The effect of a particle travelling through a laminar boundary layer on transition

This study investigates how a particle travelling through an initially laminar boundary layer can lead to its breakdown to turbulence With increasing kerosene costs and an awareness of limited available oil reserves, laminar flow technologies are again being considered to realize the necessary efficiency increases of aircraft, and more detailed information on the operational issues is required. The adverse impact of flying through cirrus clouds has been simplified to the effect of a single particle on a laminar boundary layer over a zero-pressure gradient flat plate. First results indicate that the critical values could be substantially smaller than initially assumed

A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies

Preclinical studies using genetically engineered mouse models (GEMM) have the potential to expedite the development of effective new therapies; however, they are not routinely integrated into drug development pipelines. GEMMs may be particularly valuable for investigating treatments for less common cancers, which frequently lack alternative faithful models. Here, we describe a multicenter cooperative group that has successfully leveraged the expertise and resources from philanthropic foundations, academia, and industry to advance therapeutic discovery and translation using GEMMs as a preclinical platform. This effort, known as the Neurofibromatosis Preclinical Consortium (NFPC), was established to accelerate new treatments for tumors associated with neurofibromatosis type 1 (NF1). At its inception, there were no effective treatments for NF1 and few promising approaches on the horizon. Since 2008, participating laboratories have conducted 95 preclinical trials of 38 drugs or combinations through collaborations with 18 pharmaceutical companies. Importantly, these studies have identified 13 therapeutic targets, which have inspired 16 clinical trials. This review outlines the opportunities and challenges of building this type of consortium and highlights how it can accelerate clinical translation. We believe that this strategy of foundation-academic-industry partnering is generally applicable to many diseases and has the potential to markedly improve the success of therapeutic development

Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation

Noonan syndrome (NS) is characterized by short stature, facial dysmorphisms and congenital heart defects. PTPN11 mutations are the most common cause of NS. Patients with NS have a predisposition for leukemia and certain solid tumors. Data on the incidence of malignancies in NS are lacking. Our objective was to estimate the cancer risk and spectrum in patients with NS carrying a PTPN11 mutation. In addition, we have investigated whether specific PTPN11 mutations result in an increased malignancy risk. We have performed a cohort study among 297 Dutch NS patients with a PTPN11 mutation (mean age 18 years). The cancer histories were collected from the referral forms for DNA diagnostics, and by consulting the Dutch national registry of pathology and the Netherlands Cancer Registry. The reported frequencies of cancer among NS patients were compared with the expected frequencies using population-based incidence rates. In total, 12 patients with NS developed a malignancy, providing a cumulative risk for developing cancer of 23% (95% confidence interval (CI), 8–38%) up to age 55 years, which represents a 3.5-fold (95% CI, 2.0–5.9) increased risk compared with that in the general population. Hematological malignancies occurred most frequently. Two malignancies, not previously observed in NS, were found: a malignant mastocytosis and malignant epithelioid angiosarcoma. No correlation was found between specific PTPN11 mutations and cancer occurrence. In conclusion, this study provides first evidence of an increased risk of cancer in patients with NS and a PTPN11 mutation, compared with that in the general population. Our data do not warrant specific cancer surveillance

IMCE2003-43546 ACOUSTIC RADIATION FROM SEPARATED BOUNDARY-LAYER FLOW OVER A REARWARD-FACING STEP ON A FLAT PANEL

ABSTRACT The acoustic radiation from a turbulent boundary layer that occurs downstream of a rearward facing step discontinuity and reattaches to a flat plate is considered experimentally. The step is exposed to a zero incidence, uniform subsonic flow. A quiet wall jet facility situated in an anechoic chamber is used for the studies. The "point" wall pressure spectra are measured by small, "pinhole" microphones located at various locations under the layer, including a point directly in the 90º corner of the step. The wall pressure fluctuations measured at the various locations are correlated with the signal detected by a far-field microphone. The measured cross-spectral densities are thus used to identify the relative contributions of the various flow regimes to the direct radiation. It is shown that the separation of the flow over the corner of the step is a dominant acoustic source, which is supported not only by the measured cross spectra, but also by the favorable comparison of the measured velocity power law to the theoretical value