Gas-to-wall absorbed dose conversion factors for neutron energies of 25 to 250 MeV

Cavity chamber absorbed dose measurements do not usually strictly adhere to the conditions of the Fano theorem and therefore the differences in the gas and wall mass stopping powers must be taken into account. Values of gas-to-wall absorbed dose conversion factors rm,g were calculated for neutron energies of 25 to 250 MeV for detectors with walls of C, O, Mg, Al, Si, Fe, Zr, AlN, Al2O3, SiO2, ZrO2, and A-150 tissue-equivalent (TE) plastic and with gas cavities of acetylene, dry air, Ar, an Ar-CO2 mixture, CO2, isobutane, isobutane-based TE, methane, methane-based TE, propane, and propane-based TE. The rm,g calculations required initial spectral fluences of 1H, 2H, 3H, 3He, and 4He ions released by neutron reactions in the walls, and these were calculated with the Los Alamos High Energy Transport code. Mass-stopping-power data were taken from Ziegler and co-workers. Additional calculations were made in order to test the sensitivity of rm,g to input data from other sources, i.e., ion spectral fluences from the ALICE nuclear reaction code and mass-stopping powers from the recent ICRU evaluation. © 1997 Academic Press

CGM2, a Member of the Carcinoembryonic Antigen Gene Family is Down- Regulated in Colorectal Carcinomas

We have determined the precise chromosomal location, the exon structure, and the expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene family. CGM2 cDNA was amplified by reverse transcription-polymerase chain reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective exon is missing from this cDNA clone, leading to a novel domain organization for the human CEA family with two immunoglobulin-like domains. The derived C-terminal domain predicts that the CGM2 protein is membrane-bound through a glycosyl phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic tissue, but not in other tumors including leukocytes from six chronic myeloid leukemia patients. Thus, unlike several other family members, CGM2 is not expressed in granulocytes but reveals a more CEA-like expression pattern. Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down-regulated in colonic adenocarcinomas compared with adjacent colonic mucosa, suggesting a possible tumor suppressor function. In addition, a 3.2- kilobase transcript was observed in a number of colon tumors that is not detectable in normal colonic tissue. This mRNA species could represent a tumor-specific CGM2 splice variant

Experimental Investigation of the Interaction between Purge and Main Annulus Flow upstream of a Guide Vane in a Low Pressure Turbine

In modern gas turbines or jet engines, the ingestion of hot gas through the hub-side gap between rotor and stator blades has to be prevented successfully in order to shield the turbine discs from high temperatures. For this purpose, compressor air is fed into the rotor-stator wheelspace. There it purges and hence seals the unavoidable gap between the rotor and the stator row which is referred to as the rim seal. In general, this so-called purge flow has detrimental effects. On the one hand, it does not fully contribute to the thermodynamic cycle of the engine. On the other hand, it spoils the main flow aerodynamics when it re-enters into the turbine. To reduce these detrimental effects and minimise the necessary amount of purge flow, a detailed understanding of the interaction between purge and main annulus flow is necessary. For this purpose, this topic has been investigated by several projects. Whereas in most of these projects the interaction between purge and main annulus flow has been investigated upstream of a rotor row in a high pressure turbine, in this thesis the purge flow injection upstream of the stator row of a low pressure turbine is examined. This aims to broaden the general understanding of the interaction between purge and main annulus flow. Furthermore, a comparison of the effects upstream of a rotor row and upstream of a stator row is carried out. For this investigation numerous experiments have been conducted during the EU Project MAGPI using the Large Scale Turbine Rig (LSTR) at Technische Universität Darmstadt. This test rig is equipped with different measurement techniques, including pressure taps, 5-hole probes, PIV and a tracer gas system. In their combination these measurement techniques offer the possibility to study the purge flow induced effects in great detail. The measurements reveal a significant influence of purge flow on the flow field within the main annulus and the rim seal. With increasing purge flow, a negative incidence develops at the stator row. This increases the crossflow within the passage and amplifies secondary flows. In addition to this amplification of secondary flows, which is generally similar to results observed for purge flow injection upstream of a rotor row, a significant influence of the purge flow delivery is observed. Especially in low pressure turbines, the purge flow is often supplied through discrete holes in the rotor drum. At sufficiently high pressure ratios, the purge flow may leave these holes in the form of discrete jets. These so-called drive arm hole jets are examined to influence the flow field in the rim seal significantly in the current configuration. That is, they form a purge flow filled vortex in the rim seal, which suppresses the typical flow structure. In addition, these jets promote hot gas ingestion. Overall, the method of the purge flow delivery is assessed to play a significant role on the effects caused by purge flow injection. Furthermore, the flow field measurements yield a detailed insight into the interaction between purge and main annulus flow. Based on the results examined in this thesis, two different design proposals havebeen elaborated, which aim to reduce losses and hence increased the efficiency of the turbin

Formation de futurs médecins pouvant servir les communautés francophones en situation minoritaire au Canada : une étude de cas

Background: Over one million Francophone Canadians live in official language minority communities (OLMC) outside of Québec. Availability and accessibility of linguistically appropriate care to these OLMCs is lacking, resulting in poorer quality of care. To help address this health equity gap, the FrancoDoc program was created in 2015 to identify Francophone/Francophile medical students enrolled at medical faculties that use English as their primary language of instruction and equip them with skills to increase their medical French abilities. Little is known, however, about the affordances and limitations of this educational endeavour. Methods: Our qualitative instrumental single case study explored participants’ experiences with FrancoDoc, while also examining factors shaping the delivery of linguistically appropriate healthcare services to OLMCs. We conducted semi-structured interviews with medical students from across Canada and thematically analyzed these using a reflexive, inductive approach. Results: Four main themes were derived from 12 interviews: factors facilitating French language learning; barriers to French language learning; contextual factors shaping linguistically appropriate healthcare provision; and recommendations to improve healthcare education to better prepare learners to provide care to OLMCs. Conclusions: Medical student participants are highly motivated to engage in educational activities linked to FrancoDoc. Their efforts are nonetheless frequently impeded by barriers such as time constraints, irregular event programming, lack of regular clinical learning opportunities, and lukewarm support from faculties of medicine. If medical faculties are to realize their obligations to the OLMCs that they serve, recognition of language as a specific social determinant of health and more robust institutional supports for initiatives like FrancoDoc are paramount.Contexte : Plus d’un million de Canadiens francophones vivent dans des communautés de langue officielle en situation minoritaire (CLOSM) hors Québec. L’accessibilité de soins linguistiquement appropriés aux CLOSM est limitée. Par conséquent, la qualité des services qui leur sont offerts en souffre. Le programme FrancoDoc a été créé en 2015 pour aider à combler cette lacune sur le plan de l’équité en matière de santé. Il vise à offrir aux étudiants en médecine francophones ou francophiles dont l’anglais est la principale langue d’enseignement les moyens d’améliorer leurs compétences en français médical. Cependant, on sait peu de choses sur les possibilités et les limites de cette initiative éducative. Méthodes : Notre étude qualitative instrumentale de cas unique a exploré les expériences des participants au programme FrancoDoc, tout en examinant les facteurs qui influencent la prestation de services de santé linguistiquement appropriés aux CLOSM. Nous avons mené des entrevues semi-structurées avec des étudiants en médecine de tout le Canada et nous en avons analysé le contenu thématiquement en utilisant une approche réflexive et inductive. Résultats : Quatre thèmes principaux ont été dégagés des 12 entrevues réalisées : les facteurs facilitant l’apprentissage du français; les obstacles à l’apprentissage du français; les facteurs contextuels influençant la prestation de soins de santé linguistiquement appropriés; et les recommandations visant à améliorer l’enseignement en soins de santé de manière à préparer les apprenants à servir les CLOSM. Conclusions : Bien que très motivés par le programme FrancoDoc, les étudiants participants se heurtent à des obstacles comme les contraintes de temps, la programmation irrégulière des activités, le manque d’occasions d’apprentissage clinique régulier et la réticence des facultés de médecine. Or, pour remplir leurs obligations envers les CLOSM qu’elles servent, il est essentiel que les facultés de médecine reconnaissent la langue comme un déterminant social spécifique de la santé et qu’elles offrent un soutien solide aux initiatives comme le programme FrancoDoc

Cloning of the Complete Gene for Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) is a widely used tumor marker, especially in the surveillance of colonic cancer patients. Although CEA is also present in some normal tissues, it is apparently expressed at higher levels in tumorous tissues than in corresponding normal tissues. As a first step toward analyzing the regulation of expression of CEA at the transcriptional level, we have isolated and characterized a cosmid clone (cosCEA1), which contains the entire coding region of the CEA gene. A close correlation exists between the exon and deduced immunoglobulin-like domain borders. We have determined a cluster of transcriptional starts for CEA and the closely related nonspecific cross-reacting antigen (NCA) gene and have sequenced their putative promoters. Regions of sequence homology are found as far as approximately 500 nucleotides upstream from the translational starts of these genes, but farther upstream they diverge completely. In both cases we were unable to find classic TATA or CAAT boxes at their expected positions. To characterize the CEA and NCA promoters, we carried out transient transfection assays with promoter-indicator gene constructs in the CEA-producing adenocarcinoma cell line SW403, as well as in nonproducing HeLa cells. A CEA gene promoter construct, containing approximately 400 nucleotides upstream from the translational start, showed nine times higher activity in the SW403 than in the HeLa cell line. This indicates that cis-acting sequences which convey cell type-specific expression of the CEA gene are contained within this region

Learning induced neuronal activation pattern measured by c-fos expression in murine hippocampus and nucleus accumbens

Neuronale Aktivierungen, induziert durch räumliches Lernen, wurden anhand der c-fos Genexpression in Mäusen untersucht. Das Immediate-Early Gene c-fos, wichtig zur Konsolidierung von Langzeit-Gedächtnis, ermöglicht mit ubiquitärer und transienter Expression die nicht-invasive Analyse neuronaler Aktivierung verschiedener Gehirn-Areale mit hoher zeitlich-räumlicher Auflösung auf zellulärem Niveau. Ein Circular-Maze-Task wurde etabliert, um hippocampus-spezifisches räumliches Lernen unter optimierten Bedingungen für die c-fos Analyse zu erzielen. Die c-fos Expressionsmuster verdeutlichten die funktionelle Untergliederung des Hippocampus und Nucleus Accumbens in räumlichen Lernprozessen anhand einer starken spezifischen Aktivierung im gyrus dentatus und der CA1- im Gegensatz zur CA3-Region des Hippocampus und einer schwachen Involvierung der Shell-Region des Nucleus Accumbens. Ein reiner Novelty-Effekt wurde ausgeschlossen, da ein Novelty-Task keine Veränderung der c-fos Expression ergab

Efficient production of the Nylon 12 monomer ω-aminododecanoic acid methyl ester from renewable dodecanoic acid methyl ester with engineered Escherichia coli

The expansion of microbial substrate and product scopes will be an important brick promoting future bioeconomy. In this study, an orthogonal pathway running in parallel to native metabolism and converting renewable dodecanoic acid methyl ester (DAME) via terminal alcohol and aldehyde to 12-aminododecanoic acid methyl ester (ADAME), a building block for the high-performance polymer Nylon 12, was engineered in Escherichia coli and optimized regarding substrate uptake, substrate requirements, host strain choice, flux, and product yield. Efficient DAME uptake was achieved by means of the hydrophobic outer membrane porin AlkL increasing maximum oxygenation and transamination activities 8.3 and 7.6-fold, respectively. An optimized coupling to the pyruvate node via a heterologous alanine dehydrogenase enabled efficient intracellular L-alanine supply, a prerequisite for self-sufficient whole-cell transaminase catalysis. Finally, the introduction of a respiratory chain-linked alcohol dehydrogenase enabled an increase in pathway flux, the minimization of undesired overoxidation to the respective carboxylic acid, and thus the efficient formation of ADAME as main product. The completely synthetic orthogonal pathway presented in this study sets the stage for Nylon 12 production from renewables. Its effective operation achieved via fine tuning the connectivity to native cell functionalities emphasizes the potential of this concept to expand microbial substrate and product scopes

Lack of functional and expression homology between human and mouse aldo-keto reductase 1C enzymes: implications for modelling human cancers

<p>Abstract</p> <p>Background</p> <p>Over recent years, enzymes of the aldo-keto reductase (AKR) 1C subfamily have been implicated in the progression of prostate, breast, endometrial and leukemic cancers. This is due to the ability of AKR1C enzymes to modify androgens, estrogens, progesterone and prostaglandins (PGs) in a tissue-specific manner, regulating the activity of nuclear receptors and other downstream effects. Evidence supporting a role for AKR1C enzymes in cancer derives mostly from studies with isolated primary cells from patients or immortalized cell lines. Mice are ideal organisms for <it>in vivo </it>studies, using knock-out or over-expression strains. However, the functional conservation of AKR1C enzymes between human and mice has yet to be described.</p> <p>Results</p> <p>In this study, we have characterized and compared the four human (AKR1C1,-1C2, -1C3 and -1C4) and the eight murine (AKR1C6, -1C12, -1C13, -1C14, -1C18, -1C19, -1C20 and -1C21) isoforms in their phylogeny, substrate preference and tissue distribution. We have found divergent evolution between human and murine AKR1C enzymes that was reflected by differing substrate preference. Murine enzymes did not perform the 11β-ketoreduction of prostaglandin (PG) D₂, an activity specific to human AKR1C3 and important in promoting leukemic cell survival. Instead, murine AKR1C6 was able to perform the 9-ketoreduction of PGE₂, an activity absent amongst human isoforms. Nevertheless, reduction of the key steroids androstenedione, 5α-dihydrotestosterone, progesterone and estrone was found in murine isoforms. However, unlike humans, no AKR1C isoforms were detected in murine prostate, testes, uterus and haemopoietic progenitors.</p> <p>Conclusions</p> <p>This study exposes significant lack of phylogenetic and functional homology between human and murine AKR1C enzymes. Therefore, we conclude that mice are not suitable to model the role of AKR1C in human cancers and leukemia.</p

Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

MED12 regulates a transcriptional network of calcium-handling genes in the heart

The Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is composed of 4 proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium-handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and we found that MED12 localizes to transcription factor consensus sequences within calcium-handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes and that MED12 and MEF2 co-occupy promoters of calcium-handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and that overexpression of both increases expression of calcium-handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium-handling genes, consequently mediating contractility in the mammalian heart