gebhart/patrepeval huggingface dataset:
Internalization and down-regulation of the prostacyclin receptor in human platelets (1997)

The internalization of [3H]iloprost, a prostacyclin analogue, was studied in human platelets by binding studies. After incubation with [3H]iloprost at 37 degrees C, addition of unlabelled ligand at either 37 degrees C or 4 degrees C caused dissociation of 74% and 52% of the bound ligand respectively, suggesting that a portion had been internalized. The percentage of [3H]iloprost bound at equilibrium to the surface (evaluated by acid treatment) at either 37 degrees C or 4 degrees C was markedly different (80% versus 25%). Internalization was dependent on time and on the ligand nature and concentration. Energy-depleting agents (dinitrophenol and 2-deoxyglucose) completely inhibited internalization, whereas probenecid (inhibitor of organic anion transporters) did not affect it significantly. Subcellular fractionation indicated that, at 4 degrees C or in the absence of ligand, most of the receptor was present in membrane fractions (pellet at 27000 or 105000 g), whereas, when platelets were preincubated at 37 degrees C with iloprost, the receptor was found mainly in the cytosolic fraction. In platelets preincubated with iloprost at 4 degrees C, two classes of binding sites were present, whereas after preincubation at 37 degrees C only the lower-affinity sites were detected. After exposure to the agonist, iloprost-induced inhibition of platelet aggregation and activation of adenylate cyclase and cAMP production were significantly lower. Taken together, these data demonstrate that human platelets can internalize a high-affinity binding site for iloprost, presumably the prostacyclin receptor.
Creation of a pericardial window using thoracoscopic techniques. (1992)

The aforementioned minimally invasive technique allows the surgeon to create a large pericardial window with minimal morbidity. Adequate long term drainage is provided and sufficient specimen for pathologic examination is obtained.
Development and use of a conditional antisense mutagenesis system in mycobacteria (2006)

Expression from a 2.3 kb region upstream of the inducible acetamidase gene from Mycobacterium smegmatis was shown to be upregulated by acetamide. A DNA fragment containing the start of the M. smegmatis hisD gene was cloned in front of the promoter, such that the antisense message was produced. When this construct was induced in vivo, the bacteria became phenotypically histidine auxotrophs; this auxotrophy was restored by histidine supplementation. Auxotrophy was not observed under non-induced conditions. Antisense mutagenesis may be useful for observing the phenotypic inactivation of specific mycobacterial genes, and an inducible system such as that described would allow the study of essential genes.
Molecular genetics and targeted therapy of WNT-related human diseases (Review) (2017)

Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription. Germline mutations in WNT signaling molecules cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 mutations in colorectal, endometrial and prostate cancers activate the WNT/β-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in breast, colorectal, gastric, pancreatic and other cancers activate the WNT/β-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, ROR1, tankyrase and β-catenin are targets of anti-WNT signaling therapy, and ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for cancer patients. Different classes of anti-WNT signaling therapeutics are necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST and glycogen synthase kinase 3β (GSK3β) are targets of pro-WNT signaling therapy, and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (blosozumab, BPS804 and romosozumab) monoclonal antibodies are being tested in clinical trials for cancer patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine.
Will Dna Methylation Inhibitors Work In Solid Tumors? A Review Of The Clinical Experience With Azacitidine And Decitabine In Solid Tumors (2010)

The recent approval of azacitidine (Vidaza®), decitabine (Dacogen®) and vorinostat (Zolinza™) for myelodysplastic syndrome and cutaneous T-cell lymphoma has led to a wave of interest in epigenetic therapy. These DNA methylation inhibitors and the histone deacetylase inhibitor clearly have demonstrated activity in hematologic malignancies, but the future role of epigenetic therapy in solid tumors is still unknown. What is not commonly known is that azacitidine and decitabine were originally developed as cytotoxic nucleoside analogs and clinical trials were previously conducted in a variety of cancer types prior to the knowledge of their ability to inhibit DNA methylation. We review the experience of azacitidine and decitabine in early clinical trials and demonstrate the activity of epigenetic therapy in solid tumors.
A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue (2014)

Electroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-µs PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs.
Linear fluorescent oligonucleotide probes with an acridine quencher generate a signal upon hybridisation (2001)

Linear, single stranded probes incorporating a fluorophore and an acridine moiety are weakly fluorescent until hybridised to a complementary target nucleic acid whereupon fluorescence increases due to reduced quenching.
Real-time demonstration of split skin graft inosculation and integra dermal matrix neovascularization using confocal laser scanning microscopy. (2009)

