Quantum error correction for continuously detected errors

We show that quantum feedback control can be used as a quantum-error-correction process for errors induced by a weak continuous measurement. In particular, when the error model is restricted to one, perfectly measured, error channel per physical qubit, quantum feedback can act to perfectly protect a stabilizer codespace. Using the stabilizer formalism we derive an explicit scheme, involving feedback and an additional constant Hamiltonian, to protect an (n-1)-qubit logical state encoded in n physical qubits. This works for both Poisson (jump) and white-noise (diffusion) measurement processes. Universal quantum computation is also possible in this scheme. As an example, we show that detected-spontaneous emission error correction with a driving Hamiltonian can greatly reduce the amount of redundancy required to protect a state from that which has been previously postulated [e.g., Alber , Phys. Rev. Lett. 86, 4402 (2001)].

Cutting edge: Granzymes A and B are not essential for perforin-mediated tumor rejection

Controversy still exists regarding the biological function of granzyme serine proteases released with perforin from the cytotoxic granules of NK cells and CTLs. In particular, it is not clear whether the major granzymes, A and A play an essential role in tumor rejection mediated by the perforin pathway. We have now examined the relative importance of perforin and granzyme A and B clusters in five different tumor models that stringently distinguish their importance. We conclude that granzyme A and B clusters are not essential for CTL- and NK cell-mediated rejection of spontaneous and experimental tumors, raising the likelihood that either perforin alone or in combination with an additional granzyme or granule component(s) mediates cytotoxicity of tumor cells in vivo.

Quantum control and quantum entanglement

We discuss quantum error correction for errors that occur at random times as described by, a conditional Poisson process. We shoo, how a class of such errors, detected spontaneous emission, can be corrected by continuous closed loop, feedback.

Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice

The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli. We examined the effects of the spa and ot mutations on GlyR- and GABA(A)R-mediated synaptic transmission in the superficial dorsal horn (SFDH), a spinal cord region where inhibition is important for nociceptive processing. Spontaneous mIPSCs were recorded from visually identified neurones in parasagittal spinal cord slices. Neurones received exclusively GABA(A)R-mediated mIPSCs, exclusively GlyR-mediated mIPSCs or both types of mIPSCs. In control mice (wild-type and spa/+) over 40 % of neurones received both types of mIPSCs, over 30 % received solely GABA(A)R-mediated mIPSCs and the remainder received solely GlyR-mediated mIPSCs. In spa/spa animals, 97 % of the neurones received exclusively GABA(A)ergic or both types of mIPSCs. In ot/ot animals, over 80 % of the neurones received exclusively GABA(A)R-mediated mIPSCs. GlyR-mediated mIPSC amplitude and charge were reduced in spa/spa and ot/ot animals. GABA,Rmediated mIPSC amplitude and charge were elevated in spa/spa but unaltered in ot/ot animals. GlyR- and GABA(A)R-mediated mIPSC decay times were similar for all genotypes, consistent with the mutations altering receptor numbers but not kinetics. These findings suggest the spastic and oscillator mutations, traditionally considered motor disturbances, also disrupt inhibition in a sensory region associated with nociceptive transmission. Furthermore, the spastic mutation results in a compensatory increase in GABA(A)ergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse.

The role of impulsivity in the development of substance use and eating disorders

Impulsivity is now widely viewed as a multidimensional construct consisting of a number of related dimensions. Although many measures of impulsivity are correlated, most recent factor analyses support at least a two-factor model. In the current paper, these two factors have been labelled reward sensitivity, reflecting one of the primary dimensions of Gray's personality theory, and rash-spontaneous impulsiveness. The evidence supporting the existence of two dimensions of impulsivity is reviewed in relation to substance misuse and binge eating. (C) 2004 Elsevier Ltd. All rights reserved.

Report of the equine herpesvirus-1 Havermeyer Workshop, San Gimignano, Tuscany, June 2004

Amongst the infectious diseases that threaten equine health, herpesviral infections remain a world wide cause of serious morbidity and mortality. Equine herpesvirus-1 infection is the most important pathogen, causing an array of disorders including epidemic respiratory disease abortion, neonatal foal death, myeloencephalopathy and chorioretinopathy. Despite intense scientific investigation, extensive use of vaccination, and established codes of practice for control of disease outbreaks, infection and disease remain common. While equine herpesvirus-1 infection remains a daunting challenge for immunoprophylaxis, many critical advances in equine immunology have resulted in studies of this virus, particularly related to MHC-restricted cytotoxicity in the horse. A workshop was convened in San Gimignano, Tuscany, Italy in June 2004, to bring together clinical and basic researchers in the field of equine herpesvirus-1 study to discuss the latest advances and future prospects for improving our under-standing of these diseases, and equine immunity to herpesviral infection. This report highlights the new information that was the focus of this workshop, and is intended to summarize this material and identify the critical questions in the field. (c) 2006 Elsevier B.V. All rights reserved.

Multifidus muscle recovery is not automatic after resolution of acute, first-episode low back pain

Study Design. A clinical study was conducted on 39 patients with acute, first-episode, unilateral low back pain and unilateral, segmental inhibition of the multifidus muscle. Patients were allocated randomly to a control or treatment group. Objectives. To document the natural course of lumbar multifidus recovery and to evaluate the effectiveness of specific, localized, exercise therapy on muscle recovery. Summary of Background Data. Acute low back pain usually resolves spontaneously, but the recurrence rate is high. Inhibition of multifidus occurs with acute, first-episode, low back pain, and pathologic changes in this muscle have been linked with poor outcome and recurrence of symptoms. Methods. Patients in group 1 received medical treatment only. Patients in group 2 received medical treatment and specific, localized, exercise therapy. Outcome measures for both groups included 4 weekly assessments of pain, disability, range of motion, and size of the multifidus cross-sectional area. Independent examiners were blinded to group allocation. Patients were reassessed at a 10-week follow-up examination. Results. Multifidus muscle recovery was not spontaneous on remission of painful symptoms in patients in group 1. Muscle recovery was more rapid and more complete in patients in group 2 who received exercise therapy (P = 0.0001). Other outcome measurements were similar for the two groups at the 4-week examination. Although they resumed normal levels of activity, patients in group 1 still had decreased multifidus muscle size at the 10-week follow-up examination. Conclusions. Multifidus muscle recovery is not spontaneous on remission of painful symptoms. Lack of localized, muscle support may be one reason for the high recurrence rate of low back pain following the initial episode.

A peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice

The class II major histocompatibility complex molecule I-A(g7) is strongly linked to the development of spontaneous insulin-dependent diabetes mellitus (IDDM) in non obese diabetic mice and to the induction of experimental allergic encephalomyelitis in Biozzi AB/H mice. Structurally, it resembles the HLA-DQ molecules associated with human IDDM, in having a non-Asp residue at position 57 in its beta chain. To identify the requirements for peptide binding to I-A(g7) and thereby potentially pathogenic T cell epitopes, we analyzed a known I-A(g7)-restricted T cell epitope, hen egg white lysozyme (HEL) amino acids 9-27. NH2- and COOH-terminal truncations demonstrated that the minimal epitope for activation of the T cell hybridoma 2D12.1 was M12-R21 and the minimum sequence for direct binding to purified I-A(g7) M12-Y20/K13-R21. Alanine (A) scanning revealed two primary anchors for binding at relative positions (p) 6 (L) and 9 (Y) in the HEL epitope. The critical role of both anchors was demonstrated by incorporating L and Y in poly(A) backbones at the same relative positions as in the HEL epitope. Well-tolerated, weakly tolerated, and nontolerated residues were identified by analyzing the binding of peptides containing multiple substitutions at individual positions. Optimally, p6 was a large, hydrophobic residue (L, I, V, M), whereas p9 was aromatic and hydrophobic (Y or F) or positively charged (K, R). Specific residues were not tolerated at these and some other positions. A motif for binding to I-A(g7) deduced from analysis of the model HEL epitope was present in 27/30 (90%) of peptides reported to be I-A(g7)-restricted T cell epitopes or eluted from I-A(g7). Scanning a set of overlapping peptides encompassing human proinsulin revealed the motif in 6/6 good binders (sensitivity = 100%) and 4/13 weak or non-binders (specificity = 70%). This motif should facilitate identification of autoantigenic epitopes relevant to the pathogenesis and immunotherapy of IDDM.

Spectral linewidth narrowing by a narrow bandwidth squeezed vacuum in a cavity

The fluorescence spectrum of a strongly driven two-level atom located inside an optical cavity damped by a narrow-bandwidth squeezed vacuum is studied. We use a dressed atom model approach, first applied to squeezed vacuum problems by Yeoman and Barnett, to derive the master equation of the system and discuss the role of the cavity and the squeezed vacuum in the narrowing of the spectral lines and the population trapping effect. We find that in the presence of a single-mode cavity the effect of squeezing on the fluorescence spectrum is more evident in the linewidths of the Rabi sidebands rather than in the linewidth of the central component. Even in the absence of squeezing, the cavity can reduce the linewidth of the central component almost to zero, whereas the Rabi sidebands can be narrowed only to some finite value. In the presence of a two-mode cavity and a two-mode squeezed vacuum the signature of squeezing is evident in the linewidths of all spectral lines. We also establish that the narrowing of the spectral lines is very sensitive to the detuning of the driving field from the atomic resonance. Moreover, we find that the population trapping effect, predicted for the broadband squeezed vacuum case, may appear in a narrow-bandwidth case only if the input squeezed modes are perfectly matched to the cavity modes and if there is non-zero squeezing at the Rabi sidebands.

Infrared seeded parametric four-wave mixing for sensitive detection of molecules

We have developed a sensitive resonant four-wave mixing technique based on two-photon parametric four-wave mixing with the addition of a phase matched ''seeder'' field. Generation of the seeder field via the same four-wave mixing process in a high pressure cell enables automatic phase matching to be achieved in a low pressure sample cell. This arrangement facilitates sensitive detection of complex molecular spectra by simply tuning the pump laser. We demonstrate the technique with the detection of nitric oxide down to concentrations more than 4 orders of magnitude below the capability of parametric four-wave mixing alone, with an estimated detection threshold of 10(12) molecules/cm(3).

Bioactivation of Phenytoin by Human Cytochrome P450: Characterization of the Mechanism and Targets of Covalent Adduct Formation

The cytochrome P450-dependent covalent binding of radiolabel derived fi om phenytoin (DPH) and its phenol and catechol metabolites, 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH) and 5-(3',4'-dihydroxyphenyl)-5-phenylhydantoin (CAT), was examined in liver microsomes. Radiolabeled HPPH and CAT and unlabeled CAT were obtained from microsomal incubations and isolated by preparative HPLC. NADPH-dependent covalent binding was demonstrated in incubations of human liver microsomes with HPPH. When CAT was used as substrate, covalent adduct formation was independent of NADPH, was enhanced in the presence of systems generating reactive oxygen species, and was diminished under anaerobic conditions or in the presence of cytoprotective reducing agents. Fluorographic analysis showed that radiolabel derived from DPH and HPPH was selectively associated with proteins migrating with approximate relative molecular weights of 57-59 kDa and at the dye front (molecular weights < 23 kDa) on denaturing gels. Lower levels of radiolabel were distributed throughout the molecular weight range. In contrast, little selectivity was seen in covalent adducts formed from CAT. HPPH was shown to be a mechanism-based inactivator of P450, supporting the contention that a cytochrome P450 is one target of covalent binding. These results suggest that covalent binding of radiolabel derived from DPH in rat and human Liver microsomes occurs via initial P450-dependent catechol formation followed by spontaneous oxidation to quinone and semiquinone derivatives that ultimately react with microsomal protein. Targets for covalent binding may include P450s, though the catechol appears to be sufficiently stable to migrate out of the P450 active site to form adducts with other proteins. In conclusion, we have demonstrated that DPH can be bioactivated in human liver to metabolites capable of covalently binding to proteins. The relationship of adduct formation to DPH-induced hypersensitivity reactions remains to be clarified.

Phase-dependent fluorescence linewidth narrowing in a three-level atom damped by a finite-bandwidth squeezed vacuum

We examine subnatural phase-dependent linewidths in the fluorescence spectrum of a three-level atom damped by a narrow-bandwidth squeezed vacuum in a cavity. Using the dressed-atom model approach of a strongly driven three-level cascade system, we derive the master equation of the system from which we obtain simple analytical expressions for the fluorescence spectrum. We show that the phase effects depend on the bandwidths of the squeezed vacuum and the cavity relative to the Rabi frequency of the driving fields. When the squeezing bandwidth is much larger than the Rabi frequency, the spectrum consists of five lines with only the central and outer sidebands dependent on the phase. For a squeezing bandwidth much smaller than the Rabi frequency the number of lines in the spectrum and their phase properties depend on the frequency at which the squeezing and cavity modes are centered. When the squeezing and cavity modes are centered on the inner Rabi sidebands, the spectrum exhibits five lines that are completely independent of the squeezing phase with only the inner Rabi sidebands dependent on the squeezing correlations. Matching the squeezing and cavity modes to the outer Rabi sidebands leads to the disappearance of the inner Rabi sidebands and a strong phase dependence of the central line and the outer Rabi sidebands. We find that in this case the system behaves as an individual two-level system that reveals exactly the noise distribution in the input squeezed vacuum. [S1050-2947(97)00111-X].

Disturbances in microbiota - cause or effect?

IBD are a group of complex polygenetic diseases also involving environmental factors. Evidence for a role for bacteria in IBD include an increased abundance of mucosa-associated bacteria in IBD (which occurs even where there is no intestinal inflammation), and the positive impact of antibiotics on the progress of both Crohn's disease (CD) and ulcerative colitis (UC) of the pouch - pouchitis. Bacteria are necessary for most animal models of IBD. The increased abundance of mucosal bacteria in IBD is not non-specific because while some mucosal bacteria are more abundant this is not the case for all mucosal bacteria including the very abundant Bacteroides vulgatus. On the other hand, antibiotic treatments are not curative, and the humoral immune Ig response to bacterial antigens which is more evident in CD, appears to be polyclonal. While this argues against a role for specific bacteria causing a classical infection, certain mucosal bacteria may damage the mucosal barrier. This would promote invasion by other commensal mucosal bacteria triggering an immune response. Altered adaptive, and to a lesser extent, innate immunity have been extensively studied, and genetic defects in the CARD15 (or NOD2) gene that encodes a bacterial sensing protein modulating innate and adaptive immunity are strongly associated with ileal CD. However, the penetrance of the homozygous CARD15 frameshift mutation, which is the most strongly CD-associated genotype, is very low with only 4% of humans with this developing CD. Furthermore, mice with the same defects in CARD15 do not develop spontaneous ileitis or colitis. Therefore, there have to be other aetiological factor(s). Altered permeability is a consistent finding in subclinical CD. There are other data to suggest that altered mucin is an early event in UC. We propose that the pathogenesis of IBD is multifactorial involving specific mucosal bacteria, defective barrier function and altered mucosal immunity in an aetiology triangle.