Численное исследование влияния условий распыления воды на температуру в следе "водяного снаряда"

С использованием нескольких моделей "водяных снарядов" малых размеров выполнено численное исследование макроскопических закономерностей испарения монодисперсной совокупности капель тонкораспыленной воды при прохождении через высокотемпературные продукты сгорания. Установлены зависимости интегральных характеристик тепломассопереноса от отношения площадей испарения и площадей, занимаемых "водяным снарядом". Определены условия распыления воды для эффективного снижения температуры в зоне горения

Analysis of microsatellite instability in colorectal carcinoma by microfluidic-based chip electrophoresis

Microsatellite analysis is an important tool in clinical research and molecular diagnostics because microsatellite instability (MSI) occurs frequently in various types of cancer. Approximately 10–15% of colorectal, gastric and endometrial carcinomas are associated with MSI, and this has an impact on clinical prognosis. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250, recommended by the Bethesda guidelines, were analysed by microfluidic-based on-chip electrophoresis in 40 cases of colon carcinoma with known MSI status. In all cases, microfluidic separation of the PCR amplicons resulted in highly resolved, distinct patterns of each of the five microsatellite loci. Detection of MSI could be demonstrated by microsatellite-loci-associated, well-defined deviations in the electropherogram profiles of tumour and non-tumour material, and confirmed the classification of MSI cases performed by conventional technology. In conclusion, microfluidic chip technology is a simple and reliable approach for MSI detection that allows label-free and very fast analysis of microsatellite amplicons

Структурные изменения в системе гемостаза у больных меланомой кожи на ранней стадии ее развития

Мета дослідження – оцінка показників системи гемостазу у 27 хворих на меланому шкіри. Виявлено подовження активованого часткового тромбопластинового часу, подовження часткового тромбопластинового часу, подовження часу рекальцифікації, зниження рівня антитромбіну III, підвищення рівня розчинних фібрін-мономерних комплексів. Таким чином, мають місце серйозні структурні зміни системного гемостазу - гіпокоагуляція і гіперфібриноліз. Діагностика та корекція цих змін допоможе поліпшити клінічний перебіг і прогноз захворювання.A research aim is an estimation of indexes of the system of hemostasis at 27 patients by the melanoma of skin. Lengthening of the activated partial tromboplastin time, lengthening of partial tromboplastin time, lengthening of time of recalcification, decline of level of antithrombin of III, increase of level of soluble fibrinmonomers complexes is educed. Thus, the serious structural changes in the system of hemostasis - incoagulability and hyperfibrinolysis take place. Diagnostics and correction of these changes will help to improve a clinical flow and prognosis of disease

Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress

The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress

Deactivation and regeneration of solid acid and base catalyst bodies used in cascade for bio-oil synthesis and upgrading

The modes of deactivation -and the extent to which their properties can be restored- of two catalyst bodies used in cascade for bio-oil synthesis have been studied. These catalysts include a solid acid granulate (namely ZrO2/desilicated zeolite ZSM-5/attapulgite clay) employed in ex-situ catalytic fast pyrolysis of biomass, and a base extrudate (K-exchanged zeolite USY/attapulgite clay) for the subsequent bio-oil upgrading. Post-mortem analyses of both catalyst bodies with Raman spectroscopy and confocal fluorescence microscopy revealed the presence of highly poly-aromatic coke distributed in an egg-shell manner. Deactivation due to coke adsorption onto acid sites affected the zeolite ZSM-5-based catalyst, while for the base catalyst it is structural integrity loss, resulting from KOH-mediated zeolite framework collapse, the main deactivating factor. A hydrothermal regeneration process reversed the detrimental effects of coke in the acid catalyst, largely recovering catalyst acidity (∼80%) and textural properties (∼90%), but worsened the structural damage suffered by the base catalyst

Crystal structures of self-assembled nanotubes from flexible macrocycles by weak interactions

8 páginas, 7 figuras, 2 tablas, 2 esquemas.Herein we report the crystal structures of tubular self-assemblies of flexible macrooligolides. The assembly is driven by the propensity of the macrocycles to create nearly flat structures displaying a void space within them and the cooperativity of weak directional interactions such as dipole–dipole interactions and CH***Ohydrogen bonds and non-directional interactions such as van der Waals contacts. The significance of the stereochemistry and the size of the cavity in the formation of the nanotubes are also studied.This research was supported by the Spanish MICINN-FEDER (CTQ2008-03334/BQU, CTQ2008-06806-C02-01/BQU and CTQ2008-06754-C04-01/PPQ), the MSC (RTICC RD06/0020/ 1046) and the Canary Islands FUNCIS (PI 01/06).Peer reviewe

Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations

A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93–07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL

An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogenous malignancy with poor prognosis in relapsed adult patients. The genetic basis for relapse in aneuploid subtypes such as near haploid (NH) and high hyperdiploid (HeH) BCP-ALL is only poorly understood. Pathogenic genetic alterations remain to be identified. To this end, we investigated the dynamics of genetic alterations in a matched initial diagnosis-relapse (ID-REL) BCP-ALL cohort. Here, we firstly report the identification of the novel genetic alteration CYB5Aalt, an alternative transcript of CYB5A, in two independent cohorts. Methods: We identified CYB5alt in the RNAseq-analysis of a matched ID-REL BCP-ALL cohort with 50 patients and quantified its expression in various molecular BCP-ALL subtypes. Findings were validated in an independent cohort of 140 first diagnosis samples from adult BCP-ALL patients. Derived from patient material, the alternative open reading frame of CYB5Aalt was cloned (pCYB5Aalt) and pCYB5Aalt or the empty vector were stably overexpressed in NALM-6 cells. RNA sequencing was performed of pCYB5Aalt clones and empty vector controls followed by differential expression analysis, gene set enrichment analysis and complementing cell death and viability assays to determine functional implications of CYB5Aalt. Results: RNAseq data analysis revealed non-canonical exon usage of CYB5Aalt starting from a previously undescribed transcription start site. CYB5Aalt expression was increased in relapsed BCP-ALL and its occurrence was specific towards the shared gene expression cluster of NH and HeH BCP-ALL in independent cohorts. Overexpression of pCYB5Aalt in NALM-6 cells induced a distinct transcriptional program compared to empty vector controls with downregulation of pathways related to reported functions of CYB5A wildtype. Interestingly, CYB5A wildtype expression was decreased in CYB5Aalt samples in silico and in vitro. Additionally, pCYB5Aalt NALM-6 elicited a more resistant drug response. Conclusions: Across all age groups, CYB5Aalt was the most frequent secondary genetic event in relapsed NH and HeH BCP-ALL. In addition to its high subgroup specificity, CYB5Aalt is a novel candidate to be potentially implicated in therapy resistance in NH and HeH BCP-ALL. This is underlined by overexpressing CYB5Aalt providing first evidence for a functional role in BCL2-mediated apoptosis