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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.

Progression of human melanoma toward increasing malignant behavior is associated with several nonrandom chromosomal aberrations, most commonly involving chromosomes 1, 6, 7, 9, and 10. We previously showed that introduction of human chromosome 6 into the highly metastatic human malignant melanoma cell line C8161 completely suppressed metastasis without altering tumorigenicity (Welch DR, Chen P, Miele ME, et al., Oncogene 9:255-262, 1994). Alterations of chromosome 1 are the most frequent chromosome abnormality observed in melanomas, and they frequently arise late in tumor progression. The purpose of the study presented here was to compare the effects of chromosomes 1 and 6 on malignant melanoma metastasis. By using microcell-mediated chromosome transfer, single copies of neo-tagged human chromosomes 1 or 6 were introduced into the human melanoma cell line MelJuSo. The presence of the added chromosome was verified by G banding of karyotypes, fluorescence in situ hybridization, and screening for polymorphic markers on each chromosome. The incidence and number of metastases per lung after intravenous or intradermal injection of parental MelJuSo cells was significantly (P0.01) greater than those of hybrids containing either chromosome 1 or chromosome 6, although chromosome 1 was a less potent inhibitor of metastasis than chromosome 6. Cultures established from primary tumors and metastases remained neomycin resistant, suggesting that portions of the added chromosomes were retained. These results strengthen the evidence for the presence of a melanoma metastasis suppressor gene on chromosome 6. neo6/MelJuSo hybrids expressed 2.4- to 3.4-fold more of the melanoma differentiation-associated gene mda-6 (previously shown to be identical to WAF1/CIP1/Sdi1/CAP20) than parental metastatic cells. mda-6/WAF1 is among the candidate genes on chromosome 6. These results also demonstrate, for the first time, the existence of metastasis suppressor genes on human chromosome 1, although these genes appear to be less potent than the one encoded on chromosome 6.

To determine the relevance of genetic information on chromosome 11 in the development of metastatic breast tumors, we introduced a normal human chromosome 11 into the highly metastatic MDA-MB-435 breast carcinoma cell line via the microcell-mediated chromosome transfer technique. Although the MDA-MB-435 recipient cell line and four randomly selected microcell hybrid clones remained tumorigenic in nude mice, the hybrids were95% suppressed for metastasis to lung and regional lymph nodes (p0.01). We also tested whether chromosome 6 harbors a metastasis-suppressor gene for breast cancer as observed previously for human melanoma. Grouped together, the four neo6 microcell hybrids had no statistically significant reduction in the incidence or number of lung or lymph node metastases compared to the weakly metastatic, subcloned parent cell line, MDA-MB-453.7. Expression of nm23-H1 (NME1), a known metastasis-suppressor gene in this breast cancer cell line, did not correlate with metastasis suppression in the microcell hybrids. These results further demonstrate that control of metastasis is molecularly distinct from tumorigenic potential. They also indicate that chromosome 11 encodes a metastasis-suppressor gene for human breast cancer.

Differentially regulated expression of activators and inhibitors of cyclin-dependent kinases (cdks) modulate cell cycle progression. In normal fibroblasts, these complexes consist of the cdk inhibitor p21WAF1/PCNA/G1 cyclin/cdk. We now show that bromodeoxyuridine (BrdUrd), a thymidine analogue and radiation sensitizer, inhibits growth and activity of cyclin A-cdk2 kinase in metastatic C8161 and nonmetastatic neo 6.3/C8161 human melanoma cells. Inhibition is not due to altered levels of cyclin D or catalytic cdk2 but involves a decrease in cyclin A and proliferating cell nuclear antigen, paralleled by higher levels of p21WAF1 without increases in p53. In contrast to serum starvation, which prevents accumulation of cyclins A and D in normal fibroblasts, such treatment did not down-regulate either cyclin in these melanoma cells, implying an aberrant control for G1 cyclins in these tumor cells. However, cyclin A was decreased by BrdUrd, suggesting that this pyrimidine analogue arrests melanoma cells at a G1 transition point, unlike that of serum starvation. This is the first report indicating that the antitumor therapeutic action of BrdUrd may be mediated by a p53-independent reciprocal effect on activators and inhibitors of cdk kinases.

Low loss coupling and passive alignment of lasers to single mode fibers are key technologies for opto-electronic packaging. Single-mode fiber coupling of semiconductor lasers usually results in a significant insertion loss of several dB. This excess loss stems from the undesirable waveguide properties of laser diodes. A new design for 980 nm laser featuring low divergence (15°) and low ellipticity (1.5) is presented and shown to result in less than 1 dB coupling loss into a cleaved fiber. The active alignment cost of the singlemode fiber to the laser laser has a important impact on the the cost of photonic packages. We also report on a low-cost packaging technique based on passive alignment of a laser array to a Silica-on-Silicon waveguide array, with 36% coupling efficiency.

It is shown by means of multi-fluid particle-in-cell simulations that convergence of the spherical shock wave that propagates through the inner gas of inertial confinement fusion-relevant experiments is accompanied by a separation of deuterium (D) and tritium (T) ions across the shock front. Deuterons run ahead of the tritons due to their lower mass and higher charge-to-mass ratio and can reach the center several tens of picoseconds before the tritons. The rising edge of the DD and TT fusion rate is also temporally separated by the same amount, which should be an observable in experiments and would be a direct proof of the “stratification conjecture” on the shock front [Amendt et al., Phys. Plasmas 18, 056308 (2011)]. Moreover, dephasing of the D and T shock components in terms of density and temperature leads to a degradation of the DT fusion yield as the converging shock first rebounds from the fuel center (shock yield). For the parameters of this study, the second peak in the fusion yield (compression yield) is strongly dependent on the choice of the flux limiter.

Manganese superoxide dismutase (MnSOD, encoded by the SOD2 gene mapping to chromosome 6q25) has been implicated as a tumor suppressor and as a metastasis suppressor in some tumor cell lines. We showed that introduction of an intact chromosome 6 into the metastatic melanoma cell line C8161 completely suppressed metastasis but did not affect tumorigenicity (Welch et al., (1994) Oncogene 9:255). The purpose of this study was to test whether SOD2 is the gene responsible for metastasis suppression. MnSOD protein levels of C8161 (measured by Western blot), before and after transfer of chromosome 6, showed no correlation with metastatic potential. To determine whether the lack of correlation was due to mutant, nonfunctional SOD2, a highly metastatic subclone of C8161 (C8161c1.9) was transfected with functional SOD2 or vector control (pSFFV). Metastatic potential and tumorigenicity were unchanged. Southern and Northern blots confirmed the presence of the transfected SOD2; however, total MnSOD protein and antioxidant activity were not significantly altered. These results suggest that levels of MnSOD are highly regulated within C8161 melanoma cells and that SOD2 does not suppress tumor formation nor metastatic potential in all human melanomas.

The combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (MEZ) induces terminal differentiation with an irreversible loss of proliferative capacity in human melanoma cells. Using subtraction hybridization, cDNAs were identified that display enhanced expression in terminally differentiated and growth arrested human melanoma cells (Jiang and Fisher, 1993; Jiang et al., 1994a). A specific melanoma differentiation-associated (mda) cDNA, mda-6, is described whose expression inversely correlates with melanoma progression and growth. mda-6 is identical to WAF1/CIP1/SDI1 that encodes the M(r) 21,000 protein (p21) that is an inhibitor of cyclin-dependent kinases. Actively growing normal melanocyte, SV40-immortalized human melanocyte and dysplastic nevus cell lines synthesize elevated levels of mda-6 mRNA; whereas, actively proliferating radial and early vertical growth phase primary melanomas as well as metastatic human melanoma cells produce reduced levels of mda-6 mRNA. Treatment of primary and metastatic human melanoma cells with IFN-beta + MEZ results in growth inhibition and an increase in mda-6 expression. mda-6 expression also increases when human melanoma cells are grown to high saturation densities or when grown in serum-free medium. Using anti-p53 and anti-p21 antibodies, an inverse correlation is found between p53 and p21 protein levels during growth arrest and differentiation. Induction of growth arrest and terminal differentiation in H0-1 human melanoma cells by IFN-beta + MEZ results in a temporal decrease in wild-type p53 protein levels with a corresponding increase in p21 levels. In the Matrigel-assisted melanoma progression model, mda-6 expression decreases in early vertical growth phase primary human melanoma cells selected for autonomous or enhanced tumor formation in nude mice. In metastatic human melanoma cells displaying a loss of metastatic potential resulting from introduction of a normal human chromosome 6, mda-6 mRNA levels increase. Taken together, these studies indicate that mda-6 (p21) may function as a negative regulator of melanoma growth, progression and metastasis.

The ability of tumor cell lines to form experimental pulmonary metastases is determined in part by characteristics which are stable over many cell generations; in part by characteristics that are acquired by adaptation or phenotypic instability; but also in part by characteristics which may change over less than one cell generation. This study was designed to examine the hypothesis that tumor cells secrete and respond to paracrine factors which can reversibly modulate metastasis. The number of experimental lung metastases increased for 13762NF rat mammary adenocarcinoma cell clones MTF7 and MTLn3 as they approach 100% confluence. This observation corresponded to increased attachment to bovine brain capillary and bovine corneal endothelial monolayers and to ability of tumor cells to invade reconstituted basement membrane barriers in the Membrane Invasion Culture System (MICS), but did not correspond to cell cycle distribution, susceptibility to NK or PMN cell killing or average cell size/Coulter volume. While changing confluence did not qualitatively alter metastatic potential, modification of metastasis in a quantitative manner suggested that some properties pertinent to metastasis are transient and manipulatable. Tumor cell-conditioned medium (CM) collected from donor cells grown to defined levels of confluence when placed onto recipient cells reversibly raised or lowered metastatic potential depending upon the medium source and confluence of the recipient cells. CM from 20% confluent donor cultures reduced recipient cell metastatic potential. In contrast CM from 100% confluent cultures increased metastatic potential of subconfluent cells. Replacement with fresh unconditioned medium or leaving the medium unchanged did not alter experimental metastasis. These data suggest that metastasis involves steps which may be influenced by paracrine factors elaborated by tumor cells.

Extensive lifetesting is ongoing for single spatial mode 980 nm laser diodes suitable for pumping fiber amplifiers. Reliability estimates for commercially available lasers exceed the requirements for terrestrial deployment. Testing is currently being initiated on a new generation of devices that are expected to produce even better reliability at even higher powers that simplify amplifier design and reduce cost. New device designs, such as the master oscillator power amplifier (MOPA), have demonstrated radically higher single-mode fiber coupled powers and coupling efficiencies. Recently, coupling efficiencies into single-mode fiber of 68 % have been achieved with total fiber coupled power in excess of 800 mW. This represents more than an 8 fold increase over the maximum commercially available power of 90 mW, and should open new applications to fiber amplifiers. These fiber coupled powers are available at both 980 nm and 1017 nm.

