DisCharge: Spin-On Anti-Charging Agent for Electron Beam Lithography

This report documents the chemical DisCharge from DisChem, Inc. used as an anti-charging agent for electron beam lithography at the University of Pennsylvania Singh Center for Nanotechnology Quattrone Nanofabrication Facility. Charge accumulation while exposing atop an electrically insulating substrate can severely impact positional accuracy of the beam yielding poor litho. Using DisCharge has been shown to reduce charge accumulation for insulating substrates such as fused silica pieces, glass slides, and PDMS for positive resists such as PMMA, ZEP520A, CSAR 62 and mr-PosEBR

High-Performance Compression of Multibeam Echosounders Water Column Data

Over the last few decades, multibeam echosounders (MBES) have become the dominant technique to efficiently and accurately map the seafloor. They now allow to collect water column acoustic images along with the bathymetry, which is providing a wealth of new possibilities in oceans exploration. However, water column imagery generates vast amounts of data that poses obvious logistic, economic, and technical challenges. Surprisingly, very few studies have addressed this problem by providing efficient lossless or lossy data compression solutions. Currently, the available options are only lossless, providing low compression ratios at low speeds. In this paper, we adapt a data compression algorithm, the Fully Adaptive Prediction Error Coder (FAPEC), which was created to offer outstanding performance under the strong requirements of space data transmission. We have added to this entropy coder a specific pre-processing stage tailored to theKongsbergMaritime water column file formats. Here, we test it on data acquired with Kongsberg MBES models EM302, EM710, andEM2040.With this bespoke pre-processing, FAPEC provides good lossless compression ratios at high speeds, whereas lossy ratios reach water column file sizes even smaller than bathymetry raw files still with good image quality. We show the advantages over other lossless compression solutions, both in terms of compression ratios and speed.We illustrate the quality of water column images after lossy FAPEC compression, as well as its resilience to datagram errors and its potential for automatic detection of water column targets. We also show the successful integration in ARM microprocessors (like those used by smartphones and also by autonomous underwater vehicles), which provides a real-time solution for MBES water column data compression

Protocol for the detection and nutritional management of high-output stomas

Introduction: An issue of recent research interest is excessive stoma output and its relation to electrolyte abnormalities. Some studies have identified this as a precursor of dehydration and renal dysfunction. A prospective study was performed of the complications associated with high-output stomas, to identify their causes, consequences and management.Materials and methods: This study was carried out by a multidisciplinary team of surgeons, gastroenterologists, nutritionists and hospital pharmacists. High-output stoma (HOS) was defined as output ≥1500 ml for two consecutive days. The subjects included in the study population, 43 patients with a new permanent or temporary stoma, were classified according to the time of HOS onset as early HOS (<3 weeks after initial surgery) or late HOS (≥3 weeks after surgery). Circumstances permitting, a specific protocol for response to HOS was applied. Each patient was followed up until the fourth month after surgery.Results: Early HOS was observed in 7 (16 %) of the sample population of 43 hospital patients, and late HOS, in 6 of the 37 (16 %) non-early HOS population. By type of stoma, nearly all HOS cases affected ileostomy, rather than colostomy, patients. The patients with early HOS remained in hospital for 18 days post surgery, significantly longer than those with no HOS (12 days). The protocol was applied to the majority of EHOS patients and achieved 100 % effectiveness. 50 % of readmissions were due to altered electrolyte balance. Hypomagnesaemia was observed in 33 % of the late HOS patients.Conclusion: The protocol developed at our hospital for the detection and management of HOS effectively addresses possible long-term complications arising from poor nutritional status and chronic electrolyte alteration

Greenhouse gas mitigation scenarios for major emitting countries Analysis of current climate policies and mitigation commitments: 2022 update

The 21st session of the Conference of the Parties (COP21) to the United Nations Framework Convention on Climate Change (UNFCCC) held in 2015 adopted the Paris Agreement as the main international climate policy agreement for the post-2020 period (UNCCC, 2015). Parties to the Paris Agreement communicate Nationally Determined Contributions (NDCs), which are pledges containing their contribution to the challenge of reducing global emissions and keeping end-of-century warming below 1.5 °C. There is no yardstick to measure the adequacy of NDCs or the actual progress towards them. Therefore, to measure progress on the implementation of countries’ policies and targets is essential to make the Paris Agreement work. Most countries have updated their NDCs and adopted additional policies since the Paris Agreement came into force. The latest submitted targets are an improvement in comparison to the original ones but remain globally insufficient to curb global emissions (den Elzen et al., 2022a). Policies have also improved since 2015 but projections under currently adopted policies suggest emissions are still expected to increase up to 2030 (Nascimento et al., 2022). Despite these improvements, a global ambition gap exists between countries’ target and policies and the collective mitigation goals of the Paris Agreement. It is, therefore, crucial to continually track countries’ progress towards their NDCs and inform policymakers with up-to-date knowledge to ensure effective implementation of the ratcheting mechanism under the Paris Agreement. This report is prepared by NewClimate Institute, PBL Netherlands Environmental Assessment Agency and IIASA and presents a preliminary assessment of progress by 25 countries toward the achievement of the mitigation components of their 2030 targets. More specifically, the report provides an overview of projected greenhouse gas (GHG) emissions up to 2030, considering existing, and in some cases planned, climate and energy policies, and compares them with the emissions implied by the NDCs. In this year’s update, we compare updated NDC submissions to the original ones submitted between 2014 and 2016 to assess how countries’ NDCs compare to each other and whether current policies are sufficient to meet them

Greenhouse gas mitigation scenarios for major emitting countries - Analysis of current climate policies and mitigation commitments: 2019 update

This report by NewClimate Institute, PBL Netherlands Environmental Assessment Agency and the International Institute for Applied Systems Analysis (IIASA) provides an overview of projected greenhouse gas (GHG) emissions in 25 major emitting countries/regions up to 2030, taking into account the emission trajectories based on current policies and the implementation of nationally determined contributions (NDCs). The report concludes that 12 out of the 25 countries and regions analysed are not on track to achieve the NDC targets they have set for themselves. This report updates the 2018 report, and for the first time presents additional key indicators next to greenhouse gas emissions

Mechanism of Protein Kinetic Stabilization by Engineered Disulfide Crosslinks

The impact of disulfide bonds on protein stability goes beyond simple equilibrium thermodynamics effects associated with the conformational entropy of the unfolded state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional association and strongly affect the rates of irreversible enzyme inactivation, highly relevant in biotechnological applications. While these kinetic-stability effects remain poorly understood, by analogy with proposed mechanisms for processes of protein aggregation and fibrillogenesis, we propose that they may be determined by the properties of sparsely-populated, partially-unfolded intermediates. Here we report the successful design, on the basis of high temperature molecular-dynamics simulations, of six thermodynamically and kinetically stabilized variants of phytase from Citrobacter braakii (a biotechnologically important enzyme) with one, two or three engineered disulfides. Activity measurements and 3D crystal structure determination demonstrate that the engineered crosslinks do not cause dramatic alterations in the native structure. The inactivation kinetics for all the variants displays a strongly non-Arrhenius temperature dependence, with the time-scale for the irreversible denaturation process reaching a minimum at a given temperature within the range of the denaturation transition. We show this striking feature to be a signature of a key role played by a partially unfolded, intermediate state/ensemble. Energetic and mutational analyses confirm that the intermediate is highly unfolded (akin to a proposed critical intermediate in the misfolding of the prion protein), a result that explains the observed kinetic stabilization. Our results provide a rationale for the kinetic-stability consequences of disulfide-crosslink engineering and an experimental methodology to arrive at energetic/structural descriptions of the sparsely populated and elusive intermediates that play key roles in irreversible protein denaturation.This work was supported by grants BIO2009-09562, CSD2009-00088 from the Spanish Ministry of Science and Innovation, and FEDER Funds (JMS-R)

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

Background:There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study.Methods:The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed.Results:MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C–1298C) and diplotypes (CA–TA and TA–TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response.Conclusion:MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug