gebhart/patrepeval huggingface dataset:
Crystal Structure of CD14 and Its Implications for Lipopolysaccharide Signaling (2005)

Lipopolysaccharide, the endotoxin of Gram-negative bacteria, induces extensive immune responses that can lead to fatal septic shock syndrome. The core receptors recognizing lipopolysaccharide are CD14, TLR4, and MD-2. CD14 binds to lipopolysaccharide and presents it to the TLR4/MD-2 complex, which initiates intracellular signaling. In addition to lipopolysaccharide, CD14 is capable of recognizing a few other microbial and cellular products. Here, we present the first crystal structure of CD14 to 2.5 angstroms resolution. A large hydrophobic pocket was found on the NH2-terminal side of the horseshoe-like structure. Previously identified regions involved in lipopolysaccharide binding map to the rim and bottom of the pocket indicating that the pocket is the main component of the lipopolysaccharide-binding site. Mutations that interfere with lipopolysaccharide signaling but not with lipopolysaccharide binding are also clustered in a separate area near the pocket. Ligand diversity of CD14 could be explained by the generous size of the pocket, the considerable flexibility of the rim of the pocket, and the multiplicity of grooves available for ligand binding.
Total Synthesis of (+)-Gelsedine (1999)

A novel iodide-promoted, allene-terminated cyclization of an N-acyliminium ion, a stereoselective Heck spirocyclization, and a chemoselective demethylation at the nitrogen atom of an oxindole are the key transformations in the first total synthesis of the indole alkaloid (+)-gelsedine (1). This dextrorotatory form of natural gelsedine was formed as a single enantiomer in 21 steps from (S)-malic acid.
The influence of downstream protein-coding sequence on internal ribosome entry on hepatitis C virus and other flavivirus RNAs (2001)

Some studies suggest that the hepatitis C virus (HCV) internal ribosome entry site (IRES) requires downstream 5' viral polyprotein-coding sequence for efficient initiation of translation, but the role of this RNA sequence in internal ribosome entry remains unresolved. We confirmed that the inclusion of viral sequence downstream of the AUG initiator codon increased IRES-dependent translation of a reporter RNA encoding secretory alkaline phosphatase, but found that efficient translation of chloramphenicol acetyl transferase (CAT) required no viral sequence downstream of the initiator codon. However, deletion of an adenosine-rich domain near the 5' end of the CAT sequence, or the insertion of a small stable hairpin structure (deltaG = -18 kcal/mol) between the HCV IRES and CAT sequences (hpCAT) substantially reduced IRES-mediated translation. Although translation could be restored to both mutants by the inclusion of 14 nt of the polyprotein-coding sequence downstream of the AUG codon, a mutational analysis of the inserted protein-coding sequence demonstrated no requirement for either a specific nucleotide or amino acid-coding sequence to restore efficient IRES-mediated translation to hpCAT. Similar results were obtained with the structurally and phylogenetically related IRES elements of classical swine fever virus and GB virus B. We conclude that there is no absolute requirement for viral protein-coding sequence with this class of IRES elements, but that there is a requirement for an absence of stable RNA structure immediately downstream of the AUG initiator codon. Stable RNA structure immediately downstream of the initiator codon inhibits internal initiation of translation but, in the case of hpCAT, did not reduce the capacity of the RNA to bind to purified 40S ribosome subunits. Thus, stable RNA structure within the 5' proximal protein-coding sequence does not alter the capacity of the IRES to form initial contacts with the 40S subunit, but appears instead to prevent the formation of subsequent interactions between the 40S subunit and viral RNA in the vicinity of the initiator codon that are essential for efficient internal ribosome entry.
Antimicrobial Strategies in the Prevention of Dental Caries (1993)

Antimicrobial agents, applied either professionally or delivered from dentifrices or mouthwashes, could reduce caries by controlling plaque formation, suppressing cariogenic species, or by inhibiting bacterial metabolism. Chlorhexidine has proven anticaries activity; other agents might also prevent caries by means of their antiplaque properties. Sugar substitutes stabilize the microflora by reducing the number of acid challenges to plaque and stimulating saliva flow; some also have antimicrobial properties, especially against mutans streptococci. Vaccines have been prepared from purified antigens of mutans streptococci. These vaccines confer protection in non-human primates, but have yet to be tested in a human clinical trial.
709. Heterocyclic syntheses with malonyl chloride. Part VI. 3-Substituted pyridine derivatives from α-methylene-nitriles (1962)

S. J. Davis, J. A. Elvidge and A. B. Foster, J. Chem. Soc., 1962, 3638 DOI: 10.1039/JR9620003638
Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor. (1987)

We have developed an approach for deriving and characterizing antigen-receptor (CD3/Ti) signal-transduction mutants. This strategy combines receptor-mediated growth inhibition and fluorescence-activated cell sorting with the Ca2+-indicator indo-1. Despite the expression of structurally normal CD3/Ti complexes, one such mutant (J.CaM1) fails to exhibit inositolphospholipid metabolism or Ca2+ mobilization in response to anti-CD3 or anti-Ti monoclonal antibodies and fails to produce lymphokines in response to these antibodies. Surprisingly, anti-Ti antibody retains its effectiveness as a stimulus for the down-regulation of CD3/Ti surface expression. These cells remain responsive to AIF-4, at least one anti-CD3 antibody, and some combinations of nonagonist anti-Ti and anti-CD3 antibodies. The mutation in J.CaM1 appears to lie in a proximal component of the signal-transduction apparatus.
Role of Target Membrane Structure in Fusion with Influenza Virus: Effect of Modulating Erythrocyte Transbilayer Phospholipid Distribution (1993)

To study the role of the target membrane in influenza virus fusion we chose erythrocyte membranes whose phospholipid arrangement can readily be modified. The phospholipids of normal erythrocytes are arranged asymmetrically across the plasma membrane; phosphatidylcholine (PC) and sphingomyelin are predominantly on the outer surface, whereas others such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are predominantly restricted to the inner leaflet. However, erythrocytes can be lyzed and resealed under conditions where the asymmetric distribution of phospholipids is lost or retained. Low pH-induced fusion of the A/PR 8 strain of influenza virus, monitored spectrofluorometrically by the octadecylrhodamine dequenching assay, was more rapid with lipid-symmetric erythrocyte ghosts than with lipid-asymmetric ghosts or intact erythrocytes. Neither conversion of PS in the lipid-symmetric ghost membrane to PE by means of the enzyme PS decarboxylaze, nor incorporation of spin-labeled phospholipid analogs with PS, PC or PE headgroups into the outer leaflet of lipid-asymmetric erythrocytes altered rates or extents of fusion of A/PR 8 with the modified target. These results indicate that effects on influenza virus fusion are not associated with any particular phospholipid headgroup, but rather related to the packing characteristics of the target membrane.
Ethers will play key role in clean gasoline blends (1989)

The author discusses how there is enough information to speculate what the final gasoline specification may be. Within the guidelines developed in this article, low-emission gasoline will have lower volatility, lower aromatics, and lower concentrations of volatile olefins than today's gasolines. It will also contain some oxygen. Gasoline specifications to reduce ozone-related emissions are presented.
Involvement of the 55- and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells (1991)

In this study we investigated the expression of the 55 kDa (p55) and the 75 kDa (p75) TNF receptors in CD56+ NK cells and their role in NK and lymphokine-activated killer cells cell functions. By using mAb against the p55 and p75 TNF-R, NK cells were found to express both p55 and p75 upon activation, and both receptors were involved in the generation of lymphokine-activated killer cells activity. Proliferative activity of IL-2 stimulated NK cells was inhibited by anti-TNF-alpha mAb, indicating that endogenously produced TNF-alpha is important for optimal proliferation of NK cells. Furthermore, addition of rTNF-alpha increased the IL-2-induced proliferation of NK cells. mAb to p55 and p75 inhibited the IL-2-induced proliferation indicating that both TNF-R are involved in mediating this effect.
Prodrug Strategy for Enhancing Drug Delivery via Skin (2006)

Skin as a route for drug delivery has been extensively investigated. However, because of the predominant barrier function of stratum corneum in skin, the clinical application is limited. One strategy to solve this problem of drug permeation via skin is the use of prodrugs. Prodrugs are inactive compounds which are metabolized either chemically or enzymatically in a controlled or predictable manner to its parent active drug. Prodrugs can enhance dermal/transdermal drug delivery via different mechanisms, including increased skin partitioning, increased aqueous solubility, and reduced crystallization, etc. Besides the prodrug itself, the optimization of vehicle is important as well. The prodrug partitioning between skin and vehicle as well as prodrug-vehicle interaction may influence the enhancing efficacy on skin permeation. This review explores the synthesis and enhancing mechanisms of prodrugs for topical drug delivery. The prodrugs categorized by the therapeutic use of the parent drugs, including anticancer drugs, analgesics, anti-inflammatory drugs and vitamins, are systemically introduced in this review.
Effects of music on target‐controlled infusion of propofol requirements during combined spinal‐epidural anaesthesia* (2005)

The sedative effects of music were evaluated using the bispectral index (BIS) during target-controlled infusion (TCI) propofol. A total of 110 women undergoing hysterectomy were randomly allocated to receive either music or no music. Propofol was administered using target-controlled infusion and the concentration adjusted gradually to achieve an observer's assessment of alertness/sedation (OAA/S) score of 3 intra-operatively. The haemodynamic and bispectral index values during the sedation phase were recorded. Interleukin-6 was evaluated before, immediately after and 1 h following intervention. The music group had a significant reduction in mean (SD) induction time of sedation: 12 (12) min vs. 18 (12) min, p < 0.01; propofol target concentration: 1.6 (0.3) microg.ml(-1) vs. 2.4 (0.4) microg.ml(-1), p < 0.0001; intra-operative amount of propofol: 171 (98) mg vs. 251 (92) mg, p < 0.0001; and significantly higher levels of satisfaction with their peri-operative care: 9.6 (0.6) compared to the control group: 8.1 (1.0), p < 0.0001. No other differences were found. The results show the influence of music on the induction time of sedation, concentration and level of propofol during surgery, and suggest sedative benefits of music.
High-Intensity Focused Ultrasound Therapy: an Overview for Radiologists (2008)

High-intensity focused ultrasound therapy is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. This completely non-invasive technology has great potential for tumor ablation as well as hemostasis, thrombolysis and targeted drug/gene delivery. However, the application of this technology still has many drawbacks. It is expected that current obstacles to implementation will be resolved in the near future. In this review, we provide an overview of high-intensity focused ultrasound therapy from the basic physics to recent clinical studies with an interventional radiologist's perspective for the purpose of improving the general understanding of this cutting-edge technology as well as speculating on future developments.
Pathophysiology and treatment of airway mucociliary clearance. A moving tale. (2001)

Airway hygiene depends largely on mucociliary clearance (MCC) which in turn depends upon the movement of viscoelastic mucus along the airway by the beating of the ciliary appendages of airway epithelial cells. Failure to keep the airways sterile by MCC results in a host inflammatory response to the persistent microorganisms which, if it becomes chronic, causes damage to the airway wall and upregulation of mucus production manifest clinically as bronchiectasis, sinusitis and otitis. There are three principal disorders of MCC. Firstly, primary ciliary dyskinesia (PCD), a rare genetic deficiency of the ultrastructural apparatus required to propel the cilium, in which nasal nitric oxide is very low due to a deficiency of inducible nitric oxide synthase. Secondly, secondary ciliary dyskinesia due principally to microbial toxin-induced dysfunction of the energy pathways required for ciliary beating. Thirdly, abnormalities in the physicochemical properties of mucus, including reduced salt content/osmolality which results in it being unsuitable in quality for cilia to move it. Methods of rectifying this defect promise to restore MCC to normal and interfere in the vicious circle of inflammatory lung damage.
Synchronization, Anticipation, and Consistency in Motor Timing of Children with Dimensionally Defined Attention Deficit Hyperactivity Behaviour (1999)

We tested the hypothesis that children with hyperactive behaviour are impaired in the temporal organization of their motor output. The performance of 11 boys, scoring above a cut-off on standard scales of overactivity and inattention, was compared to that of controls in progressively more complex Motor-timing tasks. The tasks administered required self-paced and externally paced Sensorimotor Synchronization and Sensorimotor Anticipation. Deficits at a perceptual level were investigated with a Time-discrimination task. As hypothesized, we found that hyperactive children had no deficits in their perception of time but were impaired in timing their motor output. Hyperactive children were more inconsistent than controls in maintaining a freely chosen tapping rhythm, in synchronizing and in anticipating their motor response to external visual stimulation.
Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase (PDE1) Is a Pharmacological Target of Differentiation-Inducing Factor-1, an Antitumor Agent Isolated from Dictyostelium (2004)

The differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum is a potent antiproliferative agent that induces growth arrest and differentiation in mammalian cells in vitro. However, the specific target molecule(s) of DIF-1 has not been identified. In this study, we have tried to identify the target molecule(s) of DIF-1 in mammalian cells, examining the effects of DIF-1 and its analogs on the activity of some candidate enzymes. DIF-1 at 10-40 micro M dose-dependently suppressed cell growth and increased the intracellular cyclic AMP concentration in K562 leukemia cells. It was then found that DIF-1 at 0.5-20 micro M inhibited the calmodulin (CaM)-dependent cyclic nucleotide phosphodiesterase (PDE1) in vitro in a dose-dependent manner. Kinetic analysis revealed that DIF-1 acted as a competitive inhibitor of PDE1 versus the substrate cyclic AMP. Because DIF-1 did not significantly affect the activity of other PDEs or CaM-dependent enzymes and, in addition, an isomer of DIF-1 was a less potent inhibitor, we have concluded that PDE1 is a pharmacological and specific target of DIF-1.
A Collagenous Cementum-Derived Attachment Protein Is a Marker for Progenitors of the Mineralized Tissue-Forming Cell Lineage of the Periodontal Ligament (1997)

The periodontal ligament (PDL) is a fibrous and cellular connective tissue that mediates tooth attachment to bone, and it comprises fibroblastic and mineralized tissue-forming (MTF) progenitors. The MTF progenitors are believed to give rise to the cementoblastic and osteoblastic lineages. Cementum attachment protein (CAP) is a collagenous cementum-derived protein which binds strongly to osteoblasts, moderately to PDL cells, and weakly to gingival fibroblasts. The aim of the present study was to determine the relationship between the capacity of PDL progenitors to bind CAP and their potential to express alkaline phosphatase (ALP) and form mineralized-like tissue in culture. Cloned human PDL progenitor populations obtained from nine human donors were assayed for their constitutive capacity to bind CAP and express ALP, and for the dexamethasone-induced potential to form mineralized-like tissue in culture in the presence of ascorbic acid and beta-glycerophosphate. Forty percent of the progenitor clones produced mineralized-like tissue. Two patterns of mineralization were observed: a spread and flat pattern similar to that produced by human bone cells in culture and a nodular ridge-like type resembling that formed by human cementoma-derived cells. A direct correlation was found between the percentage of ALP positive cells in each progenitor clone and the amount of mineralized-like tissue formed (r = 0.565). Similar correlations were found between the number of ALP positive cells and the binding capacity of each clone (r = 0.392) and between the CAP binding capacity and mineralized-like tissue formation (r = 0.584). Multiple regression analysis indicated that the constitutive capacity of a clone to bind CAP and express ALP is directly correlated to its dexamethasone-induced potential to form mineralized tissue (r = 0.675). These results indicate that CAP binding and ALP expression can serve as markers for the identification of MTF progenitors in the heterogeneous cultured population of the human periodontal ligament. These data show for the first time that binding capacity to extracellular components of mineralized tissues can be a marker for mineralized tissue-forming progenitors.
Studies on antibacterial agents. III. Synthesis of N,N'-bis(4-quinolyl-, 4-quinaldinyl-, 4-quinazolinyl-, or 9 acridinyl)polymethylenediamines and their sulfonamides. (1975)

Polymethylene bis-amines, with heterocycle as a carrier moiety, and their sulfonamides were synthesized and tested against S. aureus, E. coli and M. tuberculosis (H37Rv strain). Structure-activity relationship has been discussed.
Long-term stability of electroenzymatic glucose sensors implanted in mice. An update. (1989)

Protection of the enzyme layer of glutaraldehyde vapor-stabilized glucose oxidase-based glucose sensors from attack by proteolytic enzymes and peritoneal macrophages can be accomplished by covering with a regenerated cellulose (viscose) membrane, as commonly used for laboratory dialysis. These implanted sensors are not externally polarized, but continuously consume oxygen and glucose and generate gluconic acid and hydrogen peroxide. On the average (sensors in 45 mice) the activity declines with time, almost vanishing by 600 days. However, the fact that some sensors retain nearly all of their activity for over 500 days indicates that glucose sensors can be made with a life span compatible with the requirements for an artificial pancreas (glucose sensor/insulin pump). Limited observation with similar implanted lactate sensors indicates their life span to be shorter.
13·9%‐efficient CdTe polycrystalline thin‐film solar cells with an infrared transmission of ∼50% (2005)

Abstract To fabricate a high‐efficiency polycrystalline thin‐film tandem cell, the most critical work is to make a high‐efficiency top cell ( &gt; 15%) with high bandgap (E g = 1·5–1·8 eV) and high transmission (T &gt; 70%) in the near‐infrared (NIR) wavelength region. The CdTe cell is one of the candidates for the top cell, because CdTe state‐of‐the‐art single‐junction devices with efficiencies of more than 16% are available, although its bandgap (1·48 eV) is slightly lower for a top cell in a current‐matched dual‐junction device. In this paper, we focus on the development of a: (1) thin, low‐bandgap Cu x Te transparent back‐contact; and (2) modified CdTe device structure, including three novel materials: cadmium stannate transparent conducting oxide (TCO), ZnSnO x buffer layer, and nanocrystalline CdS:O window layer developed at NREL, as well as the high‐quality CdTe film, to improve transmission in the NIR region while maintaining high device efficiency. We have achieved an NREL‐confirmed 13·9%‐efficient CdTe transparent solar cell with an infrared transmission of ∼50% and a CdTe/CIS polycrystalline mechanically stacked thin‐film tandem cell with an NREL‐confirmed efficiency of 15·3%. Copyright © 2005 John Wiley &amp; Sons, Ltd.
Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen. (1984)

Anti-Tac monoclonal antibody identifies the receptor for interleukin 2 (IL 2, or T cell growth factor) present on activated human T lymphocytes. By using tritiated anti-Tac, we now report a sensitive and specific binding assay to evaluate cell surface IL 2 receptor expression. IL 2 receptors on human peripheral blood lymphocytes can be detected within 6 hr after PHA stimulation. PHA-induced receptor expression is inhibited by actinomycin D and cycloheximide, but not by mitomycin C, suggesting a requirement for de novo RNA and protein synthesis, but not DNA synthesis. Scatchard analysis of [3H]-anti-Tac binding to lymphocytes stimulated with PHA for 3 days revealed from 20,000 to 60,000 molecules of antibody bound per cell, and a Kd of 1 to 3 x 10(-10) mol/l. Sequential binding studies of activated human lymphocytes maintained in long-term culture with IL 2 demonstrated a progressive decline in receptor number correlating with diminished growth rate. Restimulation with lectin or antigen increased the number of IL 2 receptors, suggesting that IL 2 dependent immune responses may be regulated, at least in part, by IL 2 receptor expression. Receptor number was also increased by PMA. Moreover, similar effects were produced by incubation with phospholipase C but not interleukin 1. Because both PMA and phospholipase C result in activation of protein kinase C, these data suggest the possibility that activation of protein kinase C may induce IL 2 receptor expression.
Time-reversal with limited signature precision: Tradeoff between complexity and performance (2014)

The success of time-reversal (TR) technique relies on the design of TR signature from the multi-path profile. In practice, the signature is of limited precision instead of being infinite due to the finite resolution in hardware. Such limited signature precision will degrade the TR focusing effect and thus the system performance. Although several works have been proposed to study the performance of TR system with one-bit signature, a general relation between the resolution of signature and the system performance has not been established to answer the question: how many bits are needed for TR systems to achieve desirable system performance? In the paper, we address the question by studying the TR system with limited signature precision. We derive theoretically the relationship between the received signal-to-interference-plus-noise ratio (SINR) and the quantization step. Through simulations, we find that for a typical TR system, 4-bit resolution for the signature is good enough to achieve good system performance.