Izrada i značajke tankih polikristaliničnih hetero-spojeva n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2

CuGa0.3In0.7Se2 polycrystalline thin films were prepared by thermal evaporation under vacuum of about 10-4Pa, with a deposition rate of about 200 nm/min. The selenization of these films at 723 K improves their properties. The activation energy as well as the optical energy gap of the investigated samples decreased with annealing and selenization. Polycrystalline thin film n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2 heterojunctions were fabricated and the current density - voltage and capacitance - voltage characteristics of the junction were studied. The heterojunctions were exposed to light, and under illumination of 1000 mWcm-2, the open circuit voltage was 580 mV, the short circuit current density 4.8 mAcm-2, the fill factor 0.682 and the electrical conversion efficiency was 1.898% for cells of active area of 1 cm2.Tanke polikristalinične slojeve CuGa0.3In0.7Se2 pripremali smo naparavanjem u vakuumu oko 10−4 Pa, brzinom polaganja oko 200 nm/min. Seleniranje tih slojeva na 723 K poboljšava im svojstva. Aktivacijska energija i optički energijski procijep smanjuju se opuštanjem i seleniranjem. Pripremali smo i polikristalinične tankoslojne hetero-spojeve n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2 i proučavali njihova značajke: gustoća struje – napon i kapacitet – napon. Ćelije ploštine 1 cm2 heterospojeva osvijetlili smo svjetlošću jakosti 1000 mW/cm2 i izmjerili napon otvorenog kruga od 580 mV, gustoću struje kratkog spoja 4.8 mAcm−2 , faktor punjenja 0.682 i učinkovitost pretvorbe 1.898%

Izrada i značajke tankih polikristaliničnih hetero-spojeva n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2

CuGa0.3In0.7Se2 polycrystalline thin films were prepared by thermal evaporation under vacuum of about 10-4Pa, with a deposition rate of about 200 nm/min. The selenization of these films at 723 K improves their properties. The activation energy as well as the optical energy gap of the investigated samples decreased with annealing and selenization. Polycrystalline thin film n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2 heterojunctions were fabricated and the current density - voltage and capacitance - voltage characteristics of the junction were studied. The heterojunctions were exposed to light, and under illumination of 1000 mWcm-2, the open circuit voltage was 580 mV, the short circuit current density 4.8 mAcm-2, the fill factor 0.682 and the electrical conversion efficiency was 1.898% for cells of active area of 1 cm2.Tanke polikristalinične slojeve CuGa0.3In0.7Se2 pripremali smo naparavanjem u vakuumu oko 10−4 Pa, brzinom polaganja oko 200 nm/min. Seleniranje tih slojeva na 723 K poboljšava im svojstva. Aktivacijska energija i optički energijski procijep smanjuju se opuštanjem i seleniranjem. Pripremali smo i polikristalinične tankoslojne hetero-spojeve n-Cd0.9Zn0.1S/p-CuGa0.3In0.7Se2 i proučavali njihova značajke: gustoća struje – napon i kapacitet – napon. Ćelije ploštine 1 cm2 heterospojeva osvijetlili smo svjetlošću jakosti 1000 mW/cm2 i izmjerili napon otvorenog kruga od 580 mV, gustoću struje kratkog spoja 4.8 mAcm−2 , faktor punjenja 0.682 i učinkovitost pretvorbe 1.898%

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting “PVQLSY” motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 M(pro), NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS: We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS: Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION: Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. FUNDING: Bill & Melinda Gates Foundation

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained