Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiatherogenic mitochondrial genotype in patients with type 2 diabetes.

OBJECTIVE To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C --> A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS Mt5178 typing was done by polymerase chain reaction-restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mrt5178A group than in the Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 mm, mean +/- SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.
Stimulus Feature Selectivity in Excitatory and Inhibitory Neurons in Primary Visual Cortex

Although several lines of evidence suggest that stimulus selectivity in somatosensory and visual cortices is critically dependent on unselective inhibition, particularly in the thalamorecipient layer 4, no comprehensive comparison of the responses of excitatory and inhibitory cells has been conducted. Here, we recorded intracellularly from a large population of regular spiking (RS; presumed excitatory) and fast spiking (FS; presumed inhibitory) cells in layers 2–6 of primary visual cortex. In layer 4, where selectivity for orientation and spatial frequency first emerges, we found no untuned FS cells. Instead, the tuning of the spike output of layer 4 FS cells was significantly but moderately broader than that of RS cells. However, the tuning of the underlying synaptic responses was not different, indicating that the difference in spike-output selectivity resulted from differences in the transformation of synaptic input into firing rate. Layer 4 FS cells exhibited significantly lower input resistance and faster time constants than layer 4 RS cells, leading to larger and faster membrane potential (Vm) fluctuations. FS cell Vm fluctuations were more broadly tuned than those of RS cells and matched spike-output tuning, suggesting that the broader spike tuning of these cells was driven by visually evoked synaptic noise. These differences were not observed outside of layer 4. Thus, cell type-specific differences in stimulus feature selectivity at the first level of cortical sensory processing may arise as a result of distinct biophysical properties that determine the dynamics of synaptic integration.
Online text independent writer identification using character prototypes distribution

Recently, with the advances in digital pen and paper technology, renewed attention was given on research for writer identification of online documents. This paper proposes a method to retrieve the writer of a document by comparing his handwriting with those stored in a reference database of documents. The query will consist of a testing online handwriting document, the output will be a ranked list of writers whose online handwriting documents are stored in the reference database. The proposed method is text independent and does not impose any constraint on the writing style; it is based on a distance measurement between the distributions of reference patterns defined at the character level. Experiment has been carried out on a database which consists of 82 subjects each providing two online handwritten documents, one stored as the reference and the second one is for retrieval purposes. The Top 1 rate reported is 95% accuracy.
Retargeting FX-binding-ablated HAdV-5 to vascular cells by inclusion of the RGD-4C peptide in hexon hypervariable region 7 and the HI loop

Recent studies have generated interest in the function of human adenovirus serotype 5 (HAdV-5) hexon: factor X (FX) binding and subsequent hepatocyte transduction and interaction with the immune system. Here, we retargeted adenovirus serotype 5 vectors, ablated for FX interaction, by replacing amino acids in hexon HVR7 with RGD-4C or inserting the peptide into the fibre HI loop. These genetic modifications in the capsid were compatible with virus assembly, and could efficiently retarget transduction of the vector via the αvβ3/5 integrin-mediated pathway, but did not alter immune recognition by pre-existing human neutralizing anti-HAdV-5 antibodies or by natural antibodies in mouse serum. Thus, FX-binding-ablated HAdV-5 can be retargeted but remain sensitive to immune-mediated attack. These findings further refine HAdV-5-based vectors for human gene therapy and inform future vector development.
Comparison of Arterial Spin Labeling and Bolus Perfusion-Weighted Imaging for Detecting Mismatch in Acute Stroke

Background and Purpose— The perfusion-weighted imaging (PWI)–diffusion-weighted imaging (DWI) mismatch paradigm is widely used in stroke imaging studies. Arterial spin labeling (ASL) is an alternative perfusion method that does not require contrast. This study compares the agreement of ASL-DWI and PWI-DWI mismatch classification in patients with stroke. Methods— This was a retrospective study drawn from all 1.5-T MRI studies performed in 2010 at a single institution. Inclusion criteria were: symptom onset <5 days, DWI lesion >10 mL, and acquisition of both PWI and ASL. DWI and PWI time to maximum >6 seconds lesion volumes were determined using automated software. Patients were classified into reperfused, matched, or mismatch groups. Two radiologists classified ASL-DWI qualitatively into the same categories blinded to DWI-PWI. Agreement between both individual readers and methods was assessed. Results— Fifty-one studies met the inclusion criteria. Seven cases were excluded (1 due to PWI susceptibility artifact, 2 due to motion, and 4 due to severe ASL border zone sign), resulting in 44 studies for comparison. Interrater agreement for ASL-DWI mismatch status was high (&kgr;=0.92; 95% CI, 0.80–1.00). ASL-DWI and PWI-DWI mismatch categories agreed in 25 of 44 cases (57%). In the 16 of 19 discrepant cases (84%), ASL overestimated the PWI lesion size. In 34 of 44 cases (77%), they agreed regarding the presence of mismatch versus no mismatch. Conclusion— Mismatch classification based on ASL and PWI agrees frequently but not perfectly. ASL tends to overestimate the PWI time to maximum lesion volume. Improved ASL methodologies and/or higher field strength are necessary before ASL can be recommended for routine use in acute stroke.
Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses

Compelling evidence indicates that type 2 diabetes mellitus, insulin resistance (IR), and metabolic syndrome are often accompanied by cognitive impairment. However, the mechanistic link between these metabolic abnormalities and CNS dysfunction requires further investigations. Here, we evaluated whether adipose tissue IR and related metabolic alterations resulted in CNS changes by studying synapse lipid composition and function in the adipocyte‐specific ecto‐nucleotide pyrophosphate phosphodiesterase over‐expressing transgenic (AtENPP1‐Tg) mouse, a model characterized by white adipocyte IR, systemic IR, and ectopic fat deposition. When fed a high‐fat diet, AtENPP1‐Tg mice recapitulate essential features of the human metabolic syndrome, making them an ideal model to characterize peripherally induced CNS deficits. Using a combination of gas chromatography and western blot analysis, we found evidence of altered lipid composition, including decreased phospholipids and increased triglycerides (TG) and free fatty acid in hippocampal synaptosomes isolated from high‐fat diet‐fed AtENPP1‐Tg mice. These changes were associated with impaired basal synaptic transmission at the Schaffer collaterals to hippocampal cornu ammonis 1 (CA1) synapses, decreased phosphorylation of the GluN1 glutamate receptor subunit, down‐regulation of insulin receptor expression, and up‐regulation of the free fatty acid receptor 1.
Work Stress and Metabolic Syndrome in Police Officers. A Prospective Study

Objective The aim of this longitudinal study was to evaluate the association between occupational stress and metabolic syndrome (MetS) in a rapid response police unit. Method Work-related stress was continuously monitored during the 5-year period with both the Demand-Control-Support (DCS) and the Effort-Reward Imbalance (ERI) models. Blood pressure, body mass index (BMI), waist circumference, triglycerides, HDL-cholesterol, and fasting blood glucose were measured at baseline in January 2009, and in January 2014. 234 out of 290 police officers (81%) completed the follow-up. Results The majority of police officers had high stress levels. At follow-up, police officers in the highest quartile of stress had significantly higher mean levels of triglycerides, and lower levels of HDL-cholesterol than their colleagues in the lowest quartile. Police officers with high stress had an increased adjusted risk of developing MetS (aOR = 2.68; CI95% = 1.08–6.70), and hypertriglyceridemia (aOR = 7.86; CI95 = 1.29–48.04). Demand and Effort were significant predictors of MetS. Conclusion Our study supports the hypothesis that work-related stress induces MetS, particularly through its effects on blood lipids. Future longitudinal studies with continuous monitoring of stress levels will definitively confirm this hypothesis.
A comparison of τc and τpmax for magnitude estimation in earthquake early warning

We determined the τc and τpmax parameters from the K‐NET strong motion records of 16 earthquakes in Japan with moment magnitude (Mw) ranging from 6.0 to 8.3. A 0.075 Hz high‐pass Butterworth filter was applied for determination of τc based on our previous studies. It was found that different pole selections of the Butterworth filter lead to different uncertainty in magnitude determination. Our results show that using two poles in the filters results in the best magnitude estimates, i.e., minimized the standard deviation in magnitude determination in comparison to Mw using τc. The τpmax parameters (Allen and Kanamori, 2003) were also determined with the same dataset using the Wurman et al. (2007) procedure. It was found that τpmax values obtained from this dataset, and using the Wurman procedure, had a larger uncertainty. However, when a 0.075 Hz high‐pass Butterworth filter with five poles was added, the uncertainty in τpmax‐derived magnitude estimates decreased minimizing the standard deviation in magnitude determination using τpmax. This difference in the behavior of τc and τpmax can be used to further reduce the uncertainty in rapid magnitude determination for earthquake early warning. When the magnitude estimations from τc and τpmax of each event are averaged to provide a new magnitude estimate, the standard deviation in magnitude estimates is reduced further to 0.27 magnitude units.
In vitro Activity of Dalbavancin against Staphylococci Isolated in Istanbul, Turkey

