gebhart/patrepeval huggingface dataset:
The liver as a site of T-cell apoptosis: graveyard, or killing field? (2000)

The liver is a site at which apoptotic CD8+ cells accumulate during the clearance phase of peripheral immune responses. Normal mouse liver contains an unusual mixture of lymphocytes in which natural killer (NK) and NK-T cells are abundant and apoptotic T cells are present, and we interpret these cell populations as, respectively, agents and targets of an intrahepatic T-cell trapping and killing mechanism. In support of this idea, direct perfusion of activated lymphocyte populations through the normal liver results in the selective retention of activated CD8+ T cells. T cells trapped in this manner undergo apoptosis in the liver. This mechanism could explain the importance of the liver in oral tolerance, the phenomenon of tolerance induced by portal vein infusion of antigenic cells, the tolerance to allogeneic liver allografts, and the persistence of some liver pathogens including hepatitis C.
Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery (2003)

We present a method of constructing a database of intraoperatively observed human subcortical electrophysiology. In this approach, patient electrophysiological data are standardized using a multiparameter coding system, annotated to their respective magnetic resonance images (MRIs), and nonlinearly registered to a high-resolution MRI reference brain. Once registered, we are able to demonstrate clustering of like interpatient physiologic responses within the thalamus, globus pallidus, subthalamic nucleus, and adjacent structures. These data may in turn be registered to a three-dimensional patient MRI within our image-guided visualization program enabling prior to surgery the delineation of surgical targets, anatomy with high probability of containing specific cell types, and functional borders. The functional data were obtained from 88 patients (106 procedures) via microelectrode recording and electrical stimulation performed during stereotactic neurosurgery at the London Health Sciences Centre. Advantages of this method include the use of nonlinear registration to accommodate for interpatient anatomical variability and the avoidance of digitized versions of printed atlases of anatomy as a common database coordinate system. The resulting database is expandable, easily searched using a graphical user interface, and provides a visual representation of functional organization within the deep brain.
Materials and Mechanics for Stretchable Electronics (2010)

Recent advances in mechanics and materials provide routes to integrated circuits that can offer the electrical properties of conventional, rigid wafer-based technologies but with the ability to be stretched, compressed, twisted, bent, and deformed into arbitrary shapes. Inorganic and organic electronic materials in microstructured and nanostructured forms, intimately integrated with elastomeric substrates, offer particularly attractive characteristics, with realistic pathways to sophisticated embodiments. Here, we review these strategies and describe applications of them in systems ranging from electronic eyeball cameras to deformable light-emitting displays. We conclude with some perspectives on routes to commercialization, new device opportunities, and remaining challenges for research.
Reverse Mortgages and Interest Rate Risk (1994)

We develop and apply a valuation model that quantifies the interest rate risk inherent in fixed‐rate reverse mortgages. Consistent with intuition, our results show that the interest rate risk of a reverse mortgage is greater than that of either a typical coupon bond or a regular mortgage. Somewhat surprisingly, we find that this difference in interest rate risk is extremely large. In fact, the interest rate risk of a reverse mortgage often is several orders of magnitude greater than the interest rate risk of other fixed‐income securities.
Engineering High-Affinity T Cell Receptor/ Cytokine Fusions for Therapeutic Targeting (2012)

Jennifer D. Stone1, Yiyuan Yin2, Min Mo2, K. Scott Weber3, David L. Donermeyer3, Paul M. Allen3,Roy A. Mariuzza2,4 and David M. Kranz 1 1Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, 2Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, 3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, 4Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, USA
The sequence and structure of a new serum amyloid A gene (1986)

The acute phase response is characterized by changes in the serum concentrations of many proteins. A 1000-fold increase in the concentration of serum amyloid A (SAA) protein occurs within 24 hours of LPS injection in the mouse. We have isolated a cDNA clone and its corresponding genomic phage for a third, previously unreported SAA protein. The sequence of the cDNA, the gene's exons and neighboring DNA are presented along with the mapping evidence supporting the gene structure.
Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis (2010)

Multiple sclerosis (MS) is a human demyelinating disease characterized by multifocal regions of inflammation, progressive myelin loss within the central nervous system (CNS), and eventual failure to remyelinate damaged axons. These problems suggest deficiencies in recruiting and/or maturation of oligodendrocyte progentior cells (OPCs) and highlight cell replacement therapies to promote remyelination. We have used a model of viral-induced demyelination to characterize signaling cues associated with positional migration of transplanted remyelination-competent cells. Although successful transplantation of rodent-derived glial cell types into models of MS has been performed, the mechanisms by which these cells navigate within an inflammatory environment created by a persistent virus has not been defined. Infection of the mouse CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an immune-mediated demyelinating disease with clinical and histologic similarities to MS. Surgical engraftment of GFP+ neural stem cells (NSCs) into spinal cords of JHMV-infected mice with established demyelination results in migration, proliferation, and differentiation of the cells into OPCs and mature oligodendrocytes that is associated with increased axonal remyelination. Treatment with anti-CXCL12 [stromal derived factor-1alpha, (SDF-1alpha)] blocking serum resulted in a marked impairment in migration and proliferation of engrafted stem cells. Moreover, small molecule-mediated antagonism of CXCR4, but not CXCR7, impaired migration and proliferation, to an extent similar to that with anti-CXCL12 treatment. These data highlight the importance of the CXCL12:CXCR4 pathway in regulating homing of engrafted stem cells to sites of tissue damage within the CNS of mice persistently infected with a neurotropic virus undergoing immune-mediated demyelination.
Model-based domain ontology engineering (2009)

Business Process Models describe sequences of activities, expressed in a certain modeling language, with the model elements being labeled following the business terminology in use in the applicable domain. In case no predefined vocabulary or rules for assigning those labels are in place, terms are chosen individually on a case-by-case-basis. As a result, models are often semantically heterogeneous concerning the domain language. For resolving these ambiguities when comparing or integrating models, support through a consensus terminology is required. We show in this discussion paper how to reuse models to capture the domain knowledge contained and relate it for usage and further collaborative evolution, so that over time an authentic domain ontology can emerge.
High-Yield Organic Dispersions of Unfunctionalized Graphene (2009)

We report a simple, high-yield, method of producing homogeneous dispersions of unfunctionalized and nonoxidized graphene nanosheets in ortho-dichlorobenzene (ODCB). Sonication/centrifugation of various graphite materials results in stable homogeneous dispersions. ODCB dispersions of graphene avert the need for harsh oxidation chemistry and allow for chemical functionalization of graphene materials by a range of methods. Additionally, films produced from ODCB-graphene have high conductivity.
High-resolution accurate mass measurements of biomolecules using a new electrospray ionization ion cyclotron resonance mass spectrometer (1993)

A novel electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer based on a 7-T superconducting magnet was developed for high-resolution accurate mass measurements of large biomolecules. Ions formed at atmospheric pressure using electrospray ionization (ESI) were transmitted (through six differential pumping stages) to the trapped ion cell maintained below 10(-9) torr. The increased pumping speed attainable with cryopumping (> 10(5) L/s) allowed brief pressure excursions to above 10(-4) torr, with greatly enhanced trapping efficiencies and subsequent short pumpdown times, facilitating high-resolution mass measurements. A set of electromechanical shutters were also used to minimize the effect of the directed molecular beam produced by the ES1 source and were open only during ion injection. Coupled with the use of the pulsed-valve gas inlet, the trapped ion cell was generally filled to the space charge limit within 100 ms. The use of 10-25 ms ion injection times allowed mass spectra to be obtained from 4 fmol of bovine insulin (Mr 5734) and ubiquitin (Mr 8565, with resolution sufficient to easily resolve the isotopic envelopes and determine the charge states. The microheterogeneity of the glycoprotein ribonuclease B was examined, giving a measured mass of 14,898.74 Da for the most abundant peak in the isotopic envelope of the normally glycosylated protein (i.e., with five mannose and two N-acetylglucosamine residues (an error of approximately 2 ppm) and an average error of approximately 1 ppm for the higher glycosylated and various H3PO4 adducted forms of the protein. Time-domain signals lasting in excess of 80 s were obtained for smaller proteins, producing, for example, a mass resolution of more than 700,000 for the 4(+) charge state (m/z 1434) of insulin.
Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats (2015)

Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis. Osteogenic differentiation of hPSCs with and without NELL-1 was tested in vitro. The results indicated that NELL-1 significantly increased the osteogenic potential of hPSCs in both osteoporotic and nonosteoporotic donors. Next, spinal fusion was performed by implanting scaffolds with regular or high doses of hPSCs, with or without NELL-1 in ovariectomized rats (n = 41). Regular doses of hPSCs or NELL-1 achieved the fusion rates of only 20%-37.5% by manual palpation. These regular doses had previously been shown to be effective in nonosteoporotic rat spinal fusion. Remarkably, the high dose of hPSCs+NELL-1 significantly improved the fusion rates among osteoporotic rats up to approximately 83.3%. Microcomputed tomography imaging and quantification further confirmed solid bony fusion with high dose hPSCs+NELL-1. Finally, histologically, direct in situ involvement of hPSCs in ossification was shown using undecalcified samples. To conclude, hPSCs combined with NELL-1 synergistically enhances spinal fusion in osteoporotic rats and has great potential as a novel therapeutic strategy for osteoporotic patients.
Enhancement of the proliferation of human marrow erythroid (BFU-E) progenitor cells by prostaglandin E requires the participation of OKT8- positive T lymphocytes and is associated with the density expression of major histocompatibility complex class II antigens on BFU-E (1986)

