gebhart/patrepeval huggingface dataset:
Intratumor Heterogeneity: Seeing the Wood for the Trees (2012)

Most advanced solid tumors remain incurable, with resistance to chemotherapeutics and targeted therapies a common cause of poor clinical outcome. Intratumor heterogeneity may contribute to this failure by initiating phenotypic diversity enabling drug resistance to emerge and by introducing tumor sampling bias. Envisaging tumor growth as a Darwinian tree with the trunk representing ubiquitous mutations and the branches representing heterogeneous mutations may help in drug discovery and the development of predictive biomarkers of drug response.
IL-6-Deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis: Roles of IL-6 in the Activation and Differentiation of Autoreactive T Cells (1998)

Although autoreactive T cells recognizing self myelin Ags are present in most individuals, autoimmune disease of the central nervous system is a relatively rare medical condition. Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a second signal delivered by costimulatory molecules or cytokines. Although in vitro studies have suggested that cytokines, especially proinflammatory cytokines such as IL-1, IL-6, and TNF are involved in T cell activation, their precise roles in vivo are not clear. To determine the roles of proinflammatory cytokines in T cell activation in vivo and in the development of autoimmune disease, we have studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in IL-6. We found that IL-6-deficient mice were completely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal inflammation and demyelination in the central nervous system and deficiency in neurologic functions. Furthermore, we established that the resistance to EAE in IL-6-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo. These results strongly suggest that IL-6 plays a crucial role in the activation and differentiation of autoreactive T cells in vivo and that blocking IL-6 function can be an effective means to prevent EAE.
Subthreshold Regime has the Optimal Sensitivity for Nanowire FET Biosensors (2009)

Nanowire field-effect transistors (NW-FETs) are emerging as powerful sensors for detection of chemical/biological species with various attractive features including high sensitivity and direct electrical readout. Yet to date there have been limited systematic studies addressing how the fundamental factors of devices affect their sensitivity. Here we demonstrate that the sensitivity of NW-FET sensors can be exponentially enhanced in the subthreshold regime where the gating effect of molecules bound on a surface is the most effective due to the reduced screening of carriers in NWs. This principle is exemplified in both pH and protein sensing experiments where the operational mode of NW-FET biosensors was tuned by electrolyte gating. The lowest charge detectable by NW-FET sensors working under different operational modes is also estimated. Our work shows that optimization of NW-FET structure and operating conditions can provide significant enhancement and fundamental understanding for the sensitivity limits of NW-FET sensors.
Elastic constants of hexagonal transition metals: Theory (1995)

The five different elastic constants of all the hexagonal 4d transition metals (Y, Zr, Tc, and Ru) and the 5d transition metals Re and Os have been calculated by means of first-principles electronic-structure calculations using the full-potential linear muffin-tin orbital method. The calculated data agree with the experimental values within \ensuremath{\sim}30%. We demonstrate, using experimental data, that the hexagonal transition metals obey the Cauchy relations much better than the cubic ones. This is due to the fact that the shape of the density of states for the hexagonal materials retains its form to a larger extent, for all types of shears, than it does for the cubic metals. We introduce normalized elastic constants ${\mathrm{C}}_{\mathrm{ij}}^{\ensuremath{'}}$=${\mathrm{C}}_{\mathrm{ij}}$/B, where B is the bulk modulus, which show a regular behavior for the hexagonal transition metals, in contrast to the cubic transition metals, where large irregularities are observed. These regular as well as irregular behaviors are well reproduced by the full-potential calculations.
Suppression of Virus Accumulation in Transgenic Plants Exhibiting Silencing of Nuclear Genes (1996)

James J. English, Elisabeth Mueller, David C. Baulcombe, Suppression of Virus Accumulation in Transgenic Plants Exhibiting Silencing of Nuclear Genes, The Plant Cell, Vol. 8, No. 2 (Feb., 1996), pp. 179-188
A lattice‐gas and lattice Boltzmann study of mixing at continuous fracture Junctions: Importance of boundary conditions (1997)

The lattice‐gas automata and lattice Boltzmann (BGK) methods were used to estimate the mixing of fluid streams at a continuous fracture junction, for Peclet number ( Pe ) from 0 to 1547. Agreement with experimental results is good, particularly at Pe ≤ 25. At low Pe , a large fracture length/width is needed to obtain accurate mixing ratios ( M r ). For a 90° intersection of two fractures with equal widths and flow rates, M r approaches 0.5 (complete mixing) at Pe ≈ 1. At the highest Pe studied, M r =0.022, in contrast with the streamline routing prediction M r =0.
TICSync: Knowing when things happened (2011)

Modern robotic systems are composed of many distributed processes sharing a common communications infrastructure. High bandwidth sensor data is often collected on one computer and served to many consumers. It is vital that every device on the network agrees on how time is measured. If not, sensor data may be at best inconsistent and at worst useless. Typical clocks in consumer grade PCs are highly inaccurate and temperature sensitive. We argue that traditional approaches to clock synchronization, such as the use of NTP are inappropriate in the robotics context. We present an extremely efficient algorithm for learning the mapping between distributed clocks, which typically achieves better than millisecond accuracy within just a few seconds. We also give a probabilistic analysis providing an upper-bound error estimate.
A 3-V, 2%-mW multibit current-mode ΣΔ DAC with 100 dB dynamic range (1996)

The area ratio of analog to digital for mixed-mode chip has been inversely proportional to the process design rule for a given dynamic range objective, in contradiction to the LSI trend. This paper presents a design approach to realize a high degree of size reduction with process design rules for analog circuitry and a signal processing architecture for digital circuitry. A five-level current-mode /spl Sigma//spl Delta/ digital-to-analog converter (DAC) system reveals full scale total harmonic: distortion plus noise (THD+N) of -90 dB and dynamic-range of 100 dB at 3 V (low power of 22 mW). Analog-area down-scaling can be accomplished by this architecture to be 1.09 mm/sup 2/, using 0.6-/spl mu/m double-poly double-metal (DPDM) CMOS. For the digital filter, a pipeline instruction sequence with multiplierless architecture also gives small area of 1.98 mm/sup 2/.
Prevention of Protein Adsorption by Tethered Poly(ethylene oxide) Layers:  Experiments and Single-Chain Mean-Field Analysis (1998)

Prevention of protein adsorption by the surface-grafted poly(ethylene oxide) (PEO) chains has been well-known. We have examined the mechanisms of how the grafted PEO prevents protein adsorption. PEO−poly(propylene oxide)−PEO (PEO−PPO−PEO) triblock copolymers were used to graft PEO to the trichlorovinylsilane (TCVS)-modified glass by γ-irradiation. The surface density of the PEO chains was varied up to 60 pmol/cm2 and the number of the ethylene oxide (EO) units of the PEO segment was varied from 75 to 128. The adsorption of lysozyme and fibrinogen to the PEO-grafted glass was examined using radiolabeled proteins. The surface protein concentration decreased as the surface density of the grafted PEO increased, but surface protein concentration never reached zero. The experimental data were compared with the predictions by the single-chain mean-field theory. There was very good agreement between the predictions of the theory and the experimental observations. It was found that the mechanism for prevention of protein adsorption by the grafted PEO chains in the hydrophobic surfaces was due to the blocking by the PEO segments of the adsorbing sites of the proteins. The mechanism of the grafted chains to prevent protein adsorption was shown to depend upon the interactions of the surface with the segments of the grafted polymers. Surfaces that did not attract the polymer segments present effective kinetic barriers but were not very good for equilibrium prevention. On the other hand, hydrophobic surfaces, such as the ones used in the experimental work, were very effective for reducing the equilibrium amount of proteins adsorbed. It was found that the most important parameter in preventing protein adsorption by grafted polymers is the surface density of the grafted polymer. The polymer molecular weight, or the chain length, was found to have a weak effect.
Binding of plasma fibronectin to cell layers of human skin fibroblasts. (1983)

Human plasma fibronectin bound to confluent cell layers of cultured human-skin fibroblasts in two distinct pools. Initial binding of fibronectin occurred in a deoxycholate-soluble pool (Pool I). Binding in Pool I was reversible and reached a steady state after 3 h. After longer periods of incubation, fibronectin became bound in a deoxycholate-insoluble pool (Pool II). Binding in Pool II was irreversible and proceeded at a linear rate for 30 h. After 30 h of incubation, a significant proportion of fibronectin bound in Pool II was present as disulfide-bonded multimers. HT1080 cells, a human sarcoma cell line, did not bind fibronectin in either pool. Also, isolated cell matrices prepared by deoxycholate extraction did not bind fibronection. Binding of fibronectin in Pool I of normal fibroblasts occurred via specific, saturable receptors. There were 128,000 binding sites per cell, and KDiss was 3.6 X 10(-8) M. Fluorescence microscopic localization of fibronectin bound in Pool I and Pool II was performed using fluorescein-conjugated fibronectin. Fluorescent staining in Pool I was present in a punctate pattern and in short, fine fibrils. Pool II fluorescence was exclusively in coarse, dense fibrils. These data indicate that plasma fibronectin may become incorporated into the tissue extracellular matrix via specific cell-surface receptors.
Preclinical pharmacokinetics and metabolism of a potent non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase (2005)

The disposition of compound A, a potent inhibitor of the hepatitis C virus (HCV) NS5B polymerase, was characterized in animals in support of its selection for further development. Compound A exhibited marked species differences in pharmacokinetics. Plasma clearance was 44 ml min-1 kg-1 in rats, 9 ml min-1 kg-1 in dogs and 16 ml min-1 kg-1 in rhesus monkeys. Oral bioavailability was low in rats (10%) but significantly higher in dogs (52%) and monkeys (26%). Compound A was eliminated primarily by metabolism in rats, with biliary excretion accounting for 30% of its clearance. Metabolism was mainly mediated by cyclohexyl hydroxylation, with N-deethylation and acyl glucuronide formation constituting minor metabolic pathways. Qualitatively, the same metabolites were identified using in vitro systems from all species studied, including humans. The low oral bioavailability of compound A in rats was mostly due to poor intestinal absorption. This conclusion was borne out by the findings that hepatic extraction in the rat was only 30%, intraperitoneal bioavailability was good, and compound A was poorly absorbed from the rat isolated intestinal loop, with no detectable intestinal metabolism. Compound A was not an inhibitor of major human cytochrome P450 enzymes, indicating minimal potential for clinical drug-drug interactions. The metabolic clearance of compound A in rat, dog and monkey hepatocytes correlated with the systemic clearance observed in these species. Since compound A was very stable in human hepatocytes, the results suggest that it will be a low clearance drug in humans.
Absorption and tissue distribution of zeaxanthin and lutein in rhesus monkeys after taking Fructus lycii (Gou Qi Zi) extract. (2001)

