gebhart/patrepeval huggingface dataset:
Anti–IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss (2011)

IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about the role of IL-20 in bone destruction. We explored the function of IL-20 in osteoclastogenesis and the therapeutic potential of anti-IL-20 monoclonal antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20 mediates osteoclastogenesis by up-regulating the receptor activator of NF-κB (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected mice from OVX-induced bone loss in vivo. Furthermore, IL-20R1-deficient mice had significantly higher bone mineral density (BMD) than did wild-type controls. IL-20R1 deficiency also abolished IL-20-induced osteoclastogenesis and increased BMD in OVX mice. We have identified a pivotal role of IL-20 in osteoclast differentiation, and we conclude that anti-IL-20 monoclonal antibody is a potential therapeutic for protecting against osteoporotic bone loss.
Enzymic polymerization of α-D-maltosyl fluoride utilizing α-amylase as catalyst: a new approach for synthesis of maltooligosaccharides (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzymic polymerization of α-D-maltosyl fluoride utilizing α-amylase as catalyst: a new approach for synthesis of maltooligosaccharidesShiro Kobayashi, Junji Shimada, Keita Kashiwa, and Shinichiro ShodaCite this: Macromolecules 1992, 25, 12, 3237–3241Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June 1992https://pubs.acs.org/doi/10.1021/ma00038a032https://doi.org/10.1021/ma00038a032research-articleACS PublicationsRequest reuse permissionsArticle Views213Altmetric-Citations51LEARN 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
Nutrient Deprivation of Cultured Rat Hepatocytes Increases the Desferrioxamine-available Iron Pool and Augments the Sensitivity to Hydrogen Peroxide (1997)

Primary cultures of rat hepatocytes were subjected to amino acid and serum deprivation for 4 h. This treatment augmented the sensitivity to ensuing hydrogen peroxide exposure for 30 min. The by nutrient deprivation-increased autophagocytosis was confirmed by transmission electron microscopy and uptake of the lysosomotropic weak base acridine orange within the intracellular acidic vacuolar apparatus. The desferrioxamine-available pool of iron increased 2.5-fold during deprivation, compared with control cells. Furthermore, amino acid deprivation increased the cellular protein turnover, measured by radioactive labeling with -3H-Leu. Exposure to 40 microM ascorbic acid specifically decreased the turnover of ferritin, as estimated by enzyme-linked immunosorbent assay, and prevented an increase of the desferrioxamine-available iron pool, resulting in protection against hydrogen peroxide-induced cell killing. Thus, hepatocytes with nutrient deprivation-enhanced autophagocytosis contain a larger pool of catalytically active iron than control cells. This iron pool is mainly derived from the turnover (autophagocytosis) of cytosolic ferritin and is probably situated in the lysosomes. Furthermore, nutrient-deprived cells show augmented sensitivity to hydrogen peroxide-induced oxidative stress, since the enhanced availability of iron in low molecular weight form results in an increased potential of intralysosomal Fenton chemistry, that may cause lysosomal rupture with release of potent hydrolytic enzymes.
CD4+CD25+ CELLS REGULATE CD8 CELL ANERGY IN NEONATAL TOLERANT MICE1,2 (1999)

These data indicate that CD8 anergy is associated with the state of tolerance, and that CD4+CD25+ cells from tolerant mice function to maintain A/J-specific CD8 cell anergy in vitro.
Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein (2005)

sorLA (Sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduced in the brain of patients with Alzheimer's disease (AD), we tested involvement of this receptor in intracellular transport and processing of the amyloid precursor protein (APP) to the amyloid beta-peptide (Abeta), the principal component of senile plaques. We demonstrate that sorLA interacts with APP in vitro and in living cells and that both proteins colocalize in endosomal and Golgi compartments. Overexpression of sorLA in neurons causes redistribution of APP to the Golgi and decreased processing to Abeta, whereas ablation of sorLA expression in knockout mice results in increased levels of Abeta in the brain similar to the situation in AD patients. Thus, sorLA acts as a sorting receptor that protects APP from processing into Abeta and thereby reduces the burden of amyloidogenic peptide formation. Consequently, reduced receptor expression in the human brain may increase Abeta production and plaque formation and promote spontaneous AD.
Population Pharmacokinetic‐Pharmacodynamic Modeling of Biological Agents: When Modeling Meets Reality (2010)

The pharmacokinetics (PK) and pharmacodynamics (PD) of many biological agents (biologics) have inherent complexities requiring specialized approaches to develop reliable, unbiased models. Three cases are covered: preponderance of zero values, nonresponder subpopulations, and adaptive dosing. Engineered biologics exhibit high affinity for target receptors. Biologics can saturate receptors, abolishing free receptor levels for protracted periods. Consequently, the distribution of observations can be heavy at, and near, the boundary. A 2-part model (ie, a truncated δ log-normal distribution) may be appropriate. Mixture models identify subpopulations based on bimodal or multimodal distributions of η values. With biologics, PD may be compromised because of lack of receptors, or the PD may be affected because of other events resulting in erratic excursions. Nonresponders exhibit a random walk-around placebo trajectory, resulting in high residual variability. The distributions of etas are often badly skewed or polymodal. An indescribable mixture model separates subjects who are nonresponders, providing diagnostic pharmacologic information on the drug. Many biologics use PD-based adaptive dosing. During model development, data used for model development include adaptive dosing. For simulation, adaptive dosing must be implemented. Failure to account for dose adjustments results in biased or inflated prediction intervals because subjects in the simulated data undergo inappropriate dose adjustments.
A new implantable microstimulator dedicated to selective stimulation of the bladder (2002)

Presents a new implantable functional electrical stimulation (FES) system specially designed for the purpose of selective stimulation of the bladder in spinal cord injured patients. This system, composed of an external controller and an implantable microstimulator (implant), is used to induce low-pressure micturition. After receiving both energy and the stimulation parameters via radio-frequency coupling from the controller, the implant starts stimulation of the S/sub 2/ sacral nerve. The stimulation, composed of two independent frequencies, mainly stimulates the detrusor while blocking the stimulation of the sphincter even thought both muscles are linked to the S/sub 2/ nerve. A computer controlled controller is used by the physician to determine the best parameters for the patient. These parameters are then stored in a portable handheld unit that is used by the medical staff or patient. Acute studies in dogs were carried out to validate the authors' technique and chronic studies started five months ago.
Hydrogels for Engineering of Perfusable Vascular Networks (2015)

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.
Contact lens care (2012)

The first contact lenses, made of glass, were invented in the 1880s. Decades later, major advancements led to the production of a large variety of contact lenses that are now available today.

Contact lenses are a safe, convenient, cosmetically acceptable form of vision correction. They offer a suitable alternative to prescription spectacles for many individuals, including those who engage in physical activities where eye glasses may interfere.
Synthetic antibodies and peptides recognizing progressive multifocal leukoencephalopathy-specific point mutations in polyomavirus JC capsid viral protein 1 (2015)

Polyomavirus JC (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal brain disease that afflicts a small fraction of the immune-compromised population, including those affected by AIDS and transplantation recipients on immunosuppressive drug therapy. Currently there is no specific therapy for PML. The major capsid viral protein 1 (VP1) involved in binding to sialic acid cell receptors is believed to be a key player in pathogenesis. PML-specific mutations in JCV VP1 sequences present at the binding pocket of sialic acid cell receptors, such as L55F and S269F, abolish sialic acid recognition and might favor PML onset. Early diagnosis of these PML-specific mutations may help identify patients at high risk of PML, thus reducing the risks associated with immunosuppressive therapy. As a first step in the development of such early diagnostic tools, we report identification and characterization of affinity reagents that specifically recognize PML-specific mutations in VP1 variants using phage display technology. We first identified 2 peptides targeting wild type VP1 with moderate specificity. Fine-tuning via selection of biased libraries designed based on 2 parental peptides yielded peptides with different, yet still moderate, bindinspecificities. In contrast, we had great success in identifying synthetic antibodies that recognize one of the PML-specific mutations (L55F) with high specificity from the phage-displayed libraries. These peptides and synthetic antibodies represent potential candidates for developing tailored immune-based assays for PML risk stratification in addition to complementing affinity reagents currently available for the study of PML and JCV.
COMBINED IMMUNOSUPPRESSIVE THERAPY WITH LOW DOSE FK506 AND ANTIMETABOLITES IN RAT ALLOGENEIC HEART TRANSPLANTATION (1994)

Following rat heterotopic heart allotransplantation, low to lethal doses of the antimetabolites mizoribine (MIZ), RS-61443 (RS), and AZA were given alone or in combination with subtherapeutic doses of FK506 (0.04 mg/kg/day) for 14 days after transplantation. With the median effect analysis of Chou and Kahan for quantitative drug interactions, substantial therapeutic synergism was demonstrated between FK506 and non-toxic doses of MIZ (2.5, 5, and 10 mg/kg/day) or AZA (5, 30, and 45 mg/kg/day), which was particularly evident with the lowest dose MIZ (2.5 mg/kg/day). When FK506 was used in combination with MIZ or AZA but not with RS, the maximum effect (peak median graft survival) was enhanced significantly from 15 days (MIZ alone) to 26 days (P < 0.05), and from 19 days (AZA alone) to 32 days (P < 0.01). In contrast, RS interacted with FK506 no more than additively. Although RS was the most powerful single antimetabolite, the best overall survival was obtained by combining AZA and FK506. The addition of FK506 did not significantly increase the percent mortality and LD50 of the antimetabolites.
Biological Effects of the Immunomodulator β1‐3d Polyglucose are Strongly Potentiated by Conjugation to Biodegradable Microbeads (1997)

It is demonstrated that the biological effects of the immunomodulator beta 1-3D polyglucose, when covalently linked to polymethacrylate or biodegradable albumin microbeads, are strongly potentiated. The potentiation is recorded as an increased protection effect of the conjugates in Escherichia coli sepsis in mice, and as increased IL-1 production by murine macrophages in vitro.
Increased type IV collagen-degrading activity in metastases originating from primary tumors of the human colon. (1997)

The secretion of specific matrix metalloproteinases (MMPs) is considered a prerequisite step for tumor cell invasion and metastasis. In the present study we investigated the expression of type IV collagen-degrading activity in primary tumors of the human colon in correlation to tumor grade and in comparison to activity expressed in arising metastases. We observed that type IV collagen-degrading activity (MMP-2 and MMP-9), purified by ion exchange, gel filtration and affinity chromatography and characterized by gelatin zymography, correlates to tumor grade. Furthermore, in surgical specimens identified as metastases originating from primary tumors of the colon, we observed that enzyme activity was significantly enhanced, relatively to that identified in the primary tumor. This observation should be considered when targeting MMPs as a therapeutic intervention to prevent cancer progression.
Reduction of the major porcine xenoantigen Galoc(1,3)Gal by expression of α(1,2)fucosyltransferase (1996)

Abstract: Although removal of the Galα(1,3)Gal antigen from pigs would prevent hyperacute graft rejection, the technique of homologous recombination to knock out the α 1,3 galactosyltransferase gene is not available for pigs, and an alternative strategy is presented. As both α 1,3 galactosyltransferase and α 1,2 fucosyltransferase use the same substrate (N‐acetyl lacto‐samine), competition between the transferases in vitro and in vivo was examined. The data show that there is indeed a hierarchy of these gly‐cosyltransferases competing for the same substrate, and that α 1,2 fuco‐syltransferase takes precedence over α 1,3 galactosyltransferase: a) COS cells simultaneously transfected with cDNA clones encoding α, 2 fuco‐syltransferase and α 1,3 galactosyltransferase show preferential expression of the H substance (synthesised by α 1,2fucosyltransferase) rather than Galα(1,3)Gal (synthesised by α 1,3galactosyltransferase), even though α 1,3galactosyltransferase mRNA and functional enzyme was present, b) In a pig kidney cell line that expressed both the Galα(1,3)Gal and H, the increased expression of H induced by the transfection and stable expression of α 1,2fucosyltransferase resulted in decreased expression of Galα(1,3)Gal. c) Coexpression of α 1,2fucosyltransferase and α 1,3galactosyltransferase in either COS cells or the pig cell line resulted in decreased human antibody binding and complement‐mediated cell lysis, d) Transgenic mice, ubiquitously expressing α 1,2fucosyltransferase show a major decrease in Galα‐(1,3)Gal expression and a decrease in natural human antibody binding. These findings have important implications for xenotransplantation in that α,2fucosyltransferase transgenic pigs could be a source of donors for xenotransplantation to humans.
High-ratio Electro-optical Data Compression for Massive Accessing Networks Using AOM-based Ultrafast Pulse Shaping (2001)

Article High-ratio Electro-optical Data Compression for Massive Accessing Networks Using AOM-based Ultrafast Pulse Shaping was published on January 1, 2001 in the journal Journal of Optical Communications (volume 22, issue 1).
Audio-visual copyright and education (1989)

Earlier this year legislation significantly amending the Copyright Act was passed by the Australian Parliament. This article examines the background to some of these changes, and indicates how they will affect the use of copyright audio-visual materials in educational institutions.
The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer (2014)

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI3K/AKT, as well as the MEK/ERK-mediated signaling pathways. Conversely, knockdown of CAMK2N1 had a significant opposite effects on these phenotypes. Our analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome, indicating that CAMK2N1 may serve as a biomarker. The inhibition of tumor growth by expressing CAMK2N1 established a role of CAMK2N1 as a therapeutic target.
Characterization of a Meiotic Crossover in Maize Identified by a Restriction Fragment Length Polymorphism-Based Method (1996)

Genetic map lengths do not correlate directly with genome size, suggesting that meiotic recombination is not uniform throughout the genome. Further, the abundance of repeated sequences in plant genomes requires that crossing over is restricted to particular genomic regions. We used a physical mapping approach to identify these regions without the bias introduced by phenotypic selection. This approach is based on the detection of nonparental polymorphisms formed by recombination between polymorphic alleles. In an F2 population of 48 maize plants, we identified a crossover at two of the seven restriction fragment length polymorphism loci tested. Characterization of one recombination event revealed that the crossover mapped within a 534-bp region of perfect homology between the parental alleles embedded in a 2773-bp unique sequence. No transcripts from this region could be detected. Sequences immediately surrounding the crossover site were not detectably methylated, except for an SstI site and at the flanking repetitive sequences were faithfully inherited by the recombinant allele. Our observations suggest that meiotic recombination in maize occurs between perfectly homologous sequences, within unmethylated, nonrepetitive regions of the genome.
Gastric Secretion in Dogs Treated with Histamine Antagonist, Thymoxyethyldiethylamine (1941)

SummaryStudies on gastric secretion in dogs provided with Heidenhain pouches definitely indicated that 929F, given subcutaneously, did not induce gastric secretion. However, following an injection of histamine in animals thus treated, the gastric secretion was markedly increased in volume and acidity over that which was obtained during control periods when only the histamine stimulus was employed.These findings indicate that 929F, in the doses employed, neither destroys histamine nor antagonizes the action of histamine as a gastric secretory stimulant.
Wound repair and regeneration: Mechanisms, signaling, and translation (2014)

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies.
Amino acid sequence motifs essential to 3‘–>5‘ exonuclease activity of Escherichia coli DNA polymerase II. (1994)

Many DNA polymerases have conserved sequences required for 3'-->5' exonuclease activity, which contributes to the accuracy of DNA replication by removing misincorporated nucleotides prior to chain elongation. Using amino acid sequence alignments, we predicted the putative active site of the 3'-->5' exonuclease of Escherichia coli DNA polymerase II. Site-directed mutagenesis at D155A, E157A, D155A/E157A, D228A, Y330F, and D334A, which are in the predicted exonuclease active regions, specifically inactivated 3'-->5' exonucleolytic activity but not DNA-polymerizing activity of E. coli DNA polymerase II. Furthermore, all of the mutants were diminished in the in vitro proofreading ability, as judged by their increased insertion and extension of wrong nucleotides. These findings indicate that the 3'-->5' exonuclease region of the E. coli DNA polymerase II is in the amino-terminal part of the protein, as it is in other DNA polymerases, and are consistent with the proposal of an evolutionary conserved 3'-->5' exonuclease active site in most DNA-dependent DNA polymerases of both prokaryotic and eukaryotic origin by Bernad et al. (Bernad, A., Blanco, L., Lazaro, J. M., Martin, G., and Salas, M. (1989) Cell 59, 219-228).