Аналитический метод решения нестационарных дифференциальных игр сближения

Досліджено ігрову задачу зближення для нестаціонарних динамічних процесів, що функціонують в умовах невизначеності та протидії. При цьому термінальна множина представляє собою циліндричне багатозначне відображення. На основі методу розв’язуючих функцій отримано достатні умови завершення гри в класі квазі- та стробоскопічних стратегій для різних схем методу. Проведено порівняння гарантованих часів. Результати ілюструються на моделі з інтегральним блоком керування та ігрових задачах з простим рухом.The game problem of pursuit is studied for dynamic processes evolving under uncertainty and counteraction. The terminal set is supposed to be a cylindrical set-valued mapping. The method of resolving functions is used to derive the sufficient conditions for the game termination in the class of quasi- and stroboscopic strategies for various schemes of the method. The guaranteed times are compared. The results are illustrated using the model with integral control unit and game problems with simple motion

A Cross Sectional Study of Medical Students’ Perception of Their Educational Environment in Ghana

Background: The quality of medical education is affected by many factors, one of which is the educational environment of medical education. However, there is paucity of studies addressing the educational environment from African medical schools. The aim of this study was to determine the clinical year students’ perceptions of their educational environment at a medical school in Ghana. This was done with the goal of identifying factors that may impact positive changes in the school. Methods: A cross-sectional study was undertaken using the DREEM questionnaire. The questionnaire was administered to students in clinical years 1, 2, & 3 at the time of the study. 298 students participated in the study by convenience sampling. Data was analyzed using SPSS version 24. The total score and the five subscales of DREEM scores were used in the final analysis. Results: A total of 298 out of 300 students completed the questionnaire out of which Fifty six percent of respondents were male. There was no significant gender differences in the total DREEM scores [F(1, 274) = 1.019, p=0.314]. The overall educational environment was positive M=117.32 ± 15.45. Areas for improvement were students’ perception of the teachers (26.09 ± 3.59) and students’ perception of the atmosphere (25.71 ± 5.62). The students’ perception of learning (30.70 ± 5.20), and students’ academic self-perceptions (21.11 ± 3.74) were positive. Students’ social self-perceptions (13.71 ± 2.99) was neutral. There was no significant difference in perception by clinical year [F(2, 274) = 0.298, p = 0.742]. Conclusion: The perception of students at this Ghanaian medical school can be described as positive and negative. The school should consider the two domains with negative perceptions as areas for improvement. Students reported problem-based learning as a preferred method of teaching versus the traditional method. Attention to the learning atmosphere and student-focused learning is likely to increase perception

Toward the understanding of DNA fluorescence : The singlet excimer of cytosine

By using the multiconfigurational second-order perturbation method CASPT2, including corrections for the basis set superposition error, the lowest-singlet excited state of the face-to-face π-stacked cytosine homodimer is revealed to be bound by about half an eV, being the source of an emissive feature consistent with the observed redshifted [email protected] [email protected] [email protected] [email protected]

Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH –induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems

Protein Block Expert (PBE): a web-based protein structure analysis server using a structural alphabet

Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning

Detection and imaging of the free radical DNA in cells—Site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy

Oxidative stress-related damage to the DNA macromolecule produces lesions that are implicated in various diseases. To understand damage to DNA, it is important to study the free radical reactions causing the damage. Measurement of DNA damage has been a matter of debate as most of the available methods measure the end product of a sequence of events and provide limited information on the initial free radical formation. We report a measurement of free radical damage in DNA induced by a Cu(II)-H2O2 oxidizing system using immuno-spin trapping supplemented with electron paramagnetic resonance. In this investigation, the short-lived radical generated is trapped by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) immediately upon formation. The DMPO adduct formed is initially electron paramagnetic resonance active, but is subsequently oxidized to the stable nitrone adduct, which can be detected and visualized by immuno-spin trapping and has the potential to be further characterized by other analytical techniques. The radical was found to be located on the 2′-deoxyadenosine (dAdo) moiety of DNA. The nitrone adduct was repaired on a time scale consistent with DNA repair. In vivo experiments for the purpose of detecting DMPO–DNA nitrone adducts should be conducted over a range of time in order to avoid missing adducts due to the repair processes

Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein

Histone methyltransferase DOT1L catalyzes mono-, di-and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect