2,172 research outputs found
Constraining New Physics with a Positive or Negative Signal of Neutrino-less Double Beta Decay
We investigate numerically how accurately one could constrain the strengths
of different short-range contributions to neutrino-less double beta decay in
effective field theory. Depending on the outcome of near-future experiments
yielding information on the neutrino masses, the corresponding bounds or
estimates can be stronger or weaker. A particularly interesting case, resulting
in strong bounds, would be a positive signal of neutrino-less double beta decay
that is consistent with complementary information from neutrino oscillation
experiments, kinematical determinations of the neutrino mass, and measurements
of the sum of light neutrino masses from cosmological observations. The keys to
more robust bounds are improvements of the knowledge of the nuclear physics
involved and a better experimental accuracy.Comment: 23 pages, 3 figures. Minor changes. Matches version published in JHE
Constructing living buildings: a review of relevant technologies for a novel application of biohybrid robotics
Biohybrid robotics takes an engineering approach to the expansion and exploitation of biological behaviours for application to automated tasks. Here, we identify the construction of living buildings and infrastructure as a high-potential application domain for biohybrid robotics, and review technological advances relevant to its future development. Construction, civil infrastructure maintenance and building occupancy in the last decades have comprised a major portion of economic production, energy consumption and carbon emissions. Integrating biological organisms into automated construction tasks and permanent building components therefore has high potential for impact. Live materials can provide several advantages over standard synthetic construction materials, including self-repair of damage, increase rather than degradation of structural performance over time, resilience to corrosive environments, support of biodiversity, and mitigation of urban heat islands. Here, we review relevant technologies, which are currently disparate. They span robotics, self-organizing systems, artificial life, construction automation, structural engineering, architecture, bioengineering, biomaterials, and molecular and cellular biology. In these disciplines, developments relevant to biohybrid construction and living buildings are in the early stages, and typically are not exchanged between disciplines. We, therefore, consider this review useful to the future development of biohybrid engineering for this highly interdisciplinary application.publishe
The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer
Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al
Relation between awareness of circulatory disorders and smoking in a general population health examination
BACKGROUND: Little is known about proportions of smokers who maintain smoking after they are aware of a circulatory disorder. The goal was to analyze the extent to which the number of circulatory disorders may be related to being a current smoker. METHODS: Cross-sectional survey study with a probability sample of residents in Germany investigated in health examination centers. Questionnaire data of 3,778 ever smoking participants aged 18 – 79 were used, questions included whether the respondent had ever had hypertension, myocardial infarction, other coronary artery disease, heart failure, stroke, other cerebrovascular disease, peripheral vascular disease, and venous thrombosis. Logistic regression was calculated for circulatory disorders and their number with current smoking as the dependent variable, and odds ratios (OR) are presented adjusted for physician contact, inpatient treatment, smoking cessation counseling, heavy smoking, exercise, overweight and obesity, school education, sex and age. RESULTS: Among ever smokers who had 1 circulatory disorder, 52.1 % were current smokers and among those who reported that they had 3 or more circulatory disorders 28.0 % were current smokers at the time of the interview. The adjusted odds of being a current smoker were lower for individuals who had ever smoked in life and had 2 or more central circulatory disorders, such as myocardial infarction, heart failure or stroke, than for ever smokers without central circulatory disorder (2 or more disorders: adjusted OR 0.6, 95 % confidence interval, CI, 0.4 to 0.8). CONCLUSION: Among those with central circulatory disorders, there is a substantial portion of individuals who smoke despite their disease. The data suggest that only a portion of smokers among the general population seems to be discouraged from smoking by circulatory disorders or its accompanying cognitive or emotional processes
Cancer treatment: the combination of vaccination with other therapies
Harnessing of the immune system by the development of ‘therapeutic’ vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending on the specific chemotherapeutics. Also, chemotherapy represents one of several options available for clearance of CD4+ Foxp3+ regulatory T cells. Moreover, therapies based on monoclonal antibodies may have synergistic potential in combination with vaccination, both when used for targeting of tumor cells and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system
Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer
<p>Abstract</p> <p>Background</p> <p>We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to <b>c</b>linically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.</p> <p>Methods</p> <p>We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.</p> <p>Results</p> <p>In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.</p> <p>Conclusion</p> <p>This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.</p
Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses
The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus
Chest Wall Resection for Adult Soft Tissue Sarcomas and Chondrosarcomas: Analysis of Prognostic Factors
Background: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. Methods: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. Results: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. Conclusions: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis
Sail or sink: novel behavioural adaptations on water in aerially dispersing species
Background
Long-distance dispersal events have the potential to shape species distributions and ecosystem diversity over large spatial scales, and to influence processes such as population persistence and the pace and scale of invasion. How such dispersal strategies have evolved and are maintained within species is, however, often unclear. We have studied long-distance dispersal in a range of pest-controlling terrestrial spiders that are important predators within agricultural ecosystems. These species persist in heterogeneous environments through their ability to re-colonise vacant habitat by repeated long-distance aerial dispersal (“ballooning”) using spun silk lines. Individuals are strictly terrestrial, are not thought to tolerate landing on water, and have no control over where they land once airborne. Their tendency to spread via aerial dispersal has thus been thought to be limited by the costs of encountering water, which is a frequent hazard in the landscape.
Results
In our study we find that ballooning in a subset of individuals from two groups of widely-distributed and phylogenetically distinct terrestrial spiders (linyphiids and one tetragnathid) is associated with a hitherto undescribed ability of those same individuals to survive encounters with both fresh and marine water. Individuals that showed a high tendency to adopt ‘ballooning’ behaviour adopted elaborate postures to seemingly take advantage of the wind current whilst on the water surface.
Conclusions
The ability of individuals capable of long-distance aerial dispersal to survive encounters with water allows them to disperse repeatedly, thereby increasing the pace and spatial scale over which they can spread and subsequently exert an influence on the ecosystems into which they migrate. The potential for genetic connectivity between populations, which can influence the rate of localized adaptation, thus exists over much larger geographic scales than previously thought. Newly available habitat may be particularly influenced given the degree of ecosystem disturbance that is known to follow new predator introductions
CellCognition : time-resolved phenotype annotation in high-throughput live cell imaging
Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Methods 7 (2010): 747-754, doi:10.1038/nmeth.1486.Fluorescence time-lapse imaging has become a powerful tool to investigate complex
dynamic processes such as cell division or intracellular trafficking. Automated
microscopes generate time-resolved imaging data at high throughput, yet tools for
quantification of large-scale movie data are largely missing. Here, we present
CellCognition, a computational framework to annotate complex cellular dynamics.
We developed a machine learning method that combines state-of-the-art classification
with hidden Markov modeling for annotation of the progression through
morphologically distinct biological states. The incorporation of time information into
the annotation scheme was essential to suppress classification noise at state
transitions, and confusion between different functional states with similar
morphology. We demonstrate generic applicability in a set of different assays and
perturbation conditions, including a candidate-based RNAi screen for mitotic exit
regulators in human cells. CellCognition is published as open source software,
enabling live imaging-based screening with assays that directly score cellular
dynamics.Work in the Gerlich
laboratory is supported by Swiss National Science Foundation (SNF) research grant
3100A0-114120, SNF ProDoc grant PDFMP3_124904, a European Young
Investigator (EURYI) award of the European Science Foundation, an EMBO YIP
fellowship, and a MBL Summer Research Fellowship to D.W.G., an ETH TH grant, a
grant by the UBS foundation, a Roche Ph.D. fellowship to M.H.A.S, and a Mueller
fellowship of the Molecular Life Sciences Ph.D. program Zurich to M.H. M.H. and
M.H.A.S are fellows of the Zurich Ph.D. Program in Molecular Life Sciences. B.F.
was supported by European Commission’s seventh framework program project
Cancer Pathways. Work in the Ellenberg laboratory is supported by a European
Commission grant within the Mitocheck consortium (LSHG-CT-2004-503464). Work
in the Peter laboratory is supported by the ETHZ, Oncosuisse, SystemsX.ch (LiverX)
and the SNF
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