Time-dependent Mechanics and Lagrangian submanifolds of Dirac manifolds

A description of time-dependent Mechanics in terms of Lagrangian submanifolds of Dirac manifolds (in particular, presymplectic and Poisson manifolds) is presented. Two new Tulczyjew triples are discussed. The first one is adapted to the restricted Hamiltonian formalism and the second one is adapted to the extended Hamiltonian formalism

Bioengineering of Antibody Fragments: Challenges and Opportunities.

Antibody fragments are used in the clinic as important therapeutic proteins for treatment of indications where better tissue penetration and less immunogenic molecules are needed. Several expression platforms have been employed for the production of these recombinant proteins, from which E. coli and CHO cell-based systems have emerged as the most promising hosts for higher expression. Because antibody fragments such as Fabs and scFvs are smaller than traditional antibody structures and do not require specific patterns of glycosylation decoration for therapeutic efficacy, it is possible to express them in systems with reduced post-translational modification capacity and high expression yield, for example, in plant and insect cell-based systems. In this review, we describe different bioengineering technologies along with their opportunities and difficulties to manufacture antibody fragments with consideration of stability, efficacy and safety for humans. There is still potential for a new production technology with a view of being simple, fast and cost-effective while maintaining the stability and efficacy of biotherapeutic fragments

Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1, and Spp1 in western diet-induced obesity.

BACKGROUND: Environmental factors are critical in the development of age-related cognitive decline and dementia. A western diet (WD) can cause nutrient deficiency and inflammation that could impact cognition directly. It is increasingly recognized that innate immune responses by brain myeloid cells, such as resident microglia, and infiltrating peripheral monocytes/macrophages may represent an essential link between a WD, cognitive decline, and dementia. Our previous data demonstrated that chronic consumption of a WD induced inflammation through brain myeloid cells in aging mice and a mouse model of Alzheimer\u27s disease (AD). However, the subtypes of myeloid cells that contribute to the WD-induced inflammation remain unclear. METHODS: C57BL/6J (B6), myeloid cell reporter mice (B6.Ccr2 RESULTS: Ccr2::RFP expressing myeloid cells were significantly increased in brains of WD- compared to CD-fed mice, but were not elevated in Ccr2-deficient WD-fed mice. The percent of CD11b+CD45 CONCLUSIONS: These data further support the model that peripheral myeloid cells enter the brain in response to diet-induced obesity. Elucidating their contribution to age-related cognitive decline and age-related neurodegenerative diseases should offer new avenues for therapeutic intervention in Alzheimer\u27s disease and related dementias, where diet/obesity are major risk factors

Bioluminescence imaging of human embryonic stem cells transplanted in vivo in murine and chick models

Research into the behavior, efficacy, and biosafety of stem cells with a view to clinical transplantation requires the development of noninvasive methods for in vivo imaging of cells transplanted into animal models. This is particularly relevant for human embryonic stem cells (hESCs), because transplantation of undifferentiated hESCs leads to tumor formation. The present study aimed to monitor hESCs in real time when injected in vivo. hESCs were stably transfected to express luciferase, and luciferase expression was clearly detected in the undifferentiated and differentiated state. When transfected hESCs were injected into chick embryos, bioluminescence could be detected both ex and in ovo. In the SCID mouse model, undifferentiated hESCs were detectable after injection either into the muscle layer of the peritoneum or the kidney capsule. Tumors became detectable between days 10-30, with approximately a 3 log increase in the luminescence signal by day 75. The growth phase occurred earlier in the kidney capsule and then reached a plateau, whilst tumors in the peritoneal wall grew steadily throughout the period analysed. These results show the widespread utility of bioluminescent for in vivo imaging of hESCs in a variety of model systems for preclinical research into regenerative medicine and cancer biology. © Copyright 2009, Mary Ann Liebert, Inc

Implementing a public web based GIS service for feedback of surveillance data on communicable diseases in Sweden

