Thermal conductivity of the ionic liquid [HMIm][Tf2N] with compressed carbon dioxide

The liquid thermal conductivity of the ionic liquid (IL), 1-hexyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)amide ([HMIm][Tf₂N]), saturated with compressed vapor and supercritical carbon dioxide was measured over three isotherms (298.15, 323.15, and 348.15 K) and pressures up to approximately 20 MPa using a transient hot-wire technique. Pure [HMIm][Tf₂N] thermal conductivity was also measured over a temperature range of 293.15–353.15 K at ambient pressure and with hydrostatic pressure to approximately 20 MPa. Literature vapor–liquid equilibrium data were used to predict the liquid CO₂ composition at the conditions investigated. Initially, the liquid thermal conductivity slightly decreased with pressure/composition of CO₂ followed by a gradual increase that is mainly attributed to hydrostatic pressure effects. Simple composition-based mixing rules for mixture properties are not qualitatively nor quantitatively accurate. These data could be used to engineer heat transfer equipment required for a variety of proposed IL applications in CO₂ capture, absorption refrigeration, biphasic CO₂/IL reaction platforms, etc.     

Intense broadband photoemission from Bi-doped ZrO2 embedded in vitreous aluminoborate via direct melt-quenching

Tuning the optical properties of active species embedded within a glass matrix by modifying the ligand environment is of interest for luminescence-based technologies, for example, in optical sensing, data transmission, or spectral conversion. Here, we discuss a facile synthesis procedure for a glass-crystal composite material comprising of bismuth (Bi)-doped zirconia within an aluminoborate glass phase. The approach offers tunable and broad photoemission characteristics in the visible spectral region from 400 to 750 nm. Incorporation of Bi ions into the crystal phase enhances the photoemission intensity by two orders of magnitude, with an external quantum efficiency of about 29%. At higher ZrO₂ dopant concentration, we observe a red-shift of both the excitation and the emission bands to match commodity ultra-violet light emitting diodes as excitation sources. Encapsulation within the aluminoborate glass phase provides advantageous thermal behavior, with the emission intensity remaining at >80 % of its initial value up to a temperature of 400 K.     

The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.     

T cells enhance gold nanoparticle delivery to tumors <Emphasis Type="Italic">in vivo</Emphasis>

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.     

Synthesis of freestanding HfO<Subscript>2</Subscript> nanostructures

Two new methods for synthesizing nanostructured HfO₂ have been developed. The first method entails exposing HfTe₂ powders to air. This simple process resulted in the formation of nanometer scale crystallites of HfO₂. The second method involved a two-step heating process by which macroscopic, freestanding nanosheets of HfO₂ were formed as a byproduct during the synthesis of HfTe₂. These highly two-dimensional sheets had side lengths measuring up to several millimeters and were stable enough to be manipulated with tweezers and other instruments. The thickness of the sheets ranged from a few to a few hundred nanometers. The thinnest sheets appeared transparent when viewed in a scanning electron microscope. It was found that the presence of Mn enhanced the formation of HfO₂ by exposure to ambient conditions and was necessary for the formation of the large scale nanosheets. These results present new routes to create freestanding nanostructured hafnium dioxide.     

An Aqueous Phase Equilibrium Calculation Algorithm

A multiphase chemical equilibrium algorithm is developed which can be used with aqueous systems. The algorithm uses an average chemical potential for each species as a reference chemical potential. Incipient phases can be identified and their proximity to appearance can be determined through their tangent plane distance. Illustrative examples include the calculation of CaSO₄ solubility and the calculation of vapour pressures above an SO₂‐NaCl‐H₂O system, including the prediction of a three‐phase equilibrium. The algorithm proved robust and versatile. The appearance of incipient phases was easily tracked. Future work needs to be done to optimize damping/acceleration coefficients in the calculations.     

Bacteria Associated with a Tree-Killing Insect Reduce Concentrations of Plant Defense Compounds

Bark beetles encounter a diverse array of constitutive and rapidly induced terpenes when attempting to colonize living conifers. Concentrations of these compounds at entry sites can rapidly reach levels toxic to beetles, their brood, and fungal symbionts. Large numbers of beetles can overwhelm tree defenses via pheromone-mediated mass attacks, but the mechanisms are poorly understood. We show that bacteria associated with mountain pine beetles can metabolize monoterpenes and diterpene acids. The abilities of different symbionts to reduce concentrations of different terpenes appear complementary. Serratia reduced concentrations of all monoterpenes applied to media by 55–75 %, except for α-pinene. Beetle-associated Rahnella reduced (?)- and (+)-α-pinene by 40 % and 45 %, respectively. Serratia and Brevundimonas reduced diterpene abietic acid levels by 100 % at low concentrations. However, high concentrations exhausted this ability, suggesting that opposing rates of bacterial metabolism and plant induction of terpenes are critical. The two major fungal symbionts of mountain pine beetle, Grosmannia clavigera and Ophiostoma montium were highly susceptible to abietic acid. Grosmannia clavigera did not reduce total monoterpene concentrations in lodgepole pine turpentine. We propose the ability of bark beetles to exert landscape-scale impacts may arise partly from micro-scale processes driven by bacterial symbionts.     

Phospholipid Cyclosporine Prodrugs Targeted at Inflammatory Bowel Disease (IBD) Treatment: Design,Synthesis, and in Vitro Validation

Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A₂ (PLA₂), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA₂-catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract.     

Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor

The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.     

Additively patterned ferroelectric thin films with vertical sidewalls

The functional properties of electroceramic thin films can be degraded by subtractive patterning techniques used for microelectromechanical (MEMS) applications. This work explores an alternative deposition technique, where lead zirconate titanate (PZT) liquid precursors are printed onto substrates in a desired geometry from stamp wells (rather than stamp protrusions). Printing from wells significantly increased sidewall angles (from ~1 to >35 degrees) relative to printing solutions from stamp protrusions. Arrays of PZT features were printed, characterized, and compared to continuous PZT thin films of similar thickness. Three‐hundred‐nanometer‐thick printed PZT features exhibit a permittivity of 730 and a loss tangent of 0.022. The features showed remanent polarizations of 26 μC/cm², and coercive fields of 95 kV/cm. The piezoelectric response of the features produced an e_31,f of ?5.2 C/m². This technique was also used to print directly atop prepatterned substrates. Optimization of printing parameters yielded patterned films with 90° sidewalls. Lateral feature sizes ranged from hundreds of micrometers down to one micrometer. In addition, several device designs were prepatterned onto silicon on insulator (SOI) wafers (Si/SiO₂/Si with thicknesses of 0.35/1/500 μm). The top patterned silicon was released from the underlying material, and PZT was directly printed and crystallized on the free‐standing structures.