Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural characterization of a mutant peptide derived from ubiquitin: Implications for protein folding

The formation of the N‐terminal β‐hairpin of ubiquitin is thought to be an early event in the folding of this small protein. Previously, we have shown that a peptide corresponding to residues 1–17 of ubiquitin folds autonomously and is likely to have a native‐like hairpin register. To investigate the causes of the stability of this fold, we have made mutations in the amino acids at the apex of the turn. We find that in a peptide where Thr9 is replaced by Asp, U(1–17)T9D, the native conformation is stabilized with respect to the wild‐type sequence, so much so that we are able to characterize the structure of the mutant peptide fully by NMR spectroscopy. The data indicate that U(1–17)T9D peptide does indeed form a hairpin with a native‐like register and a type I turn with a G1 β‐bulge, as in the full‐length protein. The reason for the greater stability of the U(1–17)T9D mutant remains uncertain, but there are nuclear Overhauser effects between the side chains of Asp9 and Lys11, which may indicate that a charge‐charge interaction between these residues is responsible.
Inhibition Of Cytokine Release By And Cardiac Effects Of Type Iv Phosphodiesterase Inhibition In Early, Profound Endotoxaemia In Vivo

1. In rats, inhibition of type IV phosphodiesterase (PDE4) attenuates acute renal failure and early (hours) mortality induced by high‐dose endotoxin. Because it is unlikely that protection of renal function accounts for improved early survivability, most likely PDE4 inhibition exerts multiple beneficial effects in endotoxaemia and the purpose of the present study was to test this hypothesis.
Curcumin prevents lipopolysaccharide‐induced atrogin‐1/MAFbx upregulation and muscle mass loss

Because elevated ubiquitin ligase atrogin‐1/MAFbx and MuRF1 mediate skeletal muscle wasting associated with various catabolic conditions, the signaling pathways involved in the upregulation of these genes under pathological conditions are considered therapeutic targets. AKT and NF‐κB have been previously shown to regulate the expression of atrogin‐1/MAFbx or MuRF1, respectively. In addition, we recently found that p38 MAPK mediates TNF‐α upregulation of atrogin‐1/MAFbx expression, suggesting that multiple signaling pathways mediate muscle wasting in inflammatory diseases. To date, however, these advances have not resulted in a practical clinical intervention for disease‐induced muscle wasting. In the present study, we tested the effect of curcumin—a non‐toxic anti‐inflammatory reagent that inhibits p38 and NF‐κB—on lipopolysaccharide (LPS)‐induced muscle wasting in mice. Daily intraperitoneal (i.p.) injection of curcumin (10–60 µg/kg) for 4 days inhibited, in a dose‐dependent manner, the LPS‐stimulated (1 mg/kg, i.p.) increase of atrogin‐1/MAFbx expression in gastrocnemius and extensor digitorum longus (EDL) muscles, resulting in the attenuation of muscle protein loss. It should also be noted that curcumin administration did not alter the basal expression of atrogin‐1/MAFbx, nor did it affect LPS‐stimulated MuRF1 and polyubiquitin expression. LPS activated p38 and NF‐κB, while inhibiting AKT; whereas, curcumin administration inhibited LPS‐stimulated p38 activation, without altering the effect of LPS on NF‐κB and AKT. These results indicate that curcumin is effective in blocking LPS‐induced loss of muscle mass through the inhibition of p38‐mediated upregulation of atrogin‐1/MAFbx. J. Cell. Biochem. 100: 960–969, 2007. © 2006 Wiley‐Liss, Inc.
Tooth erosion caused by chewing aspirin.

BACKGROUND Although the effects of aspirin on the oral mucosa are well-documented, there is little documentation of the effects of aspirin-chewing on the enamel and dentin. CASE DESCRIPTION The authors present two cases of patients with damage to their tooth enamel and dentin. Both patients had similiar symptoms, but had not been told that chewing aspirin could harm tooth structure. The authors identify clinical signs and symptoms and discuss ways to prevent erosion. CLINICAL IMPLICATIONS The common factor in these cases is that aspirin was the only possible cause of the tooth erosion. Dentists should be aware of the effects of aspirin-chewing on tooth structure and advise their patients accordingly.
Perception of information security

The objective of this study was to investigate people's perception of information security and to unveil the factors that influence people's perception of different threats to information security. In the survey study, 602 respondents were asked to evaluate one of 21 common threats to information security with regard to its rank related to each of the 20 threat-related features. An exploratory factor analysis was then conducted, and a six-factor structure was derived, which includes factors of Knowledge, Impact, Severity, Controllability, Possibility and Awareness. Using this factor structure, the characteristics of the five most dangerous threats (hackers, worms, viruses, Trojan horses and backdoor programs) and the five least dangerous threats (spam, piratical software, operation accidents, users' online behaviour being recorded and deviation in quality of service) were discussed and compared. The relationships between the factors and the perceived overall danger of threats were found and then tested by multiple regression analyses. Significant effects were also found in people's perception of information security related to computer experience and types of loss.
Familial Association of Neuropsychological Traits in Patients With Generalized and Partial Seizure Disorders

To investigate familial effects of neuropsychological deficits associated with seizure disorders, we studied 65 families, in which 1 member had epilepsy. The disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered to assess sustained attention, encoding and verbal memory, executive and focused attention and attentional flexibility/impulsivity. CAE probands attained lower scores than other probands in visual sustained attention and the ability to focus on and execute a visual-motor task. Scores of the unaffected relatives tended to fall between those of the probands and the controls. JME relatives had lower scores than other relatives in tests of visual and auditory sustained attention and attentional flexibility, and showed greater variability in response time. Behavioral information of this type may aid in the specification and differentiation of genetic linkages in affected families.
Astrocytic Regulation of Human Monocytic/Microglial Activation1

Recent reports have described reduced immunological responsiveness and stimulatory capacity among monocytes/microglia that infiltrate malignant human gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or primary human microglia with tumor cells isolated from glioblastoma multiforme (GBM) specimens renders them tolerogenic, capable of suppressing the function of ex vivo monocytes in the absence of tumor cells or their soluble factors. We demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells is not associated with interference with the signaling cascade associated with TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to up-regulate pathways that antagonize positive signaling pathways, including but not limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic properties of GBM tumor cells amplify properties inherent to nontransformed astrocytes. Future studies that identify all of the molecular mechanisms by which astrocytes and malignant gliomas suppress monocyte/microglial function will have dual therapeutic benefits: suppressing these pathways may benefit patients with astrocytic tumors, while enhancing them may benefit patients with autoimmune processes within the CNS, such as multiple sclerosis.
Redefining virality in less broad strokes: Predicting viral behavioral intentions from motivations and uses of Facebook and Twitter

With the growing sophistication of social media, virality of online content has become an indicator of online message effectiveness. We argue for a comprehensive definition that extends virality to social networking and microblogging sites, by emphasizing users’ behaviors beyond shear access and viewership. Across two studies, we investigate viral behavioral intentions (VBIs) toward pro-social messages shared on Facebook and Twitter. We further explore how motivations and uses of Facebook and Twitter predict VBIs toward messages shared on these websites.
Myogenic tone and reactivity of the rat ophthalmic artery.

PURPOSE To study and quantify myogenic behavior and reactivity of the rat ophthalmic artery to pressure and different vasoactive substances in vitro. METHODS Rat ophthalmic arteries (diameter of 217 +/- 6 microm, n = 22) were isolated, cannulated with glass pipettes in an arteriograph and pressurized in a physiological buffer. Internal diameter was continuously monitored. The effect of intraluminal pressure on the diameter was assessed and concentration-response curves to different constrictor and dilator agonists were obtained at an intraluminal pressure of 70 mm Hg. RESULTS Myogenic tone developed at an intraluminal pressure of 30 to 40 mm Hg, continued to increase, and was maintained up to a pressure of 199 mm Hg in these arteries. Arteries dilated and constricted in response to 16 and 60 mM potassium, respectively. Endothelin-1 was the most potent and efficacious constrictor, with a biphasic concentration-response curve, followed by vasopressin, serotonin, U-46619 and phenylephrine. Carbachol was the most efficacious dilator, followed by isoprenaline. The peptide dilators calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were potent but less efficacious than carbachol and isoprenaline. Histamine and adenosine were even less potent and less efficacious dilators. NG-nitro-L-arginine methyl ester (L-NAME) constricted and indomethacin dilated the arteries. CONCLUSIONS This study provides the first direct evidence for myogenic autoregulatory properties and pharmacological heterogeneity in the rat ophthalmic artery.
How Chimeric Antigen Receptor Design Affects Adoptive T Cell Therapy

Chimeric antigen receptor (CAR) T cells have been developed to treat tumors and have shown great success against B cell malignancies. Exploiting modular designs and swappable domains, CARs can target an array of cell surface antigens and, upon receptor‐ligand interactions, direct signaling cascades, thereby driving T cell effector functions. CARs have been designed using receptors, ligands, or scFv binding domains. Different regions of a CAR have each been found to play a role in determining the overall efficacy of CAR T cells. Therefore, this review provides an overview of CAR construction and common designs. Each CAR region is discussed in the context of its importance to a CAR's function. Additionally, the review explores how various engineering strategies have been applied to CAR T cells in order to regulate CAR T cell function and activity. J. Cell. Physiol. 231: 2590–2598, 2016. © 2016 Wiley Periodicals, Inc.
Results of bone marrow examination in 275 patients with histological features that suggest an indolent type of cutaneous B‐cell lymphoma

Whether or not bone marrow biopsies should be performed routinely in patients with skin lesions that show histological features consistent with an indolent B‐cell lymphoma [marginal zone lymphoma (MZL) or follicle centre lymphoma (FCL)] has been debated. As no studies have addressed this question for this group of lymphomas, we evaluated the results of bone marrow biopsy examination in 275 patients with histological features consistent with MZL (n = 82) or FCL (n = 193) first presenting in the skin. In the MZL group, two of 82 patients (2%) showed bone marrow involvement, which was the only extracutaneous localization in one of these patients. In the FCL group, 22 of 193 patients (11%) had bone marrow involvement and was the only extracutaneous localization in nine of them. FCL patients with skin lesions and a positive bone marrow had a significantly worse prognosis when compared with patients with only skin lesions (5‐year disease‐specific survival 63% vs. 95%; P = 0·001). These results indicate that bone marrow investigation is essential for staging patients with a FCL first presenting in the skin. Bone marrow examination appears to have limited value in patients with MZL presenting in the skin.
Recent progress in ankylosing spondylitis treatment

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and loss of functional capacity. The therapeutic management of AS includes regular physical exercise together with the use of NSAIDs. Second-line treatments, such as sulfasalazine, are required in cases of NSAID-refractory AS. Some patients have severe and inadequately controlled disease, explaining the need for the development of new treatments. This therapeutic development in AS involves the assessment of new NSAIDs, namely COX2 selective agents and new second-line treatments, such as methotrexate (MTX), pamidronate and anti-TNFα agents. Controlled studies are lacking for MTX. Pamidronate showed to be effective in NSAID refractory AS patients in open and controlled trials. Anti-TNFα agents (infliximab and etanercept) gave promising results with dramatic improvement of AS symptoms in open and preliminary controlled trials, but further studies are required to evaluate the real long-term effects and tolerability of these drugs.
Hybrid Norm Pursuit Method for Hyperspectral Image Reconstruction

This paper proposes a hybrid I0 and I1 norm pursuit (HNP) method for reconstructing hyperspectral image with high speed and high fidelity. The HNP method provides an approximate result by a simple and fast I0 norm algorithm [such as the orthogonal matching pursuit (OMP)] first and then regulates it to an accurate result by a good but slow I1 norm algorithm [such as the gradient projection for sparse reconstruction (GPSR)]. We build a mathematic model for the HNP method and formulate it to be a constraint optimization problem. How to choose the best switch point is investigated to ensure that the HNP method is able to provide the best reconstruction performance. Experimental results demonstrate that the HNP method is fast and offers high accuracy for hyperspectral image reconstruction and classification.
Source-specific oppositional defiant disorder: comorbidity and risk factors in referred elementary schoolboys.

OBJECTIVE To examine differences in risk factors and comorbid conditions for oppositional defiant disorder (ODD) symptom groups in a sample of 248 elementary schoolboys (ages 6-10) recruited from 1994 to 1996. METHOD The boys and their mothers received multiple assessments of cognitive, behavioral, academic, and family functioning, including a clinic-based evaluation in Stony Brook, NY. ODD was defined using four different strategies for aggregating data from mother and teacher reports of DSM-IV symptoms. RESULTS Source-specific ODD symptom groups had better internal validity and were more differentiated than groups defined using the other strategies. The mother-defined ODD symptom group (ODD/M) had higher levels of maternal detachment than the teacher-defined symptom group (ODD/T), and the ODD/T group had more social problems than the ODD/M group. The classification agreement group (ODD/M + T) evidenced higher levels of sensation-seeking, maternal control, and comorbid symptoms than the ODD/M and ODD/T groups. Controlling for co-occurring attention-deficit/hyperactivity disorder and conduct disorder symptoms altered some of the relationships among ODD, comorbid symptoms, and psychosocial correlates. CONCLUSIONS Patterns of co-occurring psychiatric symptoms and psychosocial correlates of ODD symptom groups varied depending on the rater(s) used to determine group membership. Results support continued research into source specificity for conceptualizing ODD.
Studies on serum selenium and tocopherol in white muscle disease of foal.

In order to clarify the cause of white muscle disease (W.M.D.) in foals, tocopherol and selenium concentrations in serum and glutathione peroxidase activities in blood were measured. Examination was made on the samples from horses affected with W.M.D., the foal kept with them in the same stable, the foals kept in the stables without affected foals, and respective mares. The heavy-breed horses in Fukuoka prefecture and Tokachi district were also examined for comparison. Serum tocopherol levels of these foals were normal because after intake of colostrum. Mares of affected foals showed lower tocopherol levels than other examined mares (p less than 0.01). Serum selenium levels of all foals were below 65 ppb, showing deficient levels. The mares of affected foals had lower selenium levels than other mares (p less than 0.01). There was a good correlation between serum selenium concentration and blood glutathione peroxidase activity (r = 0.81). Selenium levels in the liver of affected foals were lower than the foals which succumbed with other diseases. Diet supplied in the stables with affected foals showed low alpha-tocopherol and selenium contents. These findings suggest that W.M.D. in foals is attributed to nutritional muscular dystrophy caused by tocopherol and selenium deficiency of their mares in late gestation period.
Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

PURPOSE The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. DESIGN We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. RESULTS Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). CONCLUSIONS The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.
Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis: Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial.

IMPORTANCE Intracranial arterial stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS. OBJECTIVE To investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS. DESIGN, SETTING, AND PARTICIPANTS A post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015. MAIN OUTCOMES AND MEASURES Risk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression. RESULTS Of 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (P < .001), systolic blood pressure, 149 (22) mm Hg (P < .001), glucose level, 130 (50) mg/dL (P = .03), and lower Montreal Cognitive Assessment scores (median, ≥24 [interquartile range, 20-26]; P = .02). Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; P = .003), coronary artery disease (46 [29.7%]; P = .004), stroke before the qualifying event (59 [38.1%]; P < .001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; P < .001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; P = .005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); P = . 07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95% CI, 0.8-3.8]; P = .20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses. CONCLUSIONS AND RELEVANCE Although SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00576693.