225 research outputs found

    Theory of monolayers with boundaries: Exact results and Perturbative analysis

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    Domains and bubbles in tilted phases of Langmuir monolayers contain a class of textures knows as boojums. The boundaries of such domains and bubbles may display either cusp-like features or indentations. We derive analytic expressions for the textures within domains and surrounding bubbles, and for the shapes of the boundaries of these regions. The derivation is perturbative in the deviation of the bounding curve from a circle. This method is not expected to be accurate when the boundary suffers large distortions, but it does provide important clues with regard to the influence of various energetic terms on the order-parameter texture and the shape of the domain or bubble bounding curve. We also look into the effects of thermal fluctuations, which include a sample-size-dependent effective line tension.Comment: replaced with published version, 21 pages, 16 figures include

    Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity

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    The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements

    A Soluble Guanylate Cyclase–Dependent Mechanism Is Involved in the Regulation of Net Hepatic Glucose Uptake by Nitric Oxide in Vivo

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    OBJECTIVE We previously showed that elevating hepatic nitric oxide (NO) levels reduced net hepatic glucose uptake (NHGU) in the presence of portal glucose delivery, hyperglycemia, and hyperinsulinemia. The aim of the present study was to determine the role of a downstream signal, soluble guanylate cyclase (sGC), in the regulation of NHGU by NO. RESEARCH DESIGN AND METHODS Studies were performed on 42-h–fasted conscious dogs fitted with vascular catheters. At 0 min, somatostatin was given peripherally along with 4× basal insulin and basal glucagon intraportally. Glucose was delivered at a variable rate via a leg vein to double the blood glucose level and hepatic glucose load throughout the study. From 90 to 270 min, an intraportal infusion of the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) was given in −sGC (n = 10) and −sGC/+NO (n = 6), whereas saline was given in saline infusion (SAL) (n = 10). The −sGC/+NO group also received intraportal SIN-1 (NO donor) to elevate hepatic NO from 180 to 270 min. RESULTS In the presence of 4× basal insulin, basal glucagon, and hyperglycemia (2× basal ), inhibition of sGC in the liver enhanced NHGU (mg/kg/min; 210–270 min) by ∼55% (2.9 ± 0.2 in SAL vs. 4.6 ± 0.5 in −sGC). Further elevating hepatic NO failed to reduce NHGU (4.5 ± 0.7 in −sGC/+NO). Net hepatic carbon retention (i.e., glycogen synthesis; mg glucose equivalents/kg/min) increased to 3.8 ± 0.2 in −sGC and 3.8 ± 0.4 in −sGC/+NO vs. 2.4 ± 0.2 in SAL (P < 0.05). CONCLUSIONS NO regulates liver glucose uptake through a sGC-dependent pathway. The latter could be a target for pharmacologic intervention to increase meal-associated hepatic glucose uptake in individuals with type 2 diabetes

    Economic predictors of differences in interview faking between countries : economic inequality matters, not the state of economy

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    Many companies recruit employees from different parts of the globe, and faking behavior by potential employees is a ubiquitous phenomenon. It seems that applicants from some countries are more prone to faking compared to others, but the reasons for these differences are largely unexplored. This study relates country-level economic variables to faking behavior in hiring processes. In a cross-national study across 20 countries, participants (N = 3839) reported their faking behavior in their last job interview. This study used the random response technique (RRT) to ensure participants anonymity and to foster honest answers regarding faking behavior. Results indicate that general economic indicators (gross domestic product per capita [GDP] and unemployment rate) show negligible correlations with faking across the countries, whereas economic inequality is positively related to the extent of applicant faking to a substantial extent. These findings imply that people are sensitive to inequality within countries and that inequality relates to faking, because inequality might actuate other psychological processes (e.g., envy) which in turn increase the probability for unethical behavior in many forms

    Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma

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    BackgroundImage- guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma.ProcedureA multi- institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3- year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children’s Oncology Group for risk stratification.ResultsA total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy.ConclusionsPCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real- time pathology assessment of specimen quality.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/1/pbc28153_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/2/pbc28153.pd

    Different degrees of malnutrition and immunological alterations according to the aetiology of cirrhosis: a prospective and sequential study

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    OBJECTIVES: In this work we investigated how immunological dysfunction and malnutrition interact in alcoholic and viral aetiologies of cirrhosis. METHODS: To investigate the matter, 77 cirrhotic patients divided in three aetiologies [Alcohol, HCV and Alcohol + HCV) and 32 controls were prospectivelly and sequentially studied. Parameters of humoral immunity (Components 3 and 4 of seric complement and immunoglobulins A M, G and E) and of cellular immunity (total leukocytes and lymphocytes in peripheral blood, T lymphocytes subpopulations, CD4+ and CD8+, CD4+/CD8+ ratio and intradermic tests of delayed hypersensitivity), as well as nutrititional parameters: anthropometric measures, serum albumin and transferrin were evaluated. RESULTS: Multiple statistical comparisons showed that IgM was higher in HCV group; IgG was significantly elevated in both HCV and Alcohol + HCV, whereas for the Alcohol group, IgE was found at higher titles. The analysis of T- lymphocytes subpopulations showed no aetiologic differences, but intradermic tests of delayed hypersensitivity did show greater frequency of anergy in the Alcohol group. For anthropometric parameters, the Alcohol +HCV group displayed the lowest triceps skinfold whereas creatinine – height index evaluation was more preserved in the HCV group. Body mass index, arm muscle area and arm fat area showed that differently from alcohol group, the HCV group was similar to control. CONCLUSION: Significant differences were found among the main aetiologies of cirrhosis concerning immunological alterations and nutritional status: better nutrition and worse immunology for HCV and vice-versa for alcohol

    Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

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    Background: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology
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