Miracle-dz/UniFAR-FTUs huggingface dataset:
NOS2 Regulation of NF-κB by S-Nitrosylation of p65*

Signal transduction in the NF-κB transcription factor pathway is inhibited by inducible nitric oxide synthase (NOS2) activity, although the molecular mechanism(s) are incompletely understood. We have previously shown that nitric oxide (NO), derived from NOS2 consequent upon cytokine stimulation, attenuates NF-κB p50-p65 heterodimer DNA binding and have identified the p50 monomer as a locus for inhibitory S-nitrosylation. We now show that the binding partner of p50, NF-κB p65, is also targeted by NO following cytokine stimulation of respiratory epithelial cells and macrophages and identify a conserved cysteine within the Rel homology domain that is the site for S-nitrosylation. S-Nitrosylation of p65 inhibits NF-κB-dependent gene transcription, and nuclear levels of S-nitrosylated p65 correlate with decreased DNA binding of the p50-p65 heterodimer. NOS2 regulates cytokine-induced S-nitrosylation of p65, resulting in decreased NF-κB binding to the NOS2 promoter, thereby inhibiting further NOS2 expression. Collectively, these findings delineate a mechanism by which NOS2 modulates NF-κB activity and regulates gene expression in inflammation.
Host group formation decreases exposure to vector-borne disease: a field experiment in a ‘hotspot’ of West Nile virus transmission

Animals can decrease their individual risk of predation by forming groups. The encounter-dilution hypothesis extends the potential benefits of gregariousness to biting insects and vector-borne disease by predicting that the per capita number of insect bites should decrease within larger host groups. Although vector-borne diseases are common and can exert strong selective pressures on hosts, there have been few tests of the encounter-dilution effect in natural systems. We conducted an experimental test of the encounter-dilution hypothesis using the American robin (Turdus migratorius), a common host species for the West Nile virus (WNV), a mosquito-borne pathogen. By using sentinel hosts (house sparrows, Passer domesticus) caged in naturally occurring communal roosts in the suburbs of Chicago, we assessed sentinel host risk of WNV exposure inside and outside of roosts. We also estimated per capita host exposure to infected vectors inside roosts and outside of roosts. Sentinel birds caged inside roosts seroconverted to WNV more slowly than those outside of roosts, suggesting that social groups decrease per capita exposure to infected mosquitoes. These results therefore support the encounter-dilution hypothesis in a vector-borne disease system. Our results suggest that disease-related selective pressures on sociality may depend on the mode of disease transmission.
The Swedish Childhood Coeliac Disease Working Group after 20 years: history and future

On the occasion of the 20th anniversary of the Swedish Childhood Coeliac Disease Working Group, the members of the Group are presented, our accomplishments are reviewed and our vision for the future is declared. The epidemiology of childhood coeliac disease (CD) has undergone dramatic changes over recent decades in Sweden. Up to the early 1980s, the incidence of CD in Swedish children was about 1 ⁄ 1000. During the mid and late 1980s, a sharp increase was observed by paediatric gastroenterologists at several Swedish paediatric clinics. This finding was reported at the annual meeting of the Section for Gastroenterology of the Swedish Paediatric Association in 1989. The outcome was the creation of the Childhood Coeliac Disease Working Group (CDWG) to establish the current incidence of CD. It was decided that each of Sweden’s seven health-care regions be represented by one paediatric gastroenterologist with special interest in CD. Table 1 presents the members of the original CDWG formed in 1989. As all members were clinical practitioners as well as coeliac researchers, it later became obvious that two individuals from each region were needed to ensure a sufficient attendance at the Group meetings (Table 1). Initially the meetings were located at a university hospital. However, the Swedish Society of Medicine in Stockholm soon became the main meeting venue for practical reasons. The CDWG acts on behalf of the board of the Section for Gastroenterology of the Swedish Paediatric Association. The work of the CDWG is presented to the members of the Section for Gastroenterology at the annual meetings of the Section. The mandate of the CDWG is renewed by the board of the Section, which also appoints members of the Group. The CDWG has, on average, two meetings each year and since the start in May 1989 up to 2009 the Group has had 47 meetings, each with an average participation of seven (median; range 2–11) participants. A record of each meeting is kept and the memoranda (in Swedish) are available on the internet (http://www.blf.net). The initial assignment to study the incidence of childhood CD in Sweden was effected using a questionnaire to all paediatric clinics performing small bowel biopsy. The result was published in 1992 (1), presenting data showing the increasing incidence of childhood CD. Later on the mandate of the CDWG was widened to include other aspects of childhood CD, such as the definition of diagnostic criteria and coeliac research, thereby acting as a source of CD information available to both clinicians and research workers. The CDWG was commissioned to establish national guidelines for the diagnosis and treatment of children with Table 1 Members of the Swedish Working Group for Childhood Coeliac Disease. The health-care regions are presented from the South to the North of Sweden
Shift‐and‐persist: A protective factor for elevated BMI among low‐socioeconomic‐status children

Low socioeconomic status (SES) is associated with many adverse health outcomes, including childhood overweight and obesity. However, little is understood about why some children defy this trend by maintaining a healthy weight despite living in obesogenic environments. The objective of this study is to test the hypothesis that the psychological strategy of “shift‐and‐persist” protects low‐SES children from overweight and obesity. Shift‐and‐persist involves dealing with stressors by reframing them more positively while at the same time persisting in optimistic thoughts about the future.
Validation of the PVLife model using 3 million module-years of live site data

Establishing a strong basis for confidence in a solar technology requires being able to prove a low-degradation track record in the real world, and rationalize it with strong physical understanding and investigation. This paper briefly reviews our previously-published physical model for calculating degradation and reliability, PVLife, which computes hour-by-hour degradation of PV modules using weather files and degradation sub-models developed from accelerated test data. We then demonstrate a validation of this model against a large statistical data set obtained from 266 systems powered by SunPower modules (data from over 179 systems installed by Powerlight, using non-SunPower modules are also shown). In total these data represent over 800,000 modules and a total of 3.2 million module-years of experience. The data analysis technique requires little manual data processing and can be derived from live sites without special experimental treatment. We also discuss returnrate data on modules incorporating SunPower's back-contact cell, as well as front contact modules in SunPower's fleet. Implications for failure prediction are discussed.
ATM Protein-dependent Phosphorylation of Rad50 Protein Regulates DNA Repair and Cell Cycle Control*

The Mre11/Rad50/NBN complex plays a central role in coordinating the cellular response to DNA double-strand breaks. The importance of Rad50 in that response is evident from the recent description of a patient with Rad50 deficiency characterized by chromosomal instability and defective ATM-dependent signaling. We report here that ATM (defective in ataxia-telangiectasia) phosphorylates Rad50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair. Although a Rad50 phosphosite-specific mutant (S635G) supported normal activation of ATM in Rad50-deficient cells, it was defective in correcting DNA damage-induced signaling through the ATM-dependent substrate SMC1. This mutant also failed to correct radiosensitivity, DNA double-strand break repair, and an S-phase checkpoint defect in Rad50-deficient cells. This was not due to disruption of the Mre11/Rad50/NBN complex revealing for the first time that phosphorylation of Rad50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity.
Differences in stroke outcome based on sex

Objective: Stroke thrombolysis may have a differential effect by sex. We sought to examine the relationship between sex and outcome after thrombolysis. Methods: This is a retrospective cohort study of stroke patients from the Registry of Canadian Stroke Network phase 1 (June 2001-February 2002) and phase 2 (June 2002-December 2002). Variables including demographics, history, clinical data, process measures, and outcome were analyzed. The primary outcomes were the Stroke Impact Scale-16 score (SIS-16) and mortality at 6 months. We compared the outcomes of the thrombolyzed and nonthrombolyzed cohorts and examined the data for a tissue plasminogen activator (tPA)-by-sex interaction on the 2 primary outcomes. Results: The overall proportion of patients who achieved an excellent outcome (SIS-16 >75) was not different by gender. However, the proportion of patients achieving an excellent outcome in the non-tPA cohort was much greater in males, with an absolute risk difference of 11.8%. A multiplicative treatment by sex interaction was evident (p = 0.054). This interaction was not present for stroke case fatality. Conclusions: Women fared poorly compared to men in the placebo groups, but this negative prognostic sex effect was neutralized by thrombolysis.
The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women.

OBJECTIVE The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy. METHODS We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test. RESULTS The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05). CONCLUSIONS VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values.
Herceptin-directed nanoparticles activated by an alternating magnetic field selectively kill HER-2 positive human breast cells in vitro via hyperthermia

Purpose: HER-2 is in the EGF tyrosine kinase receptor family, overexpressed by many human cancers and minimally expressed by normal adult tissues. HER-2 expression in human cancers is correlated with reduced survival, increased metastasis, reduced apoptosis and increased proliferation. Herceptin is a humanised mouse antibody that targets and inactivates HER-2. In the present study, Herceptin was used to deliver ferric oxide-enriched nanoparticles to HER-2+ cancer cells. If exposed to alternating magnetic field (AMF), the nanoparticles heat. We tested the ability of AMF-activated Herceptin-directed nanoparticles to selectively kill HER-2+ human cancer cells. Methods: Herceptin-conjugated nanoparticles were incubated with normal human mammary epithelial cells (HMEC)(HER-2-) or malignant human mammary epithelial cells (SK-BR-3)(HER-2+). Cells were stained to detect Herceptin or iron and the kinetics of binding quantified. Once conditions were optimised for binding, cells were exposed to either antibody-directed or non-antibody-conjugated nanoparticles, washed and sham-treated or exposed to AMF and cell death quantified. Results: SK-BR-3 cells bound Herceptin-directed nanoparticles in increasing amounts over 3 h but did not retain non-antibody conjugated nanoparticles. HMECs did not retain either nanoparticles. SK-BR-3 cells with bound Herceptin-directed-nanoparticles, exposed to AMF, died by apoptosis, quantifiable by Live/Dead and nuclear morphology assays and released LDH. Sham-treated SK-BR-3 cells with Herceptin-directed nanoparticles, HMECs with either nanoparticles, with or without AMF treatment, exhibited no increase in toxicity above baseline cell death using these three assays. Conclusions: These studies demonstrate Herceptin-directed nanoparticles can selectively kill HER-2+ cancer cells via hyperthermia after AMF activation.
Effect of Chronic ACE Inhibition on Glucose Tolerance and Insulin Sensitivity in Hypertensive Type 2 Diabetic Patients

The question, of whether long‐term treatment of essential hypertension with angiotensin‐converting enzyme (ACE) inhibitors is capable of modifying glucose tolerance or insulin sensitivity in Type 2 (non‐insulin dependent) diabetes, is still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run‐in period and again after 3 months of antihypertensive treatment with the ACE inhibitor, Captopril. Glucose tolerance was tested with a 75‐g oral glucose load and insulin sensitivity was measured by the insulin suppression test, while dietary and drug treatment of the diabetes remained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 ± 3 mmHg to a final value of 115 ± 2 mmHg (p < 0.005); in six patients, the change in MBP was < 5 mmHg (non‐responders), thus giving a clinical response rate of ˜60%. After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycated haemoglobin concentrations were unchanged from baseline. During the oral glucose tolerance test, the incremental glucose area‐under‐curve was 0.75 ± 0.05 mol 120 min I−1 before and 0.76 ± 0.06 mol 120 min I−1 after treatment (p = ns). Endogenous insulin response and suppression of plasma FFA levels were superimposable on the two occasions. During the insulin suppression test, steady‐state plasma glucose levels were 14.4 ± 1.3 vs 14.2 ±1.1 mmol I−1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 ± 21 vs 287 ± 14 pmol I−1). Neither endogenous (oral glucose) nor exogenous (insulin suppression test) insulin caused any change in plasma potassium concentrations. This resistance to the hypokalemic action of insulin was not affected by Captopril. The eight blood pressure responders, or the seven patients with less fasting hyperglycaemia, had similar baseline characteristics as the whole group, and likewise showed no significant treatment‐related change in glucose tolerance or insulin sensitivity.
Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences

Renewed interest in axonal injury in multiple sclerosis has significantly shifted the focus of research into this disease toward neurodegeneration. During the past year magnetic resonance and morphologic studies have continued to confirm and extend the concept that axonal transection begins at disease onset, and that cumulative axonal loss provides the pathologic substrate for the progressive disability that most long-term MS patients experience. Although inflammation and chronic demyelination are probable causes of axonal transection, little is known about the molecular mechanisms that are involved. The view that MS can also be considered an inflammatory neurodegenerative disease has important clinical implications for therapeutic approaches, monitoring of patients, and future treatment strategies.
Constantine

THE purpose of the enterprising ' Teach Yourself History' series in which this volume appears is to 'open up a significant historical theme' by way of a biography of some leading figure. This accounts for the double title, though one feels that a more apposite one could have been found. For Europe was, in fact, predominantly pagan at the death of Constantine. Christianity, even within the Empire, though enjoying imperial favour was as yet no more than a religio lidta. Half a century was to elapse before it could properly be described as the official religion of the Roman Empire, and another two centuries had passed before the conversion of the West can be said to have started on its final course with Augustine's mission to this country. Such later developments are, save in his concluding pages, rightly disregarded by the author. The background and the achievements of the first Christian emperor are the theme of this carefully planned study, and a title more indicative of its contents, one might suggest, would have been 'Constantine and the End of the Ancient World'.
JPEG recompression detection

Re-quantization commonly occurs when digital multimedia content is being tampered with. Detecting requantization is therefore an important element for assessing the authenticity of digital multimedia content. In this paper, we introduce three features based on the observation that re-quantization (i) induces periodic artifacts and (ii) introduces discontinuities in the signal histogram. After validating the discriminative potential of these features with synthetic signals, we propose a system to detect JPEG re-compression. Both linear (FLD) and non-linear (SVM) classifications are investigated. Experimental results clearly demonstrate the ability of the proposed features to detect JPEG re-compression, as well as their competitiveness compared to prior approaches to achieve the same goal.
The human periodontal membrane – focusing on the spatial interrelation between the epithelial layer of Malassez, fibers, and innervation

Objective. The purpose of the present study was to map the spatial interrelation of fibers, peripheral nerves, and epithelial layer of Malassez in human periodontal membrane in areas close to the root surfaces. Material and Methods. Four healthy permanent teeth extracted from four patients during puberty due to orthodontic treatment planning were analyzed. The extracted teeth, fixed in 4% neutral buffered formaldehyde for 5 days, were decalcified in 0.5 M EDTA. Paraffin blocks were sagittally cut in 5 µm thick serial sections and mounted on Superfrost® Plus microscope slides. For survey, every fifth slide was stained with Alcian Blue/Van Gieson. Immunohistochemical reactions: Cytokeratin (wide spectrum screening) for epithelium, anti-vimentin for fibers, and anti-neuronal nuclei (NeuN) for innervation.Results The study indicates that the epithelial layer of Malassez is a border between different fiber morphologies and innervation patterns. Innervation is identified predominantly in the periodontal layer with tightly packed fibers close to the root surface.Conclusion It is suggested that the genetic composition of the epithelial layer of Malassez in the periodontal membrane may be the key to understanding the different functions of the periodontal membrane and also the individual differences of these functions.
Measuring Working Memory With Digit Span and the Letter-Number Sequencing Subtests From the WAIS-IV: Too Low Manipulation Load and Risk for Underestimating Modality Effects

The Wechsler Adult Intelligence Scale (WAIS) is one of the most frequently used tests among psychologists. In the fourth edition of the test (WAIS-IV), the subtests Digit Span and Letter-Number Sequencing are expanded for better measurement of working memory (WM). However, it is not clear whether the new extended tasks contribute sufficient complexity to be sensitive measures of manipulation WM, nor do we know to what degree WM capacity differs between the visual and the auditory modality because the WAIS-IV only tests the auditory modality. Performance by a mixed sample of 226 patients referred for neuropsychological examination on the Digit Span and Letter-Number Sequencing subtests from the WAIS-IV and on Spatial Span from the Wechsler Memory Scale-Third Edition was analyzed in two confirmatory factor analyses to investigate whether a unitary WM model or divisions based on modality or level/complexity best fit the data. The modality model showed the best fit when analyzing summed scores for each task as well as scores for the longest span. The clinician is advised to apply tests with higher manipulation load and to consider testing visual span as well before drawing conclusions about impaired WM from the WAIS-IV.
What is a feral cat?

Study rationale: The definition of a true feral cat is an area of much contention, with many variations used worldwide. In this study, opinions were gathered from feral cat rescue workers and veterinary surgeons working in the United Kingdom to identify a practical definition of a feral cat, suitable for use in the field, education and research. Protocol: A mixed methods approach, using questionnaires and focus groups, was used to collect data from feral cat workers and veterinary surgeons. Findings: Conflicts in opinion on the implications of taming feral cats exist. The rescue workers typically felt that most cats could be tamed, whereas the veterinary surgeons felt this was generally inappropriate, except in the case of young kittens. A consistent definition of feral cats would enable better communication regarding the welfare and management of these animals, and would be useful for further research and education of the public. Proposed definition: A feral cat is proposed by this study to be a cat that is unapproachable in its free-roaming environment and is capable of surviving with or without direct human intervention, and may additionally show fearful or defensive behaviour on human contact.
Prosodic cues to semantic structure in native and nonnative listening

Listeners efficiently exploit sentence prosody to direct attention to words bearing sentence accent. This effect has been explained as a search for focus, furthering rapid apprehension of semantic structure. A first experiment supported this explanation: English listeners detected phoneme targets in sentences more rapidly when the target-bearing words were in accented position or in focussed position, but the two effects interacted, consistent with the claim that the effects serve a common cause. In a second experiment a similar asymmetry was observed with Dutch listeners and Dutch sentences. In a third and a fourth experiment, proficient Dutch users of English heard English sentences; here, however, the two effects did not interact. The results suggest that less efficient mapping of prosody to semantics may be one way in which nonnative listening fails to equal native listening.