gebhart/patrepeval huggingface dataset:
Transforming growth factor-beta potentiates vitamin D3-induced terminal monocytic differentiation of human leukemic cell lines (1993)

We have investigated the effects of 1,25-dihydroxyvitamin D3 (D3) and/or transforming growth factor (TGF)-beta on one monocytic (U-937) and two human promyelocytic (HL-60 and AML-193) leukemic cell lines. D3 addition induces a partial monocytic maturation of the cell lines, whereas TGF-beta treatment is largely ineffective. Combined treatment with TGF-beta and D3 causes terminal monocytic maturation, as evaluated both by assessment of a large spectrum of membrane Ag and by functional assays. Furthermore, sequential addition of the two inducers showed that pretreatment with TGF-beta 1 followed by incubation with D3, but not vice versa, induces monocytic maturation as effectively as simultaneous treatment with both agents. In liquid culture the proliferative activity of these cell lines is slightly decreased by D3 and virtually unaffected by TGF-beta, whereas combined treatment with D3 and TGF-beta induces a markedly potentiated inhibitory effect. Furthermore, TGF-beta/D3 treatment (but not D3 alone) elicits the expression of membrane CD14, FcRI, FcRII, CD11a, CD11b, CD11c, ICAM-1, and PECAM-1 Ag at a level comparable to that observed on normal human monocytes. It is noteworthy that several of these Ag play an important role in monocyte physiology (e.g., CD14 Ag mediates the binding of bacterial LPS to monocytes). Treatment with both TGF-beta and D3 (but not D3 alone) induces superoxide anions and H2O2 production similar to that of circulating monocytes. In semisolid culture, D3 and TGF-beta alone cause, respectively, a marked and slight loss of cloning efficiency of the cell lines, whereas their combined addition synergistically results in a complete loss of the cloning capacity. These findings suggest a physiologic role for TGF-beta in monocyte maturation. Furthermore, they may pave the way to the design of clinical protocols combining D3 and TGF-beta in the differentiation therapy of acute promyelocytic/myelomonocytic leukemia.
Slim-Hole Drilling in Harsh Environments (1991)

Summary Wells with small liners occasionally require unique methods of drilling, completion, and reworking, especially deep-hole wells and wells with severe doglegs. Innovative drilling procedures were used successfully on two wells with those downhole conditions. On the first well, cement was drilled in a 3½-in. liner with a small mud motor and heavyweight mud. On the second well, a large mud motor was used as a downhole power swivel to drill in a 3½-in. liner. Both jobs were completed at depths of 13, 000 to 20, 000 ft with mud weights &amp;gt; 18 lbm/gal and bottomhole temperatures (BHT's) &amp;gt;300°F.
Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice (2016)

Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.
Isolation of peptides that inhibit binding of basic fibroblast growth factor to its receptor from a random phage-epitope library. (1993)

Basic fibroblast growth factor (bFGF) is known to bind to its cell-surface receptors with high affinity and in a heparin-dependent manner. In an attempt to predict the receptor recognition site on bFGF we screened phage-epitope libraries with monoclonal antibodies DG2 and DE6, which inhibit bFGF binding to its receptor. On the affinity-isolated phages, we identified several peptide sequences as the putative antibody-binding epitopes on bFGF. The identified library epitopes shared the consensus sequence Pro-(Pro/Ser)-Gly-His-(Tyr/Phe)-Lys, corresponding to two continuous protein sequences of bFGF: Pro-Pro-Gly-His-Phe-Lys and Arg-Thr-Gly-Gln-Tyr-Lys at amino acids 13-18 and 120-125 of bFGF, respectively. Synthetic peptides of the corresponding phage epitopes or of the above bFGF sequences specifically inhibited binding of the antibodies to bFGF, blocked binding of bFGF to its high-affinity receptor, and inhibited basal and bFGF-induced proliferation of vascular endothelial cells at submicromolar peptide concentrations. The potent inhibition of bFGF binding and biological activity by peptides recognized by the antibodies suggests that these sequences are functionally involved in receptor binding and may constitute part of the receptor-binding determinants on bFGF.
Humanized 3F8 Anti-GD2Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma (2018)

<h3>Importance</h3> Chimeric and murine anti-G<sub>D2</sub>antibodies are active against neuroblastoma, but the development of neutralizing antibodies can compromise efficacy. To decrease immunogenicity, hu3F8, a humanized anti-G<sub>D2</sub>antibody, was constructed. <h3>Objective</h3> To find the maximum-tolerated dose of hu3F8 with granulocyte-macrophage colony-stimulating factor. <h3>Design, Setting, and Participants</h3> This phase 1 clinical trial used a 3 + 3 dose-escalation design in a single referral center (Memorial Sloan Kettering Cancer Center, New York, New York). Participants were enrolled from December 24, 2012, through May 3, 2016, with follow-up and analyses through February 28, 2018. Eligibility criteria included older than 1 year and resistant or recurrent neuroblastoma regardless of the number or kinds of prior treatments. All 57 participants met the eligibility criteria, received treatment according to the protocol, and were included in all analyses. <h3>Interventions</h3> Treatment cycles were monthly, if human antihuman antibody remained negative. Each cycle comprised hu3F8 infused intravenously for 30 minutes on Monday, Wednesday, and Friday as well as granulocyte-macrophage colony-stimulating factor administered subcutaneously daily from 5 days before infusion through the last day of infusion. After cycle 2, hu3F8 was increased to the highest dose level that had been confirmed as safe. <h3>Main Outcomes and Measures</h3> Toxicity, pharmacokinetics, immunogenicity, and disease response. <h3>Results</h3> Of the 57 participants, 34 (60%) were male and 23 (40%) were female (male-to-female ratio of 1.5), with a median (range) age of 6.8 (2.4-31.3) years at enrollment and a median (range) time of 3.1 (0.6-9.0) years since initial chemotherapy. Participants received a median (range) of 4 (1-15) cycles. Treatment was outpatient with reversible neuropathic pain and without unexpected toxic effects. No maximum-tolerated dose was identified. Dose escalation was associated with increased serum levels and proceeded through dosage of 9.6 mg/kg/cycle (approximately 288 mg/m<sup>2</sup>), which is more than 2.5 times higher than the standard dosage of 75 mg/m<sup>2</sup>/cycle or 100 mg/m<sup>2</sup>/cycle of dinutuximab and m3F8. Human antihuman antibody positivity developed in 5 of 57 patients (9%) after cycle 1, including in 1 of 10 patients (10%) not previously treated with anti-G<sub>D2</sub>antibody and in 4 of 47 patients (9%) previously exposed to 1 or 2 anti-G<sub>D2</sub>antibodies. Antineuroblastoma activity included major responses associated with higher dosing and prolonged progression-free survival despite a history of relapses. <h3>Conclusions and Relevance</h3> This phase 1 clinical trial found hu3F8 to be associated with modest toxic effects, low immunogenicity, and substantial antineuroblastoma activity; phase 2 trials are in progress. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01757626
Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections (2012)

Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes doublestranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections. Keywords: Coronavirus, influenza, innate immune system, respiratory syncytial virus, rhinovirus, poly (ICLC), Toll-like receptor 3
Use of guanylyl cyclase c for detecting micrometastases in lymph nodes of patients with colon cancer (1998)

Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.
Boolector 2.0 (2015)

In this paper, we discuss the most important changes and new features introduced with version 2.0 of our SMT solver Boolector, which placed first in the QF_BV and QF_ABV tracks of the SMT competition 2014. We further outline some features and techniq
Modeling, Synthesis and Biological Evaluation of Potential Retinoid X Receptor (RXR) Selective Agonists: Novel Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) (2009)

This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased triglyceride concentrations, presumably by disruption of RXR heterodimerization with other nuclear receptors. The novel analogues in the present study have been evaluated for RXR activation in an RXR mammalian-2-hybrid assay as well as an RXRE-mediated transcriptional assay and for their ability to induce apoptosis as well as for their mutagenicity and cytotoxicity. Analysis of 11 novel compounds revealed the discovery of three analogues that best induce RXR-mediated transcriptional activity, stimulate apoptosis, have comparable K(i) and EC(50) values to 1, and are selective RXR agonists. Our experimental approach suggests that rational drug design can develop new rexinoids with improved biological properties.
Multiuser spreading codes retaining orthogonality through unknown time- and frequency-selective fading (2002)

Suppression of multiuser interference (MUI) and mitigation of time- and frequency-selective effects constitute major challenges in the design of third-generation wireless mobile systems. Relying on block spreading and judiciously chosen time-frequency guard intervals, we propose a multiuser transceiver that eliminates MUI deterministically and guarantees symbol detectability in the presence of unknown time- and frequency-selective fading. Blind channel estimation is also investigated. Simulation results demonstrate the validity of the theoretical results and show improved performance of the proposed transceiver over a multi-user time-frequency RAKE receiver.
Analytic Anti‐Aliasing of Linear Functions on Polytopes (2012)

