gebhart/patrepeval huggingface dataset:
Inducible binding to the c- fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein. (1994)

The proto-oncogene c-fos is an immediate-early gene, and one of the first genes transcribed after stimulation of most cells with a variety of ligands. Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype. The serum response element (SRE) in the c-fos regulatory region participates in induction of transcription by various growth factors and by phorbol esters and subsequent squelching of transcription. We show that an inducible protein complex (Band A) binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T, and becomes nondetectable by 60 min. Band A contains the serum response factor plus additional factor(s). A protein that is phosphorylated on a tyrosine residue in resting PBL-T suppresses binding of a component of Band A to the SRE motif. Upon stimulation of the cells, this protein no longer prevents binding of DNA by Band A, and suppression of binding is restored within 30 min. The phosphorylated tyrosine residue itself is important for the protein-protein interaction.
The effects of cantharidin analogues on xanthine oxidase. (1997)

Norcantharidin[3], the demethylated product of cantharidin[1] has been used for the treatment of hepatoma, carcinomas of esophagus and gastric cardia, leukopenia and hepatitis. Since the enzyme xanthine oxidase is involved in the diseases mentioned above, and the reactive oxygen species produced by the enzyme induces DNA damage and oxidative damage of tissues, fourteen cantharidin analogues and cantharidimide derivatives were tested for their effects on xanthine oxidase. The results showed that these compounds, listed in Figure 1, displayed very weak inhibitory effects on xanthine oxidase. Contrary to expectation, disodium cantharidate [2], Norcantharidin [3], dehydronorcantharidin [4], disodium dehydronorcantharidate [5], N-(2-pyridyl) cantharidimide [12], N-(3pyridyl) cantharidimide [13] and N-(4-pyridyl) cantharidimide [14] showed a slight stimulating effect on xanthine oxidase at several concentrations.
Single Component, Multiphase Fluids Flow Simulation in Porous Media with Lattice Boltzmann Method (2012)

In this paper, a single component, two-phase flow simulator is developed to investigate the behavior of isothermal two-phase fluid flow in porous media. The simulator is based on the lattice-Boltzmann method and the Shan-Chen multiphase model of nonideal fluids that allow coexistence of two phases of a single substance. We reproduce some different idealized situations in which the results are already known from theory or laboratory measurements and show the validity of the implementation for the physical two-phase flow in porous media. Application of the method to fluid intrusion in porous media is discussed and shows the effect of wettability on the fluid flow. The capability of reproducing critical flooding phenomena under strong wettability conditions is also proved.
Enhanced Effector Responses in Activated CD8+ T Cells Deficient in Diacylglycerol Kinases (2013)

Recent clinical trials have shown promise in the use of chimeric antigen receptor (CAR)-transduced T cells; however, augmentation of their activity may broaden their clinical use and improve their efficacy. We hypothesized that because CAR action requires proteins essential for T-cell receptor (TCR) signal transduction, deletion of negative regulators of these signaling pathways would enhance CAR signaling and effector T-cell function. We tested CAR activity and function in T cells that lacked one or both isoforms of diacylglycerol kinase (dgk) expressed highly in T cells, dgkα and dgkζ, enzymes that metabolize the second messenger diacylglycerol (DAG) and limit Ras/ERK activation. We found that primary murine T cells transduced with CARs specific for the human tumor antigen mesothelin showed greatly enhanced cytokine production and cytotoxicity when cocultured with a murine mesothelioma line that stably expresses mesothelin. In addition, we found that dgk-deficient CAR-transduced T cells were more effective in limiting the growth of implanted tumors, both concurrent with and after establishment of tumor. Consistent with our studies in mice, pharmacologic inhibition of dgks also augments function of primary human T cells transduced with CARs. These results suggest that deletion of negative regulators of TCR signaling enhances the activity and function of CAR-expressing T cells and identify dgks as potential targets for improving the clinical potential of CARs.
Super‐Soft Hydrogel Particles with Tunable Elasticity in a Microfluidic Blood Capillary Model (2014)

Super-soft PEG hydrogel particles with tunable elasticity are prepared via a mesoporous silica templating method. The deformability behavior of these particles, in a microfluidic blood-capillary model, can be tailored to be similar to that of human red blood cells. These results provide a new platform for the design and development of soft hydrogel particles for investigating bio-nano interactions.
Autoimmune T cell repertoire in optic neuritis and multiple sclerosis: T cells recognising multiple myelin proteins are accumulated in cerebrospinal fluid. (1994)

Monosymptomatic unilateral optic neuritis is a common first manifestation of multiple sclerosis. Abnormal T cell responses to myelin components including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated glycoprotein (MAG) have been implicated in the pathogenesis of multiple sclerosis. Antigen-reactive T helper type 1 (Th1)-like cells that responded by interferon gamma (IFN-gamma) secretion on antigen stimulation in vitro were counted. Untreated patients with optic neuritis and multiple sclerosis had similarly raised levels of T cells recognising MBP, PLP, and MAG in peripheral blood. Such T cells were strongly enriched in CSF. None of these myelin antigens functioned as immunodominant T cell antigen characteristic for optic neuritis or multiple sclerosis. The autoimmune T cell repertoire was not more restricted in optic neuritis (as an example of early multiple sclerosis). The autoreactive T cell repertoires differed in blood compared with CSF in individual patients with optic neuritis and multiple sclerosis. No relations were found between specificity or quantity of autoreactive T cells in blood or CSF, and clinical variables of optic neuritis or multiple sclerosis, or occurrence of oligoclonal IgG bands in CSF. The role of raised MBP, PLP, and MAG reactive Th1-like cells found in optic neuritis and multiple sclerosis remains unexplained.
Modeling of Programming and Read Performance in Phase-Change Memories—Part I: Cell Optimization and Scaling (2008)

One of the major concerns for the feasibility of phase-change memories is the reduction of the programming current. To this aim, several efforts have been dedicated both on cell geometry and on material engineering. This paper addresses programming-current minimization by the optimization of the cell geometry and materials, programming-current scaling, and the tradeoff between programming and readout performances of the cell. A general procedure to find the optimum-cell geometry is proposed and applied to a prototype vertical cell. Then, the evolution of program and read performances through technology nodes is analyzed by numerical simulations with the aid of an analytical model, for both the isotropic- and nonisotropic-scaling approaches. The two scaling approaches are discussed and compared in terms of program and read cell performances. Finally, material optimization is considered for further program-read improvement.
Loss of Matrix Adhesion Triggers Rapid Transformation-Selective Apoptosis in Fibroblasts (1997)

Cell-matrix and cell-cell adhesion are recognized physiological determinants of cell growth and survival. In epithelial and endothelial cell systems, oncogenic transformation has in several cases been shown to confer resistance to apoptosis upon depriving cells of substrate adhesion. We examined the effects of oncogenic transformation in adherent versus adhesion- deprived primary embryonic fibroblasts. Whereas untransformed early passage fibroblasts undergo cell cycle arrest, their Myc/Ras- or E1A/Ras-transformed counterparts rapidly enter apoptosis when placed into suspension. This phenomenon also occurs upon incubation with a soluble, RGD-containing integrin ligand and is blocked by a peptide antagonist to ICE family proteases or by aggregation of cells plated at high density. Loss of wild-type p53 modulates the kinetics but does not abrogate this death pathway. Transformation with activated Src rather than Ras rendered fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect likely related to Src's role in integrin signaling, while simultaneously sensitizing the cells to radiation-induced apoptosis. Thus cell adhesion events regulate transformation-selective apoptosis in fibroblasts and provide potentially important targets for understanding and interfering with tumor cell viability.
A Correlative Morphologic Study of Human Breast and Endometrium in the Menstrual Cycle (1986)

From the Department of Pathology, University of New Mexico School of Medicine, and Albuquerque Veterans Administration Medical Center, Albuquerque, New Mexico
Why are ?natively unfolded? proteins unstructured under physiologic conditions? (2000)

"Natively unfolded" proteins occupy a unique niche within the protein kingdom in that they lack ordered structure under conditions of neutral pH in vitro. Analysis of amino acid sequences, based on the normalized net charge and mean hydrophobicity, has been applied to two sets of proteins: small globular folded proteins and "natively unfolded" ones. The results show that "natively unfolded" proteins are specifically localized within a unique region of charge-hydrophobicity phase space and indicate that a combination of low overall hydrophobicity and large net charge represent a unique structural feature of "natively unfolded" proteins.
A Thin-Layer Amperometric Sensor for Hydrogen Sulfide:  The Use of Microelectrodes To Achieve a Membrane-Independent Response for Clark-Type Sensors (2003)

An electrochemical cell design of the Clark type including a thin layer of electrolyte in contact with a microelectrode has been successfully applied for the determination of sulfide utilizing its electrochemically initiated reaction with aqueous diethyl-p-phenylenediamine. The analytical parameters obtained were independent of the membrane used to separate the inner chamber and the outside sulfide-containing solution. The independence arises since the thickness of the diffusion layer associated with the microelectrode is small and, in contrast to the conventional macroelectrode Clark electrode, does not impinge on the membrane. This provides an improvement in gas sensor design and development as it obviates the need for membrane calibration and should simplify the application of Clark cells for variable-temperature measurements.
Invariant chain retains MHC class II molecules in the endocytic pathway (1993)

During exocytosis of MHC class II, the class II alpha beta heterodimer associates with a third polypeptide termed invariant chain (Ii). Class II and Ii are coordinately processed and transported until proteolytic cleavage of Ii in an acidic compartment immediately before class II surface expression. Although the lysosomotropic agent chloroquine (CQ) prevents dissociation of class II/Ii within the cell, the ultimate fate of these complexes has not been determined. We considered two alternative possibilities. If Ii encodes an intracellular retention signal, then persistent association of Ii with class II could lead to intracellular accumulation of class II/Ii complexes. Alternatively, if Ii does not block further transport of class II, then CQ treatment should result in aberrant expression of class II/Ii complexes at the cell surface. Ltk- and EL4 cells transfected with I-A(d) alone or I-A(d) plus Ii were treated with CQ and examined for changes in surface class II and Ii expression. Anti-Ii mAb surface staining did not increase with prolonged CQ treatment, but a dramatic decrease in surface class II staining was observed. This decrease in class II was observed both with genomic Ii and p31 cDNA transfectants and was rapidly reversed upon drug removal. Accumulation of Ii and class II within treated cells was directly observed by intracellular staining. Similar effects on MHC surface expression were observed with the lysosomotropic agents primaquine and NH4Cl and the cysteine protease inhibitor leupeptin. Ii-negative cells treated in parallel displayed no effect of the lysosomotropic agents or leupeptin on class II surface staining. These results indicate that dissociation of Ii from newly synthesized class II is required for transport of the alpha beta dimer to the cell surface, and suggest that Ii serves to retain class II molecules in a post-Golgi endocytic compartment.
Purification and characterization of murine retroviral reverse transcriptase expressed in Escherichia coli. (1985)

Expression of a region of the Moloney murine leukemia virus (M-MuLV) pol gene in Escherichia coli resulted in the synthesis of reverse transcriptase activity which could be detected in crude extracts. Construction of deletions at the 3' terminus of this gene resulted in a 4-fold increase in the level of the reverse transcriptase activity in the soluble fraction of crude lysates and yielded the high level production of a stable protein species of Mr = 71,000. Purification of this protein by column chromatography on DEAE-cellulose, phosphocellulose, polyribocytidylic acid-agarose, and hydroxylapatite indicated that it was a multifunctional enzyme containing RNase H and reverse transcriptase activity. The Mr = 71,000 species had a sedimentation coefficient of 4.65 S by glycerol gradient centrifugation, indicating that the enzyme was a monomer. Using poly(A)+ mRNAs primed with oligo(dT), the enzyme synthesized double-stranded DNA copies between 1.3 and 9.9 kilobases in length. Synthesis of long cDNA required 8 mM Mg2+, 4 mM Mn2+, 2 mM dNTPs, and saturating levels of enzyme. Actinomycin D efficiently limited the enzyme to the first strand synthesis. Additional characteristics of the fusion protein are described.
Purification and Characterization of Adenosine Triphosphate: Ribonucleic Acid Adenyltransferase from Escherichia coli (1973)

