gebhart/patrepeval huggingface dataset:
The physical map of the chromosome of a serogroup A strain of Neisseria meningitidis shows complex rearrangements relative to the chromosomes of the two mapped strains of the closely related species N. gonorrhoeae (1995)

A physical map of the chromosome of N. meningitidis Z2491 (serogroup A, subgroup IV-1) has been constructed. Z2491 DNA was digested with NheI, SpeI, SgfI, PacI, BglII, or PmeI, resulting in a limited number of fragments that were resolved by contour-clamped homogeneous electric field (CHEF) electrophoresis. The estimated genome size for this strain was 2,226 kb. To construct the map, probes corresponding to single-copy genes or sequences were used on Southern blots of chromosomal DNA digested with the different mapping enzymes and subjected to CHEF electrophoresis. By determining which fragments from different digests hybridized to each specific probe, it was possible to walk back and forth between digests to form a circular macrorestriction map. The intervals between mapped restriction sites range from 10 to 143 kb in size. A total of 117 markers have been placed on the map; 75 represent identified genes, with the remaining markers defined by anonymous cloned fragments of neisserial DNA. Comparison of the arrangement of genetic loci in Z2491 with that in gonococcal strain FA1090, for which a physical map was previously constructed, revealed complex genomic rearrangements between the two strains. Although gene order is generally conserved over much of the chromosome, a region of approximately 500 kb shows translocation and/or inversion of multiple blocks of markers between the two strains. Even within the relatively conserved portions of the maps, several genetic markers are in different positions in Z2491 and FA1090.
Aminopyridinate‐Stabilized Lanthanoid Complexes: Synthesis, Structure and Polymerization of Ethylene and Isoprene (2010)

Abstract A series of aminopyridinate‐stabilized dialkyl‐lanthanoid complexes has been synthesized and characterized. The complexes were prepared by alkane elimination reacting [Ln(CH 2 SiMe 3 ) 3 (thf) 2 ] (Ln = Er, Yb, Lu) or [Ln(CH 2 Ph) 3 (thf) 3 ] (Ln = Y, Er, Lu) with one equivalent of the bulky aminopyridine (2,6‐diisopropylphenyl)‐[6‐(2,4,6‐triisopropylphenyl)pyridin‐2‐yl]amine. Single‐crystal X‐ray analyses were carried out for all of the benzyl derivatives. The reaction of these compounds with ammonium borate leads to the elimination of one of the two alkyl functions and affords organolanthanoid cations. The aminopyridinate‐stabilized dialkyl‐lanthanoid compounds can initiate the polymerization of isoprene after activation with perfluorinated tetraphenyl borates. The obtained polymers have a 3,4‐content of 60–95 %. The metal ion size as well as the addition of alkylaluminium compounds influences the microstructure of the obtained polymer. Aminopyridinate‐stabilized organolanthanoid cations of Sc, Lu, Er and Y can polymerize ethylene in the presence of alkylaluminium compounds. The Lu, Er and Y complexes act as a CCTP catalyst and the erbium compound exhibits the highest activity.
Biomembranes: molecular structure and function (1989)

New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical thermody namics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the graduate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases, the availability of texts in active research areas should help stimulate the creation of new courses.
The CYP26 inhibitor R115866 potentiates the effects of all-transretinoic acid on cultured human epidermal keratinocytes (2008)

These results strongly suggest that R115866 potentiates the effects of RA on epidermal keratinocytes when RA is present at low concentrations.
SPIRiT: Iterative self‐consistent parallel imaging reconstruction from arbitrary k‐space (2010)

A new approach to autocalibrating, coil-by-coil parallel imaging reconstruction, is presented. It is a generalized reconstruction framework based on self-consistency. The reconstruction problem is formulated as an optimization that yields the most consistent solution with the calibration and acquisition data. The approach is general and can accurately reconstruct images from arbitrary k-space sampling patterns. The formulation can flexibly incorporate additional image priors such as off-resonance correction and regularization terms that appear in compressed sensing. Several iterative strategies to solve the posed reconstruction problem in both image and k-space domain are presented. These are based on a projection over convex sets and conjugate gradient algorithms. Phantom and in vivo studies demonstrate efficient reconstructions from undersampled Cartesian and spiral trajectories. Reconstructions that include off-resonance correction and nonlinear l(1)-wavelet regularization are also demonstrated.
Drug carrier systems (1989)

Targeting of Drugs: Implications in Medicine (G. Gregoriadis). The Use of Antibodies and Polymers as Carriers of Cytotoxic Drugs in the Treatment of Cancer (R. Arnon, et al.). The Application of Drug-Polymer Conjugates in Chemotherapy (C. Hoes & J. Feijen). Biodegradable Polymers for Controlled Release of Peptides and Proteins (F. Hutchinson & B. Furr). Microspheres as Drug Carriers (S. Davis & L. Illum). Pharmacological Uses of Resealed and Modified Red Cell Carriers (G. Ihler). Liposomes as a Drug Delivery System in Cancer Chemotherapy (A. Gabizon). The Use of Liposomes as Drug Carriers in the Immunotherapy of Cancer (I. Fidler). Liposomes as Drug Carriers in the Therapy of Infectious Diseases (R. Juliano). Targeting of Liposomes to Liver Cells (G. Scherphof, et al.). Implantable Infusion Pumps for Drug Delivery in Man: Theoretical and Practical Considerations (P. Blackshear & T. Rohde). Index.
The story of barbituric acid (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe story of barbituric acidMary Kathleen Carter Cite this: J. Chem. Educ. 1951, 28, 10, 524Publication Date (Print):October 1, 1951Publication History Received3 August 2009Published online1 October 1951Published inissue 1 October 1951https://doi.org/10.1021/ed028p524RIGHTS & PERMISSIONSArticle Views361Altmetric-Citations19LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
New Compounds. New Compounds as Plant Growth Regulators (1947)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Compounds. New Compounds as Plant Growth RegulatorsMelvin Newman, William Fones, and Mary RenollCite this: J. Am. Chem. Soc. 1947, 69, 3, 718–723Publication Date (Print):March 1, 1947Publication History Published online5 November 2002Published inissue 1 March 1947https://pubs.acs.org/doi/10.1021/ja01195a604https://doi.org/10.1021/ja01195a604research-articleACS PublicationsRequest reuse permissionsArticle Views305Altmetric-Citations22LEARN 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
Selective disruption of the DNA polymerase III - complex by the umuD gene products (2012)

DNA polymerase III (DNA pol III) efficiently replicates the Escherichia coli genome, but it cannot bypass DNA damage. Instead, translesion synthesis (TLS) DNA polymerases are employed to replicate past damaged DNA; however, the exchange of replicative for TLS polymerases is not understood. The umuD gene products, which are up-regulated during the SOS response, were previously shown to bind to the α, β and ε subunits of DNA pol III. Full-length UmuD inhibits DNA replication and prevents mutagenic TLS, while the cleaved form UmuD' facilitates mutagenesis. We show that α possesses two UmuD binding sites: at the N-terminus (residues 1-280) and the C-terminus (residues 956-975). The C-terminal site favors UmuD over UmuD'. We also find that UmuD, but not UmuD', disrupts the α-β complex. We propose that the interaction between α and UmuD contributes to the transition between replicative and TLS polymerases by removing α from the β clamp.
Novel biomaterials for drug delivery (2001)

Safety and efficacy of pharmaceutical agents can be greatly improved by encapsulation within, or covalent attachment to, a biomaterial carrier. Such drug delivery systems differ from conventional drug dosage forms (pills, tablets, ointments, creams, injectables and ‘tiny time capsules’) in that a localised depot of drug provides patterned release of the active agent with a pre-determined time course. The pattern of drug release may be constant, oscillating, declining continuously, or even pulsatile. The need to engineer different release patterns for drugs of different molecular sizes, potency, stability and hydrophobicity provides the impetus for active study of the design of new biomaterials, intelligent delivery systems and approaches for delivery through different portals in the body. The field of controlled drug delivery provides a driving force for current innovations in biomaterials. For most drug delivery systems, polymers function simply as inert, biocompatible carriers. In other systems, polymers can be designed with targeting or pathology-responsive functions. This review summarises some of the recently developed intellectual property in the field of biomaterials applied to drug delivery systems. Included are implantable ceramics and other inorganic materials, non-degradable and degradable synthetic polymers, natural polymers and hybrid biomaterials derived from synthetic and natural polymers.
Biodistribution of 89Zr-trastuzumab and PET Imaging of HER2-Positive Lesions in Patients With Metastatic Breast Cancer (2010)

We performed a feasibility study to determine the optimal dosage and time of administration of the monoclonal antibody zirconium-89 ((89)Zr)-trastuzumab to enable positron emission tomography (PET) imaging of human epidermal growth factor receptor 2 (HER2)-positive lesions. Fourteen patients with HER2-positive metastatic breast cancer received 37 MBq of (89)Zr-trastuzumab at one of three doses (10 or 50 mg for those who were trastuzumab-naive and 10 mg for those who were already on trastuzumab treatment). The patients underwent at least two PET scans between days 2 and 5. The results of the study showed that the best time for assessment of (89)Zr-trastuzumab uptake by tumors was 4-5 days after the injection. For optimal PET-scan results, trastuzumab-naive patients required a 50 mg dose of (89)Zr-trastuzumab, and patients already on trastuzumab treatment required a 10 mg dose. The accumulation of (89)Zr-trastuzumab in lesions allowed PET imaging of most of the known lesions and some that had been undetected earlier. The relative uptake values (RUVs) (mean +/- SEM) were 12.8 +/- 5.8, 4.1 +/- 1.6, and 3.5 +/- 4.2 in liver, bone, and brain lesions, respectively, and 5.9 +/- 2.4, 2.8 +/- 0.7, 4.0 +/- 0.7, and 0.20 +/- 0.1 in normal liver, spleen, kidneys, and brain tissue, respectively. PET scanning after administration of (89)Zr-trastuzumab at appropriate doses allows visualization and quantification of uptake in HER2-positive lesions in patients with metastatic breast cancer.
Placental Alkaline Phosphatase: A Model for Studying COOH-Terminal Processing of Phosphatidylinositol-Glycan-Anchored Membrane Proteins (1992)

Placental alkaline phosphatase (PLAP) has been used as a model for studying the biosynthesis of the phosphatidylinositol-glycan (PI-G)-protein linkage in intact cells and in cell-free systems. However, for the study of processing in cell-free systems, a small protein devoid of glycosylation sites is preferable. A PLAP-derived cDNA was engineered that codes for a nascent protein (mini-PLAP) of 28 kDa in which the NH2- and COOH-termini are retained but most of the interior of PLAP is deleted. In vitro translation of mini-PLAP mRNA in the presence of rough microsomal membranes yields mature PI-G-tailed mini-PLAP. Processing of nascent mutant proteins occurs only when a small amino acid is located at the site of cleavage and PI-G attachment (omega site). Mutations adjacent and COOH-terminal to the omega site have revealed that the omega + 1 site is promiscuous in its requirements but that only glycine and alanine are effective at the omega + 2 site. Rough microsomal membranes from T cells deficient in PI-G biosynthesis do not support processing of mini-PLAP; addition of exogenous PI-G restores activity. Translocation of the proprotein, most likely requiring ATP and GTP, precedes COOH-terminal processing.
DNA tris intercalation: first acridine trimer with DNA affinity in the range of DNA regulatory proteins. Kinetic studies (1985)

A trimer made up of three acridine chromophores linked by a positively charged poly(aminoalkyl) chain was synthesized as a potential tris-intercalating agent. The length of the linking chain was selected to allow intercalation of each chromophore according to the excluded site model. 1H NMR studies have shown that, at 5 mM sodium, pH 5, the acridine trimer occurred under a folded conformation stabilized by stacking interactions between the three aromatic rings. DNA tris-intercalation of the dye at a low dye/base pair ratio was shown by measurements of both the unwinding of PM2 DNA and the lengthening of sonicated rodlike DNA. The trimer exhibits a high DNA affinity for poly[d(A-T)] (Kapp = 8 X 10(8) M-1, 1 M sodium) as shown by competition experiments with ethidium dimer. Kinetic studies of both the association with poly[d(A-T)] and the exchange between poly[d(A-T)] and sonicated calf thymus DNA have been performed as a function of the ionic strength. In 0.3 M sodium the on-rate constant (k1 = 2.6 X 10(7) M-1 s-1) is similar to that reported for other monoacridines or bis(acridines), whereas the off-rate constant is much smaller (k-1 = 1.2 X 10(-4) s-1), leading to an equilibrium binding constant as large as Kapp = 2.2 X 10(11) M-1. A plot of log (k1/k-1) as a function of log [Na+] yielded a straight line whose slope shows that 5.7 ion pairs (out of 7 potential) are formed upon the interaction with DNA. From this linear relationship a Kapp value of 10(14) M-1 in 0.1 M sodium can be estimated. Such a value reaches and even goes beyond that of some DNA regulatory proteins. This acridine trimer appears to be the first synthetic ligand with such a high DNA affinity.
Pyrrolinone, II. Azaisoindole, IV. Diaminopyrrolinone (1976)

Abstract Aus den Fyrrolidindionen 1,2 und 7 werden die Dioxime 5,6 und 11 gewonnen, deren Hydrierung die Lösungen der Diaminopyrrolinone 22, 23 und 24 ergeben. Diese bilden mit a‐Di‐carbonylverbindungen die Pyrazincarbonsäurelactame 25‐28 und mit Acetessigester über 34 und 35 die Diazepinone 38 und 39. Außerdem werden die aus 25‐27 gebildeten Diaza‐isoindole 29‐33 beschrieben.
Reactions of nitro sugars. V. Some reactions with methyl 3-deoxy-3-nitro-α-d-hexopyranosides (1967)

The acetylations and catalytic hydrogenations of derivatives of methyl 3-deoxy-3-nitro-α-d-hexopyranosides were compared with the analogous reactions previously performed in the β-anomeric series. The acetylation of methyl 4,6-O-benzylidene-3-deoxy-3-nitro-α-d-glucopyranoside (II) gave its 2-O-acetyl derivative III, which, upon base-catalyzed elimination of acetic acid, yielded the nitroolefin, methyl 4,6-O-benzylidene-2,3-dideoxy-3-nitro-α-d-erythro-hexopyranos-2-enide (IV), whereas acetylation of the corresponding α-d-talopyranoside XI proceeded with dehydration, giving directly the α-d-threo nitroolefin XIII. These courses of reaction had their counterparts in the β-series and are believed to depend on the configurations at C-4. On the other hand, palladium-catalyzed hydrogenations of the nitroolefins IV and XIII gave results that were similar to each other but different from those obtained in the β-series. Besides the expected saturated nitro glycosides with α-d-arabino (V) and α-d-lyxo (XV) configurations, two oximes (VI and XIV) were produced in yields of 49 and 30%, respectively. This may be attributed to a measure of steric interference by the glycosidic methoxyl group during the hydrogenation of the olefinic double bonds in IV and XIII. Amino glycosides were obtained from V and XV by debenzylidenation and platinum-catalyzed hydrogenation.
Analysing the effect of novel therapies on cytokine expression in experimental arthritis (2005)

Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro-inflammatory cytokines, such as tumour necrosis factor alpha and interleukin-1beta, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small-molecular-weight inhibitors of pro-inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention.
Infection of the SCID-hu Mouse by HIV-1 (1988)

SCID-hu mice with human fetal thymic or lymph node implants were inoculated with the cloned human immunodeficiency virus-1 isolate, HIV-1JR-CSF. In a time- and dose-dependent fashion, viral replication spread within the human lymphoid organs. Combination immunohistochemistry and in situ hybridization revealed only viral RNA transcripts in most infected cells, but some cells had both detectable viral transcripts and viral protein. Infected cells were always more apparent in the medulla than in the cortex of the thymus. These studies demonstrate that an acute infection of human lymphoid organs with HIV-1 can be followed in the SCID-hu mouse.
Clinical Pharmacokinetics and Pharmacodynamics of Afatinib (2016)

Afatinib is an oral, irreversible ErbB family blocker that covalently binds to the kinase domains of epidermal growth factor receptor (EGFR), human EGFRs (HER) 2, and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation. Studies in healthy volunteers and patients with advanced solid tumours have shown that once-daily afatinib has time-independent pharmacokinetic characteristics. Maximum plasma concentrations of afatinib are reached approximately 2-5 h after oral administration and thereafter decline, at least bi-exponentially. Food reduces total exposure to afatinib. Over the clinical dose range of 20-50 mg, afatinib exposure increases slightly more than dose proportional. Afatinib metabolism is minimal, with unchanged drug predominantly excreted in the faeces and approximately 5 % in urine. Apart from the parent drug afatinib, the major circulation species in human plasma are the covalently bound adducts to plasma protein. The effective elimination half-life is approximately 37 h, consistent with an accumulation of drug exposure by 2.5- to 3.4-fold based on area under the plasma concentration-time curve (AUC) after multiple dosing. The pharmacokinetic profile of afatinib is consistent across a range of patient populations. Age, ethnicity, smoking status and hepatic function had no influence on afatinib pharmacokinetics, while females and patients with low body weight had increased exposure to afatinib. Renal function is correlated with afatinib exposure, but, as for sex and body weight, the effect size for patients with severe renal impairment (approximately 50 % increase in AUC) is only mildly relative to the extent of unexplained interpatient variability in afatinib exposure. Afatinib has a low potential as a victim or perpetrator of drug-drug interactions, especially with cytochrome P450-modulating agents. However, concomitant treatment with potent inhibitors or inducers of the P-glycoprotein transporter can affect the pharmacokinetics of afatinib. At a dose of 50 mg, afatinib does not have proarrhythmic potential.
A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor. (1990)

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.