The effect of normal and insulating layers on 0-πtransitions in Josephson junctions with a ferromagnetic barrier

Using the Usadel approach, we provide a formalism that allows us to calculate the critical current density of 21 different types of Josephson junctions (JJs) with a ferromagnetic (F) barrier and additional insulating (I) or/and normal (N) layers inserted between the F layer and superconducting (S) electrodes. In particular, we obtain that in SFS JJs, even a thin additional N layer between the S layer and F layer may noticeably change the thickness ${d}_{{\rm{F}}}$ of the F layer at which the 0-π transitions occur. For certain values of ${d}_{{\rm{F}}},$ a 0-π transition can even be achieved by changing only the N layer thickness. We use our model to fit experimental data of SIFS and SINFS tunnel junctions

Single cell transcriptomics reveal polyclonal memory T cell responses in abacavir patch test positive skin

Capsule Summary. Single-cell responses in HLA-B*57:01 abacavir patch test positive skin remote to the acute hypersensitivity reaction demonstrate polyclonal T-cell activation and proliferation characterized by a transcriptional and cellular response consistent with memory responses to altered peptides

Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors

Pre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Polymorphisms in TLR2 are associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus Type 2 infection.

Clinical and virologic manifestations of genital herpes simplex virus type 2 (HSV-2) infection vary widely. We examined frequencies of single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 2, 3, 4, and 9 in a prospective cohort of 128 HSV-2-infected persons whose viral shedding and lesion frequency was measured by daily sampling from genital secretions. Two TLR2 haplotypes (2 and 4) were associated with increased lesional (P=.008 and P=.03) and shedding (P=.02 and P=.001) rates. An SNP in haplotype 2 (-15607A/G) was also associated with shedding (P=.01) and lesional (P=.008) rates. Polymorphisms in TLR2 may be in part responsible for differences in the severity of HSV-2 infection

HLA A*01 and B*08 are associated with increased genital shredding of HSV-2

No abstract availabl

T-cell immunity to human alphaherpesviruses

Human alphaherpesviruses (aHHV) - herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (V

HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions

Variation at HLA and KIR loci is associated with the severity of viral infections. To assess associations of genital HSV-2 infection with human HLA and KIR genetic loci, we measured the frequencies of genital herpes simplex virus (HSV) DNA detection and of genital lesions in HSV-2 seropositive persons. We followed 267 HSV-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days. All persons were laboratory-documented as HIV-seronegative, and all were Caucasian by self-report. HSV detection rate and lesion frequency were compared by genotype using Poisson regression. Overall, HSV was detected on 19.1% of days and lesions on 11.6% of days. The presence of HLA-A*01 was directly associated with HSV detection frequency, whereas the presence of HLA-C*12 was inversely associated with HSV detection frequency. The presence of HLA-A*01 was directly associated with lesion rate, while HLA-A*26, -C*01 and -DQB1*0106 were associated with decreased lesions. We observed an interaction between the absence of both 2DS4del and HLA-Bw4 and higher lesion rate. Heterozygosity of HLA was also associated with reduced lesion frequency. Immune control of genital HSV infection relies on multiple interacting immunogenetic elements, including epistatic interactions between HLA and KIR