A non-oriented first passage percolation model and statistical invariance by time reversal

We introduce and study a non-oriented first passage percolation model having a property of statistical invariance by time reversal. This model is defined in a graph having directed edges and the passage times associated with each set of outgoing edges from a given vertex are distributed according to a generalized Bernoulli-Exponential law and i.i.d. among vertices. We derive the statistical invariance property by time reversal through a zero-temperature limit of the random walk in Dirichlet environment model.Comment: In honor of Francis Comet

[11C]Carbon Dioxide: Starting Point for Labeling PET Radiopharmaceuticals

Positron emission tomography (PET) is a powerful in vivo imaging technique capable of providing dynamic information on biochemical processes in the living human subject. Applications of PET in oncology, neurology, psychiatry, cardiology and other medical specialties continue to grow. The use of PET relies on the characteristics and availability of appropriately labeled radiopharmaceuticals. Carbon-11 is one of the most useful radionuclides for PET chemistry, since its introduction into a biologically active molecule dose not modify the biochemical properties of the compound. [11C]Carbon dioxide (11CO2), produced by cyclotron, is the most common and versatile primary labeling precursor in the production of 11C–labeled radiopharmaceuticals

Assessment of the Energy Consumption and Drivability Performance of an IPMSM-Driven Electric Vehicle Using Different Buried Magnet Arrangements

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)This study investigates the influence of the buried magnet arrangement on the efficiency and drivability performance provided by an on-board interior permanent magnet synchronous machine for a four-wheel-drive electric car with two single-speed on-board powertrains. The relevant motor characteristics, including flux-linkage, inductance, electromagnetic torque, iron loss, total loss, and efficiency, are analyzed for a set of six permanent magnet configurations suitable for the specific machine, which is controlled through maximum-torque-per-ampere and maximum-torque-per-voltage strategies. Moreover, the impact of each magnet arrangement is analyzed in connection with the energy consumption along four driving cycles, as well as the longitudinal acceleration and gradeability performance of the considered vehicle. The simulation results identify the most promising rotor solutions, and show that: (i) the appropriate selection of the rotor configuration is especially important for the driving cycles with substantial high-speed sections; (ii) the magnet arrangement has a major impact on the maximum motor torque below the base speed, and thus on the longitudinal acceleration and gradeability performance; and (iii) the configurations that excel in energy efficiency are among the worst in terms of drivability, and vice versa, i.e., at the vehicle level, the rotor arrangement selection is a trade-off between energy efficiency and longitudinal vehicle dynamics.Peer reviewedFinal Published versio

Electromagnetic Performance Comparison between 12-Phase Switched Flux and Surface-Mounted PM Machines for Direct-Drive Wind Power Generation

In this article, the 12-phase switched flux permanent magnet (PM) (SFPM) machine and three surface-mounted PM (SPM) machines designed for direct-drive wind power generation are comparatively analyzed. First, feasible stator-slot/rotor-pole combinations for symmetrical 12-phase winding layout are investigated for both machine topologies. Second, the key design parameters of the PM generators including the split ratio and stator teeth width ratio are optimized by finite element analysis to achieve a high phase fundamental EMF per turn and a low cogging torque, both of which are desired by the direct-drive wind power generator. Third, electromagnetic performances including air-gap field, cogging torque, static torque, inductance, output voltage and its regulation factor, output power, and efficiency of the generators are compared. A 10-kW 24-slot/22-pole SFPM prototype is built and tested to validate the FE predicted results.</p

High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

<p>Abstract</p> <p>Background</p> <p>An accurate test for <it>Mycobacterium tuberculosis </it>infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT)-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in <it>bacillus Calmette-Guerin </it>(BCG)-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the <it>M. tuberculosis </it>ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST) was performed for all recruited subjects.</p> <p>Results</p> <p>The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32), group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46) and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22). In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST <5 mm were 50% (16/32) and 41.3% (19/46), respectively. Individuals in group HIV+ATB and HIV+LTB with CD4+ T cells <500/μl, T-SPOT.TB showed a higher sensitivity than TST (64.5% vs. 22.6% and 62.2% vs. 29.7%, respectively, both <it>P </it>< 0.0001). In addition, the sensitivity of T-SPOT.TB assay in group HIV+ATB increased to >85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells <200/μl, the sensitivity was decreased to only 33.3%. Furthermore, the results could be generated by T-SPOT.TB assay within 24 hours, which was more rapid than TST with 48–72 hours.</p> <p>Conclusion</p> <p>ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.</p

Rv1985c, a promising novel antigen for diagnosis of tuberculosis infection from BCG-vaccinated controls

<p>Abstract</p> <p>Background</p> <p>Antigens encoded in the region of difference (RD) of <it>Mycobacterium tuberculosis </it>constitute a potential source of specific antigens for immunodiagnosis. In the present study, recombinant protein Rv1985c from RD2 was cloned, expressed, purified, immunologically characterized and investigated for its potentially diagnostic value for tuberculosis (TB) infection among BCG-vaccinated individuals.</p> <p>Methods</p> <p>T-cell response to Rv1985c was evaluated by IFN-γ ELISPOT in 56 TB patients, 20 latent TB infection (LTBI) and 30 BCG-vaccinated controls in comparison with the commercial T-SPOT. <it>TB </it>kit. Humoral response was evaluated by ELISA in 117 TB patients, 45 LTBI and 67 BCG-vaccinated controls, including all those who had T-cell assay, in comparison with a commercial IgG kit.</p> <p>Results</p> <p>Rv1985c was specifically recognized by cellular and humoral responses from both TB and LTBI groups compared with healthy controls. Rv1985c IgG-ELISA achieved 52% and 62% sensitivity respectively, which outperformed the sensitivity of PATHOZYME-MYCO kit (34%) in detecting active TB (P = 0.011), whereas IFN-γ Rv1985c-ELISPOT achieved 71% and 55% sensitivity in detecting active and LTBI, respectively. Addition of Rv1985c increased sensitivities of ESAT-6, CFP-10 and ESAT-6/CFP-10 combination in detecting TB from 82.1% to 89.2% (P = 0.125), 67.9% to 87.5% (P < 0.001) and 85.7% to 92.9% (P = 0.125), respectively.</p> <p>Conclusions</p> <p>In conclusion, Rv1985c is a novel antigen which can be used to immunologically diagnose TB infection along with other immunodominant antigens among BCG-vaccinated population.</p

nCD64 index as a novel inflammatory indicator for the early prediction of prognosis in infectious and non-infectious inflammatory diseases: An observational study of febrile patients

BackgroundGenerally, febrile patients admitted to the Department of Infectious Diseases, Fudan University Affiliated Huashan Hospital, China may eventually be diagnosed as infectious (ID) or non-infectious inflammatory diseases (NIID). Furthermore, mortality from sepsis remains incredibly high. Thus, early diagnosis and prognosis evaluation of sepsis is necessary. Here, we investigated neutrophil (n)CD64 index profile in a cohort of febrile patients and explored its diagnostic and prognostic value in ID and NIID.MethodsThis observational cohort study enrolled 348 febrile patients from the Emergency Department and Department of Infectious Diseases. nCD64 index were detected using flow cytometry, and dynamically measured at different timepoints during follow-up. Procalcitonin (PCT), C-reactive protein (CRP), and ferritin levels were measured routinely. Finally, the diagnostic and prognostic value of nCD64 index were evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier curve analysis.ResultsOf included 348 febrile patients, 238, 81, and 29 were categorized into ID, NIID, and lymphoma groups, respectively. In ID patients, both SOFA score and infection site had impact on nCD64 index expression. In NIID patients, adult-onset Still’s disease patients had the highest nCD64 index value, however, nCD64 index couldn’t distinguish between ID and NIID. Regardless of the site of infection, nCD64 index was significantly higher in bacterial and viral infections than in fungal infections, but it could not discriminate between bacterial and viral infections. In bloodstream infections, gram-negative (G-) bacterial infections showed an obvious increase in nCD64 index compared to that of gram-positive (G+) bacterial infections. nCD64 index has the potential to be a biomarker for distinguishing between DNA and RNA virus infections. The routine measurement of nCD64 index can facilitate septic shock diagnosis and predict 28-day hospital mortality in patients with sepsis. Serial monitoring of nCD64 index in patients with sepsis is helpful for evaluating prognosis and treatment efficacy. Notably, nCD64 index is more sensitive to predict disease progression and monitor glucocorticoid treatment in patients with NIID.ConclusionsnCD64 index can be used to predict 28-day hospital mortality in patients with sepsis and to evaluate the prognosis. Serial determinations of nCD64 index can be used to predict and monitor disease progression in patients with NIID

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA

Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P &lt; 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity

Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells

BACKGROUND: Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB&LTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%. CONCLUSIONS/SIGNIFICANCE: The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI