Maternal first trimester serum levels of free-beta human chorionic gonadotropin and male genital

Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy

Characterizing Hydrogen Storage Media: Understanding the Interior Pore Structure of a Cu3BTC2 Metal-Organic Framework Infiltrated with NaAlH4

Preliminary results support the nano-confinement of sodium alanate within the pores of a Cu{sub 3}BTC{sub 2} MOF substrate. Increased {sup 1}H and {sup 27}Al NMR T{sub 1} relaxation rates indicate a close proximity of infiltrated sodium alante to the paramagnetic Cu{sup 2+} ions on the BTC paddlewheel units. This is in support of the theory that an interaction due to the electronegative framework with the sodium alanate facilitates thermodynamically-favorable hydrogen adsorption and desorption. Further studies can elucidate the local electronic environment of the sodium ions, further supporting a charge-transfer mechanism as the driving force for thermodynamically-favorable hydrogen adsorption and desorption

Development neurobiology of the stress response: multilevel regulation of corticotropin-releasing hormone function.

The ability to respond to adverse environmental cues is present in the neonatal and infant rat, although in an immature form: A number of laboratories have demonstrated stress-induced elevations of plasma glucocorticoids during the first two postnatal weeks. The limbic and hypothalamic mechanisms controlling the hormonal stress-response during this period are not fully understood and are, therefore, the focus of this report. Both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin contribute to the release of ACTH from the pituitary in the adult. The relative roles of these two peptides during the neonatal (first week) and infant (second week) developmental period, are controversial. Evidence is presented that argues strongly for a major role for CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased with cold stress by ninth postnatal day, but not during the first postnatal week. Further, down-regulation of CRH gene expression by glucocorticoids (GC) constitutes a critical "shut-down" mechanism for the hormonal stress response. In vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH synthesis during the first postnatal week are described. CRH-mediated neurotransmission, in both the endocrine and neuronal effector arms of the response to stress may be modulated via alteration of receptor number. The first member of the CRH receptor family, CRF1, probably mediates the neuroendocrine effects of CRH. The developmental profile of CRF1-mRNA reveals several distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at 180% of adult values). In cortex, a steady decline from high postnatal day 2 levels results in adult levels by 12. These findings demonstrate distinct, regional, age-specific control of the synthesis of CRF1. Receptor expression profile may provide important information regarding modulation of the age-specific roles of CRH in different regions. For example, a high ratio of hippocampus/amygdala receptors may preferentially activate negative hippocampal input to the hypothalamus during the neonatal period. Additionally, increased CRH receptor mRNA in the infant compared with the adult provides a mechanism for enhanced excitatory effect of the peptide at this age. In conclusion, increasing evidence exists for multiple control points of the early postnatal response and adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity to GC feedback, and the abundance and distribution of at least two distinct CRH receptors in the limbic central nervous system and the pituitary are developmentally regulated. All serve as control points permitting an effective endocrine, autonomic, and behavioral response to stressful environmental cues

Structure of the icosahedral Ti-Zr-Ni quasicrystal

The atomic structure of the icosahedral Ti-Zr-Ni quasicrystal is determined by invoking similarities to periodic crystalline phases, diffraction data and the results from ab initio calculations. The structure is modeled by decorations of the canonical cell tiling geometry. The initial decoration model is based on the structure of the Frank-Kasper phase W-TiZrNi, the 1/1 approximant structure of the quasicrystal. The decoration model is optimized using a new method of structural analysis combining a least-squares refinement of diffraction data with results from ab initio calculations. The resulting structural model of icosahedral Ti-Zr-Ni is interpreted as a simple decoration rule and structural details are discussed.Comment: 12 pages, 8 figure

Desalination utilizing clathrate hydrates (LDRD final report).

Advances are reported in several aspects of clathrate hydrate desalination fundamentals necessary to develop an economical means to produce municipal quantities of potable water from seawater or brackish feedstock. These aspects include the following, (1) advances in defining the most promising systems design based on new types of hydrate guest molecules, (2) selection of optimal multi-phase reactors and separation arrangements, and, (3) applicability of an inert heat exchange fluid to moderate hydrate growth, control the morphology of the solid hydrate material formed, and facilitate separation of hydrate solids from concentrated brine. The rate of R141b hydrate formation was determined and found to depend only on the degree of supercooling. The rate of R141b hydrate formation in the presence of a heat exchange fluid depended on the degree of supercooling according to the same rate equation as pure R141b with secondary dependence on salinity. Experiments demonstrated that a perfluorocarbon heat exchange fluid assisted separation of R141b hydrates from brine. Preliminary experiments using the guest species, difluoromethane, showed that hydrate formation rates were substantial at temperatures up to at least 12 C and demonstrated partial separation of water from brine. We present a detailed molecular picture of the structure and dynamics of R141b guest molecules within water cages, obtained from ab initio calculations, molecular dynamics simulations, and Raman spectroscopy. Density functional theory calculations were used to provide an energetic and molecular orbital description of R141b stability in both large and small cages in a structure II hydrate. Additionally, the hydrate of an isomer, 1,2-dichloro-1-fluoroethane, does not form at ambient conditions because of extensive overlap of electron density between guest and host. Classical molecular dynamics simulations and laboratory trials support the results for the isomer hydrate. Molecular dynamics simulations show that R141b hydrate is stable at temperatures up to 265K, while the isomer hydrate is only stable up to 150K. Despite hydrogen bonding between guest and host, R141b molecules rotated freely within the water cage. The Raman spectrum of R141b in both the pure and hydrate phases was also compared with vibrational analysis from both computational methods. In particular, the frequency of the C-Cl stretch mode (585 cm{sup -1}) undergoes a shift to higher frequency in the hydrate phase. Raman spectra also indicate that this peak undergoes splitting and intensity variation as the temperature is decreased from 4 C to -4 C

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

BACKGROUND: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data was donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Male Oxidative Stress Infertility (MOSI):proposed terminology and clinical practice guidelines for management of idiopathic male infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause