Pee power urinal-microbial fuel cell technology field trials in the context of sanitation

This paper reports on the pee power urinal field trials, which are using microbial fuel cells for internal lighting. The first trial was conducted on Frenchay Campus (UWE, Bristol) from February-May 2015 and demonstrated the feasibility of modular MFCs for lighting, with University staff and students as the users; the next phase of this trial is ongoing. The second trial was carried out during the Glastonbury Music Festival at Worthy Farm, Pilton in June 2015, and demonstrated the capability of the MFCs to reliably generate power for internal lighting, from a large festival audience (∼1000 users per day). The power output recorded for individual MFCs is 1-2 mW, and the power output of one 36-MFC-module, was commensurate of this level of power. Similarly, the real-time electrical output of both the pee power urinals was proportional to the number of MFCs used, subject to temperature and flow rate: the campus urinal consisted of 288 MFCs, generating 75 mW (mean), 160 mW (max) with 400 mW when the lights were connected directly (no supercapacitors); the Glastonbury urinal consisted of 432 MFCs, generating 300 mW (mean), 400 mW (max) with 800 mW when the lights were connected directly (no supercapacitors). The COD removal was >95% for the campus urinal and on average 30% for the Glastonbury urinal. The variance in both power and urine treatment was due to environmental conditions such as temperature and number of users. This is the first time that urinal field trials have demonstrated the feasibility of MFCs for both electricity generation and direct urine treatment. In the context of sanitation and public health, an independent power source utilising waste is essential in terms of both developing and developed world

Sirt1 protects from K-Ras-driven lung carcinogenesis.

The NAD+-dependent deacetylase SIRT1 can be oncogenic or tumor suppressive depending on the tissue. Little is known about the role of SIRT1 in non-small cell lung carcinoma (NSCLC), one of the deadliest cancers, that is frequently associated with mutated K-RAS Therefore, we investigated the effect of SIRT1 on K-RAS-driven lung carcinogenesis. We report that SIRT1 protein levels are downregulated by oncogenic K-RAS in a MEK and PI3K-dependent manner in mouse embryo fibroblasts (MEFs), and in human lung adenocarcinoma cell lines. Furthermore, Sirt1 overexpression in mice delays the appearance of K-RasG12V-driven lung adenocarcinomas, reducing the number and size of carcinomas at the time of death and extending survival. Consistently, lower levels of SIRT1 are associated with worse prognosis in human NSCLCs. Mechanistically, analysis of mouse Sirt1-Tg pneumocytes, isolated shortly after K-RasG12V activation, reveals that Sirt1 overexpression alters pathways involved in tumor development: proliferation, apoptosis, or extracellular matrix organization. Our work demonstrates a tumor suppressive role of SIRT1 in the development of K-RAS-driven lung adenocarcinomas in mice and humans, suggesting that the SIRT1-K-RAS axis could be a therapeutic target for NSCLCs.We thank Jesus Herranz for his biostatistical advice; and Alba de Martino, Patricia Gonzalez, Maria Gomez, and Zaira Vega, from the Histopathology Unit at the CNIO, for their work in mouse histopathology. Work in the laboratory of P.J.F.-M. was funded by the IMDEA Food, the Spanish Association against Cancer (aecc) and the Ramon Areces (CIVP18A3891) Foundation. Work in the laboratory of M.S. was funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF project), the European Research Council (ERC Advanced Grant), the European Union (RISK-IR project), and the Botin Foundation and Banco Santander (Santander Universities Global Division). Work in the laboratory of DH was funded by Rutgers Cancer Institute of New Jersey, the Alex's Lemonade Stand Foundation Shark Tank Award and by the National Institutes of Health Grant K99/R00 CA197869. Work in the laboratory of M.S.C. was supported by a grant (SAF2012-40026) from the Spanish Ministry of Science and Innovation. L.F.C-M. was supported by a PhD Fellowship from the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016).S

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Logistics and maintenance research activities for DONES facility

DONES is planned to operate on a continuous basis with only two beam stop periods per year for maintenance. The planned operational availability is 70 %, which calls for a carefully analyzed preventive maintenance. The purpose of the research is to propose a realistic and comprehensive logistics and maintenance plan. All the maintenance activities are included in a Maintenance Matrix based on the Plant Breakdown Structure of the project. This is the basis for the creation of a maintenance plan that will lead to a Work Schedule. Special mention within this matrix will be given to those Maintenance operations that must be included in order to comply with regulation. The need of replacement of components impose some requirements on the dimensions of architec tural features of the main building such as doors, airlocks, corridors and shipping bays. To enable these re placements, the flow of materials has been developed and analyzed by an intralogistics simulation with AnyLogic. The results of this simulation lead to modifications on either the building or the components such that the replacements are feasible. The periodic replacement of an activated component has been analyzed using FMEA methodology resulting in proposals for the plant equipment designers as well as the remote handling equipment designers. Virtual reality simulations are used for a staged approach to the maintenance operation. The simulation of the HEBT scraper helped to define in detail each step or the maintenance operation. This tool has proven to be very useful to prompt changes in both the plant equipment design and the remote handling equipment. Also, the procedure of the operation itself can be refined and optimized. The conclusion of the research activities is the contribution to the definition of the building, plant equipment and achievement of the target availability.European Commission 10105220

Beam-facing material selection for mitigation of residual doses in the HEBT of IFMIF-DONES

IFMIF-DONES will be an irradiation facility based on a 40 MeV deuteron accelerator. Unavoidable beam losses along the accelerator result in deuterium interactions with the beam facing materials of the vacuum beam pipe, some of them leading to material activation. The initial design of the beam pipe was based on stainless steel, but an evaluation of the residual doses from the pipe showed high values after operation of the accelerator. The accelerator beam line must be periodically maintained, and excessive cooling times for reaching acceptable dose levels may result in poorer availability of the facility. A deeper study of the High Energy Beam Transport line (HEBT) showed that a direct reaction between deuterons and iron in steel resulted in the production of Co-56, with a half-life of 77 days. This radioisotope is the main source of the radiation and makes it impractical to wait for a proper attenuation of the radiation field. A redesign of beam line elements has been performed to avoid the presence of stainless steel as a beam facing material and to replace it with aluminum where possible, resulting in faster decay of residual doses. This work contains a summary of the nuclear analysis performed for the computation of residual doses with stainless steel beam pipe, stressing the uncertainties of the calculations, based on the limited availability of nuclear data for the relevant nuclear reaction Fe56 (d,2n). The proposed replacement of element materials is also described, and an updated nuclear analysis shows the reduction of residual radiation, and its impact on possible maintenance operations

Synergistic antileukemic therapies in NOTCH1-induced T-ALL

The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo. Mechanistically, network perturbation analyses showed eIF2A-phosphorylation-mediated inhibition of protein translation as a critical mediator of the antileukemic effects of withaferin A and its interaction with NOTCH1 inhibition. Overall, these results support a role for anti-NOTCH1 therapies and protein translation inhibitor combinations in the treatment of T-ALL.status: publishe

NADPH oxidase 4 (Nox4) deletion accelerates liver regeneration in mice

Liver is a unique organ in displaying a reparative and regenerative response after acute/chronic damage or partial hepatectomy, when all the cell types must proliferate to re-establish the liver mass. The NADPH oxidase NOX4 mediates Transforming Growth Factor-beta (TGF-β) actions, including apoptosis in hepatocytes and activation of stellate cells to myofibroblasts. Aim of this work was to analyze the impact of NOX4 in liver regeneration by using two mouse models where Nox4 was deleted: 1) general deletion of Nox4 (NOX4-/-) and 2) hepatocyte-specific deletion of Nox4 (NOX4hepKO). Liver regeneration was analyzed after 2/3 partial hepatectomy (PH). Results indicated an earlier recovery of the liver-to-body weight ratio in both NOX4-/- and NOX4hepKO mice and an increased survival, when compared to corresponding WT mice. The regenerative hepatocellular fat accumulation and the parenchyma organization recovered faster in NOX4 deleted livers. Hepatocyte proliferation, analyzed by Ki67 and phospho-Histone3 immunohistochemistry, was accelerated and increased in NOX4 deleted mice, coincident with an earlier and increased Myc expression. Primary hepatocytes isolated from NOX4 deleted mice showed higher proliferative capacity and increased expression of Myc and different cyclins in response to serum. Transcriptomic analysis through RNA-seq revealed significant changes after PH in NOX4-/- mice and support a relevant role for Myc in a node of regulation of proliferation-related genes. Interestingly, RNA-seq also revealed changes in the expression of genes related to activation of the TGF-β pathway. In fact, levels of active TGF-β1, phosphorylation of Smads and levels of its target p21 were lower at 24 h in NOX4 deleted mice. Nox4 did not appear to be essential for the termination of liver regeneration in vivo, neither for the in vitro hepatocyte response to TGF-β1 in terms of growth inhibition, which suggest its potential as therapeutic target to improve liver regeneration, without adverse effects.This work was supported by grants from: 1) Agencia Estatal de Investigación and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (MICINN), Spain, cofounded by FEDER funds/European Regional Development Fund – a way to build Europe- (SAF2015-64149-R and RTI2018-094079-B-I00 to I.F.; PT17/0009/0019 to A.E.-C.; Programa Operativo FEDER: Plurirregional de España (POPE) 2014–2020 and Catalunya 2014–2020 to CNAG-CRG authors; 2) NIH 2R01DK083283 (to N.J.T.). M.H.-I. was recipient of a predoctoral grant from IDIBELL-Oncobell Program. D.C-D. was recipient of a pre-doctoral grant from the FPI program. J.L-L. was recipient of Boehringer Ingelheim Fonds Travel grant. The CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, is funded by the Instituto de Salud Carlos III, Spain. We thank the Generalitat de Catalunya through the CERCA Programme and the Departament de Salut and Departament d’Empresa i Coneixement, the Centro de Excelencia Severo Ochoa and the MICINN to the EMBL partnership for institutional suppor