Weak-Hamiltonian dynamical systems

A big-isotropic structure $E$ is an isotropic subbundle of $TM\oplus T^*M$, endowed with the metric defined by pairing. The structure $E$ is said to be integrable if the Courant bracket $[\mathcal{X},\mathcal{Y}]\in\Gamma E$, $\forall\mathcal{X},\mathcal{Y}\in\Gamma E$. Then, necessarily, one also has $[\mathcal{X},\mathcal{Z}]\in\Gamma E^\perp$, $\forall\mathcal{Z}\in\Gamma E^\perp$ \cite{V-iso}. A weak-Hamiltonian dynamical system is a vector field $X_H$ such that $(X_H,dH)\in E^\perp$ $(H\in C^\infty(M))$. We obtain the explicit expression of $X_H$ and of the integrability conditions of $E$ under the regularity condition $dim(pr_{T^*M}E)=const.$ We show that the port-controlled, Hamiltonian systems (in particular, constrained mechanics) \cite{{BR},{DS}} may be interpreted as weak-Hamiltonian systems. Finally, we give reduction theorems for weak-Hamiltonian systems and a corresponding corollary for constrained mechanical systems.Comment: 19 pages, minor improvement

Matching in the method of controlled Lagrangians and IDA-passivity based control

This paper reviews the method of controlled Lagrangians and the interconnection and damping assignment passivity based control (IDA-PBC)method. Both methods have been presented recently in the literature as means to stabilize a desired equilibrium point of an Euler-Lagrange system, respectively Hamiltonian system, by searching for a stabilizing structure preserving feedback law. The conditions under which two Euler-Lagrange or Hamiltonian systems are equivalent under feedback are called the matching conditions (consisting of a set of nonlinear PDEs). Both methods are applied to the general class of underactuated mechanical systems and it is shown that the IDA-PBC method contains the controlled Lagrangians method as a special case by choosing an appropriate closed-loop interconnection structure. Moreover, explicit conditions are derived under which the closed-loop Hamiltonian system is integrable, leading to the introduction of gyroscopic terms. The $\lambda$-method as introduced in recent papers for the controlled Lagrangians method transforms the matching conditions into a set of linear PDEs. In this paper the method is extended, transforming the matching conditions obtained in the IDA-PBC method into a set of quasi-linear and linear PDEs.\u

Symmetry Reduction of Optimal Control Systems and Principal Connections

This paper explores the role of symmetries and reduction in nonlinear control and optimal control systems. The focus of the paper is to give a geometric framework of symmetry reduction of optimal control systems as well as to show how to obtain explicit expressions of the reduced system by exploiting the geometry. In particular, we show how to obtain a principal connection to be used in the reduction for various choices of symmetry groups, as opposed to assuming such a principal connection is given or choosing a particular symmetry group to simplify the setting. Our result synthesizes some previous works on symmetry reduction of nonlinear control and optimal control systems. Affine and kinematic optimal control systems are of particular interest: We explicitly work out the details for such systems and also show a few examples of symmetry reduction of kinematic optimal control problems.Comment: 23 pages, 2 figure

Virus-induced hepatocellular carcinomas cause antigen-specific local tolerance

T cell surveillance is often effective against virus-associated tumors because of their high immunogenicity. It is not clear why surveillance occasionally fails, particularly against hepatitis B virus- or hepatitis C virus-associated hepatocellular carcinoma (HCC). We established a transgenic murine model of virus-induced HCC by hepatocyte-specific adenovirus-induced activation of the oncogenic SV40 large T antigen (TAg). Adenovirus infection induced cytotoxic T lymphocytes (CTLs) targeted against the virus and TAg, leading to clearance of the infected cells. Despite the presence of functional, antigen-specific T cells, a few virus-infected cells escaped immune clearance and progressed to HCC. These cells expressed TAg at levels similar to HCC isolated from neonatal TAg-tolerant mice, suggesting that CTL clearance does not select for cells with low immunogenicity. Virus-infected mice revealed significantly greater T cell infiltration in early-stage HCC compared with that in late-stage HCC, demonstrating progressive local immune suppression through inefficient T cell infiltration. Programmed cell death protein-1 (PD-1) and its ligand PD-L1 were expressed in all TAg-specific CD8+ T cells and HCC, respectively, which contributed to local tumor-antigen-specific tolerance. Thus, we have developed a model of virus-induced HCC that may allow for a better understanding of human HCC

The minimal incubation period from the onset of Barrett's oesophagus to symptomatic adenocarcinoma

Background:The interval between the onset of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) can be termed the incubation period. However, the unrecorded onset of BO precludes its direct observation.Methods:Determining the range of intervals between BO diagnosis and OAC within the longest observational BO follow-up study. Exclusion criteria were presence of high-grade dysplasia (HGD) or OAC at baseline, death within <2 years of BO diagnosis, oesophagectomy without HGD/OAC and loss to follow-up. A total of 133 patients (M/F 73/60) were taken into account.Results:In 1967 person years of follow-up there were 13 cases of HGD/OAC, (0.66% p.a.; 95% CI 0.58-0.74), 96 patients died without HGD/OAC and 24 survived without HGD/OAC. The mean intervals between BO diagnosis and either HGD/OAC, death or end of follow-up were 10.8, 12.6 and 25.5 years, respectively, and the mean ages at endpoint were 72.5, 80.0 and 68.3 years, respectively. The survivors without HGD/OAC had a lower age at BO diagnosis (mean 42.8 vs 61.2 and 67.4 years, P=0.001). Baseline presence of low-grade dysplasia was associated with progression to HGD/OAC (log rank P=0.001).Conclusion:The Rotterdam BO follow-up cohort revealed a long incubation period between onset of BO and development of HGD/OAC, in patients without HGD/OAC at baseline as illustrated by 24 patients diagnosed with BO at a young age and followed for a mean period of 25.5 years. Their tumour-free survival established a minimum incubation period, suggesting a true incubation period of three decades or more

Effect of Raloxifene Treatment on Osteocyte Apoptosis in Postmenopausal Women

Increased osteocyte apoptosis, as the result of estrogen deficiency, could play a role in the decrease of bone mass and bone strength seen in postmenopausal osteoporosis. We investigated whether treatment with raloxifene of postmenopausal women with osteoporosis affects osteocyte apoptosis. Transiliac bone biopsies were obtained from 26 osteoporotic women at baseline and after 2 years of treatment with placebo or raloxifene. Immunohistochemical detection of cleaved caspase-3 was performed on sections from nondecalcified bone biopsies to visualize apoptosis. In the trabecular bone total osteocytes, positively stained osteocytes and empty lacunae were counted and percent positive cells and percent empty lacunae determined. Statistical evaluation was performed by Wilcoxon’s paired t-test and Spearman’s rank correlations. There was no significant difference in percentage positive osteocytes between baseline and follow-up biopsies in both the placebo and the raloxifene groups. The percentage empty lacunae increased significantly in the placebo group (11.20 ± 1.43 vs. 9.00 ± 2.25, P = 0.014) but not in the raloxifene group. At baseline in both groups combined, there was a negative correlation between indices of bone remodeling and the percentage positive osteocytes (bone formation rate/bone volume r = −0.67, P = 0.001). We found no direct evidence for an effect of raloxifene treatment on osteocyte apoptosis, but small effects of raloxifene treatment cannot be excluded. The percent of apoptotic osteocytes was dependent on the level of bone remodeling in an individual

The role of CD4 T cells in rejection of solid tumors

The focus in cancer immunotherapy has mainly been on CD8 T cells, as they can directly recognize cancer cells. CD4 T cells have largely been neglected, because most cancers lack MHC II expression and cannot directly be recognized by CD4 T cells. Yet, tumor antigens can be captured and cross-presented by MHC II-expressing tumor stromal cells. Recent data suggest that CD4 T cells act as a swiss army knife against tumors. They can kill cancer cells, if they express MHC II, induce tumoricidal macrophages, induces cellular senescence of cancer cells, destroy the tumor vasculature through cytokine release and help CD8 T cells in the effector phase. We foresee a great future for CD4 T cells in the clinic, grafted with tumor antigen specificity by T cell receptor gene transfer, either alone or in combination with engineered CD8 T cells

Views of parents, adults born preterm and professionals on linkage of real-world data of preterm babies

Objective To explore views of parents of preterm babies, adults born preterm and professionals, on the linkage of real-world health and education data for research on improving future outcomes of babies born preterm. Design Three-stage mixed-methods participatory design involving focus groups, a national survey and interviews. Survey participants who expressed uncertainty or negative views were sampled purposively for invitation to interview. Mixed methods were used for data analysis. Setting and participants All data collection was online. Participants were: focus groups—17 parents; survey—499 parents, 44 adults born preterm (total 543); interviews—6 parents, 1 adult born preterm, 3 clinicians, 2 teachers. Results Three key themes were identified: (1) Data linkage and opt-out consent make sense for improving future outcomes. We found clear demand for better information on long-term outcomes and strong support for data linkage with opt-out consent as a means of achieving this. (2) Information requirements—what, how and when. There was support for providing information in different formats and discussing linkage near to, or following discharge from, the neonatal unit, but not sooner. (3) Looking to the future; the rights of young people. We identified a desire for individuals born preterm to be consulted in the future on the use of their data. Conclusion With appropriate information provision, at the right time, parents, adults born preterm and professionals are supportive of data linkage for research, including where temporary identifiers and opt-out consent are used. Resources are being co-produced to improve communication about routine data linkage