394 research outputs found

    Influencia de la revibración sobre las propiedades de la pasta de cemento endurecida y de los hormigones

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    Not availableEste trabajo forma parte de una serie de estudios e investigaciones experimentales efectuadas desde 1962 en los laboratorios de la cátedra de Hormigón Armado del Instituto Politécnico de Timisoara y de la Sección de Materiales de Construcción de la Academia Rumana. El trabajo se centra, desde el punto de vista teórico, en la aclaración de ciertos aspectos nuevos de la formación de la estructura de la pasta de cemento endurecida bajo la acción de la vibración repetida (revibración) durante el fraguado del cemento y, desde el punto de vista práctico, en la obtención de hormigones de gran resistencia y gran durabilidad junto con la reducción de las deformaciones bajo cargas de corta y larga duración

    Alternative reconstruction after pancreaticoduodenectomy

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    <p>Abstract</p> <p>Background</p> <p>Pancreaticoduodenectomy is the procedure of choice for tumors of the head of the pancreas and periampulla. Despite advances in surgical technique and postoperative care, the procedure continues to carry a high morbidity rate. One of the most common morbidities is delayed gastric emptying with rates of 15%–40%. Following two prolonged cases of delayed gastric emptying, we altered our reconstruction to avoid this complication altogether. Subsequently, our patients underwent a classic pancreaticoduodenectomy with an undivided <it>Roux-en-Y </it>technique for reconstruction.</p> <p>Methods</p> <p>We reviewed the charts of our last 13 Whipple procedures evaluating them for complications, specifically delayed gastric emptying. We compared the outcomes of those patients to a control group of 15 patients who underwent the Whipple procedure with standard reconstruction.</p> <p>Results</p> <p>No instances of delayed gastric emptying occurred in patients who underwent an undivided <it>Roux-en-Y </it>technique for reconstruction. There was 1 wound infection (8%), 1 instance of pneumonia (8%), and 1 instance of bleeding from the gastrojejunal staple line (8%). There was no operative mortality.</p> <p>Conclusion</p> <p>Use of the undivided <it>Roux-en-Y </it>technique for reconstruction following the Whipple procedure may decrease the incidence of delayed gastric emptying. In addition, it has the added benefit of eliminating bile reflux gastritis. Future randomized control trials are recommended to further evaluate the efficacy of the procedure.</p

    Increased Expression of Bcl11b Leads to Chemoresistance Accompanied by G1 Accumulation

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    BACKGROUND: The expression of BCL11B was reported in T-cells, neurons and keratinocytes. Aberrations of BCL11B locus leading to abnormal gene transcription were identified in human hematological disorders and corresponding animal models. Recently, the elevated levels of Bcl11b protein have been described in a subset of squameous cell carcinoma cases. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open. METHODOLOGY/PRINCIPAL FINDINGS: Here, by employing an overexpression strategy we revealed formerly unidentified features of Bcl11b. Two different T-cell lines were forced to express BCL11B at levels similar to those observed in primary T-cell leukemias. This resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A. CONCLUSIONS: The data presented here suggest a potential role of BCL11B in tumor survival and encourage developing Bcl11b-inhibitory approaches as a potential tool to specifically target chemoresistant tumor cells

    Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression

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    Background: Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities of monoamine neurotransmission, including dopamine, are theorized to contribute to the pathophysiology of depression, evidence linking dopamine-related genes to depression has been mixed. The current study sought to address this knowledge-gap by examining whether the combined effect of dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and individuals with depression. Methods: Data were drawn from three independent samples: (1) a discovery sample of healthy adult participants (n = 273); (2) a replication sample of adults with depression (n = 1,267); and (3) a replication sample of healthy adult participants (n = 382). A genetic risk score was created by combining functional polymorphisms from five genes involved in synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3). Results: In the discovery sample, the genetic risk score was associated with depressive symptomatology (β = −0.80, p = 0.003), with lower dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. This result was replicated with a similar genetic risk score based on imputed genetic data from adults with depression (β = −0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (β = −0.86, p = 0.15). Conclusions: Sequence variation in multiple genes regulating dopamine neurotransmission may influence depressive symptoms, in a manner that appears to be additive. Further studies are required to confirm the role of genetic variation in dopamine metabolism and depression

