2,777 research outputs found
Patient-Derived Induced Pluripotent Stem Cell Models for Phenotypic Screening in the Neuronal Ceroid Lipofuscinoses
Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare, fatal, inherited neurodegenerative lysosomal storage disorders. Numerous genes (CLN1-CLN8, CLN10-CLN14) were identified in which mutations can lead to NCL; however, the underlying pathophysiology remains elusive. Despite this, the NCLs share some of the same features and symptoms but vary in respect to severity and onset of symptoms by age. Some common symptoms include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and in the rare adult-onset, dementia. Currently, all forms of NCL are fatal, and no curative treatments are available. Induced pluripotent stem cells (iPSCs) can differentiate into any cell type of the human body. Cells reprogrammed from a patient have the advantage of acquiring disease pathogenesis along with recapitulation of disease-associated phenotypes. They serve as practical model systems to shed new light on disease mechanisms and provide a phenotypic screening platform to enable drug discovery. Herein, we provide an overview of available iPSC models for a number of different NCLs. More specifically, we highlight findings in these models that may spur target identification and drug development
Regularity for eigenfunctions of Schr\"odinger operators
We prove a regularity result in weighted Sobolev spaces (or
Babuska--Kondratiev spaces) for the eigenfunctions of a Schr\"odinger operator.
More precisely, let K_{a}^{m}(\mathbb{R}^{3N}) be the weighted Sobolev space
obtained by blowing up the set of singular points of the Coulomb type potential
V(x) = \sum_{1 \le j \le N} \frac{b_j}{|x_j|} + \sum_{1 \le i < j \le N}
\frac{c_{ij}}{|x_i-x_j|}, x in \mathbb{R}^{3N}, b_j, c_{ij} in \mathbb{R}. If u
in L^2(\mathbb{R}^{3N}) satisfies (-\Delta + V) u = \lambda u in distribution
sense, then u belongs to K_{a}^{m} for all m \in \mathbb{Z}_+ and all a \le 0.
Our result extends to the case when b_j and c_{ij} are suitable bounded
functions on the blown-up space. In the single-electron, multi-nuclei case, we
obtain the same result for all a<3/2.Comment: to appear in Lett. Math. Phy
MARS, the MAGIC Analysis and Reconstruction Software
With the commissioning of the second MAGIC gamma-ray Cherenkov telescope
situated close to MAGIC-I, the standard analysis package of the MAGIC
collaboration, MARS, has been upgraded in order to perform the stereoscopic
reconstruction of the detected atmospheric showers. MARS is a ROOT-based code
written in C++, which includes all the necessary algorithms to transform the
raw data recorded by the telescopes into information about the physics
parameters of the observed targets. An overview of the methods for extracting
the basic shower parameters is presented, together with a description of the
tools used in the background discrimination and in the estimation of the
gamma-ray source spectra.Comment: 4 pages, 0 figures, submitted to the 31st International Cosmic Ray
Conference, {\L}odz 200
Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants
Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis
Thermodynamic limits of sperm swimming precision
Sperm swimming is crucial to fertilise the egg, in nature and in assisted
reproductive technologies. Modelling the sperm dynamics involves elasticity,
hydrodynamics, internal active forces, and out-of-equilibrium noise. Here we
demonstrate experimentally the relevance of energy dissipation for sperm
beating fluctuations. For each motile cell, we reconstruct the time-evolution
of the two main tail's spatial modes, which together trace a noisy limit cycle
characterised by a maximum level of precision . Our results indicate
, remarkably close to the estimated precision of a
dynein molecular motor actuating the flagellum, which is bounded by its energy
dissipation rate according to the Thermodynamic Uncertainty Relation. Further
experiments under oxygen deprivation show that decays with energy
consumption, as it occurs for a single molecular motor. Both observations can
be explained by conjecturing a high level of coordination among the
conformational changes of dynein motors. This conjecture is supported by a
theoretical model for the beating of an ideal flagellum actuated by a
collection of motors, including a motor-motor nearest neighbour coupling of
strength : when is small the precision of a large flagellum is much
higher than the single motor one. On the contrary, when is large the two
become comparable.Comment: Main Text with Appendices (14 pages, 9 figures) plus Supplementary
Information, Accepted for Publication in PRX-Lif
1-D Harmonic Oscillator in Snyder Space, the Classic and the Quantum
The 1-D dimension harmonic oscillator in Snyder space is investigated in its
classical and quantum versions. The classical trajectory is obtained and the
semiclassical quantization from the phase space trajectories is discussed. In
the meanwhile, an effective cutoff to high frequencies is found. The quantum
version is developed and an equivalent usual harmonic oscillator is obtained
through an effective mass and an effective frequency introduced in the model.
This modified parameters give us an also modified energy spectra.Comment: 8 pages, 2 figure
Cellulose nanocrystals from fibers of Macauba (Acrocomia Aculeata) and Gravata (Bromelia Balansae) from Brazilian Pantanal.
Cellulose nanocrystals (CNC) were obtained from macauba and gravata fibers. Macauba (or Bocaiuva) is a palm tree found throughout most of Brazil and Gravata is an abundant kind of bromeliab with 1-2m long leaves, found in Brazilian Pantanal and Cerrado. The raw fibers of both fibers were mercerized with NaOH solutions and bleached; they were then submitted to acid hydrolysis using H2SO4 at 45 ?C, varying the hydrolysis time from 15 up to 75 min. The fibers were analyzed by X-ray diffraction (XRD), FTIR Spectroscopy, scanning electron microscopy (SEM) and thermal stability by thermogravimetric analysis (TG). XRD patterns did not present changes in the crystal structure of cellulose after mercerization, but it was observed a decrease of hemicellulose and lignin contents, and consequently an increase of cellulose content with the increase of NaOH solution concentration in the mercerization. After acid hydrolysis, the cellulose nanocrystals (CNC) were also analyzed by transmission electron microscopy (TEM) which showed an acicular or rod-like aspect and nanometric dimensions of CNC from both fibers, but the higher values of aspect ratio (L/D) were found on CNC obtained from gravata after 45 min of acid hydrolysis. The mercerization and subsequent bleaching of fibers influenced the crystallinity index and thermal stability of the resulting CNC, but their properties are mainly influenced by the hydrolysis time, i. e., there is an increase in crystallinity and thermal stability up to 45 min of hydrolysis, after this time, both properties decrease, probably due to the cellulose degradation by the sulfuric acid
Directed polymer in a random medium of dimension 1+1 and 1+3: weights statistics in the low-temperature phase
We consider the low-temperature disorder-dominated phase of the
directed polymer in a random potentiel in dimension 1+1 (where )
and 1+3 (where ). To characterize the localization properties of
the polymer of length , we analyse the statistics of the weights of the last monomer as follows. We numerically compute the probability
distributions of the maximal weight , the probability distribution of the parameter as well as the average values of the higher order
moments . We find that there exists a
temperature such that (i) for , the distributions
and present the characteristic Derrida-Flyvbjerg
singularities at and for . In particular, there
exists a temperature-dependent exponent that governs the main
singularities and as well as the power-law decay of the moments . The exponent grows from the value
up to . (ii) for , the
distribution vanishes at some value , and accordingly the
moments decay exponentially as in . The
histograms of spatial correlations also display Derrida-Flyvbjerg singularities
for . Both below and above , the study of typical and
averaged correlations is in full agreement with the droplet scaling theory.Comment: 13 pages, 29 figure
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