gebhart/patrepeval huggingface dataset:
trans-2,3-Dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline:  Synthesis, Resolution, and Preliminary Pharmacological Characterization of a New Dopamine D1Receptor Full Agonist (2006)

We report the synthesis of trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline hydrochloride 6 and the resolution of its enantiomers. This new compound is an oxygen bioisostere of the potent dopamine D1-selective full agonist dihydrexidine. The initial synthetic approach involved, as a key step, a Suzuki coupling between a chromene triflate and a boronate ester, followed by isoquinoline formation and reduction of the resulting isoquinoline. Subsequently, a more efficient route was developed that involved conjugate addition of an aryl Grignard reagent to a 2-nitrochromene. The title compound possessed high affinity (Ki=20-30 nM) for porcine D1-like receptors in native striatal tissue and full intrinsic activity at cloned human dopamine D1 receptors but had much lower affinity at dopamine D2-like receptors (Ki=3000 nM). The binding and functional properties of this compound illustrate again the utility of constructing dopamine D1 agonist ligands around the beta-phenyldopamine pharmacophore template.
Rab5-family guanine nucleotide exchange factors bind retromer and promote its recruitment to endosomes (2015)

The retromer complex facilitates the sorting of integral membrane proteins from the endosome to the late Golgi. In mammalian cells, the efficient recruitment of retromer to endosomes requires the lipid phosphatidylinositol 3-phosphate (PI3P) as well as Rab5 and Rab7 GTPases. However, in yeast, the role of Rabs in recruiting retromer to endosomes is less clear. We identified novel physical interactions between retromer and the Saccharomyces cerevisiae VPS9-domain Rab5-family guanine nucleotide exchange factors (GEFs) Muk1 and Vps9. Furthermore, we identified a new yeast VPS9 domain-containing protein, VARP-like 1 (Vrl1), which is related to the human VARP protein. All three VPS9 domain-containing proteins show localization to endosomes, and the presence of any one of them is necessary for the endosomal recruitment of retromer. We find that expression of an active VPS9-domain protein is required for correct localization of the phosphatidylinositol 3-kinase Vps34 and the production of endosomal PI3P. These results suggest that VPS9 GEFs promote retromer recruitment by establishing PI3P-enriched domains at the endosomal membrane. The interaction of retromer with distinct VPS9 GEFs could thus link GEF-dependent regulatory inputs to the temporal or spatial coordination of retromer assembly or function.
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation (2016)

This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.
The role of patch review in software evolution (2009)

Patch review is the basic mechanism for validating the design and implementation of patches and maintaining consistency in some commercial and Free/Libre/Open Source Software (FLOSS) projects. We examine the inner-workings of the development process of the successful and mature Mozilla foundation and highlight how different parties involved affect and steer the process. Although reviewers are the primary actors in the patch review process, success in the process can only be achieved if the community supports reviewers adequately. Peer developers play the supporting role by offering insight and ideas that help create more quality patches. Moreover, they reduce the huge patch backlog reviewers have to clear by identifying and eliminating immature patches.
Testing Ada fixed point operations. (1997)

Since errors have been noted in Ada 83 compilers in handling fixed point operations, a study has been undertaken to ensure such errors can be located easily. The report describes an automatic test case generator written in Prolog. Results of applying the generator to three Ada compilers are given, none of which were entirely satisfactory.
Optical and acoustical monitoring of femtosecond laser-induced intracellular contrast agents: initial cell culture studies (2005)

Acoustical monitoring of laser-induced optical breakdown can be used as an important tool for diagnostics and therapeutics in living cells. Laser-induced intracellular microbubbles provide measurable contrast when detected with high-frequency ultrasound, and the bioeffects of these bubbles can be controlled to be within two distinct regimes. In the nondestructive regime, a single, transient, detectable bubble can be generated within a cell, without affecting its viability. In the destructive regime, the induced photodisruption can kill a target cell. To generate and monitor this range of effects in real time, we have developed a system integrating a femtosecond pulsed laser source with optical and acoustical microscopy. Experiments were performed on monolayers of Chinese hamster ovary cells. A Ti:Sapphire laser (793 nm wavelength, 100 fs pulse duration) was pulsed at 3.8 kHz and tightly focused to a 1 &mu;m spot within each cell, and a high-frequency (50 MHz) ultrasonic transducer monitored the generated bubble with continuous pulse-echo recordings. The photodisruption was also observed with bright field optical microscopy, and cell viability was assessed after laser exposure using a colorimetric live/dead stain. By controlling laser pulse fluence, exposure duration, and the intracellular location of the laser focus, either nondestructive or destructive bubbles could be generated.
Neutralizing Epitopes in the Membrane-Proximal External Region of HIV-1 gp41 Are Influenced by the Transmembrane Domain and the Plasma Membrane (2012)

Failure to elicit broadly neutralizing (bNt) antibodies (Abs) against the membrane-proximal external region of HIV-1 gp41 (MPER) reflects the difficulty of mimicking its neutralization-competent structure (NCS). Here, we analyzed MPER antigenicity in the context of the plasma membrane and identified a role for the gp41 transmembrane domain (TM) in exposing the epitopes of three bNt monoclonal Abs (MAbs) (2F5, 4E10, and Z13e1). We transiently expressed DNA constructs encoding gp41 ectodomain fragments fused to either the TM of the platelet-derived growth factor receptor (PDGFR) or the gp41 TM and cytoplasmic tail domain (CT). Constructs encoding the MPER tethered to the gp41 TM followed by a 27-residue CT fragment (MPER-TM1) produced optimal MAb binding. Critical binding residues for the three Nt MAbs were identified using a panel of 24 MPER-TM1 mutants bearing single amino acid substitutions in the MPER; many were previously shown to affect MAb-mediated viral neutralization. Moreover, non-Nt mutants of MAbs 2F5 and 4E10 exhibited a reduction in binding to MPER-TM1 and yet maintained binding to synthetic MPER peptides, indicating that MPER-TM1 better approximates the MPER NCS than peptides. Replacement of the gp41 TM and CT of MPER-TM1 with the PDGFR TM reduced binding by MAb 4E10, but not 2F5, indicating that the gp41 TM plays a pivotal role in orienting the 4E10 epitope, and more globally, in affecting MPER exposure.
The Role of Associative Cortices and Hippocampus during Movement Perturbations (2017)

Although motor control has been extensively studied, most research involving neural recordings has focused on primary motor cortex, pre-motor cortex, supplementary motor area, and cerebellum. These regions are involved during normal movements, however, associative cortices and hippocampus are also likely involved during perturbed movements as one must detect the unexpected disturbance, inhibit the previous motor plan, and create a new plan to compensate. Minimal data is available on these brain regions during such "robust" movements. Here, epileptic patients implanted with intracerebral electrodes performed reaching movements while experiencing occasional unexpected force perturbations allowing study of the fronto-parietal, limbic and hippocampal network at unprecedented high spatial, and temporal scales. Areas including orbitofrontal cortex (OFC) and hippocampus showed increased activation during perturbed trials. These results, coupled with a visual novelty control task, suggest the hippocampal MTL-P300 novelty response is modality independent, and that the OFC is involved in modifying motor plans during robust movement.
Effect of Phosphate, Sulfate, Arsenate, and Pyrite on Surface Transformations and Chemical Retention of Gold Nanoparticles (Au–NPs) in Partially Saturated Soil Columns (2019)

The understanding of engineered nanoparticle (ENP) fate and transport in soil-water environments is important for the evaluation of potential risks of ENPs to the ecosystem and human health. The effects of pyrite grains and three types of oxyanions-sulfate, phosphate, and arsenate-on the retention of citrate-coated gold nanoparticles (citrate-Au-NPs) were studied in partially saturated soil column experiments. The mobility of Au-NP was found to be in the order: Au-NP-sulfide (originating from pyrite) > Au-NP-sulfate > citrate-Au-NP > Au-NP-arsenate > Au-NP-phosphate. Chemical retention mechanisms, including hydrogen bonding and calcium bridging, are proposed and discussed. The retention of Au-NPs in soil columns increases with the increased ability of transformed Au-NP surfaces to create strong hydrogen bonding through adsorbed oxyanions with soil surfaces. Oxyanions were also found to reduce aggregation and aggregate size of Au-NPs upon interaction with Ca<sup>2+</sup> solution. While the effects of cationic substances on ENP transport and stability have been studied frequently, the results here demonstrate that anionic substances have a substantial effect on Au-NP transport and stability. Furthermore, this study highlights the importance of examining ENPs under environmentally relevant condition, and the significant effect of ENP transformations on their mobility in soils.
Chemoprevention of upper aerodigestive tract cancers: A report of the third upper aerodigestive cancer task force workshop (1990)

The National Cancer Institute Organ Systems Program-sponsored Upper Aerodigestive Cancer Task Force workshops are specifically designed to enhance interactions between basic science and clinical investigators and between academic institutions and the community, and ultimately will contribute to more expeditious clinical advances. The third workshop in this series focused on the rapidly expanding area of chemoprevention of upper aerodigestive epithelial cancers. The first two sessions were devoted to discussion of in vitro and animal-model data documenting the multistep process of squamous differentiation and carcinogenesis, associated molecular and biochemical alterations, and modulation by chemopreventive agents. Animal-model studies have identified several promising chemopreventive agents and synergistic combinations for clinical trial. The last two sessions reviewed nutritional epidemiology, major methodologic issues of large intervention studies, and the novel concept of biologic markers as intermediate endpoints for chemoprevention trials.
The Fixation of Hydrocyanic Acid by a Psychrophilic Basidiomycete (1966)

α-Aminopropionitrile-1-14C was identified in cultures of a psychrophilic basidiomycete fed H14CN. The results of the study suggest that this compound is a precursor of alanine. This suggestion is supported by experiments with H14C15N as well as by a time course evaluation of 14C labeling in α-aminopropionitrile and alanine in fungal mats. Evidence is presented for the presence of a nitrile synthetase in cell-free extracts of this fungus. The enzyme catalyzes the condensation reaction of acetaldehyde, ammonia, and hydrogen cyanide to form α-aminopropionitrile.
Full Waveform Inversion for Reservoir Monitoring - Pushing the Limits of Subsurface Resolution (2017)

Fluid movement in the subsurface and the associated changes in saturation translate into changes of the subsurface elastic parameters. Stress changes, whether due to fluid extraction/injection or deformation such as slips on preexisting faults, affect the elastic parameters as well. Detecting and inverting the imprint of changing subsurface elastic parameters on seismic data lies at the heart of time-lapse seismic imaging for reservoir monitoring. In this work we demonstrate that the recently proposed technique of simultaneous time-lapse full-waveform inversion with a model-difference regularization can be used to extract high-resolution information on magnitude and location of subsurface velocity and stress anomalies, potentially providing valuable input for reservoir monitoring and assessment of geohazards.
Management of chronic hepatitis C. (2007)

Chronic hepatitis C is a major cause of cirrhosis and primary liver cancer (hepatocellular carcinoma). Decompensated cirrhosis or hepatocellular carcinoma secondary to hepatitis C is the first cause of liver transplantation in Europe and in the United States. The prognosis of chronic hepatitis C depends on the progression of fibrosis which determines the risk of developing cirrhosis and its complications. Knowledge of the natural history and the factors associated with the progression of fibrosis is essential for the patient's management. The risk of the progression of fibrosis is difficult to predict in one particular patient. Liver biopsy remains the best test to evaluate the severity of fibrosis, determine its prognosis and discuss the therapeutic options. At present, in a patient with hepatitis C, combined therapy associating pegylated alpha interferon and ribavirin results in a sustained response in approximately 55% of cases. Based on existing results, the sustained virological response with this treatment option appears to be long lasting, to be associated with a histological benefit and is also probably associated with a reduction in the risk of cirrhosis and hepatocellular carcinoma. The management of hepatitis C virus infections must include better knowledge of the natural history of the disease and existing available antiviral treatments (pegylated interferon and ribavirin) as well as in depth knowledge of the aims of treatment, the results obtained, the predictive factors of response and side effects. With close follow-up, doses can be rapidly modified and erythropoietin more frequently administered; new molecules may also be developed in this context. This paper will discuss the natural history, the factors associated with the progression of fibrosis, the predictive factors of response to treatment, and existing and future treatments for hepatitis C.
Superconductivity at 38 K in an electrochemical interface between ionic liquid and Fe(Se0.8Te0.2) on various substrates (2018)

Superconducting FeSe0.8Te0.2 thin films on SrTiO3, LaAlO3 and CaF2 substrates were electrochemically etched in an ionic liquid DEME-TFSI electrolyte with a gate bias of 5 V. Superconductivity at 38 K was commonly observed on all substrates after etching the films with a thickness above 30 nm, in spite of different Tc of 8 K, 12 K and 19 K before the etching on SrTiO3, LaAlO3 and CaF2 substrates, respectively. Tc returned to the original value by removing the gate bias. The Tc enhancement on the thick film indicates no relationship between the Tc enhancement and any interface effects between the film and the substrate. The sheet resistance and the Hall coefficient of the surface conducting layer were estimated from the gate bias dependence of the transport properties. The sheet resistance of the surface conducting layer of the films on LaAlO3 and CaF2 showed an identical temperature dependence, and the Hall coefficient is almost temperature independent and -0.05 to -0.2 m2/C, corresponding to 4-17 electrons per one FeSe0.8Te0.2 unit cell area in two dimension. These common transport properties on various substrates suggest that the superconductivity at 38 K appeared in the surface conducting layer produced by electrochemical reaction between the surface of the FeSe0.8Te0.2 thin film and the ionic liquid electrolyte.
Acoustic modes of the phonon dispersion relation ofNbDxalloys (1975)

The acoustic modes of the phonon dispersion relation in Nb, Nb${\mathrm{D}}_{0.15}$, and Nb${\mathrm{D}}_{0.45}$ have been measured at 473 K for phonons with wave vectors along the [100], [110], and [111] axes by coherent neutron scattering. The observed neutron groups for both alloys were well defined, with little or no apparent broadening. The results are compared to similar data for Nb-Mo alloys and with previous lattice-dynamics results for Pd${\mathrm{D}}_{0.63}$. This comparison shows that despite differences in detail, the general features of the dispersion relations of $\mathrm{Nb}{\mathrm{D}}_{x}$ and Nb-Mo are similar after allowing for the differences in lattice parameters for the two alloys. The measured dispersion curves and derived phonon frequency distributions for the Nb-D alloys are quite different from the analogous results for Pd${\mathrm{D}}_{0.63}$ in that the average acoustic phonon frequencies increase with increasing deuterium concentration and lattice parameter.
Path Selection to Minimize Energy Consumption of an Electric Vehicle using Synthetic Speed Profiles and Predictive Terminal Energy (2017)

Manufacturers of passenger vehicles are experiencing increased pressure from consumers and legislators due to the impact of transportation on the environment. Automotive manufacturers are responding by designing more sustainable forms of transportation through a variety of efforts, including increased vehicle efficiency and the electrification of vehicle powertrains (plug in hybrid electric vehicles (PHEV) and battery electric vehicles (BEV)). An additional method for reducing the environmental impact of personal transport is eco-routing, a methodology which selects routes on the basis of energy consumption. Standard navigation systems offer route alternatives between a user clarified origin and destination when there are multiple paths available. These alternatives are commonly weighted on the basis of minimizing either total travel time (TTT) or trip distance. Eco-routing offers an alternative criterion – minimizing route energy consumption. Calculation of the energy consumption of a route necessitates the creation of a velocity profile which models how the route will be driven and a powertrain model which relates energy consumption to the constructed velocity profile. Existing research efforts related to both of these aspects typically require complex analysis and proprietary vehicle properties. A new approach to weighting the energy consumption of different routes is presented within this paper. The process of synthesizing velocity profiles is an improvement upon simpler models while requiring fewer variables as compared to more complex models. A single input, the maximum acceleration, is required to tune driver aggressiveness throughout an entire route. Additionally, powertrain results are simplified through the application of a new parameter, predictive terminal energy. The parameter uses only glider properties as inputs, as compared to dedicated powertrain models which use proprietary vehicle information as inputs which are not readily available from manufacturers. Application of this research reduces computation time and increases the number of vehicles for which this analysis can be applied. An example routing scenario is presented, demonstrating the capability of the velocity synthesis and predictive terminal energy methodologies.
Data from EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;DNA methylation alterations have emerged as front-runners in cell-free DNA (cfDNA) biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers.&lt;/p&gt;Experimental Design:&lt;p&gt;Herein, we performed a genome-wide DNA methylation analysis of multiple GI cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1,781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMR) between individual GI cancers and adjacent normal, as well as across GI cancers. We next prioritized a list of 67,832 tissue DMRs by incorporating all significant DMRs across various GI cancers to design a custom, targeted bisulfite sequencing platform. We subsequently validated these tissue-specific DMRs in 300 cfDNA specimens and applied machine learning algorithms to develop three distinct categories of DMR panels&lt;/p&gt;Results:&lt;p&gt;We identified three distinct DMR panels: (i) cancer-specific biomarker panels with AUC values of 0.98 (colorectal cancer), 0.98 (hepatocellular carcinoma), 0.94 (esophageal squamous cell carcinoma), 0.90 (gastric cancer), 0.90 (esophageal adenocarcinoma), and 0.85 (pancreatic ductal adenocarcinoma); (ii) a pan-GI panel that detected all GI cancers with an AUC of 0.88; and (iii) a multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85–0.95 for most GI cancers.&lt;/p&gt;Conclusions:&lt;p&gt;Using a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.&lt;/p&gt;&lt;/div&gt;
Transcellular progression of infection threads in Medicago truncatula roots is controlled by locally confined cell wall modifications (2022)

Abstract The root nodule symbiosis with its global impact on nitrogen fertilization of soils is characterized by an intracellular colonization of legume roots by rhizo-bacteria. While the symbionts are initially taken up by morphologically adapted root hairs, rhizobia persistently progress within a membrane-confined infection thread through several root cortical and later nodular cell layers. Throughout this transcellular passaging, rhizobia have to repeatedly pass host plasma membranes and cell walls. Here, we genetically dissected this essential process and describe the concerted action of the symbiosis-specific pectin methyl esterase SyPME and the pectate lyase NPL at the infection thread and transcellular passage sites. Their coordinated function mediates spatially confined pectin alterations in the cell-cell interface that result in the establishment of an apoplastic compartment where bacteria are temporarily released into and taken up from the subjacent cell. This process allows successful intracellular progression of infection threads through the entire root cortical tissue.