Influence of post-post processing technology and laser radiation parameters on the optical breakdown threshold of a ZnGeP2 single crystal

The aim of this work is to determine the influence of the parameters of post-growth technological operations and experimental conditions on the threshold of optical breakdown of the surface of ZGP crystals under the action of laser radiation at a wavelength of 2091 nm

Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions

Excess contributions to the free energy due to interfaces occur for many problems encountered in the statistical physics of condensed matter when coexistence between different phases is possible (e.g. wetting phenomena, nucleation, crystal growth, etc.). This article reviews two methods to estimate both interfacial free energies and line tensions by Monte Carlo simulations of simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is based on thermodynamic integration. This method is useful to study flat and inclined interfaces for Ising lattices, allowing also the estimation of line tensions of three-phase contact lines, when the interfaces meet walls (where "surface fields" may act). A generalization to off-lattice systems is described as well. The second method is based on the sampling of the order parameter distribution of the system throughout the two-phase coexistence region of the model. Both the interface free energies of flat interfaces and of (spherical or cylindrical) droplets (or bubbles) can be estimated, including also systems with walls, where sphere-cap shaped wall-attached droplets occur. The curvature-dependence of the interfacial free energy is discussed, and estimates for the line tensions are compared to results from the thermodynamic integration method. Basic limitations of all these methods are critically discussed, and an outlook on other approaches is given

Simultaneous measurement of the muon neutrino charged-current cross section on oxygen and carbon without pions in the final state at T2K

This paper reports the first simultaneous measurement of the double differential muon neutrino charged-current cross section on oxygen and carbon without pions in the final state as a function of the outgoing muon kinematics, made at the ND280 off-axis near detector of the T2K experiment. The ratio of the oxygen and carbon cross sections is also provided to help validate various models\u27 ability to extrapolate between carbon and oxygen nuclear targets, as is required in T2K oscillation analyses. The data are taken using a neutrino beam with an energy spectrum peaked at 0.6 GeV. The extracted measurement is compared with the prediction from different Monte Carlo neutrino-nucleus interaction event generators, showing particular model separation for very forward-going muons. Overall, of the models tested, the result is best described using local Fermi gas descriptions of the nuclear ground state with RPA suppression

Влияние гуминовых веществ угля и биокомпозиций с наночастицами серебра на их основе на баланс аргинина в перитонеальных макрофагах интактных мышей

Background. Antigen-presenting cells (APCs), especially macrophages, play an important role in the body defense against various pathogens. Their dysfunction and polarization are associated with most inflammatory and autoimmune diseases. The inflammatory process is regulated by activation and / or inhibition of genes differentially expressed by macrophages. Successful correction of inflammation leads firstly to elimination of inflammatory stimuli and then to remodeling and restoration of tissues and organs. It was experimentally confirmed that silvercontaining bionanocomposites based on natural humic substances (HS) obtained from coal of different origin, as well as initial matrices of these HS, are capable of activating pro- and anti-inflammatory properties of macrophages.Aim. To study cytotoxic, pyrogenic, and immunomodulatory properties (arginine balance) of initial HS samples and samples of silver nanoparticles ultradispersed in these HS matrices (HS-AgNPs) in the cell culture of peritoneal macrophages, as well as their effect on pro- and anti-inflammatory properties of APCs.Materials and methods. Cultural and biochemical methods were used in the study.Results. The study showed that the samples CHE-K, CHE-AgNPs, CHS-K, and CHP-K increased M1 macrophage polarization due to stimulation of the NO-synthase activity and inhibition of arginase. The samples CHI-K, CHIAgNPs, CHP-AgNPs, and CHS-AgNPs modulated an alternative M2 or M2-like state of macrophage activation. At the same time, HS are not cytotoxic at effective concentrations, and three out of four studied samples did not contain pyrogenic impurities.Conclusion. The use of HS and their silver-containing bionanocomposites, which have the ability to greatly affect the polarization of antigen-presenting cells, is a promising research area in correction of the inflammatory response for solving an important social and medical problem of treating chronic wounds. Введение. Антигенпрезентирующие клетки, особенно макрофаги, играют важную роль в защите организма от различных патогенов, их дисфункции, и поляризация связана с большинством воспалительных и аутоиммунных заболеваний. Воспалительный процесс жестко регулируется активацией и (или) ингибированием дифференциально экспрессируемых макрофагами генов. Успешная коррекция воспалительного процесса приводит к устранению воспалительных стимулов и далее ремоделированию и восстановлению тканей и органов. Экспериментально доказано, что биокомпозиции с наночастицами серебра на основе природных гуминовых веществ (ГВ) угля различного генеза, а также исходные матрицы данных ГВ способны активировать про- и противовоспалительные свойства макрофагов.Цель. Исследование в культуре клеток перитонеальных макрофагов цитотоксических, пирогенных и иммуномодулирующих свойств (баланс аргинина) исходных образцов ГВ и образцов наночастиц серебра, ультрадиспергированных в данных матрицах гуминовых веществ (ГВ-AgNPs),а также их влияния на про- и противовоспалительные свойства антигенпрезентирующих клеток. Материалы и методы. Использовались культуральные и биохимические методы.Результаты. Показано, что образцы CHE-K, CHE-AgNPs, CHS-K, CHP-K за счет усиления активности NOсинтазы и ингибиции аргиназы способствуют поляризации перитонеальных макрофагов по классическому типу (М1). Образцы CHI-K, CHI-AgNPs, CHP-AgNPs и CHS-AgNPs модулируют альтернативный М2 или M2-подобный тип (M2-like state) активации макрофагов. При этом ГВ не цитотоксичны в эффективных концентрациях, а также три из четырех исследуемых образцов не содержат пирогенных примесей.Заключение. Применение ГВ и серебросодержащих бионанокомпозиций на основе ГВ, обладающих способностью широко влиять на поляризацию антигенпрезентирующих клеток, является перспективным направлением исследований коррекции воспалительной реакции и, в частности, для решения острой социальной и медицинской проблемы – лечения хронических ран.

Stable interference of EWS–FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target

BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS–FLI1 target genes still remain unknown and many have been identified in heterologous model systems

Ribosomal S6 Kinase 2 (RSK2) Maintains Genomic Stability by Activating the Atm/p53-Dependent DNA Damage Pathway

10.1371/journal.pone.0074334PLoS ONE89-POLN

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy

УРОВЕНЬ ГОРМОНОВ В ТКАНИ РАКА ТЕЛА МАТКИ И ИНТАКТНЫХ ЯИЧНИКАХ АССОЦИИРОВАННЫЙ С РАЗЛИЧНЫМИ ВИРУСНЫМИ ИНФЕКЦИЯМИ

Oncogenic impact of transformative viruses on the risk of cancer is well known. Today there are no studies focused on the effect of widespread, often persisting infections, such as herpes simplex virus (HSV), cytomegalovirus (CMV) and chlamydial infections on the level of hormones in the reproductive organs and their role in the pathogenesis of endometrial cancer.  The aim of this study is to evaluate the effect of infectious agents in the substantive and concomitant conditions on the local hormone production in tissue of uterus and ovaries in patients with cancer of the body of uterus in menopausal age.In the tumor, in perifocal zone and in unaltered ovaries in patients with cancer of the body of uterus ELISA and PCR method determines the presence of herpes simplex virus types 1 and 2, cytomegalovirus and chlamydial infection. Depending on the level of infection in the tissues the local level of saturation of sex hormones, sex hormone binding globulin, prolactin were evaluated in samples of endometrium and ovaries. The presence of infectious agents have a modifying effect on local hormone production, increasing the intensity of disorders resulting in an imbalance of steroids, estrogen metabolites disturbance ratio and strengthening prolactinemia not only in tumor tissue but also in unchanged ovaries in patients  with cancer of the body of uterus.Известно онкогенное влияние трансформирующих вирусов на риск развития онкологических заболеваний.  Практически не исследовано влияние широко распространенных,  зачастую персистирующих инфекций, типа вируса простого герпес  (ВПГ), цитомегаловируса  (ЦМВ) и хламидийных инфекций на гормональный фон в органах репродуктивной системы и роль их в патогенезе рака тела матки. Целью работы явилось изучение влияния инфекционных агентов в самостоятельном и сочетанных вариантах на локальный гормоногенез  тканей матки и яичников у больных раком тела матки менопаузального  возраста.  В опухоли, перифокальной  зоне и неизмененных  яичниках у больных раком  тела матки ИФАи ПЦР методами определяли наличие вируса простого герпеса 1-го и 2-го типов, цитомегаловирусную и хламидийную инфекции. В зависимости  от инфицированности тканей изучали уровень локальной насыщенности образцов  эндометрия  и яичников половыми гормонами, секстероидсвязывающим  глобулином, пролактином. Присутствие инфекционных агентов оказывает модифицирующее влияние на локальный гормоногенез,  увеличивая интенсивность нарушений, что приводит к дисбалансу стероидов,  нарушению соотношения метаболитов эстрогенов и усилению пролактинемии не только в опухолевой ткани, но и в неизмененных  яичниках у больных раком тела матки

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life