gebhart/patrepeval huggingface dataset:
Evaluation of Intradural Stimulation Efficiency and Selectivity in a Computational Model of Spinal Cord Stimulation (2014)

Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS, which, in turn, provides predictions that can be tested in future clinical studies assessing the potential therapeutic benefits of intradural SCS.
Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells (2004)

Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a cornerstone in the treatment of this malignancy. Unfortunately, the efficacy of paclitaxel is limited by the development of drug resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1) overexpression, and in vitro paclitaxel resistance typically demonstrates overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel-resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the role of these transporters in paclitaxel-resistant ovarian cancer cells, small interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the paclitaxel-resistant SKOV-3TR and OVCAR8TR ovarian cancer cell lines. Treatment of these lines with either chemically synthesized siRNAs or transfection with specific vectors that express targeted siRNAs demonstrated decreased mRNA and protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4-fold reduction of paclitaxel resistance in the lines treated with the synthesized siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the cell lines transfected with siRNA of ABCB1 expressing vectors. ABCB4 siRNA-treated cell lines showed minor reduction in paclitaxel resistance. These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance.
Alanine Point-Mutations in the Reactive Region of Bovine Pancreatic Trypsin Inhibitor:  Effects on the Kinetics and Thermodynamics of Binding to β-Trypsin and α-Chymotrypsin (1996)

In an effort to relate structural, kinetic, and thermodynamic features in a model macromolecular recognition process, the amino acid residues in the reactive surface of bovine pancreatic trypsin inhibitor (BPTI) and surrounding residues were substituted individually by alanine, and the effects of the point-mutations on the kinetics and thermodynamics of inhibition by BPTI toward trypsin and chymotrypsin were investigated. Fifteen alanine mutants were produced. The majority of the BPTI mutants exhibited a binding affinity similar to that of the wild-type protein. The exceptions were the primary specificity site (PI) mutant and those mutants that seem to have nonlocal perturbations of structure, as revealed by circular dichroism and thermostability measurements. The mutation at the P1 site caused a reduction in the binding free energy of 10 and 1.8 kcal mol-1 for trypsin and chymotrypsin, respectively. The losses in binding affinity were determined almost exclusively by an increase in the dissociation rate constant. However, the rate of association of the P1 mutant, Lys-15-Ala, with trypsin was also drastically reduced (> 200-fold). Calorimetric measurements of the heats of binding for the association of chymotrypsin with the wild-type inhibitor and its alanine mutants allowed determination of the relative contributions of the changes in enthalpy and entropy to the free energy of binding. Compensatory changes in the two parameters were observed in several cases, which were attributed to desolvation effects at the binding interface.
An in depth study into using EMI signatures for appliance identification (2014)

Energy conservation is a key factor towards long term energy sustainability. Real-time end user energy feedback, using disaggregated electric load composition, can play a pivotal role in motivating consumers towards energy conservation. Recent works have explored using high frequency conducted electromagnetic interference (EMI) on power lines as a single point sensing parameter for monitoring common home appliances. However, key questions regarding the reliability and feasibility of using EMI signatures for non-intrusive load monitoring over multiple appliances across different sensing paradigms remain unanswered. This work presents some of the key challenges towards using EMI as a unique and time invariant feature for load disaggregation. In-depth empirical evaluations of a large number of appliances in different sensing configurations are carried out, in both laboratory and real world settings. Insights into the effects of external parameters such as line impedance, background noise and appliance coupling on the EMI behavior of an appliance are realized through simulations and measurements. A generic approach for simulating the EMI behavior of an appliance that can then be used to do a detailed analysis of real world phenomenology is presented. The simulation approach is validated with EMI data from a router. Our EMI dataset - High Frequency EMI Dataset (HFED) is also released.
ANALYSIS OF MECHANICAL AND METABOLIC FACTORS IN THE GAIT OF CONGENITAL BELOW KNEE AMPUTEES (1992)

