Miracle-dz/UniFAR-FTUs huggingface dataset:
Protease-resistant and Detergent-insoluble Prion Protein Is Not Necessarily Associated with Prion Infectivity*

PrPSc, an abnormal isoform of PrPC, is the only known component of the prion, an agent causing fatal neurodegenerative disorders such as bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD). It has been postulated that prion diseases propagate by the conversion of detergent-soluble and protease-sensitive PrPC molecules into protease-resistant and insoluble PrPSc molecules by a mechanism in which PrPSc serves as a template. We show here that the chemical chaperone dimethyl sulfoxide (Me2SO) can partially inhibit the aggregation of either PrPSc or that of its protease-resistant core PrP27–30. Following Me2SO removal by methanol precipitation, solubilized PrP27–30 molecules aggregated into small and amorphous structures that did not resemble the rod configuration observed when scrapie brain membranes were extracted with Sarkosyl and digested with proteinase K. Interestingly, aggregates derived from Me2SO-solubilized PrP27–30 presented less than 1% of the prion infectivity obtained when the same amount of PrP27–30 in rods was inoculated into hamsters. These results suggest that the conversion of PrPC into protease-resistant and detergent-insoluble PrP molecules is not the only crucial step in prion replication. Whether an additional requirement is the aggregation of newly formed proteinase K-resistant PrP molecules into uniquely structured aggregates remains to be established.
RNA editing in plant mitochondria and chloroplasts

In the mitochondria and chloroplasts of flowering plants (angiosperms), transcripts of protein‐coding genes are altered after synthesis so that their final primary nucleotide sequence differs from that of the corresponding DNA sequence. This posttranscriptional mRNA editing consists almost exclusively of C‐to‐U substitutions. Editing occurs predominantly within coding regions, mostly at isolated C residues, and usually at first or second positions of codons, thereby almost always changing the amino acid from that specified by the unedited codon. Editing may also create initiation and termination codons. The net effect of C‐to‐U RNA editing in plants is to make proteins encoded by plant organelles more similar in sequence to their nonplant homologs. In a few cases, a strong argument can be made that specific C‐to‐U editing events are essential for the production of functional plant mitochondrial proteins. Although the phenomenon of RNA editing in plants is now well documented, fundamental questions remain to be answered: What determines the specificity of editing? What is the biochemical mechanism (deamination, base exchange, or nucleotide replacement)? How did the system evolve? RNA editing in plants, as in other organisms, challenges our traditional notions of genetic information transfer. — Gray, M. W. ; Covello, P. S. RNA editing in plant mitochondria and chloroplasts. FASEB J. 7: 64‐71; 1993.
Prevalence and distribution of different diarrhoeagenic Escherichia coli virulotypes in major water bodies in Bangladesh

SUMMARY Escherichia coli, a prominent waterborne pathogen, causes a variety of gastrointestinal and extraintestinal infections that depend on virulence determinants. To monitor natural aquatic systems for virulence-associated genes of E. coli, multiplex PCR was used in a survey covering 46 major natural water bodies in Bangladesh. DNA was extracted directly from water samples as well as from pre-enriched and enriched cultures during three successive seasons and assessed for E. coli virulotype distribution. From the five virulotypes, genes from the enterotoxigenic (ETEC), enteropathogenic (EPEC), and enterohaemorrhagic (EHEC) virulotypes were detected consistently, but genes from the enteroinvasive (EIEC) and enteroaggregative (EAEC) virulotypes were traced only occasionally. ETEC was the most prevalent virulotype, followed by EPEC. However, EIEC and EAEC virulotypes could not be detected in winter or the rainy season, respectively. Specific regional distribution patterns of different E. coli virulotypes and their temporal fluctuations were identified. These observations may assist with assessing seasonal risk and identifying vulnerable areas of the country prone to E. coli-associated outbreaks.
FIRST: Fast Interactive Attributed Subgraph Matching

Attributed subgraph matching is a powerful tool for explorative mining of large attributed networks. In many applications (e.g., network science of teams, intelligence analysis, finance informatics), the user might not know what exactly s/he is looking for, and thus require the user to constantly revise the initial query graph based on what s/he finds from the current matching results. A major bottleneck in such an interactive matching scenario is the efficiency, as simply rerunning the matching algorithm on the revised query graph is computationally prohibitive. In this paper, we propose a family of effective and efficient algorithms (FIRST) to support interactive attributed subgraph matching. There are two key ideas behind the proposed methods. The first is to recast the attributed subgraph matching problem as a cross-network node similarity problem, whose major computation lies in solving a Sylvester equation for the query graph and the underlying data graph. The second key idea is to explore the smoothness between the initial and revised queries, which allows us to solve the new/updated Sylvester equation incrementally, without re-solving it from scratch. Experimental results show that our method can achieve (1) up to 16x speed-up when applying on networks with 6M$+$ nodes; (2) preserving more than 90% accuracy compared with existing methods; and (3) scales linearly with respect to the size of the data graph.
Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.