Abstract This paper presents an analytic formulation for anti‐aliased sampling of 2D polygons and 3D polyhedra. Our framework allows the exact evaluation of the convolution integral with a linear function defined on the polytopes. The filter is a spherically symmetric polynomial of any order, supporting approximations to refined variants such as the Mitchell‐Netravali filter family. This enables high‐quality rasterization of triangles and tetrahedra with linearly interpolated vertex values to regular and non‐regular grids. A closed form solution of the convolution is presented and an efficient implementation on the GPU using DirectX and CUDA C is described.
Sensorineural hearing loss (1990)

We report 2 patients over the age of 70 who, while on valproate (VPA) for complex partial seizures, developed sensorineural hearing loss. Following discontinuation of VPA for nonaudiologic reasons, the patients reported improved hearing which was confirmed by audiometry. These findings represent VPA-induced sensorineural hearing loss, possibly in preexisting presbycusis.
The use of temporal information in the regularization of the inverse problem of electrocardiography (1992)

The inverse problem of electrocardiography is solved in order to reconstruct electrical events within the heart from information measured noninvasively on the body surface. These electrical events can be deduced from measured epicardial potentials; therefore, a noninvasive method of recovering epicardial potentials from body surface data is useful in clinical and experimental work. The ill-posed nature of this problem necessitates the use of regularization in the solution procedure. Inversion using Tikhonov zero-order regularization, a quasi-static method, had been employed previously and was able to reconstruct, with relatively good accuracy, important events in cardiac excitation (maxima, minima, etc.). Taking advantage of the fact that the process of cardiac excitation is continuous in time, one can incorporate information from the time progression of excitation in the regularization procedure using the Twomey technique. Methods of this type were tested on data obtained from a human-torso tank in which a beating canine heart was placed in the correct human anatomical position. The results show a marked improvement in the inverse solution when these temporal methods are used, and demonstrate that important physiological events (e.g., right ventricular breakthrough) not detected by the quasi-static approach, are reconstructed using these methods. In addition, the results indicate that as the time interval between sampled maps is reduced, the quality of the solutions that use this temporal regularization is greatly improved.
Cre‐mediated site‐specific gene integration for consistent transgene expression in rice (2004)

To minimize expression variability amongst transgenic lines, we have utilized the strategy of Cre/lox-mediated site-specific gene integration. This method allows the precise integration of a transgene in a lox site previously placed in the genome. Using the biolistic method for DNA delivery, we have generated several site-specific integrant lines, derived from three different target lines. About 80% of the selected lines contain precise integration of the gusA reporter gene and fall into two categories: single-copy (SC) lines that contain site-specific integration without additional random integrations, and multicopy (MC) lines that contain random integrations in addition to the site-specific integration. The expression of the gusA gene was studied in callus cells and regenerated plants. The isogenic SC lines displayed significantly lower expression variation, whereas much higher expression variation was observed in MC lines. Furthermore, stable inheritance of the gusA gene was observed in T1 plants derived from a subset of SC lines. This demonstrates that consistent gene expression can be obtained in rice by Cre-mediated site-specific integration.
Increased intraplatelet levels of platelet‐derived growth factor and transforming growth factor‐β in patients with myelofibrosis with myeloid metaplasia (1991)

Platelet-derived growth factor (PDGF) is thought to play some role in the genesis of fibrosis associated with myeloproliferative disorders. In addition, transforming growth factor-beta (TGF-beta) has been confirmed to promote fibrotic process. Both PDGF and TGF-beta have been shown to cooperate with epidermal growth factor (EGF) in regulating the growth of human marrow fibroblasts. All three are contained in platelet alpha-granules. We report the results of a study in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF, TGF-beta and EGF-like activities in circulating platelets from patients compared to healthy subjects. In contrast to EGF-like intraplatelet levels which were similar in patients and in normal donors (1-4 ng/10(9) platelets), we found constantly higher values for both PDGF and TGF-beta in MMM patients. In both radioimmunoassay (RIA) and assay for mitogenic activity on human bone marrow fibroblasts, PDGF levels were increased on the average 2-3.5-fold over the levels found in normal donors (P less than 0.01 and P less than 0.001, respectively). PDGF serum levels in patients were consistent with those found in platelets. In platelet-poor plasma (PPP), PDGF concentrations were undetectable or congruent to 2 ng/ml in patients and in control donors as well. The total TGF-beta activity in platelet lysates, determined using a competitive radioreceptor binding assay on Swiss 3T3 mouse cells and an inhibition growth assay on CCL64 cells, was found 2-3-fold increased in patients with MMM as compared to control subjects (P less than 0.003). These results emphasize that, not only PDGF, but also TGF-beta are implicated in the myelofibrosis with myeloid metaplasia.
The Nithsdale Schizophrenia Surveys. XIV: Plasma Lipid Peroxide and Serum Vitamin E Levels in Patients with and Without Tardive Dyskinesia, and in Normal Subjects (1995)

The results do not support the hypothesis that TD is mediated through free radical damage to neurons, but suggest increased free radical activity in schizophrenia.
/sup 6/LiI(Eu) in neutron and /spl gamma/-ray spectrometry-a highly sensitive thermal neutron detector (2005)

Europium doped /sup 6/LiI crystals (enriched to 96%/sup 6/Li) have been studied in neutron detection and /spl gamma/-ray spectrometry. Two crystals, 50 mm/spl times/5 mm and 30 mm/spl times/3 mm in size were coupled to a calibrated Photonis XP5200 photomultiplier, were tested. The response of /sup 6/LiI(Eu) to neutrons emitted from a paraffin moderated Pu-Be source has been investigated and the thermal neutron peak has been found at a Gamma Equivalent Energy (GEE) of about 3.5 MeV. The high sensitivity of the /sup 6/LiI(Eu) crystal is demonstrated by the observation of a neutron peak at a dose equivalent as low as 0.05 /spl mu/Sv/h. Apart from the neutron response, the light output, energy resolution and nonproportionality of the /sup 6/LiI(Eu) crystals versus /spl gamma/-ray energies have been measured. The light yield of 1.5/spl times/10/sup 4/ ph/MeV (about 40% of NaI(Tl)) was obtained and the energy resolution at 662 keV (/sup 137/Cs) of 7.5/spl plusmn/0.1% was found for the large crystal. The linearity of the light output with energy has been measured and is better compared to NaI(Tl). Due to the high sensitivity to thermal neutrons and good proportionality against /spl gamma/-ray energy, the /sup 6/LiI(Eu) crystal was tested with a few samples of nuclear materials. Shielded samples can be recognized via detection of neutrons following spontaneous fission.
Xenon: elemental anaesthesia in clinical practice (2005)

The 'noble' gases have been known to have anaesthetic properties for 50 years yet only recently has their application become a clinical reality. In this review we describe the preclinical and clinical studies that have led to a resurgence of interest in the use of the element xenon as an anaesthetic. Furthermore, we highlight specific areas where xenon demonstrates advantages over other anaesthetics, including safety, beneficial pharmacokinetics, cardiovascular stability, analgesia and neuroprotection.
Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein. (1991)

The p21ras GTPase-activating protein (GAP) down-regulates p21ras by stimulating its intrinsic GTPase activity. GAP is found predominantly as a monomer in the cytosol of normal cells. However, in cells expressing an activated cytoplasmic protein-tyrosine kinase, p60v-src, or stimulated with epidermal growth factor, GAP becomes phosphorylated on tyrosine and serine and forms distinct complexes with two phosphoproteins of 62 and 190 kDa (p62 and p190). In v-src-transformed Rat-2 cells, a minor fraction of GAP associates with the highly tyrosine phosphorylated p62 to form a complex that is localized at the plasma membrane and in the cytosol. In contrast, the majority of GAP enters a distinct complex with p190 that is exclusively cytosolic and contains predominantly phosphoserine. Epidermal growth factor stimulation also induces a marked conversion of monomeric GAP to higher-molecular-weight species in rat fibroblasts. The GAP-p190 complex is dependent on phosphorylation and shows reduced GAP activity. These results indicate that protein-tyrosine kinases induce GAP to form multiple heteromeric complexes, which are strong candidates for regulators or targets of p21ras.
A Practical Synthesis of l-Azatyrosine (1996)

Oncogenic Ras genes and the G-proteins which they encode are important targets for anticancer research. Ras proteins have been implicated to function as components of the cellular signal transduction pathways related to cell proliferation and differentiation. In their oncogenic form, the natural GTP-ase activity of Ras proteins is inhibited, leading to overstimulation of the signaling pathway for cell growth. The potential importance of oncogenic Ras genes and gene products as targets for cancer chemotherapy is underscored by the observation that up to 40% of human colon tumors and 95% of human pancreatic tumors have been found to contain oncogenic Ras genes.