Does management capacity increase organizational performance? An empirical analysis of public housing agencies

Since the 1990s, scholars have paid special attention to public management’s role in theory and research under the assumption that effective management is one of the primary means for achieving superior performance. To some extent, this was influenced by popular business writings of the 1980s as well as the reinventing literature of the 1990s. A number of case studies but limited quantitative research papers have been published showing that management matters in the performance of public organizations. ^ My study examined whether or not management capacity increased organizational performance using quantitative techniques. The specific research problem analyzed was whether significant differences existed between high and average performing public housing agencies on select criteria identified in the Government Performance Project (GPP) management capacity model, and whether this model could predict outcome performance measures in a statistically significant manner, while controlling for exogenous influences. My model included two of four GPP management subsystems (human resources and information technology), integration and alignment of subsystems, and an overall managing for results framework. It also included environmental and client control variables that were hypothesized to affect performance independent of management action. ^ Descriptive results of survey responses showed high performing agencies with better scores on most high performance dimensions of individual criteria, suggesting support for the model; however, quantitative analysis found limited statistically significant differences between high and average performers and limited predictive power of the model. My analysis led to the following major conclusions: past performance was the strongest predictor of present performance; high unionization hurt performance; and budget related criterion mattered more for high performance than other model factors. As to the specific research question, management capacity may be necessary but it is not sufficient to increase performance. ^ The research suggested managers may benefit by implementing best practices identified through the GPP model. The usefulness of the model could be improved by adding direct service delivery to the model, which may also improve its predictive power. Finally, there are abundant tested concepts and tools designed to improve system performance that are available for practitioners designed to improve management subsystem support of direct service delivery.^

Epibenthic foraminiferal d13C in the Recent deep Arctic Ocean

Low planktic and benthic d18O and d13C values in sediments from the Nordic seas of cold stadials of the last glaciation have been attributed to brines, formed similar to modern ones in the Arctic Ocean. To expand on the carbon isotopes of this hypothesis I investigated benthic d13C from the modern Arctic Ocean. I show that mean d13C values of live epibenthic foraminifera from the deep Arctic basins are higher than mean d13C values of upper slope epibenthic foraminifera. This agrees with mean high d13C values of dissolved inorganic carbon (DIC) in Arctic Bottom Water (ABW), which are higher than mean d13CDIC values from shallower water masses of mainly Atlantic origin. However, adjustments for oceanic 13C-Suess depletion raise subsurface and intermediate water d13CDIC values over ABW d13CDIC ones. Accordingly, during preindustrial Holocene times, the d13CDIC of ABW was as high or higher than today, but lower than the d13CDIC of younger subsurface and intermediate water. If brine-enriched water significantly ventilated ABW, brines should have had high d13CDIC values. Analogously, high-d13CDIC brines may have been formed in the Nordic seas during warm interstadials. During cold stadials, when most of the Arctic Ocean was perennially sea-ice covered, a cessation of high-d13CDIC brine rejection may have lowered d13CDIC values of ABW, and ultimately the d13CDIC in Nordic seas intermediate and deep water. So, in contrast to the idea of enhanced brine formation during cold stadials, the results of this investigation imply that a cessation of brine rejection would be more likely.

Detecting and discriminating novel objects : The impact of perirhinal cortex disconnection on hippocampal activity patterns

Funded by Wellcome Trust. Grant Numbers: WT087955, WT09520

Interaction between Candida albicans and Pseudomonas aeruginosa

Fungal pathogen Candida albicans causes serious nosocomial infections in patients, in part, due to formation of drug-resistant biofilms. Protein kinases (PK) and transcription factors (TF) mediate signal transduction and transcription of proteins involved in biofilm development. To discover biofilm-related PKs, a collection of 63 C. albicans PK mutants was screened twice independently with microtiter plate-based biofilm assay (XTT). Thirty-eight (60%) mutants showed different degrees of biofilm impairment with the poor biofilm formers additionally possessing filamentation defects. Most of these genes were already known to encode proteins associated with Candida morphology and biofilms but VPS15, PKH3, PGA43, IME2 and CEX1, were firstly associated with both processes in this study. Previous studies of Holcombe et al. (2010) had shown that bacterial pathogen, Pseudomonas aeruginosa can impair C. albicans filamentation and biofilm development. To investigate their interaction, the good biofilm former PK mutants of C. albicans were assessed for their response to P. aeruginosa supernatants derived from two strains, wildtype PAO1 and homoserine lactone (HSL)-free mutant ΔQS, without finding any nonresponsive mutants. This suggested that none of the PKs in this study was implicated in Candida-Pseudomonas signaling. To screen promoter sequences for overrepresented TFs across C. albicans gene sets significantly up/downregulated in presence of bacterial supernatants from Holcombe et al. (2010) study, TFbsST database was created online. The TFbsST database integrates experimentally verified TFs of Candida to analyse promoter sequences for TF binding sites. In silico studies predicted that Efg1p was overrepresented in C. albicans and C. parapsilosis RBT family genes.

Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models

BACKGROUND: The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. METHODS: Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. RESULTS: Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. CONCLUSIONS: These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression.

C1-C8 hydrocarbons in marine sediments

Light hydrocarbon (C1-C8) profiles are compared for three wells of varying maturities: two immature DSDP wells (Site 397 near the Canary Islands and Site 530A near the Walvis Ridge in the south-east Atlantic) and a mature well, the East Cameron well in the Texas Gulf Coast. Primary migration of C1 and C2 appears to be occurring in all of the sedimentary rocks examined. Primary migration of C3+ components becomes important only as fine-grained sedimentary rocks enter the catagenetic hydrocarbon generation zone or over short distances in more permeable sections. Lateral migration along bedding planes was more important than vertical migration in sedimentary rocks of all maturities. The lightest (methane, ethane and propane gases) hydrocarbon show greater fractionation than do the C4-C8 alkanes which generally show minimal fractionation during the migrational process. Subsurface diffusion coefficients for these p.p.b. quantities of C2-C5 alkanes from immature sediments from DSDP Site 530 are estimated to be several orders of magnitude less than values reported in the literature for diffusion of much larger amounts of these compounds from mature water wet sediments into air or sandstones. Since our calculations suggest light hydrocarbons are present in amounts less than their reported solubilities in pure water at 25°C, we postulate that the sediment organic matter has a substantial effect on retarding the movement of these light hydrocarbons.

Tegument Glycoproteins and Cathepsins of Newly Excysted Juvenile Fasciola hepatica Carry Mannosidic and Paucimannosidic N-glycans

<p>Recently, the prevalence of Fasciola hepatica in some areas has increased considerably and the availability of a vaccine to protect livestock from infection would represent a major advance in tools available for controlling this disease. To date, most vaccine-target discovery research on this parasite has concentrated on proteomic and transcriptomic approaches whereas little work has been carried out on glycosylation. As the F. hepatica tegument (Teg) may contain glycans potentially relevant to vaccine development and the Newly Excysted Juvenile (NEJ) is the first lifecycle stage in contact with the definitive host, our work has focused on assessing the glycosylation of the NEJTeg and identifying the NEJTeg glycoprotein repertoire. After in vitro excystation, NEJ were fixed and NEJTeg was extracted. Matrix-assisted laser desorption ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) analysis of released N-glycans revealed that oligomannose and core-fucosylated truncated N-glycans were the most dominant glycan types. By lectin binding studies these glycans were identified mainly on the NEJ surface, together with the oral and ventral suckers. NEJTeg glycoproteins were affinity purified after targeted biotinylation of the glycans and identified using liquid chromatography and tandem mass spectrometry (LC-MS/MS). From the total set of proteins previously identified in NEJTeg, eighteen were also detected in the glycosylated fraction, including the F. hepatica Cathepsin B3 (FhCB3) and two of the Cathepsin L3 (FhCL3) proteins, among others. To confirm glycosylation of cathepsins, analysis at the glycopeptide level by LC-ESI-ion-trap-MS/MS with collision-induced dissociation (CID) and electron-transfer dissociation (ETD) was carried out. We established that cathepsin B1 (FhCB1) on position N80, and FhCL3 (BN1106_s10139B000014, scaffold10139) on position N153, carry unusual paucimannosidic Man2GlcNAc2 glycans. To our knowledge, this is the first description of F. hepatica NEJ glycosylation and the first report of N-glycosylation of F. hepatica cathepsins. The significance of these findings for immunological studies and vaccine development is discussed.p>

TRPV4: Molecular Conductor of a Diverse Orchestra

<p>Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led by Schultz (Nat Cell Biol 2: 695-702, 2000) and Liedtke (Cell 103: 525-535, 2000). TRPV4 is now recognized as being a polymodal ionotropic receptor that is activated by a disparate array of stimuli, ranging from hypotonicity to heat and acidic pH. Importantly, this ion channel is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions, as does its widespread dissemination throughout the body and its capacity to interact with other proteins. Not surprisingly, therefore, it has emerged more recently that TRPV4 fulfills a great number of important physiological roles and that various disease states are attributable to the absence, or abnormal functioning, of this ion channel. Here, we review the known characteristics of this ion channel's structure, localization and function, including its activators, and examine its functional importance in health and disease.p>

Unexpected Activity of a Novel Kunitz-Type Inhibtior: Inhibition of Cysteine Proteases but not Serine Proteases

<p>Kunitz-type (KT) protease inhibitors are low molecular weight proteins classically defined as serine protease inhibitors. We identified a novel secreted KT inhibitor associated with the gut and parenchymal tissues of the infective juvenile stage of Fasciola hepatica, a helminth parasite of medical and veterinary importance. Unexpectedly, recombinant KT inhibitor (rFhKT1) exhibited no inhibitory activity towards serine proteases but was a potent inhibitor of the major secreted cathepsin L cysteine proteases of F. hepatica, FhCL1 and FhCL2, and of human cathepsins L and K (Ki = 0.4 nM - 27 nM). FhKT1 prevented the auto-catalytic activation of FhCL1 and FhCL2 and formed stable complexes with the mature enzymes. Pull-down experiments from adult parasite culture medium showed that rFhKT1 interacts specifically with native secreted FhCL1, FhCL2 and FhCL5. Substitution of the unusual P1 Leu15 within the exposed reactive loop of FhKT1 for the more commonly found Arg (FhKT1Leu15/Arg15) had modest adverse effects on the cysteine protease inhibition but conferred potent activity against the serine protease trypsin (Ki = 1.5 nM). Computational docking and sequence analysis provided hypotheses for the exclusive binding of FhKT1 to cysteine proteases, the importance of the Leu15 in anchoring the inhibitor into the S2 active site pocket, and the inhibitor's selectivity towards FhCL1, FhCL2 and human cathepsins L and K. FhKT1 represents a novel evolutionary adaptation of KT protease inhibitors by F. hepatica, with its prime purpose likely in the regulation of the major parasite-secreted proteases and/or cathepsin L-like proteases of its host.p>

Fasciola hepatica surface tegument: glycoproteins at the interface of parasite and host

<p>Fasciola hepatica, commonly known as liver fluke, is a trematode which causes Fasciolosis in ruminants and humans. The outer tegumental coat of F. hepatica (FhTeg) is a complex metabolically active biological matrix that is continually exposed to the host immune system and therefore makes a good vaccine target. F. hepatica tegumental coat is highly glycosylated and helminth-derived immunogenic oligosaccharide motifs and glycoproteins are currently being investigated as novel vaccine candidates. This report presents the first systematic characterisation of FhTeg glycosylation using lectin microarrays to characterise carbohydrates motifs present, and lectin histochemistry to localize these on the F. hepatica tegument. We discovered that FhTeg glycoproteins are predominantly oligomannose oligosaccharides that are expressed on the spines, suckers and tegumental coat of F. hepatica and lectin blot analysis confirmed the abundance of N- glycosylated proteins. While some oligosaccharides are widely distributed on the fluke surface other subsets are restricted to distinct anatomical regions. We selectively enriched for FhTeg mannosylated glycoprotein subsets using lectin affinity chromatography and identified 369 proteins by mass spectrometric analysis. Among these proteins are a number of potential vaccine candidates with known immune modulatory properties including proteases, protease inhibitors, paramyosin, Venom Allergen-like II, Enolase and two proteins, nardilysin and TRIL, that have not been previously associated with F. hepatica Furthermore, we provide a comprehensive insight regarding the putative glycosylation of FhTeg components which could highlight the importance of further studies examining glycoconjugates in host-parasite interactions in the context of F. hepatica infection and the development of an effective vaccine.p>

Dynamic Coculture of a Prevascularized Engineered Bone Construct

The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of tissue engineered bone constructs can succeed, in vitro fabrication needs to address limitations in large-scale tissue development, including controlled osteogenesis and an inadequate vasculature network to prevent necrosis of large constructs. The tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cell (hMSC)-seeded scaffolds while they are developed in vitro. To further enhance this process, we developed a novel osteogenic growth factors delivery system for dynamically cultured hMSCs using microparticles encapsulated in three-dimensional alginate scaffolds. In light of this increased differentiation, we characterized the endogenous cytokine distribution throughout the TPS bioreactor. An advantageous effect in the ‘outlet’ portion of the uniaxial growth chamber was discovered due to the system’s downstream circulation and the unique modular aspect of the scaffolds. This unique trait allowed us to carefully tune the differentiation behavior of specific cell populations. We applied the knowledge gained from the growth profile of the TPS bioreactor to culture a high-volume bone composite in a 3D-printed femur mold. This resulted in a tissue engineered bone construct with a volume of 200cm3, a 20-fold increase over previously reported sizes. We demonstrated high viability of the cultured cells throughout the culture period as well as early signs of osteogenic differentiation. Taking one step closer toward a viable implant and minimize tissue necrosis after implantation, we designed a composite construct by coculturing endothelial cells (ECs) and differentiating hMSCs, encouraging prevascularization and anastomosis of the graft with the host vasculature. We discovered the necessity of cell to cell proximity between the two cell types as well as preference for the natural cell binding capabilities of hydrogels like collagen. Notably, the results suggested increased osteogenic and angiogenic potential of the encapsulated cells when dynamically cultured in the TPS bioreactor, suggesting a synergistic effect between coculture and applied shear stress. This work highlights the feasibility of fabricating a high-volume, prevascularized tissue engineered bone construct for the regeneration of a critical size defect.

The Effect of Architecture and Shear Stress on Endothelialization of 3D Printed Vascular Networks

Despite significant progress in the field of tissue engineering within the last decade, a number of unsolved problems still remain. One of the most relevant issues is the lack of proper vascularization that limits the size of engineered tissues to smaller than clinically relevant dimensions. In particular, the growth of engineered tissue in vitro within bioreactors is plagued with this challenge. Specifically, the tubular perfusion system bioreactor has been used for large scale bone constructs; however these engineered constructs lack inherent vasculature and quickly develop a hypoxic core, where no nutrient exchange can occur, thus leading to cell death. Through the use of 3D printed vascular templates in conjunction with a tubular perfusion system bioreactor, we attempt to create an endothelial cell monolayer on 3D scaffolds that could potentially serve as the foundation of inherent vasculature within these engineered bone grafts.

Experimental and diagnostic protocol for the physical component of the CMIP6 Ocean Model Intercomparison Project (OMIP)

The Ocean Model Intercomparison Project (OMIP) aims to provide a framework for evaluating, understanding, and improving the ocean and sea-ice components of global climate and earth system models contributing to the Coupled Model Intercomparison Project Phase 6 (CMIP6). OMIP addresses these aims in two complementary manners: (A) by providing an experimental protocol for global ocean/sea-ice models run with a prescribed atmospheric forcing, (B) by providing a protocol for ocean diagnostics to be saved as part of CMIP6. We focus here on the physical component of OMIP, with a companion paper (Orr et al., 2016) offering details for the inert chemistry and interactive biogeochemistry. The physical portion of the OMIP experimental protocol follows that of the interannual Coordinated Ocean-ice Reference Experiments (CORE-II). Since 2009, CORE-I (Normal Year Forcing) and CORE-II have become the standard method to evaluate global ocean/sea-ice simulations and to examine mechanisms for forced ocean climate variability. The OMIP diagnostic protocol is relevant for any ocean model component of CMIP6, including the DECK (Diagnostic, Evaluation and Characterization of Klima experiments), historical simulations, FAFMIP (Flux Anomaly Forced MIP), C4MIP (Coupled Carbon Cycle Climate MIP), DAMIP (Detection and Attribution MIP), DCPP (Decadal Climate Prediction Project), ScenarioMIP (Scenario MIP), as well as the ocean-sea ice OMIP simulations. The bulk of this paper offers scientific rationale for saving these diagnostics.