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Specific aspects of vocal performance in opera art, timbre, important stages in the singing process were explained practically and theoretically.

The classification of voices in opera performance was explained.

Maqolada Xorazm viloyatining Qo‘shko‘pir tumani Shix qishlogʻi shevasi tadqiq ostiga olindi. Shix qishlogʻida tarixan turkmanlar yashab kelishgan keying davrda o‘zbeklar bilan yaqin yashash natijasida ularning shevalarida anchayin o‘zgarishlar yuzaga kelgan., {"references":["1.\tAtaniyazov S. Türkmen boylarinin geçmişi, yayilişi, bugünkü durumu ve geleceği // Bilig. 2.\tKuhn W. Deutsche Sprachinsel-Forschung. Geschichte, Aufgaben, Verfahren. Plauen im Vogtland. Berlin: Wolff, 1934. 407 S. 3.\tOlloyorov Q. Areal lingvistika fanini oʻqitish asoslari (o'quv-uslubiy qo'llanma). –Toshkent: Adabiyot uchqunlari, 2020. –63 b. 4.\tO'zbekiston milliy inseklopediyasi, 10-jild. Toshkent, O'zbekiston milliy inseklopediyasi nashriyoti, 2005. 5.\tАбдуллаев Ф. Хоразм шеваларининг таснифи масаласи // Ўзбек диалектологиясидан материаллар. II жилд. –Тошкент: ЎзФАН. 1960. 6.\tАразкулиев С. Гарагалпагыстан АССР-ның Дɵртгүл районындакы түркмен геплешиклери. Ашгабат, 1961. 7.\tМуллаев Қ. Шайхликлар. Урганч: Хоразм, 2013. 214 b. 8.\tБўриев О. \"Темурийлар даври ёзма манбаларида Марказий Осиё\". Т.: \"Ўзбекистон\". –Б 44. 9.\tДевидов С.М. «Туркменские авляды». – Ашхабад, «Ылм», 1976. –С. 108-109. 10.\tБрегель Ю.Э. «Хорезмские Туркмены в веке». –Москва. «Восточной литературы», 1967."]}

The liquid-phase oxidation of 4-ethylecyclohexene by oxygen in the presence of a catalytic system (NH4)6Mo7O24 CoBr2) was investigated. The influence of various factors (temperature, duration, quantity of catalyst, molar ratios of reagents) on the oxidation reaction rates (conversion of feedstock, selectivity of reaction on oxy products) is determined

Recombinant adeno-associated viral (rAAV) vector-based gene therapy has been adapted for use in more than 100 clinical trials. This is mainly because of its excellent safety profile, ability to target a wide range of tissues, stable transgene expression, and significant clinical benefit. However, the major challenge is to produce a high-titer, high-potency vector to achieve a better therapeutic effect. Even though the three plasmid-based transient transfection method is currently being used for AAV production in many clinical trials, there are complications associated with scalability and it is not cost-effective. Other methods require either large-scale production of two herpes simplex viruses, rHSV-RepCap and rHSV-GOI (gene of interest), with high titers, or a stable cell line with high titer wild-type adenovirus infection. Both of these options make the process even more complex. To address this issue, we have developed a stable cell line-based production with the use of only one rHSV-RepCap virus. Using this new methodology in small-scale production, we achieved ∼1–6 E + 04 vg/cell of AAV9 in the top producer clones. Large-scale production in 10-CS (10-Cell Stack) of one of the top producing clones resulted in ∼1–2 E + 13 vg/10-CS with 50% of full capsid ratio after purification. This method could potentially be adapted to suspension cells. The major advantage of this novel methodology is that by using the rHSV-RepCap virus, high titer AAV can be produced with any GOI containing a stable adherent or suspension producer cell line. The use of this AAV production platform could be beneficial for the treatment of many diseases.

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC

Liquid-phase oxidation of styrene with hydrogen peroxide in the presence of a catalytic system based on (NH4)10W12O41 + Ce(NO3)3 + H3PO4, supported on a microstructured carbon material and treated with an aqueous Н2О2 solution, was studied. The major reaction products are phenyloxirane and benzaldehyde, with phenylacetaldehyde, 1-phenylethane-1,2-diol, and benzoic acid also present. The kinetic relationships of the process were studied, and a kinetic model according to which phenyloxirane is the primary reaction product was suggested. Aldehydes are accumulated by parallel routes: oxidation of phenyloxirane and of its hydrolysis product, 1-phenylethane-1,2-diol. With an increase in the styrene: Н2О2 molar ratio, oxidation of 1-phenylethane-1,2-diol becomes the major pathway of the aldehyde formation.

Hermansky–Pudlak syndrome (HPS) is a rare genetic disorder which, in its most common and severe form, HPS‐1, leads to fatal adult‐onset pulmonary fibrosis (PF) with no effective treatment. We evaluated the role of the endocannabinoid/CB1R system and inducible nitric oxide synthase (iNOS) for dual‐target therapeutic strategy using human bronchoalveolar lavage fluid (BALF), lung samples from patients with HPS and controls, HPS‐PF patient‐derived lung fibroblasts, and bleomycin‐induced PF in pale ear mice (HPS1ep/ep). We found overexpression of CB1R and iNOS in fibrotic lungs of HPSPF patients and bleomycin‐infused pale ear mice. The endocannabinoid anandamide was elevated in BALF and negatively correlated with pulmonary function parameters in HPSPF patients and pale ear mice with bleomycin‐induced PF. Simultaneous targeting of CB1R and iNOS by MRI‐1867 yielded greater antifibrotic efficacy than inhibiting either target alone by attenuating critical pathologic pathways. Moreover, MRI‐1867 treatment abrogated bleomycin‐induced increases in lung levels of the profibrotic interleukin‐11 via iNOS inhibition and reversed mitochondrial dysfunction via CB1R inhibition. Dual inhibition of CB1R and iNOS is an effective antifibrotic strategy for HPSPF., Overactivity of CB1R and iNOS contributes to HPSPF development and progression via multiple critical pathological processes including dysregulation of mitochondrial function and IL‐11. Simultaneous inhibition of lung CB1R and iNOS by a hybrid inhibitor (MRI‐1867) is a rational therapeutic strategy for achieving therapeutic efficacy in HPSPF with attenuating fibrosis, improving pulmonary function and survival.

Creatine transporter deficiency (CTD) is caused by a defect in the X-linked creatine transporter SLC6A8 gene leading to severe neurologic and physiologic conditions. Cyclocreatine and phosphocyclocreatine supplementation is seen as a potential treatment, but the presence of these compounds within commercially available dietary supplements presents the risk of self-medication. High-performance liquid chromatography-mass spectrometry (HPLC-MS) is an excellent technique to assess composition of complex amino acid mixtures. Herein, we have developed a facile HPLC-MS method using a cyano column in hydrophilic interaction liquid chromatography (HILIC) mode with isocratic elution over 4 min to identify the main components of two commercially available dietary supplements. The relative standard deviation (RSD) for retention time and extracted ion integrated area are

Conditions for the condensation of cyclopentanone and n-valeric aldehyde to 2-pentylidenecyclopentanone in the presence of an alcoholic solution of piperidine have been developed. The isomerization of the latter in a continuous-flow system over γ-Al2O3 yields 2-pentylcyclopent-2-en-1-one. The condensation of the obtained unsaturated ketones with ethane-1,2-diol in the presence of a heterogeneous catalyst, a natural aluminosilicate (perlite) modified with zirconyl sulfate, has been studied. The optimum conditions for the preparation of the corresponding unsaturated spiroacetals have been found. The synthesized compounds can be used as synthetic fragrances for different purposes.

The following article describes the general issues of classification of sand rocks, the principles of classification into certain sizes, methods of sampling in field research, the process of preparation and conduct of sieve analysis., {"references":["1. Методы изучения осадочных пород. – М., 1957. -Т.1. – С. 314-343.","2. Петелин В.П. Гранулометрический анализ морских донных осадков. - М., 1967. –128 с.","3. Рухин Л.Б. Основы литологии. Учение об осадочных породах. – Л., 1969. – 704с.","4. Рухин Л.Б. Новый метод определения условий отложения древних песков// Проблемы современной геологии. -1937. - Т. VII, №11. – С. 230-254."]}

The development of marine tourism content is a much-needed challenge at this point. Audio augmented reality (AAR) is a new and fast-growing technology. We assume that AAR will improve the quality of services provided by marine tourism. In this research, the actual potential of AAR in marine tourism was studied by developing an AAR prototype using the Unity engine. We have used whale images with 3D sounds. The prototype can localize several 3D sounds in real-world locations. We conducted a listening test comparing the normal whale audios with the 3D whale audios generated by AAR. 81% of the participants were positive for 3D sounds and whale images. Interviewees felt better engagement in the service. They considered that the technology can be useful for receiving more information easily and making them more physically active. We conclude that the main contributions of AAR may be giving insightful knowledge about marine life in an interesting way and stimulating people to engage in nature closer.

Increased expression of developmentally silenced fetal globin (HBG) reduces the clinical severity of β-hemoglobinopathies. Benserazide has a relatively benign safety profile having been approved for 50 years in Europe and Canada for Parkinson's disease treatment. Benserazide was shown to activate HBG gene transcription in a high throughput screen, and subsequent studies confirmed fetal hemoglobin (HbF) induction in erythroid progenitors from hemoglobinopathy patients, transgenic mice containing the entire human β-globin gene (β-YAC) and anemic baboons. The goal of this study is to evaluate efficacies and plasma exposure profiles of benserazide racemate and its enantiomers to select the chemical form for clinical development. Intermittent treatment with all forms of benserazide in β-YAC mice significantly increased proportions of red blood cells expressing HbF and HbF protein per cell with similar pharmacokinetic profiles and with no cytopenia. These data contribute to the regulatory justification for development of the benserazide racemate. Additionally, dose ranges and frequencies required for HbF induction using racemic benserazide were explored. Orally administered escalating doses of benserazide in an anemic baboon induced γ-globin mRNA up to 13-fold and establish an intermittent dose regimen for clinical studies as a therapeutic candidate for potential treatment of β-hemoglobinopathies.