UNICORE 6 — Recent and Future Advancements

UNICORE is a European Grid Technology with more than 10 years of history. Originating from the Supercomputing domain, the latest version UNICORE 6 has turned into a general-purpose Grid technology that follows established standards and offers a rich set of features to its users. The paper starts with an architectural insight into UNICORE 6, highlighting the workflow features, standards and the different clients. Next, the current state of advancement is presented by describing recent developments. The paper closes with an outlook on future planned developments.     

基于虚拟现实的恐惧测量模型建立

恐惧程度的客观评价在心理健康评估和职业能力评测中具有重要的作用。在沉浸式训练过程中,生理和运动数据有助于提升交互界面设计,增加虚拟训练的安全性。文中使用头戴式VR系统HTC Vive实现沉浸式VR体验,利用OpenVR开源软件包采集控制器和头部的位置信息,并结合Equivital belt EQ02 Lifemonitor所采集的心电信号、躯体加速度实现多种信号的特征提取。文中使用递归特征消除的特征排序方法和支持向量回归从50个生理及运动特征中选取了10个特征。基于自测恐惧值和特征的多元多项式回归实现了准确率为90%的二分类,即完成了对受试者恐惧或者非恐惧的分类。     

Selectively Promoting or Preventing Osteoblast Growth on Titanium Functionalized with Polyelectrolyte Multilayers

Titanium plays an important role in medical applications, such as hip joint implants or fixation plates. These implants must perform differently depending on their clinical application. In particular, the osseointegrative properties required of the implant vary with clinical application. The present work is aimed at the functionalization of titanium surface using polyelectrolyte multilayers consisting of natural biopolymers and testing their cell adhesive properties with respect to the osseointegration capacity. Multilayered coatings were created from chitosan (Chi), hyaluronic acid (HA), and gelatine (Gel) through layer‐by‐layer deposition. Cell adhesion, proliferation, and viability were tested in vitro with the human osteoblast cell line CAL‐72 at timescales up to 7 d. Two multilayer coatings consisting of alternated chitosan/gelatin or chitosan/hyaluronic acid layers with the outmost layer of gelatin (Chi/Gel) or hyaluronic acid (Chi/HA), respectively, were tested. The experimental results showed that surfaces functionalized with Chi/Gel and Chi/HA multilayers demonstrated a good initial adhesion of osteoblasts. After 4 d culturing, osteoblast cells were almost completely detached from the substrates functionalized with Chi/HA multilayers. In contrast to Chi/HA, the proliferation of osteoblasts on substrates with Chi/Gel multilayer coatings was statistically significantly higher compared to the control titanium. We have shown that the growth of osteoblasts can be enhanced or completely prevented on a titanium surface functionalized with polyelectrolyte multilayers consisting of natural biopolymers, as desired. Both multilayer coatings, Chi/Gel and Chi/HA, have potential for applications in the field of titanium implants, where rapid osseointegration is essential, and/or where no ingrowth of the implant is desired, respectively.     

APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the APOB gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry APOB missense variants of uncertain significance (VUS). We here aimed to develop a proof-of-principle experiment to assess the pathogenicity of VUS using the genome editing of human liver cells. We identified a novel heterozygous APOB-VUS (p.Leu351Arg), in a FHBL family. We generated APOB knock-out (KO) and APOB-p.Leu351Arg knock-in Huh7 cells using CRISPR-Cas9 technology and studied the APOB expression, synthesis and secretion by digital droplet PCR and ELISA quantification. The APOB expression was decreased by 70% in the heterozygous APOB-KO cells and almost abolished in the homozygous-KO cells, with a consistent decrease in apoB production and secretion. The APOB-p.Leu351Arg homozygous cells presented with a 40% decreased APOB expression and undetectable apoB levels in cellular extracts and supernatant. Thus, the p.Leu351Arg affected the apoB secretion, which led us to classify this new variant as likely pathogenic and to set up a hepatic follow-up in this family. Therefore, the functional assessment of APOB-missense variants, using gene-editing technologies, will lead to improvements in the molecular diagnosis of FHBL and the personalized follow-up of these patients.     

Silicon-doped hydroxyapatite prepared by a thermal technique for hard tissue engineering applications

Hydroxyapatite (HA, Ca₅(PO₄)₃OH) has been extensively used for bone implantation due to its similarity to the mineral component of bone, which makes it strongly osteoconductive. However, HA has low resorbability, and it is difficult to replace by a newly regenerated bone. Si doping can enhance the resorbability of HA by modifying its crystal structure. Here, we developed a simple thermal technique for preparing Si-doped HA from silica (SiO₂) and HA precursors, both of which are inexpensive and commercially available. This method included the physical binding of SiO₂ and HA particles, followed by pressing and sintering the mixture at an elevated temperature, which enhanced the atomic diffusion of Si into HA unit cells. We also evaluated the simulated body fluid (SBF) activity of the Si-doped HA prepared by this technique and showed that it significantly had higher resorbability and mineralizing potential compared to the pure HA. Our experimental design including, the individual precipitation and resorption assays enabled us to explain the mechanism behind the improved activity of Si-doped HA in SBF. This was attributed to the formation of new phases, such as β-tricalcium phosphate (β-TCP) and calcium silicate (Ca₂SiO₄) with higher solubility than HA on the SiO₂-contating HA during the sintering stage. This can provide some guidelines for designing new calcium phosphate-based materials for hard tissue engineering applications.     

Effect of Pluronic F127 on the 3D pore morphology of poly(N-isopropylacrylamide-co-acrylic acid) hydrogels and their nitric oxide release from S-nitrosoglutathione

Changing the pore morphology of hydrogels can be an effective strategy to modulate their drug release profiles. Herein, Pluronic F127 was used to change the three-dimensional pore morphology of crosslinked poly(N-isopropylacrylamide-co-acrylic acid) (P[NIPAm-co-AAc]) hydrogels. F127 reduced the pore diameters from 20 ± 4 to 2.9 ± 0.4 μm and from 11 ± 1 to 1.4 ± 0.4 μm in hydrogels synthesized at 8 and 30°C, respectively. Small-angle X-ray scattering indicates that the segregation of the F127 during the polymerization process induces F127 phase transitions from unimers (at 8°C) or cubic-packed micelles (at 30°C) to a lamellar structure. P(NIPAm-co-AAc) hydrogels charged with S-nitrosoglutathione (GSNO), released nitric oxide (NO) spontaneously during hydration. The decrease in the pore diameter led to a twofold to threefold increase in the rate of water absorption and a fourfold to sixfold increase in the rate of NO release of the hydrogels. F127 can be used to change the pore morphology of P(NIPAm-co-AAc) hydrogels, with concomitant changes in their rate of hydration and NO release from GSNO, opening a new perspective for their use in topical NO delivery.     

Quantification of Mixtures of C2 and C3 Hydroxy Acids and Products of Glycerol Oxidation by High-Performance Liquid Chromatography and Quantitative 13C NMR

The aim of this study was to develop an improved general method for detecting and quantifying mixtures of hydroxy acids and other products of glycerol oxidation in aqueous media, to prevent the confusions that can occur due to similarities and interactions between these compounds depending on media conditions. Standard potential products of glycerol oxidation—glycerol, glyceraldehyde, dihydroxyacetone, glyceric acid, lactic acid, glycolic acid, glyoxylic acid, oxalic acid, tartronic acid, and mesoxalic acid—were analyzed by high-performance liquid chromatography (HPLC) and quantitative ¹³C nuclear magnetic resonance (NMR), in mixtures of known composition. The results obtained were concordant with the known compositions tested. HPLC was more accurate than quantitative ¹³C NMR for simple mixtures, but ¹³C NMR was required for complex mixtures containing dihydroxyacetone and glycerol, oxalic acid and mesoxalic acid, or glyoxylic acid and tartronic acid, pairs of compounds not well separated or detected by HPLC. As proof-of-concept, an unknown mixture generated by glycerol oxidation was analyzed by HPLC and quantitative ¹³C NMR. The results obtained were concordant and allowed accurate determination of the composition of the sample, which contained mesoxalic acid as the major product, with oxalic acid, tartronic acid, and glyceric acid as by-products.     

Characterization of the Polishing‐Induced Contamination of Fused Silica Optics

In this work, the polishing‐induced contamination layer at the fused silica optics surface was studied with various interface analysis techniques: Secondary Ion Mass Spectroscopy (SIMS), Electron Probe Microanalysis (EPMA), X‐Ray Photoelectron Spectroscopy (XPS), and Inductively Coupled Plasma—Optical Emission Spectroscopy (ICP‐OES). Samples were prepared using an MRF polishing machine and cerium‐based slurry. The cerium and iron penetration and concentration were measured in the surface out of defects. Cerium is embedded at the surface in a 60 nm layer and concentrated at 1200 ppmw in this layer while iron concentration falls down at 30 nm. Spatial distribution and homogeneity of the pollution were also studied in the scratches and bevel using SIMS and EPMA techniques. We saw evidence that surface defects, such as scratches, are specific places that hold the pollutants. This overconcentration is also observed in the chamfer. These new insights into the polishing‐induced contamination of fused silica optics and it repartition have been obtained using various characterization methods. Advantages and disadvantages of each one are discussed.     

Effects of urban coarse particles inhalation on oxidative and inflammatory parameters in the mouse lung and colon

Background

Air pollution is a recognized aggravating factor for pulmonary diseases and has notably deleterious effects on asthma, bronchitis and pneumonia. Recent studies suggest that air pollution may also cause adverse effects in the gastrointestinal tract. Accumulating experimental evidence shows that immune responses in the pulmonary and intestinal mucosae are closely interrelated, and that gut-lung crosstalk controls pathophysiological processes such as responses to cigarette smoke and influenza virus infection. Our first aim was to collect urban coarse particulate matter (PM) and to characterize them for elemental content, gastric bioaccessibility, and oxidative potential; our second aim was to determine the short-term effects of urban coarse PM inhalation on pulmonary and colonic mucosae in mice, and to test the hypothesis that the well-known antioxidant N-acetyl-L-cysteine (NAC) reverses the effects of PM inhalation.

Results

The collected PM had classical features of urban particles and possessed oxidative potential partly attributable to their metal fraction. Bioaccessibility study confirmed the high solubility of some metals at the gastric level. Male mice were exposed to urban coarse PM in a ventilated inhalation chamber for 15 days at a concentration relevant to episodic elevation peak of air pollution. Coarse PM inhalation induced systemic oxidative stress, recruited immune cells to the lung, and increased cytokine levels in the lung and colon. Concomitant oral administration of NAC reversed all the observed effects relative to the inhalation of coarse PM.

Conclusions

Coarse PM-induced low-grade inflammation in the lung and colon is mediated by oxidative stress and deserves more investigation as potentiating factor for inflammatory diseases.