Hypersonic research engine project. Phase 2: Aerothermodynamic Integration Model (AIM) data reduction computer program, data item no. 54.16

The data reduction program used to analyze the performance of the Aerothermodynamic Integration Model is described. Routines to acquire, calibrate, and interpolate the test data, to calculate the axial components of the pressure area integrals and the skin function coefficients, and to report the raw data in engineering units are included along with routines to calculate flow conditions in the wind tunnel, inlet, combustor, and nozzle, and the overall engine performance. Various subroutines were modified and used to obtain species concentrations and transport properties in chemical equilibrium at each of the internal and external engine stations. It is recommended that future test plans include the configuration, calibration, and channel assignment data on a magnetic tape generated at the test site immediately before or after a test, and that the data reduction program be designed to operate in a batch environment

Symmetry Breaking in Jetting

In the bubble-jet printing process, it has been observed that the drop that ultimately pinches off from the ink jet sometimes moves sideways rather than straight relative to the symmetry axis of the liquid jet. We examined various mechanisms that might lead to the deflection of the ink drop. In particular, we focused on whether the liquid filament that connects the lead drop to the nozzle is capable of supporting lateral waves which might propagate from the nozzle toward the lead drop and break the symmetry at pinch-off

CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen.

INTRODUCTION: Tamoxifen is one of the most effective adjuvant breast cancer therapies available. Its metabolism involves the phase I enzyme, cytochrome P4502D6 (CYP2D6), encoded by the highly polymorphic CYP2D6 gene. CYP2D6 variants resulting in poor metabolism of tamoxifen are hypothesised to reduce its efficacy. An FDA-approved pre-treatment CYP2D6 gene testing assay is available. However, evidence from published studies evaluating CYP2D6 variants as predictive factors of tamoxifen efficacy and clinical outcome are conflicting, querying the clinical utility of CYP2D6 testing. We investigated the association of CYP2D6 variants with breast cancer specific survival (BCSS) in breast cancer patients receiving tamoxifen. METHODS: This was a population based case-cohort study. We genotyped known functional variants (n = 7; minor allele frequency (MAF) > 0.01) and single nucleotide polymorphisms (SNPs) (n = 5; MAF > 0.05) tagging all known common variants (tagSNPs), in CYP2D6 in 6640 DNA samples from patients with invasive breast cancer from SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity); 3155 cases had received tamoxifen therapy. There were 312 deaths from breast cancer, in the tamoxifen treated patients, with over 18000 years of cumulative follow-up. The association between genotype and BCSS was evaluated using Cox proportional hazards regression analysis. RESULTS: In tamoxifen treated patients, there was weak evidence that the poor-metaboliser variant, CYP2D6*6 (MAF = 0.01), was associated with decreased BCSS (P = 0.02; HR = 1.95; 95% CI = 1.12-3.40). No other variants, including CYP2D6*4 (MAF = 0.20), previously reported to be associated with poorer clinical outcomes, were associated with differences in BCSS, in either the tamoxifen or non-tamoxifen groups. CONCLUSIONS: CYP2D6*6 may affect BCSS in tamoxifen-treated patients. However, the absence of an association with survival in more frequent variants, including CYP2D6*4, questions the validity of the reported association between CYP2D6 genotype and treatment response in breast cancer. Until larger, prospective studies confirming any associations are available, routine CYP2D6 genetic testing should not be used in the clinical setting.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Carboplatin-cyclophosphamide or paclitaxel without or with bevacizumab as first-line treatment for metastatic triple-negative breast cancer (BOOG 2013-01)

Background: The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. Methods: The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC +/- B or P +/- B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. Results: In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33-1.08; p = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (p(interaction) = 0.69). Conclusions:CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.Experimentele farmacotherapi

Mechanical environment alters tissue formation patterns during fracture repair

Fracture repair has previously been shown to be sensitive to mechanical environment, yet the specific relationship between strain character, magnitude and frequency, as well as other mechanical parameters, and tissue formation is not well understood. This study aimed to correlate strain distribution within the healing fracture gap with patterns of tissue formation using a rat model of a healing osteotomy subject to mechanical stimulation in bending. Finite element models based on realistic tissue distributions were used to estimate both the magnitude and spatial distribution of strains within the fracture gap. The spatial distribution of regenerating tissue was determined by microcomputed tomography and histology, and was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Results suggest that tensile strains suppress chondrogenesis during the mechanical stimulation period. After stimulation ends, however, tensile strains increased chondrogenesis followed by rapid bone formation. In contrast, in compressive environments, bone is formed primarily via intramembranous ossification. Taken together, these results suggest that intermittent tensile strains during fracture repair stimulate endochondral ossification and promote eventual bone healing compared to intermittent compressive strains and unstimulated fractures. Further understanding of these relationships may allow proposal of optimal therapeutic strategies for improvement of the fracture repair process. © 2004 Orthopaedic Research Society. Published y Elsevier Ltd. All rights reserved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34921/1/1100220523_ftp.pd

Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study

<p>Abstract</p> <p>Background</p> <p>Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. We studied Caucasian individuals (n = 1121) from 190 families in Utah and Minnesota. Of these, 859 individuals from 175 families had both baseline and post-fenofibrate treatment measurements for adiponectin. Plasma adiponectin concentrations were measured with an ELISA assay. All participants were typed for microsatellite markers included in the Marshfield Mammalian Genotyping Service marker set 12, which includes 407 markers spaced at approximately 10 cM regions across the genome. Variance components analysis was used to estimate heritability and to perform genome-wide scans. Adiponectin was adjusted for age, sex, and field center. Additional models also included BMI adjustment.</p> <p>Results</p> <p>Baseline and post-fenofibrate adiponectin measurements were highly correlated (r = 0.95). Suggestive (LOD > 2) peaks were found on chromosomes 1p35.2 and 3q28 (near the location of the adiponectin gene).</p> <p>Conclusion</p> <p>Two candidate genes, <it>IL22RA1 </it>and <it>IL28RA</it>, lie under the chromosome 1 peak; further analyses are needed to identify the specific genetic variants in this region that influence circulating adiponectin concentrations.</p