Miracle-dz/UniFAR-FTUs huggingface dataset:
Quadriceps muscle function after exercise in men and women with a history of anterior cruciate ligament reconstruction.

CONTEXT Sex differences in lower extremity neuromuscular function have been reported after anterior cruciate ligament reconstruction (ACLR). Research evidence supports different levels of fatigability in men and women and between patients with ACLR and healthy controls. The influence of sex on the response to continuous exercise in patients with ACLR is not clear. OBJECTIVE To compare quadriceps neuromuscular function after exercise between men and women with ACLR. DESIGN Descriptive laboratory study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Twenty-six active volunteers (13 men [50%]: age = 24.1 ± 4.4 years, height = 179.1 ± 9.8 cm, mass = 80.1 ± 9.4 kg, months since surgery = 43.5 ± 37.0; 13 women [50%]: age = 24.2 ± 5.6 years, height = 163.0 ± 5.9 cm, mass = 62.3 ± 8.3 kg, months since surgery = 45.8 ± 42.7) with a history of unilateral primary ACLR at least 6 months earlier. INTERVENTION(S) Thirty minutes of continuous exercise comprising 5 separate 6-minute cycles, including 5 minutes of uphill walking and 1 minute of body-weight squatting and step-ups. MAIN OUTCOME MEASURE(S) Normalized knee-extension maximal voluntary isometric contraction torque, quadriceps superimposed-burst torque, and quadriceps central activation ratio before and after exercise. We performed separate 2 (sex: men, women) × 2 (time: preexercise, postexercise) repeated-measures analyses of variance for the 3 variables. Separate, independent-samples t tests were calculated to compare preexercise with postexercise change in all dependent variables between sexes. RESULTS A significant group-by-time interaction was present for knee-extension torque (P = .04). The percentage reduction in knee-extension maximal voluntary isometric contraction torque (men = 1.94%, women = -10.32%; P = .02) and quadriceps central activation ratio (men = -1.45%, women = -8.69%; P = .03) experienced by men was less than that observed in women. CONCLUSIONS In the presence of quadriceps dysfunction, female participants experienced greater-magnitude reductions in quadriceps function after 30 minutes of exercise than male participants. This indicates a reduced ability to absorb knee-joint loads, which may have significant implications for reinjury and joint osteoarthritis in women after ACLR.
Functional expression of β2 adrenergic receptors responsible for protection against oxidative stress through promotion of glutathione synthesis after Nrf2 upregulation in undifferentiated mesenchymal C3H10T1/2 stem cells

Adrenaline is believed to play a dual role as a neurotransmitter in the central nervous system and an adrenomedullary hormone in the peripheral tissues. In contrast to accumulating evidence for the involvement in endochondral ossification, osteoblastogenesis, and osteoclastogenesis, little attention has been paid to the role of adrenergic signals in the mechanisms underlying proliferation and differentiation of mesenchymal stem cells with self‐renewal capacity and multi‐potentiality to differentiate into osteoblast, chondrocyte, adipocyte, and myocyte lineages. Expression of mRNA was seen for different adrenergic receptor (AdR) subtypes, including β2AdR, in the mesenchymal stem cell line C3H10T1/2 cells and mouse bone marrow mesenchymal stem cells before differentiation. Exposure to adrenaline not only increased cAMP formation, phosphorylation of cAMP responsive element (CRE) binding protein (CREB) on serine133 and CRE reporter activity in a manner sensitive to propranolol, but also rendered C3H10T1/2 cells resistant to the cytotoxicity of hydrogen peroxide, but not of either 2,4‐dinitirophenol or tunicamycin. Adrenaline induced a rapid but transient increase in mRNA expression of the antioxidative gene nuclear factor E2 p45‐related factor‐2 (Nrf2) along with an increase in the cystine/glutamate antiporter subunit xCT mRNA expression. Hydrogen peroxide was less cytotoxic in cells overexpressing Nrf2, moreover, while adrenaline significantly increased xCT promoter activity with an increase in endogenous glutathione levels. These results suggest that adrenaline may selectively protect mesenchymal C3H10T1/2 cells from oxidative stress through a mechanism related to the promoted biosynthesis of glutathione in association with transient Nrf2 expression after activation of β2AdR. J. Cell. Physiol. 218: 268–275, 2009. © 2008 Wiley‐Liss, Inc.
Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure

Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown. In this study, we have examined the influence of chromatin state on the activation of the FA pathway. We describe potent activation of FANCD2 and FANCI monoubiquitination and nuclear foci formation following treatment of cells with the histone methyltransferase inhibitor BRD4770. BRD4770-induced activation of the pathway does not occur via the direct induction of DNA damage or via the inhibition of the G9a histone methyltransferase, a mechanism previously proposed for this molecule. Instead, we show that BRD4770-inducible FANCD2 and FANCI monoubiquitination and nuclear foci formation may be a consequence of inhibition of the PRC2/EZH2 chromatin-modifying complex. In addition, we show that inhibition of the class I and II histone deacetylases leads to attenuated FANCD2 and FANCI monoubiquitination and nuclear foci formation. Our studies establish that chromatin state is a major determinant of the activation of the FA pathway and suggest an important role for the PRC2/EZH2 complex in the regulation of this critical tumor suppressor pathway.
Effect of cyclical forces on the periodontal ligament and alveolar bone remodeling during orthodontic tooth movement.

OBJECTIVE To investigate the effect of externally applied cyclical (vibratory) forces on the rate of tooth movement, the structural integrity of the periodontal ligament, and alveolar bone remodeling. METHODS Twenty-six female Sprague-Dawley rats (7 weeks old) were divided into four groups: CTRL (unloaded), VBO (molars receiving a vibratory stimulus only), TMO (molars receiving an orthodontic spring only), and TMO+VB (molars receiving an orthodontic spring and the additional vibratory stimulus). In TMO and TMO+VB groups, the rat first molars were moved mesially for 2 weeks using Nickel-Titanium coil spring delivering 25 g of force. In VBO and TMO+VB groups, cyclical forces at 0.4 N and 30 Hz were applied occlusally twice a week for 10 minutes. Microfocus X-ray computed tomography analysis and tooth movement measurements were performed on the dissected rat maxillae. Tartrate-resistant acid phosphatase staining and collagen fiber assessment were performed on histological sections. RESULTS Cyclical forces significantly inhibited the amount of tooth movement. Histological analysis showed marked disorganization of the collagen fibril structure of the periodontal ligament during tooth movement. Tooth movement caused a significant increase in osteoclast parameters on the compression side of alveolar bone and a significant decrease in bone volume fraction in the molar region compared to controls. CONCLUSIONS Tooth movement was significantly inhibited by application of cyclical forces.
The Role of Mass Spectrometry and Proteogenomics in the Advancement of HLA Epitope Prediction

A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer‐specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA‐peptide binding data that may not completely capture the rules associated with endogenous processing and presentation. The field of MS has made great improvements in instrumentation speed and sensitivity, chromatographic resolution, and proteogenomic database search strategies to facilitate the identification of HLA‐ligands from a variety of cell types and tumor tissues. As such, these advances have enabled MS profiling of HLA‐binding peptides to be a tractable, orthogonal approach to lower throughput biochemical assays for generating comprehensive datasets to train epitope prediction algorithms. In this review, we will highlight the progress made in the field of HLA‐ligand profiling enabled by MS and its impact on current and future epitope prediction strategies.
Pooled analysis of tobacco use and risk of Parkinson disease.

CONTEXT Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention. OBJECTIVE To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. DESIGN, SETTING, AND PARTICIPANTS We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets. MAIN OUTCOME MEASURE Incident PD. RESULTS We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. CONCLUSIONS Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.
Speech and music shape the listening brain: evidence for shared domain-general mechanisms

Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This review summarizes a large body of behavioral and neuroscientific findings which suggest that the musical experience of trained musicians does modulate speech processing, and a sparser set of data, largely on pitch processing, which suggest in addition that linguistic experience, in particular learning a tone language, modulates music processing. Although research has focused mostly on music on speech effects, we argue that both directions of influence need to be studied, and conclude that the picture which thus emerges is one of mutual interaction across domains. In particular, it is not simply that experience with spoken language has some effects on music perception, and vice versa, but that because of shared domain-general subcortical and cortical networks, experiences in both domains influence behavior in both domains.
Influence of dietary sodium on waterborne copper toxicity in rainbow trout, Oncorhynchus mykiss

Juvenile rainbow trout were fed diets containing control (0.26 mmol/g) or elevated (1.3 mmol/g) dietary Na+ in combination with either background (19 nmol/L) or moderately elevated levels (55 or 118 nmol/L) of waterborne Cu for 21 d. Unidirectional waterborne Na+ uptake rates (measured with 22Na) were up to four orders of magnitude higher than those of Cu (measured with 64Cu). Chronic exposure to elevated dietary Na+ alone or in combination with elevated waterborne Cu decreased whole‐body uptake rates of waterborne Na+ and Cu. Accumulation of new Cu and Na+ at the gills was positively and highly significantly correlated and responded to the experimental treatments in a similar fashion, suggesting that Na+ and Cu have common branchial uptake pathways and that dietary Na+ preexposure modifies these pathways. Chronic exposure to elevated waterborne Cu significantly increased Cu concentrations in the liver but caused only modest increases in total Cu concentrations in the whole body and gill. Chronic exposure to elevated dietary Na+ slightly decreased whole‐body Cu concentration on day 14 and greatly reduced liver Cu concentration on days 14 and 21; new Cu accumulation in whole‐body, gill, and internal organs was reduced on all days. Chronic exposure to elevated waterborne Cu or dietary Na+ alone reduced short‐term gill Cu binding at low waterborne Cu concentrations. At high waterborne Cu concentrations, chronic exposure to elevated waterborne Cu had no effect, while elevated dietary Na+ increased Cu binding to the gills. Combined chronic exposure to elevated dietary Na+ and waterborne Cu decreased gill Cu binding over the entire range of Cu concentrations tested. Clearly, chronic exposure to elevated dietary Na+ and waterborne Cu appears to modify gill Cu‐binding characteristics and may be important considerations in future development of a chronic biotic ligand model for Cu.
Properly colored Hamilton cycles in edge-colored complete graphs

It is shown that for every 2 > 0 and n > n0(2), any complete graph K on n vertices whose edges are colored so that no vertex is incident with more than (1 − 1 √ 2 − 2)n edges of the same color, contains a Hamilton cycle in which adjacent edges have distinct colors. Moreover, for every k between 3 and n any such K contains a cycle of length k in which adjacent edges have distinct colors.
Risk Perception of Climate Change: Empirical Evidence for Germany

The perception of risks associated with climate change appears to be a key factor for the support of climate policy measures. Using a generalized ordered logit approach and drawing on a unique data set originating from two surveys conducted in 2012 and 2014, each among more than 6,000 German households, we analyze the determinants of individual risk perception associated with three kinds of natural hazards: heat waves, storms, and floods. Our focus is on the role of objective risk measures and experience with these natural hazards, whose frequency is likely to be affected by climate change. In line with the received literature, the results suggest that personal experience with adverse events and personal damage therefrom are strong drivers of individual risk perception.
Hepatitis C virus treatment in the real world: optimising treatment and access to therapies

Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in ‘hard-to-treat’ groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.
Effects of rotation frequency and task order on localised muscle fatigue and performance during repetitive static shoulder exertions

Though widely considered to reduce physical exposures and increase exposure variation, there is limited evidence that rotating between tasks is effective in reducing the risk of work-related musculoskeletal disorders (WMSDs). The purpose of this study was to assess the effects of rotation, specifically focusing on rotation frequency and task order, on muscle fatigue and performance when rotating between tasks that load the same muscle group. Twelve participants completed six experimental sessions during which repetitive static shoulder abduction tasks were performed at two exertion levels for one hour either with or without rotation. Compared to only performing a higher or lower exertion task, rotating between the two tasks decreased and increased fatigue, respectively. Increasing rotation frequency adversely affected task performance, and task order had a minor effect on muscle fatigue. These rotation parameters may be important considerations when implementing rotation in the workplace. Practitioner Summary: Rotation is widely used and assumed to reduce the risk of WMSDs, yet little research supports that it is effective in doing so. Results here show that specific aspects of a rotation scheme may influence muscle fatigue and task performance, though further research is needed under more realistic task conditions.
Improved Brain Insulin/IGF Signaling and Reduced Neuroinflammation with T3D-959 in an Experimental Model of Sporadic Alzheimer's Disease.

BACKGROUND Alzheimer's disease (AD) is associated with progressive impairments in brain insulin, insulin-like growth factor (IGF), and insulin receptor substrate (IRS) signaling through Akt pathways that regulate neuronal growth, survival, metabolism, and plasticity. The intracerebral streptozotocin (i.c. STZ) model replicates the full range of abnormalities in sporadic AD. T3D-959, an orally active PPAR-delta/gamma agonist remediates neurocognitive deficits and AD neuropathology in the i.c. STZ model. OBJECTIVE This study characterizes the effects of T3D-959 on AD biomarkers, insulin/IGF/IRS signaling through Akt pathways, and neuroinflammation in an i.c. STZ model. METHODS Long Evans rats were treated with i.c. STZ or saline, followed by daily oral doses of T3D-959 (1 mg/kg) or saline initiated 1 day (T3D-959-E) or 7 days (T3D-959-L) later through Experimental Day 28. Protein and phospho-protein expression and pro-inflammatory cytokine activation were measured in temporal lobe homogenates by duplex or multiplex bead-based ELISAs. RESULTS i.c. STZ treatments caused neurodegeneration with increased pTau, AβPP, Aβ42, ubiquitin, and SNAP-25, and reduced levels of synaptophysin, IGF-1 receptor (R), IRS-1, Akt, p70S6K, mTOR, and S9-GSK-3β. i.c. STZ also broadly increased neuroinflammation. T3D-959 abrogated or reduced most of the AD neuropathological and biomarker abnormalities, increased/normalized IGF-1R, IRS-1, Akt, p70S6K, and S9-GSK-3β, and decreased expression of multiple pro-inflammatory cytokines. T3D-959-E or -L effectively restored insulin/IGF signaling, whereas T3D-959-L more broadly resolved neuroinflammation. CONCLUSION AD remediating effects of T3D-959 are potentially due to enhanced expression of key insulin/IGF signaling proteins and inhibition of GSK-3β and neuroinflammation. These effects lead to reduced neurodegeneration, cognitive impairment, and AD biomarker levels in the brain.
Novel roles of ascorbate in plants: induction of cytosolic Ca2+ signals and efflux from cells via anion channels

Ascorbate is not often considered as a signalling molecule in plants. This study demonstrates that, in Arabidopsis roots, exogenous l-ascorbic acid triggers a transient increase of the cytosolic free calcium activity ([Ca2+]cyt.) that is central to plant signalling. Exogenous copper and iron stimulate the ascorbate-induced [Ca2+]cyt. elevation, while cation channel blockers, free radical scavengers, low extracellular [Ca2+], transition metal chelators, and removal of the cell wall inhibit this reaction. These data show that apoplastic redox-active transition metals are involved in the ascorbate-induced [Ca2+]cyt. elevation. Exogenous ascorbate also induces a moderate increase in programmed cell death symptoms in intact roots, but it does not activate Ca2+ influx currents in patch-clamped root protoplasts. Intriguingly, the replacement of gluconate with ascorbate in the patch-clamp pipette reveals a large ascorbate efflux current, which shows sensitivity to the anion channel blocker, anthracene-9-carboxylic acid (A9C), indicative of the ascorbate release via anion channels. EPR spectroscopy measurements demonstrate that salinity (NaCl) triggers the accumulation of root apoplastic ascorbyl radicals in an A9C-dependent manner, confirming that l-ascorbate leaks through anion channels under depolarization. This mechanism may underlie ascorbate release, signalling phenomena, apoplastic redox reactions, iron acquisition, and control the ionic and electrical equilibrium (together with K+ efflux via GORK channels).
Differential expression of key subunits of SWI/SNF chromatin remodeling complexes in porcine embryos derived in vitro or in vivo

In vitro embryo production is an established method for both humans and animals, but is fraught with inferior development and health issues in offspring born after in vitro fertilization procedures. Analysis of epigenetic changes caused by exposure to in vitro conditions should shed light on potential sources of these phenotypes. Using immunocytochemistry, we investigated the localization and relative abundance of components associated with the SWI/SNF (Switch/Sucrose non‐fermentable) chromatin‐remodeling complex—including BAF155, BAF170, BAF180, BAF53A, BAF57, BAF60A, BAF45D, ARID1A, ARID1B, ARID2, SNF5, and BRD7—in oocytes and in in vitro‐produced and in vivo‐derived porcine embryos. Differences in the localization of BAF155, BAF170, BAF60A, and ARID1B among these sources indicate that improper timing of chromatin remodeling and cellular differentiation might occur in early preimplantation embryos produced and cultured in vitro.
Control of preferences in social networks

We consider the problem of deriving optimal advertising policies for the spread of innovations in a social network. We seek to compute policies that account for i) endogenous network influences, ii) the presence of competitive firms, that also wish to influence the network, and iii) possible uncertainties in the network model. Contrary to prior work in optimal advertising, which also accounts for network influences, we assume a dynamic model of preferences and we compute optimal policies for either finite or infinite horizons. We also compute robust optimal policies in the case where the evolution of preferences is also affected by external disturbances. Finally, in the presence of a competitive firm, we compute optimal Stackelberg and Nash solutions.