gebhart/patrepeval huggingface dataset:
Designed oligomers of cyanovirin-N show enhanced HIV neutralization (2011)

Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN(2)) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN(2) variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants.
Widespread Silent Transmission of Pertussis in Families: Antibody Correlates of Infection and Symptomatology (1990)

Four children with pertussis and their 18 family members were subjects of a 1-year study to detect infection and antibody responses to Bordetella pertussis. Attack rate for pertussis infection in contacts was 83%. Two-thirds of cases in these immunized contacts were subclinical. All infected family contacts had diagnostically elevated serologic tests for pertussis at the time the index case was diagnosed. Culture identified only 20% of infected contacts. Infected individuals had a mean of 5.5 of 10 antibody tests diagnostic for recent infection. ELISA assay for IgG to pertussis toxin and assay for IgA to filamentous hemagglutinin on serum and nasal secretions were the most discriminating diagnostic tests. Index cases and immunized contacts had different type and timing of antibody responses, making a single assay or sampling unable to identify all infected individuals. Symptomatic infection was characterized by higher magnitude of pertussis toxin antibody response and asymptomatic infection by filamentous hemagglutinin. After pertussis immunization, immunity to disease is greater than is protection from infection.
Near-optimal region selection for feature space reduction: novel preprocessing methods for classifying MR spectra (1998)

We introduce a global feature extraction method specifically designed to preprocess magnetic resonance spectra of biomedical origin. Such preprocessing is essential for the accurate and reliable classification of diseases or disease stages manifest in the spectra. The new method is genetic algorithm-guided. It is compared with our enhanced version of the standard forward selection algorithm. Both seek and select optimal spectral subregions. These subregions necessarily retain spectral information, thus aiding the eventual identification of the biochemistry of disease presence and progression. The power of the methods is demonstrated on two biomedical examples: the discrimination between meningioma and astrocytoma in brain tissue biopsies, and the classification of colorectal biopsies into normal and tumour classes. Both preprocessing methods lead to classification accuracies over 97% for the two examples.
RASand Leukemia: From Basic Mechanisms to Gene-Directed Therapy (1999)

An increasing body of data suggests that disruption of Ras signaling pathways, either directly through mutations or indirectly through other genetic aberrations, is important in the pathogenesis of a wide variety of cancers. Molecules such as farnesyl transferase inhibitors that interfere with the function of Ras may be exploitable in leukemia (as well as in solid tumors) as novel antitumor agents.
Optimizing Machine Learning Workloads in Collaborative Environments (2020)

Effective collaboration among data scientists results in high-quality and efficient machine learning (ML) workloads. In a collaborative environment, such as Kaggle or Google Colabratory, users typically re-execute or modify published scripts to recreate or improve the result. This introduces many redundant data processing and model training operations. Reusing the data generated by the redundant operations leads to the more efficient execution of future workloads. However, existing collaborative environments lack a data management component for storing and reusing the result of previously executed operations. In this paper, we present a system to optimize the execution of ML workloads in collaborative environments by reusing previously performed operations and their results. We utilize a so-called Experiment Graph (EG) to store the artifacts, i.e., raw and intermediate data or ML models, as vertices and operations of ML workloads as edges. In theory, the size of EG can become unnecessarily large, while the storage budget might be limited. At the same time, for some artifacts, the overall storage and retrieval cost might outweigh the recomputation cost. To address this issue, we propose two algorithms for materializing artifacts based on their likelihood of future reuse. Given the materialized artifacts inside EG, we devise a linear-time reuse algorithm to find the optimal execution plan for incoming ML workloads. Our reuse algorithm only incurs a negligible overhead and scales for the high number of incoming ML workloads in collaborative environments. Our experiments show that we improve the run-time by one order of magnitude for repeated execution of the workloads and 50% for the execution of modified workloads in collaborative environments.
The synthetic furanonaphthoquinone induces growth arrest, apoptosis and differentiation in a variety of leukaemias and multiple myeloma cells (2005)

2-methyl-naphtho[2,3-b]furan-4,9-dione (FNQ3), a synthetic analogue of the quinone kigelinone, has demonstrated a real potential for use in the treatment of a variety of solid tumours. Unlike other quinones, such as mitomycin-C and adriamycin, the cytotoxicity of FNQ3 is often 10- to 14-fold more potent towards the tumour cells than their normal counterparts. We report, for the first time, that the drug had activity against a broad spectrum of leukaemias and multiple myeloma cells. It decreased the growth of acute myeloid leukaemia (AML) and multiple myeloma cell lines in a dose-dependent fashion (50% inhibitory concentration approximately 1.25 microg/ml against most of the leukaemia cell lines). This dose apparently initiated mitochondrial collapse as measured by depolarisation of the mitochondrial membrane. FNQ3 potentiated the differentiation of HL-60 myeloid cells in the presence of either 1alpha, 25(OH)(2) dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or all-trans-retinoic acid (ATRA). FNQ3 inhibited the proliferation of primary AML cells while inducing apoptosis. Eleven of 14 (79%) AML marrow samples had a prominent decrease in their clonogenic growth when cultured in the presence of the drug. In summary, this drug has growth inhibitory, apoptotic and differentiative effects against myeloid leukaemias and multiple myeloma cells. FNQ3 may represent a new therapeutic approach to these malignancies.
Evaluation of 9-cis-Retinyl Acetate Therapy inRpe65−/−Mice (2009)

Treatment with 9-cis-R-Ac improves visual function and preserves retinal morphology in Rpe65(-/-) mice.
GEOMETRIC MODELING ISSUES IN COMPUTER AIDED DESIGN OF MARINE STRUCTURES (1988)

This article discusses the application of geometric modeling in computer aided engineering of complex systems such as ships and offshore structures. Modern methods of geometric modeling promise to provide a common framework to conduct design, analysis and simulation, and manufacturing of engineering artifacts in a unified computer environment. Methods of shape representation and interrogation in the computer are identified and their salient features are analyzed to allow understanding of their strengths and limitations in the context of different applications. Issues of data exchange between systems of different inherent capabilities are also discussed. Finally, some other open problems in this field are identified.
Inhibition by cyclopropene fatty acids of the desaturation of stearic acid in hen liver (1967)

The mechanism of the hardening of body fats of animals by dietary lipids which contain cyclopropene fatty acids has been studied. Dietary methyl sterculate increased the stearic acid content of egg yolk lipid and decreased the activity of the stearic acid desaturase system of hen liver. The cyclopropene fatty acids were specific inhibitors of the stearic acid desaturase system of hen livers since other fatty acids, including two possible metabolites of sterculic acid, failed to inhibit the system at equivalent concentrations. Sterculic acid was a more effective inhibitor of the system than malvalic acid. Kinetic studies have shown that the inhibition is irreversible. Apparent kinetic constants were determined for the system.The results support the hypotheses that cyclopropene fatty acids inactivate an essential component of the desaturase system, probably by combination with-SH groups, and that this inhibition causes many of the effects of dietary cyclopropene fatty acids, including permeability disorders of eggs.
Effects of local treatment with salmeterol and terbutaline on anti-IgE-induced wheal, flare, and late induration in human skin (1996)

The capacity of terbutaline and the long-acting beta 2-agonist salmeterol to suppress wheal-and-flare reactions (WFRs) to intradermal antihuman IgE and to histamine was evaluated in 36 healthy volunteers. We also examined effects of the two drugs on the subsequent late cutaneous reaction (LCR) to anti-IgE. Salmeterol (10(-10)-10(-6) M) and terbutaline (10(-10)-10(-5) M), injected intradermally 2 or 15 min before anti-IgE challenge, produced a dose-dependent inhibition of the WFRs to anti-IgE (titer 1 : 10000) with a maximal effect of approximately 60% (wheal) and approximately 75% (flare) by both drugs. On a molar basis, salmeterol was approximately 10-100 times more potent than terbutaline in inhibiting the WFRs. Moreover, the wheal response to histamine (4 nmol) was antagonized by approximately 40% after pretreatment with either salmeterol (10(-5) M) or terbutaline (10(-4) M). We found that both salmeterol and terbutaline exhibited anti-WFR activity for up to 24 h, salmeterol being significantly more potent in this regard. When selecting a 15-min pretreatment interval with equieffective anti-WFR doses from the first dose-response experiments (i.e., a salmeterol: terbutaline ratio of 1 : 10), the WFRs to high-dose anti-IgE (titer 1 : 100) were inhibited by terbutaline (10(-5) M) by 25-30%, but not by salmeterol (10(-6)). On the other hand, salmeterol attenuated (by up to approximately 35%) the subsequent LCR more effectively than terbutaline. As compared to the pretreatment procedure, infiltration of the drugs (single doses) into the wheals 30 min after challenge with anti-IgE (titer 1 : 100) proved to be less effective on the development of LCRs. Taken together, salmeterol was found to express higher potency and have longer duration of action than terbutaline in inhibition of IgE-mediated inflammation in human skin.
The Pharmacokinetics of TNP‐470, a New Angiogenesis Inhibitor (1997)

Concentrations of TNP-470 that have in vitro activity were achievable in vivo. The drug was rapidly cleared from the circulation after a single 1-hour infusion. There was considerable interpatient variability in the clearance, but no evidence of saturable elimination. If more prolonged exposure is necessary for activity, administration of TNP-470 by continuous infusion may be suitable.
Unraveling the Web services web: an introduction to SOAP, WSDL, and UDDI (2002)

This tutorial explores the most salient and stable specifications in each of the three major areas of the emerging Web services framework. They are the simple object access protocol, the Web Services Description Language and the Universal Description, Discovery, and Integration directory, which is a registry of Web services descriptions.
Transient expression vectors for functional genomics, quantification of promoter activity and RNA silencing in plants (2005)

In developing a series of vectors ideally suited to transient expression analysis we have provided a resource that further advances the application of this technology. These minimal vectors are ideally suited to conventional cloning methods and we have used them to demonstrate their flexibility to investigate enzyme activity, transcription regulation and post-transcriptional regulatory processes in transient assays.
Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis (2000)

Epidemiological studies have indicated that reduced DNA repair capacity and increased DNA adduct levels are associated with increased risk of lung cancer. Nucleotide excision repair (NER) is the major pathway in humans for repairing DNA adducts induced by smoking-related carcinogens, such as benzo[a]pyrene diol epoxide. We hypothesized that genetically determined baseline expression level of genes involved in NER is associated with risk of lung cancer. In a pilot case-control study, we measured the relative expression levels of five NER genes [ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6 and XPC (ERCC, excision repair cross-complementing; CSB, Cockayne's syndrome complementary group B)] in phytohemagglutinin-stimulated peripheral lymphocytes obtained from 75 lung cancer patients and 95 controls using a newly developed multiplex RT-PCR assay. Cases and controls were matched on age, sex, ethnicity and tobacco use. The expression level of the beta-actin gene was used as an internal control for the relative quantitation. We observed a 12.2 and 12.5% decrease in the baseline expression levels of XPG/ERCC5 and CSB/ERCC6, respectively, in cases compared with controls. These differences were statistically significant (P < 0.01) when the median expression level in the controls was used as the cut-off point, the lung cancer patients were significantly more likely than the controls to have reduced expression levels of XPG/ERCC5 [odds ratio (OR), 2.32; 95% confidence interval (CI), 1.22-4.43] and CSB/ERCC6 (OR, 2.49; 95% CI, 1.28-4.84). There was also a dose-response relationship between reduced expression levels and increased lung cancer risk (trend test: P < 0.01). Our results suggest that individuals whose expression levels of XPG/ERCC5 and CSB/ERCC6 are reduced may be at higher risk of lung cancer.
Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells (2010)

