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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

High Activity and Selectivity for Catalytic Alkane–Alkene Transfer (De)hydrogenation by ( tBu PPP)Ir and the Importance of Choice of a Sacrificial Hydrogen Acceptor

The triphosphorus-coordinating pincer iridium fragment ( tBu PPP)Ir was recently reported to be highly active for the catalytic dehydrogenation of n-alkanes. Dehydrogenation is calculated to be highly regioselective for the terminal position of n-alkanes. Here, the extremely high intermolecular selectivity observed in n-alkane/cycloalkane competition experiments supports the prediction of extremely high regioselectivity for dehydrogenation of n-alkanes. The use of sterically unhindered hydrogen acceptors is key to observing the high activity of the ( tBu PPP)Ir fragment. 4,4-Dimethylpent-1-ene (TBP) is found to be particularly convenient for this purpose. With the commonly used hydrogen acceptor 3,3-dimethylbut-1-ene (TBE), ( tBu PPP)Ir affords n-alkane dehydrogenation at a rate no different than that obtained with the well-known fragment ( iPr PCP)Ir. However, with the use of TBP as acceptor, ( tBu PPP)Ir shows much greater activity for n-alkane transfer dehydrogenation than previously reported catalysts, affording appreciable rates even at 50 °C, an unprecedentedly low temperature for catalytic alkane transfer dehydrogenation. Also critical to the identification of ( tBu PPP)Ir as a highly effective catalyst is the use of n-alkane substrate rather than the commonly used “model” dehydrogenation substrate, cyclooctane, with which dehydrogenation rates are much lower than those with n-alkanes.

10 SYNTHETIC FUELS↗
DOE OSTI2016

Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C

Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, in this work we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure–activity relationship studies and analysis of high-resolution (1.25 Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Reactivity of Iridium Complexes of a Triphosphorus-Pincer Ligand Based on a Secondary Phosphine. Catalytic Alkane Dehydrogenation and the Origin of Extremely High Activity

The selective functionalization of alkanes and alkyl groups is a major goal of chemical catalysis. Toward this end, a bulky triphosphine with a central secondary phosphino group, bis(2-di-t-butyl-phosphinophenyl)phosphine ( tBu P H PP), has been synthesized. When complexed to iridium, it adopts a meridional (“pincer”) configuration. The secondary phosphino H atom can undergo migration to iridium to give an anionic phosphido-based–pincer ( tBu PPP) complex. Stoichiometric reactions of the ( tBu PPP)Ir complexes reflect a distribution of steric bulk around the iridium center in which the coordination site trans to the phosphido group is quite crowded; one coordination site cis to the phosphido is even more crowded; and the remaining site is particularly open. The ( tBu PPP)Ir precursors are the most active catalysts reported to date for dehydrogenation of n-alkanes, by about 2 orders of magnitude. The electronic properties of the iridium center are similar to that of well-known analogous ( R PCP)Ir catalysts. Accordingly, DFT calculations predict that ( tBu PPP)Ir and ( tBu PCP)Ir are, intrinsically, comparably active for alkane dehydrogenation. While dehydrogenation by ( R PCP)Ir proceeds through an intermediate trans-(PCP)IrH 2 (alkene), ( tBu PPP)Ir follows a pathway proceeding via cis-(PPP)IrH 2 (alkene), thereby circumventing unfavorable placement of the alkene at the bulky site trans to phosphorus. ( tBu PPP)Ir and ( tBu PCP)Ir, however, have analogous resting states: square planar (pincer)Ir(alkene). Alkene coordination at the crowded trans site is therefore unavoidable in the resting states. Furthermore, the resting state of the ( tBu PPP)Ir catalyst is destabilized by the architecture of the ligand, and this is largely responsible for its unusually high catalytic activity.

02 PETROLEUM↗
DOE OSTI2023

Shear-aligned large-area organic semiconductor crystals through extended π–π interaction

Small molecule-based organic semiconductors are of broad interest in organic field-effect transistors (OFETs) due to their potential for high crystallinity and electrical performance. The 2D molecule, TIPS-peri-pentacenopentacene (TIPS-PPP), which is the vertical extension of the 1D TIPS-pentacene (TIPS-PEN) molecule, offers a lower bandgap, higher aromaticity, and an enhanced π–π interaction with neighboring molecules in the solid state when compared to TIPS-PEN. However, an in-depth understanding of the relationship between the molecule structure, solid-state molecular packing, and the electronic properties has not been reported due to poor control over the TIPS-PPP crystallite size. In this work, we successfully engineered highly oriented large-area TIPS-PPP crystals through the solution shear coating technique. Additionally, compared with narrow ribbon-like TIPS-PEN crystals, TIPS-PPP crystals can grow centimeters long and over 500 μm wide. TIPS-PPP molecules are less susceptible to forming metastable polymorphs than TIPS-PEN molecules upon fast evaporation. The crystal structure of TIPS-PPP is also thermally stable at 250 °C. Notably, the anisotropic charge carrier mobility of TIPS-PPP crystals is resolved through fabricating bottom-gate top-contact devices, with a hole mobility of 3.1 cm 2 V -1 s -1 along the preferred packing direction. Further device optimization using top-gate bottom-contact devices improved the mobility up to 6.5 cm 2 V -1 s -1 , which is among the highest for pentacene-derivative-based organic semiconductors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Multiport Control with Partial Power Processing in Solid-State Transformer for PV, Storage, and Fast-Charging Electric Vehicle Integration

This article proposes a multiport control method to enable partial power processing (PPP) in a medium-voltage (MV) multiport solid-state transformer (SST). MV multiport SSTs are promising in integrating low-voltage DC sources or loads such as solar photovoltaic, energy storage, and electric vehicles into smart grids without bulky line-frequency transformers. Compared to voltage-source SST, current-source (CS) SST features single-stage isolated bidirectional AC/AC, AC/DC, or DC/DC conversion using an inductive DC link. For a multiport CS SST, it is revealed in this article that the PPP capability can be enabled through the proposed control without extra hardware, different from the case of voltage-source converters where special hardware architecture is required for the PPP. With the PPP, most power exchange between LV ports is processed by only a fraction of the entire conversion stage, leading to reduced DC-link current, volume, loss, and improved efficiency. The proposed multiport PPP control scheme is analyzed to verify the advantages across a wide voltage and power range against conventional full power processing (FPP) multiport control, using the soft-switching solid-state transformer (S4T) with reduced conduction loss as an example. Comparative experimental results based on a SiC three-port S4T prototype verify the effectiveness of the proposed PPP scheme against the FPP scheme under both steady state and dynamic conditions. Here, the DC-link current reduction is measured to be more than 36%. Significantly, the proposed multiport PPP control scheme is generic and applicable to any hard-switching or soft-switching CS SSTs without extra hardware.

14 SOLAR ENERGY↗
DOE OSTI2018

Magnify: A Final Technical Report of the American Energy and Manufacturing Competitiveness Partnership

The energy landscape has undergone profound transformation, with dramatic shifts having an impact on U.S. productivity, global investment, manufacturing operations, and job creation. The sense of urgency for a tighter linkage between clean technologies, energy and advanced manufacturing has only grown. Prior to 2009, the tone of the nation’s energy conversation was centered on how to deal with long-standing energy security challenges and scarcity. Today, the tone is focused on seizing emerging energy growth opportunities to transform America’s industrial base and job creation outlook—centering on energy abundance and strength. In this context, the Council on Competitiveness and the Department of Energy’s Office of Energy Efficiency & Renewable Energy (EERE) teamed in the American Energy & Manufacturing Competitiveness (AEMC) Partnership to tackle two major goals via a multi-year partnership. The AEMC Partnership identified means to: • Increase U.S. competitiveness in the production of clean energy products • Increase U.S. manufacturing competitiveness across the board by increasing energy productivity The AEMC Partnership has engaged hundreds of leaders from industry, academia, labor and government in a series of 9 regional, progressive dialogues; original research; and 4 national summits. The AEMC dialogues and summits spanned the United States—taking place in our nation’s greatest manufacturing, research, technology and innovation hotspots. The goals of the AEMC Partnership have been straightforward: • State and define key barriers, challenges, and problems in U.S. competitiveness in manufacturing of clean energy products, energy efficiency products, and advanced manufacturing products. • Dive deeply into these problems and generate policies, solutions, concepts and models where the U.S. public and private sectors can work together to solve these problems. • Catalyze policy solutions—including models for public-private partnership (PPP) pilots—to increase competitive manufacturing of clean energy and energy efficiency products in the USA. • Elevate and increase awareness of the importance and benefits of competitive clean energy manufacturing. • Understand how energy game-changers, like breakthrough technologies, impact U.S. clean energy and energy efficient manufacturing. The Council on Competitiveness worked with its stakeholder network to generate potential PPP concepts and proposals to advance the goals of the AEMC Partnership. Magnify outlines 2 PPP concepts—honed by dialogues, conversations, interviews and research—that could be carried out by EERE and/or the Council to increase the competitive production of clean energy products, energy efficient products, and advanced manufacturing in the USA. Magnify’s 2 PPP concepts aim to bridge very specific gaps in the nation’s innovation ecosystem: • Clean Energy Materials Accelerator: This PPP concept focuses on reducing the risks associated with deploying newly developed materials in commercial products and processes by creating a platform to identify and address common challenges; increasing access to existing materials qualification and characterization tools; and creating standards for advanced materials with leaders in industry, academic, government, and other organizations. Why accelerate materials production? As the AEMC Partnership Dialogue and supporting research from the public and private sectors have documented, countries that lead in making next-generation materials will gain significant competitive advantage by unleashing a new wave of manufacturing innovation. • Manufacturing and Energy Technology Accelerator: This PPP concept is a new, physical and virtual collaborative resource platform designed to connect the nation’s world-class innovation institutions—SMEs, large multinational companies, universities, national laboratories, etc.—to facilitate the transition of cutting-edge clean energy technologies into products, processes, or services that are manufactured in the United States. Why should public and private sector leaders in innovation partner to co-create a scale-up platform? The United States is already a mecca for the world’s greatest minds in science and technology—drawn to our shores by world-class universities and opportunities to work with global leaders in innovation. Unfortunately, when it comes time to bring their ideas to market, technologists and entrepreneurs often choose, or are forced, to locate manufacturing overseas. The United States must regain its position in the world as a national scale-up platform for next-generation technologies. A thorough explanation of these PPP concepts and the rationale behind these recommendations is provided in Part 3 of Magnify. Magnify is an important step on the critical journey to define barriers, challenges and problems in the manufacturing of clean energy products and energy efficient products—and further honing concepts for scalable, public-private partnerships—to increase the competitive manufacturing of clean energy and energy efficient products, and the energy productivity throughout the U.S. manufactur¬ing sector. The rest of the world is waking up to the opportunities associated with a strategic focus on manufacturing and energy competitiveness. Global competition is on the rise, and the stakes are high for the United States to act now, to act decisively, and to leverage inherent strengths to ensure a more prosperous, competitive future for decades to come.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2021

Pentose Phosphate Pathway Reactions in Photosynthesizing Cells

The pentose phosphate pathway (PPP) is divided into an oxidative branch that makes pentose phosphates and a non-oxidative branch that consumes pentose phosphates, though the non-oxidative branch is considered reversible. A modified version of the non-oxidative branch is a critical component of the Calvin–Benson cycle that converts CO2 into sugar. The reaction sequence in the Calvin–Benson cycle is from triose phosphates to pentose phosphates, the opposite of the typical direction of the non-oxidative PPP. The photosynthetic direction is favored by replacing the transaldolase step of the normal non-oxidative PPP with a second aldolase reaction plus sedoheptulose-1,7-bisphosphatase. This can be considered an anabolic version of the non-oxidative PPP and is found in a few situations other than photosynthesis. In addition to the strong association of the non-oxidative PPP with photosynthesis metabolism, there is recent evidence that the oxidative PPP reactions are also important in photosynthesizing cells. These reactions can form a shunt around the non-oxidative PPP section of the Calvin–Benson cycle, consuming three ATP per glucose 6-phosphate consumed. A constitutive operation of this shunt occurs in the cytosol and gives rise to an unusual labeling pattern of photosynthetic metabolites while an inducible shunt in the stroma may occur in response to stress.

13C↗
DOE OSTI2016

Structural basis for m7G recognition and 2'-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I

RNAs with 5'-triphosphate (ppp) are detected in the cytoplasm principally by the innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I), whose activation triggers a Type I IFN response. It is thought that self RNAs like mRNAs are not recognized by RIG-I because 5'ppp is capped by the addition of a 7-methyl guanosine (m7G) (Cap-0) and a 2'-O-methyl (2'-OMe) group to the 5'-end nucleotide ribose (Cap-1). Here we provide structural and mechanistic basis for exact roles of capping and 2'-O-methylation in evading RIG-I recognition. Surprisingly, Cap-0 and 5'ppp double-stranded (ds) RNAs bind to RIG-I with nearly identical K d values and activate RIG-I’s ATPase and cellular signaling response to similar extents. On the other hand, Cap-0 and 5'ppp single-stranded RNAs did not bind RIG-I and are signaling inactive. Three crystal structures of RIG-I complexes with dsRNAs bearing 5'OH, 5'ppp, and Cap-0 show that RIG-I can accommodate the m7G cap in a cavity created through conformational changes in the helicase-motif IVa without perturbing the ppp interactions. In contrast, Cap-1 modifications abrogate RIG-I signaling through a mechanism involving the H830 residue, which we show is crucial for discriminating between Cap-0 and Cap-1 RNAs. Furthermore, m7G capping works synergistically with 2'-O-methylation to weaken RNA affinity by 200-fold and lower ATPase activity. Interestingly, a single H830A mutation restores both high-affinity binding and signaling activity with 2'-O-methylated dsRNAs. Our work provides new structural insights into the mechanisms of host and viral immune evasion from RIG-I, explaining the complexity of cap structures over evolution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

A Plug-and-Play Priors Approach for Solving Nonlinear Imaging Inverse Problems

In the past two decades, nonlinear image reconstruction methods have led to substantial improvements in the capabilities of numerous imaging systems. Such methods are traditionally formulated as optimization problems that are solved iteratively by simultaneously enforcing data consistency and incorporating prior models. Recently, the Plug-and-Play Priors (PPP) framework suggested that by using more sophisticated denoisers, not necessarily corresponding to an optimization objective, it is possible to improve the quality of reconstructed images. Here in this letter, we show that the PPP approach is applicable beyond linear inverse problems. In particular, we develop the fast iterative shrinkage/thresholding algorithm variant of PPP for model-based nonlinear inverse scattering. The key advantage of the proposed formulation over the original ADMM-based one is that it does not need to perform an inversion on the forward model. We show that the proposed method produces high quality images using both simulated and experimentally measured data.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

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↗
DOE OSTI2025

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↗
DOE OSTI2016

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↗
DOE OSTI2015

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↗
DOE OSTI2016

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↗
DOE OSTI2018

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↗
DOE OSTI2014

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↗
DOE OSTI2016

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↗