Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clinical Potential of C-Peptide Replacement in Type 1 Diabetes

It is well known that C-peptide fulfills an important function in the synthesis of insulin. After cleavage of proinsulin in the pancreatic β-cells, the 31-amino acid C-peptide is secreted into the portal circulation in equimolar concentrations with insulin. After its discovery in 1967 (1), it was believed that C-peptide might exert physiological effects similar to those of insulin. However, no influence on glucose or lipid metabolism could be demonstrated, and C-peptide was subsequently regarded as a waste product of insulin synthesis. Nevertheless, it was found to be useful as an indicator of β-cell function, and since the mid-1970s, C-peptide has been used as a surrogate marker for monitoring the course of type 1 and type 2 diabetes and determining the effects of interventions designed to preserve and improve residual β-cell function. Several studies demonstrate that patients with type 1 diabetes who show a degree of remaining β-cell activity are considerably less prone to develop microvascular complications than those who are totally C-peptide deficient (2). The possibility that C-peptide may exert direct effects of its own was reevaluated in the early 1990s. A series of studies was undertaken involving administration of the peptide to patients with type 1 diabetes, who lack C-peptide. This approach gave positive results, and it became apparent that replacement of C-peptide in physiological concentrations resulted in significant improvements in several diabetes-induced functional abnormalities (3–7). These surprising findings prompted a renewed interest in C-peptide physiology, and during the past 15 years, a steadily increasing number of reports on new aspects of C-peptide physiology have emerged. The information available today includes studies of the peptide’s interaction with cell membranes and its intracellular signaling properties (8). In vivo studies in animal models of type 1 diabetes have defined a beneficial influence of C-peptide on diabetes-induced functional and structural …
Effects of Stimulus Symmetry on Hierarchical Processing in Six-Month-Old Short- and Long-Looking Infants

The current study investigated the effects of stimulus symmetry on the processing of global and local stimulus properties by 6-month-old shortand long-looking infants through the use of event-related potentials (ERPs). When compared with asymmetry, symmetry has been associated with more efficient stimulus processing and more accurate memory for stimulus configuration (Attneave, 1955; Perkins, 1932). Previous research has shown that individual differences in infant visual attention are related to hierarchical stimulus processing, such that short lookers show a precedence effect for global processing, while long lookers demonstrate a local processing precedence (Guy, Reynolds, & Zhang, 2013). Based on the Information Processing Principles proposed by Cohen and colleagues (Cohen, Chaput, & Cashon, 2002), the presence of asymmetry was expected to direct attention to the local features of stimuli, leading short lookers to regress to a local processing strategy. Analysis of the late slow wave (LSW) indicated that short lookers attended to global stimulus properties, while long lookers attended to local stimulus properties. Nc analyses revealed an interaction of familiarization condition, looker type, and stimulus type at midline central electrodes. Short lookers in the asymmetric familiarization condition showed a greater amplitude Nc response to the familiar stimulus than stimuli novel in global configuration, which indicates that these infants maintained interest in the familiar stimulus after familiarization. It is likely that interest was maintained because the familiar stimulus was not fully processed. These findings indicate that infants’ ERP responses to hierarchical stimuli are impacted by individual differences in visual attention and stimulus symmetry.
Architectures and algorithms for synthesizable embedded programmable logic cores

As integrated circuits become more and more complex, the ability to make post-fabrication changes will become more and more attractive. This ability can be realized using programmable logic cores. Currently, such cores are available from vendors in the form of a "hard" layout. In this paper, we focus on an alternative approach: vendors supply a synthesizable version of their programmable logic core (a "soft" core) and the integrated circuit designer synthesizes the programmable logic fabric using standard cells. Although this technique suffers increased speed, density, and power overhead, the task of integrating such cores is far easier than the task of integrating "hard" cores into an ASIC. For very small amounts of logic, this ease of use may be more important than the increased overhead. This paper presents two synthesizable programmable logic core architectures, describes the associated place and route CAD tools, and compares the two architectures to each other, and to a "hard" programmable logic core. It also shows how these cores can be made more efficient by creating a non-rectangular architecture, an option not available to "hard" core vendors.
Determinants of Bone and Blood Lead Levels among Minorities Living in the Boston Area

We measured blood and bone lead levels among minority individuals who live in some of Boston’s neighborhoods with high minority representation. Compared with samples of predominantly white subjects we had studied before, the 84 volunteers in this study (33:67 male:female ratio; 31–72 years of age) had similar educational, occupational, and smoking profiles and mean blood, tibia, and patella lead levels (3 μg/dL, 11.9 μg/g, and 14.2 μg/g, respectively) that were also similar. The slopes of the univariate regressions of blood, tibia, and patella lead versus age were 0.10 μg/dL/year (p < 0.001), 0.45 μg/g/year (p < 0.001), and 0.73 μg/g/year (p < 0.001), respectively. Analyses of smoothing curves and regression lines for tibia and patella lead suggested an inflection point at 55 years of age, with slopes for subjects ≥ 55 years of age that were not only steeper than those of younger subjects but also substantially steeper than those observed for individuals > 55 years of age in studies of predominantly white participants. This apparent racial disparity at older ages may be related to differences in historic occupational and/or environmental exposures, or possibly the lower rates of bone turnover that are known to occur in postmenopausal black women. The higher levels of lead accumulation seen in this age group are of concern because such levels have been shown in other studies to predict elevated risks of chronic disease such as hypertension and cognitive dysfunction. Additional research on bone lead levels in minorities and their socioeconomic and racial determinants is needed.
Changes in haematopoietic progenitor colony differentiation and proliferation and the production of different abzymes in EAE mice treated with DNA

Immunization of experimental autoimmune encephalomyelitis (EAE)‐prone C57BL/6 mice with MOG35‐55 (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE‐prone mice. In contrast to MOG, immunization with DNA leads to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA and a reduction in abzyme production. Immunization with DNA only resulted in a significant increase in DNase activity over 40 days where it became 122‐fold higher than before immunization, and fivefold higher when comparing to the maximal activity obtained after MOG treatment. DNA and MOG immunization had different effects on the differentiation profiles of HSCs, lymphocyte proliferation, and the level of apoptosis in bone marrow and other organs of mice. The data indicate that for C57BL/6 mice, DNA may have antagonistic effects with respect to MOG immunization. The usually fast immune response following MOG injection in C57BL/6 mice is strongly delayed after immunization with DNA, which is probably due to a rearrangement of the immune system following the response to DNA.
The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues

Ryanodine receptors (RyRs) are intracellular calcium release channels that participate in controlling cytosolic calcium levels. At variance with the probably ubiquitous inositol 1,4,5-trisphosphate-operated calcium channels (1,4,5-trisphosphate receptors), RyRs have been mainly regarded as the calcium release channels controlling skeletal and cardiac muscle contraction. Increasing evidence has recently suggested that RyRs may be more widely expressed, but this has never been extensively examined. Therefore, we cloned three cDNAs corresponding to murine RyR homologues to carry a comprehensive analysis of their expression in murine tissues. Here, we report that the three genes are expressed in almost all tissues analyzed, where tissue-specific patterns of expression were observed. In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs. In the testis, expression of RyR1 and RyR3 was detected in germ cells. RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum. In situ analysis revealed a cell type-specific pattern of expression in the different regions of the central nervous system. The differential expression of the three ryanodine receptor genes in the central nervous system was also confirmed using specific antibodies against the respective proteins. This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized.
How is the Mobile Internet Different?

We explore how internet browsing behavior varies between mobile phones and personal computers. Smaller screen sizes on mobile phones increase the cost to the user of browsing for information. In addition, a wider range of offline locations for mobile internet usage suggests that local activities are particularly important. Using data on user behavior at a (Twitter-like) microblogging service, we exploit exogenous variation in the ranking mechanism of posts to identify the ranking effects. We show (1) Ranking effects are higher on mobile phones suggesting higher cognitive load: Links that appear at the top of the screen are especially likely to be clicked on mobile phones and (2) The benefit of browsing for geographically close matches is higher on mobile phones: Stores located in close proximity to a user’s home are much more likely to be clicked on mobile phones. Thus, the mobile internet is somewhat less “internet-like”: search costs are higher and distance matters more. We speculate on how these changes may affect the future direction of internet commerce.
Drug eluting stents versus coronary artery bypass surgery in patients with isolated proximal lesion in left anterior descending artery suffering from chronic stable angina

Objective: To compare the efficacy of drug eluting stents (DES) compared with bypass surgery (CABG) with left internal mammary artery (LIMA) in patients with single vessel disease suffering from chronic stable angina. Background: There are a limited number of studies investigating this group of patients. Methods: We included 257 consecutive patients with isolated lesion in the proximal segment of left anterior descending artery (LAD). All patients suffered from chronic stable angina or from stress‐induced ischemia. Of 257 patients, 147 underwent DES implantation and 110 CABG with LIMA. All patients were followed‐up clinically for major adverse cardiac events. Results: The baseline demographic and angiographic characteristics were similar between the two groups. In the DES group we used sirolimus‐, paclitaxel‐, and ABT‐578‐eluting stents. The mean duration of hospitalization after CABG was 7.86 ± 3.84 days vs. 1.02 ± 0.19 days after PCI (P < 0.01). The incidence of MACE was 2.72% in the DES and 2.72% in the surgical group during a mean follow‐up period of 18.71 ± 6.27 months for PCI and 18.70 ± 7.31 months for CABG (P = 0.99). There was one cardiac related death in the DES group and two in the surgical group (P = 0.58). There were three reinterventions in the DES group versus none in the surgical group (P = 0.26). Recurrence of angina was observed in 4.08% of pts in the DES group versus 6.36% in the CABG group (P = 0.57). Conclusions: The present study demonstrated that patients suffering from chronic stable angina with isolated lesion in the proximal segment of LAD have excellent long‐term outcome in both surgical and DES treatment. © 2007 Wiley‐Liss, Inc.
Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils

Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, which is termed endotoxin tolerance. The role and mechanism of lipopolysaccharide (LPS)–tolerized monocytes in inflammatory responses in neutrophils are currently unclear. Here, conditioned supernatants were collected from THP-1 cells treated with or without repeated 1 μg/ml Porphyromonas gingivalis (P.gingivalis) LPS. The chemotactic response of freshly isolated neutrophils recruited by supernatants was determined by a transwell migration assay, which demonstrated a reduced migration of neutrophils stimulated with supernatants from tolerized THP-1 cells in comparison to non-tolerized THP-1 cells. In addition, there was a marked increase in reactive oxygen species (ROS) generation and a significant decrease in Caspase 3 activities in neutrophils treated with supernatants from THP-1 cells that were treated repeatedly with P.gingivalis LPS in comparison to single treatment. A cytokine antibody array was then used to assess cytokine expression patterns in THP-1 cells. In tolerized THP-1 cells, 43 cytokine (43/170) expression levels were decreased, including chemokine ligand 23 (CCL23) and IFN-γ, while 11 cytokine (11/170) expression levels were increased, such as death receptor 6 (DR6). Furthermore, there was decreased production of IFN-γ and epithelial neutrophil activating peptide-78 (ENA-78) in THP-1 cells after stimulation with repeated P. gingivalis LPS in comparison to single challenge, which was confirmed by ELISA. Therefore, P.gingivalis LPS- tolerized THP-1 cells were able to depress neutrophil chemotaxis and apoptosis, and contribute to respiratory burst, which might be related to the changes in cytokine expression patterns in THP-1 cells.
Immobilization of β‐Fructofuranosidases from Aspergillus on Methacrylamide‐Based Polymeric Beads for Production of Fructooligosaccharides

β‐Fructofuranosidases from Aspergillus niger ATCC 20611 and Aspergillus japonicusTIT‐KJ1 were purified and immobilized covalently onto methacrylamide‐based polymeric beads. The porous, oxriane‐containing support was reactive and could bind enzymes in a buffered solution at room temperature with a density up to 0.4 mg of protein g−1 of support with 100% immobilized yield. Neither the optimum temperature for the highest enzymatic activities nor the batch reaction pattern for fructooligosaccharides formation catalyzed by β‐fructofuranosidases was changed by immobilization. The amount of fructooligosaccharides produced from 50% (w/w) sucrose solution using the prepared immobilized enzymes was determined to be approximately 60% of the total sugars in the reaction mixtures. This level of fructooligosaccharides produced by the immobilized enzymes was comparable to that resulting from processes employing other immobilized biocatalysts as shown in the literature. The fraction of total fructooligosaccharides presented in the final mixture increased with the initial sucrose concentration, while fractions of glucose and fructose decreased with an increase sucrose concentration.
Plasma C-Reactive Protein and Risk of Breast Cancer in Two Prospective Studies and a Meta-analysis

Background: C-reactive protein (CRP) has been evaluated as a risk factor for breast cancer in epidemiologic studies. However, results from prospective studies are inconsistent. Methods: We evaluated the association using prediagnostic blood samples in a case–control study nested within the Nurses' Health Study (NHS) and the full cohort of the Women's Health Study (WHS). A total of 943 cases in the NHS and 1,919 cases in the WHS contributed to the analysis. Conditional logistic regression and Cox proportional hazards model were used in the NHS and WHS, respectively. We pooled our results with prior prospective studies using random effect meta-analysis. Results: In the NHS, higher CRP levels were associated with a suggestively increased risk of breast cancer [quintile 5 vs. 1: relative risk (RR), 1.27; 95% confidence interval (CI), 0.93–1.73; Ptrend = 0.02]; results did not vary significantly by tumor invasiveness or hormone receptor status. However, no association was observed in the WHS for overall risk (quintile 5 vs. 1: RR, 0.89; 95% CI, 0.76–1.06; Ptrend = 0.38) or by tumor invasiveness or hormone receptor status. The meta-analysis (including 5,371 cases from 11 studies) showed a modestly increased risk among women in the highest versus lowest categories of CRP (RR, 1.26; 95% CI, 1.07–1.49). Conclusions: Existing data from prospective studies suggest that CRP, a nonspecific marker of inflammation, is modestly positively associated with breast cancer risk. Impact: Our findings provide support to the concept that inflammation can influence breast cancer development. Cancer Epidemiol Biomarkers Prev; 24(8); 1199–206. ©2015 AACR.
Streptococcus gallolyticus infection in colorectal cancer and association with biological and clinical factors

There is an unambiguous association of Streptococcus gallolyticus infection with colorectal cancer, although there is limited information about epidemiology or interaction between molecular and environmental factors. We performed an original quantitative analysis of S. gallolyticus in unselected colorectal cancer patients (n = 190) and their association with clinical, pathological tumor molecular profiles (microsatellite instability, hypermethylator phenotype and chromosomal instability pathways), and other biological factors in colorectal tumor and normal tissues (cytomegalovirus and Epstein-Barr virus infection). We developed a new quantitative method to assess bacterial load. Analytical validation was reached with a very high sensitivity and specificity. Our results showed a 3.2% prevalence of S. gallolyticus infection in our unselected cohort of colorectal cancer cases (6/190). The average S. gallolyticus copy number was 7,018 (range 44–34,585). No previous reports relating to S. gallolyticus infection have been published for unselected cohorts of patients. Finally, and despite a low prevalence of S. gallolyticus in this study, we were able to define a specific association with tumor tissue (p = 0.03) and with coinfection with Epstein-Barr virus (p = 0.042; OR: 9.49; 95% IC: 1.1–82.9). The prevalence data provided will be very useful in the design of future studies, and will make it possible to estimate the sample size needed to assess precise objectives. In conclusion, our results show a low prevalence of S. gallolyticus infection in unselected colorectal cancer patients and an association of positive S. gallolyticus infection with tumor tissue and Epstein-Barr virus coinfection. Further studies will be needed to definitively assess the prevalence of S. gallolyticus in colorectal cancer and the associated clinicopathological and molecular profiles.
Taste responses in mice lacking taste receptor subunit T1R1

• The taste receptor heterodimer T1R1 + T1R3, metabotropic glutamate receptors (mGluRs) and/or their variants may function as umami taste receptors. • Here, we used newly developed T1R1−/− mice and examined the role of T1R1 and mGluRs in taste detection. • The T1R1−/− mice exhibited seriously diminished synergistic responses to glutamate and inosine monophosphate but not to glutamate alone and significantly smaller responses to sweeteners. • Addition of mGluR antagonists significantly inhibited responses to glutamate in both T1R1−/− and heterozygous T1R1+/− mice. • Taken together, these results suggest that T1R1 mainly contributes to umami taste synergism and partly to sweet sensitivity, while mGluRs are involved in the detection of umami compounds.
Prevalence, genetic relationships and pathogenicity of intestinal spirochaetes infecting Australian Poultry

The prevalence of infection with intestinal spirochaetes in chickens in Western Australia was assessed by selective culture of faecal samples. Colonisation was common, with 35.1% of layer flocks and 53.3% of broiler breeder flocks being positive. Spirochaetes were recovered significantly more frequently from flocks with diarrhoea or reduced production than from clinically normal flocks. The genetic identity and diversity of 56 selected isolates from Australia, the USA and Europe were examined using multilocus enzyme electrophoresis: these were divided into six diverse genetic groups. Three groups contained isolates previously shown to be pathogenic for chickens: (i) "Serpulina intermedia ", (ii) an unnamed group (not identified in Australia), and (iii) Serpulina pilosicoli. Most pathogenic isolates from Australia were "S. intermedia ". Day-old broiler chicks were infected orally with Australian isolates either of "S. intermedia" (3), a commonly isolated but unnamed group (3), or S. pilosicoli (1). All spirochaetes induced diarrhoea, but this occurred earlier and more birds were colonised with "S. intermedia" and S. pilosicoli strains than with strains from the unnamed group. Infection of laying hens with an "S. intermedia " strain caused wet faeces and reduced egg production.
Cavities in protein–DNA and protein–RNA interfaces

An analysis of cavities present in protein–DNA and protein–RNA complexes is presented. In terms of the number of cavities and their total volume, the interfaces formed in these complexes are akin to those in transient protein–protein heterocomplexes. With homodimeric proteins protein–DNA interfaces may contain cavities involving both the protein subunits and DNA, and these are more than twice as large as cavities involving a single protein subunit and DNA. A parameter, cavity index, measuring the degree of surface complementarity, indicates that the packing of atoms in protein–protein/DNA/RNA is very similar, but it is about two times less efficient in the permanent interfaces formed between subunits in homodimers. As within the tertiary structure and protein–protein interfaces, protein–DNA interfaces have a higher inclination to be lined by β-sheet residues; from the DNA side, base atoms, in particular those in minor grooves, have a higher tendency to be located in cavities. The larger cavities tend to be less spherical and solvated. A small fraction of water molecules are found to mediate hydrogen-bond interactions with both the components, suggesting their primary role is to fill in the void left due to the local non-complementary nature of the surface patches.