gebhart/patrepeval huggingface dataset:
Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures (1992)

The anatomic forms of diarthrodial joints are important structural features which provide and limit the motions required for the joint. Typically, the length scale of topographic variation of anatomic forms ranges from 0.5 to 15 cm. Articular cartilage is the thin layer of hydrated soft tissue (0.5-5.0 mm thick) covering the articulating bony ends in diarthrodial joints. This tissue has a set of unique mechanical and physicochemical properties which are responsible for its load-carrying capabilities and near-frictionless qualities. The mechanical properties of articular cartilage are determined at the tissue-scale level and these properties depend on the composition of the tissue, mainly collagen and proteoglycan, and their molecular and ultrastructural organization (ultra-scale: 10(-8)-10(-6) m). Because proteoglycans possess a high density of fixed negative charges, articular cartilage exhibits a significant Donnan osmotic pressure effect. This physicochemically derived osmotic pressure is an important component of the total swelling pressure; the other component of the total swelling pressure stems from the charge-to-charge repulsive force exerted by the closely spaced (1-1.5 nm) negative charge groups along the proteoglycan molecules. Thus these interactions take place at a nano-scale level: 10(-10)-10(-9) m. Finally, cartilage biochemistry and organization are maintained by the chondrocytes which exist at a micro-scale level (10(-7)-10(-6) m). Significant mechanoelectrochemical transduction occurs within the extracellular matrix at the micro-scale level which affects and modulates cellular anabolic and catabolic activities. At present, the exact details of these transduction mechanisms are unknown. In this review, we present a summary of the hierarchical features for articular cartilage and diarthrodial joints and tables of known material properties for cartilage. Also we summarize how the multi-scale interactions in articular cartilage provide for its unique material properties and tribological characteristics.
Lipoproteins as potential site-specific delivery systems for diagnostic and therapeutic agents (1982)

Despite the paucity of literature dealing with the effect of plasma lipoproteins upon drug disposition, evidence is accumulating that shows that these macromolecular complexes can play important roles in the absorption and transport of lipid-soluble agents. Moreover, preliminary studies have demonstrated that radiotracers can be directed to specific tissues by prior incorporation into the hydrophobic core of specific lipoproteins. Although these studies offer encouragement for the possible use of lipoproteins in the site-specific delivery of radiopharmaceuticals that are used in tracer doses, the use of lipoproteins in the transport of drugs at pharmacological concentrations represents a much greater challenge. Nothing is known at this time about the saturation kinetics of drug incorporation into lipoproteins or partially delipidated lipoproteins. Nor is there any assurance that drug-laden lipoproteins will participate in receptor-mediated uptake processes similar to native lipoproteins. Moreover, receptor-mediated uptake of lipoproteins is a saturable process and may not permit attainment of sufficient drug concentrations within cells. It could be argued, however, that receptor-mediated uptake could be enhanced by prior treatment with hypocholesterolemic drugs as has been shown for cholestyramine. In any event, the possible use of lipoproteins for the site-specific delivery of intravenously administered radiodiagnostics or highly potent drugs (e.g., anticancer agents) appears promising. Only the results of ongoing studies will determine the practicality of this approach.
LRRK2 activation in idiopathic Parkinson’s disease (2018)

Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial Parkinson's disease (PD). However, a potential role of wild-type LRRK2 in idiopathic PD (iPD) remains unclear. Here, we developed proximity ligation assays to assess Ser1292 phosphorylation of LRRK2 and, separately, the dissociation of 14-3-3 proteins from LRRK2. Using these proximity ligation assays, we show that wild-type LRRK2 kinase activity was selectively enhanced in substantia nigra dopamine neurons in postmortem brain tissue from patients with iPD and in two different rat models of the disease. We show that this occurred through an oxidative mechanism, resulting in phosphorylation of the LRRK2 substrate Rab10 and other downstream consequences including abnormalities in mitochondrial protein import and lysosomal function. Our study suggests that, independent of mutations, wild-type LRRK2 plays a role in iPD. LRRK2 kinase inhibitors may therefore be useful for treating patients with iPD who do not carry LRRK2 mutations.
Electrogenerated chemiluminescence. 41. Electrogenerated chemiluminescence and chemiluminescence of the Ru(2,21 - bpy)32+-S2O82- system in acetonitrile-water solutions (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrogenerated chemiluminescence. 41. Electrogenerated chemiluminescence and chemiluminescence of the Ru(2,21 - bpy)32+-S2O82- system in acetonitrile-water solutionsHenry S. White and Allen J. BardCite this: J. Am. Chem. Soc. 1982, 104, 25, 6891–6895Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://doi.org/10.1021/ja00389a001RIGHTS & PERMISSIONSArticle Views1707Altmetric-Citations275LEARN 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 (571 KB) Get e-Alerts Get e-Alerts
Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. (1992)

Macrophages activated by exposure to cytokines and/or to endotoxin produce nitric oxide (NO.), a free radical that is a mediator of the host response to infection. Activation induces the expression of nitric oxide synthase, the enzyme that catalyzes formation of NO. from L-arginine and molecular oxygen. We report the cloning of a cDNA encoding the inducible nitric oxide synthase from a murine macrophage cell line, RAW264.7, exposed to interferon-gamma and lipopolysaccharide. Oocytes injected with mRNA transcribed from this cDNA demonstrate arginine-dependent production of nitrite, a stable metabolite of NO.. Nitric production is blocked by the enzyme inhibitor, NG-monomethylarginine, and is independent of calcium/calmodulin. RAW264.7 cells demonstrate rapid accumulation of the nitric oxide synthase-encoding mRNAs upon activation. Comparison of the deduced amino acid sequence to the calcium/calmodulin-dependent nitric oxide synthase previously purified (Bredt, D. S., and Synder, S.H. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 682-685) and cloned (Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C., Reed, R. R., and Synder, S. H. (1991) nature 351, 714-718) from rat brain identifies shared binding sites for the cofactors NADPH and flavins in the C-terminal half of both proteins and an additional conserved region near the N terminus that may recognize L-arginine and/or contribute to the active site.
CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation (2015)

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) nuclease system represents an efficient tool for genome editing and gene function analysis. It consists of two components: single-guide RNA (sgRNA) and the enzyme Cas9. Typical sgRNA and Cas9 intracellular delivery techniques are limited by their reliance on cell type and exogenous materials as well as their toxic effects on cells (for example, electroporation). We introduce and optimize a microfluidic membrane deformation method to deliver sgRNA and Cas9 into different cell types and achieve successful genome editing. This approach uses rapid cell mechanical deformation to generate transient membrane holes to enable delivery of biomaterials in the medium. We achieved high delivery efficiency of different macromolecules into different cell types, including hard-to-transfect lymphoma cells and embryonic stem cells, while maintaining high cell viability. With the advantages of broad applicability across different cell types, particularly hard-to-transfect cells, and flexibility of application, this method could potentially enable new avenues of biomedical research and gene targeting therapy such as mutation correction of disease genes through combination of the CRISPR-Cas9-mediated knockin system.
Comparison of Responses to Influenza A/New Jersey /76-A/Victoria/75 Virus Vaccine Administered Intradermally or Subcutaneously to Adults with Chronic Respiratory Disease (1979)

Serum HAI (hemagglutination inhibition) antibody responses were compared in two groups of 70 age-matched patients (age range, 17 to 82 years) who were vaccinated with bivalent influenza A/New Jersey/76-A/Victoria/75 whole-virus vaccine. The group that was vaccinated intradermally received 40 chick cell-agglutinating units of each viral antigen in 0.1 ml, and the group that was vaccinated subcutaneously received 200 chick cell-agglutinating units of each antigen in 0.5 ml. The serum HAI antibody response to A/New Jersey/76 antigen was significantly higher in the group that was vaccinated subcutaneously; this difference was particularly evident in patients less than or equal to 50 years old. The serologic response to A/Victoria/75 antigen did not differ significantly between the two groups. Levels of antibody before vaccination indicated previous widespread exposure of patients to influenza A/Victoria/75 virus, but not to influenza A/New Jersey/76 virus. Such differences in prior immunologic experience with a particular strain of influenza virus probably determine whether the intradermal route of vaccination is as effective as, or inferior to, the subcutaneous route.
Mutation of the principal sigma factor causes loss of virulence in a strain of the Mycobacterium tuberculosis complex. (1995)

Tuberculosis continues to be responsible for the deaths of millions of people, yet the virulence factors of the causative pathogens remain unknown. Genetic complementation experiments with strains of the Mycobacterium tuberculosis complex have identified a gene from a virulent strain that restores virulence to an attenuated strain. The gene, designated rpoV, has a high degree of homology with principal transcription or sigma factors from other bacteria, particularly Mycobacterium smegmatis and Streptomyces griseus. The homologous rpoV gene of the attenuated strain has a point mutation causing an arginine-->histidine change in a domain known to interact with promoters. To our knowledge, association of loss of bacterial virulence with a mutation in the principal sigma factor has not been previously reported. The results indicate either that tuberculosis organisms have an alternative principal sigma factor that promotes virulence genes or, more probably, that this particular mutant principal sigma factor is unable to promote expression of one or more genes required for virulence. Study of genes and proteins differentially regulated by the mutant transcription factor should facilitate identification of further virulence factors.
Introduction to Heavy Chain Antibodies and Derived Nanobodies (2012)

The immune response of infected or immunized dromedaries contains a diverse repertoire of conventional and heavy chain-only antibodies, both functional in antigen binding. By definition, a heavy chain antibody is devoid of a light chain and in the case of the heavy chain antibodies in camelids the CH1 domain is also missing. Consequently a camelid heavy chain antibody associates with its cognate antigen via a single domain, the variable heavy chain domain of a heavy chain antibody or VHH. An antigen-specific VHH, also known as Nanobody, with excellent biochemical properties can be obtained in various ways. Their recombinant expression provides access to user-friendly tools for a wide variety of applications.
Engineering lymph node homing of ex vivo–expanded human natural killer cells via trogocytosis of the chemokine receptor CCR7 (2012)

Natural killer (NK) cells have gained significant attention in adoptive immunotherapy for cancer. Consequently, novel methods of clinical-grade expansion of NK cells have emerged. Subsets of NK cells express a variety of chemokine receptors. However, to expand the scope of adoptively transferred NK cell homing to various malignancies, expression of corresponding chemokine receptors on NK cells is essential. Here, we have explored the use of trogocytosis as a tool to transiently express the chemokine receptor CCR7 on expanded human NK cells with the aim to enhance their homing to lymph nodes. We generated a K562-based "donor" cell line expressing CCR7, Clone9.CCR7, to transfer CCR7 onto NK cells via trogocytosis. CCR7 expression occurred in 80% of expanded NK cells within 1 hour after coculture with Clone9.CCR7. After removal of the donor cells from the coculture, the CCR7 expression on NK cells steadily declined to baseline levels by 72 hours. The acquired CCR7 receptors mediated in vitro migration of NK cells toward CCL19 and CCL21 and increased the lymph node homing by 144% in athymic nude mice. This is the first report on exploiting trogocytosis to rapidly and transiently modify lymphocytes, without direct genetic intervention, for adoptive transfer.
A General Strategy to Convert the MerR Family Proteins into Highly Sensitive and Selective Fluorescent Biosensors for Metal Ions (2003)

The MerR family metal-regulatory proteins are converted into fluorescent biosensors that can detect different metal ions with high sensitivity and selectivity.
The amino blocking reagent 1-isopropyl-3-ethoxy-4-nitro-2-oxo-3-pyrroline and the N-hydroxysuccinimide esters of N-(1-cyclohexyl- and 1-isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl)glycine. Reagents for the introduction of N-glycyl residues (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe amino blocking reagent 1-isopropyl-3-ethoxy-4-nitro-2-oxo-3-pyrroline and the N-hydroxysuccinimide esters of N-(1-cyclohexyl- and 1-isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl)glycine. Reagents for the introduction of N-glycyl residuesPhilip L. Southwick, George K. Chin, Mark A. Koshute, James R. Miller, Kimberly E. Niemela, Cheryl A. Siegel, Robert T. Nolte, and William E. BrownCite this: J. Org. Chem. 1984, 49, 6, 1130–1134Publication Date (Print):March 1, 1984Publication History Published online1 May 2002Published inissue 1 March 1984https://pubs.acs.org/doi/10.1021/jo00180a036https://doi.org/10.1021/jo00180a036research-articleACS PublicationsRequest reuse permissionsArticle Views135Altmetric-Citations7LEARN 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
Control of acute, chronic, and constitutive hyperammonemia by wild‐type and genetically engineered Lactobacillus plantarum in rodents† (2008)

Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.
Variants of the carboxyl-terminal KDEL sequence direct intracellular retention. (1990)

