Spin-flip reflection at the normal metal-spin superconductor interface

We study spin transport through a normal metal-spin superconductor junction. A spin-flip reflection is demonstrated at the interface, where a spin-up electron incident from the normal metal can be reflected as a spin-down electron and the spin $2\times \hbar/2$ will be injected into the spin superconductor. When the (spin) voltage is smaller than the gap of the spin superconductor, the spin-flip reflection determines the transport properties of the junction. We consider both graphene-based (linear-dispersion-relation) and quadratic-dispersion-relation normal metal-spin superconductor junctions in detail. For the two-dimensional graphene-based junction, the spin-flip reflected electron can be along the specular direction (retro-direction) when the incident and reflected electron locates in the same band (different bands). A perfect spin-flip reflection can occur when the incident electron is normal to the interface, and the reflection coefficient is slightly suppressed for the oblique incident case. As a comparison, for the one-dimensional quadratic-dispersion-relation junction, the spin-flip reflection coefficient can reach 1 at certain incident energies. In addition, both the charge current and the spin current under a charge (spin) voltage are studied. The spin conductance is proportional to the spin-flip reflection coefficient when the spin voltage is less than the gap of the spin superconductor. These results will help us get a better understanding of spin transport through the normal metal-spin superconductor junction.Comment: 11 pages, 9 figure

Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study

IntroductionThe causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR).MethodsWe performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses.ResultsThe study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88–0.99, p = 0.014), higher interleukin (IL)-1β, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01–1.18, p = 0.027; OR = 1.08, 95% CI: 1.02–1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87–0.98, p = 0.006; OR = 0.95, 95% CI: 0.91–1.00, p = 0.031), higher levels of IL-1β, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00–1.19, p = 0.042; OR = 1.07, 95% CI: 1.01–1.15, p = 0.035; OR = 1.06, 95% CI: 1.00–1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28–0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors.ConclusionIn summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition

Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis

BACKGROUND: Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii. METHODS: Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines. RESULTS: TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection. CONCLUSIONS: T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines

Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice

There is no effective protective vaccine against human toxoplasmosis, which is a potential threat to nearly a third of the world population. Vaccines based on virus-like particles (VLPs) have been highly successful in humans for many years, but have rarely been applied against Toxoplasma gondii infection. In this study, we inserted a B cell epitope (SAG182−102 or SAG1301−320), a CD8+ cell epitope (HF10 or ROP7), and a CD4+ cell epitope (AS15) of T. gondii into a truncated HBcΔ(amino acids1–149) particle to construct four chimeric VLP vaccine formulations, i.e., HBcΔH82, HBcΔH301, HBcΔ R82, and HBcΔ R301. When these chimeric HBc particles were expressed in Escherichia coli, they showed icosahedral morphology similar to that of the original VLPs and were evaluated as vaccine formulations against acute and chronic toxoplasmosis in a mouse model (BALB/c mice (H-2d). All these chimeric HBc VLPs induced strong humoral and cellular immune responses with high IgG antibody titers and interferon(IFN)-γ production. Only the mice immunized with HBcΔH82 showed prolonged survival time (15.6 ± 3.8 vs. 5.6 ± 0.8 days) against acute infection with RH tachyzoites and decrease in brain parasite load (1,454 ± 239 vs. 2,091 ± 263) against chronic infection with Prugniuad cysts, as compared to the findings for the control group. These findings suggest that HBc VLPs would act as an effective carrier for delivering effective multiple antigenic epitopes and would be beneficial for developing a safe and long-acting vaccine against toxoplasmosis

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

Identification of Important Chemical Features of 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors: Application of Ligand Based Virtual Screening and Density Functional Theory

11β-Hydroxysteroid dehydrogenase type1 (11βHSD1) regulates the conversion from inactive cortisone to active cortisol. Increased cortisol results in diabetes, hence quelling the activity of 11βHSD1 has been thought of as an effective approach for the treatment of diabetes. Quantitative hypotheses were developed and validated to identify the critical chemical features with reliable geometric constraints that contribute to the inhibition of 11βHSD1 function. The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA features, was validated using Fischer’s randomization method, a test and a decoy set. The well validated, Hypo1, was used as 3D query to perform a virtual screening of three different chemical databases. Compounds selected by Hypo1 in the virtual screening were filtered by applying Lipinski’s rule of five, ADMET, and molecular docking. Finally, five hit compounds were selected as virtual novel hit molecules for 11βHSD1 based on their electronic properties calculated by Density functional theory

Reduction of Secondary Transmission of SARS-CoV-2 in Households by Face Mask Use, Disinfection and Social Distancing: A Cohort Study in Beijing, China

Introduction Transmission of COVID-19 within families and close contacts accounts for the majority of epidemic growth. Community mask wearing, hand washing and social distancing are thought to be effective but there is little evidence to inform or support community members on COVID-19 risk reduction within families. Methods: A retrospective cohort study of 335 people in 124 families and with at least one laboratory confirmed COVID-19 case was conducted from 28 February to 27 March 2020, in Beijing, China. The outcome of interest was secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the family. Characteristics and practices of primary cases, of well family contacts and household hygiene practices were analysed as predictors of secondary transmission. Results: The secondary attack rate in families was 23.0% (77/335). Face mask use by the primary case and family contacts before the primary case developed symptoms was 79% effective in reducing transmission (OR=0.21, 95% CI 0.06 to 0.79). Daily use of chlorine or ethanol based disinfectant in households was 77% effective (OR=0.23, 95% CI 0.07 to 0.84). Wearing a mask after illness onset of the primary case was not significantly protective. The risk of household transmission was 18 times higher with frequent daily close contact with the primary case (OR=18.26, 95% CI 3.93 to 84.79), and four times higher if the primary case had diarrhoea (OR=4.10, 95% CI 1.08 to 15.60). Household crowding was not significant. Conclusion: The study confirms the highest risk of transmission prior to symptom onset, and provides the first evidence of the effectiveness of mask use, disinfection and social distancing in preventing COVID-19. We also found evidence of faecal transmission. This can inform guidelines for community prevention in settings of intense COVID-19 epidemics

Lean Body Mass, Interleukin 18, and Metabolic Syndrome in Apparently Healthy Chinese

OBJECTIVE: We aimed to investigate how lean body mass is related to circulating Interleukin 18 (IL-18) and its association with metabolic syndrome (MetS) among apparently healthy Chinese. METHODS: A population-based sample of 1059 Chinese men and women aged 35-54 years was used to measure plasma IL-18, glucose, insulin, lipid profile, inflammatory markers and high-molecular-weight (HMW)-adiponectin. Fat mass index (FMI) and lean mass index (LMI) were measured by dual-energy X-ray absorptiometry. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: Circulating IL-18 was positively correlated with LMI after adjustment for FMI (correlation coefficient = 0.11, P<0.001). The association with the MetS (odds ratio 3.43, 95% confidence interval 2.01-5.85) was substantially higher in the highest than the lowest quartile of IL-18 after multiple adjustments including body mass index. In the stratified multivariable regression analyses, the positive association between IL-18 and MetS was independent of tertiles of FMI, inflammatory markers and HMW-adiponectin, but significantly interacted with tertile of LMI (P for interaction = 0.010). CONCLUSION: Elevated plasma IL-18 was associated with higher MetS prevalence in apparently healthy Chinese, independent of traditional risk factors, FMI, inflammatory markers and HMW-adiponectin. More studies are needed to clarify the role of lean mass in IL-18 secretion and its associated cardio-metabolic disorders

energy consumption optimization for high-speed railway based on particle swarm algorithm

From the point of the perspective of train control strategies, energy saving for high-speed railway will be explored in this paper. The energy consumption of high-speed railway is mainly used for train operation, accounting for about 87%. This paper definitely presents a particle swarm algorithm to compute the energy consumption, which aims to reduce the railway energy by obtaining optimal train control strategies. The algorithm establishes a fresh mathematical model, setting energy consumption, running time and stop accuracy as objects, setting limited velocity and motion as constraint condition, and develops an improved adaptive novel multi-population particle swarm with novel crossover and mutation strategies, in order to reduce the computational complexity and ensure the accuracy of the energy consumption results. Over all, a simulation system has been built to resolute problems of high-speed railway. According to the simulation results, the algorithm is proved to be efficient and helpful on energy saving. &copy; 2012 IEEE.From the point of the perspective of train control strategies, energy saving for high-speed railway will be explored in this paper. The energy consumption of high-speed railway is mainly used for train operation, accounting for about 87%. This paper definitely presents a particle swarm algorithm to compute the energy consumption, which aims to reduce the railway energy by obtaining optimal train control strategies. The algorithm establishes a fresh mathematical model, setting energy consumption, running time and stop accuracy as objects, setting limited velocity and motion as constraint condition, and develops an improved adaptive novel multi-population particle swarm with novel crossover and mutation strategies, in order to reduce the computational complexity and ensure the accuracy of the energy consumption results. Over all, a simulation system has been built to resolute problems of high-speed railway. According to the simulation results, the algorithm is proved to be efficient and helpful on energy saving. &copy; 2012 IEEE