29 research outputs found

    Критерии формы поперечного сечения взрывной скважины

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    Предложены критерии оценки форм поперечного сечения скважины, полностью заполненной удлиненным зарядом взрывчатого вещества. Критерии рассмотрены с точки зрения эффективности взрывного воздействия на горную породу и могут быть использованы при создании и обосновании конструкций бурового инструмента. Анализ геометрических форм поперечных сечений взрывной полости в виде правильных фигур показал, что имеется взаимосвязь критериев, конкретное значение которых может быть определено для имеющихся конструкций бурового инструмента.Proposed criteria for the assessment of the bag of cross-section of the borehole is completely filled elongated explosive charge. Criteria considered from the point of view of the ability to influence the result of the explosive impact and can be used to create and justify the constructions of the drilling tool. The analysis of geometrical forms of cross sections of the explosive borehole in the form of correct figures have shown that there is a relationship of the considered criteria, however, a specific value can be determined for the existing designs of drilling tools

    Determination of rhodium content by the method of Stripping voltammetry in ores and technogenic raw materials

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    The method of determination of rhodium by the method of Stripping voltammetry in ores and technogenic raw materials has been developed. Determination of rhodium (III) in solution by Stripping voltammetry method was carried out by peak of selective electrooxidation of bismuth from intermetallic compound Bi2Rh. 1 M KSCN was selected as a background electrolyte. The method of melting of the sample with potassium tetrafluoroborate (KBrF4) at a temperature of 500 was used for the conversion of the rhodium solution.The method of deposition of most ions present in solution of alkali metals was used to separate ions of rhodium (III) from the matrix of the samples. Ions of Pt (IV), Rh (III) and Ir (IV) remain in solution after precipitation. Ions of iridium (IV) and 10- fold excess of platinum (IV) do not interfere with the determination of rhodium (III) against the background of 1 M KSCN

    SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

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    The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML

    The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis

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    Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0-163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD3

    Impact of High-Cut-Off Dialysis on Renal Recovery in Dialysis-Dependent Multiple Myeloma Patients: Results from a Case-Control Study

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    <div><p>Background</p><p>High-cut-off hemodialysis (HCO-HD) can effectively reduce high concentrations of circulating serum free light chains (sFLC) in patients with dialysis-dependent acute kidney injury (AKI) due to multiple myeloma (MM). Therefore, the aim of this study was to analyze renal recovery in a retrospective single-center cohort of dialysis-dependent MM patients treated with either conventional HD (conv. HD) or HCO-HD.</p><p>Methods and Results</p><p>The final cohort consisted of 59 patients treated with HCO-HD (n = 42) or conv. HD (n = 17). A sustained sFLC response was detected in a significantly higher proportion of HCO-HD patients (83.3%) compared with conv. HD patients (29.4%; p = 0.007). The median duration of sFLC required to reach values <1000 mg/l was 14.5 days in the HCO-HD group and 36 days in the conv. HD group. The corresponding rates of renal recovery were 64.3% and 29.4%, respectively (chi-squared test, p = 0.014). Multivariate regression and decision tree analysis (recursive partitioning) revealed HCO-HD (adjusted odds ratio [OR] 6.1 [95% confidence interval (CI) 1.5–24.5], p = 0.011) and low initial uric acid values (adjusted OR 1.3 [95%CI 1.0–1.7], p = 0.045) as independent and paramount variables associated with a favorable renal outcome.</p><p>Conclusions</p><p>In summary, the results from this retrospective case-control study suggest in addition to novel agent-based chemotherapy a benefit of HCO-HD in sFLC removal and renal outcome in dialysis-dependent AKI secondary to MM. This finding was especially pertinent in patients with low initial uric acid values, resulting in a promising renal recovery rate of 71.9%. Further prospective studies are warranted.</p></div

    Outdoor air pollution and hormone-assessed pubertal development in children: Results from the GINIplus and LISA birth cohorts

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    Background Air pollution is hypothesized to affect pubertal development. However, the few studies on this topic yielded overall mixed results. These studies did not consider important pollutants like ozone, and none of them involved pubertal development assessed by estradiol and testosterone measurements. We aimed to analyze associations between long-term exposure to four pollutants and pubertal development based on sex hormone concentrations among 10-year-old children. Methods These cross-sectional analyses were based on the 10-year follow-up medical examinations of 1945 children from the Munich and Wesel centers of the GINIplus and LISA German birth cohorts. Female and male pubertal development was assessed by dichotomizing the concentration of hormones in serum at 18.4 pmol/L and 0.087 nmol/L using the lower limits of quantification for estradiol and testosterone, respectively. Land-use regression models derived annual average concentrations of particulate matter with an aerodynamic diameter < 2.5 and 10 µm (PM2.5 and PM10), as well as spatial models assessed yearly average concentrations of nitrogen dioxide (NO2) and ozone, were calculated at the 10-year residential addresses. To evaluate associations, we utilized logistic regressions adjusted for potential covariates. The analyses were stratified by area and sex. Results Around 73% of the 943 females and 25% of the 1002 males had a high level of hormones and had already started puberty at the age of 10. Overall, we found no statistically significant associations between exposure to particles (PM2.5 or PM10) and pubertal development. Results on NO2 and ozone were not significant as well; for instance, per 10 µg/m3 increase in ozone concentration, odds ratios and 95% confidence intervals were 0.900 (0.605, 1.339) and 0.830 (0.573, 1.203) for females and males, respectively. Stratified by area, the aforementioned results did not reveal any associations either. Conclusions Our study did not observe the associations between ambient air pollutants and pubertal development determined by estradiol and testosterone levels in children. However, due to the current limited number of studies on this topic, our results should be cautiously interpreted. Future longitudinal studies are needed to assess the association

    Clonal heterogeneity of FLT3-ITD detected by high-throughput amplicon sequencing correlates with adverse prognosis in acute myeloid leukemia

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    In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of FLT3 are frequent mutations associated with unfavorable prognosis. At diagnosis, the FLT3-ITD status is routinely assessed by fragment analysis, providing information about the length but not the position and sequence of the ITD. To overcome this limitation, we performed cDNA-based high-throughput amplicon sequencing (HTAS) in 250 FLT3-ITD positive AML patients, treated on German AML Cooperative Group (AMLCG) trials. FLT3-ITD status determined by routine diagnostics was confirmed by HTAS in 242 out of 250 patients (97%). The total number of ITDs detected by HTAS was higher than in routine diagnostics (n = 312 vs. n = 274). In particular, HTAS detected a higher number of ITDs per patient compared to fragment analysis, indicating higher sensitivity for subclonal ITDs. Patients with more than one ITD according to HTAS had a significantly shorter overall and relapse free survival. There was a close correlation between FLT3-ITD mRNA levels in fragment analysis and variant allele frequency in HTAS. However, the abundance of long ITDs (≥75nt) was underestimated by HTAS, as the size of the ITD affected the mappability of the corresponding sequence reads. In summary, this study demonstrates that HTAS is a feasible approach for FLT3-ITD detection in AML patients, delivering length, position, sequence and mutational burden of this alteration in a single assay with high sensitivity. Our findings provide insights into the clonal architecture of FLT3-ITD positive AML and have clinical implications

    Flow chart displaying the patient selection.

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    <p><u>Abbrev</u>.: MM—Multiple Myeloma; AKI—acute kidney injury; sFLC—serum free light chain; HCO-HD—High cut-off dialysis; conv. HD—conventional hemodialysis</p
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