Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein‐DNA interactions at the H4‐Site III upstream transcriptional element of a cell cycle regulated histone H4 gene: Differences in normal versus tumor cells

Upstream sequences of the H4 histone gene FO108 located between nt –418 to –213 are stimulatory for in vivo transcription. This domain contains one protein/DNA interaction site (H4‐Site III) that binds factor H4UA‐1. Based on methylation interference, copper‐phenanthroline protection, and competition assays, we show that H4UA‐1 interacts with sequences between nt −345 to −332 containing an element displaying sequence‐similarity with the thyroid hormone response element (TRE). Using gel retardation assays, we also demonstrate that H4UA‐1 binding activity is abolished at low concentrations of Zn2+ (0.75 mM), a characteristic shared with the thyroid hormone (TH) receptor DNA binding protein. Interestingly, phosphatase‐treatment of nuclear proteins inhibits formation of the H4UA‐1 protein/DNA complex, although a complex with higher mobility (H4UA‐1b) can be detected; both complexes share identical protein‐DNA contacts and competition behaviors. These findings suggest that phosphorylation may be involved in the regulation of H4‐Site III protein/DNA interactions by directly altering protein/protein associations. H4‐Site III interactions were examined in several cell culture systems during cell growth and differentiation. We find that H4UA‐1 binding activity is present during the cell cycle of both normal diploid and transformed cells. However, during differentiation of normal diploid rat calvarial osteoblasts, we observe a selective loss of the H4UA‐1/H4‐Site III interaction, concomitant with an increase of the H4UA‐1b/H4‐Site III complex, indicating modifications in the heteromeric nature of protein/DNA interactions during downregulation of transcription at the cessation of proliferation. Transformed cells have elevated levels of H4UA‐1, whereas H4UA‐1b is predominantly present in normal diploid cells; this alteration in the ratio of H4UA‐1 and H4UA‐1b binding activities may reflect deregulation of H4‐Site III interactions in transformed cells. We propose that H4‐Site III interactions may contribute, together with protein/DNA interactions at proximal regulatory sequences, in determining the level of H4‐FO108 histone gene transcription.
Challenging trade-offs of temporary skilled migrants

Temporary skilled migrants are frequently portrayed as mobile individuals who freely trade off short-term disadvantage in the destination country for long-term economic gains that can secure their future in the departure country. This paper examines and queries the 'trade-off' argument on the basis of recently completed research on the experiences of temporary migrant nurses on 457 visas. It challenges three assumptions that underpin the common interpretation of temporary skilled migration: a) that migration decisions are well-informed and centred on economic considerations; b) that this form of migration always results in financial returns; and c) that temporary migrants return to their departure country once these target returns have been achieved. The findings highlight the complex, contingent and evolving nature of migration decisions and the individual and structural constraints on temporary skilled migrants' agency in shaping their pathways.
Growth and metabolism of Saccharomyces cerevisiae in chemostat cultures under carbon-, nitrogen-, or carbon- and nitrogen-limiting conditions

Aerobic chemostat cultures of Saccharomyces cerevisiae were performed under carbon-, nitrogen-, and dual carbon- and nitrogen-limiting conditions. The glucose concentration was kept constant, whereas the ammonium concentration was varied among different experiments and different dilution rates. It was found that both glucose and ammonium were consumed at the maximal possible rate, i.e., the feed rate, over a range of medium C/N ratios and dilution rates. To a small extent, this was due to a changing biomass composition, but much more important was the ability of uncoupling between anabolic biomass formation and catabolic energy substrate consumption. When ammonium started to limit the amount of biomass formed and hence the anabolic flow of glucose, this was totally or at least partly compensated for by an increased catabolic glucose consumption. The primary response when glucose was present in excess of the minimum requirements for biomass production was an increased rate of respiration. The calculated specific oxygen consumption rate, at D = 0.07 h-1, was more than doubled when an additional nitrogen limitation was imposed on the cells compared with that during single glucose limitation. However, the maximum respiratory capacity decreased with decreasing nitrogen concentration. The saturation level of the specific oxygen consumption rate decreased from 5.5 to 6.0 mmol/g/h under single glucose limitation to about 4.0 mmol/g/h at the lowest nitrogen concentration tested. The combined result of this was that the critical dilution rate, i.e., onset of fermentation, was as low as 0.10 h-1 during growth in a medium with a low nitrogen concentration compared with 0.20 h-1 obtained under single glucose limitation.
Australian occupational therapy driver assessors' opinions on improving on-road driver assessment procedures.

OBJECTIVE We collected practitioner opinions to improve the validity and reliability of the on-road driver assessment procedures used in Australia. METHOD We used focus groups to document the views of experienced occupational therapy driver assessors using a purposive sampling method. RESULTS Eight focus groups were conducted with 55 clinicians practicing in urban and rural regions. There was strong support for greater standardization of procedures for all tests. For drivers seeking unrestricted (open) licenses, use of standard routes with predetermined assessment points was important where practicable. Where use of a nonstandard route for this purpose was unavoidable, it was important to specify a minimum set of requirements related to route characteristics and assessment items. CONCLUSION Australian occupational therapy driver assessors support greater standardization of test routes and procedures to improve reliability and validity. However, the extent to which standardization can be achieved is limited by variable road traffic environments where assessments are conducted.
Roles of BCL6 in normal and transformed germinal center B cells

Summary: BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post‐transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high‐affinity antibodies of different isotypes. The critical functions exerted by BCL6 during normal B‐cell development can be hijacked by the malignant transformation process. Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC‐derived lymphomas. The aberrations affecting BCL6 interfere with the multiple levels of regulation that grant a fine tuning of BCL6 expression and activity in physiologic conditions. This review summarizes the current knowledge on BCL6 function and its role in lymphomagenesis.
Roles of the three transcriptional attenuators of the Bacillus subtilis pyrimidine biosynthetic operon in the regulation of its expression

Expression of the Bacillus subtilis pyr operon is regulated by exogenous pyrimidines and the protein product of the first gene of the operon, PyrR. It has been proposed that PyrR mediates transcriptional attenuation at three untranslated segments of the operon (R.J. Turner, Y. Lu, and R.L. Switzer, J. Bacteriol., 176:3708-3722, 1994). In this study, transcriptional fusions of the pyr promoter followed by the pyr attenuation sequences, either individually or in tandem to a lacZ reporter gene, were used to examine the physiological functions of all three attenuators through their ability to affect beta-galactosidase expression. These fusions were studied as chromosomal integrants in various B. subtilis strains to examine the entire range of control by pyrimidines, PyrR dependence, amd developmental control of pyr gene expression. The nutritional regulation of each attenuator separately was roughly equivalent to that of the other two and was totally dependent upon PyrR, and that of tandem attenuators was cumulative. The regulation of a fusion of the spac promoter followed by the pyrP:pyrB intercistronic region to lacZ produced results similar to those obtained with the corresponding fusion containing the pyr promoter, demonstrating that attenuator-dependent regulation is independent of the promoter. Extreme pyrimidine starvation gave rise to two- to threefold-higher levels of expression of a pyr-lacZ fusion that lacked attenuators, independent of PyrR, than were obtained with cells that were not starved. Increased expression of a similar spac-lacZ fusion during pyrimidine starvation was also observed, however, indicating that attenuator-independent regulation is not a specific property of the pyr operon. Conversion of the initiator AUG codon in a small open reading frame in the pyrP:pyrB intercistronic region to UAG reduced expression by about half but did not alter regulation by pyrimidines, which excludes the possibility of a coupled transcription-translation attenuation mechanism. Developmental regulation of pyr expression during early stationary phase was found to be dependent upon the attenuators and PyrR, and the participation of SpoOA was excluded.
Factor XIII – Circulating Levels and the Val34Leu Polymorphism in the Healthy Male Relatives of Patients with Severe Coronary Artery Disease

Summary We aimed to investigate whether increased levels of FXIII and/or a low prevalence of the protective Leu allele (of the Val34Leu FXIII polymorphism) occur in relatives of patients with severe CAD. 185 healthy male relatives aged 65 or less were recruited from 125 patients with multi-vessel CAD and compared to 185 healthy, agematched controls. The relatives and controls were similar in terms of clinical parameters. FXIII B-subunit levels were elevated in relatives, 1.11 µg/mL (1.08-1.14), compared with controls, 1.00 µg/mL (0.97-1.04), P<0.0001 but FXIII A2B2 levels did not differ between the groups. There was a strong correlation between FXIII B-subunit and the insulin resistance syndrome, however, adjusted B-subunit levels remained significantly higher in relatives. There was no difference in genotype frequency at the FXIII Val34Leu polymorphism between relatives and controls. FXIII B-subunit levels are elevated in the relatives of CAD patients and this is independent of other cardiovascular risk factors.
The Association of Meibomian Gland Dysfunction and Other Common Ocular Diseases With Dry Eye: A Population-Based Study in Spain

Purpose: To investigate the relationship of meibomian gland dysfunction (MGD) and other prevalent ocular diseases with dry eye (DE) in a general adult population. Methods: An age-stratified random sample of 1155 subjects aged ≥40 years was selected in O Salnés, Spain. From 937 eligible subjects, 654 (69.8%) participated (mean age (SD): 63.6 (14.4) years; range: 40-96; and 37.2% males). A standardized DE questionnaire was administered. Objective evaluation included the Schirmer test, tear film breakup time (TBUT), fluorescein staining, and rose bengal staining. DE was defined as the simultaneous presence of symptoms and at least one sign. The relationship of MGD and other ocular diseases with DE was investigated. A design-based analysis was performed, and all calculations were weighted to give unbiased estimates. Results: DE and MGD prevalence were 11.0% [95% confidence interval (CI), 8.6-13.3] and 30.5% (95% CI, 26.9-34.1), respectively. MGD was present in 45.8% (95% CI, 34.8-57.2) of subjects with DE and was associated, after controlling for age and sex, with DE [adjusted odds ratios (ORa), 1.81]; with symptoms (ORa, 2.26); and with TBUT (ORa, 1.97), fluorescein staining (ORa, 2.09) and rose bengal staining (ORa, 3.25). The remaining ocular diseases were not associated with symptoms. However, pterygium was significantly associated with fluorescein staining (ORa, 1.89); cataract surgery with TBUT (ORa, 2.79); trauma and pseudoexfoliation with rose bengal staining (ORa, 2.75 and ORa, 4.04); and glaucoma with TBUT (ORa, 3.26), fluorescein staining (ORa, 3.40), and rose bengal staining (ORa, 3.46). Conclusions: DE and MGD are common diseases in this population. MGD is strongly associated with symptoms and signs of DE. Nearly half of the subjects with DE have MGD. Pterygium, trauma, cataract surgery, pseudoexfoliation, and glaucoma are associated with signs of DE.
Acquired Resistance but Not Innate Resistance toMycobacterium bovis Bacillus Calmette-Guérin Is Compromised by Interleukin-12 Ablation

ABSTRACT Interleukin-12 (IL-12) is one of the first cytokines produced by macrophages, key mediators of innate resistance, during the host’s immune response to infections. Therefore, in this study we propose that IL-12 has an important role in the early phase of the immune response to Mycobacterium bovis BCG. IL-12 has been shown to enhance the maturation of protective Th1 cells and gamma interferon (IFN-γ) production during mycobacterial infection. Therefore, it may play a crucial role during the immune phase of infection as well. To examine the role of IL-12 in both the innate and the immune phase of infection, we compared BCG-resistant mice, B10.A (Bcgr), to the susceptible congenic strain B10.A (Bcgs) following administration of a blocking monoclonal antibody to IL-12 (10F6). Anti-IL-12-treated susceptible animals exhibited a two- to threefold increase in spleen CFU by day 21. In contrast, anti-IL-12 treatment had little or no effect on the response of the genetically resistant animals to infection. The B10.A (Bcgr) but not the B10.A (Bcgs) mice had an increase in IFN-γ mRNA relative to baseline levels as early as day 1 of infection irrespective of anti-IL-12 treatment. By day 14, B10.A (Bcgr) mice showed a decrease in IFN-γ mRNA while the B10.A (Bcgs) mice showed a significant increase in IFN-γ mRNA levels. Thus, during BCG infection, the B10.A (Bcgr) mice mount an early IFN-γ response against BCG whereas the B10.A (Bcgs) mice have a delayed IFN-γ response correlating with their genetic permissiveness expressed as an increased mycobacterial load by day 21. Overall, our data demonstrate that the inherent resistance of B10.A (Bcgr) mice to mycobacteria does not depend on optimal levels of IL-12 to maintain effective control of the bacteria, whereas IL-12 is important for the susceptible animals’ response to BCG during the peak of infection.
Research on reciprocal power-fed AC drive test rig for electric traction applications

