Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical thickness is associated with altered autonomic function in cognitively impaired and non‐impaired older adults

The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. Alzheimer's disease (AD), via frontal compensatory processes, may affect PNS regulation, thereby compromising older adults’ capacity for adaptation, and increasing morbidity and mortality risk. Here we found that AD‐associated neurodegeneration accompanied an overactive anterior cingulate cortex, which in turn resulted in a high level of PNS activity at rest, as well as strong PNS activity withdrawal in response to the mental effort. This discovery provides the first line of evidence to suggest that AD‐associated neurodegeneration links to altered PNS regulation during mental effort in older adults, and that the compensatory processes accompanying frontal hyperactivation appear to be responsible for these alterations.
Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers

Appropriate quantification of added usefulness offered by new markers included in risk prediction algorithms is a problem of active research and debate. Standard methods, including statistical significance and c statistic are useful but not sufficient. Net reclassification improvement (NRI) offers a simple intuitive way of quantifying improvement offered by new markers and has been gaining popularity among researchers. However, several aspects of the NRI have not been studied in sufficient detail.
Common variants in genes that mediate immunity and risk of multiple myeloma

Multiple myeloma (MM) is a B‐cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21–84 years and 545 population‐based controls, we examined the risk of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation‐maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (−28120T, rs2107356) and FCGR2A (−120G, rs1801274) (OR = 1.91, 95% CI 1.08–3.38 and 1.95, 95% CI 1.06–3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering part of the LTA*TNF complex (LTA −82C/−90G *TNF −1036C/−487G/−417G, OR = 1.63, 95% CI 1.02–2.16) compared with the most frequently occurring haplotype observed among controls (LTA −82A/−90A *TNF −1036C/−487G/−417G). Our findings provide preliminary evidence that common genetic variants in specific immune‐mediated pathways could influence the risk of MM. © 2007 Wiley‐Liss, Inc.
Dual-Gate JFET Modeling II: Source Pinchoff Voltage and Complete  $I_{\textrm {ds}}$  Modeling Formalism

This paper studies the phase diagram of source pinchoff of dual-gate JFETs and presents a source pinchoff modeling formalism that is smooth across the phase boundaries. Based on this, an Ids model is derived, which is numerically robust for any value of top- and bottom-gate voltages. The method is applied to both the exact model for Ids and an approximated form based on mid-point-potential linearization, and is verified by comparison with numerical simulation. Modeling of short-channel effects is included.
Measuring coronary calcium on CT images adjusted for attenuation differences.

PURPOSE To quantify scanner and participant variability in attenuation values for computed tomographic (CT) images assessed for coronary calcium and define a method for standardizing attenuation values and calibrating calcium measurements. MATERIALS AND METHODS Institutional review board approval and participant informed consent were obtained at all study sites. An image attenuation adjustment method involving the use of available calibration phantom data to define standard attenuation values was developed. The method was applied to images from two population-based multicenter studies: the Coronary Artery Risk Development in Young Adults study (3041 participants) and the Multi-Ethnic Study of Atherosclerosis (6814 participants). To quantify the variability in attenuation, analysis of variance techniques were used to compare the CT numbers of standardized torso phantom regions across study sites, and multivariate linear regression models of participant-specific calibration phantom attenuation values that included participant age, race, sex, body mass index (BMI), smoking status, and site as covariates were developed. To assess the effect of the calibration method on calcium measurements, Pearson correlation coefficients between unadjusted and attenuation-adjusted calcium measurements were computed. Multivariate models were used to examine the effect of sex, race, BMI, smoking status, unadjusted score, and site on Agatston score adjustments. RESULTS Mean attenuation values (CT numbers) of a standard calibration phantom scanned beneath participants varied significantly according to scanner and participant BMI (P < .001 for both). Values were lowest for Siemens multi-detector row CT scanners (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese (BMI, > or =40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0-39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and normal-weight or underweight (BMI, <25.0 kg/m(2)) (120.1 HU) participants. Agatston score calibration adjustments ranged from -650 to 1071 (mean, -8 +/- 50 [standard deviation]) and increased with Agatston score (P < .001). The direction and magnitude of adjustment varied significantly according to scanner and BMI (P < .001 for both) and were consistent with phantom attenuation results in that calibration resulted in score decreases for images with higher phantom attenuation values. CONCLUSION Image attenuation values vary by scanner and participant body size, producing calcium score differences that are not due to true calcium burden disparities. Use of calibration phantoms to adjust attenuation values and calibrate calcium measurements in research studies and clinical practice may improve the comparability of such measurements between persons scanned with different scanners and within persons over time.
Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy.

Aims Ischemic cardiomyopathy (ICM) resulting from myocardial infarction is a major cause of heart failure (HF). Recently, thousands of long non-coding RNAs (lncRNAs) have been discovered and implicated in a variety of biological processes. However, the role of most lncRNAs in HF remains largely unknown. The aim of this study is to test the hypothesis that the expression and function of lncRNAs are differentially regulated in diseased hearts. Methods and results In this study, we performed RNA deep sequencing of protein-coding and non-coding RNAs from cardiac samples of patients with ICM ( n = 15) and controls ( n = 15). Genome-wide transcriptome analysis confirmed that many protein-coding genes previously known to be involved in HF were altered in ICM hearts. Among the 145 differentially expressed lncRNAs identified in ICM hearts, we found a set of 35 lncRNAs that display strong positive expression correlation. Expression correlation coefficient analyses of differentially expressed lncRNAs and protein-coding genes revealed a strong association between lncRNAs and extracellular matrix (ECM) protein-coding genes. We overexpressed or knocked down selected lncRNAs in cardiac fibroblasts and our results suggest that lncRNAs are important regulators of fibrosis and the expression of ECM synthesis genes. Moreover, we show that lncRNAs participate in the TGF-β pathway to modulate the expression of ECM genes and myofibroblast differentiation. Conclusion Our studies demonstrate that the expression of many lncRNAs is dynamically regulated in ICM. lncRNAs regulate the expression and function of ECM and cardiac fibrosis during the development of ICM. Our results further indicate that lncRNAs may represent novel regulators of heart function and cardiac disorders, including ICM.
Immune Responses to Vi Capsular Polysaccharide Typhoid Vaccine in Children 2 to 16 Years Old in Karachi, Pakistan, and Kolkata, India

ABSTRACT The geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P < 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P < 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.
Contextual Fisher kernels for human action recognition

In the literature of human action recognition, despite promising results have been obtained by the traditional bag-of-words model, the relationship among spatiotemporal points has rarely been considered. Furthermore, serious quantization error also exists in this kind of strategy. In this paper, we propose a novel coding strategy named contextual Fisher kernels to overcome these limitations. We add a Gaussian function to represent contextual information into the generative model. In this way, our method explicitly considers the spatio-temporal contextual relationships between interest points and alleviates quantization error. Our method is verified on two challenging datasets (KTH and UCF sports), and the experimental results demonstrate that our method achieves better results than the state-of-the-art methods in human action recognition.
The cytoplasmic and transmembrane domains of secretor type α1,2fucosyltransferase confer atypical cellular localisation

Carbohydrate structures influence many aspects of cell biology. Manipulating the glycosyltransferase enzymes, that sequentially add carbohydrate moieties to proteins and lipids as they pass through the Golgi and secretory pathway, can alter these carbohydrate epitopes. We previously demonstrated that the eight amino acid cytoplasmic tail of α1,2fucosyltransferase (FT) contained a sequence for Golgi localisation. In this study, we examined the localisation of the closely related secretor type α1,2fucosyltransferase (Sec) which has a smaller, yet apparently unrelated, five amino acid cytoplasmic tail. In contrast to the Golgi localisation of FT, Sec displayed atypical cytoplasmic vesicular‐like staining. However, replacing just the five amino acid tail of Sec with FT was sufficient to relocalise the enzyme to a perinuclear region with Golgi‐like staining. The biological significance of this relocalisation was this chimaeric enzyme was more effective than FT at competing for N‐Acetyl‐lactosamine and thus was superior in reducing expression of the Galα(1,3)Gal xenoepitope. Copyright © 2009 John Wiley & Sons, Ltd.
Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells

It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser‐capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi‐lineage differentiation within CCO‐deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO‐deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Cationic modulation of follicle-stimulating hormone binding to granulosa cell receptor.

Magnesium (Mg2+) increases binding of follicle-stimulating hormone (FSH) to membrane-bound receptors and increases adenylyl cyclase activity. We examined the effects of divalent and monovalent cations on FSH binding to receptors in granulosa cells from immature porcine follicles. Divalent and monovalent cations increased binding of [125I]iodo-porcine FSH (125I-pFSH). The divalent cations Mg2+, calcium (Ca2+) and manganese, (Mn2+) increased specific binding a maximum of 4- to 5-fold at added concentrations of 10 mM. Mg2+ caused a half-maximal enhancement of binding at 0.6 mM, whereas Ca2+ and Mn2+ had half-maximal effects at 0.7 mM and 0.8 mM, respectively. The monovalent cation potassium (K+) increased binding a maximum of 1.5-fold at an added concentration of 50 mM, whereas the monovalent cation (Na+) did not increase binding at any concentration tested. The difference between K+ and Na+ suggested that either enhancement of binding was not a simple ionic effect or Na+ has a negative effect that suppresses its positive effect. Ethylenediamine tetraacetic acid, a chelator of Mg2+, prevented binding of 125I-pFSH only in the presence of Mg2+, whereas pregnant mare's serum gonadotropin, a competitor with FSH for the receptor, prevented binding in both the absence and the presence of Mg2+. Guanyl-5-ylimidodiphosphate (Gpp[NH]p) inhibited binding of 125I-pFSH in the absence or presence of Mg2+, but only at Gpp(NH)p concentrations greater than 1 mM. We used Mg2+ to determine if divalent cations enhanced FSH binding by increasing receptor affinity or by increasing the apparent number of binding sites. (ABSTRACT TRUNCATED AT 250 WORDS)
Collagen Fibril Ultrastructure in Mice Lacking Discoidin Domain Receptor 1

Abstract The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson’s trichrome. Collagen ultrastructure was evaluated in situ using transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Although the mean fibril diameter was not significantly different, DDR1 KO mice had a higher percentage of fibrils with larger diameter compared with their wild-type littermates. No significant differences were observed in the length of D-periods. In addition, collagen fibrils from DDR1 KO mice exhibited a small, but statistically significant, increase in the depth of the fibril D-periods. Consistent with these observations, a reduction in the depth of D-periods was observed in collagen fibrils reconstituted with recombinant DDR1-Fc. Our results elucidate how DDR1 modulates collagen fibril ultrastructure in vivo, which may have important consequences in the functional role(s) of the underlying ECM.
IP mining: Extracting knowledge from the dynamics of the Internet addressing space

Going back to the Internet of one decade ago, HTTP-based content and web services were provided by centralized or barely distributed servers. Single hosts providing exclusive services at fixed IP addresses was the standard approach. Current situation has drastically changed, and the mapping of IPs to different content and services is nowadays extremely dynamic. The adoption of large CDNs by major Internet players, the extended usage of transparent content caching, the explosion of Cloud-based services, and the decoupling between content providers and the hosting infrastructure have created a difficult to manage Internet landscape. Understanding such a complex scenario is paramount for network operators, both to control the traffic on their networks and to improve the quality experienced by their customers, specially when something goes wrong. Using a full week of HTTP traffic traces collected at the mobile broadband network of a major European ISP, this paper studies the associations between web services, the hosting organizations/ASes, and the content servers' IPs. By mining correlations among these, we extract useful insights about the dynamics of the IP addressing space used by the top web services, and the way content providers and hosting organizations deliver their services to the mobile end-users. The extracted knowledge is applied on two specific use-cases, the former on hosting and service delivery characterization, the latter on automatic IP-based HTTP services classification.
Oxygen consumption and mitochondrial membrane potential indicate developmental adaptation in energy metabolism of rat cortical neurons

Neuronal energy needs are mainly covered via mitochondrial oxidative phosphorylation. Even if the energy supply appears identical in immature and adult brain, nevertheless quantitative differences exist. The present study focuses on the adaptations in cellular energy metabolism caused by the neuronal maturation. As main parameters of oxidative phosphorylation, cellular oxygen consumption and mitochondrial membrane potential were measured in isolated rat cortical cells using a Clark‐type oxygen electrode and microfluorometric techniques. In four age groups (E18–P2, P8–P12, P16–P20, ≥ P28), unstimulated neurons showed a significant age‐dependent increase in basal oxygen consumption (6.1 up to 10.2 nm/min/107 cells). The excitatory neurotransmitter glutamate induced a further, but age‐ and concentration‐independent, elevation of oxygen consumption to a plateau ≥ 14 nm/min/107 cells and a complete depolarization of mitochondrial membrane in neurons ≥ P8. Stimulation using K+ (5–50 mm) effected a concentration‐ and age‐dependent increase in oxygen consumption, but a similar nearby complete depolarization of mitochondrial membrane in all tested age groups. Furthermore, uncoupling mitochondrial membrane function followed by a complete depolarization of mitochondrial membrane showed a maximal oxygen consumption (14–15 nm/min/107 cells) only in neurons ≥ P8. These data suggest that developing and adult cortical neurons cover their increased need of energy following stimulation by an efficiency improvement of mitochondrial oxidative phosphorylation. The age‐independent limited capacity of mitochondrial oxidative phosphorylation, however, causes a reduction in cellular energy disposal in mature neurons and therefore may play a critical role in the increased sensitivity of adult neurons against excitotoxicity and ischaemia.
Conformational change in full-length mouse prion: a site-directed spin-labeling study

Title Conformational change in full-length mouse prion: a site-directed spin-labeling study. Author(s) Inanami, Osamu; Hashida, Shukichi; Iizuka, Daisuke; Horiuchi, Motohiro; Hiraoka, Wakako; Shimoyama, Yuhei; Nakamura, Hideo; Inagaki, Fuyuhiko; Kuwabara, Mikinori Citation Biochemical and Biophysical Research Communications, 335(3), 785-792 https://doi.org/10.1016/j.bbrc. 2005.07. 148 Issue Date 2005-09-30 Doc URL http://hdl.handle. net/2115/27969 Type article (author version) File Information BBRC335-3.pdf
Generation and Protective Ability of Influenza Virus-Specific Antibody-Dependent Cellular Cytotoxicity in Humans Elicited by Vaccination, Natural Infection, and Experimental Challenge.

BACKGROUND Nonneutralizing antibodies (Abs) involved in antibody-dependent cellular cytotoxicity (ADCC) may provide some protection from influenza virus infection. The ability of influenza vaccines to induce ADCC-mediating Abs (ADCC-Abs) in adults and children is unclear. METHODS We quantified ADCC-Abs in serum samples from adults who received a dose of inactivated subunit vaccine (ISV) targeting monovalent 2009 pandemic influenza A(H1N1) virus or live-attenuated influenza vaccine (LAIV) or who had laboratory-confirmed influenza A(H1N1) virus infection. We also measured ADCC-Abs in children who either received a dose of trivalent seasonal ISV followed by trivalent seasonal LAIV or 2 doses of LAIV. Finally, we assessed the ability of low and high ADCC-Ab titers to protect adults from experimental challenge with influenza A/Wisconsin/67/131/2005(H3N2) virus. RESULTS Adults and children who received a dose of ISV had a robust increase in ADCC-Ab titers to both recombinant hemagglutinin (rHA) protein and homologous virus-infected cells. There was no detectable increase in titers of ADCC-Abs to rHA or virus-infected cells in adults and children who received LAIV. Higher titers (≥320) of preexisting ADCC-Abs were associated with lower virus replication and a significant reduction in total symptom scores in experimentally infected adults. CONCLUSIONS ADCC-Ab titers increased following experimental influenza virus infection in adults and after ISV administration in both children and adults.
Reviewing birthweight standards

Summary. The standardization of birthweight for gestational age, taking into accounhd sex of infant and maternal height and weight, is clinically useful and essential for some research purposes. In Britain, the most commonly used standards for singletons are those derived from Thomson et al. (1968) from a series of births to women in Aberdeen between 1948 and 1964. The present study starts with the observation that the present population of births in Aberdeen is different. This prompted work to ‘update’ the standards at least for research purposes, and in so doing a number of problems have been encountered which complicate the task of developing universally applicable standards.