The Acoustic Change Complex in Response to Frequency Changes and Its Correlation to Cochlear Implant Speech Outcomes.

One of the biggest challenges that face cochlear implant (CI) users is the highly variable hearing outcomes of implantation across patients. Since speech perception requires the detection of various dynamic changes in acoustic features (e.g.

Cortical processing of location and frequency changes of sounds in normal hearing listeners.

Sounds we hear in our daily life contain changes in the acoustic features (e.g., frequency, intensity, and duration or "what" information) and/or changes in location ("where" information).

A Preliminary Study of the Effects of Attentive Music Listening on Cochlear Implant Users' Speech Perception, Quality of Life, and Behavioral and Objective Measures of Frequency Change Detection.

Introduction: Most cochlear implant (CI) users have difficulty in listening tasks that rely strongly on perception of frequency changes (e.g., speech perception in noise, musical melody perception, etc.

Advancing Healthcare Reform: The American Heart Association's 2020 Statement of Principles for Adequate, Accessible, and Affordable Health Care: A Presidential Advisory From the American Heart Association.

The mission of the American Heart Association is to be a relentless force for a world of longer, healthier lives. The American Heart Association has consistently prioritized the needs and perspective of the patient in taking positions on healthcare reform while recognizing the importance of biomedical research, providers, and healthcare delivery systems in advancing the care of patients and the prevention of disease. The American Heart Association's vision for healthcare reform describes the foundational changes needed for the health system to serve the best interests of patients and to achieve health care and coverage that are adequate, accessible, and affordable for everyone living in the United States.

Nanoparticle-based photothermal heating to drive chemical reactions within a solid: using inhomogeneous polymer degradation to manipulate mechanical properties and segregate carbonaceous by-products.

Photothermal heating via metal nanoparticles is utilized to degrade polyethylcyanoacrylate (PECA), which undergoes a thermally-driven depolymerization process, resulting in (i) monomer loss from the sample, (ii) repolymerization to form shorter chains (oligomer), and (iii) formation of carbonaceous by-products which are graphene-like and luminescent. These unique PECA properties are used to demonstrate the heterogeneous temperature distribution present during photothermal processing and the results are compared to degradation via conventional methods where a uniform temperature is present. Photothermal heating results in formation of pockets of depolymerized material around each nanoscale heating site.

Photothermally-driven thermo-oxidative degradation of low density polyethylene: heterogeneous heating plus a complex reaction leads to homogeneous chemistry.

Photothermal heating from embedded nanoparticles, a process whereby visible light is converted into heat resulting in a high temperature in each particle's immediate vicinity, was utilized to degrade low density polyethylene (LDPE) via thermo-oxidation. The spatially-varying steady-state photothermal temperature field is a potential mechanism by which ambient light (e.g.

1-Benzyl-indole-3-carbinol is a highly potent new small molecule inhibitor of Wnt/β-catenin signaling in melanoma cells that coordinately inhibits cell proliferation and disrupts expression of microphthalmia-associated transcription factor isoform-M.

1-Benzyl-indole-3-carbinol (1-benzyl-I3C), a synthetic analogue of the crucifer-derived natural phytochemical I3C, displayed significantly wider sensitivity and anti-proliferative potency in melanoma cells than the natural compound. Unlike I3C, which targets mainly oncogenic BRAF-expressing cells, 1-benzyl-I3C effectively inhibited proliferation of melanoma cells with a more extensive range of mutational profiles, including those expressing wild-type BRAF. In both cultured melanoma cell lines and in vivo in melanoma cell-derived tumor xenografts, 1-benzyl-I3C disrupted canonical Wnt/β-catenin signaling that resulted in the downregulation of β-catenin protein levels with a concomitant increase in levels of the β-catenin destruction complex components such as glycogen synthase kinase-3β (GSK-3β) and Axin.

Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein.

Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR.

In situ curing of liquid epoxy via gold-nanoparticle mediated photothermal heating.

Metal nanoparticles incorporated at low concentration into epoxy systems enable in situ curing via photothermal heating. In the process of nanoparticle-mediated photothermal heating, light interacts specifically with particles embedded within a liquid or solid material and this energy is transformed into heat, resulting in significant temperature increase local to each particle with minimal warming of surroundings. The ability to use such internal heating to transform the mechanical properties of a material (e.

Indole-3-carbinol (I3C) analogues are potent small molecule inhibitors of NEDD4-1 ubiquitin ligase activity that disrupt proliferation of human melanoma cells.

The HECT domain-containing E3 ubiquitin ligase NEDD4-1 (Neural precursor cell Expressed Developmentally Down regulated gene 4-1) is frequently overexpressed in human cancers and displays oncogenic-like properties through the ubiquitin-dependent regulation of multiple protein substrates. However, little is known about small molecule enzymatic inhibitors of HECT domain-containing ubiquitin ligases. We now demonstrate that indole-3-carbinol (I3C), a natural anti-cancer phytochemical derived from cruciferous vegetables such as cabbage and broccoli, represents a new chemical scaffold of small molecule enzymatic inhibitors of NEDD4-1.

Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells.

Inhibition of oncogenic BRAF activity by indole-3-carbinol disrupts microphthalmia-associated transcription factor expression and arrests melanoma cell proliferation.

Indole-3-carbinol (I3C), an anti-cancer phytochemical derived from cruciferous vegetables, strongly inhibited proliferation and down-regulated protein levels of the melanocyte master regulator micropthalmia-associated transcription factor (MITF-M) in oncogenic BRAF-V600E expressing melanoma cells in culture as well as in vivo in tumor xenografted athymic nude mice. In contrast, wild type BRAF-expressing melanoma cells remained relatively insensitive to I3C anti-proliferative signaling. In BRAF-V600E-expressing melanoma cells, I3C treatment inhibited phosphorylation of MEK and ERK/MAPK, the down stream effectors of BRAF.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

Phytochemical regulation of the tumor suppressive microRNA, miR-34a, by p53-dependent and independent responses in human breast cancer cells.

The tumor suppressive microRNA miR-34a is transcriptionally regulated by p53 and shown to inhibit breast cancer cell proliferation as well as being a marker of increased disease free survival. Indole-3-carbinol (I3C) derived from cruciferous vegetables, artemisinin, extracted from the sweet wormwood plant, and artesunate, a semi-synthetic derivative of artemisinin, are phytochemicals with anti-tumorigenic properties however, little is known about the role of microRNAs in their mechanism of action. Human breast cancer cells expressing wild-type (MCF-7) or mutant p53 (T47D) were treated with a concentration range and time course of each phytochemical under conditions of cell cycle arrest as detected by flow cytometry to examine the potential connection between miR-34a expression and their anti-proliferative responses.

Essential role of the cancer stem/progenitor cell marker nucleostemin for indole-3-carbinol anti-proliferative responsiveness in human breast cancer cells.

Background: Nucleostemin is a nucleolus residing GTPase that is considered to be an important cancer stem/progenitor cell marker protein due to its high expression levels in breast cancer stem cells and its role in tumor-initiation of human mammary tumor cells. It has been proposed that nucleostemin may represent a valuable therapeutic target for breast cancer; however, to date evidence supporting the cellular mechanism has not been elucidated.

Results: Expression of exogenous HER2, a member of the EGF receptor gene family, in the human MCF-10AT preneoplastic mammary epithelial cell line formed a new breast cancer cell line, 10AT-Her2, which is highly enriched in cells with stem/progenitor cell-like character.

Minireview: Steroid/nuclear receptor-regulated dynamics of occluding and anchoring junctions.

A diverse set of physiological signals control intercellular interactions by regulating the structure and function of occluding junctions (tight junctions) and anchoring junctions (adherens junctions and desmosomes). These plasma membrane junctions are comprised of multiprotein complexes of transmembrane and cytoplasmic peripheral plasma membrane proteins. Evidence from many hormone-responsive tissues has shown that expression, modification, molecular interactions, stability, and localization of junctional complex-associated proteins can be targeted by nuclear hormone receptors and their ligands through transcriptional and nontranscriptional mechanisms.

The antiproliferative response of indole-3-carbinol in human melanoma cells is triggered by an interaction with NEDD4-1 and disruption of wild-type PTEN degradation.

Unlabelled: Human melanoma cells displaying distinct PTEN genotypes were used to assess the cellular role of this important tumor-suppressor protein in the antiproliferative response induced by the chemopreventative agent indole-3-carbinol (I3C), a natural indolecarbinol compound derived from the breakdown of glucobrassicin produced in cruciferous vegetables such as broccoli and Brussels sprouts. I3C induced a G1-phase cell-cycle arrest and apoptosis by stabilization of PTEN in human melanoma cells that express wild-type PTEN, but not in cells with mutant or null PTEN genotypes. Importantly, normal human epidermal melanocytes were unaffected by I3C treatment.

Artemisinin triggers a G1 cell cycle arrest of human Ishikawa endometrial cancer cells and inhibits cyclin-dependent kinase-4 promoter activity and expression by disrupting nuclear factor-κB transcriptional signaling.

Relatively little is known about the antiproliferative effects of artemisinin, a naturally occurring antimalarial compound from Artemisia annua, or sweet wormwood, in human endometrial cancer cells. Artemisinin induced a G1 cell cycle arrest in cultured human Ishikawa endometrial cancer cells and downregulated cyclin-dependent kinase-2 (CDK2) and CDK4 transcript and protein levels. Analysis of CDK4 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK4 gene expression was accounted for by the loss of CDK4 promoter activity.

3,3'-diindolylmethane rapidly and selectively inhibits hepatocyte growth factor/c-Met signaling in breast cancer cells.

3,3'-Diindolylmethane (DIM), an indole derivative from vegetables of the Brassica genus, has antiproliferative activity in breast cancer cells. Part of this activity is thought to be due to DIM inhibition of Akt signaling, but an upstream mechanism of DIM-induced Akt inhibition has not been described. The goals of this study were to investigate the kinetics of inhibition of Akt by physiologically relevant concentrations of DIM and to identify an upstream factor that mediates this effect.

The serum- and glucocorticoid-induced protein kinase-1 (Sgk-1) mitochondria connection: identification of the IF-1 inhibitor of the F(1)F(0)-ATPase as a mitochondria-specific binding target and the stress-induced mitochondrial localization of endogenous Sgk-1.

The expression, localization and activity of the serum- and glucocorticoid-induced protein kinase, Sgk-1, are regulated by multiple hormonal and environmental cues including cellular stress. Biochemical fractionation and indirect immunofluorescence demonstrated that sorbitol induced hyperosmotic stress stimulated expression and triggered the localization of endogenous Sgk-1 into the mitochondria of NMuMG mammary epithelial cells. The immunofluorescence pattern of endogenous Sgk-1 was similar to that of a green fluorescent linked fusion protein linked to the N-terminal Sgk-1 fragment that encodes the mitochondrial targeting signal.

Minireview: regulation of gap junction dynamics by nuclear hormone receptors and their ligands.

Gap junctions are plasma membrane channels comprising connexin proteins that mediate intercellular permeability and communication. The presence, composition, and function of gap junctions can be regulated by diverse sets of physiological signals. Evidence from many hormone-responsive tissues has shown that connexin expression, modification, stability, and localization can be targeted by nuclear hormone receptors and their ligands through both transcriptional and nontranscriptional mechanisms.