gebhart/patrepeval huggingface dataset:
Simplified recombinant plasmin: Production and functional comparison of a novel thrombolytic molecule with plasma-derived plasmin (2008)

A simplified and fully functional deletion mutant of plasminogen was created in which the middle portion of the molecule was removed, resulting in kringle 1 attachment to the serine protease domain. This recombinant plasminogen deletion mutant, Delta(K2-K5)Pg, was produced in the form of inclusion bodies at the yield of up to 200 mg/l in an Escherichia coli T7 expression system. Following protein refolding and purification on lysine-Sepharose, the conversion of the recombinant molecule Delta(K2-K5)Pg to the active enzyme mutant Delta(K2-K5)Pm by plasminogen activators was evaluated, and functional characteristics of the simplified plasmin were studied. Properties of Delta(K2-K5)Pg were similar to native, human plasma-derived plasminogen. Delta(K2-K5)Pg effectively bound epsilon-aminocaproic acid (K(d)=11.3+/-2.3 microM) and fibrin (C(50) approximately 0.3 microM). The plasminogen activators streptokinase, urokinase, and tissue plasminogen activator effectively converted the recombinant zymogen Delta(K2-K5)Pg to the active recombinant enzyme, Delta(K2-K5)Pm. Additionally, Delta[K2-K5]Pm was rapidly inhibited by alpha(2)-antiplasmin (1.1+/-0.1 x 10(7) M(-1) s(-1)) and alpha(2)-macroglobulin (7.6+/-0.6 x 10(5) M(-1) s(-1)). In an in-vitro model, Delta(K2-K5)Pm demonstrated fibrinolytic potency comparable to human plasma-derived plasmin. Because of their unique biochemistry, including fibrin-binding properties and rapid inhibition by alpha(2)-antiplasmin, both native plasmin and a simplified deletion mutant of plasmin are potentially safe and effective direct thrombolytic agents for various thrombotic conditions. Further studies evaluating the in-vivo pharmacologic safety and clinical efficacy of this simplified plasmin (i.e. Delta[K2-K5]Pm) are warranted.
SYSTEMS-BASED PROCESS REENGINEERING IN DEMAND CHAINS (2003)

Demand chain management is a set of practices aimed at managing and coordinating the entire chain, motivated by the final customer and working back to raw material suppliers.The Internet enables the consumer and provides the consumer with greater knowledge.By matching products to the appropriate value stream, product development time can be reduced, manufacturing costs can be reduced, and delivery times can be dramatically reduced.Analysis and design of focused demand chains involve a number of alternative channels and forms.In this paper, we propose a soft systems version of goal analysis with the intent of viewing information systems design as a system with interacting parts with a shared purpose.Identification of goals can be a way to develop conceptual models to better understand problems in interaction among system parts.Analysis of systems models can lead to identification of weak points, which can lead to redesign to overcome such problems, thus leading to the analysis of the system leading to better system solutions.
Investigation of the effect of finite grating size on the performance of guided-mode resonance filters (2000)

We evaluate the effect of finite aperture gratings on the spectral and efficiency characteristics of guided-mode resonance filters. A simple analytical model based on the attenuation properties of the waveguide and a fixed length of the grating aperture is developed. The results from this model are in good agreement with experimental filters formed with subwavelength period photoresist gratings and solgel waveguides.
Stochastic kriging for simulation metamodeling (2008)

We extend the basic theory of kriging, as applied to the design and analysis of deterministic computer experiments, to the stochastic simulation setting. Our goal is to provide flexible, interpolation-based metamodels of simulation output performance measures as functions of the controllable design or decision variables. To accomplish this we characterize both the intrinsic uncertainty inherent in a stochastic simulation and the extrinsic uncertainty about the unknown response surface. We use tractable examples to demonstrate why it is critical to characterize both types of uncertainty, derive general results for experiment design and analysis, and present a numerical example that illustrates the stochastic kriging method.
Field Performance of a Genetically Engineered Strain of Pink Bollworm (2011)

Pest insects harm crops, livestock and human health, either directly or by acting as vectors of disease. The Sterile Insect Technique (SIT)--mass-release of sterile insects to mate with, and thereby control, their wild counterparts--has been used successfully for decades to control several pest species, including pink bollworm, a lepidopteran pest of cotton. Although it has been suggested that genetic engineering of pest insects provides potential improvements, there is uncertainty regarding its impact on their field performance. Discrimination between released and wild moths caught in monitoring traps is essential for estimating wild population levels. To address concerns about the reliability of current marking methods, we developed a genetically engineered strain of pink bollworm with a heritable fluorescent marker, to improve discrimination of sterile from wild moths. Here, we report the results of field trials showing that this engineered strain performed well under field conditions. Our data show that attributes critical to SIT in the field--ability to find a mate and to initiate copulation, as well as dispersal and persistence in the release area--were comparable between the genetically engineered strain and a standard strain. To our knowledge, these represent the first open-field experiments with a genetically engineered insect. The results described here provide encouragement for the genetic control of insect pests.
Rapid identification of bacteria on the basis of polymerase chain reaction-amplified ribosomal DNA spacer polymorphisms (1993)

To facilitate genus and species level identification of a broad range of bacteria without the requirement of presumptive identification, we have developed a unified set of primers and polymerase chain reaction conditions to amplify spacer regions between the 16S and 23S genes in the prokaryotic rRNA genetic loci. Spacer regions within these loci show a significant level of length and sequence polymorphism across both genus and species lines. A generic pair of priming sequences was selected for the amplification of these polymorphisms from highly conserved sequences in the 16S and 23S genes occurring adjacent to these polymorphic regions. This single set of primers and reaction conditions was used for the amplification of 16S-23S spacer regions for over 300 strains of bacteria belonging to eight genera and 28 species or serotypes, including Listeria, Staphylococcus, and Salmonella species and additional species related to these pathogenic organisms. When the spacer amplification products were resolved by electrophoresis, the resulting patterns could be used to distinguish all of the species of bacteria within the test group. Unique elements in the amplification product patterns generally clustered at the species level, although some genus-specific characteristics were also observed. On the basis of the results obtained with our test group of 300 bacterial strains, amplification of the 16S-23S ribosomal spacer region is a suitable process for generating a data base for use in a polymerase chain reaction-based identification method, which can be comprehensively applied to the bacterial kingdom.
Inhibitory Activities of Semicarbazide-Sensitive Amine Oxidase and Angiotensin Converting Enzyme of Pectin Hydroxamic Acid (2003)

Solutions of 100 mL of 1% commercial pectin each with a different degree of esterification (DE), DE94, DE65, and DE25, were reacted with 100 mL of 2 M alkaline hydroxylamine (pH 12.0) at room temperature for 4 or 18 h. These pectin hydroxamic acids (PHAs; DE94T4, DE94T18, DE65T4, and DE25T4) were used to test the inhibitory activities against semicarbazide-sensitive amine oxidase (SSAO) and angiotensin-converting enzyme (ACE). Compared to different DE pectins (DE94, DE65, and DE25), the PHAs of DE94T4, DE94T18, DE65T4, and DE25T4 showed different inhibition activities against SSAO or ACE. Commercial pectins with different DE values showed negligible SSAO or ACE inhibitions. The order of SSAO inhibition was DE65T4 > DE94T18 approximately DE25T4 >> DE94T4. However, the order of ACE inhibition was DE94T4 > DE94T18 >> DE65T4 > DE25T4. The SSAO activity staining or ACE-hydrolyzed products on TLC chromatogram also confirmed the inhibitory activities of PHAs against SSAO or ACE.
Generation of CD34 Fluorescent Reporter Human Induced Pluripotent Stem Cells for Monitoring Hematopoietic Differentiation (2018)

Hematopoietic stem and progenitor cells (HSPCs) derived from human induced pluripotent stem cells (hiPSCs) hold great promise for disease modeling, drug screens, and eventually cell therapy approaches. During in vitro differentiation of hiPSCs into hematoendothelial progenitors, the emergence of CD34-positive cells indicates a critical step of lineage specification. To facilitate the monitoring of hematopoietic differentiation of hiPSCs, we established fluorescent reporter cells for the stem and progenitor cell marker CD34. An IRES-GFP (internal ribosome entry site green fluorescent protein) construct was introduced by CRISPR/Cas9 into the 3' untranslated region of one endogenous CD34 allele. Single-cell clones were generated after excision of the floxed puromycin resistance cassette by Cre recombination and correct insertion was confirmed by genotyping polymerase chain reaction and Southern blot. To validate their functionality, the reporter hiPSCs were in vitro differentiated toward CD34<sup>+</sup> cells using the STEMdiff Hematopoietic Kit combined with short-term inhibition of GSK3 (glycogen synthase kinase 3). All cells expressing nuclear GFP were positive for cell surface CD34, thus allowing the direct monitoring of the differentiation of hiPSCs into CD34<sup>+</sup> cells either by flow cytometry or confocal microscopy. After fluorescence-activated cell sorting, cells displaying high GFP expression exhibited increased colony-forming potential in the MethoCult colony-forming unit assays as compared with CD34<sup>+</sup> cells obtained by magnetic-activated cell sorting. In summary, we have generated functional CD34 GFP reporter hiPSCs, which not only permit label-free separation of HSPCs, but also tracing of the emergence and fate of CD34<sup>+</sup> progenitors at the single-cell level.
Southern blot detection of immunoglobulin lambda light chain gene rearrangements for clonality studies. (1995)

Southern blot analysis of immunoglobulin (Ig) genes has proven to be important for detection of clonal rearrangements in patients with lymphoproliferative diseases. To improve the detection of clonal Ig lambda (Ig lambda) gene rearrangements, we carefully determined the precise restriction map of the J-C lambda gene region, developed a suitable C lambda probe (IGLC3), and evaluated relevant restriction enzymes in combination with the IGLC3 probe. For the latter purpose, we selected 75 B cell malignancies with proven expression of Ig lambda protein chains in order to be sure that each malignancy contained at least one clonally rearranged IG lambda allele. Our extensive Southern blot analyses with the IGLC3 probe in EcoRI and/or HindIII digests revealed that combined EcoRI/HindIII digestion detected Ig lambda gene rearrangements in 95% of the 75 patients and 94% of the 98 rearranged alleles. In contrast, HindIII and EcoRI single digests allowed detection of rearrangements in only 78% and 83% of the patients, and 67% and 79% of rearranged alleles, respectively. We conclude that the use of the IGLC3 probe in combined EcoRI/HindIII digests is superior to EcoRI and HindIII single digests. This probe/enzyme combination is informative for clonality studies in approximately 95% of patients.
Oxidative Cyclization of N‐Methyl‐ and N‐Benzoylpyridylthioureas. Preparation of New Thiazolo[4,5‐b] and [5,4‐b]pyridine Derivatives. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Catalytic Materials, Membranes, and Fabrication Technologies Suitable for the Construction of Amperometric Biosensors (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleCatalytic Materials, Membranes, and Fabrication Technologies Suitable for the Construction of Amperometric BiosensorsJeffrey D. Newman, Stephen F. White, Ibtisam E. Tothill, and Anthony P. F. TurnerCite this: Anal. Chem. 1995, 67, 24, 4594–4599Publication Date (Print):December 15, 1995Publication History Published online1 May 2002Published inissue 15 December 1995https://doi.org/10.1021/ac00120a027RIGHTS & PERMISSIONSArticle Views627Altmetric-Citations84LEARN 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 InReddit PDF (622 KB) Get e-Alerts Get e-Alerts
Dissociation Between Symptoms and Histological Severity in Pediatric Eosinophilic Esophagitis (2009)

Children with untreated EE had a higher PEESS than treated subjects. Symptoms persisted in 85% of EE patients despite histological resolution and 10% with active EE reported no symptoms. Our data indicate a dissociation between symptoms and histology in pediatric EE.
Learning to recognize shadows in monochromatic natural images (2010)

This paper addresses the problem of recognizing shadows from monochromatic natural images. Without chromatic information, shadow classification is very challenging because the invariant color cues are unavailable. Natural scenes make this problem even harder because of ambiguity from many near black objects. We propose to use both shadow-variant and shadow-invariant cues from illumination, textural and odd order derivative characteristics. Such features are used to train a classifier from boosting a decision tree and integrated into a Conditional random Field, which can enforce local consistency over pixel labels. The proposed approach is evaluated using both qualitative and quantitative results based on a novel database of hand-labeled shadows. Our results show shadowed areas of an image can be identified using proposed monochromatic cues.
Prostaglandins in the patent literature (2007)

Prostaglandins are regulatory compounds that play principal roles in many physiologic processes. Importantly, prostaglandins have been demonstrated to be potent vasodilators in humans and animals, indicating their potential role as therapeutic agents. However, administration of prostaglandins for therapeutic purposes has been hampered by their inherent pharmacokinetic properties, such as limited bioavailability and short half-life, as well as their pleiotropism with resultant side effects. Despite these difficulties, considerable work has been done over the past few decades in the development of prostaglandin derivatives and their use as therapeutic agents. Recently, numerous prostaglandin analogs, agonists and antagonists have emerged. This review will focus on prostaglandins in general and various types of prostaglandin derivatives that are patented and have therapeutic use as vasodilators.
Abrogation of hepatitis C virus NS3 helicase enzymatic activity by recombinant human antibodies (2003)

The hepatitis C virus (HCV) NS3 protein possesses both protease and helicase activities and is essential for virus replication and maturation. Specific inhibition of NS3 enzymatic activity can be achieved by antibody binding. Transduction of hepatocytes with encoding cDNA leading to intracellular expression of antibody fragments is expected to terminate HCV replication in infected cells. The objective of the present study was the generation of human antibody fragments that neutralize the viral NS3 helicase activity for gene therapeutic applications and drug design. A human immunoglobulin phage-display library cloned from bone marrow aspirate of patients infected with HCV was used for affinity selection against HCV NS3 helicase. Antibody fragments with high affinity to HCV helicase were isolated. To evaluate the inhibitory potential of isolated single-chain antibody fragments, a helicase-mediated, DNA-unwinding enzymatic assay was developed in ELISA format. Recombinant protein comprising the full-length HCV NS3 helicase domain was expressed in the baculovirus expression system. Recombinant antibodies that inhibit the HCV helicase at nanomolar concentrations, with efficacies ranging from 20 % to complete abrogation of enzymatic unwinding activity, were identified. These antibody fragments may be useful for novel gene therapeutic strategies that employ intracellular immunization and may provide new insights into the design of small molecule inhibitors of essential HCV proteins.
STIM1–Orai1 interactions and Orai1 conformational changes revealed by live‐cell FRET microscopy (2008)

Ca(2+) entry through store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels initiates key functions such as gene expression and exocytosis of inflammatory mediators. Activation of CRAC channels by store depletion involves the redistribution of the ER Ca(2+) sensor, stromal interaction molecule 1 (STIM1), to peripheral sites where it co-clusters with the CRAC channel subunit, Orai1. However, how STIM1 communicates with the CRAC channel and initiates the subsequent events culminating in channel opening is unclear. Here, we show that redistribution of STIM1 and Orai1 occurs in parallel with a pronounced increase in fluorescence resonance energy transfer (FRET) between STIM1 and Orai1, supporting the idea that activation of CRAC channels occurs through physical interactions with STIM1. Co-expression of Orai1-CFP and Orai1-YFP results in a high degree of FRET in resting cells, indicating that Orai1 exists as a multimer. However, store depletion triggers molecular rearrangements in Orai1 resulting in a decline in Orai1-Orai1 FRET. The decline in Orai1-Orai1 FRET is not seen in the absence of STIM1 co-expression and is abolished in Orai1 mutants with impaired STIM1 interaction. Both the STIM1-Orai1 interaction as well as the molecular rearrangements in Orai1 are altered by two powerful modulators of CRAC channel activity: extracellular Ca(2+) and 2-APB. These studies identify a STIM1-dependent conformational change in Orai1 during the activation of CRAC channels and reveal that STIM1-Orai1 interaction and the downstream Orai1 conformational change can be independently modulated to fine-tune CRAC channel activity.
Radio-frequency Ablation Increases Intratumoral Liposomal Doxorubicin Accumulation in a Rat Breast Tumor Model (2002)

RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin.
Rayleigh fading compensation for QAM in land mobile radio communications (1993)

A pilot symbol-aided Rayleigh fading compensation is investigated for M-ary quadrature amplitude modulation (QAM) to achieve highly spectrally efficient land mobile communication systems. The optimum parameters for fading compensation, bit error rate (BER) performance against E/sub b//N/sub 0/ (energy per bit to the noise power spectrum density), adjacent channel interference, and cochannel interference for 16-QAM, 64-QAM, and 256-QAM, and the spectral efficiencies for these modulation schemes in Rayleigh fading environments are investigated by computer simulation. To further verify the effect of pilot symbol-aided fading compensation from a a practical point of view, a 16-QAM modem is implemented, laboratory experiments are executed, and the impact of the dynamic range limitation due to the resolution of the analog-to-digital (A/D) converters is evaluated, along with the imperfection of the analog circuits. It is demonstrated by computer simulation and laboratory experiments that the pilot symbol-aided fading compensation can sufficiently compensate for fast varying Rayleigh fading, and 16-QAM gives the highest spectral efficiency in the case of cellular systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tissue plasminogen activator: A new thrombolytic agent (1987)

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, contraindications, and dosage and administration of tissue plasminogen activator are reviewed. Tissue plasminogen activator (t-PA) is a serine protease that binds to fibrin-plasminogen complex, catalyzing the conversion of plasminogen to plasmin. Unlike streptokinase or urokinase, t-PA binds slowly, if at all, to free circulating plasminogen. This clot specificity suggests t-PA will not produce a systemic lytic effect; however, clot specificity appears to be dose-related, and concentrations similar to those achieved in recent clinical trials have been associated with hemostatic defects. Most clinical trials have used a recombinant DNA product (rt-PA). In the treatment of acute myocardial infarction, intravenous infusions of rt-PA appear to be more effective than intravenous streptokinase. Similar rates of hemorrhage, reperfusion arrhythmias, and reocculsion have been reported. Contraindications to rt-PA use are similar to those for other thrombolytic agents. Preliminary studies of rt-PA in various thromboembolic disorders are encouraging. Marketing approval of a t-PA product (rt-PA, Activase, Genentech, Inc.) is expected in the United States by mid-1987. Clinical trials suggest that rt-PA is more effective and as safe as intravenous streptokinase in lysing occlusive coronary-artery thrombi; however, safety and efficacy appear to be dose-related, and further study is needed to determine the optimal dose.
SLC15A2 genomic variation is associated with the extraordinary response of sorafenib treatment: whole-genome analysis in patients with hepatocellular carcinoma (2015)

Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC.