gebhart/patrepeval huggingface dataset:
Production of Human Monoclonal Rheumatoid Factor Secreting Hybridomas Derived from Rheumatoid Synovial Cells (1989)

Abstract : Although the cellular arm of the immune system is undoubtedly important in the pathogenesis of rheumatoid arthritis (RA), RA is an autoimmune extravascular immune complex disease involving synovium and interstitial tissues. The major autoantibody present is rheumatoid factor (RF), a polyclonal autoantibody directed to the Fc portion of IgG. Several observations point to RF-IgG complexes and their subsequent activation of complement as being important in the pathogenesis of RA. RF are heterogeneous in many qualitative characteristics including complement activating properties, specificity and avidity. For example, exhaustive studies attempting to demonstrate unique antigenic determinants on IgG Fc towards which serum RF is directed have been inconclusive, although many RA serum RF react with an antigen in the Fc that binds staphylococcal protein A. Characterizing the molecular genetic basis of RF in RA could provide exciting new understanding of important genetic and triggering factors in RA. However, this has not been possible because of the polyclonality of RF in RA. Hybridoma technology should overcome these difficulties and allow more precise characterization of these polyclonal RF, but reports to date using peripheral blood lymphocytes (PBL) have described only limited success. We herein describe successful production of human monoclonal IgM RF (mRF) secreting hybridomas derived from rheumatoid synovial cells (RSC). Reprints.
Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation (2023)

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.
Clonal analysis of Escherichia coli of serogroups O9, O20, and O101 isolated from Australian pigs with neonatal diarrhea (1993)

The genetic diversity of 87 isolates of Escherichia coli recovered from Australian pigs with neonatal diarrhea was examined by multilocus enzyme electrophoresis. The isolates were of serogroups O9, O20, and O101, and although most isolates lacked K88(F4), K99(F5), 987P(F6), and F41 fimbriae, they were considered to be involved in the etiology of the diarrhea. The isolates were extremely diverse, considering their origin from a single pathological condition in one country. There were estimated to be 18, 16, and 12 clones of the three respective serogroups in the collection, with serogroup diversities of 0.387, 0.448, and 0.275, respectively. Comparison with the results previously obtained for isolates from piglets with postweaning diarrhea suggested that bacteria from piglets with these two conditions did not come from any particular common genetic background. The overall genetic diversity for the combined collection was the same as that reported by others for representative isolates selected from throughout the species (0.47). The current results indicate that if isolates of these O groups are involved in porcine diarrhea, their pathogenicity is directly linked to their O somatic antigen type and is not simply due to the wide distribution of a small number of virulent clones.
The high affinity Fc epsilon receptor gamma subunit (Fc epsilon RI gamma) facilitates T cell receptor expression and antigen/major histocompatibility complex-driven signaling in the absence of CD3 zeta and CD3 eta (1991)

The T cell receptor (TCR) is a molecular complex formed by at least seven transmembrane proteins: the antigen/major histocompatibility complex recognition unit (Ti alpha-beta heterodimer) and the invariant CD3 chains (gamma, delta, epsilon, zeta, and eta). In addition to targeting partially assembled Ti alpha-beta CD3 gamma delta epsilon TCR complexes to the cell surface, CD3 zeta appears to be essential for interleukin-2 production after TCR stimulation with antigen/major histocompatibility complex. The gamma chain of the high affinity Fc receptor for IgE (Fc epsilon RI gamma) has significant structural homology to CD3 zeta and the related CD3 eta subunit. To identify the functional significance of sequence homologies between CD3 zeta and Fc epsilon RI gamma in T cells, we have transfected a Fc epsilon RI gamma cDNA into a T cell hybridoma lacking CD3 zeta and CD3 eta proteins. Herein we show that a Fc epsilon RI gamma-gamma homodimer associates with TCR components to up-regulate TCR surface expression. A TCR composed of Ti alpha-beta CD3 gamma delta epsilon Fc epsilon RI gamma-gamma is sufficient to restore the coupling of TCR antigen recognition to the interleukin-2 induction pathway, demonstrating the functional significance of structural homology between the above receptor subunits. These results, in conjunction with the recent finding that CD3 zeta, CD3 eta, and Fc epsilon RI gamma are coexpressed in certain T cells as subunits of an unusual TCR isoform, suggest that Fc epsilon RI gamma is likely to play a role in T cell lineage function.
Foundry-fabricated Inverse Designed Photonics (2019)

Fabrication-constrained inverse-designed silicon photonic devices are fabricated at a foundry and experimentally characterized, including a spatial mode demultiplexer with measured &lt; 1.25 dB insertion loss.
Immunological mimicry of PrPC-PrPSc interactions: antibody-induced PrP misfolding (2009)

Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to an abnormal protease-resistant conformational isoform (PrP(Sc)) by template-directed conversion. The interaction between PrP(C) and PrP(Sc) is mediated by specific sites which have been mapped to six putative 'binding and conversion domains' (PrP-BCD) through peptide and antibody competition studies. Monoclonal antibodies (mAbs) directed against the bityrosine motif Tyr-Tyr-Arg (YYR) specifically recognize PrP(Sc) and other misfolded PrP species. Here, we report that select bead-bound PrP-BCD mAbs induce exposure of bityrosine epitopes on mouse brain PrP. By competition immunoprecipitation, we show that PrP-BCD mAb-induced bityrosine exposure occurs at alpha-helices 1 and 3. However, PrP-BCD mAb-induced PrP(C) misfolding is not accompanied by beta-sheet dissociation, a key event in PrP(C) conversion to PrP(Sc), and is not associated with acquisition of protease resistance, or the capacity to recruit additional molecules of PrP. Our data suggest that mAb mimics of the physical interaction of PrP(C) with PrP(Sc) can induce unfolding of specific PrP domains, but that subsequent processes (including the energetically unfavorable beta-sheet dissociation) effect isoform conversion in prion disease.
A Novel Innovation and Entrepreneurship (I&E) Training Program for Biomedical Research Trainees (2022)

E4B is well accepted, and this preliminary evaluation suggests the program is effective. It could serve to support medical school curricula, business competitions, and technology transfer efforts, which are opportunities for future exploration. A more robust evaluation is planned and recruitment will be expanded to increase participation from women and underrepresented populations.
Medical 3D Printing: Tools and Techniques, Today and Tomorrow (2022)

Three-dimensional printing is a still-emerging technology with high impact for the medical community, particularly in the development of tissues for the clinic. Many types of printers are under development, including extrusion, droplet, melt, and light-curing technologies. Herein we discuss the various types of 3D printers and their strengths and weaknesses concerning tissue engineering. Despite the advantages of 3D printing, challenges remain in the development of large, clinically relevant tissues. Advancements in bioink development, printer technology, tissue vascularization, and cellular sourcing/expansion are discussed, alongside future opportunities for the field. Trends regarding in situ printing, personalized medicine, and whole organ development are highlighted.
In situmonitoring of crystallographic changes in Pd induced by diffusion of D (1998)

Crystallographic changes in a palladium wire cathode were monitored in situ, as deuterium was electrochemically deposited on the surface and diffused radially into the wire. Initially, the wire was pure Pd. A constant electrolysis current density of 1 ${\mathrm{m}\mathrm{A}/\mathrm{c}\mathrm{m}}^{2}$ was maintained and D slowly diffused into the wire. As the D concentration increased, the wire transformed from pure Pd, to the \ensuremath{\alpha} phase, and finally into the \ensuremath{\beta} phase. This reversible phase transformation begins on the surface and progresses radially inward. During the experiment, x-ray-diffraction data were collected from a volume element of about 180 pl. This volume element was systematically moved in 50-\ensuremath{\mu}m steps from the edge to the center of a 1.0 mm diameter Pd wire. Throughout the course of the experiment, the bulk value of x in ${\mathrm{PdD}}_{x},$ as determined from simultaneous measurements of the electrical resistivity, increased from 0 to \ensuremath{\sim}0.72. For each setting of the volume element, a monotonic increase in the volume of the \ensuremath{\alpha} phase was observed, until the material entered the two-phase region. Once the \ensuremath{\beta} phase appeared, the volumes of both phases decreased slightly with continued loading. The integrated intensities of diffraction peaks from each phase were used in conjunction with the known phase diagram to estimate the rate of compositional change within the volume element. The diffusion rate for the solute atoms was estimated to be $57\ifmmode\pm\else\textpm\fi{}8\mathrm{n}\mathrm{m}/\mathrm{s},$ based on the temporal and spatial dependence of the integrated intensities of the diffraction peaks from each phase. These data also were used to evaluate the time dependence of the concentration of the solute atoms $\ensuremath{\partial}c/\ensuremath{\partial}t$ and their diffusivity D. The value of $\ensuremath{\partial}c/\ensuremath{\partial}t$ increased linearly from $6.2\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}{\mathrm{s}}^{\mathrm{\ensuremath{-}}1}$ at the surface, to $7.6\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}{\mathrm{s}}^{\mathrm{\ensuremath{-}}1}$ midway into the wire. D was computed to be $(3.1\ifmmode\pm\else\textpm\fi{}1.0)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}11}{\mathrm{m}}^{2}/\mathrm{s}$ when the transition began at $r=250\ensuremath{\mu}\mathrm{m};$ 2 ks later it had decreased to $(2.1\ifmmode\pm\else\textpm\fi{}0.3)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}11}{\mathrm{m}}^{2}/\mathrm{s}.$ This may be due to the fact that the volume of the \ensuremath{\beta} lattice also decreased during this period.
Color Constancy for Scenes with Varying Illumination (Color Constancy with Varying Illumination) (1997)

We present an algorithm which uses information from both surface reflectance and illumination variation to solve for color constancy. Most color constancy algorithms assume that the illumination across a scene is constant, but this is very often not valid for real images. The method presented in this work identifies and removes the illumination variation, and in addition uses the variation to constrain the solution. The constraint is applied conjunctively to constraints found from surface reflectances. Thus the algorithm can provide good color constancy when there is sufficient variation in surface reflectances, or sufficient illumination variation, or a combination of both. We present the results of running the algorithm on several real scenes, and the results are very encouraging.
An in vitro Chondro-osteo-vascular Triphasic Model of the Osteochondral Complex (2020)

Abstract The generation of engineered models of the osteochondral complex to study its pathologies and develop possible treatments is hindered by the distinctly different properties of articular cartilage and subchondral bone, with the latter characterized by vascularization. In vitro models of the osteochondral complex have been mainly engineered as biphasic constructs containing just cartilage and bone cells, a condition very dissimilar from the in vivo environment. The different cellular components of the osteochondral complex are governed by interacting biochemical signaling; hence, to study the crosstalk among chondrocytes, osteoblasts, and endothelial cells, we have developed a novel triphasic model of the osteochondral tissue interface. Wet-spun poly(ε-caprolactone) (PCL) and PCL/hydroxyapatite (HA) scaffolds in combination with a methacrylated gelatin (gelMA) hydrogel were used as the polymeric backbone of the constructs. The scaffold components were engineered with human bone marrow derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs), and differentiated using a dual chamber microphysiological system (MPS) bioreactor that allows the simultaneous, separate flow of media of different compositions for induced differentiation of each compartment towards a cartilaginous or osseous lineage. Within the engineered Microphysiological Vascularized Osteochondral System (microVOCS), hMSCs showed spatially distinct chondrogenic and osteogenic markers in terms of histology and gene expression. HUVECs formed a stable capillary-like network in the engineered bone compartment and enhanced both chondrogenic and osteogenic differentiation of hMSCs, resulting in the generation of an in vitro system that mimics a vascularized osteochondral interface tissue.
Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning (2004)

To examine the role of the p53 homolog p73 in brain development, we studied p73-/-, p73+/-, E2F1-/-, and reeler mutant mice. p73 in developing brain is expressed in Cajal-Retzius (CR) cells, the cortical hem, and the choroid plexus. p73-expressing CR cells are lost in p73-/- embryos, although Reelin is faintly expressed in the marginal zone. Ectopic neurons in the p73-/- preplate and cortical hem at embryonic day 12 implicate p73 in the early developmental program of the cortex; however, preplate partition and early cortical plate formation are not disturbed. Postnatal p73-/- mice show a mild hypoplasia of the rostral cortex and a severely disrupted architecture of the posterior telencephalon. In the developing p73-/- hippocampus, the most striking abnormality is the absence of the hippocampal fissure, suggesting a role of p73 in cortical folding. p73+/- mice have a less severe cortical phenotype; they display a dorsal shift of the entorhinal cortex and a reduced size of occipital and posterior temporal areas, which acquire entorhinal-like features such as Reelin-positive cells in layer II. CR cells appear unaffected by heterozygosity. We relate the malformations of the posterior pole in p73 mutant mice to alterations of p73 expression in the cortical hem and suggest that p73 forms part of an early signaling network that controls neocortical and archicortical regionalization. In mice deficient for the transcription factor E2F1, a main activator of the TAp73 (transactivating p73) isoform, we find a defect of the caudal cortical architecture resembling the p73+/- phenotype along with reduced TAp73 protein levels and propose that an E2F1-TAp73 dependent pathway is involved in cortical patterning.
Adoptive immunotherapy of newly induced murine sarcomas. (1985)

Two newly induced methylcholanthrene sarcomas of C57BL/6 mouse origin were selected for studies of the adoptive immunotherapy of established tumors. The MCA 105 and MCA 106 tumors, used during their first five transplant generations, possessed weakly immunogenic tumor-associated transplantation antigens as revealed by failure to elicit immunity to reject 10(6) tumor cells by tumor growth and excision. Specific immunity to reject a 10(6) tumor cell challenge could be elicited in less than 50% of mice by immunization with a mixture of viable tumor cells and Corynebacterium parvum. Adoptive transfer of spleen cells from properly immunized mice consistently mediated the regression of established MCA 105 and MCA 106 tumors. Following systemic administration of 10(8) immune cells into mice bearing palpable tumor, the tumor grew for at least 1 week and then completely regressed. The adoptive immunotherapy was immunologically specific for each of these tumors and was mediated by sensitized T-lymphocytes. Irradiation (1000 R) of the transferred cells abrogated their in vivo activity. With both tumors, successful therapy required prior immune suppression of the host. This latter finding suggested the existence of suppression mechanisms mediated by tumor-bearing mice although we have been unable to reconstitute this suppression by giving T-cell-depleted mice syngeneic spleen cells. The two new animal tumor models characterized in this study not only demonstrate the feasibility of adoptive immunotherapy to weakly immunogenic tumors but also provide unique opportunities for mechanistic studies of the specificity of adoptive immunotherapy.
Extended propagation of sub-mm incoherent space-time fields over 110 m distance (2021)

