Progress toward phidianidine analogues containing a 1,2,3-triazole ring

Phidianidines are a class of compound that has been extracted from the sea mollusk Phidianis militaris. These compounds have been shown to exhibit a variety of useful properties such as antihistamine effects, anti-cancer activity, agonism of the µ-opioid receptor and neuroprotection. The biological activities are thought to be caused by the 1,2,4- oxadiazole ring found within the molecule. The goal of this project is to synthesize analogues of phidianidine that contain a 1,2,3-triazole instead of the 1,2,4 oxadiazole ring using a method that will allow for other regions of the molecule to be changed. This will help to elucidate the role of the 1,2,4-oxadiazole ring in biological activity as well as probe if the 1,2,3-triazole analogue can provide significant improvement to any activities

Nanosecond Time Resolved Electron Diffraction Studies of the (Alpha) to (Beta) Transition in Pure Ti Thin Films using the Dynamic Transmission Electron Microscope (DTEM)

The transient events of the {alpha}-{beta} martensitic transformation in nanocrystalline Ti films were explored via single shot electron diffraction patterns with 1.5 ns temporal resolution. The diffraction patterns were acquired with a newly constructed dynamic transmission electron microscope (DTEM), which combines nanosecond pulsed laser systems and pump-probe techniques with a conventional TEM. With the DTEM, the transient events of fundamental material processes, that are far too fast to be studied by conventional bulk techniques, can be captured in the form of electron diffraction patterns or images with nanosecond temporal resolution. The transient phenomena of the martensitic transformations in nanocrystalline Ti is ideally suited for study in the DTEM, with their rapid nucleation, characteristic interface velocities {approx}1 km/s, and significant irreversible microstructural changes. Free-standing 40-nm-thick Ti films were laser-heated at a rate of {approx}10{sup 10} K/s to a temperature above the 1155 K transition point, then probed at various time intervals with a 1.5-ns-long, intense electron pulse. Diffraction patterns show an almost complete transition to the {beta} phase within 500 ns. Postmortem analysis (after the sample is allowed to cool) shows a reversion to the {alpha} phase coupled with substantial grain growth, lath formation, and texture modification. The cooled material also shows a complete lack of apparent dislocations, suggesting the possible importance of a ''massive'' short-range diffusion transformation mechanism

Impact of Vitamin C on Endothelial Function and Exercise Capacity in Patients with a Fontan Circulation

Objective.  To evaluate the impact of antioxidant therapy on functional health status in Fontan‐palliated patients. Design.  Prospective, randomized, double‐blind, placebo‐controlled trial. Patients.  Fifty‐three generally asymptomatic Fontan patients. Interventions.  Patients were randomized to receive either high‐dose ascorbic acid (vitamin C) or placebo for 4 weeks. Outcome Measures.  Peripheral vascular function, as measured with endothelium‐dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. Results.  Twenty‐three vitamin C‐ and 21 placebo‐assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7–18.2) and 11.9 years (IQR 9.0–15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). Conclusions.  Short‐term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92126/1/j.1747-0803.2011.00605.x.pd

Training of child and adolescent psychiatry fellows in autism and intellectual disability

Patients with autism spectrum disorders and intellectual disability can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in autism spectrum disorder and intellectual disability, we surveyed training directors of child and adolescent psychiatry fellowship programs. On average, child and adolescent psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum disorder and intellectual disability, respectively. Training directors commonly reported that trainees see 1-5 patients with autism spectrum disorder or intellectual disability per year for outpatient pharmacological management and inpatient treatment. Overall, 43% of directors endorsed the need for additional resources for training in autism spectrum disorder and intellectual disability, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ≥17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted.Seaside Therapeutics Inc

LoCuSS: Comparison of Observed X-ray and Lensing Galaxy Cluster Scaling Relations with Simulations

The Local Cluster Substructure Survey (LoCuSS, Smith et al.) is a systematic multi-wavelength survey of >100 X-ray luminous galaxy clusters (0.14<z<0.3) selected from the ROSAT all sky survey. We used data on 37 LoCuSS clusters from the XMM-Newton archive to investigate the global scaling relations of galaxy clusters. The scaling relations based solely on the X-ray data obey empirical self-similarity and reveal no additional evolution beyond the LSS growth. Weak lensing mass measurements are also available in the literature for 19 of the clusters with XMM-Newton data. The average of the weak lensing mass to X-ray based mass ratio is 1.09+/-8, setting the limit of the non-thermal pressure support to 9+/-8%. The mean of the weak lensing mass to X-ray based mass ratio of these clusters is ~1 with 31-51% scatter. The scatter in the mass--observable relations (M-Y_X, M-M_{gas} and M-T) is smaller using X-ray based masses than using weak lensing masses by a factor of 2. Using the scaled radius defined by the Y_X profile, we obtain lower scatter in the weak lensing mass based mass--observable relations. The normalization of the M-Y_X relation (also M-M_{gas} and M-T relations) using X-ray (weak lensing) mass estimates is lower than the one from simulations by up to 20% at ~3 sigma (~2 sigma) significance. Despite the large scatter in the X-ray to lensing comparison, the agreement between these two completely independent observational methods is an important step towards controlling astrophysical and measurement systematics in cosmological scaling relations.Comment: 56 pages, 32 figure, 2008A&A...482..451Z, typos corrected in Table A.

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito anopheles gambiae

Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria