Miracle-dz/UniFAR-FTUs huggingface dataset:
Degradation of the Basic Helix-Loop-Helix/Per-ARNT-Sim Homology Domain Dioxin Receptor Via the Ubiquitin/Proteasome Pathway*

The basic helix-loop-helix/Per-ARNT-Sim homology domain dioxin receptor (DR) translocates to the nucleus upon binding of aromatic hydrocarbon ligands typified by dioxin, whereupon it partners the Ah receptor nuclear translocator and initiates transcription. Concurrently, ligand binding down-regulates receptor levels via an unknown mechanism. In this study we show that receptor levels are dependent upon cellular compartmentalization, with entry into the nucleus leading to the rapid destruction of the DR. Ligand-induced DR translocation was bypassed by adding a heterologous nuclear localization signal to the DR, creating a constitutively nuclear form of the dioxin receptor (DRNLS). The DRNLS protein was shown to be unstable with a half-life of ≤1 h whether partnering ARNT or HSP90. Thus, the structural changes induced by ligand binding have no inherent effect on DR stability but are critical in transporting the receptor prior to degradation. The proteolytic pathway that degrades the nuclear receptor is suggested to involve ubiquitination as it was inhibited by the proteasome inhibitor MG132 or co-expression of DRNLS with the ubiquitin mutant UbK48R. Incubation of cells expressing DRNLS with the phosphatase inhibitor calyculin resulted in the rapid phosphorylation and ubiquitination of DRNLS, suggesting that a nuclear kinase is required to trigger receptor proteolysis. Overall, this study demonstrates a novel mechanism of proteolysis whereby the simple relocation of a transcription factor from cytoplasm to nucleus initiates its rapid destruction.
Impact of age and gender on in-hospital and late mortality after acute myocardial infarction: increased early risk in younger women: results from the French nation-wide USIC registries.

AIMS To determine whether sex differences of in-hospital and after-discharge mortality differ according to the age. METHODS AND RESULTS Data of 4347 consecutive patients hospitalized within 48 h of the onset of acute myocardial infarction (AMI) were analysed. Patients were classified according to median age (68 years): Group 1 (G1) (308 women, 30-67 years), G2 (1878 men, 30-67 years), G3 (860 women, 68-89 years), and G4 (1301 men, 68-89 years). In both age groups, women were older, had more frequent co-morbidities, lower rate of reperfusion therapy, and received less anti-platelet agents, beta-blockers, and statins than men. The overall 1-year mortality was higher in women (25% vs. 16% in men, P<0.0001). After adjustment, in-hospital mortality was higher only for the women in the younger age group. (G1 vs. G2: OR=2.2, 95%CI=1.3-3.8; G3 vs. G4: OR=1.1, 95%CI=the risk of death, after hospital discharge, was no longer related to gender in any age group. CONCLUSION The higher 1-year mortality following AMI in women is explained by the higher risk of death in young women during the first days of hospitalization. Further investigations are crucial to determine the cause in order to improve the chance of survival in younger women.
Grade Information and Grade Inflation: The Cornell Experiment

Grade inflation and high grade levels have been subjects of concern and public debate in recent decades. In the mid-1990s, Cornell University's Faculty Senate had a number of discussions about grade inflation and what might be done about it. In April 1996, the Faculty Senate voted to adopt a new grade reporting policy which had two parts: 1) the publication of course median grades on the Internet; and 2) the reporting of course median grades in students' transcripts. The policy change followed the determination of a university committee that "it is desirable for Cornell University to provide more information to the reader of a transcript and produce more meaningful letter grades. " It was hoped that "More accurate recognition of performance may encourage students to take courses in which the median grade is relatively low. " The median grade policy has remained to date only partially implemented: median grades have been reported online since 1998 but do not yet appear in transcripts. We evaluate the effect of the implemented policy on patterns of course choice and grade inflation. Specifically, we test two related hypotheses: First, all else being equal, the availability of online grade information will lead to increased enrollment into leniently graded courses. Second, high-ability students will be less attracted to the leniently graded courses than their peers. Building on these results we perform an exercise that identifies the extent to which the change in student behavior resulted in an increase in the university-wide mean grade.
The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation.

The HIF1A gene encodes the HIF-1alpha subunit of hypoxia-inducible factor 1, a transcription factor that is essential for cardiovascular development and systemic O2 homeostasis. HIF1A consists of 15 exons that are interrupted by introns at the same locations as in the mouse Hif1a gene, although sequences mediating alternative splicing and alternative translation initiation events in the mouse are not present in the human gene. Placement of introns differs between HIF1A and EPAS1, which encodes the human HIF-2alpha protein. Transcription of the HIF1A gene was initiated over a 15-nt region downstream of two SP1 sites. A 0.7-kb region of 5' flanking sequences functioned as a strong promoter in transient expression assays. Comparison of 0.8 kb of 5' flanking and 5' untranslated sequences from the HIF1A and Hif1a genes revealed 70% identity. The proximal 300 bp of 5' flanking sequences was 83% identical, including the SP1 sites and transcription initiation sites. These results suggest evolutionary selection for maintenance of HIF1A structure, function, and regulation.
Future Directions in Housing and Public Health: Findings From Europe With Broader Implications for Planners

Problem: Chronic diseases such as asthma are rising at alarming rates in the United States and worldwide. Housing environments play an important, underappreciated role in these trends. Purpose: In this article, we document the magnitude of the association between housing conditions and asthma and related respiratory symptoms, present examples of new systems for addressing adverse effects of housing on health, and discuss how planners might require or encourage such innovations. Methods: We use logistic regressions based on household survey data from seven European cities to show the magnitude of the association between housing conditions and noise annoyance and the exacerbation of asthma and related respiratory symptoms. To support our argument that new housing intervention systems show great promise for alleviating current housing-related health challenges, we offer several different examples of green building criteria that incorporate health measures. Results and conclusions: After taking into consideration individual-level characteristics, we found that respondents across a range of cities who were strongly annoyed by general neighborhood noise had twice the odds of a doctor-diagnosed asthma attack or related respiratory symptom than those not at all annoyed. Those strongly annoyed by traffic noise had 68% higher odds. Drainage problems at the housing unit were associated with 54% higher odds of experiencing respiratory symptoms, building structural problems with 27% higher odds, and a leaky roof with 35% higher odds. We identify healthy housing development, construction, and housing rehabilitation systems as promising initiatives for addressing the web of associations between housing and health. We suggest that funds such as Community Development Block Grants or housing trusts could subsidize such efforts, and various existing planning processes could incorporate health requirements or scoring criteria. Takeaway for practice: There is compelling evidence that housing conditions are associated with poor health. Planners should inform themselves about these and identify opportunities to incorporate health considerations into planning that affects housing. Research support: None.
[Visual acuty after trabeculectomy].

BACKGROUND/AIM In this study we compared the two groups of glaucoma patients who had underwent trabeculectomy, with or without intraoperative application of antimetabolite 5-Fluorouracile (5 FU). METHODS We followed up 50 glaucoma patients (group I) in a four-years period after trabeculectomy alone (antimetabolites were not applied), and 50 patients in whom antimetabolite 5 FU was applied (group II). We followed up intraocular pressure (IOP), visual acuity (VA), lens transparency, optic disc changes, visual fields (VF perimetry). The IOP at the time of the surgery, and the period of the treatment before the surgery were the important data for the follow-up. RESULTS The results that we got in the first group were: in 8 patients (16%) there was no change of VA, and of optic disc with a mild VF deterioration; in 18 patients (33%) the worsening of VA by 1 Snellen line (3 years after the surgery) with no change of the disc and a mild VF progressing; in 10 patients (20%) VA decreased by 2 Snellen lines with the progressive VF changes and cataract appearance, (cataract and VA worsening appeared mainly 3 years after the surgery); in 6 patients (12%) by 3 Snellen lines, and in 4 patients (8%) by 4 Snellen lines. In 4 patients (8%), the highest worsening of VA--(0.2) and the best (0.9) at the time of the surgery were observed. The VA ranging from 0.4-0.6 at the time of the surgery yielded the longest preservation of vision. In the group II (5 FU applied intra-operatively): in 5 patients (10%) there was no change of VA and of optic disc with a mild VF deterioration; in 20 patients (40%) the worsening of VA by 1 Snellen line, with no change of the disc and a mild VF progressing. In 14 patients (28%) VA decreased by 2 Snellen lines with the progressive VF changes and cataract appearance; in 7 patients (14%) by 3 Snellen lines, and in 4 patints (8%) by 4 Snellen lines. CONCLUSION All of the checked parameters were better in the group II of the patients, (5 FU applied intraoperatively). Also, in the group of the patients with the longest treatment before the surgery and with the good VA, and in the patients with the shorter treatment and with the bad VA, the quickest progression of the vision losts was observed. The best preservation of VA was recordered in the patients with a mild IOP, and in those who had not been treated more than 1 or 2 years with the drops before the surgery. The VA ranging from 0.4-0.6 at the time of the surgery allowed the longest preservation of vision.
Criteria for Comparing Economic Impact Models of Tourism

There are substantial differences between models of the economic impacts of tourism. Not only do the nature and precision of results vary, but data demands, complexity and underlying assumptions also differ. Often, it is not clear whether the models chosen are appropriate for the specific situation to which they are applied. The goal of this article is to provide an overview and evaluation of criteria for the selection of economic impact models. A literature review produced 52 potential criteria, subdivided into 10 groups. Based on an analysis of experts' opinions, the perceived importance of each criterion was determined and a set of essential criteria created. To illustrate the usage of these essential criteria, five models (export base, Keynesian, ad hoc, input–output and computable general equilibrium) were evaluated and compared based on their performance on these criteria. This paper builds on the existing literature by showing that it is possible to make a more informed choice among economic impact models of tourism.
Regulating Complementary Products: A Comparative Institutional Analysis

Optimal regulation, subject to informational constraints, is analyzed for industries for which production requires complementary inputs. An issue for regulatory policy is whether supply in these industries should be "bundled" or "unbundled. " Bundled supply calls for regulation of an integrated industry. Unbundled supply has each component regulated separately. A main result is that unbundling introduces into regulation an additional component of information cost that is similar to "double marginalization" in the monopoly pricing of complementary products. Unbundling may be advantageous if it allows sufficient competition in nonmonopoly services, but the information cost can exceed the benefits of competition.
An Intracellular Calcium Signal Activates p70 but Not p90 Ribosomal S6 Kinase in Liver Epithelial Cells*

In the rat liver epithelial cell lines GN4 and WB, angiotensin II (Ang II) activates the Gq class of regulatory G-proteins, increasing intracellular calcium, protein kinase C activity, and protein tyrosine phosphorylation. We compared the ability of Ang II and other compounds that increase intracellular calcium (i.e. the calcium ionophore A23187 and thapsigargin) or protein kinase C activity (the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) to activate p70 ribosomal S6 kinase (p70S6K) and p90 ribosomal S6 kinase (p90RSK). In GN4 cells, increasing intracellular calcium stimulated p70S6K activity in a rapamycin- and wortmannin- sensitive manner, but did not affect p90RSK activity. In contrast, 12-O-tetradecanoylphorbol-13-acetate strongly activated p90RSK but only weakly stimulated p70S6K. The ability of calcium to activate p70S6K was confirmed by blocking the A23187-dependent activation through chelation of extracellular calcium with EGTA; the effect of thapsigargin was inhibited by the cell permeant chelator bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM). Similarly, BAPTA-AM prevented the activation of p70S6K by Ang II, suggesting that this signal was largely calcium-dependent. In contrast, the Ang II-dependent activation of mitogen-activated protein kinase and p90RSK was not inhibited but was enhanced by BAPTA-AM. These results show that in GN4 cells, Ang II selectively activates p70S6K through effects on calcium, p90RSK through effects on protein kinase C. The activation of p70S6K by calcium stimuli or Ang II was independent of calmodulin but correlated well with the activation of the recently identified, nonreceptor calcium-dependent tyrosine kinase (CADTK)/PYK-2. Both calcium- and Ang II-dependent activation of p70S6K were attenuated by the tyrosine kinase inhibitor genistein, and activation of p70S6K was higher in GN4 than WB cells, correlating with the increased expression and activation of CADTK/PYK-2 in GN4 cells. In summary, these results demonstrate that intracellular calcium selectively activates p70S6K in GN4 cells, consistent with increased CADTK/PYK-2 signaling in these cells.
Predation Alters Relationships between Biodiversity and Temporal Stability

Ecologists disagree on how diversity affects stability. At the heart of the controversy is the relationship between diversity and population stability, with conflicting findings from both theoretical and empirical studies. To help reconcile these results, we propose that this relationship may depend on trophic complexity, such that positive relations tend to emerge in multitrophic but not single‐trophic communities. This hypothesis is based on the premise that stabilizing weak trophic interactions restrain population oscillations associated with strong trophic interactions in diverse multitrophic communities. We tested this hypothesis using simple freshwater bacterivorous protist communities differing in diversity with and without a predatory protist species. Coupling weak and strong trophic interactions reduced population temporal variability of the strong‐interacting species, supporting the stabilizing role of weak interactions. In keeping with our hypothesis, predation altered the overall effect of diversity on population temporal stability and, in particular, caused a reversal of the diversity‐stability relationship (negative without predators and positive with predators) for the strong‐interacting species. A similar role of predation was also observed when examining the relationship between diversity and temporal stability of community biomass. Together, these findings demonstrated strong interactive effects of trophic interactions and diversity on temporal stability of population and community properties.
Extended daclizumab monotherapy for rejection‐free survival in non‐adherent adolescent recipients of renal allografts

Abstract: Acute rejection episodes are almost inevitable in the face of immunosuppression non‐adherence and a known risk factor for developing chronic allograft nephropathy and accelerated graft loss. Daclizumab, a humanized monoclonal antibody directed against the alpha chain of the IL‐2 receptor, is an important advance for induction therapy in renal transplant immunosuppression, reducing early acute graft rejection without affecting the tolerability of standard immunosuppression, for both steroid‐based and steroid‐free immunosuppressive protocols, in children and adults. In the absence of depot immunosuppression for maintenance therapy, we explored extended daclizumab therapy as temporary maintenance immunosuppression for acute rejection prophylaxis in two patients with recalcitrant immunosuppression non‐adherence. Both patients had prior episodes of aggressive acute rejection associated with their non‐adherence but achieved stable and rejection‐free renal allograft function with daclizumab monotherapy in the presence of documented non‐adherence thus providing an effective bridge for up to 12 months until immunosuppression adherence was re‐established with ongoing psychosocial support. This report suggests that daclizumab monotherapy over an extended period of time during the period of non‐adherence in the post transplant period could be a rescue modality to avoid immune activation and thereby prevent acute rejection in the face of erratic maintenance immunosuppression.
Mapping Subsurface Geology in Sahara Using L-Band SAR: First Results From the ALOS/PALSAR Imaging Radar

Within the framework of Kyoto & Carbon Initiative of the Japanese Space Agency (JAXA), we used JERS-1 and ALOS/PALSAR radar images to build regional and continental scale mosaics of Sahara. The unique capability of L-band SAR to map subsurface structures in arid areas revealed previously unknown geological features: craters, faults, paleo-rivers. The latter are of particular interest for water resource detection in arid regions.
IMPROVING THE PROVISION OF FINANCIAL SERVICES TO MICRO-ENTREPRENEURS, EMERGING FARMERS AND AGRIBUSINESS: LESSONS FROM KWAZULU-NATAL

Three development finance institutions (DFIs) which operate in KwaZulu-Natal (KZN) province were assessed in 1996/97 to see how they could improve financial viability and outreach to emerging farmers, agribusiness and micro-entrepreneurs. Improved service quality and emphasis on mobilising savings would help clients and enable the DFIs to diversify their portfolios. Better access to branches and lower loan approval times (improved screening and administrative procedures) could also lower client transaction costs. Charging a suitable interest rate spread is necessary but not sufficient for lenders to achieve subsidy independence. Reducing arrears through stricter loan contract enforcement (borrower accountability for loan repayment, lower collateral specific risks, secure and transferable collateral) will also promote financial viability. Providing both savings and loan services together would reduce borrower access costs, and allow savings to serve as a form of collateral and borrower information for lenders.
Commodity price stabilization in imperfect or cartelized markets

Most studies of commodity price stabilization assume that all agents behave competitively. However, many commodities suitable for stockpiling are produced by countries with a significant share of the world market, and commodity agreements themselves often result in cartelization of the market. The paper explores the consequences of market power for the choice of storage rule and the degree of price stabilization. It finds that with linear demand, dominant producers choose more stable prices than under perfect competition and price stability increases with their market share. With constant elastic demand the competitive degree of price stabilization is achieved.
Overcoming the identity crisis in human resources

Purpose – Dissects “partnership” and “strategy” in the context of the work of HR. Design/methodology/approach – Shows that it is not that HR is unclear about its role in the corporate world but that the exhortations of commentators are too simplistic. Findings – Reveals that the continuing and continual debate over HR's role is a product of the role conflict inherent in the HR profession itself. Emphasizes the importance of balancing the needs of employees with those of managers, which is at the heart of HR. Practical implications – Contends that divorcing the operational from the strategic denies the strategic the field intelligence that informs and proves strategy. The disparate, mundane operational tasks associated with HR specialists aggregate into the field intelligence that feeds their strategic perspective. Severing the connection between HR strategy and HR operations impoverishes any kind of strategic input available to HR. Social implications – Advances the view that managers and employees see th.
Mitogen-Activated Protein Kinase-Activated Protein Kinases 2 and 3 Regulate SERCA2a Expression and Fiber Type Composition To Modulate Skeletal Muscle and Cardiomyocyte Function

ABSTRACT The mitogen-activated protein kinase (MAPK)-activated protein kinases 2 and 3 (MK2/3) represent protein kinases downstream of the p38 MAPK. Using MK2/3 double-knockout (MK2/3−/−) mice, we analyzed the role of MK2/3 in cross-striated muscle by transcriptome and proteome analyses and by histology. We demonstrated enhanced expression of the slow oxidative skeletal muscle myofiber gene program, including the peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α). Using reporter gene and electrophoretic gel mobility shift assays, we demonstrated that MK2 catalytic activity directly regulated the promoters of the fast fiber-specific myosin heavy-chain IId/x and the slow fiber-specific sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) gene. Elevated SERCA2a gene expression caused by a decreased ratio of transcription factor Egr-1 to Sp1 was associated with accelerated relaxation and enhanced contractility in MK2/3−/− cardiomyocytes, concomitant with improved force parameters in MK2/3−/− soleus muscle. These results link MK2/3 to the regulation of calcium dynamics and identify enzymatic activity of MK2/3 as a critical factor for modulating cross-striated muscle function by generating a unique muscle phenotype exhibiting both reduced fatigability and enhanced force in MK2/3−/− mice. Hence, the p38-MK2/3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function.