192 research outputs found
Nonequilibrium Quantum Thermodynamics of a Particle Trapped in a Controllable Time-Varying Potential
Many advanced quantum techniques feature non-Gaussian dynamics, and the ability to manipulate the system in that domain is the next stage in many experiments. One example of meaningful non-Gaussian dynamics is that of a double-well potential. Here we study the dynamics of a levitated nanoparticle undergoing the transition from a harmonic potential to a double well in a realistic setting, subjected to both thermalization and localization. We characterize the dynamics of the nanoparticle from a thermodynamic point of view, investigating the dynamics with the Wehrl entropy production and its rates. Furthermore, we investigate coupling regimes where the the quantum effect and thermal effect are of the same magnitude, and look at suitable squeezing of the initial state that provides the maximum coherence. The effects and the competitions of the unitary and the dissipative parts onto the system are demonstrated. We quantify the requirements to relate our results to a bonafide experiment with the presence of the environment, and discuss the experimental interpretations of our results in the end
Combined effect of bumetanide, bromide, and GABAergic agonists: An alternative treatment for intractable seizures
Univ Fed Sao Joao del Rei, Lab Neurociencia Expt & Computac, Programa Inst Bioengn, Sao Joao Del Rei, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Expt Neurol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Fisiol, São Paulo, BrazilPontificia Univ Catolica Rio Grande do Su, Inst Cerebro, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Expt Neurol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Fisiol, São Paulo, BrazilWeb of Scienc
Classification of patients with knee osteoarthritis in clinical phenotypes: data from the osteoarthritis initiative
<div><p>Objectives</p><p>The existence of phenotypes has been hypothesized to explain the large heterogeneity characterizing the knee osteoarthritis. In a previous systematic review of the literature, six main phenotypes were identified: Minimal Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP), Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism (BCM). The purpose of this study was to classify a sample of individuals with knee osteoarthritis (KOA) into pre-defined groups characterized by specific variables that can be linked to different disease mechanisms, and compare these phenotypes for demographic and health outcomes.</p><p>Methods</p><p>599 patients were selected from the OAI database FNIH at 24 months’ time to conduct the study. For each phenotype, cut offs of key variables were identified matching the results from previous studies in the field and the data available for the sample. The selection process consisted of 3 steps. At the end of each step, the subjects classified were excluded from the further classification stages. Patients meeting the criteria for more than one phenotype were classified separately into a ‘complex KOA’ group.</p><p>Results</p><p>Phenotype allocation (including complex KOA) was successful for 84% of cases with an overlap of 20%. Disease duration was shorter in the MJD while the CP phenotype included a larger number of Women (81%). A significant effect of phenotypes on WOMAC pain (F = 16.736 p <0.001) and WOMAC physical function (F = 14.676, p < 0.001) was identified after controlling for disease duration.</p><p>Conclusion</p><p>This study signifies the feasibility of a classification of KOA subjects in distinct phenotypes based on subgroup-specific characteristics.</p></div
Structural and functional characterization of endothelial microparticles released by cigarette smoke
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium. CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice. The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis. Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages. These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers
Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications
The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes
English language proficiency and the accommodations for language non-concordance amongst patients utilizing chiropractic college teaching clinics
Background: The number of households in the United States that are not proficient in the English language is growing and presenting a challenge to the health care system. Over nineteen percent of the US population speak a language other than English in the home. This increase in language discordance generates a greater need to find and implement accommodations in the clinical setting to insure accurate and efficient diagnosis and treatment as well as provide for patient safety. Aim: The purpose of this study is to determine the percentage of patients accessing the chiropractic college teaching clinics who are not proficient in the English language and to what extent the colleges provide accommodations for that language disparity. Methods: The clinic directors and deans of the Association of Chiropractic Colleges were surveyed via an on-line survey engine. The survey queried the percentage of the patient population that is not English language proficient, the accommodations the college currently has in place, if the college has a language specific consent to treat document and if the college has a written policy concerning patients without English proficiency. Results: Fifty percent of the contacted chiropractic colleges responded to the survey. In the respondent college clinics 16.5% of the patient population is not proficient in English, with over 75% speaking Spanish. All but one of the respondents provide some level of accommodation for the language non-concordance. Forty five percent of the responding colleges employ a language specific consent to treat form. The implementation of accommodations and the use of a language specific consent to treat form is more prevalent at colleges with a higher percentage of non-English speaking patients. Conclusions: The percentage of patients with limited English proficiency accessing services at the teaching clinics of the chiropractic colleges mirrors the numbers in the general population. There is a wide disparity in the accommodations that the individual colleges make to address this language discordance. There is a need to further develop accurate and meaningful accommodations to address language disparity in the chiropractic teaching clinics.https://doi.org/10.1186/2045-709X-21-
Constitutive activation of signal transducer and activator of transcription 3 regulates expression of vascular endothelial growth factor in human meningioma differentiation
Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis
Contribution of an Aged Microenvironment to Aging-Associated Myeloproliferative Disease
The molecular and cellular mechanisms of the age-associated increase in the incidence of acute myeloid leukemia (AML) remain poorly understood. Multiple studies support that the bone marrow (BM) microenvironment has an important influence on leukemia progression. Given that the BM niche itself undergoes extensive functional changes during lifetime, we hypothesized that one mechanism for the age-associated increase in leukemia incidence might be that an aged niche promotes leukemia progression. The most frequent genetic alteration in AML is the t(8;21) translocation, resulting in the expression of the AML1-ETO fusion protein. Expression of the fusion protein in hematopoietic cells results in mice in a myeloproliferative disorder. Testing the role of the age of the niche on leukemia progression, we performed both transplantation and in vitro co-culture experiments. Aged animals transplanted with AML1-ETO positive HSCs presented with a significant increase in the frequency of AML-ETO positive early progenitor cells in BM as well as an increased immature myeloid cell load in blood compared to young recipients. These findings suggest that an aged BM microenvironment allows a relative better expansion of pre-leukemic stem and immature myeloid cells and thus imply that the aged microenvironment plays a role in the elevated incidence of age-associated leukemia
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