Ion-irradiation-assisted tuning of phase transformations and physical properties in single crystalline Fe7Pd3ferromagnetic shape memory alloy thin films

Control of multi-martensite phase transformations and physical properties constitute greatly unresolved challenges in Fe7Pd3-based ferromagnetic shape memory alloys. Single crystalline Fe7Pd3 thin films reveal an austenite to martensite phase transformation, continuously ranging from the face-centered cubic (fcc) to the face-centered tetragonal (fct) and body-centered cubic (bcc) phases upon irradiation with 1.8 MeV Kr+ ions. Within the present contribution, we explore this scenario within a comprehensive experimental study: employing atomic force microscopy (AFM) and high resolution transmission electron microscopy (HR-TEM), we first clarify the crystallography of the ion-irradiation-induced austenite $\Rightarrow$ martensite and inter-martensite transitions, explore the multi-variant martensite structures with c-a twinning and unravel a very gradual transition between variants at twin boundaries. Accompanying magnetic properties, addressed locally and globally, are characterized by an increasing saturation magnetization from fcc to bcc, while coercivity and remanence are demonstrated to be governed by magnetocrystalline anisotropy and ion-irradiation-induced defect density, respectively. Based on reversibility of ion-irradiation-induced materials changes due to annealing treatment and a conversion electron Mößbauer spectroscopy (CEMS) study to address changes in order, a quantitative defect-based physical picture of ion-irradiation-induced austenite ⇔ martensite transformation in Fe7Pd3 is developed. The presented concepts thus pave the way for ion-irradiation-assisted optimization strategies for tailored functional alloys

Ion-irradiation-assisted tuning of phase transformations and physical properties in single crystalline Fe₇Pd₃ ferromagnetic shape memory alloy thin films

Control of multi-martensite phase transformations and physical properties constitute greatly unresolved challenges in Fe7Pd3-based ferromagnetic shape memory alloys. Single crystalline Fe7Pd3 thin films reveal an austenite to martensite phase transformation, continuously ranging from the facecentered cubic (fcc) to the face-centered tetragonal (fct) and body-centered cubic (bcc) phases upon irradiation with 1.8 MeV Kr+ ions. Within the present contribution, we explore this scenario within a comprehensive experimental study: employing atomic force microscopy (AFM) and high resolution transmission electron microscopy (HR-TEM), we first clarify the crystallography of the ionirradiation-induced austenite⇒martensite and inter-martensite transitions, explore the multivariant martensite structures with c-a twinning and unravel a very gradual transition between variants at twin boundaries. Accompanying magnetic properties, addressed locally and globally, are characterized by an increasing saturation magnetization from fcc to bcc, while coercivity and remanence are demonstrated to be governed by magnetocrystalline anisotropy and ion-irradiationinduced defect density, respectively. Based on reversibility of ion-irradiation-induced materials changes due to annealing treatment and a conversion electron Mößbauer spectroscopy (CEMS) study to address changes in order, a quantitative defect-based physical picture of ion-irradiation-induced austenite⇔martensite transformation in Fe7Pd3 is developed. The presented concepts thus pave the way for ion-irradiation-assisted optimization strategies for tailored functional alloys

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Background Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration > 10 BAU/mL and a previous SARS-CoV-2 infection as N IgG > 14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wildtype (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

Overscholing in Nederland: trends en scheidslijnen in de periode 1977-1995

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