A region within murine chromosome 7F4, syntenic to the human 11q13 amplicon, is frequently amplified in 4NQO-induced oral cavity tumors

Our previous reports have shown that two thirds of 4-nitroquinoline-1-oxide (4NQO)-induced murine oral squamous cell carcinomas (SCC) have Hras1 mutations. Loss of heterozygosity (LOH) involving the distal portion of chromosome (Chr) 7 occurred in half of the tumors with Hras1 mutations. Here, we demonstrate that five of six tumors with LOH have 4-8-fold amplification involving the distal portion of Chr 7 (7F4). Ccnd1. Fgf4 and Fgf3, within the most telomeric region of Chr 7 (70.5 cM), are co-amplified. The region is syntenic to a previously identified human amplicon at 11q13. Only one out of eight tumors without LOH at Chr 7 had twofold amplification; the other seven had no detectable amplification. Significant amplification is restricted to the chromosome with the Hras1 mutation. Gene amplification occurred without overexpression since only one of five tumors with amplification and one of six tumors without Ccnd1 amplification expressed increased protein. Although amplification of 11q13 occurs rather frequently in human tumors, 4NQO-induced oral cavity tumors in inbred mice are the first example of a murine tumor with consistent amplification. Our observations are strikingly similar to human head and neck SCC where overexpression of genes within the 11q13 amplicon is inconsistently detected. The amplification of genes localized to human 11q13 and the syntenic region on murine Chr 7 during tumorigenesis suggests that similar structural elements are present which predispose these regions to amplification during malignant transformation.     

Fatty acid desaturase activities and polyunsaturated fatty acid composition in human liver between the seventeenth and thirty-sixth gestational weeks

OBJECTIVE: The aim of the study was to characterize n-3 and n-6 fatty acid delta5- and delta6-desaturase activities and their time course variations in human fetal liver between the 17th and 36th gestational week. STUDY DESIGN: Twenty-one biologic samples were obtained after legally approved medical abortion, according to French law. The desaturase activities were measured in the 21 liver samples by a radiochemical method by means of reverse-phase high-performance liquid chromatography. The fatty acid composition (percentage by weight) of liver phospholipids was assessed in 16 samples by gas-liquid chromatographic analysis. RESULTS: Both delta5- and delta6-desaturase activities were significantly expressed between the 17th and 36th gestational weeks. During the second trimester n-6 fatty acid delta5- and delta6-desaturase activities showed opposite patterns of variation; both then remained stable between the 25th and 36th weeks. Delta6-desaturation was higher in n-3 than n-6 fatty acids and peaked at the 18th gestational week. The percentages of linoleic and docosahexaenoic acids in liver microsomes were positively correlated with the gestation age (P < .01), whereas arachidonic acid remained stable. CONCLUSION: Significant n-3 and n-6 delta5- and delta6-desaturase activities are expressed in human fetal liver as early as the 17th gestational week and are stable throughout the third trimester. Their theoretic capacity evaluated from in vitro measurements appears lower than polyunsaturated fatty acid requirements and is not directly related to liver microsomal membrane fatty acid composition.     

Planetary exploration by robotic aerovehicles

Planetary aerobots are a new type of telerobotic science platform that can fly and navigate in a dynamic 3-dimensional atmospheric environment, thus enabling the global in situ exploration of planetary atmospheres and surfaces. Aerobots are enabled by a new concept in planetary balloon altitude control, developed at JPL, which employs reversible-fluid changes to permit repeated excursions in altitude. The essential physics and thermodynamics ofreversible-fluid altitude control have been demonstrated in a series of altitude-control experiments conducted in the Earth's atmosphere, which are described. Aerobot altitude-control technology will be important in the exploration of seven planets and satellites in our solar system. Three of these objects—Venus, Mars, and the Saturnian satellite Titan—have accessible solid surfaces and atmospheres dominated by the dense gases nitrogen or carbon dioxide. They will be explored with aerobots using helium or hydrogen as their primary means of buoyancy. The other four planets—Jupiter, Saturn, Uranus, and Neptune—have deep atmospheres that are predominantly hydrogen. It may be possible to explore these atmospheres with aerobots inflated with atmospheric gas that is then radiatively heated from the hotter gaseous depths below. To fulfill their potential, aerobots to explore the planets will need autonomous state estimators to guide their observations and provide information to the altitude-control systems. The techniques of acquiring these data remotely are outlined. Aerobots will also use on board altitude control and navigation systems to execute complex flight paths including descent to the surface and exploiting differential wind velocities to access different latitude belts. Approaches to control of these systems are examined. The application of aerobots to Venus exploration is explored in some detail: The most ambitious mission described, the Venus Flyer Robot (VFR), would have the capability to make repeated short excursions to the high-temperature surface environment of Venus to acquire data and then return to the Earth-like upper atmosphere to communicate and recool its electronic systems. Finally a Planetary Aerobot Testbed is discussed which will conduct Earth atmospheric flights to validate autonomous-state-estimator techniques and flight-path-control techniques needed for future planetary missions.     

Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation

The evaluation of dyspnea is problematic when a cause is inapparent after initial diagnostic studies. We examined the results and role of cardiopulmonary exercise testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1 and FVC. The CPET studies were interpreted by a panel and a consensus reached. Subsequent tests ordered by the primary physician were reviewed, and a final diagnosis was agreed on by the panel. Seven of 50 patients had cardiac limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either psychogenic dyspnea or no identifiable disease. Five patients had more than one clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a normal CPET had a higher VO2max and O2 pulse than those with cardiac disease, deconditioning, or hyperactive airways disease (HAD) (p < 0.05). Electrocardiographic changes identified cardiac disease while studies demonstrating ventilatory limitation identified a pulmonary process. In 24, deconditioning could not be distinguished from cardiac limitation. Of these, 14 responded to exercise training and/or weight loss, whereas 3 had cardiac disease, 7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable disease. We conclude that a diagnosis can be made in most patients with chronic dyspnea; however, further studies including bronchoprovocation are often required. Cardiopulmonary exercise testing is useful in identifying a cardiac or pulmonary process, but it is insensitive in distinguishing cardiac disease from deconditioning.     

Classifier Ensembles with a Random Linear Oracle

We propose a combined fusion-selection approach to classifier ensemble design. Each classifier in the ensemble is replaced by a miniensemble of a pair of subclassifiers with a random linear oracle to choose between the two. It is argued that this approach encourages extra diversity in the ensemble while allowing for high accuracy of the individual ensemble members. Experiments were carried out with 35 data sets from UCI and 11 ensemble models. Each ensemble model was examined with and without the oracle. The results showed that all ensemble methods benefited from the new approach, most markedly so random subspace and bagging. A further experiment with seven real medical data sets demonstrates the validity of these findings outside the UCI data collection     

Microstructural Modelling of Nb Microalloyed Steels during Thin Slab Direct Rolling Processing

The microstructural evolution during the hot rolling of coarse grain sized austenite has been modeled considering all the microstructural mechanisms (dynamic, static and metadynamic recrystallization, strain induced precipitation) that can take place during an industrial TSDR production of three Nb microalloyed steels. Based on the results obtained from the model, processing maps have been drawn for 0.02%, 0.035% and 0.05% Nb microalloyed steels. Optimum processing conditions to exploit all the benefits of the Nb microalloying have been defined considering a final gauge thickness range between 1.5 and 12.65 mm. In addition, and facing the difficulties present in the production of thick hot strip, several alternative thermomechanical schedules are proposed, which would originate microstructures with a suitable combination of homogeneity and retained strain prior to transformation.     

Comparisons of Urban Travel Forecasts Prepared with the Sequential Procedure and a Combined Model

Detailed analyses and comparisons of urban travel forecasts prepared by applying the state-of-practice sequential procedure and the solution of a combined network equilibrium model are presented. The sequential procedure for solving the trip distribution, mode choice and assignment problems with feedback is the current practice in most transportation planning agencies, although its important limitations are well known. The solution of a combined model, in contrast, results from a single mathematical formulation, which ensures a well-converged and consistent result. Using a real network, several methods for solving the sequential procedure with feedback are compared to the solution of the combined model ESTRAUS. The results of these methods are shown to have various levels of instability. The paper concludes with a call for a new paradigm of travel forecasting practice based on an internally consistent model formulation that can be solved to a level of precision suitable for comparing alternative scenarios.