gebhart/patrepeval huggingface dataset:
THE NOD MOUSE: A Model of Immune Dysregulation (2004)

Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
Computational Studies on Transthyretin (2012)

Among the 23 different fibril proteins described in human amyloidosis, transthyretin is associated with the most common hereditary form of the disease and its knowledge is corroborated through about 150 crystal structures in addition to thousands of small ligands tested as fibril formation inhibitors. In spite of the large amount of available data, the mechanism of transthyretin aggregation and its inhibition through binding with small ligands is not clear. In the last decade, many groups of researchers have attempted to apply computational procedures to simulate these phenomena, with the aim of understanding them in depth and in order to rationalize the design of new promising inhibitors. A summary of the main molecular dynamics, docking, and structure-activity relationship studies carried out on transthyretin are reviewed here, and the most successful results and new trends are described in detail.
Terahertz emission by plasma waves in 60 nm gate high electron mobility transistors (2004)

We report on the resonant, voltage tunable emission of terahertz radiation (0.4–1.0 THz) from a gated two-dimensional electron gas in a 60 nm InGaAs high electron mobility transistor. The emission is interpreted as resulting from a current driven plasma instability leading to oscillations in the transistor channel (Dyakonov–Shur instability).
DNA Microarrays in Otolaryngology‐Head and Neck Surgery (2002)

These highly parallel experimental techniques promise to revolutionize gene discovery, disease characterization, and drug development.
Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte–Induced Apoptosis (2001)

Dendritic cells (DCs) play a central role in the immune system as they drive activation of T lymphocytes by cognate interactions. However, as DCs express high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and thereby limit induction of immunity. We show here that immature DCs are indeed susceptible to CTL-induced killing, but become resistant upon maturation with anti-CD40 or lipopolysaccharide. Protection is achieved by expression of serine protease inhibitor (SPI)-6, a member of the serpin family that specifically inactivates granzyme B and thereby blocks CTL-induced apoptosis. Anti-CD40 and LPS-induced SPI-6 expression is sustained for long periods of time, suggesting a role for SPI-6 in the longevity of DCs. Importantly, T helper 1 cells, which mature DCs and boost CTL immunity, induce SPI-6 expression and subsequent DC resistance. In contrast, T helper 2 cells neither induce SPI-6 nor convey protection, despite the fact that they trigger DC maturation with comparable efficiency. Our data identify SPI-6 as a novel marker for DC function, which protects DCs against CTL-induced apoptosis.
Enterprise Grid Computing (2005)

I have to admit a great measure of sympathy for the IT populace at large, when it is confronted by the barrage of hype around grid technology, particularly within the enterprise. Individual vendors have attempted to plant their flags in the notionally virgin technological territory and proclaim it as their own, using terms such as grid, autonomic, self-healing, self-managing, adaptive, utility, and so forth. Analysts, well, analyze and try to make sense of it all, and in the process each independently creates his or her own map of this terra incognita, naming it policy-based computing, organic computing, and so on. Unfortunately, this serves only to further muddy the waters for most people. All of these terms capture some aspect of the big picture—they all describe parts of solutions that seek to address essentially the same problems in similar ways—but they’re never quite synonymous.
Peptide nucleic acid (PNA) is capable of enhancing hammerhead ribozyme activity with long but not with short RNA substrates (1997)

Long RNA substrates are inefficiently cleaved by hammerhead ribozymes in trans. Oligonucleotide facilitators capable of affecting the ribozyme activity by interacting with the substrates at the termini of the ribozyme provide a possibility to improve ribozyme mediated cleavage of long RNA substrates. We have examined the effect of PNA as facilitator in vitro in order to test if even artificial compounds have facilitating potential. Effects of 12mer PNA- (peptide nucleic acid), RNA- and DNA-facilitators of identical sequence were measured with three substrates containing either 942, 452 or 39 nucleotides. The PNA facilitator enhances the ribozyme activity with both, the 942mer and the 452mer substrate to a slightly smaller extent than RNA and DNA facilitators. This effect was observed up to PNA facilitator:substrate ratios of 200:1. The enhancement becomes smaller as the PNA facilitator:substrate ratio exceeds 200:1. With the 39mer substrate, the PNA facilitator decreases the ribozyme activity by more than 100-fold, even at PNA facilitator:substrate ratios of 1:1. Although with long substrates the effect of the PNA facilitator is slightly smaller than the effect of identical RNA or DNA facilitators, PNA may be a more practical choice for potential applications in vivo because PNA is much more resistant to degradation by cellular enzymes.
Twist-induced tuning in tapered fiber couplers (1989)

The power-splitting ratio of fused tapered single-mode fiber couplers can be reversibly tuned by axial twisting without affecting loss. The twist-tuning behavior of a range of different tapered couplers is described. A simple expression for twist-tuning can be derived by representing the effects of twist by a change in the refractive index profile. Good agreement between this expression and experimental results is demonstrated. Repeated tuning over tens of thousands of cycles is found not to degrade coupler performance, and a number of practical applications, including a freely tunable tapered coupler, are described.
APIGENIN INHIBITS PANCREATIC CANCER CELL PROLIFERATION VIA DOWN-REGULATION OF THE GLUT-1 GLUCOSE TRANSPORTER THROUGH THE PHOSPHOINOSITIDE 3-KINASE (PI3K)/AKT SIGNALING PATHWAY (2006)

Introduction: Pancreatic cancer remains a formidable disease despite the current available therapeutics. The facilitative glucose transporter GLUT-1 is over-expressed in several tumors and correlates with poor prognosis and malignant pathology. The PI3K/Akt pathway is important for growth and proliferation. Apigenin is a plant flavonoid with anti-proliferative effects and has been shown to inhibit the PI3K/Akt pathway. We hypothesized that Apigenin inhibits pancreatic cancer cell proliferation and down-regulates GLUT-1 expression via the PI3K/Akt pathway. Methods and Results: GLUT-1 expression was significantly increased in human pancreatic adenocarcinoma samples versus controls as determined by immunohistochemistry with anti-GLUT-1 antibody (P < 0.001). Apigenin (50 μM) inhibited cell growth in CD18 and S2-013 human pancreatic cancer cells (48 and 72 hours; P < 0.001). CD18 and S2-013 cells treated with Apigenin (0-50 μM) demonstrated a concentration and time-dependant decrease in GLUT-1 mRNA and protein expression as evaluated by real-time RT-PCR and western blot analysis respectively. Apigenin (50 μM) also down-regulated pAkt mRNA and protein expression in both CD18 and S2-013 human pancreatic cancer cells. Administration of the pAkt inhibitors (LY294022 and Wortmannin) down-regulated GLUT-1 mRNA and protein expression suggesting that Apigenin and the pAkt inhibitors both down-regulate GLUT-1 expression and may be working via the same pathway. Conclusions: We find that apigenin induces growth inhibition in human pancreatic cancer cells. Apigenin-mediated anti-proliferative activity may be in part via down-regulation of GLUT-1 expression through the PI3K/Akt signaling pathway. Future directions will be to over-express pAkt and assess GLUT-1 expression in response to Apigenin treatment.
The pulsed Nd:YAG dental laser: review of clinical applications. (1991)

Since the first demonstration of a laser in 1960, numerous applications of this unique form of energy have been developed for the manufacturing, electronic, consumer and medical industries. Recent technological innovations have permitted development of lasers appropriate for use in the dental operatory. The carbon dioxide laser has been used for soft tissue surgery; the Nd:YAG laser has both soft and hard tissue applications. Advantages of laser treatment over conventional methods include minimal cellular destruction and tissue swelling, hemostasis, increased visualization of surgical sites and reduced post-operative pain. Additionally, it is possible to perform many procedures without needing anesthesia. Soft tissue clinical applications of the Nd:YAG laser include gingivectomies, gingivoplasties, operculectomies, biopsies, incising and draining procedures, frenectomies and treatment of aphthous ulcers; hard tissue clinical applications include vaporizing decay, etching enamel and dentin, desensitizing exposed root structure and creating temporary analgesia. As both clinical experiences and scientific investigations expand, possible future applications of the dental laser may well include development of new dental adhesives and composite systems, new methods for managing caries and new endodontic treatments. With its numerous benefits, the laser is having a positive impact on patients and the dental team.
IKKβ Is Required for Peripheral B Cell Survival and Proliferation (2003)

