Numerical Simulation of Siphon Breaker of an Open-Pool Type Research Reactor

A numerical investigation of the siphon breaker of an open-pool type nuclear research reactorwas performed by Computational Fluid Dynamics. The computational model was assessed by solving a siphon break line design, for which experimental and numerical data are available. The multiphaseproblem was solved with Volume of Fluid Method and k-epsilon for turbulence modeling. Numerical results were in very good agreement with experimental data. The siphon breaker occurrence was verified and the undershooting height, measured from the pool level to the siphon break line end as well as the liquid mass flow rate inside the main pipe were well captured. The implemented model showed to bereliable for assessing this kind of passive safety systems.Publicado en: Mecánica Computacional vol. XXXV no.31Facultad de Ingenierí

An additional set of phages to characterize epidemic methicillin-resistant Staphylococcus aureus strains from Spain (1989-92).

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) isolates in Spain have increased dramatically; in 1986 there were only 1.2% MRSA amongst all nosocomial Staphylococcus aureus (SA) isolates, by 1989 this percentage had risen to 44% in some hospital causing a very serious epidemic situation in the country. We have characterized these isolates by direct, reverse and Fisk phage typing and we have also looked for an additional local set of phages to help us to differentiate these strains. We have been able to differentiate an epidemic strain from other MRSA strains which cause sporadic hospital outbreaks, and we have also distinguished between some variants of the epidemic strain.This research has been supported by a grant from the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), Ministerio de Sanidad y Consumo, Spain; No. 93/0144.S

NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML-M2

The t(7;11)(p15;p15.4) has been reported to fuse the NUP98 gene (11p15), a component of the nuclear pore complex, with the class-1 homeobox gene HOXA9 at 7p15. This translocation has been associated with myeloid leukemias, predominantly acute myeloid leukemia (AML) M2 subtype with trilineage myelodysplastic features, and with a poor prognosis. The derived fusion protein retains the FG repeat motif of NUP98 N-terminus and the homeodomain shared by the HOX genes, acting as an oncogenic transcription factor critical for leukemogenesis. We report here a new complex t(7;11)-variant, i.e., t(7;11;13;17)(p15;p15;p?;p1?2) in a patient with AML-M2 and poor prognosis. The NUP98-HOXA9 fusion transcript was detected by RT-PCR, suggesting its role in the malignant transformation as it has been postulated for other t(7;11)-associated leukemias. No other fusion transcripts involving the NUP98 or HOXA9 genes were present, although other mechanisms involving several genes on chromosomes 13 and 17 may also be involved. To our knowledge, this is the first t(7;11) variant involving NUP98 described in hematological malignancies

Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas

Activation of an oncogene via its juxtaposition to the IGH locus by a chromosomal translocation or, less frequently, by genomic amplification is considered a major mechanism of B-cell lymphomagenesis. However, amplification of an IGH/oncogene fusion, coined a complicon, is a rare event in human cancers and has been associated with poor outcome and resistance to treatment. In this article are descriptions of two cases of germinal-center-derived B-cell lymphomas with IGH/BCL2 fusion that additionally displayed amplification of an IGH/MYC fusion. As shown by fluorescence in situ hybridization, the first case contained a IGH/MYC complicon in double minutes, whereas the second case showed a BCL2/IGH/MYC complicon on a der(8)t(8;14)t(14;18). Additional molecular cytogenetic and mutation analyses revealed that the first case also contained a chromosomal translocation affecting the BCL6 oncogene and a biallelic inactivation of TP53. The second case harbored a duplication of REL and acquired a translocation affecting IGL and a biallelic inactivation of TP53 during progression. Complicons affecting Igh/Myc have been reported previously in lymphomas of mouse models simultaneously deficient in Tp53 and in genes of the nonhomologous end-joining DNA repair pathway. To the best of our knowledge, this is the first time that IGH/MYC complicons have been reported in human lymphomas. Our findings imply that the two mechanisms resulting in MYC deregulation, that is, translocation and amplification, can occur simultaneously

Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth

MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34+ cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML

Hypercholesterolemia Impaired Sperm Functionality in Rabbits

Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events

Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptors (PPARs) have emerged as important drug targets for diabetes. Drugs that activate PPARγ, such as the thiazolidinediones (TZDs), are widely used for treatment of Type 2 diabetes mellitus. PPARγ signaling could also play an anti-neoplastic role in several <it>in vitro </it>models, although conflicting results are reported from <it>in vivo </it>models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes.</p> <p>Methods</p> <p>A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs.</p> <p>Results</p> <p>In a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides), age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, <it>P </it>= 0.04). This association was particularly strong among patients using rosiglitazone (OR = 1.89, <it>P </it>= 0.02), and among women (OR = 2.07, <it>P </it>= 0.01).</p> <p>Conclusion</p> <p>These data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.</p

Optimal taxation under different concepts of justness

A common assumption in the optimal taxation literature is that the social planner maximizes a welfarist social welfare function with weights decreasing with income. However, high transfer withdrawal rates in many countries imply very low weights for the working poor in practice. We reconcile this puzzle by generalizing the optimal taxation framework by Saez (2002) to allow for alternatives to welfarism. We calculate weights of a social planners function as implied by the German tax and transfer system based on the concepts of welfarism, minimum absolute and relative sacrifice, as well as subjective justness. For the latter we use a novel question from the German Socio-Economic Panel. We find that the minimum absolute sacrifice principle is in line with social weights that decline with net income. Absolute subjective justness is roughly in line with decreasing social weights, which is reflected by preferences of men, West Germans, and supporters of the grand coalition parties

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle

<p>Abstract</p> <p>Background</p> <p>D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis.</p> <p>Methods</p> <p>By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels.</p> <p>Results</p> <p>IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited.</p> <p>Conclusion</p> <p>Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.</p