3,188 research outputs found

    Mr. Justice Emmett Matthew Hall

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    Mr. Justice Emmett Matthew Hall

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    Noble metal penetrating cortical stimulating electrode array: preliminary results

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    Journal ArticleElectrical stimulation of the visual cortex causes subjects to see spots of light (phosphenes) in their visual fields. We have developed arrays of penetrating electrodes which may from the basis of a visual prosthesis centered around electrical stimulation of the visual cortex. These arrays have been constructed of inert materials, and have been implanted into cats to test array insertability and biocompatibility. Tests to determine electrode wire insertion force have also been performed. Preliminary acute histological results have shown little cortical damage due to the implants

    Myocardial Relaxation Is Accelerated by Fast Stretch, Not Reduced Afterload

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    Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the speed of myocardial relengthening at end systole (end systolic strain rate), and not afterload, modulates relaxation rate and tested this hypothesis using electrically-stimulated trabeculae from mice, rats, and humans. We used load-clamp techniques to vary afterload and end systolic strain rate independently. Our data show that the rate of relaxation increases monotonically with end systolic strain rate but is not altered by afterload. Computer simulations mimic this behavior and suggest that fast relengthening quickens relaxation by accelerating the detachment of cross-bridges. The relationship between relaxation rate and strain rate is novel and upends the prevailing theory that afterload modifies relaxation. In conclusion, myocardial relaxation is mechanically modified by the rate of stretch at end systole. The rate of myocardial relengthening at end systole may be a new diagnostic indicator or target for treatment of diastolic dysfunction

    Correlations of Seismic Velocity with Depth

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    Correlations of seismic velocity have been made with depth for various geotechnical classifications of soil and rock described. The seismic velocities have been found to be dependent upon geologic age, gravel content, water table depth, dry density and depth of overburden

    Evaluation of Reproductive Function in Turkana Women with Enzyme Immunoassays of Urinary Hormones in the Field

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    The frequently reported observation that nomadic populations have lower fertility than their settled counterparts is often attributed to what are perceived as harsh, stressful conditions under which the nomads live. But the consequences of the hypothesized stresses for the reproductive biology or demography of these populations have been documented only a little. Traditionally, the Turkana of northwest Kenya are nomadic herders, but increasing numbers have settled on agricultural development schemes. We used an array of hormonal assays along with anthropometric indexes of nutritional status and interviews covering reproductive history, recent menstruation, diet, and health to compare reproductive function in nomadic and settled Turkana women. First morning urine samples were collected for three consecutive days during a series of surveys. Human choriogonadotropin (hCG; a marker for pregnancy), luteinizing hormone (LH; an indicator of ovulation), and pregnanediol glucuronide (PdG; an indicator of postovulatory luteal function) were assessed in the field with commercially available dipstick enzyme immunoassays. These assays along with the interview data allowed us to determine the reproductive status (e.g., pregnant or cycling, and if cycling, which phase of the ovarian cycle) of 166 nomadic and 194 settled Turkana women. The cross-sectional classifications allowed inferences of conception rates and normality of ovarian function. Follow-up surveys provided rates of pregnancy loss. Compared with the settled women, the nomadic women exhibited lower pregnancy rates and cycling nomadic women were less likely to show evidence of ovulation or luteal function. These results suggest that reproductive function of the nomadic women is diminished relative to the settled women. However, the settled women experienced a much higher rate of pregnancy loss, which may mean that their effective fecundability is in fact lower than that of the nomadic women. This study is the first to apply such a wide range of hormonal assays in the field. It demonstrates that field-based assays are feasible and robust and can play an important role in epidemiological and biodemographic studies, even in remote locations under conditions that would ordinarily be considered incompatible with on-site laboratory analysis

    DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network

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    During DNA replication, stalled replication forks and DSBs arise when the replication fork encounters ICLs (interstrand crosslinks), covalent protein/DNA intermediates or other discontinuities in the template. Recently, homologous recombination proteins have been shown to function in replication-coupled repair of ICLs in conjunction with the Fanconi anemia (FA) regulatory factors FANCD2-FANCI, and, conversely, the FA gene products have been shown to play roles in stalled replication fork rescue even in the absence of ICLs, suggesting a broader role for the FA network than previously appreciated. Here we show that DNA2 helicase/nuclease participates in resection during replication-coupled repair of ICLs and other replication fork stresses. DNA2 knockdowns are deficient in HDR (homology-directed repair) and the S phase checkpoint and exhibit genome instability and sensitivity to agents that cause replication stress. DNA2 is partially redundant with EXO1 in these roles. DNA2 interacts with FANCD2, and cisplatin induces FANCD2 ubiquitylation even in the absence of DNA2. DNA2 and EXO1 deficiency leads to ICL sensitivity but does not increase ICL sensitivity in the absence of FANCD2. This is the first demonstration of the redundancy of human resection nucleases in the HDR step in replication-coupled repair, and suggests that DNA2 may represent a new mediator of the interplay between HDR and the FA/BRCA pathway
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