161 research outputs found

    Erratum to: Daphnia revisited: local stability and bifurcation theory for physiologically structured population models explained by way of an example

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    In the original publication, the addresses of the authors Dr. J.A.J. Metz and Dr. S. Nakaoka were incorrectly published. The correct address list for the authors are: J.A.J. Metz: Institute of Biology and Institute of Mathematics, Leiden University, P.O. Box 9516, 2300RA Leiden, The Netherlands. S. Nakaoka: Graduate School of

    Estimate of the Collins fragmentation function in a chiral invariant approach

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    We predict the features of the Collins function, which describes the fragmentation of a transversely polarized quark into an unpolarized hadron, by modeling the fragmentation process at a low energy scale. We use the chiral invariant approach of Manohar and Georgi, where constituent quarks and Goldstone bosons are considered as effective degrees of freedom in the non-perturbative regime of QCD. To test the approach we calculate the unpolarized fragmentation function and the transverse momentum distribution of a produced hadron, both of which are described reasonably well. In the case of semi-inclusive deep-inelastic scattering, our estimate of the Collins function in connection with the transversity distribution gives rise to a transverse single spin asymmetry of the order of 10%, supporting the idea of measuring the transversity distribution of the nucleon in this way. In the case of e+ e- annihilation into two hadrons, our model predicts a Collins azimuthal asymmetry of about 5%.Comment: 12 pages, 15 figures. Figs. 11-14 changed, minor changes in discussion, few typos fixed and some references added. Final version to appear in PR

    Intestinal Fatty Acid Binding Protein as a Predictor of Early Mesenteric Injury Preceding Clinical Presentation:A Case Report

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    Introduction: Diagnosing non-occlusive mesenteric ischaemia (NOMI) in patients is complicated, due to poor signs and symptoms and non-specific laboratory tests, leading to a high mortality rate. This case study presents the rare case of a patient who developed mesenteric ischaemia after an emergency thoracic endovascular aneurysm repair (TEVAR) for a type B aortic dissection (TBAD) and peri-operative cardiogenic shock. Study outcomes revealed that intestinal fatty acid binding protein (I-FABP) identified early mucosal damage two days before the clinical presentation. Report: A 43 year old male patient was admitted to the emergency department with an acute TBAD and a dissection of the superior mesenteric artery (SMA), for which TEVAR was performed with additional stent placement in the SMA. Peri-operatively, the patient went into cardiogenic shock with a sustained period of hypotension. Post-operatively, the plasma I-FABP levels were measured prospectively, revealing an initial increase on post-operative day five (551.1 pg/mL), which continued beyond day six (610.3 pg/mL). On post-operative day seven, the patient developed a fever and demonstrated signs of peritonitis and bowel perforation. He underwent an emergency laparotomy, followed by an ileocaecal resection (&lt;100 cm) with a transverse ileostomy. Pathological analysis confirmed the diagnosis of mesenteric ischaemia. Discussion: The diagnosis of NOMI in critically ill patients is often complicated, and the currently available diagnostic markers lack the specificity and sensitivity to detect early intestinal injury. This case report highlights that elevated I-FABP in plasma levels may indicate the presence of early mesenteric injury. Further research needs to be conducted before I-FABP can be applied in daily practice.</p

    Physiological temperatures reduce dimerization of dengue and Zika virus recombinant envelope proteins

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    The spread of dengue (DENV) and Zika virus (ZIKV) is a major public health concern. The primary target of antibodies that neutralize DENV and ZIKV is the envelope (E) glycoprotein, and there is interest in using soluble recombinant E (sRecE) proteins as subunit vaccines. However, the most potent neutralizing antibodies against DENV and ZIKV recognize epitopes on the virion surface that span two or more E proteins. Therefore, to create effective DENV and ZIKV vaccines, presentation of these quaternary epitopes may be necessary. The sRecE proteins from DENV and ZIKV crystallize as native-like dimers, but studies in solution suggest that these dimers are marginally stable. To better understand the challenges associated with creating stable sRecE dimers, we characterized the thermostability of sRecE proteins from ZIKV and three DENV serotypes, DENV2– 4. All four proteins irreversibly unfolded at moderate temperatures (46 –53 °C). At 23 °C and low micromolar concentrations, DENV2 and ZIKV were primarily dimeric, and DENV3– 4 were primarily monomeric, whereas at 37 °C, all four proteins were predominantly monomeric. We further show that the dissociation constant for DENV2 dimerization is very temperature-sensitive, ranging from <1 M at 25 °C to 50 M at 41 °C, due to a large exothermic enthalpy of binding of 79 kcal/mol. We also found that quaternary epitope antibody binding to DENV2– 4 and ZIKV sRecE is reduced at 37 °C. Our observation of reduced sRecE dimerization at physiological temperature highlights the need for stabilizing the dimer as part of its development as a subunit vaccine

    A mechanism for the T-odd pion fragmentation function

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    We consider a simple rescattering mechanism to calculate a leading twist TT-odd pion fragmentation function, a favored candidate for filtering the transversity properties of the nucleon. We evaluate the single spin azimuthal asymmetry for a transversely polarized target in semi-inclusive deep inelastic scattering (for HERMES kinematics). Additionally, we calculate the double TT-odd cos2ϕ\cos2\phi asymmetry in this framework.Comment: 6 pages revtex, 7 eps figures, references added and updated in this published versio

    Generalized Polarizabilities of the Nucleon in Chiral Effective Theories

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    Using the techniques of chiral effective field theories we evaluate the so called generalized polarizabilities of the nucleon, which characterize the structure dependent components in virtual Compton scattering (VCS) as probed in the electron scattering reaction e N \to e' N gamma. Results are given for both spin-dependent and spin-independent structure effects to O(p^3) in SU(2) Heavy Baryon Chiral Perturbation Theory and to O(epsilon^3) in the SU(2) Small Scale Expansion. Finally we compare our calculations with results from the pioneering VCS experiment on the proton from Mainz.Comment: 39 pages, 12 figures, revte

    Role of zika virus envelope protein domain iii as a target of human neutralizing antibodies

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    Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIIItargeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIIIspecific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines

    Oligomeric state of the ZIKV E protein defines protective immune responses

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    The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines
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