Comparison of two techniques for reliable characterization of thin metal-dielectric films

In the present study we determine the optical parameters of thin metal-dielectric films using two different characterization techniques based on nonparametric and multiple oscillator models. We consider four series of thin metal-dielectric films produced under various deposition conditions with different optical properties. We compare characterization results obtained by nonparametric and multiple oscillator techniques and demonstrate that the results are consistent. The consistency of the results proves their reliability.     

Design, production, and reverse engineering of two-octave antireflection coatings

We deal with design and production of optimal two-component antireflection (AR) coatings for an ultra broadband spectral range from 450 nm to 1800 nm. We demonstrate the whole design-production chain including design selection, choosing monitoring technique, coating production, and reverse engineering of the deposited coatings. At each step of this chain we provide thorough analysis on the basis of theoretical results and adequate computational manufacturing experiments. In order to produce the designed AR coatings we use magnetron sputtering deposition technique and accurate time monitoring.     

Verification of Hypertorus Communication Grids by Infinite Petri Nets and Process Algebra

A model of a hypertorus communication grid has been constructed in the form of an infinite Petri net. A grid cell represents either a packet switching device or a bioplast cell. A parametric expression is obtained to allow a finite specification of an infinite Petri net. To prove properties of an ideal communication protocol, we derive an infinite Diophantine system of equations from it, which is subsequently solved. Then we present the programs htgen and ht-mcrl2-gen, developed in the C language, which generate Petri net and process algebra models of a hypertorus with a given number of dimensions and grid size. These are the inputs for the respective modeling tools Tina and mCRL2, which provide model visualization, step simulation, state space generation and reduction, and structural analysis techniques. Benchmarks to compare the two approaches are obtained. An ad-hoc induction-like technique on invariants, obtained for a series of generated models, allows the calculation of a solution of the Diophantine system in a parametric form. It is proven that the basic solutions of the infinite system have been found and that the infinite Petri net is bounded and conservative. Some remarks regarding liveness and liveness enforcing techniques are also presented.      

Cu/TiBN电接触材料的导电性及抗电弧侵蚀机理

采用渗硼烧结法合成了一种新型TiBN粉体材料,它兼有陶瓷性和金属性,电阻率为2.6×10-3Ω·cm。以TiBN和TiN为增强相,采用粉末冶金法制备了Cu/TiBN和Cu/TiN电接触材料,系统的研究了不同含量TiBN和TiN的电接触材料的微观结构和物理性能。结果表明,与TiN相比,TiBN增强相能明显改善Cu基电接触材料的导电性能、抗氧化性能、硬度和抗电弧侵蚀性能。当含量为5wt.%时,Cu/TiBN电接触材料的抗电弧侵蚀能力最好,重量损失仅为1.5mg。电弧侵蚀时,在Cu/TiBN表面生成TixOy、B2O3和N2等产物,这些产物能明显改善Cu/TiBN电接触材料的抗电弧侵蚀能力。新开发的Cu/TiBN电接触材料具有优异的物理性能和抗电弧侵蚀性能,在电接触行业中拥有广阔的应用前景。     

Isolating Linum usitatissimum L. Nuclear DNA Enabled Assembling High-Quality Genome

High-quality genome sequences help to elucidate the genetic basis of numerous biological processes and track species evolution. For flax (Linum usitatissimum L.)—a multifunctional crop, high-quality assemblies from Oxford Nanopore Technologies (ONT) data were unavailable, largely due to the difficulty of isolating pure high-molecular-weight DNA. This article proposes a scheme for gaining a contiguous L. usitatissimum assembly using Nanopore data. We developed a protocol for flax nuclei isolation with subsequent DNA extraction, which allows obtaining about 5 μg of pure high-molecular-weight DNA from 0.5 g of leaves. Such an amount of material can be collected even from a single plant and yields more than 30 Gb of ONT data in two MinION runs. We performed a comparative analysis of different genome assemblers and polishers on the gained data and obtained the final 447.1-Mb assembly of L. usitatissimum line 3896 genome using the Canu—Racon (two iterations)—Medaka combination. The genome comprised 1695 contigs and had an N50 of 6.2 Mb and a completeness of 93.8% of BUSCOs from eudicots_odb10. Our study highlights the impact of the chosen genome construction strategy on the resulting assembly parameters and its eligibility for future genomic studies.     

