gebhart/patrepeval huggingface dataset:
Creation of a Constitutively Activated State of the 5‐HT2A Receptor by Site‐directed Mutagenesis: Revelation of Inverse Agonist Activity of Antagonists (1998)

Constitutively active GPCR have revealed novel properties of drugs that exhibit classical competitive antagonism at the native forms of GPCR. These drugs reverse basal levels of constitutive activity, indicating that they have inverse agonist activity. We were interested in determining if competitive antagonists of the native 5-HT2A receptor, in particular, antipsychotic drugs, exhibit inverse agonist activity at the constitutively active 5-HT2A receptor. All of the drugs tested reduced basal IP production of constitutively active 5-HT2A receptors, indicating that they all exhibited inverse agonist activity. Risperidone and ketanserin produced the greatest inhibition of basal IP production resulting in a reduction of basal activity in the C322K mutant receptor of 82% and 80%, respectively. Antipsychotic drugs display inverse agonist activity, indicating that stabilization of the inactive conformation of the 5-HT2A receptor may be a key component of their mechanism of action.
Gentamicin-PMMA beads. Pharmacokinetic and nephrotoxicological study. (1986)

Five patients treated with gentamicin-polymethylmethacrylate (PMMA) beads were monitored during the treatment of nine to 14 days. Kinetic data of the gentamicin delivery were gathered constantly by multiple samples of blood and urine. The treatment with 48-360 beads caused a gentamicin serum concentration of 0.03-0.4 micrograms/ml and a renal excretion rate of 3-40 micrograms/min. The total amount of gentamicin excreted after the whole treatment was 20%-70%, with an in vivo half-life of 5.7-10 days. The gentamicin appeared to be released constantly during the entire treatment (nine to 14 days); the beads are kinetically slow release carriers. Despite precise measurement of tubular and glomerular renal function, no nephrotoxicity could be demonstrated. This local antibiotic gentamicin therapy may use the blood bone barrier effectively as a protection of the body against a very high local gentamicin concentration.
Defining the sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: analysis of yeast GCN4 protein. (1989)

We describe a new method for accurately defining the sequence recognition properties of DNA-binding proteins by selecting high-affinity binding sites from random-sequence DNA. The yeast transcriptional activator protein GCN4 was coupled to a Sepharose column, and binding sites were isolated by passing short, random-sequence oligonucleotides over the column and eluting them with increasing salt concentrations. Of 43 specifically bound oligonucleotides, 40 contained the symmetric sequence TGA(C/G)TCA, whereas the other 3 contained sequences matching six of these seven bases. The extreme preference for this 7-base-pair sequence suggests that each position directly contacts GCN4. The three nucleotide positions on each side of this core heptanucleotide also showed sequence preferences, indicating their effect on GCN4 binding. Interestingly, deviations in the core and a stronger sequence preference in the flanking region were found on one side of the central C . G base pair. Although GCN4 binds as a dimer, this asymmetry supports a model in which interactions on each side of the binding site are not equivalent. The random selection method should prove generally useful for defining the specificities of other DNA-binding proteins and for identifying putative target sequences from genomic DNA.
Water As Proppant (2011)

Abstract The horizontal well with multiple transverse fractures, has proven to be a successful approach for production of gas from shale. As many as 80 fractures and nearly 10 million gallons of fracture fluid have been employed in a single well. However, unlike for conventional hydraulic fractures, in shale gas wells most of the treatment water never flows back. In this paper we postulate that the water has actually stayed in the created fractures and/or in enhanced natural fractures. The reason why fractures exhibit high conductivity flow behavior even with very little proppant is because the water injected in the fractures cannot leak off into the shale matrix, and relative permeability in the fracture impairs the water from flowing back. Water remaining in the fractures actually prevents them from closing. Gas bubbles or channels to the horizontal borehole through water in the fractures. In shale gas formations some diagnostic fluid injection tests appear to never exhibit closure or close with indicated fluid efficiency of 90% or more. In the period during execution and before flow back, water is too viscous for the large fluid volumes injected to flow into the extremely low permeability shale matrix. If treatment water could leak off, unpropped fractures in shale would likely close. Because the gas is water-saturated as it enters the water filled fracture, there is little tendency to vaporize the water. Therefore, water as proppant resolves both the question why so much treatment water never flows back and why fracture complexity can remain open indefinitely without proppant slurry.
Antibodies Reactive with Human T-Lymphotropic Retroviruses (HTLV-III) in the Serum of Patients with AIDS (1984)

In cats, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or T-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I can cause T-cell proliferation and leukemia. The subgroup HTLV-II also induces T-cell proliferation in vitro, but its role in disease is unclear. Viruses of a third subgroup of human T-lymphotropic retroviruses, collectively designated HTLV-III, have been isolated from cultured cells of 48 patients with acquired immunodeficiency syndrome (AIDS). The biological properties of HTLV-III and immunological analyses of its proteins show that this virus is a member of the HTLV family, and that it is more closely related to HTLV-II than to HTLV-I. Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.
Pseudopotential calculations on alkali silicide clusters with Si2 and tetrahedral Si4 backbones (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPseudopotential calculations on alkali silicide clusters with Si2 and tetrahedral Si4 backbonesA. Savin, K. Vogel, H. Preuss, H. Stoll, R. Nesper, and H. G. Von SchneringCite this: J. Am. Chem. Soc. 1988, 110, 2, 373–375Publication Date (Print):January 1, 1988Publication History Published online1 May 2002Published inissue 1 January 1988https://pubs.acs.org/doi/10.1021/ja00210a009https://doi.org/10.1021/ja00210a009research-articleACS PublicationsRequest reuse permissionsArticle Views129Altmetric-Citations13LEARN 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
Effect of antibiotic treatment on toxin production by Alexandrium tamarense. (2003)

The results indicate that antibiotics can enhance algal growth and toxin production not only through their inhibition of the growth and hence competition for nutrients, but also through their effects on the physiology of the algae.
Widely bandwidth-tunable silicon filter with an unlimited free-spectral range (2015)

Next-generation high-capacity optical networks require flexible allocation of spectrum resources, for which low-cost optical filters with an ultra-wide bandwidth tunability beyond 100 GHz are desired. We demonstrate an integrated band-pass filter with the bandwidth continuously tuned across 670 GHz (117-788 GHz) which, to the best of our knowledge, is the widest tuning span ever demonstrated on a silicon chip. The filter also features simultaneous wavelength tuning and an unlimited free spectral range. We measured an out-of-band contrast of up to 55 dB, low in-band ripples of less than 0.3 dB, and in-band group delay variation of less than 8 ps. This result was achieved using cascaded Bragg-grating-assisted contra-directional couplers and micro-heaters on the 220 nm silicon-on-insulator platform with a very compact footprint of less than 7000 μm2. Another design with the bandwidth continuously tunable from 50 GHz to 1 THz is also presented.
Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion. (1988)

Specified regions of the myocardium can be labeled in magnetic resonance (MR) imaging to serve as markers during contraction. The technique is based on locally perturbing the magnetization of the myocardium with selective radio-frequency (RF) saturation of multiple, thin tag planes during diastole followed by conventional, orthogonal-plane imaging during systole. The technique was implemented on a 0.38-T imager and tested on phantoms and volunteers. In humans, tags could be seen 60-450 msec after RF saturation, thus permitting sampling of the entire contractile phase of the cardiac cycle. Tagged regions appear as hypointense stripes, and their patterns of displacement reflect intervening cardiac motion. In addition to simple translation and rotation, complex motions such as cardiac twist can be demonstrated. The effects of RF pulse angle, relaxation times, and heart rate on depiction of the tagged region are discussed.
Halozeotypes: a New Generation of Zeolite‐Type Materials (1997)

The first non-oxide, direct analogues of aluminosilicate zeolites are materials with the anionic partial structure [CunZnm–nCl2m]n−. Varying the templating alkylammonium counterion results in different framework structures: [HNMe3][CuZn5Cl12] adopts the known sodalite structure, whereas [H2NEt2][CuZn5Cl12] exhibits a novel three-dimensional channel structure with eleven- and eight-ring channels (the latter is depicted on the right). Controlled addition of methanol or water results in formation of colloidal particles that are implicated as intermediates in the construction of open frameworks.
Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V (1993)

This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.
A Trotting Horse Model (2000)

A new control strategy is used to stabilize numerical simulations of a horse model in the trotting quadrupedal gait. Several well-established experimental findings are predicted by the model, including how stride frequency and stride length change with forward running speed. Mass is distributed throughout the model's legs, trunk, and head in a realistic manner. Leg and trunk flexion is modeled using four flexible legs, a back joint, and a neck joint. In the control model, pitch stabilization is achieved without directly controlling body pitch, but rather by controlling both the aerial time and the foot speed of each stance leg. The legs behave as ideal springs while in contact with the ground, enabling the model to rebound from the ground with each trotting step. Numerical experiments are conducted to test the model's capacity to overcome a change in ground impedance. Model stability is maximized and the metabolic cost of trotting is minimized within a narrow range of leg stiffness where trotting horses of similar body size have been observed to operate. This work suggests that a horselike robot will exhibit behavior that is mechanically similar to that of a trotting horse if it operates in a narrow range of leg stiffness and employs simple control strategies where postural stabilization is an emergent property of the system.
Existence and Properties of Two Malic Enzymes in Escherichia coliEspecially of NAD-linked Enzyme (1969)

Journal Article Existence and Properties of Two Malic Enzymes in Escherichia coliEspecially of NAD-linked Enzyme Get access KANJI TAKEO KANJI TAKEO From the Department of Chemistry, Faculty of Science, Kyoto UniversityKyoto) Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 66, Issue 3, September 1969, Pages 379–387, https://doi.org/10.1093/oxfordjournals.jbchem.a129156 Published: 01 September 1969 Article history Received: 13 February 1969 Published: 01 September 1969
Construction of a transducing virus from double-stranded RNA bacteriophage phi6: establishment of carrier states in host cells (1992)

Bacteriophage phi 6 contains three double-stranded RNA (dsRNA) genomic segments. We have constructed a plasmid that contains a cDNA copy of the middle (M) segment, with a gene for kanamycin resistance (kan) inserted into the PstI site. A transcript of this cDNA was incorporated in vitro into procapsids along with natural transcripts of the S and L segments. The procapsids were coated with nucleocapsid surface protein P8 and transfected into Pseudomonas syringae pv. phaseolicola. The resulting infectious virus, phi 6 K1, was found to contain an M segment that was 1.2 kbp larger than the normal 4.1 kbp. K1 formed small, turbid plaques, and its genome was unstable. Preparations of K1 contained from about 0.1 to 10% large, clear-plaque forms of the virus which were usually missing the kan gene, and in some cases, the resulting segment M was smaller than its normal size. Cells picked from lawns of host cells infected with K1 yielded colonies that were resistant to kanamycin (Kan). These colonies could be passaged on kanamycin-containing medium. The cells were found to contain large amounts of dsRNA corresponding to the viral genomic segments. Some strains continued to produce viable phage, while others lost this ability. One strain completely lost the small genomic segment S. Approximately 1 in 10,000 infected cells acquired the carrier state with the original phage isolate K1. However, we isolated a viral mutant that was able to induce the carrier state in 10 to 20% of the infected cells. The ability to use drug resistance as a test for the carrier state makes this system very useful for the study of the mechanisms of induction of persistent infections.
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5 (2016)

5-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway. The MTAP gene is frequently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene CDKN2A. By interrogating data from a large-scale short hairpin RNA-mediated screen across 390 cancer cell line models, we found that the viability of MTAP-deficient cancer cells is impaired by depletion of the protein arginine methyltransferase PRMT5. MTAP-deleted cells accumulate the metabolite methylthioadenosine (MTA), which we found to inhibit PRMT5 methyltransferase activity. Deletion of MTAP in MTAP-proficient cells rendered them sensitive to PRMT5 depletion. Conversely, reconstitution of MTAP in an MTAP-deficient cell line rescued PRMT5 dependence. Thus, MTA accumulation in MTAP-deleted cancers creates a hypomorphic PRMT5 state that is selectively sensitized toward further PRMT5 inhibition. Inhibitors of PRMT5 that leverage this dysregulated metabolic state merit further investigation as a potential therapy for MTAP/CDKN2A-deleted tumors.
Crystal Structure of Inhibitor-Bound Human 5-Lipoxygenase-Activating Protein (2007)

Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.
ZEB1 and c-Jun Levels Contribute to the Establishment of Highly Lytic Epstein-Barr Virus Infection in Gastric AGS Cells (2007)

The induction of lytic infection has been proposed as a therapeutic strategy for treating Epstein-Barr virus (EBV)-positive malignancies. To succeed, efficient methods are needed for activating the EBV immediate-early (IE) promoters, Zp and Rp. Here we compared factors which regulate Zp and Rp in AGS gastric carcinoma cells that support a remarkably high level of persistently lytic EBV infection with HeLa cervical cells that permit only tightly latent infection. We found that the level of Zp activity assayed by transient transfection assays with reporter plasmids was high in AGS cells but low in HeLa cells. The level of Rp activity was low in both cell types. Mutational analysis indicated that sequences within Zp located between -70 and +27 relative to the transcription initiation site were sufficient to confer a high level of Zp activity in AGS cells. The Zp CRE motif was necessary for this constitutive activity, while the ZIA and ZIB MEF2D motifs were not. Consistent with these findings, immunoblot analysis indicated that phosphorylated c-Jun, which activates Zp through the CRE motif, was expressed at a much higher level in EBV-infected AGS cells than in EBV-infected HeLa cells. In contrast, ZEB1, which represses Zp via the ZV motif located near the transcription initiation site, was abundant in HeLa cells, while it was absent from AGS cells. Exogenous addition of ZEB1 led to the repression of Zp in AGS cells. We conclude that the unusually high Zp activity level in AGS cells is due to the high abundance of positively acting transcription factors such as c-Jun combined with the low abundance of negatively acting factors such as ZEB1.
Solid Phase Peptide Synthesis (1976)

Abstract The last two decades have been an era of rapid progress in peptide research. This era was begun by the work of Sanger on the amino acid sequence determination of insulin and by du Vigneaud on the structure determination and synthesis of oxytocin. This period has seen impressive progress in the structure elucidation and synthesis of many peptides of natural origin and of great biological significance, as well as in methods for sequence determination and chemical synthesis of peptides [1–4]. Perfection of techniques and instruments for automatic determination of the amino acid sequence of peptides and proteins has made possible a greatly broadened understanding of genetics and evolution as well as the more chemical areas of mechanism of action of enzymes and hormones, and physical chemistry of peptides and proteins. Effective methods of peptide synthesis are crucial to progress in this area, because only by synthesis can adequate amounts of important peptides be made available for chemical, biological, and physical studies, as well as for exploration of the structure-function aspects of biological molecules. In general, progress in peptide synthesis has lagged far behind that in amino acid sequence determination. This is not surprising since effective peptide synthesis requires a very sophisticated system of selectively removable protecting groups for functions of the amino acids involved, and the synthesis of a large heteropolytner of defined sequence requires near perfection of each one of the many steps of the assembly. The classical approach to peptide synthesis, using standard organic chemical methods of synthesis and purification of intermediates, has yielded impressive results during these two decades. However, the special problems associated with the assembly of large molecules make staggering investments in time and materials necessary for the synthesis of large peptides or proteins by classical methods.
Abrupt Onset of Mutations in a Developmentally Regulated Gene during Terminal Differentiation of Post-Mitotic Photoreceptor Neurons in Mice (2014)

For sensitive detection of rare gene repair events in terminally differentiated photoreceptors, we generated a knockin mouse model by replacing one mouse rhodopsin allele with a form of the human rhodopsin gene that causes a severe, early-onset form of retinitis pigmentosa. The human gene contains a premature stop codon at position 344 (Q344X), cDNA encoding the enhanced green fluorescent protein (EGFP) at its 3' end, and a modified 5' untranslated region to reduce translation rate so that the mutant protein does not induce retinal degeneration. Mutations that eliminate the stop codon express a human rhodopsin-EGFP fusion protein (hRho-GFP), which can be readily detected by fluorescence microscopy. Spontaneous mutations were observed at a frequency of about one per retina; in every case, they gave rise to single fluorescent rod cells, indicating that each mutation occurred during or after the last mitotic division. Additionally, the number of fluorescent rods did not increase with age, suggesting that the rhodopsin gene in mature rod cells is less sensitive to mutation than it is in developing rods. Thus, there is a brief developmental window, coinciding with the transcriptional activation of the rhodopsin locus, in which somatic mutations of the rhodopsin gene abruptly begin to appear.
Cloning of the cDNA for human 12-lipoxygenase. (1990)

A full-length cDNA clone encoding 12-lipoxygenase (arachidonate:oxygen 12-oxidoreductase, EC 1.13.11.31) was isolated from a human platelet cDNA library by using a cDNA for human reticulocyte 15-lipoxygenase as probe for the initial screening. The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75,590. Three independent clones revealed minor heterogeneities in their DNA sequences. Thus, in three positions of the deduced amino acid sequence, there is a choice between two different amino acids. The deduced sequence from the clone plT3 showed 65% identity with human reticulocyte 15-lipoxygenase and 42% identity with human leukocyte 5-lipoxygenase. The 12-lipoxygenase cDNA recognized a 3.0-kilobase mRNA species in platelets and human erythroleukemia cells (HEL cells). Phorbol 12-tetradecanoyl 13-acetate induced megakaryocytic differentiation of HEL cells and 12-lipoxygenase activity and increased mRNA for 12-lipoxygenase. The identity of the cloned 12-lipoxygenase was assured by expression in a mammalian cell line (COS cells). Human platelet 12-lipoxygenase has been difficult to purify to homogeneity. The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme.