Flight Planning Tool an Aid for Efficient Flight Evaluation

Airborne surveillance systems have multiple sensors and communication links on board a suitable platform. They work in a cohesive manner to provide effective surveillance over the region of interest. The performance proving of such a system is challenging and requires flight trails extending over years. The test results often have to be interpreted using statistical analysis of the flight test data. An efficient way is to carefully design the flight test profiles such that enough samples can be collected during the test and multiple requirements can be tested in a single sortie. Such meticulous test strategies where both own ship platform and test targets are moving with high dynamics call for software based tool for planning of test sorties and the test points. Flight Planning Tool (FPT) plays an important role in pre-flight stage during developmental trials for analysis of the MOEs and MOPs of overall system and of various on-board sensors of an airborne multi-sensor system. The FPT provides statistical & graphical analysis for sensor behaviour for various scenarios (flight trials) before actual flight test is conducted. It provides prior information on number of valid samples for sensor testing during flight trials. In addition, the tool aids in assessing number of profiles to be flown for proving each MOE. The profiles can also be optimised such that valid samples are collected for evaluation

Theoretical calculations that determine the stability of the knife holder milling tool on a support sliding in the process of operation

In this regard at department of woodworking machines and tools the mill which has an opportunity to change the angles of cutting and an axial corner at the same time is designed and made. It will allow to reduce power by cutting, to increase quality of the processed sur-face and to increase the period of firmness of the tool.На кафедре деревообрабатывающих станков и инструментов спроектирована и изготовлена фреза, у которой есть возможность изменять углы резания и осевой угол одновременно. Это позволит уменьшить мощность на резание, повысить качество обработанной поверхности и увеличить период стойкости инструмента

Association between Diabetes Consequences and Quality of Life among Patients with Diabetes Mellitus in the Aseer Province of Saudi Arabia

BACKGROUND: Diabetes mellitus (DM) is a major health-care burden worldwide. AIM: The aim of the study was to explore how the quality of life (QoL) of DM patients could be affected in the Aseer Province of the Kingdom of Saudi Arabia (KSA). METHODS: A cross-sectional, multicenter study in DM patients of both sexes and all age groups in Aseer Province were done using a validated self-administered questionnaire. The study was conducted between April 1, 2018 and November 25, 2018. RESULTS: A total of 418 patients completed our questionnaire, of which 240 (58%) were male and 178 (42%) were female. Furthermore, 50.23% were married and 104 (24.16%) were illiterate. We found that 403 (96.42%) respondents had type-2 DM and 315 (75.35%) had a family history of DM. In addition, 132 (31.57%) respondents were on monotherapy whereas only 61 (14.59%) were using combination therapy. Hypertension was the most prevalent comorbidity (166, 39.71%) and peripheral neuropathy the most prevalent complication of DM (157, 37.56%). CONCLUSION: DM had a significant impact on QoL among patients from Aseer Province in KSA. Our study underscores the importance of generating data on QoL among DM patients

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Cauchy's infinitesimals, his sum theorem, and foundational paradigms

Cauchy's sum theorem is a prototype of what is today a basic result on the convergence of a series of functions in undergraduate analysis. We seek to interpret Cauchy's proof, and discuss the related epistemological questions involved in comparing distinct interpretive paradigms. Cauchy's proof is often interpreted in the modern framework of a Weierstrassian paradigm. We analyze Cauchy's proof closely and show that it finds closer proxies in a different modern framework. Keywords: Cauchy's infinitesimal; sum theorem; quantifier alternation; uniform convergence; foundational paradigms.Comment: 42 pages; to appear in Foundations of Scienc

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Although most colorectal cancer develops based on the adenoma–adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutations are preferentially associated with polypoid growth of colorectal cancer; however, little is known about the molecular mechanism that determines ulcerative growth of colorectal cancer. β-catenin complex plays a critical role both in tumorigenesis and morphogenesis. We examined the differential expression of β-catenin and its related factors among different types of colorectal cancer in order to determine any relationship with gross tumour morphology. Immunohistochemical staining of β-catenin, E-cadherin and MMP-7 was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative tumours. Protein truncation tests and single-strand conformational polymorphism for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as single-strand conformational polymorphism for the mutation of β-catenin exon 3 were also done. Nuclear expression of β-catenin was observed in 18 out of 25 (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of polypoid colorectal cancer. A significant relationship of nuclear β-catenin expression with ulcerative colorectal cancer was found (P<0.001). However, this finding was independent of adenomatous polyposis coli tumour suppressor gene mutation and E-cadherin expression. Together with previous data, we propose that different combinations of genetic alterations may underlie different morphological types of colorectal cancer. These findings should be taken into consideration whenever developing a new genetic diagnosis or therapy for colorectal cancer

AV-65, a novel Wnt/β-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model

Multiple myeloma (MM) is a malignant neoplasm of plasma cells. Although new molecular targeting agents against MM have been developed based on the better understanding of the underlying pathogenesis, MM still remains an incurable disease. We previously demonstrated that β-catenin, a downstream effector in the Wnt pathway, is a potential target in MM using RNA interference in an in vivo experimental mouse model. In this study, we have screened a library of more than 100 000 small-molecule chemical compounds for novel Wnt/β-catenin signaling inhibitors using a high-throughput transcriptional screening technology. We identified AV-65, which diminished β-catenin protein levels and T-cell factor transcriptional activity. AV-65 then decreased c-myc, cyclin D1 and survivin expression, resulting in the inhibition of MM cell proliferation through the apoptotic pathway. AV-65 treatment prolonged the survival of MM-bearing mice. These findings indicate that this compound represents a novel and attractive therapeutic agent against MM. This study also illustrates the potential of high-throughput transcriptional screening to identify candidates for anticancer drug discovery

BMI-1 Autoantibody as a New Potential Biomarker for Cervical Carcinoma

BMI-1 is overexpressed in a variety of cancers, which can elicit an immune response leading to the induction of autoantibodies. However, BMI-1 autoantibody as a biomarker has seldom been studied with the exception of nasopharyngeal carcinoma. Whether BMI-1 autoantibodies can be used as a biomarker for cervical carcinoma is unclear. In this study,BMI-1 proteins were isolated by screening of a T7 phage cDNA library from mixed cervical carcinoma tissues. We analyzed BMI-1 autoantibody levels in serum samples from 67 patients with cervical carcinoma and 65 controls using ELISA and immunoblot. BMI-1 mRNA or protein levels were over-expressed in cervical carcinoma cell lines. Immunoblot results exhibited increased BMI-1 autoantibody levels in patient sera compared to normal sera. Additionally, the results for antibody affinity assay showed that there was no difference between cervical polyps and normal sera of BMI-1 autoantibody levels, but it was significantly greater in patient sera than that in normal controls (patient 0.827±0.043 and normal 0.445±0.023; P<0.001). What's more, the levels of BMI-1 autoantibody increased significantly at stage I (0.672±0.019) compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were increased gradually during the tumor progression (stage I 0.672±0.019; stage II 0.775 ±0.019; stage III 0.890 ±0.027; stage IV 1.043±0.041), which were significantly correlated with disease progression of cervical carcer (P<0.001). Statistical analyses using logistic regression and receiver operating characteristics (ROC) curves indicated that the BMI-1 autoantibody level can be used as a biomarker for cervical carcinoma (sensitivity 0.78 and specificity 0.76; AUC = 0.922). In conclusion, measuring BMI-1 autoantibody levels of patients with cervical cancer could have clinical prognostic value as well as a non-tissue specific biomarker for neoplasms expressing BMI-1