    Queues with Lévy input and hysteretic control

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    We consider a (doubly) reflected Lévy process where the Lévy exponent is controlled by a hysteretic policy consisting of two stages. In each stage there is typically a different service speed, drift parameter, or arrival rate. We determine the steady-state performance, both for systems with finite and infinite capacity. Thereby, we unify and extend many existing results in the literature, focusing on the special cases of M/G/1 queues and Brownian motion. © The Author(s) 2009

    Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes

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    Endogenous formaldehyde is abundantly present in our bodies, at around 100 µM under normal conditions. While such high steady state levels of formaldehyde may be derived by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is unclear whether endogenous formaldehyde can initiate and/or promote diseases in humans. Here, we show that fluorescent malondialdehyde-formaldehyde (M2FA)-lysine adducts are immunogenic without adjuvants in mice. Natural antibody titers against M2FA are elevated in atherosclerosis-prone mice. Staining with an antibody against M2FA demonstrated that M2FA is present in plaque found on the aortic valve of ApoE mice. To mimic inflammation during atherogenesis, human myeloperoxidase was incubated with glycine, H O , malondialdehyde, and a lysine analog in PBS at a physiological temperature, which resulted in M2FA generation. These results strongly suggest that the 1,4-dihydropyridine-type of lysine adducts observed in atherosclerosis lesions are likely produced by endogenous formaldehyde and malondialdehyde with lysine. These highly fluorescent M2FA adducts may play important roles in human inflammatory and degenerative diseases

    Практические аспекты организации медицинской помощи пациентам с впервые развившимся судорожным припадком

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    ПРИПАДКИ /ТЕРНЕВРОЛОГИЧЕСКИЕ СИМПТОМЫ ПРИ ПАТОЛОГИЧЕСКИХ СОСТОЯНИЯХЭПИЛЕПСИЯ, АБСАНС /ТЕРМОЗГА ГОЛОВНОГО БОЛЕЗНИ /ТЕРДИАГНОСТИКА ДИФФЕРЕНЦИАЛЬНАЯЛЕЧЕБНО-ДИАГНОСТИЧЕСКИХ МЕРОПРИЯТИЙ ГРАФИКМЕДИЦИНСКОЙ ПОМОЩИ ОРГАНИЗАЦИЯПРОГНОЗИРОВАНИЕУХОДА ЗА БОЛЬНЫМ МЕНЕДЖМЕН

    CTIP2 Expression in Human Head and Neck Squamous Cell Carcinoma Is Linked to Poorly Differentiated Tumor Status

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    We have demonstrated earlier that CTIP2 is highly expressed in mouse skin during embryogenesis and in adulthood. CTIP2 mutant mice die at birth with epidermal differentiation defects and a compromised epidermal permeability barrier suggesting its role in skin development and/or homeostasis. CTIP2 has also been suggested to function as tumor suppressor in cells, and several reports have described a link between chromosomal rearrangements of CTIP2 and human T cell acute lymphoblast leukemia (T-ALL). The aim of the present study was to look into the pattern of CTIP2 expression in Head and Neck Squamous Cell Carcinoma (HNSCC).In the present study, we analyzed CTIP2 expression in human HNSCC cell lines by western blotting, in paraffin embedded archival specimens by immunohistochemistry (IHC), and in cDNA samples of human HNSCC by qRT-PCR. Elevated levels of CTIP2 protein was detected in several HNSCC cell lines. CTIP2 staining was mainly detected in the basal layer of the head and neck normal epithelium. CTIP2 expression was found to be significantly elevated in HNSCC (p<0.01), and increase in CTIP2 expression was associated with poorly differentiated tumor status. Nuclear co-localization of CTIP2 protein and cancer stem cell (CSC) marker BMI1 was observed in most, if not all of the cells expressing BMI1 in moderately and poorly differentiated tumors.We report for the first time expression of transcriptional regulator CTIP2 in normal human head and neck epithelia. A statistically significant increase in the expression of CTIP2 was detected in the poorly differentiated samples of the human head and neck tumors. Actual CTIP2, rather than the long form of CTIP2 (CTIP2(L)) was found to be more relevant to the differentiation state of the tumors. Results demonstrated existence of distinct subsets of cancer cells, which express CTIP2 and underscores the use of CTIP2 and BMI1 co-labeling to distinguish tumor initiating cells or cancer stem cells (CSCs) from surrounding cancer cells

    A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease.

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    The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV
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