gebhart/patrepeval huggingface dataset:
mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy (2019)

The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression. In addition, mTOR also negatively regulates autophagy via different ways. We discuss mTOR signaling and its key upstream and downstream factors, the specific genetic changes in the mTOR pathway and the inhibitors of mTOR applied as therapeutic strategies in eight solid tumors. Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.
Supramolecular effects and molecular discrimination by macrocyclic hosts embedded in synthetic bilayer membranes. (1993)

Hybrid assemblies were prepared in combinations of a synthetic lipid, involving an L-alanine residue interposed between an anionic head group and a hydrophobic double-chain segment, with cage-type cyclophanes having a three-dimensionally extended hydrophobic cavity. Incorporation behavior of the cage-type hosts into the multi- and single-walled vesicules was characterized by highly sensitive differential scanning calorimetry and dynamic light-scattering measurements as well as by gel-filtration chromatography and electronic absorption spectroscopy. Both hosts were found to be completely incorporated into a relatively polar domain close to the vesicular surface. Anionic guest molecules, such as naphthol yellow S, dimethylsulfonazo III, bromopyrogallol red, and orange G, were effectively incorporated into the hydrophobic cavities provided by the cage-type cyclophanes embedded in the single-walled bilayer membrane, as confirmed by circular dichroism spectroscopy; the formation constants for 1:1 host-guest complexes were in the order of 10(4)-10(5) mol.dm-3. This means that the binding affinities of the cage-type hosts are largely retained even when the hosts are incorporated into the vesicle. Moreover, the pyridinium moieties bound to the chiral L-valine residues in the bridging components of the hosts underwent conformational changes upon inclusion of the guest, as confirmed by circular dichroism spectroscopy and molecular mechanics and dynamics calculations.
Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. (1994)

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
Characterization of two site-specifically mutated human dihydrolipoamide dehydrogenases (His-452—-Gln and Glu-457—-Gln). (1992)

Two site-specifically mutated human dihydrolipoamide dehydrogenases (His-452----Gln and Glu-457----Gln) were expressed in pyruvate dehydrogenase complex-deletion mutant Escherichia coli JRG1342. The expressed mutant E3s were purified to near homogeneity using DEAE-Sephacel and hydroxyapatite columns. The initial velocity measurements in the absence of products for the Gln-452 mutant E3 in the direction of NAD+ reduction showed parallel lines in double-reciprocal plots, indicating that the mutant E3, like wild-type enzyme, catalyzed E3 reaction via a ping-pong mechanism. The specific activity of the Gln-452 mutant E3 was about 0.2% of that of wild-type enzyme. Its Km for dihydrolipoamide was dramatically increased by 63-fold. The substitution of His-452 to Gln resulted in a destabilization of the transition state of human E3 catalysis by about 6.4 kcal mol-1. The Gln-457 mutant E3, unlike wild-type enzyme, catalyzed E3 reaction via a sequential mechanism in the direction of NAD+ reduction based on the intersecting lines shown on double-reciprocal plots. Its specific activity decreased to 28% of that of wild-type enzyme. Its Km for dihydrolipoamide increased about 4.3-fold. The substitution of Glu-457 to Gln resulted in a destabilization of the transition state by about 1.7 kcal mol-1. These results indicate that His-452, which is a possible proton acceptor/donor in human E3 reaction, is critical to human E3 catalysis and that the local environment around His-452 and Glu-457, which are suggested to be hydrogen-bonded, is important in the binding of dihydrolipoamide to the enzyme.
Principles of Plasma Spectroscopy (1997)

This monograph presents a comprehensive description of the theoretical foundations and experimental applications of spectroscopic methods in plasma physics research. The first three chapters introduce the classical and quantum theory of radiation, with detailed descriptions of line strengths and high density effects. The next chapter describes theoretical and experimental aspects of spectral line broadening. The following five chapters are concerned with continuous spectra, level kinetics and cross sections, thermodynamic equilibrium relations, radiative energy transfer, and radiative energy losses. The book concludes with three chapters covering the basics of various applications of plasma spectroscopy to density and temperature measurements and to the determination of some other plasma properties. Over one thousand references not only guide the reader to original research covered in the chapters, but also to experimental details and instrumentation. This will be an important text and reference for all those working on plasmas in physics, optics, nuclear engineering, and chemistry, as well as astronomy, astrophysics and space physics.
Inhibitory effects of recombinant human cystatin C on human coronaviruses (1991)

Cystatin C, a potent inhibitor of cysteine proteases such as papain and cathepsin B, was examined for its effect on human coronaviruses OC43 and 229e. Both viruses were greater than 99% inhibited by 0.1 mM inhibitor. Endpoint titrations showed that inhibiting activity paralleled that of leupeptin, a serine and cysteine protease inhibitor, and indicated that 1 to 2 microM inhibitor, slightly above physiologic levels, was effective.
Regulatable Gene Expression Systems for Gene Therapy (2006)

It is feasible to restrict transgene expression to a tissue or region in need of therapy by using promoters that respond to focusable physical stimuli. The most extensively investigated promoters of this type are radiation-inducible promoters and heat shock protein gene promoters that can be activated by directed, transient heat. Temporal regulation of transgenes can be achieved by various two- or three-component gene switches that are triggered by an appropriate small molecule inducer. The most commonly considered gene switches that are reviewed herein are based on small molecule-responsive transactivators derived from bacterial tetracycline repressor, insect or mammalian steroid receptors, or mammalian FKBP12/FRAP. A new generation of gene switches combines a heat shock protein gene promoter and a small molecule-responsive gene switch and can provide for both spatial and temporal regulation of transgene activity.
Maximum size of drops levitated by an air cushion (2009)

Liquid drops can be kept from touching a plane solid surface by a gas stream entering from underneath, as it is observed for water drops on a heated plate, kept aloft by a stream of water vapor. We investigate the limit of small flow rates, for which the size of the gap between the drop and the substrate becomes very small, to obtain a full analytical description of stationary drop states and their stability. Above a critical drop radius no stationary drops can exist, below the critical radius two solutions coexist. However, only the solution with the smaller gap width is stable, the other is unstable. We compare to experimental data and use boundary integral simulations to show that unstable drops develop a gas "chimney" that breaks the drop in its middle.
All Optical Scalar Atomic Magnetometer Capable of Vector Measurement (2020)

Vector field measurement is demonstrated with an all-optical scalar atomic magnetometer using intrinsic parameters related to its scalar operation. The Bell-Bloom type atomic magnetometer measures the Larmor precession of cesium atoms through on-resonant absorption of a probe beam. While the AC component of the probe signal is used for the field magnitude measurement, the probe DC signal contains information about the polar angle, defined as the angle between the magnetic field and the probe beam. Additional polar angle information is obtained from the light-shift-induced magnetic field caused by the frequency modulation of the probe beam. With a measurement time of 100 milliseconds, better than 0.02 degree sensitivity has been achieved using a commercial miniaturized sensor at the optimal sensor orientation. The angle measurement accuracy is checked against an optical encoder over the entire polar angle range of 0 to 180 degrees. Better than 1 degree error is recorded over most set polar angles. Azimuthal angle measurement is also exhibited with an additional orthogonally oriented sensor.
Evidence That an Interaction between EB1 and p150 Glued Is Required for the Formation and Maintenance of a Radial Microtubule Array Anchored at the Centrosome (2002)

EB1 is a microtubule tip-associated protein that interacts with the APC tumor suppressor protein and components of the dynein/dynactin complex. We have found that the C-terminal 50 and 84 amino acids (aa) of EB1 were sufficient to mediate the interactions with APC and dynactin, respectively. EB1 formed mutually exclusive complexes with APC and dynactin, and a direct interaction between EB1 and p150(Glued) was identified. EB1-GFP deletion mutants demonstrated a role for the N-terminus in mediating the EB1-microtubule interaction, whereas C-terminal regions contributed to both its microtubule tip localization and a centrosomal localization. Cells expressing the last 84 aa of EB1 fused to GFP (EB1-C84-GFP) displayed profound defects in microtubule organization and centrosomal anchoring. EB1-C84-GFP expression severely inhibited microtubule regrowth, focusing, and anchoring in transfected cells during recovery from nocodazole treatment. The recruitment of gamma-tubulin and p150(Glued) to centrosomes was also inhibited. None of these effects were seen in cells expressing the last 50 aa of EB1 fused to GFP. Furthermore, EB1-C84-GFP expression did not induce Golgi apparatus fragmentation. We propose that a functional interaction between EB1 and p150(Glued) is required for microtubule minus end anchoring at centrosomes during the assembly and maintenance of a radial microtubule array.
The user as social actor (2006)

This paper provides an innovative example for understanding systems development method (SDM) enactment by conceptualizing the IT worker as a social actor and method user. The paper shows how IT workers can be seen as acting in constrained ways, rather than as simple "users" of the SDM; and secondly shows the potential contribution of social actor theory.
CMOS active pixel image sensors fabricated using a 1.8-V, 0.25-μm CMOS technology (1998)

This paper reports the experimental results of the first CMOS active pixel image sensors (APS) fabricated using a high-performance 1.8-V, 0.25-/spl mu/m CMOS logic technology. No process modifications were made to the CMOS logic technology so that the impact of device scaling on the image sensing performance can be studied. This paper highlights the device and process design considerations required to enable CMOS as an image sensor technology.
Interleukin 4 induces interleukin 6 production by endothelial cells: Synergy with interferon‐γ (1991)

Interleukin (IL)4 induces IL6 production by human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner, as shown by bioassay and immunoprecipitation. Interferon (IFN)-gamma, which antagonizes IL4 effects on leukocytes, synergized with IL4 in the induction of IL6 production by HUVEC. Contamination with endotoxin was excluded by heat-inactivated IL4, preincubating with anti-IL4 polyclonal antibody and the use of polymyxin B. The presence of IL4 receptors on HUVEC was shown by affinity cross-linking with 125I-IL4, revealing a 110-kDa binding protein. However, compared with the amount seen on T cells the 60-70-kDa cross-linked doublet was present at much lower levels. Additional lower molecular weight cross-linked proteins were isolated only with HUVEC, but the origin of these is unclear. IL6 is a pluripotent cytokine produced by many cells which promotes the differentiation and growth of lymphocytes and the production of acute phase protein by hepatocytes, and is important in the regulation of immunity at the systemic and local levels. Since IL4 and IFN-gamma are produced by T cells, which are frequently associated with vascular endothelium during chronic inflammation, IL4 is likely to be an important cytokine in the regulation of IL6 and perhaps other cytokine production by endothelium in vivo.
Statistics of spatial cone-excitation ratios in natural scenes (2002)

For some sets of surfaces, the spatial ratios of cone-photoreceptor excitations produced by light reflected from pairs of surfaces are almost invariant under illuminant changes. These sets include large populations of spectral reflectances, some of which represent individual natural surfaces but not their relative abundances in nature. The aim of this study was to determine whether spatial cone-excitation ratios are preserved under illuminant changes within the natural visual environment. A fast hyperspectral imaging system was used to obtain populations of 640,000 reflectance spectra from each of 30 natural scenes. The statistics of spatial cone-excitation ratios for randomly selected pairs of points in these scenes were determined for two extreme daylights. Almost-invariant ratios were common, suggesting that they represent a reliable property of the natural visual environment and a suitable foundation for visual color constancy.
Percutaneous absorption of coumarin, griseofulvin and propranolol across human scalp and abdominal skin. (1989)

The objective of this study was to investigate the role of the transfollicular pathway in the diffusion process of chemicals through excised human skin in vitro. Skin was obtained from 5 cadavers (3 males, 3 females) within 24 h of death. The age of the subjects varied between 18-77 years. Three radiolabelled drugs, namely 14C-coumarin, 3H-propranolol and 3H-griseofulvin, were studied. The permeation parameters such as flux, lag time, diffusion coefficient and permeability constant were determined across scalp and abdominal skin using the Thomas Diffusion Cell. For all tested substances the flux through scalp skin was higher than across abdominal skin and the lag time was decreased. The differences were statistically significant at p less than 0.05 for coumarin and propranolol. These data suggest that the transfollicular pathway in permeation might have a significant impact on the diffusion parameters for some drugs. Also, in the case of coumarin, permeability seems to be epidermis/dermis-controlled, whereas for griseofulvin and propranolol the Stratum corneum apparently is the permeability limiting barrier.
Optimally Distributed Transport Properties Can Produce Highest Performance Thermoelectric Systems (2019)

