Electrical spin protection and manipulation via gate-locked spin-orbit fields

The spin-orbit (SO) interaction couples electron spin and momentum via a relativistic, effective magnetic field. While conveniently facilitating coherent spin manipulation in semiconductors, the SO interaction also inherently causes spin relaxation. A unique situation arises when the Rashba and Dresselhaus SO fields are matched, strongly protecting spins from relaxation, as recently demonstrated. Quantum computation and spintronics devices such as the paradigmatic spin transistor could vastly benefit if such spin protection could be expanded from a single point into a broad range accessible with in-situ gate-control, making possible tunable SO rotations under protection from relaxation. Here, we demonstrate broad, independent control of all relevant SO fields in GaAs quantum wells, allowing us to tune the Rashba and Dresselhaus SO fields while keeping both locked to each other using gate voltages. Thus, we can electrically control and simultaneously protect the spin. Our experiments employ quantum interference corrections to electrical conductivity as a sensitive probe of SO coupling. Finally, we combine transport data with numerical SO simulations to precisely quantify all SO terms.Comment: 5 pages, 4 figures (color), plus supplementary information 18 pages, 8 figures (color) as ancillary arXiv pd

Stretchable persistent spin helices in GaAs quantum wells

The Rashba and Dresselhaus spin-orbit (SO) interactions in 2D electron gases act as effective magnetic fields with momentum-dependent directions, which cause spin decay as the spins undergo arbitrary precessions about these randomly-oriented SO fields due to momentum scattering. Theoretically and experimentally, it has been established that by fine-tuning the Rashba $\alpha$ and Dresselhaus $\beta$ couplings to equal $\it{fixed}$ strengths $\alpha=\beta$, the total SO field becomes unidirectional thus rendering the electron spins immune to dephasing due to momentum scattering. A robust persistent spin helix (PSH) has already been experimentally realized at this singular point $\alpha=\beta$. Here we employ the suppression of weak antilocalization as a sensitive detector for matched SO fields together with a technique that allows for independent electrical control over the SO couplings via top gate voltage $V_T$ and back gate voltage $V_B$. We demonstrate for the first time the gate control of $\beta$ and the $\it{continuous\,locking}$ of the SO fields at $\alpha=\beta$, i.e., we are able to vary both $\alpha$ and $\beta$ controllably and continuously with $V_T$ and $V_B$, while keeping them locked at equal strengths. This makes possible a new concept: "stretchable PSHs", i.e., helical spin patterns with continuously variable pitches $P$ over a wide parameter range. The extracted spin-diffusion lengths and decay times as a function of $\alpha/\beta$ show a significant enhancement near $\alpha/\beta=1$. Since within the continuous-locking regime quantum transport is diffusive (2D) for charge while ballistic (1D) for spin and thus amenable to coherent spin control, stretchable PSHs could provide the platform for the much heralded long-distance communication $\sim 8 - 25$ $\mu$m between solid-state spin qubits.Comment: 5 color figures, with supplementary info available on arXiv. arXiv admin note: substantial text overlap with arXiv:1403.351

A possible case of caprine-associated malignant catarrhal fever in a domestic water buffalo (Bubalus bubalis) in Switzerland

ABSTRACT: BACKGROUND: Malignant catarrhal fever (MCF) is a fatal herpesvirus infection, affecting various wild and domestic ruminants all over the world. Water buffaloes were reported to be particularly susceptible for the ovine herpesvirus-2 (OvHV-2) causing the sheep-associated form of MCF (SA-MCF). This report describes the first case of possibly caprine-associated malignant catarrhal fever symptoms in a domestic water buffalo in Switzerland. CASE PRESENTATION: The buffalo cow presented with persistent fever, dyspnoea, nasal bleeding and haematuria. Despite symptomatic therapy, the buffalo died and was submitted to post mortem examination. Major findings were an abomasal ulceration, a mild haemorrhagic cystitis and multifocal haemorrhages on the epicardium and on serosal and mucosal surfaces. Eyes and oral cavity were not affected. Histopathology revealed a mild to moderate lymphohistiocytic vasculitis limited to the brain and the urinary bladder. Although these findings are typical for MCF, OvHV-2 DNA was not detected in peripheral blood lymphocytes or in paraffin-embedded brain, using an OvHV-2 specific real time PCR. With the aid of a panherpesvirus PCR, a caprine herpesvirus-2 (CpHV-2) sequence could be amplified from both samples. CONCLUSIONS: To our knowledge, this is the first report of malignant catarrhal fever in the subfamily Bovinae, where the presence of CpHV-2 could be demonstrated. The etiological context has yet to be evaluated

Development of hybrid immunity during a period of high incidence of Omicron infections.

Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants. We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n = 739) and north-eastern (n = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron). Seroprevalence remained stable from March 2022 (97.6%, n = 1894) to June/July 2022 (98.4%, n = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%). This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population

Limited added value of fungal ITS amplicon sequencing in the study of bovine abortion.

Bovine mycotic abortion is sporadic and caused by different ubiquitous and opportunistic fungi. Recently, a broad spectrum of bacterial opportunists involved in bovine abortion was revealed by 16S rRNA gene amplicon sequencing. We hypothesized that fungal organisms potentially involved in bovine abortion also might remain undetected by conventional culture. In this retrospective study, we therefore applied fungal internal transcribed spacer 2 (ITS2) region amplicon sequencing to 74 cases of bovine abortion submitted to our diagnostic service. The investigation was complemented by fungal culture and, retrospectively, by data from bacteriological, virological and parasitological analyses and histopathological examination of placentas. Fungal DNA was found in both the placentas and abomasal contents, with 92 fungal genera identified. In 18 cases, >75% of the reads belonged to one specific fungal genus: <i>Candida</i> (n = 7), <i>Malassezia</i> (n = 4), <i>Cryptococcus</i> (n = 3), unidentified <i>Capnodiales</i> (n = 3), <i>Actinomucor</i> (n = 1), <i>Cystofilobasidium</i> (n = 1), <i>Penicillium</i> (n = 1), <i>Verticillum</i> (n = 1) and <i>Zymoseptoria</i> (n = 1) with one case harboring two different genera. By culture, in contrast, fungal agents were detected in only 6 cases. Inflammatory and/or necrotizing lesions were found in 27/40 histologically assessed placentas. However, no lesion-associated fungal structures were detected in HE- and PAS-stained specimens. Complementary data revealed the presence of one or more non-fungal possible abortifacient: <i>Chlamydiales</i> , <i>Coxiella burnetii</i> , <i>Leptospira</i> spp., <i>Campylobacter fetus</i> subsp. <i>fetus</i> , <i>Streptococcus uberis</i> , <i>Escherichia coli</i> , <i>Streptococcus pluranimalium</i> , <i>Bacillus licheniformis</i> , <i>Campylobacter fetus</i> subsp. <i>fetus</i> , <i>Serratia marcescens</i> , <i>Trueperella pyogenes</i> , Schmallenbergvirus, <i>Neospora caninum</i> . The mycobiota revealed by sequencing did not differ between cases with or without a possible infectious etiology. Our study suggests that amplicon sequencing of the ITS2 region from DNA isolated from bovine abortion does not provide additional information or new insight into mycotic abortion and without complementary analyses may easily lead to a false interpretation of the role of fungal organisms in bovine abortion

Vaccination with designed neopeptides induces intratumoral, cross-reactive CD4+ T cell responses in glioblastoma

Purpose: The low mutational load of some cancers is considered one reason for the difficulties to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutation to enhance their immunogenicity. Experimental Design: Exome- and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T cell receptor contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TILs) were characterized in detail both at the bulk and clonal level. Results: The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100% respectively of the vaccine peptides. Further, TIL-derived CD4+ T cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor. Conclusions: Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T cell responses in a cold tumor like glioblastoma

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

In silico toxicology protocols

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information