gebhart/patrepeval huggingface dataset:
NF-κB, the first quarter-century: remarkable progress and outstanding questions (2012)

The ability to sense and adjust to the environment is crucial to life. For multicellular organisms, the ability to respond to external changes is essential not only for survival but also for normal development and physiology. Although signaling events can directly modify cellular function, typically signaling acts to alter transcriptional responses to generate both transient and sustained changes. Rapid, but transient, changes in gene expression are mediated by inducible transcription factors such as NF-κB. For the past 25 years, NF-κB has served as a paradigm for inducible transcription factors and has provided numerous insights into how signaling events influence gene expression and physiology. Since its discovery as a regulator of expression of the κ light chain gene in B cells, research on NF-κB continues to yield new insights into fundamental cellular processes. Advances in understanding the mechanisms that regulate NF-κB have been accompanied by progress in elucidating the biological significance of this transcription factor in various physiological processes. NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease. As our appreciation of the fundamental role of inflammation in disease pathogenesis has increased, so too has the importance of NF-κB as a key regulatory molecule gained progressively greater significance. However, despite the tremendous progress that has been made in understanding the regulation of NF-κB, there is much that remains to be understood. In this review, we highlight both the progress that has been made and the fundamental questions that remain unanswered after 25 years of study.
Expression of Streptococcus sanguis antigens in Escherichia coli: cloning of a structural gene for adhesion fimbriae (1987)

Chromosomal DNA from Streptococcus sanguis FW213 was partially digested with EcoRI and ligated into the positive-selection cloning vector pOP203(A2+). The ligation mixture was used to transform Escherichia coli K-12, and 4,500 transformants were examined. The tetracycline-resistant colonies had inserts averaging 3.2 kilobases. The entire colony bank was screened by colony immunoassay with polyclonal rabbit serum raised against S. sanguis FW213 whole cells. Thirty recombinant colonies produced stable positive reactions of various intensities, indicating that S. sanguis antigens could be expressed in E. coli. Restriction endonuclease digestion of these clones suggested that 26 of the clones were unique. Only two clones, VT616 and VT618, gave positive reactions with fimbria-specific antisera. That the gene coding for the antigen was located on the plasmid was confirmed by demonstrating that the presence of the plasmid was linked to antigen production. Western immunoblot analyses of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed that both clones produced a fimbrial peptide of Mr 30,000. The two recombinant plasmids were shown by Southern analysis and restriction mapping to contain the same 6-kilobase EcoRI fragment inserted in opposite orientations. Southern hybridization confirmed that this fragment is present in S. sanguis genomic DNA. The Mr 30,000 protein gene was expressed in both orientations, suggesting that the fimbrial promoter is located on the 6-kilobase fragment. These results show that at least one streptococcal fimbrial gene can be cloned and expressed in E. coli.
A secure distributed capability based system (extended abstract) (1985)

Article A secure distributed capability based system (extended abstract) Share on Authors: Howard L. Johnson Information Intelligence Sciences, Inc., University of Denver, New College Information Intelligence Sciences, Inc., University of Denver, New CollegeView Profile , John F. Koegel Department of Mathematics and Computer Science, University of Denver, Denver, Colorado Department of Mathematics and Computer Science, University of Denver, Denver, ColoradoView Profile , Rhonda M. Koegel View Profile Authors Info & Claims ACM '85: Proceedings of the 1985 ACM annual conference on The range of computing : mid-80's perspective: mid-80's perspectiveOctober 1985 Pages 392–402https://doi.org/10.1145/320435.320550Published:01 October 1985 1citation253DownloadsMetricsTotal Citations1Total Downloads253Last 12 Months7Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
The Free Radical Scavenger NecroX-7 Attenuates Acute Graft-versus-Host Disease via Reciprocal Regulation of Th1/Regulatory T Cells and Inhibition of HMGB1 Release (2015)

Graft-versus-host disease (GVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation. Despite the prominent role of the adaptive immune system, the importance of controlling the innate immune system in the pathogenesis of GVHD has recently been rediscovered. High-mobility group box 1 (HMGB1) is a crucial damage-associated molecular pattern signal that functions as a potent innate immune mediator in GVHD. In the present study, we investigated treatment of experimental GVHD through HMGB1 blockade using the compound cyclopentylamino carboxymethylthiazolylindole (NecroX)-7. Treated animals significantly attenuated GVHD-related mortality and inhibited severe tissue damage. These protective effects correlated with the decrease in HMGB1 expression and lower levels of reactive oxidative stress. Additionally, NecroX-7 inhibited the HMGB1-induced release of TNF and IL-6, as well as the expression of TLR-4 and receptor for advanced glycation end products. We also observed increased regulatory T cell numbers, which may be associated with regulation of differentiation signals independent of HMGB1. Taken together, these data indicate that NecroX-7 protects mice against lethal GVHD by reciprocal regulation of regulatory T/Th1 cells, attenuating systemic HMGB1 accumulation and inhibiting HMGB1-mediated inflammatory response. Our results indicate the possibility of a new use for a clinical drug that is effective for the treatment of GVHD.
Inheritance and Divorce in the Change of Jingdezhen Ceramic Culture in Modern Times (2017)

In the twentieth century, during the 100 years of traditional and modern cultural conflict and reconciliation, Jingdezhen ceramic culture since more than 100 years of traditional and modern cultural conflict reconciliation, shows different models and development under the influence of political rights and economic factors, and also has gone through several stages. From the grid of traditional and modern to the final production technology, artifacts and other aspects of the development of communion, this proved that in the ceramic art production of traditional culture and modern culture can coexist, civilized system can be compatible with each other.
Patient privacy in the era of medical computer networks: a new paradigm for a new technology. (1995)

For twenty five years the legal system has tried to protect the privacy of identified patient data contained in information systems. The rapid development of such technology has repeatedly frustrated the public policies incorporated into the legal system. However the newest information technologies provide the possibility of fundamentally changing the way information is stored in the health care system and, by "De personalizing the data," allow restoration of a reasonable level of personal privacy, without interfering with the legitimate needs for medical data. The system would require a secure "identifier control facility" and act as a network "file access table" able to reconstruct widely distributed bits of the patients record. A disaggregated "virtual record" would replace the integrated patient file, and the risks to data privacy inherent in the use of names or permanent identification numbers would be eliminated.
Activity-Dependent Arc Expression and Homeostatic Synaptic Plasticity Are Altered in Neurons from a Mouse Model of Angelman Syndrome (2017)

Angelman syndrome (AS) is a neurodevelopmental disorder that results from deletions or mutations in chromosome 15, which usually includes the <i>UBE3A</i> gene. Ube3A protein is an E3 ubiquitin ligase that ubiquitinates proteins and targets them for degradation. The immediate-early gene Arc, a master regulator of synaptic plasticity, was identified as a putative substrate of Ube3A, but there have been conflicting reports on whether Arc is a bona fide E3 ligase substrate. Using multiple approaches, we found no evidence for a physical interaction between Arc and Ube3A <i>in vivo</i>. Nonetheless, activity-induced subcellular distribution of Arc is altered in brains from <i>Ube3a</i><sup><i>m</i>-/<i>p</i>+</sup> mice, with abnormal concentration of Arc at synapses. Furthermore, although activation of Arc transcription is normal, the stability of Arc protein is enhanced in dendrites of hippocampal neurons cultured from <i>Ube3a</i><sup><i>m</i>-/<i>p</i>+</sup> mice. Finally, homeostatic synaptic scaling of surface AMPA receptors does not occur in <i>Ube3a</i><sup><i>m</i>-/<i>p</i>+</sup> hippocampal neurons, reminiscent of neurons that lack Arc protein. Although Ube3A does not seem to bind Arc in a canonical E3 ligase-substrate interaction, Arc-dependent synaptic plasticity is still altered in <i>Ube3a</i><sup><i>m</i>-/<i>p</i>+</sup> mice, which may underlie the cognitive deficits observed in AS.
Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex–Encoded Molecules (1997)

In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag-/- H-2d fetal thymi, CD4+8- peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor gamma chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of T cells.
Inactivation of viruses in labile blood derivatives. I. Disruption of lipid‐enveloped viruses by tri(n‐butyl)phosphate detergent combinations (1985)

Use of the organic solvent, tri(n-butyl)phosphate (TNBP), and detergents for the inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation obtained with TNBP plus Tween 80 was superior to that observed with ethyl ether plus Tween 80, a condition previously shown to inactivate greater than or equal to 10(6.9) CID50 of hepatitis B and greater than or equal to 10(4) CID50 of Hutchinson strain non-A, non-B hepatitis. The AHF recovery after TNBP/Tween treatment was greater than or equal to 90 percent. Following the reaction, TNBP could be removed from the protein by gel exclusion chromatography on Sephadex G25; however, because of its large micelle size, Tween 80 could not be removed from protein by this method. Attempts to remove Tween 80 by differential precipitation of protein were only partially successful. An alternate detergent, sodium cholate, when combined with TNBP, resulted in almost as efficient virus inactivation and an 80 percent recovery of AHF. Because sodium cholate forms small micelles, it could be removed by Sephadex G25 chromatography. Electrophoretic examination of TNBP/cholate-treated AHF concentrates revealed few, if any, changes in protein mobility, except for plasma lipoprotein(s).
Real-time approximate Range Motif discovery & data redundancy removal algorithm (2011)

Removing redundancy in the data is an important problem as it helps in resource and compute efficiency for downstream processing of massive (10 million to 100 million records) datasets. In application domains such as IR, stock markets, telecom and others there is a strong need for real-time data redundancy removal of enormous amounts of data flowing at the rate of 1Gb/s or higher. We consider the problem of finding Range Motifs (clusters) over records in a large dataset such that records within the same cluster are approximately close to each other. This problem is closely related to the approximate nearest neighbour search but is more computationally expensive. Real-time scalable approximate Range Motif discovery on massive datasets is a challenging problem. We present the design of novel sequential and parallel approximate Range Motif discovery and data de-duplication algorithms using Bloom filters. We establish asymptotic upper bounds on the false positive and false negative rates for our algorithm. Further, time complexity analysis of our parallel algorithm on multi-core architectures has been presented. For 10 million records, our parallel algorithm can perform approximate Range Motif discovery and data de-duplication, on 4 sets (clusters), in 59s, on 16 core Intel Xeon 5570 architecture. This gives a throughput of around 170K records/s and around 700Mb/s (using records of size 4K bits). To the best of our knowledge, this is the highest real-time throughput for approximate Range Motif discovery and data redundancy removal on such massive datasets.
Comprehensive Assessment of Human Pharmacokinetic Prediction Based on In Vivo Animal Pharmacokinetic Data, Part 2: Clearance (2012)

A comprehensive analysis on the prediction of human clearance based on intravenous pharmacokinetic data from rat, dog, and monkey for approximately 400 compounds was undertaken. This data set has been carefully compiled from literature reports and expanded with some in-house determinations for plasma protein binding and rat clearance. To the authors- knowledge, this is the largest publicly available data set. The present examination offers a comparison of 37 different methods for prediction of human clearance across compounds of diverse physicochemical properties. Furthermore, this work demonstrates the application of each prediction method to each charge class of the compounds, thus presenting an additional dimension to prediction of human pharmacokinetics. In general, the observations suggest that methods employing monkey clearance values and a method incorporating differences in plasma protein binding between rat and human yield the best overall predictions as suggested by approximately 60% compounds within 2-fold geometric mean-fold error. Other single-species scaling or proportionality methods incorporating the fraction unbound in the corresponding preclinical species for prediction of free clearance in human were generally unsuccessful.
ENGINEERING PRINCIPLES OF CLINICAL CELL-BASED TISSUE ENGINEERING (2004)

Tissue engineering is a rapidly evolving discipline that seeks to repair, replace, or regenerate specific tissues or organs by translating fundamental knowledge in physics, chemistry, and biology into practical and effective materials, devices, systems, and clinical strategies. Stem cells and progenitors that are capable of forming new tissue with one or more connective tissue phenotypes are available from many adult tissues and are defined as connective tissue progenitors. There are four major cell-based tissue-engineering strategies: (1) targeting local connective tissue progenitors where new tissue is desired, (2) transplanting autogenous connective tissue progenitors, (3) transplanting culture-expanded or modified connective tissue progenitors, and (4) transplanting fully formed tissue generated in vitro or in vivo. Stem cell function is controlled by changes in stem cell activation and self-renewal or by changes in the proliferation, migration, differentiation, or survival of the progeny of stem cell activation, the downstream progenitor cells. Three-dimensional porous scaffolds promote new tissue formation by providing a surface and void volume that promotes the attachment, migration, proliferation, and desired differentiation of connective tissue progenitors throughout the region where new tissue is needed. Critical variables in scaffold design and function include the bulk material or materials from which it is made, the three-dimensional architecture, the surface chemistry, the mechanical properties, the initial environment in the area of the scaffold, and the late scaffold environment, which is often determined by degradation characteristics. Local presentation or delivery of bioactive molecules can change the function of connective tissue progenitors (activation, proliferation, migration, differentiation, or survival) in a manner that results in new or enhanced local tissue formation. All cells require access to substrate molecules (oxygen, glucose, and amino acids). A balance between consumption and local delivery of these substrates is needed if cells are to survive. Transplanted cells are particularly vulnerable. Theoretical calculations can be used to explore the relationships among cell density, diffusion distance, and cell viability within a graft and to design improved strategies for transplantation of connective tissue progenitors. Rational strategies for tissue engineering seek to optimize new tissue formation through the logical selection of conditions that modulate the performance of connective tissue progenitors in a graft site to produce a desired tissue. This increasingly involves strategies that combine cells, matrices, inductive stimuli, and techniques that enhance the survival and performance of local or transplanted connective tissue progenitors.
Safety and Immunogenicity of Heptavalent Pneumococcal Vaccine Conjugated to CRM197 in United States Infants (1998)

Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.
Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia (2010)

Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL.
Local drug delivery for oral mucosal diseases: challenges and opportunities (2011)

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.
Gene replacement and expression of foreign DNA in mycobacteria (1990)

A system that permits molecular genetic manipulation of mycobacteria was developed on the basis of the yeast paradigm of gene replacement by homologous recombination. A shuttle vector that can replicate autonomously at a high copy number in Escherichia coli but must integrate into homologous DNA for survival in Mycobacterium smegmatis was constructed. The vector contains a ColE1 origin of replication, antibiotic resistance markers for ampicillin and kanamycin, a nutritional marker (pyrF) that allows both positive and negative selection in E. coli and M. smegmatis, and unique restriction sites that permit insertion of foreign DNA. Transformation of mycobacteria with this vector results in integration of its DNA into the genomic pyrF locus by either a single or a double homologous recombination event. With this system, the 65-kilodalton Mycobacterium leprae stress protein antigen was inserted into the M. smegmatis genome and expressed. This gene replacement technology, together with a uniquely useful pyrF marker, should be valuable for investigating mycobacterial pathobiology, for the development of candidate mycobacterial vaccine vehicles, and as a model for the development of molecular genetic systems in other pathogenic microorganisms.
F-box protein complex FBXL19 regulates TGFβ1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation (2014)

Collectively these data unveil that FBXL19 functions as an antagonist of Rac3 by regulating its stability and regulates the TGFβ1-induced E-cadherin down-regulation. This study will provide a new potential therapeutic strategy to regulate TGFβ1 signaling, thus suppressing esophageal tumorigenesis.
Endothelin stimulates c‐fos and c‐myc expression and proliferation of vascular smooth muscle cells (1988)

Recently, a potent vasoconstrictor peptide, endothelin (EDT), was isolated from vascular endothelial cells. We examined its effect on rat vascular smooth muscle cells (VSMCs). EDT induced the elevation of intracellular calcium, which was dependent on extracellular calcium and inhibited by a calcium-channel antagonist in a competitive manner. EDT caused a rapid and transient increase in the c-fos and c-myc mRNA levels and stimulated the DNA synthesis of VSMCs in a dose-dependent manner. This effect of EDT on the proliferation of VSMCs might be related to the development of atherosclerosis.