NF-kappaB activity in mammalian cells is regulated through the IkappaB kinase (IKK) complex, consisting of two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit (IKKgamma). Targeted deletion of Ikkbeta results in early embryonic lethality, thus complicating the examination of IKKbeta function in adult tissues. Here we describe the role of IKKbeta in B lymphocytes made possible by generation of a mouse strain that expresses a conditional Ikkbeta allele. We find that the loss of IKKbeta results in a dramatic reduction in all peripheral B cell subsets due to associated defects in cell survival. IKKbeta-deficient B cells are also impaired in mitogenic responses to LPS, anti-CD40, and anti-IgM, indicating a general defect in the ability to activate the canonical NF-kappaB signaling pathway. These findings are consistent with a failure to mount effective Ab responses to T cell-dependent and independent Ags. Thus, IKKbeta provides a requisite role in B cell activation and maintenance and thus is a key determinant of humoral immunity.
Signaling via ErbB2 and ErbB3 Associates with Resistance and Epidermal Growth Factor Receptor (EGFR) Amplification with Sensitivity to EGFR Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cells (2006)

EGFR amplification may predict sensitivity to gefitinib in HNSCC. However, other EGFR/ErbB receptor family members than EGFR may contribute to resistance to gefitinib. ErbB2 and ErbB3 may have potential as predictive markers and as therapeutic targets for combination therapy in treatment of HNSCC with gefitinib.
Design of an Internet‐based system for remote Dutch auctions (1995)

Outlines the principle of the Dutch auction, whereby the price begins at a high level and decreases by steps until a bid is made. Describes an integrated hardware and software system which uses Internet communications to enable remotely created bidders to participate in real‐time Dutch auctions and which meets the stringent requirement that synchrony be maintained among bidders’ terminals to ensure that each bidder has a fair chance to bid at the current offer price. Defines the principal functions of the system and characterizes its available resources. Illustrates implementation using a prototype design. Pays particular attention to bidder terminal synchronization, bidder authentication, and auction client security. Includes the possibility of a system variant using ISDN interconnect and PC‐based bidders’ terminals.
Epstein-Barr Virus Latent Membrane Protein 2A Regulates c-Jun Protein through Extracellular Signal-Regulated Kinase (2002)

Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is widely expressed in both EBV-infected cells and EBV-associated malignancies. However, the function of LMP2A is still veiled. In this study, LMP2A was found to induce the kinase activities of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase/stress-activated protein kinase JNK/SAPK. Furthermore, the downstream effector c-Jun showed hyperphosphorylation under LMP2A expression. The phosphorylation could be inhibited by the ERK pathway inhibitor PD98059, indicating that ERK may contribute to the phosphorylation of c-Jun in LMP2A-expressing cells. The impact on c-Jun phosphorylation by mitogen-activated protein kinase (MAPK) is suggested to increase c-Jun protein stability, and this was also observed in LMP2A-expressing cells by a protein synthesis inhibition assay. Moreover, LMP2A-induced cell invasion was inhibited in the presence of the ERK pathway inhibitor. Taken together, we suggest that LMP2A may exploit MAPK kinases and affect both the phosphorylation and stability of c-Jun protein. Additionally, LMP2A may thereby promote the mobility of the cells. In doing so, it may enhance the mobility of EBV-infected cells and contribute to the metastatic process of malignant cells. Here we demonstrated the first evidence of LMP2A-induced migration and the underlying pathways accounting for it.
Evolving therapies for non-alcoholic steatohepatitis (2014)

Treatment of NAFLD is still in its infancy, although large controlled studies have demonstrated some efficacy for pioglitazone or vitamin E. The natural course of this disease demands long-term treatments besides diet and lifestyle changes. Based on the current view of NAFLD pathophysiology, effective therapies have to target metabolic inflammation, glucose and lipid metabolism. The search for agents interfering with all of these pathways has recently generated promising candidates for the treatment of NAFLD such as farnesoid X receptor, peroxisome proliferator-activated receptor-α/δ agonists or AdipoR small-molecule agonists.
A Novel Lattice-Hardening Process To Achieve Highly Efficient and Thermally Stable Nonlinear Optical Polymers (2004)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTA Novel Lattice-Hardening Process To Achieve Highly Efficient and Thermally Stable Nonlinear Optical PolymersMarnie Haller, Jingdong Luo, Hongxiang Li, Tae-Dong Kim, Yi Liao, Bruce H. Robinson, Larry R. Dalton, and Alex K.-Y. JenView Author Information Department of Materials Science and Engineering and Department of Chemistry, University of Washington, Seattle, Washington 98195-2120 Cite this: Macromolecules 2004, 37, 3, 688–690Publication Date (Web):January 14, 2004Publication History Received17 September 2003Revised3 December 2003Published online14 January 2004Published inissue 1 February 2004https://doi.org/10.1021/ma035393bCopyright © 2004 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views709Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (67 KB) Get e-AlertsSUBJECTS:Chromophores,Nonlinear optics,Nucleic acid structure,Plastics,Polymers Get e-Alerts
Trichostatin A reduces hormone‐induced transcription of the MMTV promoter and has pleiotropic effects on its chromatin structure (2004)

