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Chaque année en France, le Ministère chargé de la santé finance des programmes de recherche via des appels à projets nationaux. Depuis 2013, les soins primaires sont l'une des thématiques prioritaires. Le bilan des projets soumis et retenus avec la qualification de soins primaires n'est pas connu. L'objectif était d'identifier et de décrire les projets en soins primaires financés par des fonds publics entre 2013 et 2019.

Die Begriffe Rotation, Rotationskapazität = Rotationsvermögen = Rotationsfähigkeit und Rotationsanforderung werden nicht eindeutig verwendet. In der Vornorm zum Eurocode 3 wird für Bauwerke, die nicht Hochbauten zuzuordnen sind, ein Rotationssicherheitsnachweis gefordert. Angaben für das Vorgehen werden nicht gemacht. Daher wird auf einige offene Fragen eingegangen.

Nach einem Überblick über die Entwicklung des Beulsicherheitsnachweises für Platten wird ein leistungsfähiges Verfahren für den Beulsicherheitsnachweis für unversteifte und versteifte Platten vorgestellt, das bei gleichzeitiger Wirkung mehrerer Randspannungen anwendbar ist und das auf einer Verallgemeinerung der Vergleichsspannung beruht. Stetigkeitsforderungen, die aus Symmetrieeigenschaften der Spannungszustände folgen können, werden befriedigt. Die stabilisierende Wirkung von Zugspannungen wird zum Vorteil der Wirtschaftlichkeit ausgenutzt. Für gedrungene Platten ohne Beulgefahr geht das Verfahren in den Sicherheitsnachweis gegen Erreichen der Streckgrenze über. Der Beulsicherheitsnachweis enthält als Sonderfall exakt den üblichen Nachweis für die alleinige Wirkung einer Randspannung. Die Treffsicherheit wird an neuen Ergebnissen von FEM‐Tragspannungsberechnungen geprüft.

Arranging target atoms in a plane monolayer, one may produce by atomic or nuclear reaction an ensemble of particles with small initial position spread without disturbing their momentum spread. This would either allow a violation of Heisenberg's uncertainty relation, by creating a situation not described by quantum mechanics hence rendering quantum mechanics incomplete, or, if the uncertainty relation should hold also in this non-disturbative situation, it would mean a permanent violation of energy conservation. Thus an uncertainty relation for position and momentum and energy conservation appear to be mutually exclusive.

The mean Br/Pb ratio in Cairo street dust is 0.23 (raw data), or 0.395 (Pb background corrected), resp. It is calculated that 60-70% of the Pb found in city center dust are traffic-related, the remainder is due to industrial emissions.

On heating mixtures of a platinum metal with an alkali carbonate in different ratios and at different temperatures in an oxygen stream, two kinds of compounds are formed:(1) the cubic compounds NaxPt3O4and NaxPd3O4,and(2) a series of oxide complexes with compositions ABO2or A2BO3, both isomorphous with Na2SnO3.

Charged particle spectra from the reactions Si28(n, a), Si28(n,p), Si28(n, d) were measured by irradiating solid state detectors with 14 MeV neutrons. The background due to escape effects was reduced by pulse shape discrimination. From coincidence measurements between two detectors facing each other information on angular distributions and the spectrum of protons only was obtained.

From the experiments presented, it follows that the specific precipitation and the production of anaphylactic shock with certain azodyes, as described previously, is due to these substances themselves and is not dependent upon formation of azoproteins by interaction of the dyes with proteins in the test tube or the animal body. Besides these, some other azodyes which in our tests did not give precipitation with corresponding immune sera were also found, in very small quantities, to induce anaphylactic contraction of the uterus of sensitized guinea pigs.

The phenomena observed on absorption of immune sera to azoproteins with heterologous azoantigens lead to the conclusion that in general the sera do not contain a single antibody but antibody fractions somewhat different in their reactivity for heterologous antigens. From the constitution of the azocomponent it follows that these fractions cannot be specific for distinct chemical groups in the molecule. In fact, inhibition experiments showed that in the cases examined the various antibodies are all specifically directed towards the whole molecule of the homologous hapten.

In testing several egg lecithin preparations prepared by ourselves it was found that they did not react in complement fixation tests with immune sera made by injections with commercial egg lecithin Merck. With the flocculation method two of the preparations reacted only faintly. Also the brain lecithin and hydrolecithin gave no distinct reactions. The immunization experiments of Sachs and Klopstock could easily be confirmed when commercial egg lecithin Merck was used for the injections. Immunizations with brain lecithin and hydrolecithin yielded no active sera. With an egg lecithin (No. 1) prepared by us the results were not satisfactory though a great number of injections was made. Only one serum gave reactions of medium strength by complement fixation and in flocculation tests with emulsions of Merck lecithin. It did not react however with the lecithin preparation No. 1 itself. In this respect the results resemble to a certain degree those of Sachs and Klopstock with their lecithin Bohringer immune serum. While the reactions of Merck lecithin were slightly diminished by the removal of cholesterol) addition of cholesterol to the lecithin No. 1 had no marked effect on the complement fixation tests, even when a larger amount was added than that present in the Merck preparation. The cholesterol content of this lecithin therefore does not suffice to account for the difference in the results. It is noteworthy that our lecithin immune serum No. 967 gave complement fixation with emulsions of cholesterol although this substance was not present in the injected material. There are several plausible explanations for our results. According to one, the production of antibodies for lecithin would depend on certain physicochemical conditions of the emulsion injected or upon the presence of auxiliary substances in the lecithin preparation (cf. Sachs and Klopstock). Another possibility is that the active agent inducing the formation of antibodies is not lecithin itself but some other substance present in the active lecithin preparations. With regard to the latter assumption it may be mentioned that we obtained definite immunization effects from several injections of quantities as little as 0.2 mg. of purified preparations of Forssman's heterogcnetic haptene mixed with pig serum.2 To decide between the alternative explanations, further studies are necessary.

Since it is known that positive Wassermann reactions prevail in trypanosomiasis of rabbits, similar to those in syphilis, trypanosomes were used for an inquiry into the cause of this reaction. Injections with dead trypanosomes into rabbits proved that these microbes are highly active antigens and suffice in themselves to produce strongly positive Wassermann sera, in analogy to the findings reported by F. Klopstock with Spirochæta pallida. Although a number of questions require further study, yet it seems likely that this antigenic activity of the microbes or their products plays a part in the production of the Wassermann reagins in infections with spirochetes and trypanosomes.

The method of partial synthesis of antigens as employed in the foregoing experiments obviously cannot be substituted for the chemical study of natural antigens. But some questions of a rather general nature not easily accessible to investigations of the latter sort, may be approached by the use of artificial protein compounds. Thus the results reported indicate a peculiarity of certain chemical structures such as acid radicals. The group of immune sera obtained by injecting azoproteins made from non-acid azo components had a wide range of activity. Substituents like CH3, OCH3, NO2, Cl, Br, I, in the aromatic nucleus altered the reactions to a moderate degree only, in most cases. The effects were dependent more on the position than on the nature of the substituents. Two substances were found, however, which had a pronounced effect on the specificity of the compound protein, namely acetyl-para-phenylenediamine and para-aminoacetophenone. In consideration of the above facts it is uncertain whether the antigenic changes noticed by Obermayer and Pick (7) after treating proteins with nitric acid, nitrous acid or iodine are mainly due to the substitution of hydrogen in the benzene ring by NO2 and I, as is the general belief, or to other changes of the protein. This question had been raised already by the observation that the proteins treated with HNO3 or HNO2 containing respectively the nitro or the diazo group, did not differ substantially in their serological properties (8). The antigens made from acid compounds form a group with distinctive features. In the first place the presence of acid radicals destroys the reactivity with the immune sera for the non-acid substances. This influence is so marked that even the reaction with the species specific part of the protein, if such is present, appears to be diminished. Also the sera produced with the acid antigens react but feebly with the non-acid azoproteins. Accordingly it was possible to show that by hydrolysis of the ester of an aromatic acid contained in an azoprotein the serological reactions of the antigen underwent a radical change. The presence of a free carboxyl group in the antigens not only determines the characteristics mentioned but there is reason to believe that it increases markedly the degree of specificity exhibited by the antigens and the corresponding immune sera, when cross-tests are made with a number of acid azoproteins and their antisera. This is brought out by a comparison of the results of the present investigation with those described previously (3). It is of interest in this respect that the specific carbohydrates found by Avery and Heidelberger in pneumococci and pneumobacilli are mostly, if not in all cases, compounds of distinctly acid character.

Zusammenfassung Nach der Injektion von Azoalbumosen entstanden bei Kaninchen Präcipitine, die auf Azohetero- und Azoprotoalbumosen einwirkten, aber diese zwei Präparate nicht differenzierten. Spezifische Unterschiede ließen sich zwischen den aus verschiedenen Proteinen bereiteten Azoalbumosen nachweisen.

The tests presented in Tables I, II, and III show that only in the higher concentration cross reactions do take place, and that there is definite specificity of the two sorts of immune sera for the homologous antigens. Thus it is easy to differentiate the l- and d-antigens in dilutions 1:100 and upwards. The occurrence of cross reactions can readily be ascribed to the fact that the l- and d-acids present in the two antigens are identical in every respect but the position of the groups connected with the asymetric carbon atom. The i-antigen reacts with both sorts of immune sera as could be expected since it must consist of a mixture of equal parts of l- and d-antigen. The reactions of the i-antigen appear to be only slightly weaker than those of the homologous ones owing to the fact that the intensity of the reactions diminishes but slowly with increasing dilution of the antigens. It is also to be considered that small differences cannot be judged very accurately. Tests with two l- and four d-immune sera not recorded in the tables confirmed the results already discussed. Considering that ferments are known to be adapted ordinarily to one type of steric isomers it may be worth noting that antibodies were formed by the same species of animals for optical antipodes. From the results summarized in Tables IV,a and IV,b one sees that the l- and d-immune sera also differentiate clearly between the l- and d-acids when they are not diazotized and not combined with protein. The l-acid inhibits much more the precipitation of the l-antigen by the homologous immune serum than the d-acid and the converse effect occurs if the inhibiting action is tested on the precipitation of d-antigen by d-immune serum. The inactive phenyl (para-aminobenzoylamino) acetic acid behaved in such tests as a mixture of l- and d-acids, i.e., it acted markedly in both cases, more than the heterologous and less than the homologous acid. The experiments reported bring a definite proof for the view that the steric configuration of antigenic groups is one of the factors determining serological specificity. In the particular case under consideration the mere difference in the position of H and COOH as indicated in the following formulas sufficed to alter the reactivity. See PDF for Equation. The fact that steric isomers are acted upon selectively by immune sera may be supposed to play a significant part in the serological specificity of carbohydrates such as those discovered in bacterial antigens.

Experiments are described which show that anaphylactic shock can be induced in animals sensitized with azoproteins by injecting them with azodyes containing the same azo components as the sensitizing antigen. The anaphylactic reactions are specific and occur with quantities of the dyes as small as fractions of milligrams.

Experiments are described demonstrating the precipitation of azodyes by immune sera prepared by the injection of azoproteins containing the same azo component. These precipitin reactions prove conclusively the view already advanced on the basis of inhibition reactions that antibodies combine specifically with substances of small molecular weight. Although in this respect both phenomena have the same significance, the precipitin reactions with dyes are simpler in that the aid of a protein antigen is eliminated. That specific serological precipitin reactions can take place with substances other than proteins has been amply demonstrated by studies on bacterial antigens (14) (polysaccharides (15)). The present findings show that for the precipitation with immune sera not even a high molecular weight of the reactive substance is required. Factors determining the tendency to separate out from the liquid upon combination with antibody seem to be the colloidal state of the solution and the chemical composition of the substance. With regard to the influence of chemical composition, a striking example is provided by the suberic acid dye which gives particularly strong precipitin reactions, most probably on account of its long aliphatic side chains. The results reported may be of use for studies on the mechanism of serological precipitation.

With the idea that studies on the serological properties of peptides may ultimately aid in the understanding of the precipitin reactions of proteins, antigens have been prepared containing aminobenzoylated dipeptides, namely glycyl-glycine, glycyl-d, l-leucine, d, l-leucyl-glycine and d, l-leucyl-d, l-leucine. These four antigens were found to be different serologically, their specificity depending on the structure of the terminal amino acid carrying the free carboxyl group, and to a less degree also on the second amino acid. The results were obtained by means of precipitin and inhibition tests. Analogies to observations on enzyme specificity are discussed.

In continuation of studies on the stereochemical specificity of serum reactions, antigens were examined containing the acyl radicals of the levo-, dextro-, and meso-tartaric acids. It was found that in this case also, immune sera can readily be obtained which differentiate sharply the three antigens identical in every other respect but possessing stereoisomeric groups. Since the tartaric acids by their chemical constitution belong to the same class of substances as sugar acids the results have a bearing upon the question of the specificity of natural antigens containing carbohydrates such as have been described by Avery and Heidelberger.

The results of recent work1on the possibility of producing anti-bodies by means of substances apparently belonging to the class of lipoids have stimulated renewed investigation on the cause of the production of the Wassermann reagins.Several main hypotheses relative to this subject have been considered. One of these implies that the reagins are no antibodies at all; others suppose that they are antibodies for spirochetes with an affinity also to lipoids of common origin; still another assumes that antibody formation is brought about by lipoids of the infected organism.In analogy to the experiments on the production of hetero-genetic antibodies by mixtures of proteins and alcoholic extract of organs,1Sachs and his coworkers2thought of the possibility that the production of antibodies is due to a combined action of components of the spirochetes with lipoids derived from the infected animals. As a support of this hypothesis they report experiments in which it is shown that Wassermann positive sera can be produced in rabbits by the injection of alcoholic extracts of rabbit organs along with diluted pig serum.Among our own experiments dealing with the question were such concerning the possibility of obtaining Wassermann positive sera by injections of dead trypanosomes (T. equiperdum). It had been shown previously that infection of rabbits with trypanosomes (T. equiperduwz) often results in the development of a positive Wassermann reaction.3Experiments by Klopstock in which he succeeded in eliciting Wassermann reactions by injecting dead Spirocheta pallidahave been published very recently.4For the selection of rabbits the Sachs Georgi flocculation test was employed and only such whose sera gave completely negative reactions were taken for the experiments. One set of animals was treated with dead trypanosomes which had been kept over night in the icebox in a saline soluti'on containing 0.25 per cent phenol.

In continuation of previous studies immune sera for azoproteins made from aminobenzoyl dipeptides and tripeptides were tested with various peptide azoproteins by precipitin tests and with nitrobenzoyl derivatives of peptides by means of inhibition reactions. When examined with the latter method, the immune sera exhibited a high degree of specificity and permitted the recognition of distinctions among peptides of similar structure.

A study was made of the specificity of artificial compound-antigens containing aliphatic chains. Striking specificity was exhibited in the reactions of compounds with short chains containing a carboxyl group; for instance succinic acid could be differentiated from malonic or glutaric acid which contain one fewer and one more carbon atom respectively. With the substances containing longer chains, reactions were observed which, although specific to a certain extent, appear to depend mainly on the general physicochemical properties of long aliphatic chains. With a limited number of substances the influence of substituents —halogen, OH, NH2—on the serological specificity was investigated. By means of inhibition reactions it was possible to demonstrate the serological specificity of cis-trans isomers such as maleic and fumaric acid.

Zusammenfassung Metallic calcium has been irradiated by 29 MeV and 34 MeV Bremsstrahlung. Yields of the induced activities have been obtained relative to the reaction C12(?, n) C11 by measuring the annihilation quanta with a Na J-spectrometer. The sum of the cross sections integrated to 33 MeV for the reactions Ca40(?, n) Ca39, Ca40(?, 2 n) Ca38, Ca40(?, np) K38m, and Ca40 (?, np) K38 was determined to be 116 ± 17 MeVmb. At 29 MeV maximum energy the branching ratio Ca40 (?, n p) K38m to Ca40(?, n p)K38 was found to be larger than four. As a byproduct the half lives of Ca39, K38m and S31 were observed to be 0,873 ±0,008 sec, 0,944 ±0,012 sec, and 2,61 ±0,05 sec, respectively.

Experiments are described which confirm the result that the specificity of inhibitory reactions involving substituted aromatic acids is decidedly influenced by the position of the substituent. When antigens with specific groups of very simple constitution are used for the tests, inhibiting effects are obtained also with substances distantly related to those determining the reactivity of the antigens. On the other hand, if antigens are built up from protein and chemical compounds of somewhat higher complexity, the specificity of the inhibition reactions with synthetic crystallized substances is of the same order as that of the usual serum reactions; in other words, it is possible to distinguish such compounds by serological tests as readily as proteins can be differentiated with the aid of precipitating sera.

Experiments are presented on the cross reactions of hen egg albumin immune sera with egg albumins of other species by means of exhaustion with heterologous proteins and by inhibition tests. From the results it can be concluded that the sera contain multiple, qualitatively distinct antibodies. For this, two not mutually exclusive explanations come into consideration: the presence in proteins of a number of different, perhaps similar, complex determinants, and the fact, established by previous results, that one antigenic grouping can call forth the formation of diverse antibodies. It is inferred that cross reactions between proteins of kindred species are ascribable, in general, to similarity in determinant structures, and not to the distribution of identical determinant groups among the related proteins.

Experiments are described dealing with immune sera to pentapeptides and peptide amides. Absorption and inhibition tests gave no indication of the presence in the immune sera of special antibodies for portions of a peptide molecule but the antibodies appeared to be specific for an entire pentapeptide even though the sera contained qualitatively different fractions. Marked disparity was found between the reactions of peptides and corresponding amides indicating differences between acid and other polar groups in their influence on serological specificity.

Azoproteins have been prepared with azocomponents possessing two serologically active groups. On immunization with such antigens immune sera were obtained containing two separate, unrelated antibodies, each specific for one of the two groups and separable by absorption. In other cases one of the two structures was dominant, in that antibodies were formed only towards this and not towards the other grouping. The specificity of the antibodies was in general found to be influenced to some extent by the presence of a second group in the antigen. The relevancy of these observations for antibodies directed against natural antigens has been noted.

A relationship between spatial configuration and serological specificity has been established in several instances.1, 2, 3, 4In recent studies it has been found that the cis-trans isomerism of maleic and fumaric acid can be detected serologically. The immune serum used was obtained by injection of an antigen consisting of protein to which was coupled diazotized p-aminosuccinanilic acid. The reaction of this immune serum with the corresponding antigen was inhibited by succinic acid (as sodium salt) and moreover by maleic, but not by fumaric acid. This differentiation of the cis and transforms extended to the monoesters of the two acids and furthermore to the methyl substituted compounds (citraconic and mesaconic acid).On the basis of our former results the suggestion was made5that in certain cases serological reactions could be used for determining spatial configuration, in a way similar to that in which enzymes have been applied to this purpose. At the same time a first example was cited dealing with the correlation between the optically active forms of malic and tartaric acids. Since no details have been given, a description of the experiments will follow.For the tests immune sera were used specific for levo and dextrotartaric acids, prepared as described previously2and in addition an immune serum specific for levo-malic acid. This was obtained by injections of rabbits with an antigen made by coupling diazotized levo-para-aminomalanilic acid to horse serum. Levo and dextrorotatory para-aminomalanilic acids were prepared by reduction of the corresponding nitro-compounds.∗For the preparation of these compounds the two optically active malic acids were condensed with para-nitraniline. ∗Which of the two possible levo or dextro-nitranilides the substances isolated represent remains to be determined; but it seems probable that the condensation would take place more readily with the carboxyl next to the hydroxyl group.

In the experiments presented, hydrolysis by peptic digestion or acid-heat treatment induced a marked loss of activity of ACTH as measured by adrenal weight increase, but these treatments had little or no influence upon the activity of the hormone as measured by adrenal ascorbic acid depletion.

The photoproton spectrum from C12, irradiated with 31 MeV bremsstrahlung, was measured with an average resolution of 130 keV using a solid state detector. No essential difference to spectra obtained with other methods was found.

Recent work has shown that certain antitoxins can be partially digested1with pepsin without losing their abilities to neutralize toxin. The chemical changes2that accompany this alteration are apparently small; the immunological modification3is, however, clearly set forth in the seriously impaired antigenicity of digested antitoxins. We have made electrophoretic studies of a number of such digested antitoxic sera. In this way it has been possible to follow the course of the enzymatic digestion and to obtain an objective record of the changes that occur when sera are modified.In these experiments diphtheria and tetanus antitoxic horse sera have been digested with pepsin at 37°C and pH 4. Electrophoretic analyses have been made of the original sera and of samples of the digest mixture taken at various intervals during the digestion process.Previous work has shown that powerfully antitoxic horse sera contain large new T-components4which develop during the course of hyperimmunization. Such a T-peak appears in the electrophoretic pattern of the diphtheria and tetanus antitoxic sera shown in Figs. 1 and 4. A study of areas and mobilities in the electrophoretic diagrams demonstrates that during digestion this T-component is more or less rapidly converted into a slower component that moves at substantially the same rate as the normal γ-globulin. As can be seen from Fig. 2 no T is left in a diphtheria antitoxin after one half hour's digestion. A great advantage of digested antitoxin lies in the comparatively slight reactions that follow its injection into man; in order to modify it to this extent, however, a serum must be digested for many hours. Loss of reactivity is not therefore the immediate consequence of the transformation of the T-globulin.

In a previous communication it was stated that by adding inactivated hemolytic immune sera to emulsions of alcoholic extracts of blood, flocculation reactions can be obtained.1In continuation of our experiments, tests were made with rabbit anti-human blood immune sera. It was found that in this case also a certain number of the immune sera gave positive reactions under the conditions of our experiments. The immune sera were prepared by injections of Group I and of Group II blood corpuscles (American nomenclature).2Some of the most active anti-group II immune sera showed a distinctly stronger flocculation with the extracts of II corpuscles than with those of Groups I and III (as shown in the table). To make the emulsions, 1 cc. of the filtered alcoholic extract prepared as described previously1was blown with a pipette into 5 cc. of saline solution.

In a previous paper1we described an electrophoretic analysis of several antipneumococcal horse sera that showed antibody activity in the γ-component. Since then 2 of the horses have been used to produce tetanal antitoxin. Subsequent electrophoretic analyses detected the appearance of a new component apparently associated with the freshly developed antitoxic activity.Early in September, 1939, horses No. 9514 and No. 6225 began to receive tetanal toxin instead of Types 1 and 2 pneumococcal antigens. Three months later they had high antitoxin-titers. Electrophoretic analyses of sera taken then, and before immunization with toxin had begun, are reproduced in Figs. 1 to 4. Only traces of antipneumococcal precipitin could be found in the sera taken in December and areas underlying the γ-peaks had obviously decreased greatly. With the development of antitoxin there had appeared, however, a strong new component (labeled T) with a mobility, -2.2 × 10-5cm2sec-1volts-1, midway between β and γ. The same component was present in the strongly antitoxic serum of horse No. 756, which had never been used before for antibody-production, and in the sera of other horses producing tetanal antitoxin.