The production and evaluation of Pasteurella haemolytica leukotoxin in the supernatant of submerged cultures in fermenters

The optimal production of P. haemolytica leukotoxin in the culture supernatant of a fluid medium is dependent on a number of factors. The leukotoxin has to be produced by using a strain that is known for its ability to produce high quantities of leukotoxin, inoculated into the most suitable type of medium at the correct culture density containing the necessary supplements and harvested after a certain growth period. The volume in which it is produced may also have an influence. Two different procedures are described to produce the leukotoxin in 5 to 15-ℓ quantities in RPMI 1640 medium. The first method used to produce leukotoxin is one that has been repeatedly described since the presence of the leukotoxin was first established in 1978. Using this method seven batches of leukotoxin were produced in litre quantities with leukotoxin activity ranging from 23-67 u/mℓ. The seed culture inoculum is prepared in brain heart infusion broth, which is centrifuged before the organisms are inoculated into RPMI 1640 medium containing 3,5% foetal calf serum and incubated for only 1 h in a fermenter, after, which the leukotoxin is harvested. An improved alternative method was devised which yielded higher levels of leukotoxin activity by utilising the ability of the P. haemolytica organisms to grow and produce leukotoxin during the logarithmic growth phase in a fermenter. A seed culture harvested in the log phase was prepared in brain heart infusion broth by means of a series of cultures and inoculated into RPMI 1640 containing 3,5% foetal calf serum. Three hours of active growth were allowed during which the leukotoxin was measured by its biological activity and an ELISA assay, and the increase in cell mass by means of the optical density every 30 min. The average leukotoxin biological activity measured 260 u/mℓ and by means of the ELISA test the leukotoxin concentration measured 315 u/ℓ which is a substantial increase in leukotoxin production. In comparison the average optical density only measured 0,469 at 650 nm. Previous findings were substantiated that the highest cell density was not reflected in the highest leukotoxin activity. It is possible to induce high levels of leukotoxin secretion in submerged cultures with RPMI1640 medium containing foetal calf serum in the controlled environment of a fermenter in large enough quantities for use as a vaccine by the improved preparation of the seed culture inoculum.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat v.9 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Language and Culture modulate online Semantic Processing

Language has been shown to influence non-linguistic cognitive operations such as colour perception, object categorization and motion event perception. Here, we show that language also modulates higher level processing, such as semantic knowledge. Using event-related brain potentials, we show that highly fluent Welsh-English bilinguals require significantly less processing effort when reading sentences in Welsh which contain factually correct information about Wales, than when reading sentences containing the same information presented in English. Crucially, culturally irrelevant information was processed similarly in both Welsh and English. Our findings show that even in highly proficient bilinguals, language interacts with factors associated with personal identity, such as culture, to modulate online semantic processing

Fate of the first traversible wormhole: black-hole collapse or inflationary expansion

We study numerically the stability of Morris & Thorne's first traversible wormhole, shown previously by Ellis to be a solution for a massless ghost Klein-Gordon field. Our code uses a dual-null formulation for spherically symmetric space-time integration, and the numerical range covers both universes connected by the wormhole. We observe that the wormhole is unstable against Gaussian pulses in either exotic or normal massless Klein-Gordon fields. The wormhole throat suffers a bifurcation of horizons and either explodes to form an inflationary universe or collapses to a black hole, if the total input energy is respectively negative or positive. As the perturbations become small in total energy, there is evidence for critical solutions with a certain black-hole mass or Hubble constant. The collapse time is related to the initial energy with an apparently universal critical exponent. For normal matter, such as a traveller traversing the wormhole, collapse to a black hole always results. However, carefully balanced additional ghost radiation can maintain the wormhole for a limited time. The black-hole formation from a traversible wormhole confirms the recently proposed duality between them. The inflationary case provides a mechanism for inflating, to macroscopic size, a Planck-sized wormhole formed in space-time foam.Comment: 10 pages, RevTeX4, 11 figures, epsf.st

Squark anti-squark pair production at the LHC: the electroweak contribution

We present the complete NLO electroweak contribution of $\mathcal{O}(\alpha^2_s \alpha)$ to the production of diagonal squark--anti-squark pairs in proton--proton collisions. Compared to the lowest-order $\mathcal{O}(\alpha_s\alpha + \alpha^2)$ electroweak terms, the NLO contributions are also significant. We discuss the LO and NLO electroweak effects in cross sections and distributions at the LHC for the production of squarks different from top squarks, in various supersymmetric benchmark scenarios.Comment: 38 pages, 21 figures. Replaced with the version published in JHE

The modulation effect for supersymmetric dark matter detection with asymmetric velocity dispersion

The detection of the theoretically expected dark matter is central to particle physics cosmology. Current fashionable supersymmetric models provide a natural dark matter candidate which is the lightest supersymmetric particle (LSP). Such models combined with fairly well understood physics like the quark substructure of the nucleon and the nuclear form factor and the spin response function of the nucleus, permit the evaluation of the event rate for LSP-nucleus elastic scattering. The thus obtained event rates are, however, very low or even undetectable. So it is imperative to exploit the modulation effect, i.e. the dependence of the event rate on the earth's annual motion. In this review we study such a modulation effect in directional and undirectional experiments. We calculate both the differential and the total rates using symmetric as well as asymmetric velocity distributions. We find that in the symmetric case the modulation amplitude is small, less than 0.07. There exist, however, regions of the phase space and experimental conditions such that the effect can become larger. The inclusion of asymmetry, with a realistic enhanced velocity dispersion in the galactocentric direction, yields the bonus of an enhanced modulation effect, with an amplitude which for certain parameters can become as large as 0.46.Comment: 35 LATEX pages, 7 Tables, 8 PostScript Figures include

Biological effects of fulvestrant on estrogen receptor positive human breast cancer: Short, medium and long-term effects based on sequential biopsies.

We report the first study of the biological effect of fulvestrant on ER positive clinical breast cancer using sequential biopsies through to progression. Thirty-two locally/systemically advanced breast cancers treated with first-line fulvestrant (250 mg/month) were biopsied at therapy initiation, 6 weeks, 6 months and progression and immunohistochemically-analyzed for Ki67, ER, EGFR and HER2 expression/signaling activity. This series showed good fulvestrant responses (duration of response [DoR] = 25.8 months; clinical benefit = 81%). Ki67 fell (p < 0.001) in 79% of tumours by 6 months and lower Ki67 at all preprogression time-points predicted for longer DoR. ER and PR significantly decreased in all tumours by 6 months (p < 0.001), with some declines in ER (serine 118) phosphorylation and Bcl-2 (p = 0.007). There were modest HER2 increases (p = 0.034, 29% tumours) and loss of any detectable EGFR phosphorylation (p = 0.024, 50% tumours) and MAP kinase (ERK1/2) phosphorylation (p = 0.019, 65% tumours) by 6 months. While ER remained low, there was some recovery of Ki67, Bcl-2 and (weakly) EGFR/MAPK activity in 45–67% patients at progression. Fulvestrant's anti-proliferative impact is related to DoR, but while commonly downregulating ER and indicators of its signaling and depleting EGFR/MAPK signaling in some patients, additional elements must determine response duration. Residual ER at fulvestrant relapse explains reported sensitivity to further endocrine therapies. Occasional modest treatment-induced HER2 and weakly detectable EGFR/HER2/MAPK signaling at relapse suggests targeting of such activity might have value alongside fulvestrant in some patients. However, unknown pathways must drive relapse in most. Ki67 has biomarker potential to predict fulvestrant outcome and as a quantitative measure of response

Exclusion limits on the WIMP-nucleon cross-section from the Cryogenic Dark Matter Search

The Cryogenic Dark Matter Search (CDMS) employs low-temperature Ge and Si detectors to search for Weakly Interacting Massive Particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. For recoil energies above 10 keV, events due to background photons are rejected with >99.9% efficiency, and surface events are rejected with >95% efficiency. The estimate of the background due to neutrons is based primarily on the observation of multiple-scatter events that should all be neutrons. Data selection is determined primarily by examining calibration data and vetoed events. Resulting efficiencies should be accurate to about 10%. Results of CDMS data from 1998 and 1999 with a relaxed fiducial-volume cut (resulting in 15.8 kg-days exposure on Ge) are consistent with an earlier analysis with a more restrictive fiducial-volume cut. Twenty-three WIMP candidate events are observed, but these events are consistent with a background from neutrons in all ways tested. Resulting limits on the spin-independent WIMP-nucleon elastic-scattering cross-section exclude unexplored parameter space for WIMPs with masses between 10-70 GeV c^{-2}. These limits border, but do not exclude, parameter space allowed by supersymmetry models and accelerator constraints. Results are compatible with some regions reported as allowed at 3-sigma by the annual-modulation measurement of the DAMA collaboration. However, under the assumptions of standard WIMP interactions and a standard halo, the results are incompatible with the DAMA most likely value at >99.9% CL, and are incompatible with the model-independent annual-modulation signal of DAMA at 99.99% CL in the asymptotic limit.Comment: 40 pages, 49 figures (4 in color), submitted to Phys. Rev. D; v.2:clarified conclusions, added content and references based on referee's and readers' comments; v.3: clarified introductory sections, added figure based on referee's comment

A LOW COST PHYSICS AND ENGINEERING TRAINING REACTOR. Reactor Design and Feasibility Study

The conceptual design of a low cost training reactor for the instruction of physicists and engineers is covered. It is conceived as an instructional tool for a course such as that given at the Oak Ridge School of Reactor Technology. The reactor is of a modified pool type, and is designed for a maximum power level of one Mw. This arrangement will accommodate engineering experiments, shielding experiments, and critical experiments as well as being useful as a neutron and gamma source. (auth

Dark matter and Colliders searches in the MSSM

We study the complementarity between dark matter experiments (direct detection and indirect detections) and accelerator facilities (the CERN LHC and a $\sqrt{s}= 1$ TeV $e^+e^-$ Linear Collider) in the framework of the constrained Minimal Supersymmetric Standard Model (MSSM). We show how non--universality in the scalar and gaugino sectors can affect the experimental prospects to discover the supersymmetric particles. The future experiments will cover a large part of the parameter space of the MSSM favored by WMAP constraint on the relic density, but there still exist some regions beyond reach for some extreme (fine tuned) values of the supersymmetric parameters. Whereas the Focus Point region characterized by heavy scalars will be easily probed by experiments searching for dark matter, the regions with heavy gauginos and light sfermions will be accessible more easily by collider experiments. More informations on both supersymmetry and astrophysics parameters can be thus obtained by correlating the different signals.Comment: 25 pages, 10 figures, corrected typos and reference adde