Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure and vascular resistance, typically leading to right heart failure and death. Current therapies improve quality of life of the patients but have a modest effect on long-term survival. A detailed transcriptomics and systems biology view of the PAH lung is expected to provide new testable hypotheses for exploring novel treatments. We completed transcriptomics analysis of PAH and control lung tissue to develop disease-specific and clinical data/tissue pathology gene expression classifiers from expression datasets. Gene expression data were integrated into pathway analyses. Gene expression microarray data were collected from 58 PAH and 25 control lung tissues. The strength of the dataset and its derived disease classifier was validated using multiple approaches. Pathways and upstream regulators analyses was completed with standard and novel graphical approaches. The PAH lung dataset identified expression patterns specific to PAH subtypes, clinical parameters, and lung pathology variables. Pathway analyses indicate the important global role of TNF and transforming growth factor signaling pathways. In addition, novel upstream regulators and insight into the cellular and innate immune responses driving PAH were identified. Finally, WNT-signaling pathways may be a major determinant underlying the observed sex differences in PAH. This study provides a transcriptional framework for the PAH-diseased lung, supported by previously reported findings, and will be a valuable resource to the PAH research community. Our investigation revealed novel potential targets and pathways amenable to further study in a variety of experimental systems.

We report a theoretical study of single molecule conduction switching of photochromic dithienylethene molecules. The light-induced intramolecular transformation drives a swapping of the highest occupied molecular orbital and lowest unoccupied molecular orbital between two distinct conjugated paths. The shuffling of single and double bonds produces a significant conductance change when the molecule is sandwiched between metal electrodes. We model the switching event using quantum molecular dynamics and the conductance changes using Green's function electronic transport theory. We find large on-off conductance ratios (between 10 and over 100) depending on the side group outside the switching core.

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Scanning gate microscopy (SGM) is used to image scar structures in an open quantum dot, which is created in an InAs quantum well by electron-beam lithography and wet etching. The scanned images demonstrate periodicities in magnetic field that correlate to those found in the conductance fluctuations. Simulations have shown that these magnetic transform images bear a strong resemblance to actual scars found in the dot that replicate through the modes in direct agreement with quantum Darwinism.

We report theoretical simulations of the effects of different binding sites and metal contact geometries on the conductance through single alkanedithiol molecules on gold. Examined are the current -voltage (I -V) characteristics and the projected density of states when a one-atom-thick filament is formed at the molecule-metal interface. Filaments similar to these are believed to be formed in gold STM break-junction experiments. I -V characteristics with these contacts are compared to those of planar gold contacts at hollow or on-top sites. The results reveal that a gold filament contact produces a large change in the Fermi level lineup which significantly affects its I -V curve. The conductance decreases by a factor of 4 ~ 6 when gold atoms are placed between the molecule and the gold surface to form a filament, and non-linearities develop. The hollow and on-top planar contacts show similar conductivities to each other and produce linear I -V curve.

These results provide additional evidence that there may be differences by sex in genetic risk for glioma. Additional analyses may further elucidate the biological processes through which this risk is conferred.

A network dependency platform was generated to define a landscape of cancer drug mechanisms in pulmonary hypertension.

We present theoretical results for the electron transport properties of the organic molecule polyaniline, especially leucoemeraldine (LEB), the fully reduced form. The electron tunnelling characteristics of these chain-like molecules are described by their complex band-structure. We explore how the bandgap and tunnelling decay parameter β depend on the oxidation state of the molecule and on the torsion angle between rings. It is found that the metal Fermi level lies near the HOMO for gold contacts with a single leucoemeraldine molecule, which results in non-linear I -V characteristics. The conductance of a hepta-aniline (LEB) oligomer is obtained from a first-principles I -V curve and compared with the recent experimental results. We examine the effect of stretching of the molecule on its conductance to explain the discrepancy between the theoretical simulations and single-molecule conductance measurement experiment.