Soluble proteins which reside in the lumen of the endoplasmic reticulum share a common carboxyl-terminal tetrapeptide Lys-Asp-Glu-Leu (KDEL). Addition of the tetrapeptide to a normally secreted protein is both necessary and sufficient to cause retention in the endoplasmic reticulum. In order to characterize the critical residues in the KDEL signal, cDNAs encoding proneuropeptide Y (pro-NPY) with the 4-amino acid carboxyl-terminal extension KDEL or a series of KDEL variants were expressed in the AtT-20 cell line. AtT-20 cells, a mouse anterior pituitary corticotrope cell line, synthesize, process, and secrete the pro-ACTH/endorphin precursor. Since post-translational processing in AtT-20 cells has been extensively characterized, it provides a model system in which the processing of a foreign peptide precursor (pro-NPY) and the endogenous precursor (pro-ACTH/endorphin) can be compared. Altered cDNAs encoding pro-NPY with KDEL, DKEL, RDEL, KNEL, KDQL, or KDEA at the COOH terminus were used to generate stable AtT-20 cell lines. The processing of pro-NPY to neuropeptide Y and the carboxyl-terminal peptide was studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, tryptic peptide mapping, and radiosequencing. Addition of the tetrapeptides KDEL, DKEL, RDEL, or KNEL to the COOH terminus of the neuropeptide Y precursor, a peptide hormone normally processed and secreted from neuronal cells, caused complete intracellular retention of the unprocessed prohormone in AtT-20 cells. However, KDQL and KDEA-extended pro-NPY molecules were processed and secreted like wild-type pro-NPY when expressed in AtT-20 cells. The secretion of proNPY-derived peptides in these cell lines paralleled secretion of endogenous pro-ACTH/endorphin-derived products under both basal and stimulated conditions. These mutagenesis studies demonstrate that variants of the KDEL retention signal can direct intracellular retention.
Insights into Editing from an Ile-tRNA Synthetase Structure with tRNA Ile and Mupirocin (1999)

Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNA(Ile) at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with tRNA(Ile) and Mupirocin shows the acceptor strand of the tRNA(Ile) in the continuously stacked, A-form conformation with the 3' terminal nucleotide in the editing active site. To position the 3' terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNA(Gln) complexed with its synthetase. The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases.
In vitro selection and characterization of a highly efficient Zn(II)-dependent RNA-cleaving deoxyribozyme (2000)

A group of highly efficient Zn(II)-dependent RNA-cleaving deoxyribozymes has been obtained through in vitro selection. They share a common motif with the '8-17' deoxyribozyme isolated under different conditions, including different design of the random pool and metal ion cofactor. We found that this commonly selected motif can efficiently cleave both RNA and DNA/RNA chimeric substrates. It can cleave any substrate containing rNG (where rN is any ribo-nucleotide base and G can be either ribo- or deoxy-ribo-G). The pH profile and reaction products of this deoxyribozyme are similar to those reported for hammerhead ribozyme. This deoxyribozyme has higher activity in the presence of transition metal ions compared to alkaline earth metal ions. At saturating concentrations of Zn(2+), the cleavage rate is 1.35 min(-1)at pH 6.0; based on pH profile this rate is estimated to be at least approximately 30 times faster at pH 7.5, where most assays of Mg(2+)-dependent DNA and RNA enzymes are carried out. This work represents a comprehensive characterization of a nucleic acid-based endonuclease that prefers transition metal ions to alkaline earth metal ions. The results demonstrate that nucleic acid enzymes are capable of binding transition metal ions such as Zn(2+)with high affinity, and the resulting enzymes are more efficient at RNA cleavage than most Mg(2+)-dependent nucleic acid enzymes under similar conditions.
Nomadic computing—an opportunity (1995)

We are in the midst of some truly revolutionary changes in the field of computer-communications, and these offer opportunities and challenges to the research community. One of these changes has to do with nomadic computing and communications. Nomadicity refers to the system support needed to provide a rich set of capabilities and services to the nomad as he moves from place to place in a transparent and convenient form. This new paradigm is already manifesting itself as users travel to many different locations with laptops, PDA's, cellular telephones, pagers, etc. In this paper we discuss some of the open issues that must be addressed as we bring about the system support necessary for nomadicity. In addition, we present some of the considerations with which one must be concerned in the area of wireless communications, which forms one (and only one) component of nomadicity.
Raman Spectroscopic Study of 1,4-Benzenedithiol Adsorbed on Silver (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRaman Spectroscopic Study of 1,4-Benzenedithiol Adsorbed on SilverSeong Ho Cho, Hyouk Soo Han, Du-Jeon Jang, Kwan Kim, and Myung Soo KimCite this: J. Phys. Chem. 1995, 99, 26, 10594–10599Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://doi.org/10.1021/j100026a024RIGHTS & PERMISSIONSArticle Views1310Altmetric-Citations103LEARN 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 (686 KB) Get e-Alerts