The Multifragmentation Freeze--Out Volume in Heavy Ion Collisions

The reduced velocity correlation function for fragments from the reaction Fe + Au at 100 A~MeV bombarding energy is investigated using the dynamical--statistical approach QMD+SMM and compared to experimental data to extract the Freeze--Out volume assuming simultaneous multifragmentation.Comment: 8 pages; 3 uuencoded figures available with figures command, LateX, UCRL-J-1157

The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics

Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression

Identificación de nematodos gastrointestinales en búfalos faenados en un frigorífico de Corrientes, Argentina

The objective of this work was to identify and quantify the adult specimens of gastrointestinal nematodes in buffaloes slaughtered in Virasoro (Corrientes, Argentina) by means of necropsy of the digestive tract, and through coprological studies, in order to correlate them with the count of eggs per gram of fecal stool and the proportion of parasite genera of third stage larvae of stool culture. A total of 4 necropsies corresponding to young male buffaloes were carried out, of which 50% presented adult specimens of Trichostrongylus sp and Haemonchus sp located only in the abomasum. In the coprological studies, 75% of the samples presented counts of egg per gram of fecal stool, with only 2 cases with the identification of third stage larvae of Haemonchus sp in stool cultures.El objetivo del trabajo fue identificar y cuantificar los ejemplares adultos de nematodos gastrointestinales en los búfalos faenados en el frigorífico de Virasoro (Corrientes) mediante la necropsia parasitaria del tubo digestivo y, por intermedio de estudios coprológicos, correlacionarlos con el recuento de huevos por gramo de materia fecal y la proporción de géneros parasitarios de larvas de tercer estadio de los coprocultivos. Se realizaron en total 4 necropsias parasitarias que correspondieron a búfalos machos jóvenes, de los cuales el 50% presentó ejemplares adultos de Trichostrongylus sp y Haemonchus sp ubicados solamente en el abomaso. En los estudios coprológicos, el 75% de las muestras presentaron recuentos de huevos por gramo de materia fecal, de los cuales únicamente en dos casos se pudieron identificar larvas de tercer estadio de Haemonchus sp en los coprocultivos

Toward An Understanding Of The Retinal Chromophore In Rhodopsin Mimics

Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combine computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (lambda(a)(max)), fluorescence (lambda(f)(max)), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age.Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential

Statistical Multifragmentation of Non-Spherical Expanding Sources in Central Heavy-Ion Collisions

We study the anisotropy effects measured with INDRA at GSI in central collisions of Xe+Sn at 50 A.MeV and Au+Au at 60, 80, 100 A.MeV incident energy. The microcanonical multifragmentation model with non-spherical sources is used to simulate an incomplete shape relaxation of the multifragmenting system. This model is employed to interpret observed anisotropic distributions in the fragment size and mean kinetic energy. The data can be well reproduced if an expanding prolate source aligned along the beam direction is assumed. An either non-Hubblean or non-isotropic radial expansion is required to describe the fragment kinetic energies and their anisotropy. The qualitative similarity of the results for the studied reactions suggests that the concept of a longitudinally elongated freeze-out configuration is generally applicable for central collisions of heavy systems. The deformation decreases slightly with increasing beam energy.Comment: 35 pages, 19 figures, submitted to Nuclear Physics

Consensus statement of the European guidelines on clinical management of HIV-1 tropism testing

Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UKIntroduction: Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. To date, in most European countries HIV tropism is determined using a phenotypic test. Recently, new data have emerged supporting the use of a genotypic HIV V3-loop sequence analysis as the basis for tropism determination. The European guidelines group on clinical management of HIV-1 tropism testing was established to make recommendations to clinicians and virologists. Methods: We searched online databases for articles from Jan 2006 until March 2010 with the terms: tropism or CCR5-antagonist or CCR5 antagonist or maraviroc or vicriviroc. Additional articles and/or conference abstracts were identified by hand searching. This strategy identified 712 potential articles and 1240 abstracts. All were reviewed and finally 57 papers and 42 abstracts were included and used by the panel to reach a consensus statement. Results: The panel recommends HIV-tropism testing for the following indications: i) drug-naïve patients in whom toxicity or limited therapeutic options are foreseen; ii) patients experiencing therapy failure whenever a treatment change is considered. Both the phenotypic Enhanced Trofile assay (ESTA) and genotypic population sequencing of the V3-loop are recommended for use in clinical practice. Although the panel does not recommend one methodology over another it is anticipated that genotypic testing will be used more frequently because of its greater accessibility, lower cost and shorter turnaround time. The panel also provides guidance on technical aspects and interpretation issues. If using genotypic methods, triplicate PCR amplification and sequencing testing is advised using the G2P interpretation tool (clonal model) with an FPR of 10%. If the viral load is below the level of reliable amplification, proviral DNA can be used, and the panel recommends performing triplicate testing and use of an FPR of 10%. If genotypic DNA testing is not performed in triplicate the FPR should be increased to 20%. Conclusions: The European guidelines on clinical management of HIV-1 tropism testing provide an overview of current literature, evidence-based recommendations for the clinical use of tropism testing and expert guidance on unresolved issues and current developments. Current data support both the use of genotypic population sequencing and ESTA for co-receptor tropism determination. For practical reasons genotypic population sequencing is the preferred method in Europe.Ye