gebhart/patrepeval huggingface dataset:
Melanoma-mediated dissolution of extracellular matrix: contribution of urokinase-dependent and metalloproteinase-dependent proteolytic pathways. (1993)

Constitutive overexpression of both urokinase and matrix metalloproteinase (MMP) activity is frequently observed in individual malignant tumors. In this study we describe the combined contribution of these distinct enzyme systems to the invasive phenotype of a highly metastatic human melanoma cell line (M24met). M24met cells were found to secrete a spectrum of MMPs, including interstitial collagenase, type IV collagenases (M(r) 92,000 and 72,000 progelatinases), and stromelysin. Urokinase, but not tissue-type plasminogen activator, was detected in M24met-conditioned media and on cell surfaces. The contribution of these enzymes to extracellular matrix dissolution was determined by exploiting specific inhibitors, namely tissue inhibitor of the metalloproteinases-2 and plasminogen activator inhibitor-2. Due to the coexpression of urokinase and MMP-dependent activity, M24met cells were observed to degrade multiple components of the extracellular matrix and to significantly degrade both interstitial and basement membrane matrices. Urokinase-dependent removal of matrix glycoprotein was observed to precede MMP-dependent collagenolysis as a prerequisite rate-limiting step. We present evidence which suggests that this temporal relationship is imposed by the structural architecture of the matrix such that matrix glycoprotein serves to protect associated collagen from MMP-dependent degradation. In addition to mediating significant collagenolysis, MMP activity was further implicated in the dissolution of matrix tropoelastin. Urokinase/plasmin activity was not found to be required for MMP-zymogen activation.
Potassium Channel Distribution, Clustering, and Function in Remyelinating Rat Axons (1998)

The K+ channel alpha-subunits Kv1.1 and Kv1.2 and the cytoplasmic beta-subunit Kvbeta2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination by intraneural injection of lysolecithin, and during remyelination, the subcellular distributions of Kv1.1, Kv1.2, and Kvbeta2 were reorganized. At 6 d postinjection (dpi), axons were stripped of myelin, and K+ channels were found to be dispersed across zones that extended into both nodal and internodal regions; a few days later they were undetectable. By 10 dpi, remyelination was underway, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ranvier. By 14 dpi, K+ channels were detected but were in the nodal gap between Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kvbeta2, which precisely colocalized. However, this nodal distribution was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that overlapped with Na+ channel immunoreactivity. Inhibition of Schwann cell proliferation delayed both remyelination and the development of the K+ channel distributions described. Conduction studies indicate that neither 4-aminopyridine (4-AP) nor tetraethylammonium alters normal nerve conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of this effect matched closely the nodal presence of these voltage-dependent K+ channels. Our results suggest that K+ channels may have a significant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.
A surfactant-mediated relaxed Si0.5Ge0.5 graded layer with a very low threading dislocation density and smooth surface (1999)

A method to grow a relaxed Si0.5Ge0.5 graded layer with a very smooth surface and a very low threading dislocation density using solid-source molecular-beam epitaxy is reported. This method included the use of Sb as a surfactant for the growth of a 2 μm compositionally graded SiGe buffer with the Ge concentration linearly graded from 0% to 50% followed by a 0.3 μm constant Si0.5Ge0.5 layer. The substrate temperature was kept at 510 °C during the growth. Both Raman scattering and x-ray diffraction were used to determine the Ge mole fraction and the degree of strain relaxation. Both x-ray reflectivity and atomic force microscopy measurements show a surface root mean square roughness of only 20 Å. The threading dislocation density was determined to be as low as 1.5×104 cm−2 as obtained by the Schimmel etch method. This study shows that the use of a Sb surfactant and low temperature growth is an effective method to fabricate high-quality graded buffer layers.
Discovery of Benzo[cd]indol-2(1H)-ones as Potent and Specific BET Bromodomain Inhibitors: Structure-Based Virtual Screening, Optimization, and Biological Evaluation (2016)

The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one containing compounds as a new class of BET bromodomain inhibitors, starting from structure-based virtual screening (SBVS). Through structure-based optimization, potent compounds were obtained with significantly improved activity. The two most potent compounds bind to the BRD4 bromodomain, with Kd values of 124 and 137 nM. Selected compounds exhibited high selectivity over other non-BET subfamily members. Notably, compound 85 demonstrated a reasonable antiproliferation effect on MV4;11 leukemia cells and exhibited a good pharmacokinetic profile with high oral bioavailability (75.8%) and moderate half-life (T1/2 = 3.95 h). The resulting lead molecule 85 represents a new, potent, and selective class of BET bromodomain inhibitors for the development of therapeutics to treat cancer and inflammatory diseases.
Narrowband, high power light from diode lasers (1989)

We have used a 100-mW cw laser diode array to amplify the light from a low power, single stripe diode laser (both lasers commercially available). The input light was spectrally narrowed and frequency stabilized to <300 kHz using optical feedback from a Fabry-Perot cavity, and the amplified beam had the same spectral characteristics. Also, the ~90-mW amplified beam had a single diffraction-limited spatial mode corresponding to the full 100-microm width of the array, indicating that all its stripes were coherent. When viewing the output of the free-running laser array, we observe that the input light causes its output spectrum and spatial distribution to be dramatically narrowed. We have tested a simple quantitative model of this process.
Current Disease-Modifying Therapies in Multiple Sclerosis (2003)

In recent years, the usefulness of interferon beta and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis (RRMS) has been established. Interferon beta has also been shown to be efficacious in secondary-progressive multiple sclerosis (SPMS) as well as in patients with isolated syndromes at risk to develop clinically definite multiple sclerosis (MS). Mitoxantrone is another disease-modifying drug that is available for SPMS and severe cases of RRMS. The clinical utility of disease-modifying agents in MS will be reviewed with respect to the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available. Symptomatic therapies will not be considered.
MicroRNAs in Common Human Diseases (2012)

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that have attracted tremendous attention from the biological and biomedical research communities over the past decade. With over 1900 miRNAs discovered in humans to date, many of them have already been implicated in common human disorders. Facilitated by high-throughput genomics and bioinformatics in conjunction with traditional molecular biology techniques and animal models, miRNA research is now positioned to make the transition from laboratories to clinics to deliver profound benefits to public health. Herein, we overview the progress of miRNA research related to human diseases, as well as the potential for miRNA to becoming the next generation of diagnostics and therapeutics.
From CO Oxidation to CO2 Activation:  An Unexpected Catalytic Activity of Polymer-Supported Nanogold (2005)

A simple, clean, safe, and reproducible catalyst system, polymer-supported nanogold, was successfully developed for the fixation of CO2 to cyclic carbonate and for the carbonylation of amines to disubstituted ureas with unprecedented catalytic activity (TOF > 50 000 mol/mol/h and TOFP approximately 3000 mol/mol/h, respectively). To the best of our knowledge, it was the first to report that nanogold catalysts have exclusive catalytic activity for activation of carbon dioxide, and that the catalytic activity of the polymer-immobilized nanogold catalysts could be controlled by the particle size of the nanogold.
The Pickup Problem: Consumers' Locational Preferences in Flow Interception (2009)

This article addresses the pickup problem , wherein patrons briefly interrupt their predetermined journeys to obtain a simple good, such as fast food or a video, and then resume their journeys. This is a problem from the class known as the flow‐interception location problems. Traditional flow‐interception location models (FILMs) are used to select service locations such that the intercepted flows are maximized. In these traditional models, only flow quantities are considered; these models do not consider where a pickup is made in a journey. However, in the real world, consumers often wish to obtain a product or service at or near a specific location along their trips. The pickup model (PUP) proposed here considers consumers' locational preferences, providing a much broader, more realistic approach than FILM (a special case of PUP) to problems in the private and public sectors. By considering which patrons are served where, PUP transforms the FILM into a flow‐interception location‐allocation model, providing a fruitful garden for further research. Geographic information systems and optimization engines are integrated to investigate the PUP model in real‐world transportation systems. Reported findings demonstrate that the optimal locations identified by traditional models arise solely from network flow structure, whereas the optimal locations identified by PUP result from trade‐offs between network flow structure and the importance of proximity to preferred locations. One important discovery is that PUP solutions are superior to those of traditional FILMs if consumers have locational preferences. Up‐to‐date, real‐world transportation networks provide a realistic test‐bed for this and other models of the flow‐interception type.
Characterization of the major protein-tyrosine-phosphatases of human placenta. (1988)

In the preceding article (Tonks, N. K., Diltz, C. D., and Fischer, E. H. (1988) J. Biol. Chem. 263, 6722-6730), the purification of the major protein-tyrosine-phosphatases from human placenta, some to apparent homogeneity, was described. This report compares the characteristics of these enzymes and clearly identifies at least two distinct protein-tyrosine-phosphatase catalytic subunits. All were absolutely specific for phosphotyrosyl residues and showed no activity on any of the phosphoseryl/phosphothreonyl-containing proteins tested; they exhibited a high affinity for substrate with Km values in the submicromolar range. All were absolutely dependent on sulfhydryl compounds and appeared to contain at least one highly reactive cysteinyl residue essential for activity. Subtypes 1A and 1B could be distinguished by their response to polyanionic and polycationic compounds. The 1B enzymes were activated by EDTA, spermine, spermidine, and myelin basic protein to a greater extent than the 1A subtypes. Furthermore, they were inhibited by approximately 2 orders of magnitude lower concentrations of heparin (IC50 approximately 20 nM) and 1:1 or 4:1 poly (glutamate/tyrosine) (IC50 approximately 50 nM) than the 1A subtypes. Surprisingly, inhibition by the glutamate/tyrosine copolymers was strictly noncompetitive. Peptide mapping following digestion with Achromobacter protease I or Staphylococcus aureus V8 protease supported the view that, whereas protein-tyrosine-phosphatase subtypes 1A and 1B are different, their soluble and particulate counterparts are closely related structurally and are distinct from serine/threonine phosphatases 1 and 2A.
Gaussian-based edge-detection methods-a survey (2002)

The Gaussian filter has been used extensively in image processing and computer vision for many years. We discuss the various features of this operator that make it the filter of choice in the area of edge detection. Despite these desirable features of the Gaussian filter, edge detection algorithms which use it suffer from many problems. We review several linear and nonlinear Gaussian-based edge detection methods.
Unexpected crucial role of residue 225 in serine proteases (1999)

Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr in more than 95% of nearly 300 available sequences. Proteases with Y225 (like some blood coagulation and complement factors) are almost exclusively found in vertebrates, whereas proteases with P225 (like degradative enzymes) are present from bacteria to human. Saturation mutagenesis of Y225 in thrombin shows that residue 225 affects ligand recognition up to 60,000-fold. With the exception of Tyr and Phe, all residues are associated with comparable or greatly reduced catalytic activity relative to Pro. The crystal structures of three mutants that differ widely in catalytic activity (Y225F, Y225P, and Y225I) show that although residue 225 makes no contact with substrate, it drastically influences the shape of the water channel around the primary specificity site. The activity profiles obtained for thrombin also suggest that the conversion of Pro to Tyr or Phe documented in the vertebrates occurred through Ser and was driven by a significant gain (up to 50-fold) in catalytic activity. In fact, Ser and Phe are documented in 4% of serine proteases, which together with Pro and Tyr account for almost the entire distribution of residues at position 225. The unexpected crucial role of residue 225 in serine proteases explains the evolutionary selection of residues at this position and shows that the structural determinants of protease activity and specificity are more complex than currently believed. These findings have broad implications in the rational design of enzymes with enhanced catalytic properties.
Catechol-Grafted Poly(ethylene glycol) for PEGylation on Versatile Substrates (2010)

