138 research outputs found
Process control & instrumentation for titanium sponge plant
A large scale facility for establishing the technology of production of titanium sponge in 4000 kg batches by high temperature reduction of titanium tetrachloride has been set up at the Defence Metallurgical Research Laboratory, Hyderabad. The steps involved in the process are (i) two stage distillation for the purification of titanium tetrachloride (ii) high temperature reduction of titanium tetrachloride by molten magnesium followed by pyro-vacuum distillation of sponge in a combined reductionvacuum disti-llation furnace and (iii) processing of the sponge produ-ced which include sponge ejection, cutting, crushing and blending. To produce high purity sponge in a reproducible manner batch after batch, very close monitoring & control of process parameters is essential. In view of the highly
reactive nature of the metal, any post reduction purifica-tion is totally ruled out. This paper discusses in detail the process control scheme adopted for the titanium tetra-chloride purification and reduction operations, highlight-ing the type of instrumentation adopted considering the corrosive nature of titanium tetrachloride. A microproce-ssor based Distributed Control System has been installed for controlling the process operation. Salient features of this system are also described in this paper
GRADES: Gradient descent for similarity caching
International audienceA similarity cache can reply to a query for an object with similar objects stored locally. In some applications of similarity caches, queries and objects are naturally represented as points in a continuous space. Examples include 360° videos where user's head orientation-expressed in spherical coordinates determines what part of the video needs to be retrieved, and recommendation systems where the objects are embedded in a finite-dimensional space with a distance metric to capture content dissimilarity. Existing similarity caching policies are simple modifications of classic policies like LRU, LFU, and qLRU and ignore the continuous nature of the space where objects are embedded. In this paper, we propose GRADES, a new similarity caching policy that uses gradient descent to navigate the continuous space and find the optimal objects to store in the cache. We provide theoretical convergence guarantees and show GRADES increases the similarity of the objects served by the cache in both applications mentioned above
GRADES: Gradient descent for similarity caching
A similarity cache can reply to a query for an object with similar objects stored locally. In some applications of similarity caches, queries and objects are naturally represented as points in a continuous space. Examples include 360° videos where user's head orientation - expressed in spherical coordinates - determines what part of the video needs to be retrieved, and recommendation systems where the objects are embedded in a finite-dimensional space with a distance metric to capture content dissimilarity. Existing similarity caching policies are simple modifications of classic policies like LRU, LFU, and qLRU and ignore the continuous nature of the space where objects are embedded. In this paper, we propose Grades, a new similarity caching policy that uses gradient descent to navigate the continuous space and find the optimal objects to store in the cache. We provide theoretical convergence guarantees and show Grades increases the similarity of the objects served by the cache in both applications mentioned above
Blockade of adenosine A2B receptors ameliorates murine colitis
Background and purpose: The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein expression are increased during human and murine colitis. However, the effect of the A2B receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A2B receptor antagonism on murine colitis. Experimental approach: Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10/ mice were used as animal models of colitis. The A2B receptor-selective antagonist, ATL-801, was given in the diet. Key results: Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased epithelial hyperplasia in piroxicam-treated IL-10/ mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration. Conclusions and implications: Taken together, these data demonstrate that the intestinal epithelial A2B receptor is an important mediator of pro-inflammatory responses in the intestine and that A2B receptor blockade may be an effectiv
The Radish Gene Reveals a Memory Component with Variable Temporal Properties
Memory phases, dependent on different neural and molecular mechanisms, strongly influence memory performance. Our understanding, however, of how memory phases interact is far from complete. In Drosophila, aversive olfactory learning is thought to progress from short-term through long-term memory phases. Another memory phase termed anesthesia resistant memory, dependent on the radish gene, influences memory hours after aversive olfactory learning. How does the radish-dependent phase influence memory performance in different tasks? It is found that the radish memory component does not scale with the stability of several memory traces, indicating a specific recruitment of this component to influence different memories, even within minutes of learning
104-week efficacy and safety of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease:a phase III open-label extension study (ATB200-07)
The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa + mig) with alglucosidase alfa + placebo (alg + pbo) in adults with late-onset Pompe disease (LOPD). This ongoing open-label extension (OLE; NCT04138277) evaluates long-term safety and efficacy of cipa + mig. Outcomes include 6-min walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels, patient-reported outcomes and safety. Data are reported as change from PROPEL baseline to OLE week 52 (104 weeks post-PROPEL baseline). Of 118 patients treated in the OLE, 81 continued cipa + mig treatment from PROPEL (cipa + mig group; 61 enzyme replacement therapy [ERT] experienced prior to PROPEL; 20 ERT naïve) and 37 switched from alg + pbo to cipa + mig (switch group; 29 ERT experienced; 8 ERT naive). Mean (standard deviation [SD]) change in % predicted 6MWD from baseline to week 104 was + 3.1 (8.1) for cipa + mig and − 0.5 (7.8) for the ERT-experienced switch group, and + 8.6 (8.6) for cipa + mig and + 8.9 (11.7) for the ERT-naïve switch group. Mean (SD) change in % predicted FVC was − 0.6 (7.5) for cipa + mig and − 3.8 (6.2) for the ERT-experienced switch group, and − 4.8 (6.5) and − 3.1 (6.7), respectively, in ERT-naïve patients. CK and Hex4 levels improved in both treatment groups by week 104 with cipa + mig treatment. Three patients discontinued the OLE due to infusion-associated reactions. No new safety signals were identified. Cipa + mig treatment up to 104 weeks was associated with overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) from baseline with continued durability, and was well tolerated, supporting long-term benefits for patients with LOPD. Trial registration number: NCT04138277; trial start date: December 18, 2019.</p
Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect
<p>Abstract</p> <p>Background</p> <p>In insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear.</p> <p>Results</p> <p>We studied the roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in olfactory and visual conditioning in crickets. We found that pharmacological blockade of octopamine and dopamine receptors impaired aversive memory recall and appetitive memory recall, respectively, thereby suggesting that activation of octopaminergic and dopaminergic neurons and the resulting release of octopamine and dopamine are needed for appetitive and aversive memory recall, respectively. On the basis of this finding, we propose a new model in which it is assumed that two types of synaptic connections are formed by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus to neurons inducing conditioned response and the other being connections from neurons representing conditioned stimulus to octopaminergic or dopaminergic neurons representing appetitive or aversive unconditioned stimulus, respectively. The former is called 'stimulus-response connection' and the latter is called 'stimulus-stimulus connection' by theorists studying classical conditioning in higher vertebrates. Our model predicts that pharmacological blockade of octopamine or dopamine receptors during the first stage of second-order conditioning does not impair second-order conditioning, because it impairs the formation of the stimulus-response connection but not the stimulus-stimulus connection. The results of our study with a cross-modal second-order conditioning were in full accordance with this prediction.</p> <p>Conclusion</p> <p>We suggest that insect classical conditioning involves the formation of two kinds of memory traces, which match to stimulus-stimulus connection and stimulus-response connection. This is the first study to suggest that classical conditioning in insects involves, as does classical conditioning in higher vertebrates, the formation of stimulus-stimulus connection and its activation for memory recall, which are often called cognitive processes.</p
A Cell-Free Microtiter Plate Screen for Improved [FeFe] Hydrogenases
, a potential renewable fuel. Attempts to exploit these catalysts in engineered systems have been hindered by the biotechnologically inconvenient properties of the natural enzymes, including their extreme oxygen sensitivity. Directed evolution has been used to improve the characteristics of a range of natural catalysts, but has been largely unsuccessful for [FeFe] hydrogenases because of a lack of convenient screening platforms. [FeFe] hydrogenase HydA1 with a specific activity ∼4 times that of the wild-type enzyme. cell extracts, which allows unhindered access to the protein maturation and assay environment
Steering hyper-giants' traffic at scale
Large content providers, known as hyper-giants, are responsible for sending the majority of the content traffic to consumers. These hyper-giants operate highly distributed infrastructures to cope with the ever-increasing demand for online content. To achieve 40 commercial-grade performance of Web applications, enhanced end-user experience, improved reliability, and scaled network capacity, hyper-giants are increasingly interconnecting with eyeball networks at multiple locations. This poses new challenges for both (1) the eyeball networks having to perform complex inbound traffic engineering, and (2) hyper-giants having to map end-user requests to appropriate servers. We report on our multi-year experience in designing, building, rolling-out, and operating the first-ever large scale system, the Flow Director, which enables automated cooperation between one of the largest eyeball networks and a leading hyper-giant. We use empirical data collected at the eyeball network to evaluate its impact over two years of operation. We find very high compliance of the hyper-giant to the Flow Director’s recommendations, resulting in (1) close to optimal user-server mapping, and (2) 15% reduction of the hyper-giant’s traffic overhead on the ISP’s long-haul links, i.e., benefits for both parties and end-users alike.EC/H2020/679158/EU/Resolving the Tussle in the Internet: Mapping, Architecture, and Policy Making/ResolutioNe
Targeted Deletion of Neuropeptide Y (NPY) Modulates Experimental Colitis
Neurogenic inflammation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). We examined the role of neuropeptide Y (NPY) and neuronal nitric oxide synthase (nNOS) in modulating colitis.Colitis was induced by administration of dextran sodium sulphate (3% DSS) or streptomycin pre-treated Salmonella typhimurium (S.T.) in wild type (WT) and NPY (NPY(-/-)) knockout mice. Colitis was assessed by clinical score, histological score and myeloperoxidase activity. NPY and nNOS expression was assessed by immunostaining. Oxidative stress was assessed by measuring catalase activity, glutathione and nitrite levels. Colonic motility was assessed by isometric muscle recording in WT and DSS-treated mice.DSS/S.T. induced an increase in enteric neuronal NPY and nNOS expression in WT mice. WT mice were more susceptible to inflammation compared to NPY(-/-) as indicated by higher clinical & histological scores, and myeloperoxidase (MPO) activity (p<0.01). DSS-WT mice had increased nitrite, decreased glutathione (GSH) levels and increased catalase activity indicating more oxidative stress. The lower histological scores, MPO and chemokine KC in S.T.-treated nNOS(-/-) and NPY(-/-)/nNOS(-/-) mice supported the finding that loss of NPY-induced nNOS attenuated inflammation. The inflammation resulted in chronic impairment of colonic motility in DSS-WT mice. NPY -treated rat enteric neurons in vitro exhibited increased nitrite and TNF-alpha production.NPY mediated increase in nNOS is a determinant of oxidative stress and subsequent inflammation. Our study highlights the role of neuronal NPY and nNOS as mediators of inflammatory processes in IBD
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