316 research outputs found

    Nonlinear Optical studies of the Transient Coherence in the Quantum Hall System

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    We review recent investigations of the femtosecond non-linear optical response of the two-dimensional electron gas (2DEG) in a strong magnetic field. We probe the Quantum Hall (QH) regime for filling factors ν1\nu \sim 1. Our focus is on the transient coherence induced via optical excitation and on its time evolution during early femtosecond timescales. We simultaneously study the interband and intraband coherence in this system by using a nonlinear spectroscopic technique, transient three-pulse four wave mixing optical spectroscopy, and a many-body theory. We observe striking differences in the temporal and spectral profile of the nonlinear optical signal between a modulation doped quantum well system (with the 2DEG) and a similar undoped quantum well (without a 2DEG). We attribute these qualitative differences to Coulomb correlations between the photoexcited electron-hole pairs and the 2DEG. We show, in particular, that intraband many-particle coherences assisted by the inter-Landau-level magnetoplasmon excitations of the 2DEG dominate the femtosecond nonlinear optical responce. The most striking effect of these exciton-magnetoplasmon coherences is a large off-resonant four-wave-mixing signal in the case of very low photoexcited carrier densities, not observed in the undoped system, with strong temporal oscillations and unusually symmetric temporal profile.Comment: 22 pages, 9 figures; review article to be published in Solid State Communication

    A unitary model for structure functions and diffractive production at small x

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    We propose a unified approach which describes both structure functions in the small-xx region and diffractive production in γp\gamma^*p-interactions. It is shown that the model, based on reggeon calculus and a quark-parton picture of the interaction, gives a good description of available experimental data in a broad region of Q2Q^2 (including Q2=0Q^2 =0) with a single Pomeron of intercept αP(0)=1.2\alpha_P(0) = 1.2. Predictions for very small xx are given and the problem of saturation of parton densities is discussed.Comment: 43 pages, latex, 15 postscript figure

    One-year safety and efficacy of mitapivat in sickle cell disease:follow-up results of a phase 2, open-label study

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    Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD. Here, the 1-year fixed-dose extension period is reported in which 9 of 10 included patients (90%) aged ≥16 years with SCD (HbSS, HbS/β0, or HbS/β+) continued with mitapivat. Mostly mild treatment-emergent adverse events (AEs) (most commonly, transaminase increase and headache) were still reported. Apart from the reported nontreatment-related serious AE (SAE) of a urinary tract infection in the dose-finding period, 1 nontreatment-related SAE occurred in the fixed-dose extension period in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvement in Hb level (mean increase, 1.1 ± 0.7 g/dL; P = .0014) was seen, which was accompanied by decreases in markers of hemolysis. In addition, the annualized rate of vaso-occlusive events reduced significantly from a historic baseline of 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) when combining the dose-finding period and fixed-dose extension period. Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced. Overall, this study demonstrated 1-year safety and efficacy of treatment with mitapivat in SCD, supporting further evaluation in ongoing phase 2/3 study (RISE UP, NCT05031780). This trial was registered at https://www.clinicaltrialsregister.eu/as NL8517 and EudraCT 2019-003438-18.</p

    Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease

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    Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted p &lt; 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p &lt; 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.</p

    Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease

    Get PDF
    Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted p &lt; 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p &lt; 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.</p

    Forward jet production in deep inelastic ep scattering and low-x parton dynamics at HERA

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    Differential inclusive jet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector. Three phase-space regions have been selected in order to study parton dynamics where the effects of BFKL evolution might be present. The measurements have been compared to the predictions of leading-logarithm parton shower Monte Carlo models and fixed-order perturbative QCD calculations. In the forward region, QCD calculations at order alpha_s^1 underestimate the data up to an order of magnitude at low x. An improved description of the data in this region is obtained by including QCD corrections at order alpha_s^2, which account for the lowest-order t-channel gluon-exchange diagrams, highlighting the importance of such terms in parton dynamics at low x.Comment: 25 pages, 4 figure

    Deep inelastic inclusive and diffractive scattering at Q2Q^2 values from 25 to 320 GeV2^2 with the ZEUS forward plug calorimeter

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    Deep inelastic scattering and its diffractive component, epeγpeXNep \to e^{\prime}\gamma^* p \to e^{\prime}XN, have been studied at HERA with the ZEUS detector using an integrated luminosity of 52.4 pb1^{-1}. The MXM_X method has been used to extract the diffractive contribution. A wide range in the centre-of-mass energy WW (37 -- 245 GeV), photon virtuality Q2Q^2 (20 -- 450 GeV2^2) and mass MXM_X (0.28 -- 35 GeV) is covered. The diffractive cross section for 2<MX<152 < M_X < 15 GeV rises strongly with WW, the rise becoming steeper as Q2Q^2 increases. The data are also presented in terms of the diffractive structure function, F2D(3)F^{\rm D(3)}_2, of the proton. For fixed Q2Q^2 and fixed MXM_X, \xpom F^{\rm D(3)}_2 shows a strong rise as \xpom \to 0, where \xpom is the fraction of the proton momentum carried by the Pomeron. For Bjorken-x<1103x < 1 \cdot 10^{-3}, \xpom F^{\rm D(3)}_2 shows positive logQ2\log Q^2 scaling violations, while for x5103x \ge 5 \cdot 10^{-3} negative scaling violations are observed. The diffractive structure function is compatible with being leading twist. The data show that Regge factorisation is broken.Comment: 89 pages, 27 figure

    Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

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    Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

    Influence of Conversion and Anastomotic Leakage on Survival in Rectal Cancer Surgery; Retrospective Cross-sectional Study

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