gebhart/patrepeval huggingface dataset:
Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells (1991)

We have used the nested polymerase chain reaction (PCR) combined with fluorescence-activated cell sorting to define sites of latency of human cytomegalovirus (HCMV) in the peripheral blood of healthy subjects. Peripheral blood mononuclear (PBM) cells were separated into T cell or non-T cell populations and monocytes, and were then analysed by PCR for the presence of HCMV DNA. In five of six seropositive subjects, HCMV was found predominantly in the non-T cell population. Further analysis suggested that the virus was present in adherent cells and CD14+ cells. In three of nine seronegative subjects we could demonstrate HCMV DNA, which we do not believe was due to contamination, reproducibly by PCR. In one of these seronegative subjects, HCMV DNA was present predominantly in the non-T cell fraction of PBM cells. No HCMV DNA was detectable in the remaining six seronegative subjects. We conclude that, within the PBM cells of normal asymptomatic seropositive and some seronegative subjects, HCMV is present predominantly in the monocyte fraction. In addition, the detection of HCMV sequences in seronegative subjects may indicate that infection with HCMV is more widespread than conventional seroepidemiology suggests.
Highly Stretchable Resistive Pressure Sensors Using a Conductive Elastomeric Composite on a Micropyramid Array (2014)

A stretchable resistive pressure sensor is achieved by coating a compressible substrate with a highly stretchable electrode. The substrate contains an array of microscale pyramidal features, and the electrode comprises a polymer composite. When the pressure-induced geometrical change experienced by the electrode is maximized at 40% elongation, a sensitivity of 10.3 kPa(-1) is achieved.
Comparative trial of Viokase®, pancreatin and Pancrease® pancrelipase (enteric coated beads) in the treatment of malabsorption in cystic fibrosis (1982)

ABSTRACT. Pancreatic extracts, even in high doses, usually fail to completely control steatorrhoea in cystic fibrosis (CF), due to inactivation of the enzymes by acid and pepsin. Pancrease is a new formulation consisting of pH-sensitive, enteric coated beads which protect the pancreatic enzymes from acid and pepsin denaturation. Twelve patients with CF entered an outpatient study to examine the effectiveness of this product compared with that of a conventional product (Viokase®). Two doses for each product were used during four sequential 4-week periods. Twenty-two capsules of Pancrease® daily was significantly better than 32 capsules of Viokase® daily (faecal fat excretion 8.7 ± 4.1 g/day, 17.3 ± 9.1 g/day, p < 0.01; coefficient of absorption 89.5 ± 4.2%, 79.3 ± 9.9%, p < 0.01; bowel actions/day 1.7 ± 0.7, 2.2 ± 0.9, p < 0.05; rank scores of stool odour and stool consistency, both p < 0.05; parent's treatment preference p < 0.01). No difference was detected between Viokase® 32 capsules daily and Pancrease® 11 capsules daily, but both were significantly better than 16 capsules of Viokase® daily.
Imaging Concrete Structures Using Air-Coupled Impact-Echo (2007)

In this paper, air-coupled impact-echo is successfully applied for nondestructive evaluation of concrete. The air-coupled sensor is a small (6.3mm diameter) measurement microphone located several centimeters above the top surface of the concrete being evaluated. Unwanted ambient acoustic noise is attenuated by a specially designed sound insulation enclosure. Test results show that air-coupled sensors are effective for impact-echo when appropriate impactors are used. Impact-echo data obtained by air-coupled sensors are equivalent to those obtained by conventional contact sensors. Test results from concrete slabs containing artificial delaminations and voids are reported, where an air-coupled impact-echo scan is conducted over the entire slab area. Defects are located in the generated two-dimensional contour image. The areal size of defects are accurately determined when the measurement point spacing in the scan is smaller than half of the expected defect size. Test results from air-coupled impact-echo scans carried out over internal metal and plastic ducts within another concrete slab are also reported. The goal of the experiment is to investigate the grouting condition inside the ducts. Impact-echo line scan images differentiate poorly grouted sections from the well-grouted sections within the metal duct.
Structure-Based Identification of Small Molecule Antiviral Compounds Targeted to the gp41 Core Structure of the Human Immunodeficiency Virus Type 1 (1999)

Recent X-ray crystallographic determination of the HIV-1 envelope glycoprotein gp41 core structure opened up a new avenue to discover antiviral agents for chemotherapy of HIV-1 infection and AIDS. We have undertaken a systematic study to search for anti-HIV-1 lead compounds targeted to gp41. Using molecular docking techniques to screen a database of 20 000 organic molecules, we found 16 compounds with the best fit for docking into the hydrophobic cavity within the gp41 core and with maximum possible interactions with the target site. Further testing of these compounds by an enzyme-linked immunosorbent assay and virus inhibition assays discerned two compounds (ADS-J1 and ADS-J2) having inhibitory activity at micromolar concentrations on the formation of the gp41 core structure and on HIV-1 infection. These two compounds will be used as leads to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure.
The Role of Cyclooxygenase and Lipoxygenase in Cancer Chemoprevention (2000)

The involvement of prostaglandins (PGs) and other eicosanoids in the development of human cancer has been known for over two decades. Importantly, an increase in PG synthesis may influence tumor growth in human beings and experimental animals, and numerous studies have illustrated the effect of PG synthesis on carcinogen metabolism, tumor cell proliferation and metastatic potential. PGs produced by cyclooxygenases (COXs) are represented by a large series of compounds that mainly enhance cancer development and progression, acting as carcinogens or tumor promoters, with profound effects on carcinogenesis. Further investigations suggest that arachidonic acid (AA) metabolites derived from lipoxygenase (LOX) pathways play an important role in growth-related signal transduction, implying that intervention through these pathways should be useful for arresting cancer progression. We discuss here the implications of COX and LOX in colon, pancreatic, breast, prostate, lung, skin, urinary bladder and liver cancers. Select inhibitors of COX and LOX are described, including nonsteroidal antiinflammatory drugs (NSAIDs), selective COX-2 inhibitors, curcumin, tea, silymarin and resveratrol, as well as a method useful for evaluating inhibitors of COX. Although a substantial amount of additional work is required to yield a better understanding of the role of COX and LOX in cancer chemoprevention, it is clear that beneficial therapeutic effects can be realized through drug-mediated modulation of these metabolic pathways.
The conclusion of a comparative efficacy study of fluralaner and sarolaner against the tick Amblyomma americanum on dogs is based on results obtained at study times that are outside the fluralaner label recommendations (2017)

The only fluralaner-related conclusion presented in a study comparing the efficacy of fluralaner and sarolaner for control of the tick Amblyomma americanum on dogs is based on study times that are outside the label administration recommendations. Label recommendations for fluralaner treatment of A. americanum on dogs in the USA require re-administration at 56 days. This 56 day re-administration was not conducted in the study; therefore, all assessed time points following 56 days post-treatment in the study present comparisons that are not consistent with fluralaner administration recommendations. The only comparative time point assessed prior to 56 days showing a difference between treatments was at 42 days post-administration, a time point when methodological problems were identified by the investigators. Therefore, the only comparative study conclusion that a difference was shown between fluralaner and sarolaner beyond 6 weeks (42 days) after treatment is not based on recommended product use. Furthermore, if the study does not show that there is a difference between the treatments at times when the products are used as recommended, then there also can be no comparative discussion of the risk of tick-borne pathogen transmission risk between treatments.
Nonstimulated Human Uncommitted Mesenchymal Stem Cells Express Cell Markers of Mesenchymal and Neural Lineages (2005)

Ex vivo cultures of human bone marrow-derived mesenchymal stem cells (MSCs) contain subsets of progenitors exhibiting dissimilar properties. One of these subsets comprises uncommitted progenitors displaying distinctive features, such as morphology, a quiescent condition, growth factor production, and restricted tissue biodistribution after transplantation. In this study, we assessed the competence of these cells to express, in the absence of differentiation stimuli, markers of mesoderm and ectodermic (neural) cell lineages. Fluorescence microscopy analysis showed a unique pattern of expression of osteogenic, chondrogenic, muscle, and neural markers. The depicted "molecular signature" of these early uncommitted progenitors, in the absence of differentiation stimuli, is consistent with their multipotentiality and plasticity as suggested by several in vitro and in vivo studies.
Tandem Stille/Suzuki−Miyaura Coupling of a Hetero-Bis-metalated Diene. Rapid, One-Pot Assembly of Polyene Systems (2005)

The synthesis of a hetero-bis-metallo 1,3-butadiene is reported, and its use as an orthogonal Stille and Suzuki−Miyaura coupling partner is detailed. The tin/boron diene participated successfully in a one-pot, sequential Stille and Suzuki−Miyaura coupling protocol, and its utility was demonstrated in the two-step construction of the pentaene side chain of the Fusarium metabolite lucilactaene.
3D modelling and visualization of the human lung (2004)

A method for modelling and visualizing human lungs using knowledge of lung anatomy and high resolution CT (HRCT) images is presented. The model consists of a symbolic description of lung anatomy and a 3D atlas. The 3D atlas is constructed using HRCT volume data. A few anatomical landmarks are determined and are used to divide the lungs into anatomically and diagnostically important regions. The landmarks and the lung regions enable accurate mapping of the model to patient data and enable the system to deal with image and human variability. The model can be displayed as a set of labelled axial slices and as a 3D model of the lungs. The 3D visualization enables rotation and viewing of lung structures, lung features and lung regions from different angles.
Influences of Analyte Injection Volumes and Concentrations on Capillary Chromatography Based on Tube Radial Distribution of Carrier Solvents under Laminar Flow Conditions (2011)

A capillary chromatography called the tube radial distribution chromatography (TRDC) system has been developed using an open capillary tube and a water-hydrophilic/hydrophobic organic solvent mixture carrier solution. In this study, we examined the effects of the analyte injection volume (injection time) and concentration on the chromatograms in the TRDC system using a fused-silica capillary tube (50 µm i.d. and 100 cm effective length) and a water-acetonitrile-ethyl acetate mixture carrier solution (volume ratio, 3: 8: 4). Analyte solutions of 1-naphthol and 2,6-naphthalenedisulfonic acid (1 mM each) were injected into the system with various injection times of 10-1500 s from a height of 20 cm by gravity. They were separated and detected in this order with good reproducibility up to an injection time of 150 s. The analyte solutions (0.075-3.0 mM) were analyzed with the definite injection time of 30 s from a height of 20 cm by gravity. They were separated and detected with a baseline separation and their calibration curves showed linearity up to 1.5 mM. It was confirmed that the TRDC system worked well as a quantitative analysis.
Abstract DDT02-04: A novel PRMT5 inhibitor with potent in vitro and in vivo activity in preclinical lung cancer models (2017)

Abstract PRMT5 is a type II methyltransferase that specifically adds methyl groups to arginine as a long-lasting post-translational modification. The PRMT5/MEP50 complex regulates a plethora of cellular processes, such as epigenetics and splicing, which are notable events involved in tumorigenesis. Although not frequently mutated or amplified in tumors, elevated PRMT5 protein levels in lung and hematologic cancers are correlated with poorer survival. The PRMT5 inhibitor JNJ-64619178 has been selected as a clinical candidate based on its high selectivity and potency (subnanomolar range) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties. JNJ-64619178 binds into the SAM binding pocket and reaches the substrate binding pocket to inhibit PRMT5/MEP50 function in a time-dependent manner. Broad cell line panel profiling of JNJ-64619178 revealed a wide range of sensitivity, which is indicative of a genomic dependency instead of a general cytotoxic on-target consequence of PRMT5 inhibition. Further investigations indicate a synthetic lethal correlation between PRMT5 inhibition and key cancer driver pathways. JNJ-64619178, dosed orally (10 mg/kg, every day), showed selective and efficient blockage of the methylation of SMD1/3 proteins, which are crucial components of the spliceosome and substrates of PRMT5/MEP50. JNJ-64619178 also demonstrated tumor regression in a biomarker-driven human small cell lung cancer xenograft model (NCI-H1048) and prolonged tumor growth inhibition after dosing cessation. In rodent and nonrodent toxicology studies, a tolerated dose of JNJ-64619178 has been identified, with the observed toxicity consistent with on-target activity. In summary, JNJ-64619178 has a favorable preclinical package that supports clinical testing in patients diagnosed with lung cancer and hematologic malignancies. Citation Format: Dirk Brehmer, Tongfei Wu, Geert Mannens, Lijs Beke, Petra Vinken, Dana Gaffney, Weimei Sun, Vineet Pande, Jan-Willem Thuring, Hillary Millar, Italo Poggesi, Ivan Somers, An Boeckx, Marc Parade, Erika van Heerde, Thomas Nys, Carol Yanovich, Barbara Herkert, Tinne Verhulst, Marc Du Jardin, Lieven Meerpoel, Christopher Moy, Gaston Diels, Marcel Viellevoye, Wim Schepens, Alain Poncelet, Joannes T. Linders, Edward C. Lawson, James P. Edwards, Dushen Chetty, Sylvie Laquerre, Matthew V. Lorenzi. A novel PRMT5 inhibitor with potent in vitro and in vivo activity in preclinical lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr DDT02-04. doi:10.1158/1538-7445.AM2017-DDT02-04
Bortezomib (Velcade?) in the treatment of multiple myeloma (2006)

The introduction of bortezomib, a novel first-in-class proteasome inhibitor, has been a major break through in the treatment of multiple myeloma. It is currently approved for the treatment of myeloma in the relapsed setting post transplant or as a second line treatment in patients unsuitable for transplantation. In pre-clinical studies bortezomib showed a number of different anti-myeloma effects including disruption of the cell cycle and induction of apoptosis, alteration of the bone marrow microenvironment and inhibition of nuclear factor kappa B (NFkappaB). Due to its novel mechanism of action, bortezomib has been shown to induce responses in previously refractory patients (including those with poor risk cytogenetics), and results in an increased progression free and overall survival in relapsed patients when compared with dexamethasone treatment alone. It is well tolerated and can be administered in the outpatient setting with manageable toxicities. Peripheral neuropathy is the most common dose limiting toxicity and thrombocytopenia can generally be managed with platelet transfusions without reducing or omitting doses. Bortezomib shows a synergistic effect in combination with dexamethasone and also sensitises myeloma cells to the effects of other chemotherapeutic agents with major response rates of over 50% being shown in the relapsed setting. Initial data from ongoing trials in front line therapy are encouraging with response rates of 80%-90% when bortezomib is given in combination with other agents and importantly, the ability to mobilize peripheral blood stem cells is not impaired.
Hepatitis C virus detection by single-round PCR specific for the terminal 3' noncoding region (1996)

A single-round PCR method with primers specific for the 3' noncoding region (NCR) of hepatitis C virus (HCV) has been developed. Using a double RNAzol-B extraction, a high-temperature reverse-transcription step with SuperScript II reverse transcriptase, and a 40-cycle two-temperature PCR with a TaqStart antibody hot-start procedure, we were able to detect a 92-nucleotide fragment of the recently discovered 98-nucleotide highly conserved sequence at the 3' terminus of the HCV genome. Direct sequencing of the PCR products confirmed the specificity of the PCR and demonstrated conservation in this region. Only one nucleotide change in 14 specimens was found. End point dilution titration of sera with known viral RNA titers showed the sensitivity of the single-round 3' NCR PCR to be comparable to those of the established nested 5' NCR assays (fewer than 25 HCV genome equivalents). To evaluate specificity and sensitivity, a panel of 116 serum samples characterized by nested 5'-end PCR, genotyping, and quantitative assays was tested. A high degree of concordance (96%) between the 3' NCR and 5' NCR PCR results was found. The sequence conservation at the 3' end of the HCV genome among common genotypes and the savings in time, labor, and reagents from a single-round PCR make this assay a useful addition to the detection systems available to identify and monitor HCV infection.
Abstract 1798: Identification of pan-Trk inhibitors for the treatment of Trk-driven cancers (2012)

Abstract The Trk family of genes, which includes trkA/NTRK1, trkB/NTRK2 and trkC/NTRK3, encode the tyrosine kinase receptors for the neurotrophin family of nerve growth factors. Deregulated kinase activity of trk family members is associated with human cancer. Oncogenic translocations involving trkC kinase domain have been identified in AML, salivary gland carcinoma, adult secretory breast cancer, congenital fibrosarcoma, and pediatric nephroma. Oncogenic trkA translocations have been reported in papillary thyroid and colorectal cancers. We have identified orally bioavailable, potent and selective ATP-competitive inhibitors of the trk family of receptor tyrosine kinases and are developing these for the treatment of Trk-driven cancers. AR523 is a pan-Trk inhibitor which demonstrates similar activity against TrkA, TrkB and TrkC receptors in a cell based assay (IC50 ∼10 nM). In a screen at 1 µM against a panel of 230 kinases, AR523 inhibited only three additional kinases more than 50% (TNK2, Bmx and Txk). In cell culture AR523 was found to exhibit selective anti-proliferative activity toward the cell line KM12, which harbors the oncogenic TPM-TrkA translocation, while exhibiting no activity toward HT29, a cell line with no trk gene rearrangements. Studies in mice engrafted with KM12 tumors revealed significant anti-tumor and pharmacodynamic activity of AR523. Administration of a single oral dose of AR523 reduced tyrosine phosphorylation of TrkA by nearly 80% at twelve hours after dosing. Parallel analysis of Akt and Erk revealed reduced phosphorylation of these downstream effectors. Administration of 100 mg AR523 daily for two weeks to mice with KM12 xenografts produced mean tumor growth inhibition of 86% and a mean of 42% tumor regression. AR523 exhibits dose dependent inhibition of tumor growth at 10 and 30 mg/kg in KM12 xenografts with 54 and 72% TGI respectively. AR523 was well-tolerated, causing no weight loss or deaths compared with vehicle control. Increasingly Trk mutations have been shown to be activating and the use of Trk inhibitors may provide a new therapeutic strategy for targeted treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1798. doi:1538-7445.AM2012-1798
Biological applications of atomic force microscopy (1994)

The newly developed atomic force microscope (AFM) provides a unique window to the microworld of cells, subcellular structures, and biomolecules. The AFM can image the three-dimensional structure of biological specimens in a physiological environment. This enables real-time biochemical and physiological processes to be monitored at a resolution similar to that obtained for the electron microscope. The process of image acquisition is such that the AFM can also measure forces at the molecular level. In addition, the AFM can interact with the sample, thereby manipulating the molecules in a defined manner--nanomanipulation! The AFM has been used to image living cells and the underlying cytoskeleton, chromatin and plasmids, ion channels, and a variety of membranes. Dynamic processes such as crystal growth and the polymerization of fibrinogen and physicochemical properties such as elasticity and viscosity in living cells have been studied. Nanomanipulations, including dissection of DNA, plasma membranes, and cells, and transfer of synthetic structures have been achieved. This review describes the operating principles, accomplishments, and the future promise of the AFM.
Targeting LGR5 + cells with an antibody-drug conjugate for the treatment of colon cancer (2015)

Cancer stem cells (CSCs) are hypothesized to actively maintain tumors similarly to how their normal counterparts replenish differentiated cell types within tissues, making them an attractive therapeutic target for the treatment of cancer. Because most CSC markers also label normal tissue stem cells, it is unclear how to selectively target them without compromising normal tissue homeostasis. We evaluated a strategy that targets the cell surface leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a well-characterized tissue stem cell and CSC marker, with an antibody conjugated to distinct cytotoxic drugs. One antibody-drug conjugate (ADC) demonstrated potent tumor efficacy and safety in vivo. Furthermore, the ADC decreased tumor size and proliferation, translating to improved survival in a genetically engineered model of intestinal tumorigenesis. These data demonstrate that ADCs can be leveraged to exploit differences between normal and cancer stem cells to successfully target gastrointestinal cancers.
A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration. (2000)

Stable clinically useful sensor performance was demonstrated as early as 7 days after implantation and for a sensor lifetime of 3-5 months. This type of subcutaneous glucose sensor appears to be promising as a continuous and painless long-term method for monitoring blood glucose. Specifically sensors with top-layer materials that stimulate angiogenesis at the sensor/tissue interface may have better dynamic measurement range, longer lifetimes, and better calibration stability than our previously reported sensors.