Изменение параметров прокатки при скоростях валков менее 1 м/с

Приведены результаты экспериментальных исследований по влиянию скорости прокатки на контактные касательные напряжения и коэффициент трения в очаге деформации. Опытами установлено, что с увеличением скорости валков от 0,2 до 0,8 м/с при прокатке полос с технологической смазкой опережение и коэффициент трения существенно уменьшаются; при прокатке полос в сухих валках величины опережения и коэффициента трения возрастают с увеличением скорости прокатки v до 0,5 м/с, а при прокатке с v > 0,5 м/с параметры стабилизируются. Дано физическое толкование изменения исследуемых параметров.Наведено результати експериментальних досліджень по впливу швидкості прокатки на контактні дотичні напруження і коефіцієнт тертя в осередку деформації. Дослідами встановлено, що при збільшенні швидкості валків від 0,2 до 0,8 м/с при прокатуванні штаб із технологічним мастилом випередження і коефіцієнт тертя істотно зменшуються; при прокатуванні штаб у сухих валках величини випередження і коефіцієнта тертя зростають при збільшенні швидкості прокатки v до 0,5 м/с, а при прокатуванні з v > 0,5 м/с параметри стабілізуються. Наведено фізичне тлумачення зміни досліджуваних параметрів.The tests investigation results of rolling velocity influence on contact tangents strain and fiction coefficient in the point (site) of deformation are concerned. It was determined by experiments that with increasing of rolls velocity from 0,2 to 0,8 m/s while strips are being rolled with rolling lubricant, the forward creep and friction coefficient are clearly reduction. But while strips are being rolled in dry rolls the value of forward creep and friction coefficient are rising with an increase of rolling velocity to ≈ 0,5 m/s. At the same time when rolling velocity excesses 0,5 m/s, the given parameters are stafilized. Physical explanation of the investigated parameters is given

Cell Death Triggers Induce MLKL Cleavage in Multiple Myeloma Cells, Which may Promote Cell Death

Necroptosis is a type of caspase-independent programmed cell death that has been implicated in cancer development. Activation of the canonical necroptotic pathway is often characterized with successive signaling events as the phosphorylation of mixed lineage kinase domain-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3), followed by MLKL oligomerization and plasma membrane rupture. Here, we demonstrate that omega-3 polyunsaturated fatty acids DHA/EPA and the proteasome inhibitor bortezomib induce necroptosis in human multiple myeloma (MM) cells in a RIPK3 independent manner. In addition, it seemed to be that phosphorylation of MLKL was not essential for necroptosis induction in MM cells. We show that treatment of MM cells with these cytotoxic compounds induced cleavage of MLKL into a 35 kDa protein. Furthermore, proteolytic cleavage of MLKL was triggered by activated caspase-3/8/10, and mutation of Asp140Ala in MLKL blocked this cleavage. The pan-caspase inhibitor ZVAD-FMK efficiently prevented DHA/EPA and bortezomib induced cell death. In addition, nuclear translocation of total MLKL and the C-terminus were detected in treated MM cells. Collectively, this present study suggests that caspase-mediated necroptosis may occur under (patho)physiological conditions, delineating a novel regulatory mechanism of necroptosis in RIPK3-deficient cancer cells

The Assessment of Immune Fitness

Immune fitness (i.e., adequate functioning of the immune system) is essential to maintain health, prevent and resolve disease, and improve quality of life. This article provides an overview of how to assess immune fitness. It discusses how a single-item rating scale can be used to assess immune fitness. The scale can be used in conjunction with a single “yes” or “no” question asking whether the individual is experiencing reduced immune fitness. Retrospective assessments can be complemented with the Immune Status Questionnaire (ISQ) to provide more insight into the type and frequency of experiencing specific immune-related complaints. Momentary assessments of immune fitness can be complemented with biomarker measurements in body fluids. As individuals may be unaware of systemic inflammation (e.g., biomarker concentrations outside the normal range), it remains critical to combine immune fitness assessments with biomarker measurements of immune functioning

