Synthesis of indoles via alkylidenation of acyl hydrazides

Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones

Modeling energy and reproductive costs in caribou exposed to low flying military jet aircraft

We used simulation modeling to estimate the effect of low-flying military jet aircraft on the productivity of caribou. The base model (CARIBOU, CWS Whitehorse, Yukon Territory) uses daily intake and expenditure of energy to assess the condition of female caribou throughout the annual cycle. The activity budget of the model caribou was adjusted based on field observations of responses to noise disturbance. A subroutine was added that predicted the likelihood of conception based on fall body fat weight. Caribou responses to overflights were evaluated by equipping free-ranging caribou with radio collars and activity sensors that could distinguish between resting and active periods. Collared animals were exposed to 110 overflights by A-10, F-15 and F- 16 jet aircraft during late-winter, post-calving and the insect season. Noise exposure levels for individual animals either were measured directly with collar-mounted dosimeters or were estimated based on the proximity of the caribou to the aircraft during the overflight. A Time-averaged Sound Level (LT) was calculated from the total daily noise exposure for each animal and linear regression was used to evaluate the influence of daily noise exposure on daily hours spent resting. Results of these analyses then were used to modify the time budgets in the CARIBOU model. That is, if time spent resting declined, then time spent in the two rest classes (lying and standing) were proportionately redistributed into the three active classes (foraging, walking and running). Model simulations indicated that caribou increased forage intake in response to increased noise exposure, but it also predicted that increased noise exposure would cause a reduced accumulation of body fat. Because body fat in fall has successfully been used to predict the probability of pregnancy (see Gerhart et al, 1993), this relationship was used in the model. Preliminary model simulations indicate that increased noise exposure decreases the probability of pregnancy and that unfavorable environmental conditions (e.g., deep snow and severe insect harassment) exacerbate the situation. The threshold at which point the caribou fail to conceive has not been determined at this time, but appears to be well beyond the exposure to aircraft that caribou in the Delta herd are currently experiencing

Surface Roughness Enhancement of Indirect-SLS Metal Parts by Laser Surface Polishing

Laser polishing by means of shallow surface melting of indirect-SLS metal parts was achieved using high power CO2 and Nd:YAG lasers raster scanned at high speed. This was an effective technique for reducing surface roughness. The fast moving laser beam provides just enough heat energy to cause melting of the surface peaks. The molten mass then flows into the surface valleys by surface tension, gravity and laser pressure, thus diminishing the roughness. Surface roughness Ra data were obtained by profilometry measurements of the polished samples. An analytical model was developed based on the assumption that the surface of an SLS part consists of semi-spherical caps. The model was used to predict the Ra values as a function of laser power, scan speed and precursor powder particle size. The modeled results fit the empirical data within a 15% error.The Laboratory of Freeform Fabrication gratefully acknowledges the support of the Office of Naval Research for funding the project “Surface Engineering for SFF Processes”, Grant Nº: N00014-00-1-0334Mechanical Engineerin

Cryo-EM studies of Drp1 reveal cardiolipin interactions that activate the helical oligomer

Dynamins are mechano-chemical GTPases involved in the remodeling of cellular membranes. In this study, we have investigated the mechanism of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission. To date, it is unclear how Drp1 assembles on the mitochondrial outer membrane in response to different lipid signals to induce membrane fission. Here, we present cryo-EM structures of Drp1 helices on nanotubes with distinct lipid compositions to mimic membrane interactions with the fission machinery. These Drp1 polymers assemble exclusively through stalk and G-domain dimerizations, which generates an expanded helical symmetry when compared to other dynamins. Interestingly, we found the characteristic gap between Drp1 and the lipid bilayer was lost when the mitochondrial specific lipid cardiolipin was present, as Drp1 directly interacted with the membrane. Moreover, this interaction leads to a change in the helical structure, which alters G-domain interactions to enhance GTPase activity. These results demonstrate how lipid cues at the mitochondrial outer membrane (MOM) can alter Drp1 structure to activate the fission machinery

Tunneling ``zero-bias'' anomaly in the quasi-ballistic regime

For the first time, we study the tunneling density of states (DOS) of the interacting electron gas beyond the diffusive limit. A strong correction to the DOS persists even at electron energies exceeding the inverse transport relaxation time, which could not be expected from the well-known Altshuler-Aronov-Lee (AAL) theory. This correction originates from the interference between the electron waves scattered by an impurity and by the Friedel oscillation this impurity creates. Account for such processes also revises the AAL formula for the DOS in the diffusive limit.Comment: 4 pages, 2 .eps figures, submitted to Phys. Rev. Let

Recovery from addiction: Behavioral economics and value-based decision making.

Behavioral economics provides a general framework to explain the shift in behavioral allocation from substance use to substance-free activities that characterizes recovery from addiction, but it does not attempt to explain the internal processes that prompt those behavioral changes. In this article we outline a novel analysis of addiction recovery based on computational work on value-based decision making (VBDM), which can explain how people with addiction are able to overcome the reinforcement pathologies and decision-making vulnerabilities that characterize the disorder. The central tenet of this account is that shifts in molar reinforcer preferences over time from substance use to substance-free activities can be attributed to changes in evidence accumulation rates and response thresholds in the context of choices involving substance use and substance-free alternatives. We discuss how this account can be reconciled with the established mechanisms of action of psychosocial interventions for addiction and demonstrate how it has the potential to empirically address longstanding debates regarding the nature of impairments to self-control in addiction. We also highlight conceptual and methodological issues that require careful consideration in translating VBDM to addiction and recovery

3D Printing of a Polymer Bioactive Glass Composite for Bone Repair

A major limitation of synthetic bone repair is insufficient vascularization of the interior region of the scaffold. In this study, we investigated the 3D printing of adipose derived mesenchymal stem cells (AD-MSCs) with polycaprolactone (PCL)/bioactive glass composite in a single process. This offered a three-dimensional environment for complex and dynamic interactions that govern the cell’s behavior in vivo. Borate based bioactive (13-93B3) glass of different concentrations (10 to 50 weight %) was added to a mixture of PCL and organic solvent to make an extrudable paste. AD-MSCs suspended in Matrigel was extruded as droplets using a second syringe. Scaffolds measuring 10x10x1 mm3 in overall dimensions with a filament width of ~500 μm and pore sizes ranging from 100 to 200 μm were fabricated. Strut formability dependence on paste viscosity, scaffold integrity, and printing parameters for droplets of ADMSCs suspended in Matrigel were investigated

Isospin Response of the 4-He Continuum

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

Anisotropic low field behavior and the observation of flux jumps in CeCoIn5

The magnetic behavior of the heavy fermion superconductor CeCoIn5 has been investigated. The low field magnetization data show flux jumps in the mixed state of the superconducting phase in a restricted range of temperature. These flux jumps begin to disappear below 1.7 K, and are completely absent at 1.5 K. The magnetization loops are asymmetric, suggesting that surface and geometrical factors dominate the pinning in this system. The lower critical field (Hc1), obtained from the magnetization data, shows a linear temperature dependence and is anisotropic. The calculated penetration depth is also anisotropic, which is consistent with the observation of an anisotropic superconducting gap in CeCoIn5. The critical currents, determined from the high field isothermal magnetization loops, are comparatively low (around 4000 A/cm2 at 1.6 K and 5 kOe).Comment: 4 pages 3 figure

Correlation of tissue-typing tests in baboon renal allotransplants

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