Miracle-dz/UniFAR-FTUs huggingface dataset:
Aryl Hydrocarbon Receptor-Mediated Down-Regulation of Sox9b Causes Jaw Malformation in Zebrafish Embryos

Exposure to environmental contaminants can disrupt normal development of the early vertebrate skeleton. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) impairs craniofacial skeletal development across many vertebrate species, and its effects are especially prominent in early life stages of fish. TCDD activates the aryl hydrocarbon receptor, a transcription factor that mediates most if not all TCDD responses. We investigated the transcriptional response in the developing zebrafish jaw after TCDD exposure using DNA microarrays. Zebrafish larvae were exposed to TCDD at 96 h after fertilization, and jaw cartilage tissue was harvested for microarray analysis at 1, 2, 4, and 12 h after exposure. Numerous chondrogenic transcripts were misregulated by TCDD in the jaw. Comparison of transcripts altered by TCDD in jaw with transcripts altered in embryonic heart showed that the transcriptional responses in the jaw and the heart were strikingly different. Sox9b, a critical chondrogenic transcription factor, was the most significantly reduced transcript in the jaw. We hypothesized that the TCDD reduction of sox9b expression plays an integral role in affecting the formation of the embryonic jaw. Morpholino knockdown of sox9b expression demonstrated that partial reduction of sox9b expression alone was sufficient to produce a TCDD-like jaw phenotype. Loss of a single copy of the sox9b gene in sox9b(+/-) heterozygotes increased sensitivity to jaw malformation by TCDD. Finally, embryos injected with sox9b mRNA and then exposed to TCDD blocked TCDD-induced jaw toxicity in approximately 14% of sox9b-injected embryos. These results suggest that reduced sox9b expression in TCDD-exposed zebrafish embryos contributes to jaw malformation.
The fall, and rise, of civilian power Europe?

The central focus of this paper is the concept of ‘civilian power Europe’, which has been associated with the characterisation and examination of the international role of the EU for almost thirty years. The paper outlines the notion of civilian power Europe as originally formulated, examines how the idea has been used and adapted (or refuted) across time, and explores whether the idea has continuing utility in the early twenty-first century. Central to this analysis is a consideration of whether the conception of civilian power Europe was undermined by the creation of the Common Foreign and Security Policy and the subsequent development of the Common European Security and Defence Policy. The paper concludes that civilian power Europe still has empirical and theoretical purchase when the EU is considered in the context of the contemporary international relations of Europe. It demonstrates the need to develop a clear conception of the international capabilities of the EU if appropriate forms of understanding of the international role of the EU are to be developed.
A Prospective Morphologic Evaluation of Hepatic Toxicity of Chenodeoxycholic Acid in Patients with Cholelithiasis: The National Cooperative Gallstone Study

A sample of 126 patients with cholelithiasis was treated with chenodeoxycholic acid (CDCA) (375 or 750 mg g.d.) for 2 years. Hepatotoxicity was assessed by sequential light (LM) and electron microscopic (EM) analysis of liver biopsies obtained before and after 9 and 24 months of therapy. Patients were without symptoms of biliary colic for 3 months prior to biopsy, less than 70 years old, and had normal tests of liver function. All light microscopy was read blindly by two morphologists, and electron microscopy by one. Only four biopsies (3%) showed severe (3+) abnormalities preventing admission to the study. On evaluation, moderate (2+) LM changes were present in less than 12% of biopsies, while milder changes (1+) were seen more frequently. No severe, dose‐related abnormalities were seen in LM over the 2 years of study. However, mild changes (hepatocyte ballooning and lipofuscin, binucleate cells, glycogen nuclei, ductular proliferation, enlarged and fibrotic triads, and sinusoidal congestion) became more prevalent with time (p ≤ 0.01) regardless of CDCA dose, according to 1 of the 2 morphologists. Because patients with “proven” cholelithiasis for greater than 2 years (33% of the study population) did not have a greater incidence of morphologic abnormalities than those with the diagnosis for less than 2 years, it is unlikely that these changes were due to the natural History of gallstone disease. Furthermore, electron microscopic findings demonstrated worsening intrahepatic cholestasis and a lesion in two patients which was identical to that produced in animals administered lithocholic acid, the 7‐a‐dehydroxylated metabolite of CDCA. The possibility that clinically significant hepatotoxicity could develop with CDCA therapy greater than 24 months thus cannot be excluded by this study.
Democracy and Authoritarianism in South Asia: A Comparative and Historical Perspective

l. The colonial legacy in India and Pakistan 2. State formation and political processes in India and Pakistan, 1947-1971 3. The 'populist' era and its aftermath in India, Pakistan and Bangladesh, 1971-1993 4. The state and political economy: 1947-1993 5. Central power and regional dissidence 6. Societies, cultures and ideologies: hybrids in contrived monoliths.
Political Advertising in Western Democracies: Parties and Candidates on Television

An Introduction to Parties and Candidates on Television - Lynda Lee Kaid and Christina Holtz-Bacha A Comparative Perspective on Political Advertising - Christina Holtz-Bacha and Lynda Lee Kaid Media and Political System Characteristics Political Advertising on Television - Margaret Scammell and Holli A Semetko The British Experience The Role of Television Broadcasts in Promoting French Presidential Candidiates - Anne Johnston and Jacques Gerstle Television Spots in the German National Elections - Christina Holtz-Bacha and Lynda Lee Kaid Content and Effects The Presentation of Italian Candidates and Parties in Television Advertising - Gianpietro Mazzoleni and Cynthia S Roper Overcoming Advertising and Diversity - Akiba A Cohen and Gadi Wolfsfeld The Utility of Television Political Advertising in Israel Political Advertising in Denmark - Karen Siune The Blank Spot - Kees Brants Political Advertising in the Netherlands The Northern European Exception - Tom Moring Political Advertising on TV in Finland Political Commercials in American Presidential Elections - L Patrick Devlin Political Advertising across Cultures - Lynda Lee Kaid and Christina Holtz-Bacha Comparing Content, Styles and Effects
Promoting Physical Activity in a Low-Income Multiethnic District: Effects of a Community Intervention Study to Reduce Risk Factors for Type 2 Diabetes and Cardiovascular Disease

OBJECTIVE—The aim was to assess the net effects on risk factors for type 2 diabetes and cardiovascular disease of a community-based 3-year intervention to increase physical activity. RESEARCH DESIGN AND METHODS—A pseudo-experimental cohort design was used to compare changes in risk factors from an intervention and a control district with similar socioeconomic status in Oslo, Norway, using a baseline investigation of 2,950 30- to 67-year-old participants and a follow-up investigation of 1,776 (67% of those eligible, 56% women, 18% non-Western immigrants) participants. A set of theory-based activities to promote physical activity were implemented and tailored toward groups with different psychosocial readiness for change. All results reported are net changes (the difference between changes in the intervention and control districts). At both surveys, the nonfasting serum levels of lipids and glucose were adjusted for time since last meal. RESULTS—The increase in physical activity measured by two self-reported questionnaires was 9.5% (P = 0.008) and 8.1% (P = 0.02), respectively. The proportion who increased their body mass was 14.2% lower in the intervention district (P < 0.001), implying a 50% relative reduction compared with the control district, and was lower across subgroups. Beneficial effects were seen for triglyceride levels (0.16 mmol/l [95% CI 0.06–0.25], P = 0.002), cholesterol–to–HDL cholesterol ratio (0.12 [0.03–0.20], P = 0.007), systolic blood pressure (3.6 mmHg [2.2–4.8], P < 0.001), and for men also in glucose levels (0.35 mmol/l [0.03–0.67], P = 0.03). The net proportion who were quitting smoking was 2.9% (0.1–5.7, P = 0.043). CONCLUSIONS—Through a theory-driven, low-cost, population-based intervention program, we observed an increase in physical activity levels, reduced weight gain, and beneficial changes in other risk factors for type 2 diabetes and cardiovascular disease.
Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases

Background For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. Methods CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing. The predictive cutoff value was independently validated using cohort I of 339 PCa patients (Southern China) and cohort II of 328 case patients (Germany, across China). Mann-Whitney U test, the receiver operating characteristic curve, McNemar's test, and logistic regression were used to assess data. All statistical tests were two-sided. Results In the training set, CRMP4 promoter methylation (≥15.0% methylated) was statistically significantly associated with LNM (P < 001). Successful validations were achieved in both cohorts I and II (sensitivity = 92.3%, 95% confidence interval [CI] = 79.3 to 97.9, and sensitivity = 92.2%, 95% CI = 81.1 to 97.8, respectively; specificity = 92.7%, 95% CI = 80.2 to 99.1, and specificity = 91.3%, 95% CI = 87.4 to 94.4, respectively). The sensitivity of CRMP4 promoter methylation is superior to conventional MRI (cohort I: 92.3% vs 26.2%, P < 001; cohort II: 92.2% vs 33.3%, P < 001). CRMP4 promoter methylation is an independent predictor of LNM (cohort I: hazard ratio [HR] = 8.35, 95% CI = 5.64 to 12.35, P < 001; cohort II: HR = 12.46, 95% CI = 5.82 to 26.70, P < 001) in a multivariable analysis model. Conclusion CRMP4 promoter methylation in diagnostic biopsies could be a robust biomarker for LNM in PCa.
Complex Networks Theory For Modern Smart Grid Applications: A Survey

This paper provides a survey of studying complex network theory for modern smart grid applications. A brief overview of complex network theory will be explored first. Topological characteristics, statistic characteristics, such as self-organized criticality and critically slow down, and dynamical characteristics, including synchronizations, consensus control, and pinning control, will be briefly addressed. Then, we will illustrate how complex network theory can be applied to modern smart grids in structural vulnerability assessment, cascading blackouts, grid synchronization, network reconfigurations, distributed droop control, pinning control for micro-grid autonomous operations, and effective grid expansions. Some emerging topics and future perspectives are also addressed.
Rates of hippocampal atrophy correlate with change in clinical status in aging and AD

Background: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. Objectives: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). Methods: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 ± 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. Results: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3.5%. Conclusion: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.
Glucose and Lipid Metabolism During Long-Term Lisinopril Therapy in Hypertensive Patients

Summary: The effects of long-term lisinopril therapy on glucose tolerance and serum lipid profiles were investigated prospectively in 30 hypertensive patients: 15 with normal glucose tolerance and the remaining 15 with glucose intolerance. The levels of plasma glucose, serum lipids, and plasma glycosylated hemoglobin A1c were determined before and during long-term (6 months) therapy with lisinopril. A 75 g oral glucose tolerance test was performed before and during long-term lisinopril therapy. Lisinopril produced significant falls in both systolic and diastolic blood pressure in both patient groups during the long-term therapy. Neither fasting nor post-glucose-load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (Δ IRI/Δ BS at 30 min post-glucose load) in both patient groups. No significant changes in fasting levels of serum cholesterol, triglycerides, and HDL-cholesterol were observed in either group during long-term lisinopril therapy. Long-term lisinopril therapy does not compromise glucose or lipid metabolism in hypertensive patients. Lisinopril may have an advantage as an antihypertensive agent that can be given to hypertensive patients without concern that it might alter their serum lipid concentrations or impair glucose tolerance.
Quantitative prediction of biodegradability, metabolite distribution and toxicity of stable metabolites

An evaluation of the capability of organic chemicals to mineralize is an important factor to consider when assessing their fate in the environment. Microbial degradation can convert a toxic chemical into an innocuous one, and vice versa , or alter the toxicity of a chemical. Moreover, primary biodegradation can convert chemicals into stable products that can be difficult to mineralize. In this paper, we present some new results obtained on the basis of a recently developed probabilistic approach to modeling biodegradation based on microbial transformation pathways. The metabolic transformations and their hierarchy were calibrated by making use of the ready biodegradability data from the MITI-I test and expert knowledge for the most probable transformation pathways. A model was developed and integrated into an expert software system named CATABOL that is able to predict the probability of biodegradation of organic chemicals directly from their structure. CATABOL simulates the effects of microbial enzyme systems, generates the most plausible transformation pathways, and quantitatively predicts the persistence and toxicity of the biodegradation products. A subset of 300 organic chemicals were selected from Canada's Domestic Substances List and subjected to CATABOL to compare predicted properties of the parent chemicals with their respective first stable metabolite. The results show that most of the stable metabolites have a lower acute toxicity to fish and a lower bioaccumulation potential compared to the parent chemicals. In contrast, the metabolites appear to be generally more estrogenic than the parent chemicals.
Influence of anisotropic white matter modeling on EEG source localization

We study the influence of the anisotropic white matter within the ElectroEncephaloGraphy source localization problem. To this end, we consider three cases of the anisotropic white matter modeled in two concrete cases: by fixed or variable ratio. We extract information about highly anisotropic areas of the white matter from real Diffusion Weighted Imaging data. To validate the compared anisotropic models, we introduce the localization dipole and orientation errors. Obtained results show that the white matter model with a fixed anisotropic ratio leads to values of dipole localization error close to 1cm and may be enough in those cases avoiding localized analysis of neural brain activity. In contrast, modeling based on the anisotropic variable rate assumption becomes important in tasks regarding analysis and localization of deep sources neighboring the white matter tissue.
Lag Times between Lymphoproliferative Disorder and Clinical Diagnosis of Chronic Lymphocytic Leukemia: A Prospective Analysis Using Plasma Soluble CD23

Background: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. Methods: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. Results: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90–1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86–0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65–0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. Conclusions: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL. Impact: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538–45. ©2014 AACR.
THE CORRELATION OF A BIPHASIC METABOLIC RESPONSE WITH A BIPHASIC RESPONSE IN RESISTANCE TO TUBERCULOSIS IN RABBITS

We have found a phase of susceptibility associated with a reduced metabolic activity on the part of peritoneal mononuclear phagocytes taken from BCG-vaccinated rabbits. A second stage of heightened resistance to infection was found to be associated with a heightened metabolic activity. The period of susceptibility in BCG vaccination is primarily concerned with initiation of the infection and not with the progression of the disease, which in both stages is increased. These reactions are discussed in relation to other conditions, such as nonspecific protein therapy and the administration of endotoxin, which also have similiar biphasic stages of resistance. Of incidental interest is the fact that rabbits who received 400 roentgen units are two years later still unable to respond to BCG vaccination with an increase in resistance. We conclude that there is a relationship between the level of certain metabolic activities of reticuloendothelial cells and resistance to tuberculosis.
Targeted Metabolomics Analysis of Campylobacter coli VC167 Reveals Legionaminic Acid Derivatives as Novel Flagellar Glycans*

Glycosylation of Campylobacter flagellin is required for the biogenesis of a functional flagella filament. Recently, we used a targeted metabolomics approach using mass spectrometry and NMR to identify changes in the metabolic profile of wild type and mutants in the flagellar glycosylation locus, characterize novel metabolites, and assign function to genes to define the pseudaminic acid biosynthetic pathway in Campylobacter jejuni 81-176 (McNally, D. J., Hui, J. P., Aubry, A. J., Mui, K. K., Guerry, P., Brisson, J. R., Logan, S. M., and Soo, E. C. (2006) J. Biol. Chem. 281, 18489-18498). In this study, we use a similar approach to further define the glycome and metabolomic complement of nucleotide-activated sugars in Campylobacter coli VC167. Herein we demonstrate that, in addition to CMP-pseudaminic acid, C. coli VC167 also produces two structurally distinct nucleotide-activated nonulosonate sugars that were observed as negative ions at m/z 637 and m/z 651 (CMP-315 and CMP-329). Hydrophilic interaction liquid chromatography-mass spectrometry yielded suitable amounts of the pure sugar nucleotides for NMR spectroscopy using a cold probe. Structural analysis in conjunction with molecular modeling identified the sugar moieties as acetamidino and N-methylacetimidoyl derivatives of legionaminic acid (Leg5Am7Ac and Leg5AmNMe7Ac). Targeted metabolomic analyses of isogenic mutants established a role for the ptmA-F genes and defined two new ptm genes in this locus as legionaminic acid biosynthetic enzymes. This is the first report of legionaminic acid in Campylobacter sp. and the first report of legionaminic acid derivatives as modifications on a protein.
Feature weighting for antimicrobial peptides classification: A multi-objective evolutionary approach

Antimicrobial peptides might become crucial in fighting antibiotic resistant bacteria and other infections. Next Generation Sequencing technologies are generating a large amount of data where peptides with antimicrobial activity could be found. Therefore, algorithms that can efficiently determine whether or not a short sequence of amino acids is antimicrobial are needed. In this context, Quantitative Structure-Activity Relationship modeling has paved the way toward the association of the physicochemical properties of peptides to their biological activity. Nowadays, there are algorithms that can compute thousands of physicochemical properties known as molecular descriptors. However, some of these descriptors are irrelevant and some might even mislead the correct classification of the peptide activity. To mitigate this problem, a descriptor selection process must be performed, this will help to improve the classification accuracy and to decrease the computational time required for classification. In a recent work, a general method to weight and select features has been proposed. The method models the descriptor selection problem as a multi-objective optimization problem (MOOP). The main idea is to optimize simultaneously the intra- and inter-class distances. We follow this approach and apply it to the feature selection problem for the classification of antimicrobial peptides. To this aim we modify the original MOOP formulation to avoid bringing together non-antimicrobial peptides. Preliminary results indicate that our approach can substantially reduce the number of required molecular descriptors and improve the performance of classification with respect to the original formulation.