Exploring the Structure of the Bound Proton with Deeply Virtual Compton Scattering.

In the past two decades, deeply virtual Compton scattering of electrons has been successfully used to advance our knowledge of the partonic structure of the free proton and investigate correlations between the transverse position and the longitudinal momentum of quarks inside the nucleon. Meanwhile, the structure of bound nucleons in nuclei has been studied in inclusive deep-inelastic lepton scattering experiments off nuclear targets, showing a significant difference in longitudinal momentum distribution of quarks inside the bound nucleon, known as the EMC effect. In this Letter, we report the first beam spin asymmetry (BSA) measurement of exclusive deeply virtual Compton scattering off a proton bound in ^{4}He. The data used here were accumulated using a 6 GeV longitudinally polarized electron beam incident on a pressurized ^{4}He gaseous target placed within the CLAS spectrometer in Hall-B at the Thomas Jefferson National Accelerator Facility. The azimuthal angle (ϕ) dependence of the BSA was studied in a wide range of virtual photon and scattered proton kinematics. The Q^{2}, x_{B}, and t dependencies of the BSA on the bound proton are compared with those on the free proton. In the whole kinematical region of our measurements, the BSA on the bound proton is smaller by 20% to 40%, indicating possible medium modification of its partonic structure.

First Exclusive Measurement of Deeply Virtual Compton Scattering off

We report on the first measurement of the beam-spin asymmetry in the exclusive process of coherent deeply virtual Compton scattering off a nucleus. The experiment uses the 6 GeV electron beam from the Continuous Electron Beam Accelerator Facility (CEBAF) accelerator at Jefferson Lab incident on a pressurized ^{4}He gaseous target placed in front of the CEBAF Large Acceptance Spectrometer (CLAS). The scattered electron is detected by CLAS and the photon by a dedicated electromagnetic calorimeter at forward angles. To ensure the exclusivity of the process, a specially designed radial time projection chamber is used to detect the recoiling ^{4}He nuclei. We measure beam-spin asymmetries larger than those observed on the free proton in the same kinematic domain. From these, we are able to extract, in a model-independent way, the real and imaginary parts of the only ^{4}He Compton form factor, H_{A}. This first measurement of coherent deeply virtual Compton scattering on the ^{4}He nucleus, with a fully exclusive final state via nuclear recoil tagging, leads the way toward 3D imaging of the partonic structure of nuclei.

[Entomological factors of arboviruses emergences]. / Facteurs entomologiques d'émergence des arboviroses.

Arboviruses - viruses transmitted by haematophagous arthropods - are responsible for febrile syndromes, which sometimes include haemorrhagic or neurological symptoms. Human activities have facilitated the emergence of these originally zoonotic viruses and the domestication and spread throughout the world of their major vectors. The last decade has seen significant changes in the epidemiology of arboviruses transmitted by mosquitoes of the genus Aedes, particularly in relation to the intercontinental spread of Aedes albopictus. Here, we address the epidemiological consequences of the invasion by this species into Central Africa and Europe in a context of viral globalization. The risk of transmission in these areas is influenced by virus-vector adaptation phenomena as well as environmental phenomena including climate. Faced with these new risks, it is essential to develop competences in entomological and virological surveillance, risk assessment and forecasting of epidemic risk in order to develop strategies for the prevention and control of epidemics.

[Food allergy in children: anything new in its management?]. / Allergie alimentaire chez l'enfant: quelle prise en charge en 2011?

The prevalence of food allergy in children is increasing, in particular in its most severe presentation, i.e. anaphylaxis. Food allergy has an important impact on children's and their parent's quality of life, because of the fear of accidental ingestion and limitations of social activities. Quality of life questionnaires adapted to food allergy are now available, as well as new diagnostic procedures using recombinant technology. Their interpretation and their clinical correlation remain difficult, especially in children, in the absence of references values. Various oral and subcutaneous immunotherapy strategies are currently under evaluation, using modified or native allergens.

Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests.

Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.

Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription.

Caffeine is a widely used psychostimulant freely crossing the placental barrier. At the doses usually absorbed, it acts as an antagonist of both A1 and A2A adenosine receptors. Pregnant women are generally not advised to limit their caffeine consumption and thus expose their progeny to the drug during the whole of gestation and lactation. The possibility that such caffeine exposure may have long-term consequences on brain development has led to several behavioral investigations on animal models. Despite the crucial role played by adenosine receptor systems in neonatal breathing control, few studies in vitro have been concerned with the consequences of maternal caffeine absorption on breathing, and none in the unrestrained intact animal. The present investigation analyzed the influence of caffeine exposure via placental and milk transfer on resting ventilation and on the response to moderate alveolar hypoxia of 0 to 2-day-old newborn rat (P0-P2) together with the possible underlying mechanisms. Dams absorbed caffeine (46+/-3 mg/kg/day) via drinking fluid (0.2 g/L) throughout gestation, in conditions mimicking moderate human consumption. Caffeine exposure did not significantly affect basal respiratory parameters. In contrast, it attenuated both the early increase and the secondary decrease in ventilation triggered by moderate alveolar hypoxia (11% O2 inhaled). The abolition of Fos protein expression evoked by hypoxia suggested that caffeine exposure may decrease the activity of O2-sensing peripheral chemoreceptor pathway. From real-time PCR data, those functional alterations were associated to increases in A2A adenosine receptor and alpha2 GABA(A) receptor subunit mRNAs in the medulla. This indicates that, even at moderate doses, maternal caffeine consumption may induce a series of subtle developmental alterations that may affect modulation of breathing control in the neonate in pathological situations such hypoxia.