Conjugates of Methylene Blue with Cycloalkaneindoles as New Multifunctional Agents for Potential Treatment of Neurodegenerative Disease

The development of multi-target-directed ligands (MTDLs) would provide effective therapy of neurodegenerative diseases (ND) with complex and nonclear pathogenesis. A promising method to create such potential drugs is combining neuroactive pharmacophoric groups acting on different biotargets involved in the pathogenesis of ND. We developed a synthetic algorithm for the conjugation of indole derivatives and methylene blue (MB), which are pharmacophoric ligands that act on the key stages of pathogenesis. We synthesized hybrid structures and performed a comprehensive screening for a specific set of biotargets participating in the pathogenesis of ND (i.e., cholinesterases, NMDA receptor, mitochondria, and microtubules assembly). The results of the screening study enabled us to find two lead compounds (4h and 4i) which effectively inhibited cholinesterases and bound to the AChE PAS, possessed antioxidant activity, and stimulated the assembly of microtubules. One of them (4i) exhibited activity as a ligand for the ifenprodil-specific site of the NMDA receptor. In addition, this lead compound was able to bypass the inhibition of complex I and prevent calcium-induced mitochondrial depolarization, suggesting a neuroprotective property that was confirmed using a cellular calcium overload model of neurodegeneration. Thus, these new MB-cycloalkaneindole conjugates constitute a promising class of compounds for the development of multitarget neuroprotective drugs which simultaneously act on several targets, thereby providing cognitive stimulating, neuroprotective, and disease-modifying effects.     

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations

Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.     

Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides

Mycothiol (MSH), the major cellular thiol in Mycobacterium tuberculosis (Mtb), plays an essential role in the resistance of Mtb to various antibiotics and oxidative stresses. MshC catalyzes the ATP-dependent ligation of 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol (GlcN-Ins) with l-cysteine (l-Cys) to form l-Cys-GlcN-Ins, the penultimate step in MSH biosynthesis. The inhibition of MshC is lethal to Mtb. In the present study, five new cysteinyl-sulfonamides were synthesized, and their binding affinity with MshC was evaluated using a thermal shift assay. Two of them bind the target with EC₅₀ values of 219 and 231 µM. Crystal structures of full-length MshC in complex with these two compounds showed that they were bound in the catalytic site of MshC, inducing dramatic conformational changes of the catalytic site compared to the apo form. In particular, the observed closure of the KMSKS loop was not detected in the published cysteinyl-sulfamoyl adenosine-bound structure, the latter likely due to trypsin treatment. Despite the confirmed binding to MshC, the compounds did not suppress Mtb culture growth, which might be explained by the lack of adequate cellular uptake. Taken together, these novel cysteinyl-sulfonamide MshC inhibitors and newly reported full-length apo and ligand-bound MshC structures provide a promising starting point for the further development of novel anti-tubercular drugs targeting MshC.     

Metformin Attenuates Slow-to-Fast Fiber Shift and Proteolysis Markers Increase in Rat Soleus after 7 Days of Rat Hindlimb Unloading

Muscle unloading leads to signaling alterations that cause muscle atrophy and weakness. The cellular energy sensor AMPK can regulate myofiber-type shift, calcium-dependent signaling and ubiquitin-proteasome system markers. We hypothesized that the prevention of p-AMPK downregulation during the first week of muscle unloading would impede atrophy development and the slow-to-fast shift of soleus muscle fibers, and the aim of the study was to test this hypothesis. Thirty-two male Wistar rats were randomly assigned to four groups: placebo control (C), control rats treated with metformin (C + M), 7 days of hindlimb suspension (HS) + placebo (7HS), and 7 days of HS + metformin administration (7HS + M). In the soleus of the 7HS rats, we detected a slow-to-fast fiber-type shift as well as a significant downregulation of MEF-2D and p300 in the nuclei. In the 7HS group, we also found decreases in p-ACC (AMPK target) protein level and in the expression of E3 ubiquitin ligases and p-CaMK II protein level vs. the C group. The 7-day metformin treatment for soleus muscle unloading (1) prevented slow-to-fast fiber-type shift; (2) counteracted changes in the p-ACC protein level; (3) hindered changes in the nuclear protein level of the slow myosin expression activators MEF-2D and p300, but did not affect NFATc1 signaling; and (4) attenuated the unloading-induced upregulation of MuRF-1, atrogin-1, ubiquitin and myostatin mRNA expression, but did not prevent soleus muscle atrophy. Thus, metformin treatment during muscle disuse could be useful to prevent the decrease in the percentage of slow-type fatigue-resistant muscle fibers.