gebhart/patrepeval huggingface dataset:
Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury (2019)

Severe acute kidney injury has a high mortality and is a risk factor for progressive chronic kidney disease. None of the potential therapies that have been identified in preclinical studies have successfully improved clinical outcomes. This failure is partly because animal models rarely reflect the complexity of human disease: most preclinical studies are short term and are commonly performed in healthy, young, male mice. Therapies that are effective in preclinical models that share common clinical features seen in patients with acute kidney injury, including genetic diversity, different sexes, and comorbidities, and evaluate long-term outcomes are more likely to predict success in the clinic. Here, we evaluated susceptibility to chronic kidney disease after ischemia-reperfusion injury with delayed nephrectomy by monitoring long-term functional and histological responses to injury. We defined conditions required to induce long-term postinjury renal dysfunction and fibrosis without increased mortality in a reproducible way and evaluate effect of mouse strains, sexes, and preexisting diabetes on these responses.
Maximal Adjuvant Activity of Nasally Delivered IL-1α Requires Adjuvant-Responsive CD11c+ Cells and Does Not Correlate with Adjuvant-Induced In Vivo Cytokine Production (2012)

IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered IL-1α as determined by the acute induction of cytokine responses and induction of Bacillus anthracis lethal factor (LF)-specific adaptive immunity. Cytokine and chemokine responses induced by vaccination with IL-1α were predominantly derived from the stromal cell compartment and included G-CSF, IL-6, IL-13, MCP-1, and keratinocyte chemoattractant. Nasal vaccination of Il1r1(-/-) (knock-out [KO]) mice given wild-type (WT) BM (WT→KO) and WT→WT mice with LF + IL-1α induced maximal adaptive immune responses, whereas vaccination of WT mice given Il1r1(-/-) BM (KO→WT) resulted in significantly decreased production of LF-specific serum IgG, IgG subclasses, lethal toxin-neutralizing Abs, and mucosal IgA compared with WT→KO and WT→WT mice (p < 0.05). IL-1α adjuvant activity was not dependent on mast cells. However, the ability of IL-1α to induce serum LF-specific IgG2c and lethal toxin-neutralizing Abs was significantly impaired in CD11c-Myd88(-/-) mice when compared with WT mice (p < 0.05). Our results suggest that CD11c(+) cells must be directly activated by nasally administered IL-1α for maximal adjuvant activity and that, although stromal cells are required for maximal adjuvant-induced cytokine production, the adjuvant-induced stromal cell cytokine responses are not required for effective induction of adaptive immunity.
Clinicopathologic and molecular characteristics of gastric cancer showing gastric and intestinal mucin phenotype (2015)

Gastric cancer (GC), one of the most common human cancers, can be classified into gastric or intestinal phenotype according to mucin expression. TP53 mutation, allelic deletion of the APC gene and nuclear staining of β-catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC. Our Serial Analysis of Gene Expression (SAGE) and Escherichia coli ampicillin secretion trap (CAST) analyses revealed that CDH17, REG4, OLFM4, HOXA10, DSC2, TSPAN8 and TM9SF3 are upregulated in GC and that CLDN18 is downregulated in GC. Expression of CDH17, REG4, HOXA10 and DSC2 and downregulation of CLDN18 are observed in the intestinal phenotype of GC. In contrast, OLFM4 is expressed in the gastric phenotype of GC. Expression of TSPAN8, TM9SF3 and HER2 are not associated with either gastric or intestinal phenotypes. Ectopic CDX2 expression plays a key function in the GC intestinal phenotype. MUC2, CDH17, REG4, DSC2 and ABCB1 are direct targets of CDX2. Importantly, these genes encode transmembrane/secretory proteins, indicating that the microenvironment as well as cancer cells are also different between gastric and intestinal phenotypes of GC.
Topical Antigen Provocation Increases the Number of Immunoreactive IL-4-, IL-5- and IL-6-Positive Cells in the Nasal Mucosa of Patients with Perennial Allergic Rhinitis (1997)

To evaluate the role of Th2-type cytokines in the nasal mucosa which has been repeatedly exposed to antigen, an immunohistological study for IL-4, IL-5 and IL-6 was performed in patients with perennial allergic rhinitis and non allergic rhinosinusitis. The numbers of immunoreactive (ir)-IL-4, ir-IL-5 and ir-IL-6-positive cells were significantly higher in allergic mucosa than in nonallergic mucosa. In allergic mucosa, the numbers of these ir-cytokine-positive cells were significantly higher in the antigen-challenged site than in the control site. When the patients were divided into an early group (4-6 h after challenge) and a later group (15-25 h after challenge), only the change of ir-IL-4-positive cells was remarkable in the former group, whereas those of the ir-IL-4, ir-IL-5 and ir-IL-6-positive cells were significant in the latter group. These results suggest that antigen-induced upregulation of IL-4, IL-5 and IL-6 is important in the pathogenesis of perennial allergic rhinitis.
Toxicity and Repellency of 4–Allylanisole and Monoterpenes from White Spruce and Tamarack to the Spruce Beetle and Eastern Larch Beetle (Coleoptera: Scolytidae) (1995)

Journal Article Toxicity and Repellency of 4–Allylanisole and Monoterpenes from White Spruce and Tamarack to the Spruce Beetle and Eastern Larch Beetle (Coleoptera: Scolytidae) Get access Richard A. Werner Richard A. Werner Institute of Northern Forestry, Pacific Northwest Research Station, USDA Forest Service, Fairbanks, AK 99775-5500 Search for other works by this author on: Oxford Academic PubMed Google Scholar Environmental Entomology, Volume 24, Issue 2, 1 April 1995, Pages 372–379, https://doi.org/10.1093/ee/24.2.372 Published: 01 April 1995 Article history Received: 24 March 1994 Accepted: 16 September 1994 Published: 01 April 1995
Catalytic Phenylborylation Reaction by Iridium(0) Nanoparticles Produced from Hydridoiridium Carborane (2008)

Well-dispersed iridium(0) nanoparticles stabilized with the ionic liquid, trihexyltetradecylphosphonium methylsulfonate, [THTdP][MS], have been successfully prepared by reduction of the precursor hydridoiridium carborane, (Ph 3P) 2Ir(H)(7,8- nido-C 2B 9H 11). The iridium nanoparticles were found to be active catalysts for arylborylation, forming boric acids. The activity of the catalyst has been investigated as a function of the activating base, and reaction conditions. The highest yield of 91% was achieved in a microwave reactor using the base, tetra-2-pyridinylpyrazine, in the presence of [THTdP][MS]. The catalytic system could be recycled at least six times with less than a 0.5% loss of activity.
Development of intra-arterial hyperthermia using a dextran-magnetite complex (1994)

Dextran-magnetite complex (DM) is a colloidal sol of subdomain magnetite particles (i.e. a 'magnetic fluid'). The specific absorption rate of DM in an AC magnetic field is much higher than those of multidomain ferrite particles due to its different mechanism of heat generation. We designed two DM-containing embolic materials (a DM/Lipiodol emulsion and a DM/degradable starch microsphere suspension) to heat target tissues with the use of an external AC magnetic field. In vitro experiments showed that the heat-generating capacity of DM was not reduced in these mixtures. When these materials were injected into the renal arteries of Japanese white rabbits, they both achieved embolization of the artery and selective heating of the embolized kidney by exposure to a 100 kHz AC magnetic field of approximately 15,000 A/m. Histological examination showed a homogeneous distribution of DM in the embolized kidney. These results suggest the possibility of using DM-containing embolic materials for inductive hyperthermia.
Electrospinning of Nanomaterials and Applications in Electronic Components and Devices (2010)

Electrospinning of nanomaterial composites are gaining increased interest in the fabrication of electronic components and devices. Performance improvement of electrospun components results from the unique properties associated with nanometer-scaled features, high specific surface areas, and light-weight designs. Electrospun nanofiber membrane-containing polymer electrolytes show improved ionic conductivity, electrochemical stability, low interfacial resistance, and improved charge-discharge performance than those prepared from conventional membranes. Batteries with non-woven electrospun separators have increased cycle life and higher rate capabilities than ones with conventional separators. Electrospun nanofibers may also be used as working electrodes in lithium-ion batteries, where they exhibit excellent rate capability, high reversible capacity, and good cycling performance. Moreover, the high surface area of electrospun activated carbon nanofibers improves supercapacitor energy density. Similarly, nanowires having quasi-one-dimensional structures prepared by electrospinning show high conductivity and have been used in ultra-sensitive chemical sensors, optoelectronics, and catalysts. Electrospun conductive polymers can also perform as flexible electrodes. Finally, the thin, porous structure of electrospun nanofibers provides for the high strain and fast response required for improved actuator performance. The current review examines recent advances in the application of electrospinning in fabricating electronic components and devices.
DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement (2008)

Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
Nanostructure, hydrogen bonding and rheology in choline chloride deep eutectic solvents as a function of the hydrogen bond donor (2016)

Deep eutectic solvents (DESs) are a mixture of a salt and a molecular hydrogen bond donor, which form a eutectic liquid with a depressed melting point. Quantum mechanical molecular dynamics (QM/MD) simulations have been used to probe the 1 : 2 choline chloride-urea (ChCl : U), choline chloride-ethylene glycol (ChCl : EG) and choline chloride-glycerol (ChCl : Gly) DESs. DES nanostructure and interactions between the ions is used to rationalise differences in DES eutectic point temperatures and viscosity. Simulations show that the structure of the bulk hydrogen bond donor is largely preserved for hydroxyl based hydrogen bond donors (ChCl:Gly and ChCl:EG), resulting in a smaller melting point depression. By contrast, ChCl:U exhibits a well-established hydrogen bond network between the salt and hydrogen bond donor, leading to a larger melting point depression. This extensive hydrogen bond network in ChCl:U also leads to substantially higher viscosity, compared to ChCl:EG and ChCl:Gly. Of the two hydroxyl based DESs, ChCl:Gly also exhibits a higher viscosity than ChCl:EG. This is attributed to the over-saturation of hydrogen bond donor groups in the ChCl:Gly bulk, which leads to more extensive hydrogen bond donor self-interaction and hence higher cohesive forces within the bulk liquid.
Targeting loss of heterozygosity for cancer-specific immunotherapy (2021)

Developing therapeutic agents with potent antitumor activity that spare normal tissues remains a significant challenge. Clonal loss of heterozygosity (LOH) is a widespread and irreversible genetic alteration that is exquisitely specific to cancer cells. We hypothesized that LOH events can be therapeutically targeted by "inverting" the loss of an allele in cancer cells into an activating signal. Here we describe a proof-of-concept approach utilizing engineered T cells approximating NOT-gate Boolean logic to target counterexpressed antigens resulting from LOH events in cancer. The NOT gate comprises a chimeric antigen receptor (CAR) targeting the allele of human leukocyte antigen (HLA) that is retained in the cancer cells and an inhibitory CAR (iCAR) targeting the HLA allele that is lost in the cancer cells. We demonstrate that engineered T cells incorporating such NOT-gate logic can be activated in a genetically predictable manner in vitro and in mice to kill relevant cancer cells. This therapeutic approach, termed NASCAR (Neoplasm-targeting Allele-Sensing CAR), could, in theory, be extended to LOH of other polymorphic genes that result in altered cell surface antigens in cancers.
Detection of conformational changes in human chorionic gonadotropin upon binding to rat gonadal receptors. (1987)

After binding to rat testicular or ovarian luteinizing hormone (LH) receptors, human chorionic gonadotropin (hCG) and mammalian LH can be detected with monoclonal antibodies directed against a conserved epitope on the beta subunit of the hormones. Two such anti-hCG/anti-LH monoclonal antibodies, known as B105 and B110, compete with one another for binding to this epitope region on free and receptor-bound hormone. By comparing the affinities of B105 and B110 for these two forms of hCG, we have detected apparent changes in the structure of the hormone which develop subsequent to receptor binding. Whereas the affinity of B105 for receptor-bound hCG is approximately 10-fold lower than that for free hCG, the affinity of B110 for receptor-bound hCG is nearly 20-fold greater than that for free hCG. Both B105.hCG and B110.hCG complexes bind to the receptor; however, they have approximately 25 and 50% lower affinity than hCG. Thus, although B110 binds better to the form of hCG which is bound to receptors, binding of B110 to hCG does not appear to induce a conformational change in the hormone which facilitates hormone-receptor binding. Consequently, both B105 and B110 partially inhibit binding of hCG to its receptors. Fab fragments of B105 and B110 are as effective as intact B105 and B110 in inhibiting the binding of labeled B105 and B110 to hCG-receptor complexes, suggesting that circular complexes which might be formed by the interaction of divalent antibody, two molecules of hCG, and two membrane-bound receptors or one divalent receptor are not contributing to the affinity of the antibodies for receptor-bound hCG. Alternatively, formation of circular complexes can explain an increase in apparent affinity of B105 for ovine or bovine LH-receptor complexes. Data obtained with B105 suggest either that the structure of the epitope is altered following binding or that a portion of the epitope is partially obscured when hCG binds to the receptor. In contrast, the data obtained using B110 are not explained by models in which steric factors reduce the affinity of the antibody for the hormone-receptor complex. Therefore, as a minimal explanation for these observations, we postulate that the conformation of the B105/B110 epitope region is altered following binding of the hormone to receptors. The nature of the conformational change and its relationship to LH/hCG action is unknown.
A 2‐oxoglutarate‐dependent dioxygenase from Ruta graveolens L. exhibits p‐coumaroyl CoA 2′‐hydroxylase activity (C2′H): a missing step in the synthesis of umbelliferone in plants (2011)

Coumarins are important compounds that contribute to the adaptation of plants to biotic or abiotic stresses. Among coumarins, umbelliferone occupies a pivotal position in the plant phenylpropanoid network. Previous studies indicated that umbelliferone is derived from the ortho-hydroxylation of p-coumaric acid by an unknown biochemical step to yield 2,4-dihydroxycinnamic acid, which then undergoes spontaneous lactonization. Based on a recent report of a gene encoding a 2-oxoglutarate-dependent dioxygenase from Arabidopsis thaliana that exhibited feruloyl CoA 6'-hydroxylase activity (Bourgaud et al., 2006), we combined a bioinformatic approach and a cDNA library screen to identify an orthologous ORF (Genbank accession number JF799117) from Ruta graveolens L. This ORF shares 59% amino acid identity with feruloyl CoA 6'-hydroxylase, was functionally expressed in Escherichia coli, and converted feruloyl CoA into scopoletin and p-coumaroyl CoA into umbelliferone with equal activity. Its bi-functionality was further confirmed in planta: transient expression of JF799117 in Nicotiana benthamiana yielded plants with leaves containing high levels of umbelliferone and scopoletin when compared to control plants, which contained barely detectable traces of these compounds. The expression of JF799117 was also tightly correlated to the amount of umbelliferone that was found in UV-elicited R. graveolens leaves. Therefore, JF799117 encodes a p-coumaroyl CoA 2'-hydroxylase in R. graveolens, which represents a previously uncharacterized step in the synthesis of umbelliferone in plants. Psoralen, which is an important furanocoumarin in R. graveolens, was found to be a competitive inhibitor of the enzyme, and it may exert this effect through negative feedback on the enzyme at an upstream position in the pathway.
A robust content based digital signature for image authentication (2002)

A methodology for designing content based digital signatures which can be used to authenticate images is presented. A continuous measure of authenticity is presented which forms the basis of this methodology. Using this methodology signature systems can be designed which allow certain types of image modification (e.g. lossy compression) but which prevent other types of manipulation. Some experience with content based signatures is also presented. The idea of signature based authentication is extended to video, and a system to generate signatures for video sequences is presented. This signature also allows smaller segments of the secured video to be verified as unmanipulated.
Ultrasonic Flexural-Plate-Wave Sensor for Detecting the Concentration of SettlingE.coliW3110 Cells (1999)

The flexural-plate-wave (FPW) sensor, a type of ultrasonic sensor, can detect changes in E. coli W3110 concentration in solution as the cells settle onto the sensor under the influence of gravity. A model of the sensor's response to cell settling has been developed and is in good agreement with the experimental data. The FPW technique improves on conventional methods for determining cell concentrations; this technique allows for on-line data collection, is nondestructive, and requires only small sample volumes. The FPW sensor has applications as a device to measure cell concentrations and growth rates in industrial fermentors, biofilms, and wastewater treatment facilities.
Incorporation of Anionic Monomer to Tune the Reversible Catechol–Boronate Complex for pH-Responsive, Reversible Adhesion (2018)

Up to 30 mol % of acrylic acid (AAc) was incorporated into a pH-responsive smart adhesive consisting of dopamine methacrylamide and 3-acrylamido phenylboronic acid. Fourier transform infrared spectroscopy and rheometry confirmed that the incorporation of AAc shifted the pH of catechol-boronate complexation to a more basic pH. Correspondingly, adhesive formulations with elevated AAc contents demonstrated strong adhesion to quartz substrate at a neutral to mildly basic pH (7.5-8.5) based on Johnson-Kendall-Roberts contact mechanics test. When pH was further increased to 9.0, there was a drastic reduction in the measured work of adhesion (18- and 7-fold reduction compared to values measured at pHs 7.5 and 8.5, respectively) due to the formation of catechol-boronate complex. The complex remained reversible, and the interfacial binding property of the adhesive was successfully tuned with changing pH in successive contact cycles. However, an acidic pH (3.0) was required to break the catechol-boronate complex to recover the elevated adhesive property. Adding AAc enables the smart adhesive to function in physiological or marine pH ranges.
Catalysis of thiol/disulfide exchange: single-turnover reduction of protein disulfide-isomerase by glutathione and catalysis of peptide disulfide reduction (1989)

Protein disulfide-isomerase, a protein localized to the lumen of the endoplasmic reticulum of eukaryotic cells, catalyzes the posttranslational formation and rearrangement of protein disulfide bonds. As isolated from bovine liver, the enzyme contains 0.8 free sulfhydryl group per mole of protein monomer and 3.1 disulfide bonds. Single-turnover experiments in which the disulfide bonds of the native enzyme are reduced by glutathione reveal three distinct reduction steps corresponding to the sequential reduction of the three disulfide bonds. The fastest disulfide to be reduced undergoes a change in the rate-determining step with increasing GSH concentration from a step which is second-order with respect to GSH concentration to a step which is first-order in GSH concentration. The disulfide which is reduced at an intermediate rate displays kinetics that are first-order in GSH concentration, and the slowest disulfide to be reduced exhibits kinetics which are second-order in GSH concentration. The enzyme catalyzes the steady-state reduction of a disulfide-containing hexapeptide (CYIQNC) by GSH. Initial velocity kinetic experiments are consistent with a sequential addition of the substrates to the enzyme. Saturation behavior is not observed at high levels of both substrates (Km for GSH much greater than 14 mM, Km for CYIQNC much greater than 1 mM). Only one of the three disulfides appears to be kinetically competent in the steady-state reduction of CYIQNC by GSH. The second-order thiol/disulfide exchange reactions catalyzed by the enzyme are 400-6000-fold faster than the corresponding uncatalyzed reactions.