Comparison of PCR ribotyping and multilocus variable-number tandem-repeat analysis (MLVA) for improved detection of Clostridium difficile

<p>Abstract</p> <p>Background</p> <p>Polymerase chain reaction (PCR) ribotyping is one of the globally accepted techniques for defining epidemic clones of <it>Clostridium difficile </it>and tracing virulence-related strains. However, the ambiguous data generated by this technique makes it difficult to compare data attained from different laboratories; therefore, a portable technique that could supersede or supplement PCR ribotyping should be developed. The current study attempted to use a new multilocus variable-number tandem-repeat analysis (MLVA) panel to detect PCR-ribotype groups. In addition, various MLVA panels using different numbers of variable-number tandem-repeat (VNTR) loci were evaluated for their power to discriminate <it>C. difficile </it>clinical isolates.</p> <p>Results</p> <p>At first, 40 VNTR loci from the <it>C. difficile </it>genome were used to screen for the most suitable MLVA panel. MLVA and PCR ribotyping were implemented to identify 142 <it>C. difficile </it>isolates. Groupings of serial MLVA panels with different allelic diversity were compared with 47 PCR-ribotype groups. A MLVA panel using ten VNTR loci with limited allelic diversity (0.54-0.83), designated MLVA10, generated groups highly congruent (98%) with the PCR-ribotype groups. For comparison of discriminatory power, a MLVA panel using only four highly variable VNTR loci (allelic diversity: 0.94-0.96), designated MLVA4, was found to be the simplest MLVA panel that retained high discriminatory power. The MLVA10 and MLVA4 were combined and used to detect genetically closely related <it>C. difficile </it>strains.</p> <p>Conclusions</p> <p>For the epidemiological investigations of <it>C. difficile</it>, we recommend that MLVA10 be used in coordination with the PCR-ribotype groups to detect epidemic clones, and that the MLVA4 could be used to detect outbreak strains. MLVA10 and MLVA4 could be combined in four multiplex PCR reactions to save time and obtain distinguishable data.</p

Thermal States as Universal Resources for Quantum Computation with Always-On Interactions

Measurement-based quantum computation utilizes an initial entangled resource state and proceeds with subsequent single-qubit measurements. It is implicitly assumed that the interactions between qubits can be switched off so that the dynamics of the measured qubits do not affect the computation. By proposing a model spin Hamiltonian, we demonstrate that measurement-based quantum computation can be achieved on a thermal state with always-on interactions. Moreover, computational errors induced by thermal fluctuations can be corrected and thus the computation can be executed fault tolerantly if the temperature is below a threshold value

Maximal entanglement versus entropy for mixed quantum states

Maximally entangled mixed states are those states that, for a given mixedness, achieve the greatest possible entanglement. For two-qubit systems and for various combinations of entanglement and mixedness measures, the form of the corresponding maximally entangled mixed states is determined primarily analytically. As measures of entanglement, we consider entanglement of formation, relative entropy of entanglement, and negativity; as measures of mixedness, we consider linear and von Neumann entropies. We show that the forms of the maximally entangled mixed states can vary with the combination of (entanglement and mixedness) measures chosen. Moreover, for certain combinations, the forms of the maximally entangled mixed states can change discontinuously at a specific value of the entropy. Along the way, we determine the states that, for a given value of entropy, achieve maximal violation of Bell's inequality

Quantum computation by local measurement

Quantum computation is a novel way of information processing which allows, for certain classes of problems, exponential speedups over classical computation. Various models of quantum computation exist, such as the adiabatic, circuit and measurement-based models. They have been proven equivalent in their computational power, but operate very differently. As such, they may be suitable for realization in different physical systems, and also offer different perspectives on open questions such as the precise origin of the quantum speedup. Here, we give an introduction to the one-way quantum computer, a scheme of measurement-based quantum computation. In this model, the computation is driven by local measurements on a carefully chosen, highly entangled state. We discuss various aspects of this computational scheme, such as the role of entanglement and quantum correlations. We also give examples for ground states of simple Hamiltonians which enable universal quantum computation by local measurements.Comment: 36 pages, single column, 6 figures, not published version (as restricted by the journal), please refer to ARCMP for the final published versio

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.</p> <p>Methods</p> <p>Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons.</p> <p>Results</p> <p>In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation.</p> <p>Conclusions</p> <p>In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.</p

Experimental measurement-based quantum computing beyond the cluster-state model

The paradigm of measurement-based quantum computation opens new experimental avenues to realize a quantum computer and deepens our understanding of quantum physics. Measurement-based quantum computation starts from a highly entangled universal resource state. For years, clusters states have been the only known universal resources. Surprisingly, a novel framework namely quantum computation in correlation space has opened new routes to implement measurement-based quantum computation based on quantum states possessing entanglement properties different from cluster states. Here we report an experimental demonstration of every building block of such a model. With a four-qubit and a six-qubit state as distinct from cluster states, we have realized a universal set of single-qubit rotations, two-qubit entangling gates and further Deutsch's algorithm. Besides being of fundamental interest, our experiment proves in-principle the feasibility of universal measurement-based quantum computation without using cluster states, which represents a new approach towards the realization of a quantum computer.Comment: 26 pages, final version, comments welcom

Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients

BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas

The Effect of Intra-Abdominal Hypertension Incorporating Severe Acute Pancreatitis in a Porcine Model

Introduction: Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention