Some numerical characteristics of Sylvester and Hadamard matrices

We introduce numerical characteristics of Sylvester and Hadamard matrices and give their estimates and some of their applications

The Regularities of Electrolytic Dissociation of Weak Dibasic and Tribasic Organic Wine Acids

The weak dibasic and tribasic organic acids in wine: tartaric, malic, citric and succinic acids are the important components having direct influence on various properties of wine. The regularities of electrolytic dissociation of these acids determine all their useful properties. With the aid of suggested by authors original method for analysis the complex equilibria of the processes of dissociation of weak multibasic organic acids the main dissociation parameters of tartaric, malic, citric and succinic acids in their dilute solutions: the values of usual and “partial†degrees of dissociation of all steps, the concentrations of all anions, hydrogen ions and undissociated acid molecules are determined. The concentration intervals of predominance of various charged and uncharged substances in dilute solutions of all above mentioned acids are also determined. The simple empirical equations for fast approximate calculation of the dissociation degrees and pH values are also suggested

Automatic Diagnosis of Lung Diseases (Pneumonia, Cancer) with given Reliabilities on the Basis of an Irradiation Images of Patients

The article proposes algorithms for the automatic diagnosis of human lung diseases pneumonia and cancer, based on images obtained by radiation irradiation, which allow us to make decisions with the necessary reliability, that is, to restrict the probabilities of making possible errors to a pre-planned level. Since the information obtained from the observation is random, Wald’s sequential analysis method and Constrained Bayesian Method (CBM) of statistical hypothesis testing are used for making a decision, which allow us to restrict both types of possible errors. Both methods have been investigated using statistical simulation and real data, which fully confirmed the correctness of theoretical reasoning and the ability to make decisions with the required reliability using artificial intelligence. The advantage of CBM compared to Wald’s method is shown, which is expressed in the relative scarcity of observation results needed to make a decision with the same reliability. The possibility of implementing the proposed method in modern computerized X-ray equipment due to its simplicity and promptness of decision-making is also shown

HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

სტუდენტების დამოკიდებულება ქორწინება/განქორწინების მიმართ

Introduction: Divorce rates around the world are increasing over time. Therefore, it is important to study how parental divorce affects young people’s attitudes toward marriage/divorce. Parents play a crucial role in the lives of young people. Adults observe the behaviour of their parents and from their observation they learn what marriage and family life should be like. Research Aim studying students’ attitudes towards marriage and divorce. Methods: The qualitative research method was used, purposive sampling with the help of the snowball. In-depth interviews were conducted with a total of 16 respondents, students aged 18-23. Result: Marriage is important, and they view the institution of marriage positively. Divorce for students is not a tragedy and is acceptable, although the exception group is demonstrated with men whose parents aren’t divorced and divorce is unacceptable for them. Conclusion: Students to some extent repeat the actions of their parents and don’t completely reflect their behaviour and attitudes, which may be caused by the influence of modernization and changes in gender ideology.შესავალი: განქორწინების მაჩვენებელი მთელს მსოფლიოში იზრდება, შესაბამისად მნიშვნელოვანია ვიკვლიოთ, თუ როგორ მოქმედებს მშობლების განქორწინება ახალგაზრდების დამოკიდებულებების ჩამოყალიბებაზე ქორწინება/განქორწინების მიმართ. მშობლები მნიშვნელოვან როლს ასრულებენ ახალგაზრდების ცხოვრებაში. მოზარდები აკვირდებიან მშობლების ქცევას და ამ დაკვირვების საფუძველზე სწავლობენ, თუ როგორი უნდა იყოს ქორწინება და ოჯახური ცხოვრება. კვლევის მიზანია ქორწინებისა და განქორწინების მიმართ სტუდენტების დამოკიდებულებების შესწავლა. მეთოდოლოგია: გამოყენებულ იქნა თვისებრივი კვლევის მეთოდი, მიზნობრივი შერჩევა თოვლის გუნდის მეშვეობით. 18-23 წლამდე 16 სტუდენტთან ჩატარდა სიღრმისეული ინტერვიუები. კვლევის შედეგები: რესპონდენტისთვის ქორწინება მნიშვნელოვანია და პოზიტიურად უყურებენ ქორწინების ინსტიტუტს. სტუდენტებისთვის განქორწინება არ წარმოადგენს ტრაგედიას და მისაღებია, თუმცა გამონაკლის ჯგუფს წარმოადგენენ კაცები განუქორწინებელი ოჯახებიდან, რომლებისთვისაც მიუღებელია განქორწინება. დასკვნა: სტუდენტები გარკვეულწილად იმეორებენ მშობლების ქმედებებს და სრულიად არ ასახავენ მათ ქცევას და დამოკიდებულებებს, რაც შესაძლოა გამოწვეულია მოდერნიზაციის გავლენით და გენდერული იდეოლოგიის ცვლილებით

An Allosteric Mechanism for Inhibiting HIV-1 Integrase with a Small Molecule

HIV-1 integrase (IN) is a validated target for developing antiretroviral inhibitors. Using affinity acetylation and mass spectrometric (MS) analysis, we previously identified a tetra-acetylated inhibitor (2E)-3-[3,4-bis(acetoxy)phenyl]-2-propenoate-N-[(2E)-3-[3,4-bis(acetyloxy)phenyl]-1-oxo-2-propenyl]-L-serine methyl ester; compound 1] that selectively modified Lys173 at the IN dimer interface. Here we extend our efforts to dissect the mechanism of inhibition and structural features that are important for the selective binding of compound 1. Using a subunit exchange assay, we found that the inhibitor strongly modulates dynamic interactions between IN subunits. Restricting such interactions does not directly interfere with IN binding to DNA substrates or cellular cofactor lens epithelium-derived growth factor, but it compromises the formation of the fully functional nucleoprotein complex. Studies comparing compound 1 with a structurally related IN inhibitor, the tetra-acetylated-chicoric acid derivative (2R,3R)-2,3-bis[[(2E)-3-[3,4-bis(acetyloxy)phenyl]-1-oxo-2-propen-1-yl]oxy]-butanedioic acid (compound 2), indicated striking mechanistic differences between these agents. The structures of the two inhibitors differ only in their central linker regions, with compounds 1 and 2 containing a single methyl ester group and two carboxylic acids, respectively. MS experiments highlighted the importance of these structural differences for selective binding of compound 1 to the IN dimer interface. Moreover, molecular modeling of compound 1 complexed to IN identified a potential inhibitor binding cavity and provided structural clues regarding a possible role of the central methyl ester group in establishing an extensive hydrogen bonding network with both interacting subunits. The proposed mechanism of action and binding site for the small-molecule inhibitor identified in the present study provide an attractive venue for developing allosteric inhibitors of HIV-1 IN

Molecular mechanisms of retroviral integration site selection

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic