Miracle-dz/UniFAR-FTUs huggingface dataset:
Basis for the Checkpoint Signal Specificity That Regulates Chk1 and Cds1 Protein Kinases

ABSTRACT Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1 is required to prevent mitosis when DNA is damaged by ionizing radiation (IR), whereas either kinase is sufficient to prevent mitosis when DNA replication is inhibited by hydroxyurea (HU). Checkpoint Rad proteins are required for IR-induced phosphorylation of Chk1 and HU-induced activation of Cds1. IR activates Cds1 only during the DNA synthesis (S) phase, whereas HU induces Chk1 phosphorylation only in cds1 mutants. Here, we investigate the basis of the checkpoint signal specificity of Chk1 phosphorylation and Cds1 activation. We show that IR fails to induce Chk1 phosphorylation in HU-arrested cells. Release from the HU arrest following IR causes substantial Chk1 phosphorylation. These and other data indicate that Cds1 prevents Chk1 phosphorylation in HU-arrested cells, which suggests that Cds1 actively suppresses a repair process that leads to Chk1 phosphorylation. Cds1 becomes more highly concentrated in the nucleus only during the S phase of the cell cycle. This finding correlates with S-phase specificity of IR-induced activation of Cds1. However, constitutive nuclear localization of Cds1 does not enhance IR-induced activation of Cds1. This result suggests that Cds1 activation requires DNA structures or protein activities that are present only during S phase. These findings help to explain how Chk1 and Cds1 respond to different checkpoint signals.
Research Summary: How Does Globalization Affect Developing Countries?

Over the past two decades, the world economy has become increasingly integrated as flows of goods, labor, and capital across countries have expanded rapidly. Although there is a general belief that globalization has important long-term benefits through its impacts on growth and productivity, a large body of literature has focused on the distributional impacts of globalization, especially its effects on labor markets, and the short-term adjustment costs associated with countries’ integration into the world economy. This article reviews the most recent IMF research on two important channels of globalization—emigration and trade—and focuses primarily on their impacts in developing countries.
miR-29b induces SOCS-1 expression by promoter demethylation and negatively regulates migration of multiple myeloma and endothelial cells

Epigenetic silencing of tumor suppressor genes frequently occurs and may account for their inactivation in cancer cells. We previously demonstrated that miR-29b is a tumor suppressor microRNA (miRNA) that targets de novo DNA methyltransferases and reduces the global DNA methylation of multiple myeloma (MM) cells. Here, we provide evidence that epigenetic activity of miR-29b leads to promoter demethylation of suppressor of cytokine signaling-1 (SOCS-1), a hypermethylated tumor suppressor gene. Enforced expression of synthetic miR-29b mimics in MM cell lines resulted in SOCS-1 gene promoter demethylation, as assessed by Sequenom MassARRAY EpiTYPER analysis, and SOCS-1 protein upregulation. miR-29b-induced SOCS-1 demethylation was associated with reduced STAT3 phosphorylation and impaired NFκB activity. Downregulation of VEGF-A and IL-8 mRNAs could be detected in MM cells transfected with miR-29b mimics as well as in endothelial (HUVEC) or stromal (HS-5) cells treated with conditioned medium from miR-29b-transfected MM cells. Notably, enforced expression of miR-29b mimics increased adhesion of MM cells to HS-5 and reduced migration of both MM and HUVEC cells. These findings suggest that miR-29b is a negative regulator of either MM or endothelial cell migration. Finally, the proteasome inhibitor bortezomib, which induces the expression of miR-29b, decreased global DNA methylation by a miR-29b-dependent mechanism and induced SOCS-1 promoter demethylation and protein upregulation. In conclusion, our data indicate that miR-29b is endowed with epigenetic activity and mediates previously unknown functions of bortezomib in MM cells.
The ExsA Protein of Bacillus cereus Is Required for Assembly of Coat and Exosporium onto the Spore Surface

ABSTRACT The outermost layer of spores of the Bacillus cereus family is a loose structure known as the exosporium. Spores of a library of Tn917-LTV1 transposon insertion mutants of B. cereus ATCC 10876 were partitioned into hexadecane; a less hydrophobic mutant that was isolated contained an insertion in the exsA promoter region. ExsA is the equivalent of SafA (YrbA) of Bacillus subtilis, which is also implicated in spore coat assembly; the gene organizations around both are identical, and both proteins contain a very conserved N-terminal cortex-binding domain of ca. 50 residues, although the rest of the sequence is much less conserved. In particular, unlike SafA, the ExsA protein contains multiple tandem oligopeptide repeats and is therefore likely to have an extended structure. The exsA gene is expressed in the mother cell during sporulation. Spores of an exsA mutant are extremely permeable to lysozyme and are blocked in late stages of germination, which require coat-associated functions. Two mutants expressing differently truncated versions of ExsA were constructed, and they showed the same gross defects in the attachment of exosporium and spore coat layers. The protein profile of the residual exosporium harvested from spores of the three mutants—two expressing truncated proteins and the mutant with the original transposon insertion in the promoter region—showed some differences from the wild type and from each other, but the major exosporium glycoproteins were retained. The exsA gene is extremely important for the normal assembly and anchoring of both the spore coat and exosporium layers in spores of B. cereus.
The Effects of an Exercise Program on Anxiety Levels and Metabolic Functions in Patients With Anxiety Disorders

The purpose of this study was to evaluate the effects of a home-based (HB) exercise program on anxiety levels and metabolic functions in patients with anxiety disorders in Taiwan. Purposive sampling was used to recruit 86 participants for this randomized, experimental study. Participants were asked to complete a pretest before the 3-month exercise program, a posttest at 1 week, and a follow-up test at 3 months after the exercise program. Study measures included four Self-Report Scales and biophysical assessments to collect and assess personal data, lifestyle behaviors, anxiety levels, and metabolic control functions. Of the 86 study participants, 83 completed the posttest and the 3-month follow-up test, including 41 in the experimental group and 42 in the control group. Participants in the experimental group showed significant improvements in body mass index, high-density lipoprotein cholesterol levels, and the level of moderate exercise after the program relative to the control group, as analyzed by generalized estimating equations mixed-model repeated measures. State and trait anxiety levels were also significantly improved from pretest to follow-up test in the experimental group. Finally, the prevalence of metabolic syndrome declined for participants in the experimental group. The HB exercise program produced positive effects on the metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders. Health providers should consider using similar HB exercise programs to help improve the mental and physical health of patients with anxiety disorders in their communities.
Invisible and at risk: STDs among young adult sexual minority women in the United States.

CONTEXT Sexual minority women are not adequately assessed by national STD surveillance systems, and research regarding STD burden in nationally representative samples of such women is rare. Moreover, few studies have assessed STD risk exclusively among young adult women. METHODS Wave 4 (2007-2008) data from the National Longitudinal Study of Adolescent Health on 7,296 females aged 24-32 were used to examine the relationship between sexual orientation and receipt of an STD diagnosis in the past year. Multivariate logistic regression analyses used two measures of sexual orientation: sexual identity and gender of sex partners. RESULTS Eighty percent of women considered themselves straight; 16% mostly straight; and 4% bisexual, mostly gay or gay. Eighty-five percent had had only male partners, while 7% had had one female partner, and 8% two or more female partners. In unadjusted models, women who identified themselves as mostly straight were more likely than straight women to have had an STD (odds ratio, 1.4); mostly gay or gay women were at lower risk (0.4). Women who had had two or more female partners had a higher STD risk than did women who had had only male partners (1.7). Adjusting for social and demographic characteristics did not substantially alter these results; however, the associations between sexual identity, gender of sex partners and STD diagnosis were eliminated after adjustment for sexual behaviors (e.g., having had anal sex). CONCLUSIONS Sexual identity, gender of sex partners and sexual behaviors should be taken into account in assessments of women's STD risk.
The neurotrophin receptors, trkB and p75, differentially regulate motor axonal regeneration.

Neurotrophic factors that support neuronal survival are implicated in axonal regeneration after injury. Specifically, a strong role for BDNF in motor axonal regeneration has been suggested based on its pattern of expression after injury, as well as the expression of its receptors, trkB and p75. Despite considerable in vitro evidence, which demonstrate specific and distinct physiological responses elicited following trkB and p75 activation, relatively little is known about the function of these receptors in vivo. To investigate the roles of the trkB and p75 receptors in motor axonal regeneration, we have used a tibial (TIB)- common peroneal (CP) cross suture paradigm in p75 homozygous (-/-) knockout mice, trkB heterozygous (+/-) knockout mice, as well as in their wild-type controls. Contralateral intact TIB motoneurons, and axotomized TIB motoneurons that regenerated their axons 10 mm into the CP distal nerve stump were identified by fluorescent retrograde tracers and counted in the T11-L1 spinal segments. Regeneration was evaluated 2, 3, 4, 6, and 8 weeks after nerve repair. Compared to wild-type animals, there are significantly fewer intact TIB motoneurons in p75 (-/-), but not trkB (+/-) mice. The number of motoneurons that regenerated their axons was significantly increased in the p75 (-/-) knockout mice, but significantly attenuated in the trkB (+/-) mice compared to wild-type controls. These results suggest that p75 is important for motoneuronal survival during development, but p75 expression after injury serves to inhibit motor axonal regeneration. In addition, full expression of trkB is critical for complete axonal regeneration to proceed.
The Role of Financial Slack, Employee Creative Self-Efficacy and Learning Orientation in Innovation and Organizational Performance

Organizational performance development and financial slack have drawn extensive attention in management research. Recent studies have indicated that financial slack has a positive effect on innovation outcomes and organizational performance. However, some other studies have proposed adverse effects. This paper aimed to explore the causal linkages between employee creative self-efficacy, learning orientation, financial slack, innovation outcomes and organizational performance. It also examined the influence of innovation performance and creative self-efficacy as mediating variables in the connection between learning orientation and organizational performance. By doing so, we used a structural equation modelling (SEM) method to test the model using data from 267 small medium enterprises (SMEs) in Vietnam. The findings illustrated that SMEs had not utilized financial slack to invest in innovation activities and improve firm performance. Furthermore, the results indicated that learning orientation had both direct and indirect impacts on innovation and firm performance. It is worth noting that employee creative self-efficacy had a positive effect on innovation performance. The findings also verified a statistically significant association between innovation and organizational performance. Finally, the results provided some managerial implications to stimulate employees to work creatively and improve innovation outcomes for sustainable development.
The relationship between nursing leadership and patient outcomes: a systematic review.

AIM The purpose of this review was to describe findings of a systematic review of studies that examine the relationship between nursing leadership and patient outcomes. BACKGROUND With recent attention directed to the creation of safer practice environments for patients, nursing leadership is called on to advance this agenda within organizations. However, surprisingly little is known about the actual association between nursing leadership and patient outcomes. METHODS Published English-only research articles that examined formal nursing leadership and patient outcomes were selected from computerized databases and manual searches. Data extraction and methodological quality assessment were completed for the final seven quantitative research articles. RESULTS Evidence of significant associations between positive leadership behaviours, styles or practices and increased patient satisfaction and reduced adverse events were found. Findings relating leadership to patient mortality rates were inconclusive. CONCLUSION The findings of this review suggest that an emphasis on developing transformational nursing leadership is an important organizational strategy to improve patient outcomes.
How, When, and Why Do Physicians Choose Careers in Academic Medicine? A Literature Review

Purpose Medicine has different pathways in which physicians pursue their vocation. Clinical practice, research, and academia are common paths. The authors examined the literature to identify research-based factors influencing physicians to choose a career path in academic medicine. Method In the fall of 2006, the authors searched the PubMed database from 1960 to 2006 using the term career academic medicine. Review of articles resulted in the identification of nine themes relating to academic medicine career paths. The authors summarized the important and relevant articles to capture what the literature contributed as a whole to the larger question, “How, when, and why do physicians choose an academic career in medicine? ” Results A synthesis of articles revealed that (1) values are essential to understanding the decision to enter a career in academic medicine, (2) factors associated with academic medicine career choice include research-oriented programs, gender, and mentors and role models, (3) an obstacle to pursuing this career path is loss of interest in academic careers during residency as residents learn about factors associated with academic careers in medicine, and (4) debt may be a barrier to choosing an academic career in medicine for some individuals in some specialties. Conclusions Despite the study findings, the larger question (stated above) remains essentially unanswered in the literature. The authors propose a call to action by various professional groups and organizations to use rigorous and complex research efforts to seek answers to this very important question.
A survey on shortcut tree routing protocols for Zibee based wireless networks

Zigbee is a wireless networking standard which is broadly used in applications such as remote control and sensor applications. They are suited for operation in coarse radio environments and in isolated locations. In Zigbee based wireless networks, various routing protocols such as reactive routing protocols and Zigbee Tree Routing (ZTR) protocol were initially proposed. Among them, ZTR is widely used, since it neither makes use of routing table nor requires route discovery overhead and it can be used among devices that are limited in their resources. But it suffers from a serious limitation, (i.e) in ZTR the packets are routed through fundamental tree topology. Therefore, ZTR do not provide optimal routing paths. In order to surpass the limitation of ZTR, Shortcut Tree Routing (STR) protocols were proposed. These protocols find the optimal next hop node that has the smallest remaining hop counts to the destination. Hence, this paper presents a survey on various STR protocols and also compares the performance of network using STR under two cases. The first case is the one in which the nodes are static and the second is the one in which the nodes are mobile. The simulations are done using ns2 and the performance of STR is evaluated and analyzed using metrics such as average residual energy and Packet Delivery Ratio (PDR).
Dominant/recessive behavior in the expression of molecular information: Self-assembly of inorganic macrocyclic architectures containing coordinatively unsaturated ligands

The polytopic ligand 1 contains three different metal ion binding subunits forming two substructures that code for the self-assembly of two different coordination structures (helicate and grid type) under metal ion complexation. Reaction with Cu(II) and Zn(II) ions generates the coordinatively unsaturated architectures 8 and 9 resulting from the formation of two double helicate arrangements. Their crystal structure has been determined by x-ray diffraction. These results show that the double helical motif is expressed at the expense of the grid type one, indicating the dominant/recessive behavior of the system. Together with earlier studies on the linear combination and crossover processing schemes, the dominant/recessive generation of 8 and 9 completes the demonstration of principle of the modes of multiple expression of molecular information in a multicode programmed chemical system.
Myths about fundamental indexing1

ABSTRACT Fundamental indexing starts from the observation that in a value-weighted portfolio, any overpricing affects the stock’s portfolio weight upward and its typical return downward, and vice versa; but on average the ‘drag’ on the portfolio’s expected return caused by this negative interaction is avoided if weights are based instead on accounting-based instruments for true value. We find that the drag effect is statistically and economically unimportant. Our empirical work avoids regression-based alphas, which are flawed by demonstrable instabilities in the exposures.
Up‐regulation of ephrin‐a1 during melanoma progression