Optimum cooling of conventional thermoelectric (TE) devices is limited to about ⅙ Carnot efficiency for TE materials with figure of merit, ZT ≈ 1. This is ¼ to ½ the efficiency of typical two‐phase refrigeration systems and limits the use of TE materials to specialized applications where a combination of small size, solid‐state operation, and simplicity outweighs device performance limitations. Similarly, TE heating and power generation systems exhibit low efficiency in comparison with most current energy conversion systems. Herein, it is shown that performance efficiencies of TE couples with suitable distributed transport properties (DTP) exceed those of all other TE systems. TE material fabrication methods, including spark plasma sintering, additive manufacturing, and nanoscale material production processes, are evolving, making TE materials with controlled spatially dependent properties more practical to fabricate. Therefore, it is important to determine the performance advantages achievable through the fabrication of such TE couples. Governing equations for the optimum performance of DTP TE systems are derived and solved in a closed analytical form for the spatially dependent Seebeck coefficient, thermal conductivity, and electrical resistivity. Results are presented as analytical solutions for optimum efficiency, optimum spatial distribution of DTP properties, and other operating conditions of interest.
Variation in the Nucleotide Sequence of Cottontail Rabbit Papillomavirus a and b Subtypes Affects Wart Regression and Malignant Transformation and Level of Viral Replication in Domestic Rabbits (2000)

ABSTRACT We previously reported the partial characterization of two cottontail rabbit papillomavirus (CRPV) subtypes with strikingly divergent E6 and E7 oncoproteins. We report now the complete nucleotide sequences of these subtypes, referred to as CRPVa4 (7,868 nucleotides) and CRPVb (7,867 nucleotides). The CRPVa4 and CRPVb genomes differed at 238 (3%) nucleotide positions, whereas CRPVa4 and the prototype CRPV differed by only 5 nucleotides. The most variable region (7% nucleotide divergence) included the long regulatory region (LRR) and the E6 and E7 genes. A mutation in the stop codon resulted in an 8-amino-acid-longer CRPVb E4 protein, and a nucleotide deletion reduced the coding capacity of the E5 gene from 101 to 25 amino acids. In domestic rabbits homozygous for a specific haplotype of the DRA and DQA genes of the major histocompatibility complex, warts induced by CRPVb DNA or a chimeric genome containing the CRPVb LRR/E6/E7 region showed an early regression, whereas warts induced by CRPVa4 or a chimeric genome containing the CRPVa4 LRR/E6/E7 region persisted and evolved into carcinomas. In contrast, most CRPVa, CRPVb, and chimeric CRPV DNA-induced warts showed no early regression in rabbits homozygous for another DRA-DQA haplotype. Little, if any, viral replication is usually observed in domestic rabbit warts. When warts induced by CRPVa and CRPVb virions and DNA were compared, the number of cells positive for viral DNA or capsid antigens was found to be greater by 1 order of magnitude for specimens induced by CRPVb. Thus, both sequence variation in the LRR/E6/E7 region and the genetic constitution of the host influence the expression of the oncogenic potential of CRPV. Furthermore, intratype variation may overcome to some extent the host restriction of CRPV replication in domestic rabbits.
[Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture]. (1987)

Explants and cell cultures of embryonic chick ganglia trigeminalia, telencephalon and retina or hippocampus from fetal rats were incubated in maximow chambers in the presence of cyclic AMP and the dipeptide cyclo(Lys-Pro).HCL under various conditions. Maintenance of nerve cells and growth of nerve fibers were observed by morphometrical methods. 1. Cyclo(Lys-Pro).HCL promoted the maintenance of neuroblasts and the growth of nerve fibres in explants of the ganglion trigeminal and retinal cell cultures. The effect depended on the presence of serum in the medium by use of poly-I-lysine substrate. 2. Extern applicated cyclic AMP and the dipeptide SP3-4 = cyclo(Lys-Pro).HCL facilitated neurite growth in PNS cultures. In the presence of the drugs the length of nerve fibers increased for a short term. On CNS explants substance P (SP1-11) and SP3-4 were without effect. Cyclic AMP stimulated the growth of nerve fibers in CNS explants and cell cultures in number and length. 3. Discussed is the effect of SP1-11 and cyclo(Lys-Pro).HCL for competence of nerve fibre regeneration in vitro in relation to increasing cAMP levels, which may then act as an initial second messenger. It is suggested that explants and cell cultures of nervous tissues will be useful as a tool for the further characterisation of factors with neuronotrophic activities.