Targeted tumor cell internalization and imaging of multifunctional quantum dot-conjugated immunoliposomes in vitro and in vivo

Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages in the development and application of nanomedicines. To incorporate the unique optical properties of luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis and treatment, we describe the synthesis, biophysical characterization, tumor cell-selective internalization, and anticancer drug delivery of QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic properties and in vivo imaging capability of QD-ILs were also investigated. Freeze-fracture electron microscopy was used to visualize naked QDs, liposome controls, nontargeted QD-conjugated liposomes (QD-Ls), and QD-ILs. QD-ILs prepared by insertion of anti-HER2 scFv exhibited efficient receptor-mediated endocytosis in HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells but not in control MCF-7 cells as analyzed by flow cytometry and confocal microscopy. In contrast, nontargeted QD-Ls showed minimal binding and uptake in these cells. Doxorubicin-loaded QD-ILs showed efficient anticancer activity, while no cytotoxicity was observed for QD-ILs without chemotherapeutic payload. In athymic mice, QD-ILs significantly prolonged circulation of QDs, exhibiting a plasma terminal half-life ( t 1/2) of approximately 2.9 h as compared to free QDs with t 1/2 < 10 min. In MCF-7/HER2 xenograft models, localization of QD-ILs at tumor sites was confirmed by in vivo fluorescence imaging.     

Effects of contaminant metal ions on precipitation recovery of rare earth elements using oxalic acid

Solution equilibrium calculations were performed in this study to understand the impact of contaminant metal ions on the precipitation efficiency of selected ra...     

Oxytocin and Food Intake Control: Neural,Behavioral, and Signaling Mechanisms

The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin’s anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin’s effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.     

Effects of secretion removal on bovine mammary gland function following an extended milk stasis.

The objective of this study was to determine whether lactation function could be reinitiated after a period of extended milk stasis. Involution was induced by milk stasis in lactating Holstein cows for a period of 11 d. On d 11, one side of the mammary gland was milked twice daily for 3 d. The contralateral side remained unmilked for the 14-d experimental period. Cows were slaughtered, and mammary tissue was collected from both udder halves for further analysis. Mammary secretion volume was partially restored in the milked udder half, but reestablished milk yields were variable among cows. A partial recovery of lactation function was further indicated by elevated levels of lactose and protein profiles resembling milk in mammary secretions from the milked glands. Lactose and protein profiles from the unmilked glands were similar to those of glands undergoing involution. Lactoferrin levels were elevated in secretions from the milked and unmilked udder halves. Casein and lactoferrin synthesis by mammary explants and beta-casein and lactoferrin mRNA abundance in mammary tissues corresponded to protein profiles from milked and unmilked mammary secretions. alpha-Lactalbumin mRNA was variable but was more abundant in the milked glands compared with the unmilked glands. Lectin fluorescence microscopy for soybean agglutinin preferentially stained the apical surface of the mammary epithelial cells from the milked glands. Staining was absent in the unmilked glands and suggested resumption of lactation function in all such milked glands. These results suggest that mammary involution can be partially reversible after 11 d of milk stasis.     

Analysis of peptide MS/MS spectra from large-scale proteomics experiments using spectrum libraries

A widespread proteomics procedure for characterizing a complex mixture of proteins combines tandem mass spectrometry and database search software to yield mass spectra with identified peptide sequences. The same peptides are often detected in multiple experiments, and once they have been identified, the respective spectra can be used for future identifications. We present a method for collecting previously identified tandem mass spectra into a reference library that is used to identify new spectra. Query spectra are compared to references in the library to find the ones that are most similar. A dot product metric is used to measure the degree of similarity. With our largest library, the search of a query set finds 91% of the spectrum identifications and 93.7% of the protein identifications that could be made with a SEQUEST database search. A second experiment demonstrates that queries acquired on an LCQ ion trap mass spectrometer can be identified with a library of references acquired on an LTQ ion trap mass spectrometer. The dot product similarity score provides good separation of correct and incorrect identifications.     

Resource-conserving agriculture increases yields in developing countries

Despite great recent progress, hunger and poverty remain widespread and agriculturally driven environmental damage is widely prevalent. The idea of agricultural sustainability centers on the need to develop technologies and practices that do not have adverse effects on environmental goods and services, and that lead to improvements in food productivity. Here we show the extent to which 286 recent interventions in 57 poor countries covering 37 M ha (3% of the cultivated area in developing countries) have increased productivity on 12.6 M farms while improving the supply of critical environmental services. The average crop yield increase was 79% (geometric mean 64%). All crops showed water use efficiency gains, with the highest improvement in rainfed crops. Potential carbon sequestered amounted to an average of 0.35 t C ha(-1) y(-1). If a quarter of the total area under these farming systems adopted sustainability enhancing practices, we estimate global sequestration could be 0.1 Gt C y(-1). Of projects with pesticide data, 77% resulted in a decline in pesticide use by 71% while yields grew by 42%. Although it is uncertain whether these approaches can meet future food needs, there are grounds for cautious optimism, particularly as poor farm households benefit more from their adoption.     

Interaction between dual cavity modes in a planar photonic microcavity

Abstract

We theoretically study the interaction between dual cavity modes in a planar photonic microcavity structure in the optical communication wavelength range. The merging and splitting of cavity mode is analysed with realistic microcavity structures. The merging of dual cavity resonance into a single cavity resonance is achieved by changing the number of layers between the two cavities. The splitting of single cavity resonance into dual cavity resonance is obtained with an increase in the reflectivity of mirrors in the front and rear side of the microcavity structure. The threshold condition for the merging and splitting of cavity mode is established in terms of structural parameters. The physical origin of the merging of dual cavity modes into a single cavity resonance is discussed in terms of the electric field intensity distribution in the microcavity structure. The microcavity structure with dual cavity modes is useful for the generation of entangled photon pairs, for achieving the strong-coupling regime between exciton and photon and for high-resolution multi-wavelength filters in optical communication.     

Survey of current methods and guidance for strategic environmental assessment

This paper examines methods promoted and used in strategic environmental assessment (SEA) practice, practitioner choices about methodology and the nature of SEA guidance. Results show that SEA is not challenged by a lack of methods, but the range of methods promoted and used is restrictive. A major challenge to practice is making the ‘right choices’ about methods and methodology. Much SEA guidance is focused on flexibility in SEA, providing high-level principles, and is too generic to facilitate such choices. It is assumed that there is sufficient expertise amongst SEA practitioners, and that practitioners will simply know what methods and methodologies are best. Our results indicate that more detailed operational guidance is needed at the practitioner level on how to make sound methodological choices and how to select the best available methods for the SEA tier and context at hand.     

Reversible H2 storage using a SAPO-34 zeolite layer

A SAPO-34 zeolite membrane was made essentially impermeable to high-pressure hydrogen at room temperature by adsorbing methanol in the SAPO-34 layer. Hydrogen permeance decreased three orders of magnitude when the methanol feed activity was 0.1, and it decreased more than six orders of magnitude when the methanol feed activity was higher than 0.85 at 293 K. The hydrogen permeance at 293 K was below 10⁻¹⁴ mol/m² s Pa for at least five days for a H₂ feed pressure of 6.6 MPa. At higher temperatures, methanol desorbed and the H₂ flux increased. The hydrogen permeance could be controlled by the activity of the methanol on the feed side. These results demonstrate that the SAPO-34 membrane had low fluxes through defects, and H₂ flow through these defects was blocked by capillary condensation of methanol at high methanol activities.