Semantics of Imperative Statements in the Modern Kyrgyz Language

The cognitive features of imperative utterances in the modern Kyrgyz language have been investigated. As you know, the imperative has two different meanings: one means urgency, necessity and importance, and the other - attempts to influence the actions of other people. Imperative means something extremely important or necessary. It also means order. The analyzed imperative statements are considered in the mainstream of conceptual grammar, which allows you to highlight syntactic concepts, or mental images that stand behind linguistic signs and are reflected in the analyzed syntactic structures. The purpose of the article is to identify and describe imperative utterances in the Kyrgyz language, to reveal the mechanisms for changing the prototypical meaning of the verb lexicon in the structure of the imperative using theories such as the theory of functional styles, the theory of discourse, the theory of speech acts and the theory of grammar of constructions. The relevance of the article is due to the need to study the semantic features of the imperative statements of the modern Kyrgyz language. The purpose of this work is to show the features of imperatives, to carefully study the types and functions of imperatives in the Kyrgyz language. The data were analyzed using a comparative analysis to find out the differences and similarities of the imperatives of the Kyrgyz language with other languages. The study belongs to qualitative research, as it was conducted using the method of contrast analysis as a comparison of languages. The object of the research is the data imperatives were taken from the sources that were needed for the research.

Prioritization of the Destination Attributes

This chapter aims to identify the destination attributes and compare them based on two assumptions that form either a symmetric or an asymmetric relationship between destination attribute performance and tourist satisfaction. For this purpose, data were collected from tourists coming to Fethiye, Turkey. Multivariate regression analysis was performed on the obtained data based on the linear assumption first. The results revealed that the attitudes of staff and the attitudes of the shopkeepers are the main determinants of tourist satisfaction. Then, penalty-reward-contrast analysis was performed based on the nonlinear assumption. According to analysis results, attitudes of the staff are performance factors; and travel agency services, attitudes of the shopkeepers, security/safety, and beach/sea are classified as excitement factors. The elements that take part in the excitement factor are the attributes that contribute to satisfaction the most.

Targeting Proteinase Activated Receptor-4 Reduces Mechanonociception During the Acute Inflammatory Phase but not the Chronic Neuropathic Phase of Osteoarthritis in Rats

Serine proteases are elevated in arthritic joints where they can cleave protease activated receptors (PARs) to modulate pain and inflammation. Activation of protease-activated receptor 4 (PAR4) has been implicated in inflammatory joint pain. Whether PAR4 is involved in osteoarthritis (OA) pain has not yet been explored. The aim of this study was to compare the role of PAR4 in modulating early versus late stage OA pain using two models of OA viz. monoiodoacetate (MIA) and medial meniscal transection (MMT). G-ratio calculation and electron microscopy analysis revealed saphenous nerve demyelination and structural damage during late stage but not early OA in both models. Using immunohistochemistry, neuronal expression of PAR4 was higher in early versus late OA. Systemic administration of the PAR4 antagonist pepducin P4pal10 reduced both secondary allodynia (von Frey hair algesiometry) and joint nociceptor firing (single unit recordings) in MMT and MIA animals compared to vehicle-treated animals in early OA. The PAR4 antagonist was ineffective at altering pain or joint afferent firing in post-inflammatory OA. During the acute phase of the models, joint inflammation as determined by laser speckle contrast analysis and intravital microscopy could be partially blocked by pepducin P4pal10. Compared to late-stage disease, inflammatory cytokines were elevated in early MIA and MMT rats. These findings suggest that PAR4 may be a viable target to treat the pain of early onset OA or during episodic inflammatory flares.

Experimental Research on Narrowband Interference Suppression of GNSS Signals

The navigation satellites are running at a high altitude of 20000 km from the ground, and the satellite signals arriving at the ground are very weak, such as the C/A code on the L1 band, which is only -160 dBW. In complex urban environments, especially when there is an occlusion, the signal power will be even lower. Low power causes the signal to be easily disturbed, where suppressed interference is the most common method of interference. The purpose of this paper is to experiment with the BPSK and BOC signal system to do the narrowband suppression of interference analysis and set up the actual test environment, based on the commonly used LMS algorithm for the two systems of narrowband interference performance contrast analysis, and throughout the simulation, it can be seen that the two improved algorithms can effectively suppress narrowband interference, thus improving the anti-interference performance of satellite navigation receiver.

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex

Background In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response. Methods Incomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20–40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4–5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K+ concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis. Results Ischemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K+ concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15–20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD. Conclusions We propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.

Pharmacogenetics of induction therapy-related toxicities in childhood acute lymphoblastic leukemia patients treated with UKALL 2003 protocol

Chemotherapy related toxicities have been the major factor limiting the success of acute lymphoblastic leukemia (ALL) induction therapy. Several factors, including the pharmacogenetics of asparaginase and anthracyclines, could contribute to difference in treatment outcome in ALL. We investigated the significance of variations in genes involved in hepatic and cardiac toxicity in acute lymphoblastic leukemia (ALL). Genotyping of SOD2 (rs4880), PNPL3 (rs738409) and ABCC1 (rs4148350), CBR1 (rs9024) and ABCG2 (rs2231142) was performed by Tetra-ARMS PCR-based technique to evaluate the genotype–phenotype correlation. Our results showed only minor allele G of SOD2 rs4880 increase the risk of hepatic toxicity [OR 2.63 (1.42–4.84), P = < 0.05] while minor alleles of other SNPs showed protective impact. However, the genetic contrast analysis showed a recessive form of SOD2 rs4880 [OR 7.82 (3.86–15.85), P = < 0.05] and PNPLA3 I148M [OR 5.82 (3.43–9.87), P = < 0.05] variants whereas dominant genotype of ABCC1 rs4148350 [OR 2.52 (1.55–4.10), P = < 0.05] significantly predisposes hepatotoxicity. Furthermore, heterozygous form of ABCG2 rs2231142 [OR 5.25 (1.84–14.95), P = < 0.05] and recessive genotype of 3′UTR variant CBR1 rs9024 [OR 2.31 (1.31–4.07), P = < 0.05] were strongly associated with cardiotoxicity. The information obtained from these genetic variations could offer biomarkers for individualization of therapeutic intervention in ALL.

A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps

Background Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement – magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. Methods A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226 mg or placebo, once daily, at bedtime, for a 60-day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher’s Exact Test for comparison of groups by categorical variables was used. The Student’s test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. Results 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p < 0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p = 0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (− 3.4 vs − 2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p < 0.007) and greater improvement in sleep quality (p < 0.001) as compared to placebo. Conclusions MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. Trial registration NCT03807219, retrospectively registered on January 16, 2019.