Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant DNA-PKcs and ERGIC1 expression may be involved in initiation of gastric cancer

AIM To investigate the molecular mechanisms of gastric carcinogenesis. METHODS We used label-free quantification technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in 160 specimens of normal gastric mucosa, gastric mucosa with mild dysplasia, moderate dysplasia, severe dysplasia, and early mucosal gastric cancer (GC) collected at the Second Hospital of Lanzhou University from 2010 to 2015. Immunohistochemistry was used to verify the differentially expressed proteins detected by LC-MS/MS. RESULTS With a threshold of a 1.2-fold change and a P-value < 0.05 between mild dysplasia, moderate dysplasia, severe dysplasia or early mucosal GC and matched normal gastric mucosa tissues, proteomic analysis identified 365 significantly differentially expressed proteins. ERGIC1 expression decreased, while DNA-PKcs expression increased gradually along with different stages of GC initiation based on the tendency of fold change. The expression patterns of ERGIC1 and DNA-PKcs revealed by immunohistochemistry were consistent with the LC-MS/MS results. CONCLUSION The results suggest that aberrant ERGIC1 and DNA-PKcs expression may be involved in GC initiation.
An active learning method based on Markov random fields for hyperspectral images classification

Spectral-spatial classification of hyperspectral images using Markov random fields (MRFs) has been demonstrated effective to improve the classification accuracy. However, it still suffers from the little availability of labeled samples. In order to collect the most informative samples and train an effective classifier, active learning (AL) methods are often used. In this paper, we present a new AL approach which takes advantage of MRF and iteratively selects the most inconsistent and conflicting instances from the unlabeled set. Experimental results on the AVIRIS Indian Pines data set demonstrated the superior performance of the proposed AL approach with respect to the state-of-the-art AL techniques.
The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury.
Unique Genomic Arrangements in an Invasive Serotype M23 Strain of Streptococcus pyogenes Identify Genes That Induce Hypervirulence

ABSTRACT The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF−) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ΦM23ND. 1 to ΦM23ND. 4, harboring genes encoding streptococcal superantigen (ssa), streptococcal pyrogenic exotoxins (speC, speH, and speI), and DNases (spd1 and spd3), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The covS sensor in M23ND was identified as a pseudogene, resulting in the attenuation of speB function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (mga), M protein (emm23), C5a peptidase (scpA), fibronectin-binding proteins (sfbI and fbp54), streptolysin O (slo), hyaluronic acid capsule (hasA), streptokinase (ska), and DNases (spd and spd3), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors.
One-dimensional plasmon dispersion and dispersionless intersubband excitations in GaAs quantum wires.

The energy and the wave-vector dispersion of single-particle and collective excitations of the one-dimensional (1D) electron gas in GaAs quantum wires have been determined by resonant inelastic light scattering. In the 1D quantum limit the intrasubband plasmon displays the linear dispersion characteristic of 1D free-electron behavior. Quantitative agreement is found with calculations based on the random-phase approximation. In contrast, collective 1D intersubband excitations appear as dispersion-less and have a negligible shift from the single-particle energy
Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions

Oligodendrocyte and axon pathology was studied in 11 autopsy cases of clinically silent multiple sclerosis. A total of 54 lesions, either demyelinated or late remyelinated, were distributed through the whole brain and spinal cord with 39% of the lesions located in periventricular areas. Determination of axon density revealed an average reduction of 64% and 59% in demyelinated and remyelinated lesions with an extreme variation between different plaques and cases. Oligodendrocytes were identified by immunocytochemistry for myelin oligodendrocyte glycoprotein (MOG) and in situ hybridization for proteolipid protein (PLP) mRNA. Oligodendrocytes were almost completely lost in demyelinated lesions; remyelinated lesions revealed preservation of a considerable number of oligodendrocytes within the lesions. At the border between plaques and the periplaque white matter, similar oligodendrocyte numbers as in remyelinated lesions were found. Different factors including lesion site, axonal preservation and remyelination may thus contribute to the clinical nonappearance of multiple sclerosis lesions.
Use of Proteomics to Demonstrate a Hierarchical Oxidative Stress Response to Diesel Exhaust Particle Chemicals in a Macrophage Cell Line*

Epidemiological studies demonstrate an association between short term exposure to ambient particulate matter (PM) and cardiorespiratory morbidity and mortality. Although the biological mechanisms of these adverse effects are unknown, emerging data suggest a key role for oxidative stress. Ambient PM and diesel exhaust particles (DEP) contain redox cycling organic chemicals that induce pro-oxidative and pro-inflammatory effects in the lung. These responses are suppressed by N-acetylcysteine (NAC), which directly complexes to electrophilic DEP chemicals and exert additional antioxidant effects at the cellular level. A proteomics approach was used to study DEP-induced responses in the macrophage cell line, RAW 264.7. We demonstrate that in the dose range 10–100 μg/ml, organic DEP extracts induce a progressive decline in the cellular GSH/GSSG ratio, in parallel with a linear increase in newly expressed proteins on the two-dimensional gel. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and electrospray ionization-liquid chromatography/mass spectrometry/mass spectrometry analysis, 32 newly induced/NAC-suppressed proteins were identified. These include antioxidant enzymes (e.g. heme oxygenase-1 and catalase), pro-inflammatory components (e.g. p38MAPK and Rel A), and products of intermediary metabolism that are regulated by oxidative stress. Heme oxygenase-1 was induced at low extract dose and with minimal decline in the GSH/GSSG ratio, whereas MAP kinase activation required a higher chemical dose and incremental levels of oxidative stress. Moreover, at extract doses >50 μg/ml, there is a steep decline in cellular viability. These data suggest that DEP induce a hierarchical oxidative stress response in which some of these proteins may serve as markers for oxidative stress during PM exposures.
Nonparametric Bootstrap Estimation for Implicitly Weighted Robust Regression

Implicitly weighted robust regression estimators for linear and nonlinear regression models include linear and nonlinear versions of the least trimmed squares and least weighted squares. After recalling known facts about these estimators, a nonparametric bootstrap procedure is proposed in this paper for estimates of their variances. These bootstrap estimates are elaborated for both the linear and nonlinear model. Practical contributions include several examples investigating the performance of the nonlinear least weighted squares estimator and comparing it with the classical least squares also by means of the variance estimates. Another theoretical novelty is a proposal of a twostage version of the nonlinear least weighted squares estimator with adaptive (data-dependent) weights.
Adhésion et phagocytose de gouttes d'émulsions fonctionnalisées

La phagocytose par les macrophages est un processus biologique essentiel au systeme immunitaire et joue un role cle dans le maintien de l’homeostasie cellulaire. Les cibles a eliminer varient en terme de tailles, des bacteries (µm) aux cellules cancereuses ou senescentes (10 – 20 µm). La plupart des etudes quantitatives sur la phagocytose reposent sur l'utilisation de microparticules de polymere rigides en tant que cibles modeles pour la comprehension des parametres qui regissent ce processus. Cependant, ces particules ne rendent pas compte de la mobilite laterale des ligands a leur surface malgre la pertinence de ce parametre dans le contexte immunologique. Cette etude a pour but de synthetiser un materiau biomimetique qui constitue un nouveau systeme modele pour l’etude de la phagocytose. Il s’agit de gouttes d’emulsions monodisperses fonctionnalisees avec des IgGs libres de diffuser sur toute la surface. Dans le cadre de cette these, nous avons obtenu differentes densites controlees de fonctionnalisation, caracterisees de facon quantitative. Ainsi, il nous a ete possible de determiner une densite minimale d’IgGs necessaire a induire une internalisation efficace des gouttes. Pour des densites superieures d’IgGs, ces gouttes sont efficacement et specifiquement internalisees par phagocytose induite par les recepteurs FcR in vitro. Nous avons plus precisement cherche a approfondir la comprehension de certains aspects mecaniques. Nous montrons que, contrairement a des billes de polymeres solides, l’internalisation des gouttes est efficace meme pour de faibles densites d’IgGs. La phagocytose s’accompagne, pendant la phase d’adhesion a la surface du macrophage, d’une mobilite laterale des ligands en zone de contact. Il apparait donc que la mobilite laterale des proteines a l'interface d'une cible ameliore considerablement sa phagocytose par les macrophages. Ainsi, ces gouttes permettrons d’aborder de nouvelles questions biologiques pour approfondir certaines mecanismes moleculaires et/ou mecaniques.
Lipopolysaccharide exposure makes allergic airway inflammation and hyper‐responsiveness less responsive to dexamethasone and inhibition of iNOS

Allergic airway disease can be refractory to anti‐inflammatory treatment, whose cause is unclarified. Therefore, in the present experiment, we have tested the hypothesis that co‐exposure to lipopolysacharide (Lps) and allergen results in glucocorticoid‐resistant eosinophil airway inflammation and hyper‐responsiveness (AHR). Ovalbumin (Ova)‐sensitized BALB/c mice were primed with 10 μg intranasal Lps 24 h before the start of Ova challenges (20 min on 3 consecutive days). Dexamethasone (5 mg/kg/day) was given on the last 2 days of Ova challenges. AHR, cellular build‐up, cytokine and nitrite concentrations of bronchoalveolar lavage fluid (BALF) and lung histology were examined. To assess the role of iNOS‐derived NO in airway responsiveness, mice were treated with a selective inhibitor of this enzyme (1400W) 2 h before AHR measurements. More severe eosinophil inflammation and higher nitrite formation were found in Lps‐primed than in non‐primed allergized mice. After Lps priming, AHR and concentrations of T‐helper type 2 cytokines in BALF were decreased, but still remained significantly higher than in controls. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps‐primed allergized animals. 1400W effectively and rapidly diminished the AHR in Ova‐sensitized and challenged mice, but failed to affect it after Lps priming plus allergization. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti‐inflammatory treatment in allergic airway disease.
Hepatitis C: The clinical spectrum of disease

Hepatitis C virus (HCV) accounts for approximately 20% of cases of acute hepatitis, 70% of chronic hepatitis, and 30% of end‐stage liver disease in the United States. The acute infection has an incubation period of 7 weeks (range, 4‐20 weeks) and is symptomatic and icteric in only one third of patients. Serum aminotransferase levels generally increase greater than 10‐fold elevated and as symptoms and signs resolve decrease into the normal range. Antibody to HCV is usually but not always present at the time of onset of symptoms. HCV RNA appears in the serum early during the incubation period, increases in titer and peaks at the time of symptoms, and then disappears in resolving disease. Importantly, 85% of patients with acute HCV infection develop chronic infection. In these patients, HCV RNA remains present and in approximately two thirds of patients, aminotransferases remain elevated in the range of 1.5‐ to 10‐fold the upper limit of normal. The course of chronic hepatitis C is variable. Probably fewer than 20% of patients have symptoms and they are usually intermittent, vague, and nonspecific, largely being malaise and easy fatiguability. A small percentage of patients develop extrahepatic manifestations of hepatitis C, including cryoglobulinemia and glomerulonephritis. It is estimated that 20% to 30% of patients with chronic hepatitis C develop cirrhosis, but the process is generally slow and insidious. Once cirrhosis develops, symptoms are more common and the signs of end‐stage liver disease can appear with jaundice, weakness, wasting, and gastrointestinal bleeding. Patients with cirrhosis are also at risk for developing hepatocellular carcinoma. Thus, this important liver disease has protean manifestations but is often insidious and can lead to end‐ stage liver disease despite the presence of few symptoms and signs of illness.
Technical Note - Joint Inventory and Pricing Control with General Additive Demand

This paper analyzes a periodic-review, joint inventory and pricing control problem for a firm that faces stochastic, price-sensitive demand under a nonstationary environment with fixed ordering costs. Any unsatisfied demand is backlogged. The objective is to maximize expected profit over a finite selling horizon by coordinating the inventory and pricing decisions in each period. We show that for an additive demand model, an s, S, p policy is optimal when the expected revenue is quasi-concave in price, the inventory cost of holding and/or backlogging is quasi-convex, and the nonnegative random demand has a Polya or uniform density function. For the special case with no fixed ordering cost, the optimality of a base stock list price policy is demonstrated for more general demand distributions and convex inventory cost. These sets of sufficient conditions generalize the existing conditions in the literature that require, for example, the demand and/or revenue functions to be concave or the model parameters to be stationary in time. Our generalization makes the structural results applicable to models broadly supported by economic theory and empirical data. In addition, our proof uses a distinct sequential optimization technique for iteratively establishing the quasi-K-concavity of dynamic optimal value functions.
Integrating Patient Reported Outcomes With Clinical Cancer Registry Data: A Feasibility Study of the Electronic Patient-Reported Outcomes From Cancer Survivors (ePOCS) System

Background Routine measurement of Patient Reported Outcomes (PROs) linked with clinical data across the patient pathway is increasingly important for informing future care planning. The innovative electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system was developed to integrate PROs, collected online at specified post-diagnostic time-points, with clinical and treatment data in cancer registries. Objective This study tested the technical and clinical feasibility of ePOCS by running the system with a sample of potentially curable breast, colorectal, and prostate cancer patients in their first 15 months post diagnosis. Methods Patients completed questionnaires comprising multiple Patient Reported Outcome Measures (PROMs) via ePOCS within 6 months (T1), and at 9 (T2) and 15 (T3) months, post diagnosis. Feasibility outcomes included system informatics performance, patient recruitment, retention, representativeness and questionnaire completion (response rate), patient feedback, and administration burden involved in running the system. Results ePOCS ran efficiently with few technical problems. Patient participation was 55.21% (636/1152) overall, although varied by approach mode, and was considerably higher among patients approached face-to-face (61.4%, 490/798) than by telephone (48.8%, 21/43) or letter (41.0%, 125/305). Older and less affluent patients were less likely to join (both P<.001). Most non-consenters (71.1%, 234/329) cited information technology reasons (ie, difficulty using a computer). Questionnaires were fully or partially completed by 85.1% (541/636) of invited participants at T1 (80 questions total), 70.0% (442/631) at T2 (102-108 questions), and 66.3% (414/624) at T3 (148-154 questions), and fully completed at all three time-points by 57.6% (344/597) of participants. Reminders (mainly via email) effectively prompted responses. The PROs were successfully linked with cancer registry data for 100% of patients (N=636). Participant feedback was encouraging and positive, with most patients reporting that they found ePOCS easy to use and that, if asked, they would continue using the system long-term (86.2%, 361/419). ePOCS was not administratively burdensome to run day-to-day, and patient-initiated inquiries averaged just 11 inquiries per month. Conclusions The informatics underlying the ePOCS system demonstrated successful proof-of-concept – the system successfully linked PROs with registry data for 100% of the patients. The majority of patients were keen to engage. Participation rates are likely to improve as the Internet becomes more universally adopted. ePOCS can help overcome the challenges of routinely collecting PROs and linking with clinical data, which is integral for treatment and supportive care planning and for targeting service provision.
Amino Acid Residues within Conserved Domain VI of the Vesicular Stomatitis Virus Large Polymerase Protein Essential for mRNA Cap Methyltransferase Activity

ABSTRACT During mRNA synthesis, the polymerase of vesicular stomatitis virus (VSV) copies the genomic RNA to produce five capped and polyadenylated mRNAs with the 5′-terminal structure 7mGpppAmpApCpApGpNpNpApUpCp. The 5′ mRNA processing events are poorly understood but presumably require triphosphatase, guanylyltransferase, [guanine-N-7]- and [ribose-2′-O]-methyltransferase (MTase) activities. Consistent with a role in mRNA methylation, conserved domain VI of the 241-kDa large (L) polymerase protein shares sequence homology with a bacterial [ribose-2′-O]-MTase, FtsJ/RrmJ. In this report, we generated six L gene mutations to test this homology. Individual substitutions to the predicted MTase active-site residues K1651, D1762, K1795, and E1833 yielded viruses with pinpoint plaque morphologies and 10- to 1,000-fold replication defects in single-step growth assays. Consistent with these defects, viral RNA and protein synthesis was diminished. In contrast, alteration of residue G1674 predicted to bind the methyl donor S-adenosylmethionine did not significantly perturb viral growth and gene expression. Analysis of the mRNA cap structure revealed that alterations to the predicted active site residues decreased [guanine-N-7]- and [ribose-2′-O]-MTase activity below the limit of detection of our assay. In contrast, the alanine substitution at G1674 had no apparent consequence. These data show that the predicted MTase active-site residues K1651, D1762, K1795, and E1833 within domain VI of the VSV L protein are essential for mRNA cap methylation. A model of mRNA processing consistent with these data is presented.
Reduction of artifacts in T2‐weighted PROPELLER in high‐field preclinical imaging

A simple technique is implemented for correction of artifacts arising from nonuniform T2‐weighting of k‐space data in fast spin echo–based PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction). An additional blade with no phase‐encoding gradients is acquired to generate the scaling factor used for the correction. Results from simulations and phantom experiments, as well as in vivo experiments in free‐breathing mice, demonstrate the advantages of the proposed method. This technique is developed specifically for high‐field imaging applications where T2 decay is rapid. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
Regulated expression of genes injected into early Drosophila embryos.

DNA of cloned genes injected into 15‐30 min Drosophila embryos reaches nearly all the cells of the later embryo and its expression can be detected by Northern blot hybridisation. The injected DNA continues to be expressed at least up to the first instar larval stage and some developmental control of expression is retained. Genes normally expressed in the embryo are strongly transcribed upon injection while genes characteristic of later stages are not, or only very weakly expressed. Some transcription was detected with a larval salivary gland secretion gene (sgs‐4) and with the adult promoter of the alcohol dehydrogenase gene (Adh) but not from the Adh larval promoter or from larval cuticle genes. A foreign gene (Semliki Forest virus capsid protein) was used to monitor the activity of promoters attached to it. In situ immunofluorescence of thin sections showed that the copia promoter is active mostly in yolk cells. In contrast, the hsp‐70 heat‐shock promoter is active, upon heat‐shock, in nearly all cells in the embryo but most of the injected DNA is gradually lost so that in first instar larvae only 15% of the cells still express it.
The Blood Donor Identity Survey: a multidimensional measure of blood donor motivations

Evidence indicates that donor identity is an important predictor of donation behavior; however, prior studies have relied on diverse, unidimensional measures with limited psychometric support. The goals of this study were to examine the application of self‐determination theory to blood donor motivations and to develop and validate a related multidimensional measure of donor identity.