Steady pressure measurements in the strap-on booster interference Region of 1/20 scale aslv configuration

Wind tunnel studies were carried out to obtain pressure distribution in the strap-on booster interference region of 1/20th scale Augmented Satellite Launch Vehicle model configuration. Tests were done in the 1 .2m tunnel at NAL in the Mach number range of 0 .5 to 2.5 for the clean configuration as well as with spring housing attachments on the strap-on boosters. Both the model configurations with the boosters strapped on to the core vehicle in the horizontal plane (pitch) and in the vertical plane (yaw) were tested for incidences at 0, 4 and -4 deg. In addition pressure measurements were also done on the core vehicle alone at Mach numbers 2.1, 2.5 and 3.0 for 0, +4 degree incidences. The test Reynolds number was varied from 0.7 to 1.3 millions based on the maximum diameter of the model. The pressure distribution showed significant interference effects of boosters on the core vehicle. It is observed that the positive pressure peak associated with flow compression at the flare junction increases with increase in Mach number. In the pitch plane the normal force distribution remains positive along the core vehicle whereas in the yaw plane it is of less magnitude

ETS Transcription Factors Control Transcription of EZH2 and Epigenetic Silencing of the Tumor Suppressor Gene Nkx3.1 in Prostate Cancer

ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated.We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1) and tumor suppressor (i.e., ESE3) properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high), ESE1(high), ESE3(low) and NoETS tumors) were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high) and ESE3(low) tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2.These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies

Modulation of Androgen Receptor Signaling in Hormonal Therapy-Resistant Prostate Cancer Cell Lines

Background: Prostate epithelial cells depend on androgens for survival and function. In (early) prostate cancer (PCa) androgens also regulate tumor growth, which is exploited by hormonal therapies in metastatic disease. The aim of the present study was to characterize the androgen receptor (AR) response in hormonal therapy-resistant PC346 cells and identify potential disease markers. Methodology/Principal Findings: Human 19K oligoarrays were used to establish the androgen-regulated expression profile of androgen-responsive PC346C cells and its derivative therapy-resistant sublines: PC346DCC (vestigial AR levels), PC346Flu1 (AR overexpression) and PC346Flu2 (T877A AR mutation). In total, 107 transcripts were differentially-expressed in PC346C and derivatives after R1881 or hydroxyflutamide stimulations. The AR-regulated expression profiles reflected the AR modifications of respective therapy-resistant sublines: AR overexpression resulted in stronger and broader transcriptional response to R1881 stimulation, AR down-regulation correlated with deficient response of AR-target genes and the T877A mutation resulted in transcriptional response to both R1881 and hydroxyflutamide. This AR-target signature was linked to multiple publicly available cell line and tumor derived PCa databases, revealing that distinct functional clusters were differentially modulated during PCa progression. Differentiation and secretory functions were up-regulated in primary PCa but repressed i

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs

Epigenetic modulators as therapeutic targets in prostate cancer

Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.info:eu-repo/semantics/publishedVersio

Force measurements on RH-560 (APC-REX)

Scaled models of the RH-560 ,(APC-REX) were tested in the 1.2m Trisonic wind tunnel of National Aeronautical Laboratory . The tests were conducted in two phases, the first phase covered the tests on complete model (1/7.5 scale model of booster and sustainer) and the second phase covered the tests on sustainer alone model (1/6 scale model) . These tests were aimed to get the aerodynamic forces and moments covering a Mach number range of 0.5 to 4.0 on complete model and 1 .0 to 4.0 on sustainer model and an angle of attack range of -6° to 6 °. The results in the form of aerodynamic force and moment coefficients and center of pressure location are presented in this report. Effects of fins, end plates and protrusions are also investigated in these tests

Steady pressure measurements in the strap on booster interference Region of 1/20 scale ASLV configuration

Windˇtunnelˇstudiesˇwereˇcarriedˇoutˇtoˇobtainˇpressureˇdistribution inˇtheˇstrapˇonˇboosterˇ interferenceˇregionˇof ˇ1/20thˇscaleˇAugmented Satelliteˇ Launchˇ Vehicleˇ modelˇconfigurationˇˇTestsˇwereˇ doneˇinˇthe 1.2mˇtunnelˇatˇNALˇinˇtheˇMachˇnumberˇrangeˇofˇ0.5ˇtoˇ2.5ˇforˇthe cleanˇconfigurationˇ asˇ wellˇasˇwithˇ springˇhousingˇattachmentsˇonˇthe strapˇonˇ boostersˇ Bothˇtheˇmodelˇconfigurationsˇwithˇtheˇboosters strapped onˇtoˇtheˇcore ˇ vehicleˇinˇtheˇhorizontalˇplaneˇ ˇpitchˇˇandˇin theˇverticalˇplaneˇˇyawˇˇwereˇ testedˇforˇincidencesˇatˇ0ˇˇ4ˇandˇˇ4ˇdeg ˇ Inˇadditionˇpressureˇmeasurementsˇwereˇalsoˇdoneˇonˇtheˇcoreˇvehicle aloneˇatˇMachˇnumbersˇ2ˇ1ˇˇ2ˇ5ˇ andˇ3ˇ0ˇforˇ0ˇˇt4ˇdegreeˇincidences. The ˇˇtestˇReynoldsˇ numberˇwasˇvariedˇfromˇ0.7ˇtoˇ1.3 ˇmillionsˇbased onˇtheˇmaximumˇdiameterˇ ofˇtheˇmodel ˇ Theˇpressureˇdistributionˇshowedˇsignificantˇinterferenceˇeffects ofˇboostersˇonˇtheˇcoreˇvehicle Itˇisˇobservedˇthatˇtheˇpositiveˇpressure peakˇassociatedˇ withˇ flowˇcompressionˇatˇtheˇflareˇjunctionˇincreases withˇincreaseˇinˇMachˇnumber ˇ inˇtheˇpitchˇplaneˇ theˇnormalˇforce distributionˇremainsˇpositiveˇ alongˇtheˇcoreˇvehicleˇwhereasˇinˇtheˇyaw planeˇitˇ isˇofˇlessˇmagnitude