Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation of p21 WAF1 Sensitizes Cells to Apoptosis via an Increase of Both p14ARF and p53 Levels and an Alteration of the Bax/Bcl-2 Ratio*

p21WAF1 appears to be a major determinant of the cell fate in response to anticancer therapy. It was shown previously that HCT116 human colon cancer cells growing in vitro enter a stable arrest upon DNA damage, whereas cells with a defective p21WAF1 response undergo apoptosis. Here we report that the enhanced sensitivity of HCT116/p21−/−cells to chemotherapeutic drug-induced apoptosis correlates with an increased expression of p53 and a modification of their Bax/Bcl-2 ratio in favor of the pro-apoptotic protein Bax. Treatment of HCT116/p21−/− cells with daunomycin resulted in a reduction of the mitochondrial membrane potential and in activation of caspase-9, whereas no such changes were observed in HCT116/p21+/+ cells, providing evidence that p21WAF1 exerts an antagonistic effect on the mitochondrial pathway of apoptosis. Moreover, the role of p53 in activation of this pathway was demonstrated by the fact that inhibition of p53 activity by pifithrin-α reduced the sensitivity of HCT116/p21−/−cells to daunomycin-induced apoptosis and restored a Bax/Bcl-2 ratio similar to that observed in HCT116p21+/+ cells. Enhancement of p53 expression after disruption of p21 WAF1 resulted from a stabilization of p53, which correlated with an increased expression of the tumor suppressor p14ARF, an inhibitor of the ubiquitin ligase activity of Mdm2. In accordance with the role of p14ARF in p53 stabilization, overexpression of p14ARF in HCT116/p21+/+ cells resulted in a strong increase in p53 activity. Our results identify a novel mechanism for the anti-apoptotic effect of p21WAF1 consisting in maintenance of mitochondrial homeostasis that occurs in consequence of a negative control of p14ARF expression.
There be Dragons! An Ethnographic Inquiry into the Strategic Practices and Process of World of Warcraft Gaming Groups

We argue that taking ethnography seriously is a way to increase the relevance of strategic management research. We identify and elaborate on three distinct forms of ethnographic research: direct observation, participant observation, and immersive participation. In particular, we call for an immersive participation approach to research that builds on indepth local engagement as an active agent in a position of responsibility. We argue that immersive participation provides access to privileged knowledge and enables natural on-going dialogue between knowledge with practical relevance and that with academic relevance.
Sexual functioning in long‐term survivors of Hodgkin's lymphoma

Objective: Studies of Hodgkin's lymphoma (HL) survivors have reported long‐term adjustment problems including sexual dysfunction, but the prevalence and persistence of sexual problems in HL survivors have not been well characterized. This study aimed to address these questions by comparing sexual health in a large cohort of long‐term HL survivors with a noncancer control group.
Prevalence of dementia and dementing diseases in Japan: the Tajiri project.

BACKGROUND Vascular dementia (VaD) has been considered to be more prevalent than Alzheimer disease in Japan. However, this might be the result of overdiagnosis stemming from some problematic diagnosis of VaD or of the frequent use of magnetic resonance imaging to detect cerebrovascular disease in older adults. OBJECTIVES We investigated the prevalence of dementia and the ratios of dementing diseases. The effects of different criteria for VaD (DSM-IV, Alzheimer's Disease Diagnostic and Treatment Centers [ADDTC], and National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN]) were considered. Hippocampal atrophy and vascular contribution to dementia were evaluated using magnetic resonance imaging findings. METHODS We targeted all residents 65 years and older (n = 3207) in Tajiri, Japan, and examined 1654 (participant group 1). Of these, 564 (participant group 2) were randomly selected, and 497 underwent magnetic resonance imaging and diagnosis of dementing diseases. RESULTS We found the overall prevalence of dementia to be 8.5% (141/1654) in participant group 1. Of these, 21 (14.9%) had a history of stroke. Of the 113 participants who had a history of stroke independent of dementia, 18.6% (21/113) were demented. For participant group 2 (n = 497), 32 were demented. The ratio among the dementia for probable VaD based on the NINDS-AIREN criteria was 18.8% (6/32), whereas that for ischemic vascular dementia was 31.3% (10/32) according to the ADDTC criteria. CONCLUSION We confirmed the overall prevalence of dementia in adults 65 years and older to be 8.5%. We found that VaD was not a common disorder according to the NINDS-AIREN criteria. Rather, the condition of possible Alzheimer disease with cerebrovascular disease was more common.
Relations of respiration and growth in the Avena coleoptile.

THE AVENA coleoptile is a classical obj ect for the study of the effect of auxin in inducing plant growth. A particularly simple system for the study of the auxin response is constituted by excised sections of the coleoptile which when floated on aqueous solutions containing an active auxin, are capable of extensive and rapid growth (Bonner, 1933). It is known that there is a relation between the auxin induced growth of such sections and their respiration. Thus response to auxin does not occur in an 02 free atmosphere (Bonner, 1933), while HCN, which inhibits respiration of the coleoptile, inhibits response to auxin in a parallel manner (Bonner, 1933, 1936). As a preliminary step in the elucidation of the relation of auxin to respiration, the respiratory systems of the coleoptile have been reviewed and reported in a previous paper (Bonner, 1948). The oxygen uptake of the coleoptile is mediated by the cytochrome-cytochrome oxidase system. Hexose is converted to fructose diphosphate through a series of reactions involving ATP and evidence that pyruvate is the product of initial hexose breakdown has been presented (Bonner, 1948). Pyruvate in turn is metabolized through a system involving succinic dehydrogenase and resembling in general terms the cycle of Krebs. Thus the Avena coleoptile possesses so far as present information goes what might be termed an orthodox respiratory mechanism, one resembling that of animal tissues. The previous paper in this series (Bonner, 1949) has dealt with the influence of several factors including respiratory substrates and inhibitors on the auxin induced growth of A4vena coleoptile sections. This paper deals with experiments which bear on the relation of auxin to respiration. MATERIALS AND METHODS. -A4vena seedlings (var. Siegeshafer) were grown from intact fruits (glumes not removed) in flats in vermiculite and incubated under occasional orange light at 260C. for 5 days before use. At this time the plants were approximately 2 cm. tall and were identical with those used for growth measurements in the preceding paper. For the respiration measurements, tips 2-3 mm. long were removed from the coleoptile and one 5 mm. section cut from each hollow coleoptile cylinder with a double bladed cutting tool. The segments were thoroughly randomized and dispensed into Warburg vessels, twenty per vessel. At the same time one lot of twenty sections was weighed directly in the fresh condition and all respiratory rates are calculated to the basis of 100 mg. fresh wt. , twenty sections weighing in general 75-85 mg. Measure1 Received for publication August 28, 1948. Report of work supported in part by the Herman Frasch Foundation. ments of respiration were made in single side-arm conical Warburg vessels of approximately 16 cc. capacity and provided with a central well which contained 5 per cent KOH where oxygen uptake was to be determined. A bath temperature of 30? C. was used throughout. M/100 KH2PO4, pH 4.5,
Extracting Findings from Narrative Reports: Software Transferability and Sources of Physician Disagreement

Abstract: While natural language processing systems are beginning to see clinical use, it remains unclear whether they can be disseminated effectively through the health care community. MedLEE, a general-purpose natural language processor developed for Columbia-Presbyterian Medical Center, was compared to physicians' ability to detect seven clinical conditions in 200 Brigham and Women's Hospital chest radiograph reports. Using the system on the new institution's reports resulted in a small but measurable drop in performance (it was distinguishable from physicians at p = 0.011). By making adjustments to the interpretation of the processor's coded output (without changing the processor itself), local behavior was better accommodated, and performance improved so that it was indistinguishable from the physicians. Pairs of physicians disagreed on at least one condition for 22% of reports; the source of disagreement appeared to be interpretation of findings, gauging likelihood and degree of disease, and coding errors.
Brain glucose concentrations in healthy humans subjected to recurrent hypoglycemia

Mechanisms responsible for hypoglycemia unawareness remain unknown. Previously, we found that patients with type 1 diabetes and hypoglycemia unawareness had increased brain glucose concentrations as measured by 1H‐magnetic resonance spectroscopy (MRS) compared with controls measured under the same metabolic condition, suggesting that an alteration in brain glucose transport and/or metabolism may play a role in the pathogenesis of hypoglycemia unawareness. To determine whether the brain glucose concentration is altered in normal subjects subjected to recurrent hypoglycemia, we compared the brain glucose concentrations measured in healthy subjects after three episodes of hypoglycemia to blunt the counterregulatory response over 24 hr and compared this value with that measured at a time remote from the antecedent hypoglycemia protocol. Sixteen subjects (9 M/7 F, age 36 ± 10 years, mean ± SD) underwent three hypoglycemic clamps for 30 min at 8 AM (0 hr), 5 PM (9 hr), and 7 AM (24 hr). After the third hypoglycemic clamp, subjects underwent a hyperglycemic clamp during which brain glucose concentration was measured by MRS at 4 T. Brain glucose concentration after repeated hypoglycemia was not different from the brain glucose concentration measured in the same subjects during a control study (5.1 ± 0.8 vs. 4.5 ± 0.5 μmol/g wet weight, respectively, P = 0.05). These observations suggest that brain glucose transport or metabolism is not altered following short episodes of recurrent hypoglycemia in healthy human volunteers. © 2005 Wiley‐Liss, Inc.
Cross-Cultural Cyborgs: Greek and Canadian Women's Discourses on Fetal Ultrasound

For millions of women in North America, Australia, Europe, and, increasingly, elsewhere as well, at least one or two ultrasounds have become an expected and routine part of pregnancy.l For physicians and sonographers, ultrasound represents a necessary, passive, and neutral technology, capable of providing, as one obstetrical text describes it, "a window of unsurpassed clarity into the gravid uterus . [and] exquisite detail regarding the fetus and the intrauterine environment. "2 The possibilities of seeing, we are told, are numerous: the state of fetal anatomy; growth and development; numerous fetal pathologies; the sex of the fetus as early as eleven weeks; and fetal sleep, rest, and activity patterns. There are even claims of witnessing fetal masturbation3 and, as Lisa Cartwright has pointed out, enough fetal behavior for one psychiatrist to begin the practice of fetal psychoanalysis.4 For women, ultrasound has become firmly lodged as a "normal" part of pregnancy, allowing a sneak preview of our baby's sex, age, size, physical normality, and possible personality. So convincing is the cognitive and sensual apprehension of the fetus via the electronic mediation of ultrasound technology that women may routinely experience a "technological quickening" several weeks before they sense fetal movement in their own bodies.5 This article examines what we call the cyborg fetus of ultrasound imaging: the mode of knowing and feeling the fetus through the coupling of human and machine. As Donna Haraway has described it, the cyborg is a "coconstruction" of humans and nonhumans.6 Thus, any exploration of the cyborg fetus must dwell both on the distinctive features of the ultra-
Urinary Bladder Cancer Susceptibility Markers. What Do We Know about Functional Mechanisms?

Genome-wide association studies (GWAS) have been successful in the identification of the several urinary bladder cancer (UBC) susceptibility loci, pointing towards novel genes involved in tumor development. Despite that, functional characterization of the identified variants remains challenging, as they mostly map to poorly understood, non-coding regions. Recently, two of the UBC risk variants (PSCA and UGT1A) were confirmed to have functional consequences. They were shown to modify bladder cancer risk by influencing gene expression in an allele-specific manner. Although the role of the other UBC risk variants is unknown, it can be hypothesized—based on studies from different cancer types—that they influence cancer susceptibility by alterations in regulatory networks. The insight into UBC heritability gained through GWAS and further functional studies can impact on cancer prevention and screening, as well as on the development of new biomarkers and future personalized therapies.
Prognostic utility of carotid ultrasound and cardiac SPECT imaging in coronary artery bypass patients.

BACKGROUND The aim of our study was to evaluate the role of myocardial perfusion imaging (MPI) and common carotid artery intima-media thickness (CCA IMT) in the prognosis of patients with coronary artery disease referred for coronary artery bypass surgery (CABG) in a newly made prognostic model. MATERIAL AND METHODS 63 patients (age 60.36 +/- 8.28 years) with angiographically established coronary artery disease referred for CABG were evaluated for: age, smoking, family disposition, dyslipidaemia, arterial hypertension, obesity, diabetes mellitus, previous myocardial infarction and revascularization. Patients underwent nitrate enhanced Gated SPECT myocardial perfusion imaging, with 17-segment analysis for calculation of perfusion scores and viability index. Common carotid artery IMT was measured by B-mode ultrasound. Patients were followed for cardiovascular events 12 months after CABG. RESULTS The obtained data reported mean values of left ventricular ejection fraction (LVEF) 46.2 +/- 14.4%, viability index 0.76 +/- 0.55, SRS 17.76 +/- 13.81 and summed nitrate score 12.89 +/- 10.36. Ultrasound detected CCA IMT 0.90 +/- 0.24 mm, with increased value in 67.2% and presence of carotid plaques in 27.1% of pts. We registered 14 events and 8.8% mortality rate. Multiple regression modelling showed bilateral carotid plaque presence as a predictor of total events. Viability index and CCA IMT have been found as independent death predictors. CONCLUSIONS Myocardial perfusion viability index and CCA IMT are predictors, independently associated with prognosis of patients referred for CABG.
The Gut Microbiota and Irritable Bowel Syndrome: Friend or Foe?

Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper.
Inadequate visualization and reporting of ventricular function from transthoracic echocardiography after cardiac surgery.

OBJECTIVES The purpose of this study was to determine the incidence of and risk factors for inadequate reporting of ventricular function from transthoracic echocardiography after cardiac surgery. DESIGN AND SETTING A retrospective study of cardiac surgical patients at 1 university hospital. PATIENTS The first 300 consecutive patients who had transthoracic echocardiogram within the first 7 days after cardiac surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The primary outcomes for this study were inadequate visualization of the left ventricle, the right ventricle, or both ventricles. Analysis of data from 300 patients identified inadequate imaging of the left ventricle in 50 (17%) cases, inadequate imaging of the right ventricle in 112 (37%) cases, inadequate imaging of both ventricles in 37 (12%) cases, and inadequate imaging of either the left or right ventricle in 125 (42%) cases. Increasing age, earlier postoperative day, male sex, and median sternotomy were associated with inadequate imaging. CONCLUSIONS Transthoracic imaging is often inadequate in patients who have undergone recent cardiac surgery. Patient and surgical characteristics influence reporting of right and left ventricular function.
Epidermal Growth Factor-Like Domain-Containing Protein 7 (EGFL7) Enhances EGF Receptor−AKT Signaling, Epithelial−Mesenchymal Transition, and Metastasis of Gastric Cancer Cells

Epidermal growth factor-like domain-containing protein 7 (EGFL7) is upregulated in human epithelial tumors and so is a potential biomarker for malignancy. Indeed, previous studies have shown that high EGFL7 expression promotes infiltration and metastasis of gastric carcinoma. The epithelial–mesenchymal transition (EMT) initiates the metastatic cascade and endows cancer cells with invasive and migratory capacity; however, it is not known if EGFL7 promotes metastasis by triggering EMT. We found that EGFL7 was overexpressed in multiple human gastric cancer (GC) cell lines and that overexpression promoted cell invasion and migration as revealed by scratch wound and transwell migration assays. Conversely, shRNA-mediated EGFL7 knockdown reduced invasion and migration. Furthermore, EGFL7-overexpressing cells grew into larger tumors and were more likely to metastasize to the liver compared to underexpressing CG cells following subcutaneous injection in mice. EGFL7 overexpression protected GC cell lines against anoikis, providing a plausible mechanism for this enhanced metastatic capacity. In excised human gastric tumors, expression of EGFL7 was positively correlated with expression levels of the mesenchymal marker vimentin and the EMT-associated transcription repressor Snail, and negatively correlated with expression of the epithelial cell marker E-cadherin. In GC cell lines, EGFL7 knockdown reversed morphological signs of EMT and decreased both vimentin and Snail expression. In addition, EGFL7 overexpression promoted EGF receptor (EGFR) and protein kinase B (AKT) phospho-activation, effects markedly suppressed by the EGFR tyrosine kinase inhibitor AG1478. Moreover, AG1478 also reduced the elevated invasive and migratory capacity of GC cell lines overexpressing EGFL7. Collectively, these results strongly suggest that EGFL7 promotes metastasis by activating EMT through an EGFR−AKT−Snail signaling pathway. Disruption of EGFL7−EGFR−AKT−Snail signaling may a promising therapeutic strategy for gastric cancer.
Globalization and Peace: Assessing New Directions in the Study of Trade and Conflict

`Globalization' has largely superseded the term `economic interdependence' to describe the rapidly growing links between nations, economies, and societies. The effects that the internationalization of the world system has on social equality, the environment, and economic growth are, however, still largely disputed. In this article, we discuss the literature that covers another intensively debated issue and which attempts to assess the relationship between trade and interstate conflict. Although liberal economists maintain that economic interdependence exerts an unconditionally pacifying influence on interstate relations, we show that the most recent formal work expects that trade will have a negligible and, in the perspective of one important model at least, even an amplifying effect on conflict. Much empirical work, by contrast, supports the claim that the relationship between trade and conflict is direct and not mitigated by contextual factors. We review the different controversies on the link between economic interdependence and militarized disputes and outline some major challenges that have not yet been adequately dealt with in the scientific study of war and peace.
Tier Two Interventions Implemented within the Context of a Tiered Prevention Framework

Despite a growing body of evidence demonstrating the value of Tier 1 and Tier 3 interventions, significantly less is known about Tier 2 level treatments when they are added within the context of a tiered continuum of support. The purpose of this article is to systematically review the existing research base for Tier 2 small group intervention studies conducted within a tiered prevention framework. Results indicated that few studies documented fidelity of Tier 7 implementation prior to the addition of Tier 2 interventions. Methods for identifying students to receive Tier 2 supports varied across investigations, but included teacher nomination, use of student data, and/or screening score results. More than half of the reviewed studies demonstrated use of the Behavior Intervention Program: Check-in/Check-out (BEP/CICO), although social skill instructional groups and academic instructional groups were also employed as Tier 2 interventions. Overall, positive results for reducing problem behavior were reported. In addition, school-based personnel implemented the Tier 2 intervention in nearly half of the investigations. Among studies that reported measures of social validity teacher and student perceptions of the treatments were largely positive. Implications for future research are evaluated using criteria from the Society for Prevention Research (Flay et al., 2005).
Expression of c‐myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer

Archival biopsy specimens from transitional cell bladder tumours (n=185) were analysed immunohistochemically for expression of c‐myc protein. The results were compared with compared with histopathological and clinical parameters and survival. Forty‐three per cent of the tumours were negative for c‐myc protein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c‐myc protein was detected in 35 per cent of tumours and nuclear opositivity was related to overexpression of c‐erb B‐2 (P=0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p<0.05). Cytoplasmic expression of c‐myc protein was related to histological grade (P=0.005), papillary status (P=0.007), the S‐phase fraction (P=0.008), the mitotic index (P=0.021), overexpression of epidermal growth factor receptor (P=0.045), and c‐erb B‐2 (P=0.17). Expression of c‐myc protein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T‐category (P<0.001), papillary status. (P=0.001), and S‐phase fraction (P=0.061). The results show that while c‐myc gene product participates in growth regulation of human bladder cancer cells, it has no independent prognostic significance.