494 research outputs found
Tecnicas del collage y la expresion corporal en niños del nivel inicial de la I.E. N° 20501 Santa Rosa De Pativilca
Objetivo: La técnica empleada se localiza intrínsecamente del análisis elemental es de muestra Básica, de condición descriptiva, correlativa, no práctica y la teoría trazada es: “técnicas del Collage se conciernen con las expresiones corporales en infantes del nivel inicial del C.E. No 20501 Santa Rosa de Pativilca.”. en el análisis, el modelo total es de 102 discípulos. La herramienta vital empleada en el análisis es las preguntas, empleadas a la inicial y sucesiva mudable. Cada efecto evidencia la existencia de una correspondencia en las técnicas de Collage y expresión corporal en niños de nivel inicial del C.E. No 20501 Santa Rosa de Pativilca. La analogía es de dimensión aceptabl
An efficient semiparametric maxima estimator of the extremal index
The extremal index , a measure of the degree of local dependence in
the extremes of a stationary process, plays an important role in extreme value
analyses. We estimate semiparametrically, using the relationship
between the distribution of block maxima and the marginal distribution of a
process to define a semiparametric model. We show that these semiparametric
estimators are simpler and substantially more efficient than their parametric
counterparts. We seek to improve efficiency further using maxima over sliding
blocks. A simulation study shows that the semiparametric estimators are
competitive with the leading estimators. An application to sea-surge heights
combines inferences about with a standard extreme value analysis of
block maxima to estimate marginal quantiles.Comment: 17 pages, 7 figures. Minor edits made to version 1 prior to journal
publication. The final publication is available at Springer via
http://dx.doi.org/10.1007/s10687-015-0221-
Biological measurement beyond the quantum limit
Quantum noise places a fundamental limit on the per photon sensitivity
attainable in optical measurements. This limit is of particular importance in
biological measurements, where the optical power must be constrained to avoid
damage to the specimen. By using non-classically correlated light, we
demonstrated that the quantum limit can be surpassed in biological
measurements. Quantum enhanced microrheology was performed within yeast cells
by tracking naturally occurring lipid granules with sensitivity 2.4 dB beyond
the quantum noise limit. The viscoelastic properties of the cytoplasm could
thereby be determined with a 64% improved measurement rate. This demonstration
paves the way to apply quantum resources broadly in a biological context
Broad targeting of resistance to apoptosis in cancer
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer
Computational Integration of Homolog and Pathway Gene Module Expression Reveals General Stemness Signatures
The stemness hypothesis states that all stem cells use common mechanisms to regulate self-renewal and multi-lineage potential. However, gene expression meta-analyses at the single gene level have failed to identify a significant number of genes selectively expressed by a broad range of stem cell types. We hypothesized that stemness may be regulated by modules of homologs. While the expression of any single gene within a module may vary from one stem cell type to the next, it is possible that the expression of the module as a whole is required so that the expression of different, yet functionally-synonymous, homologs is needed in different stem cells. Thus, we developed a computational method to test for stem cell-specific gene expression patterns from a comprehensive collection of 49 murine datasets covering 12 different stem cell types. We identified 40 individual genes and 224 stemness modules with reproducible and specific up-regulation across multiple stem cell types. The stemness modules included families regulating chromatin remodeling, DNA repair, and Wnt signaling. Strikingly, the majority of modules represent evolutionarily related homologs. Moreover, a score based on the discovered modules could accurately distinguish stem cell-like populations from other cell types in both normal and cancer tissues. This scoring system revealed that both mouse and human metastatic populations exhibit higher stemness indices than non-metastatic populations, providing further evidence for a stem cell-driven component underlying the transformation to metastatic disease
Control of Glycogen Content in Retina: Allosteric Regulation of Glycogen Synthase
Retinal tissue is exceptional because it shows a high level of energy metabolism. Glycogen content represents the only energy reserve in retina, but its levels are limited. Therefore, elucidation of the mechanisms controlling glycogen content in retina will allow us to understand retina response under local energy demands that can occur under normal and pathological conditions. Thus, we studied retina glycogen levels under different experimental conditions and correlated them with glucose-6-phosphate (G-6-P) content and glycogen synthase (GS) activity
Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors
Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders
Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02 TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δϕ modulation for all ΣETPb ranges and particle pT
Asymmetric reduction of 2,2-dimethyl-6-(2-oxoalkyl/oxoaryl)-1,3-dioxin-4-ones and application to the synthesis of (+)-yashabushitriol
The asymmetric transfer hydrogenation of a series of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and 2,2-dimethyl-6-(2-oxoaryl)-1,3-dioxin-4-ones was achieved in high enantiomeric excess using a Ru(II) catalyst. The aryl substrates were most compatible with the methodology and this process facilitated a total synthesis of enantiomerically pure (+)-yashabushitriol
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