gebhart/patrepeval huggingface dataset:
Definition of a C-reactive protein binding determinant on histones (1991)

C-reactive protein (CRP) is an acute phase inflammatory protein in man which binds to phosphocholine, chromatin, histones, and the 70-kDa protein of the U1 small nuclear ribonucleoprotein particle in a calcium-dependent, phosphocholine-inhibitable manner. CRP also binds to other proteins including fibronectin. The determinants involved in CRP binding to these diverse proteins have not been identified. The binding of CRP to histones was examined as these proteins are available in large quantity at high purity and subject to protease digestion with well characterized products. Histone H1 was digested with thrombin and trypsin to produce three distinct fragments, N-terminal, central globular, and C-terminal. CRP was shown only to bind to the C-terminal fragment. Binding to histone H2A was also examined. CRP binding was not diminished by cleavage of the C-terminal fragment but was greatly decreased when the central globular region of H2A was tested. Peptides were prepared to be identical to the N- and C-terminal fragments of H2A. The N-terminal (15 amino acid) fragment of H2A blocked CRP-induced precipitation of phosphocholine-coupled bovine serum albumin and histone H2A, whereas the C-terminal fragment showed no inhibition. Thus we have defined the first reported CRP binding determinant on a protein.
HIV-1 Nef increases T cell activation in a stimulus-dependent manner (1999)

Lentiviral Nef increases viral replication in vivo, plays a direct role in pathogenesis, and increases viral particle infectivity. We now find that HIV Nef also increases the activation of T cells, a cellular state required for optimal viral replication. This enhancement is stimulant-dependent. As defined by IL-2 generation, activation of T cells stimulated with classical mitogens [phorbol 12-myristate 13-acetate (PMA) + anti-CD3, PMA + phytohemagglutinin, and PMA + ionomycin] is unaffected by the expression of Nef. However, Nef increases IL-2 secretion when cells are stimulated through the T cell receptor and the costimulus receptor (CD28). This increase in activation, which depends on Nef myristylation, is caused by an increase in the number of cells reaching full activation and not by an increase in the amount of IL-2 secreted per cell. These findings demonstrate that Nef lowers the threshold of the dual-receptor T cell activation pathway. The capacity of Nef to increase T cell activity may be very important in vivo when Nef is the predominant or the only viral gene product expressed.
Immune response to cyclin B1 in hepatocellular carcinoma (1997)

Proteins expressed by plasmids encoding human cyclins and cyclin-dependent kinase 2 (CDK2) were used as antigens in immunoblotting. Fifteen of 100 patients with hepatocellular carcinoma (HCC) were found to have autoantibodies reactive with cyclin B1 and with a 40-kd degradation product of cyclin B1-glutathione-S-transferase (GST) fusion protein. Only one serum was found to react with cyclin A and another single serum with CDK2 but no antibodies were detected to cyclin D1 and E. The basis for autoimmune responses to cyclin B1 in HCC are unknown at the present time but the possibilities might include aberrations in cyclin B1 regulation leading to altered product or its expression which resulted in stimulation of immune reactions.
The porphobilinogen synthase family of metalloenzymes (2000)

The porphobilinogen synthase (PBGS) family of enzymes catalyzes the first common step in the biosynthesis of the essential tetrapyrroles such as chlorophyll and porphyrin. Although PBGSs are highly conserved at all four levels of protein structure, there is considerable diversity in the use of divalent cations for the catalytically essential and allosteric roles. Assumptions regarding commonalities among the PBGS proteins coupled with the diversity of usage of metal ions has led to a confused literature. The recent publication of crystal structures for three PBGS proteins coupled with more than 50 individual PBGS sequences allows an evaluation of these assumptions. This topical review focuses on the usage of metals by the PBGS family of proteins. It raises doubt concerning a dogma that there has been an evolutionary shift between Zn(II) and Mg(II) at one or more of the divalent metal-binding sites. It also raises the possibility that there may be up to four specific divalent metal ion-binding sites, each serving a unique function that can be alternatively filled by amino acids in some of the PBGSs.
Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla (1992)

Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla.
Bidirectional LSTM-CRF Models for Sequence Tagging (2015)

At the moment, the vast majority of Portuguese archives with an online presence use a software solution to manage their finding aids: e.g. Digitarq or Archeevo. Most of these finding aids are written in natural language without any annotation that would enable a machine to identify named entities, geographical locations or even some dates. That would allow the machine to create smart browsing tools on top of those record contents like entity linking and record linking. In this work we have created a set of datasets to train Machine Learning algorithms to find those named entities and geographical locations. After training several algorithms we tested them in several datasets and registered their precision and accuracy. These results enabled us to achieve some conclusions about what kind of precision we can achieve with this approach in this context and what to do with the results: do we have enough precision and accuracy to create toponymic and anthroponomic indexes for archival finding aids? Is this approach suitable in this context? These are some of the questions we intend to answer along this paper.
Expression of Macrophage Migration Inhibitory Factor in Different Stages of Human Atherosclerosis (2002)

MIF is produced abundantly by various cells in all types of human atherosclerotic lesions and thus may play an important role in early plaque development and advanced complicated lesions. MIF-Jab1 complexes could serve critical regulatory functions in atherosclerotic lesion evolution.
Eat Dirt: CpG DNA and Immunomodulation of Asthma (2007)

Asthma is a disorder of increasing prevalence and severity that has been linked with reduced early-life exposure to microbes and microbial products. Populations with increased environmental exposures to pathogen-associated molecular patterns (e.g., children who have large numbers of older siblings, who were raised on farms, and who have earlier out-of-home day-care attendance) have fewer and less severe atopic disorders. The mechanism(s) responsible for these observations remain uncertain, but modulation by pathogen-associated molecular patterns of the inflammatory milieu (and thus the setting in which allergens may be encountered) has received strong support. One microbial product with marked immunostimulatory properties is bacterial DNA, which differs from mammalian DNA in the frequency of cytosine-guanine (CpG) dinucleotides; many of the effects of bacterial DNA can be recapitulated by oligodeoxynucleotides (ODNs) containing CpG in specific base sequence motifs (CpG ODNs). Because CpG ODNs induce Th1-type cytokines (which can suppress the Th2-type responses that cause many of the manifestations of allergic disease), we speculated that they may be useful in preventing or reversing the eosinophilic inflammation of atopic asthma. We found this to be the case, using murine models of incipient and established allergic asthma, but learned that the Th1-type cytokines were not critical for efficacy. Subsequent work has suggested that induction of regulatory-type responses (from T cells and antigen-presenting cells) is involved in the protection provided by CpG ODNs. Ongoing clinical trials are examining the utility of CpG ODNs alone and as an adjuvant for immunotherapy in human populations with atopic disease.
Optimization of tetracycline‐responsive recombinant protein production and effect on cell growth and ER stress in mammalian cells (2005)

The inducible T-REx system and other inducible expression systems have been developed in order to control the expression levels of recombinant protein in mammalian cells. In order to study the effects of heterologous protein expression on mammalian host behavior, the gene for recombinant Human transferrin (hTf) was integrated into HEK-293 cells and expressed under the control of the T-REx inducible technology (293-TetR-Hyg-hTf) or using a constitutive promoter (293-CMV-hTf). A number of inducible clones with variable expression levels were identified for the T-REx system with levels of hTf for the high expressing clones nearly double those obtained using the constitutive cytomegalovirus (CMV) promoter. The level of transferrin produced was found to increase proportionately with tetracycline concentration between 0 and 1 mug/mL with no significant increases in transferrin production above 1 mug/mL. As a result, the optimal induction time and tetracycline concentrations were determined to be the day of plating and 1 mug/mL, respectively. Interestingly, the cells induced to express transferrin, 293-TetR-Hyg-hTf, exhibited lower viable cell densities and percent viabilities than the uninduced cultures for multiple clonal isolates. In addition, the induction of transferrin expression was found to cause an increase in the expression of the ER-stress gene, BiP, that was not observed in the uninduced cells. However, both uninduced and induced cell lines containing the hTf gene exhibited longer survival in culture than the control cells, possibly as a result of the positive effects of hTf on cell survival. Taken together, these results suggest that the high level expression of complex proteins in mammalian cells can limit the viable cell densities of cells in culture as a result of cellular stresses caused by generating proteins that may be difficult to fold or are otherwise toxic to cells. The application of inducible systems such as the T-REx technology will allow us to optimize protein production while limiting the negative effects that result from these cellular stresses.
Improved vascular organization enhances functional integration of engineered skeletal muscle grafts (2011)

Severe traumatic events such as burns, and cancer therapy, often involve a significant loss of tissue, requiring surgical reconstruction by means of autologous muscle flaps. The scant availability of quality vascularized flaps and donor site morbidity often limit their use. Engineered vascularized grafts provide an alternative for this need. This work describes a first-time analysis, of the degree of in vitro vascularization and tissue organization, required to enhance the pace and efficacy of vascularized muscle graft integration in vivo. While one-day in vitro was sufficient for graft integration, a three-week culturing period, yielding semiorganized vessel structures and muscle fibers, significantly improved grafting efficacy. Implanted vessel networks were gradually replaced by host vessels, coupled with enhanced perfusion and capillary density. Upregulation of key graft angiogenic factors suggest its active role in promoting the angiogenic response. Transition from satellite cells to mature fibers was indicated by increased gene expression, increased capillary to fiber ratio, and similar morphology to normal muscle. We suggest a "relay" approach in which extended in vitro incubation, enabling the formation of a more structured vascular bed, allows for graft-host angiogenic collaboration that promotes anastomosis and vascular integration. The enhanced angiogenic response supports enhanced muscle regeneration, maturation, and integration.
Submersible Online Oxygen Removal System Coupled to an in Situ Voltammetric Probe for Trace Element Monitoring in Freshwater (2000)

A new online oxygen removal system specifically built to allow in situ deoxygenation of freshwater before in situ voltammetric detection of trace elements using a submersible probe is described. It is based on the permeation of oxygen through a silicone tubing surrounded by an enzymatic cross-linked O2 scavenging gel. The main advantages of the enzyme cross-linked gel compared to the chemical O2 reducing solutions proposed in the literature for laboratory online deoxygenation coupled to other devices are as follows: (i) ease of preparation and storage under normal room condition, (ii) good long-term stability (maximum time tested 1 month), (iii) no formation of insoluble oxidized chemical compounds adsorbed on the external silicone tubing wall that may interfere with the O2 diffusion, and (iv) easy in situ applications thanks to the convenience of chemical gel for transport and pressure compensation. Detailed description of the construction of the system as well as the systematic laboratory tests performed to optimize its performance are reported. Examples of environmental applications are also given. In particular, in situ monitoring and profiling of Cu(II), Pb(II), and Zn(II) in oxygenated lake water have been performed using this new online oxygen removal device coupled to a submersible voltammetric probe. The results indicate that the online oxygen removal system is robust and efficient for in situ, online deoxygenation and allows reliable subsequent voltammetric measurements of trace metals present at sub-nM level in oxygen saturated freshwater.
Capillary endothelial cell cultures: phenotypic modulation by matrix components. (1983)

Capillary endothelial cells of rat epididymal fat pad were isolated and cultured in media conditioned by bovine aortic endothelial cells and substrata consisting of interstitial or basement membrane collagens. When these cells were grown on interstitial collagens they underwent proliferation, formed a continuous cell layer and, if cultured for long periods of time, formed occasional tubelike structures. In contrast, when these cells were grown on basement membrane collagens, they did not proliferate but did aggregate and form tubelike structures at early culture times. In addition, cells grown on basement membrane substrata expressed more basement membrane constituents as compared with cells grown on interstitial matrices when assayed by immunoperoxidase methods and quantitated by enzyme-linked immunosorbent inhibition assays. Furthermore, when cells were grown on either side of washed, acellular amnionic membranes their phenotypes were markedly different. On the basement membrane surface they adhered, spread, and formed tubelike structures but did not migrate through the basement membrane. In contrast, when seeded on the stromal surface, these cells were observed to proliferate and migrate into the stromal aspect of the amnion and ultimately formed tubelike structures at high cell densities at longer culture periods (21 d). Thus, connective tissue components play important roles in regulating the phenotypic expression of capillary endothelial cells in vitro, and similar roles of the collagenous components of the extracellular matrix may exist in vivo following injury and during angiogenesis. Furthermore, the culture systems outlined here may be of use in the further study of differentiated, organized capillary endothelial cells in culture.
Wound-Associated Skin Fibrosis: Mechanisms and Treatments Based on Modulating the Inflammatory Response (2010)

Skin fibrosis, in its mildest form, may present only a minor aesthetic problem, but in the most severe cases it can lead to debilitating pathologies of the skin, for example keloid and hypertrophic scars, and systemic sclerosis. In recent years, extensive basic research aimed at understanding the molecular mechanisms underlying fibrosis has revealed an impressive but baffling number of genes, molecules, and cell types that may contribute to this problem. However, one recurring and consistent theme in these studies is that inflammatory cells and their secreted mediators appear to be leading culprits in activating dermal fibroblasts to become fibrotic. This review will first describe the histology of normal versus fibrotic skin, and will also describe the process of wound repair, a primary cause of skin fibrosis. We will then focus on what is currently known about the molecular mechanisms underlying skin fibrosis, with particular attention paid to how inflammation contributes. Finally, current treatment strategies and emerging therapeutic targets will be discussed.
Component Signal Separation and Recombination for Linear Amplification with Nonlinear Components (1975)

LINC is a technique that uses signal processing to produce linear amplification of bandpass signals with grossly nonlinear circuit components. Two important signal-processing functions of LINC are 1) forming two constant envelope phase-modulated signal components from the bandpass input signal and 2) recombining the amplified components to produce an amplified replica of the input signal. Two-tone laboratory tests of a LINC component separator and combiner, not including a limiter and envelope detector, show that, at full output, spurious levels 40 dB below tone level are achievable over a 1-MHz band. Because the laboratory model operated at relatively low frequencies (hundreds of megahertz), scaling up in frequency should result in a LINC with <40-dB spurious over a 10-MHz band. Spurious 30 dB below tone level should be achievable over a bandwidth of 50 to 100 MHz using the same technique of component signal separation. Lower spurious levels or greater bandwidths will require a sin <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> phase modulator that is less sensitive to delay in a feedback loop.
Purification and properties of a nerve growth-promoting factor isolated from mouse sarcoma 180. (1957)

Summary A heat-labile, nondialyzable factor with nerve growth-promoting properties has been partially purified from Sarcoma 180. The data indicate that the active material is a protein or is bound to a protein and that nucleic acids are not involved in its effectiveness. The factor must be continuously present in the cultures for the outgrowth of the nerve fibers to proceed. The outgrowth of nerve fibers was inhibited by iodoacetate, but not by cyanide, dinitrophenol, or fluoride.
Background and foreground modeling using nonparametric kernel density estimation for visual surveillance (2002)

Automatic understanding of events happening at a site is the ultimate goal for many visual surveillance systems. Higher level understanding of events requires that certain lower level computer vision tasks be performed. These may include detection of unusual motion, tracking targets, labeling body parts, and understanding the interactions between people. To achieve many of these tasks, it is necessary to build representations of the appearance of objects in the scene. This paper focuses on two issues related to this problem. First, we construct a statistical representation of the scene background that supports sensitive detection of moving objects in the scene, but is robust to clutter arising out of natural scene variations. Second, we build statistical representations of the foreground regions (moving objects) that support their tracking and support occlusion reasoning. The probability density functions (pdfs) associated with the background and foreground are likely to vary from image to image and will not in general have a known parametric form. We accordingly utilize general nonparametric kernel density estimation techniques for building these statistical representations of the background and the foreground. These techniques estimate the pdf directly from the data without any assumptions about the underlying distributions. Example results from applications are presented.
Dynamic Configuration for Distributed Systems (1985)

Dynamic system configuration is the ability to modify and extend a system while it is running. The facility is a requirement in large distributed systems where it may not be possible or economic to stop the entire system to allow modification to part of its hardware or software. It is also useful during production of the system to aid incremental integration of component parts, and during operation to aid system evolution. The paper introduces a model of the configuration process which permits dynamic incremental modification and extension. Using this model we determine the properties required by languages and their execution environments to support dynamic configuration. CONIC, the distributed system which has been developed at Imperial College with the specific objective of supporting dynamic configuration, is described to illustrate the feasibility of the model.
Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). (2002)

Iressa (ZD1839) is a p.o.-active, selective, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and host-dependent processes promoting cancer growth. EGFR is up-regulated in primary malignant tumors of the central nervous system (CNS) and in many systemic tumors that metastasize to the CNS. The purpose of our study was to evaluate the efficacy and toxicity of p.o.-administered ZD1839 for the treatment of established intracerebral (i.c.) tumors expressing EGFR or the tumorigenic mutated variant EGFRvIII, which is constitutively phosphorylated. Oral administration of ZD1839 at 50 or 100 mg/kg/day for 3 weeks in athymic mice with established i.c. A431 human epidermoid carcinoma expressing EGFR increased median survival by 88% (P = 0.009) and 105% (P < 0.001), respectively. Additionally, there was no evidence of systemic or CNS toxicity. However, ZD1839 failed to inhibit either s.c. or i.c. in vivo tumor growth when tumorigenicity was conferred by EGFRvIII. Western blotting revealed that treatment with ZD1839 virtually ablated phosphorylation of EGFR Tyr-1173 in A431 tumors. However, treatment of NR6M tumors with ZD1839 only partially decreased phosphorylation of EGFRvIII Tyr-1173 while up-regulating overall expression, suggesting that EGFRvIII may not be susceptible to the same molecular mechanisms of tyrosine kinase inhibition as EGFR. In conclusion, ZD1839 is active in a brain tumor model expressing EGFR, but not EGFRvIII, as EGFR mutations may lead to relative therapeutic resistance. On the basis of these observations, we believe that clinical trials of ZD1839 against brain tumors expressing EGFR are warranted, but that special consideration should be given to tumors that coexpress EGFRvIII.
A Comparison of Low-Molecular-Weight Heparin Administered Primarily at Home with Unfractionated Heparin Administered in the Hospital for Proximal Deep-Vein Thrombosis (1996)

Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home.