gebhart/patrepeval huggingface dataset:
Influence of Solvent on Carbene Intersystem Crossing Rates (2008)

The influence of coordinating solvents on singlet-to-triplet carbene intersystem crossing (ISC) rates has been studied with diphenylcarbene (DPC) and para-biphenyltrifluoromethylcarbene (BpCCF 3) by using ultrafast time-resolved spectroscopy. DPC has a triplet ground state in all of the solvents considered, and the concentration of singlet carbene at equilibrium is too small to be measured. It is found that the lifetime of (1)DPC is extended in acetonitrile, benzene, tetrahydrofuran, dichloromethane, and halobenzene solvents relative to cyclohexane. The solvent effect does not well correlate with bulk measures of solvent polarity. The singlet-triplet energy separation of BpCCF 3 is close to zero. The data demonstrates that BpCCF 3 has a triplet ground state in benzene, fluorobenzene, and hexafluorobenzene. Halogenated solvents are found to dramatically retard the rate of ISC in (1)BpCCF 3. We postulate that the empty p orbital of a singlet carbene coordinates with a nonbonding pair of electrons of a halogen atom of the solvent to form a pseudoylide solvent complex, stabilize the singlet carbene, and decrease the singlet-triplet (S-T) energy gap. The "golden rule" of radiationless transitions posits that the smaller the energy gap between the two states, the faster their rate of interconversion. To explain the apparent violation of the golden rule of radiationless transitions for the carbene ISC processes monitored in this study, we propose that the significantly different specific solvation of the singlet and triplet carbenes imposes a Franck-Condon-like factor on the ISC process. Those solvents that most solvate the singlet carbene will also have the greatest structural difference between singlet carbene-solvent complex and their triplet spin isomer-solvent complex, the smallest S-T gap, and the slowest ISC rate. Alternatively, one can propose that a highly solvated singlet carbene must desolvate prior to ISC, and that this requirement decelerates the radiationless transition.
Plasmonic color filter based on a hetero-metal-insulator-metalgrating (2020)

Plasmonic color filters are expected to be candidates for application to complementary metal-oxide-semiconductor (CMOS) image sensor arrays with reduced pixel size, owing to the subwavelength mode volume of plasmons. Designs of metallic gratings based on the guided-mode resonance effect suffer from the sideband transmission issue due to high-order diffraction. Here, we propose a plasmonic color filter structure based on a hetero-metal-insulator-metal grating. The guided mode, in resonance with the second-order diffraction, is highly attenuated by the forbidden band, such that the sideband transmission can be suppressed. As calculated by using the transfer matrix method and the finite-difference time-domain method, the Al-ZnO-Ag waveguide-based structure presents a color filter characteristic with the peak transmittance greater than 70% and the peak wavelength tunable in the visible light band. It may find application in displays, image sensors, and biomedical imaging technologies.
Adhesion of Nanoparticles (2010)

We have developed a new model of nanoparticle adhesion which explicitly takes into account the change in the nanoparticle surface energy. Using combination of the molecular dynamics simulations and theoretical calculations we have showed that the deformation of the adsorbed nanoparticles is a function of the dimensionless parameter beta proportional, variant gamma(p)(GR(p))(-2/3)W(-1/3), where G is the particle shear modulus, R(p) is the initial particle radius, gamma(p) is the polymer interfacial energy, and W is the particle work of adhesion. In the case of small values of the parameter beta < 0.1, which is usually the case for strongly cross-linked large nanoparticles, the particle deformation can be described in the framework of the classical Johnson, Kendall, and Roberts (JKR) theory. However, we observed a significant deviation from the classical JKR theory in the case of the weakly cross-linked nanoparticles that experience large shape deformations upon particle adhesion. In this case the interfacial energy of the nanoparticle plays an important role controlling nanoparticle deformation. Our model of the nanoparticle adhesion is in a very good agreement with the simulation results and provides a new universal scaling relationship for nanoparticle deformation as a function of the system parameters.
Prognostic Value of Controlled Attenuation Parameter by Transient Elastography (2017)

Neither the presence nor the severity of hepatic steatosis as measured by CAP predict LRE, cancer, or CVE in the short term.
Artifact reduction from metallic dental materials in T1‐weighted spin‐echo imaging at 3.0 tesla (2012)

The SEMAC technique can mitigate artifact caused by metallic dental materials for T1w-SE imaging.
Oncogenic transformation and experimental models of human cancer (2007)

