Miracle-dz/UniFAR-FTUs huggingface dataset:
Localized 1H NMR measurement of glucose consumption in the human brain during visual stimulation.

Spatially localized 1H NMR spectroscopy has been applied to measure changes in brain glucose concentration during 8-Hz photic stimulation. NMR spectroscopic measurements were made in a 12-cm3 volume centered on the calcarine fissure and encompassing the primary visual cortex. The average maximum change in glucose levels was 0.34 mumol.g-1 (n = 5) at 15 min; glucose level had turned toward resting level at 25 min. The glucose change was used to calculate the increase of glucose cerebral metabolic rate in the visual cortex region for individual subjects by using the Michaelis-Menten model of glucose transport on the assumption of constant transport kinetics. The glucose cerebral metabolic rate was calculated to increase over the nonstimulated rate by 22% during the first 15 min of photic stimulation. A model in which the glucose metabolic rate gradually decreases during stimulation was proposed as a possible explanation for the recovery of brain glucose and previously measured lactate concentrations to prestimulus values after 15 min.
Blockade of TNFR1 signaling: A role of oscillatory fluid shear stress in osteoblasts

Fluid shear stress protects cells from TNF‐α‐induced apoptosis. Oscillatory fluid shear stress (OFSS) is generally perceived as physiologically relevant biophysical signal for bone cells. Here we identify several cellular mechanisms responsible for mediating the protective effects of OFSS against TNF‐α‐induced apoptosis in vitro. We found that exposure of MC3T3‐E1 osteoblast‐like cells to as little as 5 min of OFSS suppressed TNF‐α‐induced activation of caspase‐3, cleavage of PARP and phosphorylation of histone. In contrast, H2O2‐induced apoptosis was not inhibited by OFSS suggesting that OFSS might not be protecting cells from TNF‐α‐induced apoptosis via stimulation of global pro‐survival signaling pathways. In support of this speculation, OFSS inhibition of TNF‐α‐induced apoptosis was unaffected by inhibitors of several pro‐survival signaling pathways including pI3‐kinase (LY294002), MAPK/ERK kinase (PD98059 or U0126), intracellular Ca2+ release (U73122), NO production (L‐NAME), or protein synthesis (cycloheximide) that were applied to cells during exposure to OFSS and during TNF‐α treatment. However, TNF‐α‐induced phosphorylation and degradation of IκBα was blocked by pre‐exposure of cells to OFSS suggesting a more specific effect of OFSS on TNF‐α signaling. We therefore focused on the mechanism of OFSS regulation of TNF‐receptor 1 (TNFR1) signaling and found that OFSS (1) reduced the amount of receptor on the cell surface, (2) prevented the association of ubiquitinated RIP in TNFR1 complexes with TRADD and TRAF2, and (3) reduced TNF‐α‐induced IL‐8 promoter activity in the nucleus. We conclude that the anti‐apoptotic effect of OFSS is not mediated by activation of universal pro‐survival signaling pathways. Rather, OFSS inhibits TNF‐α‐induced pro‐apoptotic signaling which can be explained by the down‐regulation of TNFR1 on the cell surface and blockade of TNFR1 downstream signaling by OFSS. J. Cell. Physiol. 226: 1044–1051, 2011. © 2010 Wiley‐Liss, Inc.
Impaired D-myo-Inositol 1,4,5-Triphosphate Generation from Cord Blood Polymorphonuclear Leukocytes

D-myo-Inositol 1,4,5-triphosphate (IP3) is a key second messenger in many cells, including macrophages, T and B cells, and neutrophils, in which it regulates free intracellular calcium ion levels. In human polymorphonuclear leukocytes the rise of intracellular [Ca2+] is the signal that activates a number of functions such as adherence, aggregation, chemotaxis, and degranulation, which are typically depressed in newborn infants. IP3 generation can be stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) tripeptide, which mimics the naturally occurring bacterial oligopeptides. In this study both neonatal and adult polymorphonuclear leukocytes were stimulated by fMLP (1 × 10−6 M) and the levels of IP3 were assayed by a specific radiometric method. The time course of IP3 generation was studied for up to 60 s in a total of 10 samples. The response appeared reduced in cord blood samples. To confirm this observation, we extended our study to a larger number of samples, quantitating [IP3] at the time peak of 10 s. As expected IP3 generation was significantly (F test, p < 0.0001, n = 39) lower in newborns than in adults (means ± SD = 0.64 ± 0.25; 1.26 ± 0.36, ng/106 cells, respectively). Besides soluble stimulus, neutrophils were treated with a particulate stimulus, namely serumtreated zymosan, which is also able to stimulate IP3 synthesis from polymorphonuclear leukocytes. Serum-treated zymosan produced a prolonged elevation in the level of IP3, reaching a plateau within 120 s in both cord blood and in control samples. At the 120-s time point significantly (F test, p < 0.002, n = 10) lower amounts of IP3 were found in newborn samples than in adult preparations (mean ± SD = 1.09 ± 0.45; 2.54 ± 0.55, ng/106 cells, respectively). These data suggest that an impaired synthesis of IP3 is involved in the defective signal transduction of neonatal polymorphonuclear leukocytes and could represent an important biochemical mechanism behind the defective functions of neonatal neutrophils.
Use of a digitally reconstructed radiograph-based computer simulation for the optimisation of chest radiographic techniques for computed radiography imaging systems.

OBJECTIVES The purpose of this study was to derive an optimum radiographic technique for computed radiography (CR) chest imaging using a digitally reconstructed radiograph computer simulator. The simulator is capable of producing CR chest radiographs of adults with various tube potentials, receptor doses and scatter rejection. METHODS Four experienced image evaluators graded images of average and obese adult patients at different potentials (average-sized, n=50; obese, n=20), receptor doses (n=10) and scatter rejection techniques (average-sized, n=20; obese, n=20). The quality of the images was evaluated using visually graded analysis. The influence of rib contrast was also assessed. RESULTS For average-sized patients, image quality improved when tube potential was reduced compared with the reference (102 kVp). No scatter rejection was indicated. For obese patients, it has been shown that an antiscatter grid is indicated, and should be used in conjunction with as low a tube potential as possible (while allowing exposure times <20 ms). It is also possible to reduce receptor air kerma by 50% without adversely influencing image quality. Rib contrast did not interfere at any tube potential. CONCLUSIONS A virtual clinical trial has been performed with simulated chest CR images. Results indicate that low tube potentials (<102 kVp) are optimal for average and obese adults, the former acquired without scatter rejection, the latter with an anti-scatter grid. Lower receptor (and therefore patient doses) than those used clinically are possible while maintaining adequate image quality.
Knockdown of hTERT and Treatment with BIBR1532 Inhibit Cell Proliferation and Invasion in Endometrial Cancer Cells

Telomerase activity and expression of the catalytic protein hTERT are associated with cell proliferation and advanced stage in endometrial cancer. Our objective was to evaluate the effect of inhibition of hTERT by siRNA and BIBR1532 on cell growth, apoptosis and invasion in endometrial cancer cells. Knockdown of hTERT or treatment of the cells with BIBR1532 decreased telomerase activity, inhibited cell proliferation, induced apoptosis, and reduced cell invasion in Ishikawa and ECC-1 cells. Either hTERT siRNA or BIBR1532 in combination with paclitaxel promoted a synergistic inhibitory effect on cell growth through induction of Annexin V expression and a remarkable reduction in cell invasion through reduction of protein expression of MMP9, MMP2, and MMP3. Increased telomerase activity and hTERT protein expression by transfections enhanced the protein expression of MMPs and increased the cell invasion ability. BIBR1532 significantly antagonized cell invasion induced by increased hTERT expression. These findings suggest that telomerase and hTERT facilitate cell invasion via MMP family in human endometrial cancer cells.
Mitochondrial and pedigree analysis in Przewalski's horse populations: implications for genetic management and reintroductions

Abstract Background and Aims: Przewalski’s horses have been imported from the western zoos to China since 1985. Yet the genetic diversity in China’s populations has not been studied, thus lacking of such knowledge inevitably affects this population’s management. The aim of this study was to assess genetic diversity in Chinese population of Przewalski’s horses via mitochondrial DNA (mtDNA) control region and pedigree analysis. Materials and methods: Two captive and one reintroduced populations were examined based on mitochondrial DNA control region variation via fecal sampling from 2010 to 2012, together with pedigree analysis. Results: Amplification success rates of fecal mtDNA were as high as 96.2% (93.8%–100%), and were higher for sample in winter than in summer and autumn. Two haplotypes were identified and shared among three populations, but the proportion of individuals with each haplotype varied among the three populations (FST = 0.10874, p = 0.00978). Haplotype diversity in the released population (0.153) was much lower than that in the two captive populations (0.4011 and 0.4966), in accordance with the direction of increase in probability of identity at the dam lines. Conclusion: Future concerns in Przewalski’s horse population management should emphasize on strict reproduction control to minimize inbreeding in captivity, followed by long-term genetic diversity guidelines and non-invasive monitoring in the reintroduction programmes.
Balance appointment information leaflets: Employing performance-based user-testing to improve understanding

Abstract Objective: To use performance-based user-testing to evaluate the effectiveness of balance appointment patient information leaflets (PILs) in conveying important information. Design: The study used a sequential groups design. Twenty participants were asked to find and demonstrate understanding of 11 key points of information contained within two NHS leaflets, A and B (10 participants each), through individual structured-interviews. Participants’ views of the leaflets were explored through a short semi-structured interview. Following analysis, a revised leaflet was developed and tested on a further 20 participants. Study sample: 40 participants (25F/15M, aged 46–72) with no experience of balance problems or balance assessment appointments. Results: Participants exhibited difficulties with finding and/or understanding 5/11 and 6/11 points of information within leaflets A and B, respectively. Five out of eleven points of the revised leaflet also posed problems. Ten out of eleven points were understood by > 90% of participants testing the revised leaflet compared with 6/11 points for leaflets A and B. Conclusions: Some balance appointment PILs contain information which is difficult to find and/or understand for some readers. PILs should be evaluated prior to use using performance-based methods, since poor information provision may lead to increased patient anxiety and appointment non-attendance, cancellation, or postponement.
At the Heart of Discontent Measuring Public Violence in South Africa

ProteSt Action hAS been part of South African political expression for decades. in 1994, as a result of ongoing political violence from the 1980s, South Africa’s national homicide rate stood at 67 murders per 100 000 people. twenty-two years on from the end of apartheid and the factors that drove the high murder rate at the birth of democracy have abated, resulting in fewer than half of that number of murders taking place. however, challenges such as rapid urbanisation and high levels of unemployment, poverty and inequality, along with uneven service delivery and unaccountable governance, continue to plague the country. Moreover, murders have again started to increase, from 30.2 murders per 100 000 in 2011/12 to 32.9 in 2014/15. this means that South Africa still has one of the highest homicide rates in the world. the murder rate is driven primarily by interpersonal conflict, with contributions from armed robberies and collective violence such as taxi and gang warfare, vigilantism and xenophobic attacks.
John Kingdon and the evolutionary approach to public policy and agenda setting

Political science in the 1960s was riven by disputes that were both intellectual and political. E.E. Schattschneider’s (1960) proposal that the scope and dimensions of political conflict were themselves the result of political mobilization led to various discussions of agenda control, agenda setting, and agenda building (see Cobb and Elder, 1972; Cobb, Ross, and Ross, 1976). Bachrach and Baratz’s (1962) introduction of the concept of the “second face of power” further fanned the flames of radical criticism, soon picked up by Jack Walker (1966) in his “Critique of the elitist theory of democracy. ” As described by Bryan Jones in the previous chapter in this volume, Roger Cobb and Charles Elder (1972) were the first to produce a booklength study of the agenda setting process, and John Kingdon’s book followed in 1984 (with later editions in 1995 and 2010). In this short essay I put Kingdon’s contribution in its historical context with a focus on the reasons why the book may have come about when and how it did, paying particular attention to the intellectual community and context at the time of its development. I will not review the extensive literature that has followed Kingdon’s contribution or even focus so much on the theory itself, as several reviews have recently appeared that do exactly that. For example, Zahariadis (2014) explains the development of the multiple streams literature; Greer (2015) summarizes the contribution of the work; Cairney and Jones (2015) discuss the intellectual impact of Kingdon’s work on future scholars (including my own development with Bryan Jones of punctuated equilibrium theory); and Jones et al. (2015) provide a comprehensive metaanalysis of works using the multiple streams approach. With almost 14,000 citations as of September 2015, and with these four recent and highly prominent reviews, it is clear that the book has had a major impact, and that there are many sources available for scholars interested in learning why.1 My focus therefore will be quite different: I focus on where the book came from.2
A Miniature Magnetic-Piezoelectric Thermal Energy Harvester

In this paper, we report a miniature thermal energy harvester with a novel magnetic-piezoelectric design. The harvester consists of a soft magnetic Gd cantilever beam, a piezoelectric lead zirconate titanate sheet, an NdFeB hard magnet, silicon clamps, and a silicon frame. In this design, the harvester is driven by a temperature difference between a cold side and room temperature ambient air, unlike other magnetic-piezoelectric thermal energy harvesters that are driven by a temperature difference between a cold side and a hot side or between two hot sides. Experimental results show that with a temperature difference of 20 °C (cold side: 6.7 °C, hot side: 26.7 °C), the harvester produces a maximum peak-to-peak voltage of 37 mV and a root mean square voltage of 1.98 mV. The estimated maximum instantaneous power density and average power density is 21.7 nW/cm3 and 62.9 pW/cm3, respectively. Moreover, the total volume of our harvester (length × width x height: 6 × 3.5 × 3 mm) is 217 times lower than that of previous experimental harvesters and 38 times smaller than that of previous theoretical-modeled harvesters. Therefore, our harvester is the smallest machined magnetic-piezoelectric thermal energy harvester designed to date. These features enable our harvester to be more easily implemented and integrated with micro wireless sensors and thereby increase more self-powered wireless-sensing applications.
Dihydropyridine enantiomers block recombinant L‐type Ca2+ channels by two different mechanisms

1 The molecular basis of the state‐dependent block of L‐type Ca2+ channels by dihydropyridines is still poorly understood. Therefore, we studied the enantioselectivity of Ca2+ channel block by isradipine enantiomers at three holding potentials (‐80, −60 and −40 mV) in Chinese hamster ovary (CHO) cells stably expressing the rabbit lung α1C‐b‐subunit. 2 The extent of enantioselectivity did not markedly change with the holding potential (IC50 ratios of 104–138), whereas the potency of both isradipine enantiomers increased with depolarisation of the holding potential. 3 In addition to its block of the peak Ca2+ channel current, Ipeak, (−)‐isradipine inhibited the relative current at the end of the test pulse, the so‐called Ilate, normalised to Ipeak (Ilate/Ipeak). This effect was unaffected by the holding potential and revealed distinct kinetics compared to the development of conventional block of Ipeak. 4 When these effects were studied using an α1C‐b‐mutant lacking the high‐affinity dihydropyridine binding site, expressed in human embryonic kidney (HEK 293) cells, both enantiomers blocked Ilate/Ipeak to a similar degree. 5 Our data are discussed within the framework of the ‘guarded receptor’ and the ‘modulated receptor’ hypotheses. The very different properties of the block of Ilate/Ipeak compared to those of the conventional high‐affinity block of Ipeak suggest the existence of an additional mechanism possibly mediated via a second, distinct binding site.
Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure

Rationale: Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. This study investigates whether green tea extract (GTE), an antioxidant, could ameliorate the nephrotoxic effect of GM in uninephrectomized rats. Objectives: The right kidneys of 40 rats were surgically removed and 1 week later the animals were divided into four groups (n = 10). Group 1 served as control, Group 2 as GTE group, Group 3 as GM group, and Group 4 as GM+GTE group. Kidney function, inflammatory cytokine TNF-α, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Main findings: Injecting uninephrectomized rats with GM induced renal dysfunction as shown by significant elevations in serum creatinine and urea. Serum TNF-α and oxidative stress parameters (superoxide anion and lipid peroxides) were also significantly increased. On the contrary, antioxidative parameters [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)] were significantly decreased. Histopathological examination of renal tissue illustrated features of degeneration, marked cellular infiltration, tubular dilatation, and varying degrees of necrosis. GTE given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and TNF-α were almost normalized in the GM+GTE group. The oxidative stress parameters were significantly decreased and the antioxidative parameters were significantly increased. Conclusion: GTE ameliorates GM-induced nephrotoxicity and oxidative damage by improving antioxidant defense and tissue integrity. Further human studies are necessary to demonstrate the antioxidant effects of GTE on renal diseases. Nevertheless, green tea (GT) may offer an inexpensive, nontoxic, and effective intervention strategy in subjects with a risk for GM-induced nephrotoxicity.
Marginal Models for Longitudinal Continuous Proportional Data

Summary. Continuous proportional data arise when the response of interest is a percentage between zero and one, e.g., the percentage of decrease in renal function at different follow‐up times from the baseline. In this paper, we propose methods to directly model the marginal means of the longitudinal proportional responses using the simplex distribution of Barndorff‐Nielsen and Jørgensen that takes into account the fact that such responses are percentages restricted between zero and one and may as well have large dispersion. Parameters in such a marginal model are estimated using an extended version of the generalized estimating equations where the score vector is a nonlinear function of the observed response. The method is illustrated with an ophthalmology study on the use of intraocular gas in retinal repair surgeries.
Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database*

Objective:To gain a better understanding of the epidemiology, microbiology, and outcomes of early-onset, culture-positive, community-acquired, healthcare-associated, and hospital-acquired bloodstream infections. Design:We analyzed a large U.S. database (Cardinal Health, MediQual, formerly MedisGroups) to identify patients with bacterial or fungal bloodstream isolates from 2002 to 2003. Setting:The data set included administrative and clinical variables (physiologic, laboratory, culture, and other clinical) from 59 hospitals. Bloodstream infections were identified in those hospitals collecting clinical and culture data for at least the first 5 days of admission. Patients:Patients with bloodstream infection within 2 days of admission were classified as having community-acquired bloodstream infection. Those with a prior hospitalization within 30 days, transfer from another facility, ongoing chemotherapy, or long-term hemodialysis were classified as having healthcare-associated bloodstream infection. Bloodstream infections that developed after day 2 of admission were classified as hospital-acquired bloodstream infection. A total of 6,697 patients were identified as having bloodstream infection. Interventions:None. Measurements and Main Results:Healthcare-associated bloodstream infection accounted for more than half (55.3%) of all bloodstream infections. Nearly two thirds (62.3%) of hospitalized patients with bloodstream infection suffered from either hospital-acquired bloodstream infection or healthcare-associated bloodstream infection and had higher morbidity and mortality rates than those with community-acquired bloodstream infection. Of all bloodstream infection pathogens, fungal organisms were associated with the highest crude mortality, longest length of stay in hospital, and greatest total charges. Of all bacterial bloodstream infections, methicillin-resistant Staphylococcus aureus was associated with the highest crude mortality rate (22.5%), the longest mean length of stay (11.1 ± 10.7 days), and the highest median total charges ($36,109). After we controlled for confounding factors, methicillin-resistant S. aureus was associated with the highest independent mortality risk (odds ratio 2.70; confidence interval 2.03–3.58). S. aureus was the most commonly encountered pathogen in all types of early-onset bacteremia. Conclusions:Healthcare-associated bloodstream infection constitutes a distinct entity of bloodstream infection with its unique epidemiology, microbiology, and outcomes. Methicillin-resistant Staphylococcus aureus carries the highest relative mortality risk among all pathogens.