gebhart/patrepeval huggingface dataset:
Immunohistological studies with A1-3, a monoclonal antibody to activated human monocytes and macrophages. (1986)

A wide variety of monoclonal antibodies (mAb) have now been produced which recognize cell surface antigens on human peripheral blood monocytes. However, few of these mAb demonstrate specificity for monocytes, and fewer still recognize antigens exclusively on monocytes activated by one or more stimuli and/or block specific monocyte functions. The mAb A1-3 binds to lipopolysaccharide (LPS)-stimulated monocytes but not to resting blood monocytes, and inhibits the procoagulant activity of these LPS-activated cells. By using this mAb, we examined the reactivity of monocytes/macrophages (MO) in a broad range of normal and inflammatory tissues by means of a sensitive, four-layer immunoperoxidase technique. Cells of the MO system, in addition to lymphocytes and dendritic cells resident in lymphoid tissues, liver, lung, and other organs, were nonreactive with the A1-3 mAb. In contrast, intense staining of inflammatory MO was found in biopsies from patients with renal allograft rejection, acute glomerulonephritis, or granulomatous diseases. This apparent restriction of A1-3 binding to inflammatory, "activated" MO suggests that A1-3 mAb will be useful for the analysis of MO "activation" in many pathologic processes.
Neuroactive Toxins of Spider Venoms (1991)

A variety of neuroactive toxins have been found in the venom of spiders. The venom of Latrodectus mactans(black widow spider) is known as a potent neurotoxin, fatal to humans and animals. The effective component, α-latrotoxin (Mr=130,000) acts on the nerve terminals, causing massive release of transmitters and depletion of the synaptic vesicles, by inducing influx of cations such as Ca2+and Na+through the channels existing in the presynaptic nerve terminals.In the venom of Araneidspiders, a different type of toxin from the black widow spider venom was found. Joro spider toxin (JSTX) from Nephila clavat, NSTX from Nephila maculata, and argiopine (argiotoxin) from Argiope lobataact postsynaptically on glutamate receptors. These toxins share a common structure of a phenolic moiety connected to a polyamine. Chemical synthesis of these low molecular weight toxins has enabled morphological and biochemical studies of the glutamate receptors.Recently, a third group of neurotoxins was found in genus Agelenidae. A number of toxins isolated from the venom of Agelenopsis aperta, Hololena curtaand Agelena opulentawere found to block synaptic transmission by a presynaptic mechanism. The structures of a number of Agelenidaetoxins have been characterized, and it has been shown that they block presynaptic calcium channels. These toxins should serve as useful tools for isolating and characterizing neuronal calcium channel proteins.
T-cell lines established from human T-lymphocytic neoplasias by direct response to T-cell growth factor. (1980)

Long-term growth of lymphoblastoid T cells from tissue samples from six of six patients with cutaneous T-cell lymphoma (CTCL) and six of six patients with acute T-lymphoblastic leukemia (ALL) has been achieved by using partially purified mitogen-free human T-cell growth factor (pp-TCGF). One cell line, CTCL-2, is now independent of added growth factor; the others continue to show absolute dependency on its presence. All lines have been in continuous culture for at least 4 months and some for > 1 year. They are erythrocyte-rosette positive and are negative for Epstein-Barr virus nuclear antigen. Most of the lines are negative for Fc and complement receptors and for surface immunoglobulin except that CTCL-1 and CTCL-2 have some cells positive for these cell surface markers. Results of histochemical studies on these cell lines are similar to the known patterns for fresh cells from their disease of origin. Cell line CTCL-3 has an abnormal karyotype, but no detectable chromosomal abnormalities were found in the other lines, consistent with the karyologic features of their clinical sources. Because T cells from normal donors do not respond to pp-TCGF unless the cells are first "activated" by a lectin mitogen such as phytohemagglutinin or an antigen, the direct response to pp-TCGF of T cells from patients with T-cell neoplasias suggests that the cell lines represent a transformed neoplastic cell population. Although some of the cell lines may be normal T cells activated by the malignant cells, the morphologic and histochemical properties of the cell lines, the abnormal karyotype of CTCL-3, and the independent growth of CTCL-2 support the conclusion that most of these cell lines are of malignant origin.
Epidermal Growth Factor Receptor vIII Expression in U87 Glioblastoma Cells Alters Their Proteasome Composition, Function, and Response to Irradiation (2008)

