Insomnia commonly occurs along with other psychiatric disorders. I aim to address two issues that arise from this observation. First, insomnia is commonly assumed to be epiphenomenal to the so-called “primary” psychiatric disorder. On the basis of new evidence, I argue instead that insomnia may be an important but under-recognized mechanism in the multifactorial cause and maintenance of psychiatric disorders. Second, insomnia may be a transdiagnostic process—a process that is common across psychiatric disorders. The move to identify and study transdiagnostic processes contrasts with the standard “disorder focused” approach in which classification systems and research programs specialize in a single disorder. The latter approach can neglect the intriguing and potentially important similarities across disorders. If it were feasible to develop transdiagnostic treatments, the public health implications would be startling. Research on the role of sleep in psychiatric disorders and tests of the validity and utility of a transdiagnostic approach provide rich opportunities for improving our understanding of, and the treatment of, psychiatric disorders.
We investigate the thermodynamics of impurity segration between the separating atomic planes of a decohering solid from first principles. We find that the traction curve for decohesion at constant impurity chemical potential differs qualitatively from that at constant impurity concentration. In fact, for hydrogen and oxygen segregation between separating (111) planes during decohesion of fcc aluminum, a first-order van der Waals transition is predicted above a critical impurity chemical potential that results in a dramatic drop in the maximum stress of decohesion.
A series of small dendritic structures containing one of two efficient multiphoton absorbing dyes at the periphery and a nile red derivative at the core have been synthesized. These molecules display efficient (>96%) fluorescence resonance energy transfer (FRET) from the periphery to the core on selective excitation of the two-photon absorbing chromophore by either UV (linear absorption) or high-intensity IR (nonlinear absorption) radiation. In addition, a significant increase in core emission is observed on excitation of the peripheral chromophores, compared to direct excitation of the core. This "antenna effect" essentially doubles between increasing dendrimer generations within a series. The combination of the ability of the peripheral chromophores to absorb high-intensity IR radiation, coupled with a very efficient energy transfer process and a significant increase in the fluorescence of the acceptor chromophore, makes these molecules potentially useful for a variety of applications, including optical power limiting and biomedical imaging.
The gold(I)-catalyzed carboalkoxylation of alkynes to form indanone derivatives from readily available ortho-acetylenic benzylic ethers is described. Importantly, the gold(I)-catalyzed rearrangement of enantioenriched benzylic ethers proceeds with chirality transfer, thus providing a practical method for the enantioselective synthesis of indenyl ethers.
Insulin is a peptide hormone that regulates the metabolism of carbohydrates, proteins and fats. Pancreatic beta cells specifically synthesize and secretes insulin into blood circulation. Type II diabetes is characterized as the inability to respond to and produce insulin. As a progressive disease from a normal to a diabetic state, patients exhibit severe hyperglycemia, beta cell exhaustion and inability to synthesize insulin. There is currently minimal knowledge to measure insulin kinetics and methods to monitor the transition over the course of diabetic disease, however. Our objective is to measure the kinetics of insulin synthesis and secretion from pancreatic beta cells into blood in humans by use of stable isotopic metabolic labeling with heavy water ( 2 H 2 O) and mass spectrometry. We hypothesize that pancreatic reserve or treatment thereof can be monitored or diagnosed by measuring plasma insulin kinetics as a non‐invasive metric of pancreatic insulin. To test our hypothesis, insulin was isolated by immunoprecipitation from plasma in humans and its synthesis rate measured by 2 H 2 O labeling and mass spectrometry. We recently determined by metabolic labeling that insulin in the human body has a half‐life of 4.9 days, reflecting the turnover (replacement) of insulin in beta cell secretory granules by newly synthesized molecules. After breakfast and lunch, the contribution from recently synthesized insulin in plasma fell slightly from ~ 60% new at day 6, suggesting secretion from a less labeled reserve or secretory pool. There was no difference in labeled plasma insulin after each meal that suggests a steady state contribution of newly synthesized pancreatic insulin secreted into the plasma. In 2 subjects’ post‐bariatric surgery for morbid obesity, insulin in blood was almost 100% replaced by newly synthesized molecules after 6 days consistent with reduced beta cell secretory reserve for insulin. In pre‐diabetic fatty liver disease patients, the half life of insulin was determined as 7.2 days suggesting slower synthesis and potential onset of diabetes as compared to normal healthy controls that exhibited a half‐life of 4.9 days (*p=0.01). These are the first insulin turnover direct experimental data in humans and the results are very promising, suggesting that pancreatic beta cell reserve, the key factor in progression from insulin resistance to type II diabetes, can be monitored by measuring plasma insulin kinetics in human subjects.
In this grant period, the authors have explored the single-source precursor route to silicate materials containing various main group and transition metals. They have also explored the development of polymeric precursors to zinc silicate materials. In addition, they have begun to examine precursors for phosphate materials, based on the di(tert-butyl)phosphate ligand, {minus}O{sub 2}P(O{sup t}Bu){sub 2}. A primary focus of these studies is the development of molecular precursors to homogeneous, ultrapure metal silicates and phosphates. More recently, the authors have attempted to develop template-assisted network-forming reactions that could lead to micro- or mesoporous materials. Findings are summarized below for Zr and HF systems, Al systems, Cr systems, Cu systems, metal phosphate precursors, zinc silicate luminescent materials, and syntheses of inorganic materials using dendrimeric polymers as templates.
Abstract Die Methanolyse der Halogenide (Ia), (Ib) (bekannte Verbindungen), (Ic), (VIIc) und (VIId) unter verschiedenen Bedingungen [ a), b), c) bzw. d)] wird untersucht.
Screening the volatiles of cempedak [<i>Artocarpus integer</i> (Thunb.) Merr.] pulp for odor-active compounds by aroma extract dilution analysis and gas chromatography (GC)-olfactometry of static headspace samples revealed a total of 55 odorants, among which 47 were identified. Using stable isotopically substituted odorants as internal standards, these compounds were quantitated by GC-mass spectrometry, and odor activity values (OAVs) were calculated as ratios of the natural concentrations in cempedak pulp to the orthonasal odor detection thresholds. An aroma reconstitution model based on the 41 compounds with OAVs >1 in their natural concentrations successfully mimicked the characteristic aroma of cempedak pulp including the pronounced sulfury, oniony note which is intense in cempedak pulp but absent in jackfruit pulp. Further sensory tests finally showed that 2-(methylsulfanyl)propane, 2-(methylsulfanyl)butane, and 2-(methylsulfanyl)pentane are the key compounds responsible for this unique aroma note in cempedak pulp and vitally contribute to the aroma difference between cempedak pulp and jackfruit pulp.
