gebhart/patrepeval huggingface dataset:
Corticosteroid effects on cell signalling (2006)

Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kappaB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex. Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects. In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids. The therapeutic implications of these new findings are discussed.
Holographic Honeycomb Microlens (1985)

A honeycomb close-packed microstructure can be recorded in a positive photoresist layer by a simultaneous exposure of three coherent laser beams. A close-packed square structure results from a simultaneous four-beam exposure. The structure consists of parabolic-shaped depressions in the surface. By replication and embossing techniques, it is possible to impress the mirror image of the microstructure into plastic, such that the top surface consists of parabolic-shaped posts, or microlenses. The size of each microlens can be varied from around one micrometer to a millimeter or more. There are wide-ranging applications for such regularly spaced and precise structures, extending from solar concentrators to three-dimensional imaging devices.
Quantitative Fluorescence Microscopy Measures Vascular Pore Size in Primary and Metastatic Brain Tumors (2016)

Tumors residing in the central nervous system (CNS) compromise the blood-brain barrier (BBB) via increased vascular permeability, with the magnitude of changes dependent on the tumor type and location. Current studies determine penetrability of a cancer therapeutic by administering progressively larger molecules until cutoff is observed where little to no tumor accumulation occurs. However, decades-old experimental work and mathematical modeling document methods to calculate both the size of the vascular opening (pore) with solute permeability values. In this study, we updated this classic mathematical modeling approach with quantitative fluorescence microscopy in two preclinical tumor models, allowing simultaneous administration of multiple sized tracers to determine vascular permeability at a resolution of nearly one micron. We observed that three molecules ranging from 100 Da to 70 kDa permeated into a preclinical glioblastoma model at rates proportional to their diffusion in water. This suggests the solutes freely diffused from blood to glioma across vascular pores without steric restriction, which calculates to a pore size of >140 nm in diameter. In contrast, the calculated pore size of a brain metastasis of breast cancer was approximately 10-fold smaller than glioma vasculature. This difference explains why antibodies are effective against glioblastoma but generally fail in brain metastases of breast cancer. On the basis of our observations, we hypothesize that trastuzumab most likely fails in the treatment of brain metastases of breast cancer because of poor CNS penetration, while the similar sized antibody bevacizumab is effective in the same tumor type not because it penetrates the CNS degree better, but because it scavenges VEGF in the vascular compartment, which reduces edema and permeation. Cancer Res; 77(2); 238-46. ©2016 AACR.
Surface Tension of Lung Extracts (1957)

Saline-extractable surface-active material has been found in the lungs of rat. cat. and dog. This material, probably mucoprotein. imparts large hysteresis and characteristic elasticity to the fluid surface. Its effect on lung mechanics has been studied. Its possible influence on diffusion across the alveolar barrier remains to be elucidated.
Agrobacterium tumefaciens Transformation of Monocotyledons (1995)

Agrobacterium tumefaciens (Smith and Townsend, 1907) has been an extremely useful vector to transfer foreign genes into dicotyledonous plants. Monocotyledonous plants, particularly the cereals, have been considered outside the host range for A. tumefaciens , which has necessitated the development of other transformation systems such as naked DNA delivery to protoplasts and, most recently, microprojectile bombardment delivery of DNA to cells and tissues. Both systems have worked, but there are still many difficulties encountered in routine transformation of any monocotyledon. Recently, there has been renewed interest in using the A. tumefaciens system to transform economically important grasses and other monocotyledons. This paper examines the literature and steps involved in transformation of monocotyledons by A. tumefaciens . The many recent advances in understanding the biology of the infection process (meristematic target cell, vir gene inducing compounds, and wide host range strains of A. tumefaciens ), and availability of more monocotyledon gene promoters and improved selectable markers greatly improve the opportunities of developing monocotyledon transformation systems with A. tumefaciens .
Synthesis of a low molecular weight collagen by chondrocytes from the presumptive calcification region of the embryonic chick sterna: the influence of culture with collagen gels. (1984)

The mature chick sternum is divisible almost equally into cephalic calcified and caudal cartilagenous regions. Isolation and culture of cells derived from embryonic precursors of these regions has revealed two discrete populations of cells with distinct morphological features and synthetic capabilities. Both cell populations grew well in culture within or upon collagen gels or upon plastic and maintained morphologies similar to those observed in the parent tissue. Polyacrylamide gel electrophoresis of radiolabeled proteins synthesized by the cells in culture demonstrated large differences in the types of collagens synthesized. Both chondrocyte populations synthesized type II and minor cartilage collagens but only chondrocytes isolated from the presumptive calcification region synthesized the previously identified, low molecular weight collagen, termed G collagen. Synthesis of G collagen was stimulated by culture within or upon collagen gels such that it represented an average of 65% of the total collagen synthesized by presumptive calcification region chondrocytes after 7 d of culture within collagen gels. Light and scanning electron microscopy demonstrated that the two chondrocyte types exhibited distinct morphological features and accumulated different extracellular matrices in culture.
Beta‐catenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E‐cadherin and accumulation of p53, but not with expression of conventional WNT‐1 target genes (2003)

Beta-catenin integrates intracellular WNT signalling and the intercellular E-cadherin-catenin adhesion system. To date, little is known about the role of beta-catenin activation and nuclear accumulation in hepatocarcinogenesis. This study has analysed beta-catenin expression patterns in human dysplastic nodules (DNs), as well as in hepatocellular carcinomas (HCCs) in comparison with proliferation, expression of WNT-1 target genes, E-cadherin, and p53. One hundred and seventy HCCs and 25 DNs were categorized according to established criteria and analysed for the expression pattern of beta-catenin. Analysis of the proliferative activity and expression of E-cadherin, cyclin D1, MMP-7, c-myc, and p53 was performed on a representative subgroup of cases. All DNs lacked nuclear beta-catenin, while 36% of all HCCs were positive, with the number of nuclear stained cells ranging from less than 1% to more than 90%. Increasing nuclear accumulation of beta-catenin correlated with reduced membranous E-cadherin expression and nuclear p53 but not with proliferation. Cyclin D1, MMP-7, and c-myc expression was detected in 54%, 26%, and 65% of HCCs, respectively, but did not correlate with nuclear beta-catenin, proliferation, or grading. Sequence analysis of the beta-catenin gene revealed no detectable mutations in DNs, but mutations in the GSK-3beta binding site were present in 14.3% of the HCCs. In conclusion, this study has demonstrated that nuclear accumulation of beta-catenin is a frequent progression event in human hepatocarcinogenesis which correlates with nuclear p53 accumulation and loss of membranous E-cadherin, but not with the expression pattern of established WNT-1 target genes. It is hypothesized that the role of beta-catenin in human HCC differs significantly from its established function in colon carcinogenesis.
Penetration of Brain and Brain Tumor by Aromatic Compounds as a Function of Molecular Substituents. III (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPenetration of Brain and Brain Tumor by Aromatic Compounds as a Function of Molecular Substituents. IIIA. H. Soloway, B. Whitman, and J. R. MesserCite this: J. Med. Chem. 1962, 5, 1, 191–196Publication Date (Print):January 1, 1962Publication History Published online1 May 2002Published inissue 1 January 1962https://doi.org/10.1021/jm01236a018RIGHTS & PERMISSIONSArticle Views123Altmetric-Citations9LEARN 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 (322 KB) Get e-Alerts
Electron transport chain defects in Alzheimer's disease brain (1994)

Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer's disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (p < 0.001). Concentrations of cytochromes b, c1, and aa3 were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX.
THE EFFECT OF EPHEDRINE ON FETAL OUTCOME IN TREATMENT OF MATERNAL HYPOTENSION CAUSED BY SPINAL ANESTHESIA DURING CESAREAN SECTION (2010)

Objective: To compare maternal complications and labor outcome in obese and non-obese women. Materials and methods: It is a retrospective comparative study conducted at the Department of obstetrics and gynecology, Unit 1, Civil Hospital, Karachi from December 2008 to December 2009. A sample size of 220 gravid women is selected by Non Probability Convenience sampling technique. In these 110 obese women as cases was compared with 110 non-obese women as controls, booked at <20 weeks of gestation. Data were collected regarding maternal complication, mode of delivery and neonatal outcome by trained medical officers. Data were entered and analyzed by SPSS version 11.0 through descriptive analysis, chi-square test and independent sample t test. The p-value of <0.05 was considered significant. Results: Pregnancy induced hypertension was present in 9 (8.2%) women in control group and 21 (19.1%) in cases (p=0.01). Gestational diabetes was seen in one (0.9%) in control compared to 8 (7.3%) in obese women (p=0.01). Obese women were found to be at increased risk of caesarean section [17 (15.5%) Vs. 39 (35.4%), p=0.002]. Apgar score at 1 and 10 minute were lower in cases compared to controls (p=0.0001). Conclusion: Obese women are at increased risk of pregnancy induced obesity and associated with an increased risk of hypertension, gestational diabetes mellitus, thromboembolic disease and urinary tract infection.
Anhydrophenacetylglutamic Acid (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnhydrophenacetylglutamic AcidJohn A. King, Freeman H. McMillan, and Jerome D. GenzerCite this: J. Am. Chem. Soc. 1952, 74, 20, 5202–5203Publication Date (Print):October 1, 1952Publication History Published online1 May 2002Published inissue 1 October 1952https://pubs.acs.org/doi/10.1021/ja01140a066https://doi.org/10.1021/ja01140a066research-articleACS PublicationsRequest reuse permissionsArticle Views33Altmetric-Citations1LEARN 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
Long-term hemopoietic repopulation by Thy-1lo, Lin-, Ly6A/E+ cells. (1992)

Murine bone marrow Thy-1lo, Lin-, Ly6A/E+ cells have been isolated by fluorescence-activated cell sorting (FACS). This population contained up to 27% in vitro colony-forming cells (CFC) when stimulated by interleukin 3 (IL-3) and 5% day-12 spleen colony-forming units (CFU-S) (uncorrected for seeding efficiency). As few as 100 cells were able to reconstitute the myeloid and lymphoid compartments of lethally irradiated recipients for periods of up to 72 weeks. Over the range of 30-560 transplanted cells, three patterns of engraftment were observed; the proportion of donor cells increased gradually to values of > 90%, gradually declined, or remained static over the 72-week observation period. When the donor cell percentage in the peripheral blood exceeded 60%, both myeloid (neutrophils and monocytes) and lymphoid (T- and B-lymphocytes) cells were of donor origin. Primary animals containing > 60% donor cells in their peripheral blood were able to engraft secondary recipients with donor cells of both myeloid and lymphoid lineages. Primary animals with < 20% donor cells in their peripheral blood contained bone marrow cells that were only able to produce lymphoid cells in the peripheral blood of secondary recipients. With > 90% of animals, including both primary and secondary recipients, there were no large fluctuations in the proportion of donor myeloid or lymphoid cells in the peripheral blood. Where changes occurred, with three exceptions, these were gradual. These data suggest that the Thy-1lo, Lin-, Ly6A/E+ population is heterogeneous and contains in vitro CFC, day-12 CFU-S, and long-term repopulating cells for both the myeloid and lymphoid lineages and cells capable of long-term repopulation of only the lymphoid lineage.
Sequences within Apolipoprotein(a) Kringle IV Types 6−8 Bind Directly to Low-Density Lipoprotein and Mediate Noncovalent Association of Apolipoprotein(a) with Apolipoprotein B-100 (1998)

Lipoprotein(a) [Lp(a)] particle formation is a two-step process in which initial noncovalent interactions between apolipoprotein(a) [apo(a)] and the apolipoprotein B-100 (apoB-100) component of low-density lipoprotein (LDL) precede disulfide bond formation. To identify kringle (K) domains in apo(a) that bind noncovalently to apoB-100, the binding of a battery of purified recombinant apo(a) [r-apo(a)] species to immobilized human LDL has been assessed. The 17K form of r-apo(a) (containing all 10 types of kringle IV sequences) as well as other truncated r-apo(a) derivatives exhibited specific binding to a single class of sites on immobilized LDL, with Kd values ranging from approximately 340 nM (12K) to approximately 7900 nM (KIV5-8). The contribution of kringle IV types 6-8 to the noncovalent interaction of r-apo(a) with LDL was demonstrated by the decrease in binding affinity observed upon sequential removal of these kringle domains (Kd approximately 700 nM for KIV6-P, Kd approximately 2000 nM for KIV7-P, Kd approximately 5100 nM for KIV8-P, and no detectable specific binding of KIV9-P). Interestingly, KIV9 also appears to participate in the noncovalent binding of apo(a) to LDL since the binding of KIV5-8 (Kd approximately 7900 nM) was considerably weaker than that of KIV5-9 (Kd approximately 2000 nM). Finally, it is demonstrated that inhibition of Lp(a) assembly by proline, lysine, and lysine analogues, as well as by arginine and phenylalanine, is due to their ability to inhibit noncovalent association of apo(a) and apoB-100 and that these compounds directly exert their effects primarily through interactions with sequences contained within apo(a) kringle IV types 6-8. On the basis of the obtained data, a model is proposed for the interaction of apo(a) and LDL in which apo(a) contacts the single high-affinity binding site on apoB-100 through multiple, discrete interactions mediated primarily by kringle IV types 6-8.
Somitic origin of limb muscle satellite and side population cells (2006)

Repair of mature skeletal muscle is mediated by adult muscle progenitors. Satellite cells have long been recognized as playing a major role in muscle repair, whereas side population (SP) cells have more recently been identified as contributing to this process. The developmental source of these two progenitor populations has been considerably debated. We explicitly tested and quantified the contribution of embryonic somitic cells to these progenitor populations. Chick somitic cells were labeled by using replication-defective retroviruses or quail/chick chimeras, and mouse cells were labeled by crossing somite-specific, Pax3-derived Cre driver lines with a Cre-dependent reporter line. We show that the majority of, if not all, limb muscle satellite cells arise from cells expressing Pax3 specifically in the hypaxial somite and their migratory derivatives. We also find that a significant number of, but not all, limb muscle SP cells are derived from the hypaxial somite. Notably, the heterogeneity in the developmental origin of SP cells is reflected in their functional heterogeneity; somitically derived SP cells are intrinsically more myogenic than nonsomitically derived ones. Thus, we show that the somites, which supply embryonic and fetal myoblasts, are also an important source of highly myogenic adult muscle progenitors.
RH 5849, a Nonsteroidal Ecdysone Agonist: Effects on Larval Lepidoptera (1988)

The ecdysone agonist RH 5849 (1,2-dibenzoyl-1-tert-butylhydrazine) causes the premature initiation of molting at all stages of larval development of the tobacco hornworm, Manduca sexta. This phenomenon occurs without an increase in the endogenous ecdysone (20-hydroxyecdysone) titers. RH 5849 likewise provokes the initiation of molting in larval abdomens in the absence of a source of endogenous hormone. Although substantially less active than 20-hydroxyecdysone in vitro, RH 5849 was 30 to >670 times as active as the authentic molting hormone in bioassays with isolated larval abdomens or intact hornworms. This reversal in potency can be attributed to the superior transport properties and metabolic stability of RH 5849 relative to 20-hydroxyecdysone. Thus RH 5849 and its analogs are relatively persistent ecdysone agonists that halt feeding in larval lepidoptera by forcing an ultimately lethal, developmentally premature molt.
ret Transforming Gene Encodes a Fusion Protein Homologous to Tyrosine Kinases (1987)

The ret transforming gene was activated by recombination between two unlinked segments of human DNA, most likely during transfection of NIH 3T3 cells. To further define this transforming gene, we isolated and sequenced ret cDNA clones. The nucleotide sequence indicates that the active ret transforming gene encodes a fusion protein with a carboxy-terminal domain which is 40 to 50% homologous to members of the tyrosine kinase gene family. This tyrosine kinase domain is preceded by a hydrophobic sequence characteristic of a transmembrane domain. Transcription of the ret tyrosine kinase sequence was detected in the SK-N-SH neuroblastoma, HL-60 promyelocytic leukemia, and THP-1 monocytic leukemia cell lines, but not in 25 other human tumor cell lines surveyed. The ret tyrosine kinase may thus represent a cell surface receptor which is expressed in a restricted range of human cells.