Background: Staphylococci are a major cause of both community- and hospital-acquired infections. Dalbavancin is a new bactericidal second-generation lipoglycopeptide antibiotic to use in the treatment of multidrug-resistant staphylococcal infections. It is important to determine its activity against staphylococci isolated in Turkey. Dalbavancin has not yet been used in antimicrobial therapy in our country. Method: Dalbavancin was tested against a total of 453 staphylococcal strains by using the reference broth microdilution method. Organisms tested included: methicillin-resistant Staphylococcus aureus (MRSA; 237 strains), methicillin-susceptible S. aureus (MSSA; 144 strains) and methicillin- resistant coagulase-negative staphylococci (MR-CoNS; 72 strains). Results: MIC50 and MIC90 values of dalbavancin against MRSA, MSSA and MR-CoNS were found as ≤0.008 and 0.25 mg/l; 0.016 and 0.125 mg/l; and 0.016 and 0.5 mg/l, respectively. The overall distribution of dalbavancin MIC values ranged from ≤0.008 to 2 mg/l. If the interpretive breakpoint MIC value is ≤1 mg/l, the susceptibility rates of MRSA, MSSA and MR-CoNS strains were determined as 99.6, 100 and 98.6%, respectively. Conclusion: The MIC results for dalbavancin have demonstrated a good activity against both methicillin-sensitive and -resistant staphylococci isolated from hospitalized patients.
Inflexibly Focused under Stress: Acute Psychosocial Stress Increases Shielding of Action Goals at the Expense of Reduced Cognitive Flexibility with Increasing Time Lag to the Stressor

Dynamically adjusting the right amount of goal shielding to varying situational demands is associated with the flexibility of cognitive control, typically linked with pFC functioning. Although stress hormones are found to also bind to prefrontal receptors, the link between stress and cognitive control remains elusive. Based on that, we aimed at investigating effects of acute psychosocial stress on dynamic control adjustments. Forty-eight healthy volunteers were exposed to either a well-established stress induction protocol (the Trier Social Stress Test, TSST) or a standardized control situation before a selective attention (Simon) task involving response conflicts. The individual physiological stress response was monitored by analyzing levels of free cortisol and α-amylase activity in saliva samples showing that the TSST reliably induced an increase of endogenous stress hormone levels. Acute stress did not inevitably impair cognitive functioning, however, as stressed participants showed tonically increased goal shielding (to reduce interference) at the expense of decreased cognitive flexibility. Importantly, as a novel finding in humans, stress effects on cognitive functions were not present immediately after the stress experience but developed gradually over time and, therefore, paralleled the time course of the hypothalamus–pituitary–adrenal (HPA) stress response. In addition, the total increase of individual cortisol levels reflecting HPA activity, but not the total changes in α-amylase activity associated with sympathetic activity, was reversely related to the amount of cognitive flexibility in the final block of testing. Our study provides evidence for a stress-induced time-dependent decrease of cognitive flexibility that might be related to changes in cortisol levels.
Heterogeneity of stress gene expression and stress resistance among individual cells of Saccharomyces cerevisiae

Knowledge of gene expression and cellular responses in microorganisms is derived from analyses of populations consisting of millions of cells. Analytical techniques that provide data as population averages fail to inform of culture heterogeneity. Flow cytometry and fluorescence techniques were used to provide information on the heterogeneity of stress‐responsive gene expression and stress tolerance in individual cells within populations. A sequence of DNA encoding the heat shock and stress response elements of the Saccharomyces cerevisiae HSP104 gene was used to express enhanced green fluorescent protein (EGFP). When integrated into the genome of yeast strain W303‐1A, intrinsic expression of EGFP increased about twofold as cells progressed from growth on glucose to ethanol utilization in aerobic batch cultures. Staining of cells with orange/red fluorescent propidium iodide (PI), which only enters cells that have compromised membrane integrity, revealed that the population became more tolerant to 52°C heat stress as it progressed from growth on glucose and through the ethanol utilization phase of aerobic batch culture. Exposure of cultures growing on glucose to a mild heat shock (shift from 25°C to 37°C) resulted in significantly increased expression of EGFP in the population. However, there was heterogeneity in the intensity of fluorescence of individual cells from heat‐shocked cultures, indicating variability in the strength of stress response in the clonal population. Detailed analysis of the heterogeneity showed a clear positive trend between intensity of stress response and individual cell resistance, measured in terms of PI exclusion, to heat stress at 52°C. Further experiments indicated that, although the mean gene expression by a population is influenced by the genetic background, the heterogeneity among individual cells in clonal populations is largely physiologically based.
A simpler primate brain: the visual system of the marmoset monkey

Humans are diurnal primates with high visual acuity at the center of gaze. Although primates share many similarities in the organization of their visual centers with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity, and aging. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organization to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans.
Pulmonary tuberculosis in the border region of Chiapas, Mexico.

OBJECTIVES To estimate the prevalence of pulmonary tuberculosis (PTB) in chronic cough patients seeking care at a second level hospital for any complaint, and to identify groups more likely to test TB smear-positive, within the Border Region of Chiapas, Mexico. METHODS Active case finding of patients with chronic cough (cough of 15 days or more) was carried out among all patients aged over 14 years seeking care for whatever reason in the only hospital in the region for patients not covered by insurance. The coughers identified (n=221) were interviewed and three sputum samples requested for acid-fast smears. In order to identify groups at greater risk a logistic regression model was constructed. RESULTS A rate of 21 positive PTB smears per hundred patients was found (95% Confidence Interval [CI]=15.5-26.6). The main factors associated with positive PTB were age, occupation and weight loss. The subgroup of chronic cough patients of those aged 35-44 years, agricultural workers and those who had lost weight, had the greatest likelihood of positive PTB smears (68.7%). CONCLUSION In hospitals that treat rural patients, special efforts should be made to make health personnel more aware of the need to investigate respiratory symptoms in all of their patients, particularly in the subgroups identified with the greatest likelihood of being positive for TB.
Historical Patterns and Recent Changes in the Relationship between Bank Holding Company Size and Risk

What is the relationship between a bank holding company's size and the risk it takes? The authors find that although the level of risk at large and small bank holding companies has not differed significantly, important distinctions exist in the nature of that risk. Historically, large companies' diversification advantages were offset by lower capital ratios and the pursuit of risk-enhancing activities. More recently, however, differences between the capital ratios and activities of large and small companies have narrowed. As a result, an inverse relationship between risk and bank holding company size has begun to emerge.
Impaired IFN-γ Production by Viral Immunodominant Peptide-specific Tetramer+ CD8+ T Cells in HIV-1 Infected Patients is not Secondary to HAART

Studies on PBMC samples from HIV-1 infected patients have shown that despite substantial number of HIV specific CTLs, these patients gradually progress to AIDS. The present study was conducted to determine whether this paradox was secondary to the influence of protease inhibitors being utilized by these patients. Thus, aliquots of PBMC samples from 10 HIV infected humans with no prior history of anti-retroviral drug therapy (ART) and 6 HIV-infected patients that had been on HAART for >1 year were analyzed for the frequency of HIV-1 Nef and Gag dominant peptide specific tetramer+ cells, respectively. The tetramer+ PBMCs were analyzed for their ability to synthesize specific peptide induced IFN-γ utilizing both the ELISPOT and the intracellular cytokine (ICC) assays. Results of the studies showed that there was an overall correlation between the frequency of Nef and Gag peptide tetramer+ cells and the frequency of IFN-γ synthesizing cells as assayed by either ICC or ELISPOT assay, markedly reduced values of IFN-γ synthesizing cells per unit tetramer+ cells were noted in both group of patients. These data suggest that the frequency of HIV-specific CD8+T cells is maintained during the chronic phase of infection, their ability to function is compromised and is not a reflection of ART. While the addition of IL-2, anti-CD40L and allogeneic cells led to partial increase in the ability of the tetramer+ cells to synthesize IFN-γ, the addition of IL-4, IL-12, anti-CD28 or a cocktail of anti-TGF-β, TNF-α and IL-10 failed to augment the IFN-γ response.