94 research outputs found

    Analysis of laser usage in machining technology.

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    Základním cílem této bakalářské práce je analyzovat laser a jeho aplikace v oblasti strojírenství a to především v odvětví obrábění materiálů. Práce uvádí rozbor základních typů laseru a laserových systémů, jež jsou v dnešní průmyslové praxi využívány. Dále je potom rozebírána problematika interakce laserového paprsku s obráběným materiálem a v neposlední řadě práce analyzuje technologické procesy obrábění materiálů laserem, jež se ve strojírenství dnešní doby vyskytují nejhojněji. Autor se především zaměřuje na obecné a komplexní shrnutí daného problému.The main object of this bachelor’s thesis is analyzing the laser and its application in mechanical engineering especially in material machining. The work introduces basic laser´s types and laser´s systems analysis used in current industrial profession. The problems of laser ray interaction with machined material are analysed and the most occurred technological processes in machining of material by laser in engineering in current time are analysed. The author is focused on general and complex summary of relevant problem firstly.

    Solution technology of part "víko" in the condition of a middle-sized company

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    Diplomová práce se zabývá zhodnocením stávající technologie výroby součásti „víko hydrauliky“ a návrhem nové progresivní varianty obrobení této součásti. Řešení je zaměřeno především na racionalizaci řezných nástrojů a volbu vhodných progresivních řezných nástrojů. Snahou je docílení kratších výrobních časů a tím snížení nákladů na výrobu komponenty. S tímto problémem souvisí změna technologické dokumentace a technicko-ekonomické zhodnocení pro stanovení doby návratnosti investice do progresivních nástrojů.The diploma thesis is concerned with evaluation of actual production technology of part “hydraulics cover” and with design of new, progressive variation machining of this part. Solution is focused at first on rationalization of cutting tools and choice of suitable cutting tools. An effort is to achieve shorter production time and decrease costs on production of component. With this problem is related alteration of technological documentation and technical economic evaluation for determination return rate of investments into progressive cutting tools.

    Structural insight into the calcium ion modulated interdomain electron transfer in cellobiose dehydrogenase

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    AbstractCellobiose dehydrogenase (CDH) from wood degrading fungi represents a subclass of oxidoreductases with unique properties. Consisting of two domains exhibiting interdomain electron transfer, this is the only known flavocytochrome involved in wood degradation. High resolution structures of the separated domains were solved, but the overall architecture of the intact protein and the exact interface of the two domains is unknown. Recently, it was shown that divalent cations modulate the activity of CDH and its pH optimum and a possible mechanism involving bridging of negative charges by calcium ions was proposed. Here we provide a structural explanation of this phenomenon confirming the interaction between negatively charged surface patches and calcium ions at the domain interface

    Who Is In Charge, and Who Should Be? The Disciplinary Role of the Commander in Military Justice Systems

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    BackgroundStandard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma. MethodsWe randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. ResultsA total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). ConclusionsThe addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo.

    Counterintuitive structural and functional effects due to naturally occurring mutations targeting the active site of the disease-associated NQO1 enzyme*

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    Our knowledge on the genetic diversity of the human genome is exponentially growing. However, our capacity to establish genotype–phenotype correlations on a large scale requires a combination of detailed experimental and computational work. This is a remarkable task in human proteins which are typically multifunctional and structurally complex. In addition, mutations often prevent the determination of mutant high-resolution structures by X-ray crystallography. We have characterized here the effects of five mutations in the active site of the disease-associated NQO1 protein, which are found either in cancer cell lines or in massive exome sequencing analysis in human population. Using a combination of H/D exchange, rapid-flow enzyme kinetics, binding energetics and conformational stability, we show that mutations in both sets may cause counterintuitive functional effects that are explained well by their effects on local stability regarding different functional features. Importantly, mutations predicted to be highly deleterious (even those affecting the same protein residue) may cause mild to catastrophic effects on protein function. These functional effects are not well explained by current predictive bioinformatic tools and evolutionary models that account for site conservation and physicochemical changes upon mutation. Our study also reinforces the notion that naturally occurring mutations not identified as disease-associated can be highly deleterious. Our approach, combining protein biophysics and structural biology tools, is readily accessible to broadly increase our understanding of genotype–phenotype correlations and to improve predictive computational tools aimed at distinguishing disease-prone against neutral missense variants in the human genome

    Control of catalytic activity of proteins in vivo by nanotube ropes excited with infrared light

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    We discuss the possibility of controlling biological systems, by exciting in the near infrared region {\it hybrid} metallic nanotube ropes, dressed with proteins and embedded in the biosystems. If one nanotube, in a double-tube rope, is filled with metallofullerenes and the other is empty, the two tubes change their opposite equilibrium charging during the irradiation. The resulting change of the local electric field can deform proteins attached to the tubes, and change their catalytic properties.Comment: 4 pages, 3 Postscript figure

    Staged hepatectomy for bilobar colorectal hepatic metastases

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    AbstractObjectivesThis study describes the management of patients with bilobar colorectal liver metastases (CRLM).MethodsA retrospective collection of data on all patients with CRLM who were considered for staged resection (n= 85) from January 2003 to January 2011 was performed. Patients who underwent one hepatic resection were considered to have had a failed staged resection (FSR), whereas those who underwent a second or third hepatic resection to produce a cure were considered to have had a successful staged resection (SSR). Survival was calculated from the date of diagnosis of liver metastases. Complete follow-up and dates of death were obtained from the Government of Quebec population database.ResultsMedian survival was 46months (range: 30–62months) in the SSR group and 22months (range: 19–29months) in the FSR group. Rates of 5-year survival were 42% and 4% in the SSR and FSR groups, respectively. Fifteen of the 19 patients who remained alive at the last follow-up date belonged to the SSR group.ConclusionsIn patients in whom staged resection for bilobar CRLM is feasible, surgery would appear to offer benefit
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