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We present observations of the four 2 Pi 3/2 J = 3/2 ground-rotational state transitions of the hydroxyl molecule (OH) along 107 lines of sight both in and out of the Galactic plane: 92 sets of observations from the Arecibo telescope and 15 sets of observations from the Australia Telescope Compact Array (ATCA). Our Arecibo observations included off-source pointings, allowing us to measure excitation temperature (Tex) and optical depth, while our ATCA observations give optical depth only. We perform Gaussian decomposition using the Automated Molecular Excitation Bayesian line-fitting Algorithm 'AMOEBA' (Petzler, Dawson, and Wardle 2021) fitting all four transitions simultaneously with shared centroid velocity and width. We identify 109 features across 38 sightlines (including 58 detections along 27 sightlines with excitation temperature measurements). While the main lines at 1665 and 1667 MHz tend to have similar excitation temperatures (median Tex(main) difference = 0.6 K, 84% show Tex(main) difference < 2 K), large differences in the 1612 and 1720 MHz satellite line excitation temperatures show that the gas is generally not in LTE. For a selection of sightlines we compare our OH features to associated (on-sky and in velocity) HI cold gas components (CNM) identified by Nguyen et al. (2019) and find no strong correlations. We speculate that this may indicate an effective decoupling of the molecular gas from the CNM once it accumulates., Accepted for publication to PASA. 41 pages, 27 figures

Using the Australian Square Kilometre Array Pathfinder to measure 21-cm absorption spectra toward continuum background sources, we study the cool phase of the neutral atomic gas in the far outer disk, and in the inner Galaxy near the end of the Galactic bar at longitude 340 degrees. In the inner Galaxy the cool atomic gas has a smaller scale height than in the solar neighborhood, similar to the molecular gas and the superthin stellar population in the bar. In the outer Galaxy the cool atomic gas is mixed with the warm, neutral medium, with the cool fraction staying roughly constant with Galactic radius. The mean spin temperature, i.e. the ratio of the emission brightness temperature to the absorption, is roughly constant for velocities corresponding to Galactic radius greater than about twice the solar circle radius. The ratio has a value of about 300 K, but this does not correspond to a physical temperature in the gas. If the gas causing the absorption has kinetic temperature of about 100 K, as in the solar neighborhood, then the value 300 K indicates that the fraction of the gas mass in this phase is one-third of the total HI mass., Comment: 29 pages, 12 figures, submitted to Astrophysical Journal

Pulsar timing array collaborations have recently reported evidence for a noise process with a common spectrum among the millisecond pulsars in the arrays. The spectral properties of this common-noise process are consistent with expectations for an isotropic gravitational-wave background (GWB) from inspiralling supermassive black-hole binaries. However, recent simulation analyses based on Parkes Pulsar Timing Array data indicate that such a detection may arise spuriously. In this paper, we use simulated pulsar timing array datasets to further test the robustness of the inference methods for spectral and spatial correlations from a GWB. Expanding on our previous results, we find strong support (Bayes factors exceeding $10^5$) for the presence of a common-spectrum noise process in datasets where no common process is present, under a wide range of timing noise prescriptions per pulsar. We show that these results are highly sensitive to the choice of Bayesian priors on timing noise parameters, with priors that more closely match the injected distributions of timing noise parameters resulting in diminished support for a common-spectrum noise process. These results emphasize shortcomings in current methods for inferring the presence of a common-spectrum process, and imply that the detection of a common process is not a reliable precursor to detection of the GWB. Future searches for the nanohertz GWB should remain focussed on detecting spatial correlations, and make use of more tailored specifications for a common-spectrum noise process., Comment: 12 pages, 12 figures. Accepted for publication in MNRAS

We present the full data release for the Southern Parkes Large-Area Survey in Hydroxyl (SPLASH), a sensitive, unbiased single-dish survey of the Southern Galactic Plane in all four ground-state transitions of the OH radical at 1612, 1665, 1667, and 1720 MHz. The survey covers the inner Galactic Plane, Central Molecular Zone, and Galactic Centre over the range |b| < 2°, 332∘, JRD acknowledges the support of an Australian Research Council (ARC) DECRA Fellowship (project number DE170101086). HI is supported by JSPS KAKENHI grant no. JP21H00047. JFG acknowledges support from the State Agency for Research (AEI/10.13039/501100011033) of the Spanish MCIU, through grant no. PID2020-114461GB-I00 and the ‘Center of Excellence Severo Ochoa’ award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709). This research made use of the Duchamp source finder, produced at the ATNF, CSIRO, by M. Whiting. The Parkes radio telescope is part of the ATNF (grid.421683.a) which is funded by the Australian Government for operation as a National Facility managed by CSIRO. We acknowledge the Wiradjuri people as the traditional owners of the Observatory site.

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.--Full list of authors: Pingel, N. M.; Dempsey, J.; McClure-Griffiths, N. M.; Dickey, J. M.; Jameson, K. E.; Arce, H.; Anglada, G.; Bland-Hawthorn, J.; Breen, S. L.; Buckland-Willis, F.; Clark, S. E.; Dawson, J. R.; Denes, H.; Di Teodoro, E. M.; For, B-Q; Foster, Tyler J.; Gomez, J. F.; Imai, H.; Joncas, G.; Kim, C-G; Lee, M-Y; Lynn, C.; Leahy, D.; Ma, Y. K.; Marchal, A.; McConnell, D.; Miville-Deschenes, M-A; Moss, V. A.; Murray, C. E.; Nidever, D.; Peek, J.; Staveley-Smith, L.; Tepper-Garcia, T.; Tremblay, C. D.; Uscanga, L.; van Loon, J. Th; Vazquez-Semadeni, E.; Allison, J. R.; Anderson, C. S.; Ball, Lewis; Bell, M.; Bock, D. C-J; Bunton, J.; Cooray, F. R.; Cornwell, T.; Koribalski, B. S.; Gupta, N.; Hayman, D. B.; Harvey-Smith, L.; Lee-Waddell, K.; Ng, A.; Phillips, C. J.; Voronkov, M.; Westmeier, T.; Whiting, M. T.; Stanimirovic, S., We present the most sensitive and detailed view of the neutral hydrogen ( HI ) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal HI in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ( 1.6mJy beam−1 ) per 0.98km s−1 spectral channel with an angular resolution of 30′′ ( ∼10pc ). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ∼25deg2 field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes HI test observations. c The Author(s), 2022. Published by Cambridge University Press on behalf of the Astronomical Society of Australia., The Australian SKA Pathfinder is part of the Australia Telescope National Facility which is managed by CSIRO. Operation of ASKAP is funded by the Australian Government with support from the National Collaborative Research Infrastructure Strategy. ASKAP uses the resources of the Pawsey Supercomputing Centre. Establishment of ASKAP, the Murchison Radio-astronomy Observatory and the Pawsey Supercomputing Centre are initiatives of the Australian Government, with support from the Government of Western Australia and the Science and Industry Endowment Fund. We acknowledge the Wajarri Yamatji people as the traditional owners of the Observatory site. Pipeline development was tested on the OzSTAR supercomputer under the project code, oz145, which is available through Swinburne University’s Centre of Astrophysics and Supercomputing. This research was supported by the Australian Research Council (ARC) through grant DP190101571. N.M.-G. acknowledges the support of the ARC through Future Fellowship FT150100024. G. A. and J. F. G. acknowledge support from the State Agency for Research (10.13039/501100011033) of the Spanish MCIU, through grants AYA2017-84390-C2-1-R and PID2020-114461GB-I00 (co-funded by FEDER) and the ‘Center of Excellence Severo Ochoa’ award for the Instituto de Astrofsica de Andaluca (SEV-2017-0709). C. E. M. is supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-1801471.

"Comparatively little experimental data are as yet available concerning these problems of raising heifers. The purpose of the author in conducting the experiments reported in this thesis was to add to the data now available regarding the wintering of heifers, by festing the suitability of certain rations for this purpose."

Human-to-human transmission of symbiotic, anaerobic bacteria is a fundamental evolutionary adaptation essential for membership of the human gut microbiota. However, despite its importance, the genomic and biological adaptations underpinning symbiont transmission remain poorly understood. Here, we show that sporulation ability, which promotes transmission of anaerobic bacteria, has been independently lost in many distinct evolutionary lineages of gut bacteria belonging to the Firmicutes phyla. Analysis of 1358 genome-sequenced Firmicutes reveals loss of sporulation is associated with features of host-adaptation such as genome reduction and specialized metabolic capabilities. Consistent with these data, analysis of 28,000 gut metagenomes from people around the world demonstrates that bacteria now incapable of sporulation are more abundant but less prevalent in the human population compared to spore-forming bacteria. Our results suggest host adaptation in gut Firmicutes is an evolutionary trade-off between transmission range and colonisation abundance, leading to distinct transmission cycles. We reveal host transmission as an underappreciated process that shapes the evolution, assembly and functions of gut Firmicutes.

Dense, star-forming gas is believed to form at the stagnation points of large-scale ISM flows, but observational examples of this process in action are rare. We here present a giant molecular cloud (GMC) sandwiched between two colliding Milky Way supershells, which we argue shows strong evidence of having formed from material accumulated at the collision zone. Combining 12CO, 13CO and C18O(J=1-0) data with new high-resolution, 3D hydrodynamical simulations of colliding supershells, we discuss the origin and nature of the GMC (G288.5+1.5), favoring a scenario in which the cloud was partially seeded by pre-existing denser material, but assembled into its current form by the action of the shells. This assembly includes the production of some new molecular gas. The GMC is well interpreted as non-self-gravitating, despite its high mass (MH2 ~ 1.7 x 10^5 Msol), and is likely pressure confined by the colliding flows, implying that self-gravity was not a necessary ingredient for its formation. Much of the molecular gas is relatively diffuse, and the cloud as a whole shows little evidence of star formation activity, supporting a scenario in which it is young and recently formed. Drip-like formations along its lower edge may be explained by fluid dynamical instabilities in the cooled gas., Comment: 13 pages, 9 figures, accepted for publication in ApJ

Platelet activation is an important pre-thrombotic event. The elucidation of its pathophysiology could contribute to a reduction in the mortality associated with coronary artery disease-the foremost cause of death in the UK. We examined the platelets of 27 patients with angiographically documented coronary artery disease. All patients had stable angina and were taking their regular medication-including aspirin. We demonstrated significantly increased expression of GP53 and activated GPIIb/IIIa on the platelet surface using a sensitive flow cytometric method of detection. Comparison was made with a control group of 35 patients. Seventeen of the patients had coronary angioplasty carried out. Serial studies of these patients demonstrate an immediate and sustained increase in platelet activation and this has important implications for prevention of restenosis after angioplasty.

The human leukemic cell line, CEM, and an NK-resistant variant of CEM, called CEM-NKR, were analyzed for protein differences by two-dimensional gel electrophoresis. One protein was found to be completely absent in CEM-NKR. This protein has been identified as calnexin. CEM-NKR also completely lacks calnexin RNA. Calnexin is thought to act as a molecular chaperone by assisting in the assembly and/or retention of MHC class I and many other membrane and secreted proteins. The surface expression of class I molecules on CEM-NKR was compared with CEM by several Abs. There was no significant class I expression differences between CEM and CEM-NKR using w6/32 (a conformational and beta 2-microglobulin-dependent mAb), HC-10 (a conformational and beta 2-microglobulin-independent mAb), and an anti-class I antiserum that reacts with native and denatured class I. The transport rate of class I in both cell lines was examined by pulse-chase experiments, immunoprecipitating class I with w6/32 and anti-class I antiserum. The results show that class I molecules in the calnexin-deficient cell line and its parent cell line are transported at similar rates. These results indicate that calnexin is not absolutely required for the viability of CEM or the transport and surface expression of human MHC class I molecules.

Treponema denticola has been shown to bind to immobilized fibronectin (Fn) by its tips. Yet labeling of cells in suspension with an Fn-gold conjugate to localize the Fn adhesins shows that they are distributed in patches along the entire cell length. Subsequent experiments have shown that the number and proportion of tip-oriented cells increase with time, suggesting that Fn contact stimulates T. denticola to rearrange adhesins toward its tips. To test this hypothesis, T. denticola cells were allowed to migrate in a 2% methylcellulose column toward nitrocellulose filters coated with Fn, laminin, bovine serum albumin, or phosphate-buffered saline. Cells close to and distant from the filters were collected, labeled with Fn-gold probes, and examined by transmission electron microscopy. The number of gold particles on each of 20 cells was counted, dividing each cell into thirds along its length: the end third with the most label (end 1), the middle third, and the end with the least label (end 2). The mean number (+/- standard deviation) of gold probes per third was calculated. Fn-gold probes clustered toward one end of T. denticola cells when in contact with Fn-coated nitrocellulose, with > 55% of probes in end 1. In contrast, no clustering toward T. denticola ends occurred with laminin-, bovine serum albumin, or phosphate-buffered saline-coated filters or in the absence of a filter. Blocking access of the T. denticola cells to the Fn-coated nitrocellulose filter by placing an uncoated filter between them prevented clustering of Fn-gold. Removal of T. denticola cells from direct contact with the Fn-coated filter did not promote redistribution of clustered probes. These data suggest that T. denticola is stimulated to cluster Fn adhesins irreversibly toward its tips when it migrates into contact with immobilized Fn. This might be significant for establishing multiple adhesive interactions with host cells and ligands.

A comparison was made of the properties of microsomes prepared from the small intestines of guinea pigs and rats. The NADPH2 cytochrome c reductase activity and cytochrome b5 and cytochrome P-450 content in rat microsomes was 42, 47 and 64% of that in the guinea pig, ethoxycoumarin deethylase activity was comparable, while arylesterase activity was twice as active in rats as guinea pigs. Investigation of the distribution of these and other parameters in rat intestinal epithelia revealed a preferential location of cytochrome P-450 in the villous tip while other parameters showed a more similar distribution between microsomes prepared from the villous tip and crypt.

1. The profile of the hepatic mixed-function oxidase system of male rats has been examined following treatment with prochloraz (I) and three of its major metabolites (II, III and IV). 2. The overall induction profile of prochloraz reflected the contribution of the individual metabolites. There was a slight increase of lauric acid hydroxylase, but by far the major induction was seen in the activity of aldrin epoxidase and 7-pentoxyresorufin-O-dealkylase (7- and 14-fold respectively). 3. N-Propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]urea (II), a primary intermediate in the metabolism of prochloraz, was a phenobarbitone-type inducer, increasing the activity of aldrin epoxidase and 7-pentoxyresorufin-O-dealkylase by 120% and 8-fold respectively. 4. The prochloraz metabolites, trichlorophenoxyethanol (III) and trichlorophenoxyacetic acid (IV) were both inducers of the clofibrate type, increasing the activity of lauric acid 12-hydroxylase. 5. The induction profile of prochloraz was of a mixed type, but the predominant characteristics were those of phenobarbitone induction.

Tonsil B cells were analyzed for their capacity to interact directly with NK cells in vitro. A specific, direct interaction between NK cells and B cells could be detected by direct conjugation and by cold target inhibition using the B lymphoblastoid cell line BJA.B as a labeled target. The data further suggest that the B cell interaction with NK cells specifically activates the NK effectors and induces their production of IFN-gamma. The NK-interactive population of tonsil B cells were characterized as low-buoyant density cells (by Percoll gradient fractionation) that stained more brightly with Hoechst 33342, both characteristics of activated B cells. Immunofluorescent staining of NK cell-B cell conjugates allowed determination of the cell-surface antigenic phenotype of conjugate-forming B cells. B cell targets were ICAM-1bri, 4F2+, TfR+, CD32+, BB1+, and CD77-. They tended to be CD38-, but overlapped the CD38+ population. No correlation was seen with CD37, CD44, CD75, CD76, HC2, or Ig kappa. This phenotype is most consistent with a late activation stage of differentiation, just before and overlapping the expression of CD38. These B cells do not appear significantly sensitive to NK-mediated cytolysis, suggesting that NK cell cytokine synthesis and secretion (e.g., IFN-gamma) may be more important in the NK cell regulation of the humoral response.

The relative collection efficiency of several different types of dustfall collector was assessedover different collection intervals in a piggery. Flat plate collectors and collectors with sidewalls 10 and 50 mm high were placed on a slow-speed turntable to minimize positional effects. For each sampler type, collection intervals of 1, 3, 6 and 12 weeks were used. The collection medium was generally a 47 mm glass fibre filter located on a 75 mm diameter aluminium disc. Cellulose nitrate membrane filters were used for one treatment. The dust sedimentation rate determined from the weekly samples varied from 80 to 200 mg m −2 h −1 over the 12-week period. Dust deposits on the filters varied linearly with time from 2·3 mg/cm 2 of collector surface for the 1-week interval to 27·9 mg/cm 2 over 12 weeks. The measured dust sedimentation rate was about 3·0% less on the membrane filters than on the glass fibre filters and also for those collectors with the 50 mm high sidewall when compared with the flat plate collectors. The length of sample collection interval did not significantly affect the measured dust sedimentation rate. It is suggested that handling errors and edge effects may affect accuracy when deposits are greater than about 7 mg/cm 2 of collector surface.

An experiment was conducted to assess the spatial variability of dust within theairspace of an occupied piggery. Measurements of airborne and settled dust were made for 16 days at 16 locations within a 180 place, partially slatted-floor, grower-finisher piggery. Eight locations were in a vertical cross-section covering half the width of the building. Two of these locations were used in conjunction with eight further locations over the remaining pen barriers to establish a horizontal sampling plane. Aerial dust samples were collected every 24h and settled dust samples every 4 days. Particle size analysis was carried out on all of the settled dust and half of the aerial dust samples. Measurements were made of airspace temperature and air velocity at each sampling location, and of pen cleanliness throughout the building. The mean aerial dust concentration was 2·2 mg/m 3 , ranging from a minimum of1·6 mg/m 3 to a maximum of 2·74 mg/m 3 . The mean dust sedimentation rate was 137 mg m −2 h −1 and varied from 70 mg m −2 h −1 to 295 mg m −2 h −1 . The lowest values for both measures of dust occurred at pen barrier height over the slatted portion of a centrally located pen and the highest values occurred at floor level within the solid-floor portion of the pen. The average mass mean diameter of the particles in the airborne samples was 14 μ m compared with 18 ,um for the settled dust samples. In general, there was a greater percentage of larger particles in both the airborne and settled dust at the front of the pens. The spatial variability of dust from end to end of the building was smaller than the variability within a building cross-section. These results were consistent with what was expected given an intuitive knowledge of where the dust was produced and the direction of air currents. In this building with sidewall extraction fans and centre air inlets, sampling at a location near the front of the pen, just above the pen barrier top, gave data representative of the dust levels to which the operator would be subjected. The spatial distribution of dust did not change appreciably from day to day; however, the day to day variability was large, such that health risks should not be assessed on data taken on one or two days only.

Previous studies investigating the appropriateness of invasive management of coronary disease had not reported the internal consistency of their ratings and may now be out of date. The aim of this study was to measure the influence of clinical factors on contemporary ratings of the appropriateness of coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) in the Appropriateness of Coronary Revascularisation (ACRE) study.The Delphi-RAND technique was used, in which an expert panel (four cardiologists, three cardiothoracic surgeons, a general physician and a general practitioner), meeting in 1995, rated mutually exclusive indications (n = 2178 for angiography, n = 995 for PTCA and n = 984 for CABG). The main outcome measures were the appropriateness category (inappropriate, uncertain or appropriate) for each of the three procedures and treatment preference.For revascularization, the strongest determinant of inappropriateness was coronary anatomy. The odds ratio (OR) for inappropriate PTCA was 10.6 (95 per cent confidence interval (CI) 4.8-23.5) for the effect of left main stem or three-vessel disease versus single-vessel disease, and for CABG it was 0.06 (95 per cent CI 0.03-0.15). The number of diseased vessels was strongly related to preference for medical, PTCA or CABG treatment (p for linear trend0.001). Mild versus severe anginal symptoms were associated with inappropriate angiography (OR 2.0 (95 per cent CI 0.9-9.8), although this effect was stronger when only the cardiologists' ratings were considered (OR 10.1 (95 per cent CI 2.4-42.6)).These are the first UK ratings of appropriateness covering all three procedures. The associations with clinical factors provide evidence of the internal consistency of these ratings. Prospective validation of these ratings against clinical outcomes is under way in the ACRE study.

OBJECTIVE—To determine whether ratings of coronary angiography appropriateness derived by an expert panel on hypothetical patients are associated with actual angiographic findings, mortality, and subsequent revascularisation in the ACRE (appropriateness of coronary revascularisation) study. DESIGN—Population based, prospective study. The ACRE expert panel rated hypothetical clinical indications as inappropriate, uncertain, or appropriate before recruitment of a cohort of real patients. SETTING—Royal Hospitals Trust, London, UK. PARTICIPANTS—3631 consecutive patients undergoing coronary angiography (no exclusion criteria). MAIN OUTCOME MEASURES—Angiographic findings, mortality (n = 226 deaths), and revascularisation (n = 1556 procedures) over 2.5 years of follow up. RESULTS—The indications for coronary angiography were rated appropriate in 2253 (62%) patients. 166 (5%) coronary angiograms were performed for indications rated inappropriate, largely for asymptomatic or atypical chest pain presentations. The remaining 1212 (33%) angiograms were rated uncertain, of which 47% were in patients with mild angina and no exercise ECG or in patients with unstable angina controlled by inpatient management. Three vessel disease was more likely among appropriate cases and normal coronaries were more likely among inappropriate cases (p

The changing climate of health care, with the associated increasing financial constraints, challenges faculty and residents to find time for mentoring and pursuing research. Departments and institutions can encourage residents to conduct research by assuring them that they have a supportive infrastructure. Only when the institution and faculty value research will residents do the same. More than half of academic surgeons spend less than 20% of their effort in research; how can residency programs expect residents to enthusiastically pursue research when members of the teaching faculty are themselves not writing and publishing? If the ACGME is serious about asking residents to devote their time and energy to becoming more active in research activities, we must be prepared to decrease service commitments, and we must provide clinically active mentors and visible career models.

NK cells may mediate effector functions other than target cell cytotoxicity. To explore such noncytotoxic effector mechanisms, we tested whether human PBL and purified NK (CD56+) cells might induce expression of tissue factor by cultured porcine aortic endothelial cells. Tissue factor is the major coagulation factor that binds to factor VIIa and initiates coagulation. The addition of freshly isolated NK cells but not T cells to endothelial cells resulted in the induction of tissue factor activity. NK-depleted (CD56-) effector cells did not induce tissue factor activity; however, the combination of CD56+ cells and NK-depleted cells induced tissue factor activity to the same extent as unseparated cells. PBL induced tissue factor mRNA in porcine endothelial cells and NK depletion resulted in a significant decrease of the induction. Induction of tissue factor activity in porcine endothelial cells by human NK cells required direct cell-to-cell contact, as transfer of supernatants from NK-endothelial cell cultures to secondary cultures did not induce tissue factor activity, and anti-LFA-1alpha Abs inhibited the induction of tissue factor activity. Induction of tissue factor activity in endothelial cells by NK cells may represent one of a variety of ways in which NK cells mediate noncytotoxic effects.

The use of baboons as a model for the study of allo- and xenotransplantation has become increasingly important, but there are few studies on the basic immunological responses in baboons that might be relevant for a rejection reaction. In present study, the cell-surface phenotype, cytokine-induced activation and growth, and cytotoxicity of baboon and human natural killer (NK) and lymphokine-activated killer (LAK) cells were compared. A panel of murine monoclonal antibodies specific for human cell-surface markers expressed on lymphocytes was used to compare relevant baboon and human peripheral blood lymphocytes (PBL). Baboon PBL were 52.1+/-2.9% CD8+, 18.5+/-2.2% CD16+, 3.0+/-0.5% CD25+, and 5.5+/-1.8% CD69+. The corresponding proportions in humans were 23.8+/-7.1%, 12.8+/-3.2%, 4.5+/-1.0%, and 2.3+/-1.1%. In contrast to human PBL, less than 1% of baboon lymphocytes expressed CD56, CD57, and CD122 (interleukin [IL]-2Rbeta). Baboon lymphocytes showed NK cytotoxic activity against the human K562 and CEM cell lines, which was comparable to human NK activity. Depletion of baboon CD16+ or CD8+ cells led to dramatic decreases in NK cytotoxicity, and removal of both subsets completely abrogated NK activity. Incubation of baboon lymphocytes with human recombinant IL-2 for 1 week led to the appearance of CD56+ cells (11.3+/-2.8%). Most of the baboon CD56+ cells induced in culture were in S and G2 phases of cell cycle. Both baboon and human IL-2-activated lymphocytes were highly cytotoxic against the human LAK-sensitive cell line Daudi. Depletion of baboon CD8+ but not CD56+ cells significantly decreased LAK activity. These studies revealed differences in the NK system of humans and baboons that should be taken into consideration when analyzing immune responses to allo- and xenotransplantation in baboons.

In this study, we have investigated the early in vitro effects of natural killer (NK) cells on porcine aortic endothelial cell (PAEC) monolayers. Incubation of effector cells containing about 70% CD56+ cells on PAEC monolayer led to time-dependent changes in PAEC monolayer morphology. As little as 20 min of incubation resulted in changes in PAEC shape and in the appearance of gaps between the cells. These effects have been observed for up to 6 hr, but not before 20 min or after 6 hr. When NK-depleted effector cells were used, no morphological changes were observed in comparison with the same effectors before depletion; if CD56+ cells were added back, the effects were comparable with those on nondepleted effector cells. There was no detectable NK cell-mediated cytolytic activity during the 1-6 hr of incubation of peripheral blood lymphocytes with PAEC monolayers. These data indicate that NK cells may participate in endothelial cell changes leading to xenograft rejection.

We have previously shown that the capacity of class I molecules to confer resistance to NK in transfected target cells maps to the Ag-binding site (ABS) of the HLA class I structure. Here we examine the effect of peptide (reagents specific for the ABS) pretreatment on the NK sensitivity of class I+ target cells. Synthetic peptides (10-17 amino acids in length) were used to pretreat C1R target cells expressing either no serologically detectable HLA-A, B class I molecules, or C1R transfectants expressing individual HLA-A or -B locus class I molecules. In each case in which the class I allele had previously been shown to directly bind a given peptide, peptide-pulsing of target cells resulted in increased sensitivity to NK-mediated conjugation and cytolysis. The NK susceptibility of C1R target cells expressing no HLA-A, B class I molecules or the nonprotective HLA-A2.1 or HLA-A2M70 mutant class I molecules was unaffected by pretreatment with HLA-A2-binding peptides. These results support the intimate involvement of the HLA class I ABS and potentially ABS-bound peptides in determining target cell sensitivity to NK. Furthermore, these findings form the basis of an effective screening procedure for discerning peptide class I allele-specific interactions.

Natural killer (NK) cells comprise an important immune effector population that has been implicated in surveillance against tumor metastases and virally infected host cells, suppression of the humoral immune response, and regulation of hematopoiesis. These diverse functions require an initial cognate interaction between the NK effector cell and the target cell of interest. This specific interaction triggers the secretion of NK factors (i.e., lymphokines, cytolytic substances) which mediate NK activity. The target structures (TS) that stimulate the NK response remain ill-defined. While apparent TS heterogeneity may contribute to the difficulty in isolating distinct NK-TS, the proposed multifactorial nature of the NK cell-target cell interaction may represent the major complexity in the search for specific TS. Adhesion molecules such as ICAM-1 and LFA-3 may strengthen, while MHC antigens may weaken, the NK cell-target cell interaction. The following article analyzes the molecular interactions currently held to be relevant in target cell recognition by NK cells.

The adherence of Treponema denticola to ligands on cell surfaces or in basement membranes of periodontal tissues might play an important role in its pathogenicity. A direct microscopic assay was used to examine the binding of T. denticola to fibronectin and other protein substrates adsorbed on plastic cover slips. All strains of T. denticola that were tested adhered to fibronectin but to different degrees. The strains which bound in high numbers frequently bound by their tips. Type strain ATCC 33520 bound to fibronectin in high numbers (149 +/- 11.3 bacteria per microscopic field), with 60% bound by the tips. Strain e' bound in high numbers (140 +/- 10.2) and had the highest percentage of tip binding (98%); strain e bound in lowest numbers (39 +/- 8.2) and had the lowest percentage of tip binding (15%). Laminin supported binding at a level similar to that of fibronectin, as did fibronectin fragments which contained the cell binding domain peptides, RGDS. Type IV collagen and non-RGDS peptides did not support binding. Binding to fibronectin and laminin was inhibited by the addition of antifibronectin and antilaminin antibodies. By lowering the incubation temperature from 37 to 4 degrees C, the number of cells that attached decreased by 60% and tip binding was reduced by 50%. Pretreatment of the cells with collagen did not affect binding, whereas fibronectin pretreatment enhanced binding by 50% and laminin pretreatment resulted in a decrease of 60%. T. denticola adheres by its tips to fibronectin-coated surfaces, which suggests that fibronectin-specific adhesins cluster at the tips.

The haemodynamic effects of oral and intravenous salbutamol were investigated in 22 patients with chronic heart failure. Intravenous salbutamol (13 micrograms/min) increased cardiac index by 53 per cent from 1.5 +/- 0.13 1/min per m2 to 2.3 +/- 0.23 1/min per m2 and decreased systemic vascular resistance by 28 per cent from 29.4 +/- 3.9 units to 21.2 +/- 2.5 units. Heart rate rose by 10 per cent from 101 +/- 3.5 beats per minute to 111 +/- 3.2 beats per minute and pulmonary artery end-diastolic pressure fell by 13 per cent from 26.3 +/- 1.8 mmHg to 22.8 +/- 2.1 mmHg. Similar results were obtained after oral salbutamol (8 mg). Cardiac index rose by 40 per cent and systemic vascular resistance fell by 30 per cent. There was a small rise in heart rate and a variable and not significant change in pulmonary artery end-diastolic pressure. Experiments on isolated rabbit papillary muscle showed that salbutamol, at the concentration which exists in patients, had no detectable positive inotropic effect. It is probable that the increase in cardiac output in patients is primarily the result of reduced afterload caused by vasodilatation. Salbutamol is a useful drug in the treatment of chronic heart failure.

THE tractive performance of a forestry tire (FOR) was determined on three field surfaces using the single wheel tester of the National Institute of Agricultural Engineering (NIAE), Silsoe, England and was compared with the performance of an agricultural tire (AGR) of the same dimensions (67X34-25). The tractive efficiency of the AGR tire was 6% to 10% higher than the FOR tire; similarly, the motion resistance ratio of the FOR tire was higher than the AGR tire (0.11 vs 0.07) because of the difference in design and construction of the two tires.

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.

A study has been made of the microstructure of rigid closed-cell polyurethane foams in the density range 35 to 420 kg m−3. Existing models for the structure of foams of this type have been evaluated using optical and scanning electron microscope techniques. Foams with a density of the order of 35 kg m−3 are shown to be best represented as a pentagonal dodecahedron. Medium density foams from 70 to 300 kg m−3 have a structure described as rounded polyhedra and high-density foams from 300 to 420 kg m−3 have an isolated spherical structure. A relationship between average cell size and density is given.

The expression of transfected HLA class I Ag has previously been shown to protect human target cells from NK-mediated conjugation and cytolysis. In this same system, transfected H-2 class I Ag fail to impart resistance to NK. In this study, we have mapped the portion of the HLA class I molecule involved in this protective effect by exploiting this HLA/H-2 dichotomy. Hybrid class I genes were produced by exon-shuffling between the HLA-B7 and H-2Dp genes, and transfected into the class I Ag-deficient B-lymphoblastoid cell line (B-LCL) C1R. Only those transfectants expressing class I Ag containing the alpha 1 and alpha 2 domains of the HLA molecule are protected from NK, suggesting the "protective epitope" is located within these domains. Since a glycosylation difference exists between HLA and H-2 class I Ag within these domains (i.e., at amino acid residue 176), the role of carbohydrate in the class I protective effect was examined. HLA-B7 mutant genes encoding proteins which either lack the normal carbohydrate addition site at amino acid residue 86 (B7M86-) or possess an additional site at residue 176 (B7M176+) were transfected into C1R. Transfectants expressing either mutant HLA-B7 Ag were protected from NK. Thus, carbohydrate is probably not integral to a class I "protective epitope." The potential for allelic variation in the ability of HLA class I Ag to protect C1R target cells from NK was examined in HLA-A2, A3, B7, and Bw58 transfectants. Although no significant variation exists among the HLA-A3, B7, and Bw58 alleles, HLA-A2 appears unable to protect. Comparison of amino acid sequences suggests a restricted number of residues which may be relevant to the protective effect.

The human T lymphoblastoid cell line CEM was subjected to immunoselection by co-culture with peripheral blood mononuclear cells (PBMC) for resistance to natural killer (NK) cell-mediated lysis. The NK susceptibility of the resulting subline, CEM.NKR, was 8.4 to 20.6% of that of CEM when PBMC or adherent cell-depleted PBMC were used as effector cells, and -7.1 to 12.1% of that of CEM when Percoll gradient-enriched large granular lymphocytes (LGL) were used. However, CEM and CEM.NKR exhibited comparable sensitivity to antibody-dependent cellular cytotoxicity. Unlabeled CEM was eight- to 32-fold more effective than unlabeled CEM.NKR in inhibiting the NK lysis of labeled CEM target cells, and CEM bound 1.9 to 3.9-fold more Percoll gradient-enriched LGL than CEM.NKR in single cell-binding assays, suggesting that the NK-resistant variant has lost the expression of NK target antigens. However, CEM.NKR was comparable to CEM in its ability to induce interferon (IFN)-alpha production by PBMC in vitro, and the NK-resistant variant maintained its susceptibility to the antiproliferative effects of IFN-alpha, indicating that these phenomena may be mediated by molecules other than NK target structures. Comparison of CEM and CEM.NKR by indirect immunofluorescence with monoclonal antibodies specific for leukocyte antigens and the transferrin receptor, and by microcytotoxicity typing for HLA-A and B specificities, revealed no major differences.

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The determinants of aortic pressure and flow are generally studied using impedance methods, the results of which indicate that reflected waves are important, particularly during aortic flow deceleration. An alternative analysis of measured aortic pressure and velocity, using the method of characteristics to calculate the energy flux per unit area of the waves, suggests a different conclusion. We suggest that aortic deceleration is caused by a discrete expansion wave propagating from the left ventricle, and that energy thus recovered by the ventricle may be coupled to early filling of the ventricle.

Left ventricular diastolic function was studied in 11 patients with coronary artery disease. Single plane ventriculography (30 degrees right anterior oblique projection) was performed at rest and during an episode of angina immediately after a period of rapid atrial pacing. Left ventricular pressure was recorded simultaneously by a micromanometer tipped catheter. The ventriculograms were digitised frame by frame to derive continuous plots of left ventricular shape, volume, and rate of change of volume. The time constant (tau) of the fall in left ventricular pressure was determined from the exponential portion of pressure decay during isovolumic relaxation. Ventricular pressure-volume loops were constructed to study the left ventricular diastolic pressure-volume relation. The time of minimum left ventricular pressure was used to divide diastole into an early phase and a late phase. Angina was associated with an increase in end systolic volume and a fall in ejection fraction with no significant change in end diastolic volume. Peak left ventricular pressure was unchanged but left ventricular minimum and end diastolic pressures were both increased and the diastolic pressure-volume relation was moved upwards. The time constant of left ventricular pressure fall was prolonged. At rest more than 50% of the stroke volume entered the left ventricle during the period of early diastole. This proportion was significantly reduced during angina and as a consequence a significantly greater proportion of the stroke volume entered the ventricle during late diastole. Despite this, and although the left ventricular diastolic pressure-volume relation was moved upwards with angina, the mean slope of the relation during late diastole--that is, chamber stiffness--was not significantly altered. The upward shift of the left ventricular diastolic pressure-volume relation seen during angina is thus already apparent in early diastole, and its extent does not change during the later phase of diastole, which alone shows the property of passive stiffness. A primary increase in the passive stiffness of the ventricle cannot therefore be the cause of the upward shift of the diastolic pressure-volume relation, and events occurring in early diastole have to be looked to for an explanation. The study findings show that left ventricular function in early diastole is profoundly disturbed during angina pectoris and it is suggested that loss of elastic recoil and dissipation of this restoring force by asynchronous onset of relaxation and abnormal changes in shape are important factors contributing to this disturbance of function.

The metabolic, hormonal and haemodynamic effects of oral pirbuterol, a new beta 2-adrenoceptor agonist, were studied acutely (n = 19) and after 3 months treatment (n = 11) in patients with severe heart failure receiving chronic frusemide therapy. In the acute study fasted patients (n = 10) showed reductions in plasma K+ (P less than 0.005) and cortisol (P less than 0.01) and increases in plasma glucose (P less than 0.005), insulin (P less than 0.01), lactate (P less than 0.005) and pyruvate (P less than 0.0025). These acute changes were less in unfasted subjects (n = 9). Maximal increase in stroke volume occurred at approximately half the plasma pirbuterol concentration required for maximal effect on plasma insulin. Treatment with pirbuterol for 3 months was associated with sustained increases in stroke volume and fasting plasma glucose and insulin, but there was loss of all other acute metabolic effects. Despite concurrent frusemide and digoxin therapy acute hypokalaemia caused no adverse effects. Hypokalaemia did not occur with chronic pirbuterol administration.

The lysosome content of lymphocytes has been analyzed with lysosomotropic vital stains and the fluorescence-activated cell sorter (FACS). Large granular lymphocytes (LGL), which account for virtually all natural killing activity in peripheral blood, are quantitatively different from small lymphocytes (SL) in this respect. LGL obtained by Percoll gradient density centrifugation accumulate more of the lysosomotropic vital dyes than SL do, staining with either neutral red or mepacrine (quinacrine). Furthermore among the LGL-rich, low density lymphocyte population highly, granulated cells can be separated from less granulated ones by mepacrine staining and FACS. Thus, separated highly granulated LGL express very high natural killing, whereas the less granulated low density large lymphocytes do not kill.

Male Anthonomus grandis Boheman fed 0.08% busulfan + 0.4% hempa for 6 days were as competitive as untreated males about ½ the time (occurripg randomly), and ½ the time the treated males were ¼–⅓% as competitive as untreated males. After an average of 7 matings, the treated males had depleted their supply of sperm. Determinations of sterility based on testes examination were in full agreement 91% of the time with determinations based on egg hatch and adult emergence.

When 13 B cell lines were phenotyped with a panel of B cell, stage-specific monoclonal antibodies and ordered with respect to differentiation state; their sensitivity to natural killer (NK) cell-mediated conjugate formation and cytolysis was found to be stage dependent. Target cell lines expressing an early B cell phenotype (B1+B2-CALLA+DU-ALL1 +/-) or an intermediate phenotype (B1+B2+CALLA-DU-ALL1+) were NK resistant. Late phenotypic B cells (B1+B2-CALLA-DU-ALL1-) were highly susceptible to NK cytolysis. Individual B cell lines when induced with sodium butyrate or retinoic acid expressed altered B cell phenotype and NK susceptibility. For example, SB, an intermediate B cell line and initially NK resistant, when induced to express a later B cell phenotype became NK sensitive. BJA.B, a late B cell line and initially NK sensitive, when induced to differentiate lost most of its sensitivity to natural killing. Since loss of the B2 antigen is associated with B cell activation, we further phenotyped the B cell lines and induced B cell lines with the 4F2 and 5E9 (anti-transferrin receptor) monoclonal reagents. All cell lines tested expressed each of these antigens, but with varying intensities. While the intensity of 4F2 expression appeared to correlate well with NK sensitivity on both resting and differentiated B cell lines, the intensity of 5E9 expression did not. Peripheral blood B cells express a similar pattern of reactivity to natural killing when stimulated with pokeweed mitogen (PWM) in vitro. B cell sensitivity to NK-mediated events peaked at day 4 of incubation and correlated with the loss of the B2 antigen and acquisition of the 4F2 and 5E9 antigens; sensitivity to natural killing was diminished in the presence of the PCA-1 antigen. The expression of the NK-susceptible phenotype among B cells appears to be differentiation stage- and activation state-dependent. It is during this period of ontogeny that the NK cell may cytolytically regulate the B cell transition to a plasma cell.

Fractionated doses of 6,250–8,000 rads of gamma irradiation when administered to pupae of the boll weevil, Anthonomus grandis Boh., sexually sterilized both sexes. Mortality of males thus treated with 6,250 and 8,000 rads via fractionation was 14% and 27% respectively, by 5 days posttreatment compared with 46% mortality when an equivalent acute dose was administered to newly emerged adults. Pheromone production of males irradiated at 6,250 rads was one-third that of the control for the first 4 days, but equal that of the control during 5–11 days posttreatment. This procedure lends itself to the large-scale sterilization of weevils needed in an eradication program. This technique is applicable to other insects that are highly susceptible to acute doses. ZUSAMMENFASSUNG STERILISATION VON BAUMWOLLKAPSELKAFERPUPPEN MIT FRAKTIONIERTEN DOSEN EINER GAMMABESTRAHLUNG Durch fraktionierte Dosen von insgesamt 6250 und 8000 rads einer Gammabestrahlung (25 bzw. 32 Teilbehandlungen zu 250 rads mit 4 h-Intervallen) wurden Puppen des Baumwollkapselkafers, Anthonomus grandis Boheman, in beiden Geschlechtern sexuell sterilisiert. Die Sterblichkeit, 5 d nach der Behandlung, betrug bei den so behandelten Mannchen bei 6250 rads 14%, bei 8000 rads 27% im Vergleich zu 46%, wenn eine aquivalente akute Dosis bei frisch geschlupften Kafern angewendet wurde. Die Pheromonproduktion der Mannchen in den ersten 4 d erreichte bei 6250 rads-Bestrahlung 1/3 derjenigen der Kontrolltiere; 5–11 d nach der Behandlung war kein Unterschied. Dieses Verfahren eignet sich fur die Massensterilisation von Kapselkafern, wie sie bei einem Ausrottungsprogramm notig ist. Diese Technik ist anwendbar auf andere Insekten, die gegenuber akuten Dosen hochempfindlich sind.

The standard method of sterilizing Anthonomus grandis Boheman (6-day feeding of 0.1% busulfan, 1-4-butanediol dimethanesulfonate) adequately sterilizes males but does not induce a high degree of sterility in females, and mortality is less than 40% after 2 weeks. Feeding higher concentrations of busulfan alone or lower concentrations of busulfan in combinations with methotrexate, hempa, or apholate for 6 days or less, or feeding 0.1-0.2% busulfan followed by low doses of gamma radiation induces virtually complete sterility in both sexes but causes fairly high mortality. A 4-day feeding of 0.2% busulfan + 0.25% methotrexate resulted in complete sterility in females and almost complete sterility in males, and mortality was less than 40% by 3 weeks after treatment.