Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence and prevalence of neutralizing antibodies to the common adenoviruses in children with cystic fibrosis: implication for gene therapy with adenovirus vectors.

OBJECTIVE Defining the infection rate and prevalence of the common adenoviruses (Ads) in cystic fibrosis (CF) children may aid in formulation of strategies for gene therapy with Ad vectors. We undertook this study to determine the incidence and prevalence of infection with the common Ads in children with CF. METHODOLOGY Thirty newly diagnosed CF children mean age 1.1 years (Group 1), 48 CF children mean age 4.6 years (Group 2), and 47 mothers of CF children (Group 3) were followed for a mean of 13 months. Group 4 consisted of 33 adult volunteers seen once. Throat and stool specimens for virus culture, and blood samples were obtained every 3 months from CF children in Group 1. Blood samples from CF children (Group 2) and their mothers (Group 3) were obtained every 6 months, and once from adults in Group 4. Neutralizing antibody to Ad serotypes 1 through 7 (Ad 1 to Ad 7) was evaluated with a microneutralization assay. RESULTS Five (16.7%) CF children in Group 1 were culture-positive for an Ad; 4 of these CF children developed a fourfold or greater rise in antibody titer. Ad 3 infection occurred frequently based on serology; seronegative (< 3.5 log 2) CF children had a higher infection rate compared with seropositive CF children (7/11 vs 1/34). The prevalence of neutralizing antibodies in CF children in order of decreasing frequency was 91.1% to Ad 3, 37.5% to Ad 2, 27.1% to Ad 1, 26.1% to Ad 7, 16.7% to Ad 5, 8.5% to Ad 4, and 2.0% to Ad 6. The neutralizing antibody titers in seropositive CF children were comparable to those in adults except to Ad 3, which was significantly greater in mothers of CF children. CONCLUSIONS CF children had a normal antibody response after Ad infection, preexisting antibody may protect against reinfection and antibody prevalence was low to the common Ads.
Watershed slope as a predictor of fluvial dissolved organic matter and nitrate concentrations across geographical space and catchment size in the Arctic

Understanding linkages between river chemistry and biological production in arctic coastal waters requires improved estimates of riverine nutrient export. Here we present the results of a synthesis effort focusing on relationships between watershed slope and seasonal concentrations of river-borne dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and nitrate ( NO 3 − ) around the pan-Arctic. Strong negative relationships exist between watershed slope and concentrations of DOC and DON in arctic rivers. Spring and summer concentration-slope relationships for DOC and DON are qualitatively similar, although spring concentrations are higher. Relationships for NO 3 − are more variable, but a significant positive relationship exists between summer NO 3 − concentrations and watershed slopes. These results suggest that watershed slope can serve as a master variable for estimating spring and summer DOC and DON concentrations, and to a lesser degree NO 3 − , from drainage areas where field data are lacking, thus improving our ability to develop pan-arctic estimates of watershed nutrient export.
Interval homogeneous domination approach for global stabilization of nonlinear systems with time-varying powers

This paper considers the problem of global stabilization for a class of nonlinear systems with time-varying powers. A new design method based on the technique of adding a power integrator and the interval homogeneous domination approach, which can be thought as an evolution of the homogeneous domination approach, is developed to explicitly construct a smooth state feedback globally stabilizing controller. The novelty of this paper is the development of a systematic scheme, which provides us a new perspective to deal with the state feedback control problem for the nonlinear systems with time-varying powers.
A Conglomerate’s Effort for Co-Prospering with Its Subcontractors and Firm Value: Evidence from Korea

Shared growth effort, which is also known as mutual growth, has emerged as one of the most important keywords in Korean economy. This study examines whether a conglomerate’s shared growth effort evaluated by the Shared Growth Commission is valued by market investors. Using our full sample, we find that firms participating in shared growth evaluation have a higher firm value. The results from the full sample show that firm’s effort on shared growth is rewarded in the Korean capital market. However, after matching firms by size of sales and return on assets to better control for firm characteristics, we find that neither the participation nor a higher (lower) rating of the shared growth evaluation is associated with firm value. This implies that the result from the full sample may be capturing firm characteristics, instead of the effects of shared growth effort, thus market investors do not consider conglomerate’s shared growth effort as a value-enhancing strategy. Using a recently introduced shared-growth index, the findings in our study provide preliminary but important evidence on how creating shared value (CSV) is related to firm value.
Lactococcus lactis is capable of improving the riboflavin status in deficient rats

Lactococcus lactis is a commonly used starter strain that can be converted from a vitamin B2 consumer into a vitamin B2 ‘factory’ by over-expressing its riboflavin biosynthesis genes. The present study was conducted to assess in a rat bioassay the response of riboflavin produced by GM or native lactic acid bacteria (LAB). The riboflavin-producing strains were able to eliminate most physiological manifestations of ariboflavinosis such as stunted growth, elevated erythrocyte glutathione reductase activation coefficient values and hepatomegalia that were observed using a riboflavin depletion–repletion model. Riboflavin status and growth rates were greatly improved when the depleted rats were fed with cultures of L. lactis that overproduced this vitamin whereas the native strain did not show the same effect. The present study is the first animal trial with food containing living bacteria that were engineered to overproduce riboflavin. These results pave the way for analysing the effect of similar riboflavin-overproducing LAB in human trials.
Glycogenin-2 is dispensable for liver glycogen synthesis and glucagon-stimulated glucose release.

CONTEXT The synthesis of glycogen is initiated by glycogenin. In humans, glycogenin-1 is expressed ubiquitously, whereas glycogenin-2 (GN2) is highly expressed in liver. It has therefore been suggested that GN2 is a liver isoform of glycogenin. In a search for possible copy number variations associated with monogenic diabetes, we identified a 102-kb deletion of the X chromosome involving the entire GYG2 gene (encoding GN2) in 2 families. OBJECTIVE The purpose of this study was to test whether male GYG2 deletion carriers had abnormal glucose metabolism and/or glycogen synthesis. DESIGN, SETTING, AND PATIENTS Two families with diabetes and a GYG2 deletion were investigated with medical history and examination, glucagon stimulation tests, and liver biopsies. RESULTS We identified a GYG2 deletion in 3 members of family 1, 8 members of family 2, and 1 blood donor. The deletion showed no clear cosegregation with diabetes. Deletion carriers reported no symptoms related to fasting. Results of cardiac examination and abdominal ultrasound imaging were normal. A glucagon stimulation test in 4 male deletion carriers showed a mean rise in plasma glucose of 3.6 mmol/L (95% confidence interval, 2.9-4.2) compared with 2.8 mmol/L (95% confidence interval, 2.2-3.4) in control subjects. Liver biopsy specimens did not show clear morphologic changes by light microscopy and showed the presence of both α- and β-glycogen by electron microscopy. We detected GYG1 but not GYG2 mRNA expression in the liver biopsy specimens. CONCLUSIONS This is the first evaluation of humans without GN2 expression. Our data indicate that GN2 is not required for liver glycogen synthesis and glucagon-stimulated glucose release.
Does the DNA Binding Mode of a Molecule Affect its Ability to Interact With Singlet Oxygen?

Singlet oxygen is known to be a potent mutagenic agent and several biologically relevant molecules have been proposed to act as scavengers for this noxious species. However, numerous studies have been conducted in homogenous solution and the reactivity of singlet oxygen scavengers known to bind DNA has never been investigated in double‐stranded DNA. In the following paper, we present the results obtained regarding the interaction between 4′,6‐diamidino‐2‐phenylindole (DAPI) and singlet oxygen. We show the molecule to be a potent scavenger of singlet oxygen in aqueous solution with an absolute rate constant (chemical and physical quenching of singlet oxygen) of (1.7 ± 0.3) × 107 m−1 s−1. In addition, we demonstrate that the binding mode of a singlet oxygen scavenger to DNA can strongly influence its reactivity toward singlet oxygen. In the case of DAPI, while the molecule exhibits a chemical reaction with singlet oxygen when the molecule is free in aqueous solution or intercalated in GC sequences of DNA, DAPI becomes chemically unreactive toward singlet oxygen when bound in the minor groove of DNA AT sequences.
A survey of oral cavity afferents to the rat nucleus tractus solitarii