BACKGROUND: Surveillance data allow for analysis, providing public health officials and policy-makers with a basis for long-term priorities and timely information on possible outbreaks for rapid response (data for action). In this article we describe the considerations and technology behind a newly introduced public web tool in Sweden for easy retrieval of county and national surveillance data on communicable diseases. METHODS: The web service was designed to automatically present updated surveillance statistics of some 50 statutory notifiable diseases notified to the Swedish Institute for Infectious Disease Control (SMI). The surveillance data is based on clinical notifications from the physician having treated the patient and laboratory notifications, merged into cases using a unique personal identification number issued to all Swedish residents. The web service use notification data from 1997 onwards, stored in a relational database at the SMI. RESULTS: The web service presents surveillance data to the user in various ways; tabulated data containing yearly and monthly disease data per county, age and sex distribution, interactive maps illustrating the total number of cases and the incidence per county and time period, graphs showing the total number of cases per week and graphs illustrating trends in the disease data. The system design encompasses the database (storing the data), the web server (holding the web service) and an in-the-middle computer (to ensure good security standards). CONCLUSIONS: The web service has provided the health community, the media, and the public with easy access to both timely and detailed surveillance data presented in various forms. Since it was introduced in May 2003, the system has been accessed more than 1,000,000 times, by more than 10,000 different viewers (over 12.600 unique IP-numbers)

Homeopathy for seasonal allergic rhinitis: rationale, design and methods of the three-armed randomized controlled HOMEOSAR trial

Background: Patients with seasonal allergic rhinitis (SAR) frequently use homeopathic therapy. Although there is some evidence that homeopathy may be effective in treating symptoms of SAR, there is a lack of high-quality clinical trials. Therefore, the aim of the homeopathy for SAR (HOMEOSAR) trial is to determine the efficacy of individualized or standardized homeopathic drug treatment compared to placebo regarding rhinitis-related quality of life in patients with SAR. Methods: This randomized, placebo-controlled, double-blind, three-armed intervention study will be conducted at two university hospital outpatient clinics for complementary and integrative medicine in Berlin and in 12 office-based practices specializing in homeopathic treatment in Germany. A total of 270 patients with clinical symptoms of SAR and positive allergy test to birch and grass pollen will receive homeopathic anamnesis and subsequently be randomized into (a) standardized homeopathic drug treatment with Galphimia Glauca (potency D6), (b) individualized homeopathic drug treatment (D6), or (c) placebo. All three groups can receive on-demand rescue medication as needed. Treatment will consist of two consultations and daily intake of the study medication for 4 weeks during the pollen season. The primary outcome is the mean overall score of the Rhinitis Quality of Life Questionnaire (RQLQ) in weeks 3 and 4, analyzed using analysis of covariance (adjusted for baseline RQLQ overall score and study center). A closed testing procedure will be used to control the overall type I error comparing the 3 treatment groups. Secondary outcomes include the overall RQLQ and its seven domain scores, responder status (decrease in RQLQ overall score of at least 0.5 points compared to the baseline value), use of rescue medication, intensity of total and individual SAR symptoms based on visual analog scale, generic health-related quality of life, safety, utilization of health care resources and associated costs. In addition, a qualitative data analysis is planned. Conclusion: The results of our study will contribute to clarifying the possible therapeutic effects of homeopathic drug treatment for patients with SAR

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

The graded Jacobi algebras and (co)homology

Jacobi algebroids (i.e. `Jacobi versions' of Lie algebroids) are studied in the context of graded Jacobi brackets on graded commutative algebras. This unifies varios concepts of graded Lie structures in geometry and physics. A method of describing such structures by classical Lie algebroids via certain gauging (in the spirit of E.Witten's gauging of exterior derivative) is developed. One constructs a corresponding Cartan differential calculus (graded commutative one) in a natural manner. This, in turn, gives canonical generating operators for triangular Jacobi algebroids. One gets, in particular, the Lichnerowicz-Jacobi homology operators associated with classical Jacobi structures. Courant-Jacobi brackets are obtained in a similar way and use to define an abstract notion of a Courant-Jacobi algebroid and Dirac-Jacobi structure. All this offers a new flavour in understanding the Batalin-Vilkovisky formalism.Comment: 20 pages, a few typos corrected; final version to be published in J. Phys. A: Math. Ge