22 research outputs found

    Изменение характеристик потока в мультициклоне при различной установке циклонных элементов

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    В работе представлены результаты численного моделирования потоков в корпусемультициклона, в двух моделях расположения циклонных элементов. Целью работы является возможность оптимизации расположения входов полуулиточных патрубков циклонных элементов в батарейном циклоне по первой и второй моделям. Они позволяют также более точно учесть гидравлическое сопротивление аппарата при определении наиболее эффективного расположения циклонных элементов.The paper presents the results of numerical simulation of flows in the case of multicyclone, in two models of the location of the cyclone elements. The aim of this work is the possibility of optimizing the location of entrances palowitch nozzles cyclone elements in the battery cyclone the first and second models. They also allow for a more accurate account of the hydraulic resistance of the device when determining the most effective location of cyclonic elements

    Mortality risk stratification in isolated severe traumatic brain injury using the revised cardiac risk index.

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    PURPOSE: Traumatic brain injury (TBI) continues to be a significant cause of mortality and morbidity worldwide. As cardiovascular events are among the most common extracranial causes of death after a severe TBI, the Revised Cardiac Risk Index (RCRI) could potentially aid in the risk stratification of this patient population. This investigation aimed to determine the association between the RCRI and in-hospital deaths among isolated severe TBI patients. METHODS: All adult patients registered in the TQIP database between 2013 and 2017 who suffered an isolated severe TBI, defined as a head AIS ≥ 3 with an AIS ≤ 1 in all other body regions, were included. Patients were excluded if they had a head AIS of 6. The association between different RCRI scores (0, 1, 2, 3, ≥ 4) and in-hospital mortality was analyzed using a Poisson regression model with robust standard errors while adjusting for potential confounders, with RCRI 0 as the reference. RESULTS: 259,399 patients met the study’s inclusion criteria. RCRI 2 was associated with a 6% increase in mortality risk [adjusted IRR (95% CI) 1.06 (1.01–1.12), p = 0.027], RCRI 3 was associated with a 17% increased risk of mortality [adjusted IRR (95% CI) 1.17 (1.05–1.31), p = 0.004], and RCRI ≥ 4 was associated with a 46% increased risk of in-hospital mortality [adjusted IRR(95% CI) 1.46 (1.11–1.90), p = 0.006], compared to RCRI 0. CONCLUSION: An elevated RCRI ≥ 2 is significantly associated with an increased risk of in-hospital mortality among patients with an isolated severe traumatic brain injury. The simplicity and bedside applicability of the index makes it an attractive choice for risk stratification in this patient population

    Acute effects of remote ischemic preconditioning on cutaneous microcirculation - a controlled prospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Therapeutic strategies aiming to reduce ischemia/reperfusion injury by conditioning tissue tolerance against ischemia appear attractive not only from a scientific perspective, but also in clinics. Although previous studies indicate that remote ischemic intermittent preconditioning (RIPC) is a systemic phenomenon, only a few studies have focused on the elucidation of its mechanisms of action especially in the clinical setting. Therefore, the aim of this study is to evaluate the acute microcirculatory effects of remote ischemic preconditioning on a distinct cutaneous location at the lower extremity which is typically used as a harvesting site for free flap reconstructive surgery in a human in-vivo setting.</p> <p>Methods</p> <p>Microcirculatory data of 27 healthy subjects (25 males, age 24 ± 4 years, BMI 23.3) were evaluated continuously at the anterolateral aspect of the left thigh during RIPC using combined Laser-Doppler and photospectrometry (Oxygen-to-see, Lea Medizintechnik, Germany). After baseline microcirculatory measurement, remote ischemia was induced using a tourniquet on the contralateral upper arm for three cycles of 5 min.</p> <p>Results</p> <p>After RIPC, tissue oxygen saturation and capillary blood flow increased up to 29% and 35% during the third reperfusion phase versus baseline measurement, respectively (both p = 0.001). Postcapillary venous filling pressure decreased statistically significant by 16% during second reperfusion phase (p = 0.028).</p> <p>Conclusion</p> <p>Remote intermittent ischemic preconditioning affects cutaneous tissue oxygen saturation, arterial capillary blood flow and postcapillary venous filling pressure at a remote cutaneous location of the lower extremity. To what extent remote preconditioning might ameliorate reperfusion injury in soft tissue trauma or free flap transplantation further clinical trials have to evaluate.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01235286">NCT01235286</a></p

    Beyond Consensus: Leveraging Inherent Biases in Fragment Based Screening Technologies

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    Fragment-based drug discovery (FBDD) has emerged as a strategy with great potential to recast the modern drug discovery process. Central to this method is the identification of small and simple molecular building blocks that bind a target of interest, and the subsequent incorporation of salient features of these fragments into larger and more complex compounds with enhanced target affinity and selectivity. A first step in FBDD often entails a fragment-based screen (FBS) to identify fragment “hits.” While there are theoretical advantages of using FBDD at the earliest stages of a drug discovery program, hurdles such as the integration of conflicting results from orthogonal screens have hindered its success. We present the meta-analysis of 35 fragment based campaigns at Novartis, which employed a generic 1,400 fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we aim to answer three questions: 1) What makes a fragment amenable for FBS? 2) How do different fragment screening technologies compare with each other? 3) What is the best way to pair FBS assay technologies? In addition to identifying properties that render fragments amenable for FBS, we compare in an unprecedented scale various screening technologies. We propose a quantitative way to compare the bias in various screening technologies, and demonstrate how this approach can be used to select technologies in order to ensure the greatest coverage of fragment hits

    Neurosurgical interventions during pregnancy and the puerperium: Clinical considerations and management

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    Neurosurgical interventions during pregnancy represent a special clinical challenge and require a meticulously selected treatment strategy. A thorough understanding of the underlying pathophysiological mechanisms involving mother and fetus is mandatory. We report our experience with neurosurgical procedures during pregnancy and the puerperium and summarize the difficulties encountered. The emerging diagnostic as well as therapeutic implications in these complex cases are also discussed

    Detecting SAM-induced conformational change of a histone methyltransferase using a homogenous time-resolved fluorescence-based binding assay

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    A homogenous time-resolved fluorescence (HTRF)-based binding assay has been established to measure the binding of the histone methyltransferase (HMT) G9a to its inhibitor CJP702 (a biotin analog of a known peptide-pocket inhibitor, BIX-01294). This assay was used to characterize G9a inhibitors. As expected, the peptide-pocket inhibitors decreased the G9a-CJP702 binding signal in a concentration-dependent manner. In contrast, the SAM-pocket compounds, SAM and sinefungin significantly increased the G9a-CJP702 binding signal; whereas SAH showed minimal effect. Enzyme kinetics studies showed that CJP702 is an uncompetitive inhibitor (vs SAM) that has a strong preference for the E:SAM form of the enzyme. Other data presented suggest that the SAM/sinefungin-induced increase in the HTRF signal is secondary to the increased E:SAM or E:sinefungin level. Thus the G9a-CJP702 binding assay can not only be used to characterize the peptide-pocket inhibitors; it can also detect the subtle conformational differences induced by the binding of different SAM-pocket compounds. To our knowledge, this is the first demonstration of using an uncompetitive inhibitor as a probe to monitor the conformational change induced by compound-binding with a HTRF assay
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