Comparison of X-31 flight, wind-tunnel, and water-tunnel yawing moment asymmetries at high angles of attack

The X-31 aircraft are being used in the enhanced fighter maneuverability (EFM) research program, which is jointly funded by the (U.S.) Advanced Research Projects Agency (ARPA) and Germany's Federal Ministry of Defense (FMOD). The flight test portion of the program, which involves two aircraft, is being conducted by an International Test Organization (ITO) comprising the National Aeronautics and Space Administration (NASA), the U.S. Navy, the U.S. Air Force, Rockwell International, and Deutsche Aerospace (DASA). The goals of the flight program are to demonstrate EFM technologies, investigate close-in-combat exchange ratios, develop design requirements, build a database for application to future fighter aircraft, and develop and validate low-cost prototype concepts. For longitudinal control the X-31 uses canards, symmetrical movement of the trailing-edge flaps, and pitch deflection of the thrust vectoring system. The trim, inertial coupling, and engine gyroscopic coupling compensation tasks are performed primarily by the trailing-edge flaps. For lateral-directional control the aircraft uses differential deflection of the trailing-edge flaps for roll coordination and a conventional rudder combined with the thrust vectoring system to provide yaw control. The rudder is only effective up to about 40 deg angle of attack (alpha), after which the thrust vectoring becomes the primary yaw control effector. Both the leading-edge flaps and the inlet lip are scheduled with the angle of attack to provide best performance

Subject preferences of fifth-grade children.

Thesis (Ed.M.)--Boston University N.B.:Pages 155 and 309 are missing from original thesis

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

An incremental modular technique for checking LTL-X properties on Petri nets

Model-checking is a powerful and widespread technique for the verification of finite state concurrent systems. However, the main hindrance for wider application of this technique is the well-known state explosion problem. Modular verification is a promising natural approach to tackle this problem. It is based on the "divide and conquer" principle and aims at deducing the properties of the system from those of its components analysed in isolation. Unfortunately, several issues make the use of modular verification techniques difficult in practice. First, deciding how to partition the system into components is not trivial and can have a significant impact on the resources needed for verification. Second, when model-checking a component in isolation, how should the environment of this component be described? In this paper, we address these problems in the framework of model-checking LTL\X action-based properties on Petri nets. We propose an incremental and modular verification approach where the system model is partitioned according to the actions occurring in the property to be verified and where the environment of a component is taken into account using the linear place invariants of the system

Reynolds Number Effects at High Angles of Attack

Lessons learned from comparisons between ground-based tests and flight measurements for the high-angle-of-attack programs on the F-18 High Alpha Research Vehicle (HARV), the X-29 forward-swept wing aircraft, and the X-31 enhanced fighter maneuverability aircraft are presented. On all three vehicles, Reynolds number effects were evident on the forebodies at high angles of attack. The correlation between flight and wind tunnel forebody pressure distributions for the F-18 HARV were improved by using twin longitudinal grit strips on the forebody of the wind-tunnel model. Pressure distributions obtained on the X-29 wind-tunnel model at flight Reynolds numbers showed excellent correlation with the flight data up to alpha = 50 deg. Above (alpha = 50 deg. the pressure distributions for both flight and wind tunnel became asymmetric and showed poorer agreement, possibly because of the different surface finish of the model and aircraft. The detrimental effect of a very sharp nose apex was demonstrated on the X-31 aircraft. Grit strips on the forebody of the X-31 reduced the randomness but increased the magnitude of the asymmetry. Nose strakes were required to reduce the forebody yawing moment asymmetries and the grit strips on the flight test noseboom improved the aircraft handling qualities

A weakness measure for GR(1) formulae

In spite of the theoretical and algorithmic developments for system synthesis in recent years, little effort has been dedicated to quantifying the quality of the specifications used for synthesis. When dealing with unrealizable specifications, finding the weakest environment assumptions that would ensure realizability is typically a desirable property; in such context the weakness of the assumptions is a major quality parameter. The question of whether one assumption is weaker than another is commonly interpreted using implication or, equivalently, language inclusion. However, this interpretation does not provide any further insight into the weakness of assumptions when implication does not hold. To our knowledge, the only measure that is capable of comparing two formulae in this case is entropy, but even it fails to provide a sufficiently refined notion of weakness in case of GR(1) formulae, a subset of linear temporal logic formulae which is of particular interest in controller synthesis. In this paper we propose a more refined measure of weakness based on the Hausdorff dimension, a concept that captures the notion of size of the omega-language satisfying a linear temporal logic formula. We identify the conditions under which this measure is guaranteed to distinguish between weaker and stronger GR(1) formulae. We evaluate our proposed weakness measure in the context of computing GR(1) assumptions refinements

Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100

Background: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. Methods: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3–5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. Results: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10−8OR=3.3) and in the cumulative dose model (P=4.7 × 10−8HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3–5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037OR=2.4). Conclusions: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials

Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer

Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the selection of breast cancer patients for trastuzumab therapy. Amplification of the gene analysed by fluorescence in situ hybridisation (FISH) or overexpression of the protein determined by immunohistochemistry (IHC) are the two major methods to establish this status. A strong correlation has been previously demonstrated between these two methods. However, FISH is not always feasible in routine practice and weakly positive IHC tumours (2+) do not always correspond to a gene amplification. Our study was performed in order to evaluate the contribution of chromogenic in situ hybridisation (CISH), which enables detection of the gene copies through an immunoperoxidase reaction. CISH was performed in 79 breast carcinomas for which the HER2 status was previously determined by IHC and FISH. The results of IHC, FISH and CISH were compared for each tumour. CISH procedures were successful in 95% of our cases. Whatever the IHC results, we found a very good concordance (96%) between CISH and FISH. Our study confirms that CISH may be an alternative to FISH for the determination of the gene amplification status in 2+ tumours. Our results allow us to think that, in many laboratories, CISH may also be an excellent method to calibrate the IHC procedures or, as a quality control test, to check regularly that the IHC signal is in agreement with the gene statu

Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the most common cancer in women in the U.S. and Western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastático HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. Here, we performed a meta-analysis of completed clinical trials of adjuvant trastuzumab in the adjuvant setting. Survival, recurrence, brain metastases, cardiotoxicity and directions for future research are discussed.</p> <p>Methods</p> <p>A meta-analysis of randomized controlled trials (RCT) was performed comparing adjuvant trastuzumab treatment for HER2-positive early breast cancer (EBC) to observation. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings were systematically searched for evidence. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria.</p> <p>Results</p> <p>Pooled results from that five randomized trials of adjuvant Trastuzumab showed a significant reduction of mortality (p < 0.00001), recurrence (p < 0.00001), metastases rates (p < 0.00001) and second tumors other than breast cancer (p = 0.007) as compared to no adjuvant Trastuzumab patients. There were more grade III or IV cardiac toxicity after trastuzumab (203/4555 = 4.5%) versus no trastuzumab (86/4562 = 1.8%). The likelihood of cardiac toxicity was 2.45-fold higher (95% CI 1.89 – 3.16) in trastuzumab arms, however that result was associated with heterogeneity. The likelihood of brain metastases was 1.82-fold higher (95% CI 1.16 – 2.85) in patients who received trastuzumab.</p> <p>Conclusion</p> <p>The results from this meta-analysis are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk: benefit ratio demonstrated in these studies. Adequate assessment of HER-2/neu status is critical, and careful cardiac monitoring is warranted because of cardiac toxicity. Clinical trials should be designed to answer unsolved questions.</p