gebhart/patrepeval huggingface dataset:
gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates. (1985)

A methotrexate (MTX) analog containing fluorine at the gamma-carbon of the glutamate moiety, gamma-fluoromethotrexate (FMTX), has been synthesized and evaluated for its biochemical and pharmacological properties. FMTX inhibition of dihydrofolate reductase from several sources is nearly equivalent to that shown by MTX. Most important, FMTX is an exceedingly poor substrate for folylpoly (gamma-glutamate) synthetase, the enzyme that catalyzes the biosynthesis of the highly-retained, cytotoxic MTX polyglutamates. Uptake experiments in H35 hepatoma cells show that FMTX accumulates to approximately the same extent as MTX at steady state. The rapid efflux of both derivatives is also very similar. The major difference detected in cells between the two compounds is the meager glutamylation of FMTX, due to the electronegative properties of the fluorine adjacent to the potential amide-forming carboxyl group. Exposure of dividing cells to 50 microM MTX for 2 and 6 hr results in the formation of 55 and 130 nmol, respectively, of the polyglutamates (more than two glutamate residues)/g of cell protein. With FMTX these values were reduced by 98% and 93%, respectively. Growth inhibition studies show that MTX is only 12-fold more toxic than FMTX when the cells are exposed to each derivative continuously for 72 hr. When the exposure time is reduced, a greater disparity between the inhibitory effects is observed; with a 2-hr pulse, MTX is 2300-fold more effective than FMTX. These data correlate with the effects of pulses of FMTX and MIX on de novo thymidylate biosynthesis in intact cells. The results indicate that of the parameters examined, the vastly reduced toxicity of FMTX after its removal from the culture medium is best correlated with impaired glutamylation. The data strongly suggest that prolonged toxicity of MTX is a result of metabolic conversion to MTX polyglutamates and that these effects are far more dramatic in short-term than in long-term exposure to the antifolates.
Effects of reactive γ‐ketoaldehydes formed by the isoprostane pathway (isoketals) and cyclooxygenase pathway (levuglandins) on proteasome function (2002)

Oxidative stress can impair proteasome function, both of which are features of neurodegenerative diseases. Inhibition of proteasome function leads to protein accumulation and cell death. We discovered recently the formation of highly reactive g-ketoaldehydes, isoketals (IsoKs), and neuroketals (NeuroKs) as products of the isoprostane and neuroprostane pathways of free radical-induced lipid peroxidation that are analogous to cyclooxygenase-derived levuglandins (LGs). Because aldehydes that are much less reactive than IsoKs have been shown to inhibit proteasome function, we explored the ability of the proteasome to degrade IsoK-adducted proteins/peptides and the effect of IsoK and IsoK-adducted proteins/peptides on proteasome function. Adduction of IsoK to model proteasome substrates significantly reduced their rate of degradation by the 20S proteasome. The ability of IsoK to inhibit proteasome function directly was observed only at very high concentrations. However, at much lower concentrations, an IsoK-adducted protein (ovalbumin) and peptide (Ab1-40) significantly inhibited chymotrypsin-like activity of the 20S proteasome. Moreover, incubation of IsoK with P19 neuroglial cultures dose-dependently inhibited proteasome activity (IC50 = 330 nM) and induced cell death (LC50 = 670 nM). These findings suggest that IsoKs/NeuroKs/LGs can inhibit proteasome activity and, if overproduced, may have relevance to the pathogenesis of neurodegenerative diseases.
Comparison of the Early Effects of Brimonidine and Apraclonidine as Topical Ocular Hypotensive Agents (1999)

Brimonidine and apraclonidine are similar in their effects on the aqueous system. Both reduce intraocular pressure in the timolol-treated eye, primarily, if not exclusively, by further suppressing aqueous flow. In contrast, latanoprost reduces intraocular pressure in the timolol-treated eye without affecting aqueous flow.
IN SITU SAPHENOUS VEIN BYPASS: PREVENTION AND MANAGEMENT OF EARLY COMPLICATIONS (1988)

Since adopting the in situ, non-reversed saphenous vein technique for bypass procedures in the leg early in 1986, 50 bypasses have been performed in selected patients, primarily for limb salvage. A Mills valvulotome was used for retrograde disruption of the saphenous valves, after exposure of the whole length of vein. Significant peri-operative complications occurred in nine patients and were strongly associated with technical factors. Early graft occlusion (n = 2) and residual arteriovenous fistulae (n = 2) were revised by timely reoperation, resulting in early (30 day) patency of all but one graft. In seven patients, angioscopic visualization of the valve division process was tested as a method of ensuring complete valvulotomy, while avoiding trauma to the vein wall. Distal anastomosis to the popliteal artery above the knee or close below the knee caused a considerable degree of graft angulation, which was exacerbated by flexion of the leg, whereas anastomosis to the more distal popliteal artery or tibial vessels resulted in a favourable curvature of the graft. Lessons learned during this initial experience and aspects of technique for prevention of complications are presented.
Using Atom Transfer Radical Polymerization To Amplify Monolayers of Initiators Patterned by Microcontact Printing into Polymer Brushes for Pattern Transfer (2000)

We report the use of atom transfer radical polymerization (ATRP) to amplify initiators patterned on films of gold into polymer brushes of poly(methyl methacrylate) (PMMA), poly(hydroxyethyl methacrylate) (PHEMMA), poly(tert-butyl methacrylate) (PTBA), poly(isobornyl methacrylate) (PIBMA), and poly((dimethylamino)ethylmethyl acrylate) (PDMAEMA). Pattern transfer into gold substrates underlying polymer brushes was achieved by using the patterned brushes as barriers to wet chemical etchants of gold. The surface-confined initiators for ATRP were prepared by the self-assembly of (BrC(CH3)2COO(CH2) 10S)2 (I) on films of gold. These monolayers were assembled from solutions of hexadecane at 60 °C so as to prevent their thermal desorption during ATRP (also performed at 60 °C). By measuring the resistance offered by these brushes to etching of underlying films of gold by aqueous solutions of KI/I2, KCN/K3Fe(CN)6, and 50 vol % aqua regia (70 vol % HNO3 and 30 vol % HCl), we conclude that both the thickness and chemical functionality of the polymer brushes as well as the choice of etchant can be tailored to control the etch resistance of polymer brushes. Thick brushes formed from hydrophobic monomers were found to be the most effective in resisting all etchants. The etch resistance of a PMMA brush was observed to be greatest when using aqua regia or KI/I2 to etch an underlying film of gold. For example, when using PMMA brushes (thickness 450 Å), we measured the brushes to slow the etching of the underlying films of gold by KI/I2 by almost 2 orders of magnitude as compared to monolayers formed from I. By using microcontact printing to pattern SAMs formed from I, we demonstrate the usefulness of ATRP in schemes for transferring patterns present in monolayers of molecules into underlying substrates.
An ICANL site visit: what can I expect? (2003)

The Intersocietal Commission for the Accreditation of Nuclear Medicine Laboratories (ICANL) has added a mandatory site visit to its accreditation process, both for first time accreditation and re-accreditation. As this is a relatively recent development (since July 2002), this article will explain
Levels of β-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment (2007)

Significant elevation of BACE1 levels and activity in CSF is an indicator of MCI, which could be an early stage of AD.
MOLECULARMECHANISMS FORGENOMICDISORDERS (2002)

Genomic rearrangements play a major role in the pathogenesis of human genetic diseases. Nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) that flank unique genomic segments results in changes of genome organization and can cause a loss or gain of genomic segments. These LCRs appear to have arisen recently during primate speciation via paralogous segmental duplication, thus making the human species particularly susceptible to genomic rearrangements. Genomic disorders are defined as a group of diseases that result from genomic rearrangements, mostly mediated by NAHR. Molecular investigations of genomic disorders have revealed genome architectural features associated with susceptibility to rearrangements and the recombination mechanisms responsible for such rearrangements. The human genome sequence project reveals that LCRs may account for 5% of the genome, suggesting that many novel genomic disorders might still remain to be recognized.
54.3: A Flexible 2‐in. QVGA LTPS‐TFT Electrophoretic Display (2005)

Abstract A flexible 2‐inch QVGA electrophoretic display was developed by combining a microencapsulated electrophoretic imaging layer and SUFTLA, a technology of transferring low‐temperature polysilicon thin‐film transistor arrays (LTPS‐TFTs) from a sacrificial substrate onto another. The resultant display panel was able to successfully switch when held rigid and when being flexed. In addition, grayscale through spatial dithering was explored, as well as ways to adjust the graytones to optimal values. As a result, a good linearity of grayscale was obtained.
Gold Nanorods Coated with Multilayer Polyelectrolyte as Contrast Agents for Multimodal Imaging (2007)

Gold nanorods coated with multilayer polyelectrolyte is reported as a biocompatible optical probe with capability for dark-field imaging and for electron microscopy of cancer cells. Transferrin (Tf) was conjugated to the polyelectrolyte-coated nanorods for targeted in vitro delivery to cancer cells. Dark-field imaging was used to confirm the receptor-mediated uptake of nanorods into HeLa cells, which is known to overexpress the transferrin receptor (TfR). Minimal uptake was observed with untargeted nanorods. Electron microscopy was used to confirm that the intracellular uptake of the nanorods predominantly occurred via the Tf−TfR interaction and the nanorods localized in vesicular structures such as endosomes.
Intranasally Administered Adjunctive Dexmedetomidine Reduces Perioperative Anesthetic Requirements in General Anesthesia (2016)

Intranasal administration of dexmedetomidine can reduce perioperative anesthetic requirements, and a dose of dexmedetomidine 2 μg/kg produces a better effect in adults. The anesthetics-sparing effect of intranasal dexmedetomidine 1 μg/kg is less than that with the same intravenous dose of dexmedetomidine.
MicroRNA “SPONGE”: PROOF OF CONCEPT FOR A NOVEL MicroRNA TARGET IDENTIFICATION TECHNIQUE (2010)

This project provides proof of concept for a microRNA "sponge", a novel microRNA sequestration technique which will aid characterization of the function of different microRNAs by showing the effects of the depletion of specific cellular microRNAs. To prove that microRNA "sponges" will effectively bind and hold native microRNA in vitro, plasmids were constructed encoding luciferase reporter mRNAs whose 3' UTRs contain four experimental sponges to bind either microRNA Let7 or miR122, or to contain two mutant sequences that do not bind miRNAs. The results showed a decreased luciferase activity for the sponge containing plasmids, but not the mutant plasmids, indicating they successfully bound their miRNAs to block reporter mRNA translation.
A Combined Corner and Edge Detector (1988)

The problem we are addressing in Alvey Project MMI149 is that of using computer vision to understand the unconstrained 3D world, in which the viewed scenes will in general contain too wide a diversity of objects for topdown recognition techniques to work. For example, we desire to obtain an understanding of natural scenes, containing roads, buildings, trees, bushes, etc., as typified by the two frames from a sequence illustrated in Figure 1. The solution to this problem that we are pursuing is to use a computer vision system based upon motion analysis of a monocular image sequence from a mobile camera. By extraction and tracking of image features, representations of the 3D analogues of these features can be constructed.
Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules. (1990)

Growth of early B precursor cells was investigated in vitro by using rIL-7 and IL-7-defective stromal cell line PA6 as separate growth signals. B cell development proceeds through three sequential stages different from the growth signal requirement. The cells in the first stage require PA6 alone for the proliferation, and differentiate into the second stage, which requires both PA6 and IL-7 for its growth. When IL-7 is available for the cells in the second stage, they proliferate extensively on the PA6 layer, and some acquire the ability to proliferate in response to IL-7 alone. This sequential change of growth signal requirement, however, does not proceed autonomously along the time schedule. The possibility that it is primarily directed by the result of Ig gene rearrangement is considered. This mode of growth control may explain why only functional B cells are selected in the error-prone process of Ig gene rearrangement during B lineage differentiation.
Electrochemical Modification of Graphene (2008)

Nanoparticles on an atomic carpet: Individual graphene sheets have been decorated with metal nanoparticles through electrochemistry. The attachment of Pd particles onto graphene renders it sensitive to hydrogen. The controlled functionalization of graphene paves the way for various electronic applications.
Rapid detection of CYP2D6 null alleles by long distance-and multiplex-polymerase chain reaction (1996)

The CYP2D6 gene on human chromosome 22 encodes a cytochrome P450 responsible for oxidative metabolism of over 30 clinically used drugs. The CYP2D6 gene is highly polymorphic with more than 20 alleles described to date. Some of these harbour loss-of-function mutations which lead to the poor metabolizer phenotype in 5-10% of Caucasians. These individuals are at increased risk of suffering from adverse side effects or to experience therapeutic failure following drug treatment. Phenotype determination requires ingestion of a probe drug and has other inherent problems. Due to the increasing number of alleles known, comprehensive CYP2D6 genotyping using the conventional assays has become cumbersome and time consuming. We have therefore developed a streamlined and more rapid CYP2D6 genotyping procedure. Use of long distance PCR allowed the amplification of a 4666 bp fragment which contains the entire CYP2D6 gene. The 4.7 kb fragment serves as a template for a multiplex allele-specific PCR assay to simultaneously identify the five PM-associated alleles, CYP2D6*3 (A), *4 (B), *6 (T), *7 (E), and *8 (G). Together with the CYP2D6 deletion allele CYP2D6*5 (D), which can be detected in a separate PCR assay, these alleles are responsible for the PM phenotype in approximately 99% of Caucasian individuals. We tested the reliability of the procedure by analysing DNA from more than 80 individuals with known CYP2D6 genotypes. Twelve different genotypes were present among these samples and all of them were correctly identified.
Differential expression of an E-selectin ligand (SLex) by two Chinese hamster ovary cell lines transfected with the same alpha (1,3)-fucosyltransferase gene (ELFT). (1994)

The mammalian cDNA encoding alpha (1,3)-fucosyltransferase (alpha (1,3)Fuc-T) termed ELAM-1 ligand fucosyltransferase (ELFT) or Fuc-TIV was previously cloned by three groups who reported different results from transfection studies Goelz et al. (Goelz, S. E., Hession, C., Goff, D., Griffiths, B., Tizard, R., Newman, B., Chi-Rosso, G., and Lobb, R. (1990) Cell 63, 1349-1356) found that Chinese hamster ovary (CHO) cells expressing the ELFT cDNA had alpha (1,3)Fuc-T activity and were able to bind to E-selectin. In contrast, Lowe et al. (Lowe, J. B., Kukowska-Latallo, J. F., Nair, R. P., Larsen, R. D., Marks, R. M., Macher, B. A., Kelly, R. J., and Ernst, L. K. (1991) J. Biol. Chem. 266, 17467-17477) and Kumar et al. (Kumar, R., Potvin, B., Muller, W. A., and Stanley, P. (1991) J. Biol. Chem. 266, 21777-21783) found no binding to E-selectin of CHO transfectants expressing the same alpha (1,3)Fuc-T gene; nor did the latter transfectants synthesize a known E-selectin ligand, sialylated Lex (SLex), although they had substantial alpha (1,3)Fuc-T activity. We now show that these discrepant results were due to a difference between the parental CHO cell lines. Following transfection of ELFT cDNA into Pro-5 or dihydrofolate reductase (DHFR)- CHO cells, only the DHFR- transfectants expressed SLex and bound to E-selectin. Indirect evidence from monoclonal antibody and lectin binding studies indicates that the range of carbohydrate structures synthesized by the Pro-5 and DHFR- CHO cell lines differs. Since DHFR-/ELFT transfectants expressed cell surface SLex but transferred fucose poorly to sialylated substrates in vitro, ELFT may be able to fucosylate a complex carbohydrate missing from Pro-5 cells. Alternatively, either CHO line may have an activity (such as an alpha (2,3)-sialyltransferase), that modifies alpha (1,3)-fucosylated lactosamines.
Efficacy of antisense morpholino oligomer targeted to c-myc in prostate cancer xenograft murine model and a Phase I safety study in humans. (2003)

The present study demonstrates that inhibition of c-Myc expression by antisense phosphorodiamidate morpholino oligomer is a promising new and safe therapeutic strategy for prostate cancer.
PCSK9 inhibitors: A new era of lipid lowering therapy (2017)

Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.
A Multi-center Retrospective Analysis of Survival Benefits of Chemotherapy for Unresectable Biliary Tract Cancer (2007)

Chemotherapy with GEM may benefit patients with BTC.
Recent Development in Poultry Waste Dizgestion and Feather Utilization—A Review , (1993)

The intensive and large-scale production of food animals and animal products has generated an enormous waste disposal problem for the animal industry. These wastes, which include animal excreta, mortalities, hair, feathers, and processing wastes, are largely organic materials and are convertible to useful resources. Making the conversion processes efficient and economical presents a great challenge to modern biotechnology. An efficient thermophilic anaerobic digester system has been developed that converts animal manure to methane for an energy source, solid residues for feed supplements, and liquid nutrients for aquaculture. This digester system also destroys pathogens and thus protects environmental health. During the development of this system, a feather-degrading bacterium was discovered and identified as a thermophilic Bacillus licheniformis, Strain PWD-1. The bacterium can ferment and convert feathers to feather-lysate, a digestible protein source for feed use. An enzyme, keratinase, secreted by this bacterium was purified and characterized. This keratinase is a potent protease that hydrolyzes all proteins tested, including collagen, elastin, and feather keratin. When the enzyme was mixed as an additive in feed, it significantly enhanced the digestibility of feather meal in chickens. In addition to feed technology, the bacterium and the enzyme are believed to have many other industrial and environmental applications.
Using state modules for adaptive query processing (2004)

We present a query architecture in which join operators are decomposed into their constituent data structures (State Modules, or SteMs), and dataflow among these SteMs is managed adaptively by an eddy routing operator [R. Avnur et al., (2000)]. Breaking the encapsulation of joins serves two purposes. First, it allows the eddy to observe multiple physical operations embedded in a join algorithm, allowing for better calibration and control of these operations. Second, the SteM on a relation serves as a shared materialization point, enabling multiple competing access methods to share results, which can be leveraged by multiple competing join algorithms. Our architecture extends prior work significantly, allowing continuously adaptive decisions for most major aspects of traditional query optimization: choice of access methods and join algorithms, ordering of operators, and choice of a query spanning tree. SteMs introduce significant routing flexibility to the eddy, enabling more opportunities for adaptation, but also introducing the possibility of incorrect query results. We present constraints on eddy routing through SteMs that ensure correctness while preserving a great deal of flexibility. We also demonstrate the benefits of our architecture via experiments in the Telegraph dataflow system. We show that even a simple routing policy allows significant flexibility in adaptation, including novel effects like automatic "hybridization " of multiple algorithms for a single join.
Multispectral fingerprint biometrics (2005)

A novel fingerprint sensor is described that combines a multispectral imager (MSI) with a conventional optical fingerprint sensor. The goal of this combination is a fingerprint sensor with improved usability and security relative to standard technology. The conventional sensor that was used in this research is a commercially available system based on total internal reflectance (TIR). It was modified to accommodate an MSI sensor in such a way that both MSI and TIR images are able to be collected when a user places his/her finger on the sensor platen. The MSI data were preprocessed to enhance fingerprint features. Both the preprocessed MSI images and the TIR images were then passed to a commercial fingerprint software package for minutiae detection and matching. A multiperson study was conducted to test the relative performance characteristics of the two types of finger data under typical office conditions. Results demonstrated that the TIR sensor performance was degraded by a large number of poor quality fingerprint images, likely due to a large percentage of samples taken on people with notably dry skin. The corresponding MSI data showed no such degradation and produced significantly better results. A selective combination of both modalities is shown to offer the potential of further performance improvements.