The New Insight into the Role of Antimicrobial Proteins-Alarmins in the Immunopathogenesis of Psoriasis

The pathognesis of psoriasis still remains not fully elucidated. Recent advances favor the idea that interactions between innate and adaptive immune response drive inflammatory process in this disease. Innate antimicrobial peptides and proteins (AMPs) are diverse group of small molecules that provide the first line of defense against invading pathogens. In recent years, the novel functions ofAMPs have been identified. There are three subclasses among AMPs that have gained the special interest as a potentially important player in the pathogenesis of psoriasis: cathelicidin, S100 proteins, and defensins. These AMPs have been shown to modulate and trigger host immune response in psoriasis acting as interplayer between innate and adaptive immune mechanisms. Overexpressed in psoriatic lesions, they prime immune cells for enhanced production of proinflammatory mediators and act as chemoattractant for leukocytes. Therefore, the novel term describing AMPs alarmins has been suggested. As multifunctional player in pathogenesis of psoriasis, AMPs may constitute potential target for therapeutic interventions. However, further investigations are required to establish the methods of downregulation of the aberrant proinflammatory functions of AMPs without increasing the risk of infections

A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients.

BACKGROUND: We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption. METHODS: We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results. RESULTS: Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using the new prognostic test. Multivariable analyses showed that physicians in academic medical centers were significantly more receptive to molecular test use than those in non-academic settings. Forty-one percent of respondents were ready to act on abnormal molecular test results. Physicians who viewed current staging methods as inaccurate and were confident in their capacity to incorporate molecular testing in practice were more likely to say they would act on abnormal test results. CONCLUSIONS: Physician receptivity to molecular diagnostic testing for early-stage colon cancer patients is likely to be influenced by practice setting and perceptions related to delivering quality care to patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01972737

Quantum fingerprinting

Classical fingerprinting associates with each string a shorter string (its fingerprint), such that, with high probability, any two distinct strings can be distinguished by comparing their fingerprints alone. The fingerprints can be exponentially smaller than the original strings if the parties preparing the fingerprints share a random key, but not if they only have access to uncorrelated random sources. In this paper we show that fingerprints consisting of quantum information can be made exponentially smaller than the original strings without any correlations or entanglement between the parties: we give a scheme where the quantum fingerprints are exponentially shorter than the original strings and we give a test that distinguishes any two unknown quantum fingerprints with high probability. Our scheme implies an exponential quantum/classical gap for the equality problem in the simultaneous message passing model of communication complexity. We optimize several aspects of our scheme.Comment: 8 pages, LaTeX, one figur

Constitutive androstane receptor 1 is constitutively bound to chromatin and ‘primed’ for transactivation in hepatocytes

The constitutive androstane receptor (CAR) is a xenobiotic sensor expressed in hepatocytes that activates genes involved in drug metabolism, lipid homeostasis, and cell proliferation. Much progress has been made in understanding the mechanism of activation of human CAR by drugs and xenobiotics. However, many aspects of the activation pathway remain to be elucidated. In this report, we have used viral constructs to express human CAR, its splice variants, and mutant CAR forms in hepatocytes from Car-/- mice in vitro and in vivo. We demonstrate CAR expression rescued the ability of Car-/- hepatocytes to respond to a wide range of CAR activators including phenobarbital. Additionally, two major splice isoforms of human CAR, CAR2 and CAR3, were inactive with almost all the agents tested. In contrast to the current model of CAR activation, ectopic CAR1 is constitutively localised in the nucleus and is loaded onto Cyp2b10 gene in the absence of an inducing agent. In studies to elucidate the role of threonine T38 in CAR regulation, we found that the T38D mutant was inactive even in the presence of CAR activators. However, the T38A mutant was activated by CAR inducers, showing that T38 is not essential for CAR activation. Also, using the inhibitor erlotinib, we could not confirm a role for the epidermal growth factor receptor in CAR regulation. Our data suggest that CAR is constitutively bound to gene regulatory regions and is regulated by exogenous agents through a mechanism which involves protein phosphorylation in the nucleus

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).

ObjectiveTo evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.MethodsWe performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).ResultsIndomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)).ConclusionIndomethacin was more effective than acetaminophen in producing ductus constriction

Non-locality and Communication Complexity

Quantum information processing is the emerging field that defines and realizes computing devices that make use of quantum mechanical principles, like the superposition principle, entanglement, and interference. In this review we study the information counterpart of computing. The abstract form of the distributed computing setting is called communication complexity. It studies the amount of information, in terms of bits or in our case qubits, that two spatially separated computing devices need to exchange in order to perform some computational task. Surprisingly, quantum mechanics can be used to obtain dramatic advantages for such tasks. We review the area of quantum communication complexity, and show how it connects the foundational physics questions regarding non-locality with those of communication complexity studied in theoretical computer science. The first examples exhibiting the advantage of the use of qubits in distributed information-processing tasks were based on non-locality tests. However, by now the field has produced strong and interesting quantum protocols and algorithms of its own that demonstrate that entanglement, although it cannot be used to replace communication, can be used to reduce the communication exponentially. In turn, these new advances yield a new outlook on the foundations of physics, and could even yield new proposals for experiments that test the foundations of physics.Comment: Survey paper, 63 pages LaTeX. A reformatted version will appear in Reviews of Modern Physic

Quasi-discretization Of The Electron Continuum Emitted In Collisions Of 0.6 Mev U−¹ Au11+ With Noble Gases

We have measured relative doubly differential cross sections for electron emission in collisions of 0.6 MeV u−1 Au11+ projectile ions with He, Ne and Ar targets for laboratory electron-detection angles between 17\u27 and 80\u27 and electron energies from 100 eV to well above the classical binary encounter region. The authors observe that, independent of the target Zt, the electron spectra display three characteristic peak-line structures whose energies are nearly invariant with observation angle. These structures are attributed to the diffraction of quasi-free target electrons in the potential of the projectile. © 1992 IOP Publishing Ltd

Generalized Courant-Snyder Theory for Charged-Particle Dynamics in General Focusing Lattices

The Courant-Snyder (CS) theory for one degree of freedom is generalized to the case of coupled transverse dynamics in general linear focusing lattices with quadrupole, skew-quadrupole, dipole, and solenoidal components, as well as torsion of the fiducial orbit and variation of beam energy. The envelope function is generalized into an envelope matrix, and the phase advance is generalized into a 4D sympletic rotation. The envelope equation, the transfer matrix, and the CS invariant of the original CS theory all have their counterparts, with remarkably similar expressions, in the generalized theory.open7

Analytical methods for describing charged particle dynamics in general focusing lattices using generalized Courant-Snyder theory

The dynamics of charged particles in general linear focusing lattices with quadrupole, skew-quadrupole, dipole, and solenoidal components, as well as torsion of the fiducial orbit and variation of beam energy is parametrized using a generalized Courant-Snyder (CS) theory, which extends the original CS theory for one degree of freedom to higher dimensions. The envelope function is generalized into an envelope matrix, and the phase advance is generalized into a 4D symplectic rotation, or a U(2) element. The 1D envelope equation, also known as the Ermakov-Milne-Pinney equation in quantum mechanics, is generalized to an envelope matrix equation in higher dimensions. Other components of the original CS theory, such as the transfer matrix, Twiss functions, and CS invariant (also known as the Lewis invariant) all have their counterparts, with remarkably similar expressions, in the generalized theory. The gauge group structure of the generalized theory is analyzed. By fixing the gauge freedom with a desired symmetry, the generalized CS parametrization assumes the form of the modified Iwasawa decomposition, whose importance in phase space optics and phase space quantum mechanics has been recently realized. This gauge fixing also symmetrizes the generalized envelope equation and expresses the theory using only the generalized Twiss function beta. The generalized phase advance completely determines the spectral and structural stability properties of a general focusing lattice. For structural stability, the generalized CS theory enables application of the Krein-Moser theory to greatly simplify the stability analysis. The generalized CS theory provides an effective tool to study coupled dynamics and to discover more optimized lattice designs in the larger parameter space of general focusing lattices.open3

Authentic Leadership: A Historical Perspective

The purpose of this paper is to interpret the historical meanings conveyed by Barnard's classic works and use them for theorizing about authenticity of leaders in executive roles. Our analysis employs an interpretative logic for meanings of historical ideas proposed by Bevir. As an outcome of this analysis, we identify the conditions that contribute to the failure, crisis, tragedy, and/or success of leader authenticity. In addition, we discuss practical and research implications of the proposed framework.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline