Model for heterogeneous catalysis on metal surfaces with application to hypersonic flows

A model for heterogeneous catalysis for Copper, Nickel, and Platinum has been devised. The model simulates the heterogeneous chemical kinetics of dissociated air flow impinging metal surfaces. Elementary phenomena such as, atomic and molecular adsorption, Eley-Rideal and Langmuir-Hinshelwood recombinations, and thermal desorptions have been accounted for. Comparisons with experimental results for Nitrogen and Oxygen recombination show good agreement. In the second part of this work, the finite rate catalysis model has been used to analyzed numerically the problems of the heterogeneous catalysis similarity between hypersonic ground testing and reentry flight. Therefore the flow around a blunt cone under these conditions has been calculated and results for heat fluxes and for a suggested similarity parameter have been compared and discussed

A Preliminary 1D-3D Analysis of the Darmstadt Research Engine under Motored Condition

In the present paper, 1D and 3D CFD models of the Darmstadt research engine undergo a preliminary validation against the available experimental dataset at motored condition. The Darmstadt engine is a single-cylinder optical research unit and the chosen operating point is characterized by a revving speed equal to 800 rpm with intake temperature and pressure of 24 \ub0C and 0.95 bar, respectively. Experimental data are available from the TU Darmstadt engine research group. Several aspects of the engine are analyzed, such as crevice modeling, blow-by, heat transfer and compression ratio, with the aim to minimize numerical uncertainties. On the one hand, a GT-Power model of the engine is used to investigate the impact of blow-by and crevices modeling during compression and expansion strokes. Moreover, it provides boundary conditions for the following 3D CFD simulations. On the other hand, the latter, carried out in a RANS framework with both highand low-Reynolds wall treatments, allow a deeper investigation of the boundary layer phenomena and, thus, of the gas-to-wall heat transfer. A detailed modeling of the crevice, along with an ad hoc tuning of both blow-by and heat fluxes lead to a remarkable improvement of the results. However, in order to adequately match the experimental mean in-cylinder pressure, a slight modification of the compression ratio from the nominal value is accounted for, based on the uncertainty which usually characterizes such geometrical parameter. The present preliminary study aims at providing reliable numerical setups for 1D and 3D models to be adopted in future detailed investigations on the Darmstadt research engine

The Impact of Spatial Heterogeneity in Land Use Practices and Aquifer Characteristics on Groundwater Conservation Policy Cost

Estimation of agricultural policy cost for a given level of groundwater conservation requires the establishment of an accurate baseline condition. This is especially critical when the benefits and cost of any conservation program are generally estimated relative to the status quo policy or baseline situation. An inaccurate baseline estimate will lead to poor estimates of potential water conservation savings and agricultural policy cost. Over a 60-year planning horizon per acre net present value is as much as 29.8% higher for a study area when aquifer characteristics are assumed to be homogenous and set to their average area value than when the heterogeneity in aquifer characteristics is explicitly modeled.Aquifer Modeling, Economics, Resource /Energy Economics and Policy,

Recognition mechanism of p63 by the E3 ligase Itch Novel strategy in the study and inhibition of this interaction.

The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer’s or Huntington’s diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly 13C-15N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534–551 residue of p63, encompassing the PP xY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PP xY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase

Al-based foams as permanent cores in al castings: Effect of surface skin thickness and composition on infiltration and core-shell bonding

An emerging and still poorly explored application of aluminum foams is their potential use as permanent cores (inserts) in the casting of aluminum alloys. In this context, Al-based foams can introduce a weight reduction, the obtainment of cavities, a strength increase, the ability to absorb impact energy and vibration, acoustic insulation ability, the possibility to simplify the technological processes (no removal/recycling of traditional sand cores), and finally, they can be fully recyclable. Cymat-type Al foams with thin outer skin were used as permanent cores in Al-alloy gravity casting in the present research. Al-foams were characterized in terms of porosity, density, cell wall and skin thickness, surface chemical composition and morphology, and compression resistance. Cast objects with foam inserts were characterized by means of optical microscopy. The preservation of up to 50% of the initial porosity was observed for foam inserts with higher density. Metallurgical bonding between the foam core and the cast metal was observed in some regions

Glutathione Decrement Drives Thermogenic Program in Adipose Cells

Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the "browning" effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes.Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the "browning" effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes

DNAJC12 deficiency: Mild hyperphenylalaninemia and neurological impairment in two siblings

Background: DNAJC12 co-chaperone protein deficiency has been recently described as a stand-alone metabolic disorder explaining many cases of mild hyperphenylalaninemia (HPA) that are not caused by variants in the PAH gene, which encodes for the hepatic enzyme phenylalanine hydroxylase (PAH), or inGCH1, PTS, QDPR, PCBD1 and DHPR, involved in tetrahydrobiopterin (BH4) biosynthesis and activity. Results: We describe two sisters born to consanguineous parents. The youngest sister (Patient 1), initially asymptomatic, tested positive at NewBorn Screening (NBS) for mild HPA. After variants in the PAH and BH4 related-genes were excluded, we performed DNAJC12 genetic analysis and found a previously described homozygous deletion [NM_021800.3: c.58_59del p.(Gly20Metfs*2)]. The older sister (Patient 2), homozygous for the same variant and exhibiting mild HPA, was diagnosed subsequently and presented with ataxia and repeated falls, upper limb dyskinesia, intentional tremor, and mild intellectual disability. Patient 1 was started on treatment with low Phenylalanine (Phe) diet, BH4, l-3,4-dihydroxyphenylalanine/carbidopa (L-DOPA) and 5-OH-Tryptophan, soon after diagnosis, and despite poor adherence to the dietary regimen, only manifested language impairment at last follow-up (age 5 years and 4 months). Patient 2, who started the same treatment at school age, experienced a minimal progression of neurological symptoms, with some improvement in her motor skills. Conclusions: These two new patients with DNAJC12-associated HPA, in addition to previous reports, point to DNAJC12 deficiency as a new metabolic syndrome that must be considered in patients with unexplained HPA

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy upon Arterial Stiffness

Context: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. Objective: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. Methods: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P <. 0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD =-0.48,-0.88 to-0.07, P =. 022). Conclusion: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies