Miracle-dz/UniFAR-FTUs huggingface dataset:
The Novel PIAS-like Protein hZimp10 Enhances Smad Transcriptional Activity*

Transforming growth factor β (TGF-β) plays critical roles in the control of cell proliferation, differentiation, and apoptosis. Smad proteins are substrates of the TGF-β type I receptor and are responsible for transducing receptor signals to target genes in the nucleus. The PIAS (protein inhibitor of activated STAT) proteins were originally identified as transcriptional co-regulators of the JAK-STAT pathway. Subsequently, cross-talk between the PIAS proteins and other signaling pathways has been shown to be involved in various cellular processes. Importantly, PIAS proteins modulate TGF-β signaling by regulating the transcriptional activity of Smad3. In this study we tested whether hZimp10, a novel PIAS-like protein, acts as other PIAS proteins to regulate Smad3-mediated transcription. We show that expression of exogenous hZimp10 enhances the transcriptional activity of Smad3, which appears to be Smad4-dependent and responsive to TGF-β induction. Furthermore, knockdown of endogenous hZimp10 reduced the transcriptional activity of Smad3. A protein-protein interaction between Smad3 and Smad4 with hZimp10 was identified in glutathione S-transferase-pulldown and co-immunoprecipitation assays. The Miz domain of hZimp10 and the MH2 domains of Smad3 and Smad4 were mapped as the regions responsible for binding. Results from immunostaining assays further demonstrated that Smad3, Smad4, and hZimp10 co-localize within cell nuclei. Finally, we demonstrated that Smad3/4-mediated transcription is significantly impaired in response to TGF-β induction in Zimp10 null (zimp10-/-) embryonic fibroblasts. Taken together, these results provide the first line of evidence to demonstrate a role for Zimp10 in regulating the TGF-β/Smad signaling pathway.
Passive vertical integration and strategic delegation

With backward acquisitions in their efficient supplier, downstream firms profitably internalize the effects of their actions on their rivals' sales, while upstream competition is also relaxed. Downstream prices increase with passive, yet decrease with controlling acquisition. Passive acquisition is profitable when controlling acquisition is not. Downstream acquirers strategically abstain from vertical control, thus delegating commitment to the supplier, and with it high input prices, allowing them to charge high downstream prices. The effects of passive backward acquisition are reinforced with the acquisition by several downstream firms in the efficient supplier. The results are sustained when suppliers charge two-part tariffs.
Enhancer-mediated role for polyomavirus middle T/small T in DNA replication

A major role for polyomavirus middle T/small T antigens in viral DNA synthesis was uncovered by examining the replication of middle T/small T-deficient mutants (hr-t mutants). hr-t mutants in the A2 genetic background showed a 16- to 100-fold defect in genome accumulation relative to the wild type when infections were carried out in exponentially growing NIH 3T3 cells in medium supplemented with low levels of serum (< 2.0%). A proportional decrease in the level of viral early transcripts was also seen. The replication defect of the hr-t mutants was partially overcome in the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The defect was also alleviated by a duplication encompassing the alpha core enhancer domain that contains binding sites for the transcriptional activators PEA1/AP-1 and PEA3/c-ets. Such a duplication is present in all naturally occurring hr-t mutants and absent in the A2 strain. The effects of 12-O-tetradecanoylphorbol-13-acetate and alpha core duplication were additive but did not fully complement the absence of middle T/small T. In mixed infection competition experiments with two hr-t mutants, a genome that carried an alpha core duplication had a replication advantage (up to 17-fold) over a genome without duplication. This result demonstrates that one effect of the duplication is exerted directly at the level of DNA replication. The advantage of the duplication-bearing genome was established during the earliest stages of replication and was not further amplified in later rounds of replication. In the presence of middle T/small T, both genomes replicated to high levels and the advantage of the duplication-bearing genome was eliminated. On the basis of these results, we propose that factors that bind the alpha core domain (presumably PEA1 and PEA3) are present in limiting amounts in exponentially growing NIH 3T3 cells and play a crucial role in polyomavirus DNA replication. We further suggest that middle T and/or small T stimulates viral DNA replication by activating these factors. The fact that all middle T-/small T-defective hr-t mutants have evolved to contain enhancer duplications that encompass the PEA1 and PEA3 binding sites in the alpha core domain and partially restore their replication defect (A. Amalfitano, M. C. Chen, and M. Fluck, unpublished data) provides an adequate explanation for the fact that the importance of the role of the middle T and/or small T function in DNA replication has not been recognized previously. Much evidence is available in support of separate elements of this model. (ABSTRACT TRUNCATED AT 400 WORDS)
Large cell/anaplastic medulloblastomas and medullomyoblastomas: clinicopathological and genetic features.

OBJECT Medulloblastoma is the most common malignant central nervous system neoplasm found in children. A distinct variant designated large cell/anaplastic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course. The authors report on their examination of the clinicopathological and genetic features of seven such cases encountered at their institution. METHODS Eighty cases of medulloblastomas were reviewed and seven (8.8%) of these were believed to fit the histological and immunohistochemical criteria for LC/A medulloblastoma. In three cases (43%) either desmoplastic or classic medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor was found within the setting of medullomyoblastoma. Fluorescence in situ hybridization was used in six of the seven cases to characterize the presence of isochromosome 17q, deletion of chromosome 22q (a deletion characteristically found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The patients' clinical histories revealed CSF dissemination in all cases and lymph node metastasis in one case. Isochromosome 17q was found in five (83%) of six cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%), and amplification of c-myc was found in three tumors (50%). No 22q deletions were encountered. CONCLUSIONS A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.
Brain imaging in neonatal hypoglycaemia

Magnetic resonance imaging studies in two cases of neonatal hypoglycaemia showed cortical and white matter cerebral damage that was most obvious in the occipital lobes. Both cases showed oedema in the parieto-occipital cortex and underlying white matter in the acute phase, with profound atrophy of these regions in the chronic phase. These findings support those of pathological studies which suggest that hypoglycaemia induces cerebral damage by a mechanism separate from the effects of cerebral hypoxia–ischaemia caused by secondary seizures.
Early Failure of Dialysis Access among the Elderly in the Era of Fistula First.

BACKGROUND AND OBJECTIVES Recent evidence indicates that fistula maturation and patency may be compromised in the elderly dialysis population compared with younger patients. The objective of this study was to characterize the short-term outcomes of arteriovenous fistulas and arteriovenous grafts for hemodialysis access in the Medicare population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a retrospective cohort study performed using Medicare Part A and B claims data from 2006 through 2011. The study population included 16,464 dialysis-dependent patients age ≥66 years undergoing arteriovenous fistula and arteriovenous graft creation. The primary outcome measure was incidence of repeat fistula/graft creation and tunneled catheter placements in the 12 months after arteriovenous fistula and graft creation. RESULTS In the 12 months postindex fistula/graft, the mortality in the fistula group was 28.2% versus 29.9% in the graft group (P=0.03). A repeat fistula/graft creation was required in 26.9% of patients in the fistula group and 16.7% in the graft group (P<0.001). There was no significant difference in the proportion of patients who required a tunneled hemodialysis catheter in the 12 months after an index fistula creation (fistula 28.4% versus graft 27.3%, P=0.19). In the index fistula group, 44.4% of patients required a repeat fistula/graft creation and/or a tunneled catheter, compared with 33.7% in the graft group (P<0.001). At 365 days after the index fistula/graft, the repeat fistula/graft/catheter-free survival was 39.7% in the fistula group versus 46.0% in the graft group (P<0.001). Index fistula was associated with a higher risk of loss of repeat fistula/graft/catheter-free survival with an odds ratio of 1.19 (95% confidence interval, 1.13 to 1.24). CONCLUSIONS Fistulas were associated with a somewhat lower mortality than grafts in the first 12 months after creation. However, the incidence of repeat fistula/graft creation and tunneled catheter placement is substantially higher in the first 12 months after fistula creation compared with grafts. One-year repeat fistula/graft/catheter-free survival is lower after fistula creation than grafts.
Quality of life of family caregivers of cancer survivors

Cancer affects not only the quality of life (QOL) of individuals with the disease but also that of their family members and close friends. The impact on various aspects of the family caregivers' QOL is significant throughout the trajectory of the illness. The authors reviewed literature on the QOL of family caregivers at the acute and middle‐ to long‐term survivorship phases as well as the bereavement phase.
Effects of Magnesium Administration on Brain Edema and Blood–Brain Barrier Breakdown After Experimental Traumatic Brain Injury in Rats

In this study, we examined the effects of magnesium sulfate administration on brain edema and blood–brain barrier breakdown after experimental traumatic brain injury in rats. Seventy-one adult male Sprague-Dawley rats were anesthetized, and experimental closed head trauma was induced by allowing a 450-g weight to fall from a 2-m height onto a metallic disk fixed to the intact skull. Sixty-eight surviving rats were randomly assigned to receive an intraperitoneal bolus of either 750 &mgr;mol/kg magnesium sulfate (group 4; n = 30) or 1 mL of saline (group 2; n = 30) 30 minutes after induction of traumatic brain injury; 39 nontraumatized animals received saline (group 1; n = 21) or magnesium sulfate (group 3; n = 18) with an identical protocol of administration. Brain water content and brain tissue specific gravity, as indicators of brain edema, were measured 24 hours after traumatic brain injury. Blood–brain barrier integrity was evaluated quantitatively 24 hours after injury by spectrophotometric assay of Evans blue dye extravasations. In the magnesium-treated injured group, brain water content was significantly reduced (left hemisphere: group 2, 83.2 ± 0.8; group 4, 78.4 ± 0.7 [P < .05]; right hemisphere: group 2, 83.1 ± 0.7; group 4, 78.4 ± 0.5. [P < .05]) and brain tissue specific gravity was significantly increased (left hemisphere: group 2, 1.0391 ± 0.0008; group 4, 1.0437 ± 0.001 [P < .05]; right hemisphere, group 2, 1.0384 ± 0.001; group 4, 1.0442 ± 0.005 [P < .05]) compared with the saline-treated injured group. Evans blue dye content in the brain tissue was significantly decreased in the magnesium-treated injured group (left hemisphere: group 2, 0.0204 ± 0.03; group 4, 0.0013 ± 0.0002 [P < .05]; right hemisphere: group 2, 0.0064 ± 0.0009; group 4, 0.0013 ± 0.0003 [P < .05]) compared with the saline-treated injured group. The findings of the present study support that beneficial effects of magnesium sulfate exist after severe traumatic brain injury in rats. These results also indicate that a blood–brain barrier permeability defect occurs after this model of diffuse traumatic brain injury, and magnesium seems to attenuate this defect.
Nucleolus in apoptosis-induced mouse preimplantation embryos

Apoptosis may occur in early embryos in which the execution of essential developmental events has failed. Thus the initiation of the apoptotic mechanism may be related to activation of the embryonic genome. In this way, developmentally incompetent cells or whole embryos are eliminated. It is likely that some link exists between failed resumption of rRNA synthesis and the incidence of apoptosis in cleaving embryos. In this context, decreased developmental potential in cleaving nucleotransferred embryos is consistent with cell loss, and very likely due to programmed cell death. The effects of apoptosis inducers on cleaving embryos have not been characterised in comparable detail to that in the case of somatic cells. Early embryos provide a very good model for study of these processes because of the specificity of rRNA transcription resumption after fertilization. In our experiments three apoptosis inducers (staurosporin 10 mM, actinomycin D 0.05 mg/ml and camptothecin 0.1 mg/ml) were used in a culture medium for 15 h at the 4-cell stage (day 2) of mouse embryos, followed by further development in a pure culture medium until fixation on days 3, 4 and 5. In staurosporin-induced embryos, light microscopy immunostaining of nucleolar proteins (fibrillarin, Nopp140, protein B23) did not reveal changes in nucleolar morphology on day 3. On days 4 and 5, more compact (roundish) nucleoli (in comparison with controls) were observed. The embryos treated with camptothecin displayed a similar staining pattern to those with staurosporin at each day. In actinomycin-D-treated embryos, marked changes in nucleolar appearance were visible as early as day 3. These changes in nucleolar morphology consisted of loss of the reticulation appearance and fragmentation of nucleoli. In addition to nucleolar changes, significantly decreased cell proliferation was observed. The induced embryos did not reach the blastocyst stage. The number of blastomeres was decreased, and staining with Hoechst 33342 revealed a significant percentage of apoptotic nuclei (condensed/fragmented nuclei) from day 4.
Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain

ABSTRACT Background: Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain. Methods: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or ‘rolled over’ for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients ≥ 75 years) or 300–400 mg once daily (patients < 75 years). Results: A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator. Conclusions: Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.
Asset Price Booms and Busts, and Expectations: Theory and Empirical Evidence

This dissertation adds to the literature on asset price booms and busts in three self-contained chapters. The first chapter presents a novel explanation for the existence of stock price booms and busts, based on subjective expectations about future stock prices. This explanation is in line with survey evidence on the expectations of representative U.S. households and allows to match the behavior of postwar U.S. stock prices. The second chapter shows that, in the presence of belief-driven booms and busts, a financial transaction tax may lead to higher stock price volatility by increasing the likelihood of booms and busts. The third chapter analyzes the efficiency of investment professionals’ expectations and documents key differences to the expectations of representative households.
The Political Economy of Performance Standards: Automotive Industrial Policy in Comparative Historical Perspective

ABSTRACT A substantial body of literature holds that industrial policies work best when their beneficiaries are subject to demanding performance standards. By conditioning access to their low-cost loans and lucrative markets on foreign sales and local content, for example, East Asian officials forced their manufacturers to improve quality, cut costs, and develop linkages to allied industries – that generated jobs and foreign exchange revenues of their own – in the so-called miracle years. But the politics of performance standards are themselves unclear. Why are they more common in some countries than others? Are they more likely to be imposed by autocratic than democratic regimes? And, if so, why? I address these questions by examining cross-national data on export and local content requirements in the auto industry in 1980; find that they all but presupposed autocracy in labour-surplus – but not labour-scarce – countries; explore the interactions of political regimes, productive assets, and performance standards in South Korea in particular; and discuss their theoretical and methodological implications. The results not only imply that efforts to build new comparative advantages over the long run by means of performance standards that put existing comparative advantages at risk in the short run are unlikely to succeed in labour-surplus democracies but, in so doing, speak to the merits of ‘middle-N’ methods and typologies that try to reconcile the at times competing goals of generality and historical detail in cross-national research.
SUBSTANCE USE PROBLEMS REPORTED BY COLLEGE STUDENTS: COMBINED MARIJUANA AND ALCOHOL USE VERSUS ALCOHOL-ONLY USE

This study examines the relationships among selected demographic characteristics, alcohol use only, alcohol plus marijuana use and substance-use related problems. Data are from 409 randomly selected undergraduate college students attending a large urban university. Poly-substance users were more likely than alcohol only users to be younger and experience all substance-use related problems studied. The relationship between poly-substance use and increased substance use-associated problems was also identified when controlling for other common predictors of substance use problems.
Glutathione depletion enforces the mitochondrial permeability transition and causes cell death in HL60 cells that overexpress Bcl‐2

Bcl‐2, a protein that blocks apoptosis by inhibiting the mitochondrial permeability transition (MPT) and release of cytochrome c appears to affect normal mitochondrial function by altering electron flow and increasing rates of reactive oxygen species (ROS) production. In this study, we show that glutathione (GSH) depletion induces ROS production and selective toxicity in HL60 cells that overexpress Bcl‐2 compared with neomycin vector control cells. Toxicity was mediated by the MPT because it was blocked with the adenine nucleotide translocator (ANT) ligand bongkrekic acid and resulted in mitochondrial cytochrome c release, caspase 3 activation, and DNA fragmentation, indicating the involvement of an apoptotic pathway. Respiratory chain inhibitors stigmatellin and antimycin A, which inhibit Qo and Qi sites of respiratory chain complex III, respectively, blocked ROS production, preserved the redox state of protein thiols, and prevented cell death. These results indicate that in the absence of GSH, endogenous ROS generated at respiratory complex III induce MPT independently of Bcl‐2. The results also suggest a new model for MPT in which the central pore protein ANT is regulated by adenine nucleotide and the activity of mitochondrial respiratory complex III.
Delay-dependent stability analysis for neutral systems with equivalent delays

This paper is concerned with the delay-dependent stability and robust stability for uncertain neutral systems with equivalent delays. Through constructing a new form of Lyapunov-Krasovskii functional, using slack matrices and integral inequality, the delay-dependent stability criteria are derived in terms of linear matrix inequalities. Numerical examples are given to illustrate the improvement on the conservatism of the delay bound over some existing results.
External cephalic version for breech presentation at term.

BACKGROUND Management of breech presentation is controversial, particularly in regard to manipulation of the position of the fetus by external cephalic version (ECV). ECV may reduce the number of breech presentations and caesarean sections, but there also have been reports of complications with the procedure. OBJECTIVES The objective of this review was to assess the effects of ECV at or near term on measures of pregnancy outcome. Methods of facilitating ECV, and ECV before term are reviewed separately. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Trials Register (7 August 2012). SELECTION CRITERIA Randomised trials of ECV at or near term (with or without tocolysis) compared with no attempt at ECV in women with breech presentation. DATA COLLECTION AND ANALYSIS Two review authors assessed eligibility and trial quality, and extracted the data. MAIN RESULTS We included seven studies. The pooled data from these studies show a statistically significant and clinically meaningful reduction in non-cephalic birth (seven trials, 1245 women; risk ratio (RR) 0.46, 95% confidence interval (CI) 0.31 to 0.66; and caesarean section (seven trials, 1245 women; RR 0.63, 95% CI 0.44 to 0.90) when ECV was attempted. There were no significant differences in the incidence of Apgar score ratings below seven at one minute (two trials, 108 women; RR 0.95, 95% CI 0.47 to 1.89) or five minutes (four trials, 368 women; RR 0.76, 95% CI 0.32 to 1.77), low umbilical artery pH levels (one trial, 52 women; RR 0.65, 95% CI 0.17 to 2.44), neonatal admission (one trial, 52 women; RR 0.36, 95% CI 0.04 to 3.24), perinatal death (six trials, 1053 women; RR 0.34, 95% CI 0.05 to 2.12), nor time from enrolment to delivery (2 trials, 256 women; weighted mean difference -0.25 days, 95% CI -2.81 to 2.31). AUTHORS' CONCLUSIONS Attempting cephalic version at term reduces the chance of non-cephalic births and caesarean section. There is not enough evidence from randomised trials to assess complications of external cephalic version at term. Large observational studies suggest that complications are rare.