PIV-LIF determination of mean velocity field and Reynolds stress tensor in a cavitating mixing layer

The purpose of this experimental study was to analyze a 2D cavitating shear layer. The global aim of this work was a better understanding and modeling of cavitation phenomena from a 2D turbulent shear flow to rocket engine turbopomp inducers. This 2D mixing layer flow provided us a well documented test case to be used for comparison between the behavior with and without cavitation. Similarities and differences led to characterize effects of the cavitation on the flow dynamic. The run fluid was liquid water. The experimental facility allowed us to set two distinct configurations with different cavitation levels: - CDM: a mixing layer flow (U1 = 15.8 m/s for the high speed side and U2= 3.5 m/s for the low speed side) - MD: a downward facing step flow (U1 = 13.5 m/s and U2 = 0 m/s). The development of Kelvin-Helmholtz instabilities was observed at the interface. Vaporizations and implosions of cavitating structures inside the vortices were also observed. PIV-LIF(Particle Image Velocimetry Laser Induced Fluorescence) system was used to measure the velocity of the liquid phase. Instantaneous velocity fields were measured in the whole flow. The self similarity of the flow was characterized by the dimensionless analysis of the mean and fluctuating velocity fields. Parameters that characterized the flow dynamic were studied and quantified: Vorticity thickness, growth rate and Reynolds tensor components. Turbulent kinetic energy and the anisotropy tensor components were also analyzed and estimated. General behaviors of the two configurations have been observed: - In the CDM case the mixing area developed along the x-axis a turbulent shear area, growing linearly, showing a constant growth rate over the studied cavitation parameter range. - The MD case was more complex, presenting a flow separation with a large recirculating area and a quite large positive pressure gradient. The reattachment point moved depending on the cavitation level. The recirculating area seemed to have an unsteady behavior and was certainly pulsing and shedding vortices downstream. Successive vaporizations and condensations of the fluid particles inside the turbulent area have generated additional velocity fluctuations due to the strong density changes associated with the vaporization and condensation processes. However, the mean spatial development of the mixing area was only barely affected over the studied cavitation number range. The main results of this study clearly showed that the turbulence-cavitation relationship inside a mixing layer is not only driven by a simple change of compressibility properties of the fluid in the turbulent field due to the presence of a twophase flow.http://deepblue.lib.umich.edu/bitstream/2027.42/84239/1/CAV2009-final38.pd

Somatostatin triggers rhythmic electrical firing in hypothalamic GHRH neurons

International audienc

Interest of pet imaging in multiple myeloma

The interest of 18Fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging in the management of patients with multiple myeloma (MM) for the workup at diagnosis and for therapeutic evaluation has recently been demonstrated. FDG-PET is a powerful imaging tool for bone lesions detection at initial diagnosis with high sensitivity and specificity values. The independent pejorative prognostic value on progression-free survival (PFS) and overall survival (OS) of baseline PET-derived parameters (presence of extra-medullary disease (EMD), number of focal bone lesions (FLs), and maximum standardized uptake values [SUVmax]) has been reported in several large independent prospective studies. During therapeutic evaluation, FDG-PET is considered as the reference imaging technique, because it can be performed much earlier than MRI which lacks specificity. Persistence of significant FDG uptake after treatment, notably before maintenance therapy, is an independent pejorative prognostic factor, especially for patients with a complete biological response. So FDG-PET and medullary flow cytometry are complementary tools for detection of minimal residual disease before maintenance therapy. However, the definition of PET metabolic complete response should be standardized. In patients with smoldering multiple myeloma, the presence of at least one hyper-metabolic lytic lesions on FDG-PET may be considered as a criterion for initiating therapy. FDG-PET is also indicated for initial staging of a solitary plasmacytoma so as to not disregard other bone or extra-medullary localizations. Development of nuclear medicine offer new perspectives for MM imaging. Recent PET tracers are willing to overcome limitations of FDG. (11)C-Methionine, which uptake reflects the increased protein synthesis of malignant cells seems to correlate well with bone marrow infiltration. Lipid tracers, such as Choline or acetate, and some peptide tracers, such as (68) Ga-Pentixafor, that targets CXCR4 (chemokine receptor-4, which is often expressed with high density by myeloma cells), are other promising PET ligands. 18F-fludarabine and immuno-PET targeting CD138 and CD38 also showed promising results in preclinical models

TRANSFAC(®) and its module TRANSCompel(®): transcriptional gene regulation in eukaryotes

The TRANSFAC(®) database on transcription factors, their binding sites, nucleotide distribution matrices and regulated genes as well as the complementing database TRANSCompel(®) on composite elements have been further enhanced on various levels. A new web interface with different search options and integrated versions of Match™ and Patch™ provides increased functionality for TRANSFAC(®). The list of databases which are linked to the common GENE table of TRANSFAC(®) and TRANSCompel(®) has been extended by: Ensembl, UniGene, EntrezGene, HumanPSD™ and TRANSPRO™. Standard gene names from HGNC, MGI and RGD, are included for human, mouse and rat genes, respectively. With the help of InterProScan, Pfam, SMART and PROSITE domains are assigned automatically to the protein sequences of the transcription factors. TRANSCompel(®) contains now, in addition to the COMPEL table, a separate table for detailed information on the experimental EVIDENCE on which the composite elements are based. Finally, for TRANSFAC(®), in respect of data growth, in particular the gain of Drosophila transcription factor binding sites (by courtesy of the Drosophila DNase I footprint database) and of Arabidopsis factors (by courtesy of DATF, Database of Arabidopsis Transcription Factors) has to be stressed. The here described public releases, TRANSFAC(®) 7.0 and TRANSCompel(®) 7.0, are accessible under

FtsK-Dependent Dimer Resolution on Multiple Chromosomes in the Pathogen Vibrio cholerae

Unlike most bacteria, Vibrio cholerae harbors two distinct, nonhomologous circular chromosomes (chromosome I and II). Many features of chromosome II are plasmid-like, which raised questions concerning its chromosomal nature. Plasmid replication and segregation are generally not coordinated with the bacterial cell cycle, further calling into question the mechanisms ensuring the synchronous management of chromosome I and II. Maintenance of circular replicons requires the resolution of dimers created by homologous recombination events. In Escherichia coli, chromosome dimers are resolved by the addition of a crossover at a specific site, dif, by two tyrosine recombinases, XerC and XerD. The process is coordinated with cell division through the activity of a DNA translocase, FtsK. Many E. coli plasmids also use XerCD for dimer resolution. However, the process is FtsK-independent. The two chromosomes of the V. cholerae N16961 strain carry divergent dimer resolution sites, dif1 and dif2. Here, we show that V. cholerae FtsK controls the addition of a crossover at dif1 and dif2 by a common pair of Xer recombinases. In addition, we show that specific DNA motifs dictate its orientation of translocation, the distribution of these motifs on chromosome I and chromosome II supporting the idea that FtsK translocation serves to bring together the resolution sites carried by a dimer at the time of cell division. Taken together, these results suggest that the same FtsK-dependent mechanism coordinates dimer resolution with cell division for each of the two V. cholerae chromosomes. Chromosome II dimer resolution thus stands as a bona fide chromosomal process

Uncovering mechanisms of transcriptional regulations by systematic mining of cis regulatory elements with gene expression profiles

<p>Abstract</p> <p>Background</p> <p>Contrary to the traditional biology approach, where the expression patterns of a handful of genes are studied at a time, microarray experiments enable biologists to study the expression patterns of many genes simultaneously from gene expression profile data and decipher the underlying hidden biological mechanism from the observed gene expression changes. While the statistical significance of the gene expression data can be deduced by various methods, the biological interpretation of the data presents a challenge.</p> <p>Results</p> <p>A method, called CisTransMine, is proposed to help infer the underlying biological mechanisms for the observed gene expression changes in microarray experiments. Specifically, this method will predict potential cis-regulatory elements in promoter regions which could regulate gene expression changes. This approach builds on the MotifADE method published in 2004 and extends it with two modifications: up-regulated genes and down-regulated genes are tested separately and in addition, tests have been implemented to identify combinations of transcription factors that work synergistically. The method has been applied to a genome wide expression dataset intended to study myogenesis in a mouse C2C12 cell differentiation model. The results shown here both confirm the prior biological knowledge and facilitate the discovery of new biological insights.</p> <p>Conclusion</p> <p>The results validate that the CisTransMine approach is a robust method to uncover the hidden transcriptional regulatory mechanisms that can facilitate the discovery of mechanisms of transcriptional regulation.</p

NFAT5 Regulates HIV-1 in Primary Monocytes via a Highly Conserved Long Terminal Repeat Site

To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5), which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E) is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor–viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5–LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS

Reproductive Strategy of the Giant Electric Ray in the Southern Gulf of California

The objective of the present study was to describe and characterize macroscopic and microscopic aspects of the reproductive biology of the Giant Electric Ray Narcine entemedor, a viviparous elasmobranch targeted by commercial fishers in Mexico. A total of 305 individual rays were captured (260 females, 45 males); all males were sexually mature. The median size at maturity for females was estimated to be 58.5 cm TL, the median size at pregnancy was 63.7 cm TL, and the median size at maternity was 66.2 cm TL. The range of ovarian follicles recorded per female was 1–69; the maximum ovarian fecundity of fully grown vitellogenic oocytes was 17, and uterine fecundity ranged from 1 to 24 embryos per female. The lengths of the oblong ovarian follicles varied significantly among months, and the largest ovarian follicles were found in July, August, and September. Median embryo size was largest in August, and the size at birth was between 12.4 and 14.5 cm TL. Histological evidence of secretions from the glandular tissue of the uterine villi indicate that this species probably has limited histotrophy as a reproductive mode. Vitellogenesis in the ovary occurred synchronously with gestation in the uterus. The Giant Electric Ray has a continuous annual reproductive cycle; a period of ovulation occurs between May and September and two peaks of parturition, one in January and one in August, occur, suggesting that embryonic diapause occurs in some individuals. These results provide useful information for the management of this important commercial species in Bahía de La Paz, Mexico, and will allow possible modification of the current Mexican regulations to enable better protection of this species

'So wide and varied': The origins and character of British information science

This paper examines some characteristics of the ‘British School’ of information science. Three main forces driving the development of the new subject in Britain are identified: the documentation movement; special libraries; and the need for better treatment of scientific and technical information. Five characteristics which, taken together, distinguish the early British approach to information science from those adopted elsewhere are identified: its subject-based nature; its broad approach to information and information science; its status as an academic subject with a strong professional remit; its involvement with, but distinction from, information technology; and its involvement with memory institutions. Lessons are drawn for the future development of the information sciences

Role of Operon aaoSo-mutT in Antioxidant Defense in Streptococcus oligofermentans

Previously, we have found that an insertional inactivation of aaoSo, a gene encoding L-amino acid oxidase (LAAO), causes marked repression of the growth of Streptococcus oligofermentans. Here, we found that aaoSo and mutT, a homolog of pyrophosphohydrolase gene of Escherichia coli, constituted an operon. Deletion of either gene did not impair the growth of S. oligofermentans, but double deletion of both aaoSo and mutT was lethal. Quantitative PCR showed that the transcript abundance of mutT was reduced for 13-fold in the aaoSo insertional mutant, indicating that gene polarity derived from the inactivation of aaoSo attenuated the expression of mutT. Enzymatic assays were conducted to determine the biochemical functions of LAAO and MutT of S. oligofermentans. The results indicated that LAAO functioned as an aminoacetone oxidase [47.75 nmol H2O2 (min·mg protein)–1]; and MutT showed the pyrophosphohydrolase activity, which removed mutagens such as 8-oxo-dGTP. Like paraquat, aaoSo mutations increased the expression of SOD, and addition of aminoacetone (final concentration, 5 mM) decreased the mutant’s growth by 11%, indicating that the aaoSo mutants are under ROS stress. HPLC did reveal elevated levels of cytoplasmic aminoacetone in both the deletion and insertional gene mutants of aaoSo. Electron spin resonance spectroscopy showed increased hydroxyl radicals in both types of aaoSo mutant. This demonstrated that inactivation of aaoSo caused the elevation of the prooxidant aminoacetone, resulting the cellular ROS stress. Our study indicates that the presence of both LAAO and MutT can prevent endogenous metabolites-generated ROS and mutagens. In this way, we were able to determine the role of the aaoSo-mutT operon in antioxidant defense in S. oligofermentans