Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the ...characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade.
We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations.
Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history.
EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.
Aligned multi-walled carbon nanotube (MWCNT)/polymer composite films are prepared by solution casting in the presence of an alternating electric field. Application of 7
kV/m at a frequency of 60
Hz ...to the polymer composite melt induces MWCNT alignment in the direction of the applied field, which is maintained after polymer crystallization. The electrical conductivity and piezoresistive response of electric-field-aligned and randomly oriented 0.1–0.75
wt% MWCNT/polysulfone films are evaluated. Electrical conductivity is 3–5 orders of magnitude higher for composites with electric-field-aligned MWCNTs than for randomly oriented composites. MWCNT alignment inside the polymer matrix also increases the film piezoresistive sensitivity, enhancing the strain sensing capabilities of the composite film.
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•CNTs were systematically fragmented by high density ultrasonic energy.•PMMA composites with fragmented CNTs exhibited lower electrical conductivity.•Electromechanical sensitivity was ...higher for composites with fragmented CNTs.•Contributions of piezoresistive mechanisms are discussed.
Multiwall carbon nanotubes (MWCNTs) were systematically fragmented using high density ultrasonic energy and used as fillers of a poly (methyl methacrylate) matrix (PMMA). MWCNT fragmentation was confirmed by scanning electron microscopy and atomic force microscopy. Dedicated MWCNT length measurements yielded a log-normal statistical distribution, with mean value of 1.33 μm for the as-received MWCNTs and 0.66 μm for the fragmented MWCNTs. Higher electrical percolation threshold and lower electrical conductivity were obtained for MWCNT/PMMA composites (0.01–1 wt.% MWCNT concentration) using the fragmented MWCNTs. Higher electro-mechanical (piezoresistive) sensitivity under tensile tests was measured for PMMA nanocomposites with fragmented MWCNTs, which was explained by a competition of mechanisms related to the MWCNT length.
A methodology for determining the Poisson’s ratio (ν) of Au films with nanometric thicknesses is proposed. Au films with thicknesses of 10, 20, and 40 nm were thermally evaporated onto polyimide ...substrates (Kapton® 300HN) and electrodes were attached for the electrical measurements. The thermal coefficient of resistance of the Au films was estimated at the first stage of heating, caused by Joule effect, where electrical resistance and temperature followed a linear dependence. When thermal stabilization of the Au/polyimide system was reached, it was subjected to axial strain within an elastic regime and the electrical resistance of the metallic film was continuously recorded. The gage factor (piezoresistive sensitivity) of the Au nanofilms was measured and used for the estimation of the Poisson’s ratio according to its definition for metallic materials. A value of ν = 0.50 was estimated for the Au thin films, being slightly higher than the Au bulk value (ν
bulk
= 0.42).
Of the solid tumor types that metastasize to the brain, melanoma has the highest propensity to form brain metastases. In addition, much remains unknown regarding the pathophysiology involved in ...melanoma cell extravasation through the blood–brain barrier, which enables interactions with the microenvironment, and melanoma cell transcriptomic responses to brain-specific cues. However, recent developments in targeted therapy and immunotherapy have generated considerable optimism regarding the treatment of metastatic melanoma. Although robust efficacy data exist on systemic therapy treatment of extracranial melanoma, data in the setting of melanoma brain metastases (MBM) are limited, primarily because patients with MBM are typically excluded from clinical trials. However, several clinical trials focusing on patients with MBM are now complete, and more are underway. Clinical evaluation of serine/threonine-protein kinase B-Raf inhibition in combination with MEK inhibition for MBM produced intracranial response rates of close to 60%, suggesting that inhibition of the mitogen-activated protein kinase pathway has the potential to further improve MBM outcomes. For immunotherapy, there is now increasing evidence that checkpoint inhibitors may also be effective in MBM with a high rate of durable intracranial responses observed with combination therapy. Furthermore, radiotherapy—particularly MBM treatment with mainstay stereotactic radiosurgery—appears to be safe and effective when combined with systemic therapy. Finally, evolving magnetic resonance imaging capabilities have inspired new approaches to the measurement of tumor burden and treatment responses. This review evaluates current published evidence describing MBM as a multifaceted disease and presents an overview of currently available and investigational treatments for patients with MBM.
Pseudomonas aeruginosa
is an opportunistic bacterium that can form a biofilm with the ability to colonize different surfaces and for increasing resistance to antibiotics. An alternative to solve this ...problem may be the use of non-glucose/mannose glycosylated proteins from
Melipona beecheii
honey, which are capable of inhibiting the growth of this pathogen. In this work, the antibiofilm activity of the conA-unbound protein fraction (F1) from
M. beecheii
was evaluated. The crude protein extract (CPE) and the F1 fraction inhibited the
P. aeruginosa
biofilm growth above 80% at 4 and 1.3 µg/mL, respectively. These proteins affected the structure of the biofilm, as well as
fle
Q and
fle
R gene expressions involved in the formation and regulation of the
P. aeruginosa
biofilm. The results demonstrated that the F1 fraction proteins of
M. beecheii
honey inhibit and affect the formation of the
P. aeruginosa
biofilm.
Cancer is one of the leading causes of annual deaths worldwide, accounting for nearly 10 million deaths each year. Metastasis, the process by which cancer spreads across the patient's body, is the ...main cause of death in cancer patients. Because the rising trend observed in statistics of new cancer cases and cancer‐related deaths does not allow for an optimistic viewpoint on the future—in relation to this terrible disease—the scientific community has sought methods to enable early detection of cancer and prevent the apparition of metastatic tumors. One such method is known as liquid biopsy, wherein a sample is taken from a bodily fluid and analyzed for the presence of CTCs or other cancer biomarkers (e.g., growth factors). With this objective, interest is growing by year in electrokinetically‐driven microfluidics applied for the concentration, capture, filtration, transportation, and characterization of CTCs. Electrokinetic techniques—electrophoresis, dielectrophoresis, electrorotation, and electrothermal and EOF—have great potential for miniaturization and integration with electronic instrumentation for the development of point‐of‐care devices, which can become a tool for early cancer diagnostics and for the design of personalized therapeutics. In this contribution, we review the state of the art of electrokinetically‐driven microfluidics for cancer cells manipulation.
We study a continuous time optimal portfolio allocation problem with volatility and co-jump risk, allowing prices, variances and covariances to jump simultaneously. Differently from the traditional ...approach, we deviate from affine models by specifying a flexible Wishart jump-diffusion for the co-precision (the inverse of the covariance matrix). The optimal portfolio weights that solve the dynamic programming problem are genuinely dynamic and proportional to the instantaneous co-precision, reconciling optimal dynamic allocation with the static Markowitz-type economic intuition. An application to the optimal allocation problem across hedge fund investment styles illustrates the importance of having jumps in volatility associated with jumps in price.
The dynamic formation of carbon nanotube (CNT) networks in liquids under the application of an alternating current electric field is investigated using the effective dipole modeling approach. Three ...mechanisms are investigated by a set of three independent nonlinear differential equations derived from dielectrophoretic theory, viz. CNT rotation, CNT-to-CNT Coulombic interactions, and CNT migration towards an electrode. The models consider the effect of the electric field magnitude and frequency, the CNT’s concentration and aspect ratio, and the viscosity of the surrounding medium. A layer at the CNT/liquid interface is included and the effect of such a layer’s permittivity, electrical conductivity and thickness is investigated. Modeling predictions allow the reconstruction of the dynamic sequence of events leading to an aligned CNT network, which strongly depends on the CNT’s aspect ratio and concentration. Experimental trends regarding the effect of frequency can only be captured by considering an interface layer in the model.
Cadmium sulfide (CdS) films were deposited on rotating substrates by the chemical bath technique. The effects of the rotation speed on the morphological, optical, and structural properties of the ...films were discussed. A rotating substrate-holder was fabricated such that substrates can be taken out from the bath during the deposition. CdS films were deposited at different deposition times (10, 20, 30, 40 and 50
min) onto Corning glass substrates at different rotation velocities (150, 300, 450, and 600
rpm) during chemical deposition. The chemical bath was composed by CdCl
2, KOH, NH
4NO
3 and CS(NH
2)
2 as chemical reagents and heated at 75
°C. The results show no critical effects on the band gap energy and the surface roughness of the CdS films when the rotation speed changes. However, a linear increase on the deposition rate with the rotation energy was observed, meanwhile the stoichiometry was strongly affected by the rotation speed, resulting a better 1:1 Cd/S ratio as speed increases. Rotation effects may be of interest in industrial production of CdTe/CdS solar cells.
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