The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Integrated carbon nanotube field emission differential amplifier: Modeling and measurement of the common-mode rejection ratio

A novel integrated vacuum field emission (VFE) differential amplifier (diff-amp) utilizing carbon nanotube (CNT) emitters has been developed. A dual-mask microfabrication process was employed to achieve a VFE diff-amp by integrating identical CNT VFE transistors with built-in split gates and integrated anodes. The identical pair of triode amplifiers was well-matched in their device characteristics. The measured ac small-signal characteristics of the diff-amp showed a common-mode-rejection ratio (CMRR) of ~ 320 (~ 50 dB). The proposed analytical model of the CMRR was verified to be in good agreement with the experimental data. The successful implementation of the CNT diff-amp demonstrates a new way to achieve temperature and radiation tolerant VFE integrated microelectronics.     

Ultralow-voltage boron-doped diamond field emitter vacuum diode

A boron-doped diamond field emitter diode with ultralow turn-on voltage and high emission current is reported. The diamond field emitter diode structure with a built-in cap was fabricated using molds and electrostatic bonding techniques. The emission current versus anode voltage of the capped diamond emitter diode with boron doping, sp² content, and vacuum thermal electric (VTE) treatment shows a very low turn-on voltage of 2 V. A high emission current of 1 μA at an anode voltage of less than 10 V can be obtained from a single diamond tip. The turn-on voltage is significantly lower than comparable silicon field emitters     

Forward-bias conduction of Schottky diodes on polysilicon thinfilms

An analysis of forward I-V characteristics for Al Schottky contacts to polycrystalline thin films is presented. Experimental results for lateral structures with various n^- doping levels show the expected twofold exponential characteristics representing a transition from electrode-limited to bulk-limited conduction. At higher doping levels the bulk-limited characteristic is not a perfect exponential. The thermionic emission theory has been modified to include crystallite resistivity between grain boundaries and successfully matches experimental data     

Alcoholism at the time of injury among trauma center patients: Vehicular crash victims compared with other patients

A structured in-depth interview employing standardized criteria was used to determine the prevalence of lifetime and current alcohol dependence (alcoholism) in unselected consecutive patients admitted to a regional Level I trauma center. Of 629 patients, 157 (25.0%) were current alcoholics at the time of injury. An additional 87 (13.8%) were diagnosed as lifetime non-current alcoholics. There was no significant difference in the rates of current alcohol dependence among patients injured in vehicular crashes (23.5%), other unintentional trauma victims (29.3%), and those injured as a result of violence (24.6%). Of BAC + (blood alcohol concentration positive) patients, 54.5% were current alcoholics. However, 14.4% of alcohol-negative patients were also diagnosed as alcohol dependent.     

Constraints on Models of Electrical Transport in Optimally Doped La2?xSrxCuO4 from Measurements of Radiation-Induced Defect Resistance

Precise measurements of the temperature dependence of additional resistivity caused by defect scattering were used to constrain models of carrier transport in La_1.84Sr_0.16CuO₄. Where previous magnetotransport studies have delineated two distinct scattering processes, proportional to T and T ², respectively, the new defect scattering results suggest strongly that the two processes act as parallel conductance channels.     

Schizotypy facets, cognitive control, and emotion.

This research examined whether facets of schizotypy were differentially related to cognitive control and emotion-processing traits. In a confirmatory factor analysis (N = 261), a 3-factor model of schizotypy exhibited good fit and fit significantly better than a 2-factor model. In addition, only disorganized schizotypy was associated with poor cognitive control (specifically, prepotent inhibition). Moreover, disorganized but not positive schizotypy was associated with increased emotional confusion and increased emotionality. In contrast, negative schizotypy was associated with increased emotional confusion but decreased emotionality. These results suggest that disorganized schizotypy is related to dysregulation of both cognition and emotion and that negative schizotypy might reflect deficits in the experience and processing of emotion and not just in emotional expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

LC/MS applications in drug development

The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a significant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative, have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development. New technologies have created a situation where the rate of sample generation far exceeds the rate of sample analysis. As a result, new paradigms for the analysis of drugs and related substances have been developed. The growth in LC/MS applications has been extensive, with retention time and molecular weight emerging as essential analytical features from drug target to product. LC/MS-based methodologies that involve automation, predictive or surrogate models, and open access systems have become a permanent fixture in the drug development landscape. An iterative cycle of "what is it?" and "how much is there?" continues to fuel the tremendous growth of LC/MS in the pharmaceutical industry. During this time, LC/MS has become widely accepted as an integral part of the drug development process. This review describes the utility of LC/MS techniques for accelerated drug development and provides a perspective on the significant changes in strategies for pharmaceutical analysis. Future applications of LC/MS technologies for accelerated drug development and emerging industry trends are also discussed.     

Circuit related issues due to radiation in hostile environments

Various types of radiation in hostile environments cause transient and permanent changes in the devices used in complex integrated circuits. The failure of a particular IC is a function not only of the basic material and device parameter changes but also of the circuit environment in which the device is located. Circuit techniques have been developed which minimize the detrimental effects of radiation on certain types of circuits. In other cases, circuit techniques are not very effective in minimizing radiation effects. This work discusses selected issues related to the interactions between device radiation effects and circuit performance or circuit failure in a hostile radiation environment. This is not meant to be a comprehensive study of circuit effects but rather several examples are selected to illustrate the issues involved in designing circuits to operate in hostile radiation environments.     

Parent–child attachment and monitoring in middle childhood.

Research on parent–child attachment and parental child rearing practices has been pursued independently. The purpose of the present study was to test whether a secure attachment relationship is related to parental monitoring and child efforts to contribute to the monitoring process. This question was examined in a cross-sectional study of third- and sixth-grade children and their parents. Attachment-based measures were used to tap child and parent perceptions of attachment. Monitoring (i.e., parents' awareness of children's whereabouts and activities) was assessed through phone interviews with children and parents. Child contributions to monitoring were assessed with parent and child questionnaires. A more secure attachment was related to closer monitoring and greater cooperation by the child in monitoring situations, especially at sixth grade. The findings illustrate the importance of embedding attachment within a larger child rearing context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)