Geometric analysis of noisy perturbations to nonholonomic constraints

We propose two types of stochastic extensions of nonholonomic constraints for mechanical systems. Our approach relies on a stochastic extension of the Lagrange-d'Alembert framework. We consider in details the case of invariant nonholonomic systems on the group of rotations and on the special Euclidean group. Based on this, we then develop two types of stochastic deformations of the Suslov problem and study the possibility of extending to the stochastic case the preservation of some of its integrals of motion such as the Kharlamova or Clebsch-Tisserand integrals

The Results of Cytoreductive Operations in Patients with Colorectal Cancer with Simultaneous Liver Polymetastases

Aim - to improve the long-term results of cytoreductive treatment of patients with simultaneous multiple bilobar liver metastases of colorectal cancer by the use of RFTA. Materials and methods. The study presents the results of treatment of 168 patients diagnosed with colorectal cancer of stage IV with simultaneous bilobar metastases in the liver. In the main group, cytoreductive tumor removal was accompanied by radiofrequency thermal ablation (RFTA) of metastatic formations. In the control group only the primary tumor was removed. Results. The use of RFTA during cytoreductive surgery does not worsen the immediate results of surgical treatment, in comparison with patients, where the effect on liver metastases has not been performed, but allows to increase medians of uneventful and overall survival from 9 and 22 months to 17 and 29 months, respectively. Conclusions. The use of RFTA for simultaneous multiple bilobar metastases in the liver during cytoreductive surgery makes it possible to achieve 22.7% of the three-year uneventfulness and 4.3% of the five-year overall survival

Anholonomic frames in constrained dynamics

We demonstrate the usefulness of anholonomic frames in the contexts of nonholonomic and vakonomic systems. We take a consistently differential-geometric approach. As an application, we investigate the conditions under which the dynamics of the two systems will be consistent. A few illustrative examples confirm the results.Comment: 33 pages, to appear in `Dynamical Systems. An international journal.

Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Large variation in ESBL-producing Escherichia coli carriers in six European countries including Russia

We investigated the faecal carriage prevalence of extended-spectrum β-lactamase production in Escherichia coli (EP-EC) and/or Klebsiella pneumoniae (EP-KP) and risk factors associated with carriage among adult study subjects in Finland, Germany, Latvia, Poland, Russia and Sweden (partner countries). The aim was to get indicative data on the prevalence of ESBL-carriage in specific populations in the region. Faecal samples were collected from four study populations and screened on ChromID-ESBL and ChromID-OXA-48 plates. Positive isolates were further characterised phenotypically. Our results show a large variation in carrier prevalence ranging from 1.6% in Latvia to 23.2% in Russia for EP-EC. For the other partner countries, the prevalence of EP-EC were in increasing numbers, 2.3% for Germany, 4.7% for Finland, 6.6% for Sweden, 8.0% for Poland and 8.1% for all partner countries in total. Carriers of EP-KP were identified only in Finland, Russia and Sweden, and the prevalence was < 2% in each of these countries. No carriers of carbapenemase-producing isolates were identified. This is the first study reporting prevalence of carriers (excluding traveller studies) for Finland, Latvia, Poland and Russia. It contributes with important information regarding the prevalence of EP-EC and EP-KP carriage in regions where studies on carriers are limited

Phosphatase of Regenerating Liver-3 Localizes to Cyto-Membrane and Is Required for B16F1 Melanoma Cell Metastasis In Vitro and In Vivo

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) is a member of the novel phosphatases of regenerating liver family, characterized by one protein tyrosine phosphatase active domain and a C-terminal prenylation (CCVM) motif. Though widely proposed to facilitate metastasis in many cancer types, PRL-3's cellular localization and the function of its CCVM motif in metastatic process remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a series of Myc tagged PRL-3 wild type or mutant plasmids were expressed in B16F1 melanoma cells to investigate the relationship between PRL-3's cellular localization and metastasis. With immuno-fluorescence microcopy and cell adhesion/migration assay in vitro, and an experimental passive metastasis model in vivo, we found that CCVM motif is critical for the localization of PRL-3 on cell plasma membrane and the lung metastasis of melanoma. In particular, Cystine170 is the key site for prenylation in this process. CONCLUSIONS/SIGNIFICANCE: These results suggest that cellular localization of PRL-3 is highly correlated with its function in tumor metastasis, and inhibition of PRL-3 prenylation might be a new approach to cancer therapy

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns