789 research outputs found
A characterization of (I,J)-regular matrices
Let I, J be two ideals on N which contain the family Fin of finite sets. We provide necessary and sufficient conditions on the entries of an infinite real matrix A = (a(n, k)) which maps I-convergent bounded sequences into J-convergent bounded sequences and preserves the corresponding ideal limits. The well-known characterization of regular matrices due to Silverman-Toeplitz corresponds to the case I = J = Fin. Lastly, we provide some applications to permutation and diagonal matrices, which extend several known results in the literature
Co-transport-induced instability of membrane voltage in tip-growing cells
A salient feature of stationary patterns in tip-growing cells is the key role
played by the symports and antiports, membrane proteins that translocate two
ionic species at the same time. It is shown that these co-transporters
destabilize generically the membrane voltage if the two translocated ions
diffuse differently and carry a charge of opposite (same) sign for symports
(antiports). Orders of magnitude obtained for the time and lengthscale are in
agreement with experiments. A weakly nonlinear analysis characterizes the
bifurcation
Optical amplification enhancement in photonic crystals
Improving and controlling the efficiency of a gain medium is one of the most
challenging problems of laser research. By measuring the gain length in an opal
based photonic crystal doped with laser dye, we demonstrate that optical
amplification is more than twenty-fold enhanced along the Gamma-K symmetry
directions of the face centered cubic photonic crystal. These results are
theoretically explained by directional variations of the density of states,
providing a quantitative connection between density of the states and light
amplification
Hype or hope – Can combination therapies with third-generation EGFR-TKIs help overcome acquired resistance and improve outcomes in EGFR-mutant advanced/metastatic NSCLC?
Three generations of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) have been developed for treating advanced/metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations, while a fourth generation is undergoing preclinical assessment. Although initially effective, acquired resistance to EGFR-TKIs usually arises within a year due to the emergence of clones harboring multiple resistance mechanisms. Therefore, the combination of EGFR-TKIs with other therapeutic agents has emerged as a potential strategy to overcome resistance and improve clinical outcomes. However, results obtained so far are ambiguous and ideal therapies for patients who experience disease progression during treatment with EGFR-TKIs remain elusive. This review provides an updated landscape of EGFR-TKIs, along with a description of the mechanisms causing resistance to these drugs. Moreover, it discusses the current knowledge, limitations, and future perspective regarding the use of EGFR-TKIs in combination with other anticancer agents, supporting the need for bench-to-bedside approaches in selected populations
Generic theory of colloidal transport
We discuss the motion of colloidal particles relative to a two component
fluid consisting of solvent and solute. Particle motion can result from (i) net
body forces on the particle due to external fields such as gravity; (ii) slip
velocities on the particle surface due to surface dissipative phenomena. The
perturbations of the hydrodynamic flow field exhibits characteristic
differences in cases (i) and (ii) which reflect different patterns of momentum
flux corresponding to the existence of net forces, force dipoles or force
quadrupoles. In the absence of external fields, gradients of concentration or
pressure do not generate net forces on a colloidal particle. Such gradients can
nevertheless induce relative motion between particle and fluid. We present a
generic description of surface dissipative phenomena based on the linear
response of surface fluxes driven by conjugate surface forces. In this
framework we discuss different transport scenarios including self-propulsion
via surface slip that is induced by active processes on the particle surface.
We clarify the nature of force balances in such situations.Comment: 22 pages, 1 figur
Novel targeted strategies to overcome resistance in small-cell lung cancer: focus on PARP inhibitors and rovalpituzumab tesirine
ABSTRACTIntroduction: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour, and its outcome is strongly conditioned by the rapid onset of resistance to conventional chemothera..
Is there a role for dacomitinib, a second-generation irreversible inhibitor of the epidermal-growth factor receptor tyrosine kinase, in advanced non-small cell lung cancer?
Introduction: Non-small cell lung cancer (NSCLC) is a highly lethal disease. During the past 20 years, the epidermal growth factor receptor (EGFR) has been a relevant target for anticancer drug-design, and a large family of EGFR tyrosine kinase inhibitors (TKI) were designed, which improved therapeutic outcomes compared to conventional chemotherapy in NSCLC patients with specific EGFR mutations. However, resistance to these inhibitors occurs; therefore, the debate on which inhibitor should be used first is still open. Dacomitinib was approved in 2018 for the first-line treatment of NSCLC with EGFR activating mutations. Areas covered: This manuscript reviews the properties of dacomitinib, including the current information from clinical trials and its potential application as stand-alone therapy, or in combination. Expert opinion: Dacomitinib is a second-generation EGFR-TKI that has demonstrated significant improvement in overall survival in a phase III randomized study compared with gefitinib, a first-generation TKI. However, the rapid development and approval of a new generation of TKIs (osimertinib), with better clinical profiles, raises the question of which role can dacomitinib play in NSCLC. Further studies are required to evaluate the efficacy of this drug on brain metastases, as a second-line treatment after third-generation TKIs, or in combination with other types of treatments
Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.
We designed an epi-illumination SPIM system that uses a single objective and has a sample interface identical to that of an inverted fluorescence microscope with no additional reflection elements. It achieves subcellular resolution and single-molecule sensitivity, and is compatible with common biological sample holders, including multi-well plates. We demonstrated multicolor fast volumetric imaging, single-molecule localization microscopy, parallel imaging of 16 cell lines and parallel recording of cellular responses to perturbations
Antibodies against the second extracellular loop of β1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat
Autoantibodies against β1-adrenoceptors (β1-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (β1-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether β1-AABs have deleterious effects on vascular reactivity in rats.
An enzyme-linked immunosorbent assay was used to detect β1-AABs in sera from immunized rats over a period of 1–3 months using the peptidic sequence of the second extracellular loop of human β1-AR. Functional studies were performed in thoracic aortic (TA) and small mesenteric artery (SMA) rings from immunized rats. Following pre-contraction with phenylephrine (0.3 μM and 3 μM for the TA and SMA respectively), cumulative concentration–response curves (CCRCs) to various β-AR agonists (isoproterenol, dobutamine, salbutamol, SR 58611A), acetylcholine, A23187, and sodium nitroprusside (SNP) were then plotted.
The relaxations induced by dobutamine, SR 58611A, and acetylcholine were significantly impaired, but salbutamol-induced relaxations were not affected, in both vessels from immunized rats. A significant impairment of isoproterenol-induced relaxation was only observed in SMA. CCRCs to SNP were not modified in either of the vessels. A23187-induced relaxation was impaired in immunized rats. Following pretreatment with l-arginine, vasorelaxation to acetylcholine and SR 58611A was restored in immunized rats.
This study demonstrates that immunization against the second extracellular loop of β1-ARs has a deleterious impact on vasorelaxations in the TA and SMA of rats, involving alterations in endothelium-dependent NO signaling pathways
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