Generalized Parton Distributions and Deep Exclusive Reactions: Present Program at JLab.

International audienceWe review briefly the physical concept of generalized parton distributions and the experimental challenges associated with the corresponding measurements of deep exclusive reactions.The first data obtained at Jefferson Lab for exclusive photon (DVCS) and vector meson (DVMP) electroproduction above the resonance-excitation region are described . Two upcoming dedicated DVCS experiments are presented in some detail

Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

<p>Abstract</p> <p>Background</p> <p>In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized <it>Hm</it>C1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of <it>Hm</it>C1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand.</p> <p>Methods</p> <p>Recombinant <it>Hm</it>C1q (r<it>Hm</it>C1q) was produced in the yeast <it>Pichia pastoris</it>. Chemotaxis assays were performed to investigate r<it>Hm</it>C1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and <it>in situ </it>hybridization techniques.</p> <p>Results</p> <p>r<it>Hm</it>C1q-stimulated microglia migrate in a dose-dependent manner. This r<it>Hm</it>C1q-induced chemotaxis was reduced when cells were preincubated with either anti-<it>Hm</it>C1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia.</p> <p>Conclusions</p> <p>A previous study showed that recruitment of microglia is observed after <it>Hm</it>C1q release at the cut end of axons. Here, we demonstrate that r<it>Hm</it>C1q-dependent chemotaxis might be driven via a <it>Hm</it>C1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech.</p

Scaling Tests of the Cross Section for Deeply Virtual Compton Scattering

We present the first measurements of the \vec{e}p->epg cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region. The Q^2 dependence (from 1.5 to 2.3 GeV^2) of the helicity-dependent cross section indicates the twist-2 dominance of DVCS, proving that generalized parton distributions (GPDs) are accessible to experiment at moderate Q^2. The helicity-independent cross section is also measured at Q^2=2.3 GeV^2. We present the first model-independent measurement of linear combinations of GPDs and GPD integrals up to the twist-3 approximation.Comment: 5 pages, 4 figures, 2 tables. Text shortened for publication. References added. One figure remove

Deeply Virtual Compton Scattering off the neutron

The present experiment exploits the interference between the Deeply Virtual Compton Scattering (DVCS) and the Bethe-Heitler processes to extract the imaginary part of DVCS amplitudes on the neutron and on the deuteron from the helicity-dependent D$({\vec e},e'\gamma)X$ cross section measured at $Q^2$=1.9 GeV$^2$ and $x_B$=0.36. We extract a linear combination of generalized parton distributions (GPDs) particularly sensitive to $E_q$, the least constrained GPD. A model dependent constraint on the contribution of the up and down quarks to the nucleon spin is deduced.Comment: Published in Phys. Rev. Let

The E00-110 experiment in Jefferson Lab's Hall A: Deeply Virtual Compton Scattering off the Proton at 6 GeV

We present final results on the photon electroproduction ($\vec{e}p\rightarrow ep\gamma$) cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region from Jefferson Lab experiment E00-110. Results from an analysis of a subset of these data were published before, but the analysis has been improved which is described here at length, together with details on the experimental setup. Furthermore, additional data have been analyzed resulting in photon electroproduction cross sections at new kinematic settings, for a total of 588 experimental bins. Results of the $Q^2$- and $x_B$-dependences of both the helicity-dependent and helicity-independent cross sections are discussed. The $Q^2$-dependence illustrates the dominance of the twist-2 handbag amplitude in the kinematics of the experiment, as previously noted. Thanks to the excellent accuracy of this high luminosity experiment, it becomes clear that the unpolarized cross section shows a significant deviation from the Bethe-Heitler process in our kinematics, compatible with a large contribution from the leading twist-2 DVCS$^2$ term to the photon electroproduction cross section. The necessity to include higher-twist corrections in order to fully reproduce the shape of the data is also discussed. The DVCS cross sections in this paper represent the final set of experimental results from E00-110, superseding the previous publication.Comment: 48 pages, 32 figure

T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children

BACKGROUND: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. METHODS: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01(E) and RTS,S/AS02(D) in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. RESULTS: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01(E) induced higher CD4 T cell responses as compared to RTS,S/AS02(D) when given on a 0,1,7-month schedule. CONCLUSIONS: These findings support further Phase III evaluation of RTS,S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230

Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.ClinicalTrials.gov NCT00307021

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369