Light-activated resistance switching in SiOx RRAM devices

We report a study of light-activated resistance switching in silicon oxide (SiOx) resistive random access memory (RRAM) devices. Our devices had an indium tin oxide/SiOx/p-Si Metal/Oxide/ Semiconductor structure, with resistance switching taking place in a 35 nm thick SiOx layer. The optical activity of the devices was investigated by characterising them in a range of voltage and light conditions. Devices respond to illumination at wavelengths in the range of 410–650 nm but are unresponsive at 1152 nm, suggesting that photons are absorbed by the bottom p-type silicon electrode and that generation of free carriers underpins optical activity. Applied light causes charging of devices in the high resistance state (HRS), photocurrent in the low resistance state (LRS), and lowering of the set voltage (required to go from the HRS to LRS) and can be used in conjunction with a voltage bias to trigger switching from the HRS to the LRS. We demonstrate negative correlation between set voltage and applied laser power using a 632.8 nm laser source. We propose that, under illumination, increased electron injection and hence a higher rate of creation of Frenkel pairs in the oxide—precursors for the formation of conductive oxygen vacancy filaments—reduce switching voltages. Our results open up the possibility of light-triggered RRAM devices

An upper bound on the Kaon B-parameter and Re(epsilon_K)

New precise data in B physics and theoretical developments in K physics lead us to reconsider the weak K^0-\bar{K}^0 transition from a large-N_c viewpoint, N_c being the number of colors. In this framework, we infer an upper limit on \hat{B}_K and the Kaon indirect CP violation.Comment: 11 pages, 4 figures. V2 : Minor corrections, final version accepted for publication in JHE

The Need for Standardizing Diagnosis, Treatment and Clinical Care of Cholecystitis and Biliary Colic in Gallbladder Disease

Gallstones affect 20% of the Western population and will grow in clinical significance as obesity and metabolic diseases become more prevalent. Gallbladder removal (cholecystectomy) is a common treatment for diseases caused by gallstones, with 1.2 million surgeries in the US each year, each costing USD 10,000. Gallbladder disease has a significant impact on the logistics and economics of healthcare. We discuss the two most common presentations of gallbladder disease (biliary colic and cholecystitis) and their pathophysiology, risk factors, signs and symptoms. We discuss the factors that affect clinical care, including diagnosis, treatment outcomes, surgical risk factors, quality of life and cost-efficacy. We highlight the importance of standardised guidelines and objective scoring systems in improving quality, consistency and compatibility across healthcare providers and in improving patient outcomes, collaborative opportunities and the cost-effectiveness of treatment. Guidelines and scoring only exist in select areas of the care pathway. Opportunities exist elsewhere in the care pathway

Combination of verteporfin-photodynamic therapy with 5-aza-2’-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2’-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood. Methods: The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients. Results: Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. Discussion: To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

Top mass dependent alpha_s^3 corrections to B-meson mixing in the MSSM

We compute the top mass dependent NLO strong interaction matching conditions to the Delta F=2 effective Hamiltonian in the general MSSM. We study the relevance of such corrections, comparing its size with that of previously known NLO corrections in the limit mt->0, in scenarios with degeneracy, alignment, and hierarchical squarks. We find that, while these corrections are generally small, there are regions in the parameter space where the contributions to the Wilson coefficients C1 and C4 could partially overcome the expected suppression m_t/M_SUSY.Comment: 15 pages, 6 figure

Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Interferon-γ couples CD8+ T cell avidity and differentiation during infection

Data availability: The mouse scRNAseq and scTCRseq data generated in this study have been deposited in the GEO database under accession code GSE244203 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244203). Datasets reused in this study: EGAS00001005493 [44] (https://ega-archive.org/studies/EGAS00001005493). All data are included in the Supplementary Information or available from the authors upon reasonable requests, as are unique reagents used in this Article. The raw numbers for charts and graphs are available in the Source Data file whenever possible. Source data (https://www.nature.com/articles/s41467-023-42455-4#Sec26) are provided with this paper.Supplementary information is available online at: https://www.nature.com/articles/s41467-023-42455-4#Sec25 .Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.This research was funded in whole, or in part, by the UKRI (BBSRC BB/R015651/1 to A.G.), Cancer Research UK (CR-UK) (C5255/A18085 through the Cancer Research UK Oxford Centre and 29549 to A.G); the Kennedy Trust for Rheumatology Research (KENN151607 and KENN202112 to A.G), John Fell Funds (0006162 to A.G), MLSTF funds (to A.G) and Kennedy Studentship (to L.F.K.U)

Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.

BACKGROUND: The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). RESULTS: We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. CONCLUSION: We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are