gebhart/patrepeval huggingface dataset:
Enzyme Redesign (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme RedesignTrevor M. Penning and Joseph M. JezView Author Information Department of Pharmacology, University of Pennsylvania School of Medicine, 135 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084 Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037 Cite this: Chem. Rev. 2001, 101, 10, 3027–3046Publication Date (Web):September 1, 2001Publication History Received16 March 2001Published online1 September 2001Published inissue 1 October 2001https://pubs.acs.org/doi/10.1021/cr000049nhttps://doi.org/10.1021/cr000049nresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2123Altmetric-Citations124LEARN 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:Chemical specificity,Genetics,Monomers,Peptides and proteins,Protein engineering Get e-Alerts
Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma (2020)

The maximum tolerated dose of nal-IRI was 50 mg/m2 every 2 weeks with TMZ 50 mg/m2/d. The dose-limiting toxicities were diarrhea and neutropenia. No activity was seen at interim analysis and the study was terminated.
Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging (1992)

We present a polarization-sensitive optical coherence-domain reflectometer capable of characterizing the phase retardation between orthogonal linear polarization modes at each reflection point in a birefringent sample. The device is insensitive to the rotation of the sample in the plane perpendicular to ranging. Phase measurement accuracy is ±0.86°, but the reflectometer can distinguish local variations in birefringence as small as 0.05° with a distance resolution of 10.8 μm and a dynamic range of 90 dB. Birefringence-sensitive ranging in a wave plate, an electro-optic modulator, and a calf coronary artery is demonstrated.
Effects of ultraviolet radiation on human epidermal cell alloantigen presentation: initial depression of Langerhans cell-dependent function is followed by the appearance of T6- Dr+ cells that enhance epidermal alloantigen presentation. (1985)

The effects of ultraviolet radiation (UV) on the immune parameters of human epidermis were studied. We determined the effects of both in vitro and in vivo UV on human epidermal cell surface markers and on epidermal immune function in the allogeneic epidermal cell-lymphocyte reaction (ELR). Epidermal cells obtained immediately after in vitro and in vivo UV exposure exhibited a dose-dependent decrease in alloantigen-presenting function in the ELR. This was not the result of a decrease in the number of T6+ Dr+ Langerhans cells but was due to their being less efficient at alloantigen presentation than equivalent numbers of Langerhans cells from unirradiated skin. The reduced stimulation in the ELR immediately after UV was not reversible by the addition of exogenous IL 1 or indomethacin and thus appeared to be due to a direct effect of UV on the alloantigen-presenting function of Langerhans cells. In contrast to this suppression of the epidermal immune function when epidermal cells were obtained immediately after UV, epidermal cells harvested 24 hr or later after in vivo UV exhibited a dose-dependent enhancement of allostimulatory capacity in the ELR that peaked 3 days after UV. The time course of the enhancement of allostimulation in the ELR after in vivo UV coincided with a decrease in the percentage of Langerhans cells and the appearance within the epidermis of T6- Dr+ cells, which are derived from the bone marrow, as evidenced by their expression of the bone marrow derivation markers HLe 1 and T200. Removal of Dr+ cells but not of T6+ cells from epidermal cell suspensions harvested 3 days after in vivo UV abrogated allostimulation in the ELR, demonstrating that the T6- Dr+ cells were responsible for the observed UV-induced enhancement of alloantigen presentation. Taken together, the results indicate that the timing and dosage of UV exposure are critical factors determining whether suppression or enhancement of epidermal immune function follows UV.
Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. (1986)

The first report from the Framingham Study that demonstrated an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and the incidence of coronary heart disease (CHD) was based on four years of surveillance. These participants, aged 49 to 82 years, have now been followed up for 12 years, and this report shows that the relationship between the fasting HDL-C level and subsequent incidence of CHD does not diminish appreciably with time. Since a second measurement of HDL-C is available eight years after the initial determination, the relationship of HDL-C measurements on the same subjects at two points in time is examined. This second HDL-C measurement is also used in a multivariate model that includes cigarette smoking, relative weight, alcohol consumption, casual blood glucose, total cholesterol, and blood pressure. It is concluded that even after these adjustments, nonfasting HDL-C and total cholesterol levels are related to development of CHD in both men and women aged 49 years and older. Study participants at the 80th percentile of HDL-C were found to have half the risk of CHD developing when compared with subjects at the 20th percentile of HDL-C.
Columnar liquid crystals in oligosaccharide derivatives. II. Two types of discotic columnar liquid-crystalline phase of cellobiose alkanoates (1992)

