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Parallel heat flux calculations at the JET divertor have been based on the assumption that all incoming heat is due to the projection of the heat flux parallel to the magnetic line, , plus a constant background. This simplification led to inconsistencies during the analysis of a series of dedicated tungsten melting experiments performed in 2013, for which infrared (IR) thermography surface measurements could not be recreated through simulations unless the parallel heat flux was reduced by 80% for L-mode and 60% for H-mode. We give an explanation for these differences using a new IR inverse analysis code, a set of geometrical corrections, and most importantly an additional term for the divertor heat flux accounting for non-parallel effects such as cross-field transport, recycled neutrals or charge exchange. This component has been evaluated comparing four different geometries with impinging angles varying from 2 to 90°. Its magnitude corresponds to 1.2%–1.9% of , but because it is not affected by the magnetic projection, it accounts for up to 20%–30% of the tile surface heat flux. The geometrical corrections imply a further reduction of 24% of the measured heat flux. In addition, the application of the new inverse code increases the accuracy of the tile heat flux calculation, eliminating any previous discrepancy. The parallel heat flux computed with this new model is actually much lower than previously deduced by inverse analysis of IR temperatures—40% for L-mode and 50% for H-mode—while being independent of the geometry on which it is measured. This main result confirms the validity of the optical projection as long as a non-constant and non-parallel component is considered. For a given total heating power, the model predicts over 10% reduction of the maximum tile surface heat flux compared to strict optical modelling, as well as a 30% reduced sensitivity to manufacturing and assembling tolerances. These conclusions, along with the improvement in the predictability of the divertor thermal behaviour, are critical for JET future DT operations, and are also directly applicable to the design of the ITER divertor monoblocks. [ABSTRACT FROM AUTHOR]

The dynamics and stability of divertor detachment in seeded, type-I, ELMy H-mode plasmas with dominant NBI heating in the JET ITER-like wall device is studied by means of an integrated analysis of diagnostic data from several systems, classifying data relative to the ELM times. It is thereby possible to study the response of the detachment evolution to the control parameters (SOL input power, upstream density and impurity fraction) prevailing during the inter-ELM periods and the effect of ELMs on the detached divertor. A relatively comprehensive overview is achieved, including the interaction with the targets at various stages of the ELM cycle, the role of ELMs in affecting the detachment process and the overall performance of the scenario. The results are consistent with previous studies in devices with an ITER-like, metal wall, with the important advance of distinguishing data from intra- and inter-ELM periods. Operation without significant degradation of the core confinement can be sustained in the presence of strong radiation from the x-point region (MARFE). [ABSTRACT FROM AUTHOR]

A parametrised spectral line profile model is formulated to investigate the diagnostic scope for recovering plasma parameters from hydrogenic Balmer and Paschen series spectroscopy in the context of JET-ILW divertor plasmas. The separate treatment of Zeeman and Stark contributions in the line model is tested against the PPP-B code which accounts for their combined influence on the spectral line shape. The proposed simplified model does not fully reproduce the Stark–Zeeman features for the α and β transitions, but good agreement is observed in the line width and wing profiles, especially for n  >  5. The line model has been applied to infer radial density profiles in the JET-ILW divertor with generally good agreement between the D , , , and lines for high recycling and detached conditions. In an L-mode detached plasma pulse the Langmuir probe measurements typically underestimated the density by a factor 2–3 and overestimated the electron temperature by a factor of 5–10 compared to spectroscopically derived values. The line model is further used to generate synthetic high-resolution spectra for low-n transitions to assess the potential for parameter recovery using a multi-parametric fitting technique. In cases with 4 parameter fits with a single Maxwellian neutral temperature component the D line yields the best results with parameter estimates within 10% of the input values. For cases with 9 parameter fits inclusive of a multi-component neutral velocity distribution function the quality of the fits is degraded. Simultaneous fitting of the D and profiles improves the fit quality significantly, highlighting the importance of complementary spectroscopic measurements for divertor plasma emission studies. [ABSTRACT FROM AUTHOR]

The ITER baseline scenario, with 500 MW of DT fusion power and Q = 10, will rely on a Type I ELMy H-mode, with ΔW = 0.7 MJ mitigated edge localized modes (ELMs). Tungsten (W) is the material now decided for the divertor plasma-facing components from the start of plasma operations. W atoms sputtered from divertor targets during ELMs are expected to be the dominant source under the partially detached divertor conditions required for safe ITER operation. W impurity concentration in the plasma core can dramatically degrade its performance and lead to potentially damaging disruptions. Understanding the physics of plasma-wall interaction during ELMs is important and a primary input for this is the energy of incoming ions during an ELM event. In this paper, coupled Infrared thermography and Langmuir Probe (LP) measurements in JET-ITER-Like-Wall unseeded H-mode experiments with ITER relevant ELM energy drop have been used to estimate the impact energy of deuterium ions (D+) on the divertor target. This analysis gives an ion energy of several keV during ELMs, which makes D+ responsible for most of the W sputtering in unseeded H-mode discharges. These LP measurements were possible because of the low electron temperature (Te) during ELMs which allowed saturation of the ion current. Although at first sight surprising, the observation of low Te at the divertor target during ELMs is consistent with the ‘Free-Streaming’ kinetic model which predicts a near-complete transfer of parallel energy from electrons to ions in order to maintain quasi-neutrality of the ELM filaments while they are transported to the divertor targets. [ABSTRACT FROM AUTHOR]

The baseline type-I ELMy H-mode scenario has been re-established in JET with the new tungsten MKII-HD divertor and beryllium on the main wall (hereafter called the ITER-like wall, JET-ILW).The first JET-ILW results show that the confinement is degraded by 20–30% in the baseline scenarios compared to the previous carbon wall JET (JET-C) plasmas. The degradation is mainly driven by the reduction in the pedestal temperature. Stored energies and pedestal temperature comparable to the JET-C have been obtained to date in JET-ILW baseline plasmas only in the high triangularity shape using N2 seeding.This work compares the energy losses during ELMs and the corresponding time scales of the temperature and density collapse in JET-ILW baseline plasmas with and without N2 seeding with similar JET-C baseline plasmas. ELMs in the JET-ILW differ from those with the carbon wall both in terms of time scales and energy losses. The ELM time scale, defined as the time to reach the minimum pedestal temperature soon after the ELM collapse, is ∼2 ms in the JET-ILW and lower than 1 ms in the JET-C. The energy losses are in the range ΔWELM/Wped ≈ 7–12% in the JET-ILW and ΔWELM/Wped ≈ 10–20% in JET-C, and fit relatively well with earlier multi-machine empirical scalings of ΔWELM/Wped with collisionality. The time scale of the ELM collapse seems to be related to the pedestal collisionality. Most of the non-seeded JET-ILW ELMs are followed by a further energy drop characterized by a slower time scale ∼8–10 ms (hereafter called slow transport events), that can lead to losses in the range ΔWslow/Wped ≈ 15–22%, slightly larger than the losses in JET-C. The N2 seeding in JET-ILW significantly affects the ELMs. The JET-ILW plasmas with N2 seeding are characterized by ELM energy losses and time scales similar to the JET-C and by the absence of the slow transport events. [ABSTRACT FROM AUTHOR]

The code COREDIV, self-consistent with respect to both the interaction of plasma core-edge and main plasma impurities, is used to simulate nitrogen-seeded discharges in JET. The model is fully described and numerical results are compared with experimental data pertaining to two series of discharges differing in input power, confinement, the level of power radiated and the puffing rate of the main gas. Impurity sources, their transport and densities are considered as functions of the edge and core parameters and consistency of their radiated power is discussed. Special emphasis is given to analysis of the fluxes of carbon and recycled deuterium. [ABSTRACT FROM AUTHOR]

Clinical trials previously demonstrated the notable capacity to elicit visual percepts in blind patients affected with retinal diseases by electrically stimulating the remaining neurons on the retina. However, these implants restored very limited visual acuity and required transcutaneous cables traversing the eyeball, leading to reduced reliability and complex surgery with high postoperative infection risks. To overcome the limitations imposed by cables, a retinal implant architecture in which near-infrared illumination carries both power and data through the pupil to a digital stimulation controller is presented. A high efficiency multi-junction photovoltaic cell transduces the optical power to a CMOS stimulator capable of delivering flexible interleaved sequential stimulation through a diamond microelectrode array. To demonstrate the capacity to elicit a neural response with this approach while complying with the optical irradiance limit at the pupil, fluorescence imaging with a calcium indicator is used on a degenerate rat retina. The power delivered by the laser at the permissible irradiance of 4 mW/mm 2 at 850 nm is shown to be sufficient to both power the stimulator ASIC and elicit a response in retinal ganglion cells (RGCs), with the ability to generate of up to 35 000 pulses per second at the average stimulation threshold. This confirms the feasibility of generating a response in RGCs with an infrared-powered digital architecture capable of delivering complex sequential stimulation patterns at high repetition rates, albeit with some limitations.

Microfluidic organ-on-chip models recapitulate increasingly complex physiological phenomena to study tissue development and disease mechanisms, where there is a growing interest in retrieving delicate biological structures from these devices for downstream analysis. Standard bonding techniques, however, often utilize irreversible sealing, making sample retrieval unfeasible or necessitating destructive methods for disassembly. To address this, several commercial devices employ reversible sealing techniques, though integrating these techniques into early-stage prototyping workflows is often ignored because of the variation and complexity of microfluidic designs. Here, we demonstrate the concerted use of rapid prototyping techniques, including 3D printing and laser cutting, to produce multi-material microfluidic devices that can be reversibly sealed. This is enhanced via the incorporation of acrylic components directly into polydimethylsiloxane channel layers to enhance stability, sealing, and handling. These acrylic components act as a rigid surface separating the multiple mechanical seals created between the bottom substrate, the microfluidic features in the device, and the fluidic interconnect to external tubing, allowing for greater design flexibility. We demonstrate that these devices can be produced reproducibly outside of a cleanroom environment and that they can withstand ~1 bar pressures that are appropriate for a wide range of biological applications. By presenting an accessible and low-cost method, we hope to enable microfluidic prototyping for a broad range of biomedical research applications.

Objective: Pedestrian accidents contribute significantly to the high number of annual traffic casualties. It is therefore crucial for pedestrians to use safety measures, such as a crosswalk, and to activate pedestrian signals. However, people often fail to activate the signal or are unable to do so - those who are visually impaired or have occupied hands may be unable to activate the system. Failure to activate the signal can result in an accident. This paper proposes an improvement to crosswalk safety by designing a system that can detect pedestrians and trigger the pedestrian signal automatically when necessary., Methods: In this study, a dataset of images was collected in order to train a Convolutional Neural Network (CNN) to distinguish between pedestrians (including bicycle riders) when crossing the street. The resulting system can capture and evaluate images in real-time, and the result can be used to automatically activate a system such as a pedestrian signal. A threshold system is also implemented that triggers the crosswalk only when the positive predictions pass the threshold. This system was tested by deploying it at three real-world environments and comparing the results with a recorded video of the camera's view., Results: The CNN prediction model is able to correctly predict pedestrian and cyclist intentions with an average accuracy of 84.96% and had an absence trigger rate of 0.037%. The prediction accuracy varies based on the location and whether a cyclist or pedestrian is in front of the camera. Pedestrians crossing the street were correctly predicted more accurately than cyclists crossing the street by up to 11.61%, while passing (i.e., non-crossing) cyclists were correctly ignored more than passing pedestrians, by up to 18.75%., Conclusion: Based on the testing of the system in real-world environments, the authors conclude that it is feasible as a back-up system that can complement existing pedestrian signal buttons, and thereby improve the overall safety of crossing the street. Further improvements to the accuracy can be achieved with a more comprehensive dataset for a specific location where the system is deployed. Implementing different computer vision techniques optimized for tracking objects should also increase the accuracy.

Low grade endometrial stromal sarcoma (LGESS) accounts for about 0.2% of all uterine cancer cases. Approximately 75% of LGESS patients are initially misdiagnosed with leiomyoma, which is a type of benign tumor, also known as fibroids. In this research, uterine tissue biopsy images of potential LGESS patients are preprocessed using segmentation and stain normalization algorithms. We then apply a variety of classic machine learning and advanced deep learning models to classify tissue images as either benign or cancerous. For the classic techniques considered, the highest classification accuracy we attain is about 0.85, while our best deep learning model achieves an accuracy of approximately 0.87. These results clearly indicate that properly trained learning algorithms can aid in the diagnosis of LGESS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The study of neurons is fundamental for basic neuroscience research and treatment of neurological disorders. In recent years ultrasound has been increasingly recognized as a viable method to stimulate neurons. However, traditional ultrasound transducers are limited in the scope of their application by self-heating effects, limited frequency range and cavitation effects during neuromodulation. In contrast, surface acoustic wave (SAW) devices, which are producing wavemodes with increasing application in biomedical devices, generate less self-heating, are smaller and create less cavitation. SAW devices thus have the potential to address some of the drawbacks of traditional ultrasound transducers and could be implemented as miniaturized wearable or implantable devices. In this mini review, we discuss the potential mechanisms of SAW-based neuromodulation, including mechanical displacement, electromagnetic fields, thermal effects, and acoustic streaming. We also review the application of SAW actuation for neuronal stimulation, including growth and neuromodulation. Finally, we propose future directions for SAW-based neuromodulation., Competing Interests: SP was a shareholder and public officer of Carbon Cybernetics Pty Ltd., a company developing diamond and carbon-based medical device components. SP was a shareholder in iBIONICS, a company developing a diamond based retinal prosthesis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peng, Tong, Collins, Ibbotson, Prawer and Stamp.)

Objective: Retinal prosthetic devices hold great promise for the treatment of retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Through electrical stimulation of the surviving retinal neurons, these devices evoke visual signals that are then relayed to the brain. Currently, the visual prostheses used in clinical trials have few electrodes, thus limiting visual acuity. Electrode arrays with high electrode densities have been developed using novel technologies, including diamond growth and laser machining, and these may provide a more promising route to achieve high visual acuity in blind patients., Approach: Here, we studied the potential spatial resolution of electrical stimulation using diamond electrodes. We did this by labeling retinal ganglion cells in whole mount retina with a calcium indicator in wild-type rats and those with retinal degeneration. We imaged the ganglion cell responses to a range of stimulation parameters, including pulse duration and return electrode configuration., Main Results: With sub-retinal stimulation, in which electrodes were in contact with the intact or degenerated photoreceptor layer, we found that biphasic pulses of 0.1 ms phase duration and a local return configuration was the most effective in confining the retinal ganglion cell activation patterns, while also remaining within the safety limits of the materials and providing the best power efficiency., Significance: These results provide an optimized stimulation strategy for retinal implants, which if implemented in a retinal prosthetic is expected to improve the achievable visual acuity.

Retinal prostheses have the potential to restore vision to blind patients that have retinitis pigmentosa or similar hereditary degenerative disorders, by electrically stimulating surviving retinal neurons through implanted electrode arrays. Current retinal prostheses provide limited visual acuity and one challenge is to spatially control neural activation following electrical stimulation. Most of the retinal prostheses are either epi-retinal - in front of the retinal ganglion cell layer, or sub-retinal - behind photoreceptor layer. In this study, we performed calcium imaging of ganglion cells from whole mounted retinas and compared the spread of neural activation between epi-retinal stimulation with a fiber electrode and sub-retinal stimulation with a disk electrode. We investigated the effects of phase durations on the spatial resolution of biphasic stimulation. Our results suggest that with fiber electrode epi-retinal stimulation, the axon bundles activation can lead to significant spread of stimulation, and cannot be avoided simply by changing the phase durations. However, sub-retinal stimulation with very short pulses (phase duration 0.033ms) can effectively confine the activation of retinal ganglion cells.

Arcs are the potentially most dangerous events related to Lower Hybrid (LH) antenna operation. If left uncontrolled they can produce damage and cause plasma disruption by impurity influx. To address this issue an arc real time control and protection imaging system for the Joint European Torus (JET) LH antenna has been implemented. The LH system is one of the additional heating systems at JET. It comprises 24 microwave generators (klystrons, operating at 3.7 GHz) providing up to 5 MW of heating and current drive to the JET plasma. This is done through an antenna composed of an array of waveguides facing the plasma. The protection system presented here is based primarily on an imaging arc detection and real time control system. It has adapted the ITER like wall hotspot protection system using an identical CCD camera and real time image processing unit. A filter has been installed to avoid saturation and spurious system triggers caused by ionization light. The antenna is divided in 24 Regions Of Interest (ROIs) each one corresponding to one klystron. If an arc precursor is detected in a ROI, power is reduced locally with subsequent potential damage and plasma disruption avoided. The power is subsequently reinstated if, during a defined interval of time, arcing is confirmed not to be present by image analysis. This system was successfully commissioned during the restart phase and beginning of the 2013 scientific campaign. Since its installation and commissioning, arcs and related phenomena have been prevented. In this contribution we briefly describe the camera, image processing, and real time control systems. Most importantly, we demonstrate that an LH antenna arc protection system based on CCD camera imaging systems works. Examples of both controlled and uncontrolled LH arc events and their consequences are shown.

