Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

Mixed-Isotope Labeling with LC-IMS-MS for Characterization of Protein–Protein Interactions by Chemical Cross-Linking

Chemical cross-linking of proteins followed by proteolysis and mass spectrometric analysis of the resulting cross-linked peptides provides powerful insight into the quaternary structure of protein complexes. Mixed-isotope cross-linking (a method for distinguishing intermolecular cross-links) was coupled with liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS) to provide an additional separation dimension to the traditional cross-linking approach. This method produced multiplet m/z peaks that are aligned in the IMS drift time dimension and serve as signatures of intermolecular cross-linked peptides. We developed an informatics tool to use the amino acid sequence information inherent in the multiplet spacing for accurate identification of the cross-linked peptides. Because of the separation of cross-linked and non-cross-linked peptides in drift time, our LC-IMS-MS approach was able to confidently detect more intermolecular cross-linked peptides than LC-MS alone.      

Upward spread of masking, hearing loss, and speech recognition in young and elderly listeners

Upward spreading of masking, measured in terms of absolute masked threshold, is greater in hearing-impaired listeners than in listeners with normal hearing. The purpose of this study was to make further observations on upward-masked thresholds and speech recognition in noise in elderly listeners. Two age groups were used: One group consisted of listeners who were more than 60 years old, and the second group consisted of listeners who were less than 36 years old. Both groups had listeners with normal hearing as well as listeners with mild to moderate sensorineural loss. The masking paradigm consisted of a continuous low-pass-filtered (1000-Hz) noise, which was mixed with the output of a self-tracking, sweep-frequency Bekesy audiometer. Thresholds were measured in quiet and with maskers at 70 and 90 dB SPL. The upward-masked thresholds were similar for young and elderly hearing-impaired listeners. A few elderly listeners had lower upward-masked thresholds compared with the young control group; however, their on-frequency masked thresholds were nearly identical to the control group. A significant correlation was found between upward-masked thresholds and the Speech Perception in Noise (SPIN) test in elderly listeners.     

The fan-pall imbedding theorem over formally real fields

The converse of the Cauchy interlacing theorem, relating eigenvalues of a symmetric real matrix and eigenvalues of a principal submatrix, first proved by Fan and Pall, is extended to the case of symmetric matrices with entries in an arbitrary formally real field.     

Utilizing Paper-Based Devices for Antimicrobial-Resistant Bacteria Detection

Antimicrobial resistance (AMR), the ability of a bacterial species to resist the action of an antimicrobial drug, has been on the rise due to the widespread use of antimicrobial agents. Per the World Health Organization, AMR has an estimated annual cost of USD 34 billion in the US and is predicted to be the number one cause of death worldwide by 2050. One way AMR bacteria can spread, and by which individuals can contract AMR infections, is through contaminated water. Monitoring AMR bacteria in the environment currently requires that samples be transported to a central laboratory for slow and labor intensive tests. We have developed an inexpensive assay using paper-based analytical devices (PADs) that can test for the presence of β-lactamase-mediated resistance. To demonstrate viability, the PAD was used to detect β-lactam resistance in wastewater and sewage and identified resistance in individual bacterial species isolated from environmental water sources.     

Optimal Put Currency Option Size for an Uncertain Convertible Amount

Currency options have been used by risk averse firms to cover foreign exchange exposure, to profit from favourable exchange rate movements and to hedge the binary bidding situation. The aim of this paper is to establish a wider scope for currency options as a hedging tool for cases where the convertible amount is uncertain. The most appropriate option size derived using the concept of risk minimization is shown always to exceed the expected uncertain convertible amount.     

Symmetry relations for orthotropic and transversely isotropic materials

Archive for Rational Mechanics and Analysis -