Visualization of myelinated fiber arrangements, cytoarchitecture, and projection fields of afferent fibers in tandem revealed input target selectivity in identified subdivisions of the nucleus tractus solitarii (NTS). The central fibers of the chorda tympani (CT), greater superficial petrosal nerve (GSP), and glossopharyngeal nerve (IX), three nerves that innervate taste buds in the oral cavity, prominently occupy the gustatory‐sensitive rostrocentral subdivision. In addition, CT and IX innervate and overlap in the rostrolateral subdivision, which is primarily targeted by the lingual branch of the trigeminal nerve (LV). In the rostrocentral subdivision, compared with the CT terminal field, GSP appeared more rostral and medial, and IX was more dorsal and caudal. Whereas IX and LV filled the rostrolateral subdivision diffusely, CT projected only to the dorsal and medial portions. The intermediate lateral subdivision received input from IX and LV but not CT or GSP. In the caudal NTS, the ventrolateral subdivision received notable innervation from CT, GSP, and LV, but not IX. No caudal subnuclei medial to the solitary tract contained labeled afferent fibers. The data indicate selectivity of fiber populations within each nerve for functionally distinct subdivisions of the NTS, highlighting the possibility of equally distinct functions for CT in the rostrolateral NTS, and CT and GSP in the caudal NTS. Further, this provides a useful anatomical template to study the role of oral cavity afferents in the taste‐responsive subdivision of the NTS as well as in subdivisions that regulate ingestion and other oromotor behaviors. J. Comp. Neurol. 520:495–527, 2012. © 2011 Wiley Periodicals, Inc.
Effects of acute ethanol gavage on intestinal integrity after hemorrhage/resuscitation

Abstract Background. In hemorrhagic shock with subsequent resuscitation (H/R), increased pro-inflammatory changes contribute to tissue injury and mortality in rodent models. Ethanol (EtOH) is assumed to modulate the inflammatory response and the subsequent organ injury after H/R. Therefore, we determined the contribution of acute ethanol gavage on intestinal inflammation and injury as well as survival after H/R in rats. Methods. Fourteen hours before H/R, female LEWIS rats were gavaged with single dose of EtOH or saline (5 g/kg, 30% EtOH, H/R_EtOH group or H/R_ctrl group). Then, rats were hemorrhaged to a mean arterial blood pressure of 30 ± 2 mmHg for 60 min and resuscitated. Control groups underwent surgical procedures and gavage without H/R (sham_ctrl group and sham_EtOH group). Tissue was harvested 2 h after resuscitation. Mortality was assessed 72 h after H/R. Results. Ethanol gavage increased survival after H/R from 20% to 80%, but amplified plasma alanineaminotransferase (ALT) release compared to saline gavage (2847 ± 406 vs. 1159 ± 200 IU/L, p < 0.05). Intestinal mucosal damage index, intestinal permeability, ileal myeloperoxidase levels as indicators of polymorphonuclear leukocyte (PMNL) infiltration and systemic IL-6 levels as well as ileal IL-6 and TNF gene expressions after H/R were reduced and partly restored after ethanol gavage when compared to the saline gavaged group after H/R. Conclusions. Taken together, we propose that acute ethanol gavage prior to H/R 1) did not enhance intestinal mucosa injury after H/R and 2) suppressed the H/R-induced inflammatory response. Both findings seem to contribute to the ethanol-induced survival benefit after H/R in our model.
Understanding Effectiveness Skepticism

Policy makers have proposed various incentive programs to curb consumption-related problems, such as traffic congestion and carbon emissions. While experts consider such programs effective in reducing those problems, consumers are more skeptical. Although this “effectiveness skepticism” is currently viewed as an important cause of public opposition, the authors argue that it may also arise as a consequence of opposition. Specifically, consumers oppose policies they consider personally unattractive or unfair. This opposition motivates them to also be skeptical about the potential effectiveness of such policies. Three studies that include a variety of methods, policies, and samples provide empirical support for this reasoning: perceptions of expected effects can be biased by consumers’ perceptions of personal attractiveness and fairness. In line with this causal ordering, the authors find that offering optimistic effectiveness estimates, although successful in reducing effectiveness skepticism, did not boost policy support. Policy makers aiming to boost support prior to implementation should thus not only communicate a policy's effectiveness, but also address other causes of opposition.
Training, skill-upgrading and settlement intention of migrants: Evidence from China

The massive rural-to-urban migration has been one of the most important features of China’s labour market in recent decades. The recent pattern of return migration and migrant wages has increased the costs of firms in urban areas and has negatively affected urbanisation. Therefore, it is important to understand the determinants of settlement intention of migrants. Using data from Rural Urban Migration in China (RUMiC), we find that migrants express higher settlement intention in a city after receiving training that is provided by firms. The effect is larger for females, high school graduates and dropouts, and wage earners. These findings suggest that training may complement migrants’ human capital and upgrade their skills. Therefore, training in cities may act as an instrument that facilitates the migration decisions and transforms a temporary migrant to a permanent resident in an urban area.
Effects of cigarette smoking on diagnostic tests for work-related hypersensitivity pneumonitis: data from an outbreak of lung disease in metalworkers.

BACKGROUND It is widely believed that development of hypersensitivity pneumonitis (HP) is forestalled in cigarette smokers. We encountered the largest outbreak of HP in metalworkers yet reported [Hodgson et al. (2001): Am J Ind Med 39:616-628] and subsequently did a chart review of the 61 patients seen in connection with the outbreak [Dangman et al. (2002a): Am J Resp Crit Care Med 165(8):A528; Dangman et al. (2002b): Am J Ind Med 42:150-162], developing a diagnostic index for this disease. METHODS A re-examination of data from the chart review was carried out to explore possible effects of cigarette smoking on the clinical tests used to diagnose HP [Hodgson et al. (2001): Am J Ind Med 39:616-628]. RESULTS Cigarette smokers with HP were less likely than non-smokers with HP to develop crackles in the lungs, elevated erythrocyte sedimentation rates (ESRs), and restrictive spirometry. Smoking habits had little effect on diffusion capacity and alveolar-arterial oxygen gradients in the patients with HP. Smokers were more likely to have abnormal gallium scans than non-smokers. CONCLUSIONS It appears that cigarette smoking can affect the physical examination findings, spirometry, and ESR changes associated with HP, making these tests less sensitive and specific, and potentially obscuring the diagnosis. Such changes may contribute to the apparent "protective" effect of smoking on the development of HP.
Inactivation of Interferon Regulatory Factor-1 Tumor Suppressor Protein by HPV E7 Oncoprotein

In studying biological roles of interferon regulatory factor (IRF)-1 tumor suppressor in cervical carcinogenesis, we found that HPV E7 is functionally associated with IRF-1. Binding assays indicate a physical interaction between IRF-1 and HPV E7in vivo and in vitro. The carboxyl-terminal transactivation domain of IRF-1 was required for the interaction. Transient co-expression of E7 significantly inhibits the IRF-1-mediated activation of IFN-β promoter in NIH-3T3 cells. Co-transfection of E7 mutants reveals that the pRb-binding portion of E7 is necessary for the E7-mediated inactivation of IRF-1. It was next determined whether histone deacetylase (HDAC) is involved in the inactivation mechanism as recently suggested, where the carboxyl-terminal zinc finger domain of E7 associates with NURD complex containing HDAC. When trichostatin A, an inhibitor of HDAC, was treated, the repressing activity of E7 was released in a dose-dependent manner. Furthermore, the mutation of zinc finger abrogates such activity without effect on the interaction with IRF-1. These results suggest that HPV E7 interferes with the transactivation function of IRF-1 by recruiting HDAC to the promoter. The immune-promoting role of IRF-1 evokes the idea that our novel finding might be important for the elucidation of the E7-mediated immune evading mechanism that is frequently found in cervical cancer.
Cutting Edge: Bacterial Flagellin Activates Basolaterally Expressed TLR5 to Induce Epithelial Proinflammatory Gene Expression1

Flagellin, the structural component of bacterial flagella, is secreted by pathogenic and commensal bacteria. Flagellin activates proinflammatory gene expression in intestinal epithelia. However, only flagellin that contacts basolateral epithelial surfaces is proinflammatory; apical flagellin has no effect. Pathogenic Salmonella, but not commensal Escherichia coli, translocate flagellin across epithelia, thus activating epithelial proinflammatory gene expression. Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-κB gene expression in response to flagellin. The response depended on both extracellular leucine-rich repeats and intracellular Toll/IL-1R homology region of TLR5 as well as the adaptor protein MyD88. Furthermore, immunolocalization and cell surface-selective biotinylation revealed that TLR5 is expressed exclusively on the basolateral surface of intestinal epithelia, thus providing a molecular basis for the polarity of this innate immune response. Thus, detection of flagellin by basolateral TLR5 mediates epithelial-driven inflammatory responses to Salmonella.
Comparative Analysis of the Biochemical and Functional Properties of C-Terminal Domains of Autotransporters

ABSTRACT Autotransporters (ATs) are the largest group of proteins secreted by Gram-negative bacteria and include many virulence factors from human pathogens. ATs are synthesized as large precursors with a C-terminal domain that is inserted in the outer membrane (OM) and is essential for the translocation of an N-terminal passenger domain to the extracellular milieu. Several mechanisms have been proposed for AT secretion. Self-translocation models suggest transport across a hydrophilic channel formed by an internal pore of the β-barrel or by the oligomerization of C-terminal domains. Alternatively, an assisted-translocation model suggests that transport employs a conserved machinery of the bacterial OM such as the Bam complex. In this work we have investigated AT secretion by carrying out a comparative study to analyze the conserved biochemical and functional features of different C-terminal domains selected from ATs of gammaproteobacteria, betaproteobacteria, alphaproteobacteria, and epsilonproteobacteria. Our results indicate that C-terminal domains having an N-terminal α-helix and a β-barrel constitute functional transport units for the translocation of peptides and immunoglobulin domains with disulfide bonds. In vivo and in vitro analyses show that multimerization is not a conserved feature in AT C-terminal domains. Furthermore, we demonstrate that the deletion of the conserved α-helix severely impairs β-barrel folding and OM insertion and thereby blocks passenger domain secretion. These observations suggest that the AT β-barrel without its α-helix cannot form a stable hydrophilic channel in the OM for protein translocation. The implications of our data for an understanding of AT secretion are discussed.
Sirolimus-induced thrombocytopenia and leukopenia in renal transplant recipients: risk factors, incidence, progression, and management.

BACKGROUND Our study assessed the factors that predispose renal transplant recipients to the occurrence of thrombocytopenia and leukopenia, as well as the severity and the time- and concentration-dependence of these side-effects, after administration of sirolimus (SRL) in combination with a cyclosporine (CsA) and prednisone (Pred) regimen. METHODS The clinical courses of two cohorts of renal transplant recipients were compared over 1 year: 119 patients received SRL in addition to CsA and Pred, and 65 demographically similar, concurrent patients received only CsA and Pred. Using an analysis of variance, pretransplant laboratory values and SRL trough concentrations (C0) were correlated with the occurrence, severity, and persistence of drug-induced thrombocytopenia (platelet count <150x10(3) cell/mm3) and/or leukopenia (white blood cell count <5,000/mm3). RESULTS Neither the ethnic background nor the pretransplant cytomegalovirus serological status was associated with the occurrence of hematological complications. Thrombocytopenia was usually observed during the first 4 weeks of treatment (P=0.004). The occurrence, but not the severity or the persistence, of both thrombocytopenia and leukopenia correlated significantly with SRL trough concentrations > or =16 ng/ml (P=0.001 and 0.0001, respectively). A significant correlation is evident between the occurrence of the two adverse effects (P=0.001). In 89% of patients, the first episode of either type of cytopenia resolved spontaneously. Among the remaining 11%, 7% responded to SRL dose reduction, and 4% to temporary suspension. No patient required permanent cessation of SRL therapy. Most patients experienced repeated, but self-limited, episodes of toxicity. CONCLUSION Thrombocytopenia and leukopenia are not infrequent occurrences with SRL treatment, and they generally resolve spontaneously.
Comparison of Completion Thyroidectomy and Primary Total Surgery for Differentiated Thyroid Cancer: A Meta-Analysis

Background: The aim of this study was to compare the complication rates between completion thyroidectomy and primary total thyroidectomy for differentiated thyroid cancer (DTC). Methods: PubMed, the Web of Knowledge, and the China Journal Net were searched for studies concerning the treatment of DTC published in 1990-2014. A meta-analysis was performed to compare the effects of different treatments. Results: 7 studies with a total of 1,208 patients were included. There were no statistically significant differences regarding the presence of temporary recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, temporary hypocalcemia, permanent hypocalcemia, hematoma, and wound infection. Conclusions: Completion thyroidectomy can be performed with acceptable morbidity in select cases of DTC who could not be properly diagnosed perioperatively or who recurred after less than total thyroidectomy.