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At least 37 records · Page 2

Conceptualizing strategic environmental assessment: Principles, approaches and research directions

Increasing emphasis has been placed in recent years on transitioning strategic environmental assessment (SEA) away from its environmental impact assessment (EIA) roots. Scholars have argued the need to conceptualize SEA as a process designed to facilitate strategic thinking, thus enabling transitions toward sustainability. The practice of SEA, however, remains deeply rooted in the EIA tradition and scholars and practitioners often appear divided on the nature and purpose of SEA. This paper revisits the strategic principles of SEA and conceptualizes SEA as a multi-faceted and multi-dimensional assessment process. It is suggested that SEA can be conceptualized as series of approaches operating along a spectrum from less to more strategic – from impact assessment-based to strategy-based – with each approach to SEA differentiated by the specific objectives of SEA application and the extent to which strategic principles are reflected in its design and implementation. Advancing the effectiveness of SEA requires a continued research agenda focused on improving the traditional SEA approach, as a tool to assess the impacts of policies, plans and programs (PPPs). Realizing the full potential of SEA, however, requires a new research agenda — one focused on the development and testing of a deliberative governance approach to SEA that can facilitate strategic innovations in PPP formulation and drive transitions in short-term policy and initiatives based on longer-term thinking. - Highlights: • SEA facilitates strategic thinking, enabling transitions toward sustainability. • SEA is conceptualized as a spectrum of approaches, from IA-based to strategy-based. • Each approach variably emphasizes strategic principles in its design and practice. • There is no one conceptualization of SEA that is best, SEA is fit for PPP purpose. • Research is needed to advance SEA to facilitate strategic PPP transformations.

54 ENVIRONMENTAL SCIENCES↗

Understanding Peelle’s Pertinent Puzzle bias in generalized least squares regression through eigenspectrum analysis

Certain correlation structures in the data covariance matrix (DCM) used for generalized least squares (GLS) regression can result in biased estimates, commonly known in the field of nuclear data evaluation as Peele’s Pertinent Puzzle (PPP). This article introduces a generative, forward modeling framework within which the PPP bias is characterized through an eigenspectrum analysis of the DCM. This analysis highlights the root cause of the bias, generalizes the problem beyond the nuclear data field, and provides insight to the problem regimes where it can occur. What follows is an understanding that the bias can show up for any experimental neutron time-of-flight data for which systematic uncertainties have been quantified. Lastly, a discussion of the adaptation of cross validation approaches that require pre-whitening to incorporate the known ‘fix’ to the PPP bias in the GLS estimator.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats

The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. As a result, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule.

59 BASIC BIOLOGICAL SCIENCES↗

Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae , Bunyaviridae , and Filoviridae Families

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5;-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1–/– and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1–/– and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this paper, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses.

59 BASIC BIOLOGICAL SCIENCES↗

Bypassing the Pentose Phosphate Pathway: Towards Modular Utilization of Xylose

The efficient use of hemicellulose in the plant cell wall is critical for the economic conversion of plant biomass to renewable fuels and chemicals. Previously, the yeast Saccharomyces cerevisiae has been engineered to convert the hemicellulose-derived pentose sugars xylose and arabinose to D-xylulose-5-phosphate for conversion via the pentose phosphate pathway (PPP). However, efficient pentose utilization requires PPP optimization and may interfere with its roles in NADPH and pentose production. Here, we developed an alternative xylose utilization pathway that largely bypasses the PPP. In the new pathway, D-xylulose is converted to D-xylulose-1-phosphate, a novel metabolite to S. cerevisiae, which is then cleaved to glycolaldehyde and dihydroxyacetone phosphate. This synthetic pathway served as a platform for the biosynthesis of ethanol and ethylene glycol. The use of D-xylulose-1-phosphate as an entry point for xylose metabolism opens the way for optimizing chemical conversion of pentose sugars in S. cerevisiae in a modular fashion.

59 BASIC BIOLOGICAL SCIENCES↗

Advanced crew procedures development techniques

The development of an operational computer program, the Procedures and Performance Program (PPP), is reported which provides a procedures recording and crew/vehicle performance monitoring capability. The PPP provides real time CRT displays and postrun hardcopy of procedures, difference procedures, performance, performance evaluation, and training script/training status data. During post-run, the program is designed to support evaluation through the reconstruction of displays to any point in time. A permanent record of the simulation exercise can be obtained via hardcopy output of the display data, and via magnetic tape transfer to the Generalized Documentation Processor (GDP). Reference procedures data may be transferred from the GDP to the PPP.

Arbet, J. D.↗

Continuation of advanced crew procedures development techniques

An operational computer program, the Procedures and Performance Program (PPP) which operates in conjunction with the Phase I Shuttle Procedures Simulator to provide a procedures recording and crew/vehicle performance monitoring capability was developed. A technical synopsis of each task resulting in the development of the Procedures and Performance Program is provided. Conclusions and recommendations for action leading to the improvements in production of crew procedures development and crew training support are included. The PPP provides real-time CRT displays and post-run hardcopy output of procedures, difference procedures, performance data, parametric analysis data, and training script/training status data. During post-run, the program is designed to support evaluation through the reconstruction of displays to any point in time. A permanent record of the simulation exercise can be obtained via hardcopy output of the display data and via transfer to the Generalized Documentation Processor (GDP). Reference procedures data may be transferred from the GDP to the PPP. Interface is provided with the all digital trajectory program, the Space Vehicle Dynamics Simulator (SVDS) to support initial procedures timeline development.