Abstract A series of cellobiose octaalkanoates, Cel-II-n (n is the carbon number of the alkyl chain), with n = 7–14 were prepared and their mesogenic properties examined by differential scanning calorimetry, optical polarizing microscopy and X-ray diffraction. All of these compounds form enantiotropic discotic columnar phases, in which the columns are built up by a regular stacking of the cellobiose moieties and are packed in a two dimensional lattice. Homologues with n = 9–14 form the Dho phase only whilst the compound with n = 7 forms the Dro phase. The n = 8 compound forms the Dho phase at higher temperatures and the Dro phase at lower temperatures. Structural parameters obtained from X-ray diffraction studies are presented for both phases.
Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding (2018)

To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.
Synthesis of Sequence-Ordered Copolymers. 4. Glass Transition and Melting Temperatures of Sequence-Ordered and Unordered Ethylene-Vinyl Alcohol and Ethylene-Vinyl Acetate Copolymers (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Sequence-Ordered Copolymers. 4. Glass Transition and Melting Temperatures of Sequence-Ordered and Unordered Ethylene-Vinyl Alcohol and Ethylene-Vinyl Acetate CopolymersYasuhiko Mori, Hiroshi Sumi, Tadamichi Hirabayashi, Yoshihito Inai, and Kenji YokotaCite this: Macromolecules 1994, 27, 4, 1051–1056Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/ma00082a026https://doi.org/10.1021/ma00082a026research-articleACS PublicationsRequest reuse permissionsArticle Views395Altmetric-Citations42LEARN 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
Design of Artificial Transcriptional Activators with Rigid Poly-l-proline Linkers (2002)

Typical eukaryotic transcriptional activators are composed of distinct functional domains, including a DNA binding domain and an activating domain. Artificial transcription factors have been designed wherein the DNA binding domain is a minor groove DNA binding hairpin polyamide linked by a flexible tether to short activating peptides, typically 16-20 residues in size. In this study, the linker between the polyamide and the peptide was altered in an incremental fashion using rigid oligoproline "molecular rulers" in the 18-45 A length range. We find that there is an optimal linker length which separates the DNA and the activation region for transcription activation.
Nasal-Associated Lymphoid Tissue Is a Site of Long-Term Virus-Specific Antibody Production following Respiratory Virus Infection of Mice (2001)

Nasal immunoglobulin A provides an initial defense against inhaled respiratory pathogens. However, it is not known whether the nasal-associated lymphoid tissues (NALT) are able to mount an effective long-lasting pathogen-specific immune response, nor is it known whether functional differences exist between the organized NALT (O-NALT) and the diffuse NALT lining the nasal passages (D-NALT). Here we show that although both the O-NALT and the D-NALT are capable of producing virus-specific antibody in response to influenza virus infection, the frequency of specific antibody-forming cells in the D-NALT is much greater than the frequency observed in the O-NALT. Furthermore, we show that the D-NALT but not the O-NALT is the site of long-term virus-specific humoral immunity which lasts for the life of the animal. These results indicate that the D-NALT is not only the major effector site of the NALT but also the site of local long-term specific antibody production.
Immunohistochemical Reactivity of a Monoclonal Antibody Prepared against Human Ovarian Carcinoma on Normal and Pathological Female Genital Tissues (1989)

The reactivity profile of the monoclonal antibody (MAb) MOv18, raised against a poorly differentiated ovarian carcinoma specimen, was studied on normal tissues and tumors from the female reproductive system and on the kidney, which like the oviducts, vagina and uterus, also derives from the intermediate mesoderm. The obtained results indicate that MOv18 recognizes an epitope present on the normal epithelium of the oviducts, on 14-week old fetal kidney and, focally, on proximal and distal tubules of normal adult kidney. A strong reactivity was found on ovarian carcinomas, on invasive squamous carcinomas of the cervix and on endometrial carcinomas and hyperplasias. The antigen recognized by MOv18 (CaMOv18) therefore seems to be an epithelial cell marker associated with intermediate mesoderm differentiation, which can be derepressed during the neoplastic transformation of the ovary and the uterus.
Oberflächenschutzverfahren und ihr Einsatz in der Werkstoff‐ und Tribo‐Technik (1984)

Hardfacing‐Methods and their Application in the Materials‐Technology and Tribology During the last few years more and more efforts have been made to reduce or even avoid material losses, caused either by mechanical or corrosive attack, by the means of protecting metal surface protection. In fact, the expenses needed in the Plastic‐Technology for the disposition of wear‐spares in West Germany amount to half a billion DM a year [1]. If all the damages by wear and corrosion are included, the losses world‐wide rise to more than 80 billion DM/year. Thus not only technical but most of all economical reasons promote the rapid development of different hardfacing methods. The various methods are presented with ascending temperature of the working materials (s. Fig. 1).
Regulatory T Cells in Human Ovarian Cancer (2012)

Multiple layers of suppressive components including regulatory T (T(Reg)) cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, T(Reg) cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of T(Reg) cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of T(Reg) cells in preclinical and clinical settings.
Inferring user interest (2001)

As the World Wide Web continues to grow, people find it impossible to access even a small portion of the information generated in a day from Usenet news, e-mail, and Web postings. Automated filters help us to prioritize and access only the information in which we're interested. Because opinions differ about the importance or relevance of information, people need personalized filters. Implicit indicators captured while users browse the Web can be as predictive of interest levels as explicit ratings.
Mild autohydrolysis: an environmentally friendly technology for xylooligosaccharide production from wood (1999)

Eucalyptus globulus wood samples were subjected to hydrothermal treatments under mild operational conditions (145–190 ° C, liquor to solid ratio 6–10 g g−1, reaction times up to 7.5 h). Residual xylan, xylooligosaccharides, other sugars, furfural, glucan and lignin contents were determined. Negligible effects were caused by hydrothermal treatments on both cellulose and lignin. Kinetic models were developed which describe the hydrolysis of hemicelluloses. Xylan degradation, xylooligosaccharide and xylose generation, and xylose dehydration to furfural were accurately described by models based on pseudohomogeneous, first-order kinetics with Arrhenius-type temperature dependence. These models are useful for a technical evaluation of this environmentally friendly technology. © 1999 Society of Chemical Industry
Novel Inhibitor of p38 MAP Kinase as an Anti-TNF-α Drug:  Discovery of N-[4-[2-Ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a Potent and Orally Active Anti-Rheumatoid Arthritis Agent (2005)

The p38 mitogen-activated protein (MAP) kinase has been implicated in the proinflammatory cytokine signal pathway, and its inhibitors are potentially useful for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease. To develop a new drug for RA, we synthesized a novel series of 4-phenyl-5-pyridyl-1,3-thiazoles and evaluated their inhibition of p38 MAP kinase, lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro, and LPS-induced TNF-alpha production in vivo in mice. During the course of the study, we found that these compounds risk the inhibition of cytochrome P450 (CYP) isoforms by coordination of the 4-pyridyl nitrogen with heme iron. We therefore investigated the effects of substitution at the 2-position of the pyridyl ring on the inhibitory activity of p38 MAP kinase and CYPs in more detail. As a result, N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (8h, TAK-715) exhibited potent inhibitory activity in these assays (inhibition of p38alpha, IC50 = 7.1 nM; LPS-stimulated release of TNF-alpha from THP-1, IC50 = 48 nM; LPS-induced TNF-alpha production in mice, 87.6% inhibition at 10 mg/kg, po) and no inhibitory activity for major CYPs, including CYP3A4. This compound also showed good bioavailability in mice and rats and significant efficacy in a rat adjuvant-induced arthritis model. Compound 8h was selected as a clinical candidate and is now under clinical investigation for the treatment of RA.
The ubiquitin‐mediated proteolytic pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins (1994)

Ubiquitin modification of a variety of protein targets within the cell plays important roles in many cellular processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, import of proteins into mitochondria, uptake of precursors into neurons, and biogenesis of mitochondria, ribosomes, and peroxisomes. The best studied modification occurs in the ubiquitin-mediated proteolytic pathway. Degradation of a protein via the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP-dependent mode to the protein substrate. The targeted protein is then degraded by a specific and energy-dependent high molecular mass protease into free amino acids, and free and reutilizable ubiquitin is released. In addition, stable mono-ubiquitin adducts are also found in the cell, for example, those involving nucleosomal histones. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, little is known on the signals that target proteins for degradation. Although mechanistic aspects of recognition via the N-terminal residue have been studied thoroughly, it is clear that the vast majority of cellular proteins are targeted by other signals. The identity of the native cellular substrates of the system is another important, yet unresolved, problem: only few proteins have been recognized so far as substrates of the system in vivo. The scope of this review is to discuss the mechanisms involved in ubiquitin activation, selection of substrates for conjugation, and degradation of ubiquitin-conjugated proteins in the cell-free system. In addition, we shall summarize what is currently known of the physiological roles of ubiquitin-mediated proteolysis in vivo.
Ultrafast broadband Fourier-transform CARS spectroscopy at 50,000 spectra/s enabled by a scanning Fourier-domain delay line (2016)

We propose and demonstrate a coherent Raman scattering (CRS) spectroscopy technique capable of acquiring 50,000 broadband Raman spectra/s. This ultrafast spectral acquisition is realized by employing a Fourier-domain delay line based on a rapidly rotating polygonal mirror array as an optical path-length scanner in a broadband Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy platform. We provide a theoretical description of the proposed FT-CARS spectroscopy technique while also presenting its proof-of-concept demonstration on a liquid toluene sample. Our use of a 54-facet polygonal mirror array rotating at 916 rotations/s achieves a record high scan rate of 50,000 CARS spectra/s, covering most of the molecular fingerprint region (200–1430 cm −1 ) with a high resolution of 4.2 cm −1 . This ultrafast broadband CRS technique is expected to be of great use in applications where high-throughput screening or real-time monitoring of unknown samples with high specificity is required, such as single-cell analysis and biomedical imaging.
Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa. (1995)

The opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors, including exotoxin A, elastase, alkaline protease, alginate, phospholipases, and extracellular rhamnolipids. The previously characterized rhlABR gene cluster encodes a regulatory protein (RhlR) and a rhamnosyltransferase (RhlAB), both of which are required for rhamnolipid synthesis. Another gene, rhII, has now been identified downstream of the rhlABR gene cluster. The putative RhlI protein shares significant sequence similarity with bacterial autoinducer synthetases of the LuxI type. A P. aeruginosa rhlI mutant strain carrying a disrupted rhlI gene was unable to produce rhamnolipids and lacked rhamnosyltransferase activity. Rhamnolipid synthesis was restored by introducing a wild-type rhlI gene into such strains or, alternatively, by adding either the cell-free spent supernatant from a P. aeruginosa wild-type strain or synthetic N-acylhomoserine lactones. Half-maximal induction of rhamnolipid synthesis in the rhlI mutant strain required 0.5 microM N-butyrylhomoserine lactone or 10 microM N-(3-oxohexanoyl)homoserine lactone. The P. aeruginosa rhlA promoter was active in the heterologous host Pseudomonas putida when both the rhlR and rhlI genes were present or when the rhlR gene alone was supplied together with synthetic N-acylhomoserine lactones. The RhlR-RhlI regulatory system was found to be essential for the production of elastase as well, and cross-communication between the RhlR-RhlI rhamnolipid regulatory system and the LasR-LasI elastase regulatory system was demonstrated.
Activation of Phosphatidylinositol-Specific Phospholipase C in Response to HDL 3 and LDL Is Markedly Reduced in Cultured Fibroblasts From Tangier Patients (1995)

We compared HDL3- and LDL-induced signal transduction in normal and Tangier fibroblasts to elucidate whether impaired signal transduction responses to lipoproteins might contribute to disturbed cellular lipid and lipoprotein metabolism in Tangier disease, a rare autosomal disorder of cellular lipid and lipoprotein metabolism. In several cell types HDL and LDL activate a currently unknown isoform of phosphatidylinositol-specific phospholipase C (PI-PLC) that results in the generation of 1,2-diacylglycerol and inositol 1,4,5-trisphosphate. Compared with normal fibroblasts, Tangier fibroblasts stimulated with HDL3 or LDL resulted in a significantly reduced accumulation of inositol phosphates and 1,2-diacylglycerol formation. Furthermore, in Tangier fibroblasts both lipoproteins failed to mobilize calcium from internal pools, and the cytosol-to-membrane redistribution of protein kinase C (in both the alpha and epsilon isoforms) was markedly reduced. Thus, the data indicate an impaired PI-PLC activation in response to lipoproteins in Tangier fibroblasts.