184 research outputs found
Error Minimization Controlling in Antenna Position
MFs are the main constituents of fuzzy sets. Also the structure of MF put an impact on the inference of system. Various shapes like trapezoidal, triangular & Gaussian are included. The main condition of MF is that value lies in 0 & 1. In this paper, a straightforward approach for designing a Fuzzy PID based controller is presented to evaluate, and presents the performance comparison of fuzzy logic controller with PID controller. The PID controller is implemented using three gains, and the same gain is used for both the input and output variables. The response was analyzed and compared and it shows that the gain is similar in response in terms of rise time and overshoot for both ?/3 and ?/6. According to Fuzzy PID controller system is getting improve in terms of stability. The stability time of the system is getting reduced
Quantitative Estimation of Biochemical and Inorganic Constituents Present in the GallStones
Carcinoma of gallbladder has an unusual geographic distribution. Gallbladder cancer is the most common type of biliary tract cancer which is the fifth most common gastrointestinal tract cancer and sixth most common digestive tract malignancy. Thus, the study was carried out based on quantitative analysis of biochemical constituents (cholesterol, bilirubin, bile acids, fatty acids, phospholipids and soluble protein) and inorganic constituents (sodium, potassium, calcium, magnesium, inorganic phosphate, oxalate and chloride) in all the three types of gallstones and also compare the present findings with other researchers findings. The results indicated that out of 179 gallstones, 41 were of cholesterol type, 77 mixed and 61 of pigment type. Cholesterol content was found to be the major component in all the three types of stones. Also, cholesterol stones had higher content of total cholesterol, fatty acids, phospholipids and inorganic phosphates as compared to mixed stones and pigment stones. While in case of pigment stones bilirubin, bile acids, soluble protein, sodium, potassium, calcium were found to be higher as compared to cholesterol and mixed stones. The overall findings with respect to biochemical constituents resulted that the cholesterol saturation is mostly responsible for crystallization sequences in human gallbladder
Protection against Radiation Induced Performance Decrement in Mice
Recognising that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, I Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40 %). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca/sup 2+/ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated
Modeling Dependence in Survival Times using Log-Skew Normal Shared Frailties
In survival studies, event times under a common influence are often grouped together in clusters. The association between and within these clusters can be studied using frailty models where randomness in the data or heterogeneity arising due to unknown covariates is described using a frailty variable. In shared frailty models, frailty value is common or shared for all observations within a cluster while it is conditionally independent for different clusters. In this article, we consider a model whose baseline distribution is Weibull and shared frailties follow log skew-normal distribution. This distribution increases flexibility of the model as it allows the frailty term to be positively or negatively skewed and estimation of skewness parameter enables us to comment on dependence structure of the random component. A simulation study is performed and Bayesian estimates of treatment effects, variance and skewness of frailty term are obtained using Metropolis-Hastings algorithm. It is shown that while bias and expected loss for estimates of all parameters reduce as dataset size increases, frailty parameters are more efficiently estimated when the random component is considered to be skewed. The model is also applied to two real-life datasets where positive and negative skewness is observed in the frailty term
Migration/mobility and vulnerability to HIV among male migrant workers: Maharashtra 2007-08
HIV prevalence in Maharashtra is one of the highest among Indian states. The specific objectives of this study were: to understand the patterns and drivers of migration/mobility of men who migrate for the purpose of work in the state of Maharashtra; to describe the characteristics of vulnerable subpopulations among migrant men; and to examine the determinants of high-risk sexual behavior among the subpopulations of migrant men with particular emphasis on the role of mobility in determining the sexual risk behavior. The present study clearly demonstrates that these male migrants, married or otherwise, retain strong connectivity to their native villages, but also show high levels of sexual activity—including significant levels of high-risk sexual activity—making it imperative to study the situation in the sending districts regarding HIV prevalence and spread. The indication from this study is clear: in the context of high-risk sexual behavior (among both married and unmarried migrants) and the low levels of knowledge, condom use, and risk perception, the chances of sending households and districts becoming areas of high HIV prevalence are great. Further exploration of the sexual behavior pattern in sending areas is necessary to obtain additional insights into the possible routes of HIV transmission
Treatment with clobetasol propionate 0.025% topical therapy in various dermatoses
Owing to their anti-inflammatory and vasoconstrictive properties. Topical corticosteroids (TCs) provide benefits in various dermatological conditions, including atopic eczema, psoriasis, chronic hand eczema, and localized vitiligo. Clobetasol propionate (CP) is the most common topical agent possessing anti-inflammatory, antimitotic, antipruritic, and immunosuppressive properties that are employed in the management of plaque psoriasis. CP 0.025% cream was approved by the United States food and drug administration for the treatment of moderate-to-severe psoriasis in adult patients. The formulation is free from known contact allergens, such as propylene glycol, short-chain alcohols, and sorbitol-based emulsifiers, and has demonstrated hypoallergenic effects. High penetration of active ingredients and a lower degree of systemic absorption make CP 0.025% an effective and safe agent. This case series discusses the clinical experience of using CP 0.025% cream in various dermatologic conditions, focusing on its efficacy and safety
Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer
Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse model of spontaneous BrM and evaluated the therapeutic effect of CBZ and NER in vivo. The combination treatment of NER and CBZ significantly inhibited proliferation and migration in ERBB2+ cell lines and reduced the organoid growth in vitro. Mechanistically, the combination treatment of NER and CBZ substantially inhibited ERK activation downstream of the c-MET/ERBB1 axis. Orthotopically implanted SKBrM3+ cells formed primary tumor in the mammary fat pad and spontaneously metastasized to the brain and other distant organs. Combination treatment with NER and CBZ inhibited primary tumor growth and predominantly prevented BrM. In conclusion, the orthotopic model of spontaneous BrM is clinically relevant, and the combination therapy of NER and CBZ might be a useful approach to prevent BrM in BC
MicroRNA-1 Attenuates the Growth and Metastasis of Small Cell Lung Cancer through CXCR4/FOXM1/RRM2 Axis
BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.
METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, identified miRNA) in patient serum samples and SCLC cell lines. To assess the therapeutic potential of miR-1, we developed various in vitro models, including miR-1 sponge (miR-1Zip) and DOX-On-miR-1 (Tet-ON) inducible stable overexpression systems. Mouse models derived from intracardiac injection of SCLC cells (miR-1Zip and DOX-On-miR-1) were established to delineate the role of miR-1 in SCLC metastasis. In situ hybridization and immunohistochemistry were used to analyze the expression of miR-1 and target proteins (mouse and human tumor specimens), respectively. Dual-luciferase assay was used to validate the target of miR-1, and chromatin immunoprecipitation assay was used to investigate the protein-gene interactions.
RESULTS: A consistent downregulation of miR-1 was observed in tumor tissues and serum samples of SCLC patients compared to their matched normal controls, and these results were recapitulated in SCLC cell lines. Gain of function studies of miR-1 in SCLC cell lines showed decreased cell growth and oncogenic signaling, whereas loss of function studies of miR-1 rescued this effect. Intracardiac injection of gain of function of miR-1 SCLC cell lines in the mouse models showed a decrease in distant organ metastasis, whereas loss of function of miR-1 potentiated growth and metastasis. Mechanistic studies revealed that CXCR4 is a direct target of miR-1 in SCLC. Using unbiased transcriptomic analysis, we identified CXCR4/FOXM1/RRM2 as a unique axis that regulates SCLC growth and metastasis. Our results further showed that FOXM1 directly binds to the RRM2 promoter and regulates its activity in SCLC.
CONCLUSIONS: Our findings revealed that miR-1 is a critical regulator for decreasing SCLC growth and metastasis. It targets the CXCR4/FOXM1/RRM2 axis and has a high potential for the development of novel SCLC therapies. MicroRNA-1 (miR-1) downregulation in the tumor tissues and serum samples of SCLC patients is an important hallmark of tumor growth and metastasis. The introduction of miR-1 in SCLC cell lines decreases cell growth and metastasis. Mechanistically, miR-1 directly targets CXCR4, which further prevents FOXM1 binding to the RRM2 promoter and decreases SCLC growth and metastasis
Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems
BackgroundHuman immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico.MethodsWe performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017.ResultsAll countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries-apart from Ecuador-across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups-the median age group among decedents ranged from 30 to 45years of age at the municipality level in Brazil, Colombia, and Mexico in 2017.ConclusionsOur subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.Peer reviewe
Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18 : a modelling study
Background: High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. Methods: In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15–49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000–18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit. Findings: The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2 ·8 (95% uncertainty interval 2·1–3·8) in Mauritania to 1585·9 (1369·4–1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7–0·9) in Mauritania to 676· 5 (513· 6–888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique, had the highest estimated HIV incidence (4661·7 [2544·8–8120·3]) cases per 100000 people in 2018 and Inhassunge District, Zambezia Province, Mozambique, had the highest estimated HIV mortality rate (1163·0 [679·0–1866·8]) deaths per 100 000 people. Further, the rate of reduction in HIV incidence and mortality from 2000 to 2018, as well as the ratio of new infections to the number of people living with HIV was highly variable. Although most second-level administrative units had declines in the number of new cases (3316 [81· 1%] of 4087 units) and number of deaths (3325 [81·4%]), nearly all appeared well short of the targeted 75% reduction in new cases and deaths between 2010 and 2020. Interpretation: Our estimates suggest that most second-level administrative units in sub-Saharan Africa are falling short of the targeted 75% reduction in new cases and deaths by 2020, which is further compounded by substantial within-country variability. These estimates will help decision makers and programme implementers expand access to ART and better target health resources to higher burden subnational areas
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