Pandemic preparedness:the importance of adequate immune fitness

Pandemic preparedness is an important issue in relation to future pandemics. The two studies described here aimed to identify factors predicting the presence and severity of coronavirus disease 2019 (COVID-19) symptoms. The CLOFIT study comprised an online survey among the Dutch population (n = 1415). Perceived immune fitness before the pandemic (2019) and during the first lockdown period (15 March–11 May 2020) and the number and severity of COVID-19 symptoms were assessed. The COTEST study, conducted between December 2020 and June 2021, replicated the CLOFIT study in n = 925 participants who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Dutch commercial test locations. The CLOFIT study revealed that immune fitness before the pandemic was the greatest predictor of the number and severity of COVID-19 symptoms (20.1% and 19.8%, respectively). Other significant predictors included immune fitness during the lockdown (5.5% and 7.1%, respectively), and having underlying diseases (0.4% and 0.5%, respectively). In the COTEST study, for those who tested positive for SARS-CoV-2, immune fitness before the pandemic was the single predictor of the number (27.2%) and severity (33.1%) of COVID-19 symptoms during the pandemic. In conclusion, for those who tested positive for SARS-CoV-2, immune fitness before the pandemic was the strongest predictor of the number and severity of COVID-19 symptoms during the pandemic. Therefore, the development of strategies to maintain an adequate immune fitness must be regarded as an essential component of pandemic preparedness

The Bidirectional Gut-Lung Axis in Chronic Obstructive Pulmonary Disease

Epidemiological studies indicate that chronic obstructive pulmonary disease (COPD) is associated with the incidence of changes in intestinal health. Cigarette smoking, as one of the major causes of COPD, can have an impact on the gastrointestinal system and promotes intestinal diseases. This points to the existence of gut-lung interactions, but an overview of the underlying mechanisms of the bidirectional connection between the lungs and the gut in COPD is lacking. The interaction between the lungs and the gut can occur through circulating inflammatory cells and mediators. Moreover, gut microbiota dysbiosis, observed in both COPD and intestinal disorders, can lead to a disturbed mucosal environment, including the intestinal barrier and immune system, and hence may negatively affect both the gut and the lungs. Furthermore, systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction and play a role in the gut-lung axis. In this review, we summarize data from clinical research, animal models, and in vitro studies that may explain the possible mechanisms of gut-lung interactions associated with COPD. Interesting observations on the possibility of promising future add-on therapies for intestinal dysfunction in patients with COPD are highlighted.</p

Perceived Immune Status and Sleep: A Survey among Dutch Students

Reduced immune functioning may have a negative impact on sleep and health, and vice versa. A survey among Dutch young adults (18-35 years old) was administered to collect information on perception of reduced immunity and its relationship to sleep disorders, sleep duration, and quality. Sleep disorders were assessed with the SLEEP-50 questionnaire subscales of sleep apnea, insomnia, circadian rhythm disorder, and daily functioning. Dutch young adults (N = 574) completed the survey. Among them, subjects (N = 209; 36.4%) reported perceived reduced immunity. Relative to those with a normal immune status, subjects reporting reduced immunity had significantly higher scores (p = 0.0001) on sleep apnea (2.6 versus 3.6), insomnia (5.1 versus 6.8), and circadian rhythm disorder (2.1 versus 2.7). Subjects reporting reduced immunity also had significantly poorer daily functioning scores (5.4 versus 7.6, p = 0.0001). No differences were observed in total sleep time, but those reporting reduced immunity had significantly poorer ratings of sleep quality (6.8 versus 7.2, p = 0.0001). Our findings suggest that perceived reduced immunity is associated with sleep disturbances, impaired daily functioning, and a poorer sleep quality. Experimental studies including the assessment of immune biomarkers and objective measures of sleep (polysomnography) should confirm the current observations

The analysis of exosomal micro-RNAs in peripheral blood mononuclear cell-derived macrophages after infection with bacillus Calmette–Guérin by RNA sequencing

AbstractObjective/BackgroundTuberculosis (TB) is a major global threat to human health, especially in low-income countries. The diagnosis of TB is challenging because of the limitations of specificity and sensitivity with the current diagnostics. Novel, selective biomarkers for TB would be of great practical value. Exosomes are bioactive vesicles with 30–100nm in diameter, which are secreted from almost all cell types and are found in virtually every human body fluid. Exosomes transport micro-RNAs (miRNAs), which are post-transcriptional regulators of gene expression, around the body and allow miRNAs to modulate biological pathways in target cells. Our aim was to investigate the potential of exosomal miRNAs as biomarkers by examining their release from human monocyte-derived macrophages (MDMs) after infection with Mycobacterium using miRNA sequencing.MethodsHuman monocytes were obtained from blood and driven to an MDM phenotype using standard protocols. MDMs were infected with Mycobacterium bovis Bacillus Calmette–Guérin (BCG) or left uninfected as control. Exosomes were collected 72 h postinfection from the cell culture medium and subjected to RNA isolation. Small RNA libraries were constructed and RNA sequencing performed. The raw reads were filtered to eliminate adaptor and primer sequences, and the sequences in FASTQ format were run against the mature human miRNA sequences available in miRBase using BLAST software using a Linux operating system. Micro-RNAs were identified using E=0.01 or 1.ResultsInfection of MDMs with BCG lead to the release of a number of exosomal miRNAs. These mainly consisted with Let-7 family members, miR-155, miR-146a, miR-145, and miR-21 all of which were predicted to target important immune-related genes and pathways.ConclusionThis study provides evidence for the release of specific miRNAs from BCG-infected MDMs. These results need to be confirmed and the presence of this panel of miRNAs tested in the blood of patients to determine their selectivity and specificity as a diagnostic in patients with TB

Инвестиционные и маркетинговые изменения на рынке мобильной связи Украины

PURPOSE OF REVIEW: Despite reaching high percentages of desensitization using allergen-specific immunotherapy (SIT) in patients with food allergy, recent studies suggest only a low number of patients to reach persistent clinical tolerance. This review describes current developments in strategies to improve safety and long-term efficacy of SIT. RECENT FINDINGS: Modified allergens or tolerogenic peptides, ultimately optimized for human leukocyte antigen background of the patient, are explored for tolerance induction, whereas anti-IgE antibody (Omalizumab) may be used to facilitate SIT safety. Adjunct therapies to enhance efficacy may make use of TH1 polarizing agents, for example, CpG-oligodeoxynucleotides combined with modified allergen packaged in nanoparticles. Preclinical studies showed insulin-like growth factor-2, intravenous immunoglobulin, Tregitopes or allergen encased oligomannose-coated liposomes capable of inducing regulatory T-cells, recognized for their importance in clinical tolerance induction. Dietary intervention strategies utilizing herbal formula 2, VSL#3, nondigestible short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) plus Bifidobacterium breve M-16V or n-3 long-chain polyunsaturated fatty acids may facilitate safety and/or a favourable milieu for tolerance induction. SUMMARY: Combining SIT using (adapted) allergens or tolerogenic peptides with adjunct therapy may be essential to improve safety and/or efficacy. Beyond using targeted approaches, specific dietary components may be explored to reduce side-effects and support clinical tolerance induction by SIT

Pandemic Preparedness: The Potential Advantage of Medicines That Prevent Acute Side Effects of Vaccination, SARS-CoV-2 as an Example

Vaccination against SARS-CoV-2 is an important and essential strategy to combat the 2019 coronavirus disease (COVID-19) pandemic. Vaccination has shown to be effective in reducing the spread of SARS-CoV-2, reducing the chances of becoming infected and developing severe COVID-19, and reducing hospitalization and mortality rates. However, the vaccinations against SARS-CoV-2 are accompanied by undesirable side effects which may be in part responsible for a reduction in the willingness to become vaccinated. At this moment (June 2022), 24.3% of the US adult population (18+ years old) is not fully vaccinated against SARS-CoV-2, and 49.5% did not receive their follow-up booster vaccination. The most important motives for refusing vaccination are the unknown long-term side effects and the known acute side effects of vaccination. Here, we discuss the importance of recognizing the impact of this reactogenicity on individuals’ willingness to vaccinate and how the development of effective and safe medicines that prevent or mitigate the unwanted side effects of the vaccination may help to increase the willingness to vaccinate