Tumorigenesis occurs when cells undergo a series of genetic and epigenetic events that upset the balance of cell death, proliferation and differentiation. In a few cases, alterations in key regulatory steps have been identified, facilitating the design of rational cancer therapies. However, the karyotypic complexity exhibited by most solid tumors makes it challenging to identify the lesions underlying specific tumor phenotypes in most cancers. Work from many laboratories indicates that the acquisition of the tumorigenic phenotype requires several cooperating events and that a finite set of genetic alterations suffices to transform cells derived from numerous different lineages. Experimental models derived from the manipulation of oncogenes, tumor suppressor genes and telomerase provide useful platforms to delineate pathways involved in cell transformation, to connect specific cancer-associated mutations with particular cancer phenotypes and to discover and validate new targets for therapeutic development. Here we review the development of such experimental models and recent work combining such model systems with increasingly powerful genetic and chemical tools to identify and validate genes involved in malignant transformation.
The antiangiogenic agent linomide inhibits tumor necrosis factor-α secretion via inhibition of its synthesis (1996)

We have previously reported that linomide, a quinoline-3-carboxamide, has antitumor effects against prostatic cancers in vivo through its ability to inhibit tumor angiogenesis. Subsequently, we reported that linomide inhibits several steps in the process of angiogenesis, including direct effects on endothelial cell proliferation and their chemotactic migration and invasion. Besides these direct effects, linomide's antiangiogenic activity also involves indirect effects secondary to inhibition of tumor infiltration of macrophages and their ability to secrete the angiogenic factor tumor necrosis factor-alpha (TNF-alpha). The current studies were conducted to gain insight into the mechanism by which linomide inhibits macrophage TNF-alpha secretion. The virally transformed RAW 264.7 mouse macrophage cell line was used as a model system. Chronic in vitro exposure (7 days) to 81-650 microM linomide is cytostatic to RAW cells. Such chronic exposure to linomide significantly decreased (P < 0.05) RAW cells' baseline ability to secrete TNF-alpha and also their ability to up-regulate TNF-alpha secretion in response to lipopolysaccharide (LPS) challenge. Ribonuclease protection assays demonstrated that linomide's ability to inhibit baseline and LPS-challenged TNF-alpha secretion is not functioning at the mRNA level, because steady-state levels of TNF-alpha mRNA do not change in response to linomide. Linomide's ability to inhibit TNF-alpha secretion is not associated with an increase in cell-associated TNF-alpha levels. Immunoprecipitation experiments demonstrated that linomide did not inhibit the normal proteolytic processing of the initial 26 kDa plasma membrane-bound TNF-alpha to the secreted 17 kDa soluble form. These results demonstrate that linomide inhibits TNF-alpha secretion by inhibition of the synthesis of the TNF-alpha protein. Linomide's ability to inhibit TNF-alpha protein synthesis is not due to an inhibition of general protein synthesis or secretion and is not mediated via a change in cyclic adenosine monophosphate levels.
Scale-Up of Trisodium [(3β,5β,12α)-3-[[4(S)-4-[Bis[2-[bis[(carboxy-kO)methyl]amino-kN]ethyl]amino-kN]-4-(carboxy-kO)-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)], a Gd(III) Complex under Development As a Contrast Agent for MRI Coronary Angiography (2009)

Process chemistry involved in the discovery and development routes to trisodium [(3β,5β,12α)-3-[[4(S)-4-[bis[2-[bis[(carboxy-kO)methyl]amino-kN]ethyl]amino-kN]-4-(carboxy-kO)-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)] (B22956/1) starting from l-glutamic acid and (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid is described. The best process is based on seven chemical steps and overcomes difficult purification protocols. Such process has been successfully implemented to prepare multikilogram batches of the target compound in 20% overall yield from (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid.
A Transcriptional Profiling Study of CCAAT/Enhancer Binding Protein Targets Identifies Hepatocyte Nuclear Factor 3β as a Novel Tumor Suppressor in Lung Cancer (2004)

Abstract We showed previously that CCAAT/enhancer binding protein α (C/EBPα), a tissue-specific transcription factor, is a candidate tumor suppressor in lung cancer. In the present study, we have performed a transcriptional profiling study of C/EBPα target genes using an inducible cell line system. This study led to the identification of hepatocyte nuclear factor 3β (HNF3β), a transcription factor known to play a role in airway differentiation, as a downstream target of C/EBPα. We found down-regulation of HNF3β expression in a large proportion of lung cancer cell lines examined and identified two novel mutants of HNF3β, as well as hypermethylation of the HNF3β promoter. We also developed a tetracycline-inducible cell line model to study the cellular consequences of HNF3β expression. Conditional expression of HNF3β led to significant growth reduction, proliferation arrest, apoptosis, and loss of clonogenic ability, suggesting additionally that HNF3β is a novel tumor suppressor in lung cancer. This is the first study to show genetic abnormalities of lung-specific differentiation pathways in the development of lung cancer.
Abstract 3654: Targeting binding function-3 site on the androgen receptor to treat Enzalutamide-resistant prostate cancer (2015)

