gebhart/patrepeval huggingface dataset:
Neuregulins Promote Survival and Growth of Cardiac Myocytes (1998)

Neuregulins (i.e. neuregulin-1 (NRG1), also called neu differentiation factor, heregulin, glial growth factor, and acetylcholine receptor-inducing activity) are known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. Unexpectedly, mice with loss of function mutations of NRG1 or of either of two of their cognate receptors, ErbB2 and ErbB4, die during midembryogenesis due to the aborted development of myocardial trabeculae in ventricular muscle. To examine the role of NRG and their receptors in developing and postnatal myocardium, we studied the ability of a soluble NRG1 (recombinant human glial growth factor 2) to promote proliferation, survival, and growth of isolated neonatal and adult rat cardiac myocytes. Both ErbB2 and ErbB4 receptors were found to be expressed by neonatal and adult ventricular myocytes and activated by rhGGF2. rhGGF2 (30 ng/ml) provoked an approximate 2-fold increase in embryonic cardiac myocyte proliferation. rhGGF2 also promoted survival and inhibited apoptosis of subconfluent, serum-deprived myocyte primary cultures and also induced hypertrophic growth in both neonatal and adult ventricular myocytes, which was accompanied by enhanced expression of prepro-atrial natriuretic factor and skeletal alpha-actin. Moreover, NRG1 mRNA could be detected in coronary microvascular endothelial cell primary cultures prepared from adult rat ventricular muscle. NRG1 expression in these cells was increased by endothelin-1, another locally acting cardiotropic peptide within the heart. The persistent expression of both a neuregulin and its cognate receptors in the postnatal and adult heart suggests a continuing role for neuregulins in the myocardial adaption to physiologic stress or injury.
Characterization of the unusual antinociceptive profile of tramadol in mice (1993)

Abstract The present study characterized the antinociceptive effects of tramadol with emphasis on the site of action, the possible development of antinociceptive tolerance, and possible cross‐tolerance to morphine. Both tramadol and morphine produced antinociception as assessed in male, ICR mice using the warm water (55°C) tail‐flick test. Intrathecal (i.t.) tramadol produced an antinociceptive response, but with a shallow dose‐response curve (DRC), but i.c.v. tramadol was ineffective up to toxic doses (&gt; 380 nmol). Simultaneous co‐administration of tramadol by the i.c.v. and i.t. routes in a 1:1 fixed dose‐ratio resulted in a synergistic interaction. Construction of a naloxone dose‐response curve against an A 90 dose of agonist yielded an AD 50 (and 95% C.L.) of 0.19 (0.14–0.33) and 0.55 (0.38–0.74) μmol/kg against morphine and tramadol, respectively; both agonists were completely antagonized by naloxone. In mice pretreated twice daily (8:00 a.m. and 5:00 p.m.) with s.c. morphine the DRC for morphine was displaced 16‐fold to the right, indicating significant development of antinociceptive tolerance. The same pretreatment resulted in only a 3‐fold right‐ward shift in the tramadol DRC. Chronic twice‐daily (8:00 a.m. and 5:00 p.m.) pretreatment with tramadol resulted in only an approximate 3‐ and 4‐fold rightward displacement in the tramadol and morphine DRCs, respectively. These results suggest that tramadol has an unusual antinociceptive mechanism which may reflect a primary site of action at spinal sites with a synergistic spinal/supraspinal interaction. Further, the lack of complete cross‐tolerance between tramadol and morphine supports the suggestion of a non‐opioid mechanism for this compound, whereas the complete antagonism by naloxone apparently reflects the opioid component of its mechanism in this test. Finally, the minimal development of tolerance to tramadol antinociception reinforces the view of a favorable tolerance‐dependence profile for this compound. © 1993 Wiley‐Liss, Inc.
Secure Scan Design with Dynamically Configurable Connection (2013)