Space-time (ST) wave packets are propagation-invariant pulsed beam endowed with a tight correlation between the underlying spatial and temporal frequencies. We present a theoretical formulation and experimental demonstration of sub-millimeter incoherent ST light sheets traversing 110 m without significant diffraction. We synthesize ST fields of beam width ~ 0.7 mm from a superluminescent diode with a bandwidth of ~20 nm centered at 840 nm and observe propagation-invariant behavior across a distance of over 100-m distance in free-space. Finally, we study the effect of the aperture on the propagation distance and far-field beam size of ST light sheets.
Ecteinascidin-743 inhibits activated but not constitutive transcription. (2002)

Ecteinascidin-743 (ET-743) is a promising chemotherapeutic agent currently in Phase III clinical trials. Previous studies indicated a novel spectrum of activity for this agent, including transcriptional inhibition. Initially hypothesized to target a single transcription factor (NF-Y), we now show that ET-743 is a more general inhibitor of activated transcription. Induction of the Sp1-regulated p21 gene by Trichostatin A (TSA) was blocked by ET-743 at concentrations that had minimal effect on uninduced (constitutive) expression. Moreover, ET-743 blocked induction of Gal4 fusion proteins by TSA without affecting activation mediated by the fusion proteins in the absence of the inducer. Finally, microarray analysis of SW620 cells treated with TSA and/or ET-743 indicated that activation of TSA-responsive promoters was blocked by ET-743 with little affect on nonresponsive promoters. These results, taken together with previous reports, leads us to suggest a mechanism whereby ET-743 is a novel, potent, and general inhibitor of activated but not uninduced transcription.
A Review of Capabilities and Scope for Hybrid Integration Offered by Silicon-Nitride-Based Photonic Integrated Circuits (2022)

In this review we present some of the recent advances in the field of silicon nitride photonic integrated circuits. The review focuses on the material deposition techniques currently available, illustrating the capabilities of each technique. The review then expands on the functionalisation of the platform to achieve nonlinear processing, optical modulation, nonvolatile optical memories and integration with III-V materials to obtain lasing or gain capabilities.
Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts (2014)

The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematologic cancers. We hypothesized that osteoblasts, components of the niche involved in hematopoietic stem cell (HSC) function, influence the fate of leukemic blasts. We show that osteoblast numbers decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion of osteoblasts in mouse models of acute leukemia increased circulating blasts and tumor engraftment in the marrow and spleen leading to higher tumor burden and shorter survival. Myelopoiesis increased and was coupled with a reduction in B lymphopoiesis and compromised erythropoiesis, suggesting that hematopoietic lineage/progression was altered. Treatment of mice with acute myeloid or lymphoblastic leukemia with a pharmacologic inhibitor of the synthesis of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss of osteoblasts. Maintenance of the osteoblast pool restored normal marrow function, reduced tumor burden, and prolonged survival. Leukemia prevention was attributable to maintenance of osteoblast numbers because inhibition of serotonin receptors alone in leukemic blasts did not affect leukemia progression. These results suggest that osteoblasts play a fundamental role in propagating leukemia in the marrow and may be a therapeutic target to induce hostility of the niche to leukemia blasts.
An Experimental Study on the Effect of Asymmetric Memory Latency of New Memory on Application Performance (2016)

As DRAM reaches its density limitation, various new memory technologies such as STT-RAM and PCM are emerging as contenders for next generation memory. As these new types of memory, which we refer to as New Memory (NM), are byte addressable and nonvolatile, they are anticipated to, partially or wholly, take on the role of main memory and storage. The goal of this study is to evaluate how the read/write latency gap between the DRAM and NM and the asymmetric read and write latency of NM will affect the performance of applications. To this end, using an in-house ARM based embedded system that allows us to individually adjust the read and write latency. First, we use controlled, synthetic workloads to evaluate the latency effects. The main finding here, among others, is that write latency has little effect on performance due to various hardware mechanisms employed in current cache hardware. We then run the Stream, LMbench and PARSEC 3.0 benchmarks that represent real life applications with various memory latency settings. We find that write latency has virtually no effect and the effect of read latency is limited only to applications with very low cache hit rates.