A Differential Game Control Problem in Finite Horizon with an Application to Portfolio Optimization

This paper considers a new class of deterministic finite-time horizon, two-player, zero-sum differential games (DGs) in which the maximizing player is allowed to take continuous and impulse controls whereas the minimizing player is allowed to take impulse control only. We seek to approximate the value function, and to provide a verification theorem for this class of DGs. We first, by means of dynamic programming principle (DPP) in viscosity solution (VS) framework, characterize the value function as the unique VS to the related Hamilton-Jacobi-Bellman-Isaacs (HJBI) double-obstacle equation. Next, we prove that an approximate value function exists, that it is the unique solution to an approximate HJBI double-obstacle equation, and converges locally uniformly towards the value function of each player when the time discretization step goes to zero. Moreover, we provide a verification theorem which characterizes a Nash-equilibrium for the DG control problem considered. Finally, by applying our results, we derive a new continuous-time portfolio optimization model, and we provide related computational algorithms.Comment: 38 page

The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Lethal meningitis triggered by the hypervirulent group B streptococcus clone ST-17 is mediated by a novel surface protein called HvgA

Sortase anchored proteins of Streptococcus uberis play major roles in the pathogenesis of bovine mastitis in dairy cattle

Streptococcus uberis, strain 0140J, contains a single copy sortase A (srtA), encoding a transamidase capable of covalently anchoring specific proteins to peptidoglycan. Unlike the wild-type, an isogenic mutant carrying an inactivating ISS1 insertion within srtA was only able to infect the bovine mammary gland in a transient fashion. For the first 24 h post challenge, the srtA mutant colonised at a similar rate and number to the wild type strain, but unlike the wild type did not subsequently colonise in higher numbers. Similar levels of host cell infiltration were detected in response to infection with both strains, but only in those mammary quarters infected with the wild type strain were clinical signs of disease evident. Mutants that failed to express individual sortase substrate proteins (sub0135, sub0145, sub0207, sub0241, sub0826, sub0888, sub1095, sub1154, sub1370, and sub1730) were isolated and their virulence determined in the same challenge model. This revealed that mutants lacking sub0145, sub1095 and sub1154 were attenuated in cattle. These data demonstrate that a number of sortase anchored proteins each play a distinct, non-redundant and important role in pathogenesis of S. uberis infection within the lactating bovine mammary gland

Sortase A Substrate Specificity in GBS Pilus 2a Cell Wall Anchoring

Streptococcus agalactiae, also referred to as Group B Streptococcus (GBS), is one of the most common causes of life-threatening bacterial infections in infants. In recent years cell surface pili have been identified in several Gram-positive bacteria, including GBS, as important virulence factors and promising vaccine candidates. In GBS, three structurally distinct types of pili have been discovered (pilus 1, 2a and 2b), whose structural subunits are assembled in high-molecular weight polymers by specific class C sortases. In addition, the highly conserved housekeeping sortase A (SrtA), whose main role is to link surface proteins to bacterial cell wall peptidoglycan by a transpeptidation reaction, is also involved in pili cell wall anchoring in many bacteria. Through in vivo mutagenesis, we demonstrate that the LPXTG sorting signal of the minor ancillary protein (AP2) is essential for pilus 2a anchoring. We successfully produced a highly purified recombinant SrtA (SrtAΔN40) able to specifically hydrolyze the sorting signal of pilus 2a minor ancillary protein (AP2-2a) and catalyze in vitro the transpeptidation reaction between peptidoglycan analogues and the LPXTG motif, using both synthetic fluorescent peptides and recombinant proteins. By contrast, SrtAΔN40 does not catalyze the transpeptidation reaction with substrate-peptides mimicking sorting signals of the other pilus 2a subunits (the backbone protein and the major ancillary protein). Thus, our results add further insight into the proposed model of GBS pilus 2a assembly, in which SrtA is required for pili cell wall covalent attachment, acting exclusively on the minor accessory pilin, representing the terminal subunit located at the base of the pilus

Dual Role for Pilus in Adherence to Epithelial Cells and Biofilm Formation in Streptococcus agalactiae

Streptococcus agalactiae is a common human commensal and a major life-threatening pathogen in neonates. Adherence to host epithelial cells is the first critical step of the infectious process. Pili have been observed on the surface of several gram-positive bacteria including S. agalactiae. We previously characterized the pilus-encoding operon gbs1479-1474 in strain NEM316. This pilus is composed of three structural subunit proteins: Gbs1478 (PilA), Gbs1477 (PilB), and Gbs1474 (PilC), and its assembly involves two class C sortases (SrtC3 and SrtC4). PilB, the bona fide pilin, is the major component; PilA, the pilus associated adhesin, and PilC, are both accessory proteins incorporated into the pilus backbone. We first addressed the role of the housekeeping sortase A in pilus biogenesis and showed that it is essential for the covalent anchoring of the pilus fiber to the peptidoglycan. We next aimed at understanding the role of the pilus fiber in bacterial adherence and at resolving the paradox of an adhesive but dispensable pilus. Combining immunoblotting and electron microscopy analyses, we showed that the PilB fiber is essential for efficient PilA display on the surface of the capsulated strain NEM316. We then demonstrated that pilus integrity becomes critical for adherence to respiratory epithelial cells under flow-conditions mimicking an in vivo situation and revealing the limitations of the commonly used static adherence model. Interestingly, PilA exhibits a von Willebrand adhesion domain (VWA) found in many extracellular eucaryotic proteins. We show here that the VWA domain of PilA is essential for its adhesive function, demonstrating for the first time the functionality of a prokaryotic VWA homolog. Furthermore, the auto aggregative phenotype of NEM316 observed in standing liquid culture was strongly reduced in all three individual pilus mutants. S. agalactiae strain NEM316 was able to form biofilm in microtiter plate and, strikingly, the PilA and PilB mutants were strongly impaired in biofilm formation. Surprisingly, the VWA domain involved in adherence to epithelial cells was not required for biofilm formation

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations

De la réforme de 2009 du diplôme d'État à la mutation de l'identité professionnelle du formateur en soins infirmiers

From the 2009 reform of the state diploma to the mutation of the professional identity of the trainer Five years after the entry into force of the nursing education reform of 2009, we began research in order to uncover, elements of response to the disaffection of the nursing trainer position. As of 2011, the number of trainers in training institutes has continued to decrease, jeopardizing the proper functioning of training establishments in Ile de France. The research was carried out in three nursing training institutes (A, B, C) located in Ile de France. The knowledge of the nursing environment and the identification of elements that could fuel the problematic of our research then began, until the end of 2015. The data collected made it possible to establish a grid of individual interviews. 29 out of 31 trainers participated in the interviews on a voluntary basis.In this process of professional transition, identity change would also be dependent on integrative transactions, which would be encouraged to succeed depending on the type of governance of the establishment. Indeed, if the environment favors the reduction of the gap between the institutional professionalization project and the personal professionalization project, the transformation of professional identity will be initiated. This change in professional identity reflects the acceptance by the individual of the new elements constituting the new professional identity. These new elements are: the position of mediator of the trainer within the nursing training system, the role of accompaniment of the professionalization of the student is accentuated, with the problem of the positioning of the trainer in front of his student (rapprochement -distancing). pedagogical engineering, which is essential to master, to meet the new educational requirements of training since the reform. This research also highlights that besides the insufficient change management on the part of the public authorities, the loss of the governance of training by nurses to to the benefit of doctors was a real drama. The core business of nursing education is dethroned by education initially targeted by and for doctors. The danger for the profession is the loss of its own identity °: the "° cure" takes precedence over the "° care".Cinq années après la mise en vigueur de la réforme de la formation en soins infirmiers de 2009, nous avons débuté la recherche afin de mettre au jour, les éléments de réponse à la désaffection du poste de formateur en soins infirmiers. En effet, dès 2011, le nombre de formateurs en institut de formation n’a cessé de décroître, mettant en péril le bon fonctionnement des établissements de formation d’Ile de France. La recherche s’est faite au sein de trois instituts de formation en soins infirmiers ( A, B, C) situés en Ile de France. La prise de connaissance du milieu infirmier et le relevé d’éléments pouvant alimenter la problématique de notre recherche a alors commencé, jusqu’en fin d’année 2015. Les données relevées ont permis d’établir une grille d’entretiens individuels. 29 formateurs sur 31 ont participé de manière volontaire aux entretiens. Les résultats révèlent l’émergence de nouvelles altérités chez le formateurs, avec les acteurs du système de formation. Ces altérités, suivant leur polarité, auraient une influence sur le mécanisme de mutation identitaire. L’équilibre est nécessaire à la transition professionnelle. Dans ce processus de transition professionnelle, la mutation identitaire serait également dépendante de transactions intégratives, lesquelles seraient encouragées à aboutir suivant le type de gouvernance de l’établissement. En effet, si l’environnement va en faveur de la réduction de l’écart entre le projet institutionnel de professionnalisation et le projet personnel de professionnalisation, la mutation de l’identité professionnelle sera enclenchée. Cette mutation identitaire professionnelle reflète l’acceptation par l’individu des nouveaux éléments constitutifs de la nouvelle identité professionnelle. Ces éléments nouveaux sont : la position de médiateur du formateur au sein du système de formation en soins infirmier, le rôle d’accompagnateur de la professionnalisation de l’étudiant , avec la problématique du positionnement du formateur face à son étudiant. L’ingénierie pédagogique aussi est l’indispensable à maîtriser depuis la réforme. Cette recherche met en évidence également qu’outre l’insuffisance de la conduite du changement de la part des pouvoirs publiques, la perte de la gouvernance de la formation par les infirmiers au profit des médecins a été un vrai drame. Le danger pour la profession est la perte de son identité propre : le « cure » supplante le "care"

From the 2009 reform of the state diploma to the change in the trainer's professional identity

Cinq années après la mise en vigueur de la réforme de la formation en soins infirmiers de 2009, nous avons débuté la recherche afin de mettre au jour, les éléments de réponse à la désaffection du poste de formateur en soins infirmiers. En effet, dès 2011, le nombre de formateurs en institut de formation n’a cessé de décroître, mettant en péril le bon fonctionnement des établissements de formation d’Ile de France. La recherche s’est faite au sein de trois instituts de formation en soins infirmiers ( A, B, C) situés en Ile de France. La prise de connaissance du milieu infirmier et le relevé d’éléments pouvant alimenter la problématique de notre recherche a alors commencé, jusqu’en fin d’année 2015. Les données relevées ont permis d’établir une grille d’entretiens individuels. 29 formateurs sur 31 ont participé de manière volontaire aux entretiens. Les résultats révèlent l’émergence de nouvelles altérités chez le formateurs, avec les acteurs du système de formation. Ces altérités, suivant leur polarité, auraient une influence sur le mécanisme de mutation identitaire. L’équilibre est nécessaire à la transition professionnelle. Dans ce processus de transition professionnelle, la mutation identitaire serait également dépendante de transactions intégratives, lesquelles seraient encouragées à aboutir suivant le type de gouvernance de l’établissement. En effet, si l’environnement va en faveur de la réduction de l’écart entre le projet institutionnel de professionnalisation et le projet personnel de professionnalisation, la mutation de l’identité professionnelle sera enclenchée. Cette mutation identitaire professionnelle reflète l’acceptation par l’individu des nouveaux éléments constitutifs de la nouvelle identité professionnelle. Ces éléments nouveaux sont : la position de médiateur du formateur au sein du système de formation en soins infirmier, le rôle d’accompagnateur de la professionnalisation de l’étudiant , avec la problématique du positionnement du formateur face à son étudiant. L’ingénierie pédagogique aussi est l’indispensable à maîtriser depuis la réforme. Cette recherche met en évidence également qu’outre l’insuffisance de la conduite du changement de la part des pouvoirs publiques, la perte de la gouvernance de la formation par les infirmiers au profit des médecins a été un vrai drame. Le danger pour la profession est la perte de son identité propre : le « cure » supplante le "care".From the 2009 reform of the state diploma to the mutation of the professional identity of the trainer Five years after the entry into force of the nursing education reform of 2009, we began research in order to uncover, elements of response to the disaffection of the nursing trainer position. As of 2011, the number of trainers in training institutes has continued to decrease, jeopardizing the proper functioning of training establishments in Ile de France. The research was carried out in three nursing training institutes (A, B, C) located in Ile de France. The knowledge of the nursing environment and the identification of elements that could fuel the problematic of our research then began, until the end of 2015. The data collected made it possible to establish a grid of individual interviews. 29 out of 31 trainers participated in the interviews on a voluntary basis.In this process of professional transition, identity change would also be dependent on integrative transactions, which would be encouraged to succeed depending on the type of governance of the establishment. Indeed, if the environment favors the reduction of the gap between the institutional professionalization project and the personal professionalization project, the transformation of professional identity will be initiated. This change in professional identity reflects the acceptance by the individual of the new elements constituting the new professional identity. These new elements are: the position of mediator of the trainer within the nursing training system, the role of accompaniment of the professionalization of the student is accentuated, with the problem of the positioning of the trainer in front of his student (rapprochement -distancing). pedagogical engineering, which is essential to master, to meet the new educational requirements of training since the reform. This research also highlights that besides the insufficient change management on the part of the public authorities, the loss of the governance of training by nurses to to the benefit of doctors was a real drama. The core business of nursing education is dethroned by education initially targeted by and for doctors. The danger for the profession is the loss of its own identity °: the "° cure" takes precedence over the "° care"