To study serum and tissue levels of zeaxanthin and lutein after feeding rhesus monkeys an extract of Fructus lycii (gou qi zi).A carotenoid-containing fraction (P1) from an extract of F. lycii (equivalent to 2.2 mg zeaxanthin) was fed to three rhesus monkeys for 6 weeks as a daily dietary supplement through a nasogastric tube. Three other monkeys were fed with the vehicle (olive oil) similarly for 4 weeks as a control. Another three animals were fed with normal diet only. All animals were killed 4 hours after the last dose. Samples of serum, liver, spleen, brain, and retina were analyzed for zeaxanthin and lutein by high-pressure liquid chromatography.The basal levels of zeaxanthin and lutein in the monkey sera were 3.0 +/- 1.6 ng/ml (range, 2.3-4.8) and 31.5 +/- 12.2 ng/ml (range, 22.3-42.5), respectively. Serum levels of zeaxanthin and lutein in the P1-fed group were significantly higher than those of vehicle control (P<0.05). Besides the retina, the liver had the highest zeaxanthin and lutein levels, whereas the levels in the brain were undetectable. P1 supplement appeared to elevate zeaxanthin levels in liver and spleen. The level of lutein was higher than that of zeaxanthin in the maculae of rhesus monkeys. However, there were no detectable carotenoids in the peripheral and the equatorial regions of the monkey retina. P1 treatment elevated zeaxanthin density but not lutein in the macula.Serum levels and macular density of zeaxanthin was raised by feeding a carotenoid-containing fraction of F. lycii. Therefore, F. lycii is a good dietary source of zeaxanthin supplement.
Pirfenidone: an anti-fibrotic therapy for progressive kidney disease (2010)

Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed to better understand long-term efficacy and safety of this medication in various patient populations.
RISK SENSITIVITY, A STRANGELY PERVASIVE CONCEPT (2002)

The theme of this paper is that the simple concept of risk sensitivity raises ideas, shows associations, and forces clarification of issues that one would have thought quite unrelated.
Photochemical Decomposition Mechanisms for AZ-Type Photoresists (1979)

The photochemical decomposition mechanism of orthonaphthoquinonediazides has been investigated principally by infrared and carbon-13 nuclear magnetic resonance spectroscopies. The results demonstrate that the decomposition proceeds via a ketene intermediate to a photoproduct, the nature of which depends on the reaction conditions. Model resist systems were prepared by mixing orthonaphthoquinonediazides and 2,3,6-trimethylphenol or the diazide plus Novolak resin. Under ambient thermal and humidity conditions, ultraviolet (UV) exposure of the diazide yields 3-indenecarboxylic acid as the final photoproduct. However, UV exposure in vacuo results in ester formation via a ketene-phenolic OH reaction. The decomposition pathway and ensuing reactions have been shown to be the same for both 1- and 3-orthonaphthoquinonediazides attached to mono- and trihydroxybenzophenones. The technological implications for resist processing derived from these studies are also discussed.
Towards organic polymers with very small intrinsic band gaps. I. Electronic structure of polyisothianaphthene and derivatives (1986)

We present valence effective Hamiltonian (VEH) band-structure calculations on polyisothianaphthene and some of its simple derivatives. Our goal is to rationalize the lowering of the band gap by about 1 eV which is experimentally observed in polyisothianaphthene (Eg=∼1 eV) relative to the parent polymer, polythiophene (Eg=∼2 eV). We show that the smaller band gap found in polyisothianaphthene can be understood on the basis of a relationship which can be established between the band gap energy and the importance of the effective quinoid contributions to the electronic structure. Our theoretical results also indicate that simple dimethyl, dimethoxy, or dicyano substitutions are not expected to affect the size of the band gap in any significant way.
Helicobacter pylori genetic diversity within the gastric niche of a single human host (2001)

Isolates of the gastric pathogen Helicobacter pylori harvested from different individuals are highly polymorphic. Strain variation also has been observed within a single host. To more fully ascertain the extent of H. pylori genetic diversity within the ecological niche of its natural host, we harvested additional isolates of the sequenced H. pylori strain J99 from its human source patient after a 6-year interval. Randomly amplified polymorphic DNA PCR and DNA sequencing of four unlinked loci indicated that these isolates were closely related to the original strain. In contrast, microarray analysis revealed differences in genetic content among all of the isolates that were not detected by randomly amplified polymorphic DNA PCR or sequence analysis. Several ORFs from loci scattered throughout the chromosome in the archival strain did not hybridize with DNA from the recent strains, including multiple ORFs within the J99 plasticity zone. In addition, DNA from the recent isolates hybridized with probes for ORFs specific for the other fully sequenced H. pylori strain 26695, including a putative traG homolog. Among the additional J99 isolates, patterns of genetic diversity were distinct both when compared with each other and to the original prototype isolate. These results indicate that within an apparently homogeneous population, as determined by macroscale comparison and nucleotide sequence analysis, remarkable genetic differences exist among single-colony isolates of H. pylori. Direct evidence that H. pylori has the capacity to lose and possibly acquire exogenous DNA is consistent with a model of continuous microevolution within its cognate host.
Method for embedding optical fibers in an aluminum matrix by ultrasonic consolidation (2005)

The overall aim of the research, part of which is outlined in this paper, was to utilize the ultrasonic consolidation (UC) process for the fabrication of smart metal structures, capable of measuring an external stimulus and responding to this stimulus by adapting its structure accordingly through embedding both active and passive functional elements. This paper presents a fundamental study of embedding methods for the fabrication of optical fibers embedded within aluminum structures. The methods considered in this paper produced embedded optical fiber specimens in which large amounts of plastic flow were observed within the matrix. The matrix material deformed around the fibers, resulting in fully embedded optical fibers capable of transmitting a bright light source and without damaging the fibers. Based on light responses, a general process window was drawn to show the range at which optical fibers can be embedded within aluminum structures using the UC process. The outcomes lay down initial investigative principles for the further development of the technology for embedding or cladding of optical fiber sensors, such as fiber Bragg grating devices, within or on metal structures: for example, the cladding of large free-form metal structures or smart "skinned" metal foam or metal honeycomb structures.
A system based on specific protein-RNA interactions for analysis of target protein-protein interactions in vitro: successful selection of membrane-bound Bak-Bcl-xL proteins in vitro (2004)

Ribosome display systems are very effective and powerful tools for in vitro screening of transcribed mRNAs that encode proteins (or peptides) with specific (known or unknown) functions. We have modified such a system by exploiting the interaction between a tandemly fused MS2 coat-protein (MSp) dimer and the RNA sequence of the corresponding specific binding motif, C-variant (or Cv). We placed the MSp dimer at the N-terminus of a nascent protein and the Cv binding motif was attached to the 5' end of the protein's mRNA. This configuration enhanced the stability of the ribosome-mRNA complex. We demonstrate here that this improved ribosome display system provides an effective method for identifying the gene for a protein that binds to a protein of interest. We visualized the formation of polysome complexes in this advanced polysome display by atomic force microscopy (AFM) and found that the AFM images of polysomes in our system were different from those observed in the case of conventional ribosome display systems. Our results suggest that our technology might usefully complement yeast two-hybrid assays.
The Pupillary Effects of Intravenous Morphine, Codeine, and Tramadol in Volunteers (2004)

Opioid analgesics have pharmacological effects in many organ systems, including the eye. Because the metabolites of morphine and codeine contribute to their overall pharmacological effect pupil diameter measurements were made over a 6-h period. We studied the pupillary effects of IV morphine (0.125 mg/kg), codeine (1 mg/kg), tramadol (1.25 mg/kg), or placebo (10 mL 0.9% w/v sodium chloride) in 10 healthy volunteers. Pupil diameter was measured every 30 min using a pupil densitometer. Comparisons of the change in pupil diameter for each drug were made using analysis of variance with repeated measures. No significant change in pupil diameter was observed after placebo. After IV morphine and codeine administration there was a 26% decrease in pupil diameter (P < 0.001). Over the course of the study period, pupil diameter gradually returned to baseline values. After administration of tramadol there were no significant changes in pupil diameter until 150 min after administration, after which there was a significant reduction for the remainder of the study period (P < 0.01). The changes in pupil diameter may be explained in part by the pharmacokinetic profiles of the opioids studied. Measurement of pupil diameter may have a place in monitoring the central effect of opioids.