A primer‐dependent poly (A)‐polymerizing activity using ATP as substrate (ATP: RNA adenyltransferase) was isolated in high yield from Escherichia coli and purified to apparent homogeneity. For this purpose an assay system had to be used which restricted a variety of infering enzyme activities. Since the enzyme aggregates to macromolecular cell components or precipitates when kept in low salt conditions (&lt;0.4 M NaCl), it was necessary to perform the entire purification procedure in high salt conditions. This was accomplished by using a high salt ribosomal supernatant, a polyethylenglycol‐dextran‐NaCl phase partition step and a very efficient final high salt phosphocellulose chromatography. At 0.5 M NaCl the enzyme has a molecular weight of approximately 58000. Dodecylsulfate gel electrophoresis shows a single polypeptide chain of molecular weight × 50000. The enzyme has a high preference for ATP as substrate. Manganese ions show higher activity as cofactors than magnesium ions. All classes of natural RNAs are used as primers. The free 3′terminal hydroxyl group of the RNA is required. The enzyme is unable to catalyze a pyrophosphorolysis or a phosphorolysis reaction. It is shown that ATP: RNA adenyl‐transferase preferentially synthesizes rather long chains of poly(A) attached to the RNA primers. No relation between the enzyme protein and subunits of the DNA‐dependent RNA polymerase could be detected.
Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R/2N Transgenic Mice (2004)

Protein tau-3R/4R isoform ratio and phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration. The underlying mechanisms were studied here in three transgenic mouse strains with identical genetic background, all expressing the tau-4R/2N isoform driven specifically in neurons by the thy1 gene promoter. Two strains, expressing human tau-4R/2N or mutant tau-4R/2N-P301L at similar, moderate levels, developed very different phenotypes. Tau-4R/2N mice became motor-impaired already around age 6-8 weeks, accompanied by axonopathy (dilatations, spheroids), but no tau aggregates, and surviving normally. In contrast, tau-P301L mice developed neurofibrillary tangles from age 6 months, without axonal dilatations and, despite only minor motor problems, all succumbing before the age of 13 months. The third strain, obtained by tau knock-out/knock-in (tau-KOKI), expressed normal levels of wild-type human tau-4R/2N replacing all mouse tau isoforms. Tau-KOKI mice survived normally with minor motor problems late in life and without any obvious pathology. Biochemically, a fraction of neuronal tau in aging tau-P301L mice was hyperphosphorylated concomitant with conformational changes and aggregation, but overall, tau-4R/2N was actually more phosphorylated than tau-P301L. Significantly, tau with changed conformation and with hyperphosphorylation colocalized in the same neurons in aging tau-P301L mice. Taken together, we conclude that excessive binding of tau-4R/2N as opposed to reduced binding of tau-P301L to microtubules is responsible for the development of axonopathy and tauopathy, respectively, in tau-4R/2N and tau-P301L mice and that the conformational change of tau-P301L is a major determinant in triggering the tauopathy.
Induction of polynucleotide‐protein cross‐linkages by ultraviolet irradiation (1986)

The efficiency and specificity of RNA-protein cross-linking in the 30S subunit of Escherichia coli ribosomes, induced by low-intensity (10(15) photons cm-2 s-1, 254 nm) and high-intensity [(1.6-6.8) X 10(24) photons cm-2 s-1, 266 nm, pulse duration 10(-8) s] ultraviolet radiation, are studied. Under the former conditions proteins S4, S7 and S9/S11, and under the latter conditions these proteins together with S3, S18 and S20, are cross-linked to 16S RNA. Biphotonic processes operate in the latter case. In the presence of 2-mercaptoethanol cross-linking occurs either directly, via a higher excited state or via activated intermediates with life-times less than 25 ns. Cross-links thus formed are specific, i.e. they are formed between regions of macromolecules which are in contact in the native (non-disturbed) complex prior to excitation. The efficiency of cross-linking (per photon absorbed) is 20-100 times higher upon two-step excitation as compared with single-step excitation and an analysable number of cross-links are produced in a single pulse. Only base U-1239 of 16S RNA is cross-linked to protein S7 by low-intensity radiation, whereas the adjacent base, G-1240 is also involved in laser-induced cross-linking. A transition from the former to the latter conditions allows one to reduce the duration of irradiation from several minutes to several nanoseconds.
Regulatory mechanisms of periodontal regeneration (2003)

The periodontal ligament, located between the cementum and the alveolar bone, has a width ranging from 0.15 to 0.38 mm. Regeneration and homeostasis of the periodontal ligament are highly significant functions in relation to periodontal therapy, tooth transplantation or replantation, and orthodontic tooth movement. The purpose of this review is to discuss the regulatory mechanisms of regenerative and homeostatic functions in the periodontal ligament based on currently published studies and also on our own experimental data. We consider the capability of the ligament tissue to promote or to suppress calcification in connection with bone and cementum formation and the maintenance of the periodontal ligament space. Also discussed are the involvement of the periodontal ligament tissue in the regenerative ability, cell proliferation, growth and differentiation factors, extracellular matrix proteins, homeostatic phenomena, function of Malassez epithelial rests, tooth movement, or occlusal loading. Regulatory mechanisms for regeneration and homeostasis of the periodontal ligament are hypothetically proposed.
Registration of head CT images to physical space using a weighted combination of points and surfaces [image-guided surgery] (1998)

Most previously reported registration techniques that align three-dimensional image volumes by matching geometrical features such as points or surfaces use a single type of feature. We recently reported a hybrid registration technique that uses a weighted combination of multiple geometrical feature shapes. In this study we use the weighted geometrical feature (WGF) algorithm to register computed tomography (CT) images of the head to physical space using the skin surface only, the bone surface only, and various weighted combinations of these surfaces and one fiducial point (centroid of a bone-implanted marker). We use data acquired from 12 patients that underwent temporal lobe craniotomies for the resection of cerebral lesions. We evaluate and compare the accuracy of the registrations obtained using these various approaches by using as a reference gold standard the registration obtained using three bone-implanted markers. The results demonstrate that a combination of geometrical features can improve the accuracy of CT-to-physical space registration. Point-based registration requires a minimum of three noncolinear points. The position of a bone-implanted marker can be determined much more accurately than that of a skin-affixed marker or an anatomic landmark. A major disadvantage of using bone-implanted markers is that an invasive procedure is required to implant each marker. By combining surface information, the WGF algorithm allows registration to be performed using only one or two such markers. One important finding is that the use of a single very accurate point (a bone-implanted marker) allows very accurate surface-based registration to be achieved using very few surface points. Finally, the WGF algorithm, which not only allows the combination of multiple types of geometrical information but also handles point-based and surface-based registration as degenerate cases, could form the foundation of a "flexible" surgical navigation system that allows the surgeon to use what he considers the method most appropriate for an individual clinical situation.
The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release (1990)

A deletion mutation affecting vpu was introduced into an infectious molecular clone of human immunodeficiency virus type 1, and the resultant phenotype was examined after infection of human T lymphocytes. The absence of vpu resulted in an accumulation of cell-associated viral proteins and impaired the release of progeny virions. Both electron microscopic and biochemical analyses indicated that a large proportion of the mutant particles was attached to the surface of infected cells. Significant variation in the size and shape of these progeny virions was observed. In addition, intracytoplasmic particles, some of which formed aberrant budding structures, were visualized in T cells infected with the vpu mutant. Indirect immunofluorescence analyses of cultures inoculated with wild-type virus with use of a vpu-specific antiserum demonstrated that vpu is mainly localized to a perinuclear region in the cytoplasm of virus-producing cells.
A Multi-Sensor System for Airborne Image Capture and Georeferencing (2000)

The development and preliminary testing of a fully digital multi-sensor system for airborne remote sensing and geo-graphic information system (GIS) applications is described.