For an optimal implementation of materials, such as, e.g. medical implants in living environments, a thorough characterization of cell adhesion, kinetics and strength is required, as well as a prerequisite e.g. for bone integration. Here we present a miniaturized (~100 μl) lab-on-a-chip implant hybrid system which allows quantification of cell adhesion under dynamic conditions mimicking those of physiological relevance. Surface acoustic waves are excited and used on optical transparent chips to induce micro acoustic streaming and to create a microfluidic shear spectrum ranging from 0 to ~35 s(-1). We demonstrate its potential for a time-efficient, dynamic screening test of new implant materials using a model of an osseointegration with SAOS-2 cells. The upside-down orientation also allows utilization of the micro reactor on non-transparent materials like titanium and diamond-like-carbon (DLC).

A new endoscope with optimised divertor view has been developed in order to survey and monitor the emission of specific impurities such as tungsten and the remaining carbon as well as beryllium in the tungsten divertor of JET after the implementation of the ITER-like wall in 2011. The endoscope is a prototype for testing an ITER relevant design concept based on reflective optics only. It may be subject to high neutron fluxes as expected in ITER. The operating wavelength range, from 390 nm to 2500 nm, allows the measurements of the emission of all expected impurities (W I, Be II, C I, C II, C III) with high optical transmittance (≥ 30% in the designed wavelength range) as well as high spatial resolution that is ≤ 2 mm at the object plane and ≤ 3 mm for the full depth of field (± 0.7 m). The new optical design includes options for in situ calibration of the endoscope transmittance during the experimental campaign, which allows the continuous tracing of possible transmittance degradation with time due to impurity deposition and erosion by fast neutral particles. In parallel to the new optical design, a new type of possibly ITER relevant shutter system based on pneumatic techniques has been developed and integrated into the endoscope head. The endoscope is equipped with four digital CCD cameras, each combined with two filter wheels for narrow band interference and neutral density filters. Additionally, two protection cameras in the λ > 0.95 μm range have been integrated in the optical design for the real time wall protection during the plasma operation of JET.

A 60 kV neutral lithium diagnostic beam probes the edge plasma of JET for the measurement of electron density profiles. This paper describes recent enhancements of the diagnostic setup, new procedures for calibration and protection measures for the lithium ion gun during massive gas puffs for disruption mitigation. New light splitting optics allow in parallel beam emission measurements with a new double entrance slit CCD spectrometer (spectrally resolved) and a new interference filter avalanche photodiode camera (fast density and fluctuation studies).

The new JET ITER-like wall (made of beryllium and tungsten) is more fragile than the former carbon fiber composite wall and requires active protection to prevent excessive heat loads on the plasma facing components (PFC). Analog CCD cameras operating in the near infrared wavelength are used to measure surface temperature of the PFCs. Region of interest (ROI) analysis is performed in real time and the maximum temperature measured in each ROI is sent to the vessel thermal map. The protection of the ITER-like wall system started in October 2011 and has already successfully led to a safe landing of the plasma when hot spots were observed on the Be main chamber PFCs. Divertor protection is more of a challenge due to dust deposits that often generate false hot spots. In this contribution we describe the camera, data capture and real time processing systems. We discuss the calibration strategy for the temperature measurements with cross validation with thermal IR cameras and bi-color pyrometers. Most importantly, we demonstrate that a protection system based on CCD cameras can work and show examples of hot spot detections that stop the plasma pulse. The limits of such a design and the associated constraints on the operations are also presented.

Aim: To investigate the presentation of a patch-stage cutaneous T-cell lymphoma (CTCL) using optical coherence tomography (OCT)., Methods: A patient with a patch caused by CTCL was photographed digitally, OCT-scanned and biopsied. A normal skin area adjacent to the patch was OCT-scanned for comparison, but not biopsied. The OCT image and the histological image were compared., Results: The OCT images illustrated a thickened and hyperreflective stratum corneum. OCT also demonstrated several elongated hyporeflective structures in the dermis. The largest structure was measured to have a width of 0.13 mm. A good immediate correlation was found between histology and OCT imaging of the sample., Conclusion: The aetiology of the elongated structures is thought to be lymphomatous infiltrates. Similar findings have been described in ocular lymphoma and may therefore be an important characteristic of cutaneous lymphoma. It may further be speculated that the differences in OCT images may reflect the biological behaviour of the infiltrate. This observation therefore suggests that OCT imaging may be a relevant tool for the in vivo investigation of mycosis fungoides and other CTCLs, but in order to verify these observed patterns in OCT imaging, further investigations will be required.

Since 1994, JET has had a mirror-link spectroscopy system with a poloidal view of 150 mm of the outer divertor split into three ranges: near-ultraviolet (near-UV) (∼ 300–450 nm), visible (450–750 nm), and near-infrared (near-IR) (750–1200 nm). The system consists of three Czerny–Turner/charge coupled device (CCD) pairs: 1 m focal length for the near-UV, 0.75 m focal length for the visible, and 0.5 m focal length for the near-IR. All were aligned along the same optical path to the divertor. As part of the JET ITER-like wall enhancements, the diagnostic system will be upgraded in five areas: (1) frame rate, (2) quantum efficiency (QE), (3) radial coverage, (4) optical throughput, and (5) for the near-UV, spectral resolution and survey capability. New CCDs for the near-UV and visible will have increased QE and allow three times frame rate. The near-UV will benefit from a 0.75 m imaging spectrometer with three gratings. The optics have been redesigned to allow ∼ 360 mm view and greater than two times throughput. This paper will look at the design and implementation as well as the new diagnostic capabilities of the system.

Approximately 40 million students in the United States and a similar number in Europe carry school rucksacks. The average student carries a rucksack weighing almost one fourth of his or her body weight. This has led to more than 7,000 A&E, referrals each year related to carrying school bags in the US. The purpose of this study was to investigate the effects of carrying a rucksack (on each shoulder or on both), on 3D spinal curvature in healthy young students. A convenience sample of 30 healthy young adults participated in this study. A Microscribe 3DX digitiser recorded the three dimensional coordinates of thirteen key anatomical landmarks along the spine in four different loading conditions; no rucksack (reference) carrying a rucksack (17% body weight) simultaneously on both shoulders and solely on the right or the left shoulder. The data obtained was analyzed using standard statistical methods. Carrying the load on both shoulders resulted in no difference in the frontal plane angle but significantly decreased the thoracic kyphosis in the sagittal plane. However, carrying the load on the right shoulder significantly increased the thoracic lateral curvature in the frontal plane and decreased the thoracic kyphosis in the sagittal plane. This study confirms that even carrying a 17% load causes significant changes in spinal alignment. It is essential that Health and Safety professionals promote the awareness and effects of diverse rucksack carriage modes and excessive rucksack weight to avoid the early onset of low back pain.

edited by Reuven Dukas, University of Chicago Press, 1998. $95.00/£75.95 hbk, $30.00/£23.95 pbk (x+420 pages) ISBN 0 226 16932 4 (hbk), 0 226 16933 2 (pbk).

The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50S of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50S of 452 microM, 56 microM and 32 microM, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 microM. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis.

In January, February and March of 1989 an epidemic of rubeola occurred on the campus of Texas Tech University. A vaccination programme was initiated as soon as the epidemic was confirmed. Extensive case histories of all confirmed cases were collected by the Lubbock City Health Department and given an exhaustive statistical analysis by a group from the Department of Mathematics at Texas Tech University. The data and statistical analysis were used to formulate stochastic and deterministic models of the measles epidemic based on the standard SEIR model. The analysis and the simulations indicate that in order to prevent a measles outbreak on a university campus a high rate of immunity may be required (> 98 per cent). The assumptions in the models raise some interesting questions regarding social contacts which require further investigation.

We developed and evaluated an in vivo athymic nude mouse model for tumor growth, angiogenesis, metastasis, and antineoplastic drug development. Melanoma cell lines expressing beta-galactosidase encoded by the Escherichia coli lac Z gene have been created by infecting an immortal murine melanocyte cell line with a recombinant retrovirus expressing the v-Ha-ras oncogene and lac Z to generate the MRB (melanoma, ras, beta-galactosidase) cell lines. The amelanotic, phorbol ester-independent, transformed melanoma cell lines developed tumors rapidly when injected subcutaneously into nude mice, as well as experimental lung metastases when injected i.v. into the tail vein. beta-galactosidase-expressing subcutaneous tumors and lung metastases stained blue with X-gal. The melanomas produced in nude mice have been characterized by using various histochemical and immunohistochemical staining methods to detect melanoma- and endothelial-cell-specific markers to determine the extent of neovascularization in MRB nude mouse tumors. Optimal staining of endothelial cells involved in tumor angiogenesis was observed by using ADPase activity and antiangiotensin-converting enzyme antibody staining. Attempts at indirect quantification of metastatic tumor cell number within the lung by either beta-galactosidase enzymatic activity or ELISA immunoreactivity were unsuccessful. However, the MRB cell lines should be useful in screening for and studying the mechanisms of action of antineoplastic, antimetastatic, and angiostatic drugs in vivo in athymic nude mice.