Miracle-dz/UniFAR-FTUs huggingface dataset:
Redox state and lactate accumulation in human skeletal muscle during dynamic exercise.

The relationship between the redox state and lactate accumulation in contracting human skeletal muscle was investigated. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal oxygen uptake [VO2(max.)], and to fatigue (4.8 +/- 0.6 min; mean +/- S.E.M.) at 100% VO2(max.). Biopsies from the quadriceps femoris muscle were analysed for NADH, high-energy phosphates and glycolytic intermediates. Muscle NADH was 0.20 +/- 0.02 mmol/kg dry wt. of muscle at rest, and decreased to 0.12 +/- 0.01 (P less than 0.01) after exercise at 40% VO2(max.), but no change occurred in the [lactate]/[pyruvate] ratio. These data, together with previous results on isolated cyanide-poisoned soleus muscle, where NADH increased while [lactate]/[pyruvate] ratio was unchanged [Sahlin & Katz (1986) Biochem. J. 239, 245-248], suggest that the observed changes in muscle NADH occurred within the mitochondria. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest to 0.27 +/- 0.03 (P less than 0.05) and 0.32 +/- 0.04 (P less than 0.001) mmol/kg respectively. Muscle lactate was unchanged after exercise at 40% VO2(max.), but increased substantially at the higher work loads. At 40% VO2(max.), phosphocreatine decreased by 11% compared with the values at rest, and decreased further at the higher work loads. The decrease in phosphocreatine reflects increased ADP and Pi. It is concluded that muscle NADH decreases during low-intensity exercise, but increases above the value at rest during high-intensity exercise. The increase in muscle NADH is consistent with the hypothesis that the accelerated lactate production during submaximal exercise is due to a limited availability of O2 in the contracting muscle. It is suggested that the increases in NADH, ADP and Pi are metabolic adaptations, which primarily serve to activate the aerobic ATP production, and that the increased anaerobic energy production (phosphocreatine breakdown and lactate formation) is a consequence of these changes.
Assessment & Evaluation in Higher Education

The requirement to provide timely formative tasks that are designed to facilitate student learning and autonomy has provoked a wider examination of the role of assessment in higher education and encouraged further investigation of the alignment of learning, teaching and assessment in curriculum design frameworks. Many current authors have proposed that the primary purpose of assessment is to enhance current and future learning and that current practice tends to overemphasise the importance of assessment for progression and certification purposes. This paper proposes that a clearer distinction be made between assessment tasks designed to facilitate and test current learning through the use of formative and summative assessments, and those tasks primarily designed to enhance future learning, which could be better termed integrative assessments. This distinction would allow students and teachers to have greater clarity around the proposed outcomes and reward mechanisms associated with assessment tasks and feedback. This paper proposes that teachers should strive to incorporate four different types of assessment tasks throughout a programme of study, namely diagnostic, formative, integrative and summative tasks, and that the outcomes and reward mechanisms for different assessment types be explained more clearly to students.
Replication Intermediates of the Linear Mitochondrial DNA of Candida parapsilosis Suggest a Common Recombination Based Mechanism for Yeast Mitochondria*

Background: Faithful mitochondrial DNA replication ensures functional oxidative phosphorylation. Results: Recombination structures and replication forks are the main intermediates detected in Candida parapsilosis mtDNA. Conclusion: Recombination driven replication initiation and not transcription primed DNA synthesis prevails in yeast mitochondria. Significance: Our findings are essential for the understanding of yeast mitochondrial DNA metabolism. Variation in the topology of mitochondrial DNA (mtDNA) in eukaryotes evokes the question if differently structured DNAs are replicated by a common mechanism. RNA-primed DNA synthesis has been established as a mechanism for replicating the circular animal/mammalian mtDNA. In yeasts, circular mtDNA molecules were assumed to be templates for rolling circle DNA-replication. We recently showed that in Candida albicans, which has circular mapping mtDNA, recombination driven replication is a major mechanism for replicating a complex branched mtDNA network. Careful analyses of C. albicans-mtDNA did not reveal detectable amounts of circular DNA molecules. In the present study we addressed the question of how the unit sized linear mtDNA of Candida parapsilosis terminating at both ends with arrays of tandem repeats (mitochondrial telomeres) is replicated. Originally, we expected to find replication intermediates diagnostic of canonical bi-directional replication initiation at the centrally located bi-directional promoter region. However, we found that the linear mtDNA of Candida parapsilosis also employs recombination for replication initiation. The most striking findings were that the mitochondrial telomeres appear to be hot spots for recombination driven replication, and that stable RNA:DNA hybrids, with a potential role in mtDNA replication, are also present in the mtDNA preparations.
Risk averse banks and excess reserve fluctuations

Abstract We develop a model to study how risk averse banks use excess reserves to manage risk on their asset portfolios. Our model predicts that risk averse banks accumulate substantial holdings of excess reserves in response to large, low-probability shocks to the risk on loans. Our findings support the hypothesis that risk aversion led banks to build-up excess reserves within the US banking system in September of 2008 following news about the failure of Lehman Brothers and the credit downgrade of AIG. Moreover, our model also explains the magnitude of excess reserve fluctuations observed in the US over typical business cycles.
Nurses' attitudes, behaviours and perceived barriers towards pressure ulcer prevention.

BACKGROUND Pressure ulcers are not a plague of modern man; they have been known to exist since ancient Egyptian times. However, despite the increasing expenditure on pressure ulcer prevention, pressure ulcers remain a major health care problem. Although nurses do not have the sole responsibility for pressure ulcer prevention, nurses have a unique opportunity to have a significant impact on this problem. AIMS AND OBJECTIVES The specific aims of the study were to identify: * Staff nurses' attitudes towards pressure ulcer prevention. * The behaviour of staff nurses' in relation to pressure ulcer prevention. * Staff nurses' perceived barriers towards pressure ulcer prevention. DESIGN A cross-sectional survey method was used. METHODS A randomly selected sample of staff nurses (n = 300) working in an acute care setting in an urban location was invited to participate. Data were collected using a prepiloted questionnaire. Data analysis was carried out using SPSS version 10 and SPSS Text Smart version 1.1. RESULTS The nurses surveyed demonstrated a positive attitude towards pressure ulcer prevention. However, prevention practices were demonstrated to be haphazard and erratic and were negatively affected by lack of time and staff. These barriers prevented the nurses' positive attitude from being reflected into effective clinical practice. Education, although poorly accessed, or made available, was rarely cited as impeding practice in this area. CONCLUSION This study suggests that positive attitudes are not enough to ensure that practice change takes place, reinforcing the complex nature of behavioural change. Implementation strategies should introduce ways in which key staff can be empowered to overcome barriers to change. RELEVANCE TO CLINICAL PRACTICE This study provides a unique exploration of Irish nurses' attitudes, behaviours and perceived barriers towards pressure ulcer prevention, thereby contributing to the body of knowledge on this subject. As tissue viability is a new and emerging speciality, this information will contribute to evidence based practice in this area of patient care and will form the basis for the development of an educational strategy for pressure ulcer prevention and management.
Mediation of Interleukin-1 (cid:1) –Induced Transforming Growth Factor (cid:1) 1 Expression by Activator Protein 4 Transcription Factor in Primary Cultures of Bovine Articular Chondrocytes Possible Cooperation With Activator Protein 1

Objective. Interleukin-1 (IL-1) and transforming growth factor (cid:1) 1 (TGF (cid:1) 1) play major roles in osteoar-ticular diseases, exerting opposite effects on both the catabolism and anabolism of cartilage matrix. Previous findings suggest that IL-1 and TGF (cid:1) 1 could function in a feedback interaction. However, the effect exerted by IL-1 on expression of TGF (cid:1) by articular chondrocytes is, so far, poorly understood. The present study was carried out to determine the influence of IL-1 (cid:1) on the expression of TGF (cid:1) 1 by bovine articular chondrocytes (BACs) in primary culture. Methods.
Regulatory Activation Is Accompanied by Movement in the C Terminus of the Na-K-Cl Cotransporter (NKCC1)*

Background: The Na-K-Cl cotransporter (NKCC1) regulates [Cl−] in many cells. Results: NKCC1 activation is associated with movement in the C termini of dimeric cotransporter. Conclusion: The NKCC1 C terminus is involved in transport activation, with dimerization appearing to play a role in the regulatory mechanism. Significance: Our findings contribute to a model for the conformational changes that bring about cotransporter regulation and provide a sensitive reporter of transporter activation. The Na-K-Cl cotransporter (NKCC1) is expressed in most vertebrate cells and is crucial in the regulation of cell volume and intracellular chloride concentration. To study the structure and function of NKCC1, we tagged the transporter with cyan (CFP) and yellow (YFP) fluorescent proteins at two sites within the C terminus and measured fluorescence resonance energy transfer (FRET) in stably expressing human embryonic kidney cell lines. Both singly and doubly tagged NKCC1s were appropriately produced, trafficked to the plasma membrane, and exhibited 86Rb transport activity. When both fluorescent probes were placed within the same C terminus of an NKCC1 transporter, we recorded an 11% FRET decrease upon activation of the transporter. This result clearly demonstrates movement of the C terminus during the regulatory response to phosphorylation of the N terminus. When we introduced CFP and YFP separately in different NKCC1 constructs and cotransfected these in HEK cells, we observed FRET between dimer pairs, and the fractional FRET decrease upon transporter activation was 46%. Quantitatively, this indicates that the largest FRET-signaled movement is between dimer pairs, an observation supported by further experiments in which the doubly tagged construct was cotransfectionally diluted with untagged NKCC1. Our results demonstrate that regulation of NKCC1 is accompanied by a large movement between two positions in the C termini of a dimeric cotransporter. We suggest that the NKCC1 C terminus is involved in transport regulation and that dimerization may play a key structural role in the regulatory process. It is anticipated that when combined with structural information, our findings will provide a model for understanding the conformational changes that bring about NKCC1 regulation.
Evaluating coagulation pretreatment on poultry processing wastewater for dissolved air flotation

Eleven metal coagulants and one polyelectrolyte were assessed for their suitability in assisting a dissolved air flotation (DAF) system aimed at treating poultry processing wastewater. Preliminary jar tests determined that a combination of 800 mg/L of FeCl3 (ferric chloride) and 900 mg/L of Floccin 1115 would provide the best treatment by removing at least 98% of the total suspended solids (TSS) and 97% of the volatile suspended solids (VSS), while providing a 97% increase in water clarity. Final flotation tests suggested that the flocculated particles could be carried to the surface with 40% recycle ratio of the DAF. The resulting supernatant indicated 94.7% increase in clarity (± 1.4%), 97.3% reduction in TSS (± 0.5%), 96.6% reduction in VSS (±1.1%), 91% reduction in chemical oxygen demand (COD), and nearly 100% removal of fats, oils, and greases (FOGs). Despite the high removal efficiencies, flotation was found not to be critically necessary for treatment because the high concentration of coagulants caused settling of the flocs to occur just as rapidly. Potential coagulant overdosing is suspected at the higher end of the tested coagulant concentrations due to limited alkalinity in the wastewater. However, lack of residual metal (coagulant) ions in water may be linked to reactions leading to phosphate precipitation. The exact effect of the competing phosphate reaction on treatment efficiency is not clearly evident from this present study.
The cyclic AMP (cAMP)-cAMP receptor protein complex functions both as an activator and as a corepressor at the tsx-p2 promoter of Escherichia coli K-12

The tsx-p2 promoter is one of at least seven Escherichia coli promoters that are activated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and negatively regulated by the CytR repressor. DNase I footprinting assays were used to study the interactions of these regulatory proteins with the tsx-p2 promoter region and to characterize tsx-p2 regulatory mutants exhibiting an altered response to CytR. We show that the cAMP-CRP activator complex recognizes two sites in tsx-p2 that are separated by 33 bp: a high-affinity site (CRP-1) overlaps the -35 region, and a low-affinity site (CRP-2) is centered around position -74 bp. The CytR repressor protects a DNA segment that is located between the two CRP sites and partially overlaps the CRP-1 target. In combination, the cAMP-CRP and CytR proteins bind cooperatively to tsx-p2, and the nucleoprotein complex formed covers a region of 78 bp extending from the CRP-2 site close to the -10 region. The inducer for the CytR repressor, cytidine, does not prevent in vitro DNA binding of CytR, but releases the repressor from the nucleoprotein complex and leaves the cAMP-CRP activator bound to its two DNA targets. Thus, cytidine interferes with the cooperative DNA binding of cAMP-CRP and CytR to tsx-p2. We characterized four tsx-p2 mutants exhibiting a reduced response to CytR; three carried mutations in the CRP-2 site, and one carried a mutation in the region between CRP-1 and the -10 sequence. Formation of the cAMP-CRP-CytR DNA nucleoprotein complex in vitro was perturbed in each mutant. These data indicate that the CytR repressor relies on the presence of the cAMP-CRP activator complex to regulate tsx-p2 promoter activity and that the formation of an active repression complex requires the combined interactions of cAMP-CRP and CytR at tsx-p2.
Bispecific Antibodies and Antibody–Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs

The properties of cell surface proteins targeted by antibody–drug conjugates (ADCs) have not been fully exploited; of particular importance are the rate of internalization and the route of intracellular trafficking. In this study, we compared the trafficking of HER2, which is the target of the clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that of prolactin receptor (PRLR), another potential target in breast cancer. In contrast to HER2, we found that PRLR is rapidly and constitutively internalized, and traffics efficiently to lysosomes, where it is degraded. The PRLR cytoplasmic domain is necessary to promote rapid internalization and degradation, and when transferred to HER2, enhances HER2 degradation. In accordance with these findings, low levels of cell surface PRLR (∼30,000 surface receptors per cell) are sufficient to mediate effective killing by PRLR ADC, whereas cell killing by HER2 ADC requires higher levels of cell surface HER2 (∼106 surface receptors per cell). Noncovalently cross-linking HER2 to PRLR at the cell surface, using a bispecific antibody that binds to both receptors, dramatically enhances the degradation of HER2 as well as the cell killing activity of a noncompeting HER2 ADC. Furthermore, in breast cancer cells that coexpress HER2 and PRLR, a HER2xPRLR bispecific ADC kills more effectively than HER2 ADC. These results emphasize that intracellular trafficking of ADC targets is a key property for their activity and, further, that coupling an ADC target to a rapidly internalizing protein may be a useful approach to enhance internalization and cell killing activity of ADCs. Mol Cancer Ther; 16(4); 681–93. ©2017 AACR.
Sequence elements determining ampC promoter strength in E. coli.

A number of spontaneous up‐promoter mutations have been isolated in the ampC beta‐lactamase gene of Escherichia coli. The mutants were analyzed by DNA sequencing, and the level of ampC gene expression was determined. Six mutants with a 21‐fold increase in promoter strength compared with the wild‐type were mutated in the ‐35 promoter region from TTGTCA to the consensus sequence TTGACA . The ‐10 region sequence TACAAT was mutated to the consensus sequence TATAAT in three mutants exhibiting an ampC promoter seven times stronger than the wild‐type. We have previously described a 1‐bp insertion mutant (Jaurin et al., 1981) that changes the inter‐region distance to the consensus 17 bp. Thus, all the up‐mutations found in the ampC promoter represent corrections of the three major discrepancies between the ampC promoter and the consensus E. coli promoter. We conclude that the three consensus elements of E. coli promoters, the ‐35 and ‐10 regions and an optimal inter‐region distance of 17 bp, are the main elements determining the promoter strength.
Passive Lossless Huygens Metasurfaces for Conversion of Arbitrary Source Field to Directive Radiation

We present a semianalytical formulation of the interaction between a given source field and a scalar Huygens metasurface (HMS), a recently introduced promising concept for wavefront manipulation based on a sheet of orthogonal electric and magnetic dipoles. Utilizing the equivalent surface impedance representation of these metasurfaces, we establish that an arbitrary source field can be converted into directive radiation via a passive lossless HMS if two physical conditions are met: local power conservation; and local impedance equalization. Expressing the fields via their plane-wave spectrum and harnessing the slowly-varying envelope approximation, we obtain semianalytical formulae for the scattered fields, and prescribe the surface reactance required for the metasurface implementation. The resulting design procedure indicates that the local impedance equalization induces a Fresnel-like reflection, while local power conservation forms a radiating virtual aperture which follows the total excitation field magnitude. The semianalytical predictions are verified by finite-element simulations of HMSs designed for different source configurations. Besides serving as a flexible design procedure for HMS radiators, the proposed formulation also provides a robust mechanism to incorporate a variety of source configurations into general HMS models, as well as physical insight on the conditions enabling purely reactive implementation of this novel type of metasurfaces.
A Social Media-Based HIV Prevention Intervention Using Peer Leaders

This study seeks to investigate qualities of peer leaders in a social media-based peer-led HIV intervention. African American and Latino men who have sex with men (MSM) peer leaders were recruited through online/offline methods. They were required to have experience with health communication and social media. More than 57% of reported using social networking for seeking sex partners within three months. Also, more than 53% spent over three hours per week online, and about 53% of peer leaders had fewer than 200 Facebook friends. Results suggest that peer leaders can be recruited for social media-based health interventions. Qualities of peer leaders are discussed.
Diastolic pressure determines autonomic responses to pressure perturbation in humans.

Arterial baroreceptors reflexly regulate sympathetic and heart rate responses to alteration of blood pressure. The primary mechanical determinant of arterial baroreceptor activity in humans remains unclear. We examined the influence of systolic, diastolic, pulse, and mean arterial pressures on efferent muscle sympathetic nerve activity (MSNA, microneurography) and heart rate responses during perturbation of arterial pressure in 10 normal human subjects [age 25 +/- 2 (SE) yr]. We directly measured arterial pressure, heart rate, and MSNA during intravenous vasodilator infusion (nitroprusside, 6 +/- 1 micrograms.kg-1.min-1, n = 6; or hydralazine, 16 +/- 2 mg, n = 4) while central venous pressure was held constant by simultaneous volume expansion. Changes in arterial pressures were compared with changes in heart rate and MSNA over 3-min periods of vasodilator infusion during which we observed increases in systolic and pulse pressures with simultaneous decreases in mean and diastolic pressures. During vasodilator infusion, there were increases in systolic (124.2 +/- 2.1 to 131.7 +/- 2.9 Torr, P less than 0.001) and pulse pressures (57.0 +/- 2.2 to 72.7 +/- 2.7 Torr, P less than 0.001) although mean arterial pressure fell (88.0 +/- 2.6 to 80.4 +/- 2.7 Torr, P less than 0.001) because of decreases in diastolic pressure (67.2 +/- 3.0 to 59.0 +/- 2.7 Torr, P less than 0.001). The changes in arterial pressures were accompanied by simultaneous increases in heart rate (66.4 +/- 3.0 to 92.6 +/- 4.8 beats/min, P less than 0.001) and MSNA (327 +/- 59 to 936 +/- 171 U, P less than 0.005). (ABSTRACT TRUNCATED AT 250 WORDS)
Changes of Nuclear Matrix in Long-Term Culture of Limbal Epithelial Cells

Purpose. This study was undertaken to investigate the changes of nuclear matrix in long-term culture of rabbit limbal epithelial cells. Methods. Epithelial cells outgrown from limbal basal epithelium were serially cultivated. Nuclear matrices of early and late passages were extracted for morphologic study and protein analysis by two-dimensional gel electrophoresis and immunoblotting. Results. Differential growth and changes in morphology were observed in limbal epithelial cells of early and late passages. Cytokeratin type 3 was expressed in cells of later passages, indicating corneal cell differentiation during the long-term culture. These cells also showed reduced density of nuclear matrix fibrils and thinning of nuclear lamina. They were shown by two-dimensional gel electrophoresis to have lost most nuclear matrix proteins, including lamin A/C and proliferating cell nuclear antigen. However, five new protein entities were also expressed. Conclusion. The nuclear matrix appeared to change along with limbal epithelial cell differentiation in culture. Whether such changes may affect the growth and viability of limbal cells after transplantation requires in vivo tissue analysis.