Abstract Interest in developing androgen receptor (AR) inhibitors with novel mechanism of action is on the rise since the commercial anti-androgens (including recently approved drug, Enzalutamide) face clinical limitations. The current therapies fail over a period of time because they all target mutation-prone hormone binding pocket on AR to which the receptor has already developed effective resistance mechanisms. Hence, there is a pressing need for novel therapeutics that inhibit the AR through alternative modes of action. Recent studies have identified a novel binding pocket on the surface of AR called binding function-3 (BF3) that is critical for the AR transcriptional activity. In order to develop promising drug-like candidates, we performed structural optimization of our lead AR BF3 inhibitor, followed by a series of experimental validation of the synthetic analogues. As a result, we have discovered a chemical series of quinoline as new lead BF3 inhibitors. One of the most potent inhibitors identified, VPC-13566, demonstrated an IC50 of 0.071μM in AR eGFP transcriptional assay. Confirming it as a true BF3 binder, VPC-13566 displaced Bag-1L peptide, a co-regulator protein that binds to AR BF3 pocket. Additionally, the Biolayer Interferometry assay detected direct reversible interactions between the AR ligand binding domain and the inhibitor. To confirm VPC-13566 binding to the BF3 pocket, a mutagenesis study was performed. Results with mutants F673E, E837A and N833W confirmed that compound did not show any binding to the protein compared with the wild type in a BLI assay. VPC-13566 demonstrated strong anti-proliferative activity against LNCaP and Enzalutamide-resistant prostate cancer cell lines (MR49F) whereas it did not affect the growth of AR independent PC3 cell line. It also reduced prostate specific antigen (PSA) in both LNCaP and MR49F and reduced expression of AR target genes, PSA and TMPRSS2. These findings suggest that VPC-13566 exhibits AR BF3 specific mechanism of action. Furthermore, VPC-13566 significantly reduced AR-dependent growth of tumors and PSA levels in LNCaP and MR49F xenograft models. Based on these outcomes, it can be anticipated that such drug prototypes will lay a foundation for the development of alternative or supplementary small-molecule therapies capable of combating PCa even in its drug resistant forms. Because the emergence of castration resistance is the lethal end stage of the disease, we anticipate that the proposed research will eventually have a substantial impact on patient survival. Citation Format: Ravi Shashi Nayana Munuganti, Mohamed DH Hassona, Eric Leblanc, Emma T. Guns, Paul S. Rennie, Artem Cherkasov. Targeting binding function-3 site on the androgen receptor to treat Enzalutamide-resistant prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3654. doi:10.1158/1538-7445.AM2015-3654
Distribution and Clinical Significance of Heparan Sulfate Proteoglycans in Ovarian Cancer (2004)

We report for the first time distinct patterns of expression of cell surface and extracellular matrix heparan sulfate proteoglycans in normal ovary compared with ovarian tumors. These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy.
Hypergraph models of biological networks to identify genes critical to pathogenic viral response (2021)

Background: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. Results: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. Conclusions: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.
Achieving optimal reverberation time in a room, using newly patented tuning tubes (2013)

The aging population has several acoustic requirements in order to optimize their ability to hear better, as well as feel better, in a room. First, there is the requirement that the reverberation time of the room must be reduced in order to assist in hearing. Secondly, there needs to be a lowering of the NC in order to increase the SNR. Increasing the SNR not only helps to assist in hearing, but also reduces some hearing aid problems. In addition to these two standard room requirements, there is also a need for the reduction of lower frequency sounds within a room, such as sounds typical of mechanical equipment. Recent data supports the fact that there is a correlation between certain diseases and low frequency intolerance. Since standard products used to absorb sound have a greater absorption in speech frequencies there is a need for products that have greater absorption in lower frequencies. Ideally these products should also be washable. This paper presents background on each of these requirements, as well as recommendations on methods to achieve these requirements.
Micrometer-Scale Grating Vertical Structure OSC Ammonia Gas Sensor with a PEDOT:PSS Coupling Layer Using the Current Spreading Effect to Achieve ppb-Regime Sensing Capability (2020)

Organic semiconductor (OSC) gas sensors have grown into a widely discussed technology because of the presence of nanoscale fabrication processes. Thanks to the rapid development of nanotechnology, the performance of the OSC gas sensor has been pushed to the peak of its own and now can be used for numerous biomedical and environmental monitoring purposes that require high-precision sensing capability. However, the sophisticated and nonstandard fabrication process of most of these sensors has become the major impediment on the way of commercialization. Here, we demonstrate a micrometer-scale structure with a coupling layer using the current spreading effect to further enhance the sensing performance. The high-conductivity material poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS PH1000) was used as the coupling layer to increase the device operational current. The sensor exhibits a remarkably enhanced operational current of the microampere level without sacrificing the ammonia sensing capability. The issues of the structural profile are discussed carefully, and the sensor was tested with human breath samples to demonstrate a promising result. With the most common micrometer-scale fabrication technology, a ppb-regime sensing capability has been achieved, and the result of this work gives us a cut-in point regarding the high-sensitivity OSC gas sensors.
Diagnosing mobile applications in the wild (2010)

There are a lot of applications that run on modern mobile operating systems. Inevitably, some of these applications fail in the hands of users. Diagnosing a failure to identify the culprit, or merely reproducing that failure in the lab is difficult. To get insight into this problem, we interviewed developers of five mobile applications and analyzed hundreds of trouble tickets. We find that support for diagnosing unexpected application behavior is lacking across major mobile platforms. Even when developers implement heavy-weight logging during controlled trials, they do not discover many dependencies that are then stressed in the wild. They are also not well-equipped to understand how to monitor the large number of dependencies without impacting the phone's limited resources such as CPU and battery. Based on these findings, we argue for three fundamental changes to failure reporting on mobile phones. The first is spatial spreading, which exploits the large number of phones in the field by spreading the monitoring work across them. The second is statistical inference, which builds a conditional distribution model between application behavior and its dependencies in the presence of partial information. The third is adaptive sampling, which dynamically varies what each phone monitors, to adapt to both the varying population of phones and what is being learned about each failure. We propose a system called MobiBug that combines these three techniques to simplify the task of diagnosing mobile applications.
Contrasting effects of FLIPL overexpression in human T cells on activation-induced cell death and cytokine production (2007)

There have been disparate findings about the role of FLIP in the survival of mouse T cells and human tumor cell lines. The role of cellular FLIP in human T cell activation and function needs to be clarified further. To study this role, we have overexpressed long transcript FLIP (FLIPL) in primary T cells, including self-antigen-reactive, melanoma-specific T cells. We found that FLIPL overexpression protects human T cells from activation-induced cell death and enhances their proliferative capacity but suppresses the ability of these cells to produce the proinflammatory cytokines IL-2 and IFN-gamma in response to CD3 or antigen-specific stimulation. The multiple effects of FLIPL indicate that this protein may influence T cell responses to antigenic stimulation.
Insulin levels in insulin resistance: phantom of the metabolic opera? (2006)

Insulin resistance is considered a core component in the pathophysiology of the metabolic syndrome. Some clinicians measure serum insulin concentrations in the mistaken belief that they can be used to diagnose insulin resistance. Serum insulin levels are poor measures of insulin resistance. Furthermore, there is no clinical benefit in measuring insulin resistance in clinical practice. Measurements of fasting serum insulin levels should be reserved for large population-based epidemiological studies, where they can provide valuable data on the relationship of insulin sensitivity to risk factors for diabetes and cardiovascular disease. Clinicians should shift from identifying "insulin resistance" to identifying risk factors, such as fasting glucose and lipid levels, hypertension and central obesity. These proven risk factors converge within the metabolic syndrome. Individuals "at risk" of diabetes and atherosclerotic cardiac disease can be identified simply and inexpensively, using classic clinical techniques, such as history-taking, physical examination, and very basic investigations.
Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis (2019)

Abstract We provide a single cell atlas of Idiopathic Pulmonary Fibrosis (IPF), a fatal interstitial lung disease, focusing on resident lung cell populations. By profiling 312,928 cells from 32 IPF, 29 healthy control and 18 chronic obstructive pulmonary disease (COPD) lungs, we demonstrate that IPF is characterized by changes in discrete subpopulations of cells in the three major parenchymal compartments: the epithelium, endothelium and stroma. Among epithelial cells, we identify a novel population of IPF enriched aberrant basaloid cells that co-express basal epithelial markers, mesenchymal markers, senescence markers, developmental transcription factors and are located at the edge of myofibroblast foci in the IPF lung. Among vascular endothelial cells in the in IPF lung parenchyma we identify an expanded cell population transcriptomically identical to vascular endothelial cells normally restricted to the bronchial circulation. We confirm the presence of both populations by immunohistochemistry and independent datasets. Among stromal cells we identify fibroblasts and myofibroblasts in both control and IPF lungs and leverage manifold-based algorithms diffusion maps and diffusion pseudotime to infer the origins of the activated IPF myofibroblast. Our work provides a comprehensive catalogue of the aberrant cellular transcriptional programs in IPF, demonstrates a new framework for analyzing complex disease with scRNAseq, and provides the largest lung disease single-cell atlas to date.