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Germilne mutations of BRCA1 confer an increased risk for breast and ovarian cancer in women and prostate cancer in men. Recent studies suggest that the tumor suppressor activity of BRCAl is due, in part, to physical/functional interactions with other tumor suppressors, including p53 and the retinoblastoma (RB) protein. Two RB binding sites on BRCAl were identified, one in the C-terminal BRCT domain and one in the N-terminus, between aa 304 and 394 (Yarden and Brody, PNAS USA 96: 4983-4988, 1999; Aprelikova et al. PNAS USA 96: l1866-ll87l, 1999). The N-terminal region of BRCAl contains a consensus RB binding motif ((358)LXCXE), but the role of this site in mediating RB binding and BRCA1/RB functional activity is unknown. Our studies indicate that the BRCA1 interacts with RB, through a binding site between aa 302 and 440, but the binding is not dependent on the LXCXE motif. Nor does the interaction require an intact A/B binding pocket of RB. Transient or stable expression of a wild-type BRCAl gene (wtBRCA1) caused down-regulation of expression of RB, plO7 and p130, associated with a chemosensitivity to DNA-damaging agents. In contrast, expression of an LXCXE-defective BRCAl mutant (LXCXE -> RXRXH) did not cause down-regulation of the RB proteins and the induction of chemoresistance. Our findings suggest that some biologic functions of BRCA1 (eg., chemosensitization) are due, in part, to down-regulation of RB family proteins mediated by an LXCXE site embedded within the N-terminal RB binding site.

Tissue inhibitors of matrix metalloproteinase (TIMPs) are multifunctional proteins with both matrix metalloproteinases (MMPs) inhibitory effects and growth regulatory activity. TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and characterized. Enzymatic kinetic studies revealed IC(50) values of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively. TIMP-4 has a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we administrated TIMP-4 both locally by transfection of the gene into breast cancer cells and systemically by a gene therapy approach with intramuscular injection of TIMP-4 expression plasmid. Overexpression of TIMP-4 locally in breast cancer cells inhibited the invasion of the cells in the in vitro and tumor growth in nude mice. However, here we report that systemic administration of human TIMP-4 by electroporation-mediated intramuscular injection of naked TIMP-4 DNA stimulates tumorigenesis of human breast cancer cells in nude mice. In consistence with tumor stimulatory effect, TIMP-4 upregulates Bcl-2 and Bcl-X(L) protein. TIMP-4 also protects apoptosis in human breast cancer cells in vitro and mammary tumors in vivo. A synthetic MMP inhibitor BB-94 did not have such anti-apoptotic effect. Analyses of TIMP-4 expression in human mammary specimens indicate that TIMP-4 protein is increased in mammary carcinoma cells compared with normal mammary epithelial cells. These data indicate an anti-apoptotic activity in breast cancer cells and a tumor-stimulating effect of TIMP-4 when administrated systemically.

We recently identified and cloned a novel breast cancer-specific gene BCSGl by direct differential cDNA sequencing. BCSG1 has a great sequence homology with Alzheimer disease (AD)-related neurotic protein synuclein, and thus was also named as synuclein gamma (SNCG). Overexpression of SNCG in breast cancer cells led to a significant increase in motility and invasiveness in vitro and a profound augmentation metastasis in vivo. Our data suggest that the member of neurotic protein synucleins might have important functions outside the central nervous system and play a role in breast cancer progression., Original contains color plates: All DTIC reproductions will be in black and white.

TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and characterized. Enzymatic kinetic studies revealed IC(50) values of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively. TIMP-4 has a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we administrated TIMP-4 both locally by transfection of the gene into breast cancer cells and systemically by a gene therapy approach with intramuscular injection of TIMP-4 expression plasmid. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls.

Analytical modeling of tribological behavior of interacting bodies is undertaken in three parts: modeling stresses at the surface and in the coatings of a coated solid, friction or traction at the interface between two contacting solids, and modeling of wear under given conditions of operation. Stress modeling of coated solids is accomplished by plane strain numerical solutions for line contact problems and finite element solutions of the more complex elliptical contacts. Both mechanical and thermal stresses in the solid are modeled. Semi-empirical relations are derived by regression analysis of experimental traction-slip data for several solid lubricants. The traction equations are readily applicable for the design and performance simulation of mechanical components. Wear is modeled as a multi-process phenomena. A generalized wear equation is developed such that one of the terms consists of Archard-type sliding wear while others represent thermally activated phenomena with varying activation energies. The model thus provides wear prediction as a function of load, speed and temperature. Similar to the traction model, coefficients of the wear equations are derived by fitting the model to experimental data. Good correlations of the model are demonstrated with two sets of experimental wear data.

We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. The expression and biological relevance of TIMP-4 on breast cancer progression were studied. TIMP-4 was primarily expressed in the stromal fibroblasts in the mammary gland. However, the TIMP-4 protein was detected in the mammary epithelial cells with an increased level in the malignant infiltrating breast epithelial cells compared with normal breast epithelial cells. Overexpression of TIMP-4 inhibited the invasion potential of human breast cancer cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4 - 10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls. Purified recombinant TIMP-4 protein demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression.

The current project is to study a previously identified breast cancer specific gene, originally designated BCSGl, in human breast cancer progression leading to metastasis. BCSG1, expressed in high abundance in metastatic breast cancer cDNA library but scarcely in normal breast cDNA library, was identified and cloned by differential cDNA sequencing. Interestingly, BCSGl revealed no homology to any other known oncogenes; rather BCSGl revealed extensive sequence homology to Alzheimer disease (AD)-related neurotic proteins synuclein alpha (SNCA) and synuclein beta (SNCB), and thus was also named as synuclein gamma (SNCG). Preliminary studies demonstrated that: 1) SNCG expression was a stage-specific in human breast: undetectable in normal or benign breast lesions, low level and partial expression in low grade ductal carcinoma in situ but extremely, hi h level in advanced infiltrating breast cancer; 2) SNCG expression in human breast cancer cells is dramatically suppressed by tumor growth inhibitor oncostatin M (OM) , a cytokine predominantly produced by activated T cells and macrophages; 3) overexpression of SNCG in breast cancer cells led to a significant increase in cell motility and invasiveness in vitro and a profound augmentation of metastasis in vivo. The overall hypothesis to be evaluated is that SNCG, a neurotic protein mainly expressed in brain and localized to presynaptic terminals, play a critical role in breast cancer malignant progression from benign or non- invasive stage to metastatic stage. In this regard, up-regulation of SNCG will increase cell motility and thus facilitate invasion and metastasis.

We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we transfected a full-length TIMP-4 cDNA into MDA-MB-43 5 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected (TIMP4-435) versus control (neo-435) clones in the mammary fat pad of athymic nude mice. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls. Purified recombinant TIMP4 protein demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression.

A novel breast cancer specific gene BCSG1 was cloned by differential cDNA sequencing. BCSG1, a Alzheimer's disease (AD) amyloid like protein, is expressed in high abundance in breast cancer cDNA library but scarcely in normal breast cDNA library. Preliminary studies suggest that: (1) BCSG1 expression is a stage-specific in human breast: undetectable in normal or benign breast lesions, low level and partial expression in low grade ductal carcinoma in situ but extremely high level in advanced infiltrating breast cancer; (2) overexpression of BCSG1 in human breast cancer cells stimulates cell growth and invasion potentials in vitro and tumor growth in nude mice; (3) BCSG1 expression in breast cancer cells is dramatically suppressed by tumor growth inhibitor oncostatin M (OM), a cytokine predominantly produced by activated T cells and macrophages. This OM-induced transcriptional suppression of BCSG1 gene is associated with OM-mediated growth inhibition. The overall hypothesis to be evaluated is that overexpression of BCSG1 may correlate with clinical aggressiveness of breast cancer and lead to their abnormal growth and malignant progression. We will study the biological functions of BCSG1 on breast cancer growth and metastasis; to define its range of expression and begin to determine the mechanisms whereby BCSG1 expression is involved in breast cancer progression.

Traction behavior of several aerospace fluids and lubricants is correlated to simplified Newtonian models based on viscosity pressure temperature relations. Model coefficients are derived by regression analysis of experimental traction data, which is obtained by a conventional rolling disk type test machine. The model provides fast computation of traction coefficient under prescribed operating conditions and it is well suited for complex computer codes for the dynamic performance simulation of rolling bearings, where the required amount of computer time often imposes severe restrictions on use of the model for practical design.

The feasibility of using a Fourier Transform Infrared (FTIR) spectrometer from an airborne platform for remote sensing of air pollution was investigated. Air Force Phillips Laboratory mounted a FTIR spectrometer into a small twin engine aircraft and obtained the data used in this investigation. The aircraft was flown over sections of New York and New England. The spectrometer was operated two different configurations, a passive configuration where the spectrometer viewed the warm ground and atmosphere below the aircraft, and an extractive mode where outside air was flushed through a 100 meter optical path gas cell. The spectral data were analyzed at AIL Systems Inc. for the presence of atmospheric pollutants.

It is known that breast cancer is dependent upon estrogenic hormones in about one-third of all clinical cases and can be inhibited by antiestrogenic antagonists. We are now hypothesizing that progestational hormones may also function as a stimulus for onset and progression of breast cancer and antiprogestin can interrupt these processes. Antiestrogen tomaxifen treatment enhances the progestational stimulation of tumor growth. Mammary derived growth inhibitor (MDGI) is a mammary epithelial cell growth inhibitor and differentiation factor.

Recently, we cloned and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we transfected a full-length TIMP-4 cDNA into MDA-MB-435 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected vs control clones in the mammary fat of athymic nude mice. Overexpression of TIMP-4 significantly inhibited tumor growth rates; reached (3.5-14)-fold smaller primary tumor volumes and at sacrifice; and gave lower rates of axillary lymph node and lung metastasis as compared with control clones. A high-throughput direct differential cDNA sequencing approach was employed to identify genes differentially expressed in normal breast as compared with breast cancer. Of many putative differentially expressed genes, a breast cancer specific gene BCSG1, which was expressed in high abundance in a breast cancer cDNA library but scarcely in a normal breast cDNA library, was identified as a putative breast cancer marker. In situ hybridization analysis demonstrated a stage-specific BCSGl expression: undetectable in normal or benign breast lesions, partial expression in ductal carcinoma in situ, but extremely high level in advanced infiltrating breast cancer. BCSG1 overexpression may indicate breast cancer malignant progression.

An animated graphics model has been developed to display the motion and interactions in rolling bearings. Graphics primitives in the standard PHIGS (Programmers Hierarchical Interactive Graphics System) libraries are used to develop graphic structures of the various bearing elements and graphic objects. Components of bearing element motion, as obtained by solution to the classical differential equations of motion for all the bearing elements, are used to edit the local transformation elements in these structures and then refresh the display as a function of time. Thus an animated motion of bearing elements is produced. Graphic capabilities, such as double buffering and z-buffers are used to present a smooth animated video. The net outcome of this project is a computer code AGORE (Animated Graphics Of Rolling Elements) which interfaces with existing bearing dynamics code, ADORE, to display the bearing motions in an animated fashion., Original contains color plates: All DTIC and NTIS reproductions will be in black and white.

It is known that breast cancer is dependent upon estrogenic hormones in about one-third of all clinical cases and can be inhibited by antiestrogenic antagonists. We are now hypothesizing that progestational hormones may also function as a stimulus for onset and progression of breast cancer and antiprogestin can interrupt these processes. The overall goals are to develop an in vivo model system for evaluating effects of progestins and antiprogestins on human breast tumor growth and metastasis. Using our recently established T47D-derived TKS-7 (FOF-4 transfected) metastatic model, we have initiated experiments designed to investigate the effects of progestational hormones and antiprogestin onapristone on the regulation of human breast cancer growth and metastasisin nude mice. In addition, we will attempt to identify mechanisms underlying these regulations. TKS-7 behaves like a hormone-independent but still hormone responsive phenotype in nude mouse. Progesterone significantly stimulates the tumor growth; and this progesterone-induced growth stimulation can be inhibited by antiprogestin onapristone. Furthermore antiestrogen tomaxifen treatment enhances the progestational stimulation of tumor growth.

(1) Using T47D cells, our lab built a system in which transfection of FGF4 into this cell line allows cells to form progressively growing tumors in athymic nude mice. The overexpression of FGF also forms lymph node metastasis. Both estrogen and progesterone stimulate the tumor growth. This hormone responsible T47D-derived tumorigenic and metastatic model will be valuable in evaluation of the biological relevance of 80kDa proteinase in breast cancer progression. (2). We recently cloned an apparently new TIMP (tissue inhibitor of metalloproteinase) named TIMP4 and examined its expression in normal, benign and malignant human breast tissues. Our results demonstrated an inverse correlation between the TIMP4 expression and breast cancer progression. In addition, in situ hybridization detected the TIMP4 transcript only in the stromal cells of normal and benign breast tissue but not in the stromals of infiltrating breast carcinomas. Our data suggest that the decreased levels of TIMP4 seen in the breast carcinomas may be too low to prevent MIAP activity and cellular invasion. We hypothesize that the down-regulation of TIMP4 contributes human breast cancer progression and correlate directly with clinical aggressiveness of breast cancer., Original contains color plates: All DTIC/NTIS reproductions will be in black and white.

A complete two dimensional LV system is described. The operation of the system is presented, along with a description of how the approach simplifies multi-dimensional measurements. The unique aspect of this system is its efficient design consisting of a single solid state laser, a single avalanche photo diode as the optical receiver, and a single frequency domain signal analysis tool. (Author)

A two dimensional animated graphics model to simulate dynamic motions of the balls and cage, in a plane normal to the bearing axis, in an angular contact ball bearing is developed. The graphics modeling is based on the primitives available under the Programmers Hierarchical Interactive Graphics System (PHIGS), which is now an international standard and it is supported on a wide range of computer systems. Appropriate transformations to produce the animated motion of bearing elements are derived from the dynamic solutions provided by the bearing dynamics computer code ADORE. Necessary modifications to ADORE to store all the required solutions in an ASCII data file are performed. This newly developed data file provides the interface between ADORE and the graphics model. Since PHIGS graphics standard is very widely supported, the graphics model developed herein can be used on a wide range of computer systems. For the present investigation an IBM-RISC/6000 work station is used., Software not fully developed for distribution.

Analyses are developed to predict the tractive forces that will occur in a rolling-sliding contact between one body of a single material and a second body containing a thin coating of solid lubricant. Isotropic materials and conditions of plane strain are assumed. The loaded coating thickness is taken to be large compared with asperity heights but small compared with contact dimensions. Contact pressures are assumed to be high compared with the shear yield stress of the coating which in turn is taken to be small compared with those of the substrates. An initial analysis is presented for approximating tractions under conditions of low slide to roll ratios which includes elastic, plastic, creep and thermal interactions. This analysis implements an approach developed for elastohydrodynamic lubrication at pressures and shear rates where the lubricant exhibits solid-like behavior but is oriented toward solid lubrication and includes a more extensive thermal analysis. Solutions are presented which show the influence of elastic modulus, rheological model, yield stress and pressure and temperature dependence of mechanical properties on predicted traction and shear stress behavior. An analysis is presented which reduces the Levy-Von Mises equations for a plastic-rigid system so as to approximate thin film behavior under conditions of high slip rate. This analysis shows the expected development of a nearly hydrostatic state of stress for the coating in the contact zone but also shows that the film cannot support a pressure gradient when yielding occurs inside the coating.

A finite element approach to model stress distributions in coated solids is developed. The personal computer based PC-ANSYS code is used to implement the approach on a personal computer system. The three types of boundary loading considered are an elliptical normal pressure distribution, a shear stress distribution proportional to the normal pressure, and a thermal flux proportional to the surface shear. The model predictions are validated against the classical Hertz theory and plane strain solution obtained independently by well established Fourier transform approaches. The deviations of the finite element model from the other available solutions is found to be less than 1%. Parametric results of the model establish practical significance of the modeling approach for optimization of coating thickness, materials selection, and for the development of coating application techniques and procedures to ensure acceptable 'break-away' stresses in the coating and at the coating/substrate interface. Extension of the finite element approach to the modeling of complex three dimensional contacts is demonstrated by modeling a rectangular contact over a semi-infinite solid. This preliminary three-dimensional model, along with the two-dimensional parametric results demonstrate technical feasibility of the overall modeling approach. In addition, the results provide a strong analytical foundation for the development of a more rigorous and sophisticated models, and wide range of practical applications. (js)

A semi-empirical approach to modeling the traction behavior of turbine engine lubricants in concentrated contacts is presented. Coefficients for the model are determined by carrying out a nonlinear least-square analysis of available traction data. The effectiveness of the modeling approach is demonstrated by incorporating the lubricant traction model in a bearing dynamics computer code and by carrying out bearing performance simulations as a function of the coefficients of the traction model. Keywords: Traction, Lubricant Modeling, Elastohydrodynamic, Lubrication, Rolling Element Bearings, oils.

The Articulated Total Body (ATB) Model was modified for improved modeling of the biomechanics of the man/seat ejection problem. The new ATB-IIIA version of the model incorporates whole-body wind tunnel data to model windblast, an improved algorithm to simulate the ACES-II STAPAC assembly, and calculates the location of the instantaneous center-of-mass for either the man or the man/seat system. The enhanced ATB Model provides for the modeling of the ACES-II ejection sequence from initiation of ejection to man/seat separation. The data for several ejection simulations are provided and discussed in detail. An extensive literature search was conducted in the area of ejection, windblast response and restraint systems. A summary of pertinent reports and available wind tunnel data is provided, as well as recommendations for future wind tunnel testing to correct for deficiencies in currently available aerodynamic data.

The primary limitation to increasing the operating speeds of robots, and hence their productivity, is the vibrations induced by high accelerations. Since these vibrations are usually only important near the endpoint of the arm trajectory, this paper proposes the use of a separate controller for this part of the trajectory, specifically designed for vibration control. This makes use of the fact that in the neighborhood of the endpoint the system can be considered linear. To solve the modeling problems accurate for the current endpoint and load conditions, it is proposed that a robot operator conduct a test run during which data is automatically taken. It is later used off-line by the robot microprocessor to obtain the system model in the neighborhood of the endpoint, and the feedback control gains. A deadbeat control law is studied here because of its time optimality and because it has a feedback form. The research here establishes, both by simulation and by experimental testing, that the overall approach has considerable promise. However, some new development is needed in the control law design to realize its promise.

Analogs of phospholipids and their biosynthetic intermediates were synthetic targets as novel potential antimalarials. Targeted analogs contained one or more types of non-hydrolyzable groups, including ether, phosphonate, and phosphinate moieties. Synthetic routes varied with each target, and were quite complex for the cytidine-containing analogs of the biosynthetic intermediates, involving a number of novel steps. The phospholipid analogs were successfully prepared and submitted. However, during the course of the contract syntheses of the major cytidine-containing target compounds could not be completed, although a monophosphonate 'model analog' was prepared and submitted. None of the thirteen compounds (including three targets and one 'model target') submitted displayed appreciable antimalarial activity in vivo in the standard test system. (Author)

The purpose of this simulation is to determine the accuracy performance capability of an aircraft positioning system based on the triangulation principle when combined with distance measuring equipment (DME), inertial elements and filtering (blending) of data from the various sensors. The simulation also determines how sensitive the overall system accuracy is to changes in certain key sensor parameters. (Author)

The Navy Vertical Takeoff and Landing Project (NAVOTLAND) has been established to improve the hover, approach and landing capabilities of Navy and Marine Corps V/STOL aircraft. These aircraft may be required to operate from aviation facilities ships (non-aviation ships), small aviation ships (such as LPH, LHA, VSS) and Marine Corps tactical sites. Common problems in the aircraft missions include operations under severe weather, day and night, often requiring the landing in a confined area. The NAVTOLAND program will correlate and investigate the development of all systems and techniques which are involved in enabling the pilot to fly V/STOL Aircraft onto Navy Ships and Marine Corps tactical sites. Guidance sensors have been identified as being critical to the NAVTOLAND program. A guidance sensor is required to determine the three dimensional position of the V/STOL relative to the landing zone. In low visibility operations, sensors are needed to enable the pilot to locate the ship and initiate his approach; and if the landing site has zero ceiling, the guidance sensors will be required for the pilot to make the final approach. This points out the stringent accuracy requirements that must be achieved for the aircraft operations to be conducted safely. In particular, three dimensional accuracies for position of + or - 1 foot and range rate of 1 foot per second and an update rate of 10 times per second are required.

Polar format storage of two-dimensional monostatic synthetic aperture radar (SAR) data (gathered in the stretch-spotlight mode of operation) allows matched two-dimensional Fourier transform processing; it eliminates range walk, allowing maximum size field of view for a given resolution or finest resolution for a given size field of view. In a bistatic SAR system, iso-range and iso-Doppler contours are orthogonal only for zero bistatic angle. The range gradient diminishes as the bistatic angle is increased. When polar format storage is used, these effects result in increasing smearing (defocusing) and geometric distortion of the imagery as the bistatic angle is increased. Hence, such formatting is not matched to two-dimensional transform processing. A solution to the bistatic SAR image processing problem is provided by a new technique called coherent unskewing and reconstitution logic (Curl). The matched processing performance of the Curl technique is demonstrated using computer simulation of received data from a bistatic SAR system with two-dimensional geometry. The resulting imagery is sharply focused and is totally free of geometric distortion. (Author)

