Multiple Input Electrode Gap Control During Vacuum Arc Remelting

Accurate control of the electrode gap in a vacuum arc remelting (VAR) furnace has been a goal of melters for many years. The size of the electrode gap has a direct influence on ingot solidification structure. At the high melting currents (30 to 40 kA) typically used for VAR of segregation insensitive Ti and Zr alloys, process voltage is used as an indicator of electrode gap, whereas drip-short frequency (or period) is usually used at the lower currents (5 to 8 kA) employed during VAR of superalloys. Modem controllers adjust electrode position or drive velocity to maintain a voltage or drip-short frequency (or period) set-point. Because these responses are non-linear functions of electrode gap and melting current, these controllers have a limited range for which the feedback gains are valid. Models are available that relate process voltage and drip-short frequency to electrode gap. These relationships may be used to linearize the controller feedback signal. An estimate of electrode gap may then be obtained by forming a weighted sum of the independent gap estimates obtained from the voltage and drip-short signals. By using multiple independent measures to estimate the gap, a controller that is less susceptible to process disturbances can be developed. Such a controller was designed, built and tested. The tests were carried out at Allvac Corporation during VAR of 12Cr steel at intermediate current levels

Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study.

BACKGROUND: Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. METHODS AND FINDINGS: We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90-1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia. CONCLUSIONS: In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease

Environmental effects of ozone depletion, UV radiation and interactions with climate change : UNEP Environmental Effects Assessment Panel, update 2017

Peer reviewe

Optimal Estimation of Electrode Gap During Vacuum ARC Remelting

Electrode gap is a very important parameter for the safe and successful control of vacuum arc remelting (VAR), a process used extensively throughout the specialty metals industry for the production of nickel base alloys and aerospace titanium alloys. Optimal estimation theory has been applied to the problem of estimating electrode gap and a filter has been developed based on a model of the gap dynamics. Taking into account the uncertainty in the process inputs and noise in the measured process variables, the filter provides corrected estimates of electrode gap that have error variances two-to-three orders of magnitude less than estimates based solely on measurements for the sample times of interest. This is demonstrated through simulations and confined by tests on the VAR furnace at Sandia National Laboratories. Furthermore, the estimates are inherently stable against common process disturbances that affect electrode gap measurement and melting rate. This is not only important for preventing (or minimizing) the formation of solidification defects during VAR of nickel base alloys, but of importance for high current processing of titanium alloys where loss of gap control can lead to a catastrophic, explosive failure of the process

Modern control strategies for vacuum arc remelting of segregation sensitive alloys

There are several process variables which are crucial to the control of vacuum arc remelting of segregation sensitive alloys. These are: electrode gap, melt rate, cooling rate, furnace annulus, furnace atmosphere and electrode quality (i.e. cleanliness and integrity). Of these variables, active, closed loop control is usually applied only to electrode gap. Other variables are controlled by controlling furnace operational parameters to preset schedules (e.g. melting current is ramped or held constant to control melt rate in an open loop fashion), through proper maintenance and calibration of equipment (e.g. to ensure proper cooling water and gas flow rates, or to accomplish an acceptable vacuum leak rate), through proper practice of procedures, and by maintaining electrode quality control. Electrode gap control is accomplished by controlling an electrode gap indicator such as drip-short frequency (or period) to a specified set-point. This type of control, though often adequate, ignores information available from other electrode gap indicators and is susceptible to upsets. A multiple input electrode gap controller is described which uses optimal estimation techniques to address this problem

Structural mechanism of RPA loading on DNA during activation of a simple pre-replication complex

We report that during activation of the simian virus 40 (SV40) pre-replication complex, SV40 T antigen (Tag) helicase actively loads replication protein A (RPA) on emerging single-stranded DNA (ssDNA). This novel loading process requires physical interaction of Tag origin DNA-binding domain (OBD) with the RPA high-affinity ssDNA-binding domains (RPA70AB). Heteronuclear NMR chemical shift mapping revealed that Tag-OBD binds to RPA70AB at a site distal from the ssDNA-binding sites and that RPA70AB, Tag-OBD, and an 8-nucleotide ssDNA form a stable ternary complex. Intact RPA and Tag also interact stably in the presence of an 8-mer, but Tag dissociates from the complex when RPA binds to longer oligonucleotides. Together, our results imply that an allosteric change in RPA quaternary structure completes the loading reaction. A mechanistic model is proposed in which the ternary complex is a key intermediate that directly couples origin DNA unwinding to RPA loading on emerging ssDNA