Miracle-dz/UniFAR-FTUs huggingface dataset:
Progestins oppose the effects of estradiol on the endothelin-1 receptor type B in coronary arteries from ovariectomized hyperlipidemic rabbits

Objective: Progestins may be associated with the adverse cardiovascular outcomes observed with estrogen plus progestogen therapy, but the mechanism is not resolved. In this study we examined the effect of 17&bgr;-estradiol (E2) alone and in combination with two progestins on the endothelin-1 (ET-1) system in coronary arteries. Design: Watanabe heritable hyperlipidemic rabbits were treated orally with either E2 (4 mg/d), medroxyprogesterone acetate (MPA) (10 mg/d), norethisterone acetate (NETA) (2 mg/d), E2 + MPA, E2 + NETA, or placebo for 16 weeks (n = 10 in each group). Coronary arteries were used for mRNA and myograph analyses. Results: E2 alone but not in combination with MPA or NETA increased ETB mRNA expression in coronary arteries. Accordingly, E2 alone but not in combination with MPA or NETA reduced the maximal contraction to ET-1, and the reduction was sustained after ETA but not after ETB blockade. E2 reduced preproendothelin-1 mRNA expression; however, this effect was not blunted by MPA or NETA. ETA and ET-converting enzyme-1 mRNA expression was unaffected by treatment. Conclusions: The data suggest that long-term E2 treatment selectively attenuates ET-1-induced vasoconstriction, possibly by increasing ETB gene expression in rabbit coronary arteries and that this effect is abolished by the two progestins investigated. This observation may help to explain how progestins oppose the supposed beneficial effects of estrogen on the arterial wall.
Evaluation of oxygen consumption and resting energy expenditure in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVE To determine whether oxygen consumption VO2), CO2 production, and resting energy expenditure (REE) in critically ill patients differ in varying grades of systemic inflammatory response syndrome (SIRS). DESIGN Prospective, clinical study. SETTING Intensive care unit at a university hospital. PATIENTS Twenty-six critically ill patients requiring mechanical ventilation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 100 metabolic measurements were performed. The grade of SIRS and the Acute Physiology and Chronic Health Evaluation II score were evaluated at the time of the metabolic cart study. VO2 and REE differed among the groups inadequate for SIRS (non-SIRS), with SIRS without infection (nonseptic SIRS), and with SIRS with infection (septic SIRS) (125 +/- 37 mL/min/m2 and 855 +/- 204 kcal/day/m2, 135 +/- 33 mL/min/m2 and 948 +/- 214 kcal/day/m2, and 166 +/- 55 mL/min/m2 and 1149 +/- 339 kcal/day/m2, respectively; p < .005). Patients with septic SIRS had higher VO2 and REE than patients with non-SIRS and nonseptic SIRS. CONCLUSION VO2 and REE differ among groups of patients with non-SIRS, nonseptic SIRS, and septic SIRS. Patients with septic SIRS have higher VO2 and REE than patients with non-SIRS or nonseptic SIRS. The present study shows that classifying patients into three grades (non-SIRS, nonseptic SIRS, and septic SIRS) is a valid predictor of metabolic stress in critically ill patients.
The Role of Selective High Schools in Equalizing Educational Outcomes: Heterogeneous Effects by Neighborhood Socioeconomic Status

We investigate whether elite Chicago public high schools can help close the achievement gap between high-achieving students from more and less affluent neighborhoods. Seats are allocated based on prior achievement with 70 percent reserved for high-achieving applicants from four neighborhood socioeconomic status (SES) categories. Using regression discontinuity design, we find no effect on test scores or college attendance for students from high- or low-SES neighborhoods and positive effects on student reports of their experiences. For students from low-SES neighborhoods, we estimate significant negative effects on rank in high school, grades and the probability of attending a selective college.
MicroRNA-200 (miR-200) Cluster Regulation by Achaete Scute-like 2 (Ascl2)

Background: Ascl2 regulates the plasticity of EMT-MET programs in colon cancer cells. Results: Ascl2 loss of function in colon cancer cells promoted MET by derepressing miR-200 expression through a direct transcriptional mechanism. Conclusion: Ascl2 promotes EMT occurrence in part via miR-200s. Significance: This study sheds new light on preventing EMT in colon cancer. Ascl2, a basic helix-loop-helix transcription factor, is a downstream target of WNT signaling that controls the fate of intestinal cryptic stem cells and colon cancer progenitor cells. However, its involvement in colon cancer and downstream molecular events is largely undefined; in particular, the mechanism by which Ascl2 regulates the plasticity of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) programs in colon cancer cells remains unknown. In this study, we systematically demonstrate that Ascl2 loss of function in colon cancer cells promotes MET by derepressing the expression of microRNA (miR)-200s (i.e. miR-200b, miR-200a, miR-429, miR-200c, and miR-141) and further activating their expression through a transcriptional mechanism that involves direct binding to the most proximal E-box (E-box2) in the miR-200b-a-429 promoter. Activation of miR-200s due to Ascl2 deficiency led to the inhibition of ZEB1/2 expression and the alteration of epithelial and mesenchymal features. Transfection of miR-200b, miR-200a, and miR-429 inhibitors into Ascl2-deficient colon cancer cells promoted the epithelial-mesenchymal transition in a reversible manner. Transfection of miR-200a or miR-429 inhibitors into Ascl2-deficient colon cancer cells increased cellular proliferation and migration. Ascl2 mRNA levels and the miR-200a, miR-200b, miR-200c, miR-141, or miR-429 levels in the colon cancerous samples were inversely correlated. These results provide the first evidence of a link between Ascl2 and miR-200s in the regulation of EMT-MET plasticity in colon cancer.
Enhanced protein fold recognition using a structural alphabet

Fold recognition from sequence can be an important step in protein structure and function prediction. Many methods have tackled this goal. Most of them, based on sequence alignment, fail for sequences of low similarity. Alignment–free approaches can provide an efficient alternative. For such approaches, the identification of efficient fold discriminatory features is critical. We propose a new fold recognition approach that relies on the encoding of the local structure of proteins using a Hidden Markov Model Structural Alphabet. This encoding provides a 1D description of the conformation of complete proteins structures, including loops. At the fold level, compared with the classical secondary structure helix, strand, and coil states, such encoding is expected to provide the means of a better discrimination between loop conformations, hence providing better fold identification. Compared with previous related approaches, this supplement of information results in significant improvement. When combining this information with supplementary information of secondary structure and residue burial, we obtain a fold recognition accuracy of 78% for 27 protein families, that is, 8% higher than the best available method so far, and of 68% for 60 families. Corresponding scores at the class level are of 92% and 90% indicating that mispredictions are mostly within structural classes. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Diffusion tensor imaging and proton magnetic resonance spectroscopy in brain tumor: Correlation between structure and metabolism

Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, peritumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.
Chinese Research on Family Tourism: Review and Research Implications

ABSTRACT With increases in disposable income in China as well as the traditional focus on family life, family tourism is one of the fastest growing segments in contemporary Chinese tourism. This study presents a systematic review of 66 research articles from Chinese academic journals published between 1995 and 2015. The general trend, themes and methods are analyzed. Listening to children’s voices, paying attention to diverse family types, the influence of social media on family travel, collaboration among researchers with different backgrounds, and thinking through the role of Chinese culture are posited as topics requiring increased attention to enhance future family tourism research in China.
Formats for Improving Risk Communication in Medical Tradeoff Decisions

ABSTRACT To make treatment decisions, patients should consider not only a treatment option's potential consequences but also the probability of those consequences. Many laypeople, however, have difficulty using probability information. This Internet-based study (2,601 participants) examined a hypothetical medical tradeoff situation in which a treatment would decrease one risk but increase another. Accuracy was assessed in terms of the ability to determine correctly whether the treatment would increase or decrease the total risk. For these tradeoff problems, accuracy was greater when the following occurred: (1) the amount of cognitive effort required to evaluate the tradeoff was reduced; (2) probability information was presented as a graphical display rather than as text only; and (3) information was presented as percentages rather than as frequencies (n in 100). These findings provide suggestions of ways to present risk probabilities that may help patients understand their treatment options.
Evolution of current filaments limiting the safe-operating area of high-voltage trench-IGBTs

An improved understanding of the physical processes leading to the formation of current filaments and latch-up in large arrays of monolithically integrated high voltage (3.3kV) trench-IGBT cells during the turn-off process of the device is the prerequisite for enhancing the robustness of the device. To this end, numerical simulations have been performed revealing the rim of the safe-operating area (SOA) and what happens beyond it.
A Mixed Methods Study Evaluating Strategies used in Organizational Visioning

The purpose of this case study is to evaluate two methods of strategic planning within organizational visioning: Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis and Appreciative inquiry (Ai). SWOT analysis is a method of strategic planning that is popular within companies and organizations due to its simple, yet thorough, approach. Ai has recently emerged as an approach to strategic visioning and planning within organizational development. However, little research has been conducted to evaluate either approach to organizational visioning, and there is a growing need to compare the two techniques. In this case study, participants within one organization were divided, with half of the staff participating in Ai and the other half participating in SWOT. Data for this mixed methods study was gathered through observation, focus group interviews, and pre‐test, post‐test, and delayed post assessments tests. Through the explanatory sequential design, quantitative data evaluated the change in organizational commitment and vision clarity as a result of the interventions; while, qualitative data further explored participants’ perception of the intervention process and resulting effects. The study found a statistically significant interaction between intervention treatments and the pre‐test and post‐test scores within the organizational commitment construct. Seven themes emerged from the qualitative data; however, only two themes were specifically associated with an intervention treatment. Participants in the SWOT intervention described the visioning process to be frustrating and negative; while, Ai participants found that the visioning process confirmed many of their beliefs and values about the A MIXED METHODS STUDY EVALUATING STRATEGIES USED IN ORGANIZATIONAL VISIONING iii department. Recommendations for future practice suggest the use of Strengths, Opportunities, Aspiration, Results (SOAR) as an approach that combines and maximizes Ai and SWOT. Suggestions for future research are to explore SWOT as a precursor to di‐ visioning within the Visioning Process Model. A MIXED METHODS STUDY EVALUATING STRATEGIES USED IN ORGANIZATIONAL VISIONING
Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase

Significance Spliceostatins are bacterial natural products that show promising anticancer activity. Understanding how the bacterium makes spliceostatins will aid efforts toward a sustainable route for their production. Moreover, altering the chemical structure of a natural product is usually necessary to improve its pharmaceutical properties. For example, the parent spliceostatin molecule contains an unstable hemiketal chemical group. Contrary to previous hypotheses, we report on the identification of a dioxygenase enzyme responsible for hemiketal biosynthesis. Deletion of the corresponding dioxygenase gene led to a strain that produces exclusively spliceostatin congeners that are more stable than, and as active as, the parent compound, when derivatized to increase cell permeability. The strain generated in this study will be the basis for future development. Spliceostatins are potent spliceosome inhibitors biosynthesized by a hybrid nonribosomal peptide synthetase−polyketide synthase (NRPS−PKS) system of the trans-acyl transferase (AT) type. Burkholderia sp. FERM BP-3421 produces hemiketal spliceostatins, such as FR901464, as well as analogs containing a terminal carboxylic acid. We provide genetic and biochemical evidence for hemiketal biosynthesis by oxidative decarboxylation rather than the previously hypothesized Baeyer–Villiger oxidative release postulated to be catalyzed by a flavin-dependent monooxygenase (FMO) activity internal to the last module of the PKS. Inactivation of Fe(II)/α-ketoglutarate–dependent dioxygenase gene fr9P led to loss of hemiketal congeners, whereas the mutant was still able to produce all major carboxylic acid-type compounds. FMO mutants, on the other hand, produced both hemiketal and carboxylic acid analogs containing an exocyclic methylene instead of an epoxide, indicating that the FMO is involved in epoxidation rather than Baeyer–Villiger oxidation. Moreover, recombinant Fr9P enzyme was shown to catalyze hydroxylation to form β-hydroxy acids, which upon decarboxylation led to hemiketal FR901464. Finally, a third oxygenase activity encoded in the biosynthetic gene cluster, the cytochrome P450 monooxygenase Fr9R, was assigned as a 4-hydroxylase based on gene inactivation results. Identification and deletion of the gene involved in hemiketal formation allowed us to generate a strain—the dioxygenase fr9P− mutant—that accumulates only the carboxylic acid-type spliceostatins, which are as potent as the hemiketal analogs, when derivatized to increase cell permeability, but are chemically more stable.
A Four‐Year Pathology Review of the Near Total Face Transplant

In December of 2008, our institution performed a near total face transplant. The patient was monitored for signs of rejection assessed by paired skin and mucosa biopsies. The results of histological review of 120 biopsies collected during the first 4 years posttransplant are discussed. All biopsies were stained with hematoxylin and eosin, periodic acid‐Schiff, immunohistochemical and TUNEL assays and graded using the Banff 2007 classification. Grade III rejection was diagnosed clinically at weeks 45 and 66, posttransplant; week 45 was determined as folliculitis while the erythema episode at week 66 confirmed an acute rejection (AR) that required hospitalization. The mucosa frequently showed interface inflammation without clinical signs of rejection and was not present in skin biopsies. In all, 34 of the 45 mucosal biopsies (75%) showed these interface changes. Clinical symptoms concurred with skin pathology in two grade III rejections. The mucosa showed histologic signs of rejection more frequently, which may indicate: increased mucosal sensitivity to rejection, a different type or subtype of AR that is specific to the mucosa, or a nonspecific process such as a drug effect. With more data and world experience, the diagnosis of face transplant rejection will be better defined and the Banff classification enhanced.
Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features.

BACKGROUND The clinical relevance of distinguishing two types of glomerulonephritis (GN) with non-amyloid organized immunoglobulin (Ig) deposits-fibrillary GN (FGN) and immunotactoid (microtubular) GN (IT/MTGN)-on the basis of ultrastructural organization, is debated. METHODS Twenty-three patients with organized glomerular Ig deposits were classified into two groups based on the fibrillar or microtubular ultrastructural appearance of the deposits. Kidney biopsy samples were studied by immunofluorescence microscopy, using anti-light chain conjugates (all cases) and anti-IgG subclass conjugates (13 patients). In each group, we studied clinicopathological features, associated monoclonal gammapathy (detected by immunoelectrophoresis and/or immunoblot) or B-cell lymphoproliferative disease, effects of chemotherapy and long-term renal outcome. RESULTS In 14 IT/MTGN and 9 FGN patients, clinical symptoms [hypertension, nephrotic syndrome (NS) and hematuria] and the mean diameters of the substructures were similar. In 13 IT/MTGN patients, glomerular (IgG1, 2 or 3) deposits were monotypic (kappa, 7 cases; lambda, 6 cases). Glomerular deposits were associated with a monoclonal Ig of the same isotype in eight patients, detected in the serum (5 cases), and/or in the cytoplasm of lymphocytes (4 cases), and with lymphoproliferative disease in seven patients. The ultrastructural features of monoclonal Ig inclusions in lymphocytes were similar to those of glomerular microtubular deposits. In contrast, none of the FGN patients presented lymphoplasmocytic proliferation or paraproteinemia. Glomerular Ig deposits were polyclonal in eight cases and contained IgG4 in all three cases studied. Although patient and renal survival did not differ significantly between the two groups, chemotherapy led to remission of NS in ten IT/MTGN patients, with parallel improvement in hematological parameters. CONCLUSIONS The identification of ultrastructural patterns in these nephropathies is important. GN with organized microtubular monoclonal deposits (GOMMID) probably accounts for a large proportion of immunotactoid (microtubular) GN cases.
IgE-binding factors and regulation of the IgE antibody response.

In rodents, IgE-bF are derived from a subset of T cells that bear Fc epsilon R or Fc gamma R, or both, and selectively enhance or suppress the IgE response. IgE-PF and IgE-SF may share a common structural gene, therefore a common polypeptide chain, and their biologic activities are decided by post-translational glycosylation process. Under physiological conditions, this process is controlled by two lymphokines, i.e. GEF and GIF. The same principle probably applies to human T cell-derived IgE-bF. In both rodent and human lymphocytes, Fc epsilon RII on B cells are degraded, and their fragments are released from the cells. The fragments of Fc epsilon RII on human B cells represent the carboxy terminal half of the receptor molecules and have affinity for IgE. In contrast, the fragment of Fc epsilon R in mouse B cells does not have an affinity for IgE. Thus, "IgE-bF" are derived from both T cells and B cells in humans, but only from T cells in rodents. The formation of T cell-derived IgE-bF was induced by interferons, while biosynthesis of Fc epsilon R in B cells and the formation of their fragments were enhanced by IL-4. IgE-bF are also formed by a subset of antigen-primed T cells upon cognate interaction with antigen-pulsed syngeneic macrophages. These antigen-primed T cells constitutively secrete either GEF or GIF, having no affinity for homologous antigen. Upon antigenic stimulation, however, GEF and GIF formed by the cells had affinity for the antigen. The antigen-specific GEF enhanced the antibody response, and antigen-specific GIF suppressed the antibody response, both in carrier specific manner. The possible relationship between antigen-specific GEF and antigen-specific TaF, and that between antigen-specific GIF and antigen-specific TsF both require further studies. Nonspecific GIF not only switches T cells from the formation of IgE-PF to the formation of IgE-SF, it also facilitates the generation of antigen-specific suppressor T cells which produce antigen-specific GIF upon antigenic stimulation. Propagation of antigen-primed T cells in the presence of GIF also facilitate the generation of antigen-specific suppressor T cells in vitro. If the same procedures would be effective for human T cells of allergic patients, it would be possible to generate antigen-specific suppressor T cells from their T cell population in vitro and to establish T cell hybridomas that produce allergen-specific GIF(TsF). (ABSTRACT TRUNCATED AT 400 WORDS)
Word length and phonological similarity effects in simple, complex, and delayed serial recall tasks: Implications for working memory

Some current models of working memory argue that a passive short-term store is not involved in more dynamic working memory tasks. Other models argue that standard short-term memory and working memory tasks rely on common storage facilities. We examine these issues by exploring two signature effects of passive short-term storage in simple span, complex span, and Brown-Peterson tasks. The finding that all three tasks show word length and phonological similarity effects suggests that common processes or storage mechanisms are involved in all tasks. The implications for models of working memory are discussed.