We investigate the observational viability of a class of α-attractors inflationary models in light of the most recent Cosmic Microwave Background (CMB) and Large-Scale Structure (LSS) data. By ...considering a double-well potential we perform a slow-roll analysis to study the behavior of this class of models, which is a continuous interpolation between the chaotic inflation for large values of α and the universal attractor, i.e., ns=1−2/N and r=α12/N2 for small α, where ns is the scalar spectral index, r is the tensor-to-scalar ratio, and N is the e-fold number. In order to explore the parameter space of the model, we also perform a MCMC analysis and find α=7.56±5.15 (1σ).
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation ...exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH
+
) and microglia markers (Iba-1
+
; CD68
+
) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68
+
/ Iba-1
+
cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.
Graphical Abstract
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
Niemann-Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and ...plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy, and ion homeostasis, including iron, manganese, and calcium. Consistently, the cytoplasm to vacuole targeting (Cvt) pathway was increased in
∆ cells and autophagy was compromised despite TORC1 inhibition. Moreover,
∆ cells exhibited iron overload mediated by the low-iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of
∆ cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity, and cell death in the yeast model of NPC1.
Cellulose is mainly produced by plants, although many bacteria, especially those belonging to the genus
, produce a very peculiar form of cellulose with mechanical and structural properties that can ...be exploited in numerous applications. However, the production cost of bacterial cellulose (BC) is very high to the use of expensive culture media, poor yields, downstream processing, and operating costs. Thus, the purpose of this work was to evaluate the use of industrial residues as nutrients for the production of BC by
UCP1619. BC pellicles were synthesized using the Hestrin-Schramm (HS) medium and alternative media formulated with different carbon (sugarcane molasses and acetylated glucose) and nitrogen sources yeast extract, peptone, and corn steep liquor (CSL). A jeans laundry was also tested. None of the tested sources (beside CSL) worked as carbon and nutrient substitute. The alternative medium formulated with 1.5% glucose and 2.5% CSL led to the highest yield in terms of dry and hydrated mass. The BC mass produced in the alternative culture medium corresponded to 73% of that achieved with the HS culture medium. The BC pellicles demonstrated a high concentration of microfibrils and nanofibrils forming a homogenous, compact, and three-dimensional structure. The biopolymer produced in the alternative medium had greater thermal stability, as degradation began at 240°C, while degradation of the biopolymer produced in the HS medium began at 195°C. Both biopolymers exhibited high crystallinity. The mechanical tensile test revealed the maximum breaking strength and the elongation of the break of hydrated and dry pellicles. The dry BC film supported up to 48 MPa of the breaking strength and exhibited greater than 96.98% stiffness in comparison with the hydrated film. The dry film supported up to 48 MPa of the breaking strength and exhibited greater than 96.98% stiffness in comparison with the hydrated film. The values obtained for the Young's modulus in the mechanical tests in the hydrated samples indicated low values for the variable rigidity. The presence of water in the interior and between the nanofibers of the hydrated BC only favored the results for the elasticity, which was 56.37% higher when compared to the dry biomaterial.
We report the discovery of 9088 new spectroscopically confirmed white dwarfs and subdwarfs in the Sloan Digital Sky Survey Data Release 10. We obtain T sub(eff), log g and mass for hydrogen ...atmosphere white dwarf stars (DAs) and helium atmosphere white dwarf stars (DBs), and estimate the calcium/helium abundances for the white dwarf stars with metallic lines (DZs) and carbon/helium for carbon-dominated spectra DQs. We found 1 central star of a planetary nebula, 2 new oxygen spectra on helium atmosphere white dwarfs, 71 DQs, 42 hot DO/PG1159s, 171 white dwarf+main-sequence star binaries, 206 magnetic DAHs, 327 continuum-dominated DCs, 397 metal-polluted white dwarfs, 450 helium-dominated white dwarfs, 647 subdwarfs and 6887 new hydrogen-dominated white dwarf stars.
Summary
The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, ...based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post‐1984 literature there are no published reports of aspiration‐associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus‐derived algorithm in which each patient is first risk‐stratified during their pre‐sedation assessment, using evidence‐based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.
Items (or indicators) that constitute "quality of life" instruments can be classified as either reflective (manifestations of some underlying construct), causal (the construct is an effect of the ...indicators), or composite (the construct is an exact linear combination of the indicators). Psychometric methods based on inter-item associations are only appropriate for reflective indicators, whereas other statistical and non-statistical validation methods can be used for composite or causal indicators. Thus, the distinction has important practical, as well as theoretical, implications. Attempts have been made to empirically identify which items of the EORTC QLQ-C30, a cancer-specific instrument, are causal and which are reflective. Such attempts, however, first require commitment to a particular definition of quality of life, of which there are many. Whether an indicator forms a composite, is causal or reflective of quality of life will depend on the definition adopted, and therefore, the reflective-composite-causal distinction is, arguably, best established on conceptual rather empirical grounds, guided by the "mental experiments" suggested by Bollen (Structural equations with latent variables, Wiley, New York, 1989). Conceptual models of health status and quality of life, as well as a cognitive-linguistic approach to quality of life assessment, may make some contribution to this practice. Theoretical consideration of indicator content can guide not only instrument development and validation, but also the selection of an appropriate instrument.
Conformal multi-Regge theory Costa, Miguel S.; Gonçalves, Vasco; Salgarkar, Aaditya ...
The journal of high energy physics,
09/2023, Letnik:
2023, Številka:
9
Journal Article
Recenzirano
Odprti dostop
A
bstract
We propose and explore the Regge limit for correlation functions of five local primary operators in conformal field theories. After reviewing some features of Regge theory for flat-space ...scattering amplitudes, we analyze the analytic structure of conformal blocks both in position and Mellin space in the Regge limit and propose an extension of conformal Regge theory for five-point functions. As a byproduct of our analysis we also introduce a new basis of three-point correlation functions for operators with spin and the associated Euclidean conformal blocks.
Purpose
To derive a health state classification system (HSCS) from the cancer-specific quality of life questionnaire, the EORTC QLQ-C30, as the basis for a multi-attribute utility instrument.
Methods
...The conceptual model for the HSCS was based on the established domain structure of the QLQ-C30. Several criteria were considered to select a subset of dimensions and items for the HSCS. Expert opinion and patient input informed a priori selection of key dimensions. Psychometric criteria were assessed via secondary analysis of a pooled dataset comprising HRQOL and clinical data from 2616 patients from eight countries and a range of primary cancer sites, disease stages, and treatments. We used confirmatory factor analysis (CFA) to assess the conceptual model’s robustness and generalisability. We assessed item floor effects (>75 % observations at lowest score), disordered item response thresholds, coverage of the latent variable and differential item function using Rasch analysis. We calculated effect sizes for known group comparisons based on disease stage and responsiveness to change. Seventy-nine cancer patients assessed the relative importance of items within dimensions.
Results
CFA supported the conceptual model and its generalisability across primary cancer sites. After considering all criteria, 12 items were selected representing 10 dimensions: physical functioning (mobility), role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems.
Conclusions
The HSCS created from QLQ-C30 items is known as the EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The next phase of the QLU-C10D’s development involves valuation studies, currently planned or being conducted across the globe.
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