The relationship between major histocompatibility complex class II antigens (MHC class II, eg, HLA-DR, Ia), T lymphocytes, and the enhancement of erythroid colony formation from BFU-E by prostaglandin E was analyzed using normal bone marrow cells. In primary methylcellulose culture, the addition of prostaglandin E1 (PGE1) to unseparated buffy coat, low-density, or nonadherent low-density (NAL) marrow cells resulted in an enhancement of the total number of erythroid (BFU-E) colonies observed. Treatment of bone marrow cells with a monoclonal antihuman MHC class II antibody plus complement (C') resulted in a reduction of the total number of colonies by approximately 50% and abrogation of the enhancing effect of PGE1. Analysis of accessory cell requirements by depletion of both adherent cells and sheep erythrocyte rosetting lymphocytes (E+ cells) and reconstitution using C' or anti-MHC class II antibody plus C'-treated T cell-depleted NAL (NALT-) marrow cells and E+ cell populations treated with C' or anti-MHC class II antibody plus C' demonstrated a requirement for MHC class II antigen-T cells, but not adherent cells, and a requirement for MHC class II antigen + BFU-E in order to observe the enhancing effect of PGE1 on erythroid colony formation. Positive selection of BFU-E in NALT- bone marrow expressing differing density distributions of MHC class II antigens was accomplished with monoclonal anti-MHC class II antibodies and sorting with a fluorescence-activated cell sorter (FACS). Addition of E+ cells to the different populations of MHC class II antigen+ NALT- cells demonstrated that the PGE-enhancing effects on erythroid colony formation were directly related to increasing density distributions of MHC class II antigens on BFU-E. Colony formation by BFU-E expressing a low density distribution of MHC class II antigens or having no detectable MHC class II antigens, as determined by FACS analysis, was not enhanced by PGE1 in the presence of MHC class II antigen-positive or -negative T cells.
Increased Antigen Presentation Efficiency by Coupling Antigens to MHC Class I Trafficking Signals (2008)

Genetic modification of vaccines by linking the Ag to lysosomal or endosomal targeting signals has been used to route Ags into MHC class II processing compartments for improvement of CD4+ T cell responses. We report in this study that combining an N-terminal leader peptide with an MHC class I trafficking signal (MITD) attached to the C terminus of the Ag strongly improves the presentation of MHC class I and class II epitopes in human and murine dendritic cells (DCs). Such chimeric fusion proteins display a maturation state-dependent subcellular distribution pattern in immature and mature DCs, mimicking the dynamic trafficking properties of MHC molecules. T cell response analysis in vitro and in mice immunized with DCs transfected with Ag-encoding RNA showed that MITD fusion proteins have a profoundly higher stimulatory capacity than wild-type controls. This results in efficient expansion of Ag-specific CD8+ and CD4+ T cells and improved effector functions. We used CMVpp65 and NY-ESO-1 Ags to study preformed immune responses in CMV-seropositive individuals and cancer patients. We show that linking these Ags to the MITD trafficking signal allows simultaneous, polyepitopic expansion of CD8+ and CD4+ T cells, resulting in distinct CD8+ T cell specificities and a surprisingly broad and variable Ag-specific CD4+ repertoire in different individuals.
Resistant Starch and Health — Himalaya 292, a Novel Barley Cultivar to Deliver Benefits to Consumers (2003)

Abstract Dietary and lifestyle change is a recognised strategy for the management and prevention of socio‐economically important non‐infectious diseases. Dietary fibre is composed largely of non‐starch polysaccharides (NSP), and greater consumption of NSP‐rich foods relieves simple constipation very effectively. Starch (as resistant starch, RS) is also receiving attention for its potential role in promoting colonic function. Resistant starch is that fraction of starch which escapes human small intestinal digestion and enters the large bowel where (together with a variable fraction of NSP) it is fermented by the resident microflora. The resulting short chain fatty acids (SCFA) are taken up by the large bowel and metabolised. SCFA mediate many of the health benefits ascribed to NSP and RS. Starch consumption is low in affluent westernised countries, despite recommendations by health agencies. In Australia, foods enriched in RS as a high amylose maize starch have gained consumer acceptance. However, scope remains for additional products and ingredients and a company, Ascentia Pty Ltd, has been established to develop a novel barley cultivar ( Hordeum vulgare var. himalaya 292 ) for this purpose. This cultivar has a specific gene alteration leading to a loss of starch synthetase lla activity resulting in a grain which is low in starch but disproportionately higher in amylose and also NSP. Animal and human studies have shown that Himalaya 292 is high in RS relative to existing products and has a low glycaemic index and the cultivar offers promise as a vehicle to deliver health benefits to consumers.
Design and development of therapies using chimeric antigen receptor‐expressing T cells (2013)

Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non-protein antigens) with the persistence, trafficking, and effector functions of a T cell. This article describes how the past two decades have seen a crescendo of research which has now begun to translate these potential benefits into effective treatments for patients with cancer. We describe the basic design of CARs, describe how antigenic targets are selected, and the initial clinical experience with CAR-T cells. Our review then describes our own and other investigators' work aimed at improving the function of CARs and reviews the clinical studies in hematological and solid malignancies that are beginning to exploit these approaches. Finally, we show the value of adding additional engineering features to CAR-T cells, irrespective of their target, to render them better suited to function in the tumor environment, and discuss how the safety of these heavily modified cells may be maintained.
Real-time automatic boundary detection in echocardiography (2003)

Echocardiographic instruments allow for a visual appreciation of the regional and the global anatomy and function of the left ventricle. Quantitative assessment of regional and global function by wall thickening and wall motion necessitates the detection of endocardial and epicardial borders. Real-time methods of echocardiographic edge detection indicate the endocardial corner in real time. The correlation lengths set the independent sample size; the resolution of border location sets the maximum number of usable independent samples. With a closed cavity border, real-time area measurements become feasible. It may be possible with real-time area measurements to assess important diagnostic aspects of regional functions of the heart within selected scanned sections.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Positive and negative selection invoke distinct signaling pathways. (1996)

During T cell development, interaction of the T cell receptor (TCR) with cognate ligands in the thymus may result in either maturation (positive selection) or death (negative selection). The intracellular pathways that control these opposed outcomes are not well characterized. We have generated mice expressing dominant-negative Ras (dnRas) and Mek-1 (dMek) transgenes simultaneously, either in otherwise normal animals, or in animals expressing a transgenic TCR, thereby permitting a comprehensive analysis of peptide-specific selection. In this system, thymocyte maturation beyond the CD4+8+ stage is blocked almost completely, whereas negative selection, assessed using an in vitro deletion protocol, is quantitatively intact. This suggests that activation of the mitogen-activated protein kinase (MAPK) cascade is necessary for positive selection, but irrelevant for negative selection. Generation of gamma/delta and of CD4-8- alpha/beta T cells proceeds normally despite blockade of the MAPK cascade. Hence, only cells that mature via conventional, TCR-mediated repertoire selection require activation of the MAPK pathway to complete their maturation.
Integrated microfluidic cell culture and lysis on a chip (2007)

We present an integrated microfluidic cell culture and lysis platform for automated cell analysis that improves on systems which require multiple reagents and manual procedures. Through the combination of previous technologies developed in our lab (namely, on-chip cell culture and electrochemical cell lysis) we have designed, fabricated, and characterized an integrated microfluidic platform capable of culturing HeLa, MCF-7, Jurkat, and CHO-K1 cells for up to five days and subsequently lysing the cells without the need to add lysing reagents. On-demand lysis was accomplished by local hydroxide ion generation within microfluidic chambers, releasing both proteinacious (GFP) and genetic (Hoescht-stained DNA) material. Sample proteins exposed to the electrochemical lysis conditions were immunodetectable (p53) and their enzymatic activity (HRP) was investigated.
Generating a High Affinity Scorpion Toxin Receptor in KcsA-Kv1.3 Chimeric Potassium Channels (2000)

The crystal structure of the bacterial K(+) channel, KcsA (Doyle, D. A., Morais, C. J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., and MacKinnon, R. (1998) Science 280, 69-77), and subsequent mutagenesis have revealed a high structural conservation from bacteria to human (MacKinnon, R., Cohen, S. L., Kuo, A., Lee, A., and Chait, B. T. (1998) Science 280, 106-109). We have explored this conservation by swapping subregions of the M1-M2 linker of KcsA with those of the S5-S6 linker of the human Kv-channel Kv1.3. The chimeric K(+) channel constructs were expressed in Escherichia coli, and their multimeric state was analyzed after purification. We used two scorpion toxins, kaliotoxin and hongotoxin 1, which bind specifically to Kv1.3, to analyze the pharmacological properties of the KcsA-Kv1.3 chimeras. The results demonstrate that the high affinity scorpion toxin receptor of Kv1.3 could be transferred to KcsA. Our biochemical studies with purified KcsA-Kv1.3 chimeras provide direct chemical evidence that a tetrameric channel structure is necessary for forming a functional scorpion toxin receptor. We have obtained KcsA-Kv1.3 chimeras with kaliotoxin affinities (IC(50) values of approximately 4 pm) like native Kv1.3 channels. Furthermore, we show that a subregion of the S5-S6 linker may be an important determinant of the pharmacological profile of K(+) channels. Using available structural information on KcsA and kaliotoxin, we have developed a structural model for the complex between KcsA-Kv1.3 chimeras and kaliotoxin to aid future pharmacological studies of K(+) channels.