[Drug interaction computer programs: which choice?]. / Bases de données informatiques d'interactions médicamenteuses: quel choix?

Adverse drug reactions represent a partly preventable cause of morbidity. Computer-based tools may be useful for the prevention of those events resulting from drug interactions. While several such tools are currently available to practitioners, they have rarely been compared regarding their performances and limits. This article presents a benchmark evaluation of seven drug interaction databases which may be elected by physicians or pharmacists as an aid to prescription on a regular basis. None of the databases tested appears to be perfect, and the systems vary in their overall completeness and ease of use.

Native and artificial reticuloplasmins co-accumulate in distinct domains of the endoplasmic reticulum and in post-endoplasmic reticulum compartments.

We compared the subcellular distribution of native and artificial reticuloplasmins in endosperm, callus, and leaf tissues of transgenic rice (Oryza sativa) to determine the distribution of these proteins among endoplasmic reticulum (ER) and post-ER compartments. The native reticuloplasmin was calreticulin. The artificial reticuloplasmin was a recombinant single-chain antibody (scFv), expressed with an N-terminal signal peptide and the C-terminal KDEL sequence for retrieval to the ER (scFvT84.66-KDEL). We found that both molecules were distributed in the same manner. In endosperm, each accumulated in ER-derived prolamine protein bodies, but also in glutelin protein storage vacuoles, even though glutelins are known to pass through the Golgi apparatus en route to these organelles. This finding may suggest that similar mechanisms are involved in the sorting of reticuloplasmins and rice seed storage proteins. However, the presence of reticuloplasmins in protein storage vacuoles could also be due to simple dispersal into these compartments during protein storage vacuole biogenesis, before glutelin deposition. In callus and leaf mesophyll cells, both reticuloplasmins accumulated in ribosome-coated vesicles probably derived directly from the rough ER.

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Original reverse transcription polymerase chain reaction method to obtain the full-length cDNA of rice tungro spherical virus.

A two-step reverse transcription reaction combined with long PCR was developed in order to obtain the full-length cDNA from the 12.2 kbp genomic RNA of rice tungro spherical virus. A first step reverse transcription, performed at 45 degrees C using a reverse transcriptase deprived of RNase H activity, allowed the synthesis of a nearly full-length cDNA of 11.7 kbp. A second step reaction, carried out at 65 degrees C using a thermostable polymerase, was necessary to destabilise secondary structures present at the 5' extremity of the RNA template which hampered the reverse transcription reaction in this region. The full-length cDNA obtained by the two-step reverse transcription was amplified successfully by long PCR and subsequently cloned into a plasmid vector. The cloned cDNA showed toxicity and proved to be unstable when amplified in E. coli.

Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies.

We investigated the suitability of transformed rice cell lines as a system for the production of therapeutic recombinant antibodies. Expression constructs encoding a single-chain Fv fragment (scFvT84.66, specific for CEA, the carcinoembryonic antigen present on many human tumours) were introduced into rice tissue by particle bombardment. We compared antibody production levels when antibodies were either secreted to the apoplast or retained in the endoplasmic reticulum (ER) using a KDEL retention signal. Production levels were up to 14 times higher when antibodies were retained in the ER. Additionally, we compared construct sencoding different leader peptides (plant codon optimised murine immunoglobulin heavy and light chain leader peptides from mAb24) and carrying alternative 5' untranslated regions (the petunia chalcone synthase gene 5' UTR and the tobacco mosaic virus omega sequence). We observed no significant differences in antibody production levels among cell lines transformed with these constructs. The highest level of antibody production we measured was 3.8 micrograms g-1 callus (fresh weight). Immunological analysis of transgenic rice callus confirmed the presence of functional scFvT84.66. We discuss the potential merits of cell culture for the production of recombinant antibodies and other valuable macromolecules.

Nuclear scattering radiography.

The quasi-elastic scattering of 1 GeV protons permits the three-dimensional reconstruction of the density distribution in extended bodies. Fast multiwire proportional chambers are used to localize the position of every incoming and outgoing charged particle and to determine the coordinates at the interaction vertex. This article describes tests on a human head fixed on formalin. The comparison with computed tomography scans and anatomical sections is encouraging. Slices with a volume element of 5.5 mm3 illustrate the sensitivity of the method. The results also demonstrate the ability of the method to select the density distribution of hydrogen by making use of the kinematic relations specific to elastic scattering. Trials of this method in living humans are being planned.

Further results in nuclear scattering radiography.

A further investigation of the nuclear scattering of 500-1000 MeV protons is described. Three-demensional information on the desity distribution within carbon, CH and H2O phantoms is obtained with a volume resolution of 2 mm3. The separation of scattering on hydrogen from that on heavier nuclei, such as carbon and oxygen, is demonstrated, providing the statistics are sufficient. Some preliminary measurements on animals are reported, but with a volume resolution limited by statistics to 43 mm3.

[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble]. / Epidémie d'amibiase autochtone hépatique et intestinale dans une localité proche de Grenoble

We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment.