gebhart/patrepeval huggingface dataset:
New Class of Polymers for the Delivery of Macromolecular Therapeutics (1999)

Cationic polymers show promise for the in vitro and in vivo delivery of macromolecular therapeutics. Known cationic polymers, e.g., poly(L)lysine (PLL) and polyethylenimine (PEI), have been employed in native and modified forms for the delivery of plasmid DNA (pDNA) and reveal varying levels of toxicity. Here, we report the preparation of a new class of cationic polymers that are specifically designed to deliver macromolecular therapeutics. Linear, cationic, beta-cyclodextrin (beta-CD)-containing polymers (CD-polymers) are synthesized by copolymerizing difunctionalized beta-CD monomers (AA) with other difunctionalized comonomers (BB) such that an AABBAABB product is formed. The beta-CD polymers are able to bind approximately 5 kbp pDNA above polymer to DNA (+/-) charge ratios of 1.5, compact the bound pDNA into particles of approximately 100-150 nm in size at charge ratios above 5+/-, and transfect cultured cells at charge ratios above 10+/-. In vitro transfections with the new beta-CD-polymers are comparable to the best results obtained in our hands with PEI and Lipofectamine. Some cell line-dependent toxicities are observed for serum-free transfections; however, no toxicity is revealed at charge ratios as high as 70+/- in transfections conducted in 10% serum. Single IV and IP doses as high as 200 mg/kg in mice showed no mortalities.
Muteins of human interleukin‐1 that show enhanced bioactivities (1987)

Using recombinant DNA techniques, we have made a series of amino-terminal muteins of human interleukin-1 (IL-1). Two of the muteins demonstrated 4-7-fold increase in bioactivity as compared to that of the native IL-1. The enhanced biological potency coincides with an increase in both receptor binding affinity and in vivo tumor inhibitory activity. By site specific mutagenesis, we have shown that the arginine at the fourth position of IL-1 is one of the key residues in the function of IL-1. Circular dichroism studies of the amino-terminus analogs showed little structural rearrangement. The change in bioactivity might be due to a change in the stability of the muteins, in the side chain interactions with receptors or in the minor change in folding near the receptor binding site.
Spectral gaps in SU ( d ) (2010)

It is shown that if <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi>g</mml:mi> <mml:mn>1</mml:mn> </mml:msub> <mml:mo>,</mml:mo> <mml:mo>…</mml:mo> <mml:mo>,</mml:mo> <mml:msub> <mml:mi>g</mml:mi> <mml:mi>k</mml:mi> </mml:msub> </mml:math> are algebraic elements in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi mathvariant="italic">SU</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>d</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:math> generating a dense subgroup, then the corresponding Hecke operator has a spectral gap.
Recognition of 5‘-(A,T)GG(A,T)2-3‘ Sequences in the Minor Groove of DNA by Hairpin Polyamides (1996)

A series of four hairpin pyrrole−imidazole polyamides, ImImPy-γ-PyPyPy-β-Dp, PyPyPy-γ-ImImPy-β-Dp, AcImImPy-γ-PyPyPy-β-Dp, and AcPyPyPy-γ-ImImPy-β-Dp (Im = N-methylimidazole-2-carboxamide, Py = N-methylpyrrole-2-carboxamide, Dp = N,N-dimethylaminopropylamide, γ = γ-aminobutyric acid, β = β-alanine, and Ac = acetyl), designed for recognition of 5‘-(A,T)GG(A,T)2-3‘ sequences in the minor groove of DNA were synthesized using solid phase methodology and analyzed with respect to DNA binding affinity and sequence specificity. Quantitative DNase I footprint titration experiments reveal that the optimal polyamide ImImPy-γ-PyPyPy-β-Dp binds a designated 5‘-TGGTT-3‘ match site with an equilibrium association constant of Ka = 1.0 × 108 M-1 and the single base pair mismatch sites, 5‘-TGTTA-3‘ and 5‘-GGGTA-3‘, with 50-fold and 100-fold-lower affinity, respectively (10 mM Tris·HCl, 10 mM KCl, 10 mM MgCl2, and 5 mM CaCl2, pH 7.0 and 22 °C). Polyamides of sequence composition AcImImPy-γ-PyPyPy-β-Dp and AcPyPyPy-γ-ImImPy-β-Dp, which differ only by the position of the γ-linker, bind with similar affinities and specificities. Recognition of sequences containing contiguous G·C base pairs expands the sequence repertoire available for targeting DNA with pyrrole−imidazole polyamides.
RecA-dependent programmable endonuclease Ref cleaves DNA in two distinct steps (2013)

The bacteriophage P1 recombination enhancement function (Ref) protein is a RecA-dependent programmable endonuclease. Ref targets displacement loops formed when an oligonucleotide is bound by a RecA filament and invades homologous double-stranded DNA sequences. Mechanistic details of this reaction have been explored, revealing that (i) Ref is nickase, cleaving the two target strands of a displacement loop sequentially, (ii) the two strands are cleaved in a prescribed order, with the paired strand cut first and (iii) the two cleavage events have different requirements. Cutting the paired strand is rapid, does not require RecA-mediated ATP hydrolysis and is promoted even by Ref active site variant H153A. The displaced strand is cleaved much more slowly, requires RecA-mediated ATP hydrolysis and does not occur with Ref H153A. The two cleavage events are also affected differently by solution conditions. We postulate that the second cleavage (displaced strand) is limited by some activity of RecA protein.
Implicit Feedback for Recommender Systems (1998)

Can implicit feedback substitute for explicit ratings in re-commender systems? If so, we could avoid the difficulties associated with gathering explicit ratings from users. How, then, can we capture useful information unobtrusively, and how might we use that information to make recommenda-tions? In this paper we identify three types of implicit feedback and suggest two strategies for using implicit feed-back to make recommendations.
Rate and pattern of migration of lineally-related olfactory bulb interneurons generated postnatally in the subventricular zone of the rat (1994)

A spatially discrete region of the anterior part of the postnatal telencephalic subventricular zone, referred to as the SVZa generates vast numbers of lineally-related neurons destined for the olfactory bulb (Luskin, 1993). The cells originating in the SVZa migrate to the olfactory bulb along a highly restricted pathway which is in a direction orthogonal to the orientation of radial glial fibers. In this study we analysed the number, distribution, orientation and rate of migration of SVZa-derived cells as they approach the olfactory bulb. In order to track the SVZa-derived cells, a retroviral lineage tracer, encoding the reporter gene E. coli beta-galactosidase (lacZ) was injected precisely into the rat SVZa at postnatal day 1 (P1). The lacZ-positive cells were visualized 1, 2 and 3 days later by X-Gal histochemistry in cryostat sections. As the number of SVZa-derived cells in the pathway increased with survival time, their distribution changed systematically. The distribution pattern of lacZ-positive cells by 2 and 3 days postinjection suggested that some of the progeny of infected progenitor cells were undergoing neurogenesis as they proceeded to the olfactory bulb; a large percentage of the lacZ-positive cells were substantially displaced from the SVZa injection site. To investigate whether lacZ-positive cells migrate in a directed fashion, their orientation preference was scored. For the majority of lacZ-positive cells (> 94%), their leading process was directed toward the olfactory bulb, possibly reflecting a response to migratory cues present along the pathway. The estimated average rate of cell migration to the olfactory bulb was 23 mu m/h, which is approximately twice the speed of radially directed neuronal migration from the telencephalic ventricular zone to the cortical plate (O'Rourke et al., 1992). Collectively, these results suggest that SVZa-derived interneurons en route to the olfactory bulb may employ a novel mode of tangential migration.
Serum Amyloid A as a Predictor of Coronary Artery Disease and Cardiovascular Outcome in Women (2004)

Our results show a strong independent relationship between SAA and future cardiovascular events, similar to that found for hs-CRP. Although SAA was independently but moderately associated with angiographic CAD, this association was not found for hs-CRP. These results are consistent with the hypothesis that systemic inflammation, manifested by high SAA or hs-CRP levels, may promote atherosclerotic plaque destabilization, in addition to exerting a possible direct effect on atherogenesis.
Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing (2018)

Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism's own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation. Crystal structures of antibodies from these lineages bound to their target antigens have revealed, at the atomic level, how antibodies evolve to penetrate the glycan shield of envelope glycoproteins, and how viruses in turn evolve to escape neutralization. Collectively, structural studies of affinity maturation have shown that increased antibody affinity can arise from any one or any combination of multiple diverse mechanisms, including improved shape complementarity at the interface with antigen, increased buried surface area upon complex formation, additional interfacial polar or hydrophobic interactions, and preorganization or rigidification of the antigen-binding site.
Bispyrenyl Excimer Fluorescence:  A Sensitive Oligonucleotide Probe (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTBispyrenyl Excimer Fluorescence: A Sensitive Oligonucleotide ProbeFrederick D. Lewis, Yifan Zhang, and Robert L. LetsingerView Author Information Department of Chemistry, Northwestern University 2145 Sheridan Road, Evanston, Illinois 60208 Cite this: J. Am. Chem. Soc. 1997, 119, 23, 5451–5452Publication Date (Web):June 11, 1997Publication History Received2 December 1996Published online11 June 1997Published inissue 1 June 1997https://pubs.acs.org/doi/10.1021/ja9641214https://doi.org/10.1021/ja9641214rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1158Altmetric-Citations134LEARN 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 SUBJECTS:Aromatic compounds,Biopolymers,Fluorescence,Hydrocarbons,Oligomers Get e-Alerts
Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields (1994)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTAb Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force FieldsP. J. Stephens, F. J. Devlin, C. F. Chabalowski, and M. J. FrischCite this: J. Phys. Chem. 1994, 98, 45, 11623–11627Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November 1994https://pubs.acs.org/doi/10.1021/j100096a001https://doi.org/10.1021/j100096a001research-articleACS PublicationsRequest reuse permissionsArticle Views22554Altmetric-Citations18558LEARN 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 options Get e-Alerts
Comparative Study of Three Proteomic Quantitative Methods, DIGE, cICAT, and iTRAQ, Using 2D Gel- or LC−MALDI TOF/TOF (2006)

A comparative study on the three quantitative methods frequently used in proteomics, 2D DIGE (difference gel electrophoresis), cICAT (cleavable isotope-coded affinity tags) and iTRAQ (isobaric tags for relative and absolute quantification), was carried out. DIGE and cICAT are familiar techniques used in gel- and LC-based quantitative proteomics, respectively. iTRAQ is a new LC-based technique which is gradually gaining in popularity. A systematic comparison among these quantitative methods has not been reported. In this study, we conducted well-designed comparisons using a six-protein mixture, a reconstituted protein mixture (BSA spiked into human plasma devoid of six abundant proteins), and complex HCT-116 cell lysates as the samples. All three techniques yielded quantitative results with reasonable accuracy when the six-protein or the reconstituted protein mixture was used. In DIGE, accurate quantification was sometimes compromised due to comigration or partial comigration of proteins. The iTRAQ method is more susceptible to errors in precursor ion isolation, which could be manifested with increasing sample complexity. The quantification sensitivity of each method was estimated by the number of peptides detected for each protein. In this regard, the global-tagging iTRAQ technique was more sensitive than the cysteine-specific cICAT method, which in turn was as sensitive as, if not more sensitive than, the DIGE technique. Protein profiling on HCT-116 and HCT-116 p53 -/- cell lysates displayed limited overlapping among proteins identified by the three methods, suggesting the complementary nature of these methods.
Valproate Reduces the Glucuronidation of Asenapine Without Affecting Asenapine Plasma Concentrations (2011)

Asenapine is indicated for treatment of schizophrenia in the United States and acute treatment of manic or mixed episodes, as monotherapy (United States and European Union) or adjunct therapy (United States only), associated with bipolar I disorder. It is extensively metabolized; the 2 main metabolites are asenapine N-glucuronide and N-desmethyl-asenapine. The authors investigated the pharmacokinetic interactions between asenapine and valproate in an open-label, randomized, 2-way crossover study. Twenty-four healthy male volunteers received sublingual doses of asenapine 5 mg alone or under steady-state valproate (500 mg bid for 9 days). Blood samples collected until 72 hours postdosing were analyzed for asenapine, N-desmethyl-asenapine, and asenapine N-glucuronide. Compared with asenapine alone, valproate substantially reduced N-glucuronide formation (area under the curve from 0 to infinity [AUC(0-∞)] reduced 7.4-fold, maximum concentration [C(max)] reduced 6.6-fold) and moderately reduced N-desmethyl-asenapine formation (AUC(0-∞) reduced 30%, C(max) unchanged). Coadministration of valproate did not affect asenapine AUC(0-∞) and C(max) (confidence intervals for the ratios of asenapine AUC(0-∞) and C(max) were contained within the predefined 0.80-1.25 acceptance range). Low-dose valproate, although almost completely inhibiting glucuronidation of asenapine, did not affect the pharmacokinetics of asenapine itself, the entity primarily responsible for the pharmacologic effects of the drug.
Implementation and Performance of Portals 3.3 on the Cray XT3 (2005)

The Portals data movement interface was developed at Sandia National Laboratories in collaboration with the University of New Mexico over the last ten years. Portals is intended to provide the functionality necessary to scale a distributed memory parallel computing system to thousands of nodes. Previous versions of Portals ran on several large-scale machines, including a 1024-node nCUBE-2, a 1800-node Intel Paragon, and the 4500-node Intel ASCI Red machine. The latest version of Portals was initially developed for an 1800-node Linux/Myrinet cluster and has since been adopted by Cray as the lowest-level network programming interface for their XT3 platform. In this paper, we describe the implementation of Portals 3.3 on the Cray XT3 and present some initial performance results from several micro-benchmark tests. Despite some limitations, the implementation of Portals is able to achieve a zero-length one-way latency of under six microseconds and a uni-directional bandwidth of more than 1.1 GB/s
Potent Stimulation of the Innate Immune System by aLeishmania brasiliensisRecombinant Protein (2001)

The interaction of the innate immune system with the microbial world involves primarily two sets of molecules generally known as microbial pattern recognition receptors and microbial pattern recognition molecules, respectively. Examples of the former are the Toll receptors present particularly in macrophages and dendritic cells. Conversely, the microbial pattern recognition molecules are conserved protist homopolymers, such as bacterial lipopolysaccharides, lipoteichoic acids, peptidoglycans, glucans, mannans, unmethylated bacterial DNA, and double-strand viral RNA. However, for protists that lack most of these molecules, such as protozoans, the innate immune system must have evolved receptors that recognize other groups of microbial molecules. Here we present evidence that a highly purified protein encoded by a Leishmania brasiliensis gene may be one such molecule. This recombinant leishmanial molecule, a homologue of eukaryotic ribosomal elongation and initiation factor 4a (LeIF), strongly stimulates spleen cells from severe combined immunodeficient (SCID) mice to produce interleukin-12 (IL-12), IL-18, and high levels of gamma interferon. In addition, LeIF potentiates the cytotoxic activity of the NK cells of these animals. Because LeIF is a conserved molecule and because SCID mice lack T and B lymphocytes but have a normal innate immune system (normal reticuloendothelial system and NK cells), these results suggest that proteins may also be included as microbial pattern recognition molecules. The nature of the receptor involved in this innate recognition is unknown. However, it is possible to exclude the Toll receptor Tlr4 as a putative LeIF receptor because the gene encoding this receptor is defective in C3H/HeJ mice, the mouse strain used in the present studies.
Monitoring Response to Anticancer Therapy by Targeting Microbubbles to Tumor Vasculature (2007)

We conclude that targeted microbubbles represent a novel and attractive tool for noninvasive, vascular-targeted molecular imaging of tumor angiogenesis and for monitoring vascular effects specific to antitumor therapy in vivo.
Resilient Subclass Discriminant Analysis (2009)

We propose a dimension reduction technique named Resilient Subclass Discriminant Analysis (RSDA) for high dimensional classification problems. The technique iteratively estimates the subclass division by embedding the Fisher Discriminant Analysis (FDA) with Expectation-Maximization (EM) in Gaussian Mixture Models (GMM). The new method maintains the adaptability of SDA to a wide range of data distributions by approximating the distribution of each class as a mixture of Gaussians, and provides superior feature selection performance to SDA with modified EM clustering that estimates a posteriori probability of latent variables in lower-dimensional Fisher's discriminant space, which also improves the robustness in problems of small training datasets compared with conventional EM algorithm. Extensive experiments and comparison results against other well-known Discriminant Analysis (DA) methods are presented using synthetic data, benchmark datasets as well as a real computational vision problem.
An Efficient Method for The Preparation of w, w′-bis-Urethane Protected Arginine Derivatives (1993)

Abstract Fmoc-Argw, w′(Boc)2-OH and Boc-Argw, w′(Cbz)2-OH were prepared in two steps: Guanylation of Cu(II)-ornithine complex at Nδ with N, N′bis-urethane protected derivatives of 1-guanylpyrazole, followed by Nα-protection using either 9-fluorenylmethyl succinimidylcarbonate or di-t-butyl-dicarbonate in the presence of EDTA. The overall yields of these products (2 steps) were 65% and 73%.
Metronidazole therapy for Crohn's disease and associated fistulae. (1984)

Because of reports suggesting the efficacy of metronidazole therapy in the healing of perianal fistulae in Crohn's disease, the effect of metronidazole on symptoms of Crohn's disease and associated perianal fistulae were evaluated in eight consecutive patients. The criterion for entry into the study was the presence of resistant fistulae in patients with Crohn's disease. The duration of intestinal Crohn's ranged from 1/2-30 years and fistulae from 1-14 years. All patients had ileocolitis or pancolitis. Two had enteroenteric fistulae in addition to perianal fistulae. All had had previous surgery, half for fistulae and half for intestinal complications, usually obstruction. All had been on Prednisone. All but one had received multiple other drugs including Azathioprine, Azulfidine, antibiotics, and rectal steroids. Patients were placed on metronidazole 1000 to 1500 mg/day orally in divided doses. The number of draining fistulae was reduced 20-fold and the number of detectable fistulous openings by 50%. All patients had relief of fistula-associated pain; general Crohn's disease symptoms improved as well. Complete resolution of all symptoms occurred in half the patients. All patients experienced side effects, six had numbness of toes and five had metallic taste. Resolution of side effects occurred on discontinuation of metronidazole after 1-3 wk off the drug in all except one patient. All patients noted continued improvement in Crohn's symptoms during 6 months of follow-up after cessation of their therapy. Other side effects that have been reported with metronidazole therapy were not seen in our patients.