gebhart/patrepeval huggingface dataset:
The Determination of Pore Volume and Area Distributions in Porous Substances. I. Computations from Nitrogen Isotherms (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Determination of Pore Volume and Area Distributions in Porous Substances. I. Computations from Nitrogen IsothermsElliott P. Barrett, Leslie G. Joyner, and Paul P. HalendaCite this: J. Am. Chem. Soc. 1951, 73, 1, 373–380Publication Date (Print):January 1, 1951Publication History Published online1 May 2002Published inissue 1 January 1951https://pubs.acs.org/doi/10.1021/ja01145a126https://doi.org/10.1021/ja01145a126research-articleACS PublicationsRequest reuse permissionsArticle Views22005Altmetric-Citations10643LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Self-Assembled Nanoreactors (2005)

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Active-site MMP-selective antibody inhibitors discovered from convex paratope synthetic libraries (2016)

Proteases are frequent pharmacological targets, and their inhibitors are valuable drugs in multiple pathologies. The catalytic mechanism and the active-site fold, however, are largely conserved among the protease classes, making the development of the selective inhibitors exceedingly challenging. In our departure from the conventional strategies, we reviewed the structure of known camelid inhibitory antibodies, which block enzyme activities via their unusually long, convex-shaped paratopes. We synthesized the human Fab antibody library (over 1.25 × 10<sup>9</sup> individual variants) that carried the extended, 23- to 27-residue, complementarity-determining region (CDR)-H3 segments. As a proof of principle, we used the catalytic domain of matrix metalloproteinase-14 (MMP-14), a promalignant protease and a drug target in cancer, as bait. In our screens, we identified 20 binders, of which 14 performed as potent and selective inhibitors of MMP-14 rather than as broad-specificity antagonists. Specifically, Fab 3A2 bound to MMP-14 in the vicinity of the active pocket with a high 4.8 nM affinity and was similarly efficient (9.7 nM) in inhibiting the protease cleavage activity. We suggest that the convex paratope antibody libraries described here could be readily generalized to facilitate the design of the antibody inhibitors to many additional enzymes.
Differential Activation of Extracellular Signal-Regulated Protein Kinase in Primary Afferent Neurons Regulates Brain-Derived Neurotrophic Factor Expression after Peripheral Inflammation and Nerve Injury (2003)

To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons.
Point-versus interval-based temporal data models (2002)

The association of timestamps with various data items such as tuples or attribute values is fundamental to the management of time varying information. Using intervals in timestamps, as do most data models, leaves a data model with a variety of choices for giving a meaning to timestamps. Specifically, some such data models claim to be point based while other data models claim to be interval based. The meaning chosen for timestamps is important it has a pervasive effect on most aspects of a data model, including database design, a variety of query language properties, and query processing techniques, e.g., the availability of query optimization opportunities. The paper precisely defines the notions of point based and interval based temporal data models, thus providing a new formal basis for characterizing temporal data models and obtaining new insights into the properties of their query languages. Queries in point based models treat snapshot equivalent argument relations identically. This renders point based models insensitive to coalescing. In contrast, queries in interval based models give significance to the actual intervals used in the timestamps, thus generally treating non identical, but possibly snapshot equivalent relations differently. The paper identifies the notion of time fragment preservation as the essential defining property of an interval based data model.
Charge redistribution and polarization energy of organic molecular crystals (2001)

We present an approach to electronic polarization in molecular solids treated as a set of quantum systems interacting classically. Individual molecules are dealt with rigorously as quantum-mechanical systems subject to classical external fields created by all other molecules and, possibly, external sources. Self-consistent equations are derived for induced dipoles and for atomic charges whose redistribution in external fields is given explicitly by an atom-atom polarizability tensor. Electronic polarization is studied in two representative organic molecular crystals, anthracene and perylenetetracarboxylic acid dianhydride, and contrasted to previous results for systems of polarizable points. The stabilization energies of the neutral lattice, of isolated anions and cations, and of cation-anion pairs are found. Charge redistribution on ions is included. The dielectric tensors of crystals are successfully related to gas-phase properties and provide consistency checks on polarization energies. The procedure is generally applicable to organic crystals in the limit of no intermolecular overlap.
A CNN Regression Approach for Real-Time 2D/3D Registration (2016)