The deacetylase inhibitor trichostatin A (TSA) has long been used to study the relationship between gene transcription and the acetylation status of chromatin. We have used Xenopus laevis oocytes to study the effects of TSA on glucocorticoid receptor (GR)-dependent transcription and we have related these effects to changes in the chromatin structure of a reporter mouse mammary tumor virus (MMTV) promoter. We show that TSA induces a low level of constitutive transcription. This correlates with a change of acetylation pattern and a more open chromatin structure over the MMTV chromatin, and with specific acetylation and remodeling events in the promoter region. Specifically, a repositioning of initially randomly positioned nucleosomes along the distal MMTV long terminal repeat is seen. This nucleosome rearrangement is similar to the translational nucleosome positioning that occurs upon hormone activation. We also note a reduced hormone response in the presence of TSA. TSA effects have for a long time been associated with transcriptional activation and chromatin opening through inhibition of the deacetylation of histones. However, our results and those of others show that TSA-induced changes in expression and chromatin structure can be quite different in different promoter contexts and, thus, the effects of TSA are more complex than previously believed.
Critical role of acrolein in secondary injury following ex vivo spinal cord trauma (2008)

The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein-Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.
New Perspectives on the Approach to Chronic Lymphocytic Leukemia (1996)

Investigation of the biological actions of loxoribine in chronic lymphocytic leukemia (CLL) was undertaken because of the pervasive immunostimulatory effects of the nucleoside on normal B cells. In vitro studies with cells from a spectrum of CLL patients demonstrate that loxoribine induces B-CLL cells to enter and traverse the cell cycle. This is reflected by marked increases in DNA synthesis, by standard morphological criteria, and by flow cytometric evaluation of cell cycle status and of cell surface activation markers. Cells from about 75% of patients studied evince this response. Analysis of a variety of biological parameters indicate that only the ratio of T cells (CD4+ or CD8+) to B-CLL cells correlates with induction and degree of proliferative response. Co-stimulation with loxoribine and IL-2 results in modest proliferative synergy, presumably due to upregulation of IL-2R alpha expression on B-CLL cells by loxoribine. Prolonged exposure of B-CLL cells to stimulatory concentrations of loxoribine frequently culminates in progression of the responsive cells to apoptosis. The capacity of loxoribine to transiently approximate the reversible transformation of a low grade B cell malignancy to one of a higher grade presents the opportunity for evaluation of cycle-active drugs under these conditions. Recent studies indicate that pre-treatment of B-CLL cells with loxoribine results in synergistic killing of leukemic cells with cycle-active drugs. The ability to induce B-CLL cells into cell cycle entry and/or into either activation-induced apoptosis or into phases of the cell cycle sensitive to cytotoxic therapy opens up new perspectives for the development of potentially curative strategies for this chronic leukemia.
Structural studies on sulfated glycopeptides from the carbohydrate-protein linkage region of chondroitin 4-sulfate proteoglycans of swarm rat chondrosarcoma. Demonstration of the structure Gal(4-O-sulfate)beta 1-3Gal beta 1-4XYL beta 1-O-Ser. (1988)

Nonsulfated, monosulfated, and disulfated glycopeptides containing the entire carbohydrate sequence of the glycosaminoglycan-specific linkage region were isolated after exhaustive enzymatic digestions of Swarm rat chondrosarcoma proteoglycans with chondroitinase ABC, papain, and Pronase. Their structures were examined by 500 MHz 1H NMR spectroscopy. The nonsulfated compound has the following structure with trace amounts of a few additional amino acids: delta 4,5-GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser. The monosulfated compound has an ester sulfate on C-4 of the GalNAc residue and the disulfated compound has an additional hitherto unrecognized ester sulfate on C-4 of the second galactose residue which is remote from the innermost xylose. This new structure was confirmed by two-dimensional homonuclear Hartmann-Hahn spectroscopy. The molar ratio of the isolated nonsulfated, monosulfated, and disulfated compounds was 53:37:10 based on the serine contents. Biological significance of the newly found sulfated linkage structure is discussed.