The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation ...at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.
Muon catalyzed
dd
fusion in D
2
and HD gases in the temperature range from 28 to 350 K was investigated in a series of experiments based on a time-projection ionization chamber operating with pure ...hydrogen. All main observables in this reaction chain were measured with high absolute precision including the resonant and non-resonant
dd
μ formation rates, the rate for hyperfine transitions in
d
μ atoms, the branching ratio of the two charge symmetric fusion channels
3
He +
n
and
t
+
p
and the muon sticking probability. The report presents the final analysis of the data together with a comprehensive comparison with calculations based on recent μCF theories. The energy of the loosely bound
dd
μ state with quantum numbers
J
= 1,
ν
= 1, which is central to the mechanism of resonant molecule formation, is extracted with precision ɛ
11
(fit) = −1.9651(7) eV. in impressive agreement with the latest theoretical results ɛ
11
(theory) = −1.9646 eV.
Preclinical studies have demonstrated that the chemotherapeutic action of oxaliplatin, a third generation platinum derivative, is improved when combined with cetuximab, a monoclonal antibody ...inhibitor of epidermal growth factor receptors. To explore the mechanism of this synergistic benefit, we used HCT-8 and HCT-116, two human colon cancer cell lines, respectively, responsive and non-responsive to the oxaliplatin/cetuximab combination. We examined the effect of drug exposure on glutathione-S-transferase-mediated oxaliplatin detoxification, DNA-platinum adducts formation, cell cycle distribution, apoptosis, and the expression of multiple targets involved in DNA replication, recombination, and repair. The major changes we found in HCT-8 were a stimulation of oxaliplatin-DNA adduct formation associated with reduced expression of the key enzyme (excision repair cross complementation group1: ERCC1) in the key repair process of oxaliplatin-DNA platinum adduct, the nucleotide excision repair (NER), both at the mRNA and protein levels. We also observed a reduced expression of factors involved in DNA replication initiation, which correlates with an enrichment of cells in the G1 phase of the cell cycle as well as an acceleration of apoptosis. None of these changes occurred in the non-responsive HCT-116 cell that we used as a negative control. These findings support the fact that cetuximab potentiates the oxaliplatin-mediated cytotoxic effect as the result of inhibition of NER and also DNA replication initiation.
► A controlled Poisson Voronoi tessellation is presented for virtual microstructures. ► A unique mapping from real to virtual microstructure parameters is proven to exist. ► An efficient algorithm is ...presented that facilitates the microstructure mapping. ► The scheme generates microstructures statistically equivalent to real cases. ► Example microstructures were tested using crystal plasticity finite element analysis.
An integrated scheme is developed based on the controlled Poisson Voronoi tessellation (CPVT) model to generate the polycrystalline grain structure for micromechanics simulations. The proposed model of CPVT involves a single control parameter that is used to produce the grain structure with regularity control, by which the yielded tessellation varies from the purely random Voronoi tessellation to the regular hexagonal tessellation. The system extends the standard CPVT model by the addition of two features: a one-parameter gamma distribution and a mapping from a set of quantitative metallographic measurements to the distribution parameter. Based on this scheme, a grain structure can be constructed such that the virtual tessellation is statistically equivalent to the expected grain size distribution. To validate the modules that utilise the physical parameters that dictate the regularity, a series of theoretical investigations is performed. Efforts are devoted to proving the uniqueness of the mapping from the physical parameters to the distribution parameter and the regularity parameter. An efficient numerical algorithm is provided to facilitate the mapping solution process. A software system (VGRAIN) is developed implementing the proposed CPVT model to generate the grain structure for crystal plasticity finite element (CPFE) analysis. To demonstrate the proposed scheme and the VGRAIN system, a plane strain CPFE analysis is conducted. Two microstructures are generated with different regularities, and the deformation under uniaxial tension is simulated.
The article reflects the results of a study of theoretical and applied aspects of the categori-cal and conceptual apparatus of legal psychology from a critical point of view. Conclusions are drawn ...about the special position of legal psychology as an applied discipline in relation to the legal sciences, in connection with which the priority role in solving its problems is given to legal concepts, which in their essence are self-sufficient and conventional. The conventional nature of legal concepts, built on an agreement between lawyers in the under-standing of certain terms, comes down to the fact that in their content they in some cases do not coincide with the content of general psychological categories and concepts. In terms of scope, they are either narrower or wider than psychological concepts. In this regard, the significant reverse influence of psychological concepts on legal ones, expressed in the re-flection of psychological patterns and mechanisms of psychological and legal phenomena, becomes a laborious and long process, since legal concepts do not aim to reflect the true structure of the world. The features of the categorical-conceptual apparatus of legal psy-chology listed in this study make it possible to more accurately determine the direction of scientific research, correctly understand the needs of legal practice and predict the long-term consequences of the results of one's scientific activity.
В статье отражены результаты исследования теоретико-прикладных аспектов категориально-понятийного аппарата юридической психологии с критической точки зрения. Сделаны выводы об особом положении юридической психологии как прикладной дисциплины в системе правовых наук, в связи с которым приоритетная роль в решении ее задач отводится правовым понятиям, по своей сущности являющимся самодостаточными и конвенциональными. Конвенциональный характер правовых понятий, построенный на соглашении между юристами в понимании тех или иных терминов, сводится к тому, что по своему содержанию они в ряде случаев не совпадают с содержанием общепсихологических категорий и понятий. Они либо шире, либо уже психологических понятий по своему объему. В связи с этим влияние психологических понятий на правовые, выраженное в отражении психологических закономерностей и механизмов правовых явлений, становится трудоемким и долгим процессом, поскольку правовые понятия не ставят цель отражения истинного устройства мира. Перечисленные в данном исследовании особенности категориально-понятийного аппарата юридической психологии позволяют более точно определять направления научных исследований, правильно понимать запросы юридической практики и прогнозировать отдаленные последствия результатов научной деятельности.
In this work, we investigated the effect of γ-glutamyltransferase (GGT) overexpression on cell viability after carboplatin treatment and compared with cisplatin. Carboplatin challenge of HeLa cells ...induced GGT and glutamate-cystine ligase (GCL) activities by 2- and 1.4-fold, respectively and concomitantly increased the intracellular reduced glutathione (GSH) level (1.5-fold). To study the role of GGT, HeLa-GGT cells, a stably transfected cell line overexpressing GGT (120–150mU/mg protein) and the parental HeLa cells (10–15mU/mg protein) were used. Both cell lines exhibited comparable viability (ic50~150μM) after carboplatin treatment when cultured in standard (250μM cystine) medium. Culture in low (50μM) cystine medium resulted in a dramatic decrease (~90%) of the intracellular GSH level and to a 2.5-fold increase of carboplatin cytotoxicity (ic50~60μM). When GSH (50μM) was included in the culture medium, only HeLa-GGT cells exhibited increased resistance to carboplatin. Using partially purified GGT from HeLa-GGT cells, we show that cisplatin forms adducts with cysteinylglycine, depending only on GGT activity whereas carboplatin did not efficiently react with cysteinylglycine. Thus, in this model system, GGT activity can affect platinum drugs cytotoxocity by two different ways: cisplatin can be detoxified extracellularly after reaction with the -SH group of cysteinylglycine; in the case of carboplatin, the supply of GSH precursors, initiated by GGT, increases the intracellular level of the tripeptide and provides enhanced defensive mechanisms to the cell.
Detailed analysis of odontogenic maxillary sinusitis clinical course allowed identifying clinical features of the disease specific for elderly and senile patients. The paper describes the ...peculiarities of odontogenic maxillary sinusitis in elderly and senile patients including those having oroantral sinus tract.
This study aimed to assess the effect of cetuximab (C225, Erbitux, a chimeric anti-epidermal growth factor receptor (EGFR) monoclonal antibody) in combination with oxaliplatin in vitro and in vivo on ...four colon cancer cell lines (HCT-8; HT-29, SW620, HCT-116) expressing different levels of EGFR. In vitro, cetuximab combined with oxaliplatin significantly decreased the IC50 values of oxaliplatin in HCT-8 (EGF-R moderate) and HT-29 (EGF-R weak) cell lines, while SW620 (EGF-R negative) and HCT-116 (EGFR strong) cell lines remained unresponsive. This combination was synergistic in HCT-8 and HT-29 cell lines while cetuximab induced no major modification of the IC50 of oxaliplatin in HCT-116 or SW620 cell lines. We then determined the effect of cetuximab on the EGF-induced EGFR phosphorylation and we highlight a correlation between the basal level of phospho-EGFR and the response to the combination. In vivo, the combination of cetuximab plus oxaliplatin significantly inhibited tumor growth of HCT-8 and HT-29 (tumor delay or Td = 21.6+/-2.9 and 18.0+/-2.9 days respectively, synergistic effect) compared to either oxaliplatin (Td=12.6+/-2.3 and 14.4+/-3.2 days respectively) or cetuximab (Td=13.4+/-2.9 and 14.5+/-2.4 days, respectively) alone in xenograft models. The combination had no effect on HCT-116 and SW-620 cell lines. The observed responses are strictly dependent on the cell type, and are not correlated with the level of EGFR expression but related to the basal level of phospho-EGFR. This study provides promising preclinical results for a possible clinical investigation of the combination of oxaliplatin plus cetuximab in chemorefractory colorectal tumors.
Muon catalyzed dd fusion in D{sub 2} and HD gases in the temperature range from 28 to 350 K was investigated in a series of experiments based on a time-projection ionization chamber operating with ...pure hydrogen. All main observables in this reaction chain were measured with high absolute precision including the resonant and non-resonant ddμ formation rates, the rate for hyperfine transitions in dμ atoms, the branching ratio of the two charge symmetric fusion channels {sup 3}He + n and t + p and the muon sticking probability. The report presents the final analysis of the data together with a comprehensive comparison with calculations based on recent μCF theories. The energy of the loosely bound ddμ state with quantum numbers J = 1, ν = 1, which is central to the mechanism of resonant molecule formation, is extracted with precision ɛ{sub 11}(fit) = −1.9651(7) eV. in impressive agreement with the latest theoretical results ɛ{sub 11}(theory) = −1.9646 eV.
PDF