Scan test is a powerful test technique which can control and observe the internal states of the circuit under test through scan chains. However, it has been reported that it's possible to retrieve secret keys from cryptographic LSIs through scan chains. Therefore new secure test methods are required to satisfy both testability and security requirements. In this paper, a secure scan design is proposed to achieve adequate security requirement as a countermeasure against scan-based attacks, while still maintain high testability like normal scan testing. In our method, the internal scan chain is divided into several sub chains, and the connection order of sub chains can be dynamically changed. In addition, how to decide the connection order of those sub chains so that it can't be identified by an attacker is also proposed in this paper. The proposed method is implemented on an AES circuit to show its effectiveness, and a security analysis is also given to show how the proposed approach can be used as a countermeasure against those known scan-based attacks.
A comprehensive survey on machine learning for networking: evolution, applications and research opportunities (2018)

Machine Learning (ML) has been enjoying an unprecedented surge in applications that solve problems and enable automation in diverse domains. Primarily, this is due to the explosion in the availability of data, significant improvements in ML techniques, and advancement in computing capabilities. Undoubtedly, ML has been applied to various mundane and complex problems arising in network operation and management. There are various surveys on ML for specific areas in networking or for specific network technologies. This survey is original, since it jointly presents the application of diverse ML techniques in various key areas of networking across different network technologies. In this way, readers will benefit from a comprehensive discussion on the different learning paradigms and ML techniques applied to fundamental problems in networking, including traffic prediction, routing and classification, congestion control, resource and fault management, QoS and QoE management, and network security. Furthermore, this survey delineates the limitations, give insights, research challenges and future opportunities to advance ML in networking. Therefore, this is a timely contribution of the implications of ML for networking, that is pushing the barriers of autonomic network operation and management.
Concentration and relative molecular mass of hyaluronate in lymph and blood (1986)

Human lymph was collected from patients with leaking lymph vessels after thoracic surgery. Ovine lymph was obtained from the mesenteric, lumbar, popliteal and prescapular lymph ducts by cannulation. The concentration of hyaluronate varied considerably (between 0.2 and 50 mg/l) and the highest concentrations were found in mesenteric lymph. The Mr of the polysaccharide showed a great polydispersity and variation between individuals and in different regions of the lymphatic system. High-Mr hyaluronate (greater than 10(6) was present in lymph both from man and sheep. Hyaluronate was also isolated by affinity chromatography in 70-80% yield from human serum and plasma obtained from healthy individuals and patients with rheumatoid arthritis and primary biliary cirrhosis. The weight (Mw)- and number (Mn)-average relative molecular masses were roughly the same in the three groups [(1.4-2.7) X 10(5) and (2.1-5.7) X 10(4) respectively]. The low Mr of hyaluronate in blood compared with that in lymph is explained by a preferential uptake of the large molecules by the liver endothelial cells.
Circadian Variation of Paroxysmal Atrial Fibrillation (1997)

Paroxysmal atrial fibrillation showed a unique circadian variation that differed from the well-known pattern for acute cardiovascular events, a point that should be kept in mind when antiarrhythmic therapy is evaluated. Identification of factors that regulate the circadian pattern of the maintenance and termination of paroxysmal atrial fibrillation may lead to better chronotherapy for preventing perpetuation of this arrhythmia.
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme (2012)

Choline and trimethylamine (TMA) are small molecules that play central roles in biological processes throughout all kingdoms of life. These ubiquitous metabolites are linked through a single biochemical transformation, the conversion of choline to TMA by anaerobic microorganisms. This metabolic activity, which contributes to methanogenesis and human disease, has been known for over a century but has eluded genetic and biochemical characterization. We have identified a gene cluster responsible for anaerobic choline degradation within the genome of a sulfate-reducing bacterium and verified its function using both a genetic knockout strategy and heterologous expression in Escherichia coli. Bioinformatics and electron paramagnetic resonance (EPR) spectroscopy revealed the involvement of a C-N bond cleaving glycyl radical enzyme in TMA production, which is unprecedented chemistry for this enzyme family. Our discovery provides the predictive capabilities needed to identify choline utilization clusters in numerous bacterial genomes, underscoring the importance and prevalence of this metabolic activity within the human microbiota and the environment.
The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. (1990)