Arbet, J. D.↗

Crystal Structure of the Catalytic Domain of a Serine Threonine Protein Phosphatase

Reversible phosphorylation of serine and threonine residues is a well-recognized mechanism in eukaryotic cells for the regulation of cell-cycle progression, cell growth and metabolism. Human serine/threonine phosphatases can be placed into two major families, PPP and PPM. To date the structure on one PPP family member (PPl) has been determined. Here we present the structure of a 323-residue catalytic domain of a second phosphatase belonging to the PPP family of enzyme. catalytic domain of the enzyme has been determined to 1.60Angstrom resolution and refined to R=17.5 and Rfree = 20.8%. The catalytic domain possesses a unique fold consisting of a largely monolithic structure, divisible into closely-associated helical and sheet regions. The catalytic site contains two manganese ions that are involved in substrate binding and catalysis. The enzyme crystallizes as a dimer that completely buries catalytic surfaces of both monomers, Also, the structure shows evidence of some flexibility around the active site cleft that may be related to substrate specificity of this enzyme.

Swinglel, Mark↗

TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel

Highlights: • TKTL1 expression is associated with ovarian cancer cell chemoresistance. • The chemo-resistant mechanism of TKTL1 played in cells was investigated. • Metabolomics was used to find the role of TKTL1 in PPP pathway. • The function of TKTL1 was investigated in vivo. Transketolase-like 1 (TKTL1) plays an important role in the pentose phosphate pathway (PPP) branch. The main obstacle of ovarian cancer treatment is chemotherapeutic resistance. We investigated whether inhibiting TKTL1 in OC3/TAX300 cells could re-sensitize paclitaxel-resistant cells to paclitaxel and proposed a mechanism of action. Western blotting revealed that TKTL1 expression levels in OC3/Tax300 cells were significantly higher than those in OC3 cells. Inhibition of TKTL1 significantly decreased the cellular proliferation rate and IC50 for paclitaxel. Metabolomics revealed that NADPH levels were reduced in the si-TKTL1 group, whereas NADP{sup +} was increased compared with the level in the negative si-TKTL1 group. A 2.2-fold increase in the ROS level and an obvious increase in the cell apoptosis rate were observed in the si-TKTL1+paclitaxel group compared with those in the negative si-TKTL1+paclitaxel and OC3/Tax300 + paclitaxel groups. Western blotting revealed that Bax and Caspase 3 proteins were up-regulated, whereas Bcl-2 expression was down-regulated. Quantitative RT-PCR revealed no changes in gst-π or mrp1 gene expression in the three groups, whereas GSH levels were reduced in the si-TKTL1 group as verified by metabolomics. TKTL1 inhibition also reduced tumor growth in vivo. Collectively, TKTL1 down-regulation sensitized paclitaxel-resistant OC3/Tax300 ovarian cancer cells to paclitaxel.

60 APPLIED LIFE SCIENCES↗

Financial sustainability in municipal solid waste management – Costs and revenues in Bahir Dar, Ethiopia

Highlights: • Cost-revenue analysis over 2 years revealed insufficient cost-recovery. • Expenses for motorized secondary collection increased by 82% over two years. • Low fee collection rate and reliance on only one revenue stream are problematic. • Different options for cost reduction and enhanced revenue streams are recommended. • Good public–private alliance is crucial to plan and implement improvement measures. - Abstract: Providing good solid waste management (SWM) services while also ensuring financial sustainability of the system continues to be a major challenge in cities of developing countries. Bahir Dar in northwestern Ethiopia outsourced municipal waste services to a private waste company in 2008. While this institutional change has led to substantial improvement in the cleanliness of the city, its financial sustainability remains unclear. Is the private company able to generate sufficient revenues from their activities to offset the costs and generate some profit? This paper presents a cost-revenue analysis, based on data from July 2009 to June 2011. The analysis reveals that overall costs in Bahir Dar’s SWM system increased significantly during this period, mainly due to rising costs related to waste transportation. On the other hand, there is only one major revenue stream in place: the waste collection fee from households, commercial enterprises and institutions. As the efficiency of fee collection from households is only around 50%, the total amount of revenues are not sufficient to cover the running costs. This results in a substantial yearly deficit. The results of the research therefore show that a more detailed cost structure and cost-revenue analysis of this waste management service is important with appropriate measures, either by the privates sector itself or with the support of the local authorities, in order to enhance cost efficiency and balance the cost-revenues towards cost recovery. Delays in mitigating the evident financial deficit could else endanger the public-private partnership (PPP) and lead to failure of this setup in the medium to long term, thus also endangering the now existing improved and currently reliable service. We present four options on how financial sustainability of the SWM system in Bahir Dar might be enhanced: (i) improved fee collection efficiency by linking the fees of solid waste collection to water supply; (ii) increasing the value chain by sales of organic waste recycling products; (iii) diversifying revenue streams and financing mechanisms (polluter-pays-, cross-subsidy- and business-principles); and (iv) cost reduction and improved cost-effectiveness. We argue that in a PPP setup such as in Bahir Dar, a strong alliance between the municipality and private enterprise is important so that appropriate solutions for improved financial sustainability of a SWM system can be sought and implemented.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

13 C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica

We report volatile fatty acids (VFAs) are an inexpensive and renewable carbon source that can be generated from gas fermentation and anaerobic digestion of fermentable wastes. The oleaginous yeast Yarrowia lipolytica is a promising biocatalyst that can utilize VFAs and convert them into triacylglycerides (TAGs). However, currently there is limited knowledge on the metabolism of Y. lipolytica when cultured on VFAs. To develop a better understanding, we used acetate as the sole carbon source to culture two strains, a control strain and a previously engineered strain for lipid overaccumulation. For both strains, metabolism during the growth phase and lipid production phase were investigated by metabolic flux analysis using two parallel sodium acetate tracers. The resolved flux distributions demonstrate that the glyoxylate shunt pathway is constantly active and the flux through gluconeogenesis varies depending on strain and phase. In particular, by regulating the activities of malate transport and pyruvate kinase, the cells divert only a portion of the glyoxylate shunt flux required to satisfy the needs for anaplerotic reactions and NADPH production through gluconeogenesis and the oxidative pentose phosphate pathway (PPP). Excess flux flows back to the tricarboxylic acid (TCA) cycle for energy production. As with the case of glucose as the substrate, the primary source for lipogenic NADPH is derived from the oxidative PPP.

13C metabolic flux analysis↗

Expression of heterologous non-oxidative pentose phosphate pathway from Bacillus methanolicus and phosphoglucose isomerase deletion improves methanol assimilation and metabolite production by a synthetic Escherichia coli methylotroph

Synthetic methylotrophy aims to develop non-native methylotrophic microorganisms to utilize methane or methanol to produce chemicals and biofuels. We report two complimentary strategies to further engineer a previously engineered methylotrophic E. coli strain for improved methanol utilization. First, we demonstrate improved methanol assimilation in the presence of small amounts of yeast extract by expressing the non-oxidative pentose phosphate pathway (PPP) from Bacillus methanolicus . Second, we demonstrate improved co-utilization of methanol and glucose by deleting the phosphoglucose isomerase gene ( pgi ), which rerouted glucose carbon flux through the oxidative PPP. Both strategies led to significant improvements in methanol assimilation as determined by 13 C-labeling in intracellular metabolites. As a result, introduction of an acetone-formation pathway in the pgi -deficient methylotrophic E. coli strain led to improved methanol utilization and acetone titers during glucose fed-batch fermentation.

59 BASIC BIOLOGICAL SCIENCES↗

Improving neutrino-nuclei interaction models: Recommendations and case studies on Peelle’s Pertinent Puzzle

Improving the modeling of neutrino-nuclei interactions using data-driven methods is crucial for high-precision neutrino oscillation experiments. This paper investigates Peelle’s Pertinent Puzzle (PPP) in the context of neutrino measurements, a longstanding challenge to fitting theoretical models to experimental data. Inconsistencies in data-model comparisons hinder efforts to enhance the accuracy and reliability of model predictions. We analyze various sources contributing to these inconsistencies and propose strategies to address them, supported by practical case studies. We advocate for incorporating model fitting exercises as a standard practice in cross section publications to enhance the robustness of results. We use a common analysis framework to explore PPP-related challenges with MicroBooNE and T2K data in an unified manner. Our findings offer valuable insights for improving the accuracy and reliability of neutrino-nuclei interaction models, particularly by systematically tuning models using data.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Advanced development of a programmable power processor

The need for the development of a multipurpose flexible programmable power processor (PPP) has increased significantly in recent years to reduce ever rising development costs. One of the program requirements the PPP specification will cover is the 25 kW power module power conversion needs. The 25 kW power module could support the Space Shuttle program during the 1980s and 1990s and could be the stepping stone to future large space programs. Trades that led to selection of a microprocessor controlled power processor are briefly discussed. Emphasis is given to the power processing equipment that uses a microprocessor to provide versatility that allows multiple use and to provide for future growth by reprogramming output voltage to a higher level (to 120 V from 30 V). Component selection and design considerations are also discussed.

Lukens, F. E.↗

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Swingle, Mark R.↗

Overview of the Project Prometheus Program

This presentation will give an overview of the Project Prometheus Program (PPP, formerly the Nuclear Systems Initiative, NSI) and the Jupiter Icy Moons Orbiter (JIMO) Project (a component of PPP), a mission to the three icy Galilean moons of Jupiter.

Prometheus nuclear systs propulsion↗