gebhart/patrepeval huggingface dataset:
Correction of Pulmonary Abnormalities in Sftpd-/- Mice Requires the Collagenous Domain of Surfactant Protein D (2006)

Surfactant protein D (SP-D) is a member of the collectin family of innate defense proteins. Members of this family share four distinct structural domains: an N-terminal cross-linking domain, a collagenous domain, a neck region, and a carbohydrate recognition domain. In this study, the function of the collagenous domain was evaluated by expressing a SP-D collagen deletion mutant protein (rSftpdCDM) in wild type and SP-D null mice (Sftpd(-/-)). rSftpdCDM formed disulfide-linked trimers that further oligomerized into higher order structures. The mutant protein effectively bound carbohydrate and aggregated bacteria in vitro. Whereas rSftpdCDM did not disrupt pulmonary morphology or surfactant phospholipid levels in wild type mice, the mutant protein failed to rescue the emphysema or enlarged foamy macrophages that are characteristic of Sftpd(-/-) mice. Moreover, rSftpdCDM partitioned with small aggregate surfactant in a manner similar to SP-D, but rSftpdCDM did not correct the abnormal surfactant ultrastructure or phospholipid levels observed in Sftpd(-/-) mice. In contrast, rSftpdCDM completely corrected viral clearance and the abnormal inflammatory response that occurs following pulmonary influenza A challenge in Sftpd(-/-) mice. Our findings indicate that the collagen domain of SP-D is not required for assembly of disulfide-stabilized oligomers or the innate immune response to viral pathogens. The collagen domain of SP-D is required for the regulation of pulmonary macrophage activation, airspace remodeling, and surfactant lipid homeostasis.
ERBB Receptor Activation Is Required for Profibrotic Responses to Transforming Growth Factor β (2010)

Engagement of the transforming growth factor-β (TGF-β) receptor complex activates multiple signaling pathways that play crucial roles in both health and disease. TGF-β is a key regulator of fibrogenesis and cancer-associated desmoplasia; however, its exact mode of action in these pathologic processes has remained poorly defined. Here, we report a novel mechanism whereby signaling via members of the ERBB or epidermal growth factor family of receptors serves as a central requirement for the biological responses of fibroblasts to TGF-β. We show that TGF-β triggers upregulation of ERBB ligands and activation of cognate receptors via the canonical SMAD pathway in fibroblasts. Interestingly, activation of ERBB is commonly observed in a subset of fibroblast but not epithelial cells from different species, indicating cell type specificity. Moreover, using genetic and pharmacologic approaches, we show that ERBB activation by TGF-β is essential for the induction of fibroblast cell morphologic transformation and anchorage-independent growth. Together, these results uncover important aspects of TGF-β signaling that highlight the role of ERBB ligands/receptors as critical mediators in fibroblast responses to this pleiotropic cytokine.
Text-level Discourse Parsing with Rich Linguistic Features (2012)

In this paper, we develop an RST-style textlevel discourse parser, based on the HILDA discourse parser (Hernault et al., 2010b). We significantly improve its tree-building step by incorporating our own rich linguistic features. We also analyze the difficulty of extending traditional sentence-level discourse parsing to text-level parsing by comparing discourseparsing performance under different discourse conditions. 1
Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival (2006)

CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule. Our studies demonstrated that CD74 regulates B-cell differentiation by inducing a pathway leading to the activation of transcription mediated by the NF-kappaB p65/RelA homodimer and its coactivator, TAF(II)105. Here, we show that CD74 stimulation with anti-CD74 antibody leads to an induction of a signaling cascade resulting in NF-kappaB activation, entry of the stimulated cells into the S phase, elevation of DNA synthesis, cell division, and augmented expression of BCL-X(L). These studies therefore demonstrate that surface CD74 functions as a survival receptor.
Antiadhesion Surface Treatments of Molds for High‐Resolution Unconventional Lithography (2006)

A new strategy to achieve antiadhesion surface coatings is introduced. The approach, which uses molds coated in a thin film of poly(dimethylsiloxane) (PDMS, see figure) to achieve the antiadhesive surfaces, is applicable to virtually any type of mold material due to the use of silane chemistry and the low surface energy of PDMS. This allows simple and rapid replication of high complexity, high-aspect-ratio nanostructures with excellent replication fidelity.
AP-2γ Induces p21 Expression, Arrests Cell Cycle, Inhibits the Tumor Growth of Human Carcinoma Cells (2006)

Activating enhancer-binding protein 2gamma (AP-2gamma) is a member of the developmentally regulated AP-2 transcription factor family that regulates the expression of many downstream genes. Whereas the effects of AP-2alpha overexpression on cell growth are fairly well established, the cellular effects of AP-2gamma overexpression are less well studied. Our new findings show that AP-2gamma significantly upregulates p21 mRNA and proteins, inhibits cell growth, and decreases clonogenic survival. Cell cycle analysis revealed that forced AP-2gamma expression induced G1-phase arrest, decreased DNA synthesis, and decreased the fraction of cells in S phase. AP-2gamma expression also led to cyclin D1 repression, decreased Rb phosphorylation, and decreased E2F activity in breast carcinoma cells. AP-2gamma binding to the p21 promoter was observed in vivo, and the absence of growth inhibition in response to AP-2gamma expression in p21(-/-) cells demonstrated that p21 caused, at least in part, AP-2-induced cell cycle arrest. Finally, the tumor growth of human breast carcinoma cells in vivo was inhibited by the expression of AP-2gamma relative to empty vector-infected cells, suggesting that AP-2gamma acts as a tumor suppressor. In summary, expression of either AP-2gamma or AP-2alpha inhibited breast carcinoma cell growth; thus, these genes may be therapeutic targets for breast cancer.
Interferon γ Enhances the Effectiveness of Tumor Necrosis Factor-Related Apoptosis–Inducing Ligand Receptor Agonists in a Xenograft Model of Ewing’s Sarcoma (2004)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces selective apoptosis in a variety of tumors, including most cell lines derived from Ewing's sarcoma family of tumors, an aggressive sarcoma that afflicts children and young adults. To determine the in vivo efficacy of TRAIL receptor agonists in Ewing's sarcoma family of tumors, mice with orthotopic xenografts were treated with anti-TRAIL-R2 monoclonal antibody or TRAIL/Apo2L in a model that can identify effects on both primary tumors and metastases. Administration of either agonist slowed tumor growth in 60% of animals and induced durable remissions in 11 to 19% but did not alter the incidence of metastatic disease. Response rates were not improved by concurrent doxorubicin treatment. Cells recovered from both TRAIL receptor agonist-treated and nontreated tumors were found to be resistant to TRAIL-induced death in vitro unless pretreated with interferon (IFN) gamma. This resistance coincided with a selective down-regulation of TRAIL receptor expression on tumor cells. In vivo treatment with IFNgamma increased tumor expression of TRAIL receptors and caspase 8, but did not increase the antitumor effect of TRAIL receptor agonists on primary tumors. However, IFNgamma treatment alone or in combination with a TRAIL receptor agonist significantly decreased the incidence of metastatic disease and the combination of TRAIL receptor agonist therapy with IFNgamma-mediated impressive effects on both primary tumors and metastatic disease. These data demonstrate that in vivo growth favors TRAIL resistance but that TRAIL receptor agonists are active in Ewing's sarcoma family of tumors and that the combination of TRAIL receptor agonists with IFNgamma is a potent regimen in this disease capable of controlling both primary and metastatic tumors.
The emerging TDP-43 proteinopathy (2018)

OAE Publishing Inc. is an international scholarly publisher specializing in peer-reviewed academic journals. To promote academic exchange and knowledge sharing, OAE provides an outstanding academic platform for biomedical experts and scholars all over the world.
A vertical/horizontal two-dimensional piezoelectric driven inertial slider micropositioner for cryogenic applications (1992)

We have developed a simple, two-dimensional piezoelectric tube device which uses the inertial slider method to achieve remote micropositioning in the vertical and horizontal directions. The motion of the slider car occurs with respect to a quartz rod which is attached to, and accelerated by the piezo tube. The vertical motion, against or with gravity, is achieved by activating the longitudinal mode of the piezo tube. The horizontal motion is a rotation about the quartz rod, achieved by activating the bending mode of the piezo tube. The device is very compact, works at cryogenic temperatures and is ultrahigh vacuum compatible. Step sizes from 10 to 3000 nm and speeds up to 0.2 mm/s are possible. A computer simulation model of the inertial slider process has been developed also, to investigate the effectiveness of various activating waveforms. It confirms the advantage of a cycloidal-like waveform recently reported in the literature. Also, the model predictions are consistent with the results obtained in the laboratory. A diagram of the analog circuit developed to produce a cycloidal-like waveform to drive the piezoelectric is included. We briefly describe an alternative design where the activating piezoelectric is attached to the slider car which moves vertically on a fixed quartz rod.
Immunological Prevention of Spontaneous Early Embryo Resorption Is Mediated by Non‐Specific Immunosimulation (1996)

The results of this study indicated that the decrease in the incidence of spontaneous embryo resorption following alloimmunization was more likely to be due to nonspecific immunomodulatory effects on the immune system of the female mice, as opposed to specific antipaternal immunity. This may, in part, explain the placebo effects observed for alloimmunization therapy for human habitual pregnancy loss. The relevance of these results to the development of immunotherapy strategies for the prevention of habitual abortion is discussed.
Divergent effects of AKI to CKD models on inflammation and fibrosis (2018)

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low-dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. We demonstrate both models instigate renal dysfunction, inflammatory cytokine responses, and fibrosis. However, the models exhibit differences in urinary excretory function, inflammatory cell infiltration, and degree of fibrotic response. UIRI without CLN demonstrated worsening perfusion and function, measured with <sup>99m</sup>Tc-mercaptoacetyltriglycine-3 imaging, and physiologic compensation in the contralateral kidney. Furthermore, UIRI without CLN elicited a robust inflammatory response that was characterized by a prolonged polymorphonuclear cell and natural killer cell infiltrate and an early expansion of kidney resident macrophages, followed by T-cell infiltration. Symmetrical diminished function occurred in RLDC kidneys and progressively worsened until day 17 of the study. Surprisingly, RLDC mice demonstrated a decrease in inflammatory cell numbers relative to controls. However, RLDC kidneys expressed increased levels of kidney injury molecule-1 (KIM-1), high mobility group box-1 ( HMGB1), and colony stimulating factor-1 ( CSF-1), which likely recruits inflammatory cells in response to injury. These data emphasize how the divergent etiologies of AKI to CKD models affect the kidney microenvironment and outcomes. This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injury-specific pathophysiologic mechanisms of the AKI to CKD transition.
Evaluation of a glycoengineered monoclonal antibody via LC-MS analysis in combination with multiple enzymatic digestion (2015)

Glycosylation affects the efficacy, safety and pharmacokinetics/pharmacodynamics properties of therapeutic monoclonal antibodies (mAbs), and glycoengineering is now being used to produce mAbs with improved efficacy. In this work, a glycoengineered version of rituximab was produced by chemoenzymatic modification to generate human-like N-glycosylation with α 2,6 linked sialic acid. This modified rituximab was comprehensively characterized by liquid chromatography-mass spectrometry and compared to commercially available rituximab. As anticipated, the majority of N-glycans were converted to α 2,6 linked sialic acid, in contrast to CHO-produced rituximab, which only contains α 2,3 linked sialic acid. Typical posttranslational modifications, such as pyro-glutamic acid formation at the N-terminus, oxidation at methionine, deamidation at asparagine, and disulfide linkages were also characterized in both the commercial and glycoengineered mAbs using multiple enzymatic digestion and mass spectrometric analysis. The comparative study reveals that the glycoengineering approach does not cause any additional posttranslational modifications in the antibody except the specific transformation of the glycoforms, demonstrating the mildness and efficiency of the chemoenzymatic approach for glycoengineering of therapeutic antibodies.
A classical mind: essays in honour of C. A. R. Hoare (1994)

To celebrate the 60th birthday and the many achievements of Tony Hoare, a rich assembly of contributors has come together to provide a volume of papers dedicated to him. Recognising the huge difference that Tony has made to computer science, each contributor has a personal way of expressing respect and thanks to him. A foreword by Robin Milner is included
Virtualizing the network forwarding plane (2010)

Modern system design often employs virtualization to decouple the system service model from its physical realization. Two common examples are the virtualization of computing resources through the use of virtual machines and the virtualization of disks by presenting logical volumes as the storage interface. The insertion of these abstraction layers allows operators great flexibility to achieve operational goals divorced from the underlying physical infrastructure. Today, workloads can be instantiated dynamically, expanded at runtime, migrated between physical servers (or geographic locations), and suspended if needed. Both computation and data can be replicated in real time across multiple physical hosts for purposes of high-availability within a single site, or disaster recovery across multiple sites.
High Sensitivity Terahertz Detection through Large-Area Plasmonic Nano-Antenna Arrays (2017)

Plasmonic photoconductive antennas have great promise for increasing responsivity and detection sensitivity of conventional photoconductive detectors in time-domain terahertz imaging and spectroscopy systems. However, operation bandwidth of previously demonstrated plasmonic photoconductive antennas has been limited by bandwidth constraints of their antennas and photoconductor parasitics. Here, we present a powerful technique for realizing broadband terahertz detectors through large-area plasmonic photoconductive nano-antenna arrays. A key novelty that makes the presented terahertz detector superior to the state-of-the art is a specific large-area device geometry that offers a strong interaction between the incident terahertz beam and optical pump at the nanoscale, while maintaining a broad operation bandwidth. The large device active area allows robust operation against optical and terahertz beam misalignments. We demonstrate broadband terahertz detection with signal-to-noise ratio levels as high as 107 dB.
Generation of stable Chinese hamster ovary pools yielding antibody titers of up to 7.6 g/L using the piggyBac transposon system (2016)

Chinese hamster ovary (CHO) cells remain the default production host for many biopharmaceutical drugs, particularly monoclonal antibodies (mAb). Production of gram and kilogram quantities of protein typically requires the generation of stable CHO clones. Unfortunately, this process takes several months, significantly slowing down the drug discovery and development process. Therefore, improved technologies are needed to accelerate biopharmaceutical drug discovery and final drug substance manufacturing. In this study, we describe the generation of stable CHO pools using the piggyBac transposon system. We evaluated the system using four model antibody molecules (3 mAbs and 1 bispecific Ab). Stable CHO pools were isolated in 7-12 days. Using a simple 16-day fed-batch process, we measured titers ranging from 2.3 to 7.6 g/L for the four model antibodies. This represented a 4- to 12-fold increase relative to the controls. Additionally, we isolated stable CHO clones. We found that the stable CHO clones isolated from the piggyBac transposon pools yielded titers two to threefold higher relative to the control clones. Taken together, these results suggest that stable CHO pool and clone generation can be significantly improved by using the piggyBac transposon system. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1301-1307, 2016.
Surfactants and experimental irritant contact dermatitis (1995)

Surface-active agents (surfactants) are characterized by the possession of 2 different moieties, both polar and non-polar regions on the same molecule. Surfactants are broadly classified as anionic, cationic, amphoteric, or non-ionic, according to the nature of the hydrophile yielded in aqueous solution. In currently marketed household, personal, and industrial cleaners, anionic surfactants are the most common class because of their relative ability to solubilize fats and oils, lower the surface tension of aqueous solutions, or form microemulsions. Many surfactants elicit irritant reactions when applied to the skin, partially due to their relative ability to solubilize lipid membranes. Hence, surfactants have become important implements in skin irritation investigations. In general, the physicochemical properties of surfactants are a crucial factor in eliciting skin irritation. Anionic surfactants are broadly accepted as potent irritants to human and animal skin. Cationic surfactants are reputedly at least equally irritating, but more cytotoxic than anionic, while the irritation potential of non-ionic surfactants is considered the lowest. Such classification of innumerable surfactants is convenient and held in high practical esteem. however, the categorization does not permit the exact determination of irritation and cytotoxicity potential of each surfactant. Ranking of surfactant skin irritancy and cytotoxicity obtained by both in vitro and in vivo assays provides a helpful orientation for future work.
Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model (1994)

A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi). An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria. The transformant was unreactive to a protein D-specific monoclonal antibody in a colony immunoassay. In addition, the mutant lacked the ability to synthesize detectable levels of protein D by protein staining, immunoblot methods, glycerophosphodiester phosphodiesterase activity, and binding studies of radiolabelled immunoglobulin D. The isogenic protein D-deficient mutant was compared with its parental strain for its ability to induce experimental otitis media in rats challenged with bacteria. An approximately 100-times-higher concentration of the mutant compared with that of the wild-type strain was required in order to cause otitis among all rats challenged with that given dose. The protein D mutant exhibited a generation time that was equal to that of the wild-type strain in complex broth medium. No difference in lipopolysaccharide expression was found between the mutant and the parental strain. These results suggest that protein D may influence the pathogenesis of NTHi in the upper respiratory tract.
The use of body surface area as a criterion of drug dosage in cancer chemotherapy. (1958)

Summary The rationale for the use of body surface area as the criterion of dosage in anticancer chemotherapy has been outlined. The similarity in the dosage per unit of surface area of methotrexate, mechlorethamine, actinomycin D, and TSPA for certain laboratory animals and man is described. This is in contrast to the dissimilarity in the dosages per unit of weight for these compounds among laboratory animals and man, and among humans of different ages. It is suggested that cancer chemotherapists consider the applicability of body surface area as a criterion of drug dosage in their laboratory and clinical studies.
Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome (2005)

The primary infection of Epstein-Barr virus (EBV) may result in fatal infectious mononucleosis or hemophagocytic syndrome (HPS) in 2 diseases; that is, X-linked lymphoproliferative disorder (XLP) and hemophagocytic lymphohistiocytosis (HLH). XLP is linked to mutations of the SAP/SH2D1A gene with dysregulated T-cell activation in response to EBV infection. Patients with sporadic HLH, however, usually have no mutation of the SAP/SH2D1A gene, and EBV latent membrane protein-1 (LMP1) can up-regulate Th1 cytokines in EBV-infected T cells. Since both diseases share common manifestations of HPS, it is important to clarify whether a cross-talk exists between signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) and LMP1-mediated pathways to explain the common pathogenesis of HPS. In this study, no mutation of the SAP/SH2D1A gene at exon 2/3 was detected in 7 HLH cases. Interestingly, EBV LMP1 could transcriptionally inhibit the expression of SAP/SH2D1A and activate downstream molecules ERK and interferon-gamma (IFN-gamma). LMP1-mediated SAP/ERK/IFN-gamma signals appear to act via the TNF receptor-associated factor (TRAF)2,5/nuclear factor kappaB (NF-kappaB) pathway, since dominant-negative TRAF2/5 and NF-kappaB inhibitor could rescue SAP expression and downregulate IFN-gamma. Although HLH is genetically distinct from XLP, our data suggest that both diseases share a common signal pathway, through either the mutation or LMP1-mediated suppression of the SAP gene, leading to overt T-cell activation and enhanced Th1 cytokine secretion in response to EBV infection.
Evaluation of cardiac function in iron deficiency anemia before and after total dose iron therapy. (2000)

Impaired ventricular performance is observed in patients with iron deficiency anemia. After TDI the left ventricular function improved before there was a significant rise in haemoglobin level proving the theory that correction of the electrophysiological abnormalities of the heart in iron deficiency patient by TDI may be the result of correction of iron at the tissue level.