Prosthetic feet have been developed with the intention that they deform during the first half of the stance phase to store energy that can be released at the end of stance and contribute to push-off. The purpose of this study was to examine the three-dimensional kinematics and kinetics of gait and metabolic energy cost in children and adolescents with below-knee amputations using the SACH and Seattle prosthetic feet. The metabolic test consisted of an 8-min walk around an oval track while expired gases were collected and analyzed. The biomechanical test consisted of 10 walking trials: 5 for each of the prosthetic and sound limbs. Stance and swing phase moments and powers were calculated for both the prosthetic and sound limbs. A four-camera VICON system recorded movements of the limb segments to calculate joint kinematics, and these were combined with ground reaction force data in a three-dimensional model to determine moments and powers about the hip, knee and ankle joints. The Seattle foot produced a small increase in stride length, which led to a small increase in walking velocity. Biomechanical data revealed that the Seattle foot was less resistant to passive dorsiflexion in midstance, and although there was no effect on the work done across the prosthetic ankle, a knee flexor moment dominated the stance phase when the SACH foot was tested, whereas the Seattle foot allowed a normal extensor moment. The profile of work was unaffected by the type of foot. On the sound side, the hip produced most of the positive work while the ankle output was below normal.(ABSTRACT TRUNCATED AT 250 WORDS)
A hybrid polymer gel with controlled rates of cross-link rupture and self-repair (2006)

A family of hybrid polymer gels is described, in which covalent cross-links create a permanent, stiff scaffold onto which reversible metal-ligand coordinative cross-links are added. The reversible metal-ligand interactions are shown to bear mechanical stress within the hybrid gel, and relaxations in response to that applied stress are consistent with the stress-free kinetics of ligand exchange in systems that model the reversible cross-links. The stress-induced dissociation of a model metal-ligand complex is examined by a single-molecule force spectroscopy, and its mechanical response is compared with a previously studied complex. The mechanical response of the individual interactions is relevant to those found in the family of hybrid gels, and the modular platform is therefore suitable for the study of stress-induced molecular dissociations, and their subsequent repair, within a macroscopic material of fixed structure.
Function of Positive Charges Following Signal-Anchor Sequences during Translocation of the N-terminal Domain (2005)

In topogenesis of membrane proteins on the endoplasmic reticulum, the orientation of the hydrophobic transmembrane (TM) segment is influenced by the charge of the flanking amino acid residues. We assessed the function of the positive charges downstream of the hydrophobic segment using synaptotagmin II. The positive charges were systematically replaced with non-charged residues. Although the original TM segment translocated the N terminus, the topology was inverted, depending on the mutations. Orientation was affected in mutants in which 6 Lys were shifted downstream, even when the 6 Lys were 25 residues from the hydrophobic segment. The Lys was functionally replaced by Arg, but not by Asp or Glu. The timing of action during polypeptide elongation indicated that the Lys functions at the ribosome exit sites. We suggest that the commitment of the TM segment to a particular orientation is influenced by far downstream parts of the polypeptide chain and that the positive charges are decoded after exiting the ribosome.
Glucosinolates and their breakdown products in food and food plants (1983)

Abstract This review surveys the occurrence, analysis, and properties of glucosinolates and derived compounds in plants and products intended for humans and animal consumption. The paper, which includes references published in 1981, is also intended to compliment existing reviews on the chemistry of these sulfur‐containing natural products. Particular emphasis is placed upon members of the Brassica family because of their importance as vegetables, condiments, oilseeds, and animal feedingstuffs. Since much of the work considered here relates to glucosinolate decomposition products, biochemical information concerning the nature, occurrence, and properties of the glucosinolate‐degrading enzyme, myrosinase, is considered in Section III. The methods available for the chemical analysis of glucosinolates and their various breakdown products are discussed critically. Factors affecting the glucosinolate content of plants and plant products arc outlined in Section VII. Particular emphasis is placed upon the effect of processing on the concentration and nature of breakdown products and on the myrosinase activity. The role of glucosinolate breakdown products on flavor development is examined in Section VIII. The more general effects, both beneficial and adverse, of these compounds in food are discussed in Section X. Since such effects in animal feedingstuffs have been the subject of regular reviews, these are considered here only briefly. Contraindications in the literature are pointed out, areas which have been inadequately explored are highlighted, and suggestions are made for future research.
Identification of a New Series of STAT3 Inhibitors by Virtual Screening (2010)

The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3. In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay. STX-0119 selectively abrogated the DNA binding activity of STAT3 and suppressed the expression of STAT3-regulated oncoproteins such as c-myc and survivin in cancer cells. In contrast, a truncated inactive analogue, STX-0872, did not exhibit those activities. Oral administration of STX-0119 effectively abrogated the growth of human lymphoma cells in a SCC-3 subcutaneous xenograft model without visible toxicity. Structure-activity relationships of STX-0119 derivatives were investigated using the docking model of the STAT3-SH2 domain/STX-0119.
Optimizing the distance for bacterial treatment using surface micro-discharge plasma (2012)

Reactive plasma species generated by a surface micro-discharge (SMD) electrode are delivered to the target by diffusion and/or convection. In humid air conditions, the diffusion process is coupled with complicated plasma chemical reactions, which affect the density profiles of bactericidal agents. One may expect that the production of reactive plasma species can be optimized at a certain distance. Our experimental results found the optimum distance for achieving the highest bactericidal efficiency with plasma treatment using an SMD electrode. The optimum distance is about 2–4 mm from the SMD electrode to the target and depends on the geometry of the experiment. The bactericidal efficiency in the plasma-treated area can be improved by a factor of 30 if the bacterial samples are placed at the optimum distance. The results show the predominant role of the long-lived reactive plasma species. It is seen that the diffusion model of multi-plasma species with coupled plasma chemical reactions would be highly important for understanding the bactericidal property of cold atmospheric plasmas and therefore for optimizing cold atmospheric plasma sources for medical and biological applications.
Quantitative Multianalyte Microarray Immunoassay Utilizing Upconverting Phosphor Technology (2012)

A quantitative multianalyte immunoassay utilizing luminescent upconverting single-crystal nanoparticles as reporters on an antibody array-in-well platform was demonstrated. Upconverting nanoparticles are inorganic rare earth doped materials that have the unique feature of converting low energy infrared radiation into higher energy visible light. Autofluorescence, commonly limiting the sensitivity of fluorescence-based assays, can be completely eliminated with photon upconversion technology because the phenomenon does not occur in biological materials. Biotinylated antibodies for three analytes (prostate specific antigen, thyroid stimulating hormone, and luteinizing hormone) were printed in an array format onto the bottom of streptavidin-coated microtiter wells. Analyte dilutions were added to the wells, and the analytes were detected with antibody-coated upconverting nanoparticles. Binding of the upconverting nanoparticles was imaged with an anti-Stokes photoluminescence microwell imager, and the standard curves for each analyte were quantified from the selected spot areas of the images. Single analyte and reference assays were also carried out to compare with the results of the multianalyte assay. Multiplexing did not have an effect on the assay performance. This study demonstrates the feasibility of upconverting single-crystal nanoparticles for imaging-based detection of quantitative multianalyte assays.
Bromination of the Two Propylbenzenes and Three Butylbenzenes (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBromination of the Two Propylbenzenes and Three ButylbenzenesJohn H. Lamneck Jr.Cite this: J. Am. Chem. Soc. 1954, 76, 4, 1106–1107Publication Date (Print):February 1, 1954Publication History Published online1 May 2002Published inissue 1 February 1954https://pubs.acs.org/doi/10.1021/ja01633a051https://doi.org/10.1021/ja01633a051research-articleACS PublicationsRequest reuse permissionsArticle Views271Altmetric-Citations10LEARN 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
Disease-dependent Differently Methylated Regions (D-DMRs) of DNA are Enriched on the X Chromosome in Uterine Leiomyoma (2011)

Uterine leiomyoma is the most common benign tumor in women. Although responsible gene mutations have not been found in leiomyomas, they represent a progressive disease with irreversible symptoms. To characterize epigenetic features of uterine leiomyomas, the DNA methylation status of a paired sample of leiomyoma and normal myometrium was subjected to a microarray-based DNA methylation analysis with restriction tag-mediated amplification (D-REAM). In the leiomyoma, we identified an aberrant DNA methylation status for 463 hypomethylated and 318 hypermethylated genes. Although these changes occurred on all chromosomes, aberrantly hypomethylated genes were preferentially located on the X chromosome. Using paired samples of normal myometrium and leiomyoma from 6 hysterectomy patients, methylation-sensitive quantitative real-time PCR revealed 14 shared X chromosome genes with an abnormal DNA hypomethylation status (FAM9A, CPXCR1, CXORF45, TAF1, NXF5, VBP1, GABRE, DDX53, FHL1, BRCC3, DMD, GJB1, AP1S2 and PCDH11X) and one hypermethylated locus (HDAC8). Expression of XIST, which is involved in X chromosome inactivation, was equivalent in the normal myometrium and leiomyoma, indicating that the epigenetic abnormality on the X chromosome did not result from aberration of XIST gene expression. Based on these data, a unique epigenetic signature for uterine leiomyomas has emerged. The 14 hypomethylated and one hypermethylated loci provide valuable biomarkers for understanding the molecular pathogenesis of leiomyoma.
Tumor targeting of the IL‐15 superagonist RLI by an anti‐GD2 antibody strongly enhances its antitumor potency (2013)

Immunocytokines (ICKs) targeting cytokines to the tumor environment using antibodies directed against a tumor-associated antigen often have a higher therapeutic index than the corresponding unconjugated cytokines. Various ICKs displaying significant antitumoral effects in several murine tumor models have already been developed, and some of them, in particular interleukin (IL)-2-based ICKs, are in Phase II clinical trials. Although sharing common biological activities with IL-2 in vitro, IL-15 is now considered as having a better potential in antitumor immunotherapeutical strategies and has been shown to be less toxic than IL-2 in preclinical studies. We previously developed the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. RLI showed better biological activities than IL-15 in vitro as well as higher antitumoral effects in vivo in murine and human cancer models. Here, we investigated, in the context of an ICK, the effect of associating RLI with an antibody targeting the GD2 ganglioside, a validated tumoral target expressed on many neurectodermal tumors. Anti-GD2-RLI fully retained the cytokine potential of RLI and the antibody effector functions (antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity). It displayed strong antitumor activities in two syngeneic cancer models in immunocompetent mice (subcutaneous EL4 and metastatic NXS2). Its therapeutic potency was higher than those of RLI and anti-GD2 alone or in combination. We suggest that this is related to its bifunctional (cytokine and antibody) nature.
Selectively Desulfated Heparin Inhibits Fibroblast Growth Factor-induced Mitogenicity and Angiogenesis (2000)

Fibroblast growth factors (FGFs) are known to induce formation of new blood vessels, angiogenesis. We show that FGF-induced angiogenesis can be modulated using selectively desulfated heparin. Chinese hamster ovary cells (CHO677) deficient in heparan sulfate biosynthesis were employed to assess the function of heparin/heparan sulfate in FGF receptor-1 (FGFR-1) signal transduction and biological responses. In the presence of FGF-2, FGFR-1 kinase and subsequent mitogen-activated protein kinase Erk2 activities were augmented in a dose-dependent manner, whereas high concentrations of heparin resulted in decreased activity. The length of the heparin oligomer, minimally an 8/10-mer, was critical for the ability to enhance FGFR-1 kinase activity. The N- and 2-O-sulfate groups of heparin were essential for binding to FGF-2, whereas stimulation of FGFR-1 and Erk2 kinases by FGF-2 also required the presence of 6-O-sulfate groups. Sulfation at 2-O- and 6-O-positions was moreover a prerequisite for binding of heparin to a lysine-rich peptide corresponding to amino acids 160-177 in the extracellular domain of FGFR-1. Selectively 6-O-desulfated heparin, which binds to FGF-2 but fails to bind the receptor, decreased FGF-2-induced proliferation of CHO677 cells, presumably by displacing intact heparin. Furthermore, FGF-2-induced angiogenesis in chick embryos was inhibited by 6-O-desulfated heparin. Thus, formation of a ternary complex of FGF-2, heparin, and FGFR-1 appears critical for the activation of FGFR-1 kinase and downstream signal transduction. Preventing complex formation by modified heparin preparations may allow regulation of FGF-2 functions, such as induction of angiogenesis.