A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease

Stabilizing the Complex Structure in Heterotic Calabi-Yau Vacua

In this paper, we show that the presence of gauge fields in heterotic Calabi-Yau compacitifications causes the stabilisation of some, or all, of the complex structure moduli of the Calabi-Yau manifold while maintaining a Minkowski vacuum. Certain deformations of the Calabi-Yau complex structure, with all other moduli held fixed, can lead to the gauge bundle becoming non-holomorphic and, hence, non-supersymmetric. This leads to an F-term potential which stabilizes the corresponding complex structure moduli. We use 10- and 4-dimensional field theory arguments as well as a derivation based purely on algebraic geometry to show that this picture is indeed correct. An explicit example is presented in which a large subset of complex structure moduli is fixed. We demonstrate that this type of theory can serve as the hidden sector in heterotic vacua and can co-exist with realistic particle physics.Comment: 17 pages, Late

D3-instantons, Mock Theta Series and Twistors

The D-instanton corrected hypermultiplet moduli space of type II string theory compactified on a Calabi-Yau threefold is known in the type IIA picture to be determined in terms of the generalized Donaldson-Thomas invariants, through a twistorial construction. At the same time, in the mirror type IIB picture, and in the limit where only D3-D1-D(-1)-instanton corrections are retained, it should carry an isometric action of the S-duality group SL(2,Z). We prove that this is the case in the one-instanton approximation, by constructing a holomorphic action of SL(2,Z) on the linearized twistor space. Using the modular invariance of the D4-D2-D0 black hole partition function, we show that the standard Darboux coordinates in twistor space have modular anomalies controlled by period integrals of a Siegel-Narain theta series, which can be canceled by a contact transformation generated by a holomorphic mock theta series.Comment: 42 pages; discussion of isometries is amended; misprints correcte

A Study of Problem Solving Using Blocks Vehicle in a STEAM Course for Lower Elementary Levels

STEAM education is currently one of the most important parts of the elementary school curriculum. If STEAM learning can cultivate good problem-solving ability, it will also help improve judgment and thinking abilities. Several voices in the literature have argued for cooperative learning in STEAM courses. Although the effectiveness of course learning often is evaluated using course feedback forms, there is comparatively little emphasis on whether a course succeeds in realizing cooperative learning. For a course involving self-propelled toy-brick cars, there is little research on the application of low-grade pupils. Therefore, based on the integration of STEAM courses into self-propelled toy-brick car learning, this study applied two learning strategies of cooperative learning and individual learning to low-grade pupils in the second grade in elementary schools. After completing the course problem-solving ability indicators were measured and analyzed using the problem-solving ability test. The results show that the mean score of the experimental group in the problem-solving ability test was higher than that of the control group. In the problem-solving ability test, the scores of the two groups were also significantly different, which suggests that cooperative learning is more effective than individual learning strategies.acceptedVersio

MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

<p>Abstract</p> <p>Background</p> <p>Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas.</p> <p>Methods</p> <p>Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated.</p> <p>Results</p> <p>MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level.</p> <p>Conclusion</p> <p>MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus or had other neuropathies related with gamma knife. MASEP GKRS may serve as a primary treatment method in some or as a salvage treatment in the others. However, treatment must be tailored to meet the patient's symptoms, tumor location, tumor morphometry, and overall health. Longer follow-up is required for a more complete assessment of late radioreaction and treatment efficacy.</p

Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

Integration of NDE Reliability and Fracture Mechanics

The Pacific Northwest Laboratory is conducting a four-phase program for measuring and evaluating the effectiveness and reliability of in-service inspection (lSI} performed on the primary system piping welds of commercial light water reactors (LWRs). Phase I of the program is complete. A survey was made of the state of practice for ultrasonic rsr of LWR primary system piping welds. Fracture mechanics calculations were made to establish required nondestrutive testing sensitivities. In general, it was found that fatigue flaws less than 25% of wall thickness would not grow to failure within an inspection interval of 10 years. However, in some cases failure could occur considerably faster. Statistical methods for predicting and measuring the effectiveness and reliability of lSI were developed and will be applied in the &quot;Round Robin Inspections&quot; of Phase II. Methods were also developed for the production of flaws typical of those found in service. Samples fabricated by these methods wilI be used in Phase II to test inspection effectiveness and reliability. Measurements were made of the influence of flaw characteristics {i.e., roughness, tightness, and orientation) on inspection reliability. These measurernents, as well as the predictions of a statistical model for inspection reliability, indicate that current reporting and recording sensitivities are inadequate