Ephrin‐A1, formerly called B61, is a new melanoma growth factor; it is angiogenic and chemoattractant for endothelial cells. EPH‐A2, or ECK (a receptor for ephrin‐A1), is ectopically expressed in most melanoma cell lines; the pathology where this expression is first manifested and the possible role of the receptor in tumor progression are unknown. To determine these, we studied the expression of this ligand and receptor in biopsies of benign and malignant melanocytic lesions. EPH‐A2 was not detected in normal melanocytes, benign compound nevi or advanced melanomas, though it was found in 2 of 9 biopsies of malignant melanoma in situ. Ephrin‐A1 was present in occasional early lesions and in advanced primary melanomas (43%) and metastatic melanomas (67%). Expression of ephrin‐A1 was induced in melanoma cells by pro‐inflammatory cytokines. Our findings are consistent with 2 possible roles for ephrin‐A1 in melanoma development: it may promote melanocytic cell growth or survival and induce vascularization in advanced melanomas. Both effects may be potentiated by inflammatory responses. Our data are consistent with earlier observations that an inflammatory infiltrate is associated with poor prognosis in thin primary melanomas. Int. J. Cancer (Pred. Oncol.) 84:494–501, 1999. © 1999 Wiley‐Liss, Inc.
Phase II Trial of Dacarbazine and Thalidomide for the Treatment of Metastatic Melanoma

Objective: This phase II study evaluated the efficacy and tolerability of dacarbazine in combination with thalidomide in metastatic melanoma patients. Methods: Chemotherapy-naïve patients with histologically confirmed, measurable metastatic melanoma with no evidence of brain metastases and adequate hematologic and organ function received dacarbazine (1,000 mg/m2 i.v. every 3 weeks) and thalidomide (starting dose of 200 mg/day orally at night, escalated every 3 weeks) as tolerated. The primary endpoint was objective tumor response, evaluated after every 3 cycles of treatment. Fifteen patients, age range 29–77 years, were accrued for this study. All had stage IV disease (1 M1a, 5 M1b, 9 M1c). Nine patients had had no prior adjuvant therapy, 6 had received prior immunotherapy. The median number of cycles was 5 (range 1–18), with 8 patients receiving ≥3 cycles. The median thalidomide dose administered was 200 mg/day with a maximum tolerated dose of 400 mg/day. Results: Of the 13 patients evaluable for response, 1 patient had a partial response, 3 patients had stable disease and 9 patients had progressive disease. No complete responses were seen. Two patients were not evaluable for response: 1 withdrew due to toxicity and 1 died of unrelated causes. Grade III neutropenia, thrombocytopenia and nausea were attributed to dacarbazine. Grade III/IV constipation, peripheral neuropathy, fatigue, edema and rash were attributed to thalidomide. Conclusion: The addition of thalidomide to dacarbazine in metastatic melanoma yielded activity insufficient to proceed with additional trials of this combination. Thalidomide dose escalation beyond 200 mg/day was limited by unacceptable toxicity. Therefore, this combination does not warrant further investigation.
The Long-Term Use of Statins Is Associated with a Decreased Incidence of Adenomatous Colon Polyps

Background/Aims: Studies have suggested that statins may protect against colorectal cancer (CRC), but it is not clear whether that protection results from effects on established adenomatous polyps (APs) or from preventing the development of new APs. We have conducted a retrospective, cohort study to explore how the long-term use of statins influences the development of new APs. Methods: We reviewed endoscopy and pathology databases to identify patients with histologically verified APs, all of which were removed during an index colonoscopy, and who had a follow-up colonoscopy 3–5 years later. Patients were categorized as users or nonusers of statins by review of their medical and pharmacy records, and the characteristics of APs found on follow-up colonoscopy in the 2 groups was compared. Results: We identified 2,626 patients (84% men, mean age 62.2 years) with APs removed during an index colonoscopy. Of 1,688 patients (35%) who used statins continuously, 583 had an AP found on follow-up colonoscopy, compared to 477 of 938 patients (51%) who did not use statins continuously [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43–0.60; p < 0.01]. Statin use was associated with a smaller mean number of polyps (2.6 vs. 3.1; p = 0.002), a smaller mean polyp size (7.1 vs. 7.9 mm; p = 0.03) and a significant reduction in the incidence of advanced APs (OR 0.74, 95% CI 0.52–0.96; p = 0.03). Conclusions: In patients with APs removed colonoscopically, long-term statin usage is associated with a decreased incidence of new and advanced APs. This suggests that statins may protect against CRC by reducing the development of new APs.