High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene.

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from 2 to 16 μm2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators

High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from < 800 nm^2 to 16 μm^2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators

Efficient Syntax-Driven Lumping of Differential Equations

We present an algorithm to compute exact aggregations of a class of systems of ordinary differential equations (ODEs). Our approach consists in an extension of Paige and Tarjan’s seminal solution to the coarsest refinement problem by encoding an ODE system into a suitable discrete-state representation. In particular, we consider a simple extension of the syntax of elementary chemical reaction networks because (i) it can express ODEs with derivatives given by polynomials of degree at most two, which are relevant in many applications in natural sciences and engineering; and (ii) we can build on two recently introduced bisimulations, which yield two complementary notions of ODE lumping. Our algorithm computes the largest bisimulations in O(r⋅s⋅logs)O(r⋅s⋅log⁡s) time, where r is the number of monomials and s is the number of variables in the ODEs. Numerical experiments on real-world models from biochemistry, electrical engineering, and structural mechanics show that our prototype is able to handle ODEs with millions of variables and monomials, providing significant model reductions

Estimating the costs of air pollution to the National Health Service and social care : An assessment and forecast up to 2035

BACKGROUND: Air pollution damages health by promoting the onset of some non-communicable diseases (NCDs), putting additional strain on the National Health Service (NHS) and social care. This study quantifies the total health and related NHS and social care cost burden due to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in England. METHOD AND FINDINGS: Air pollutant concentration surfaces from land use regression models and cost data from hospital admissions data and a literature review were fed into a microsimulation model, that was run from 2015 to 2035. Different scenarios were modelled: (1) baseline 'no change' scenario; (2) individuals' pollutant exposure is reduced to natural (non-anthropogenic) levels to compute the disease cases attributable to PM2.5 and NO2; (3) PM2.5 and NO2 concentrations reduced by 1 μg/m3; and (4) NO2 annual European Union limit values reached (40 μg/m3). For the 18 years after baseline, the total cumulative cost to the NHS and social care is estimated at £5.37 billion for PM2.5 and NO2 combined, rising to £18.57 billion when costs for diseases for which there is less robust evidence are included. These costs are due to the cumulative incidence of air-pollution-related NCDs, such as 348,878 coronary heart disease cases estimated to be attributable to PM2.5 and 573,363 diabetes cases estimated to be attributable to NO2 by 2035. Findings from modelling studies are limited by the conceptual model, assumptions, and the availability and quality of input data. CONCLUSIONS: Approximately 2.5 million cases of NCDs attributable to air pollution are predicted by 2035 if PM2.5 and NO2 stay at current levels, making air pollution an important public health priority. In future work, the modelling framework should be updated to include multi-pollutant exposure-response functions, as well as to disaggregate results by socioeconomic status

Policy implementation and priorities to create healthy food environments using the Healthy Food Environment Policy Index (Food-EPI): A pooled level analysis across eleven European countries

Background: Food environments have been recognised as highly influential on population diets. Government policies have great potential to create healthy food environments to promote healthy diets. This study aimed to evaluate food environment policy implementation in European countries and identify priority actions for governments to create healthy food environments. Methods: The Healthy Food Environment Policy Index (Food-EPI) was used to evaluate the level of food environment policy and infrastructure support implementation in Estonia, Finland, Germany, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Slovenia, and Spain in 20192021. Evidence of implementation of food environment policies was compiled in each country and validated by government officials. National experts evaluated the implementation of policies and identified priority recommendations. Findings: Finland had the highest proportion (32%, n = 7/22) of policies shaping food environments with a high level of implementation. Slovenia and Poland had the highest proportion of policies rated at very low implementation (42%, n = 10/24 and 36%, n = 9/25 respectively). Policies regarding food provision, promotion, retail, funding, monitoring, and health in all policies were identified as the most important gaps across the European countries. Experts recommended immediate action on setting standards for nutrients of concern in processed foods, improvement of school food environments, fruit and vegetable subsidies, unhealthy food and beverage taxation, and restrictions on unhealthy food marketing to children. Interpretation: Immediate implementation of policies and infrastructure support that prioritize action towards healthy food environments is urgently required to tackle the burden of obesity and diet-related non-communicable diseases in Europe. Funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 774548 and from the Joint Programming Initiative A Healthy Diet for a Healthy Life. (c) 2022 The Author(s

Human Cellular Immune Response to the Saliva of Phlebotomus papatasi Is Mediated by IL-10-Producing CD8+ T Cells and Th1-Polarized CD4+ Lymphocytes

Cutaneous leishmaniasis affects millions of people worldwide and is caused by protozoa of the genus Leishmania. The parasite is transmitted during sand fly bites. While probing the skin for a blood meal, vectors salivate into the host's skin. Sand fly saliva contains several components that increase hemorrhage and interfere with the host's inflammatory response. Data obtained in mice originally indicate that immunization against saliva protected from leishmaniasis supporting possibility that leishmaniasis could be prevented by a vaccine based on sand fly saliva. Herein we investigated the nature and the importance of the cellular immune response developed against sand fly saliva by individuals at risk of cutaneous leishmaniasis due to Leishmania major. We demonstrated that the immunity against saliva is dominated by the activation of lymphocytes producing a suppressive cytokine called IL-10. These data may preclude the protective effect of sand fly saliva pre-exposure in humans. Further experiments revealed that the production of IL-10 masked the presence of a second kind of lymphocytes producing IFN-γ, a rather protective cytokine. The latter finding highlights the importance of the identification of the proteins activating the latter lymphocytes in order to develop vaccines based on selected proteins from the saliva of sand flies

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

<p>Abstract</p> <p>Background</p> <p>Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent.</p> <p>Methods</p> <p>Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer.</p> <p>Results</p> <p>Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors.</p> <p>Conclusions</p> <p>Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.</p

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

<p>Abstract</p> <p>Background</p> <p>Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (<it>SHMT1</it>) C1420T or methylenetetrahydrofolate reductase (<it>MTHFR</it>) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated.</p> <p>Methods</p> <p>The <it>SHMT1 </it>and <it>MTHFR </it>genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.</p> <p>Results</p> <p>There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for <it>SHMT1 </it>TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for <it>MTHFR </it>CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for <it>SHMT1 </it>with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the <it>SHMT1 </it>T allele/<it>MTHFR </it>CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by <it>SHMT1 </it>polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of <it>SHMT1 </it>1420CC genotypes.</p> <p>Conclusions</p> <p>A protective effect of <it>SHMT1 </it>1420T allele or <it>SHMT1 </it>1420 T allele/<it>MTHFR </it>677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of <it>SHMT1 </it>1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in <it>SHMT1 </it>1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why <it>SHMT1 </it>and <it>MTHFR </it>polymorphisms are associated only with rectal and not colon cancer risk.</p