49 research outputs found
Ruelle-Perron-Frobenius spectrum for Anosov maps
We extend a number of results from one dimensional dynamics based on spectral
properties of the Ruelle-Perron-Frobenius transfer operator to Anosov
diffeomorphisms on compact manifolds. This allows to develop a direct operator
approach to study ergodic properties of these maps. In particular, we show that
it is possible to define Banach spaces on which the transfer operator is
quasicompact. (Information on the existence of an SRB measure, its smoothness
properties and statistical properties readily follow from such a result.) In
dimension we show that the transfer operator associated to smooth random
perturbations of the map is close, in a proper sense, to the unperturbed
transfer operator. This allows to obtain easily very strong spectral stability
results, which in turn imply spectral stability results for smooth
deterministic perturbations as well. Finally, we are able to implement an Ulam
type finite rank approximation scheme thus reducing the study of the spectral
properties of the transfer operator to a finite dimensional problem.Comment: 58 pages, LaTe
Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors
Introduction
Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's
disease (PD) often lack specificity or reliability. Investigating biomarker variance
between individuals and over time and the effect of confounding factors is essential for the
evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1).
Materials and Methods
IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22
healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual
changes in IGF-1 were compared between PD patients and HC while accounting for baseline
disease duration (19 early stage: 3.5 years; 18 moderate stage: >4 years), age, sex,
body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition,
associations of baseline IGF-1 with annual changes of motor, cognitive and depressive
symptoms and medication dose were investigated.
Results
PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1),
showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL;
p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47,
p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in
the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were
not associated with annual changes of clinical parameters.
Discussion
Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and
HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in
PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated
by several confounders
The CMS Phase-1 pixel detector upgrade
The CMS detector at the CERN LHC features a silicon pixel detector as its innermost subdetector. The original CMS pixel detector has been replaced with an upgraded pixel system (CMS Phase-1 pixel detector) in the extended year-end technical stop of the LHC in 2016/2017. The upgraded CMS pixel detector is designed to cope with the higher instantaneous luminosities that have been achieved by the LHC after the upgrades to the accelerator during the first long shutdown in 2013â2014. Compared to the original pixel detector, the upgraded detector has a better tracking performance and lower mass with four barrel layers and three endcap disks on each side to provide hit coverage up to an absolute value of pseudorapidity of 2.5. This paper describes the design and construction of the CMS Phase-1 pixel detector as well as its performance from commissioning to early operation in collision data-taking.Peer reviewe
TOWARDS AN ONTOLOGY-BASED CUSTOMIZATION APPROACH FOR SUPPORTING PEOPLE WITH SPECIAL NEEDS
People with disabilities encounter serious limitations in interacting with their home environment since their requirements are not met properly. Personal assisting devices interacting with the services offered by smart home environments can help to improve the quality of their lives. A major prerequisite for this is to provide an appropriate customization architecture which allows to reason about the personâs current situation in terms of personal, technical and natural context and to adapt the home environmentâs services accordingly. This paper proposes a customization approach based on an ontology which comprehensively represents the situation of persons with special needs for the purpose of adapting their home environmentâs services. 1
AsTeRICS, a Flexible Assistive Technology Construction Set
AbstractOver the last decades a considerable number of information and communication technology based Assistive Technology devices have become available for people with disabilities. These Assistive Technology devices often ask for adaptation of software and/or hardware to fit the users abilities before they can be used.Within the Project AsTeRICS, a flexible and affordable construction set for the implementation of user driven assistive technologies solutions will be developed. This allows the combination of different sensors to process and manipulate the sensor data to control any supported device. This paper will show how a webcam mouse (head tracker) and a single switch mouse can easily be created and tailored to the user needs and possibilities. Additionally, results of user tests with the head tracker will be presented
Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524
Abstract The kinase Bub1 functions in the spindle assembly checkpoint (SAC) and in chromosome congression, but the role of its catalytic activity remains controversial. Here, we use two novel Bub1 inhibitors, BAY-320 and BAY-524, to demonstrate potent Bub1 kinase inhibition both in vitro and in intact cells. Then, we compared the cellular phenotypes of Bub1 kinase inhibition in HeLa and RPE1 cells with those of protein depletion, indicative of catalytic or scaffolding functions, respectively. Bub1 inhibition affected chromosome association of Shugoshin and the chromosomal passenger complex (CPC), without abolishing global Aurora B function. Consequently, inhibition of Bub1 kinase impaired chromosome arm resolution but exerted only minor effects on mitotic progression or SAC function. Importantly, BAY-320 and BAY-524 treatment sensitized cells to low doses of Paclitaxel, impairing both chromosome segregation and cell proliferation. These findings are relevant to our understanding of Bub1 kinase function and the prospects of targeting Bub1 for therapeutic applications
Benefit of multidisciplinary wound care center on the volume and outcomes of a vascular surgery practice
Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RASâSOS1 interaction
Since the late 1980s, mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. Such mutations reduce the ability of the small GTPase RAS to hydrolyze GTP, keeping this molecular switch in a constitutively active GTP-bound form that drives, unchecked, oncogenic downstream signaling. One strategy to reduce the levels of active RAS is to target guanine nucleotide exchange factors, which allow RAS to cycle from the inactive GDP-bound state to the active GTP-bound form. Here, we describe the identification of potent and cell-active small-molecule inhibitors which efficiently disrupt the interaction between KRAS and its exchange factor SOS1, a mode of action confirmed by a series of biophysical techniques. The binding sites, mode of action, and selectivity were elucidated using crystal structures of KRASâSOS1, SOS1, and SOS2. By preventing formation of the KRASâSOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. The final compound 23 (BAY-293) selectively inhibits the KRASâSOS1 interaction with an IC of 21 nM and is a valuable chemical probe for future investigations