Little is known about the factors that influence the proteasome structures in cells and their activity, although this could be highly relevant to cancer therapy. We have previously shown that, within minutes, irradiation inhibits substrate degradation by the 26S proteasome in most cell types. Here, we report an exception in U87 glioblastoma cells transduced to express the epidermal growth factor receptor vIII (EGFRvIII) mutant (U87EGFRvIII), which does not respond to irradiation with 26S proteasome inhibition. This was assessed using either a fluorogenic substrate or a reporter gene, the ornithine decarboxylase degron fused to ZsGreen (cODCZsGreen), which targets the protein to the 26S proteasome. To elucidate whether this was due to alterations in proteasome composition, we used quantitative reverse transcription-PCR to quantify the constitutive (X, Y, Z) and inducible 20S subunits (Lmp7, Lmp2, Mecl1), and 11S (PA28alpha and beta) and 19S components (PSMC1 and PSMD4). U87 and U87EGFRvIII significantly differed in expression of proteasome subunits, and in particular immunosubunits. Interestingly, 2 Gy irradiation of U87 increased subunit expression levels by 16% to 324% at 6 hours, with a coincident 30% decrease in levels of the proteasome substrate c-myc, whereas they changed little in U87EGFRvIII. Responses similar to 2 Gy were seen in U87 treated with a proteasome inhibitor, NPI0052, suggesting that proteasome inhibition induced replacement of subunits independent of the means of inhibition. Our data clearly indicate that the composition and function of the 26S proteasome can be changed by expression of the EGFRvIII. How this relates to the increased radioresistance associated with this cell line remains to be established.
Principles and mechanisms of gas sensing by GaN nanowires functionalized with gold nanoparticles (2006)

Electrical properties of a chemical sensor constructed from mats of GaN nanowires decorated with gold nanoparticles as a function of exposure to Ar, N2, and methane are presented. The Au nanoparticle decorated nanowires exhibited chemically selective electrical responses. The sensor exhibits a nominal response to Ar and slightly greater response for N2. Upon exposure to methane the conductivity is suppressed by 50% relative to vacuum. The effect is fully reversible and is independent of exposure history. We offer a model by which the change in the current is caused by a change in the depletion depth of the nanowires, the change in the depletion depth being due to an adsorbate induced change in the potential on the gold nanoparticles on the surface of the nanowires.
Fast development of source-level debugging system using hardware emulation (2002)

We describe the co-development of a processor and its source-level debugging system using an emulation-based validation technology including hardware emulation, not simulation, Since a source-level debugging system is essential to develop an application system and it takes a long time to validate the functionality of the source-level debugging system, we have adopted hardware emulation for a fast validation and system development. Using this methodology, we were able to validate the source-level debugging system successfully before the chip fabrication.
Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice (2015)

Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.
Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles (2008)

Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were. A possible implication of the latter finding is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics. Particles, and perhaps other vehicles, may enhance local toxicity through indirect mechanisms.
[sup 6]Li and [sup 7]Li Magic-Angle Spinning Nuclear Magnetic Resonance and In Situ X-Ray Diffraction Studies of the Charging and Discharging of Li[sub x]Mn[sub 2]O[sub 4] at 4 V (2000)

and magic‐angle spinning (MAS) nuclear magnetic resonance (NMR) and in situ X‐ray diffraction (XRD) have been used to study lithium manganate cathode materials during and following charging and discharging. Only one major local environment is observed by MAS NMR from 0 to >50% charging, from lithium in the tetrahedral sites of the spinel structure, the resonance shifting by no more than 8 ppm in this range (from its original position at ca. 520 ppm). When the cell is charged above 50%, a new resonance is observed at ≈645 ppm, due to in a spinel local environment with nearby manganese ions in oxidation states close to +4 (e.g., in a composition such as ). The two resonances at ≈520 and 645 ppm are both observed in the range 70 to <80 and 80 to 90% for the samples annealed at 850 and 650°C, respectively. These coexistences occur over the same ranges as the two‐phase coexistence, as observed by XRD during the first charging cycle. Resonances were observed at 830 and 930 ppm, for the samples annealed at 650 and 850°C, respectively, at ≥90% charging. These same resonances were seen after multiple charging cycles and are assigned to defect spinels with high manganese oxidation states. Additional resonances are observed for electrodes with high carbon contents at −2 to −13 ppm, from nonspinel phases, which grow in intensity with the number of charging cycles. The presence of the defect spinels and the additional impurity phases contribute to the reduced capacity of these materials. Three‐phase behavior is observed by in situ XRD during the first discharging cycle. These results are discussed in terms of previous in situ XRD charging/discharging results. © 2000 The Electrochemical Society. All rights reserved.
Comparative Efficacy of Injectable Calcium and Magnesium Salts in the Therapy of Hydrofluoric Acid Burns (1981)

Hydrofluoric acid (HF) causes severe skin burns which often progress in severity despite physiologic neutralization. The currently accepted therapy is the subcutaneous injection of calcium (Ca) gluconate to precipitate the residual free fluoride ion. Magnesium (Mg) also forms an insoluble fluoride salt and is less tissue irritating than Ca. This study compared the effects of subcutaneous injection of saline, Ca gluconate, Mg acetate (MgAc), and Mg sulfate (MgSO4) on lesions resulting from HF burns in rats. Burns treated with either Mg compound healed 3.7 +/- 1.7 days faster (p less than 0.05) developed less severe lesions (p less than 0.01) and exhibited left untreated or treated with saline. There was no difference in the incidence of infection between the study groups. The effects of burns treated with calcium were statistically similar to the control groups. This study suggests that Mg may be more effective than Ca in minimizing the duration, depth, and progression of dermal HF burns.
Prostaglandin endoperoxide E isomerase from bovine vesicular gland microsomes, a glutathione-requiring enzyme. (1977)

Prostaglandin endoperoxide E isomerase catalyzes the isomerization of the endoperoxy group of prostaglandin H and produces prostaglandin E. The enzyme was solubilized with Tween 20 from bovine vesicular gland microsomes and purified 26-fold by successive column chromatography on DEAE-cellulose and omega-aminobutyl Sepharose 4B. The previously known requirement for glutathione was further investigated. The activity of freshly prepared enzyme was destroyed rapidly with a half-life of about 30 min at 24 degrees, pH 8.0. Various thiol compounds including glutathione protected the enzyme from such an inactivation. However, several findings indicated that glutathione was possibly specifically involved as a coenzyme in the isomerase reaction, but was not oxidized in a stoichiometric quantity. The enzyme also isomerized prostaglandin G at a rate approximately half of that of prostaglandin H.
Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen (2015)

WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.
Observations on the effect of massive doses of iron given intravenously to patients with hypochromic anemia. (1946)

Massive doses of iron (from 0.608 to 1.32 Gm. as colloidal terric hydroxide or colloidal ferric oxide) were given intravenously in single infusions to 8 different patients with hypochromic microcytic anemia. One patient was given a second injection after an interval of four months, so that nine administrations were made. The following observations were made:

1. The reticulocyte response was higher in each instance than would be expected in oral therapy. In 3 additional patients in whom injection had to be discontinued after 0.070, 0.180, and 0.123 Gm. of elemental iron had respectively been given, the reticulocyte rises were higher than were the average responses reported by Heath18 after oral therapy. This at least suggests that optimal oral therapy does not provide a maximal stimulus to outpouring of reticulocytes from the bone marrow. Comparable doses of iron given to 3 control subjects with normal hemoglobin levels did not cause a reticulocytosis.

2. The average rate of hemoglobin regeneration per 100 cc. of blood per day was 0.224 Gm.; the lowest value was 0.16 Gm. and the highest 0.27 Gm. These figures were calculated for the rise that occurred from the day of iron administration to the time at which the rate of hemoglobin increase was obviously becoming slower. Since correction was not made for blood loss in 3 of the patients during the period of regeneration, the figures for the rate of hemoglobin formation are lower than they otherwise would have been. Even so they are distinctly greater than those usually obtained following oral therapy (table 2), but no greater than is found in an occasional patient given iron by mouth. The data suggest that the fastest rate of hemoglobin regeneration that can be stimulated by iron in subjects with hypochromic anemia approximates 0.3 Gm. per 100 cc. per day.

3. Calculations indicated that from 71.8 to 99.7 per cent of the injected iron was apparently used for the synthesis of hemoglobin. These figures are likewise lower than they would have been if several of the patients had not lost blood during the recovery period. The observation of other workers that parenterally administered iron is almost completely retained by the body and converted into hemoglobin was therefore confirmed.

4. Toxic reactions to the injected iron are described in detail. They were severe in all but two instances, and in 3 patients were so alarming that injection of iron had to be discontinued. There can be no doubt that the reactions to iron parenterally administered in large doses are great enough to contra-indicate use of this measure as a therapeutic procedure.
RNase T1 mediated base-specific cleavage and MALDI-TOF MS for high-throughput comparative sequence analysis (2003)

Here we devise a new method for high-throughput comparative sequence analysis. The developed protocol comprises a homogeneous in vitro transcription/RNase cleavage system with the accuracy and data acquisition speed of matrix-assisted laser desorption/ionization coupled with time-of-flight mass spectrometry (MALDI-TOF MS). In summary, the target region is PCR amplified using primers tagged with promoter sequences of T7 or SP6 RNA polymerase. Using RNase T1, the in vitro transcripts are base-specifically cleaved at every G-position. This reaction results in a characteristic pattern of fragment masses that is indicative of the original target sequence. To enable high-throughput analysis, samples are processed with automated liquid handling devices and nanoliter amounts are dispensed onto SpectroCHIP arrays for reliable and homogeneous MALDI preparation. This system enables rapid automated comparative sequence analysis for PCR products up to 1 kb in length. We demonstrate the feasibility of the devised method for analysis of single nucleotide polymorphisms (SNPs) and pathogen identification.
Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia? (2000)

Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.
Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study (2010)

Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile [ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7-2.5), 1.1 (0.6-2.2) and 2.4 (1.1-5.1); P(trend) = 0.008]. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.
Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms (2009)

This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.
Diagnosis of Hemochromatosis (1998)

If untreated, hemochromatosis can cause serious illness and early death, but the disease is still substantially under-diagnosed. The cornerstone of screening and case detection is the measurement of serum transferrin saturation and the serum ferritin level. Once the diagnosis is suspected, physicians must use serum ferritin levels and hepatic iron stores on liver biopsy specimens to assess patients for the presence of iron overload. Liver biopsy is also used to establish the presence or absence of cirrhosis, which can affect prognosis and management. A DNA-based test for the HFE gene is commercially available, but its place in the diagnosis of hemochromatosis is still being evaluated. Currently, the most useful role for this test is in the detection of hemochromatosis in the family members of patients with a proven case of the disease. It is crucial to diagnose hemochromatosis before hepatic cirrhosis develops because phlebotomy therapy can avert serious chronic disease and can even lead to normal life expectancy.
Decoding Trajectories from Posterior Parietal Cortex Ensembles (2008)

High-level cognitive signals in the posterior parietal cortex (PPC) have previously been used to decode the intended endpoint of a reach, providing the first evidence that PPC can be used for direct control of a neural prosthesis (Musallam et al., 2004). Here we expand on this work by showing that PPC neural activity can be harnessed to estimate not only the endpoint but also to continuously control the trajectory of an end effector. Specifically, we trained two monkeys to use a joystick to guide a cursor on a computer screen to peripheral target locations while maintaining central ocular fixation. We found that we could accurately reconstruct the trajectory of the cursor using a relatively small ensemble of simultaneously recorded PPC neurons. Using a goal-based Kalman filter that incorporates target information into the state-space, we showed that the decoded estimate of cursor position could be significantly improved. Finally, we tested whether we could decode trajectories during closed-loop brain control sessions, in which the real-time position of the cursor was determined solely by a monkey's neural activity in PPC. The monkey learned to perform brain control trajectories at 80% success rate (for 8 targets) after just 4-5 sessions. This improvement in behavioral performance was accompanied by a corresponding enhancement in neural tuning properties (i.e., increased tuning depth and coverage of encoding parameter space) as well as an increase in off-line decoding performance of the PPC ensemble.