Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.

Development of a selective and scalable 1-indazole alkylation.

1-Alkyl indazoles are a ubiquitous and privileged motif within medicinal chemistry, yet methods to selectively furnish 1-alkyl indazoles with simple alkyl side chains remain sparse. Herein, negative data from high-throughput experimentation (HTE) enabled a confident pivot of resource from continued optimisation to the development of an alternative reaction. This workflow culminated in a methodology for the synthesis of 1-alkyl indazoles.

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids.

Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols have identified tris(-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener is found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides.

Combination of Polymeric Micelle Formulation of TGFβ Receptor Inhibitors and Paclitaxel Produce Consistent Response Across Different Mouse Models of TNBC.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor-beta (TGFβ) family of proteins and their receptors (TGFR) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with Paclitaxel (PTX) chemotherapy.

Intravenous heterologous prime-boost vaccination activates innate and adaptive immunity to promote tumor regression.

Therapeutic neoantigen cancer vaccines have limited clinical efficacy to date. Here, we identify a heterologous prime-boost vaccination strategy using a self-assembling peptide nanoparticle TLR-7/8 agonist (SNP) vaccine prime and a chimp adenovirus (ChAdOx1) vaccine boost that elicits potent CD8 T cells and tumor regression. ChAdOx1 administered intravenously (i.

Controlling Kinetic Pathways in Demixing Microgel-Micelle Mixtures.

We investigate the temperature-dependent phase behavior of mixtures of poly(-isopropylacrylamide) (pNIPAM) microgel colloids and a triblock copolymer (PEO-PPO-PEO) surfactant. Usually, gelation in these systems results from an in temperature. Here we investigate the role of the heating rate, and surprisingly, we find that this causes the mechanism of aggregation to change from one which is driven by depletion of the microgels by the micelles at low temperatures to the association of the two species at high temperatures.

Improving the accuracy of discharge medication documentation in people with kidney disease through pharmacist-led partnered prescribing.

Background: Inaccurate medication documentation in prescriptions and discharge summaries produce poorer patient outcomes, are costly to healthcare systems and result in more readmissions to hospital. Errors in medication documentation are common in Australian hospitals.

Aim: To determine whether pharmacist-led partnered prescribing (PPP) on discharge reduced errors and improved accuracy in documentation of medications in the discharge prescription and the discharge summary of people with kidney disease compared with medical prescribing (MP).

Systemic vaccination induces CD8 T cells and remodels the tumor microenvironment.

Therapeutic cancer vaccines are designed to increase tumor-specific T cell immunity. However, suppressive mechanisms within the tumor microenvironment (TME) may limit T cell function. Here, we assessed how the route of vaccination alters intratumoral myeloid cells.

Oxidative degradation of triblock-copolymer surfactant and its effects on self-assembly.

We investigate the degradation behaviour of a triblock-copolymer surfactant made from polyethylene oxide (PEO) and polypropylene oxide (PPO) (PEO-PPO-PEO), highlighting how the aggregation behaviour of this polymer in water alters with ageing. Samples aged at room temperature were compared to samples degraded using accelerated ageing at elevated temperatures. We find that large mass losses occurred to the polymer surfactant which resulted in a change in the aggregation behaviour, with larger, rod-like or planar aggregates forming at longer degradation times.

Using virtual reality for dynamic learning: an extended technology acceptance model.

Virtual reality (VR) is being researched and incorporated into curricula and training programs to expand educational opportunities and enhance learning across many fields. Although researchers are exploring the learning affordances associated with VR, research surrounding students' perceptions of the technology, and intentions to use it for training has been neglected. The goal of this research was to determine the factors that influence students' intention to use VR in a dynamic learning environment.

Real space analysis of colloidal gels: triumphs, challenges and future directions.

Colloidal gels constitute an important class of materials found in many contexts and with a wide range of applications. Yet as matter far from equilibrium, gels exhibit a variety of time-dependent behaviours, which can be perplexing, such as an increase in strength prior to catastrophic failure. Remarkably, such complex phenomena are faithfully captured by an extremely simple model-'sticky spheres'.

Preparation and Characterization of Poly(2-oxazoline) Micelles for the Solubilization and Delivery of Water Insoluble Drugs.

Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such compounds for cancer therapy, where high doses and intravenous injections are needed ( Di , 2012 ). Here, we present a poly(2-oxazoline) polymer (POx)-based nanoformulation strategy to solubilize and deliver hydrophobic drugs.

Preparation of an Orthotopic, Syngeneic Model of Lung Adenocarcinoma and the Testing of the Antitumor Efficacy of Poly(2-oxazoline) Formulation of Chemo-and Immunotherapeutic Agents.

Tumor xenograft models developed by transplanting human tissues or cells into immune-deficient mice are widely used to study human cancer response to drug candidates. However, immune-deficient mice are unfit for investigating the effect of immunotherapeutic agents on the host immune response to cancer (Morgan, 2012). Here, we describe the preparation of an orthotopic, syngeneic model of lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), to study the antitumor effect of chemo and immunotherapeutic agents in an immune-competent animal.

A high proportion of red snapper sold in North Carolina is mislabeled.

Seafood mislabeling occurs when a market label is inaccurate, primarily in terms of species identity, but also regarding weight, geographic origin, or other characteristics. This widespread problem allows cheaper or illegally-caught species to be marketed as species desirable to consumers. Previous studies have identified red snapper () as one of the most frequently mislabeled seafood species in the United States.

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma.

About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure.

Reversible temperature-controlled gelation in mixtures of pNIPAM microgels and non-ionic polymer surfactant.

We investigate the reversible gelation of poly(N-isopropylacrylamide) (pNIPAM) microgels in the presence of triblock-copolymer (PEO-PPO-PEO type) surfactant. We demonstrate that the association of these polymers with the microgel particles at elevated temperature is responsible for the gelation, due to the temperature responsive nature of the components. This is highlighted by an increase in the apparent hydrodynamic diameter of the particles in dynamic light scattering experiments, which only occurs above the volume phase transition temperature of pNIPAM.

Tetramethyl Orthosilicate (TMOS) as a Reagent for Direct Amidation of Carboxylic Acids.

Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods.

Micellization of alkyltrimethylammonium bromide surfactants in choline chloride:glycerol deep eutectic solvent.

Deep eutectic solvents have shown the ability to promote the self-assembly of surfactants in solution. However, some differences have been found compared with self-assembly in pure water and other polar organic solvents. The behaviour of alkyltrimethylammonium bromides in choline chloride:glycerol deep eutectic solvent has been studied by means of surface tension, X-ray and neutron reflectivity and small-angle neutron scattering.

Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension.

The identity of the transporter responsible for fructose absorption in the intestine in vivo and its potential role in fructose-induced hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose absorption by approximately 75% in the jejunum and decreased the concentration of serum fructose by approximately 90% relative to wild-type mice on increased dietary fructose. When fed a control (60% starch) diet, Glut5(-/-) mice had normal blood pressure and displayed normal weight gain.

Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5.

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice.

Visual copresence and conversational coordination.

Pickering & Garrod's (P&G's) theory of dialogue production cannot completely explain recent data showing that when interactants in referential communication tasks have different views of a physical space, they accommodate their language to their partner's view rather than mimicking their partner's expressions. Instead, these data are consistent with the hypothesis that interactants are taking the perspective of their conversational partners.

Choline and choline esters in human and rat milk and in infant formulas.

Large amounts of choline are required in neonates for rapid organ growth and membrane biosynthesis. Human infants derive much of their choline from milk. In our study, mature human milk contained more phosphocholine and glycerophosphocholine than choline, phosphatidylcholine, or sphingomyelin (P < 0.

Pulmonary veno-occlusive disease in an adult following bone marrow transplantation. Case report and review of the literature.

Pulmonary veno-occlusive disease (PVOD) was diagnosed in an adult following chemotherapy and bone marrow transplantation (BMT) for acute lymphoblastic leukemia. A medical literature review showed only three previous reports of PVOD following BMT occurring in children but no prior cases in adults.

Social and cognitive processes in interpersonal communication: implications for advanced telecommunications technologies.

Interactive multimedia conferencing systems, in which two or more remotely located people can work on cooperative tasks through shared audio, video, and data, appear to be the wave of the future. However, because of great advances in the underlying technology of multimedia conferencing systems, many design decisions have been driven by what is technically feasible as opposed to what will best suit the needs of the users. In this paper we provide a framework for the design and evaluation of features in advanced telecommunications products and services which is derived from empirical research on interpersonal communication.