gebhart/patrepeval huggingface dataset:
Identification of Angiotensinogen and Complement C3dg as Novel Proteins Binding the Proform of Eosinophil Major Basic Protein in Human Pregnancy Serum and Plasma (1995)

In sera from pregnant women, pregnancy-associated plasma protein-A (PAPP-A) circulates as a disulfide-bound complex (approximately 474 kDa) with the proform of eosinophil major basic protein (proMBP) (Oxvig, C., Sand, O., Kristensen, T., Gleich, G. J., and Sottrup-Jensen, L. (1993) J. Biol. Chem. 268, 12243-12246). We have produced monoclonal antibodies (mAbs) against the PAPP-A.proMBP complex and established a radioimmunoassay utilizing a mAb recognizing the PAPP-A subunit. Surprisingly, serum levels of proMBP exceed those of PAPP-A four to 10-fold on a molar basis throughout pregnancy. This result prompted an investigation of the status of proMBP in pregnancy. Using a proMBP-specific mAb two novel proMBP complexes have been isolated by chromatographic techniques. Based on sequence analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reaction with specific antibodies, one is shown to be a 2:2 disulfide-bound complex (approximately 200 kDa) between proMBP and angiotensinogen. The other is a 2:2:2 complex (approximately 300 kDa) between proMBP, angiotensinogen, and complement C3dg. Circulating proMBP in pregnancy is thus present in three types of complexes. These results suggest that specific interactions between the complexed proteins occur in pregnancy, and the possibility is raised that their interactions are important in the pathophysiology of pregnancies associated with hypertension.
Direct C–F Bond Formation Using Photoredox Catalysis (2014)

We have developed the first example of a photoredox catalytic method for the formation of carbon-fluorine (C-F) bonds. The mechanism has been studied using transient absorption spectroscopy and involves a key single-electron transfer from the (3)MLCT (triplet metal-to-ligand charge transfer) state of Ru(bpy)3(2+) to Selectfluor. Not only does this represent a new reaction for photoredox catalysis, but the mild reaction conditions and use of visible light also make it a practical improvement over previously developed UV-mediated decarboxylative fluorinations.
An active single-chain antibody containing a cellulase linker domain is secreted by Escherichia coli (1991)

Single-chain antibodies consist of the variable, antigen-binding domains of antibodies joined to a continuous polypeptide by genetically engineered peptide linkers. We have used the flexible interdomain linker region of a fungal cellulase to link together the variable domains of an anti-2-phenyloxazolone IgG1 and show here that the resulting single-chain antibody is efficiently secreted and released to the culture medium of Escherichia coli. The yield of affinity-purified single-chain antibody is 1-2 mg/l of culture medium and its affinity and stability are comparable to those of the corresponding native IgG.
In-fiber fabrication of size-controllable structured particles (2012)

We present an approach for fabricating single-material and multi-material structured spherical particles in the size range 1 millimeter to 50 nanometers that makes use of the Plateau-Rayleigh capillary instability in a multi-material fiber.
Organization of the human transferrin gene: direct evidence that it originated by gene duplication. (1985)

We present the characterization of two overlapping human transferrin genomic clones isolated from a liver DNA library. The two clones represent a total length of 24 kilobase pairs and code for 70% of the protein. The organization of this gene region was elucidated by restriction mapping and DNA sequencing. It contains 12 exons, ranging from 33 to 181 base pairs, separated by introns of 0.7-4.9 kilobase pairs. This gene can be divided into two unequal parts corresponding to the known domains of the protein. Each part is essentially composed of an equal number of exons; introns interrupt the coding sequences, creating homologous exons of similar size in each moiety. Moreover, the pattern of intron interruption of the codon sequence is identical for all the analyzed homologous exon pairs. Comparison with the organization of the ovotransferrin gene shows an identical exon size distribution. These data confirm, at the gene level, the hypothesis that transferrins originated by a gene-duplication event. A model accounting for the origin of the human transferrin gene is presented.
Diacylglycerol kinase α promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src (2014)

Diacylglycerol kinase (DGK)α converts diacylglycerol to phosphatidic acid. This lipid kinase sustains survival, migration and invasion of tumor cells, with no effect over untransformed cells, suggesting its potential as a cancer-specific target. Nonetheless the mechanisms that underlie DGKα specific contribution to cancer survival have not been elucidated. Using three-dimensional (3D) colon and breast cancer cell cultures, we demonstrate that DGKα upregulation is part of the transcriptional program that results in Src activation in these culture conditions. Pharmacological or genetic DGKα silencing impaired tumor growth in vivo confirming its function in malignant transformation. DGKα-mediated Src regulation contributed to limit the effect of Src inhibitors, and its transcriptional upregulation in response to PI3K/Akt inhibitors resulted in reduced toxicity. Src oncogenic properties and contribution to pharmacological resistance have been linked to its overactivation in cancer. DGKα participation in this central node helps to explain why its pharmacological inhibition or siRNA-mediated targeting specifically alters tumor viability with no effect on untransformed cells. Our results identify DGKα-mediated stabilization of Src activation as an important mechanism in tumor growth, and suggest that targeting this enzyme, alone or in combination with other inhibitors in wide clinical use, could constitute a treatment strategy for aggressive forms of cancer.
Multinuclear NMR studies and the kinetics of formation of platinum(II)-adenine nucleotide complexes (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMultinuclear NMR studies and the kinetics of formation of platinum(II)-adenine nucleotide complexesRathindra N. Bose, Richard D. Cornelius, and Ronald E. ViolaCite this: J. Am. Chem. Soc. 1986, 108, 15, 4403–4408Publication Date (Print):July 1, 1986Publication History Published online1 May 2002Published inissue 1 July 1986https://pubs.acs.org/doi/10.1021/ja00275a029https://doi.org/10.1021/ja00275a029research-articleACS PublicationsRequest reuse permissionsArticle Views141Altmetric-Citations35LEARN 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
Advances in diabetic gastroparesis. (2002)

This review addresses the advances in our understanding of the epidemiology and mechanisms in diabetic gastroparesis and dyspepsia. The mechanisms discussed include: blood glucose levels at the time of presentation, "autovagotomy," and the intrinsic innervation (particularly the interstitial cells of Cajal and nitrergic nerves). In animal models of diabetic gastroparesis, there is evidence that homeostatic mechanisms are activated in the enteric nervous system to compensate for the loss of extrinsic innervation. Understanding these advances is key to the development of novel therapeutic strategies and for making rational choices in the management of diabetic gastroparesis and dyspepsia.
Patterns of Chemotherapy Use in a U.S.-Based Cohort of Patients with Metastatic Pancreatic Cancer (2017)

This study examined real world metastatic pancreatic cancer treatment patterns in the United States with the goals of understanding changes in chemotherapy treatment frequencies over time and determining the individual predictors that underlie the chemotherapy choices oncologists make for their patients. Our data set is unique in that it captured not only patient-level data, but also oncologist-level data. It also captured data from private and community practices as well as academic centers. To our knowledge, this is the only data set that can give this degree of insight into oncologist decision making practices.
Testing hypotheses for risk factors for contact lens-associated infectious keratitis in an animal model. (1994)

Various risk factors contributing to contact lens related infectious corneal ulcers were tested. These factors included the presence of infectious organisms, loss of corneal surface integrity, and corneal hypoxia. High concentrations of Pseudomonas bacteria were applied to rabbit corneas under the following conditions: normal, intact corneal surface; "mild" corneal hypoxia with extended-wear soft contact lens and eyes closed; "moderate" corneal hypoxia with daily wear soft contact lens and eyes closed; "severe" corneal hypoxia with daily wear aphakic soft contact lens and eyes closed; corneal abrasion and eyes open; corneal abrasion and eyes closed; corneal abrasion with soft contact lens and closed eyes. No infectious ulcers occurred in normal intact corneas. The frequency of infectious ulcers increased with increasing degrees of corneal swelling. No ulcers were found in corneas with a mean swelling of 10%, whereas a mean swelling of 20% resulted in ulcers in half the group, and a mean swelling of 43% resulted in ulcers in all eyes. The three groups of abraded corneas resulted in infectious ulcers at a 20 to 30% frequency. The presence of infectious organisms alone does not lead to infectious corneal ulcers in rabbits. Corneal abrasions are a risk factor for infectious ulcers, but moderate and severe degrees of hypoxia are more significant.
SUSTAINED RELEASE MATRIX TYPE DRUG DELIERY SYSTEM: A REVIEW (2012)

Oral sustained release (SR) products provide an advantage over conventional dosage forms by optimizing bio-pharmaceutics, pharmacokinetics and Pharmacodynamic properties of drugs in such a way that it reduce dosing frequency to an extent that once daily dose is sufficient for penetration, polymer swelling, drug dissolution, drug diffusion and matrix erosion. Highly water soluble drugs like Diltiazem; Ranitidine has been formulated as sustained release matrix tablets. This article contains the basic information regarding design sustained release formulation and also the different types of the same. Developing oral sustained release matrix tablet with constant release rate has always been a challenge to the pharmaceutical technologist. Most of drugs, if not formulated properly, may readily release the drug at a faster rate, and are likely to produce toxic concentration of the drug on oral administration. Hydrophilic polymers have become product of choice as an important ingredient for formulating sustained release formulations.Key Words: Matrix system, Controlled drug delivery, Polymers.Â
Windowless Techniques for LPC Analysis (1980)

The purpose of this work was to study, experimentally, two windowless LPC analysis algorithms for use in speech digitization. The two algorithms are a circular autocorrelation technique which utilizes the pseudoperiodic nature of voiced speed, and a reflection coefficient estimation technique suggestion by J. P. Burg. Both techniques showed considerable promise in the experimental results.
Cardiac allograft vasculopathy: central role of endothelial injury leading to transplant ???atheroma??? (2003)

Endothelial injury plays a central role in the pathophysiologic mechanisms underlying cardiac allograft vasculopathy (CAV). Although the accelerated course of CAV and its localization to the allograft support an important role for the alloimmune response, there is considerable evidence implicating lipoprotein abnormalities, metabolic disturbances, viral infections, and systemic inflammation in the process. This multifactorial basis for CAV may be put into a pathophysiologic context in which endothelial cell injury is the triggering event that initiates and drives the proliferative and fibrotic processes characteristic of CAV. In the transplant setting, endothelial cell injury is induced by multiple factors, including brain death, ischemia-reperfusion, alloimmune responses, and viral infections. Once initiated, propagation of the proliferative processes that ultimately lead to vascular occlusion is enhanced by the abnormal metabolic environment of elevated lipoproteins and insulin resistance encountered in most patients. This review examines the evidence for the role of potential triggers of endothelial injury in the pathophysiology of CAV and discusses the central role of the nitric oxide pathway in the disease process.
Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional (1995)

An in vitro culture system demonstrating the transitions from megakaryocyte progenitors to functional platelets is described. CD34-selected cells from normal human peripheral blood are cultured under conditions that promote megakaryocyte formation. After 8 to 11 days, enriched populations of mature megakaryocytes are replated under conditions that favor the development of proplatelets. Proplatelets express the platelet-specific proteins, glycoproteins Ib and IIb (GPIb and GPIIb), and fibrinogen and also contain microtubule coils equal in size to those found in plasma-derived platelets. In addition, proplatelets have ultrastructural features in common with plasma-derived platelets. Platelet-sized particles from the proplatelet culture supernatants are examined. Ultrastructurally, these particles are identical to plasma-derived platelets. Functionally, these culture-derived platelets aggregate in response to both thrombin and adenosine diphosphate (ADP) plus fibrinogen. This aggregation is specifically inhibited by the addition of a function-blocking anti-GPIIbIIIa antibody. Culture-derived platelets stimulated with agonists also express the activation-dependent antigens P-selectin and functional fibrinogen receptor. This is the first description of an in vitro culture system that sequentially demonstrates megakaryocyte growth, development, and platelet production.
Selection, combination, and evaluation of effective software sensors for detecting abnormal computer usage (2004)

We present and empirically analyze a machine-learning approach for detecting intrusions on individual computers. Our Winnow-based algorithm continually monitors user and system behavior, recording such properties as the number of bytes transferred over the last 10 seconds, the programs that currently are running, and the load on the CPU. In all, hundreds of measurements are made and analyzed each second. Using this data, our algorithm creates a model that represents each particular computer's range of normal behavior. Parameters that determine when an alarm should be raised, due to abnormal activity, are set on a per-computer basis, based on an analysis of training data. A major issue in intrusion-detection systems is the need for very low false-alarm rates. Our empirical results suggest that it is possible to obtain high intrusion-detection rates (95%) and low false-alarm rates (less than one per day per computer), without "stealing" too many CPU cycles (less than 1%). We also report which system measurements are the most valuable in terms of detecting intrusions. A surprisingly large number of different measurements prove significantly useful.
Comparative Polymerization in the Gas Phase and in Clusters. 2. Electron Impact and Multiphoton-Induced Reactions in Isobutene and Benzene/Isobutene Clusters (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComparative Polymerization in the Gas Phase and in Clusters. 2. Electron Impact and Multiphoton-Induced Reactions in Isobutene and Benzene/Isobutene ClustersM. Samy El-Shall, George M. Daly, Zhongde Yu, and M. Meot-NerCite this: J. Am. Chem. Soc. 1995, 117, 29, 7744–7752Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ja00134a019https://doi.org/10.1021/ja00134a019research-articleACS PublicationsRequest reuse permissionsArticle Views87Altmetric-Citations31LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Selecting Optimally Diverse Compounds from Structure Databases:  A Validation Study of Two-Dimensional and Three-Dimensional Molecular Descriptors (1997)

The efficiency of the drug discovery process can be significantly improved using design techniques to maximize the diversity of structure databases or combinatorial libraries. Here, several physicochemical descriptors were investigated to quantify molecular diversity. Based on the 2D or 3D topological similarity of molecules, the relationship between physicochemical metrics and biological activity was studied to find valid descriptors. Several compounds were selected using those descriptors from a database containing diverse templates and 55 biological classes. It was evaluated whether the obtained subsets represent all biological properties and structural variations of the original database. In addition, hierarchical cluster analyses were used to group molecules from the parent database, which should have similar biological properties. Using various sets of structurally similar molecules, it was possible to derive quantitative measures for compound similarities in relation to biological properties. A similarity radius for 2D fingerprints and molecular steric fields was estimated; compounds within this radius of another molecule were shown to have comparable biological properties. This study demonstrates that 2D fingerprints alone or in combination with other metrics as the primary descriptor allow to handle global diversity. In addition, standard atom-pair descriptors or molecular steric fields can be used to correlate structural diversity with biological activity. Hence, the latter two descriptors can be classified as secondary descriptors useful for analog library design, while 2D fingerprints are applicable to design a general library for lead discovery. Based on these findings, an optimally diverse subset containing only 38% of the entire IC93 database was generated using 2D fingerprints. Here no structure is more similar than 0.85 to any other (Tanimoto coefficient), but all biological classes were selected. This reduction of redundancy led to a child database with the same physicochemical diversity space, which contains the same information as the original database.
Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis (2007)

Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n 12), MS (n 6), brain and spinal infarction (n 7) and normal control (n 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.
Flow minimal residual disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34+CD38lowCD19+ in B-lineage childhood acute lymphoblastic leukemia (2009)

Flow cytometric minimal residual disease (MRD) monitoring could become more powerful if directed towards the disease-maintaining leukemic stem cell (LSC) compartment. Using a cohort of 48 children with B-lineage acute lymphoblastic leukemia (ALL), we sought the newly proposed candidate-LSC population, CD34(+)CD38(low)CD19(+), at presentation and in end of induction bone marrow samples. We identified the candidate LSC population in 60% of diagnostic samples and its presence correlated with expression of CD38, relative to that of normal B-cell progenitors. In addition, the candidate LSC was not detectable in all MRD positive samples. The absence of the population in 40% of diagnostic and 40% of MRD positive samples does not support the use of this phenotype as a generic biomarker to track LSCs and suggests that this phenotype may be an artifact of CD38 underexpression rather than a biologically distinct LSC population. ClinicalTrials.gov Identifier: NCT00222612.