Skeletal muscle is the primary site of dietary glucose disposal, a function that depends on insulin-mediated exocytosis of GLUT4 vesicles to its cell surface. In skeletal muscle and adipocytes, this response involves Akt signaling to the Rab-GAP (GTPase-activating protein) AS160/TBC1D4. Intriguingly, the AS160-targeted Rabs appear to differ, with Rab8A participating in GLUT4 exocytosis in muscle cells and Rab10 in adipocytes, and their activation by insulin is unknown. Rabs 8A, 10, and 13 belong to the same subfamily of Rab-GTPases. Here we show that insulin promotes GTP loading of Rab13 and Rab8A but not Rab10 in rat L6 muscle cells, Rab8A activation preceding that of Rab13. siRNA-mediated Rab13 knockdown blocked the insulin-induced increase of GLUT4 at the muscle cell surface that was rescued by a Rab13 ortholog but not by Rab8A. Constitutively active AS160 lowered basal and insulin-stimulated levels of surface GLUT4, effects that were reversed by overexpressing Rab8A or Rab13, suggesting that both Rabs are targets of AS160-GAP activity in the context of GLUT4 traffic. Rab13 had a broader intracellular distribution compared with the perinuclear restriction of Rab8A, and insulin promoted Rab13 colocalization with GLUT4 at the cell periphery. We conclude that Rab13 and Rab8A are Rab-GTPases activated by insulin, and that downstream of AS160 they regulate traffic of GLUT4 vesicles, possibly acting at distinct steps and sites. These findings close in on the series of events regulating muscle GLUT4 traffic in response to insulin, crucial for whole-body glucose homeostasis.
Sinr Maximizing Equalizer Receiver For Ds-Cdma (2000)

Publication in the conference proceedings of EUSIPCO, Tampere, Finland, 2000
5′ Flanking Region of the Clara Cell Secretory Protein Gene Specifies a Unique Temporal and Spatial Pattern of Gene Expression in the Developing Pulmonary Epithelium (1994)

Expression of a transgene containing 2.25 kb of the 5' flanking region of the rat Clara cell secretory protein gene and the human growth hormone gene was examined in developing mice. Despite an absolute preservation of tissue specificity based on RNA blot analysis, transgene-specific transcripts were detectable as early as 12.5 days of gestation, at least 4 days prior to endogenous Clara cell secretory protein gene expression. As differentiation proceeded, in situ hybridization revealed an increasingly restricted pattern of transgene expression in the developing pulmonary epithelium, such that by day 16.5 of gestation endogenous and transgene expression were confined to identical cells within the bronchiolar epithelium. The temporal discordance in transgene expression suggests the presence of unique cis-acting elements within the Clara cell secretory protein gene, not present in the transgene, which transduce developmental timing within pulmonary epithelium by actively repressing Clara cell secretory protein gene expression during early development. The unique expression of this transgene serves as a lineage marker in the respiratory epithelium and unmasks a temporal and spatial pattern of gene expression not observed in any pulmonary genes.
Epigastric impedance: a non-invasive method for the assessment of gastric emptying and motility. (1985)

The impedance of the epigastrium to a 4 mA, 100 KHz AC current increases while liquids of low electrical conductivity are being drunk. Logically, the decline which follows occurs as the liquid leaves the stomach. This impedance measurement of gastric emptying proved comparable with the dye dilution method. In a placebo controlled trial the impedance method recorded significantly faster gastric emptying rates after metoclopramide. The impedance trace contains regular activity in the 2-4 cycle/min range consistent with gastric contractions. This non-invasive and technically simple method may thus provide a measure of simultaneous gastric emptying rates and motility.
Impact of a New Fusion Receptor on PD-1–Mediated Immunosuppression in Adoptive T Cell Therapy (2015)

Transduction of T cells with this new PD-1-CD28 receptor has the potential of breaking the PD-1-PD-L1-immunosuppressive axis in ACT.
Magnetic Tweezers Measurement of the Bond Lifetime−Force Behavior of the IgG−Protein A Specific Molecular Interaction (2007)

The bond lifetime-force behavior of the immunoglobulin G (IgG)-protein A interaction has been studied with magnetic tweezers to characterize the physical properties of the bond under nonequilibrium conditions. Super-paramagnetic microparticles were developed that have a high and uniform magnetization to simultaneously apply a piconewton-scale tensile force to many thousands of IgG-protein A bonds. A strong and a weak slip bond were detected with an effective bond length that is characteristic of short-range, stiff intermolecular interactions. These bonds are attributed to the interaction of protein A with the constant region (Fc) and heavy chain variable domain (VH) of IgG, respectively. The IgG-VH interaction appears to be one of the weakest specific molecular interactions that has been identified with a single molecule force measurement technique. This study demonstrates that magnetic tweezers can be used to rapidly characterize very weak biomolecular interactions as well as strong biomolecular interactions with a high degree of accuracy.
Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug (2018)

Polypeptides are promising carriers for chemotherapeutics: they have minimal toxicity, can be recombinantly synthesized with precise control over molecular weight, and enhance drug pharmacokinetics as self-assembled nanoparticles. Polypeptide-based systems also provide the ability to achieve active targeting with genetically encoded targeting ligands. While passive targeting promotes accumulation of nanocarriers in solid tumors, active targeting provides an additional layer of tunable control and widens the therapeutic window. However, fusion of most targeting proteins to polypeptide carriers exposes the limitations of this approach: the residues that are used for drug attachment are also promiscuously distributed on protein surfaces. We present here a universal methodology to solve this problem by the site-specific attachment of extrinsic moieties to polypeptide drug delivery systems without cross-reactivity to fused targeting domains. We incorporate an unnatural amino acid, p-acetylphenylalanine, to provide a biorthogonal ketone for attachment of doxorubicin in the presence of reactive amino acids in a nanobody-targeted, elastin-like polypeptide nanoparticle. These nanoparticles exhibit significantly greater cytotoxicity than nontargeted controls in multiple cancer cell lines.
Biomedical coatings by the covalent immobilization of polysaccharides onto gas-plasma-activated polymer surfaces (2000)

As the surface properties of polymeric biomaterials play an important role in the performance of biomedical devices, highly hydrophilic, ultrathin coatings were applied onto hydrophobic, perfluorinated and organosilicon polymers by the covalent immobilization of polysaccharides using a reductive amination reaction. Gas plasma (r.f. glow discharge) methods were employed to equip the surfaces of these normally unreactive polymeric substrates with chemical groups capable of reacting with polysaccharides in aqueous solution. In one variant, ammonia plasmas were used to introduce into the polymer surfaces a submonolayer of amine groups. Alternatively, an n-heptylamine process vapour was used to deposit a thin plasma polymer film that possessed surface amine groups. The polysaccharides were activated for covalent immobilization by periodate oxidation, which produced hemiacetal structures, as revealed by NMR and XPS. The hemiacetal structures in the polysaccharide chains were reacted with the surface amine groups on the polymers. The resulting Schiff base linkages were stabilized by reduction to secondary amine linkages using sodium cyanoborohydride. Detailed surface analysis is important for verification that the intended chemistries have indeed been achieved in such multilayer coating schemes. X-ray photoelectron spectroscopy provided a thickness estimate of 1 ± 0.3 nm for the polysaccharide coatings in the dehydrated state. Copyright © 2000 John Wiley & Sons, Ltd.
Inhibition of Neointima Hyperplasia of Mouse Vein Grafts by Locally Applied Suramin (1999)

Suramin inhibited SMC migration and proliferation in vivo and in vitro by blocking PDGF-initiated PDGF receptor and MAPK-AP-1 signaling. These findings indicate that locally applied suramin is effective in a mouse model of venous bypass graft arteriosclerosis.
Solid‐State NMR and DFT Studies on the Formation of Well‐Defined Silica‐Supported Tantallaaziridines: From Synthesis to Catalytic Application (2016)

Single-site, well-defined, silica-supported tantallaaziridine intermediates [≡Si-O-Ta(η(2) -NRCH2 )(NMe2 )2 ] [R=Me (2), Ph (3)] were prepared from silica-supported tetrakis(dimethylamido)tantalum [≡Si-O-Ta(NMe2 )4 ] (1) and fully characterized by FTIR spectroscopy, elemental analysis, and (1) H,(13) C HETCOR and DQ TQ solid-state (SS) NMR spectroscopy. The formation mechanism, by β-H abstraction, was investigated by SS NMR spectroscopy and supported by DFT calculations. The C-H activation of the dimethylamide ligand is favored for R=Ph. The results from catalytic testing in the hydroaminoalkylation of alkenes were consistent with the N-alkyl aryl amine substrates being more efficient than N-dialkyl amines.