AIM To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers (CRCs). METHODS We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual. Endpoints included cytokeratin 7 and CK20 expression, microsatellite instability, CpG island methylator phenotype, and KRAS and BRAF mutation statuses. Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation. RESULTS CDX2 expression was lost in 42 (5.9%) patients. Moreover, loss of CDX2 expression was associated with proximal location, infiltrative growth, advanced T, N, M and overall stage. On microscopic examination, loss of CDX2 expression was associated with poor differentiation, increased number of tumor-infiltrating lymphocytes, luminal serration and mucin production. Loss of CDX2 expression was also associated with increased CK7 expression, decreased CK20 expression, CpG island methylator phenotype, microsatellite instability and BRAF mutation. In a univariate survival analysis, patients with loss of CDX2 expression showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001). In a multivariate survival analysis, loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio (HR) = 1.72, 95%CI: 1.04-2.85, P = 0.034] and progression-free survival (HR = 1.94, 95%CI: 1.22-3.07, P = 0.005). CONCLUSION Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.
Quantifying psychiatric comorbidity--lessions from chronic disease epidemiology.

BACKGROUND Comorbidity research in psychiatric epidemiology mostly uses measures of association like odds or risk ratios to express how strongly disorders are linked. In contrast, chronic disease epidemiologists increasingly use measures of clustering, like multimorbidity (cluster) coefficients, to study comorbidity. This article compares measures of association and clustering. METHODS Narrative review, algebraical examples, a secondary analysis of an existing dataset and a pooled analysis of published data. RESULTS Odds and risk ratios, but the former more than the latter, confound clustering with coincidental comorbidity. Multimorbidity coefficients provide a pure estimate of clustering which is the proportion of the association between disorders that is of etiological interest. Odds and risk ratios can express comorbidity between no more than two disorders, whilst clustering coefficients, although computationally laboursome, can capture multimorbidity of any number of disorders. Cluster coefficients depend less on the prevalence of illness in study groups than measures of association. CONCLUSION Odds and risk ratios are well suited for comorbidity research which focuses on which sets of disorders or syndromes tend to occur in combination and the implications of this for, for instance, nosological classification, a traditional interest of psychiatric epidemiology. However, the cluster coefficient is to be preferred if the interest is more aetiological, addressing for example why certain individuals are prone to multiple health problems.
Water clarity, maternal behavior, and physiology combine to eliminate UV radiation risk to amphibians in a montane landscape

Increasing UV-B radiation (UV-B; 290–320 nm) due to stratospheric ozone depletion has been a leading explanation for the decline in amphibians for nearly 2 decades. Yet, the likelihood that UV-B can influence amphibians at the large spatial scales relevant to population declines has not yet been evaluated. A key limitation has been in relating results from individual sites to the effect of UV-B for populations distributed across heterogeneous landscapes. We measured critical embryonic exposures to UV-B for two species of montane amphibians with contrasting physiological sensitivities, long-toed salamander (Ambystoma macrodactylum) and Cascades frog (Rana cascadae), at field sites spanning a gradient of UV-B attenuation in water. We then used these experimental results to estimate the proportion of embryos exposed to harmful UV-B across a large number of breeding sites. By combining surveys of the incubation timing, incident UV-B, optical transparency of water, and oviposition depth and light exposure of embryos at each site, we present a comprehensive assessment of the risk posed by UV-B for montane amphibians of the Pacific Northwest. We found that only 1.1% of A. macrodactylum and no R. cascadae embryos across a landscape of breeding sites are exposed to UV-B exceeding lethal levels. These results emphasize that accurately estimating the risk posed by environmental stressors requires placing experimental results in a broader ecological context that accounts for the heterogeneity experienced by populations distributed across natural landscapes.
Incidence, aetiology and prevention of musculoskeletal injuries in volleyball: A systematic review of the literature

Abstract Currently, there is no overview of the incidence and (volleyball-specific) risk factors of musculoskeletal injuries among volleyball players, nor any insight into the effect of preventive measures on the incidence of injuries in volleyball. This study aimed to review systematically the scientific evidence on the incidence, prevalence, aetiology and preventive measures of volleyball injuries. To this end, a highly sensitive search strategy was built based on two groups of keywords (and their synonyms). Two electronic databases were searched, namely Medline (biomedical literature) via Pubmed, and SPORTDiscus (sports and sports medicine literature) via EBSCOhost. The results showed that ankle, knee and shoulder injuries are the most common injuries sustained while playing volleyball. Results are presented separately for acute and overuse injuries, as well as for contact and non-contact injuries. Measures to prevent musculoskeletal injuries, anterior knee injuries and ankle injuries were identified in the scientific literature. These preventive measures were found to have a significant effect on decreasing the occurrence of volleyball injuries (for instance on ankle injuries with a reduction from 0.9 to 0.5 injuries per 1000 player hours). Our systematic review showed that musculoskeletal injuries are common among volleyball players, while effective preventive measures remain scarce. Further epidemiological studies should focus on other specific injuries besides knee and ankle injuries, and should also report their prevalence and not only the incidence. Additionally, high-quality studies on the aetiology and prevention of shoulder injuries are lacking and should be a focus of future studies.
Local effects of UV radiation on immunization with contact sensitizers. I. Down-regulation of contact hypersensitivity by application of TNCB to UV-irradiated skin.

Exposure of mouse skin to UV radiation in doses comparable to those commonly received by humans has been shown to diminish the capacity of irradiated skin to mediate the induction of contact hypersensitivity to dinitrofluorobenzene (DNFB). In other studies, contact sensitization reactions to the structurally related hapten, trinitrochlorobenzene (TNCB), have been used to test the immunogenic properties of haptenated subpopulations of epidermal cells. To extend the applicability of TNCB to experiments that examine UVB modulation of immunization by epidermal cells, we examined the sensitivity of TNCB-induced contact hypersensitivity to low doses of UVB radiation. Abdominal skin of C3H mice was exposed to daily doses of 660 J/m2 broad-band UV radiation for 4 successive days. Immediately following the final exposure, 7% TNCB was applied to irradiated or non-irradiated skin of designated mice. After 5 days, mice were ear-challenged with 2% TNCB, and incremental ear-swelling responses were measured. Mice sensitized with TNCB through irradiated skin exhibited significantly diminished responses compared with UVB-treated mice sensitized through non-irradiated skin. We also found that mice initially sensitized with TNCB through irradiated skin but subsequently painted with oxazolone on normal skin developed full responses to ear-challenge with oxazolone. In contrast, mice sensitized initially with TNCB through irradiated skin failed to fully immunize even after TNCB was repainted on normal skin at a later date. We conclude that low-dose UVB radiation interrupts the induction of contact hypersensitivity to TNCB, leading to hapten-specific nonresponsiveness rather than hypersensitivity, and that this capacity to prevent successful immunization with TNCB is limited to the site of irradiation. (ABSTRACT TRUNCATED AT 250 WORDS)
Spirits and Gastrectomy Increase Risk for Chronic Pancreatitis in Japanese Male Alcoholics

Introduction Most cases of chronic pancreatitis are alcohol-related, but not all alcoholics develop pancreatitis. Aim To elucidate historical and biologic risk factors for this disease. Methodology Alcoholic Japanese men (n = 132) consecutively admitted to the National Alcoholism Center over 24 months, including 54 with chronic pancreatitis (diagnosed by endoscopic retrograde cholangiopancreatography) and 78 without, were surveyed about drinking history, smoking, education, and marital status, and tested for amylase, glycosylated hemoglobin, body mass, alcohol and aldehyde dehydrogenase genotypes, and K-ras gene mutations in pancreatic juice. Results Higher risk for chronic pancreatitis was associated with drinking spirits rather than lower-alcohol beverages (odds ratio [OR], 2.58;p = 0.01). Daily ethanol consumption by those who drank spirits was greater than that among those who drank lower-alcohol beverages; however, no differences in either daily ethanol consumption or duration of drinking were observed between alcoholics with and without chronic pancreatitis. Postgastrectomy patients were at higher risk for chronic pancreatitis than unoperated comparison subjects (OR, 4.35, P < 0.05). Elevated glycosylated hemoglobin (OR, 4.62, p < 0.01), decreased amylase (OR 4.20, P <0.02), and low body mass (OR 1.89, P <0.1) were more frequent in alcoholics with chronic pancreatitis. K-ras gene mutations existed in 18.8% of alcoholics with chronic pancreatitis but in only 11.4% of those without the disorder. The frequencies of alcohol and aldehyde dehydrogenase genotypes in alcoholics with and without pancreatitis did not differ significantly. Conclusion Our study strongly suggested that spirits and partial gastrectomy increase the risk for chronic pancreatitis in male alcoholics.
Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.

A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application.
Correlation between two markers of inflammation, serum C-reactive protein and interleukin 6, and indices of oxidative stress in patients with high risk of cardiovascular disease

Abstract As evidence of the involvement of inflammation and oxidative damage in pathogenesis of age-related chronic diseases is growing, epidemiologists need to develop measures of both conditions to study their relationships in human populations. One way of searching for appropriate biomarkers is to examine correlations between different inflammatory markers and oxidative indices. We examined cross-sectional correlations between two inflammatory markers, serum C-reactive protein (CRP) and interleukin (IL)-6, and three oxidative indices, plasma levels of α-tocopherol and β-carotene, and urinary levels of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP), in 60 individuals at high risk of cardiovascular disease. Correlations between the biomarkers were examined graphically and using the Pearson correlation coefficient. No correlation was found between plasma levels of α-tocopherol and either of the inflammatory markers. Plasma β-carotene inversely correlated with IL-6 (r=−0.46, p=0.0002) and CRP (r=−0.41, p=0.001). Although urinary F2-IsoP did not correlate with IL-6, this biomarker positively correlated with CRP (r=0.31, p=0.002). As only urinary F2-IsoP levels have been validated against known oxidative assaults, their positive association with CRP levels is interpreted as evidence of an interconnection between low-level inflammation and oxidative status. Urinary levels of F2-IsoP and serum levels of CRP represent appropriate biomarkers for future studies of inflammation and oxidative status in humans.
A Mixed-Integer Linear Programming Model for the Electric Vehicle Charging Coordination Problem in Unbalanced Electrical Distribution Systems

This paper presents a novel mixed-integer linear programming (MILP) model for the electric vehicle charging coordination (EVCC) problem in unbalanced electrical distribution systems (EDSs). Linearization techniques are applied over a mixed-integer nonlinear programming model to obtain the proposed MILP formulation based on current injections. The expressions used to represent the steady-state operation of the EDS take into account a three-phase representation of the circuits, as well as the imbalance of the loads, leading to a more realistic model. Additionally, the proposed formulation considers the presence of distributed generators and operational constraints such as voltage and current magnitude limits. The optimal solution for the mathematical model was found using commercial MILP solvers. The proposed formulation was tested in a distribution system used in the specialized literature. The results show the efficiency and the robustness of the methodology, and also demonstrate that the model can be used in the solution of the EVCC problem in EDSs.
Three-dimensional space-time shift keying with coordinate combination and joint optimisation

In this paper, the concept of three-dimensional (3-D) space-time shift keying (STSK) is introduced, which incorporates 3-D constellations into conventional STSK systems. The new 3-D STSK techniques enjoy better error resilience than their two-dimensional (2-D) counterparts. Firstly, based on different sampling rates, two three-dimensional (3-D) STSK schemes referred to as R2 3-D STSK and R3 3-D STSK, respectively, are proposed. Both schemes show improved effective spectral efficiency (ESE) than 2-D STSK at relatively low signal-to-noise ratios (SNRs). Further, the optimal combinations of the constellation coordinates for R2 3-D STSK are derived by maximising the minimal determinant of the so-called difference matrices, yielding a better system performance. In addition, a joint optimisation mechanism utilising the simplified conjugate gradient (SCG) algorithm is devised for 3-D STSK, aiming for further enhancing the achievable system performance. Finally, extensive simulation results are provided to demonstrate the benefits of the proposed schemes, exhibiting the design tradeoffs concerning date rate, link robustness and computational complexity.
Influence of endotoxin-protein in immunoglobulin G isotype responses of mice to Brucella abortus lipopolysaccharide

Brucella abortus endotoxin preparations, containing approximately 5 to 6% protein, induce strong immune and adjuvant immunoglobulin G (IgG) responses as compared with Escherichia coli endotoxin preparations, with equivalent amounts of protein, which induce responses in which IgM antibody predominates. Using an enzyme-linked immunoassay with isotype-specific conjugates, we found that antibody of all four subclasses of IgG were evoked during the course of the immune responses of C3H/HeAu mice to B. abortus endotoxin. Secondary responses of endotoxin-hyporesponsive C3H/HeJ mice were similar to those seen in C3H/HeAu mice, although lower levels of antibody were produced during their primary responses. The primary responses of BALB/c athymic mice consisted almost entirely of IgG3, and IgG1 appeared following a second injection. The effects of lipopolysaccharide (LPS)-associated protein on the immunogenic properties of B. abortus endotoxin were examined by comparing responses to endotoxin with those to a purified B. abortus LPS containing less than 1% protein. The endotoxin evoked strong primary and secondary responses in which antibody directed to LPS determinants consisted mainly of IgG3 and those to the protein determinants were largely IgG1 antibody. Primary and secondary responses to purified LPS consisted mainly of IgG3 antibody. The potential mechanism of the contribution of protein to the immunogenic properties of the endotoxin as well as possible immune mechanisms involved in these responses are discussed.