On the measurement and modelling of high pressure flows in poppet valves under steady-state and transient conditions

Flow coefficients of intake valves and port combinations were determined experimentally for a compressed nitrogen engine under steady-state and dynamic flow conditions for inlet pressures up to 3.2 MPa. Variable valve timing was combined with an indexed parked piston cylinder unit for testing valve flows at different cylinder volumes whilst maintaining realistic in-cylinder transient pressure profiles by simply using a fixed area outlet orifice. A one-dimensional modelling approach describing three-dimensional valve flow characteristics has been developed by the use of variable flow coefficients that take into account the propagation of flow jets and their boundaries as a function of downstream/upstream pressure ratios. The results obtained for the dynamic flow cases were compared with steadystate results for the cylinder to inlet port pressure ratios ranges from 0.18 to 0.83. The deviation of flow coefficients for both cases is discussed using pulsatile flow theory. The key findings include: 1. For a given valve lift, the steady-state flow coefficients fall by up to 21 percent with increasing cylinder/manifold pressure ratios within the measured range given above; 2. Transient flow coefficients deviated from those measured for the steady-state flow as the valve lift increases beyond a critical value of approximately 0.5 mm. The deviation can be due to the insufficient time of the development of steady state boundary layers, which can be quantified by the instantaneous Womersley number defined by using the transient hydraulic diameter. We show that it is possible to predict deviations of the transient valve flow from the steady-state measurements alone

L-Arginine Is Essential for Pancreatic b-Cell Functional Integrity, Metabolism and Defense From Inflammatory Challenge

In this work, our aim was to determine whether L-arginine (a known insulinotropic amino acid) can promote a shift of b-cell intermediary metabolism favoring glutathione (GSH) and glutathione disulfide (GSSG) antioxidant responses, stimulus–secretion coupling and functional integrity. Clonal BRIN-BD11 b-cells and mouse islets were cultured for 24 h at various L-arginine concentrations (0–1.15 mmol/l) in the absence or presence of a proinflammatory cytokine cocktail (interleukin 1b, tumour necrosis factor a and interferon g). Cells were assessed for viability, insulin secretion, GSH, GSSG, glutamate, nitric oxide (NO), superoxide, urea, lactate and for the consumption of glucose and glutamine. Protein levels of NO synthase-2, AMP-activated protein kinase (AMPK) and the heat shock protein 72 (HSP72) were also evaluated. We found that L-arginine at 1.15 mmol/l attenuated the loss of b-cell viability observed in the presence of proinflammatory cytokines. L-Arginine increased total cellular GSH and glutamate levels but reduced the GSSG/GSH ratio and glutamate release. The amino acid stimulated glucose consumption in the presence of cytokines while also stimulating AMPK phosphorylation and HSP72 expression. Proinflammatory cytokines reduced, by at least 50%, chronic (24 h) insulin secretion, an effect partially attenuated by L-arginine. Acute insulin secretion was robustly stimulated by L-arginine but this effect was abolished in the presence of cytokines. We conclude that L-arginine can stimulate b-cell insulin secretion, antioxidant and protective responses, enabling increased functional integrity of b-cells and islets in the presence of proinflammatory cytokines. Glucose consumption and intermediary metabolism were increased by L-arginine. These results highlight the importance of L-arginine availability for b-cells during inflammatory challeng

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights

Multidisciplinary Consensus on Assessment of Unruptured Intracranial Aneurysms Proposal of an International Research Group

Peer reviewe

Assessing the Freshwater Conservation Potential of Terrestrial Protected Areas

Physical alteration, habitat loss, water withdrawal, pollution, land use change, overexploitation, and the introduction of nonnative species together negatively influence freshwater ecosystems. Due to these stresses, freshwaters are ranked among the most at risk systems worldwide (Malmqvist and Rundle, 2002). Protected areas (PAs), defined as an area of land and/or sea especially dedicated to the protection and maintenance of biological diversity as well as natural and associated cultural resources and managed through legal or other effective means (IUCN, 1994), are an emerging tool for the protection of biodiversity and natural resources. Despite the well‐documented threatened status of freshwater ecosystems, terrestrial targets have received far more attention and resources in the designation of PAs (Abell et al., 2007). However, because many terrestrial PAs include freshwater components, use fluvial systems as borders, or affect freshwaters downstream, it is important to understand the role that terrestrial PAs play in freshwater conservation (Abell et al., 2007; Herbert et al., in press). The goal of our study was to investigate the conservation potential of terrestrial PAs. As such, using Federal‐ and Stateowned PAs within the Northern Lake Michigan, Lake Huron, and Straits of Mackinac Ecological Drainage Unit of the State of Michigan (TNC, 2001), we evaluated two broad attributes of PAs: (1) the effect of containing land in an undeveloped condition on downstream freshwater key environmental attributes (KEAs: biotic composition, connectivity, hydrologic regime, physical habitat and energy regime, and water quality), and (2) the ability of managers to identify and mitigate negative anthropogenic influences on KEAs. Our first objective was to determine the effect of total area under protection by terrestrial PAs on KEAs. To do so, data was collected on eight response variables representative of the five KEAs which included: NO2 + NO3 concentration, total phosphorus concentration, free flowing stream miles, average rate of flow response, low flow expectation, habitat quality score, fish index of biotic integrity, and percent of fish considered intolerant to anthropogenic stress. Next, using Geographic Information Systems (GIS), catchments derived from individual response variable datum locations were delineated and the total percent of land in protection within each catchment was calculated. Finally, the relationship between response variable values and percent land protected was determined using linear regressions. We found significant (p<0.05) decreases in NO2 + NO3 concentration and average rate of flow response with increasing area of catchment in protection, suggesting that by keeping land in a natural state, PAs can contribute to lowering nitrogen concentrations and reducing stream flashiness downstream. We also found significant increases in the percent of fish considered intolerant to anthropogenic stress with increasing area of catchment in protection, suggesting PAs may contribute to enhancing the total number of environmentally sensitive fish. No significant relationship was found between PAs and total phosphorus concentration, free flowing stream miles, low flow expectation, habitat quality score, or fish index of biotic integrity. Our second objective was to determine how PA management attends to freshwater conservation. To do so, we randomly selected eleven Federal‐ and State‐owned PAs located within the Northern Lake Michigan, Lake Huron, and Straits of Mackinac Ecological Drainage Unit of the State of Michigan and conducted PA management questionnaires and interviews, based on IUCN’s “Evaluating Effectiveness: A Framework for Assessing Management of Protected Areas” guidelines (Hockings et al., 2006) and the principles of integrated water resource management (IWRM; Global Water Partnership, 2009). This process identified what PA managers perceived to be greatest internal (within PA) and external (outside of PA) threats to freshwater KEAs within PAs and what specific activities PA managers conducted to protect or restore KEAs. The alignment between threats and activities was then determined as a measure of management’s attendance to freshwater conservation. This analysis revealed that management processes are, with a few exceptions, complementary to identified threats to freshwater systems. However, while our findings suggest positive alignment between management activities and identified threats, the informality of collaborative processes and absence of robust freshwater monitoring programs indicate that management is not fully engaged in IRWM, which limits the capacity for adaptive management. Our third objective was to determine the relative influences of management and catchment stressors on KEAs. Using previously delineated response variable catchments, we organized response variable values by the study PAs contained within their catchments, and calculated PA‐specific response variable scores (Response Variable Score). Next, using the same response variable catchments, we calculated a measure of catchment condition (Catchment Condition Score). Finally, using results from PA management questionnaires, we quantified the degree of activity potentially affecting KEA response variables (Management Activity Score). Catchment Condition Scores and Management Activity Scores were then compared to Response Variable Scores to identify instances where PA management activities were successful in mitigating the effects of catchment stressors on KEAs (Scenario 1) and instances where catchment stressors had an overriding effect on management activities (Scenario 2). The two Scenarios were observed in nearly identical proportions across KEAs and PAs, suggesting that both management activities and catchment stressors vary in their ability to affect freshwater KEA values. However, Scenario 1 was observed more than Scenario 2 for water quality, while the opposite was observed for biotic composition and hydrologic regime, suggesting management activities may be more successful in mitigating the effects of catchment stressors specific to nutrient concentrations. Our results suggest that terrestrial PAs likely contribute to some components of freshwater KEAs by protecting land from development and through certain management activities. However, further research is warranted to more extensively track the effect of the interaction of anthropogenic stressors and management activities on freshwater systems. If terrestrial protection were sufficient to secure freshwater integrity, we would expect the majority of indicators to be favorably related to total percent protected. Since only three of eight response variables showed the expected relationship, our findings do not support the assumption that watershed protections are synonymous with maintenance of freshwater KEAs. Our approach provides a framework for evaluating and tracking key freshwater outcomes while addressing the interacting factors of human‐induced stress and management attempts to mitigate these stresses. Furthermore, our approach holds utility for any managing entity attempting to produce favorable outcomes for freshwater systems. Future applications of this approach can be tailored to include a different set of management activities, catchment stressors, and response variables, depending on the context of the PA and what data are available for use.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/69240/1/Assessing_the_Freshwater_Conservation_Potential_of_Terrestrial_Protected_Areas.pd