Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

High-energy Neutrinos from the Inner Circumnuclear Region of NGC 1068

High-energy neutrinos are detected by the IceCube Observatory in the direction of NGC 1068, the archetypical type II Seyfert galaxy. The neutrino flux, surprisingly, is more than an order of magnitude higher than the $\gamma$-ray upper limits at measured TeV energy, posing tight constraints on the physical conditions of a neutrino production site. We report an analysis of the sub-millimeter, mid-infrared, and ultraviolet observations of the central $50$ pc of NGC 1068 and suggest that the inner dusty torus and the region where the jet interacts with the surrounding interstellar medium (ISM) may be a potential neutrino production site. Based on radiation and magnetic field properties derived from observations, we calculate the electromagnetic cascade of the $\gamma$-rays accompanying the neutrinos. Our model may explain the observed neutrino flux above $\sim 10$ TeV and contribute to 20% of the neutrino flux at 3 TeV. It predicts a unique sub-TeV $\gamma$-ray component, which could be identified by a future observation. Jet-ISM interactions are commonly observed in the proximity of jets of both supermassive and stellar-mass black holes. Our results imply that such interaction regions could be $\gamma$-ray obscured neutrino production sites, which are needed to explain the IceCube diffuse neutrino flux.Comment: 8 pages, 4 figures, 1 tabl

Effect of testing condition on the loss on ignition results of anhydrous granulated blast furnace slags determined via thermogravimetry

A key property influencing the quality of a blast furnace slag (GBFS) used in cements and concretes is the loss on ignition (LOI), which is associated with the amount of moisture and carbonates present. Both EN and ASTM standards describe determination of the LOI of GBFS, and thermogravimetric analysis (TGA) is also a valuable test which provides information that can be related to the LOI. However, the final mass loss obtained by TGA is influenced by the testing conditions including nature and flowrate of the gas used, the sample mass and heating rate, and there is no existing standard method for TGA of SCMs. As part of the efforts of RILEM TC 238-SCM, this study assesses the effect of the gas environment and gas flowrate on the observed mass loss from a GBFS, determined via TGA in nitrogen, argon or air atmospheres using different gas flowrates, and without correction for oxidation of sulfides to sulfates. Significant mass changes occur between 800–1000 C independent of the gas used, and are more notable under an oxidising atmosphere and at low gas flowrates. These results elucidate that it is required to standardise TGA testing parameters for analysis of GBFS to enable collection of meaningful results by this technique

Multi-task multiple kernel machines for personalized pain recognition from functional near-infrared spectroscopy brain signals

Currently there is no validated objective measure of pain. Recent neuroimaging studies have explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to measure alterations in brain function in evoked and ongoing pain. In this study, we applied multi-task machine learning methods to derive a practical algorithm for pain detection derived from fNIRS signals in healthy volunteers exposed to a painful stimulus. Especially, we employed multi-task multiple kernel learning to account for the inter-subject variability in pain response. Our results support the use of fNIRS and machine learning techniques in developing objective pain detection, and also highlight the importance of adopting personalized analysis in the process.Comment: International Conference on Pattern Recognition (ICPR

Measurements and analysis of large-scale fading characteristics in curved subway tunnels at 920 MHz, 2400 MHz, and 5705 MHz

ave propagation characteristics in curved tunnels are of importance for designing reliable communications in subway systems. This paper presents the extensive propagation measurements conducted in two typical types of subway tunnels—traditional arched “Type I” tunnel and modern arched “Type II” tunnel—with300- and 500-m radii of curvature with different configurations—horizontal and vertical polarizations at 920, 2400, and 5705 MHz, respectively. Based on the measurements, statistical metrics of propagation loss and shadow fading (path-loss exponent, shadow fading distribution, autocorrelation, and cross-correlation) in all the measurement cases are extracted. Then, the large-scale fading characteristics in the curved subway tunnels are compared with the cases of road and railway tunnels, the other main rail traffic scenarios, and some “typical” scenarios to give a comprehensive insight into the propagation in various scenarios where the intelligent transportation systems are deployed. Moreover, for each of the large-scale fading parameters, extensive analysis and discussions are made to reflect the physical laws behind the observations. The quantitative results and findings are useful to realize intelligent transportation systems in the subway system

Adult brain tumour research in 2024: Status, challenges and recommendations

In 2015, a groundswell of brain tumour patient, carer and charity activism compelled the UK Minister for Life Sciences to form a brain tumour research task and finish group. This resulted, in 2018, with the UK government pledging £20m of funding, to be paralleled with £25m from Cancer Research UK, specifically for neuro-oncology research over the subsequent 5 years. Herein, we review if and how the adult brain tumour research landscape in the United Kingdom has changed over that time and what challenges and bottlenecks remain. We have identified seven universal brain tumour research priorities and three cross-cutting themes, which span the research spectrum from bench to bedside and back again. We discuss the status, challenges and recommendations for each one, specific to the United Kingdom

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Gold/silver/gold trilayer films on nanostructured polycarbonate substrates for direct and label-free nanoplasmonic biosensing

Altres ajuts: CONACYT, Grant/Award Number: 225362Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commercial Blu-ray optical discs as nanoslits-based flexible polymer substrates. A thin gold film was used as an adhesion and nucleation layer to improve the chemical stability and reduce the surface roughness of the overlying silver film, without increasing ohmic plasmon losses. The structures were physically and optically characterized and compared with nanostructures of single gold layer. Ultrasmooth and chemically stable trilayer nanostructures with a surface roughness <0.5 nm were obtained following a simple and reproducible fabrication process. They showed a figure of merit (FOM) value up to 69.2 RIU which is significantly higher (more than 95%) than the gold monolayer counterpart. Their potential for biosensing was demonstrated by employing the trilayer sensor for the direct and refractometric (label-free) detection of C-reactive protein (CRP) biomarker in undiluted urine achieving a Limit of Detection (LOD) in the pM order

The Synthetic Plasmodium falciparum Circumsporozoite Peptide PfCS102 as a Malaria Vaccine Candidate: A Randomized Controlled Phase I Trial

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227