The performance of the K6 scale in a large adolescent sample.

This dissertation is an applied research study to examine the performance of the K6 scale that measures serious emotional disturbance (SED) among adolescents. As the K6 was included in the 2012 administration of the Kentucky Incentives for Prevention Survey (KIP), three specific aims are included: 1) confirm the unidimensional structure of the K6 among adolescents using factor analysis; 2) define the prevalence and correlates of adolescent SED among Kentucky students; and 3) utilize latent class analysis (LCA) to empirically derive clinically relevant subtypes of adolescents with SED. Of the 122,718 students who completed the KIP in 2012, approximately 89% provided complete data for the K6 (n=108,736). Both principal axis and confirmatory factor analysis supported the unidimensional structure of the K6. Using the unweighted scoring algorithm (i.e., 13+) to screen for SED, the 30-day prevalence for Kentucky was 13.9% in 2012. Grade, gender, race/ethnicity, and family structure emerged as significant social and demographic predictors of SED. Among students with SED, the prevalence rates for substance abuse, antisocial behavior, role impairments, and peer victimization were significantly higher than those without SED. Four distinct subtypes of SED emerged from the LCA, varying by both symptom type and severity: mixed moderate risk, mixed high-risk, anxious moderate risk, and depressed high risk. Grade, gender, race/ethnicity, family structure, substance abuse, antisocial behavior, role impairments, and peer victimization were all significant predictors of class membership, although the magnitude of these effects were stronger for the two higher risk groups. The next steps include validation of the K6 on other state surveys that use school and community-based samples of adolescents, generation of cross-state comparisons, and the implementation of validated statistical approaches to generate more precise SED estimates, especially when gold standard diagnoses are not available. These results indicate the K6 is particularly useful for inclusion in large epidemiologic surveys like the KIP that have limited space and logistics that demand timely administration. Thus, this dissertation provides a foundation for increased epidemiologic infrastructure in Kentucky through the timely surveillance of SED

Endorepellin remodels the endothelial transcriptome toward a pro-autophagic and pro-mitophagic gene signature.

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin protein ligase Parkin and the tumor suppressor mitostatin. Induction of both proteins required the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2). Furthermore, we discovered that endorepellin evoked mitochondrial depolarization in endothelial cells via a specific interaction between its two proximal LG1/2 domains and VEGFR2. We also found that following loss of membrane potential, mitostatin and parkin interact and that mitostatin associates with the established Parkin receptor mitofusin-2. In conclusion, we have identified a critical role for endorepellin in remodeling the autophagic transcriptome and influencing mitochondrial homeostasis

Prognostic factors in patients with diffuse type gastric cancer (linitis plastica) after operative treatment

<p>Abstract</p> <p>Objective</p> <p>Treatment options for patients with diffuse type gastric cancer (linitis plastica) are discussed controversial. It is sometimes discussed that these patients should be treated primarily in palliative intention conservative without resection.</p> <p>Methods</p> <p>In a single-center analysis, we investigated 120 patients with diffuse type gastric cancer. All patients underwent a total gastrectomy, 45 patients even a multivisceral resection because of infiltrating growth, or metastases. Serum tumor marker CEA, CA 72-4, and CA 19-9 were recorded in all patients before surgery. An immunocytochemical detection of free peritoneal tumor cells (FPTC) using Ber-EP4 antibody was correlated with tumor stage and survival. Median follow-up time was 38 months.</p> <p>Results</p> <p>Complete resection rate was 31% (n = 37). 61% (n = 73) of all patients had already distant metastases at the time of surgery, 80% of them peritoneal carcinomatosis. Median survival for the whole group was 8 months, after complete resection 17 months. Lavage cytology, distant metastases, resection rate, and CA19-9 levels had significant influence on survival.</p> <p>Conclusion</p> <p>A significant survival advantage for patients with diffuse type gastric cancer can only be achived after complete resection. We could define a subset of patients with an extremely poor prognosis even after surgical resection. Meticulous preoperative staging, including a diagnostic laparoscopy to exclude peritoneal carcinomatosis and free peritoneal tumor cells before resection should be mandatory in these patients.</p

СЕТЕВАЯ МОДЕЛЬ ПРИОБРЕТЕНИЯ ЗНАНИЙ ДЛЯ ПРОЦЕССА ПРИНЯТИЯ РЕШЕНИЙ ПРИ ЛИКВИДАЦИИ АВАРИЙ НА ШАХТАХ

У статті розглянуто універсальна модель процесу придбання знань, приклади онтології предметної області і бази спостережень, отримані з використанням даної моделі. Також наводяться приклади вербального (словесного) опису діалогу, що виникає між системою ке- рованою онтологією і користувачем системи при породженні прикладів. В статье рассмотрена универсальная модель процесса приобретения знаний, примеры онто- логии предметной области и базы наблюдений, полученные с использованием данной модели. Также приводятся примеры вербального (словесного) описания диалога, возникающего между системой управляемой онтологией и пользователем системы при порождении примеров

Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that decorin protein core modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin protein core to inhibit genes necessary for immunomodulatory responses while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic administration of decorin protein core and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties

Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma.

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups using Fisher\u27s exact tests. Univariate and multivariable analyses were used to correlate biomarker changes and patient survivals. Multivariable analyses were performed by constructing decision trees using the classification and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC tumors. The statistical analysis of the Truncal loss (root loss) found additional correlations between biomarker losses and tumor stages than the traditional Loss in tumor (total) . Losses of SMARCA4 or SMARCA2 significantly improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2 had the opposite effect. Thus Truncal Loss analysis revealed hidden links between protein losses and patient survival in ccRCC

Контроль параметров воздушной среды для построения систем обнаружения пожароопасного состояния

В данной статье дан анализ процесса развития пожара, показавший, что пожар развивается в течение семи стадий, каждой из которых соответствует совокупность явлений (факторов, признаков) пожароопасного состояния, характеризуемая набором определенных параметров. Показано, что понижение стадийности регистрируемого фактора приводит к построению противопожарных профилактико-диагностических систем, поскольку чем ниже регистрируемая стадия, тем неопределеннее связь факта ее обнаружения с пожаром. Указано, что с развитием электронной техники стадийность используемых для обнаружения факторов пожарных ситуаций, в целом, понижается, а также отмечено, что для каждого объекта контроля необходим выбор (выявление) оптимального фактора, в частности, по многим характеристикам оптимальным фактором для летательных аппаратов являются дымы, их ТВ-изображения. This article analyzes the development process of the fire, which showed that a fire develops over seven stages, each of which corresponds to a set of phenomena (factors, signs) fire risk condition characterized by a set of defined parameters. It was shown that the decrease of the registered staging factor leads to the construction of fire preventive and diagnostic systems as recorded by the lower stage, the more uncertain the fact of its connection with the detection of a fire. It is indicated that the development of electronic equipment staging used for the detection of the factors fire situations, in general, is reduced, and also noted that for each control object is necessary to choose (identify) the optimal factor, in particular, in many ways the best factor for aircraft are smoke their TV picture

The metastasis suppressor KISS1 lacks antimetastatic activity in the C8161.9 xenograft model of melanoma.

The objective of this study was to use the established xenograft model of human melanoma (C8161.9) to test a pharmacological approach to the effect of the metastasis suppressor KISS1. A KISS1 analog was used to inhibit the metastatic development of C8161.9 cells in nude mice. Further experiments were performed to test the validity of the C8161.9 model and test the connection between KISS1 expression and loss of metastatic potential. New clones of C8161.9 cells were obtained, with or without KISS1 expression, and were tested for metastasis formation. The absence of benefit in survival with the KISS1 analog compared with PBS prompted us to revisit the C8161.9 model. We found that the cells expressing KISS1, used in the previous study and obtained by transfection and single-cell cloning, were defective for both formation of orthotopic tumors and metastases. In mixing experiments, these cells could not suppress orthotopic tumor growth of KISS1-negative C8161.9 cells, suggesting that the suppression of metastasis by C8161.9-KISS1 cells may be intrinsic to the selected clone rather than related to KISS1 expression. Isolation of clones from parental C8161.9 cells in soft agar yielded cell populations that phenotypically and genotypically mimicked the KISS1-positive clone. In addition, new clones expressing KISS1 did not show any decrease in metastatic growth. These data demonstrate the heterogeneity of cell types in the C8161.9 cell line and the high risk of artifact linked to single-cell selection. A different xenograft model will be necessary to evaluate the use of KISS1 analogs as antimetastatic therapy

Heat Shock Response in CHO Mammalian Cells Is Controlled by a Nonlinear Stochastic Process

In many biological systems, the interactions that describe the coupling between different units in a genetic network are nonlinear and stochastic. We study the interplay between stochasticity and nonlinearity using the responses of Chinese hamster ovary (CHO) mammalian cells to different temperature shocks. The experimental data show that the mean value response of a cell population can be described by a mathematical expression (empirical law) which is valid for a large range of heat shock conditions. A nonlinear stochastic theoretical model was developed that explains the empirical law for the mean response. Moreover, the theoretical model predicts a specific biological probability distribution of responses for a cell population. The prediction was experimentally confirmed by measurements at the single-cell level. The computational approach can be used to study other nonlinear stochastic biological phenomena