Miracle-dz/UniFAR-FTUs huggingface dataset:
A Routine ‘Top-Down’ Approach to Analysis of the Human Serum Proteome

Serum provides a rich source of potential biomarker proteoforms. One of the major obstacles in analysing serum proteomes is detecting lower abundance proteins owing to the presence of hyper-abundant species (e.g., serum albumin and immunoglobulins). Although depletion methods have been used to address this, these can lead to the concomitant removal of non-targeted protein species, and thus raise issues of specificity, reproducibility, and the capacity for meaningful quantitative analyses. Altering the native stoichiometry of the proteome components may thus yield a more complex series of issues than dealing directly with the inherent complexity of the sample. Hence, here we targeted method refinements so as to ensure optimum resolution of serum proteomes via a top down two-dimensional gel electrophoresis (2DE) approach that enables the routine assessment of proteoforms and is fully compatible with subsequent mass spectrometric analyses. Testing included various fractionation and non-fractionation approaches. The data show that resolving 500 µg protein on 17 cm 3–10 non-linear immobilised pH gradient strips in the first dimension followed by second dimension resolution on 7–20% gradient gels with a combination of lithium dodecyl sulfate (LDS) and sodium dodecyl sulfate (SDS) detergents markedly improves the resolution and detection of proteoforms in serum. In addition, well established third dimension electrophoretic separations in combination with deep imaging further contributed to the best available resolution, detection, and thus quantitative top-down analysis of serum proteomes.
Treatment of type 2 endoleaks after endovascular repair of abdominal aortic aneurysms: comparison of transarterial and translumbar techniques.

OBJECTIVE The exact significance of collateral endoleaks is unknown and a topic of great debate. Because of this uncertainty, some physicians choose to watch and wait while others aggressively treat these leaks. The purpose of this investigation was the evaluation of the efficacy of the two techniques used in the treatment of collateral endoleaks that occur after endovascular aneurysm repair. METHODS Patients with 33 angiographically proven type 2 endoleaks underwent treatment with either transarterial inferior mesenteric artery embolization (n = 20) or direct translumbar embolization (n = 13) during an 18-month period. Embolization success was defined as resolution of endoleak on all subsequent computed tomography angiogram results. The likelihood of embolization failure between the two treatments was expressed as a risk ratio and was compared with Fisher exact test. RESULTS Sixteen of 20 transarterial inferior mesenteric artery embolizations (80%) failed with recanalization of the original endoleak cavity over time. A single failure (8%) in the direct translumbar embolization group occurred in a patient in whom a new attachment site leak developed. The remaining 12 translumbar endoleak embolizations (92%) were successful and durable, with a median follow-up period of 254 days. The patients who underwent transarterial inferior mesenteric artery embolization were significantly more likely to have persistent endoleak than were the patients who underwent treatment with direct translumbar embolization (risk ratio, 4.6; 95% confidence interval, 1.9 to 11.2; P =.0001). CONCLUSION The transarterial embolization of inferior mesenteric arteries for the repair of type 2 endoleaks is ineffective and should not be performed. Direct translumbar embolization of the endoleak is effective in the elimination of type 2 leaks and should be the therapy of choice when aggressive endoleak management is indicated.
A Histological, Immunological, and Electron Microscopic Study of Bovine Collagen Implants in the Human

The histological fate of an injectable form of type I bovine dermal collagen (Zyderm collagen implant) in the human dermis and subcutaneous tissue has been studied. Sequential biopsies were analyzed by hematoxylin-eosin and Weigert's stains, by immunofluorescence (using a highly specific rabbit anti-Zyderm collagen antibody and a specific anti-human type III collagen antibody), and by electron miscroscopy. The results of this study suggest that the bovine implant material stimulates a host response resulting in implant degradation and replacement by newly generated host collagen.
Learning to Fuzz: Application-Independent Fuzz Testing with Probabilistic, Generative Models of Input Data

Fuzzing is a popular technique to create test inputs for software that processes structured data. It has been successfully applied in various domains, ranging from compilers and interpreters over program analyses to rendering engines, image manipulation tools, and word processors. Existing fuzz testing techniques are tailored for a particular purpose and rely on a carefully crafted model of the data to be generated. This paper presents TreeFuzz, a generic approach for generating structured data without an a priori known model. The key idea is to exploit a given corpus of example data to automatically infer probabilistic, generative models that create new data with properties similar to the corpus. To support a wide range of different properties, TreeFuzz is designed as a framework with an extensible set of techniques to infer generative models. We apply the idea to JavaScript programs and HTML documents and show that the approach generates mostly valid data for both of them: 96.3% of the generated JavaScript programs are syntactically valid and there are only 2.06 validation errors per kilobyte of generated HTML. The performance of both learning and generation scales linearly w.r. t. the size of the corpus. Using TreeFuzz-generated JavaScript programs for differential testing of JavaScript engines exposes various inconsistencies among browsers, including browser bugs and unimplemented language features.
Postcardiac Surgery Complications: Association of Acute Renal Dysfunction and Atrial Fibrillation

Postoperative creatinine increase is associated with adverse outcome after cardiac surgery. Although postoperative stroke and renal dysfunction are associated after cardiac surgery, suggesting a common systemic insult, a similar assessment of atrial fibrillation and renal dysfunction has not been performed. Therefore, we tested the hypothesis that patients with new-onset atrial fibrillation complicating coronary bypass surgery have a greater postoperative creatinine increase. Data were obtained for 453 elective coronary bypass surgery patients with no history of atrial fibrillation. Multivariate regression analyses of factors associated with peak fractional change in creatinine demonstrated a two-way interaction between age and atrial fibrillation (variable estimate, −1.1;P = 0.002). Similar results were obtained in a secondary multivariate model analyzing factors associated with peak postoperative creatinine (variable estimate, −0.01;P = 0.04). We confirmed our hypothesis that patients with new-onset atrial fibrillation are more likely to have acute renal dysfunction after cardiac surgery. The association of atrial fibrillation and creatinine increase diminishes with advancing age. These data are consistent with a common pathophysiology that contributes in an age-dependent fashion to the etiology of both acute renal dysfunction and atrial fibrillation after coronary bypass surgery.
Are momentum crashes pervasive regardless of strategy? Evidence from the foreign exchange market

ABSTRACT This article studies the option-like behaviour of popular momentum strategies implemented in foreign exchange markets. The results confirm recent research findings of strong option-like behaviour for momenutm measures, based on the cumulative return from 12 and 6 months prior to the formation date Surprisingly, there is no such evidence for the popular momentum strategy accounting for a 1-month formation period.
The comparison of DPPH-scavenging capacity and anti-inflammatory effects of phenolic compounds isolated from the stems of Stewartia koreana Nakai

The Stewartia koreana Nakai (SK) had been used in oriental traditional medicine as a remedy for acute gastroenteritis, liver diseases, quadriplegia and pain. The antioxidant activity guided isolation 80% methyl extract from stems of SK yielded eight phenolic compounds. We evaluated the anti-oxidative and anti-inflammatory effects of these compounds via assays of 1,1-diphenyl-2-picrylhydazyl (DPPH) radicals and inhibition of nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The results demonstrated that syringaresinol (6) exhibited significant DPPH radical-scavenging activity and inhibitory effects on NO production compared with its positive controls, ascorbic acid and l-NMMA, respectively.
Patient mood and carer strain during stroke rehabilitation in the community following early hospital discharge

Purpose : Patient mood and carer stress were assessed for stroke patients in the community following early hospital discharge. Method : Patients had low Barthel Indices (13.0 (mean) - 4.9 (SD)) with high anxiety and depression scores, and carers had high stress scores, on starting rehabilitation. On starting rehabilitation, patient Barthel Indices correlated inversely with patient depression (r = -0.33, p < 0 02) and carer stress scores (r = -0.48, p < 0.001). Results : During rehabilitation improvements occurred in patient Barthel Indices, patient anxiety scores and carer stress scores, but not in patient depression scores. Incremental increases in patient Barthel Indices during rehabilitation correlated with reductions in carer stress scores (r = -0.55, R 2 29.4%, p < 0.001). Following early hospital discharge stroke patients display mood abnormalities which do not resolve during rehabilitation. Conclusion : Carer stress and patients depression scores are related to the severity of stroke-related disability. Strategies to address patient mood and carer stress should be present in community services providing early stroke rehabilitation.
Continuous Improvement in an Emerging Market: Findings from Vietnam

This study investigates the factors underpinning continuous improvement (CI) effectiveness in Vietnam. Based on survey data collected from 490 participants plus interviews and discussions with 130 business professionals with extensive knowledge of Vietnam, it identifies top management commitment as a major factor critical to the success of CI in that country. In addition, the paper highlights change agent participation as well as management and employee development as critical in facilitating CI practices in Vietnamese companies. Reward systems – though common in Vietnam – did not affect CI outcomes in the study. The reasons for this apparent anomaly need further research.
Germ line-specific expression of intracisternal A-particle retrotransposons in transgenic mice

Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like mobile elements, or retrotransposons, present at 1,000 copies in the mouse genome. These elements transpose in a replicative manner via an RNA intermediate and its reverse transcription, and their transposition should therefore be tightly controlled by their transcription level. To analyze the in vivo pattern of expression of these retrovirus-like elements, we constructed several independent transgenic mice with either a complete IAP element marked with an intron or with the IAP promoter, or long terminal repeat (LTR), alone controlling the expression of a lacZ reporter gene with a nuclear localization signal. For all transgenic lines analyzed, IAP expression as determined by reverse transcription-PCR analysis was found to be essentially restricted to the male germ line. Furthermore, in situ 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining of all organs disclosed specific beta-galactosidase-positive blue cells only within the testis, found as patches along the seminiferous tubules and often organized as assemblies of 2, 4, 8, or 16 cells. Histochemical analyses of tissues from 13.5-day-old embryos to adults demonstrated that this LTR activity is restricted to gonocytes and premeiotic undifferentiated spermatogonia. Finally, analysis of the methylation status of both transgenes and endogenous IAP LTRs demonstrated identical patterns, with methylation in somatic tissues and hypomethylation in the testis. Transgenic mice therefore reveal an intrinsic, highly restricted IAP expression which had escaped detection in previous global Northern (RNA) blot analyses and with possible strong biological relevance, as IAP activation specifically within the germ line might be a way to generate diversity at the evolutionary level without being deleterious to individuals.
Association between aggressive care and bereaved families’ evaluation of end‐of‐life care for veterans with non‐small cell lung cancer who died in Veterans Affairs facilities

To the authors’ knowledge, little is known regarding the relationship between patients’ and families’ satisfaction with aggressive end‐of‐life care. Herein, the authors examined the associations between episodes of aggressive care (ie, chemotherapy, mechanical ventilation, acute hospitalizations, and intensive care unit admissions) within the last 30 days of life and families’ evaluations of end‐of‐life care among patients with non‐small cell lung cancer (NSCLC).
Stable remission and recovery after acute-phase cognitive therapy for recurrent major depressive disorder.

OBJECTIVE Continuation-phase cognitive therapy (C-CT) or fluoxetine (FLX) reduces relapse in adults with major depressive disorder (MDD; Jarrett, Minhajuddin, Gershenfeld, Friedman, & Thase, 2013). Among patients at higher risk for relapse, we hypothesized that continuation-phase treatment reduces residual symptoms and facilitates stable remission and recovery. METHOD Outpatients (N = 241) with recurrent MDD who responded to acute-phase CT with higher risk for relapse (i.e., had unstable remission defined by any of the last 7 acute-phase scores ≥ 7 using the Hamilton Rating Scale for Depression; Hamilton, 1960) were randomized to 8 months of C-CT, FLX, or pill placebo and followed for 24 additional months. Psychiatric status ratings (Keller et al., 1987) of 1 or 2 (absent or minimal depressive symptoms) for 6 and 35 continuous weeks post-randomization defined stable remission and recovery, respectively. RESULTS Actuarial estimates of stable remission (97%) and recovery (94%) by the end of follow-up were high and did not differ among groups. Observed (unadjusted) proportions of patients remitting (70%) and recovering (47%) before relapse or attrition were lower. During the continuation phase, C-CT (d = 0.21) and FLX (d = 0.25) patients had significantly lower mean depressive symptoms than did controls, but C-CT and FLX patients did not differ from each other, nor did the 3 experimental groups differ during follow-up. CONCLUSION Many patients who responded to CT with higher relapse risk subsequently remitted and recovered after discontinuation of acute-phase treatment. After discontinuation, C-CT and FLX decreased levels of residual depressive symptoms, but neither significantly increased the likelihood of stable remission or recovery, beyond the moderate to high levels observed among patients who did not relapse.
A Mammalian Lysosomal Membrane Protein Confers Multidrug Resistance upon Expression in Saccharomyces cerevisiae *

Mouse transporter protein (MTP) is a highly conserved polytopic membrane protein present in mammalian lysosomes and endosomes. The role of MTP in regulating the in vivosubcellular distribution of numerous structurally distinct small molecules has been examined in this study by its expression in a drug-sensitive strain of the yeast Saccharomyces cerevisiae. Surprisingly, the expression of MTP in membranes of an intracellular compartment resulted in a cellular resistance or hypersensitivity to a range of drugs that included nucleoside and nucleobase analogs, antibiotics, anthracyclines, ionophores, and steroid hormones. The intracellular bioavailability of steroid hormones was altered by MTP, as determined using an in vivoglucocorticoid receptor-driven reporter assay in yeast, suggesting that the MTP-regulated drug sensitivity arose due to a change in the subcellular compartmentalization of steroid hormones and other drugs. MTP-regulated drug sensitivity in yeast was blocked to varying degrees by compounds that inhibit lysosomal function, interfere with intracellular cholesterol transport, or modulate the multidrug resistance phenotype of mammalian cells. These results indicate that MTP is involved in the subcellular compartmentalization of diverse hydrophobic small molecules and contributes to the inherent drug sensitivity or resistance of the mammalian cell.
Degradation of Monochlorinated and Nonchlorinated Aromatic Compounds under Iron-Reducing Conditions

The capacity for Fe(sup3+) to serve as an electron acceptor in the microbial degradation of monochlorinated and nonchlorinated aromatic compounds was investigated in anoxic sediment enrichments. The substrates tested included phenol, benzoate, aniline, their respective monochlorinated isomers, o-, m-, and p-cresol, and all six dimethylphenol isomers. Phenol and 2-, 3-, and 4-chlorophenol were utilized by anaerobic microorganisms, with the concomitant reduction of Fe(sup3+) to Fe(sup2+). The amount of Fe(sup2+) produced in the enrichments was 89 to 138% of that expected for the stoichiometric degradation of these substrates to CO(inf2), suggesting complete mineralization at the expense of Fe reduction. Under Fe-reducing conditions, there was initial loss of benzoate and 3-chlorobenzoate but not of 2- or 4-chlorobenzoate. In addition, there was initial microbial utilization of aniline but not of the chloroaniline isomers. There was also initial loss of o-, m-, and p-cresol in our enrichments. None of the dimethylphenol isomers, however, was degraded within 300 days. Furthermore, we tested the capacity of an Fe-reducing, benzoate-grown culture of Geobacter metallireducens GS-15 to utilize monochlorinated benzoates and phenols. G. metallireducens was able to degrade benzoate and phenol but none of their chlorinated isomers, suggesting that the degradation of chlorophenols in our sediment enrichments may be due to novel Fe-reducing organisms that have yet to be isolated.
Dendritic cells as targets or therapeutics in rheumatic autoimmune disease

Purpose of reviewAntigen-specific immunotherapy is a major goal for improvement in the treatment of autoimmune rheumatic disease. Dendritic cells are professional antigen-presenting cells, abundant at mucosal surfaces and in tissues. They also play a critical role in self-tolerance. This review covers recent advances in the field of dendritic cells as targets or therapeutics in rheumatic autoimmune disease. Recent findingsKey themes include the phenotypic and functional characterization, lineage relationships and transcription factors involved in the development of the various dendritic cell subsets. Phenotype and function of mouse and human subsets has now been much better mapped. Progress in the elucidation of targeting ligands and routes for induction of antigen-specific tolerance using either antigen-antibody fusion constructs or particulate conjugates is described. Various inflammatory molecules made by dendritic cells, including type I interferon, are important therapeutic targets in autoimmune rheumatic diseases. Approaches to block this and clinical trials in this area are discussed. SummaryThere are considerable basic science developments in the field of dendritic cells and tolerance that will speed translation to human of the large amount of knowledge generated in mouse in-vivo systems. Various antigen-specific therapy approaches are in the process of translation to the clinic.
Spread of invasive Spanish Staphylococcus aureus spa-type t067 associated with a high prevalence of the aminoglycoside-modifying enzyme gene ant(4')-Ia and the efflux pump genes msrA/msrB.

OBJECTIVES We carried out a nationwide study aimed at the determination of the molecular epidemiology and antibiotic resistance mechanisms of invasive Staphylococcus aureus in 21 Spanish hospitals. METHODS The distributions of molecular markers, including antibiotic resistance genes, were investigated in 203 S. aureus, comprising 90 methicillin-resistant S. aureus (MRSA) and 113 methicillin-susceptible S. aureus (MSSA). Antimicrobial susceptibility was determined by standard methods. Panton-Valentine leucocidin (PVL) detection, staphylococcal cassette chromosome mec (SCCmec) types and agr types were performed/determined by PCR. All isolates were genotyped by PFGE after digestion of chromosomal DNA with SmaI. Multilocus sequence typing and spa-typing were also performed. RESULTS In MRSA isolates, 74.4% were agr allotype II and were positive for SCCmec IV. Sixty-nine spa-types were identified, 18 in MRSA and 57 in MSSA. Both MRSA and MSSA variants were detected in six spa-types (8.7%). The majority of S. aureus (51.2%) were grouped into four spa-types (t067, t002, t012 and t008). The spa-type t067 was detected in 18 of the 21 (85.7%) participating hospitals, including both MRSA and MSSA in six of them; in total, 25.9% of our isolates were spa-type t067 (49% in MRSA) in comparison with 0.6% in a central spa-typing database. The prevalence of the ant(4')-Ia and msrA/msrB genes was significantly higher in the MRSA spa-type t067 than in the other MRSA spa-types. Association between spa-type t067 and ST125 is described here for the first time. A high prevalence (36.4%) of PVL-positive MSSA was detected. CONCLUSIONS A higher than expected prevalence of spa-type t067 isolates was found among invasive MRSA in Spain. The oxacillin, tobramycin, erythromycin and ciprofloxacin resistance profile of spa-type t067 isolates was linked to the presence of ant(4')-Ia and msrA or msrB genes.
The quaternary structure of RNase G from Escherichia coli

RNase G is the endoribonuclease responsible for forming the mature 5′ end of 16S rRNA. This enzyme shares 35% identity with and 50% similarity to the N‐terminal 470 amino acids encompassing the catalytic domain of RNase E, the major endonuclease in Escherichia coli. In this study, we developed non‐denaturing purifications for overexpressed RNase G. Using mass spectrometry and N‐terminal sequencing, we unambiguously identified the N‐terminal sequence of the protein and found that translation is initiated at the second of two potential start sites. Using velocity sedimentation and oxidative cross‐linking, we determined that RNase G exists largely as a dimer in equilibrium with monomers and higher multimers. Moreover, dimerization is required for activity. Four of the six cysteine residues of RNase G were mutated to serine. No single cysteine to serine mutation resulted in a complete loss of cross‐linking, dimerization or activity. However, multiple mutations in a highly conserved cluster of cysteines, including C405 and C408, resulted in a partial loss of activity and a shift in the distribution of RNase G multimers towards monomers. We propose that many of the cysteines in RNase G lie on its surface and define, in part, the subunit–subunit interface.