This is the final technical report describing the design and development of a low-cost shipboard Mast Mounted CALL ALERT (MMCA) receiver system. Three prototype MMCA systems were built to demonstrate the feasibility of the design. These engineering models were configured so that they can be tested aboard ship to demonstrate the practical utility of the MMCA system. The equipment developed on this program depended heavily upon AIL's patented fin-line 1 millimeter wave transmission techniques. By utilizing its fin-line techniques, AIL's goal in the proposed program was to evolve a design that will ultimately minimize the cost of the system to the Navy. The proposed program was dedicated to this goal by planning, specifying and designing for low cost from the inception of the project. The MMCA system is intended to be used aboard Navy ships as a means of alerting appropriate personnel of the existence of an incoming signal in the Ka frequency band and of the approximate direction of its origin. The key components of this system are: (a) A narrow-beam horn antenna, rotating in the azimuth plane, (b) A Ka-band receiver having the appropriate sensitivity and noise figure, and (c) A visual and aural display indicating the presence and direction of origin of the received signal.

Initial year's progress is described toward the synthesis of analogs of phospholipids and of their biosynthetic intermediates as possible antimalarials of a new type. Emphasis was placed on phosphonic and phosphinic acid analogs of lecithin, phosphatidic acid, cytidine diphosphate diglyceride, and cytidine diphosphate choline. Nine compounds were submitted of which one was a major target and three were secondary target compounds. None of the substances so far tested showed appreciable antimalarial activity. (Author)

The feasibility of a purely electrical excitation mechanism for HF waveguide lasers was investigated whereby HF molecules are heavily diluted in a helium buffer gas and vibrationally excited through inelastic collisions in a discharge confined to a 1 x 1 mm channel of 8 cm length. Among the many HF vibration-rotation transitions there are several candidates for laser action. The relative population of their respective initial and terminal levels was ascertained from the measured intensity of the associated fluorescence. The data indicated inversion for some of the high J-number P-transitions. But since these levels were sparsely populated the resulting gain was extremely small and blanketed by scattering losses.

The heart of the crystal oscillator is the resonator, as the performance of the oscillator is always worse than that of the resonator. An important goal of good oscillator design is to minimize the difference between the resonator and oscillator performances. In order to achieve this goal, it is necessary to have full knowledge of the resonator performance. This knowledge is gained from the resonator specifications and from calculations based upon the resonator and oscillator specifications and oscillator circuit parameters., This article is from the Proceedings of the Symposium on Frequency Control (36th Annual), 2-4 Jun 82, Philadelphia, PA., AD-A130 811, p480-485.

This contract calls for design, development, fabrication, and test of a fast warm-up Crystal Oscillator operating at 5 MHz and 10.05+ MHz. This first status report indicates that from the test results of the oscillators developed so far, further reductions of inner oven and oscillator assembly MASS is required. In addition, an approved method of coupling heat into the crystal blank will be worked upon. In order to reduce mass, redesign of the electronic circuitry from discrete circuits to IC and Hybrid circuits is necessary. A new configuration is shown in the report. The key innovation of the design is to put the heater and temperature sensing devices on a ceramic disk of approximately 1-in. in diameter. A new hybrid approach will permit the fastest warm-up ovenized oscillator of its kind and will out-perform the present model in reliability and quality. (Author)

The report describes the results of the Non-Sampling UHF Single Frequency Repeater research and exploratory development program. The effort was concentrated on the system design of a high gain, single antenna non-sampling repeater. The effort included analytical and experimental data which defined to the technical and practical limits of isolation techniques, including antenna/hybrid matching, orthogonal mixing, and frequency offset within a 50 KHz (or 100 KHz) channel. Automatic search and acquisition techniques were also developed. In addition to reporting on the exploratory model and its performance in the laboratory, this report includes the results of flight tests and recommendations for future development. (Author)

An initial design for a 10 x 10 element heterodyne array was developed using 77 K, 1500-MHz photodiodes. Five PV-HgCdTe 150-MHz MHz photodiodes were then tested on a subassembly of a heterodyne matrix array structure with NEP's below 1.5 x 10 to the minus 19th power W/Hz measured out to 150 MHz. A thermal analysis was performed for 77 and 4.2 K matrix arrays with 150 and 1500 MHz operation to determine the cooler requirement for each case and the effect of the thermal loading on photomixer performance. A thermal mockup of the 77 K, 1500-MHz, 10 x 10 array was tested verifying the multi-cable thermal load analysis, the greater than 30-dB isolation between channels, and the greater than 24-hour operating time of the thermal mockup dewar., See also report dated Oct 1972, AD0750402.

