Deactivation of Pressure-Induced Amorphization in Silicalite SiO2 by Insertion of Guest Species

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Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib.

BackgroundTransforming growth factor beta (TGF-β) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-βRI/ALK5 inhibitor galunisertib.MethodsThis phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP): Part A (AFP ≥1.5x ULN) or Part B (AFP <1.5x ULN). Baseline and postbaseline levels of AFP, TGF-β1, E-cadherin, selected miRNAs, and other plasma proteins were monitored.ResultsThe study enrolled 149 patients (Part A, 109; Part B, 40). Median OS was 7.3 months in Part A and 16.8 months in Part B. Baseline AFP, TGF-β1, E-cadherin, and an additional 16 plasma proteins (such as M-CSF, IL-6, ErbB3, ANG-2, neuropilin-1, MIP-3 alpha, KIM-1, uPA, IL-8, TIMP-1, ICAM-1, Apo A-1, CA-125, osteopontin, tetranectin, and IGFBP-1) were found to correlate with OS. In addition, a range of miRs were found to be associated with OS. In AFP responders (21% of patients in Part A with decrease of >20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-β1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036).ConclusionsConsistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-β1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results

Image analysis workflows to reveal the spatial organization of cell nuclei and chromosomes

Nucleus, chromatin, and chromosome organization studies heavily rely on fluorescence microscopy imaging to elucidate the distribution and abundance of structural and regulatory components. Three-dimensional (3D) image stacks are a source of quantitative data on signal intensity level and distribution and on the type and shape of distribution patterns in space. Their analysis can lead to novel insights that are otherwise missed in qualitative-only analyses. Quantitative image analysis requires specific software and workflows for image rendering, processing, segmentation, setting measurement points and reference frames and exporting target data before further numerical processing and plotting. These tasks often call for the development of customized computational scripts and require an expertise that is not broadly available to the community of experimental biologists. Yet, the increasing accessibility of high- and super-resolution imaging methods fuels the demand for user-friendly image analysis workflows. Here, we provide a compendium of strategies developed by participants of a training school from the COST action INDEPTH to analyze the spatial distribution of nuclear and chromosomal signals from 3D image stacks, acquired by diffraction-limited confocal microscopy and super-resolution microscopy methods (SIM and STED). While the examples make use of one specific commercial software package, the workflows can easily be adapted to concurrent commercial and open-source software. The aim is to encourage biologists lacking custom-script-based expertise to venture into quantitative image analysis and to better exploit the discovery potential of their images.Abbreviations: 3D FISH: three-dimensional fluorescence in situ hybridization; 3D: three-dimensional; ASY1: ASYNAPTIC 1; CC: chromocenters; CO: Crossover; DAPI: 4',6-diamidino-2-phenylindole; DMC1: DNA MEIOTIC RECOMBINASE 1; DSB: Double-Strand Break; FISH: fluorescence in situ hybridization; GFP: GREEN FLUORESCENT PROTEIN; HEI10: HUMAN ENHANCER OF INVASION 10; NCO: Non-Crossover; NE: Nuclear Envelope; Oligo-FISH: oligonucleotide fluorescence in situ hybridization; RNPII: RNA Polymerase II; SC: Synaptonemal Complex; SIM: structured illumination microscopy; ZMM (ZIP: MSH4: MSH5 and MER3 proteins); ZYP1: ZIPPER-LIKE PROTEIN 1

Flexibility windows and compression of monoclinic and orthorhombic silicalites

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Renewing Ranobe for Tomorrow: An Integrated Approach to Sustainable Development in Madagascar

The Spiny Forest in southwest Madagascar is home to a 90% endemic array of species and the village of Ranobe. Climate change and deforestation through charcoal production, agricultural use, and development, have degraded 43% of land cover in the last decade. This project collaborated with Ho Avy, a local nonprofit, to design a sustainable development plan for the community. The plan is based on five key perspectives: 1) land use/land cover change management, 2) energy potential, 3) water and health, 4) food security, and 5) economic growth. The plan recommends increased education, shifting incentives, and investment in renewable technologies to be implemented in Ranobe to improve the health of the region’s population and unique environment.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/83529/1/RenewingRanobeforTomorrow_SNRE_20110419.pd

Dosimetric comparison between coplanar and non coplanar field radiotherapy for ethmoid sinus cancer

<p>Abstract</p> <p>Background</p> <p>To compare non coplanar field (NCF) with coplanar field (CF) -intensity-modulated radiotherapy (IMRT) planning for ethmoid cancer.</p> <p>Methods</p> <p>Seven patients treated with NCF IMRT for ethmoid cancer were studied. A CF IMRT optimization was prepared with the same constraints as for the NCF treatment. The maximum point doses (D max) obtained for the different optic pathway structures (OPS) should differ no more than 3% from those achieved with the NCF IMRT plan. The distribution of the dose in the target volume and in the critical structures was compared between the two techniques, as well as the Conformity (CI) and the Homogeneity Indexes (HI) in the target volume.</p> <p>Results</p> <p>We noted no difference between the two techniques in the OPS for the D1, D2, and D5%, in the inner ear and controlateral lens for the average Dmax, in the temporo-mandibular joints for the average mean dose, in the cord and brainstem for the average D1%. The dose-volume histograms were slightly better with the NCF treatment plan for the planning target volume (PTV) with a marginally better HI but no impact on CI. We found a great improvement in the PTV coverage with the CF treatment plan for two patients with T4 tumors.</p> <p>Conclusion</p> <p>IMRT is one of the treatment options for ethmoid cancer. The PTV coverage is optimal without compromising the protection of the OPS. The impact of non coplanar versus coplanar set up is very slight.</p

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings

Background: Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. Methods: A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with &lt;1% variability were considered as highly conserved. Subtyping was performed by phylogeny. Results: Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P &lt; 0.001]. Conclusions: The low baseline of INSTI-DRMs (&lt;1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS

Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows

The aim of this study was to identify genomic regions associated with 305-day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single-step genomic BLUP approach and imputed high-density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305-day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305-day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and -0.52, respectively. The results identified three windows on BTA14 associated with 305-day milk yield and the parameters of lactation curve in primi- and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes

Expert-based development of a generic HACCP-based risk management system to prevent critical negative energy balance in dairy herds

The objective of this study was to develop a generic risk management system based on the Hazard Analysis and Critical Control Point (HACCP) principles for the prevention of critical negative energy balance (NEB) in dairy herds using an expert panel approach. In addition, we discuss the advantages and limitations of the system in terms of implementation in the individual dairy herd. For the expert panel, we invited 30 researchers and advisors with expertise in the field of dairy cow feeding and/or health management from eight European regions. They were invited to a Delphi-based set-up that included three inter-correlated questionnaires in which they were asked to suggest risk factors for critical NEB and to score these based on 'effect' and 'probability'. Finally, the experts were asked to suggest critical control points (CCPs) specified by alarm values, monitoring frequency and corrective actions related to the most relevant risk factors in an operational farm setting. A total of 12 experts (40 %) completed all three questionnaires. Of these 12 experts, seven were researchers and five were advisors and in total they represented seven out of the eight European regions addressed in the questionnaire study. When asking for suggestions on risk factors and CCPs, these were formulated as 'open questions', and the experts' suggestions were numerous and overlapping. The suggestions were merged via a process of linguistic editing in order to eliminate doublets. The editing process revealed that the experts provided a total of 34 CCPs for the 11 risk factors they scored as most important. The consensus among experts was relatively high when scoring the most important risk factors, while there were more diverse suggestions of CCPs with specification of alarm values and corrective actions. We therefore concluded that the expert panel approach only partly succeeded in developing a generic HACCP for critical NEB in dairy cows. We recommend that the output of this paper is used to inform key areas for implementation on the individual dairy farm by local farm teams including farmers and their advisors, who together can conduct herd-specific risk factor profiling, organise the ongoing monitoring of herd-specific CCPs, as well as implement corrective actions when CCP alarm values are exceeded

Baseline gene signatures of reactogenicity to Ebola vaccination: a machine learning approach across multiple cohorts

Introduction: The rVSVDG-ZEBOV-GP (Ervebo®) vaccine is both immunogenic and protective against Ebola. However, the vaccine can cause a broad range of transient adverse reactions, from headache to arthritis. Identifying baseline reactogenicity signatures can advance personalized vaccinology and increase our understanding of the molecular factors associated with such adverse events. Methods: In this study, we developed a machine learning approach to integrate prevaccination gene expression data with adverse events that occurred within 14 days post-vaccination. Results and Discussion: We analyzed the expression of 144 genes across 343 blood samples collected from participants of 4 phase I clinical trial cohorts: Switzerland, USA, Gabon, and Kenya. Our machine learning approach revealed 22 key genes associated with adverse events such as local reactions, fatigue, headache, myalgia, fever, chills, arthralgia, nausea, and arthritis, providing insights into potential biological mechanisms linked to vaccine reactogenicity