Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Potential mRNA Biomarkers in Peripheral Blood Lymphocytes for Human Exposure to Ionizing Radiation

Abstract Amundson, S. A. , Do, K. T. , Shahab, S. , Bittner, M. , Meltzer, P., Trent, J. and Fornace, A. J., Jr. Identification of Potential mRNA Biomarkers in Peripheral Blood Lymphocytes for Human Exposure to Ionizing Radiation. Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfactory. Using cDNA microarray hybridization to discover new potential biomarkers, we have identified genes expressed at increased levels in human peripheral blood lymphocytes after ex vivo irradiation. We recently used this technique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666–3672, 1999). The present set of radiation markers in peripheral blood lymphocytes was identified 24 h after treatment, and while the magnitude of mRNA induction generally decreased over time, many markers were still significantly elevated up to 72 h after irradiation. In all donors, the most highly responsive gene identified was DDB2, which codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known as CIP1/WAF1) and XPC showed a linear dose–response relationship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less linearity at earlier or later times. These results suggest that relative levels of gene expression in peripheral blood cells may provide estimates of environmental radiation exposures.
Raf-Induced Cell Cycle Progression in Human TF-1 Hematopoietic Cells

Ras/Raf/MEK/ERK is a crucial pathway regulating cell cycle progression, apoptosis, and drug resistance. The Ras oncogene is frequently mutated in human cancer, which can result in the activation of the downstream Raf/MEK/ERK cascade leading to cell cycle progression in the absence of a growth stimulus. Raf-induced proliferation has been observed in hematopoietic cells. However, the mechanisms by which Raf affects cell cycle progression are not well described. To investigate the importance of Raf/MEK/ERK signaling in human hematopoietic cell growth, the effects of three different Raf genes, A-Raf, B-Raf and Raf-1, on cell cycle progression and regulatory gene expression were examined in TF-1 cells transformed to grow in response to b-estradiol-regulated DRaf:ER genes. Raf activation increased the expression of cyclin A, cyclin D, cyclin E, and p21Cip1, which are associated with G1 progression. Activated DRaf-1:ER and DA-Raf:ER but not DB-Raf:ER increased Cdk2 and Cdk4 kinase activity. The regulatory role of p16Ink4a, a potent Cdk4 kinase inhibitor, on the kinase activity of Cdk2 and Cdk4 was also examined. Raf induced p16Ink4a suppressor but this did not eliminate Cdk4 kinase activity. These results indicate that human hematopoietic cells transformed to grow in response to activated Raf can be used to elucidate the mechanisms by which various cell cycle regulatory molecules effect cell cycle progression. Furthermore, the differences that the various Raf isoforms have on Cdk4 activity and other cell cycle regulatory molecules can be determined in these cells. Key Words: Cell cycle, Raf, p21Cip1, p27Kip1, Cyclins, Cdks, Hematopoietic cells
The Neurovirulence of the DA and GDVII Strains of Theiler’s Virus Correlates with Their Ability To Infect Cultured Neurons

ABSTRACT The strains of Theiler’s murine encephalomyelitis virus, a picornavirus, are divided into two groups according to their neurovirulence after intracerebral inoculation. The highly virulent GDVII strain causes an acute, fatal encephalomyelitis, whereas the DA strain causes a mild encephalomyelitis followed by a chronic inflammatory demyelinating disease associated with viral persistence. Studies with recombinant viruses showed that the capsid plays the major role in determining these phenotypes. However, the molecular basis for the effect of the capsid on neurovirulence is still unknown. In this paper, we describe a large difference in the patterns of infection of primary neuron cultures by the GDVII and DA strains. Close to 90% of the neurons were infected 12 h after inoculation with the GDVII strain, and the cytopathic effect was complete 24 h postinoculation. In contrast, with the DA strain, viral antigens were not detected in neurons until 24 h postinoculation. Infected neurons accounted for only 2% of the total number of neurons, even 6 days after inoculation. No cytopathic effect was visible, and the cultures could be kept for the same length of time as the noninfected controls. Because the neurovirulence of the GDVII strain has been mapped to the capsid, we examined the role of the capsid in this difference of phenotype. We showed, using recombinant viruses, that the capsid was indeed responsible for the pattern of infection observed in vitro, most likely through its role in viral entry. Thus, the levels of neurovirulence of the GDVII and DA strains correlate with their abilities to infect cultured neurons, and this ability is controlled by the capsid.
Computer science at school/CS teacher education

In an international study, experts reflected on their national state of computer science education in school, and the associated situation and education of computer science teachers. While these situations are shaped by local circumstances, they are also shaped by changes in the discipline. The results of the study showed a number of recurrent themes and patterns such as curriculum difficulties, training and support for teachers, as well as the understanding (e.g. computer science vs. information technology) and relevance of computer science. The study also draws attention to initiatives that are being undertaken at the local and international levels to solve these problems. Finally, the study points out trends which are -- according to the experts asked -- likely to occur within the next few years.
EEAS reloaded: recommendations for the 2013 review

The original Council Decision establishing the European External Action Service (EEAS) in 2010, called for a review of the organisation and functioning of the EEAS by mid-2013. This CEPS Commentary argues that the review process will offer a formal opportunity to address some of the Service's weaknesses and to give a new impetus to its further development. In particular, it urges stakeholders to go beyond a review of organisational matters and also look into the Service’s overall contribution to attaining the objectives of the EU’s foreign policy, into its cooperation with the member states’ diplomatic services, the services of the European Commission, the Council General Secretariat and the European Parliament. Four sets of recommendations are put forward.
Impact of macroeconomic events on shanghai stock exchange

In this study we investigate the impact of macroeconomic events (i.e. 2000 dot-com bubble, 2008 Global financial crisis and 2015 announcement of RNB consideration in the SDR basket) on returns of Shanghai Stock Exchange Composite Index for 2000 dot com bubble (t +- 30 days as the event window), 2008 Global financial crisis (t +- 60 days as the event window) and 2015 stock market crash in China aided by announcement of RNB getting listed in the basket of currencies i.e. in SDR (t +- 60 days as the event window) by applying event study technique for quantifying Average Abnormal Returns and Cumulative Average Abnormal Returns and test for statistical significance of the obtained results. We find that the Returns of Shanghai Stock Exchange Composite Index responded negatively to the events implying that Chinese stock market was negatively affected by all three events considered but varying in the degree of their impact owing to the extent of impact on the economy of China as a whole. The results of the study provide insights to potential investors, fund managers and policymakers to take an informed decision whether to invest in Shanghai Stock Exchange if such events would reoccur in future.
Somatization and the recognition of depression and anxiety in primary care.

OBJECTIVE The authors examined the effect of patients' style of clinical presentation on primary care physicians' recognition of depression and anxiety. METHOD The subjects were 685 patients attending family medicine clinics on self-initiated visits. They completed structured interviews assessing presenting complaints, self-report measures of symptoms and hypochondriacal worry, the Diagnostic Interview Schedule (DIS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Physician recognition was determined by notation of any psychiatric condition in the medical chart over the ensuing 12 months. RESULTS The authors identified three progressively more persistent forms of somatic presentations, labeled "initial," "facultative," and "true" somatization. Of 215 patients with CES-D scores of 16 or higher, 80% made somatized presentations; of 75 patients with DIS-diagnosed major depression or anxiety disorder, 76% made somatic presentations. Among patients with DIS major depression or anxiety disorder, somatization reduced physician recognition from 77%, for psychosocial presenters, to 22%, for true somatizers. The same pattern was found for patients with high CES-D scores. In logistic regression models education, seriousness of concurrent medical illness, hypochondriacal worry, and number of lifetime medically unexplained symptoms each increased the likelihood of recognition, while somatized presentations decreased the rate of recognition. CONCLUSIONS While physician recognition of psychiatric distress in primary care varied widely with different criteria for recognition, the same pattern of reduction of recognition with increasing level of somatization was found for all criteria. In contrast, hypochondriacal worry and medically unexplained somatic symptoms increased the rate of recognition.
The evolution and role of mitochondrial fusion and fission in aging and disease

Mitochondria contain their own genetic material and evolved from prokaryotic ancestors some two billion years ago. They are the main source of the cell’s energy supply and are involved in such important processes as apoptosis, mitochondrial diseases and aging. Mitochondria display a complex dynamical behavior involving cycles of fusion and fission, the function of which is as yet unknown. We recently proposed a concise theory that explains: (i) why fusion and fission have evolved, (ii) how these processes relate to the accumulation of mitochondrial mutants during aging, and (iii) why mtDNA is located close to the respiration complexes where most radicals are generated. We also believe that this ‘organelle control’ theory may explain why mutations in mitochondrial tRNA genes are the most prevalent kind of defect associated with inherited human mitochondrial diseases, despite the fact that mt-tRNA genes account for only 5% of the mtDNA coding sequence.
Helicase Delivery and Activation by DnaA and TrfA Proteins during the Initiation of Replication of the Broad Host Range Plasmid RK2*

