The Bioorganometallic Chemistry of Iron and the Diatomic Ligands CO and NO as Related to Hydrogenase Active Sites and Dinitrosyl Iron Complexes

The discovery of a diiron organometallic active site, found in the [FeFe]-Hydrogenase (H2ase) enzyme, has led to a revisiting of the classic organometallic chemistry involving the Fe-Fe bond and bridging ligands. This diiron site is connected to a mainstay of biochemistry, a redox active 4Fe4S cluster, and the combination of these units is undoubtedly connected to the enzyme’s performance. The regioselectivity of CO substitution on the diiron framework of the so-called parent model complex (μ-pdt)[Fe(CO)3]2, (pdt = propane-1,3-dithiolate), and its derivatives, informs on the interplay of electron density in the diiron core of the enzyme active site. The structural isomers (μ-pdt)[Fe(NHC)(NO)(PMe3)][Fe(CO)3]+ and (μ-pdt)(μ-CO)[Fe(NHC)(NO)][Fe(PMe3)(CO)2]+, synthesized through CO substitution by opposing nucleophilic (PMe3) and electrophilic (NO+) ligands provide insight into the reactivity of both irons as a function of their π-acidity. The intramolecular fluxional processes of a series of (μ-SRS)[Fe(CO)3]2 complexes allows for the generation of an open site mimicking the structure of the H2ase where H+ binds in the catalytic cycle of H2 production. Density Functional Theory (DFT) was used to support the dynamic 1H and 13C NMR spectroscopic studies that established the energy barriers to both the chair/boat interconversion of FeS2C2X, where X = NR or CR2, and the rotation of the Fe(CO)3 moiety, a process essential to the formation of an open site. It was determined that the rotation barrier is correlated with the steric bulk of the bridging ligand that can be directed towards the iron. This is seen with the methyl substituent in both N(CH3) and C(CH3)2 producing a lower barrier to Fe(CO)3 rotation than the NH and CH2 analogues, while the steric bulk of NC(CH3)3 cannot be directed to the iron and results in a higher barrier than both NH and N(CH)3. Another class of bioorganometallic molecules, the dinitrosyl iron complexs (DNICs), is formed in vivo as the product of NO degradation of iron-sulfur clusters; DNICs are thought to have possible NO storage and transport roles in the body. Computational investigations utilizing DFT have been used to support synthetic and kinetic studies of the reactivity of one such complex, (NHC)(SPh)Fe(NO)2, (NHC = N-heterocyclic carbene) with CO

Laser Mobile Mapping Standards and Applications in Transportation

This report describes the work that was done to support the development of a chapter for the INDOT Survey Manual on Mobile Mapping. The work includes experiments that were done, data that was collected, analysis that was carried out, and conclusions that were drawn about accuracy of Mobile Terrestrial Laser Scanning (MTLS) systems. The resulting Manual chapter, located in the appendix, defines standards and procedures for preparing, collecting, editing, delivering, exploiting, and archiving electronic mapping data that is created for Indiana Department of Transportation (INDOT). The purpose of the standards and procedures within this manual is to obtain statewide uniformity within the INDOT combined Aerial/Ground Survey process, to establish and maintain MTLS Standards for INDOT and contracted consultants, and allow for all of the project data to be effectively managed from conception to completion. These standards apply to all projects delivered to INDOT by contracted consulting firms, or exchanged internally within INDOT or between state agencies. The standards and procedures are the result of mobile terrestrial laser scanning surveys of two test sites - one urban and one freeway - created for this project. After establishing reference control points on the sites, each site was surveyed by four mobile terrestrial laser scanning vendors. The results from the vendor data over the test sites, in addition to information in published literature, are the basis for the specifications manual. The proposed chapter for the Survey Manual is in Appendix E of this report

Bin-Hash Indexing: A Parallel Method for Fast Query Processing

This paper presents a new parallel indexing data structure for answering queries. The index, called Bin-Hash, offers extremely high levels of concurrency, and is therefore well-suited for the emerging commodity of parallel processors, such as multi-cores, cell processors, and general purpose graphics processing units (GPU). The Bin-Hash approach first bins the base data, and then partitions and separately stores the values in each bin as a perfect spatial hash table. To answer a query, we first determine whether or not a record satisfies the query conditions based on the bin boundaries. For the bins with records that can not be resolved, we examine the spatial hash tables. The procedures for examining the bin numbers and the spatial hash tables offer the maximum possible level of concurrency; all records are able to be evaluated by our procedure independently in parallel. Additionally, our Bin-Hash procedures access much smaller amounts of data than similar parallel methods, such as the projection index. This smaller data footprint is critical for certain parallel processors, like GPUs, where memory resources are limited. To demonstrate the effectiveness of Bin-Hash, we implement it on a GPU using the data-parallel programming language CUDA. The concurrency offered by the Bin-Hash index allows us to fully utilize the GPU's massive parallelism in our work; over 12,000 records can be simultaneously evaluated at any one time. We show that our new query processing method is an order of magnitude faster than current state-of-the-art CPU-based indexing technologies. Additionally, we compare our performance to existing GPU-based projection index strategies

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. © 2015 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/1/jbmr2553.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/2/jbmr2553_am.pd

Using machine learning to advance synthesis and use of conservation and environmental evidence

This is the final version. Available from Wiley via the DOI in this record. National Institute for Health ResearchScience for Nature and People Partnershi

Thrombopoietin: A Novel Bone Healing Agent

poster abstractCritical-size defects in bones do not heal spontaneously and usually require the use of grafts. Unfortunately, grafts have several limitations. To improve bone formation, many clinicians now use bone morphogenetic proteins (BMP), particularly in spinal fusion, fracture healing, and in critical-size defect regeneration. However, multiple side effects of BMP treatment have been uncovered including increased incidence of cancer. Thus, there is great interest in alternatives that allow for safe and effective bone regeneration. Here we show the ability of thrombopoietin (TPO), the main megakaryocyte growth factor, to heal critical-size femoral defects rodents. 5mm or 4mm segmental defects were created in the femur of Long Evans rats or C57BL/6 mice, respectively. The defects were filled with a novel bioabsorbable scaffold which was loaded with recombinant human TPO, BMP-2, or saline, and held stable by a retrograde 1.6 mm intramedullary Kirschner wire (rats) or 23G needle (mice). Xrays were taken every 3 weeks in rats and weekly in mice. Animal were sacrificed at 15 weeks, at which time micro-computed tomography (μCT) and histological analyses were performed. The results observed in mice and rats were similar. The saline control group did not show bridging callus at any time. Both the BMP-2 and TPO groups healed the defect, although bridging callus was evident at earlier times in the BMP-2 groups. However, the TPO groups showed a much more remodeled and physiologic contour on both Xray and μCT. μCT and histological analysis confirms that compared to BMP-2, TPO-treated specimens have a thicker cortex but smaller diameter and smoother contour. TPO appears to restore the original bone contour by stimulating osteoblastogenesis, allowing for periosteal bridging and stabilization to occur, while simultaneously stimulating osteoclast formation. Thus, TPO may serve as a novel bone healing agent

Multiple-University Extension Program Addresses Postdisaster Oil Spill Needs Through Private Funding Partnership

In response to the Deepwater Horizon Oil Spill, the Gulf of Mexico Research Initiative (GoMRI) was formed to answer oil spill–related scientific questions. However, peer-reviewed scientific discoveries were not reaching people whose livelihoods depended on a healthy Gulf of Mexico. GoMRI and the four Gulf of Mexico Sea Grant programs partnered to develop a regional Extension program with a team of multidisciplinary specialists and a regional manager embedded within the Sea Grant programs. The team answered oil spill science questions from target audiences. The program leaders also identified the value of adding a regional Extension communicator to enhance their Extension products

Corporate governance and financial constraints on strategic turnarounds

The paper extends the Robbins and Pearce (1992) two-stage turnaround response model to include governance factors. In addition to the retrenchment and recovery, the paper proposes the addition of a realignment stage, referring specifically to the re-alignment of expectations of principal and agent groups. The realignment stage imposes a threshold that must be crossed before the retrenchment and hence recovery stage can be entered. Crossing this threshold is problematic to the extent that the interests of governance-stakeholder groups diverge in a crisis situation. The severity of the crisis impacts on the bases of strategy contingent asset valuation leading to the fragmentation of stakeholder interests. In some cases the consequence may be that management are prevented from carrying out turnarounds by governance constraints. The paper uses a case study to illustrate these dynamics, and like the Robbins and Pearce study, it focuses on the textile industry. A longitudinal approach is used to show the impact of the removal of governance constraints. The empirical evidence suggests that such financial constraints become less serious to the extent that there is a functioning market for corporate control. Building on governance research and turnaround literature, the paper also outlines the general case necessary and sufficient conditions for successful turnarounds

Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro

<p>Abstract</p> <p>Background</p> <p>In 2005, Ghana replaced chloroquine with artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. The aim of this work was to determine for the first time, polymorphisms in the putative <it>pfATPase6 </it>and <it>pftctp</it>, <it>pfmdr1</it>, <it>pfcrt </it>genes in Ghanaian isolates, particularly at a time when there is no report on artemisinin resistance in malaria parasites from Ghana. The sensitivity of parasite isolates to anti-malaria drugs were also evaluated for a possible association with polymorphisms in these genes.</p> <p>Methods</p> <p>The prevalence of point mutations in the above <it>Plasmodium falciparum </it>genes were assessed from filter-paper blood blot samples by DNA sequencing. <it>In vitro </it>drug sensitivity test was carried out on some of the blood samples from volunteers visiting hospitals/clinics in southern Ghana using a modified version of the standard WHO Mark III micro-test.</p> <p>Results</p> <p>All successfully tested parasite isolates were sensitive to artesunate; while 19.4%, 29.0% and 51.6% were resistant to quinine, amodiaquine and chloroquine respectively. The geometric mean of IC₅₀value for artesunate was 0.73 nM (95% CI, 0.38-1.08), amodiaquine 30.69 nM (95% CI, 14.18-47.20) and chloroquine 58.73 nM (95% CI, 38.08-79.38). Twenty point mutations were observed in <it>pfATPase6 </it>gene, with no L263E and S769N. All mutations found were low in frequency, except D639G which was observed in about half of the isolates but was not associated with artesunate response (<it>p </it>= 0.42). The <it>pftctp </it>gene is highly conserved as no mutation was observed, while CVIET which is chloroquine-resistant genotype at codon 72-76 of the <it>pfcrt </it>gene was identified in about half of the isolates; this was consistent with chloroquine IC₅₀values (<it>p </it>= 0.001). Mutations were present in <it>pfmdr1 </it>gene but were not associated with artemisinin response (<it>p </it>= 1.00).</p> <p>Conclusion</p> <p>The <it>pfATPase6 </it>gene is highly polymorphic with D639G appearing to be fixed in Ghanaian isolates. These may just be spontaneous mutations as all parasite isolates that were tested displayed satisfactory <it>in vitro </it>response to artesunate. However, there is no improvement in susceptibility of the parasites to chloroquine five years after its proscription.</p