Development of Photonic Crystal Fiber Based Gas/ Chemical Sensors

The development of highly-sensitive and miniaturized sensors that capable of real-time analytes detection is highly desirable. Nowadays, toxic or colorless gas detection, air pollution monitoring, harmful chemical, pressure, strain, humidity, and temperature sensors based on photonic crystal fiber (PCF) are increasing rapidly due to its compact structure, fast response and efficient light controlling capabilities. The propagating light through the PCF can be controlled by varying the structural parameters and core-cladding materials, as a result, evanescent field can be enhanced significantly which is the main component of the PCF based gas/chemical sensors. The aim of this chapter is to (1) describe the principle operation of PCF based gas/ chemical sensors, (2) discuss the important PCF properties for optical sensors, (3) extensively discuss the different types of microstructured optical fiber based gas/ chemical sensors, (4) study the effects of different core-cladding shapes, and fiber background materials on sensing performance, and (5) highlight the main challenges of PCF based gas/ chemical sensors and possible solutions

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results

Biochemical characterization of Acacia schweinfurthii serine proteinase inhibitor

One of the many control mechanisms of serine proteinases is their specific inhibition by protein proteinase inhibitors. An extract of Acacia schweinfurthii was screened for potential serine proteinase inhibition. It was successfully purified to homogeneity by precipitating with 80% (v/v) acetone and sequential chromatographic steps, including ion-exchange, affinity purifica- Q2 tion and RP-HPLC. Reducing SDS-PAGE conditions revealed an inhibitor (ASTI) consisting of two polypeptide chains A and B of approximate molecular weights of 16 and 10 kDa, respectively, and under non-reducing conditions, 26 kDa was observed. The inhibitor was shown to inhibit bovine trypsin (Ki of 3.45 nM) at an approximate molar ratio of inhibitor: trypsin (1:1). The A- and B-chains revealed complete sequences of 140 and 40 amino acid residues, respectively. Sequence similarity (70%) was reported between ASTI A-chain and ACTI A-chain (Acacia confusa) using the ClustalW. The B-chain produced a 76% sequence similarity between ASTI and Leucaena leucocephala trypsin inhibitor

Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Immune-mediated necrotising myopathy is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase concentrations, and autoantibodies recognising 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or the signal recognition particle (SRP). No approved therapies exist for people with immune-mediated necrotising myopathy. Previous studies have suggested that complement activation might be pathogenic in immune-mediated necrotising myopathy; therefore, zilucoplan, a complement C5 (C5) inhibitor, could be a potential therapy. We aimed to evaluate the efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive immune-mediated necrotising myopathy. METHODS: IMNM-01 was a phase 2, multicentre, randomised, double-blind, placebo-controlled study done at 15 hospital sites across the USA, the UK, France, and the Netherlands. Participants aged 18–74 years were eligible for inclusion if they had a clinically confirmed diagnosis of immune-mediated necrotising myopathy, positive serology for anti-HMGCR or anti-SRP autoantibodies, clinical evidence of weakness, serum total creatine kinase concentration of more than 1000 U/L at screening, and no change in glucocorticoids or other immunosuppressive therapies for 30 days before baseline or expected during the first 8 weeks of the study. Participants were randomly assigned (1:1) to receive daily subcutaneous zilucoplan (0·3 mg/kg) or placebo for 8 weeks by use of a computerised randomisation algorithm; with optional enrolment in the study open-label extension. Randomisation was stratified by autoantibody status. Participants and study staff were masked to treatment group assignment. Primary efficacy endpoint (in the intent-to-treat population, defined as all participants who were randomly assigned to a treatment group) was percent change from baseline to week 8 in creatine kinase concentrations. Safety analyses were performed on the safety population (participants who received at least one dose of study drug during the main study, irrespective of whether they continued to the extension period—study participants were analysed on the basis of the treatment received). This study is registered with ClinicalTrials.gov, NCT04025632. FINDINGS: Between Nov 7, 2019, and Jan 7, 2021, we randomly assigned 27 participants (13 female and 14 male) to receive zilucoplan (n=12) or placebo (n=15). All 27 participants completed the 8-week main study. At week 8 there were no significant differences between treatment groups in median percent change of creatine kinase concentrations versus baseline (–15·1% [IQR –31·1 to 3·2] in the zilucoplan group vs –16·3% [–43·8 to 5·9] in the placebo group; p=0·46) and no clinically relevant improvement over time within the treatment group despite target engagement based on mode of action. There were no unexpected adverse safety or tolerability findings. Treatment-emergent adverse events were reported in nine (75%) of 12 participants in the zilucoplan group, and in 13 (87%) of 15 participants in the placebo group, and serious treatment-emergent adverse events were reported in zero participants in the zilucoplan group and three (20%) participants in the placebo group. The most frequent treatment-emergent adverse events were headache (four [33%] participants in the zilucoplan group and four [27%] participants in the placebo group) and nausea (three [25%] participants in the zilucoplan group and three [20%] participants in the placebo group). INTERPRETATION: C5 inhibition does not appear to be an efficacious treatment modality for people with immune-mediated necrotising myopathy. Rather than being the primary driver for disease activity, complement activation might be secondary to muscle injury. FUNDING: Ra Pharmaceuticals (now part of UCB Pharma)

A new investigation of electron neutrino appearance oscillations with improved sensitivity in the MiniBooNE+ experiment

Submitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listSubmitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listWe propose the addition of scintillator to the existing MiniBooNE detector to allow a test of the neutral-current/charged-current (NC/CC) nature of the MiniBooNE low-energy excess. Scintillator will enable the reconstruction of 2.2 MeV $\gamma$s from neutron-capture on protons following neutrino interactions. Low-energy CC interactions where the oscillation excess is observed should have associated neutrons with less than a 10% probability. This is in contrast to the NC backgrounds that should have associated neutrons in approximately 50% of events. We will measure these neutron fractions with $\nu_\mu$ CC and NC events to eliminate that systematic uncertainty. This neutron-fraction measurement requires $6.5\times10^{20}$ protons on target delivered to MiniBooNE with scintillator added in order to increase the significance of an oscillation excess to over $5\sigma$. This new phase of MiniBooNE will also enable additional important studies such as the spin structure of nucleon ($\Delta s$) via NC elastic scattering, a low-energy measurement of the neutrino flux via \numu ^{12}C \rightarrow \mu^{-} ^{12}N_\textrm{g.s.} scattering, and a test of the quasielastic assumption in neutrino energy reconstruction. These topics will yield important, highly-cited results over the next 5 years for a modest cost, and will help to train Ph.D. students and postdocs. This enterprise offers complementary information to that from the upcoming liquid Argon based MicroBooNE experiment. In addition, MicroBooNE is scheduled to receive neutrinos in early 2014, and there is minimal additional cost to also deliver beam to MiniBooNE

Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.</p> <p>Methods</p> <p>Recipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.</p> <p>Results</p> <p>The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4^thweek in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all <it>P </it>< 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all <it>P </it>< 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (<it>P </it>> 0.05).</p> <p>Conclusions</p> <p>Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.</p

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one