Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients

Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

The NCBO OBOF to OWL Mapping

Two of the most significant formats for biomedical ontologies are the Open Biomedical Ontologies Format (OBOF) and the Web Ontology Language (OWL). To make it possible to translate ontologies between these two representation formats, the National Center for Biomedical Ontology (NCBO) has developed a mapping between the OBOF and OWL formats as well as inter-conversion software. The goal was to allow the sharing of tools, ontologies, and associated data between the OBOF and Semantic Web communities.

OBOF does not have a formal grammar, so the NCBO had to capture its intended semantics to map it to OWL.

This official NCBO mapping was used to make all OBO Foundry ontologies available in OWL. 

Availability: This mapping functionality can be embedded into OBO-Edit and Protégé-OWL ontology editors. This software is available at: http://bioontology.org/wiki/index.php/OboInOwl:Main_Pag

Proton Heating in Solar Wind Compressible Turbulence with Collisions between Counter-propagating Waves

Magnetohydronamic turbulence is believed to play a crucial role in heating the laboratorial, space, and astrophysical plasmas. However, the precise connection between the turbulent fluctuations and the particle kinetics has not yet been established. Here we present clear evidence of plasma turbulence heating based on diagnosed wave features and proton velocity distributions from solar wind measurements by the Wind spacecraft. For the first time, we can report the simultaneous observation of counter-propagating magnetohydrodynamic waves in the solar wind turbulence. Different from the traditional paradigm with counter-propagating Alfv\'en waves, anti-sunward Alfv\'en waves (AWs) are encountered by sunward slow magnetosonic waves (SMWs) in this new type of solar wind compressible turbulence. The counter-propagating AWs and SWs correspond respectively to the dominant and sub-dominant populations of the imbalanced Els\"asser variables. Nonlinear interactions between the AWs and SMWs are inferred from the non-orthogonality between the possible oscillation direction of one wave and the possible propagation direction of the other. The associated protons are revealed to exhibit bi-directional asymmetric beams in their velocity distributions: sunward beams appearing in short and narrow patterns and anti-sunward broad extended tails. It is suggested that multiple types of wave-particle interactions, i.e., cyclotron and Landau resonances with AWs and SMWs at kinetic scales, are taking place to jointly heat the protons perpendicularly and parallel

1970 Problems in Legal Education

Five problems in legal education, much discussed recently, were posed by the Editors of this Review to a number of administrative figures in the law school world. These questions were and are frankly difficult and controversial, but their answers are important to our system of legal education and to our society. Capsule answers given by these concerned legal education administrators are believed to be interesting and significant. Each is a personal rather than a representative opinion. Brief answers such as these, of course, are not expected to be, nor do they pretend to be, complete or profound. Their purpose is to indicate succinctly the approach of some law school administrative opinion makers to difficult policy problems of legal education

1970 Problems in Legal Education

Five problems in legal education, much discussed recently, were posed by the Editors of this Review to a number of administrative figures in the law school world. These questions were and are frankly difficult and controversial, but their answers are important to our system of legal education and to our society. Capsule answers given by these concerned legal education administrators are believed to be interesting and significant. Each is a personal rather than a representative opinion. Brief answers such as these, of course, are not expected to be, nor do they pretend to be, complete or profound. Their purpose is to indicate succinctly the approach of some law school administrative opinion makers to difficult policy problems of legal education

Effects of a Carbohydrate and Protein Recovery Beverage on Performance in Trained Weightlifters

INTRODUCTION: Previous investigations have examined nutrient timing with untrained subject and less is known about effects in trained subjects. OBJECTIVES: The purpose of this study was to examine the effects of a carbohydrate and protein supplement (CHO+PROT) on performance measures in trained weightlifters. METHODS: 10 trained weightlifters (30.8±5.1 years, 177.4 ±4.0 cm, 94.3 ± 12.4 kg, training age = 5.3 ± 2.9 years) completed a 12 week training program utilizing block periodization. Using a double blind placebo design, jump height, scaled peak power measured in vertical jumps and peak force and rate of force development measured in isometric mid-thigh pulls were compared between groups using a series of 2x4 (group x time) repeated measures ANOVA’s. RESULTS: No significant differences (p \u3e 0.05) were observed between treatment and placebo groups in respect to measures of jump height and peak power with weighted and unweighted jumps. Likewise, no statistical differences (p \u3e 0.05) were observed for peak force or rate of force development with isometric mid-thigh pulls. CONCLUSION: These findings indicate that a CHO+PROT supplement provided no additional performance benefits compared to a placebo within a 12 week block periodization protocol in trained weightlifters

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

An investigation into the preservation of microbial cell banks for alpha-amylase production during 5L fed-batch Bacillus licheniformis fermentations

Fluorescent staining techniques were used for a systematic examination of methods used to cryopreserve microbial cell banks. The aim of cryopreservation here is to ensure subsequent reproducible fermentation performance rather than just post thaw viability. Bacillus licheniformis cell physiology post-thaw is dependent on the cryopreservant (either Tween 80, glycerol or dimethyl sulphoxide) and whilst this had a profound effect on the length of the lag phase, during subsequent 5 l fed-batch fermentations, it had little effect on maximum specific growth rate, final biomass concentration or a-amylase activity. Tween 80 not only protected the cells during freezing but also helped them recover post-thaw resulting in shorter process times