1,893 research outputs found
Tau protein, A beta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies
No full textThe intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid((1-42)) (Abeta42), promising results for the diagnosis of Alzheimer's disease ( AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases. Copyright (C) 2005 S. Karger AG, Basel
Least-squares methods for identifying biochemical regulatory networks from noisy measurements
No full text<b>Background</b>:
We consider the problem of identifying the dynamic interactions in biochemical networks from noisy experimental data. Typically, approaches for solving this problem make use of an estimation algorithm such as the well-known linear Least-Squares (LS) estimation technique. We demonstrate that when time-series measurements are corrupted by white noise and/or drift noise, more accurate and reliable identification of network interactions can be achieved by employing an estimation algorithm known as Constrained Total Least Squares (CTLS). The Total Least Squares (TLS) technique is a generalised least squares method to solve an overdetermined set of equations whose coefficients are noisy. The CTLS is a natural extension of TLS to the case where the noise components of the coefficients are correlated, as is usually the case with time-series measurements of concentrations and expression profiles in gene networks.
<b>Results</b>:
The superior performance of the CTLS method in identifying network interactions is demonstrated on three examples: a genetic network containing four genes, a network describing p53 activity and <i>mdm2</i> messenger RNA interactions, and a recently proposed kinetic model for interleukin (IL)-6 and (IL)-12b messenger RNA expression as a function of ATF3 and NF-κB promoter binding. For the first example, the CTLS significantly reduces the errors in the estimation of the Jacobian for the gene network. For the second, the CTLS reduces the errors from the measurements that are corrupted by white noise and the effect of neglected kinetics. For the third, it allows the correct identification, from noisy data, of the negative regulation of (IL)-6 and (IL)-12b by ATF3.
<b>Conclusion</b>:
The significant improvements in performance demonstrated by the CTLS method under the wide range of conditions tested here, including different levels and types of measurement noise and different numbers of data points, suggests that its application will enable more accurate and reliable identification and modelling of biochemical networks
MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance
No full textThe RAS/RAF/MEK/MAPK kinase pathway has been extensively studied for more than 25 years, yet we continue to be puzzled by its intricate dynamic control and plasticity. Different spatiotemporal MAPK dynamics bring about distinct cell fate decisions in normal vs cancer cells and developing organisms. Recent modelling and experimental studies provided novel insights in the versatile MAPK dynamics concerted by a plethora of feedforward/feedback regulations and crosstalk on multiple timescales. Multiple cancer types and various developmental disorders arise from persistent alterations of the MAPK dynamics caused by RAS/RAF/MEK mutations. While a key role of the MAPK pathway in multiple diseases made the development of novel RAF/MEK inhibitors a hot topic of drug development, these drugs have unexpected side-effects and resistance inevitably occurs. We review how RAF dimerization conveys drug resistance and recent breakthroughs to overcome this resistance
Cell-based therapies of liver diseases: age-related challenges
No full textKonstantin N Yarygin, Alexei Y Lupatov, Irina V Kholodenko Laboratory of Cell Biology, Institute of Biomedical Chemistry, Moscow, Russia Abstract: The scope of this review is to revise recent advances of the cell-based therapies of liver diseases with an emphasis on cell donor’s and patient’s age. Regenerative medicine with cell-based technologies as its integral part is focused on the structural and functional restoration of tissues impaired by sickness or aging. Unlike drug-based medicine directed primarily at alleviation of symptoms, regenerative medicine offers a more holistic approach to disease and senescence management aimed to achieve restoration of homeostasis. Hepatocyte transplantation and organ engineering are very probable forthcoming options of liver disease treatment in people of different ages and vigorous research and technological innovations in this area are in progress. Accordingly, availability of sufficient amounts of functional human hepatocytes is crucial. Direct isolation of autologous hepatocytes from liver biopsy is problematic due to related discomfort and difficulties with further expansion of cells, particularly those derived from aging people. Allogeneic primary human hepatocytes meeting quality standards are also in short supply. Alternatively, autologous hepatocytes can be produced by reprogramming of differentiated cells through the stage of induced pluripotent stem cells. In addition, fibroblasts and mesenchymal stromal cells can be directly induced to undergo advanced stage hepatogenic differentiation. Reprogramming of cells derived from elderly people is accompanied by the reversal of age-associated changes at the cellular level manifesting itself by telomere elongation and the U-turn of DNA methylation. Cell reprogramming can provide high quality rejuvenated hepatocytes for cell therapy and liver tissue engineering. Further technological advancements and establishment of national and global registries of induced pluripotent stem cell lines homozygous for HLA haplotypes can allow industry-style production of livers for immunosuppression-free transplantation. Keywords: cell aging, rejuvenation, liver engineering, liver cell therap
분자 강성률에 따르는 변형된 폴리이미드의 유변학적 및 물리적 성질
No full text학위논문(박사) - 한국과학기술원 : 화학공학과, 1999.2, [ xi, 162 p. ]Advances in the theory of polymer solution dynamics have been associated with establishing a relation between the macroscopic hydrodynamic property of a polymer solution and the polymer structure. A polymer theory developed by Kholodenko, which is based on the analogy between the semiflexible polymer and Dirac fermions is applicable to a semiflexible polymer with an arbitrary flexibility ranging from a fully flexible polymer to a completely rigid polymer. This theory is modified and applied experimentally to characterize the persistence length (the flexibility) from the intrinsic viscosity data without major departure from the already developed formalism.
In CHAPTER I, the Kholodenko``s theory is explained and emphasized as an outstanding feature. In fact, this theory is based on the chain walk model with a finite length (cutoff), and only correlates the moment of statistical averages with the chain conformation. It represents the chain conformation with the persistence length and the contour length. It is derived on the assumption of the equilibrium state and is independent on the hypothetical modeling to calculate the detailed hydrodynamic properties of polymer solution. Therefore, it can be incorporated into any kind of hypothetical model to calculate the macroscopic properties of semiflexible polymer solution. The original paper of Kholodenko showed briefly that the limiting cases of flexible coil and rigid rod by adopting Zimm model were matched well with the well-known results of previous theories even though it was driven from the completely different points of view. However, it is difficult to predict the hydrodynamic property of a polymer solution and compare with the actual experimental results by the Kholodenko``s theory in its original form. This is due to fact that the Dirac propagator was 1+1 dimensional one and did not specify the role of cutoff length in the calculation of hydrodynamic property of the polymer solution with an arbitrary persisten...한국과학기술원 : 화학공학과
NA62 Charged Particle Hodoscope. Design and performance in 2016 run
No full textThe NA62 experiment at CERN SPS aims to measure the branching ratio of the ultra-rare decay K(+) → π(+)νbar nu with 10% accuracy. The experiment operates with a 75 GeV/c high intensity (750 MHz) secondary beam. A new detector, named Charged Particle Hodoscope (CHOD), designed to produce an input signal to the L0 trigger processor for events with charged particles produced in kaon decays, has been assembled, installed, integrated into NA62 Data Acquisition System (DAQ) and commissioned in 2016. During the whole 2016 run the detector has been in continuous operation. Design and performance features of the detector are presented.The NA62 experiment at CERN SPS is aimed to measure the branching ratio of the ultra-rare decay with 10\% accuracy. The experiment operates with a 75 GeV/c high intensity (750 MHz) secondary beam. A new detector, named Charged Particle Hodoscope (CHOD), designed to produce an input signal to the L0 trigger processor for events with charged particles produced in kaon decays, has been assembled, installed, integrated in NA62 Data Acquisition System (DAQ) and commissioned in 2016. During the whole 2016 run the detector has been in continuous operation. Design and performance features of the detector are presented
Quantifying gene network connectivity in silico: Scalability and accuracy of a modular approach
No full textLarge, complex data sets that are generated from microarray experiments, create a need for systematic analysis techniques to unravel the underlying connectivity of gene regulatory networks. A modular approach, previously proposed by Kholodenko and co-workers, helps to scale down the network complexity into more computationally manageable entities called modules. A functional module includes a gene\u27s mRNA, promoter and resulting products, thus encompassing a large set of interacting states. The essential elements of this approach are described in detail for a three-gene model network and later extended to a ten-gene model network, demonstrating scalability. The network architecture is identified by analysing in silico steady-state changes in the activities of only the module outputs, communicating intermediates, that result from specific perturbations applied to the network modules one at a time. These steady-state changes form the system response matrix, which is used to compute the network connectivity or network interaction map. By employing a known biochemical network, the accuracy of the modular approach and its sensitivity to key assumptions are evaluated
LHCb ECAL upgrade II
No full textThe aim of the Phase-2 Upgrade of LHCb is to collect up to 300 fb of data in a few years, operating at luminosity of cms. Because of the significant increase in particle densities and radiation doses, the present LHCb Electromagnetic Calorimeter (ECAL) will require a major revision. The increased instantaneous and integrated luminosity will result in very high particle density and radiation doses in the areas close to the beam pipe. In these conditions, ECAL has to provide high-quality energy and position measurement for electromagnetic showers, as well as separation of two closely lying showers. Another requirement for the whole ECAL, which is aimed to reduce combinatorial background at high luminosity operation, is the ability to measure the time of arrival of the photon or electron with an accuracy of few tens of picoseconds. The intrinsic time resolution of the ECAL modules is expected to be sufficient to meet this requirement, although the use of an additional timing layer is not excluded. The expected particle flow and radiation doses strongly depend on the distance from the beam pipe and determine the technology and granularity of the upgraded ECAL modules. The upgraded ECAL will be subdivided accordingly into several zones. The central part, with the highest expected doses, will be a sampling spaghetti calorimeter (SPACAL) based on radiation-hard crystal scintillators and a tungsten absorber. The peripheral areas will be instrumented with modified Shashlik type modules, similar to the modules of the present ECAL, with modifications aiming to achieve the best time resolution for this technology. The intermediate part will be a spaghetti calorimeter with polystyrene-based scintillating fibres and a moulded lead absorber. The main advantages of using lead-polystyrene spaghetti type are the possibility to modify granularity with minimal intervention and easily replace fibres damaged by radiation.
An extensive R\&D; campaign is ongoing to optimize the Upgrade 2 ECAL structure. It includes:
studies of scintillating materials, in terms of scintillation kinetics and radiation hardness, simulation studies to find the optimal detector layout, longitudinal segmentation and granularity, beam test studies of the performance of various ECAL module prototypes, both for central (SPACAL) and peripheral areas.
For the moment, a time resolution for 5 GeV electrons achieved for W-Crystal and Lead-Polystyrene Spacal prototypes is about 20 ps, and better than 40 ps for Shashlik type modules
Beam test, simulation, and performance evaluation of PbF2 and PWO-UF crystals with SiPM readout for a semi-homogeneous calorimeter prototype with longitudinal segmentation
No full textCrilin (Crystal Calorimeter with Longitudinal Information) is a semi-homogeneous, longitudinally segmented electromagnetic calorimeter based on high-, ultra-fast crystals with UV-extended SiPM readout. The Crilin design has been proposed as a candidate solution for both a future Muon Collider barrel ECAL and for the Small Angle Calorimeter of the HIKE experiment. As a part of the Crilin development program, we have carried out beam tests of small (10 × 10 × 40 mm 3 ) lead fluoride (PbF 2 ) and ultra-fast lead tungstate (PbWO 4 , PWO-UF) crystals with 120 GeV electrons at the CERN SPS to study the light yield, timing response, and systematics of light collection with a proposed readout 1 D. Paesani et al.scheme. For a single crystal of PbF 2 , corresponding to a single Crilin cell, a time resolution of better than 25 ps is obtained for >3 GeV of deposited energy. For a single cell of PWO-UF, a time resolution of better than 45 ps is obtained for the same range of deposited energy. This timing performance fully satisfies the design requirements for the Muon Collider and HIKE experiments. Further optimizations of the readout scheme and crystal surface preparation are expected to bring further improvements.Crilin (Crystal Calorimeter with Longitudinal Information) is a semi-homogeneous, longitudinally segmented electromagnetic calorimeter based on high-, ultra-fast crystals with UV-extended SiPM readout. The Crilin design has been proposed as a candidate solution for both a future Muon Collider barrel ECAL and for the Small Angle Calorimeter of the HIKE experiment. As a part of the Crilin development program, we have carried out beam tests of small (~mm) lead fluoride (PbF) and ultra-fast lead tungstate (PbWO, PWO) crystals with 120~GeV electrons at the CERN SPS to study the light yield, timing response, and systematics of light collection with a proposed readout scheme. For a single crystal of PbF, corresponding to a single Crilin cell, a time resolution of better than 25~ps is obtained for 3 GeV of deposited energy. For a single cell of \pwo, a time resolution of better than 45~ps is obtained for the same range of deposited energy. This timing performance fully satisfies the design requirements for the Muon Collider and HIKE experiments. Further optimizations of the readout scheme and crystal surface preparation are expected to bring further improvements
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