Nonlinear (time domain) and linearized (time and frequency domain) solutions to the compressible Euler equations in conservation law form

Two linearized solvers (time and frequency domain) based on a high resolution numerical scheme are presented. The basic approach is to linearize the flux vector by expressing it as a sum of a mean and a perturbation. This allows the governing equations to be maintained in conservation law form. A key difference between the time and frequency domain computations is that the frequency domain computations require only one grid block irrespective of the interblade phase angle for which the flow is being computed. As a result of this and due to the fact that the governing equations for this case are steady, frequency domain computations are substantially faster than the corresponding time domain computations. The linearized equations are used to compute flows in turbomachinery blade rows (cascades) arising due to blade vibrations. Numerical solutions are compared to linear theory (where available) and to numerical solutions of the nonlinear Euler equations

Structural, elastic and magnetic properties of spinel Co3O4

We have investigated the structural and magnetic properties of Co3O4 ceramic synthesized by solid state reaction method. Powder X-ray diffraction (XRD), Raman spectroscopic and Fourier transforms infrared (FTIR) analysis reveals single phase formation at room temperature. Analysis of XRD data indicates that the Co3O4 crystallizes in cubic symmetry with face-centered cubic (fcc) Bravais lattice. Force constants and elastic properties have been estimated at room temperature using XRD and FTIR spectra and interpreted in terms of bond lengths. An octahedral broadening of the FTIR band (vo) and large force constant (ko) has been observed and indicated the inverse proportionality relationship between the force constant and the bond length. The elastic moduli and Poisson’s ratio uncorrected and corrected to zero porosity reveals the solidification of the Co3O4 ceramic sample. The field cooled (FC) and zero field cooled (ZFC) magnetization measurements using superconducting quantum interface device (SQUID) magnetometer exhibit a well-defined long-range antiferromagnetic order below transition (TN = 40 K) temperature

Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal individuals

Analysis of the public HARPS/ESO spectroscopic archive -- Ca II H&K time series for the HARPS radial velocity database

Magnetic activity is currently the primary limiting factor in radial velocity (RV) exoplanet searches. Even inactive stars, such as the Sun, exhibit RV jitter of the order of a few ms$^{-1}$ due to active regions on their surfaces. Time series of chromospheric activity indicators, such as the Ca II H&K lines, can be utilized to reduce the impact of such activity phenomena on exoplanet search programmes. In addition, the identification and correction of instrumental effects can improve the precision of RV exoplanet surveys. We aim to update the HARPS-RVBank RV database and include an additional $3.5$ years of time series and Ca II H&K lines ($R_{\mathrm{HK}}^\prime$) chromospheric activity indicators. This additional data will aid in the analysis of the impact of stellar magnetic activity on the RV time series obtained with the HARPS instrument. Our updated database aims to provide a valuable resource for the exoplanet community in understanding and mitigating the effects of such stellar magnetic activity on RV measurements. The new HARPS-RVBank database includes all stellar spectra obtained with the HARPS instrument prior to January 2022. The RVs corrected for small but significant nightly zero-point variations were calculated using an established method. The $R_{\mathrm{HK}}^\prime$ estimates were determined from both individual spectra and co-added template spectra with the use of model atmospheres. The new version of the HARPS RV database has a total of 252615 RVs of 5239 stars. Of these, 195387 have $R_{\mathrm{HK}}^\prime$ values, which corresponds to 77\% of all publicly available HARPS spectra. Currently, this is the largest public database of high-precision (down to 1ms$^{-1}$) RVs, and the largest compilation of $R_{\mathrm{HK}}^\prime$ measurements.Comment: 6 pages, 10 figure

Identification and Characterization of Genes Involved in Leishmania Pathogenesis: The Potential for Drug Target Selection

Identifying and characterizing Leishmania donovani genes and the proteins they encode for their role in pathogenesis can reveal the value of this approach for finding new drug targets. Effective drug targets are likely to be proteins differentially expressed or required in the amastigote life cycle stage found in the patient. Several examples and their potential for chemotherapeutic disruption are presented. A pathway nearly ubiquitous in living cells targeted by anticancer drugs, the ubiquitin system, is examined. New findings in ubiquitin and ubiquitin-like modifiers in Leishmania show how disruption of those pathways could point to additional drug targets. The programmed cell death pathway, now recognized among protozoan parasites, is reviewed for some of its components and evidence that suggests they could be targeted for antiparasitic drug therapy. Finally, the endoplasmic reticulum quality control system is involved in secretion of many virulence factors. How disruptions in this pathway reduce virulence as evidence for potential drug targets is presented

Vitamin D Status and Demographic and Lifestyle Determinants Among Adults in the United States (NHANES 2001-2006)

This study looked at risk factors associated with vitamin D levels in the body among a representative sample of adults in the U.S., NHANES III (2001-2006) data were used to assess the relationship between several demographic and health risk factors and vitamin D levels in the body. The Baseline-Category Logit Model was used to test the association between vitamin D level and the potential risk factors age, education, ethnicity, poverty status, physical activity, smoking, alcohol, obesity, diabetes and total cholesterol with both genders. Vitamin D insufficiency and deficiency were significantly associated with age, race, education, physical activity, obesity, diabetes and total cholesterol level for both genders. Almost half of the adults sampled in these data had vitamin D levels lower than the recommended limits, with the highest frequency among the younger groups. Determining an individual’s vitamin D level is very difficult without proper clinical testing. Many of those who have low vitamin D levels are unaware. With such a high prevalence of individuals with low vitamin D levels in the U.S. and a better understanding of characteristics associated with these lower levels, increased education and prevention efforts should be focused toward those with higher risk characteristics

Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites

Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory. Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory. In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites

A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer.

Numerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal centrosome numbers by coupling centrosome duplication with segregation, which is achieved through sustained association of each centrosome with a mitotic spindle pole. Although the microcephaly- and primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, the molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify the minus end-directed microtubule motor protein HSET as a direct binding partner of CEP215. Targeted deletion of the HSET-binding domain of CEP215 in vertebrate cells causes centrosome detachment and results in HSET depletion at centrosomes, a phenotype also observed in CEP215-deficient patient-derived cells. Moreover, in cancer cells with centrosome amplification, the CEP215-HSET complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division. Therefore, stabilization of the centrosome-spindle pole interface by the CEP215-HSET complex could promote survival of cancer cells containing supernumerary centrosomes.S.C. is supported by UK Medical Research Council (MC_U105185859). This work was made possible by funding from Cancer Research UK (C14303/A17197). We acknowledge the support of the University of Cambridge and Hutchison Whampoa Ltd.This is the final version of the article. It first appeared from Nature Publishing Group via https://doi.org/10.1038/ncomms1100