We propose that information processing can be implemented by measuring the directional components of the macroscopic polarization of an ensemble of molecules subject to a sequence of laser pulses. We describe the logic operation theoretically and demonstrate it by simulations. The measurement of integrated stimulated emission in different phase matching spatial directions provides a logic decomposition of a function that is the discrete analog of an integral transform. The logic operation is reversible and all the possible outputs are computed in parallel for all sets of possible multivalued inputs. The number of logic variables of the function is the number of laser pulses used in sequence. The logic function that is computed depends on the chosen chromophoric molecular complex and on its interactions with the solvent and on the two time intervals between the three pulses and the pulse strengths and polarizations. The outputs are the homodyne detected values of the polarization components that are measured in the allowed phase matching macroscopic directions, k(l), k(l) = Sigma(i) l(i) k(i) where k(i) is the propagation direction of the ith pulse and \l(i) is a set of integers that encodes the multivalued inputs. Parallelism is inherently implemented because all the partial polarizations that define the outputs are processed simultaneously. The outputs, which are read directly on the macroscopic level, can be multivalued because the high dynamical range of partial polarization measurements by nonlinear coherent spectroscopy allows for fine binning of the signals. The outputs are uniquely related to the inputs so that the logic is reversible. (C) 2015 AIP Publishing LLC.
Proton-bound rare-gas dimer (RgHRg)(+), in which Rg represents a rare-gas atom, serves as a prototypical system for proton solvation by inert-gas atoms. Until now, only centrosymmetric species with Rg = Ar, Kr, or Xe have been identified with infrared spectra. We employed electron bombardment during deposition of a mixture of Xe (or Kr) in p-H-2 at 3.2 K to prepare (RgHRg)(+). Lines at 847.0 and 972.1 cm(-1) are assigned as the Rg-H-Rg antisymmetric stretching (nu(3)) mode and its combination with the RgHRg symmetric stretching (nu(1) + nu(3)) mode of (XeHXe)(+) in solid p-H-2, respectively. Lines at 871.1 and 974.0 cm(-1) are assigned as the nu(3) and nu(1) + nu(3) modes of (KrHKr)(+) in solid p-H-2, respectively. Slightly shifted and broadened lines were observed for these species in solid n-H-2. These results agree satisfactorily with reported experimental values of (XeHXe)(+) and (KrHKr)(+) in solid Xe, Kr, and Ar, and with the quantum-chemically predicted anharmonic vibrational wavenumbers of these species in the gaseous phase; the significant spectral shifts in various matrixes are rationalized with the proton affinities of the hosts. When a mixture of Xe and Kr in p-H-2 was used, an additional broad feature at 1284 cm(-1) was observed and assigned as the nu(3) mode of (KrHXe)(+) in solid p-H-2. This line shifted to 1280 cm(-1) in solid n-H-2 and the corresponding line of (KrDXe)(+) was observed at 954 cm(-1) in n-D-2. The observations of these lines are new; the wavenumbers significantly blue shifted from those of the centrosymmetric (RgHRg)(+) agree with the quantum-chemically predicted anharmonic vibrational wavenumbers of 1279 cm(-1) for (KrHXe)(+) and 916 cm(-1) for (KrDXe)(+). Analysis of the computational results shows that electronic correlation effects play a much greater role for the asymmetric than for the symmetric species. An interpretation for this is provided.
Semiconductor nanocrystals exhibit unique fluorescence properties which are tunable in size, shape and composition. The high quantum yield and enhanced stability have led to their use in biomedical imaging and flat panel displays. Here, semiconductor nanorod based inkjet inks are presented, overcoming limitations of the commonly reported quantum dots in printing applications. Fluorescent seeded nanorods were found to be outstanding candidates for fluorescent inks, due to their low particle–particle interactions and negligible self-absorption. This is manifested by insignificant emission shifts upon printing, even in highly concentrated printed layers and by maintenance of a high fluorescence quantum yield, unlike quantum dots which exhibit fluorescence wavelength shifts and quenching effects. This behavior results from the reduced absorption/emission overlap, accompanied by low energy transfer efficiencies between the nanorods as supported by steady state and time resolved fluorescence measurements. The new seeded nanorod inks enable patterning of thin fluorescent layers, for demanding light emission applications such as signage and displays.
Fibrinogen has the potential of being used as a material to harvest and grow normal mesenchymal cells (fibroblasts, endothelial cells) or to trap cancer cells from a suspension with blood as a potential circulatory trap.Insoluble fibrinogen particles (iFP) were prepared from commercial Cohn fraction I paste (source: Kedrion). The sized iFP ($\sim$60-180 µm) were not soluble in physiologic buffers, exhibited a density of 1.2 ± 0.02, and did not aggregate or clump when mixed with whole blood or thrombin, but were degraded in lytic solutions.Cell culture studies indicated that the iFP could be used to harvest, expand and transfer normal, mammalian, attachment-dependent cells, notably fibroblasts and stem cells from bone marrow, as well as numerous cancer lines. Cells attached to iFP underwent logarithmic growth kinetics and could be transferred without trypsinization. Transplanted cancer cells-on-iFP generated characteristic tumors and retained their surface marker (by Western immuno-blot). An iFP 'cell-affinity' batch column was shown to trap MCF-7 cancer cells in the presence of red blood cells (RBCs) or serum.The scalable process for fabricating iFP retained the cell attachment properties of native fibrinogen. The results indicate that iFP has the potential to be used as a 3D cell culture matrix, and possibly to trap cancer cells from blood.
Data on the past intensity of Earth’s magnetic field (paleointensity) are essential for understanding Earth’s deep interior, climatic modeling, and geochronology applications, among other items. Here we demonstrate the possibility that much of available paleointensity data could be biased by instability of thermoremanent magnetization (TRM) associated with non-single-domain (SD) particles. Paleointensity data are derived from experiments in which an ancient TRM, acquired in an unknown field, is replaced by a laboratory-controlled TRM. This procedure is built on the assumption that the process of ancient TRM acquisition is entirely reproducible in the laboratory. Here we show experimental results violating this assumption in a manner not expected from standard theory. We show that the demagnetization-remagnetization relationship of non-SD specimens that were kept in a controlled field for only 2 y show a small but systematic bias relative to sister specimens that were given a fresh TRM. This effect, likely caused by irreversible changes in micromagnetic structures, leads to a bias in paleointensity estimates.
We present an integrated approach for highly sensitive identification and validation of substrate-specific kinases as cancer biomarkers. Our approach combines phosphoproteomics for high throughput cancer-related biomarker discovery from patient tissues and an impedimetric kinase activity biosensor for sensitive validation. Using non-small-cell lung cancer (NSCLC) as a proof-of-concept study, label-free quantitative phosphoproteomic analysis of a pair of cancerous and its adjacent normal tissues revealed 198 phosphoproteins that are over-phosphorylated in NSCLC. Among the differentially regulated phosphorylation sites, the most significant alteration was in residue S165 in the Hepatoma Derived Growth Factor (HDGF) protein. Hence, HDGF was selected as a model system for the electrochemical studies. Further motif-based analysis of this altered phosphorylation site revealed that extracellular-signal-regulated kinase 1/2 (ERK1/2) are most likely to be the corresponding kinases. For validation of the kinase–substrate pair, densely packed peptide monolayers corresponding to the HDGF phosphorylation site were coupled to a gold electrode. Phosphorylation of the monolayer by ERK2 and dephosphorylation by alkaline phosphatase (AP) were detected by electrochemical impedance spectroscopy (EIS) and surface roughness analysis. Compared to other methods for quantification of kinase concentration, this label-free electrochemical assay offers the advantages of ultra-sensitivity as well as higher specificity for the detection of cancer-related kinase–substrate pair. With implementation of multiple kinase–substrate biomarker pairs, we expect this integrated approach to become a high throughput platform for discovery and validation of phosphorylation-mediated biomarkers.
Protein–protein interactions (PPI) are essential in every step of the HIV replication cycle. Mapping the interactions between viral and host proteins is a fundamental target for the design and development of new therapeutics. In this review, we focus on rational development of anti-HIV-1 peptides based on mapping viral–host and viral–viral protein interactions all across the HIV-1 replication cycle. We also discuss the mechanism of action, specificity and stability of these peptides, which are designed to inhibit PPI. Some of these peptides are excellent tools to study the mechanisms of PPI in HIV-1 replication cycle and for the development of anti-HIV-1 drug leads that modulate PPI.
The most critical stage in initiation of melanoma metastasis is the radial to vertical growth transition, yet the triggers of this transition remain elusive. We suggest that the microenvironment drives melanoma metastasis independently of mutation acquisition. Here we examined the changes in microenvironment that occur during melanoma radial growth. We show that direct contact of melanoma cells with the remote epidermal layer triggers vertical invasion via Notch signaling activation, the latter serving to inhibit MITF function. Briefly, within the native Notch ligand-free microenvironment, MITF, the melanocyte lineage master regulator, binds and represses miR-222/221 promoter in an RBPJK-dependent manner. However, when radial growth brings melanoma cells into contact with distal differentiated keratinocytes that express Notch ligands, the activated Notch intracellular domain impairs MITF binding to miR-222/221 promoter. This de-repression of miR-222/221 expression triggers initiation of invasion. Our findings may direct melanoma prevention opportunities via targeting specific microenvironments.
