Search

Characterizing the nature and spatial distribution of the lensing objects that produce the previously measured microlensing optical depth toward the Large Magellanic Cloud (LMC) remains an open problem. We present an appraisal of the ability of the SuperMACHO Project, a next-generation microlensing survey directed toward the LMC, to discriminate between various proposed lensing populations. We consider two scenarios: lensing by a uniform foreground screen of objects and self-lensing by LMC stars. We have carried out extensive simulations, based upon data obtained during the first year of the project, to assess the SuperMACHO survey's ability to discriminate between these two scenarios. We find that the event rate itself shows significant sensitivity to the choice of the LMC luminosity function, limiting the conclusions which can be drawn from the absolute rate. If instead we determine the differential event rate across the LMC, we will decrease the impact of these systematic biases and render our conclusions more robust. With this approach the SuperMACHO Project should be able to distinguish between the two categories of lens populations. This will provide important constraints on the nature of the lensing objects and their contributions to the Galactic dark matter halo., Comment: 40 pages, 9 figures, to appear in ApJ 634 (2005)

The crystalline structure of GaN epilayers on (0001) SiC substrates has been studied using x‐ray diffraction and transmission microscopy. The films were grown by metalorganic chemical vapor deposition, using AlN buffer layers. X‐ray diffraction measurements show negligible strain in the epilayer, and a long‐range variation in orientation. Transmission electron lattice images show that the AlN buffer layer consists of small crystallites. The nature of the buffer layer and its interfaces with the substrate and the GaN film is discussed. The defect structure of the GaN film away from the substrate consists mostly of threading dislocations with a density of ∼109 cm−2.

Replying to K. Davidson & R. M. Humphreys Nature486,http://dx.doi.org/10.1038/nature11166(2012). In our Letter1 reporting the light echoes of η Carinae we analysed the spectral characteristics of η Carinae during the Great Eruption of the mid-1800s, and found the line content to be similar to that of G supergiant stars. This we interpret as evidence that η Carinae’s Great Eruption was not a typical luminous blue variable (LBV) outburst, because spectra similar to those of F and A supergiant stars, earlier and hotter than G-type stars, are observed in LBV eruptions of all kinds, in agreement with theoretical predictions. Davidson & Humphreys2 object that our spectral type and temperature estimate are not sufficiently robust, and that the spectral features are in agreement with their theoretical predictions.

The crystalline structure near the substrate interface has been studied for AlGaN films grown on (0001) sapphire substrates by metalorganic chemical vapor deposition, using AlN buffer layers. Transmission electron lattice images show that the sapphire/AlN interface is coherent, with misfit dislocations separated by 2.0 nm, corresponding to relaxed bulk lattice parameters. The interface between the buffer layer and the AlGaN film is discussed. The defect structure of the epilayer near the substrate interface consists mostly of dislocations and stacking faults lying on basal planes.

Surgical resection of lung tissue is employed clinically as a therapy for pulmonary metastases; however, local cancer recurrence is a frequent post-surgical complication. In a variety of small mammals, left pneumonectomy (PNX) initiates rapid compensatory hyperplasia of the remnant lung lobes restoring normal tissue mass, structure and function. Post-PNX compensatory lung growth is known to promote lung tumor formation in carcinogen-treated mice. The present study tests the hypothesis that PNX enhances experimental metastasis to lung. C57B1/6 mice subjected to PNX were given an intravenous injection of B16F10 melanoma cells at various stages of compensatory lung growth. Animals injected with B16F10 cells during the linear phase of the response had 77% to 260% more pulmonary metastases than mice subjected to thoracotomy (P0.01). Moreover, measurements of tumor area (mm2) revealed that PNX mice harbored a substantially larger lung tumor burden than control animals. Normalization of the tumor cell inoculum to lung mass yielded similar results. PNX had no effect on growth of sub-cutaneous B16F10 melanoma tumors, suggesting that experimental melanoma metastasis was enhanced by local alterations in the lung microenvironment. These results suggest (1) that PNX is a relevant model in which to investigate mechanisms of local cancer recurrence and, (2) melanoma cell metastatic potential is influenced, at least in part, by local factors modified during post-PNX compensatory lung growth.

Once cancer cells have spread and formed secondary masses, breast cancers are largely incurable even with state-of-the-art medicine. To improve diagnosis and therapy, better markers are needed to distinguish cells which have a high probability for causing clinically relevant, macroscopic metastases. In this review, we summarize the several genes that regulate breast cancer metastasis. Two categories of genes are presented--metastasis activator (ras, MEK1, mta1, proteinases, adhesion molecules, chemoattractants/receptors, autotaxin, PKC, S100A4, RhoC, osteopontin) and metastasis suppressor (Nm23, E-cadherin, TIMPs, KiSS1, Kai1, Maspin, MKK4, BRMS1). While the mechanisms of action for most of these genes are not fully elucidated, some clues are emerging and are presented.

Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70-90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1-q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50-90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise. BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30-60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80-89%, but the decrease for MDA-MB-231 was less (13-15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.

We present a method for solving the lightcurve of an eclipsing binary system which contains a Cepheid variable as one of its components as well as the solutions for three eclipsing Cepheids in the Large Magellanic Cloud (LMC). A geometric model is constructed in which the component stars are assumed to be spherical and on circular orbits. The emergent system flux is computed as a function of time, with the intrinsic variations in temperature and radius of the Cepheid treated self-consistently. Fitting the adopted model to photometric observations, incorporating data from multiple bandpasses, yields a single parameter set best describing the system. This method is applied to three eclipsing Cepheid systems from the MACHO Project LMC database: MACHO ID's 6.6454.5, 78.6338.24 and 81.8997.87. A best-fit value is obtained for each system's orbital period and inclination and for the relative radius, color and limb-darkening coefficients of each star. Pulsation periods and parameterizations of the intrinsic color variations of the Cepheids are also obtained and the amplitude of the radial pulsation of each Cepheid is measured directly. The system 6.6454.5 is found to contain a 4.97-day Cepheid, which cannot be definitely classified as Type I or Type II, with an unexpectedly brighter companion. The system 78.6338.24 consists of a 17.7-day, W Vir Class Type II Cepheid with a smaller, dimmer companion. The system 81.8997.87 contains an intermediate-mass, 2.03-day overtone Cepheid with a dimmer, red giant secondary.

Past microlensing experiments such as the MACHO project have discovered the presence of a larger than expected number of microlensing events towards the Large Magellanic Cloud (LMC). These events could represent a large fraction of the dark matter in the halo of our Galaxy, if they are indeed due to halo lenses. However, the locations of most of the lenses are poorly defined. The SuperMacho project will detect and follow up ~ 60 microlensing events toward the LMC over the next 5 years. The expected discovery of a number of microlensing events exhibiting special properties due to binarity, etc., will allow us to better determine the location and nature of the lenses causing the LMC microlensing events.

We have conducted a systematic characterization of (111)- and (100)- oriented synthetic diamond crystals comparing the best presently available specimens of two types (Ib and IIa). The samples were grown by the two major diamond producers, namely the De Beers Industrial Diamonds (Pty) Ltd. in South Africa and the Sumitomo Electric Industries Ltd. in Japan. Double-crystal x-ray diffractometry with microscopic spatial resolution and x-ray topography were employed. The type IIa crystals showed much less pronounced defect structure than the Ib crystals for the (100)- orientation, but the (111) samples were comparable. A clear correlation between the distribution of nitrogen impurities in the Ib crystals and the defect structure was observed. The rocking curve widths from small regions of all specimens were very close to theoretical values on the arcsec level, whereas for larger sample areas they were broadened due to both local defects and crystal curvature. The quality of the IIa crystals from De Beers and Sumitomo was comparable.

We have recently characterized a human bladder cancer cell line T24 and a more aggressive lineage related variant of it, T24T. To gain further insights, we have studied their metastatic ability in an in vivo model system. Results show that T24 forms significantly fewer [4/12 (1/11) mice had metastases with 1-2 lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6) mice had metastases with a mean of 24-28 lesions/mouse]. To begin exploring the mechanisms underlying this difference, we evaluated the mRNA and protein expression levels of metastasis-suppressor genes, known to be important in the progression of other cancers, in our model of bladder cancer progression. A higher mRNA expression of BRMS1, a metastasis suppressor in breast cancer, was observed in T24 cells. In addition, RhoGDI2 mRNA expression was only observed in T24 when compared to T24T, suggesting that Rho activation might play a significant role in the metastatic cascade. However, a basal level mRNA expression of KISS1, described as metastasis suppressor in melanoma and breast, was observed in both the lines and had slightly higher expression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and E-Cadherin protein levels were noted between these two lines. In summary, it appears that the T24/T24T paired cell lines constitute a useful model for the study of human bladder cancer metastasis that will allow both the discovery and mechanistic evaluation of genes potentially involved in this process.

Dipeptidyl peptidase IV (DPPIV) is a 110-kD, trans-membrane, ectoenzyme, with ubiquitous expression. DPPIV has numerous functions including involvement in T-cell activation, cell adhesion, digestion of proline containing peptides in the kidney and intestines, HIV infection and apoptosis, and regulation of tumorigenicity in certain melanoma cells. Constitutively expressed on numerous epithelial cell types, DPPIV is often disregulated in a variety of human malignancies. The most striking evidence of DPPIV down-regulation is found in transformed melanocytes. where nearly 100% of melanomas lack DPPIV expression. We have identified DPPIV as a gene that can alter the invasive potential of a number of melanoma cell lines. By transfecting the full-length cDNA of DPPIV, we have established stable melanoma cell lines that express comparable levels of the DPPIV protein as normal epidermal melanocytes. Matrigel invasion assays were utilized to study the effects of DPPIV expression on the invasive potential of these cells. The parental and vector transfectants readily migrated across the Matrigel while the invasiveness of DPPIV transfected cells was reduced by greater than 75%. The effects on cellular invasion are not attributed to overall growth characteristics, as both DPPIV expressing and non-expressing cells behave comparably in culture. We have also constructed mutants of DPPIV that lack either the extra-cellular serine protease activity or the six amino acid cytoplasmic domain. Both mutants were stably expressed in melanoma cells. Matrigel invasion assays performed with cells expressing the two mutant forms of the protein revealed phenotypic effects similar to wild type function. In this study. we have demonstrated that expression of a proteolytically active form of the DPPIV protein inhibits the invasiveness of malignant melanoma cell lines lacking endogenous DPPIV expression. Furthermore, we have shown that neither the protease activity nor the cytoplasmic domain of DPPIV is required for its anti-invasive activity.

This research examined the impact of goal-setting conditions on memory beliefs and performance among older and younger adults. After baseline recall and assessment of beliefs, participants were assigned to goal-setting, goals plus feedback, or control. Then, additional recall trials were followed by repeated memory beliefs assessments. For both younger and older adults, performance, motivation, and self-efficacy were affected positively by goal-setting. The impact of goals plus feedback was mixed and varied as a function of age and dependent measure. Success rates for reaching memory goals, which were low for the older adults, may have been a factor in these results. Adults' self-set recall goals were predicted initially by baseline performance and self-efficacy. On the final trial, goals were predicted by last trial performance, self-efficacy, and control beliefs.

Breast cancer progresses toward increasingly malignant behavior in tumorigenic and metastatic stages. In the series of events in the metastatic stage, tumor cells leave the primary tumor in breast and travel to distant sites where they establish secondary tumors, or metastases. In this report, we demonstrate that cell-cell communication via gap junctions is restored in the metastatic human breast carcinoma cell line MDA-MB-435 when it is transfected with breast metastasis suppressor 1 (BRMS1) cDNA. Furthermore, the expression profile of connexins (Cxs), the protein subunits of gap junctions, changes. Specifically, the expression of BRMS1 in MDA-MB-435 cells increases Cx43 expression and reduces Cx32 expression, resulting in a gap junction phenotype more similar to normal breast tissue. Taken together, these results suggest that gap junctional communication and the Cx expression profile may contribute to the metastatic potential of these breast cancer cells.

Oak Ridge National Laboratory has developed a new technique to monitor the growth of cracks in structural members, and to predict when failure due to this damage is imminent. This technique requires the measurement of global loadings and local deflections/strains at critical locations to indicate the increasing growth of hidden cracks with sufficient warning time prior to failure to take preventative action to correct the problem or retire the structure before failure. The techniques, as described in the referenced report have been proven on a laboratory scale to successfully detect the onset of failure due to fatigue cracking (including cracking of corroded samples), stress corrosion cracking, and low temperature creep crack growth, with a reasonable degree of warning before failure.

In this paper, we explore the self-pinched transport of heavy ions in an inertial confinement fusion reactor chamber environment. The bulk of this work is carried out using a hybrid particle-in-cell code. The initial results show that a neutral flibe pressure of roughly 5-50 mtorr is sufficient to produce a net current capable of confining the ions at small radius (

The MACHO collaboration has analyzed 5.7years of photometry on approximately 11.7 million stars in the Large Magellanic Cloud (LMC) in a search for gravitational microlensing events. Two sets of cuts were used in the event selection process, and 13 and 17 events were found in the different sets. If the lenses are in the Galactic halo, then likelihood analysis for a standard halo model gives a halo mass fraction of about 0.2 with a 95% confidence interval of 0.08–0.5 and lens masses in the range 0.15–0.9 M⊙.