Analyses were performed on various aspects of the multielement heterodyne technology including high density cabling techniques, image plane dissection to provide 10 x 10 (100 element) spatial elements, heating effects in a matrix array, and 4 K cooler requirements to obtain the desired system sensitivity. Measurements were carried out on HgCdTe photodiodes that showed cutoff frequencies of greater than 200 MHz and a maximum noise equivalent power (NEP) of 1.7 x 10 to the minus 19th power W/Hz over the 200 MHz bandwidth. (Author), Also includes Quarterly technical status rept. no. 2. See also report dated Oct 1972, AD0750402. Sponsored in part by DARPA.

The N13 oven was redesigned to obtain additional room for insulation material and employ a longer dewar flask. A redesigned prototype N13 unit was constructed and is under test.

This report describes an investigation of circuit techniques to minimize spurious responses in varactor-tuned filters. Design equations for the center frequency, bandwidth and insertion loss of single and multiple-resonator filters are presented. Series-resonant filters with one and two resonators were constructed and measurements of their performance characteristics were made. One- and two-resonator filters were also constructed using a pair of opposingly biased varactors (push-pull circuit) for each resonator. Measurements show that such a circuit can significantly reduce the second-harmonic generation and the response to a signal at one half the tuned frequency.

The report describes the work performed during the second quarter of a study of a reflector antenna that provides zoom (variable beamwidth) and scan capability using controlled aperture amplitude and phase. The antenna consists of a primary reflector (paraboloid) and a secondary reflector/lens. It operates as a lens in conjunction with one feed for scanning in the receive mode and as a reflector in conjunction with another feed for zooming in the transmit mode. Switching between a zooming transmit mode and a scanning receive mode results in a versatile radar antenna with an inherent duplexing capability. The performance of this antenna system is being analyzed numerically with the aid of digital computers. This report describes the development of a computer program for solving the Fraunhofer aperture integral efficiently and with good accuracy.

Described is a continuation of research into the application of mathematical techniques to the evaluation of practical airport capacity and delays. Since the primary task was to develop a handbook for determining airport capacity and delays by the engineer in the field, the main effort was concentrated on developing existing mathematical models for universal application. Therefore, this report contains the background material relevant to the handbook, describes the mathematical models used, and discusses the preparation of their respective inputs. These inputs vary with runway configuration, runway use, aircraft population, and operating rules (VFR or IFR) . The airport surveys that were analyzed to provide input values and operating parameters are also described. An IBM 7090 Fortran program was written to automatically compute the inputs and model outputs in the form of delays versus operating rates and capacities of airport runway configurations. The use and application of this program is described.

Calculations of the expected performance of the unmatched Bendix circulator, as predicted by Bosma's analysis, were completed. Experimental data was obtained using the proper center conductor that agreed qualitatively with the theory. The qualitative study of idealized input impedance of a parametric amplifier, performed during the early phases of this program, was used to double-tune the balanced C-band parametric amplifier so that the phase shift would be a linear function of frequency. This technique was very successful, providing a 500-Mc instantaneous bandwidth with a gain of about 10 db, a noise figure of 3.55 db, and a relatively flat phase characteristic. The amplifier has been packaged in a standard 19 by 24 inch rack mount, and is completely self-contained.

The Federal Aviation Agency is investigating the use of the SAGE air defense system for enroute air-traffic control. The program of SAGEAIR TRAFFIC INTEGRATION AND THE EXPERIMENTAL SYSTEM USED IN THIS PROGRAM IS KNOWN AS SATIN. A beacon code-usage plan that provides for display filtering in both manual and automatic systems is developed. The performance of the AN/FST-2 as a beacon data processor is analyzed. The performance includes target detection, release, center marking, and code readout. Deficiencies in code-readout performance are indicated and possible remedies are suggested. The code- processing performance of the AN/FSQ-7 is analyzed and determined to be adequate when the AN/FST-2 deficiencies are corrected.

Several criteria relating to the handling of general aviation on airports have been developed. In many cases, modifications of existing criteria are suggested. These include the subjects of runway-length corrections, instrument-approach needs, airspace needs, annual capacity of air ports, guidance for planning separate runway facilities for general aviation, procedures for performing economic analyses, and the effects of airport accessibility. The study has concentrated on planning for general aviation in metropolitan areas. Observations of generalaviation operations at air-carrier and generalaviation airports have indicated that new criteria for determining the numbers of airports required in metropolitan areas are needed. In developing regional plans and individual airport plans,the importance of using a cost-versusbenefit economic analysis is stressed. The criteria developed have been tested by applying them to the Lambert-St. Louis airport and to regional planning for the Washington, D. C. area.

Assuming future use of runway approach and flareout guidance in extremely low visibility, this report describes an investigation of suggested techniques for aircraft guidance during landing and takeoff roll and taxiing in poor visibilities down to zero-zero conditions. The techniques examined are: ILS localizers (including DME); gyro compasses and inertial systems; infrared; magnetic cables; aircraft radar; light and line patterns from conventional light sources including lasers and radioactive materials; and miscellaneous techniques including wheel tracks. These systems are judged relative to the operational requirements and considerations, including some economic analysis. It is concluded that, for landing and takeoff ground operations, improved ILS localizer plus DME offers the best solution. For taxiing operations, magnetic leader cables show the most promise. Research programs are indicated as being necessary for both ILS/DME and leader cables.

This report describes the development and analysis of preferred circuit techniques for the reduction of certain RFI effects in reflection - type parametric amplifiers. Emphasis is placed on reducing spurious responses and increasing the saturation power of paramps. Some of the preferred-circuit techniques are incorporated in experimental models and extensive measurements are reported which support the theoretical predictions of the effects of intermodulation products on paramp performance and the effect of the balanced configuration on spurious responses. Many additional characteristic of the models are described.

Techniques for the design, construction, and evaluation of a 10-db directional coupler, a 0 to 40 db variable attenuator, a 90-degree phase shifter, and a duplexer to operate in the 300 to 1000 gc region were investigated theoretically and experimentally. Quasi-optical, oversize, trough, and Goubau-beam waveguide were studied. Quasi-optical techniques used in oversize wave guide were found to be most suitable and were used in constructing the components. These com ponents were evaluated at 0.9-mm wavelength. The experimental data showed good agreement with the design theorhus, submillimeter compo nents using quasi-optical techniques in over size waveguide can be successfully designed annd fabricated. Some components had higher inser tion loss than desired due to the dielectric dissipation effects. These losses are reduced by using a multiple-dielectric-slab coupling structure.

The capture-effect glide-slope system is explained by comparison with a standard null reference system, and the relative advantages of the glide-slope system are analyzed. A general exposition of monitor techniques leads to an analysis of capture-effect monitor problems; solutions for the particular capture-effect monitor problems are presented and logically justified. The recommended solution for the oncourse monitor is recognized as the monitordetector location is found on the antenna mast midway between the middle and bottom glide-slope antennas. An alternative solution for the course-width monitor is recognized as the monitor-detector location for the second null of the top-antenna resultant, where the middleand bottom-antenna resultants are in phase opposition at the 180-degree dephase point for middle and bottom antennas.

The report describes the results of a program investigating means of reducing the intermodulation products generated in collocated 100-watt transmitters operating in the 225 to 400 MHz frequency range. The IM reduction technique considered a cascade of four tunable isolators and a standard tunable filter to achieve a net antenna-to-transmitter isolation of 80 dB. The major accomplishment on the program was the development of a tunable, compact, lumped-parameter UHF isolator having a power handling level in excess of 100 watts with a typical forward loss of 0.5 dB, and a 20-dB isolation bandwidth of 4.3 to 7.6 percent.

This report describes the program of RF doppler detector improvement sponsored by the FAA and undertaken to eliminate deficiencies in the radio detectors used in the TRACE installation at NAFEC. Previous detectors detected aircraft but were also triggered by small, close-in, unwanted targets such as birds and rainfall. Four X-band FM-CW doppler detectors and two dual-antenna CW S-band doppler detectors that were modified from GFE supplied by the FRE DEVELOPED UNDER THIS PROGRAM AND DELIVERED TO NAFEC for test and experimentation. These detectors eliminate or greatly reduce detection of the unwanted targets by producing a dead zone immediately in front of the detector. The X-band FM-CW detector produces this zone where detection is eliminated by a frequency modulation technique, while the CW S-band unit uses physical separation of the receiver and transmitter antennas to achieve the same result. In addition, audio analysis equip ment for storing and processing received signals was furnished to the FAA to aid in testing the equipment.