The advent of confocal laser microscopy like the VivaScope 1500, together with "virtual" journals such as ePlasty, enables us to provide exciting images and distribute them widely to a "reading" audience. The development of the early Integra vasculature by neovascularization results in a large-vessel, high-volume, rapid flow circulation contrasting markedly from the inosculatory process in skin grafts and the capillary circulation in normal skin and merits further (planned) investigation.
Late Onset Death of Motor Neurons in Mice Overexpressing Wild-Type Peripherin (1999)

Peripherin, a type III intermediate filament (IF) protein, upregulated by injury and inflammatory cytokines, is a component of IF inclusion bodies associated with degenerating motor neurons in sporadic amyotrophic lateral sclerosis (ALS). We report here that sustained overexpression of wild-type peripherin in mice provokes massive and selective degeneration of motor axons during aging. Remarkably, the onset of peripherin-mediated disease was precipitated by a deficiency of neurofilament light (NF-L) protein, a phenomenon associated with sporadic ALS. In NF-L null mice, the overexpression of peripherin led to early- onset formation of IF inclusions and to the selective death of spinal motor neurons at 6 mo of age. We also report the formation of similar peripherin inclusions in presymptomatic transgenic mice expressing a mutant form of superoxide dismutase linked to ALS. Taken together, these results suggest that IF inclusions containing peripherin may play a contributory role in motor neuron disease.
Detection of 1,5-Anhydroglucitol by Electrochemical Impedance Spectroscopy (2014)

Multiple markers are used to assess glycemic control in patients with diabetes mellitus (DM). New technology that permits simultaneous detection of multiple biomarkers combined with those used at the point of care indicative of glycemic control, including glycemic variability determined from 1,5-anhydroglucitol measurement, could provide better management and further insight into the disease. This platform was based on previous research involving glucose detection and uses electrochemical impedance spectroscopy to detect a range of 1,5-anhydroglucitol concentrations at an optimal binding frequency. The enzyme pyranose oxidase was fixed to gold electrodes while a sine wave of sweeping frequencies was induced in purified solutions and in variable presence of whole blood. The optimal binding frequency for the detection of 1,5-anhydroglucitol was found to be 3.71 kHz. The impedance response compared to the concentration of target present was found to have a logarithmic slope of 7.04 with an R-squared value of 0.96. This response includes 2 experimental sets, a single test of a low concentration range and a high concentration range with 5 replicates. The relative standard deviation of the high range varied from 28% to 27% from lowest to highest concentrations. Best detection in complex solutions was found in lower blood concentrations of 0.5% and 1%, but maintained relatively high accuracy in concentrations 5% and 10%. The sensor platform was successfully evaluated at a high dynamic range of 1,5-AG in purified solutions. In the presence of whole blood, lowest percentages yielded the best results indicating that filtering interferents may be necessary in final device architecture.
Hematopoietic stem cell transplant as a platform for tumor immunotherapy. (2004)

Blood or marrow transplantation (BMT) has been utilized as a cancer therapy with varying levels of success. While it has been an important option for many hematological malignancies, it has met with less success in solid tumors. More recently, new combinations of therapies with BMT have been developed to enhance the efficacy of this therapy and to expand the number of target tumors. This review highlights current uses of BMT, rationales for experimental approaches using BMT alone or as a part of a combination therapy, and reviews some of the novel therapies that have been developed in tumor immunotherapy with BMT, in addition to the implications for translation.
THE AMINO ACIDS OF HUMAN SWEAT (1946)

We have previously described microbiological procedures for the determination of amino acids in blood plasma (1,2 ). These methods are now applied to sweat and certain experiments are carried out with the view of investigating amino acid secretion by the sweat glands. The amounts of ten individual amino acids in sweat are reported for the first time.
A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy (2015)

The last several years have witnessed exciting progress in the development of immunotherapy for the treatment of cancer. This has been due in great part to the development of so-called checkpoint blockade. That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. It is clear that tumors evade the immune response by usurping pathways that play a role in negatively regulating normal immune responses. In this regard, adenosine in the immune microenvironment leading to the activation of the A2a receptor has been shown to represent one such negative feedback loop. Indeed, the tumor microenvironment has relatively high concentrations of adenosine. To this end, blocking A2a receptor activation has the potential to markedly enhance anti-tumor immunity in mouse models. This review will present data demonstrating the ability of A2a receptor blockade to enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as several recent studies have demonstrated that under certain conditions A2a receptor blockade can enhance tumor progression, we will also explore the complexities of adenosine signaling in the immune response. Despite important nuances to the A2a receptor pathway that require further elucidation, studies to date strongly support the development of A2a receptor antagonists (some of which have already been tested in phase III clinical trials for Parkinson Disease) as novel modalities in the immunotherapy armamentarium.
A Three‐Dimensional Metal–Organic Framework with an Unprecedented Octahedral Building Unit (2005)

Unusual octahedral hexamers built up from triangular, corner-linked cobalt trimers (see figure), form the basis of a novel three-dimensional cobalt isophthalate obtained by a solvothermal route. This structure provides a new example of the concept of scale chemistry, in which an {Na6Co6O26} “super octahedron” is connected in a classical ReO3 architecture. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z502185_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Immune reconstitution of B‐cell lymphoma patients receiving CHOP‐based chemotherapy containing rituximab (2010)

Sixty-six B-cell lymphoma patients were treated with a CHOP-based chemotherapy containing rituximab (R-CHOP-like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty-five patients (83.3%) underwent six cycles of the R-CHOP-like regimen. CD19(+) and CD20(+) cells were completely eliminated from the peripheral blood after one cycle of the R-CHOP-like regimen; they were detected again 6 months after the therapy. One year after the therapy, B-cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3(+) , CD8(+) and CD56(+) cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4(+) T-cells were at their lowest after six cycles of the regimen and recovered slowly for 2 years after the therapy; however, their numbers were still lower than that at diagnosis. Immunoglobulins decreased over six cycles of the R-CHOP-like regimen and then recovered gradually for 2 years after the therapy. The percentage of IgG, IgA and IgM 2 years after the therapy compared with those at diagnosis was 93.9%, 90.1%, 76.3%, respectively. Twelve infectious complications occurred which consisted of three febrile neutropenia, three Herpes Zoster, two tympanitis, two Pneumocystis jiroveci pneumonia and two hepatitis B virus reactivation. B-cells required 1 year and CD4(+) T-cells and immunoglobulins needed 2 years to recover after the therapy.
Pure Blue Laser Diodes Based on Nonpolar m-Plane Gallium Nitride with InGaN Waveguiding Layers (2007)

Blue laser diodes (LDs) based on m-plane gallium nitride were demonstrated by using m-plane GaN substrates. The lasing wavelength and the threshold current under pulsed operation were 451.8 nm and 134 mA (22.3 kA/cm2), respectively. The device structures consisted of InGaN-based multi-quantum wells, InGaN guiding layers, and Al-containing cladding layers. The InGaN guiding layers play two roles; as appropriate optical waveguides for longer lasing wavelengths and for the prevention of macroscopic cracks parallel to the c-plane. The latter is an indispensable technology in order to fabricate nonpolar LDs for longer wavelengths beyond the blue region.
Preparation and characterization of alginate/gelatin blend fibers (2005)

Abstract Alginate and gelatin blend fibers were prepared by spinning their solution through a viscose‐type spinneret into a coagulating bath containing aqueous CaCl 2 and ethanol. The structure and properties of the blend fibers were studied with the aid of infrared spectra, scanning electron micrography, X‐ray diffraction, and thermogravimetric analysis. Mechanical properties and water‐retention properties were measured. The best values of the tensile strength and breaking elongation of blend fibers were obtained when gelatin content was 30 wt %. The water‐retention values of blend fibers increase as the amount of gelatin is raised. The structural analysis indicated that there was strong interaction and good miscibility between alginate and gelatin molecules resulted from intermolecular hydrogen bonds. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1625–1629, 2005
Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells (1995)

These results suggest that bFGF may promote angiogenesis both by a direct effect on endothelial cells and also indirectly by the upregulation of VEGF in VSMCs. The synergy demonstrated between hypoxia and either bFGF or TGF-beta 1 suggests that multiple diverse stimuli may interact via the upregulation of VEGF expression in VSMCs to amplify the angiogenic response.
Enhancement of sparc (osteonectin) synthesis in arthritic cartilage: Increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures (1996)

These findings suggest that various growth factors and cytokines, including TGF beta 1 and IL-1 beta, regulate the production of SPARC by chondrocytes at pre- and posttranslational levels, and that SPARC synthesis is markedly enhanced in arthritic joints.
Detection of Antibody to Hepatitis C Virus in Prospectively Followed Transfusion Recipients with Acute and Chronic Non-A, Non-B Hepatitis (1989)

We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.
Text Understanding with the Attention Sum Reader Network (2016)

Several large cloze-style context-questionanswer datasets have been introduced recently: the CNN and Daily Mail news data and the Children's Book Test. Thanks to the size of these datasets, the associated text comprehension task is well suited for deep-learning techniques that currently seem to outperform all alternative approaches. We present a new, simple model that uses attention to directly pick the answer from the context as opposed to computing the answer using a blended representation of words in the document as is usual in similar models. This makes the model particularly suitable for questionanswering problems where the answer is a single word from the document. Ensemble of our models sets new state of the art on all evaluated datasets.