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The coherent coupling between an optical transition and a confined optical mode, when sufficiently strong, gives rise to a new pair of mixed modes separated in frequency by the vacuum Rabi splitting. Such systems have been widely investigated for electronic-state transitions such as molecular excitons coupled to surface-plasmons and optical microcavities. However, only very recently have vibrational transitions been considered. Here we experimentally investigate the coupling between a Fabry–Perot cavity and the carbonyl stretch at an infrared frequency near 1730 cm–1 in polymethyl methacrylate. As is requisite for the “strong coupling” regime, the measured vacuum-Rabi-splitting of 132 cm–1 is much larger than the full width of either the cavity resonance (34 cm–1) or the inhomogeneously broadened carbonyl-stretch absorption (24 cm–1). With the assistance of quantitative analysis using transfer-matrix methods, we provide evidence that the mixed-state resonances are relatively immune to inhomogeneous vibrat...

Neutron and Gamma detectors have been used to monitor the nuclear radiation in the environment (Jianping in Nucl Electron Detect Technol 19(1), 1999; Chai et al. in Nucl Electron Detect Technol 25(1), 2005), during the experimental advanced superconducting tokamak (EAST) discharging. This paper is focus on the EAST’s nuclear radiation monitoring. Based on the full and real-time need for monitoring of radiation, the placement of radiation’s detectors around the EAST and the environment is studied. To get the radiation’s value, this paper gives the design of the monitoring system and presents the system’s acquisition module which transforms radiation to voltage signal. For the long distance and uneven distribution of each detector, transforming and processing module is designed, and the comparator’s principle and RS-485 transmission protocol are reviewed, the circuits of the comparator and RS-485 used in this system are designed. Then a conversion module is presented to have communication with personal computer, and framework of the whole monitoring system is introduced.

Silicon carbide inclusions in multicrystalline (polycrystalline) silicon ingots affect the cutting process and quality of silicon wafers. The higher density of SiC inclusions relative to the silicon melt suggests that they should sink, but inclusions were observed at the top, middle and bottom of industrial ingots. More inclusions were observed at the top relative to the middle and bottom of the ingot. Small SiC inclusions were found at the bottom and reticular SiC inclusions at the top of the ingot, suggesting that inclusion growth may occur during growth of the ingot. A mechanism to explain the formation and distribution of SiC in industrial silicon directionally solidified ingots, based on the thermodynamics of SiC, is proposed together with strategies to reduce carbon contamination and improve ingot quality.

There is considerable interest in the direct bonding between Si and Ge substrates and high-K nano-crystalline transition metal elemental and complex oxides. Implicit in this is the elimination of lower-K interfacial transition regions (ITRs) in gate stacks which limit device down-scaling of advanced devices to meet roadmap targets. A novel approach is presented in this article for (i) deposition of HfO 2 onto N-passivated Ge(1 1 1) and Ge(1 0 0) substrates, a process that also prevents subcutaneous oxidation of the Ge substrate during the deposition of nano-crystalline HfO 2 and non-crystalline Hf Si oxynitride dielectrics as well, and (ii) the effective removal of Ge–N, during an 800 °C rapid thermal annealing. Removal of Ge–N bonding has been confirmed by X-ray absorption N K 1 spectra (XAS). However, even though X-ray photoelectron spectroscopy (XPS) studies has indicated no detectable Ge–O bonding at the Ge-dielectric interfaces as-deposited, a significant amount of Ge–O bonding throughout the entire HfO 2 film is detected by XPS and XAS after the 800 °C anneal. Current–voltage measurements indicate significantly higher leakage for HfO 2 films on Ge(1 1 1) compared with Ge(1 0 0). These correlate with differences in band edge defect state densities obtained from spectroscopic measurements, and are consistent with a more columnar, bonding morphology for direct bonding of HfO 2 on Ge(1 1 1) than for Ge(1 0 0).

The contribution from a relatively low-K SiON (K~6) interfacial transition region (ITR) between Si and transition metal high-K gate dielectrics such as nanocrystalline HfO"2 (K~20), and non-crystalline Hf Si oxynitride (K~10-12) places a significant limitation on equivalent oxide thickness (EOT) scaling. This limitation is equally significant for metal-oxide-semiconductor capacitors and field effect transistors, MOSCAPs and MOSFETs, respectively, fabricated on Ge substrates. This article uses a novel remote plasma processing approach to remove native Ge ITRs and bond transition metal gate dielectrics directly onto crystalline Ge substrates. Proceeding in this way we identify (i) the source of significant electron trapping at interfaces between Ge and Ge native oxide, nitride and oxynitride ITRs, and (ii) a methodology for eliminating native oxide, or nitride IRTs on Ge, and achieving direct contact between nanocrystalline HfO"2 and non-crystalline high Si"3N"4 content Hf Si oxynitride alloys, and crystalline Ge substrates. We then combine spectroscopic studies, theory and modeling with electrical measurements to demonstrate the relative performance of qualitatively different nanocrystalline and non-crystalline gate dielectrics for MOS Ge test devices.

This paper presents a spectroscopic study of interfacial bonding and substrate gate dielectric reactions for crystalline Ge-high-K gate dielectric hetero-structures. A novel processing sequence has been developed for i) depositing HfO2 and Hf Si oxynitrides (HfSiON) onto N-passivated Ge(111) and (100) substrates in an attempt to prevent subcutaneous oxidation of the Ge substrate during dielectric deposition, and then ii) eliminating these Ge-N interfacial bonds during 650-800°C rapid thermal annealing in Ar. This approach has been motivated by previous spectroscopic studies which have demonstrated that the band-gaps of GeO2 and Ge3N4 are reduced with respect to their Si counterparts, and cannot be used as interfacial layers (ILs) on n-type Ge substrates, or in n-metal oxide semiconductor field effect transistors (n-MOSFETs) in which a p-type Ge substrate has been inverted. Changes in interface bonding as a function of post-deposition annealing for Ge/HfO2 and HfSiON, and HfO2/HfSiON stacks have been studied by X-ray absorption and photoelectron spectroscopies, revealing i) intrinsic, or pre-existing conduction and valence band edge defects, and ii) process-induced changes in band edge defects as well. [DOI: 10.1380/ejssnt.2009.381]

A study of changes in nano-scale morphology of thin films of nano-crystalline transition metal (TM) elemental oxides, HfO2 and TiO2, on plasma-nitrided Ge(100) substrates, and Si(100) substrates with ultra-thin (∼ 0.8 nm) plasma-nitrided Si suboxide, SiOx, x 150 eV is critical for this approach.

The contribution from relatively low-K SiON interfacial transition regions (ITRs) between Si and transition metal (TM) gate dielectrics places a significant limitation on equivalent oxide thickness (EOT) scaling for Si complementary metal-oxide-semiconductor (CMOS) devices. This limitation is equally significant and limiting for Ge CMOS devices. Low-K Ge-based ITRs in Ge devices have also been shown to limit performance and reliability, particular for n-MOS field effect transistors. This article identifies the source of significant electron trapping at interfaces between n-Ge or inverted p-Ge, and Ge oxide, nitride and oxynitride ITRs. This is shown to be an interfacial band alignment issue in which native Ge ITRs have conduction band offset energies smaller than those of TM dielectrics, and trap electrons for negative Ge substrate bias. This article also describes a novel remote plasma processing approach for effectively eliminating any significant native Ge ITRs and using a plasma-processing/annealing process sequence for bonding TM gate dielectrics directly to the Ge substrate surface.

A significant limitation in the fabrication of III-N MOSFET relates to the formation of ohmic contacts for enhancement-mode MOSFET structures. Unlike existing III-N HFET devices, which include a high free-carrier density two-dimensional electron gas (2DEG) in the semiconductor substrate, a MOSFET in either accumulation or inversion mode require low free-carrier concentrations for the semiconductor channel to have an off-state. The applied gate bias enhances the free-carrier density in the channel, turning on the FET. Unfortunately, a low free-carrier density substrate is problematic for the formation of ohmic contacts, a problem usually dealt with in silicon MOS through self-aligned ion implantation. The high annealing temperatures associated with activating implanted dopants to substitutional sites limits the use of ion implantation for III-N MOSFET fabrication. To overcome this difficulties, selected area epitaxial re-growth of doped III-N materials was developed to form source-drain contacts on otherwise low-doped III-N epitaxial substrates, yielding the needed N+/n−/N+ or N+/p−/N+ structures. Contact re-growth was performed by MOVPE using a silicon nitride dielectric mask defining plasma-etched recesses in the source-drain region. A significant acceleration in the growth rate and surface roughening was observed following re-growth relative to a non-selective area epitaxial growth due to the reduced fill-factor, motivating a general change in MOVPE-operating conditions during re-growth. As the re-growth was intentionally designed to limit the lateral extent of the source-drain regions, the MOVPE re-growth process was performed under conditions limiting lateral overgrowth. III-N MOSFET structures with epitaxial regrown contacts are projected to provide a pathway for low threshold voltage devices suitable for amplifier or logic applications.

Mullite short fiber reinforced Al-4.0Cu-1.85Mg composite and its base alloy were fabricated by squeeze casting. The age-hardening behavior, precipitation procedure, microstructure of dislocation and precipitates, and the interfacial structure have been studied by means of hardness measurement (HB), differential scanning calorimetry (DSC), and analytical transmission electron microscope (ATEM), respectively. The short mullite fiber in the composite induces high dislocation density in the near vicinity of the interface after it is solutionized and quenched in ice water, and suppresses or delays the formation of GPB zones. The aged hardness of the composite is always higher than that of its base alloy, but there appears little difference between the time needed in the composite and in the base alloy to reach the peak hardness, which means that the acceleration effect of mullite fiber in the precipitation of Al-Cu-Mg alloy is not great enough. Mg also reacts with Al and SiO2, resulting in the formation of spinel (MgAl2O4), which depletes Mg in the matrix and finally hinders the aging acceleration in the testing composite.

Larvae (late 3rd instars) of Bactrocera dorsalis (Hendel), B. cucurbitae (Coquillett), B. latifrons (Hendel), and Ceratitis capitata (Weidemann) were placed in either wet or dry sand for pupation. In dry sand, 91.1, 93.6, and 97.2% of the pupation by B. latifrons,B. cucurbitae, and B. dorsalis , respectively, occurred at a depth of 0 -5.5 mm. The remainder of the Bactrocera spp. pupated within 11 mm of the surface. More C. capitata (54.0%) pupated at 5.5-11 mm than at 0-5.5 mm (42.5%) and 3.5% moved down to 27.5 mm. In wet sand (5% water by weight), 95.5% of al14 species pupated at depths of 0-27.5 mm. Mortality of pupae was greatest in the dry sand at 0-5.5 mm. Cumulative mortality was 50% greater in dry sand than in wet sand. This indicates that both pupation depth and survival are affected by the moisture content of the sand. However, C. capitata is better adapted to the dry conditions than are the Bactrocera spp.

When released on trees inside field cages, Bactrocera latifrons (Hendel) males occupied the undersides of leaves from the middle to upper canopy. Before sunset (1/2-1 h) and at an average light intensity of 1,375 lumens/m 2 , males formed aggregations (leks) of 4-9 individuals and began calling behavior. Calling consisted of males rubbing their abdomen and wings with their hind legs, then fanning the wings in short, rapid bursts. This dispersed pheromone and perhaps created sound. After the light decreased to 1,357 ± 654.7 (mean ± SD) lumens/m 2 , females responded and mating commenced. Formation of leks and mating behavior occurred until sunset (4 min before to 15 min after sunset) and an average light intensity of 90.2 ± 50.9 lumens/m 2 . During the period 60-30 min before sunset, 29% of the total matings occurred, whereas in the final 30 min before sunset, 59.7% ofthe total matings occurred. On average, 33.9 ± 9.7% of the flies mated.

There is substantial evidence that the oceans of the world will pose the most important challenges in the area of hydrate formation. This work indicates three areas of concern for hydrate formation in the ocean: (1) deposits of natural gas in ocean hydrates, which will serve as an energy resource and environmental concern in the next tnillenium, (2) a recent proposal for the ocean storage of carbon dioxide in the form of hydrates, and (3) the prevention of hydrate formation in ocean pipelines. To address such applications, fundamental knowledge on the site of hydrate formation was determined. Results are presented for quiescent, high-pressure experiments done in a sapphire tube to determine the site of hydrate formation in deionized water and in mixtures with amorphous silica and sodium dodecyl sulfate. Visual (microscope aided) results are presented for formation with a typical gas mixture and with carbon dioxide.

Summary A model whereby a known number of coagulase-negative staphylococci were packed into capillary tubes and implanted into the peritoneal cavity of mice proved to be a satisfactory method for generating abscesses that could be easily removed free of extraneous host tissue, and that permitted measurement of the survival of the organisms and accumulation of lipid in the lesion. Strains of S. epidermidis, S. schleiferi and S. lugdunensis, differing in their ability to produce fatty acid modifying enzyme (FAME) and lipase, were packed into either glass or plastic capillary tubes and used to generate abscesses. Abscesses produced by S. aureus served as comparators. Lipids accumulated within the abscesses caused by S. aureus in the same manner as previously described for the organism inoculated without tubes.1 Lipids also accumulated within abscesses produced by all the coagulase-negative staphylococci, but the rate of accumulation was slower and the lipid droplets were smaller than seen with S. aureus. The mobilisation of lipid did not differ in response to cocci in plastic or glass tubes. Strains of S. epidermidis and S. schleiferi producing FAME and lipase were better able to survive within abscesses than strains unable to produce these enzymes. However, FAME and lipase production did not appear to be the sole determinants of survival within abscesses. Regardless of whether they produced FAME and lipase, the two S. epidermidis strains were significantly better able to survive within plastic tubes than in glass tubes. No such difference was seen with S. aureus between plastic and glass tubes.

Serotonin1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and 10-methyl-11-hydroxyaporphine, inhibited electrical stimulation-induced contraction of the guinea-pig ileum. These agonists also inhibited the pressor and tachycardiac responses to low frequency (0.25 Hz) but not to high frequency (2.0 Hz) electrical stimulation of the sympathetic nervous system in pithed rats. Serotonin1B receptor agonist RU 24969 inhibited pressor and tachycardiac responses to both low and high frequencies of stimulation in pithed rats. In the cat nictitating membrane, serotonin1A receptor agonists did not alter contractions elicited by electrical stimulation (0.1–3.0 Hz). Serotonin not only contracted the cat nicitating membrane but also facilitated contractile responses to low frequency (0.1 – 1.0 Hz) stimulation. The contractile effect of serotonin in the cat nictitating membrane was blunted by bretylium, methysergide, and ketanserin, but not by metoclopramide. The facilitatory effect of serotonin was antagonized by methysergide, but not by ketanserin, pindolol, propranolol, or metoclopramide. These results suggest that serotonin1A receptors modulate autonomic neurotransmission in the guinea-pig ileum and pithed rats, but not in the cat nictitating membrane. Serotonin contracts the cat nictitating membrane via serotonin2 subtypes, while facilitating stimulated contractile responses through the serotonin1-like receptors.Key words: guinea-pig ileum, pithed rats, nictitating membrane, serotonin receptors.

Immunization with recombinant S. pneumoniae neuraminidase NanA (rNanA) resulted in a significant reduction in pneumococcal colonization in the chinchilla model. The bacteria were eliminated from the nasopharynx 1 week earlier than that from the control cohort. Our data suggest that rNanA affords protection against pneumococcal nasopharyngeal colonization.

Streptococcus pneumoniae neuraminidase has been implicated as a virulence factor in the pathogenesis of pneumococcal otitis media. In this study, native neuraminidase was partially purified from cultures of S. pneumoniae by serial chromatography with DEAE-Sepharose and Sephacryl S-200. Recombinant neuraminidase, a 3,038-bp fragment of the neuraminidase A ( nanA ) gene, was cloned into the pET-28b vector and then expressed at high levels in Escherichia coli . Chinchillas were immunized subcutaneously with either the gel-purified native or recombinant neuraminidase, and all responded with elevated titers of antineuraminidase antibody in serum. Immunization with neuraminidase resulted in a significant reduction in nasopharyngeal colonization as well as in the incidence of otitis media with effusion. These data demonstrate for the first time that neuraminidase affords protection against S. pneumoniae nasopharyngeal colonization and experimental otitis media.

The surface quality of βSiC films grown on Si(100) by chemical vapor deposition has been assessed through synchrotron photoemission measurements of the valence band and of the linewidths and surface‐induced structure in Si 2p core‐level spectra. For these n‐type samples, band bending is small on the c(2×2) and (3×2) surfaces but larger on the (2×1), which also exhibits an increased Si 2p linewidth and evidence of elemental Si patches. All three reconstructions show emission from gap states extending from the valence band maximum to the Fermi level.

Phase variation in the colonial opacity phenotype of Streptococcus pneumoniae has been implicated as a factor in bacterial adherence, colonization, and invasion in the pathogenesis of pneumococcal otitis media (OM). The purpose of this study was to determine whether S. pneumoniae opacity variants influence the induction of gene expression for proinflammatory mediators in vivo using the rat model of OM. Both the opaque and transparent phenotype variants induced a significant up-regulation in gene expression for interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, tumor necrosis factor alpha, and inducible nitric oxide synthase (iNOS) compared to saline sham-inoculated controls at both 4 and 24 h postinoculation ( P < 0.05 in all cases). Furthermore, whereas a significant difference in gene expression was evident for only IL-6 (greater following challenge with the opaque variant) and IL-1β (greater following challenge with the transparent variant) at 4 h, by 24 h the opaque variant cohort demonstrated a significant increase in gene expression for IL-1α, IL-1β, IL-6, IL-10, and iNOS relative to animals inoculated with the transparent phenotype variant ( P < 0.05 in all cases). Enzyme-linked immunosorbent assay results confirmed the gene expression data as determined by real-time PCR. Moreover, the concentrations of the opaque variant in the middle ear lavage fluid were a full log higher than those of the transparent variant. The aforementioned results indicate that the opaque phenotype variant is more efficient at survival and multiplication within the middle ear space, resulting in the accumulation of more inflammatory cells and the enhanced expression and production of inflammatory mediators. However, when the data were normalized to account for differences in middle ear bacterial titers, it became apparent that the transparent variant of S. pneumoniae is a more potent inducer of inflammation, triggering the accumulation of more inflammatory cells and substantially greater fold increases in the expression and production of inflammatory mediators. Data from this study indicate that S. pneumoniae opacity variants influence the temporal mRNA expression of inflammatory mediators within the middle ear.

Real-time PCR and enzyme-linked immunosorbent assay were used to evaluate the ability of influenza A virus and Streptococcus pneumoniae opacity variants, either alone or in combination, to induce cytokine and chemokine genes in primary cultures of human middle ear epithelial (HMEE) cells. Following treatment with influenza A virus, the induction of gene expression, which occurred in a dose- and time-dependent manner, was strong for macrophage inflammatory protein 1α (MIP-1α) and MIP-1β; moderate for tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8; and weak for IL-1β and monocyte chemotactic peptide 1 (MCP-1). Except for TNF-α, all the gene products were detected in the cell culture supernatants. In contrast, infection of HMEE cells with S. pneumoniae alone induced low levels of mRNA expression of MIP-1α and MIP-1β and did not significantly induce the transcription of the other cytokines and chemokines examined. However, both S. pneumoniae opacity variants increased mRNA expression of MIP-1α, MIP-1β, IL-6, and MCP-1 in HMEE cells activated by a prior influenza A virus infection compared to levels in cells treated with either agent alone. Up-regulation of IL-6, IL-8, and MCP-1 mRNA expression and production by the virus in combination with opaque S. pneumoniae was two- to threefold higher than that induced by the virus combined with the transparent S. pneumoniae variant. These data indicate that the activation of HMEE cells by influenza A virus enhances the induction of cytokine and chemokine gene transcripts by S. pneumoniae and that this effect appears to be most pronounced when S. pneumoniae is in the opaque phase.

A modular, computer–controlled sampling system was developed to directly sample chopped forage material from a forage harvester spout. Pneumatic cylinders powered a deflector flap to redirect crop material from the spout. A hydraulic cylinder compressed deflected forage material into 35.6–cm long, 10.2–cm diameter PVC pipes, which served as miniature test silos. Timing of the pneumatic and hydraulic actuators was controlled by a programmable microcontroller. The control system included three operator inputs: travel speed, row length, and number of samples along the row for each silo; this provided flexibility to adapt to different harvesting situations. In two experiments, test–silo samples fermented for 48 days and then were separated into six size fractions. In the first experiment, a side–by–side comparison with a self–propelled plot harvester, statistically significant differences in the mass fractions of medium and small particles (indicated by low p–values in the range of 0.1 to < 0.001) were found between samples collected by both machines and their respective controls. No differences in the mass fractions of large particles were found. In the second experiment, the performance of the modular sampling system in sampling corn chopped at two theoretical lengths of cut (6.35 and 19.1 mm) and two whole–plant moisture levels (approximately 70 and 60% w.b.) was evaluated. Some significant statistical differences between automatic sampling and manual sampling were present; however, trends were inconclusive. The magnitudes of mass percentage and characteristic particle size differences were at most 8% and 1.6 mm, respectively.

Anorexia is defined as diminished appetite or aversion to food. Clinical manifestations of anorexia have multiple etiologies, which include systemic illness, pain, fever, stress, metabolic disorders, and decreased palatability and learned aversion to food. Disorders of appetite are common in companion and laboratory animal medicine. Anecdotal evidence and personal experience suggest that propofol (2, 6-diisopropylphenol), when given intravenously at subhypnotic doses, causes acute appetite stimulation in dogs. The establishment of a dose-response effect could have important clinical applications; therefore, this study attempts to qualify and quantify the effect of propofol on appetite stimulation in healthy young adult dogs. Six purpose-bred male dogs (age, 6 months) were obtained from a Class A vendor. Dogs were housed individually and provided water ad libitum throughout the study period. All dogs were fed ad libitum to ensure that test conditions and degree of satiety were identical. Each dog was assigned randomly to either an experimental group or control each day of the study. The experimental groups received single bolus intravenous injections of propofol at different dosage levels (0.5, 1.0, 1.5, 2.0, or 3.0 mg/kg of body weight), and the control group received saline. The administrator was blinded to the animals identification and dose. Dosages greater than 3.0 mg/kg resulted in profound sedation and ataxia, which physically inhibited the dogs from obtaining the food; therefore 3.0 mg/kg was the highest dose tested. Dogs were weighed daily to ensure accurate dosing. Dosing was performed at the same time each day to minimize variability. Food intake amounts were recorded at 15, 30, 60, 120, and 1440 min after injection. Food intake was expressed as [food intake (g)/ body weight (kg)/ unit time (min)]. After a 1-w rest period, the study was repeated. Data were analyzed with a type RBF-65 randomized-block factoral design (ANOVA). Each dog served as its own control. The two experiments were analyzed separately, and a P-value of less than 0.05 was used to declare statistical significance. A significant (P, 0.05) increase in food consumption was observed solely during the 0-to-15-min time interval; no significant increase in food consumption was observed at any other time point. This data supports propofols appetite stimulating effect in the initial 15 min after injection. Additional studies are required to explore the mechanism for this effect and to determine whether it occurs in other species.

Potential reasons for discordance between the Gleason score in biopsies and surgical specimens are: 1) pathological interpretation bias, and 2) sampling effects. The importance of sampling effects in grading errors was examined in a series where the number of biopsy cores obtained was high. Biopsies were obtained using a technique whereby 18 directed cores were systematically obtained and mapped out within the gland. Gleason scores from biopsies and matched prostatectomy specimens were compared among 28 consecutive patients with localized prostate cancer. A pooled database from 10 series (n = 2,687) served as a baseline for comparison in the accuracy of Gleason score grading. With the present biopsy technique, an exact Gleason score match was achieved in 57% of cases, compared with the pooled database (PD) mean of 42% (P = 0.055), and was within 1 point in 93% of cases compared with 78% (PD) (P = 0.029). Upgrading of biopsies was seen in 35% of cases, compared with 43% (PD) (P = 0.19). With respect to Gleason score 7, an exact match was present in 78% of cases, compared with 63% (PD) (P = 0.17), and upgrading was 0%, compared with 20% (PD) (P = 0.07). The data suggest a significant reduction in grade errors by minimizing sampling effects, one that it is of the same order of magnitude as the reduction achieved from consensus pathologic evaluation. In our study, seven patients (25%) would have had their cancers missed altogether with sextant biopsies. Sampling effects may contribute significantly to grading errors in prostate needle biopsies, although a larger study is needed to confirm this. A methodology which adopts a higher number of cores combined with a consensus pathologic evaluation could potentially reduce grading errors substantially. The optimal number of cores remains to be determined in a larger study. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 326-330 (2000).

Germline mutations of BRCA1 and BRCA2 predispose to hereditary breast, ovarian, and possibly prostate cancer, yet structural mutations in these genes are infrequent in sporadic cancer cases. To better define the involvement of these genes in sporadic cancers, we characterized expression levels of BRCA1 and BRCA2 transcripts in cancer cell lines derived from neoplasms of the ovary, prostate, and breast and compared them with those expressed in primary cultures of normal epithelial cells established from these organs. We observed upregulation of BRCA1 and/or BRCA2 expression in six of seven ovarian cancer cell lines (OVCA420, OVCA429, OVCA432, ALST, DOV13, and SKOV3) when compared with levels found in normal ovary surface epithelial cells. Furthermore, five cancerous or immortalized prostatic epithelial cell lines (BPH-1, TSU-Pr1, LNCaP, PC-3, and DU145) also expressed higher levels of BRCA1 and/or BRCA2 mRNA than did primary cultures of normal prostatic epithelial cells. In contrast, only the estrogen receptor-positive MCF-7 cell line overexpressed these messages, whereas the estrogen receptor-negative breast cancer cell lines Hs578T, MDA-MB-231, and MDA-MB-468 showed no change in expression levels when compared with normal breast epithelial cells. In addition, expanding on our recent identification of a novel BRCA2 transcript variant carrying an in-frame exon 12 deletion (BRCA2 delta 12), we report increased expression of this variant in several ovarian, prostate, and mammary cancer cell lines (OVCA420, OVCA433, ALST, DOV13, SKOV3, TSU-Pr1, DU145, and MDA-MB-468). Most notably, high levels of BRCA2 delta 12 mRNA were detected in an estrogen receptor-positive breast cancer cell line, MCF-7, and in an androgen-independent prostate cancer cell line, DU-145. Interestingly, the wild-type BRCA2 transcript was barely detectable in DU145, which could be used as a model system for future investigations on BRCA2 delta 12 function. Taken together, our data suggest disruption of BRCA1 and/or BRCA2 gene expression in certain epithelial cancer cell lines of the ovary, prostate, and breast. Because wild-type BRCA1 and BRCA2 gene products increase during cell-cycle progression and are believed to exert growth-inhibitory action, enhanced expression of these genes in cancer cells may represent a negative feedback mechanism for curbing proliferation in fast-growing cells. At present, the functionality of BRCA2 delta 12 remains elusive.

Rotating-wall vessels (RWVs) allow for the growth of cells under conditions of simulated microgravity. Information about the replication of viruses in simulated microgravity using RWVs has not been reported. Cells grown in RWVs are subjected to low shear motion, and the replication of certain viruses such as rhinoviruses has been reported to be enhanced by motion.Our research was based on the hypothesis that rhinovirus replication would be enhanced under conditions of simulated microgravity.HeLa cells were cultured in three-dimensional cultures on microcarrier beads in simulated microgravity using RWVs and in sealed Teflon roller bottles. Two-dimensional cultures of HeLa cells were also grown in tissue culture flasks (T-150s). Viral infections for all cultures were carried out under standardized conditions at 1 x g. The amount of new virus released during the first viral replication cycle and the total viral yields obtained from multiple viral replication cycles were determined.Viral quantitation during the first viral replication cycle showed that after 10-13 h RWV and Teflon roller bottle supernatants contained significantly more virus than the supernatants from T-150 cultures. After multiple viral replication cycles (at 24, 48, 72, and 96 h following infection), total viral samples (both free and cell-associated virus) from RWV cultures contained significantly more virus than Teflon roller bottle cultures.The rhinovirus replication cycle was enhanced in cultures grown in the presence of motion (Teflon roller bottle cultures and RWV cultures). Additionally, multiple rounds of rhinovirus replication yielded more virus in simulated microgravity conditions. Viral transmission in cell cultures in RWVs was efficient and was similar to or better than what occurred in the Teflon roller bottles. The cultivation of cells in simulated microgravity possibly affected the rate of viral adsorption/uptake, the viral replication cycle, and/or the viral yield. RWVs provide an effective means for culturing human rhinoviruses.

Several reports have documented that the MB isoenzyme of creatine kinase is present in prostatic tissue. However, since it has been shown that lower urinary tract manipulations, including transurethral prostatectomy, do not significantly increase serum creatine kinase isoenzyme MB levels, such elevations, which are found in patients after prostatic surgery, are believed to be specific for myocardial infarction. We examined whether cryosurgical ablation of the prostate altered serum creatine kinase or isoenzyme MB levels.In 81 consecutive patients undergoing routine cryosurgical ablation of the prostate serum levels of creatine kinase and creatine kinase isoenzyme MB were measured from peripheral blood specimens drawn preoperatively, in the recovery room and at 8 and 24 hours postoperatively. Postoperative electrocardiograms were compared to the preoperative study.In 72 of 81 patients (89%) significant elevations in creatine kinase and creatine kinase isoenzyme MB levels were noted at all time points after cryosurgical ablation of the prostate and appeared to reach a peak at 16 hours postoperatively. The mean increases within the first 8 hours after cryosurgical ablation of the prostate were 1,355 units per 1. for creatine kinase and 46.6 ng./ml. for creatine kinase isoenzyme MB. No patient had any significant changes on the postoperative electrocardiogram. All 9 patients (11%) who did not have significant creatine kinase or creatine kinase isoenzyme MB levels after cryosurgery had undergone prior cryosurgery or combined radiation and hormonal therapy.Cryosurgical ablation of the prostate appears to produce elevations in serum creatine kinase and creatine kinase isoenzyme MB, which are specific to the procedure. Assays for creatine kinase isoenzyme MB are unreliable to render a diagnosis of myocardial infarction after cryosurgical ablation of the prostate.

A case of collecting-duct carcinoma associated with abnormal urine cytology is described. The finding of an abnormal cytologic examination, yet not typical of transitional-cell carcinoma (TCC), suggests that a close relationship between the cytology and histology of this uncommon malignancy may be demonstrated.

The 4-methyl piperidine analog (A-4) of hemicholinium-3 is a tertiary amine. A-4, like hemicholinium-3, inhibits sodium-dependent, high-affinity choline transport. The present study examined whether central cholinergic systems are involved in the expression of genetic hypertension. We examined the effects of i.v. and i.c.v. administration of A-4 in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY; control). Basal mean arterial pressure and heart rate values were 108 +/- 4 mm Hg and 370 +/- 5 bpm in WKY and 167 +/- 5 mm Hg and 337 +/- 13 bpm in SHR. The i.v. injection of A-4 (5, 10 and 20 mumol/kg) evoked a dose-dependent decrease in MAP in SHR, but not in WKY. The maximal decrease in MAP was 18 +/- 6 mm Hg (P.01) in SHR. Depressor responses appeared within 1 min and reached maximum within 10 min. The reductions in MAP were not associated with reductions in peripheral vascular resistances, suggesting that the hypotension was due to a reduction in cardiac output. The i.c.v. injection of A-4 (100 nmol/rat) significantly decreased MAP in SHR (-23.8 +/- 2.4 mm Hg, P.01), but not in WKY. The maximal decrease in MAP appeared within 1 min and reached maximum 10 min later. These falls in MAP were associated with falls in vascular resistances, suggesting that the hypotension was due to peripheral vasodilation. This dose was ineffective when given i.v. in either strain. A-4-induced decreases in MAP were accompanied by significant tachycardia, which was maximal within 3 min of injection. These studies demonstrate that A-4 lowers MAP in SHR, but not in WKY. The rapid onset of hypotension in SHR after A-4 administration suggests that there is rapid turnover of brain acetylcholine which may be directly involved in maintaining elevated arterial pressure in SHR.

bis-Quaternary amines, which are acetal analogues of hemicholinium-3, were synthesized and several compounds were potent chemicals to antagonize toxicity induced by the organophosphate, paraoxon. Structural requirements were specific and included two oxygen atoms (bis-acetal substitution) within 6 or 7 atom heterocyclic rings, oxygen atoms spaced 2-carbon atoms from the quaternary nitrogen, and carbonyl substitutions adjacent to the spacing moieties, either bicyclohexyl or biphenyl. Biological testing showed a positive potency correlation between the chemicals when data from the following tests were compared: antagonism in mice of paraoxon-induced motor impairment using the incline screen and toxicity, and ability to induce contractions of guinea-pig isolated ilea. The compounds were compared with the often used protective antagonist of organophosphate-induced toxicity, pyridostigmine. One compound, MFS-3, was seven times more efficacious and possessed a much higher therapeutic index. Possible mechanisms of action for these chemicals are discussed.

The most common genetic aberration seen in nonpapillary renal cell carcinoma is believed to be the loss or inactivation of allelic material on the short arm of chromosome 3 (3p). Two patients underwent nephrectomy at our institution, each initially receiving a histologic diagnosis of renal cell carcinoma. Molecular analysis of these tissues revealed no genetic deletion on 3p, prompting further histologic and immunohistochemical evaluation of the original specimens. These additional studies confirmed alternate histologies other than renal cell carcinoma in each case. These data suggest that the loss of genetic material on the short arm of chromosome 3 may be specific for nonpapillary renal cell carcinoma. Molecular analysis may prove to be a useful adjunct in establishing the diagnosis in renal neoplasms with equivocal histologies.

Summary Eighty-six strains encompassing 11 species of coagulase-negative staphylococci were examined for the production of fatty acid modifying enzyme (FAME) and lipase. Staphylococcus schleiferi and S. saprophyticus most closely resembled S. aureus in that 80% of the strains produced both enzymes. In contrast, no strains of S. lugdunensis and S. haemolyticus tested produced these enzymes. S. simulans was unusual in that eight of 10 strains produced FAME, but only one produced lipase. Among the other species the proportion of strains producing both enzymes ranged from 10 to 60%. Generally there was a strong correlation between FAME and lipase production.

Decerebration and transection of the spinal cord totally abolished the hypotensive and tachycardiac responses to i.c.v injection of nitroglycerin (NTG) and reduced the tachycardia induced by i.v. injection of the drug. The hypotensive responses to i.v. injection of sodium nitroprusside were not altered by decerebration. Microinjection of NTG (0.1-1.0 nmol) into anterior hypothalamic medial preoptic area (AH/POA) produced dose-dependent decreases in mean arterial pressure and heart rate, but minimal responses were induced when the same doses of NTG were injected into the rostral ventrolateral medulla. Pretreatment with rauwolscine (2.5 nmol), injected into the AH/POAs, antagonized the depressor responses to NTG when it was administered into the areas or given i.v. However, rauwolscine did not alter the depressor responses induced by i.v. sodium nitroprusside. Prazosin (1.5 nmol) in the AH/POA did not alter the bradycardic effects induced by microinjection of NTG into the areas. (minus)-Epinephrine significantly interacted with alpha-2 adrenoceptor binding sites, but serotonin and NTG did not interact with [3H] clonidine binding sites in cortex membranes. Results suggest that cardiovascular responses after i.v. injection of NTG involve central and peripheral component. AH/POA is one of the central sites involved in the depressor effects of NTG. NTG-induced modulation of noradrenergic transmission appears to stimulate alpha-2 adrenoceptors in the central nervous system, but the drug does not involve direct interaction with alpha-2 adrenoceptors. Hypotensive effects of sodium nitroprusside result from its action at peripheral sites.

5-Methoxy-1-methyl-4-(2-N,N-di-n-propylaminoethyl)indole (12) was synthesized from 5-hydroxyindole by a multistep synthesis. This target compound was designed as a bioisostere of "p-dimethoxy" catechol congeners of dopaminergic agonists derived from a variety of ring systems, in some of which p-dimethoxy-substituted systems are potent, active dopaminergic agonists. To complete the indole series, all possible combinations of N- and O-demethylated derivatives of 12 were prepared and were also evaluated pharmacologically. All members of this indole-derived series showed a low order of cardiovascular activity, which appeared to be independent of dopamine receptors. The lack of dopaminergic activity of 12 is cited as yet another example of the unpredictable effect of replacement of the catechol moiety of a dopaminergic agonist with a p-dimethoxy moiety.

The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.