Structural alterations of chromosome 6, including del(6q), are often associated with metastatic melanoma; therefore, we hypothesized that a metastasis-suppressor gene could be coded on human chromosome 6. Highly metastatic C8161 human malignant melanoma cells exhibit chromosomal changes typical of late-stage melanomas. Using microcell-mediated chromosome transfer, a copy of a normal human chromosome 6 was introduced into C8161. Three randomly selected hybrid clones (neo6/C8161.1, neo6/C8161.2 and neo6/C8161.3) were assayed for metastasis in athymic nude mice. All controls - parental C8161 cells, randomly-selected single cell clones, neo-transfected cell clones, neo11/C8161.2 and neo11/C8161.3 - were tumorigenic (270/272 mice) and metastatic (208/272 mice). neo6/C8161 hybrid cells were still tumorigenic (91/93 mice) but were not metastatic (0/195 mice). The presence of the added chromosomes was verified in cultured and tumor cells by amplification of polymorphic (CA)n markers using PCR-RFLP. The neo6/C8161 hybrids display growth and morphological patterns of more differentiated cells than C8161. In Northern blot analysis an inverse relationship between metastatic ability and metastasis-suppressor gene, nm23-H1, expression is observed - with clone neo6/C8161.1 expressing the highest level of nm23 transcripts, neo6/C8161.2 and neo6/C8161.3 expressing intermediate levels, and barely detectable levels are seen in C8161. Collectively, these results suggest that a malignant melanoma metastasis-regulatory gene may be located on human chromosome 6. These results further demonstrate that tumorigenicity and metastatic ability are distinct phenotypes.

We have demonstrated a 75 % coupling efficiency from a monolithically integrated master oscillator power amplifier (MOPA) diode laser source into a single-mode optical fiber. This was then used to pump a Pr3+-doped fiber amplifier. A net fiber gain of 19 dB was demonstrated and a 4 dB receiver enhancement was observed when the Pr3+-doped fiber was used as a preamplifier in a 2.5 Gbit NRZ transmission experiment.

We present the preliminary results of a frequency analysis of 1457 fundamental mode RR Lyrae (RR0) stars in the Large Magellanic Cloud (LMC) from MACHO Project photometry. We find the same classes of pulsational behavior as were found in our earlier survey of first overtone RR Lyrae (RR1) stars. Variables whose prewhitened power spectra contain one or two peaks close to the main frequency component in the original power spectra are commonly known as Blazhko-type variables. The present analysis shows the overall frequency of Blazhko-type stars in the total RR0 population analysed to date to be ≈ 10%. This is lower than the often cited Galactic field/globular rate of 20-30% (Szeidl, 1988).The incidence rate of Blazhko-type variability in the LMC appears to be about three times higher in RR0 stars than in RR1 stars. This puts important constraints on possible models of the Blazhko effect.

SN 2007it is a bright, Type IIP supernova which shows indications of both pre-existing and newly formed dust. The visible photometry shows a bright late-time luminosity, powered by the 0.09 M$_{\sun}$ of $^{56}$Ni present in the ejecta. There is also a sudden drop in optical brightness after day 339, and a corresponding brightening in the IR due to new dust forming in the ejecta. CO and SiO emission, generally thought to be precursors to dust formation, may have been detected in the mid-IR photometry of SN 2007it. The optical spectra show stronger than average [O I] emission lines and weaker than average [Ca II] lines, which may indicate a 16 - 27 M$_{\sun}$ progenitor, on the higher end of expected Type IIP masses. Multi-component [O I] lines are also seen in the optical spectra, most likely caused by an asymmetric blob or a torus of oxygen core material being ejected during the SN explosion. Interaction with circumstellar material prior to day 540 may have created a cool dense shell between the forward and reverse shocks where new dust is condensing. At late times there is also a flattening of the visible lightcurve as the ejecta luminosity fades and a surrounding light echo becomes visible. Radiative transfer models of SN 2007it SEDs indicate that up to 10$^{-4}$ M$_{\sun}$ of new dust has formed in the ejecta, which is consistent with the amount of dust formed in other core collapse supernovae., Accepted for publication in ApJ

The expression of metalloproteinases, such as type IV collagenase/gelatinase, enables tumor cells to degrade type IV collagen present in the basement membrane and correlates with metastatic potential of several tumor types. We found that increased levels of rat serum type IV collagenolytic activity are associated with increased 13762NF mammary adenocarcinoma metastases in lungs and lymph nodes of syngeneic rats. To investigate serum metalloproteinases responsible for type IV collagenolysis, we performed zymography and Western blot analysis of rat sera. A M(r) 92,000 progelatinase (progelatinase B, M(r) 92,000 type IV procollagenase, MMP-9) was detected on zymograms of rat sera within 16 days after intramammary fat pad inoculation of highly metastatic MTLn3 cells. The activated serum M(r) 92,000 progelatinase degraded sodium dodecyl sulfate-denatured type I and IV collagens but was not active on casein, albumin, hemoglobin, and immunoglobulin. Sera from rats with fat pad tumors and lung metastases formed from highly metastatic clones possessed greater than 7 times higher levels of serum M(r) 92,000 progelatinase than control sera or sera from rats bearing similar size fat-pad tumors of low or nonmetastatic clones. The results were confirmed by Western blot analysis of rat sera using rabbit anti-human M(r) 92,000 progelatinase antibodies. Similar results were obtained from the analysis of rat plasma samples. The serum and plasma M(r) 92,000 progelatinase levels correlated with the extent of metastases in the lung and lymph nodes. The results indicate that high levels of serum and plasma M(r) 92,000 progelatinase are associated with the presence of disseminated metastatic adenocarcinoma cells and suggest that this enzyme may facilitate the invasion of blood-borne tumor cells through vascular basement membranes.

Relatively penicillin-resistant pneumococci have caused 10% of invasive pneumococcal disease in central Oklahoma during the last decade, but almost no high-level penicillin or other antibiotic resistance has been described. This study evaluated antibiotic susceptibility and serotype distribution in invasive pneumococcal disease in the Oklahoma City metropolitan area (1990 population 848,000). A total of 144 cases of invasive infection was collected in 1 year (17 with meningitis, 120 with other bacteremic infections, and 7 with other invasive infections), for a rate of 16.9/100,000 (95% confidence interval [CI], 14.0-19.5). For the population agedor = 60, invasive pneumococcal disease rates were higher among nursing home residents (352/100,000) than among nonresidents (25.6/100,000; relative risk, 13.7; 95% CI, 7.7-24.7). Antibiotic-resistant organisms caused 19.4% of the cases: relative penicillin resistance, 7.6%; high-level penicillin resistance, 1.4% (2 cases), and 11% resistance to erythromycin, trimethoprim-sulfamethoxazole, or both, with 5% sharing both resistances plus a MIC of penicillin of 0.06 microgram/mL.

Two closely related species of Rochalimaea, Rochalimaea quintana and Rochalimaea henselae, are nutritionally fastidious but can be cultivated on bacteriologic media from the blood of patients with diverse clinical presentations. We report a case of culture-proven R. henselae bacteremia in a child with persistent fever. Serologic evidence of infection by R. henselae was ascertained by testing sera at two intervals for immunoglobulin G or immunoglobulin M antibodies by enzyme immunoassay and immunoblot. The case isolate and a collection of other strains (R. henselae, R. quintana, and related organisms) were used to test commercial identification systems for their comparative utility in the identification of Rochalimaea spp. on a practical basis. Of six systems designed for testing of either fastidious or anaerobic isolates of bacteria, the MicroScan Rapid Anaerobe Panel was the only system that distinguished R. henselae from R. quintana. Four of five others gave reactions that were unique within their data bases but did not distinguish Rochalimaea isolates at the species level.

Restriction endonuclease analysis of a polymerase chain reaction-amplified DNA fragment which included the spacer region between the genes coding for 16S and 23S rRNAs and a portion of the gene coding for 23S rRNA (spacer + 23S) was done on 10 previously characterized clinical isolates of Rochalimaea henselae, one clinical isolate of Rochalimaea quintana, and the type strains of R. henselae, R. quintana, Rochalimaea vinsonii, and Bartonella bacilliformis. Brucella abortus DNA was not amplified by the primer set used. The clinical isolates of Rochalimaea were obtained from blood or tissue from patients with and without preexisting disease. The amplicon from each strain was digested with five endonucleases (AluI, HaeIII, TaqI, HinfI, and MseI). AluI and HaeIII were useful in species differentiation and subtyping of R. henselae. R. henselae isolates showed six different restriction patterns with AluI and four patterns with HaeIII. TaqI, HinfI, and MseI were useful only in species differentiation. These observations indicate that PCR amplification of the spacer + 23S region of the ribosomal DNA of Rochalimaea spp., along with restriction endonuclease analysis, allows differentiation of Rochalimaea spp. from closely related genera, differentiation among the species within Rochalimaea, and differentiation of strains within R. henselae. The subtyping potential of this method may be useful for further clinical and epidemiologic studies of the spectrum of diseases caused by R. henselae.

