gebhart/patrepeval huggingface dataset:
Structure-Based Discovery of Novel Chemotypes for Adenosine A<sub>2A</sub>Receptor Antagonists (2010)

The recent progress in crystallography of G-protein coupled receptors opens an unprecedented venue for structure-based GPCR drug discovery. To test efficiency of the structure-based approach, we performed molecular docking and virtual ligand screening (VLS) of more than 4 million commercially available "drug-like" and ''lead-like'' compounds against the A(2A)AR 2.6 A resolution crystal structure. Out of 56 high ranking compounds tested in A(2A)AR binding assays, 23 showed affinities under 10 microM, 11 of those had sub-microM affinities and two compounds had affinities under 60 nM. The identified hits represent at least 9 different chemical scaffolds and are characterized by very high ligand efficiency (0.3-0.5 kcal/mol per heavy atom). Significant A(2A)AR antagonist activities were confirmed for 10 out of 13 ligands tested in functional assays. High success rate, novelty, and diversity of the chemical scaffolds and strong ligand efficiency of the A(2A)AR antagonists identified in this study suggest practical applicability of receptor-based VLS in GPCR drug discovery.
Final Report on the Safety Assessment of EDTA, Calcium Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, Disodium EDTA, TEA-EDTA, Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, HEDTA, and Trisodium HEDTA (2002)

EDTA (ethylenediamine tetraacetic acid) and its salts are substituted diamines. HEDTA (hydroxyethyl ethylenediamine triacetic acid) and its trisodium salt are substituted amines. These ingredients function as chelating agents in cosmetic formulations. The typical concentration of use of EDTA is less than 2%, with the other salts in current use at even lower concentrations. The lowest dose reported to cause a toxic effect in animals was 750 mg/kg/day. These chelating agents are cytotoxic and weakly genotoxic, but not carcinogenic. Oral exposures to EDTA produced adverse reproductive and developmental effects in animals. Clinical tests reported no absorption of an EDTA salt through the skin. These ingredients are likely, however, to affect the passage of other chemicals into the skin because they will chelate calcium. Exposure to EDTA in most cosmetic formulations, therefore, would produce systemic exposure levels well below those seen to be toxic in oral dosing studies. Exposure to EDTA in cosmetic formulations that may be inhaled, however, was a concern. An exposure assessment done using conservative assumptions predicted that the maximum EDTA dose via inhalation of an aerosolized cosmetic formulation is below that shown to produce reproductive or developmental toxicity. Because of the potential to increase the penetration of other chemicals, formulators should continue to be aware of this when combining these ingredients with ingredients that previously have been determined to be safe, primarily because they were not significantly absorbed. Based on the available data, the Cosmetic Ingredient Review Expert Panel found that these ingredients are safe as used in cosmetic formulations.
An integrated deterministic urban/rural propagation model (1998)

Cochannel interference is one of the major causes of signal quality degradation in a radio link, and the challenge to the cellular network planner is to deploy the network in a manner that maximises the carrier to interference ratio (C/I) for each cell. To this end, most network planners make use of computer propagation prediction models, which predict signal strength in the radio environment. This paper describes an integrated 3D model, which combines the key features from previous urban and rural models. The model considers full 3D off-axis scattered paths from building walls and terrain pixels. It further considers terrain and rooftop diffraction and combinations of off-axis diffracted and scattered paths. Predictions from the model are compared with narrowband measurements made in urban and rural environments. The importance of buildings and foliage is investigated, as is the accuracy improvement of the 3D analysis compared to the simpler 2D vertical plane approach.
T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice. (1994)

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreactive T cells induced after immunization with MBP use a limited set of TCR. In contrast, we demonstrate that T cell clones that recognize the encephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TCR V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization with MBP but not with PLP. These data demonstrate the biological consequences of the usage of a more diverse T cell repertoire in the development of an autoimmune disease.
Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma (2013)

The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lung normal cells. The mitochondrial vulnerability to reactive species in H460 may induce distinctively selective responses. Differential mitochondrial membrane potential decrease, mitochondrial enzymatic dysfunction, and mitochondrial morphological alteration are exhibited in two cell lines. These results suggest the nonthermal plasma treatment as an efficacious modality in lung cancer therapy.
Selectivity in Lewis acid-mediated fragmentations of peroxides and ozonides: application to the synthesis of alkenes, homoallyl ethers, and 1,2-dioxolanes † (2000)

Fragmentation of dialkyl peroxides and ozonides is strongly influenced by the choice of Lewis acid. TiCl4 promotes C–O ionization (SN1 reaction) of tertiary peroxides while SnCl4 and BF3·OEt2 promote O–O heterolysis (Hock reaction). The cationic intermediates are trapped with allyltrimethylsilane to afford allylated alkanes and homoallyl ethers. In the absence of a nucleophile, ozonides (1,2,4-trioxolanes) invariably undergo O–O heterolysis. However, the combination of allyltrimethylsilane and SnCl4 results in formation of 1,2-dioxolanes via trapping of intermediates derived from SN1 ionization.
Cyanoacrylate Tissue Adhesives (1997)

Cyanoacrylate adhesives have been available for many years. Until recently, they have been limited by their physical properties, and their popularity has been sporadic due to their incorrect and inappropriate use. A new medical-grade cyanoacrylate adhesive has been developed that has greater strength and flexibility than previous adhesives. This new formulated octylcyanoacrylate will broaden the indications for the use of cyanoacrylate adhesives and has the potential to revolutionize wound care.
Shared Use of Experimental TCP Options (2013)

This document describes how the experimental TCP option codepoints can
concurrently support multiple TCP extensions, even within the same
connection, using a new IANA TCP experiment identifier. This approach
is robust to experiments that are not registered and to those that do
not use this sharing mechanism. It is recommended for all new TCP
options that use these codepoints.
Adsorption of detergents at the liquid-liquid interface. Part 1 (1960)

F. van Voorst Vader, Trans. Faraday Soc., 1960, 56, 1067 DOI: 10.1039/TF9605601067
CuI-catalyzed cross-coupling of diazoacetamide with terminal alkynes: an approach to synthesizing substituted dienamides and 3-butynamides (2013)

A cross-coupling reaction between diazoacetamide and terminal alkynes has been developed, which provides a practical synthetic strategy for the synthesis of substituted dienamides and 3-butynamides under mild reaction conditions.
Microbial Hydrocarbon Co-oxidation. III. Isolation and Characterization of an α, α′-Dimethyl- <i>cis, cis-</i> Muconic Acid-producing Strain of <i>Nocardia corallina</i> (1969)

A soil isolate identified as a strain of Nocardia corallina accumulated alpha, alpha'-dimethyl-cis, cis-muconic acid under co-oxidation conditions employing n-hexadecane for growth and p-xylene as the co-oxidizable substrate. N. corallina V-49 was postulated to have two pathways for the oxidation of p-xylene. One pathway proceeds throughp-benzyl alcohol, p-tolualdehyde, and p-toluic acid to 2, 3-dihydroxy-p-toluic acid, and the other pathway results in ortho ring cleavage of 3, 6-dimethylpyrocatechol and hence accumulation of alpha,alpha'-dimethyl-cis, cis-muconic acid.
On the Simultaneous Optimization of Server and Work Allocations in Production Line Systems with Variable Processing Times (1996)

The allocation of servers and the allocation of work are two important decision variables in designing production line systems. Previous studies of each variable in isolation have found that throughput is maximized by using an allocation that gives preferential treatment to interior stations (especially center stations) over the two end stations. In this paper we study the simultaneous optimization of server and work allocations and obtain some surprising results of a different nature. One key finding is the L-phenomenon, whereby the throughput is maximized by assigning all extra servers over one per station to just one of the end stations and then adjusting the work allocation so that this station has by far the greatest amount of work per server. Another key finding is the multiple-server phenomenon, whereby extra servers add far more throughput per server than the initial one-per-station servers. Both findings have important implications for the design of some production line systems in ways that will greatly improve their efficiency. Similar conclusions are drawn when lower and/or upper bounds are imposed on the number of servers per station and the number of stations is included as a decision variable.
Chicken B cells adhere to the CS‐1 site of fibronectin throughout their bursal and postbursal development (1993)

In chickens, the pre-B cell development takes place in a specialized organ, the bursa of Fabricius. In this study, we show that fibronectin can be detected in the bursa at least from the day 15 of embryonic incubation up to 10 weeks of age after which the bursa starts to involute. During the embryonic incubation, fibronectin localizes mainly in the areas between the follicles and later on also in the border zone between the cortical and medullary parts of the lymphoid follicles. By adhesion studies with synthetic peptides we show that immature bursal B cells bind in a dose-dependent manner to the CS-1 site of the type III connecting segment at the carboxy-terminal end of fibronectin throughout their bursal development. Postbursal B cells from chicken spleen also display a similar preference of binding to the CS-1 site of fibronectin, whereas peripheral blood B lymphocytes bind to the 40-kDa fragment of fibronectin, but do not adhere as strongly to the CS-1 site. Instead, they recognize to some extent also the heparin-binding YEKPGSPPREVVPRPRPGV peptide. The adhesion of the bursal B cells to the CS-1 site can partially be blocked by preincubation of cells with a synthetic CS-1 peptide and also by preincubation with a monoclonal anti-fibronectin receptor antibody. In contrast, the RGD motif present in several adhesion-associated stromal molecules did not promote any adherence of bursal lymphocytes. The bursal B cells which adhere to the fibronectin molecule in vitro form only a small fraction of the total number of B cells present in the bursa as only less than 4% of the cells remained bound to the surface coated with fibronectin in the adhesion studies. In conclusion, these results suggest that fibronectin may be involved in the differentiation of pre-B cells in the bursa of Fabricius and also in the adherence of postbursal B cells in the spleen.
Nonpolarizing and polarizing filter design (2005)

We describe a nonpolarizing filter design at oblique incidence and a polarizing filter design at normal incidence that use a uniaxially anisotropic layer. The phase thicknesses and the optical admittances of the layers are compensated for by the birefringent properties of a thin film at oblique incidence. This concept can be applied to the design of nonpolarizing bandpass and edge filters at oblique incidence and of polarizing beam splitters at normal incidence. Besides, the dependence of narrow-bandpass filters on normal incidence is discussed.
OLFACTORY BULB ABLATION IN THE RAT: BEHAVIOURAL CHANGES AND THEIR REVERSAL BY ANTIDEPRESSANT DRUGS (1977)

1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds.
Stable amorphous calcium oxalate: synthesis and potential intermediate in biomineralization (2014)

Amorphous calcium oxalate nanoparticles with sizes of 10–30 nm were synthesized at room temperature by the hydrolysis of a dimethyl oxalate from ethanol solution.
Two or three days of ofloxacin treatment for uncomplicated multidrug-resistant typhoid fever in children (1996)

An open randomized comparison of 2 days (Ofx2) versus 3 days (Ofx3) of oral ofloxacin treatment (15 mg/kg/day) was conducted with Vietnamese children between 1 and 15 years of age with suspected typhoid fever. Of 108 children enrolled, 100 were blood culture positive for Salmonella typhi, and 86% of the isolates were multidrug resistant. There were no significant adverse effects. The therapeutic responses were similar in both groups, with mean (+/- standard deviation) fever clearances of 107 +/- 60 h in the Ofx3 group and 100 +/- 64 h in the Ofx2 group (P > 0.2). There were six "clinical" failures in the Ofx2 group and two clinical failures in the Ofx3 group (P > 0.2), in which fever and symptoms persisted for more than 1 week after the start of treatment, but only one of these was culture positive (Ofx3). There was one suspected relapse, and one carrier was identified. Short courses of ofloxacin are simple, inexpensive, safe, and effective for the treatment of uncomplicated multidrug-resistant typhoid fever.
The proteasome inhibitor PS-341 in cancer therapy. (1999)

The anticancer activity of the boronic acid dipeptide proteasome inhibitor PS-341 was examined in vitro and in vivo. PS-341 was a potent cytotoxic agent toward MCF-7 human breast carcinoma cells in culture, producing an IC90 of 0.05 microM on 24 h of exposure to the drug. In the EMT-6 tumor cell survival assay, PS-341 was equally cytotoxic administered p.o. or by i.p. injection up to a dose of 2 mg/kg. PS-341 was also toxic to the bone marrow colony-forming unit-granulocyte macrophage. PS-341 increased the tumor cell killing of radiation therapy, cyclophosphamide, and cisplatin in the EMT-6/Parent tumor, but was not able to overcome the in vivo resistance of the EMT-6/CTX and EMT-6/CDDP tumors. In the tumor growth delay assay, PS-341 administered p.o. had antitumor activity against the Lewis lung carcinoma, both primary and metastatic disease. In combination, regimens with 5-fluorouracil, cisplatin, Taxol and adriamycin, PS-341 seemed to produce primarily additive tumor growth delays against the s.c. tumor and was highly effective against disease metastatic to the lungs. The proteasome is an interesting new target for cancer therapy, and the proteasome inhibitor PS-341 warrants continued investigation in cancer therapy.
Quantitation of cytoskeletal fibers in fluorescence images: Stress fiber disassembly accompanies dephosphorylation of the regulatory light chains of myosin II (1993)

Stress fibers in serum-deprived fibroblasts provide an excellent system for studying the assembly dynamics of the actin-based cytoskeleton. Previous studies suggested that fibers containing actin and myosin II are restructured via two alternative pathways: coupled solation-contraction and disassembly without contraction. The former process appears to be regulated by Ca++, but regulation of the latter process has not been extensively explored. To assess the possible role of protein phosphorylation, we examined the dynamic behavior of stress fibers in cells treated with inhibitors of protein kinases. Swiss 3T3 fibroblasts were microinjected with fluorescent analogs of actin and myosin II and fiber dynamics monitored using light-microscope imaging. Staurosporine and KT5926 caused reversible dispersal of stress fibers without contraction, along with dephosphorylation of the regulatory light chain of myosin II, LC20. In order to make direct comparisons between the dose responses of these biochemical and morphological effects, fiber disruption was quantitated using two independent measures: total edge strength in fluorescent images of actin and myosin II, and fiber length determined by automated object-identification. Loss of stress fibers was shown to parallel LC20 dephosphorylation. Quantitation of cytoskeletal organization provides a framework for testing relationships between structural events and potential biochemical regulatory signals.
Thrombotic thrombocytopenic purpura in systemic lupus erythematosus and antiphospholipid antibodies: effective treatment with plasma exchange and immunosuppression. (1992)

We describe 2 patients with systemic lupus erythematosus (SLE) with neurological complications and thrombocytopenia, who, upon further investigation, were found to have thrombotic thrombocytopenic purpura. While neither patient responded to treatment with corticosteroids, both responded to plasma exchange and intravenous cyclophosphamide. This highlights the need to carefully consider this diagnosis in patients with SLE presenting with neurological complications and thrombocytopenia.
Modes in a Sequence of Thick Astigmatic Lens-Like Focusers (1964)

Maxwell's equations are solved for a periodic sequence of lens-like focusers separated by gaps. Each focuser consists of an arbitrarily thick slab of dielectric in which the dielectric constant tapers off radially with different quadratic laws in two perpendicular directions. Since there are no limitations on the thickness of the slabs, the solutions cover the complete gamut from a sequence of infinitely thin lenses with astigmatism to a continuous dielectric waveguide, and from spherical to cylindrical lenses. The field configurations of the modes and their propagation constants, as well as the transmission and cutoff bands, are calculated. Any arbitrary input field distribution can then be expanded in terms of the normal modes, and the expansion determines the field everywhere. Formulas derived for sequences of weak lenses turn out to give very good results even for lenses whose thickness and separation are equal to the focal length.
Reversibility of the Binding of Cytochrome c to Liposomes (1995)

Studies on the membrane binding of cytochrome c revealed liposome-associated and soluble cytochrome c not to be in rapid equilibrium. In brief, cytochrome c attached to pyrene phospholipid-labeled, fluorescent liposomes containing either 17.6 mol % cardiolipin (CL) or 30 mol % egg phosphatidylglycerol (PG) is practically not at all or very slowly, respectively, detached by a subsequently added excess (up to 20-fold) of nonlabeled liposomes containing these acidic lipids. Cytochrome c was fully dissociated from PG-containing liposomes by increasing the ionic strength by NaCl, whereas dissociation from CL-containing membranes was less complete, presumably because of the scavenging of the protein within inverted intramembrane micelles. Importantly, the apparent irreversibility of the binding of cytochrome c to liposomes is strongly dependent on the structure of the acidic phospholipid. Cytochrome c bound to lyso-PG/PC liposomes could be dissociated with an excess of nonlabeled PG-containing liposomes. Cytochrome c was also efficiently bound to membranes containing the negatively charged dicetylphosphate yet could be readily dissociated by nonlabeled PG-containing liposomes. We conclude both proper geometry of the phosphate group and the presence of two acyl chains to be required for the tight binding of cytochrome c to acidic phospholipids. These data provide evidence for the membrane association of cytochrome c by an acidic phospholipid in the extended conformation (Kinnunen, P. K. J., Köiv, A., Lehtonen, J. Y. A., Rytömaa, M., and Mustonen, P. (1994) Chem. Phys. Lipids 73, 181-207) in which one of the acyl chains of the lipid becomes accommodated within a hydrophobic cavity of the protein. Based on the crystal structure of cytochrome c we putatively assign the invariant Asn-52 (horse heart cytochrome c) as the site liganding the protonated phosphate of the lipid, whereas Lys-72 and -73 should bind the deprotonated form.
Effect of Adding Formaldehyde, Glutaraldehyde, or Dimethylolurea to Alfalfa before Ensiling (1986)

Formaldehyde, glutaraldehyde, or dimethylolurea were sprayed on alfalfa wilted to approximately 35 and 62% dry matter at rates of 1, 3, and 4 g of formaldehyde; 1.7, 5.0, and 6.7 g of glutaraldehyde; and 2.5, 5.0 and 10 g of dimethylolurea/100 g of crude protein.
Why do NASDAQ Market Makers Avoid Odd‐Eighth Quotes? (1994)

ABSTRACT The NASDAQ multiple dealer market is designed to produce narrow bid‐ask spreads through the competition for order flow among individual dealers. However, we find that odd‐eighth quotes are virtually nonexistent for 70 of 100 actively traded NASDAQ securities, including Apple Computer and Lotus Development. The lack of odd‐eighth quotes cannot be explained by the negotiation hypothesis of Harris (1991) , trading activity, or other variables thought to impact spreads. This result implies that the inside spread for a large number of NASDAQ stocks is at least $0.25 and raises the question of whether NASDAQ dealers implicitly collude to maintain wide spreads.