We present photometry and analysis of the microlensing alert MACHO 96-LMC-2. The ~3% photometry provided by the Global Microlensing Alert Network follow--up effort reveals a periodic modulation in the lightcurve. We attribute this to binarity of the lensed source. Microlensing fits to a rotating binary source magnified by a single lens converge on two minima, separated by delta chi^2 ~ 1. The most significant fit X1 predicts a primary which contributes ~100% of the light, a dark secondary, and an orbital period (T) of 9.2 days. The second fit X2 yields a binary source with two stars of roughly equal mass and luminosity, and T = 21.2 days. The lensed object appears to lie on the upper LMC main sequence. We estimate the mass of the primary component of the binary system, M ~2 M_sun. For the preferred model X1, we explore the range of dark companions by assuming 0.1 M_sun and 1.4 M_sun objects in models X1a and X1b, respectively. We find lens velocities projected to the LMC in these models of v^hat_X1a = 18.3 +/- 3.1 km/s and v^hat_X1b = 188 +/- 32 k/ms. In both these cases, a likelihood analysis suggests an LMC lens is preferred over a Galactic halo lens, although only marginally so in model X1b. We also find v^hat_X2 = 39.6 +/- 6.1 k/ms, where the likelihood for the lens location is strongly dominated by the LMC disk. In all cases, the lens mass is consistent with that of an M-dwarf. The LMC self-lensing rate contributed by 96-LMC-2 is consistent with model self-lensing rates. (Abridged)

The incidence of melanoma continues to increase at a rapid rate. As for most cancers, it is melanoma metastases, rather than the primary malignancy, that is the principal cause of death. We previously showed that the introduction of a normal copy of chromosome 6 into the metastatic human melanoma cell line C8161 suppresses metastasis at a step subsequent to tumor cells entering the bloodstream. To better define the step(s) in metastasis blocked by the addition of chromosome 6 we engineered cells that constitutively express green fluorescent protein (GFP). When these tagged, chromosome 6 hybrid cells were injected intravenously into athymic mice, grossly detectable metastases did not form. However, fluorescence microscopy revealed micro-metastases (single cells or clusters of10 cells) in the lungs, suggesting that these cells lodged in the lungs but failed to proliferate. Cells isolated from lung up to 60 days post-injection grew in culture and/or formed tumors when injected into the skin, indicating that they were still viable, but dormant. This result implies that the gene(s) on chromosome 6 interfere specifically with growth regulatory response in the lung, but not in the skin. Thus, the gene(s) responsible for metastasis suppression represents a new class of metastasis inhibitors acting at the final stages of the metastatic cascade--that is, affecting the ability of the cells to survive and proliferate at a specific secondary site.

We previously showed that introduction of a normal, neomycin-tagged human chromosome 11 reduces the metastatic capacity of MDA-MB-435 (435) human breast carcinoma cells by 70-90% without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 11. To identify the gene(s) responsible, differential display comparing chromosome 11-containing (neo11/ 435) and parental, metastatic cells was done. We describe the isolation and functional characterization of a full-length cDNA for one of the novel genes, designated breast-cancer metastasis suppressor 1 (BRMS1), which maps to human chromosome 11q13.1-q13.2. Stably transfected MDA-MB-435 and MDA-MB-231 breast carcinoma cells still form progressively growing, locally invasive tumors when injected into mammary fat pads but are significantly less metastatic to lungs and regional lymph nodes. These data provide compelling functional evidence that breast-cancer metastasis suppressor 1 is a novel mediator of metastasis suppression in human breast carcinoma.

Loss, deletion or rearrangement along large portions of the long arm (q-arm) of chromosome 6 occurs in80% of late-stage human melanomas, suggesting that genes controlling malignant characteristics are encoded there. Metastasis, but not tumorigenicity, was completely suppressed in the human melanoma cell line C8161 into which an additional intact chromosome 6 had been introduced by microcell-mediated chromosome transfer. Our objective was to refine the location of a putative metastasis suppressor gene. To do this, we transferred an intact (neo6) and a deletion variant [neo6qdel; neo6(del)(q16.3-q23)] of neomycin-tagged human chromosome 6 into metastatic C8161 subclone 9 (C8161.9) by MMCT. Single cell hybrid clones were selected in G-418 and isolated. Following verification that the hybrids retained the expected regions of chromosome 6 using a panel of polymorphic sequence-tagged sites, the hybrids were tested for tumorigenicity and metastasis in athymic mice. As reported previously, intact, normal chromosome 6 suppressed metastasis whether tumor cells were injected i.v. or into an orthotopic (i.e., intradermal) site. In contrast, metastasis was not suppressed in the neo6qdel hybrids. Tumorigenicity was unaffected in hybrids prepared with either chromosome 6 donor. These data strongly suggest that a human melanoma metastasis suppressor locus maps between 6q16.3-q23 ( approximately 40 cM).

Cellular growth and differentiation are controlled by multiple extracellular signals, many of which activate extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinases. Components of the MAP kinase pathways also cause oncogenic transformation in their constitutively active forms. Moreover, expression of activated ras can confer metastatic potential upon some cells. Activation of MAP kinases requires phosphorylation of both Thr and Tyr in the catalytic domain by a family of dual-specificity kinases, called MEKs (MAP kinase/ERK kinase). MEK1 is activated by phosphorylation at Ser218 and Ser222 by Raf. Mutation of these two sites to acidic residues, specifically [Asp218], [Asp218, Asp222], and [Glu218, Glu222], results in constitutively active MEK1. Using these mutant variants of MEK1, we showed previously that transfection of NIH/3T3 or Swiss 3T3 cells causes morphological transformation and increases growth on soft agar, independent of ERK activity. The transformed cell lines show increased expression of matrix metalloproteinases 2 and 9 and cathepsin L, proteinases that have been implicated in the metastatic process. We tested NIH3T3 cells transfected with the [Asp218] or [Asp218, Asp222] for metastatic potential after i.v. injection into athymic mice. Parental 3T3 cells formed no tumors grossly or histologically. However, all MEK1 mutant transformants formed macroscopic metastases. Thus, like activated Ras, MEK1 can confer both tumorigenic and metastatic potential upon NIH3T3 cells. These results refine the mechanism through which ras could confer tumorigenic and metastatic potential (ie., the critical determinants of tumorigenic and metastatic potential are downstream of MEK1).

Since Bi2Sr2Ca2Cu3O10/Ag, [Bi2223/Ag], tapes have geometrically large aspect ratios, and have highly anisotropic properties along its crystallographic directions, it is not clear to what extent the ac loss theories, which are based on the critical-state model of an isotropic superconductor, are applicable to these conductors. We report on tests of these models against magnetically measured ac losses of a Bi2223/Ag tape, in magnetic environments similar to those in power devices. It is shown that the self-field critical currents are not appropriate for calculations of the losses in either parallel or perpendicular fields to the tape face. In addition, the use of the field- dependent critical currents, such as in Kim’s model, is important to understand the behavior of the losses in perpendicular applied fields.

The MACHO Project is a microlensing survey that monitors the brightnesses of 60 million stars in the Large Magellanic Cloud (LMC), Small Magellanic Cloud, and Galactic bulge. Our database presently contains about 80 billion photometric measurements, a significant fraction of all astronomical photometry. We describe the calibration of MACHO two-color photometry and transformation to the standard Kron-Cousins V and R system. Calibrated MACHO photometry may be properly compared with all other observations on the Kron-Cousins standard system, enhancing the astrophysical value of these data. For 9 million stars in the LMC bar, independent photometric measurements of 20,000 stars with V < 18 mag in field-overlap regions demonstrate an internal precision sigV = 0.021, sigR = 0.019, and sig(V-R) = 0.028 mag. The accuracy of the zero-point in this calibration is estimated to be +-0.035 mag for stars with colors in the range -0.1 < (V-R) < 1.2 mag. A comparison of calibrated MACHO photometry with published photometric sequences and new Hubble Space Telescope observations shows agreement. The current calibration zero-point uncertainty for the remainder of the MACHO photometry database is estimated to be +- 0.10 mag in V or R and +-0.04 mag in (V-R). We describe the first application of calibrated MACHO photometry data: the construction of a color-magnitude diagram used to calculate our experimental sensitivity to detect microlensing in the LMC., to appear in PASP, 11pt aaspp4.sty, 47 pages, includes 21 figures (4 are bitmapped)

Bacteremia with fever due to a novel subspecies of Bartonella vinsonii was found in a cattle rancher. The subspecies shared major characteristics of the genus Bartonella in terms of most biochemical features and cellular fatty acid profile, but it was distinguishable from other subspecies of B. vinsonii by good growth on heart infusion agar supplemented with X factor and by its pattern of enzymatic hydrolysis of peptide substrates. DNA relatedness studies verified that the isolate belonged to the genus Bartonella and that it was genotypically related to B. vinsonii. The highest level of relatedness was observed with recently characterized strains from naturally infected mice that were coinfected with Borrelia burgdorferi and Babesia microti. We propose the name Bartonella vinsonii subsp. arupensis subsp. nov. as the new subspecies to accommodate these human and murine isolates.

Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mammary tumor cells (MTLn3) compared with less metastatic, parental cell lines. To determine whether the increase in endogenous PKCdelta is functionally related to their increased metastatic potential, we prepared MTLn3 cells that express the inhibitory regulatory domain fragment of PKCdelta (RDdelta) under the control of a tetracycline-inducible promoter. RDdelta expression attenuated endogenous PKCdelta activity, as demonstrated by decreased phosphorylation of the PKCdelta substrate adducin in migrating cells. Thus, in MT cells, RDdelta appears to primarily influence cytoskeleton-dependent processes rather than cell cycle progression. To determine whether RDdelta expression influenced metastatic potential in vivo, MTLn3/RDdelta cells were either grown in the mammary fat pad or injected into the tail vein of syngeneic rats, and effects of doxycycline-induced RDdelta expression on pulmonary metastases were studied. Consistent with the in vitro data, induction of RDdelta significantly reduced the number of lung metastases without affecting growth of the primary tumor. These results suggest that interfering with endogenous PKCdelta activity by expressing the inhibitory RDdelta fragment inhibits cytoskeleton-regulated processes important for MTLn3 cell metastasis.

Type II epithelial cells, which line the alveolar surface of the lung, are exposed to a variety of potentially mutagenic and carcinogenic insults. The purpose of this study was to determine if type II cells are susceptible to oxidative DNA damage in vitro. Treatment of cultured rat type II lung epithelial cells with hydrogen peroxide led to increased concentrations (nmol/mg DNA) of 12 of 14 monitored DNA base modifications, suggesting oxidative damage by the hydroxyl radical. These base modifications are typically associated with oxidative stress, and elevated levels have been correlated with mutagenesis and carcinogenesis. These data demonstrate that type II cells are indeed vulnerable to oxidative DNA damage.

This report describes important future research directions in nanoscale science, engineering and technology. It was prepared in connection with an anticipated national research initiative on nanotechnology for the twenty-first century. The research directions described are not expected to be inclusive but illustrate the wide range of research opportunities and challenges that could be undertaken through the national laboratories and their major national scientific user facilities with the support of universities and industry.

The MACHO experiment is searching for dark matter in the halo of the Galaxy by monitoring more than 50 million stars in the LMC, SMC, and Galactic bulge for gravitational microlensing events. The hardware consists of a 50 inch telescope, a two-color 32 megapixel ccd camera and a network of computers. On clear nights the system generates up to 8 GB of raw data and 1 GB of reduced data. The computer system is responsible for all realtime control tasks, for data reduction, and for storing all data associated with each observation in a database. The subject of this paper is the software system that handles these functions. It is an integrated system controlled by Petri nets that consists of multiple processes communicating via mailboxes and a bulletin board. The system is highly automated, readily extensive, and incorporates flexible error recovery capabilities. It is implemented with C++ in a Unix environment.

Previous articles in this series have investigated the role of human factors engineering (HFE) in the design and development of medical devices and instrumentation. This article turns its focus to HFE within health care facilities--hospitals, clinics, nursing homes, HMOs, etc. The objective of HFE for the device manufacturer is to produce effective and safe systems. The health care facility is concerned with maintaining the safety of patients and staff, enhancing the cost efficiency of its operations, and controlling liability. Human factors engineering can be effective in realizing all of these goals. Proactive measures include (1) evaluation of currently employed systems for efficiency and error potential, (2) evaluation of systems prior to purchase, (3) evaluation and enhancement of facilities, and (4) design and evaluation of procedures. Retroactively, HFE participation in accident/incident investigations can carry such investigations beyond the placing of blame to determining what made a human error possible or even inevitable.

Using microcell-mediated transfer of a normal chromosome 11 into the highly metastatic MDA-MB-435 human breast carcinoma cell line, we previously showed that human chromosome 11 contains a metastasis-suppressor gene for breast cancer. A known metastasis-suppressor gene, kai-1, and a related family member, tapa-1, have been mapped to chromosome 11p11.2 and 11p15.5, respectively. To determine if these genes are responsible for the metastasis suppression seen in our microcell hybrids, we examined their expression by western blot analysis. Although tapa-1 expression did not significantly correlate with metastasis suppression, kai-1 production was dramatically increased in the metastasis-suppressed chromosome 11 microcell hybrids and unchanged in the metastatic chromosome 6 controls. Transfection of full-length kai-1 cDNA into MDA-MB-435 cells resulted in clones that did not have a significantly decreased in vivo incidence of lung metastases. However, western blot analysis showed that the primary tumors and the metastatic lesions of the transfectants had decreased levels of kai-1 protein compared with the inoculated cells. Furthermore, several of the transfectant clones expressed heavily modified kai-1 protein compared with that of the microcell hybrids. Our data indicate that protein modification may affect the normal function of kai-1 in vivo and that a threshold level of kai-1 protein expression may be necessary for suppression of the metastatic phenotype.

The last issue of BIT explored the nature and role of human factors engineering (HFE) in health care. That column examined how the "root cause" of an accident is often simply labeled "human error" and how human error can be a convenient way to explain away a system-wide problem. HFE is highly effective in designing and operating systems that consider human strengths and weaknesses and do not "set up" users to commit errors. Still, people will continue to commit errors, no matter how hard we try. Yet we can design systems that, if not "fail-safe", are at least "fault tolerant." In these systems errors are more difficult to commit and are more easily detected, corrected, and mitigated. Human factors engineering can be of value to the health care industry in at least three highly critical areas: Developing new systems to enhance safety, efficiency, and usability; Evaluating whether to purchase particular equipment and how to effectively integrate it into hospital systems; and Investigating accidents. This article will review the HFE analysis and design activities undertaken in developing a new system. The article in the next issue of BIT will explore HFE developmental and usability and evaluation activities.

Human error is inevitable. It happens in health care systems as it does in all other complex systems, and no measure of attention, training, dedication, or punishment is going to stop it. The discipline of human factors engineering (HFE) has been dealing with the causes and effects of human error since the 1940's. Originally applied to the design of increasingly complex military aircraft cockpits, HFE has since been effectively applied to the problem of human error in such diverse systems as nuclear power plants, NASA spacecraft, the process control industry, and computer software. Today the health care industry is becoming aware of the costs of human error and is turning to HFE for answers. Just as early experimental psychologists went beyond the label of "pilot error" to explain how the design of cockpits led to air crashes, today's HFE specialists are assisting the health care industry in identifying the causes of significant human errors in medicine and developing ways to eliminate or ameliorate them. This series of articles will explore the nature of human error and how HFE can be applied to reduce the likelihood of errors and mitigate their effects.

Based on the observation that chromosome 1q deletions are not infrequent in late-stage human breast carcinomas, we tested whether the recently discovered human melanoma metastasis suppressor gene, KiSS-1, which maps to chromosome 1q32-q41, could suppress metastasis of the human breast carcinoma cell line MDA-MB-435. Parental, vector-only transfectants and KiSS-1 transfectant clones were injected into the mammary fat pads of athymic nude mice and assessed for tumor growth and spontaneous metastasis to regional lymph nodes and lungs. Expression of KiSS-1 reduced metastatic potential by 95% compared to control cells but did not suppress tumorigenicity. Metastasis suppression correlated with a decreased clonogenicity in soft (0.3%) and hard (0.9%) agar. Although the overall rate of cell adhesion to extracellular matrix components was unaffected, KiSS-1 transfectants spread on immobilized type-IV collagen more rapidly than did control populations. Invasion and motility were unaffected by KiSS-1. Based on the predicted structure of the KiSS-1 protein, our results imply a mechanism whereby KiSS-1 regulates events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. In addition to its already described role in melanoma, our results show that KiSS-1 also functions as a metastasis suppressor gene in at least some human breast cancers.

Microcell-mediated transfer of chromosome 6 into human melanoma cell lines C8161 and MelJuSo suppresses metastasis by at least 95% without affecting tumorigenicity. Subtractive hybridization and differential display were used to identify the molecule(s) responsible for suppressing metastasis in neo6/melanoma (neo6/C8161 and neo6/MelJuSo) hybrids. Seven cDNA clones exhibiting quantitatively or qualitatively higher expression in neo6/melanoma hybrids were obtained. These genes fell into 2 categories: 1) transcription-related genes (AP-2A, HMG-I(Y) and a novel isoform of nucleophosmin B23), which have previously been shown to regulate metastasis-associated genes; and 2) novel genes. One of the novel genes, designated KiSS-1, significantly suppressed metastasis of the human malignant melanoma cell lines MelJuSo and a highly metastatic subclone of C8161, C8161cl.9, following transfection and constitutive expression. Our results illustrate the power of subtractive hybridization and differential display to identify functional metastasis-controlling genes in human melanoma.

Metastasis is suppressed more than 95% following microcell-mediated transfer of a single copy of neomycin-tagged human chromosome 6 (neo6) into the human melanoma cell lines C8161 and MelJuSo. Concomitant with metastasis suppression is upregulation of NME1 (Nm23-H1) mRNA and protein expression. The purposes of this study were to determine whether NME1 expression was responsible for metastasis suppression in neo6/melanoma hybrids, and whether genes on chromosome 6 regulate NME1. Using neo6/C8161 cells, transfection of CAT reporter constructs linked to the NME1 promoter failed to consistently induce CAT. Therefore, it does not appear that genes on chromosome 6 directly control transcription of NME1. Transfection and overexpression of NME1 in MelJuSo, under the control of the CMV promoter, resulted in 40-80% inhibition of lung metastasis following i.v. inoculation of 2 x 10(5) cells. Only one transfectant of C8161 subclone 9 (C8161cl.9) cells was suppressed for metastasis. Control transfections with pCMVneo or pSV2neo did not suppress metastasis in either cell line. Taken together, these data suggest that NME1 can reduce metastatic potential of some human melanoma cells; but, this inhibitory activity appears to be independent of the metastasis suppression following introduction of chromosome 6 into C8161 and MelJuSo human melanoma cell lines.

The current study investigated whether a concern with body shape and weight represents a distinct affective state, or whether it is better conceptualized as a highly specific form of anxiety.The color-naming performance of women with a high Drive for Thinness score was examined under three experimental conditions: when a photograph of chocolate was present, when actual chocolate was present, and a control condition. High Drive for Thinness subjects demonstrated relatively impaired color naming of body shape words in the picture condition, but not in the food or control conditions.Although there was a significant impairment in the color naming of food words, this was unaffected by condition or degree of Drive for Thinness.The results are interpreted as supporting an analogy between weight/body shape concerns and subclinical phobic anxiety.

The MACHO project is an ongoing survey project which collects photometric timeseries data on roughly 20 million stars in the LMC, SMC, and Galactic bulge. The data is irregularly time sampled, largely due to weather interruptions, and has noise which is non-stationary and non-Gaussian. The time series data is analyzed for microlensing events, rare brightenings of a star that result from an otherwise undetected massive object that passes close to the line of sight, thereby forming a gravitational lens. In addition to microlensing events, there are a much larger number of brightenings that result from intrinsic stellar variability. This background is only partially understood, since some classes of variable stars have received little study, and there are doubtless some classes yet to be discovered. Since the background can not be reliably simulated, the experiment must aim at a false alarm rate near zero, at the cost of reduced detection efficiency. At the same time, to achieve the scientific results at which it aims, the detection efficiency must be measured reliably.

We present optical photometry of the eclipsing supersoft source, CAL87. These observations comprise long term data accumulated as a by-product of the MACHO Project, and high speed white light photometry of a single eclipse. We (i) derive an improved ephemeris of To = HJD 2450111.5144(3) + 0.44267714(6)E for the time of minimum light, (ii) find the eclipse structure to be stable over a period of 4 years, and (iii) investigate the colour variation as a function of orbital phase. The resolution afforded by the high speed nature of the white light observations enables us to see new structure in the light curve morphology., Comment: 6 pages Latex, 5 figures, to appear in MNRAS

Tumor-elicited neutrophils (tcPMN) purified from 13762NF mammary adenocarcinoma tumor-bearing rats enhanced metastasis of syngeneic cells when co-injected intravenously; whereas, circulating (cPMN) and phorbol esteractivated (PMA-PMN) neutrophils did not [Welch et al. (1989) Proc. Natl. Acad. Sci. 86:5859-63]. We hypothesized that differential protein expression was responsible for functional differences between the neutrophil subtypes. Two-dimensional polyacrylamide gel electrophoresis was used to compare neutrophils (cPMN, PMA-PMN) purified from the peripheral blood of healthy, syngeneic nontumor-bearing rats, to tcPMN collected from rats with highly metastatic [clone MTLn3, subclone MTLn3(T44).5] or poorly metastatic [subclone MTLn3(T44).11] tumors growing in the mammary fat pads. Quantitative differences in polypeptide expression were observed between these functionally distinct PMN populations. Compared to cPMN, expression of a M(r) approximately 38.8 kDa (pl approximately 8) polypeptide was similar in tcPMN collected from poorly metastatic tumor-bearing rats, higher in PMA-PMN, and further increased in tcPMN from rats with highly metastatic tumors. Expression of two polypeptides, M(r) approximately 14.1 kDa (pl approximately 6) and M(r) approximately 43.3 kDa (pl approximately 5), was greater in tcPMN from rats with highly metastatic tumors compared to cPMN, PMA-PMN, or tcPMN from rats bearing poorly metastatic tumors. The latter two polypeptides thus appeared to be specifically increased in tcPMN from rats bearing highly metastatic tumors. Because it was most abundant and displayed the greatest differences between PMN subtypes, the M(r) approximately 14.1 kDa protein was further analyzed. Tryptic digests followed by internal sequence analyses of resulting peptide fragments revealed that the M(r) approximately 14.1 kDa contained amino acid sequences that were identical to those of MRP-14, a 14 kDa neutrophil calcium-binding protein belonging to the S-100 protein family of calcium-binding proteins. These results suggest a novel function for MRP-14 and suggest that MRP-14 may represent a marker for distinguishing phenotypically distinct subpopulations of neutrophils, particularly tcPMN with metastasis-enhancing abilities.