585 research outputs found
Random walks and Lévy processes as rough paths
We consider random walks and L\'evy processes in a homogeneous group . For
all , we completely characterise (almost) all -valued L\'evy
processes whose sample paths have finite -variation, and give sufficient
conditions under which a sequence of -valued random walks converges in law
to a L\'evy process in -variation topology. In the case that is the free
nilpotent Lie group over , so that processes of finite
-variation are identified with rough paths, we demonstrate applications of
our results to weak convergence of stochastic flows and provide a
L\'evy-Khintchine formula for the characteristic function of the signature of a
L\'evy process. At the heart of our analysis is a criterion for tightness of
-variation for a collection of c\`adl\`ag strong Markov processes.Comment: 36 pages. Revised from previous version. To appear in Probability
Theory and Related Field
Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers
BACKGROUND: Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens. METHODS: Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score ± SD (0 = negative/8 = highest) for each histotype was recorded. RESULTS: For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor. CONCLUSION: CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809–8817, 2005), it may be a promising target for antibody-based therapy
Cosmic rays and molecular clouds
This paper deals with the cosmic-ray penetration into molecular clouds and
with the related gamma--ray emission. High energy cosmic rays interact with the
dense gas and produce neutral pions which in turn decay into two gamma rays.
This makes molecular clouds potential sources of gamma rays, especially if they
are located in the vicinity of a powerful accelerator that injects cosmic rays
in the interstellar medium. The amplitude and duration in time of the
cosmic--ray overdensity around a given source depend on how quickly cosmic rays
diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray
observations of molecular clouds can be used both to locate the sources of
cosmic rays and to constrain the properties of cosmic-ray diffusion in the
Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics
2012, 27 pages, 10 figure
Understanding Galaxy Formation and Evolution
The old dream of integrating into one the study of micro and macrocosmos is
now a reality. Cosmology, astrophysics, and particle physics intersect in a
scenario (but still not a theory) of cosmic structure formation and evolution
called Lambda Cold Dark Matter (LCDM) model. This scenario emerged mainly to
explain the origin of galaxies. In these lecture notes, I first present a
review of the main galaxy properties, highlighting the questions that any
theory of galaxy formation should explain. Then, the cosmological framework and
the main aspects of primordial perturbation generation and evolution are
pedagogically detached. Next, I focus on the ``dark side'' of galaxy formation,
presenting a review on LCDM halo assembling and properties, and on the main
candidates for non-baryonic dark matter. It is shown how the nature of
elemental particles can influence on the features of galaxies and their
systems. Finally, the complex processes of baryon dissipation inside the
non-linearly evolving CDM halos, formation of disks and spheroids, and
transformation of gas into stars are briefly described, remarking on the
possibility of a few driving factors and parameters able to explain the main
body of galaxy properties. A summary and a discussion of some of the issues and
open problems of the LCDM paradigm are given in the final part of these notes.Comment: 50 pages, 10 low-resolution figures (for normal-resolution, DOWNLOAD
THE PAPER (PDF, 1.9 Mb) FROM http://www.astroscu.unam.mx/~avila/avila.pdf).
Lectures given at the IV Mexican School of Astrophysics, July 18-25, 2005
(submitted to the Editors on March 15, 2006
Development of SimCells as a novel chassis for functional biosensors
This work serves as a proof-of-concept for bacterially derived SimCells (Simple Cells), which contain the cell machinery from bacteria and designed DNA (or potentially a simplified genome) to instruct the cell to carry out novel, specific tasks. SimCells represent a reprogrammable chassis without a native chromosome, which can host designed DNA to perform defined functions. In this paper, the use of Escherichia coli MC1000 ∆minD minicells as a non-reproducing chassis for SimCells was explored, as demonstrated by their ability to act as sensitive biosensors for small molecules. Highly purified minicells derived from E. coli strains containing gene circuits for biosensing were able to transduce the input signals from several small molecules (glucarate, acrylate and arabinose) into the production of green fluorescent protein (GFP). A mathematical model was developed to fit the experimental data for induction of gene expression in SimCells. The intracellular ATP level was shown to be important for SimCell function. A purification and storage protocol was developed to prepare SimCells which could retain their functions for an extended period of time. This study demonstrates that SimCells are able to perform as 'smart bioparticles' controlled by designed gene circuits
Galaxies appear simpler than expected
Galaxies are complex systems the evolution of which apparently results from
the interplay of dynamics, star formation, chemical enrichment, and feedback
from supernova explosions and supermassive black holes. The hierarchical theory
of galaxy formation holds that galaxies are assembled from smaller pieces,
through numerous mergers of cold dark matter. The properties of an individual
galaxy should be controlled by six independent parameters including mass,
angular-momentum, baryon-fraction, age and size, as well as by the accidents of
its recent haphazard merger history. Here we report that a sample of galaxies
that were first detected through their neutral hydrogen radio-frequency
emission, and are thus free of optical selection effects, shows five
independent correlations among six independent observables, despite having a
wide range of properties. This implies that the structure of these galaxies
must be controlled by a single parameter, although we cannot identify this
parameter from our dataset. Such a degree of organisation appears to be at odds
with hierarchical galaxy formation, a central tenet of the cold dark matter
paradigm in cosmology.Comment: 26 pages, 14 figure
The SPINK gene family and celiac disease susceptibility
The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n = 15) and diet-treated patients (n = 31) and controls (n = 16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population
The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors
<p><b>Abstract</b></p> <p>Background</p> <p>Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity.</p> <p>Methods</p> <p>Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with <it>ERBB2 </it>(231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2.</p> <p>Results</p> <p>The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly.</p> <p>Conclusions</p> <p>Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors.</p
Changing perceptions of hunger on a high nutrient density diet
<p>Abstract</p> <p>Background</p> <p>People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet.</p> <p>Methods</p> <p>This was a descriptive study conducted with 768 participants primarily living in the United States who had changed their dietary habits from a low micronutrient to a high micronutrient diet. Participants completed a survey rating various dimensions of hunger (physical symptoms, emotional symptoms, and location) when on their previous usual diet versus the high micronutrient density diet. Statistical analysis was conducted using non-parametric tests.</p> <p>Results</p> <p>Highly significant differences were found between the two diets in relation to all physical and emotional symptoms as well as the location of hunger. Hunger was not an unpleasant experience while on the high nutrient density diet, was well tolerated and occurred with less frequency even when meals were skipped. Nearly 80% of respondents reported that their experience of hunger had changed since starting the high nutrient density diet, with 51% reporting a dramatic or complete change in their experience of hunger.</p> <p>Conclusions</p> <p>A high micronutrient density diet mitigates the unpleasant aspects of the experience of hunger even though it is lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. A high nutrient density diet provides benefits for long-term health as well as weight loss. Because our findings have important implications in the global effort to control rates of obesity and related chronic diseases, further studies are needed to confirm these preliminary results.</p
Environmental Enrichment Induces Behavioral Recovery and Enhanced Hippocampal Cell Proliferation in an Antidepressant-Resistant Animal Model for PTSD
Background: Post traumatic stress disorder (PTSD) can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel) in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS). Methodology/Principal Findings: IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC) inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE) starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE). This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus. Conclusions/Significance: This animal study shows the importance of (physical) exercise in the treatment of psychiatri
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