Micro-Welding Of High Thermal Conductive Material Aluminum-Graphite Composite By Pulsed ND:YAG Laser.

The development of advanced materials with superior high thermal properties and high specific strength has led to new metal matrix composites (MMCs) as a great attractive material in electrical and electronic industries. In order to manufacture more practical component from MMCs, a tech-nique for joining MMCs to other similar composites or monolithic materials is strongly required. Therefore, the reliable and economic joining technique is investigated to increase the applications of MMCs. In this study, the overlap welding of pure aluminum and super thermal conductive (STC) aluminum-graphite composite was experimentally and numerically investigated by using a pulsed Nd:YAG laser. In order to discuss the welding of dissimilar materials with different thermophysical properties, the temporal change of heat input was controlled by arranging the laser pulse waveform. The porosities and bumps were observed as the remarkable weld defects in the welding process without a pulse control. On the other hand, the weld bead was largely free of defects, and a size of bump was relatively small with the appropriate controlled pulse waveform. It was clarified that the laser welded joint of an aluminum and a STC aluminum-graphite composite could be successfully achieved with the better weld penetration stability by the appropriate controlled pulse waveform

A case of gastrointestinal stromal tumor with synchronous liver metastases showing long-term disease control by imatinib

　Radical surgery is the primary treatment for gastrointestinal stromal tumor (GIST), so that unrsectable GIST has been considered a fatal disease, and the median duration of survival for patients with an unresectable GIST before the era of molecular targeted therapy has been about 18 months. Since the recent development of agents for molecular targeted therapy, including imatinib mesylate, the prognosis of unrsectable GIST has been dramatically improved. The B2222 trial reported that a median time to progression and a median overall survival for advanced GIST treated with imatinib of 24 months and 57 months, respectively. We recently experienced a case of gastrointestinal stromal tumor with synchronous liver metastases maintained in whom the disease was controlled for 4 years by imatinib. The patient is 37-year-old man and he took imatinib mesylate at 400mg/day with no adverse events. Both primary and metastases lesions responded well to imatinib treatment, and this efficacy has endured for 4 years, such that surgical intervention is now considered possible. While GIST is a relatively rare disease and clinical evidence is still poor, we document our considerations for the therapy in this case as well as the results

Laser Welding of Slices of Magnetic Circuit

In electric power industry, there is a problem of achieving stable joint in different components using high productive and efficient technologies. One type of these components is packages of slices for magnetic circuit of electric motors, transformers etc., which need reliable means for their fixing. Laser welding is proposed to solve this problem as an alternative for existing technologies. The development of the laser welding process is presented based on process simulation, study of heat history and comparison with experimental results. Laser beam additional scanning technique is proposed to improve the quality and efficiency of the joining operation

Dynamics of epigenetic regulation at the single-cell level

Chromatin regulators play a major role in establishing and maintaining gene expression states. Yet how they control gene expression in single cells, quantitatively and over time, remains unclear. We used time-lapse microscopy to analyze the dynamic effects of four silencers associated with diverse modifications: DNA methylation, histone deacetylation, and histone methylation. For all regulators, silencing and reactivation occurred in all-or-none events, enabling the regulators to modulate the fraction of cells silenced rather than the amount of gene expression. These dynamics could be described by a three-state model involving stochastic transitions between active, reversibly silent, and irreversibly silent states. Through their individual transition rates, these regulators operate over different time scales and generate distinct types of epigenetic memory. Our results provide a framework for understanding and engineering mammalian chromatin regulation and epigenetic memory

Substrate Selectivities and Catalytic Activities of Marmoset Liver Cytochrome P450 2A6 Differed from Those of Human P450 2A6

ABSTRACT The common marmoset (Callithrix jacchus), a New World primate species, is potentially a useful animal model for preclinical studies in drug development. However, cytochrome P450 (P450) enzymes have not been fully identified and characterized in marmosets. In this study, we identified P450 2A6 cDNA with the sequence highly identical (91-94%) to human P450 2A6, 2A7, and 2A13 cDNA and cynomolgus monkey P450 2A23, 2A24, and 2A26 cDNA. Among the tissue types examined, marmoset P450 2A6 mRNA was most abundantly expressed in livers where P450 2A6 protein was also detected by immunoblotting. Phylogenetic analysis showed that marmoset P450 2A6 was more closely clustered with human and cynomolgus monkey P450 2As than P450 2As of dog, rat, and mouse (the species also used in drug metabolism). Marmoset P450 2A6 heterologously expressed in Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation, similar to human P450 2A6 and 2A13 and cynomolgus monkey P450 2A23, 2A24, and 2A26, but much less effectively coumarin 7-hydroxylation, showing some difference as well. Interestingly, marmoset P450 2A6 and cynomolgus monkey P450 2A23 catalyzed phenacetin O-deethylation, which is catalyzed by human P450 1A2 and 2A13, but not by P450 2A6. Marmoset P450 2A6 also exhibited catalytic activity toward testosterone by the multiple sites, but not rat P450 2A-specific testosterone 7a-hydroxylation activity. These results indicated that marmoset P450 2A6 had functional characteristics different from those of human and cynomolgus monkey P450 2As in terms of partially different substrate specificities and catalytic activities, indicating its importance of further studies for P450 2A-dependent drug metabolism in marmosets

Разработка плана мероприятий по продвижению гостиничных услуг

ВКР является маркетинговая деятельность по продвижению гостиничных услуг на примере гостиницы "Skyline Hotel". Цель работы – разработка плана мероприятий по продвижению гостиничных услуг на примере гостиницы "Skyline Hotel". В процессе исследования проводились исследования продвижения гостиничных услуг. В результате исследования разработаны мероприятия по продвижению услуг гостиницы "Skyline Hotel" на рынке гостиничных предприятий города Томска и произведен расчет эффективности мероприятий.WRC is a marketing activity to promote hotel services on the example of the hotel "Skyline Hotel". The purpose of the work is the development of a plan of measures to promote hotel services on the example of the hotel "Skyline Hotel". In the process of research, research was carried out on the promotion of hotel services. As a result of the research, measures were developed to promote the services of the hotel "Skyline Hotel" in the market of hotel companies in Tomsk and the efficiency of measures was calculated

Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey

Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84–86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1), an aberrantly spliced transcript (SV2) lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del). These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys), although its relative contribution to drug metabolism has yet to be validated

Unique Venous Drainage of a Sphenoid Wing Dural Arteriovenous Fistula with Ocular Symptoms

Background: Dural arteriovenous fistulas (DAVFs) presenting with ocular symptoms, such as exophthalmos and chemosis, are commonly situated in the cavernous sinus (CS). DAVFs at the sphenoid wing with a drainage route into the superior orbital vein (SOV) should be considered as one of the differential diagnoses of ocular symptoms. Case Description: A 41-year-old woman presented with progressive left-sided chemosis and proptosis after left pulsating tinnitus that disappeared spontaneously. Cerebral angiography showed that the fistula was situated along the inferior edge of the superior orbital fissure on the greater sphenoid wing and drained solely into the SOV without flowing into the CS that caused ocular symptoms. Transvenous selective catheterization was performed via the facial vein and SOV. The fistula was then embolized using detachable coils. Conclusions: After embolization, the ocular symptoms resolved, and the patient was discharged without neurologic deficit. Herein, we discuss the developmental mechanism of the unique drainage pattern, including the clinical symptoms and anatomic features of greater sphenoid wing DAVFs. © 2016 Elsevier Inc.Embargo Period 12 month

Prevalence of medical factors related to aging among older car drivers: a multicenter, cross-sectional, descriptive study

Aim An increasing number of older adults in Japan are at an increased risk of road traffic crashes. This study aimed to investigate the prevalence of potential underlying medical factors that increase the risk of road traffic crashes among older people. Methods This cross-sectional observational study was conducted in 11 medical institutions in Japan using self-administered questionnaires and physical examination from January to May 2021. The background and social data, data on the use of nursing care insurance, and clinical data suggestive of polypharmacy, sarcopenia, cognitive impairment, and frailty/oral frailty were obtained. The prevalence of these factors was compared between everyday and occasional drivers. Results Data of 127 patients were collected; their median (interquartile range) age was 73 (70-78) years. Of the total participants, 82 were men (64.6%) and 45 were women (35.4%). There were 77 everyday drivers and 50 occasional drivers. Of these, 121 (95.3%) had not applied for nursing care insurance, but the numbers of those who required help 1 and 2 were 1 (0.8%) and 3 (2.4%), respectively. Prevalence of medical factors was as follows: polypharmacy, 27.6%; sarcopenia, 8.7%; dementia, 16.4%; frailty, 15.0%; and oral frailty, 54.3%; it was not significantly different between every day and occasional drivers. Intention to return the car license was significantly higher among the occasional drivers (2.6% vs. 14.0%; odds ratio: 6.7, 95% confidence interval: 1.2-70.6, p = 0.024). Conclusion We uncovered the prevalence of medical factors that can be associated with road traffic crashes among Japanese older people aged >= 65 years in our community

Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone

ABSTRACT Common marmosets (Callithrix jacchus), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has not investigated in marmosets. In this study, sequence homology, tissue distribution, and enzymatic properties of marmoset P450 3A4 ortholog, 3A5 ortholog, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologs and evolutionary closeness to human and cynomolgus monkey P450 3A orthologs compared with other P450 3A enzymes. Among the five marmoset tissues examined, P450 3A4 ortholog mRNA was abundant in livers and small intestines where P450 3A4 ortholog proteins were immunologically detected. Three marmoset P450 3A proteins heterologously expressed in Escherichia coli membranes catalyzed midazolam 19-and 4-hydroxylation, alprazolam 4-hydroxylation, nifedipine oxidation, and testosterone 6b-hydroxylation, similar to cynomolgus monkey and human P450 3A enzymes. Among the marmoset P450 3A enzymes, P450 3A4 ortholog effectively catalyzed midazolam 19-hydroxylation, comparable to microsomes from marmoset livers and small intestines. Correlation analyses with 23 individual marmoset liver microsomes suggested contributions of P450 3A enzymes to 19-hydroxylation of both midazolam (human P450 3A probe) and bufuralol (human P450 2D6 probe), similar to cynomolgus monkey P450 3A enzymes. These results indicated that marmoset P450 3A forms had functional characteristics roughly similar to cynomolgus monkeys and humans in terms of tissue expression patterns and catalytic activities, suggesting marmosets as suitable animal models for P450 3A-dependent drug metabolism