gebhart/patrepeval huggingface dataset:
Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins (1988)

Scrapie and Creutzfeldt-Jakob disease are transmissible, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated PrPSc, encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designated PrPC. We established clonal cell lines which support the replication of mouse scrapie or Creutzfeldt-Jakob disease prions. Mouse neuroblastoma N2a cells were exposed to mouse scrapie prions and subsequently cloned. After limited proteinase K digestion, three PrP-immunoreactive proteins with apparent molecular masses ranging between 20 and 30 kilodaltons were detected in extracts of scrapie-infected N2a cells by Western (immuno-) blotting. The authenticity of these PrPSc molecules was established by using monospecific antiserum raised against a synthetic peptide corresponding to a portion of the prion protein. Those clones synthesizing PrPSc molecules possessed scrapie prion infectivity as measured by bioassay; clones without PrPSc failed to demonstrate infectivity. Detection of PrPSc molecules in scrapie-infected N2a cells supports the contention that PrPSc is a component of the infectious scrapie particle and opens new approaches to the study of prion diseases.
MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors. (2002)

The antitumor efficacy of the synthetic benzamide derivative MS-27-275 (MS-275), an inhibitor of histone deacetylation [T. Suzuki et al., J. Med. Chem., 42: 3001-3003, 1999], was evaluated in a series of pediatric solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma (EWS), retinoblastoma, medulloblastoma, undifferentiated sarcoma (US), osteosarcoma, and malignant rhabdoid tumors. Treatment with MS-275 results in an increase in acetylation of histones within 4 h of drug exposure. The cell lines were treated with various concentrations of MS-275 for 3 days and incubated with [(3)H]thymidine for 20 h before cell harvest. MS-275 inhibited [(3)H]thymidine uptake in a dose-dependent manner in all tumor cell lines examined. The IC(50) ranged from 50 nm in the D283 medulloblastoma cell line to 1.3 micro M in the US. A common feature of MS-275 treatment of pediatric tumor cell lines was induction of p21mRNA. However, the effects on cell cycle were diverse because in some cases MS-275 induced an increase in G(1) or G(2), whereas in others, there was an induction of apoptosis. In EWS, the EWS/fli chimeric transcription factor created by the t(11;22) suppresses transforming growth factor (TGF) betaRII transcription, however, MS-275 was able to induce an increase in TGF-betaRII mRNA and restore TGF-beta signaling. Using xenograft orthotopic models of US, EWS, and neuroblastoma, we find that the growth of established tumors is inhibited in mice treated with MS-275.
Fluorine and Trifluoromethyl Substituted Anilines: Site Selective Metalation and Electrophilic Substitution (1992)

When treated with tert-butyllithium in THF at -50 Deg, N-BOC (tert-butoxycarbonyl) protected fluoroanilines and trifluoromethylanilines, e.g., o-, m-, or p-F3CC6H4NHCO2CMe3, undergo metalation at the position adjacent to that carrying the nitrogen. If, however, the nitrogen carries two alkyl or trimethylsilyl groups as substituents and highly polar metalating reagents such as butyllithium activated by N,N,N',N\\",N\\"-pentamethyldiethylenetriamine (PMDTA) or potassium tert-butoxide are employed, the fluoroaniline derivs. are preferentially deprotonated next to the halogen atom. [on SciFinder (R)]
Synthesis and Evaluation of Estrogen Receptor Ligands with Bridged Oxabicyclic Cores Containing a Diarylethylene Motif:  Estrogen Antagonists of Unusual Structure (2005)

A new series of ligands for the estrogen receptor (ER) based on a three-dimensional structural motif consisting of a bridged oxabicyclic core (7-oxabicyclo[2.2.1]heptene or heptadiene) were synthesized and examined for their receptor binding activity and as regulators of transcription through the two ER subtypes, ER alpha and ER beta. The prototypical ligands also contain a 1,2-diarylethylene motif, common to many nonsteroidal estrogens, as an embellishment on the oxabicyclic core. Thus, these ligands bear peripheral groups typically found in ER ligands, built here upon an overall three-dimensional core topology that is unusual for these targets. Most of these compounds were conveniently synthesized by a Diels-Alder reaction of various 3,4-diarylfurans with a variety of dienophiles, neat and under mild conditions in the absence of catalysts. Some of the synthesized compounds display good binding affinity for the ER, and in transcription assays, the highest affinity compounds are antagonists on both ERs. Molecular modeling studies suggest a structural basis for the antagonist activity of these compounds. These compounds, based on the bicyclo[2.2.1]core system, expand the structural diversity of ligands that can be antagonists for the estrogen receptors.
Structure-Based Discovery of A 2A Adenosine Receptor Ligands (2010)

The recent determination of X-ray structures of pharmacologically relevant GPCRs has made these targets accessible to structure-based ligand discovery. Here we explore whether novel chemotypes may be discovered for the A(2A) adenosine receptor, based on complementarity to its recently determined structure. The A(2A) adenosine receptor signals in the periphery and the CNS, with agonists explored as anti-inflammatory drugs and antagonists explored for neurodegenerative diseases. We used molecular docking to screen a 1.4 million compound database against the X-ray structure computationally and tested 20 high-ranking, previously unknown molecules experimentally. Of these 35% showed substantial activity with affinities between 200 nM and 9 microM. For the most potent of these new inhibitors, over 50-fold specificity was observed for the A(2A) versus the related A(1) and A(3) subtypes. These high hit rates and affinities at least partly reflect the bias of commercial libraries toward GPCR-like chemotypes, an issue that we attempt to investigate quantitatively. Despite this bias, many of the most potent new ligands were novel, dissimilar from known ligands, providing new lead structures for modulation of this medically important target.
Silane Ligand Exchange to Make Hydrophobic Superparamagnetic Nanoparticles Water-Dispersible (2007)

Ferrite magnetic nanoparticles (MNPs) were functionalized with a variety of silanes bearing different functional endgroups to render them stable with respect to aggregation and keep them well-dispersed in aqueous media. The MNPs were prepared by the thermal decomposition method, widely used for the synthesis of monodisperse nanoparticles with controllable size. This method makes use of a hydrophobic surfactant to passivate the surface, which results in nanoparticles that are solely dispersible in nonpolar solvents. For use in biological applications, these nanoparticles need to be made water-dispersible. Therefore, a new procedure was developed on the basis of the exchange of the hydrophobic surface ligands with silanes bearing different endgroups to decorate ferrite magnetic nanoparticles with diverse functionalities . By this means, we could easily determine the influence of the endgroup on the nanoparticle stability and water-dispersibility. Amino-, carboxylic acid- and poly(ethylene glycol)-terminated silanes were found to render the MNPs highly stable and water-dispersible because of electrostatic and/or steric repulsion. The silane molecules were also found to form a protective layer against mild acid and alkaline environments. The ligand exchange on the nanoparticle surface was thoroughly characterized using SQUID, TEM, XPS, DLS, TGA, FTIR, UV−vis, and zeta potential measurements. The presented approach provides a generic strategy to functionalize magnetic ferrite nanoparticles and to form stable dispersions in aqueous media, which facilitates the use of these magnetic nanoparticles in biological applications.
Therapeutic Nanoparticles for Drug Delivery in Cancer (2008)

Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve the biodistribution of cancer drugs, nanoparticles have been designed for optimal size and surface characteristics to increase their circulation time in the bloodstream. They are also able to carry their loaded active drugs to cancer cells by selectively using the unique pathophysiology of tumors, such as their enhanced permeability and retention effect and the tumor microenvironment. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumor targets amplify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle that impedes the efficacy of both molecularly targeted and conventional chemotherapeutic agents, might also be overcome, or at least reduced, using nanoparticles. Nanoparticles have the ability to accumulate in cells without being recognized by P-glycoprotein, one of the main mediators of multidrug resistance, resulting in the increased intracellular concentration of drugs. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.
On Gazit and Miller's parallel algorithm for planar separators (1993)

We show how to obtain a work-efficient parallel algorithm for finding a planar separator. The algorithm requires O(rz’ ) time for any given positive constant e.
Polyanhydrides. I. Preparation of high molecular weight polyanhydrides (1987)

Abstract Polyanhydrides composed of the following diacids–sebacic acid, bis( p ‐carboxyphenoxy)propane, bis( p ‐carboxyphenoxy)hexane, isophthalic acid, 1,4‐phenylene dipropionic acid, and dodecanedioic acid–were synthesized by a melt polycondensation process. Polymers of molecular weight up to 137,010 (weight average) and intrinsic viscosity of 0.92 dL/g were achieved. These high molecular weight polymers were reached by using pure isolated mixed anhydrides of diacids and acetic acid, under optimized reaction conditions (temperature of 180°C for 90 min under vacuum of 10 ‐4 mm Hg). Polymers of higher molecular weights were synthesized in shorter times by using heterogenic coordination catalysts: cadmium acetate, ZnEt 2 ‐H 2 O (1:1), barium oxide, calcium oxide, and calcium carbonate. By using these catalysts molecular weights of up to 245,000 were reached in 30 min of reaction. Films made of high molecular weight bis( p ‐carboxyphenoxy)propane–sebacic acid copolymers showed tensile strengths of 40–160 kg/cm 2 ; the strength increased as a function of the bis( p ‐carboxyphenoxy)propane content and molecular weight.
Hyaluronic Acid Fillers in Facial Rejuvenation (2006)

Nonsurgical procedures have become very popular for the rejuvenation of the aging face. Trends now are for less invasive procedures as well as for more preventative intervention to slow the damage from ultraviolet light and environmental factors, as well as from intrinsic aging. The goal of these procedures is to eliminate or delay the need for corrective surgery. The regular use of sunscreens; retinoids and improved cosmeceuticals; injectable neurotoxins; soft-tissue augmentation products; and minimally invasive laser, light, and radiofrequency treatments are decreasing and delaying need for invasive procedures. Injectable fillers entered mainstream cosmetic medicine with the development of bovine collagen injections in the 1980s. The availability of improved fillers that are less allergenic and longer lasting has resulted in a renaissance in filler techniques. No single filler has proven to be more popular than the category of hyaluronic acids (HA). This article will review the use of the hyaluronic acid fillers that are currently approved for use by the Federal Drug Administration in the United States and describe the significant differences between them to assist the practicing cosmetic physician in choosing and using this category of dermal filler.
Epithelial ovarian cancer: Second and third line chemotherapy (Review) (2002)

Standard therapy for patients affected with advanced epithelial ovarian cancer is cytoreductive surgery followed by combination chemotherapy. With this treatment, most patients obtain clinical complete or partial response, nevertheless, relapse is common and salvage chemotherapy is often needed. The probability of response to second line chemotherapy following platinum-based treatments is usually related to the platinum-free interval, even if recent studies have reported some other clinical features as having prognostic value, such as tumour burden and histology. Salvage monochemotherapy is generally used, but when the platinum-free interval is longer than 24 months, re-treatment with platinum compounds and/or taxanes is indicated. Moreover, a number of new agents with demonstrated activity in ovarian cancer are currently available. Sequentially used in recurrent disease, these agents may improve survival and/or quality of life. Among these new drugs, the most promising are: topotecan, doxil, gemcitabine and platinum analogues such as oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473. However, the real aim of salvage chemotherapy in relapsed ovarian cancer still remains palliative care, because complete responses are very rarely reported and long lasting responses are very seldom observed.
Zone plate for arbitrarily high focal depth (1990)

We show that a zone plate with a prespecified number of foci, which are separated axially by Rayleigh's limit of resolution, can create an arbitrarily high focal depth when used as an apodizer over an otherwise clear aperture. We discuss the resolution and light gathering power of this method.
Systemic Administration of 17β-Estradiol Reduces Apoptotic Cell Death and Improves Functional Recovery following Traumatic Spinal Cord Injury in Rats (2004)

Recent evidence indicates that estrogen exerts neuroprotective effects in both brain injury and neurodegenerative diseases. We examined the protective effect of estrogen on functional recovery after spinal cord injury (SCI) in rats. 17beta-estradiol (3, 100, or 300 microg/kg) was administered intravenously 1-2 h prior to injury (pre-treatment), and animals were then subjected to a mild, weight-drop spinal cord contusion injury. Estradiol treatment significantly improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Fifteen to 30 days after SCI, BBB scores were significantly higher in estradiol-treated (100 microg/kg) rats when compared to vehicle-treated rats. Morphological analysis showed that lesion sizes increased progressively in either vehicle-treated or 17beta-estradiol-treated spinal cords. However, in response to treatment with 17beta-estradiol, the lesion size was significantly reduced 18-28 days after SCI when compared to vehicle-treated controls. Terminal deoxynucleotidyl transferase-mediated UTP nickend labeling (TUNEL) staining and DNA gel electrophoresis revealed that apoptotic cell death peaked 24-48 h after injury. Also, SCI induced a marked increase in activated caspase-3 in the spinal cord, evident by 4 h after injury. However, administration of 17beta-estradiol significantly reduced the SCI-induced increase in apoptotic cell death and caspase-3 activity after SCI. Furthermore, 17beta-estradiol significantly increased expression of the anti-apoptotic genes, bcl-2 and bcl-x, after SCI while expression of the pro-apoptotic genes, bad and bax, was not affected by drug treatment. Finally, intravenous administration of 17beta-estradiol (100 microg/kg) immediately after injury (post-treatment) also significantly improved hind limb motor function 19-30 days after SCI compared to vehicle-treated controls. These data suggest that after SCI, 17 beta-estradiol treatment improved functional recovery in the injured rat, in part, by reducing apoptotic cell death.
DEFINITION OF ITMS (2001)

This white paper discusses the definition of Integrated Transportation Management Systems (ITMS). The definition provided by the Freeway Operations Committee of the Transportation Research Board is presented and further discussion centers around costs and benefits of ITMS, the progress being made in developing ITMS, and the obstacles to be faced.
Effect of an arginine-glycine-aspartic acid-containing peptide on hematogenous candidal infections in rabbits (1992)

The adherence of Candida albicans yeast cells to the subendothelial extracellular matrix, fibronectin, laminin, and type I and IV collagen was tested. Fibronectin (10(-7) M) and a peptide, PepTite-2000 (Telios Pharmaceuticals Inc., San Diego, Calif.), containing the sequence arginine-glycine-aspartic acid (RGD) inhibited Candida adherence to these targets by greater than 90%. When C. albicans was perfused over ex vivo rabbit aortic endothelium, there was no significant difference in the amount of adherence in the presence or absence of the RGD-containing peptide. However, the RGD-containing peptide reduced the number of Candida organisms present in liver, brain, heart, and kidneys (P less than 0.05) of rabbits 4 h after intravenous inoculation of 5 x 10(7) C. albicans yeast cells. The peptide also reduced the number of macroscopic Candida abscesses in the kidneys of rabbits 72 h after intravenous inoculation of 10(7) C. albicans yeast cells (P less than 0.05). Inhibition of Candida adherence in vitro and in vivo may occur because the peptide blocks a fungal receptor that is necessary for adherence.
A wideband loop‐type ground radiation antenna using ground mode tuning and optimum impedance level (2019)

Abstract In this article, a wideband loop‐type ground radiation antenna is proposed for USB dongle applications. Wide bandwidth has been achieved using the orientation of the antenna embedded in the ground plane along with the impedance level of the feed structure. The ground clearance of the antenna is utilized so that the ground mode is tuned to the mid‐band frequency. The impedance level is controlled by using a series combination of a lumped inductor and a capacitor in the feed loop of the antenna. A good agreement between measured and simulated results has been observed. The measured bandwidth and peak total efficiency of the antenna are 1180 MHz and 88.27%, respectively.
Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain (2016)

This article presents synergistic antinociceptive effect produced by the combination of PL265 with non-opioid analgesic drugs acting via unrelated mechanisms. These multi-target-based antinociceptive strategies may bring therapeutic advantages by allowing the reduction of doses, which is of great interest in the chronic treatment of cancer pain.
Quadratic interpolation for image resampling (1997)

Nearest-neighbor, linear, and various cubic interpolation functions are frequently used in image resampling. Quadratic functions have been disregarded largely because they have been thought to introduce phase distortions. This is shown not to be the case, and a family of quadratic functions is derived. The interpolating member of this family has visual quality close to that of the Catmull-Rom cubic, yet requires only 60% of the computation time.
Nucleoid Condensation in Escherichia coli That Express a Chlamydial Histone Homolog (1992)

Chlamydial cell types are adapted for either extracellular survival or intracellular growth. In the transcriptionally inert elementary bodies, the chromosome is densely compacted; in metabolically active reticulate bodies, the chromatin is loosely organized. Condensation of the chlamydial nucleoid occurs concomitant with expression of proteins homologous to eukaryotic histone H1. When the Chlamydia trachomatis 18-kilodalton histone homolog Hc1 is expressed in Escherichia coli, a condensed nucleoid structure similar to that of chlamydiae is observed with both light and electron microscopy. These results support a role for Hc1 in condensation of the chlamydial nucleoid.
60-fsec pulse generation from a self-mode-locked Ti:sapphire laser (1991)

Pulses having durations as short as 60 fsec have been directly generated by a self-mode-locked, dispersion-compensated Ti:sapphire laser. By using an extracavity fiber-prism pulse compressor, pulse durations as short as 45 fsec have been obtained.
The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications (2003)

The proteasome inhibitor PS-341 inhibits nuclear factor-kappaB (NF-kappaB) activation, induces apoptosis in cancer cells, including multiple myeloma (MM) cells, and has marked clinical activity as a monotherapy for MM. In this study, we found that subtoxic concentrations of PS-341 potently sensitized MM cell lines and patient cells to DNA-damaging chemotherapeutic agents such as doxorubicin and melphalan, including cells resistant to these drugs and those isolated from a patient who had relapsed after PS-341 monotherapy. Moreover, PS-341 abolished cell adhesion-mediated drug resistance. Using gene expression profiling and proteomic analysis, we demonstrate that PS-341, among its other proapoptotic effects, down-regulates the expression of several effectors involved in the cellular response to genotoxic stress. These data suggest that, in addition to down-regulating the expression of apoptosis inhibitors, PS-341 inhibits genotoxic stress response pathways and thereby restores sensitivity to DNA-damaging chemotherapeutic agents. These studies, therefore, provide the framework for clinical use of this agent in combination with conventional chemotherapy.
Inhibition of HLA-DQ2-Mediated Antigen Presentation by Analogues of a High Affinity 33-Residue Peptide from α2-Gliadin (2006)

Human leukocyte antigen DQ2 is a class II major histocompatibility complex protein that plays a critical role in the pathogenesis of Celiac Sprue by binding to epitopes derived from dietary gluten and triggering the inflammatory response of disease-specific T cells. Inhibition of DQ2-mediated antigen presentation in the small intestinal mucosa of Celiac Sprue patients therefore represents a potentially attractive mode of therapy for this widespread but unmet medical need. Starting from a pro-inflammatory, proteolytically resistant, 33-residue peptide, LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF, we embarked upon a systematic effort to dissect the relationships between peptide structure and DQ2 affinity and to translate these insights into prototypical DQ2 blocking agents. Three structural determinants within the first 20 residues of this 33-mer peptide, including a PQPELPYPQ epitope, its N-terminal flanking sequence, and a downstream Glu residue, were found to be important for DQ2 binding. Guided by the X-ray crystal structure of DQ2, the L11 and L18 residues in the truncated 20-mer analogue were replaced with sterically bulky groups so as to retain high DQ2 affinity but abrogate T cell recognition. A dimeric ligand, synthesized by regiospecific coupling of the 20-mer peptide with a bifunctional linker, was identified as an especially potent DQ2 binding agent. Two such ligands were able to attenuate the proliferation of disease-specific T cell lines in response to gluten antigens and, therefore, represent prototypical examples of pharmacologically suitable DQ2 blocking agents for the potential treatment of Celiac Sprue.