An upper limit on CP violation in the Bs0−Bˉs0B^0_s-\bar{B}^0_s system

In a previous publication we noted that the time dependence of an incoherent $B^0-\bar{B}^0$ mixture undergoes a qualitative change when the magnitude of CP violation $\delta$ exceeds a critical value. Requiring, on physical grounds, that the system evolve from an initial incoherent state to a final pure state in a monotonic way, yields a new upper limit for $\delta$. The recent measurement of the wrong charge semileptonic asymmetry of $B_s^0$ mesons presented by the D0 collaboration is outside this bound by one standard deviation. If this result is confirmed it implies the existence of a new quantum mechanical oscillation phenomenon.Comment: 7 pages, 2 figures, version submitted for publication (Physical Review

A very brief introduction to quantum computing and quantum information theory for mathematicians

This is a very brief introduction to quantum computing and quantum information theory, primarily aimed at geometers. Beyond basic definitions and examples, I emphasize aspects of interest to geometers, especially connections with asymptotic representation theory. Proofs of most statements can be found in standard references

CHO cell cultures in shake flasks and bioreactors present different host cell protein profiles in the supernatant

Several studies on the impact of cell culture parameters on the profile of host cell protein (HCP) impurities have been carried out in shake flasks. Herein, we explore how transferable the findings and conclusions of such investigations are to lab-scale bioreactors. Experiments were performed in both systems in fed-batch mode under physiological temperature and with a shift to mild hypothermia and the impact on key upstream performance indicators was quantified. Under both temperatures, bioreactors produced a richer HCP pool despite the overall concentration being similar at both scales and temperatures. The number of different HCPs detected in bioreactor supernatants was four times higher than that in flasks under physiological temperature and more than eight times higher under mild hypothermia. The origin of HCPs was also altered from mostly naturally secreted proteins in flasks to mainly intracellular proteins in bioreactors at the lower temperature. Although the number of species correlated with apoptotic cell density in bioreactors, this was not the case in flasks. Even though the level of HCP impurities and mAb/HCP concentration ratio were similar under all four conditions with an average of approximately 330 μg HCP/mL culture and 0.3 mg HCP/mg IgG4, respectively, the fact that culture method significantly affects the number of species present in the supernatant can have implications for downstream processing steps

Quantum correlations from local amplitudes and the resolution of the Einstein-Podolsky-Rosen nonlocality puzzle

The Einstein-Podolsky-Rosen nonlocality puzzle has been recognized as one of the most important unresolved issues in the foundational aspects of quantum mechanics. We show that the problem is resolved if the quantum correlations are calculated directly from local quantities which preserve the phase information in the quantum system. We assume strict locality for the probability amplitudes instead of local realism for the outcomes, and calculate an amplitude correlation function.Then the experimentally observed correlation of outcomes is calculated from the square of the amplitude correlation function. Locality of amplitudes implies that the measurement on one particle does not collapse the companion particle to a definite state. Apart from resolving the EPR puzzle, this approach shows that the physical interpretation of apparently `nonlocal' effects like quantum teleportation and entanglement swapping are different from what is usually assumed. Bell type measurements do not change distant states. Yet the correlations are correctly reproduced, when measured, if complex probability amplitudes are treated as the basic local quantities. As examples we discuss the quantum correlations of two-particle maximally entangled states and the three-particle GHZ entangled state.Comment: Std. Latex, 11 pages, 1 table. Prepared for presentation at the International Conference on Quantum Optics, ICQO'2000, Minsk, Belaru

Cascading effect in bioprocessing – the impact of mild hypothermia on CHO cell behavior and host cell protein composition

A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture decisions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, i.e. antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behaviour. Mild hypothermic conditions introduced on day 5 of fed-batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra five days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones

Using structural information to change the phosphotransfer specificity of a two-component chemotaxis signalling complex.

addresses: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.notes: PMCID: PMC2817712types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2010 Bell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Two-component signal transduction pathways comprising histidine protein kinases (HPKs) and their response regulators (RRs) are widely used to control bacterial responses to environmental challenges. Some bacteria have over 150 different two-component pathways, and the specificity of the phosphotransfer reactions within these systems is tightly controlled to prevent unwanted crosstalk. One of the best understood two-component signalling pathways is the chemotaxis pathway. Here, we present the 1.40 A crystal structure of the histidine-containing phosphotransfer domain of the chemotaxis HPK, CheA(3), in complex with its cognate RR, CheY(6). A methionine finger on CheY(6) that nestles in a hydrophobic pocket in CheA(3) was shown to be important for the interaction and was found to only occur in the cognate RRs of CheA(3), CheY(6), and CheB(2). Site-directed mutagenesis of this methionine in combination with two adjacent residues abolished binding, as shown by surface plasmon resonance studies, and phosphotransfer from CheA(3)-P to CheY(6). Introduction of this methionine and an adjacent alanine residue into a range of noncognate CheYs, dramatically changed their specificity, allowing protein interaction and rapid phosphotransfer from CheA(3)-P. The structure presented here has allowed us to identify specificity determinants for the CheA-CheY interaction and subsequently to successfully reengineer phosphotransfer signalling. In summary, our results provide valuable insight into how cells mediate specificity in one of the most abundant signalling pathways in biology, two-component signal transduction

L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

Accretion Disks Around Young Objects. II. Tests of Well-Mixed Models with Ism Dust

We construct detailed vertical structure models of irradiated accretion disks around T Tauri stars with interstellar medium dust uniformly mixed with gas. The dependence of the structure and emission properties on mass accretion rate, viscosity parameter, and disk radius is explored using these models. The theoretical spectral energy distributions (SEDs) and images for all inclinations are compared with observations of the entire population of Classical T Tauri stars (CTTS) and Class I objects in Taurus. In particular, we find that the median near-infrared fluxes can be explained within the errors with the most recent values for the median accretion rates for CTTS. We further show that the majority of the Class I sources in Taurus cannot be Class II sources viewed edge-on because they are too luminous and their colors would be consistent with disks seen only in a narrow range of inclinations. Our models appear to be too geometrically thick at large radii, as suggested by: (a) larger far-infrared disk emission than in the typical SEDs of T Tauri stars; (b) wider dark dust lanes in the model images than in the images of HH30 and HK Tau/c; and (c) larger predicted number of stars extincted by edge-on disks than consistent with current surveys. The large thickness of the model is a consequence of the assumption that dust and gas are well-mixed, suggesting that some degree of dust settling may be required to explain the observations.Comment: 41 pages, 13 figures, accepted in Ap

The influence of perfusion solution on renal graft viability assessment

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall’s hypertonic citrate (HOC) and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard