The method of road signs recognition based on the evaluation of the Hamming distance and structural complexity

Проаналізовано основні принципи роботи систем розпізнавання дорожніх знаків відомих виробників. Описано алгоритм роботи та основні компоненти пристрою визначення елементів, зображених на дорожньому знаку. Запропоновано метод розпізнавання дорожніх знаків на основі оцінки Хеммінгової віддалі. Проведено аналіз дорожніх знаків категорії наказові знаки. Здійснено розбиття цієї категорії на менші підкатегорії для інформативного аналізу зображень. Виділено основні елементи наказових знаків, на основі яких запропоновано принципи кодування кожного знаку цієї категорії. Розраховано структурну складність зображень дорожніх знаків категорії наказові знаки. Наведено таблицю значень оцінок Хеммінгової віддалі для різних пар знаків запропонованих підкатегорій, на основі яких побудовано діаграми розподілу значень оцінок Хеммінгової віддалі. Проведено аналіз дорожніх знаків категорії заборонні знаки. Для цієї категорії відділено підкатегорії, запропоновано принцип кодування знаків, який базується на інформативних ознаках зображених елементів, побудовано діаграми розподілу значень отриманих оцінок Хеммінгової віддалі. Для розглянутих категорій знаків обчислено максимальні та мінімальні значення Хеммінгової віддалі. Запропоновано оцінку інформативності дорожніх знаків, на основі відношення Хеммінгової віддалі до структурної складності. Побудовано графіки, які ілюструють інформативність розглянутих знаків кожної підкатегорії. Зроблено висновки та рекомендації щодо удосконалення дорожніх знаків на основі оцінки Хеммінгової віддалі.Due to the increase in the number and dynamics of traffic flows, the task of automatic recognition of road signs becomes urgent. This is necessary to reduce the number of road traffic accidents and environmental pollution. This task is especially relevant when there is a barrier to perception and correct recognition of signs in conditions of fog, rain, dust etc. The development of the proposed method is based on the analysis of road signs images, definition of Hamming distance, structural complexity and information coding of road signs. Tables and charts based on the obtained results were constructed. Estimates of informativeness of the considered road signs were calculated. The obtained results are illustrated on the charts. The components of road signs recognition systems were classified. The basic principles of the control element operation of road signs recognition systems of well-known manufacturers were described. Prohibitive and prescriptive road signs were investigated in the work. These categories were divided into smaller subcategories. The criterion of division was the analysis of road signs features. Code values for signs of each of subcategories were offered. The values of Hamming distance estimation and structural complexity were calculated. The maximum and minimum values of the Hamming distance estimates for the signs of each of the subcategories were calculated. The analytical expression for finding the evaluation of the informativity of the road sign was obtained. Such an analytical expression is obtained on the basis of the ratio of the Hamming distance to the structural complexity. Estimates of informativity for the categories of marks considered were calculated. Charts illustrating informativity estimates for pairs of signs of the subcategories under consideration were constructed. Recommendations for the improvement of road sign images, for better computerized recognition based on the received results were proposed

The Issue of Restricting Freedom of Movement in the Face of the Global COVID-19 Pandemic

The conflict between anthropocentric and sociocentric activities of the State is vividly reflected in the situation that has arisen against the backdrop of the global problem – the worldwide coronavirus pandemic. The spread of epidemics and pandemics, both local and global, has been a challenge to humanity for millennia, and only the decisive steps of the authorities and the cooperation of international organizations have been able to fight against epidemics and pandemics. The socio-economic challenges of global development (imbalances in the economic development of different countries, poverty and hunger, low incomes in many countries, make it impossible to pay for medical services, buy essential medicines, provide healthy and nutritious food and provide an adequate level of immunity; ethnic movements of people; world economic crises; participation of the State in international trade and inability of the domestic economy to meet its needs, particularly public health needs; low financial provision of health care

Sediment-laden sea ice in southern Hudson Bay: Entrainment, transport, and biogeochemical implications

During a research expedition in Hudson Bay in June 2018, vast areas of thick (>10 m), deformed sediment-laden sea ice were encountered unexpectedly in southern Hudson Bay and presented difficult navigation conditions for the Canadian Coast Guard Ship Amundsen. An aerial survey of one of these floes revealed a maximum ridge height of 4.6 m and an average freeboard of 2.2 m, which corresponds to an estimated total thickness of 18 m, far greater than expected within a seasonal ice cover. Samples of the upper portion of the ice floe revealed that it was isothermal and fresh in areas with sediment present on the surface. Fine-grained sediment and larger rocks were visible on the ice surface, while a pronounced sediment band was observed in an ice core. Initial speculation was that this ice had formed in the highly dynamic Nelson River estuary from freshwater, but δ^{18}O isotopic analysis revealed a marine origin. In southern Hudson Bay, significant tidal forcing promotes both sediment resuspension and new ice formation within a flaw lead, which we speculate promotes the formation of this sediment-laden sea ice. Historic satellite imagery shows that sediment-laden sea ice is typical of southern Hudson Bay, varying in areal extent from 47 to 118 km2 during June. Based on an average sediment particle concentration of 0.1 mg mL^{–1} in sea ice, an areal extent of 51,924 km2 in June 2018, and an estimated regional end-of-winter ice thickness of 1.5 m, we conservatively estimated that a total sediment load of 7.8 × 106 t, or 150 t km^{–2}, was entrained within sea ice in southern Hudson Bay during winter 2018. As sediments can alter carbon concentrations and light transmission within sea ice, these first observations of this ice type in Hudson Bay imply biogeochemical impacts for the marine system

Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors

Cells adapt to endoplasmic reticulum (ER)-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD), however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1 activity does not play a major role in regulating the ER stress response in leukemic cells, phosphatase signaling nevertheless significantly limits proteasome inhibitor-mediated ER-stress and apoptosis. Inclusion of specific phosphatase inhibitors might therefore represent an option to improve current proteasome inhibitor-based treatment modalities for hematological cancers

Association Rate Constants of Ras-Effector Interactions Are Evolutionarily Conserved

Evolutionary conservation of protein interaction properties has been shown to be a valuable indication for functional importance. Here we use homology interface modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12 organisms representing the major eukaryotic branches, except plants. We find that with increasing divergence time the sequence similarity decreases with respect to the human protein, but the affinities and association rate constants are conserved as predicted by the protein design algorithm, FoldX. In parallel we have done computer simulations on a minimal network based on Ras-effector interactions, and our results indicate that in the absence of negative feedback, changes in kinetics that result in similar binding constants have strong consequences on network behavior. This, together with the previous results, suggests an important biological role, not only for equilibrium binding constants but also for kinetics in signaling processes involving Ras-effector interactions. Our findings are important to take into consideration in system biology approaches and simulations of biological networks

Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer

Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine “hot spots” involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a “conformational selection model” of the Hsp90 mechanism, whereby the protein may exist in a dynamic equilibrium between different conformational states available on the energy landscape and binding of a specific partner can bias the equilibrium toward functionally relevant complexes

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361

Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury

Kruppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)- treated mice. In mice with hepatocytespecific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes