Micro parallel liquid chromatography for high-throughput compound purity analysis and early ADMET profiling

The Nanostream (Pasadena, CA) Veloce system, together with 24-column Brio cartridges, offers a novel approach to micro parallel liquid chromatography (μPLC). This system allows users to achieve unprecedented throughput for standard assays while matching the performance of conventional LC instrumentation, thus enabling routine compound purity assessment and physiochemical property profiling early in the drug discovery and development process.The Veloce system—which includes instrumentation, software, and replaceable microfluidic cartridges—incorporates pressure-driven flow to achieve chromatograms comparable to conventional high performance liquid chromatography (HPLC) instrumentation for a broad class of analytical applications while offering a dramatic increase in sample analysis capacity. The system enables parallel chromatographic separations and simultaneous, real-time UV detection. Each Nanostream Brio cartridge, made of polymeric materials, incorporates 24 columns packed with standard (C-18) stationary phase material to achieve reverse phase separations. Mixing and distribution of the mobile phase to each of the 24 columns is precisely controlled in each cartridge. The system provides an ideal platform to accelerate assessment of compound purity and physicochemical properties (i.e., log P, CHI, etc.) for a large number of compounds. In addition, the 24-fold increase in sample analysis capacity allows standard curve generation and simultaneous analysis of multiple replicates of samples in a single run.     

Vibrio vulnificus and Vibrio parahaemolyticus in U.S. retail shell oysters: a national survey from June 1998 to July 1999.

From June 1998 to July 1999, 370 lots of oysters in the shell were sampled at 275 different establishments (71%, restaurants or oyster bars; 27%, retail seafood markets: and 2%, wholesale seafood markets) in coastal and inland markets throughout the United States. The oysters were harvested from the Gulf (49%). Pacific (14%), Mid-Atlantic (18%), and North Atlantic (11%) Coasts of the United States and from Canada (8%). Densities of Vibrio vulnificus and Vibrio parahaemolyticus were determined using a modification of the most probable number (MPN) techniques described in the Food and Drug Administration's Bacteriological Analytical Manual. DNA probes and enzyme immunoassay were used to identify suspect isolates and to determine the presence of the thermostable direct hemolysin gene associated with pathogenicity of V. parahaemolyticus. Densities of both V. vulnifcus and V. parahaemolyticus in market oysters from all harvest regions followed a seasonal distribution, with highest densities in the summer. Highest densities of both organisms were observed in oysters harvested from the Gulf Coast, where densities often exceeded 10,000 MPN/g. The majority (78%) of lots harvested in the North Atlantic, Pacific, and Canadian Coasts had V. vulnificus densities below the detectable level of 0.2 MPN/g; none exceeded 100 MPN/g. V. parahaemolyticus densities were greater than those of V. vulnificus in lots from these same areas, with some lots exceeding 1,000 MPN/g for V. parahaemolyticus. Some lots from the Mid-Atlantic states exceeded 10,000 MPN/g for both V. vulnificus and V. parahaemolyicus. Overall, there was a significant correlation between V. vulificus and V. parahaemolyticus densities (r = 0.72, n = 202, P < 0.0001), but neither density correlated with salinity. Storage time significantly affected the V. vulnificus (10% decrease per day) and V. parahaemolyticus (7% decrease per day) densities in market oysters. The thermostable direct hemolysin gene associated with V parahaemolyticus virulence was detected in 9 of 3,429 (0.3%) V. parahaemolyticus cultures and in 8 of 198 (4.0%) lots of oysters. These data can be used to estimate the exposure of raw oyster consumers to V. vulnificus and V. parahaemolyticus.     

Rotated object identification with and without orientation cues.

The time to name two-dimensional line drawings of objects increases linearly for object rotations between 00 and 1200 from the upright. Several theories attribute these effects of orientation to finding the top or the top-bottom axis of objects. By this account, prior knowledge of the location of the top or the top-bottom axis of objects should diminish effects of object orientation when they are named. When this hypothesis was tested by cuing the top or the top-bottom axis, no reduction in the effects of orientation on object naming was found. This result is inconsistent with effects of orientation on object naming being due to finding the top or the top-bottom axis. Instead, the top may be found prior to rotational normalization of the object image. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of sibling relations to the adaptation of youths with insulin-dependent diabetes mellitus.

Associations among sibling relations and the psychosocial and illness-specific adaptation of youths (N?=?66) with insulin-dependent diabetes mellitus (IDDM) were examined. The findings suggest that sibling relations, especially sibling conflict, contribute an independent source of variance above and beyond that contributed by demographic characteristics, sibling constellation variables, and important dimensions of family relations in predicting the youths' adaptation. High family-life stress and high sibling status/power contributed unique variance in predicting internalizing behaviors, and male gender and sibling conflict contributed independently to externalizing problems. Sibling conflict also contributed unique variance to the youths' general self-esteem, along with social class and family cohesion, and to their adjustment to IDDM. Data suggest that parent–child dyads and sibling dyads represent interrelated and independent subsystems within the family, and that both subsystems may influence the psychosocial functioning of youths with IDDM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Terror management and cognitive-experiential self-theory: Evidence that terror management occurs in the experiential system.

The authors hypothesized, on the basis of terror management theory and cognitive-experiential self-theory, that participants in an experiential mode of thinking would respond to mortality salience with increased worldview defense and increased accessibility of death-related thoughts, whereas participants in a rational mode would not. Results from 3 studies provided convergent evidence that when participants were in an experiential mode, mortality salience produced the typical worldview defense effect, but when participants were in a rational mode it did not. Study 4 revealed that mortality salience also led to a delayed increase in the accessibility of death-related thoughts only when participants were in an experiential mode. These results supported the notion that worldview defense is intensified only if individuals are in an experiential mode when considering their mortality. Discussion focuses on implications for understanding terror management processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

In situ TEM nanoindentation and dislocation-grain boundary interactions: a tribute to David Brandon

As a tribute to the scientific work of Professor David Brandon, this paper delineates the possibilities of utilizing in situ transmission electron microscopy to unravel dislocation-grain boundary interactions. In particular, we have focused on the deformation characteristics of Al–Mg films. To this end, in situ nanoindentation experiments have been conducted in TEM on ultrafine-grained Al and Al–Mg films with varying Mg contents. The observed propagation of dislocations is markedly different between Al and Al–Mg films, i.e. the presence of solute Mg results in solute drag, evidenced by a jerky-type dislocation motion with a mean jump distance that compares well to earlier theoretical and experimental results. It is proposed that this solute drag accounts for the difference between the load-controlled indentation responses of Al and Al–Mg alloys. In contrast to Al–Mg alloys, several yield excursions are observed during initial indentation of pure Al, which are commonly attributed to the collective motion of dislocations nucleated under the indenter. Displacement-controlled indentation does not result in a qualitative difference between Al and Al–Mg, which can be explained by the specific feedback characteristics providing a more sensitive detection of plastic instabilities and allowing the natural process of load relaxation to occur. The in situ indentation measurements confirm grain boundary motion as an important deformation mechanism in ultrafine-grained Al when it is subjected to a highly inhomogeneous stress field as produced by a Berkovich indenter. It is found that solute Mg effectively pins high-angle grain boundaries during such deformation. The mobility of low-angle boundaries is not affected by the presence of Mg.Special title: Advanced Materials and Characterization: Proceedings of the Brandon Symposium; Guest Editors: Wayne D. Kaplan and Srinivasa Ranganathan     

Intentions in teasing: When "just kidding" just isn't good enough.

Teasing is ambiguous. Although the literal content of a tease is, by definition, negative, seldom do teasers intend for their tease to be taken literally. Toward this aim, teasers often attempt to mitigate the negative surface content of the tease by communicating via gesture, facial expression, or tone of voice that they are "just kidding." The research presented here suggests that such attempts often fall on deaf ears. Despite teasers' attempts to mitigate the tease, targets are often unaware of--and unmoved by--the teaser's benign intentions. As a result, teasers and targets systematically differ in their perceptions of teasing: Although it is often seen as innocent and playful by the teaser, it tends to be construed as considerably more malicious by the target. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypervelocity impact testing of the utility distribution system for the space station freedom

The Utility Distribution System (UDS) of the Space Station Freedom (SSF) is responsible for routing avionic harnesses and fluid line utilities along the pre-integrated truss segments. These harnesses and lines are housed in a rectangular aluminum carrier that provides a functional level of protection from the impacts of meteoroid and orbital debris (M/OD) particles. An analysis completed by McDonnell Douglas Corporation-Space Station Division (MDC-SSD) estimated that the avionics and fluid utilities in the UDS carrier could experience approximately 5600 failures over the 30 year life of the SSF--of which only 2 were failures of fluid lines. This large number was based mostly on a very conservative avionic conductor failure criteria that had to be used because little is known about the affects of M/OD on avionic conductors, especially behind a protective carrier over. As a result, a two-phase joint NASA-Johnson Space Center (JSC) and MDC-SSD hypervelocity impact (HVI) test program was initiated. From this test program, it was determined that the expected number of M/OD impacts that would cause an avionic conductor/cable failure is 28 over a 30 year period. For the fluid lines, the data indicate the number of predicted fluid line failures increased slightly from the initial analysis to as many as 15 for the entire 30 year life of SSF.     

Response to “On the Radicality of New York’s Reforming the Energy Vision” by Ross Astoria

Dr. Jeff D. Makholm responds to Professor Ross Astoria’s criticms of Dr. Makholm’s submission: “The REVolution yields to a more familiar path: New York’s Reforming the Energy Visition (REV), Electricity Journal 29 (2016), 48–55 as follows.     

Climate Change, “Grid Neutrality,” and Electricity Distributors

My late colleague and friend Alfred Kahn relayed how President Jimmy Carter hired him in 1977 to head the Civil Aeronautics Board to reform and ultimately deregulate the US airline industry. Accepting the job, he told a group of airline executives (to their fury), “I really don't know one plane from the other. To me they are all marginal costs with wings.” He used that term to signal his intention of reforming the industry in keeping with economic principles, uninfluenced by the romance of air travel.