Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells

DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6–4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis.
Determination of Phytoestrogen Composition in Soybean Cultivars in Serbia

The growing clinical interest and use of soybean-based food products and extracts to increase dietary phytoestrogen intake have led to medical interest in the precise determination of the phytoestrogen composition of soybean products. We have analyzed the composition of these compounds in 20 domestic and introduced varieties of genetically non-modified soybean genotypes grown under the same agroecological conditions. The isoflavone content of soybeans cultivated in this region of Serbia has not been previously reported. The assays were performed, after extraction with methanol-water (8:2, v/v), by C18 reversed phase high-performance liquid chromatography coupled with photodiode array detection. The total phytoestrogen concentration was found to be between 2.24 and 3.79 mg g−1 dry bean weight. The total concentration of daidzein and its derivatives ranged from 0.96 to 1.82 mg g−1, total glyciteines from 0.34-0.53 mg g−1, and all genistein derivatives from 0.86-1.67 mg g−1 dry bean weight. Given the high biological potency of phytoestrogens and their metabolic conversion products, our data suggest that phytoestrogen content screening could be a useful tool in the selection of soybean genotypes with improved health promoting characteristics.
The Relation between Turnover Intention, High Performance Work Practices (HPWPs), and Organisational Commitment: A Study among Private Hospital Nurses in Malaysia

Turnover poses a serious threat in healthcare settings. The scarcity of healthcare professionals and particularly nurses is highlighted as one of the biggest obstacles to achieving health system efficiency and effectiveness. As such, healthcare administrators need to search for ways to retain qualified and competent nurses. This study provides a framework depicting how organisational commitment can mediate the relationship between three forms of high performance work practices (HPWPs) (performance appraisal, compensation, and employment security) and turnover intention. Statistical analysis using partial least squares (PLS) conducted on questionnaire data from 639 staff nurses working in private hospitals in Malaysia revealed that two forms of HPWPs (performance appraisal and compensation) lead to reduced turnover intention via organisational commitment. Finally, the implications of our findings, limitations, and future research suggestions are discussed.
The Evolving Role of the State Education Agency in the Era of ESSA and Trump: Past, Present, and Uncertain Future

Under the Every Student Succeeds Act (ESSA) of 2015, states have considerably more flexibility and authority in K-12 education than they had under the previous federal education law, No Child Left Behind (NCLB). The Trump administration and the Republican Congress, meanwhile, moved in 2017 to further loosen federal accountability rules and give states even more control over their school systems. With this increased power for states comes the increased responsibility to support the improvement of educational outcomes for every student. Leaders at the helm of state education agencies (SEAs) find themselves in a moment of both great change and great opportunity, as many agencies move away from a predominant focus on compliance with federal regulations and programmatically dictated uses of funds, and toward a broader focus on supporting districts and schools. For many advocates of low-performing students, it is also a moment of potential peril if states fail to embrace their new responsibilities or weaken their commitment to improving educational opportunity and outcomes.
3′-Deoxy-3′-18F-Fluorothymidine PET and MRI for Early Survival Predictions in Patients with Recurrent Malignant Glioma Treated with Bevacizumab

With the dismal prognosis for malignant glioma patients, survival predictions become key elements in patient management. This study compares the value of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET and MRI for early outcome predictions in patients with recurrent malignant glioma on bevacizumab therapy. Methods: Thirty patients treated with bevacizumab combination therapy underwent 18F-FLT PET immediately before and at 2 and 6 wk after the start of treatment. A metabolic treatment response was defined as a decrease of equal to or greater than 25% in tumor 18F-FLT uptake (standardized uptake values) from baseline using receiver-operating-characteristic analysis. MRI treatment response was assessed at 6 wk according to the Response Assessment in Neurooncology criteria. 18F-FLT responses at different times were compared with MRI response and correlated with progression-free survival and overall survival using Kaplan–Meier analysis. Metabolic response based on 18F-FLT was further compared with other outcome predictors using Cox regression analysis. Results: Early and late changes in tumor 18F-FLT uptake were more predictive of overall survival than MRI criteria (P < 0.001 and P = 0.01, respectively). 18F-FLT uptake changes were also predictive of progression-free survival (P < 0.001). The median overall survival for responders was 3.3 times longer than for nonresponders based on 18F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk 18F-FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%), whereas MRI identified 9 responders (7 partial response, 2 complete response, 31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7 of the 8 discrepant cases between MRI and PET, 18F-FLT PET was able to demonstrate response earlier than MRI. Among various outcome predictors, multivariate analysis identified 18F-FLT PET changes at 6 wk as the strongest independent survival predictor (P < 0.001; hazard ratio, 10.051). Conclusion: Changes in tumor 18F-FLT uptake were highly predictive of progression-free and overall survival in patients with recurrent malignant glioma on bevacizumab therapy. 18F-FLT PET seems to be more predictive than MRI for early treatment response.
Evidence that the Campylobacter fetus sap Locus Is an Ancient Genomic Constituent with Origins before Mammals and Reptiles Diverged

ABSTRACT Campylobacter fetus bacteria, isolated from both mammals and reptiles, may be either subsp. fetus or subsp.venerealis and either serotype A or serotype B. Surface layer proteins, expressed and secreted by genes in the saplocus, play an important role in C. fetus virulence. To assess whether the sap locus represents a pathogenicity island and to gain further insights into C. fetusevolution, we examined several C. fetus genes in 18 isolates. All of the isolates had 5 to 9 sapA orsapB homologs. One strain (85-387) possessed bothsapA and sapB homologs, suggesting a recombinational event in the sap locus betweensapA and sapB strains. When we amplified and analyzed nucleotide sequences from portions of housekeeping generecA (501 bp) and sapD (450 bp), a part of the 6-kb sap invertible element, the phylogenies of the genes were highly parallel. Among the 15 isolates from mammals, serotype A and serotype B strains generally had consistent positions. The fact that the serotype A C. fetus subsp. fetus and subsp. venerealis strains were on the same branch suggests that their differentiation occurred after the type A-type B split. Isolates from mammals and reptiles formed two distinct tight phylogenetic clusters that were well separated. Sequence analysis of 16S rRNA showed that the reptile strains form a distinct phylotype between mammalian C. fetus and Campylobacter hyointestinalis. The phylogenies and sequence results showing that sapD and recA have similar G + C contents and substitution rates suggest that the sap locus is not a pathogenicity island but rather is an ancient constituent of the C. fetus genome, integral to its biology.
The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group.

We analysed the incidence of amenorrhoea and its association with outcome in a cohort of 1127 premenopausal women with breast cancer randomized to International Trial V (formerly Ludwig V). For 552 patients without axillary lymph node involvement, one course of perioperative cytotoxic drugs was compared with no-adjuvant chemotherapy. For 575 patients with node-positive disease, a single course of cytotoxic chemotherapy was compared with a prolonged treatment (6 or 7 courses). Amenorrhoea was defined as having no menstrual bleeding for a 3-month interval within the first 9 months after surgery. Amenorrhoea was observed in 21% of the 199 patients with node-negative breast cancer who received no adjuvant therapy, 31% of the 353 node-negative patients who had a single course of cytotoxic therapy, 31% of the 188 patients with node-positive disease who had the same short-duration therapy, and 68% of the 387 node-positive patients who had a prolonged adjuvant therapy. Amenorrhoea was associated with an increased disease-free survival (DFS) only in the patients with prolonged cytotoxic therapy: 4-year DFS % (+/- s.e.) was 68% +/- 3% vs. 61% +/- 5% for the amenorrhoea and the no-amenorrhoea groups, respectively, (p = 0.05). In contrast, the comparison between prolonged therapy and one single course among node-positive patients showed a much larger treatment effect (4-year DFS 66% vs. 38%, p less than 0.0001). We conclude that although cytotoxics-induced amenorrhoea is associated with a better outcome, it is unlikely that this form of endocrine manipulation is the main mechanism of response to adjuvant systemic chemotherapy.
End-stage lung disease: CT findings in 61 patients.

PURPOSE To determine whether the cause of end-stage lung disease could be determined on the basis of pattern and distribution of abnormalities at computed tomography (CT). MATERIALS AND METHODS The CT scans from 61 consecutive patients with end-stage lung disease were independently assessed by two observers without knowledge of clinical or pathologic data. End-stage lung disease was defined by the presence of honeycombing, extensive cystic changes, or conglomerate fibrosis. The observers listed the three most likely diagnoses and recorded the degree of confidence in the first-choice diagnosis on a three-point scale. RESULTS The observers made a correct first-choice diagnosis in an average of 87% of cases. A correct first-choice diagnosis was made most often in silicosis (100%), Langerhans cell histiocytosis (100%), asbestosis (90%), usual interstitial pneumonia (88%), extrinsic allergic alveolitis (87%), and sarcoidosis (83%). There was good agreement between the two observers on the first-choice diagnosis (kappa statistic, 0.89). CONCLUSION The pattern and distribution of abnormalities in end-stage lung disease are determined by the underlying cause. In most cases, a specific diagnosis can be made on the basis of the CT findings.
Special Education Teachers' Response to Consistent Changes in Curriculum Standards

This research explored how the changing standards have influenced special education teachers’ efforts to meet the needs of their students, and the teachers’ perceptions of the consistent changes in standards. A narrative, qualitative design was used, which involved eight participant interviews. In each interview, the participants answered questions pertaining to their level of comfort teaching the Common Core Standards and Georgia Standards of Excellence, whether or not they received professional development on the standards, and what they think of the new standards. Currently, there is a paucity of research regarding teacher’s perspectives on curriculum standards, and this research project fills the gap. Thesis Mentor: ___________________________ Dr. Meca Williams-Johnson Honors Director: __________________________ Dr. Steven Engel April 2018 College of Education University Honors Program Georgia Southern University Changing Standards and Special Education 3 Acknowledgements I would like to extend a depth of gratitude to Dr. Meca Williams-Johnson, without your mentorship, this project would not have been possible. I am grateful for the critical eye that you have brought to this research, as well as all of the encouragement and support I have received over the past two years. I would also like to extend a special thanks to the teachers who participated in this study. Without your willingness to help and flexibility in scheduling, this project would not have been possible. Thank you for allowing me to come into your classroom and talking with you. These interviews and their implications have not only helped me with this project, but in my journey in becoming a special education teacher. Finally, I wish to thank my family and friends for supporting me through all of the highs and lows that came with completing this project. Your support has helped me reach this point. Changing Standards and Special Education 4
Changes in the precursor frequencies of IL-4 and IFN-gamma secreting CD4+ cells correlate with resolution of lesions in murine cutaneous leishmaniasis.

Limiting dilution analysis was used to estimate the frequency of clonogenic Ag-specific CD4+ T lymphocytes in draining lymph nodes of mice over the course of infection with Leishmania major, and to measure the production of IL-2, IL-3, IL-4, IFN-gamma, and TNF by the resultant clones. Infection of both genetically susceptible BALB/c ("non-healer") and resistant C57BL/6 ("healer") mice resulted in at least a fourfold increase in the frequency (to about 0.3%) and at least a 10-fold increase in the total number of lymph node CD4+ cells that formed clones when cultured with L. major Ag in vitro. At 1 wk after infection, the majority of clones from BALB/c mice secreted IL-4 (precursor frequency 0.15%) and fewer secreted IFN-gamma (0.05%); this pattern remained constant for at least 8 wk after infection. In C57BL/6 mice, however, a high precursor frequency of IL-4-secreting clones was measured in the first 1 to 2 wk when the mice had lesions, but resolution of infection was associated with a decrease in the frequency of IL-4-secreting clones (from 0.13% at 2 wk to 0.03% at 4 wk) and an increase in the frequency of IFN-gamma-secreting clones (from 0.08% to 0.22%). At all stages of infection, most clones from either mouse strain secreted IL-3 and very few secreted TNF. Analysis of PCR-amplified cDNA from draining lymph nodes of infected mice also revealed that IL-4 and IFN-gamma mRNA were expressed in both mouse strains early in infection. IL-4 mRNA was the major species at 2 and 6 wk after infection in BALB/c mice, but declined relative to IFN-gamma mRNA over this time in C57BL/6 lymph nodes. Precursor frequency estimates of lymphokine-secreting CD4+ cells in draining lymph nodes therefore correlated with lymphokine expression patterns in vivo. Analysis of a panel of individual short term clones derived from mice 1 wk after infection revealed marked heterogeneity in lymphokine production patterns. In BALB/c mice, 49% secreted IL-4 without IFN-gamma, 18% secreted IFN-gamma without IL-4, and 14% secreted both IL-4 and IFN-gamma. Similarly in C57BL/6 mice, 39% secreted IL-4, 20% secreted IFN-gamma, and 17% secreted both lymphokines. Many of the clones also produced IL-3 and/or IL-2. Together the data suggest that both IL-4 and IFN-gamma are synthesized early in infection of susceptible and resistant mice as assessed by mRNA and precursor frequency analyses. (ABSTRACT TRUNCATED AT 400 WORDS)
Changes in the expression of ion channels, connexins and Ca2+‐handling proteins in the sino‐atrial node during postnatal development

There are important postnatal changes in the sino‐atrial node (SAN), the pacemaker of the heart. Compared with the neonate, the adult has a slower intrinsic heart rate and a longer SAN action potential. These changes may be due to differences in ion channel expression. Consequently, we investigated postnatal developmental changes in the expression of ion channels and Ca2+‐handling proteins in the SAN to see whether this is indeed the case. Using quantitative PCR, in situ hybridization and immunohistochemistry, we investigated the expression of ion channels, Ca2+‐handling proteins and connexins in the SAN from neonatal (2–7 days of age) and adult (∼6 months of age) New Zealand White rabbits. The spontaneous beating rate of adult SAN preparations was 21% slower than that of neonatal preparations. During postnatal development, quantitative PCR revealed a significant decline in the SAN of the following mRNAs: HCN4 (major isoform responsible for If), NaV1.5 (responsible for INa), CaV1.3 (in part responsible for ICa,L) and NCX1 (responsible for inward INaCa). These declines could be responsible for the slowing of the pacemaker during postnatal development. There was a significant decline during development in mRNA for delayed rectifier K+ channel subunits (KV1.5, responsible for IK,ur, KVLQT1 and minK, responsible for IK,s, and ERG, responsible for IK,r) and this could explain the prolongation of the action potential. In situ hybridization confirmed the changes observed by quantitative PCR. In addition, immunohistochemistry revealed hypertrophy of nodal cells during postnatal development. Moreover, there were complex changes in the expression of Ca2+‐handling proteins with age. In summary, there are significant postnatal changes in the expression of ion channels and Ca2+‐handling proteins in the SAN that could explain the established changes in heart rate and action potential duration that occur during normal development.
In vitro model of microglial deramification: Ramified microglia transform into amoeboid phagocytes following addition of brain cell membranes to microglia‐astrocyte cocultures

Changes in the morphology of ramified microglia are a common feature in brain pathology and culminate in the appearance of small, rounded, microglia‐derived phagocytes in the presence of neural debris. Here, we explored the effect of adding brain cell membranes on the morphology of αMβ2‐integrin (CD11b/CD18, CR3) positive microglia cultured on a confluent astrocyte substrate as an in vitro model of deramification. Addition of brain membranes led to a loss of microglial ramification, with full transformation to small, rounded, macrophages at 20–40 μg/ml. Time course studies showed a rapid response, with first effects at 1–3 hours, and full transformation at 24–48 hours. Removal of cell membranes and exchange of the culture medium led to a similarly rapid process of reramification. Comparison of cell membranes from different tissues at 20 μg/ml showed strong transforming effect for the brain, more moderate for kidney and liver, and very weak for spleen and skeletal muscle. Fluorescent labeling of brain membranes revealed uptake by almost all rounded macrophages, by a subpopulation of glial fibrillary acidic protein (GFAP)‐positive astrocytes, but not by ramified microglia. Phagocytosis of inert fluorobeads did not lead to a transformation into macrophages but their phagocytosis was inhibited by brain membranes, pointing to a saturable uptake mechanism. In summary, addition of brain cell membranes and their phagocytosis leads to a rapid and reversible loss of ramification. The differences in transforming activity from different tissues and the absence of effect from phagocytosed fluorobeads suggest, however, the need for a second stimulus following the phagocytosis of cell debris. J. Neurosci. Res. 64:508–522, 2001. © 2001 Wiley‐Liss, Inc.
Developing a Model for Sustainable Hotels in Northern Cyprus

The purpose of this work is to develop a sustainable hotel building model (SHBM) that will allow for the measurement of sustainability in determining what conditions are most ideal for hotels in Northern Cyprus. This research method is based on the synthesis of international sustainable building assessment criteria from the Leadership in Energy and Environmental Design (LEED) and the localization of these criteria in Northern Cyprus. Thus, this article proposes an SHBM, which is especially localized for Northern Cyprus that can be used for new hotel buildings’ design and construction and renovations of existing buildings as well as to measure their sustainability regarding environmental, economic and socio-cultural aspects. To serve this purpose, various methods of measurement of sustainability and green certificates (both qualitative and quantitative), global in scale were studied, which provided the basis for the development of the SHBM and local conditions of Northern Cyprus. Six hotels of differing sizes were studied in order to understand localized situation, conditions and priorities. The results of this study suggest that to have a more sustainable hotel in the aimed context, hotels of different scales (based on bed capacity and classification) must be evaluated adopting the SHBM model to achieve a better result for the sustainability of large-scale as well as small-scale hotels. In addition, this model helps the tourism industry and the hotel sector of Northern Cyprus benefit from sustainability in terms of environmental, economic and sociocultural aspects, which consequently help the local community in several ways.