gebhart/patrepeval huggingface dataset:
Fluorescent phosphonate label for serine hydrolases, pyrenebutyl methylphosphonofluoridate: reaction with acetylcholinesterase (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescent phosphonate label for serine hydrolases, pyrenebutyl methylphosphonofluoridate: reaction with acetylcholinesteraseHarvey Alan Berman and Palmer TaylorCite this: Biochemistry 1978, 17, 9, 1704–1713Publication Date (Print):May 2, 1978Publication History Published online1 May 2002Published inissue 2 May 1978https://pubs.acs.org/doi/10.1021/bi00602a019https://doi.org/10.1021/bi00602a019research-articleACS PublicationsRequest reuse permissionsArticle Views211Altmetric-Citations34LEARN 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
Synthesis and Structure−Activity Relationships of Potent and Orally Active 5-HT4 Receptor Antagonists:  Indazole and Benzimidazolone Derivatives (1998)

A series of indole-3-carboxamides, indazole-3-carboxamides, and benzimidazolone-3-carboxamides was synthesized and evaluated for antagonist affinity at the 5-HT4 receptor in the rat esophagus. The endo-3-tropanamine derivatives in the indazole and benzimidazolone series possessed greater 5-HT4 receptor affinity than the corresponding indole analogues. 5-HT4 receptor antagonist affinity was further increased by alkylation at N-1 of the aromatic heterocycle. In a series of 1-isopropylindazole-3-carboxamides, replacement of the bicyclic tropane ring system with the monocyclic piperidine ring system or an acyclic aminoalkylene chain led to potent 5-HT4 receptor antagonists. In particular, those systems in which the basic amine was substituted with groups capable of forming hydrogen bonds showed increased 5-HT4 receptor antagonist activity. While some of these compounds displayed high affinity for other neurotransmitter receptors (in particular, 5-HT3, alpha1, and 5-HT2A receptors), as the conformational flexibility of the amine moiety increased, the selectivity for the 5-HT4 receptor also increased. From this series of compounds, we identified LY353433 (1-(1-methylethyl)-N-[2-[4-[(tricyclo[3.3.1.1(3, 7)]dec-1-ylcarbonyl)amino]-1-piperidinyl]ethyl]-1H-indazole-3- carboxamide) as a potent and selective 5-HT4 receptor antagonist with clinically suitable pharmacodynamics.
Collagen-induced arthritis in rats: antigen-specific suppression of arthritis and immunity by intravenously injected native type II collagen. (1983)

Collagen-induced arthritis (CIA) developed in 70 to 90% of rats immunized with heterologous type II collagen. CIA was reduced to 0 to 18% when rats were injected i.v., i.e., pretreated, with 1 mg of soluble native type II collagen before immunization. Concomitant with the suppression of CIA were significant suppression of IgM, IgG, and delayed-type hypersensitivity (DTH) responses to type II collagen. Suppression of CIA and immunity to collagen was antigen-specific, related to dose and route of administration, and occurred only when 1 mg of collagen was injected i.v. either 32, 7, or 4 days before, or 7 days after immunization. Once CIA was established, however, neither arthritis nor immunity could be suppressed. To determine if adjuvant-induced arthritis (AIA), like CIA, could be suppressed by i.v. pretreatment with type II collagen, rats were given 1 mg of type II collagen or PBS i.v. before injection with mycobacteria and oil. AIA was not suppressed, and arthritis appeared in both groups at a similar incidence and severity. Sera from 26 rats with severe AIA that was collected between days 14 and 35 after injection were assayed for IgG to homologous rat type II collagen and were found to be negative. These findings further support the hypothesis that CIA in rats is mediated by immunity to type II collagen and also suggest that CIA and AIA have different primary pathogenic mechanisms.
Using procalcitonin-guided algorithms to improve antimicrobial therapy in ICU patients with respiratory infections and sepsis (2013)

Inclusion of PCT data in clinical algorithms improves individualized decision-making regarding antibiotic treatment in patients in critical care for respiratory infections or sepsis. Future research should focus on use of repeated PCT measurements to risk-stratify patients and guide treatment to improve their outcomes.
Estrogen receptor in the human eye: influence of gender and age on gene expression. (1999)

The presence of the ERalpha in the human eye suggests that the sex steroid hormone axis may play a role in the pathogenesis of certain ocular diseases.
Disease mutations in Rab7 result in unregulated nucleotide exchange and inappropriate activation (2009)

Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.
Incremental Mining from News Streams (2005)

With the rapid growth of the World Wide Web, Internet users are now experiencing overwhelming quantities of online information. Since manually analyzing the data becomes nearly impossible, the analysis would be performed by automatic data mining techniques to fulfill users’ information needs quickly.
Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction (1996)

Reciprocal interactions between epithelium and mesenchyme mediate crucial aspects of embryonic development and direct the coordinated organogenesis, correct spatial orientation, and the timely expression of functional activity consistent with physiological demands. The mesenchymal equivalent in the adult organism is the stroma, i.e., the loose connective tissue that is separated from the epithelial compartment by an intact basement membrane. In carcinomas, the cellular organization is dramatically changed, and the stroma is extensively modified. The basement membrane is penetrated in a process of degradation and/or decreased synthesis, and direct contact between tumor cells and the surrounding stroma coincides with neovascularization, inflammatory cell influx, and extensive remodeling of extracellular matrix. In this review, we highlight our current knowledge of tumor cell stromal interactions in the mammary gland with particular emphasis on cellular origins and functional phenotypes. We focus both on normal mammary gland and breast tumors and on culture systems developed to dissect individual aspects of cell-cell and cell-extracellular matrix interactions.
Low-complex frame synchronization in OFDM systems (2002)

Orthogonal frequency-division multiplexing (OFDM) systems have gained an increased interest due to their use in wireless applications such as mobile communication systems. A novel data-based frame synchronization method for OFDM-systems is presented. OFDM frames are shown to contain sufficient information to synchronize a system without the use of pilots. The cyclic extension, preceding OFDM frames, is of decisive importance for this method. Based on only the sign bits of the in-phase and the quadrature components of the received OFDM signal, the maximum likelihood solution is derived. This solution basically consists of a correlator, a moving sum and a peak detector. The stability of the generated frame-clock is improved significantly by averaging over a few number of frames. Simulations show that this low-complex, averaging method can be used to synchronize an OFDM system on twisted pair copper wires and in slowly fading radio channels.
Changes in Chemical Composition ofTagetes minutaOil at Various Stages of Flowering and Fruiting (1993)

ABSTRACT The chemical composition of Indian Tagetes minuta L. oil was determined at different developmental stages of plant growth using GC, 1H- and 13C-NMR spectroscopy. In contrast to previous results, the characteristic components of the Indian oil were found to be (Z)-β-ocimene, (Z)-tagetenone, (E)-tagetenone, (Z)- and (E)-tagetones and dihydrotagetone. The percentage composition of these constituents changes with flower maturation. The dihydrotagetone percentage declined sharply from flower buds (48.09%) to seed shedding stage (11.90%) with a simultaneous rise in (Z)-β-ocimene (35.3%), (Z)-tagetenone and (E)-tagetenone (both 26.44%) at the time of immature fruit formation, suggesting that dihydrotagetone may biogenetically be changing into (Z)- and (E)-tagetenones.
Prediction of Hepatocellular Carcinoma Recurrence in Patients With Low Hepatitis B Virus DNA Levels and High Preoperative Hepatitis B Surface Antigen Levels (2014)

A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.
Silk protein based hybrid photonic-plasmonic crystal (2013)

We propose a biocompatible hybrid photonic platform incorporating a 3D silk inverse opal (SIO) crystal and a 2D plasmonic crystal formed on the top surface of the SIO. This hybrid photonic-plasmonic crystal (HPPC) structure simultaneously exhibits both an extraordinary transmission and a pseudo-photonic band-gap in its transmission spectrum. We demonstrate the use of the HPPC as a refractive index (RI) sensor. By performing a multispectral analysis to analyze the RI value, a sensitivity of 200,000 nm·Δ%T/RIU (refractive index unit) is achieved.
Immobilization of luciferase from a firefly lantern extract on glass strips as an alternative strategy for luminescent detection of ATP (1998)

The bioluminescent reaction catalysed by firefly luciferase has become widely established as an outstanding analytical system for assay of ATP. When used in solution, luciferase is unstable and cannot be re-used, a problem that can be partially circumvented by immobilizing the enzyme on solid substrates. Transparent glass is especially advantageous over alternative immobilizing matrices, since it allows most of the emitted photons to be detected. We report a new method for luciferase immobilization on glass which does not require prior silanization and glutaraldehyde activation, thus saving preparation time and minimizing enzyme inactivation. Our method is based on the co-immobilization by adsorption of luciferase (from a firefly lantern extract) and poly-L-lysine (PL) on non-porous glass strips. Luciferase immobilized in this way exhibits minimal variations in intersample activity, high sensitivity for ATP detection (linear luminescence responses down to 50 nmol/L) and good stability (full activity for at least 60 days when stored at −80°C). PL-mediated immobilization of luciferase on glass strips provides an attractive strategy for the design of specific ATP biosensors, with potential in industry, environmental screening, medicine and biological research. © 1998 John Wiley & Sons, Ltd.
A 28-GHz, 18-dBm, 48% PAE Stacked-FET Power Amplifier with Coupled-Inductor Neutralization in 45-nm SOI CMOS (2018)

A single stage, millimeter-wave 2-stack FET power amplifier operates with a peak saturated power of 18.2 dBm and peak PAE of 48.2%. The high PAE results from a proposed Cgd neutralization through coupled inductor feedback between the drains of the stacked FETs. The technique reuses the interstage matching shunt inductor to reduce the loss and chip area while improving the PA gain. The PA achieves 13.6 dB gain with a 3 dB bandwidth of 12 GHz at a 2.4-V power supply. The PA is implemented in a 4S-nm SOI CMOS technology using a trap-rich substrate and has an area of 520 μm×530 μm. To the author's knowledge, this work demonstrates the highest gain and power added efficiency (PAE) for a single-stage Si-based PA at 28 GHz.
Inductive text classification for medical applications (1995)

Abstract Text classification poses a significant challenge for knowledge-based technologies because it touches on all the familiar demons of artificial intelligence: the knowledge engineering bottleneck, problems of scale, easy portability across multiple applications, and cost-effective system construction. Information retrieval (IR) technologies traditionally avoid all of these issues by defining a document in terms of a statistical profile of its lexical items. The IR community is willing to exploit a superficial type of knowledge found in dictionaries and thesaurae, but anything that requires customization, application-specific engineering, or any amount of manual tinkering is thought to be incompatible with practical cost-effective system designs. In this paper those assumptions are challenged and it is shown how machine learning techniques can operate as an effective method for automated knowledge acquisition when it is applied to a representative training corpus, and leveraged against a few hours of routine work by a domain expert. A fully implemented text classification system operating on a medical testbed is described and experimental results based on that testbed are reported.
High-performance low-power CMOS circuits using multiple channel length and multiple oxide thickness (2002)

Power optimization has become an important issue for high performance designs. One way to achieve low-power and high performance circuits is to use dual-threshold voltages. High threshold transistors can be used in non-critical paths to reduce the leakage power, while lower threshold voltage is used for transistors in critical path(s) to achieve high performance. This paper proposes two low power and high performance CMOS design techniques-multiple channel length (M/sub L/CMOS) and multiple oxide thickness (M/sub ox/CMOS), based on dual V/sub th/, design technique. A comprehensive algorithm for selecting and assigning optimal transistor threshold voltage, channel length and oxide thickness is given. The simulation results on ISCAS benchmark circuits show that the total power consumption can be reduced by 21% for M/sub L/CMOS at low activity. Total power savings for M/sub ox/CMOS at low and high switching activities are about 42% and 24%, respectively.
Inteins: Localized Distribution, Gene Regulation, and Protein Engineering for Biological Applications (2018)

Inteins are self-splicing polypeptides with an ability to excise themselves from flanking host protein regions with remarkable precision; in the process, they ligate flanked host protein fragments. Inteins are distributed sporadically across all three domains of life (bacteria, archaea, and unicellular eukaryotes). However, their apparent localized distribution in DNA replication, repair, and recombination proteins (the 3Rs), particularly in bacteria and archaea, is enigmatic. Our understanding of the localized distribution of inteins in the 3Rs, and their possible regulatory role in such distribution, is still only partial. Nevertheless, understanding the chemistry of post-translational self-splicing of inteins has opened up opportunities for protein chemists to modify, manipulate, and bioengineer proteins. Protein-splicing technology is adapted to a wide range of applications, starting with untagged protein purification, site-specific protein labeling, protein biotinylation, isotope incorporation, peptide cyclization, as an antimicrobial target, and so on. This review is focused on the chemistry of splicing; the localized distribution of inteins, particularly in the 3Rs and their possible role in regulating host protein function; and finally, the use of protein-splicing technology in various protein engineering applications.
Inlining java native calls at runtime (2005)

We introduce a strategy for inlining native functions into Java™ applications using a JIT compiler. We perform further optimizations to transform inlined callbacks into semantically equivalent lightweight operations. We show that this strategy can substantially reduce the overhead of performing JNI calls, while preserving the key safety and portability properties of the JNI. Our work leverages the ability to store statically-generated IL alongside native binaries, to facilitate native inlining at Java callsites at JIT compilation time. Preliminary results with our prototype implementation show speedups of up to 93X when inlining and callback transformation are combined.
Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis (2005)

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.
Anticonvulsant drugs for management of pain: a systematic review (1995)

Anticonvulsants were effective for trigeminal neuralgia and diabetic neuropathy and for migraine prophylaxis. Minor adverse effects occurred as often as benefit.
X Windows: the great integrator (1990)

As an open standard for a graphical user interface, X Windows is bringing a new look to technical computing
PD-1 Increases PTEN Phosphatase Activity While Decreasing PTEN Protein Stability by Inhibiting Casein Kinase 2 (2013)

Programmed death 1 (PD-1) is a potent inhibitor of T cell responses. PD-1 abrogates activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but the mechanism remains unclear. We determined that during T cell receptor (TCR)/CD3- and CD28-mediated stimulation, PTEN is phosphorylated by casein kinase 2 (CK2) in the Ser380-Thr382-Thr383 cluster within the C-terminal regulatory domain, which stabilizes PTEN, resulting in increased protein abundance but suppressed PTEN phosphatase activity. PD-1 inhibited the stabilizing phosphorylation of the Ser380-Thr382-Thr383 cluster within the C-terminal domain of PTEN, thereby resulting in ubiquitin-dependent degradation and diminished abundance of PTEN protein but increased PTEN phosphatase activity. These effects on PTEN were secondary to PD-1-mediated inhibition of CK2 and were recapitulated by pharmacologic inhibition of CK2 during TCR/CD3- and CD28-mediated stimulation without PD-1. Furthermore, PD-1-mediated diminished abundance of PTEN was reversed by inhibition of ubiquitin-dependent proteasomal degradation. Our results identify CK2 as a new target of PD-1 and reveal an unexpected mechanism by which PD-1 decreases PTEN protein expression while increasing PTEN activity, thereby inhibiting the PI3K/Akt signaling axis.
Biomolecular crystallography: principles, practice, and application to structural biology (2010)

PART I: FROM SEQUENCE TO CRYSTALS 1. Introduction: Preparing Your Study 2. Protein Structure 3. Protein Crystallization 4. Proteins for Crystallography PART II: FUNDAMENTALS OF PROTEIN CRYSTALLOGRAPHY 5. Crystal Geometry 6. Diffraction Basics 7. Statistics and Probability in Crystallography PART III: FROM CRYSTALS TO DATA 8. Instrumentation and Data Collection PART IV: DETERMINING YOUR STRUCTURE 9. Reconstruction of Electron Density and the Phase Problem 10. Experimental Phasing 11. Non-Crystallographic Symmetry and Molecular Replacement 12. Model Building and Refinement PART V: MAKING SENSE OF YOUR STRUCTURE 13. Structure Validation, Analysis, and Presentation
Copper Deficiency With Pancytopenia During Total Parenteral Nutrition (1994)

Anemia and neutropenia are commonly observed hematologic changes in patients with copper (Cu) deficiency, but thrombocytopenia is rarely found. A-69-year-old patient with postoperative small-bowel obstruction underwent laparotomy three times. Because of persistent obstruction, nasoduodenal suction was continued and total parenteral nutrition was instituted. Fifteen months after the initiation of total parenteral nutrition, the patient gradually developed pancytopenia (red blood cell count 222 x 10(4)/mm3, neutrophil count 1254/mm3, and platelet count 9.2 x 10(4)/mm3). The serum Cu level was 10 micrograms/dL and the serum ceruloplasmin level was less than 5 mg/dL. After 2 weeks of Cu supplementation in a daily dose of 20 mumol, the serum Cu level increased to 81 micrograms/dL and the serum ceruloplasmin level to 20 mg/dL. Hematologic values showed a dramatic response: red blood cell count increased to 362 x 10(4)/mm3, neutrophil count to 4819/mm3, and platelet count to 22.1 x 10(4)/mm3. The improvement of pancytopenia could be attributed to Cu supplementation. This is the first case report of Cu deficiency with pancytopenia during total parenteral nutrition.