Інноваційна активність підприємств України: технологічний аспект

Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecular interaction of compounds with the neural differentiation process. Within the 11-day differentiation protocol of the assay, embryonic stem cells lost their pluripotency, evidenced by the reduced expression of stem cell markers Pou5F1 and Nanog. Moreover, stem cells differentiated into neural cells, with morphologically visible neural structures together with increased expression of neural differentiation-related genes such as beta III-tubulin, Map2, Neurogin1, Mapt and Reelin. Valproic acid (VPA) and carbamazepine (CBZ) exposure during hESTn differentiation led to concentration-dependent reduced expression of beta III-tubulin, Neurogin1 and Reelin. In parallel VPA caused an increased gene expression of Map2 and Mapt which is possibly related to the neural protective effect of VPA. These findings illustrate the added value of gene expression analysis for detecting compound specific effects in hESTn. Our findings were in line with and could explain effects observed in animal studies. This study demonstrates the potential of this assay protocol for mechanistic analysis of specific compound-induced inhibition of human neural cell differentiation. (c) 2014 Elsevier Ltd. All rights reserved

The METCRAX II Field Experiment: A Study of Downslope Windstorm-Type Flows in Arizona\u2019s Meteor Crater

The second Meteor Crater Experiment (METCRAX II) was conducted in October 2013 at Arizona\u2019s Meteor Crater. The experiment was designed to investigate nighttime downslope windstorm 12type flows that form regularly above the inner southwest sidewall of the 1.2-km diameter crater as a southwesterly mesoscale katabatic flow cascades over the crater rim. The objective of METCRAX II is to determine the causes of these strong, intermittent, and turbulent inflows that bring warm-air intrusions into the southwest part of the crater. This article provides an overview of the scientific goals of the experiment; summarizes the measurements, the crater topography, and the synoptic meteorology of the study period; and presents initial analysis results

Science to Solutions Dialogue 3 - Everyone eating well within environmental limits

EAT and the World Business Council for Sustainable Development (WBCSD) convened through FReSH a Science to Solutions Dialogue (SSD) on Everyone Eating Well within Environmental Limits. This third dialogue took place from 4-7 December 2018 in Texcoco, Mexico, and brought together business, science and civil society to explore how to feed almost 10 billion people with sustainable and healthy diets. The summary of the discussion sets out three mutually supportive narratives to focus business action and the key solutions

Chemico-calorimetric analysis of amorphous granules manufactured via continuous granulation process

The current study explores the first case of the implementation of solution calorimetry (SolCal) in order to determine the amorphous content of crystalline benzoyl-methoxy-methylindol-acetic acid (BMA)—a model poorly soluble drug, in the amorphous granules prepared via single-step continuous twin-screw dry granulations (TSG). Amorphous magnesium aluminometasilicate (Neusilin®) (US2) was used as a novel inorganic carrier via a TwinLab 10 mm twin-screw extruder. The BMA/US2 blends were processed at 180 °C and varying drug: carrier ratios of 1:4, 1:2.5 and 1:1 (w/w). Physico-chemical characterisation conducted via SEM, DSC and XRPD showed amorphous state of the drug in all granulated formulations. Reverse optical microscopy revealed a meso-porous structure of US2 in which the drug particles are adsorbed and/or entrapped within the porous network of the carrier. This phenomenon can be the underlying reason for the increase of the amorphous content in the extruded granules. Solution calorimetry (SolCal) study revealed amorphous content of the drug in all formulations quite precisely, whereas the dynamic vapour sorption (DVS) analysis complemented the results from SolCal. Furthermore, an attempt has been made for the first time to interrelate the findings from the SolCal to that of the release of the drug from the amorphous granules. It can be concluded that SolCal can be used as a novel technique to precisely quantify and interrelate the amorphous content to its physico-chemical performances such as drug release from the granulated formulations processed via TS

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without 18F-choline PET-CT detected simultaneous integrated boost

<p>Abstract</p> <p>Background</p> <p>In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without ¹⁸F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study.</p> <p>Methods</p> <p>Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq ¹⁸F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV_PET). A dose of 76Gy was prescribed to the prostate (PTV_prostate) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite).</p> <p>Results</p> <p>With a median cut-off standard uptake value (SUV) of 3, a median GTV_PETof 4.0 cm³and PTV_boost(GTV_PETwith margins) of 17.3 cm³was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D.</p> <p>Conclusions</p> <p>Treatment planning with ¹⁸F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.</p

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer

IntroductionWe hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). MethodsThe study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in >= 2 (WS2) or >= 3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. ResultsIn REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L center dot Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L center dot Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58, ConclusionIncreasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT

Carbon-sensitive pedotransfer functions for plant available water

Currently accepted pedotransfer functions show negligible effect of management-induced changes to soil organic carbon (SOC) on plant available water holding capacity (θAWHC), while some studies show the ability to substantially increase θAWHC through management. The Soil Health Institute\u27s North America Project to Evaluate Soil Health Measurements measured water content at field capacity using intact soil cores across 124 long-term research sites that contained increases in SOC as a result of management treatments such as reduced tillage and cover cropping. Pedotransfer functions were created for volumetric water content at field capacity (θFC) and permanent wilting point (θPWP). New pedotransfer functions had predictions of θAWHC that were similarly accurate compared with Saxton and Rawls when tested on samples from the National Soil Characterization database. Further, the new pedotransfer functions showed substantial effects of soil calcareousness and SOC on θAWHC. For an increase in SOC of 10 g kg–1 (1%) in noncalcareous soils, an average increase in θAWHC of 3.0 mm 100 mm–1 soil (0.03 m3 m–3) on average across all soil texture classes was found. This SOC related increase in θAWHC is about double previous estimates. Calcareous soils had an increase in θAWHC of 1.2 mm 100 mm–1 soil associated with a 10 g kg–1 increase in SOC, across all soil texture classes. New equations can aid in quantifying benefits of soil management practices that increase SOC and can be used to model the effect of changes in management on drought resilience

Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage

Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity