2-Phenyl-5-(p-tol­yl)-1,3,4-oxadiazole

The title compound, C15H12N2O, adopts the expected near-planar geometry, the phenyl and tolyl rings being inclined relative to the oxadiazole ring by 3.8 (3) and 8.3 (2)°, respectively. This allows adjacent mol­ecules to pack in a parallel fashion and form stacking along [010] via π–π inter­actions [centroid–centroid distances = 3.629 (2) and 3.723 (2) Å]. Further inter­molecular inter­actions include C—H⋯π inter­actions and weak C—H⋯N hydrogen bonds, giving rise to a crossed herringbone packing motif

The Nature of biodesigned systems: Directions for HCI

The nascent field of biodesign uses the biological affordances of organisms to address some user need. These can range from the development of novel materials, which the designer actively investigates, to applications of synthetic biology or the creation of bio-digital hybrid systems. Within biodesign there is a question for interaction design: what will interactive systems look like in a guided and grown environment, rather than a built environment? In this workshop, we will explore new technologies that rely on symbiotic relationships between the user and organisms that participate in interactive systems. The goal of this workshop is to engage the interaction design community in exploring new aspects of designing for living computational systems

ГЕМОДИНАМИЧЕСКИЕ ПАРАМЕТРЫ КРОВОТОКА В ЭКСТРАКРАНИАЛЬНЫХ ОТДЕЛАХ МОЗГОВЫХ АРТЕРИЙ И СЕРДЦЕ У БОЛЬНЫХ ОККЛЮЗИЕЙ ВНУТРЕННЕЙ СОННОЙ АРТЕРИИ ПРИ АНГИОХИРУРГИЧЕСКОМ ЛЕЧЕНИИ

HighlightsWe have analyzed the parameters of cerebral hemodynamics and left ventricular functional capacity in patients with occlusion and stenosis of the contralateral internal carotid artery during vascular surgery. Considering the importance of the left ventricular functional capacity and treatment options to ensure the stability of cerebral circulation in patients with occlusion and hemodynamically significant stenosis of the contralateral carotid artery, its detailed study at all stages of vascular surgery remains necessary. AbstractAim. To study cerebral hemodynamics and left ventricular functional capacity in patients with occlusion and stenosis of the contralateral internal carotid artery (ICA) to optimize treatment at the preoperative phase.Methods. The study compared the hemodynamic parameters of the blood flow of the ICA, vertebral arteries and left ventricular functional capacity in patients with ICA occlusion and contralateral ICA stenosis, which formed the 1 group (12 patients), and patients with unilateral hemodynamically significant stenosis, which formed the 2 group (52 patients). The blood flow in the extracranial portions of the major arteries of the head and heart was assessed using ultrasound, and the arterial vascular system and brain structure was assessed using MRI and MRA.Results. Before surgery, statistically significant differences in velocity parameters in the vertebral arteries on the occlusion side were found; on the contralateral occlusion side, velocity parameters in ICA were significantly different from the corresponding indicators in the group with unilateral stenosis; after surgery, statistically significant differences were found in the common carotid and vertebral arteries on the occlusion side; on the contralateral occlusion side, differences in velocity parameters in the common carotid, internal, and vertebral arteries were revealed in comparison with the group with unilateral stenosis. Of the indicators of the left ventricular functional capacity, only left ventricular ejection fraction differed significantly when comparing the group of patients with occlusion and stenosis of ICA and the group of patients with unilateral stenosis. Moreover, when evaluating pre- and postoperative outcomes in the group of patients with occlusion, significant differences were obtained only regarding the vertebral artery on the side of occlusion – the peak systolic blood flow velocity and the volumetric blood flow velocity significantly decreased. There were no significant differences between the common carotid, internal carotid arteries on the contralateral occlusion side, and middle cerebral arteries.Conclusion. Carrying out a comprehensive ultrasound examination of the main arteries of the head in combination with magnetic resonance imaging of the brain is a reliable and adequate way to assess cerebral hemodynamics, changes in the vascular bed and structure of the brain. Given the extreme importance of the left ventricular functional capacity to ensure the stability of cerebral circulation in patients with occlusion of the internal carotid artery and contralateral hemodynamically significant stenosis, its detailed study before carotid endarterectomy is necessary to adjust therapeutic measures.Основные положенияИзучены показатели мозговой гемодинамики и функциональной способности миокарда левого желудочка у пациентов с окклюзией и стенозом контралатеральной внутренней сонной артерии при ангиохирургическом лечении. Учитывая важность состояния функциональной способности миокарда левого желудочка и вариантов коррекции для обеспечения стабильности мозгового кровообращения у больных с окклюзией и гемодинамически значимым стенозом контралатеральной сонной артерии, ее детальное исследование на этапах ангиохирургического лечения представляется необходимым. РезюмеЦель. Исследование состояния мозговой гемодинамики и функциональной способности миокарда левого желудочка (ЛЖ) у пациентов с окклюзией и стенозом контралатеральной внутренней сонной артерии (ВСА) для оптимизации лечения на этапе предоперационной подготовки.Материалы и методы. В исследовании сравнивались гемодинамические параметры кровотока ВСА, позвоночных артерий и функциональной способности миокарда ЛЖ у пациентов с окклюзией ВСА и стенозом контралатеральной ВСА, группа 1 (12 пациентов), и пациентов с односторонним гемодинамически значимым стенозом – группа 2 (52 пациента). Состояние кровотока в экстракраниальных отделах магистральных артерий головы и сердца оценивали с использованием ультразвукового исследования, состояние артериальной сосудистой системы и структуры головного мозга – с применением магнитно-резонансной томографии и магнитно-резонансной томографии-ангиографии.Результаты. До операции на стороне окклюзии выявлены статистически значимые различия скоростных показателей в позвоночных артериях, на контралатеральной окклюзии стороне скоростные показатели в ВСА статистически значимо отличались от соответствующих показателей в группе с односторонним стенозом. После операции на стороне окклюзии определены статистически значимые различия в общих сонных и позвоночной артериях, на контралатеральной окклюзии стороне обнаружены различия скоростных показателей в общих сонных, внутренних и позвоночных артериях в сравнении с группой с односторонним гемодинамически значимым стенозом. Из показателей функциональной способности миокарда ЛЖ статистически значимо различались только фракция выброса ЛЖ при сравнении группы пациентов с сочетанием окклюзии и стеноза ВСА и односторонним гемодинамически значимым стенозом. Кроме этого, при оценке до- и послеоперационных результатов исследования непосредственно в группе пациентов с окклюзией статистически значимые различия получены лишь для позвоночной артерии на стороне окклюзии – значительно снизилась пиковая систолическая скорость и объемная скорость кровотока. В общих сонных, внутренних сонных на контралатеральной окклюзии стороне, средних мозговых артериях статистически значимых различий не выявлено.Заключение. Комплексное ультразвуковое исследование магистральных артерий головы в сочетании с магнитно-резонансной томографией головного мозга является надежным и адекватным способом оценки мозговой гемодинамики, изменений сосудистого русла и структуры головного мозга. Учитывая чрезвычайную важность состояния функциональной способности миокарда ЛЖ для обеспечения стабильности мозгового кровообращения у пациентов с окклюзией ВСА и контралатеральным гемодинамически значимым стенозом, ее детальное исследование перед каротидной эндартерэктомией представляется необходимым для коррекции лечебных мероприятий

Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

Brca1- and Brca2-deficient cells have reduced capacity to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) and consequently are hypersensitive to DNA damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore HR activity at DSBs. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARPi and cisplatin resistance is associated with replication fork (RF) protection in Brca2-deficient tumor cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of RF protection, highlighting the complexities by which tumor cells evade chemotherapeutic interventions and acquire drug resistance

2-Phenyl-5-(p-tolyl)-1,3,4-oxadiazole

Funding: University of St. Andrews and the Engineering and Physical Science Research Council (EPSRC, UK).The title compound, C15H12N2O, adopts the expected near-planar geometry, the phenyl and tolyl rings being inclined relative to the oxadiazole ring by 3.8 (3) and 8.3 (2)degrees, respectively. This allows adjacent molecules to pack in a parallel fashion and form stacking along [010] via pi-pi interactions [centroid-centroid distances = 3.629 (2) and 3.723 (2) angstrom]. Further intermolecular interactions include C-H center dot center dot center dot pi interactions and weak C-H center dot center dot center dot N hydrogen bonds, giving rise to a crossed herringbone packing motif.Publisher PDFPeer reviewe

Spin-orbit interaction effect on surface electronic structure of GdX2Si2 compound

The paper investigates the magnetic and electronic structure of GdX2Si2 (X is Cu, Ag, Au) compounds in terms of the density functional theory with the emphasis on the spin-orbit interaction affecting the electronic structure of the GdX2Si2 (001) surface. It is found that these compounds demonstrate an interlayer antiferromagnetism, which, however, does not affect the electronic structure of the GdX2Si2 (001) surface near the Fermi level. The spin-orbit splitting of two-dimensional states on the GdX2Si2 (001) surface, which combines the intrinsic spin-orbit splitting and Bychkov-Rashba splitting, grows with increasing atomic number of a noble metal in the intermetallic compound. Based on the analysis of the spatial extension of d-shells and their interaction with silicon orbitals, the spin-orbit interaction is explained for compositions containing noble metals. A comparison of rare-earth- and noble metal-based intermetallic compounds and isostructural intermetallic compounds with transition elements, shows that d-shell filling affects the spin-orbit interaction

Mutational and Kinetic Analysis of Lesion Recognition by Escherichia coli Endonuclease VIII

Escherichia coli endonuclease VIII (Endo VIII) is a DNA glycosylase with substrate specificity for a wide range of oxidatively damaged pyrimidine bases. Endo VIII catalyzes hydrolysis of the N-glycosidic bond and β, δ-elimination of 3′- and 5′-phosphate groups of an apurinic/apyrimidinic site. Single mutants of Endo VIII L70S, L70W, Y71W, F121W, F230W, and P253W were analyzed here with the aim to elucidate the kinetic mechanism of protein conformational adjustment during damaged-nucleotide recognition and catalytic-complex formation. F121W substitution leads to a slight reduction of DNA binding and catalytic activity. F230W substitution slows the rate of the δ-elimination reaction indicating that interaction of Phe230 with a 5′-phosphate group proceeds in the latest catalytic step. P253W Endo VIII has the same activity as the wild type (WT) enzyme. Y71W substitution slightly reduces the catalytic activity due to the effect on the later steps of catalytic-complex formation. Both L70S and L70W substitutions significantly decrease the catalytic activity, indicating that Leu70 plays an important role in the course of enzyme-DNA catalytic complex formation. Our data suggest that Leu70 forms contacts with DNA earlier than Tyr71 does. Therefore, most likely, Leu70 plays the role of a DNA lesion “sensor”, which is used by Endo VIII for recognition of a DNA damage site