Specific binding of the plasmid-encoded protein, TrfA, and the Escherichia coli DnaA protein to the origin region (oriV) is required for the initiation of replication of the broad host range plasmid RK2. It has been shown that the DnaA protein which binds to DnaA boxes upstream of the TrfA-binding sites (iterons) cannot by itself form an open complex, but it enhances the formation of the open complex by TrfA (Konieczny, I., Doran, K. S., Helinski, D. R., Blasina, A. (1997) J. Biol. Chem. 272, 20173). In this study an in vitroreplication system is reconstituted from purified TrfA protein andE. coli proteins. With this system, a specific interaction between the DnaA and DnaB proteins is required for delivery of the helicase to the RK2 origin region. Although the DnaA protein directs the DnaB-DnaC complex to the plasmid replication origin, it cannot by itself activate the helicase. Both DnaA and TrfA proteins are required for DnaB-induced template unwinding. We propose that specific changes in the nucleoprotein structure mediated by TrfA result in a repositioning of the DnaB helicase within the open origin region and an activation of the DnaB protein for template unwinding.
Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis

Background African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients. Method We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls. Results White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus. Conclusions We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.
Dynamic patterns and ecological impacts of declining ocean pH in a high-resolution multi-year dataset

Increasing global concentrations of atmospheric CO2 are predicted to decrease ocean pH, with potentially severe impacts on marine food webs, but empirical data documenting ocean pH over time are limited. In a high-resolution dataset spanning 8 years, pH at a north-temperate coastal site declined with increasing atmospheric CO2 levels and varied substantially in response to biological processes and physical conditions that fluctuate over multiple time scales. Applying a method to link environmental change to species dynamics via multispecies Markov chain models reveals strong links between in situ benthic species dynamics and variation in ocean pH, with calcareous species generally performing more poorly than noncalcareous species in years with low pH. The models project the long-term consequences of these dynamic changes, which predict substantial shifts in the species dominating the habitat as a consequence of both direct effects of reduced calcification and indirect effects arising from the web of species interactions. Our results indicate that pH decline is proceeding at a more rapid rate than previously predicted in some areas, and that this decline has ecological consequences for near shore benthic ecosystems.
Bone mineral density and the risk of incident nonspinal fractures in black and white women.

CONTEXT Black women have a lower rate of fracture than white women, but whether bone mineral density (BMD) predicts fracture risk as well in black women as it does in white women is not established. OBJECTIVE To examine the association between BMD and incident nonspinal fractures in older black and white women. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of baseline data collected from 1986 through 1990 (7334 white women aged 67-99 years) and from 1996 through 1998 (636 black women aged 65-94 years) at 4 US clinical centers in the Study of Osteoporotic Fractures; mean (SD) follow-up of 6.1 (1.5) years until October 1, 2004. MAIN OUTCOME MEASURES Incident nonspinal fractures were confirmed by radiograpic report. Total hip and femoral neck BMD and bone mineral content were measured by dual energy x-ray absorptiometry. RESULTS A total of 58 black women had a combined total of 61 fractures and 1606 white women had a combined total of 1712 fractures. In age-adjusted proportional hazard models, a 1-SD decrease in femoral neck BMD was associated with a 37% increased risk of fracture in black women (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.74) and a 49% increase in fracture in white women (RR, 1.49; 95% CI, 1.40-1.58). Adjustment for body weight and other risk factors for fracture weakened the association between BMD and fracture, especially among black women (multivariable adjusted RR per 1-SD decrease in femoral neck BMD for black vs white women: RR, 1.20 [95% CI, 0.93-1.55] vs RR, 1.42 [95% CI, 1.32-1.52]). The absolute incidence of fracture across the pooled BMD distribution was 30% to 40% lower among black women at every BMD tertile. The lower risk of fracture among black compared with white women was independent of BMD and other risk factors (RR, 0.48; 95% CI, 0.36-0.64). CONCLUSIONS Decreased total hip and femoral neck BMD is associated with an increased risk of fracture in both older black and white women, but this relationship was largely explained by other risk factors in black women. Black women have a lower fracture risk than white women at every level of BMD. Race-specific normative databases may be appropriate for the densitometric definition of osteoporosis.
Frequency of replication from alternative origins in the composite R plasmid NR1

The relative frequency of initiation of DNA replication within the RTF-Tc and r-determinant components of the composite drug resistance plasmid NR1 in Proteus mirabilis was evaluated. Using fractionated radioactively labeled plasmid DNA, analytical procedures that distinguished between the two components of the composite plasmid were carried out. A mixture of uniformly 14C-labeled and 3H-pulse-labeled plasmid DNA (pulse-labeled origin[s] of replication) was used in each of three experiments. First, shear products of the DNA were analyzed using CsCl density gradient centrifugation. Second, fragmented DNA was hybridized to nonradioactive RTF-Tc and r-determinant DNAs immobilized on nitrocellulose filters. Third, the radioactive plasmid DNAs immobilized on nitrocellulose filters. Third, the radioactive plasmid DNA was digested with restriction enzyme (EcoRI), producing a set of RTF-Tc and r-determinant fragments with differing 3H/14C isotpe ratios. The three experiments suggested that under the conditions used to accumulate replicating plasmid DNA molecules (DNA substrate limitation), the r-determinant origin of replication was preferentially utilized in the composite plasmid.
Electric circuit modeling of lithium-sulfur batteries during discharging state

Lithium-ion batteries are characterized by having very good performance in terms of efficiency, lifetime, and self-discharge, which allowed them to become the major player in the electric vehicle applications. However, they were not able to totally overcome the EV range anxiety. Thus, research is carried out nowadays to develop batteries with even higher gravimetric energy density, which should allow a substantial range increase. One of the technologies, which should be able to meet the range requirements is the Lithium-Sulfur (Li-S) battery. Thanks to the extensive research and development efforts, these cells are close to enter the market, being evaluate in various projects. In this paper, we have proposed an electrical circuit model for a Li-S pouch cell, which was parameterized based on extensive electrochemical impedance spectroscopy measurements. The developed model was verified using static and pulse discharge profiles, showing a good accuracy in predicting the voltage of the tested Li-S battery cell.
Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli

Generation of inflammatory mediators and leukocyte recruitment to infection at an epithelial surface were studied during Escherichia coli-induced mastitis. One uninfected gland of each of eight midlactation cows was challenged with only 30 CFU of E. coli McDonald strain 487, a serum-resistant isolate from a cow with mastitis. Bacteria grew logarithmically during the first 10 to 12 h after challenge, reaching concentrations of more than 10(5) CFU/ml with no detectable host response during this time. An intense inflammatory reaction began approximately 12 h after the challenge and was characterized by a breakdown in the blood-milk permeability barrier followed by pyrexia and a pronounced leukocytic influx. Coincident with the onset of mammary inflammation was the appearance of neutrophil chemotactic activity in the milk from infected glands. Factors able to upregulate CD18 expression on peripheral blood neutrophils also appeared in milk at this time. The lack of appearance of chemotactic and CD18-upregulating activities until 12 h after challenge indicated that delays in neutrophil recruitment resulted from an initial lack of bacterial recognition and inflammatory mediator production. Production of complement fragment C5a, tumor necrosis factor, and interleukin-1 (IL-1) occurred earlier than production of IL-6 or IL-8. The early and intense production of C5a indicates that this chemoattractant may be more important than IL-8 during the initial recruitment and activation of neutrophils to a developing E. coli infection.
Comparison of Ringer's acetate with 3% dextran 70 for volume loading before extradural caesarean section.

We have studied haemodilution and cardiovascular responses to i.v. hydration with either 3% dextran 70 (Dx70) or Ringer's acetate using a non-invasive cardiac output monitor (BoMed NCCOM3-R7) in 40 healthy parturients undergoing Caesarean section under extradural anaesthesia. Haemodilution was more pronounced, and central venous pressure, mean arterial pressure and cardiac index maintained at greater values, after treatment with Dx70. Colloid osmotic pressures (COP) decreased by 1.7 mm Hg after loading with 3% Dx70, and by 5.6 mm Hg in mothers treated with Ringer's acetate (P less than 0.001). The transthoracic fluid index decreased more after hydration with Ringer's acetate (P less than 0.001), indicating an increase in lung water. In spite of these maternal changes, there were no differences in neonatal bioimpedance or values of haemoglobin, PCV, albumin and COP in umbilical cord blood, and only one case of respiratory distress. We conclude that colloids may be preferable to crystalloids for circulatory preload for extradural Caesarean section, as greater haemodynamic stability was maintained and increases in lung water avoided.