Rochalimaea quintana and Rochalimaea henselae are closely related, fastidious, gram-negative rickettsiae. Thus far, the spectrum of human Rochalimaea sp. infections has not included endocarditis. We describe a 50-year-old human immunodeficiency virus-positive man who developed endocarditis caused by R. quintana. DNA relatedness studies, which compared our patient's blood culture isolate with known Rochalimaea species, identified the organism as R. quintana. Our report expands the spectrum of Rochalimaea sp. infections and identifies a new infectious cause of endocarditis.

The properties and low pressure organometallic vapor phase epitaxy of Gaxln1-xP/(AlGa)0.5ln0.5P quantum well (QW) laser diode heterostructures with Al0.5ln0.5P cladding layers, and having wavelength 614 660 nm), threshold current densities under 200 A/cm2 and efficiencies greater than 75% result from a biaxially-compressed GalnP QW active region. Although short wavelength laser performance is diminished by the poor electron confinement afforded by AlGalnP heterostructures, good 630 nm band performance, and extension into the 610 nm band, is achieved with strained, single QW active regions.

Significant erosion of the front of the HERMES-III electron beam in drift cells filled with N{sub 2} gas is measured for pressures greater than 100 Torr (as much as 10 ns [3 m] at 630 Torr for 11-m length cells). Little rise time (RT) sharpening or pulse width reduction of the subsequent radiation pulse generated at bremsstrahlung targets terminating the cells, however, is measured. Three-dimensional numerical simulations show that the simultaneous virulence of the resistive-hose instability with increased pressure degrades the spatial coherence of the leading edge of the beam, degrading in turn the RT of the radiation pulse. Transport in the lower-pressure ion-focused regime, on the other hand, does permit intense radiation fields to be produced near the beam axis at the target, with RTs and pulse widths that can be controlled with pressure. Over the range 5 to 50 mTorr, the RT and full-width half-maximum (FWHM) of the on-axis radiation pulse are inversely related to pressure and can be varied from {approximately}5 to {approximately}2 ns and {approximately}8 to {approximately}3 ns, respectively. At 10 mTorr, for example, the RT and FWHM are 4.2 {plus_minus} 1.7 ns and 6.1 {plus_minus} 1.3 ns, and the corresponding peak dose, peak-dose rate, andmore » useful area of exposure are {approximately}25 krad (CaF{sub 2}), {approximately}4 Trad (CaF{sub 2})/s, and {approximately}300 cm{sup 2}, respectively.« less

Summary form only given. The compound-lens diode is used to extract and inject the 19-MV, 700-kA, 25-ns electron beam from HERMES III into long, gas-filled metal drift cells for transport in the collisional regime to targets for bremsstrahlung production. Efficient and stable transport is required for optimal and repeatable bremsstrahlung production. The transport has been characterized as a function of injection parameters and gas pressure over the range 0.5 to 630 torr. It has been shown experimentally and theoretically that the region of optimal energy transport lies in a "propagation window" between two regions of instability caused by beam-plasma interactions. Below /spl sim/2 torr, as the ratio of the collision frequency to plasma-electron frequency decreases, the semi-collisionless two-stream instability disrupts the beam. Above /spl sim/80 torr, as the plasma-electron mean-free-path is reduced by dissociative recombination with gas neutrals, the resistive hose instability enhances transverse oscillations in the beam centroid.

We report the immunocytochemical identification of Rochalimaea henselae, a newly recognized fastidious, Gram-negative, Warthin-Starry-positive organism, as the common pathogen in bacillary angiomatosis (BA), bacillary peliosis (BP) of the liver and spleen, and persistent fever with bacteremia in immunocompromised patients. Immunogenic proteins of the R. henselae strain isolated from the blood of a febrile immunocompromised patient with BP of the liver were used to produce primary immune serum in rabbits. Using immunocytochemical procedures, the polyclonal antiserum reacted strongly not only with the immunizing strain of the bacteria, but also with other blood isolates of R. henselae (five cases) from both immunocompromised and immunocompetent patients and with the organisms present in the tissue lesions of cutaneous BA (five cases) and BP of the liver (two cases) and spleen (one case). The blood isolates and BA and BP tissue samples were obtained from widely separated geographic areas. The antiserum was weakly cross-reactive with cultures of Rochalimaea quintana, an organism closely related to R. henselae, but this reactivity was eliminated by specific adsorption. The antiserum did not cross-react with the Warthin-Starry-positive organisms associated with cat scratch disease (Afipia felis), syphilis (Treponema pallidum), Lyme disease (Borrelia burgdorferi) or chronic active gastritis (Helicobacter pylori). Likewise, the antiserum did not identify organisms in eight cases of Kaposi's sarcoma, a disorder of immunocompromised patients that is clinically similar to BA. Further studies are needed to determine the prevalence of this newly recognized organism as well as its possible involvement in other angioproliferative diseases.

Recent studies have demonstrated that a newly described agent of persistent bacteremia, Rochalimaea henselae, and the agent of bacillary angiomatosis are both closely related to Rochalimaea quintana. Bacillary peliosis hepatis seemed likely to have the same etiologic agent as bacillary angiomatosis. We sought these pathologic changes in patients from whom R henselae was cultivated.For two patients whose histopathologic findings we reviewed, additional light and electron microscopy were performed. Their bacterial isolates were compared by electrophoretic patterns of outer membrane proteins, restriction endonuclease digestion patterns of DNA, and reaction with murine antiserum.A previously reported human immunodeficiency virus-infected man with persistent bacteremia due to R henselae was found to have bacillary peliosis hepatis. Rochalimaea henselae was also isolated from the spleen of a woman receiving immunosuppressive therapy after allogeneic renal transplantation. She had developed fever, liver and spleen nodules, and periaortic lymphadenopathy. Bacillary peliosis of her liver and spleen, as well as bacillary angiomatosis of liver, spleen, and a lymph node, were found. The bacterial isolates had comparable electrophoretic patterns of outer membrane proteins and of restriction endonuclease-digested DNA, which differed from the respective patterns of R quintana. Murine antisera raised to the first isolate reacted strongly with the second by means of immunoblot and immunofluorescence techniques, while reacting only weakly with R quintana.Rochalimaea henselae, recently recognized to cause persistent fever and bacteremia in immunocompetent and immunocompromised persons, also causes bacillary angiomatosis and parenchymal bacillary peliosis.

Six fallow deer (Dama dama) fawns died after receiving 25 to 150 infective larvae of Parelaphostrongylus tenuis. Fawns given higher doses usually died sooner (6 to 23 days) than those given lower doses (54 to 67 days). Early deaths were associated with severe acute peritonitis resulting from perforation of the intestinal wall; later deaths were associated with paralysis and inability to rise. Numerous adult P. tenuis were found within neural tissues of the brain and spinal cord in the three fawns with paralysis. One white-tailed deer (Odocoileus virginianus) exposed to infective larvae from the same source survived infection without exhibiting clinical signs and began passing larvae in feces 88 days post-exposure. At the doses used in this study, meningeal worm caused fatal infections in fallow deer. Results are compared to published observations of fallow deer naturally-infected with P. tenuis.

We present the first massive frequency analysis of the 1200 first overtone RR Lyrae stars in the Large Magellanic Cloud observed in the first 4.3 yr of the MACHO project. Besides the many new double-mode variables, we also discovered stars with closely spaced frequencies. These variables are most probably nonradial pulsators.