gebhart/patrepeval huggingface dataset:
Azidothymidine-induced cytotoxicity and incorporation into DNA in the human colon tumor cell line HCT-8 is enhanced by methotrexate in vitro and in vivo. (1992)

We have reported that 5-fluorouracil can increase the cytotoxic and antineoplastic activity of 3'-azido-3'-deoxythymidine (AZT). To further evaluate the antineoplastic utility of AZT we now have assessed its effect in combination with methotrexate (MTX) in the human colon tumor model HCT-8. Incubation of these cells for 5 days in AZT and MTX caused a reduction in the 50% inhibitory concentration of AZT and isobologram analysis revealed additive effects which were reversed by the addition of 50 microM thymidine to the incubation media. This enhanced cytotoxicity appeared not to be related to an effect of AZT on MTX activity; in whole-cell assays the ability of MTX to inhibit de novo dTMP synthesis and deplete intracellular pools of dTTP was not affected by AZT. In contrast, although MTX did not alter AZT triphosphate production, it did affect AZT triphosphate utilization in DNA synthesis. Incubation of cells for 24 h in [3H]AZT alone (5 microM, 3 microCi/ml) resulted in 6.6 pmol AZT incorporated into cellular DNA/10(6) cells. Coincubation of these cells in [3H]AZT (5 microM) plus 5 or 15 nM MTX increased AZT incorporation into DNA to 8.0 and 20.5 pmol/10(6) cells, respectively. Biochemically, this effect appeared to correlate with the concentration-dependent ability of 5 or 15 nM MTX to deplete intracellular dTTP pools, which were reduced by 25 and 49%, respectively. Further evidence of the relationship between intracellular dTTP pools and AZT cytotoxicity was that, in the presence of both MTX and 50 microM thymidine, intracellular dTTP pools remained near normal levels and the incorporation of 5 microM AZT into DNA was not enhanced. Therapeutically, studies conducted in athymic (nude) mice bearing HCT-8 xenografts that received six weekly cycles of MTX (87.5 mg/kg) and AZT (300 mg/kg) revealed that the two-drug regimen exerted superior antineoplastic effects compared to either drug alone (treated versus control approximately 0.9 for AZT or MTX and approximately 0.3 for MTX plus AZT). In addition, the combination did not increase toxicity compared to therapy with MTX alone. These findings are discussed in light of their biochemical and clinical implications.
Ulcerative colitis and malignancy. (2001)

Ulcerative colitis is associated with an increased risk for colorectal cancer. The increase is approximately six to ten times the expected in the general population. Disease duration and extension are the major risk factors. Concomitant primary sclerosing cholangitis is an additional independent risk factor. The relative risk is approximately 14.8 for patients with pancolitis while it is 1.7 for patients with disease restricted to the rectum. The risk increases rapidly after 20 years of disease evolution. Active treatment might decrease the risk. The increased cancer risk is a major problem for longterm management of patients with ulcerative colitis. It is the rationale for various surveillance programs and the search for dysplasia. Two major types of dysplasia must be distinguished in ulcerative colitis: sporadic adenomas and ulcerative colitis-associated dysplasia. Sporadic adenomas can be treated by simple polypectomy. The diagnosis of dypsplasia relies mainly on microscopic analysis of biopsy samples. Additional techniques, including flow cytometry and the search for DNA abnormalities and immunohistochemistry or molecular techniques looking for genetic defects can help to improve the diagnostic yield.
Mouse models of colorectal cancer as preclinical models (2015)

In this review, we discuss the application of mouse models to the identification and pre-clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large-scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross-species comparative 'omics-based approaches to this problem. We highlight recent progress in modelling late-stage disease using mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection.
Design of a 3-D Fractal Heatsink Antenna (2010)

A new type of dual-function structure is presented, a 3-D fractal heatsink antenna. This design is simulated at different fractal iterations in Ansoft HFSS and ePhysics to assess its electromagnetic and thermal performance, relative to a patch antenna and a finned heatsink antenna. It compares favorably to a patch antenna, improving radiation efficiency (up to 0.98) and directivity (up to 8.21 dB). As a heatsink, it decreases thermal resistance in comparison to a typical finned heatsink by an order of magnitude.
Three-View Surveillance Video Based Face Modeling for Recogniton (2007)

3D face recognition has been researched intensively in recent decades. Most 3D data (so called range facial data) are obtained from 3D range imaging systems. Such data representations have been proven effective for face recognition in 3D space. However, obtaining such data requires subject cooperation in a constrained environment, which is not practical for many real applications of video surveillance. It is therefore in high demand to use regular video cameras to generate 3D face models for further classification. The goal of our research is to develop a method of tracking feature points on a face in multiple views in order to build 3D models of individual faces. We proposed a three-view based video tracking and model creation algorithm, which is based on the Active Appearance Model and a generic facial model. We will describe how to build useful individual models over time, and validate the created dynamic model sequences. Our experiments demonstrate the feasibility of the proposed work through the application for face recognition.
Future mission studies: Forecasting solar flux directly from its chaotic time series (1991)

The mathematical structure of the programs written to construct a nonlinear predictive model to forecast solar flux directly from its time series without reference to any underlying solar physics is presented. This method and the programs are written so that one could apply the same technique to forecast other chaotic time series, such as geomagnetic data, attitude and orbit data, and even financial indexes and stock market data. Perhaps the most important application of this technique to flight dynamics is to model Goddard Trajectory Determination System (GTDS) output of residues between observed position of spacecraft and calculated position with no drag (drag flag = off). This would result in a new model of drag working directly from observed data.
Developing status of millimeter wave tubes in China (2005)

This paper describes the developing status of millimeter wave tubes in China. These tubes include magnetrons, klystrons, traveling wave tubes (TWTs), the extended interaction oscillators (ElOs), the extended interaction amplifiers (ElAs), the diffraction radiation oscillators (DROs or orotrons) and gyrotrons. The basic research, such as new types of slow wave structures and fast wave interaction models, is also described. The further developing trends of millimeter wave tubes in China are discussed in this paper.
Fluorescent indicators based on BODIPY (2011)

This critical review covers the advances made using the 4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold as a fluorophore in the design, synthesis and application of fluorescent indicators for pH, metal ions, anions, biomolecules, reactive oxygen species, reactive nitrogen species, redox potential, chemical reactions and various physical phenomena. The sections of the review describing the criteria for rational design of fluorescent indicators and the mathematical expressions for analyzing spectrophotometric and fluorometric titrations are applicable to all fluorescent probes (206 references).
Investigating nanoscale cellular dynamics with cross-sectional spectral domain phase microscopy (2007)

We report on cross-sectional imaging of dynamic biological specimens using a spectral domain phase microscopy (SDPM) system capable of operating at a line rate of 19 kHz. This system combines the time-sensitive capabilities of SDPM with the multi-point acquisition features of related phase-sensitive techniques. The presented phase portraits and B-scan phase images of spontaneously beating embryonic cardiomyocytes and cytoplasmic flow in A. proteus offer insight into the nature and timing of the observed cellular phenomena, demonstrating the utility of this technique for dynamic cell studies.
Stroking human jejunal mucosa induces 5-HT release and Cl− secretion via afferent neurons and 5-HT4receptors (1999)

5-Hydroxytryptamine (5-HT) release and neural reflex pathways activated in response to mucosal stroking were investigated in muscle-stripped human jejunum mounted in modified Ussing chambers. The mucosa was stroked with a brush at 1/s for 1-10 s. Mucosal stroking resulted in a significant increase in the concentration of 5-HT in the mucosal bath within 5 min. It also was associated with a reproducible positive change (Delta) in short-circuit current (Isc), which was abolished by inhibitors of chloride secretion. Capsaicin and hexamethonium significantly inhibited the DeltaIsc but not the release of 5-HT. The DeltaIsc was inhibited by TTX but not by atropine. It was also inhibited by the 5-HT(3,4) receptor antagonist tropisetron (10 microM) and the 5-HT(4,3) receptor antagonist SDZ-205-557 (10 microM) but not by preferential antagonists of 5-HT(1P), 5-HT(2A), or 5-HT3 receptors. These results suggest that mucosal stroking induces release of mucosal 5-HT, which activates a 5-HT4 receptor on enteric sensory neurons, evoking a neuronal reflex that stimulates chloride secretion.
Imaging Dedicated and Multifunctional Neural Circuits Generating Distinct Behaviors (2006)

Central pattern generators (CPGs) control both swimming and crawling in the medicinal leech. To investigate whether the neurons comprising these two CPGs are dedicated or multifunctional, we used voltage-sensitive dye imaging to record from approximately 80% of the approximately 400 neurons in a segmental ganglion. By eliciting swimming and crawling in the same preparation, we were able to identify neurons that participated in either of the two rhythms, or both. More than twice as many cells oscillated in-phase with crawling (188) compared with swimming (90). Surprisingly, 84 of the cells (93%) that oscillated with swimming also oscillated with crawling. We then characterized two previously unidentified interneurons, cells 255 and 257, that had interesting activity patterns based on the imaging results. Cell 255 proved to be a multifunctional interneuron that oscillates with and can perturb both rhythms, whereas cell 257 is an interneuron dedicated to crawling. These results show that the swimming and crawling networks are driven by both multifunctional and dedicated circuitry.
Characterization of a re‐engineered, mesothelin‐targetedPseudomonasexotoxin fusion protein for lung cancer therapy (2016)

Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). Reactivity of RG7787 with sera from immunotoxin-treated patients was >1000 fold reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with picomolar potency. The pharmacokinetic properties of RG7787 in rodents were comparable to SS1P, yet it was tolerated up to 10 fold better without causing severe vascular leak syndrome or hepatotoxicity. A pharmacokinetic/pharmacodynamic model developed based on NCI-H596 xenograft studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies closely correlate. At optimal doses of 2-3 mg/kg RG7787 is more efficacious than SS1P. Even large, well established tumors (600 mm(3)) underwent remission during three treatment cycles with RG7787. Also in two patient-derived lung cancer xenograft models, Lu7336 and Lu7187, RG7787 showed anti-tumor efficacy. In monotherapy two treatment cycles were moderately efficacious in the Lu7336 model but showed good anti-tumor activity in the KRAS mutant Lu7187 model (26% and 80% tumor growth inhibition, respectively). Combination of RG7787 with standard chemotherapies further enhanced efficacy in both models achieving near complete eradication of Lu7187 tumors.
Tissue‐specific and wound‐inducible pattern of expression of the mannopine synthase promoter is determined by the interaction between positive and negative cis‐regulatory elements (1993)

In transgenic tobacco plants the regulatory region of the Agrobacterium genes involved in mannopine synthesis ( pmas ) directs expression in vascular tissues and is induced upon wounding. To identify cis ‐acting sequences required for the cell‐type‐specific and wound‐inducible expression of this regulatory region, the expression pattern of chimeric genes in which 5′ upstream deletions of the pmas1′ promoter direct the expression of the β‐glucuronidase coding sequence, was analyzed in transgenic tobacco plants. It was found that the pmas1′ promoter is specifically expressed in phloem cells and that this tissue‐specific pattern of expression is the result of the interaction of at least two negative regulatory elements with a positive element that directs expression in many cell types. It was also found that wound induction is mediated by two different mechanisms, one of them involving a dramatic change in tissue‐specific expression.
Intramuscular versus Subcutaneous Administration of Iron Dextran in Suckling Piglets (2007)

The aim of the study was to compare the development of red blood cell indices after subcutaneous versus intramuscular administration of iron dextran to suckling piglets during early postnatal period. The piglets in group I (n = 17) were injected subcutaneously (into groin) with 200 mg Fe 3+ as iron dextran on day 3 of life. In group II (n = 16), the piglets received intramuscular injection (into gluteal muscles) of 200 mg Fe 3+ as iron dextran on day 3 of life. In group III (n = 10), the piglets did not receive any iron till the age of 3 days. The blood was taken and analyzed (Hb, PCV, RBC, MCV, MCH, MCHC, Fe) on days 3, 7, 14, 21, 28 and 35. Haematological indices of piglets in group III were characteristic for hypochromic anaemia. Anaemia in group III had a detrimental effect on the growth rate of piglets. The development of red blood cell indices and iron concentration in blood plasma in subcutaneously treated piglets did not differ significantly from that of intramuscularly-treated group. Both treatments prevented development of anaemia.
Effects of Dimethyl Sulfoxide in Cholesterol-Containing Lipid Membranes: A Comparative Study of Experiments In Silico and with Cells (2012)

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca(2+)) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations.
A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function (2004)

Various in vitro and in vivo techniques exist for study of the microcirculation. Whereas in vivo systems impress with their physiological fidelity, in vitro systems excel in the amount of reduction that can be achieved. Here we introduce the autoperfused ex vivo flow chamber designed to study murine leukocytes and platelets under well-defined hemodynamic conditions. In our model, the murine heart continuously drives the blood flow through the chamber, providing a wide range of physiological shear rates. We used a balance of force approach to quantify the prevailing forces at the chamber walls. Numerical simulations show the flow characteristics in the chamber based on a shear-thinning fluid model. We demonstrate specific rolling of wild-type leukocytes on immobilized P-selectin, abolished by a blocking MAb. When uncoated, the surfaces having a constant shear rate supported individual platelet rolling, whereas on areas showing a rapid drop in shear platelets interacted in previously unreported grapelike conglomerates, suggesting an influence of shear rate on the type of platelet interaction. In summary, the ex vivo chamber amounts to an external vessel connecting the arterial and venous systems of a live mouse. This method combines the strengths of existing in vivo and in vitro systems in the study of leukocyte and platelet function.
Probing the Dynamic Features of Bis(aminocyclopentadienyl) and Bis(aminoindenyl) Zirconium Complexes (2000)

Treatment of 3-phenylcyclopent-2-enone (1) with either morpholine or pyrrolidine in the presence of 3 Å molecular sieves yielded the corresponding cyclopentadienamines 2a and 2b. Subsequent deprotonation with n-butyllithium followed by the reaction with zirconium tetrachloride led to the formation of the amino-substituted bent metallocenes 4a and 4b. Crystallization furnished the isomerically pure complex meso-bis(phenyl-3-pyrrolidinylcyclopentadienyl)zirconium dichloride (meso-4b), which was characterized by X-ray diffraction. Complex meso-4b exhibits a C(Cp)−N bond length of 1.349(3) Å. A rotational barrier of ΔG⧧(CN-rot)(248 K) = 12.1 ± 0.2 kcal mol-1 was measured for meso-4b in solution by dynamic 600 MHz 1H NMR spectroscopy. Similar treatment of 2-indanone with morpholine, followed by deprotonation and reaction with ZrCl4, gave bis(2-morpholinoindenyl)ZrCl2 (7a), which was also characterized by an X-ray crystal structure analysis (the indenyl-C2/12−N bond lengths are 1.349(5)/1.381(5) Å). Two rotational processes were subsequently frozen out on the 600 MHz 1H NMR time scale upon decreasing the temperature from ambient to give a C−N rotational barrier of ΔG⧧(CN-rot)(268 K) = 12.9 ± 0.2 kcal mol-1 and an activation energy of the rotation about the zirconium−Cp(indenyl) vector of ΔG⧧(Ind-rot)(178 K) = 7.6 ± 0.5 kcal mol-1. In solution and in the solid state only a single C2-symmetric metallocene rotamer of 7a was detected. The same is found for bis(2-pyrrolidinoindenyl)ZrCl2 (7b). By dynamic 1H NMR spectroscopy the two rotational activation barriers of complex 7b were determined as ΔG⧧(CN-rot)(338 K) = 16.4 ± 0.2 kcal mol-1 and ΔG⧧(Ind-rot)(198 K) = 9.1 ± 0.5 kcal mol-1.
Human Growth Hormone and Extracellular Domain of Its Receptor: Crystal Structure of the Complex (1992)

Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction.
The Effects of Hydrogen Peroxide Rinses on the Normal Oral Mucosa (1993)

Oral mucosal effects of hydrogen peroxide mouth rinses were investigated in normal volunteers. Following a 2-week control period, 35 subjects were randomly assigned to rinse with either normal saline, 1/4-strength hydrogen peroxide (0.75%), or 1/2-strength hydrogen peroxide (1.5%), 4 times daily for 2 weeks. Mucosal status, buccal microbial adherence, salivary flow rate (SFR), and subjective reactions were assessed weekly. In the normal saline group, no significant changes were noted in any of the observed parameters and subjective reports were unremarkable. In both hydrogen peroxide groups, significant mucosal abnormalities were observed (p < 0.001) and subjective complaints were numerous. Bacterial adherence was significantly reduced in the 1/4 hydrogen peroxide group but not in the 1/2 hydrogen peroxide group. Despite reports of dry mouth, SFRs were not altered significantly. Since hydrogen peroxide rinses are associated with mucosal abnormalities and elicit overwhelmingly negative subjective reactions in normal individuals, they are not recommended for oral care.
USING UNIX: COLLECTED TRACES OF 168 USERS (1988)

The task of collecting long-term data on real-life computer use is onerous. There is the technical difficulty of writing monitoring software, the social inertia of attracting individuals to the study, and the often overwhelming politics of obtaining an organization's permission for executing the study. To save other researchers the time and effort required to collect such data, this paper describes how command line data from 168 users of the ${UNIX sup 1}$ csh system was collected and organized. The accompanying magnetic tape includes all the data files.