Computing in Totally Anonymous Asynchronous Shared Memory Systems

In the totally anonymous shared memory model of asynchronous distributed computing, processes have no identifiers and run identical programs. Moreover, processes have identical interface to the shared memory, and in particular, there are no single-writer registers. This paper assumes that processes do not fail, and the shared memory consists only of read/write registers, which are initialized to some default value. A complete characterization of the functions and agreement tasks that can be solved in this model is presented. Furthermore, it is shown that if a function is computable, then two registers are sufficient for some algorithm to compute it. Consensus is an important agreement task that can be computed. The paper proves logarithmic lower bounds on the number of registers and rounds needed for solving consensus in this model. A consensus protocol using a linear number of shared registers and rounds is also presented.     

Konzeption einer Kollaborationsplattform für die zwischenbetriebliche Softwareerstellung

The development of business application software is increasingly based on the development of different components by various suppliers. In the next step, system vendors integrate these components. Hereby, inter-organizational collaboration becomes more and more important for the software industry. In order to strengthen the value-added processes within these established software supply chains, the Ministry of Economic Affairs in Baden-Württemberg funded the project TASK that aims at fostering inter-organizational design, integration, and implementation of software components. The present article on the one hand provides an insight into the structure as well as the progress of this project and, on the other hand, presents academic research results in terms of an empirical analysis of barriers and drivers of interorganizational collaboration and of the purposeful design of a collaboration platform. The article concludes with a summary and a discussion of current and upcoming issues in establishing and sustaining inter-organizational collaboration structures within the software industry.     

Circulating Ageing Neutrophils as a Marker of Asymptomatic Polyvascular Atherosclerosis in Statin-Naïve Patients without Established Cardiovascular Disease

Background: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). Methods: The study was carried out on 151 statin-naïve patients aged 40–64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). Results: The number of CD62L^loCXCR4^hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62L^loCXCR4^hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4–50.5% and specificity of 80.0–92.1%, in two vascular beds with sensitivity of 44.7–84.4% and specificity of 80.8–33.3%. Conclusion: In statin-naïve patients 40–64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62L^loCXCR4^hi-neutrophils. It was also concluded that the increase in the number of circulating CD62L^loCXCR4^hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617–0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis.     

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.     

Targeting Multiple Homeostasis-Maintaining Systems by Ionophore Nigericin Is a Novel Approach for Senolysis

Within the present study we proposed a novel approach for senolysis based on the simultaneous disturbance of the several homeostasis-maintaining systems in senescent cells including intracellular ionic balance, energy production and intracellular utilization of damaged products. Of note, we could not induce senolysis by applying ouabain, amiloride, valinomycin or NH₄Cl—compounds that modify each of these systems solely. However, we found that ionophore nigericin can disturb plasma membrane potential, intracellular pH, mitochondrial membrane potential and autophagy at once. By affecting all of the tested homeostasis-maintaining systems, nigericin induced senolytic action towards stromal and epithelial senescent cells of different origins. Moreover, the senolytic effect of nigericin was independent of the senescence-inducing stimuli. We uncovered that K⁺ efflux caused by nigericin initiated pyroptosis in senescent cells. According to our data, the higher sensitivity of senescent cells compared to the control ones towards nigericin-induced death was partially mediated by the lower intracellular K⁺ content in senescent cells and by their predisposition towards pyroptosis. Finally, we proposed an interval dosing strategy to minimize the negative effects of nigericin on the control cells and to achieve maximal senolytic effect. Hence, our data suggest ionophore nigericin as a new senotherapeutic compound for testing against age-related diseases.     

Complete and Prolonged Inhibition of Herpes Simplex Virus Type 1 Infection In Vitro by CRISPR/Cas9 and CRISPR/CasX Systems

Almost all people become infected with herpes viruses, including herpes simplex virus type 1 (HSV-1), during their lifetime. Typically, these viruses persist in a latent form that is resistant to all available antiviral medications. Under certain conditions, such as immunosuppression, the latent forms reactivate and cause disease. Moreover, strains of herpesviruses that are drug-resistant have rapidly emerged. Therefore, it is important to develop alternative methods capable of eradicating herpesvirus infections. One promising direction is the development of CRISPR/Cas systems for the therapy of herpesvirus infections. We aimed to design a CRISPR/Cas system for relatively effective long-term and safe control of HSV-1 infection. Here, we show that plasmids encoding the CRISPR/Cas9 system from Streptococcus pyogenes with a single sgRNA targeting the UL30 gene can completely suppress HSV-1 infection of the Vero cell line within 6 days and provide substantial protection within 9 days. For the first time, we show that CRISPR/CasX from Deltaproteobacteria with a single guide RNA against UL30 almost completely suppresses HSV-1 infection of the Vero cell line for 3 days and provides substantial protection for 6 days. We also found that the Cas9 protein without sgRNAs attenuates HSV-1 infection. Our results show that the developed CRISPR/Cas systems are promising therapeutic approaches to control HSV-1 infections.     

Impact of peroxydisulfate in the presence of zero valent iron on the oxidation of cyclohexanoic Acid and naphthenic acids from oil sands process-affected water

Large volumes of oil sands process-affected water (OSPW) are produced during the extraction of bitumen from oil sands in Alberta, Canada. The degradation of a model naphthenic acid, cyclohexanoic acid (CHA), and real naphthenic acids (NAs) from OSPW were investigated in the presence of peroxydisulfate (S(2)O(8)(2-)) and zerovalent iron (ZVI). For the model compound CHA (50 mg/L), in the presence of ZVI and 500 mg/L S(2)O(8)(2-), the concentration decreased by 45% after 6 days of treatment at 20 °C, whereas at 40, 60, and 80 °C the concentration decreased by 20, 45 and 90%, respectively, after 2 h of treatment. The formation of chloro-CHA was observed during ZVI/S(2)O(8)(2-) treatment of CHA in the presence of chloride. For OSPW NAs, in the presence of ZVI alone, a 50% removal of NAs was observed after 6 days of exposure at 20 °C. The addition of 100 mg/L S(2)O(8)(2-) to the solution increased the removal of OSPW NAs from 50 to 90%. In absence of ZVI, a complete NAs removal from OSPW was observed in presence of 2000 mg/L S(2)O(8)(2-) at 80 °C. The addition of ZVI increased the efficiency of NAs oxidation by S(2)O(8)(2-) near room temperature. Thus, ZVI/S(2)O(8)(2-) process was found to be a viable option for accelerating the degradation of NAs present in OSPW.     

Novel Melt‐Castable Energetic Pyrazole: A Pyrazolyl‐Furazan Framework Bearing Five Nitro Groups

Continuing advances in energetic pyrazole construction foster further its rational use. This work establishes an approach for the first synthesis of nitropyrazole that bear both furazan and trinitromethyl moieties. The approach to the installation of the C(NO₂)₃ group exploits the destructive nitration of N‐acetonyl group. The target 3‐(3,4‐dinitro‐1‐(trinitromethyl)‐1H‐pyrazol‐5‐yl)‐4‐methylfurazan ( 6 ) has promising explosive properties.     

Bio-based poly(ethylene terephthalate) copolyesters made from cyclic monomers derived from tartaric acid

Two cyclic acetal compounds, 2,3-O-methylene L-threitol and dimethyl 2,3-O-methylene L-threarate, both coming from naturally-occurring tartaric acid, were used as comonomers to replace ethylene glycol and dimethyl terephthalate respectively, in the preparation of PET-based copolyesters by polycondensation in the melt. Synthesis results, structure and thermal properties of the two afforded copolyester series were evaluated and compared regarding composition and type of comonomer used in each case. All the copolyesters had a random microstructure and molecular weights in the 25,000–35,000 g·mol⁻¹ range. Their thermal properties varied logically with composition along each series but they significantly changed according to which acetal comonomer was used. PET copolyesters made from acetalized L-threitol displayed thermal stability and T_g comparable to PET, whereas these two properties were depressed in the copolyesters containing threarate units. Both types of copolyesters were able to crystallize for contents in tartaric acid derived units up to around 30% by adopting the crystal structure of PET. Crystallization rates and melting temperatures decreased with copolymerization in the two series but this effect was more noticeable in copolyesters made from threitol.     

Dust dispersal and Pb enrichment at the rare-metal Orlovka-Spokoinoe mining and ore processing site: insights from REE patterns and elemental ratios

Different geological, technogenic and environmental samples from the Orlovka-Spokoinoe Ta-Nb-Sn-W mining site and ore processing complex in Eastern Transbaikalia (Russia), were analysed for Pb, Y, Zr, Hf and rare earth elements (REE) to assess the effect of dust and metal dispersal on the environment within the Orlovka-Spokoinoe mining site. Potential source material analysed included ore-bearing and barren granites, host rocks, tailing pond sediments, and ore concentrates. Lichens and birch leaves were used as receptor samples. The REE enrichment relative to chondrite, the extent of the Eu anomalies, the enrichments of heavy REE (HREE), and Zr/Hf and Yb/Y ratios suggest that tailings, barren granites, and metasedimentary host rocks are the main sources of dust in the studied mining environment. In addition, calculated lead enrichment (relative to host rocks) suggests that the environment is polluted with Pb. Our results clearly demonstrate the potential of REE patterns and elemental ratios as a reliable technique to trace dust and metals sources and dispersal within a confined mining area offering a new tool for environmental assessment studies.