidated. In our current study, we examined the expression of 14-3-3β, γ, ε, ζ, η and τ in a large series of vulvar squamous cell carcinomas to evaluate any clinical significance. METHODS: Tumor biopsies from 298 vulvar carcinomas were examined by immunohistochemistry for the expression of 14-3-3β, γ, ε, ζ, η and τ. Statistical analyses were employed to validate any associations between the expression of any 14-3-3 isoform and clinicopathologic variables for this disease. RESULTS: High cytoplasmic levels of 14-3-3β, γ, ζ, ε and η were observed in 79%, 58%, 50%, 86% and 54% of the vulvar carcinomas analyzed, respectively, whereas a low nuclear expression of 14-3-3τ was present in 80% of these cases. The elevated cytoplasmic expression of 14-3-3β, γ, ε, ζ and η was further found to be associated with advanced disease and aggressive features of these cancers. The overexpression of cytoplasmic 14-3-3β and ε significantly correlated with a poor disease-specific survival by univariate analysis (P = 0.007 and P = 0.04, respectively). The independent prognostic significance of these factors was confirmed by multivariate analysis (P = 0.007 and P = 0.009, respectively). CONCLUSIONS: We reveal for the first time that the 14-3-3β, γ, ε, ζ, η and τ isoforms may be involved in the progression of vulvar carcinomas. Furthermore, our analyses show that high cytoplasmic levels of 14-3-3β and ε independently correlate with poor disease-specific survival

Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players

Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain\u27s response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. Objective: To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. Design, Setting, and Participants: This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Main Outcomes and Measures: Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. Results: The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P \u3c .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. Conclusions and Relevance: The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms

Global Genetic Population Structure of Bacillus anthracis

Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical and current importance that is found throughout the world. The basis of its historical transmission is anecdotal and its true global population structure has remained largely cryptic. Seven diverse B. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by phylogenetic reconstruction of these characters onto an evolutionary model. This analysis identified SNPs that define the major clonal lineages within the species. These SNPs, in concert with 15 variable number tandem repeat (VNTR) markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42 countries to create an extensive genotype data set. These analyses subdivided the isolates into three previously recognized major lineages (A, B, and C), with further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221 unique MLVA15 genotypes. This rare genomic variation was used to document the evolutionary progression of B. anthracis and to establish global patterns of diversity. Isolates in the A lineage are widely dispersed globally, whereas the B and C lineages occur on more restricted spatial scales. Molecular clock models based upon genome-wide synonymous substitutions indicate there was a massive radiation of the A lineage that occurred in the mid-Holocene (3,064–6,127 ybp). On more recent temporal scales, the global population structure of B. anthracis reflects colonial-era importation of specific genotypes from the Old World into the New World, as well as the repeated industrial importation of diverse genotypes into developed countries via spore-contaminated animal products. These findings indicate humans have played an important role in the evolution of anthrax by increasing the proliferation and dispersal of this now global disease. Finally, the value of global genotypic analysis for investigating bioterrorist-mediated outbreaks of anthrax is demonstrated

Real Roots of Random Polynomials and Zero Crossing Properties of Diffusion Equation

We study various statistical properties of real roots of three different classes of random polynomials which recently attracted a vivid interest in the context of probability theory and quantum chaos. We first focus on gap probabilities on the real axis, i.e. the probability that these polynomials have no real root in a given interval. For generalized Kac polynomials, indexed by an integer d, of large degree n, one finds that the probability of no real root in the interval [0,1] decays as a power law n^{-\theta(d)} where \theta(d) > 0 is the persistence exponent of the diffusion equation with random initial conditions in spatial dimension d. For n \gg 1 even, the probability that they have no real root on the full real axis decays like n^{-2(\theta(2)+\theta(d))}. For Weyl polynomials and Binomial polynomials, this probability decays respectively like \exp{(-2\theta_{\infty}} \sqrt{n}) and \exp{(-\pi \theta_{\infty} \sqrt{n})} where \theta_{\infty} is such that \theta(d) = 2^{-3/2} \theta_{\infty} \sqrt{d} in large dimension d. We also show that the probability that such polynomials have exactly k roots on a given interval [a,b] has a scaling form given by \exp{(-N_{ab} \tilde \phi(k/N_{ab}))} where N_{ab} is the mean number of real roots in [a,b] and \tilde \phi(x) a universal scaling function. We develop a simple Mean Field (MF) theory reproducing qualitatively these scaling behaviors, and improve systematically this MF approach using the method of persistence with partial survival, which in some cases yields exact results. Finally, we show that the probability density function of the largest absolute value of the real roots has a universal algebraic tail with exponent {-2}. These analytical results are confirmed by detailed numerical computations.Comment: 32 pages, 16 figure