We report on catechol-grafted poly(ethylene) glycol (PEG-g-catechol) for the preparation of nonfouling surfaces on versatile substrates including adhesion-resistant PTFE. PEG-g-catechol was prepared by the step-growth polymerization of PEO to which dopamine, a mussel-derived adhesive molecule, was conjugated. The immersion of substrates into an aqueous solution of PEG-g-catechol resulted in robust PEGylation on versatile surfaces of noble metals, oxides, and synthetic polymers. Surface PEGylation was unambiguously confirmed by various surface analytical tools such as ellipsometry, goniometry, infrared spectroscopy, and X-ray photoelectron spectroscopy. Contrary to existing PEG derivatives that are difficult-to-modify synthetic polymer surfaces, PEG-g-catechol can be considered to be a new class of PEGs for the facile surface PEGylation of various types of surfaces.
Noncovalent Functionalization of Multiwalled Carbon Nanotubes by Anionic Polymer Poly(Sodium 4‐Styrenesulfonate) in Water (2008)

We have found that polymer poly (sodium 4‐styrenesulfonate) (PSS) is a facile and effective polymer to assist in the dispersion of MWCNTs in aqueous solutions. With the increase of the concentration of PSS solutions, the dispersibility of MWCNTs in PSS solution increases. Cast films of MWCNTs/PSS (2 wt.%) on GC electrode show a typical redox couple at scan rate of 1 V/s in phosphate buffer solution, indicating good electrical conductivity.
Quantifying and Recognizing Human Movement Patterns From Monocular Video Images—Part II: Applications to Biometrics (2004)

Biometric authentication of gait, anthropometric data, human activities, and movement disorders are presented in this paper using the continuous human movement recognition (CHMR) framework introduced in Part I. A novel biometric authentication of anthropometric data is presented based on the realization that no one is average-sized in as many as ten dimensions. These body part dimensions are quantified using the CHMR body model. Gait signatures are then evaluated using motion vectors, temporally segmented by gait dynemes, and projected into a gait space for an eigengait-based biometric authentication. Left-right asymmetry of gait is also evaluated using robust CHMR left-right labeling of gait strides. Accuracy of the gait signature is further enhanced by incorporating the knee-hip angle-angle relationship popular in biomechanics gait research, together with other gait parameters. These gait and anthropometric biometrics are fused to further improve accuracy. The next biometric identifies human activities which require a robust segmentation of the many skills encompassed. For this reason, the CHMR activity model is used to identify various activities from making coffee to using a computer. Finally, human movement disorders were evaluated by studying patients with dopa-responsive Parkinsonism and age-matched normals who were videotaped during several gait cycles to determine a robust metric for classifying movement disorders. The results suggest that the CHMR system enabled successful biometric authentication of anthropometric data, gait signatures, human activities, and movement disorders.
Three-Dimensional Computerized Reconstruction Illustration of Incremental Articular Cartilage Thinning (1997)

Incremental thinning of articular cartilage can be tracked qualitatively and quantitatively using 3-D computerized reconstructions and 2-D MR images. Errors associated with the quantitative measurements can be attributed to limitations of measurement methods and intrinsic limitation of MR resolution.
The use ofACORNin solving a 39.5 kDa macromolecule with 1.9 Å resolution laboratory source data (2004)

Data from the alkaline cellulase apo form were collected at a resolution of 1.9 A using an in-house X-ray source (Cu K alpha). By using different fragments of helices from the model solved by macromolecular crystallographic means, the direct-methods program ACORN was used to arrive at the complete model. Attempts have been made to use various percentages of input phasing information from these helices. The minimum input phasing required in feeding the fragments was about 14% of the whole structure. The phases obtained from ACORN were of superb quality, allowing automated model building to be carried out using ARP/wARP. Minimal manual model building was required and the structure determination was completed using the maximum-likelihood refinement program REFMAC. The whole process, starting from the running of ACORN and ending with the refined model, took nearly 15 h of CPU time using a Pentium III PC.
Multidentate Zwitterionic Ligands Provide Compact and Highly Biocompatible Quantum Dots (2013)

Hydrophilic functional semiconductor nanocrystals that are also compact provide greatly promising platforms for use in bioinspired applications and are thus highly needed. To address this, we designed a set of metal coordinating ligands where we combined two lipoic acid groups, bis(LA)-ZW, (as a multicoordinating anchor) with a zwitterion group for water compatibility. We further combined this ligand design with a new photoligation strategy, which relies on optical means instead of chemical reduction of the lipoic acid, to promote the transfer of CdSe-ZnS QDs to buffer media. In particular, we found that the QDs photoligated with this zwitterion-terminated bis(lipoic) acid exhibit great colloidal stability over a wide range of pHs, to an excess of electrolytes, and in the presence of growth media and reducing agents, in addition to preserving their optical and spectroscopic properties. These QDs are also stable at nanomolar concentrations and under ambient conditions (room temperature and white light exposure), a very promising property for fluorescent labeling in biology. In addition, the compact ligands permitted metal-histidine self-assembly between QDs photoligated with bis(LA)-ZW and two different His-tagged proteins, maltose binding protein and fluorescent mCherry protein. The remarkable stability of QDs capped with these multicoordinating and compact ligands over a broad range of conditions and at very small concentrations, combined with the compatibility with metal-histidine conjugation, could be very useful for a variety of applications, ranging from protein tracking and ligand-receptor binding to intracellular sensing using energy transfer interactions.
Energetics of syntrophic cooperation in methanogenic degradation (1997)

Fatty acids and alcohols are key intermediates in the methanogenic degradation of organic matter, e.g., in anaerobic sewage sludge digestors or freshwater lake sediments. They are produced by classical fermenting bacteria for disposal of electrons derived in simultaneous substrate oxidations. Methanogenic bacteria can degrade primarily only one-carbon compounds. Therefore, acetate, propionate, ethanol, and their higher homologs have to be fermented further to one-carbon compounds. These fermentations are called secondary or syntrophic fermentations. They are endergonic processes under standard conditions and depend on intimate coupling with methanogenesis. The energetic situation of the prokaryotes cooperating in these processes is problematic: the free energy available in the reactions for total conversion of substrate to methane attributes to each partner amounts of energy in the range of the minimum biochemically convertible energy, i.e., 20 to 25 kJ per mol per reaction. This amount corresponds to one-third of an ATP unit and is equivalent to the energy required for a monovalent ion to cross the charged cytoplasmic membrane. Recent studies have revealed that syntrophically fermenting bacteria synthesize ATP by substrate-level phosphorylation and reinvest part of the ATP-bound energy into reversed electron transport processes, to release the electrons at a redox level accessible by the partner bacteria and to balance their energy budget. These findings allow us to understand the energy economy of these bacteria on the basis of concepts derived from the bioenergetics of other microorganisms.
Ambient solar wind's effect on ICME transit times (2008)

Most empirical and numerical models of Interplanetary Coronal Mass Ejection (ICME) propagation use the initial CME velocity as their primary, if not only, observational input. These models generally predict a wide spread of 1 AU transit times for ICMEs with the same initial velocity. We use a 3D coupled MHD model of the corona and heliosphere to determine the ambient solar wind's effect on the propagation of ICMEs from 30 solar radii to 1 AU. We quantitatively characterize this deceleration by the velocity of the upstream ambient solar wind. The effects of varying solar wind parameters on the ICME transit time are quantified and can explain the observed spread in transit times for ICMEs of the same initial velocity. We develop an adjustment formula that can be used in conjunction with other models to reduce the spread in predicted transit times of Earth‐directed ICMEs.
Enhanced relaxation of nanoparticle-bound supercoiled DNA in X-ray radiation (2005)

A therapeutic methodology was developed based on the large X-ray absorption cross-section of gold nanoparticles at high photon energies (>81 keV). Experimental results showed that the amounts of the relaxed circular supercoiled DNA (scDNA) for gold nanoparticle-bound scDNA were more than doubled compared to that for free scDNA under otherwise identical radiation conditions.