Craig Interpolation with Clausal First-Order Tableaux

We develop foundations for computing Craig-Lyndon interpolants of two given formulas with first-order theorem provers that construct clausal tableaux. Provers that can be understood in this way include efficient machine-oriented systems based on calculi of two families: goal-oriented such as model elimination and the connection method, and bottom-up such as the hypertableau calculus. We present the first interpolation method for first-order proofs represented by closed tableaux that proceeds in two stages, similar to known interpolation methods for resolution proofs. The first stage is an induction on the tableau structure, which is sufficient to compute propositional interpolants. We show that this can linearly simulate different prominent propositional interpolation methods that operate by an induction on a resolution deduction tree. In the second stage, interpolant lifting, quantified variables that replace certain terms (constants and compound terms) by variables are introduced. We justify the correctness of interpolant lifting (for the case without built-in equality) abstractly on the basis of Herbrand’s theorem and for a different characterization of the formulas to be lifted than in the literature. In addition, we discuss various subtle aspects that are relevant for the investigation and practical realization of first-order interpolation based on clausal tableaux.

     

酚醛树脂-CarboresP结合镁碳材料的性能与应用

研究了环境友好型含碳材料CarboresP在镁碳砖中的应用。采用MT14A镁碳砖生产工艺,改变CarboresP的加入量,对试样180℃处理后的体积密度、高温抗折强度(1400℃),以及1000℃埋炭处理后的显气孔率、耐压强度等指标进行了研究和对比,确定镁碳砖中合适的CarboresP添加量为1%,并且可适量降低金属防氧化剂的加入量;分析了酚醛树脂-CarboresP结合炭的显微结构,表明其为均质炭和非均质石墨化炭的混合结构,这将有助于改善炭化结构的抗氧化性能;采用尖劈试验绘制镁碳砖试样的应力-应变曲线,表明添加CarboresP的镁碳砖的特征长度LCH值得到明显提高,说明它具有很好的韧性和吸收应力的能力;与传统工艺生产的MT14A镁碳砖相比较,采用酚醛树脂-CarboresP“软性结合”工艺生产的MT14A镁碳砖,成型性能及热处理后各项性能指标均得到改善,在国内某40tLF-VD精炼钢包渣线上进行现场使用证明,平均使用寿命比现用渣线镁碳砖提高18.4%。     

Determination of Intra- and Extracellular Metabolic Adaptations of 3D Cell Cultures upon Challenges in Real-Time by NMR

NMR flow devices provide longitudinal real-time quantitative metabolome characterisation of living cells. However, discrimination of intra- and extracellular contributions to the spectra represents a major challenge in metabolomic NMR studies. The present NMR study demonstrates the possibility to quantitatively measure both metabolic intracellular fingerprints and extracellular footprints on human control fibroblasts by using a commercially available flow tube system with a standard 5 mm NMR probe. We performed a comprehensive 3D cell culture system characterisation. Diffusion NMR was employed for intra- and extracellular metabolites separation. In addition, complementary extracellular footprints were determined. The implemented perfused NMR bioreactor system allowed the determination of 35 metabolites and intra- and extracellular separation of 19 metabolites based on diffusion rate differences. We show the reliability and sensitivity of NMR diffusion measurements to detect metabolite concentration changes in both intra- and extracellular compartments during perfusion with different selective culture media, and upon complex I inhibition with rotenone. We also demonstrate the sensitivity of extracellular footprints to determine metabolic variations at different flow rates. The current method is of potential use for the metabolomic characterisation of defect fibroblasts and for improving physiological comprehension.     

Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?

The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype’s differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization–time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.     

Variational optical flow computation in real time.

This paper investigates the usefulness of bidirectional multigrid methods for variational optical flow computations. Although these numerical schemes are among the fastest methods for solving equation systems, they are rarely applied in the field of computer vision. We demonstrate how to employ those numerical methods for the treatment of variational optical flow formulations and show that the efficiency of this approach even allows for real-time performance on standard PCs. As a representative for variational optic flow methods, we consider the recently introduced combined local-global method. It can be considered as a noise-robust generalization of the Horn and Schunck technique. We present a decoupled, as well as a coupled, version of the classical Gauss-Seidel solver, and we develop several multgrid implementations based on a discretization coarse grid approximation. In contrast, with standard bidirectional multigrid algorithms, we take advantage of intergrid transfer operators that allow for nondyadic grid hierarchies. As a consequence, no restrictions concerning the image size or the number of traversed levels have to be imposed. In the experimental section, we juxtapose the developed multigrid schemes and demonstrate their superior performance when compared to unidirectional multgrid methods and nonhierachical solvers. For the well-known 316 x 252 Yosemite sequence, we succeeded in computing the complete set of dense flow fields in three quarters of a second on a 3.06-GHz Pentium4 PC. This corresponds to a frame rate of 18 flow fields per second which outperforms the widely-used Gauss-Seidel method by almost three orders of magnitude.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.