Examining the complex relationship between innovation and regulation through a survey of wastewater utility managers

Despite pressures to increase performance and decrease costs, innovation has been slow to emerge in the municipal wastewater sector. The relationship between regulation and innovation in this sector is a particularly interesting aspect of this conundrum, given the degree to which public utility decision-making is influenced by regulation. Using a national survey, this paper examines US wastewater utility managers’ perceptions of how regulation influences the adoption of new technologies. Recognizing that the relationship between innovation and regulation is complex, we develop the concept of regulation as multifaceted and examine three interrelated aspects of regulation: (1) regulatory requirements, (2) regulators and relationships, and (3) the broader regulatory environment. Specifically, we seek to understand whether and in what ways wastewater utility managers perceive these aspects of regulation as hindering or encouraging the adoption of new technologies. We find that, although stringent effluent limitations are perceived to be a moderate barrier to innovation, most survey respondents did not identify weakening them as a way to encourage innovation. Instead, respondents generally identified factors related to regulatory relationships and factors related to the broader regulatory environment as barriers to innovation, and indicated that addressing these aspects of regulation would encourage innovation. We conclude that loosening or tightening regulatory requirements is not the most effective way to promote innovation in the municipal wastewater sector. Rather, those parties with an interest in innovation can focus on helping utilities and regulators build relationships and better navigate the processes that influence decisions about new technologies

Transcatheter Heart Valve Leaflet Assembly Tooling Improvement Final Design Report

Statement of Confidentiality: The complete senior project report was submitted to the project advisor and sponsor. The results of this project are of a confidential nature and will not be published at this time

Potentials for offset approaches in selected sectors post 2020

This report develops an evaluation framework that policymakers can use to identify whether offsets can add value and uphold environmental integrity of a compliance scheme. It uses a scoring framework on factors to: (1) identify which sectors have hard-to-abate emissions that can justify demanding offsets as cost-containment measures for ambitious climate policies; and (2) identify mitigation activities that are otherwise inaccessible, fosters sustainable development, and the extent to which it enables transformative sectoral action to be eligible to supply offsets. This evaluation framework identifies the optimal conditions that make factors successful in either having sectors demand offsets, or specific mitigation activities supply offsets. Sectoral emissions that are hard-to-abate are those that are technically unavoidable due to a lack and maturity of technologies, and therefore should be allowed to have cost-containment measures - such as offsets - to avoid adverse economic ramifications such as carbon leakage. Mitigation activities that can supply offsets are those that are currently inaccessible to local actor’s due to lack of access to technology, finance or capabilities. Allowing these mitigation activities to be eligible to supply offsets allows to pilot such activities and realize mitigation outcomes outside the original scope of the compliance scheme. This report has chosen selected sectors and mitigation activities to illustrate how this framework can be applied at the global level. It recognizes that country-specific factors can change the assessment of whether the offset approach will add value and uphold environmental integrity to proposed compliance schemes of a country. The report further proposes practical steps policymakers can do to undertake an evaluation at the national level

Suitability and success factors of offsets post-2020

Offsetting enables countries and companies to meet part of their climate change mitigation obligations by using mitigation outcomes generated elsewhere - in lieu of own emission reductions. This report explores the future role of offset approaches and how they could be successfully integrated into a post-2020 climate regime by focusing both the supply and demand side. For this purpose, the report develops a conceptual approach that derives a normative vision of what should be considered a successful offset use in a top-down manner to then link this vision to specific factors on the ground in sectors and jurisdictions where offsets will be generated and used. It explores how these factors influence the successful operationalisation of the offset approach and how they can inform its design. In addition, the report also explores six conceptual design aspects to providing recommendations on how to take these factors into account during the design of the offset approach. Based on these findings, the authors derive overarching policy recommendations on the integration of offsets into carbon pricing schemes

Mdj1p, a novel chaperone of the DnaJ family, is involved in mitochondrial biogenesis and protein folding

Mdj1p, a novel member of the DnaJ family, is a heat shock protein that is associated with the inner membrane of mitochondria of Saccharomyces cerevisiae. Disruption of the MDJ1 gene resulted in a petite phenotype, loss of mitochondrial DNA, and inviability at 37°C. Import of precursor proteins was not affected by a lack of Mdj1p, but folding of newly imported proteins was markedly impaired. The efficiency of refolding of a tester protein, dihydrofolate reductase, was significantly reduced in mitochondria lacking Mdj1p after incubation at elevated temperature. We conclude that Mdj1p is an important mitochondrial chaperone that participates in the folding of newly imported proteins and in the protection of proteins against heat denaturation and aggregation

American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer

The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non–small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy

Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense

[EN] The coat protein (CP) of Melon necrotic spot virus (MNSV) is structurally composed of three major domains. The middle S-domain builds a robust protein shell around the viral genome, whereas the C-terminal protruding domain, or P-domain, is involved in the attachment of virions to the transmission vector. Here, we have shown that the N-terminal domain, or R-domain, and the arm region, which connects the R-domain and S-domain, are involved in different key steps of the viral cycle, such as cell-to-cell movement and the suppression of RNA silencing and pathogenesis through their RNA-binding capabilities. Deletion mutants revealed that the CP RNA-binding ability was abolished only after complete, but not partial, deletion of the R-domain and the arm region. However, a comparison of the apparent dissociation constants for the CP RNA-binding reaction of several partial deletion mutants showed that the arm region played a more relevant role than the R-domain in in vitro RNA binding. Similar results were obtained in in vivo assays, although, in this case, full-length CPs were required to encapsidate full-length genomes. We also found that the R-domain carboxyl portion and the arm region were essential for efficient cell-to-cell movement, for enhancement of Potato virus X pathogenicity, for suppression of systemic RNA silencing and for binding of small RNAs. Therefore, unlike other carmovirus CPs, the R-domain and the arm region of MNSV CP have acquired, in addition to other essential functions such as genome binding and encapsidation functions, the ability to suppress RNA silencing by preventing systemic small RNA transport.This work was funded by grant BIO2014-54862-R from the Spanish Ministry of Science and Innovation and the Prometeo Program GV2014/010 from the Generalitat Valenciana. J.A.N. and M.S.-S. are the recipients of a postdoctoral contract and a PhD fellowship, respectively, from the Ministerio de Educacion y Ciencia of Spain. We thank L. Corachan for technical assistance. The authors have no conflicts of interest to declare.Serra Soriano, M.; Navarro Bohigues, JA.; Pallás Benet, V. (2017). Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense. Molecular Plant Pathology. 18(6):837-849. https://doi.org/10.1111/mpp.12448S83784918

Diverging results of areal and volumetric bone mineral density in Down syndrome

Population with Down syndrome (DS) has lower areal BMD, in association with their smaller skeletal size. However, volumetric BMD and other indices of bone microarchitecture, such as trabecular bone score (TBS) and calcaneal ultrasound (QUS), were normal. INTRODUCTION: Patients with DS have a number of risk factors that could predispose them to osteoporosis. Several studies reported that people with DS also have lower areal bone mineral density, but differences in the skeletal size could bias the analysis. METHODS: Seventy-five patients with DS and 76 controls without intellectual disability were recruited. Controls were matched for age and sex. Bone mineral density (BMD) was measure by Dual-energy X-ray Absorptiometry (DXA), and volumetric bone mineral density (vBMD) was calculated by published formulas. Body composition was also measured by DXA. Microarchitecture was measured by TBS and QUS. Serum 25-hidroxyvitamin D (25OHD), parathyroid hormone (PTH), aminoterminal propeptide of type collagen (P1NP), and C-terminal telopeptide of type I collagen (CTX) were also determined. Physical activity was assessed by the International Physical Activity Questionnaires (IPAQ-short form). To evaluate nutritional intake, we recorded three consecutive days of food. RESULTS: DS individuals had lower height (151 ± 11 vs. 169 ± 9 cm). BMD was higher in the controls (lumbar spine (LS) 0.903 ± 0.124 g/cm2 in patients and 0.997 ± 0.115 g/cm2 in the controls; femoral neck (FN) 0.761 ± .126 g/cm2 and 0.838 ± 0.115 g/cm2, respectively). vBMD was similar in the DS group (LS 0.244 ± 0.124 g/cm3; FN 0.325 ± .0.073 g/cm3) and the controls (LS 0.255 ± 0.033 g/cm3; FN 0.309 ± 0.043 g/cm3). Microarchitecture measured by QUS was slightly better in DS, and TBS measures were similar in both groups. 25OHD, PTH, and CTX were similar in both groups. P1NP was higher in the DS group. Time spent on exercise was similar in both groups, but intensity was higher in the control group. Population with DS has correct nutrition. CONCLUSIONS: Areal BMD is reduced in DS, but it seems to be related to the smaller body and skeletal size. In fact, the estimated volumetric BMD is similar in patients with DS and in control individuals. Furthermore, people with DS have normal bone microarchitecture

A Viable Hypomorphic Allele of the Essential IMP3 Gene Reveals Novel Protein Functions in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the essential IMP3 gene encodes a component of the SSU processome, a large ribonucleoprotein complex required for processing of small ribosomal subunit RNA precursors. Mutation of the IMP3 termination codon to a sense codon resulted in a viable mutant allele producing a C-terminal elongated form of the Imp3 protein. A strain expressing the mutant allele displayed ribosome biogenesis defects equivalent to IMP3 depletion. This hypomorphic allele represented a unique opportunity to investigate and better understand the Imp3p functions. We demonstrated that the +1 frameshifting was increased in the mutant strain. Further characterizations revealed involvement of the Imp3 protein in DNA repair and telomere length control, pointing to a functional relationship between both pathways and ribosome biogenesis