In this paper, we present a Convolutional Neural Network (CNN) regression approach to address the two major limitations of existing intensity-based 2-D/3-D registration technology: 1) slow computation and 2) small capture range. Different from optimization-based methods, which iteratively optimize the transformation parameters over a scalar-valued metric function representing the quality of the registration, the proposed method exploits the information embedded in the appearances of the digitally reconstructed radiograph and X-ray images, and employs CNN regressors to directly estimate the transformation parameters. An automatic feature extraction step is introduced to calculate 3-D pose-indexed features that are sensitive to the variables to be regressed while robust to other factors. The CNN regressors are then trained for local zones and applied in a hierarchical manner to break down the complex regression task into multiple simpler sub-tasks that can be learned separately. Weight sharing is furthermore employed in the CNN regression model to reduce the memory footprint. The proposed approach has been quantitatively evaluated on 3 potential clinical applications, demonstrating its significant advantage in providing highly accurate real-time 2-D/3-D registration with a significantly enlarged capture range when compared to intensity-based methods.
Obsessive-Compulsive and Related Symptoms in Children and Adolescents With Rheumatic Fever With and Without Chorea: A Prospective 6-Month Study (1998)

The association between Sydenham's chorea and OCD supports suggestions that similar mechanisms involving the basal ganglia underlie both disorders. Obsessive-compulsive symptoms occurred at the beginning of rheumatic fever, so early psychopathological assessments are essential.
Measurement of Monovalent and Polyvalent Carbohydrate−Lectin Binding by Back-Scattering Interferometry (2009)

Carbohydrate-protein binding is important to many areas of biochemistry. Here, backscattering interferometry (BSI) has been shown to be a convenient and sensitive method for obtaining quantitative information about the strengths and selectivities of such interactions. The surfaces of glass microfluidic channels were covalently modified with extravidin, to which biotinylated lectins were subsequently attached by incubation and washing. The binding of unmodified carbohydrates to the resulting avidin-immobilized lectins was monitored by BSI. Dose-response curves that were generated within several minutes and were highly reproducible in multiple wash/measure cycles provided adsorption coefficients that showed mannose to bind to concanavalin A (conA) with 3.7 times greater affinity than glucose consistent with literature values. Galactose was observed to bind selectively and with similar affinity to the lectin BS-1. The avidities of polyvalent sugar-coated virus particles for immobilized conA were much higher than monovalent glycans, with increases of 60-200 fold per glycan when arrayed on the exterior surface of cowpea mosaic virus or bacteriophage Qbeta. Sugar-functionalized PAMAM dendrimers showed size-dependent adsorption, which was consistent with the expected density of lectins on the surface. The sensitivity of BSI matches or exceeds that of surface plasmon resonance and quartz crystal microbalance techniques, and is sensitive to the number of binding events, rather than changes in mass. The operational simplicity and generality of BSI, along with the near-native conditions under which the target binding proteins are immobilized, make BSI an attractive method for the quantitative characterization of the binding functions of lectins and other proteins.
Research in Castration-Resistant Rostate Cancer: What Does the Future Hold? (2010)

Prostate cancer (PCa) is the most common non-skin cancer diagnosed in North America, and it affects 1 in 6 men. Patients with recurrent or metastatic pca will inevitably develop castration-resistant disease after an initial period of hormone responsiveness. The standard first-line treatment for men with castration-resistant pca (CRPC) is docetaxel, but further treatment options are limited. This review summarizes the research being conducted in CRPC, with specific regard to immunotherapy and to novel targeted therapies directed against the androgen axis, vascular endothelial growth factor, chaperone proteins, the phosphoinositide 3 kinase/Akt/phosphatase and tensin homolog/mammalian target of rapamycin pathway, and endothelin-1.
Tryptophan-derived Catabolites Are Responsible for Inhibition of T and Natural Killer Cell Proliferation Induced by Indoleamine 2,3-Dioxygenase (2002)

Macrophages exposed to macrophage colony-stimulating factor acquire the capacity to suppress T cell proliferation; this effect is associated with de novo expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). We have purified IDO and tested its activity in in vitro models of T cell activation. IDO was able to inhibit proliferation of CD4+ T lymphocytes, CD8+ T lymphocytes, and natural killer (NK) cells; proliferation of B lymphocytes was not affected. The inhibitory role of tryptophan and of its catabolites was then tested. In the presence of tryptophan, only l-kynurenine and picolinic acid inhibit cell proliferation. In a tryptophan-free medium cell proliferation was not affected. In the absence of tryptophan inhibition induced by l-kynurenine and picolinic acid was observed at concentrations below the lowest concentration that was effective in the presence of tryptophan, and quinolinic acid acquired some inhibitory capacity. Inhibition of cell proliferation induced by the tryptophan catabolites resulting from IDO activity was selective, applying only to cells undergoing activation. Resting cells were not affected and could subsequently activate normally. We suggest that IDO exerts its effect on cell proliferation by (i) starting the cascade of biochemical reactions that produce the three catabolites and by (ii) enhancing their inhibitory potential by depriving the extracellular microenvironment of tryptophan.
Genetic Control of the 2-Keto-3-Deoxy- d -Gluconate Metabolism in Escherichia coli K-12: kdg Regulon (1974)

2-Keto-3-deoxy-gluconate (KDG), an intermediate of the hexuronate pathway in Escherichia coli K-12, is utilized as the sole carbon source only in strains derepressed for the specific KDG-uptake system. KDG is metabolized to pyruvate and glyceraldehyde-3-phosphate via the inducible enzymes KDG-kinase and 2-keto-3-deoxy-6-phosphate-gluconate (KDPG) aldolase. However, another inducible pathway, where the KDG is the branch point, has been demonstrated. Genetic studies of the KDG degradative pathway reported in this paper led to the location of KDG kinase-negative and pleiotropic constitutive mutations. The kdgK locus, presumably the structural gene of the kinase, occurs at min 69 and is co-transducible with xyl. The mutants, simultaneously constitutive for the uptake, kinase, and aldolase, define a kdgR locus at min 36 between the co-transducible markers kdgA and oldD. As to the nature of the control exerted by the kdgR product, we have shown the following. (i) Thermosensitive mutants of the kdgR locus are inducible at low temperature but derepressed at 42 C for the three operons-kdgT (transport system), kdgK, and kdgA (KDPG aldolase). (ii) The kdgR(+) allele is dominant to the kdgR constitutive allele. (iii) A deletion in kdgA extending into the regulatory gene, kdgR, leads to a constitutive expression of the nondeleted operons-kdgT and kdgK. These properties demonstrate that the kdg regulon is negatively controlled by the kdgR product. It is presumed that differences in operator and in promotor structures could explain the strong decoordination, respectively, in the induction and catabolic repression, of these three enzymes activities.
Modulation of gene expression in Syrian hamster embryo cells following ionizing radiation. (1990)

We examined the modulation of gene expression in Syrian hamster embryo (SHE) cells at various times following exposure to low doses of ionizing radiation. Early passage SHE cells were irradiated in plateau phase (greater than 95% G0-G1 cells) with 21-cGy fission-spectrum neutrons, 75-cGy X-rays, or 90-cGy gamma-rays, none of which induced more than 10% loss in cell viability. RNA harvested at various times after exposure was examined for levels of particular RNA species by dot blot and Northern blot hybridizations. Levels of beta-actin-specific RNA decreased within 15 min after exposure of the cells. The kinetics of repression of beta-actin mRNA were similar for all qualities of radiation (X-rays, gamma-rays, and neutrons) for 12 h post-irradiation. Within 1 h after neutron exposure (21 cGy), we observed a decrease in accumulation of RNA species (relative to RNA from nonirradiated cells) encoding the enzyme ornithine decarboxylase; this decrease continued for up to 12 h. Similar results were obtained with gamma- and X-rays. RNA encoding interleukin 1, however, was induced by 3 h after neutron irradiation but reduced to background levels by 7 h. Amounts of rRNA remained constant in all experiments, although total transcription on a per cell basis was reduced within 15 min following irradiation and did not return to normal until 7 h post-irradiation. No alterations, relative to untreated control cells, in overall cell viability or the rate of cell cycle progression were observed in cells either immediately or within 24 h post-irradiation. Our results demonstrate modulation of specific genes following low-dose irradiation. In addition, our findings suggest that some molecular responses to different qualities of ionizing radiation (X-rays, gamma-rays, and neutrons) may be similar.
Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin‐1 (1995)

Our data demonstrate that signal transduction through chondrocyte integrin receptors up-regulates metalloproteinase expression and that this is likely mediated through induction of IL-1. They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL-1 required to induce stromelysin synthesis. Up-regulation of chondrocyte integrin expression by IL-1 may play a role in the synergistic effects seen with a combination of IL-1 and RGD peptides. Since elevated levels of both IL-1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our data suggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.
Targeting Anaplastic Lymphoma Kinase in Lung Cancer (2011)

Several decades of cancer research have revealed a pivotal role for tyrosine kinases as key regulators of signaling pathways, controlling cell growth and differentiation. Deregulation of tyrosine kinase-mediated signaling occurs frequently in cancer and is believed to drive the initiation and progression of disease. Chromosomal rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) occur in a variety of human malignancies including non-small cell lung cancer (NSCLC), anaplastic large cell lymphomas, and inflammatory myofibroblastic tumors. The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066). This review focuses on ALK rearrangements in NSCLC, starting with the discovery of the EML4-ALK fusion oncogene, and culminating in the recent validation of ALK as a therapeutic target in patients with ALK-rearranged NSCLC. Current efforts seek to expand the role of ALK kinase inhibition in lung and other cancers and to address the molecular basis for the development of resistance.
Removing rolling shutter wobble (2010)

We present an algorithm to remove wobble artifacts from a video captured with a rolling shutter camera undergoing large accelerations or jitter. We show how estimating the rapid motion of the camera can be posed as a temporal super-resolution problem. The low-frequency measurements are the motions of pixels from one frame to the next. These measurements are modeled as temporal integrals of the underlying high-frequency jitter of the camera. The estimated high-frequency motion of the camera is then used to re-render the sequence as though all the pixels in each frame were imaged at the same time. We also present an auto-calibration algorithm that can estimate the time between the capture of subsequent rows in the camera.
RETRACTED: The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility (2008)

The epidermal growth factor receptor (EGFR) activates cellular pathways controlling cell proliferation, differentiation, migration, and survival. It thus represents a valid therapeutic target for treating solid cancers. Here, we used an electron microscopy-based technique (Protein Tomography) to study the structural rearrangement accompanying activation and inhibition of native, individual, EGFR molecules. Reconstructed tomograms (3D density maps) showed a level of detail that allowed individual domains to be discerned. Monomeric, resting EGFR ectodomains demonstrated large flexibility, and a number of distinct conformations were observed. In contrast, ligand-activated EGFR complexes were detected only as receptor dimers with ring-like conformations. Zalutumumab, a therapeutic inhibitory EGFR antibody directed against domain III, locked EGFR molecules into a very compact, inactive conformation. Biochemical analyses showed bivalent binding of zalutumumab to provide potent inhibition of EGFR signaling. The structure of EGFR-zalutumumab complexes on the cell surface visualized by Protein Tomography indicates that the cross-linking spatially separates the EGFR molecules' intracellular kinase domains to an extent that appears incompatible with the induction of signaling. These insights into the mechanisms of action of receptor inhibition may also apply to other cell-surface tyrosine kinase receptors of the ErbB family.
Isolation and rapid sharing of the 2019 novel coronavirus ( SARS ‐CoV‐2) from the first patient diagnosed with COVID ‐19 in Australia (2020)

The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.
Preparation of polyethylene glycol-tissue plasminogen activator adducts that retain functional activity: characteristics and behavior in three animal species (1988)

Conditions were defined for the derivatization of recombinant tissue plasminogen activator (rt-PA) with polyethylene glycol (PEG) so as to retain functional activity as a possible means of producing a t-PA species with a prolonged circulating lifetime. Derivatives with a wide range of retention of activities were prepared by varying the concentration and species of activated PEG. The specific activities of the PEG-rt-PA derivatives were dependent on the method of assay. Assays using preformed fibrin gave higher estimates of retention of activity than assays using soluble components. Plasma elimination studies in mice and rats indicated prolonged circulating lifetimes for the radiolabeled PEG-rt-PA derivatives after a rapid clearance and distribution phase; however, the disappearance of functional activity was much more rapid than the disappearance of radiolabeled material. The PEG-rt-PA derivatives appeared to accumulate in tissues above their interstitial fluid concentrations and were rapidly inactivated, apparently by reaction with the plasma protease inhibitors. These results were consistent with the inactivation of the PEG-rt-PA derivatives in rat plasma in vitro. A somewhat longer half-life (t1/2) of the one derivative studied was observed in dogs (t1/2, 16 minutes) as compared with the rat (t1/2, five minutes). This was sufficient to confer thrombolytic activity upon the derivative (administered by bolus injection) in contrast to native rt-PA. The potential of PEG-modified rt-PA as a long-lived thrombolytic agent in humans will depend, however, on whether there will be a further extension of the t1/2 because of a reduction in clearance and/or a reduction in the rate of inactivation.