This paper presents a reciprocal power-fed AC drive test rig for electric traction applications. Two inverter-fed induction motors on a common shaft are used in this test rig. One is as the drive motor, and the other is as the load motor. The DC links of both inverters are connected to each other to circulate the energy, and supplied from the AC mains through a four-quadrant converter. In this paper, the dynamic model of both motors is derived firstly. Then the dynamic emulation of mechanical loads is discussed, and a control strategy for both motors is presented. Lastly, simulation results are given to verify the validity of the proposed AC drive test rig
Reactions of Potential Jurors to a Hypothetical Malpractice Suit Alleging Failure to Perform a Prostate-Specific Antigen Test

We conducted focus groups with 47 potential jurors who were presented with different scenarios in a hypothetical malpractice case involving failure to order a PSA test. Better documentation that a patient made an informed decision to decline a PSA test appeared to provide more medical-legal protection for physicians, especially with the use of a decision aid.
Factors associated with noncompletion of latent tuberculosis infection treatment in an inner-city population in Edmonton, Alberta

One of the most useful strategies to control the spread of tuberculosis is treating latent tuberculosis infections. Certain populations at higher risk for tuberculosis infection, such as homeless individuals, are also at increased risk for treatment nonadherence. This article describes the treatment completion rate for latent tuberculosis infections at a health clinic in Edmonton, Alberta, including an assessment of the correlates of noncompletion as well as potential means to improve treatment adherence.
Impact of inflammation and oxidative stress on carotid intima‐media thickness in obstructive sleep apnea patients without metabolic syndrome

Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases, and carotid intima‐media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. This study tested the hypothesis that inflammation and oxidative stress determined carotid IMT in patients with OSA. The carotid IMT, mean systolic and diastolic pressure (night and morning) were significantly higher and the level of thiols and high‐density lipoprotein were significantly lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea index was correlated positively with E‐selectin (r = 0.222, P = 0.014), total cholesterol (r = 0.185, P = 0.042), low‐density lipoprotein (r = 0.264, P = 0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high‐density lipoprotein level (r = −0.203, P = 0.025) in the 121 patients with OSA. In OSA subjects, multiple linear regression analysis revealed that age, systolic blood pressure and intercellular cell adhesion molecule‐1 level associated independently with carotid IMT. Besides both age and systolic blood pressure, our study demonstrated that intercellular cell adhesion molecule‐1 level was associated significantly with carotid IMT in those patients who had OSA but without metabolic syndrome.
Interior PM machines using Ferrite to substitute rare-earth surface PM machines

Since the cost of rare-earth permanent magnet (PM), such as NdFeB and SmCo, is more and more increasing, there is a great interest in designing PM machines without adopting such a rare-earth PMs, that is, replacing them with cheaper Ferrite magnet. Referring to the interior PM machines, the expected performance reduction is limited thanks to the anisotropic structure, compensating the use of low energy PMs by means of the reluctance torque component. This paper investigates the convenience of adopting Ferrite magnet in an interior PM machine (sometimes also referred to as PM assisted synchronous reluctance machine), instead of rare-earth surface PM machine. It is shown that, even though a slight lengthening of the stack length, the anisotropic PM machines, using Ferrite magnets, may represents a valid competitor of a surface PM machine.
Clinical course of atrial fibrillation in older adults: the importance of cardiovascular events beyond stroke.

AIMS Atrial fibrillation increases the risks of stroke, heart failure, and death, and anticoagulation therapy increases the risk of gastrointestinal haemorrhage. However, the relative event rates for these outcomes are not well described. We sought to define the risks of major clinical events in older adults after a new diagnosis of atrial fibrillation. METHODS AND RESULTS We undertook a population-based, retrospective cohort study of a nationally representative sample of fee-for-service Medicare beneficiaries 65 years or older with incident atrial fibrillation diagnosed between 1999 and 2007. The main outcome measures were mortality and hospitalization or emergency department care for heart failure, myocardial infarction, stroke, or gastrointestinal haemorrhage. Among 186 461 patients with atrial fibrillation and no recent hospitalizations for heart failure, myocardial infarction, stroke, or gastrointestinal haemorrhage, mortality was the most frequent of these major clinical events (19.5% at 1 year; 48.8% at 5 years). By 5 years, 13.7% of patients were hospitalized for heart failure, 7.1% developed new-onset stroke, and 5.7% had gastrointestinal haemorrhage. Myocardial infarction was less frequent (3.9% at 5 years). Rates of mortality, heart failure, myocardial infarction, stroke, and gastrointestinal bleeding increased with older age and higher CHADS2 scores. Among 44 479 patients with previous events, the 5-year risk of death was greatest among patients with recent bleeding events (70.1%) and stroke (63.7%) and lowest among those with recent myocardial infarction (54.9%). CONCLUSION After the diagnosis of incident atrial fibrillation in older adults, mortality was the most frequent major outcome during the first 5 years. Among non-fatal cardiovascular events, heart failure was the most common event.
Model to predict gate tunneling current of plasma oxynitrides

Two key parameters for silicon MOSFET scaling, equivalent oxide thickness (EOT) and gate leakage current density (J/sub g/) are measured and modeled for silicon oxynitride (Si-O-N) gate dielectrics formed by plasma nitridation of SiO/sub 2/. It is found that n-MOSFET inversion J/sub g/ is larger than p-MOSFET inversion J/sub g/ when the gate dielectric consists of less than 27% nitrogen atoms, indicating substrate injection of electrons is dominant for this range of plasma nitrided Si-O-N. To examine the intrinsic scaling of Si-O-N, we model EOT and n-MOSFET J/sub g/ for sub-2-nm physically thick gate dielectrics as a function of film physical thickness and nitrogen content. The model has four free fitting parameters and unlike existing models does not assume a priori the values of the oxide and nitride dielectric constant, barrier height, or effective mass. It indicates that at a given EOT, leakage current of n-MOSFETs with Si-O-N gate dielectrics reaches a minimum at a specific nitrogen content. Through the use of this model, we find that plasma nitrided Si-O-N can meet the 65-nm International Technology Roadmap for Semiconductors specifications for J/sub g/, and we estimate the nitrogen concentration required for each node and application.
Acute In Vivo Analysis of ATP Release in Rat Kidneys in Response to Changes of Renal Perfusion Pressure

Background ATP and derivatives are recognized to be essential agents of paracrine signaling. It was reported that ATP is an important regulator of the pressure‐natriuresis mechanism. Information on the sources of ATP, the mechanisms of its release, and its relationship to blood pressure has been limited by the inability to precisely measure dynamic changes in intrarenal ATP levels in vivo. Methods and Results Newly developed amperometric biosensors were used to assess alterations in cortical ATP concentrations in response to changes in renal perfusion pressure (RPP) in anesthetized Sprague–Dawley rats. RPP was monitored via the carotid artery; ligations around the celiac/superior mesenteric arteries and the distal aorta were used for manipulation of RPP. Biosensors were acutely implanted in the renal cortex for assessment of ATP. Rise of RPP activated diuresis/natriuresis processes, which were associated with elevated ATP. The increases in cortical ATP concentrations were in the physiological range (1–3 μmol/L) and would be capable of activating most of the purinergic receptors. There was a linear correlation with every 1‐mm Hg rise in RPP resulting in a 70‐nmol/L increase in ATP. Furthermore, this elevation of RPP was accompanied by a 2.5‐fold increase in urinary H2O2. Conclusions Changes in RPP directly correlate with renal sodium excretion and the elevation of cortical ATP. Given the known effects of ATP on regulation of glomerular filtration and tubular transport, the data support a role for ATP release in the rapid natriuretic responses to acute increases in RPP.