The expression of fos protein was examined in 30 cases of human osteosarcoma as formalin-fixed and paraffin-embedded tissue sections using two monoclonal antibodies and, for five cases, as frozen sections using 3 polyclonal antibodies. Nuclear antibody labeling intensities were determined either by visual scoring (3 pathologists) or by microdensitometry and included over 700 tumor, 350 normal and 150 benign tissue observations. Visual scores were shown to be linear with optical density with a correlation coefficient of 0.97. Analysis of the osteosarcoma cases at one antibody concentration revealed two groups: a minority (39%) with a low average visual score of 2 +/- 0.2 which was very similar to benign and normal tissues, and a majority (61%) with an average score of 3.1 +/- 0.3. The difference is highly significant (t-test), P less than or equal to 0.01. The results were supported by an analysis of partial immunotitration curves using a curve-fitting procedure which yielded estimates of FOSo (maximum relative fos protein concentration) which were ca. 150% increased for the majority tumor group compared to the minority group or benign or normal tissues. In previous studies of v-sis transformed cells, which exhibit ca. 300% over-expression of c-fos protein as observed here, antisense techniques were used to show that over-expression leads to increased growth and loss of contact inhibition. Thus the combined results suggest that steady state c-fos protein is significantly elevated in, and may contribute to, the aggressive growth properties of a majority of human osteosarcomas.
On Differential Variability of Expression Ratios: Improving Statistical Inference about Gene Expression Changes from Microarray Data (2001)

We consider the problem of inferring fold changes in gene expression from cDNA microarray data. Standard procedures focus on the ratio of measured fluorescent intensities at each spot on the microarray, but to do so is to ignore the fact that the variation of such ratios is not constant. Estimates of gene expression changes are derived within a simple hierarchical model that accounts for measurement error and fluctuations in absolute gene expression levels. Significant gene expression changes are identified by deriving the posterior odds of change within a similar model. The methods are tested via simulation and are applied to a panel of Escherichia coli microarrays.
Microfluidic chip-based technologies: emerging platforms for cancer diagnosis (2013)

The development of early and personalized diagnostic protocols is considered the most promising avenue to decrease mortality from cancer and improve outcome. The emerging microfluidic-based analyzing platforms hold high promises to fulfill high-throughput and high-precision screening with reduced equipment cost and low analysis time, as compared to traditional bulky counterparts in bench-top laboratories. This article overviewed the potential applications of microfluidic technologies for detection and monitoring of cancer through nucleic acid and protein biomarker analysis. The implications of the technologies in cancer cytology that can provide functional personalized diagnosis were highlighted. Finally, the future niches for using microfluidic-based systems in tumor screening were briefly discussed.
The role of antigen form and function in the primary and secondary intestinal immune responses to cholera toxin and toxoid in rats (1978)

This report describes studies of the mucosal antitoxic response in rats after enteric administration of several forms of cholera toxin or toxoid, proteins which differ primarily in their ability to bind to cell membranes and activate cellular adenyl cyclase. These two characteristics appeared to markedly enhance the local primary response to these antigens. A single dose of toxoid lacking these features was ineffective in local priming even though it was absorbed and induced a systemic immune response. Single dose mucosal priming occurred only with preparations which bind to cell membranes and was enhanced by those which also activate cellular adenyl cyclase. In contrast, single-dose mucosal boosting was best accomplished by materials with these properties but was also seen with a toxoid lacking both of these functions. The property of membrane binding appears to be most advantageous in mucosal priming, perhaps by increasing effective trapping of absorbed antigen in unprimed mucosal lymphoid tissue, whereas the ability to activate adenyl cyclase appears to enhance primary and secondary type responses about equally. Combinations of crude toxoid and toxin were also more effective in mucosal priming than purified materials, a finding which is unexplained. A single dose of this combination induced mucosal priming which was fully developed in 2 wk, undiminished after 4 too, and only modestly diminished after 8 mo, thus demonstrating relatively prolonged memory in the IgA mucosal immune system. Effective two-dose local immunizing regimens were developed, and it was shown that there was no correlation between the mucosal and systemic secondary antitoxin responses provoked by these regimens.
Stimulation of monocyte production by an endogenous mediator induced by a component from Listeria monocytogenes. (1982)

A monocytosis-producing activity (MPA) is present in a saline-extractable material (SE) from Listeria monocytogenes. The mechanism of stimulation of monocyte production by SE was studied. Serum obtained from mice at appropriate times after injection of SE induced monocytosis in normal recipients. The monocytosis-inducing activity present in serum differed from SE with respect to timing of the monocytosis, fractionation pattern on a Sephadex G-200 column, and thermolability. The minimum dose of SE capable of producing a monocytosis was 100 micrograms. Antibody to SE capable of detecting SE at a concentration of greater than 5 micrograms/ml failed to detect SE in samples of active serum. Therefore it seemed highly unlikely that activity in serum was due to the presence of trace amounts of SE. The activity present in serum was thermolabile and had a molecular weight of about 38,000. The data are consistent with the hypothesis that injection of SE caused the production or release of an endogenous mediator capable of stimulating monocytosis.
A Phase I/II, Multiple-Dose, Dose-Escalation Study of Siltuximab, an Anti-Interleukin-6 Monoclonal Antibody, in Patients with Advanced Solid Tumors (2014)

Siltuximab monotherapy appears to be well tolerated but without clinical activity in solid tumors, including ovarian and KRAS-mutant cancers. The recommended phase II doses were 11 and 15 mg/kg every 3 weeks.
Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantation in the pig-to-human model (1994)

The existence of the alpha Gal epitope in 137 pigs belonging to 23 different breeds suggests that this antigen is either monomorphic or occurs at a high incidence in the porcine species. Its histological location at the surface of pig vascular endothelial cells makes it a target for human natural anti-alpha Gal antibodies and complement, which may be responsible for the hyperacute vascular rejection of transplanted pig organs. The precursor carbohydrate chain (N-acetyllactosamine) and NeuAc-substituted epitopes are also exposed at the surface of pig vascular endothelium and were found in all pigs in this study. However, humans also have these two epitopes on vascular endothelium and, consequently, have not made natural antibodies against these carbohydrate antigens. Therefore, these two pig epitopes cannot be the main target of the hyperacute vascular rejection process. Three pig phenotypes-A+ (51%), A:H+ (38%), and A-H- I+ (11%) were identified among 37 Large-white pigs by the presence of polymorphic A, H, and I carbohydrate antigens on the brush border of the surface epithelium of small intestine. These antigens were also present in other exocrine secretions but were not detected on vascular endothelium of the same pigs, suggesting that they are not involved in the hyperacute vascular rejection, although the pig A tissue antigen can induce an immune response in 0 or B blood group recipients. Once the problem of the initial hyperacute vascular rejection directed against the alpha Gal epitope is overcome, typing donor pigs for A, H, and I, as well as for the protein swine leukocyte antigens (SLA) and other pig antigens, may help in elucidating antigens involved in acute or chronic xenograft rejection.
Non‐linear dynamics of three‐dimensional rods: Exact energy and momentum conserving algorithms (1995)

Abstract The long‐term dynamic response of non‐linear geometrically exact rods under‐going finite extension, shear and bending, accompanied by large overall motions, is addressed in detail. The central objective is the design of unconditionally stable time‐stepping algorithms which exactly preserve fundamental constants of the motion such as the total linear momentum, the total angular momentum and, for the Hamiltonian case, the total energy. This objective is accomplished in two steps. First, a class of algorithms is introduced which conserves linear and angular momentum. This result holds independently of the definition of the algorithmic stress resultants. Second, an algorithmic counterpart of the elastic constitutive equations is developed such that the law of conservation of total energy is exactly preserved. Conventional schemes exhibiting no numerical dissipation, symplectic algorithms in particular, are shown to lead to unstable solutions when the high frequencies are not resolved. Compared to conventional schemes there is little, if any, additional computational cost involved in the proposed class of energy–momentum methods. The excellent performance of the new algorithm in comparison to other standard schemes is demonstrated in several numerical simulations.
Four cell types with distinctive membrane properties and morphologies in lamina I of the spinal dorsal horn of the adult rat (2002)

Lamina I of the spinal dorsal horn plays an important role in the processing and relay of nociceptive information. Signal processing depends, in part, on neuronal membrane properties. Intrinsic membrane properties of lamina I neurons were therefore investigated using whole cell patch clamp recordings in a slice preparation of adult rat spinal cord. Based on responses to somatic current injection, four cell types were identified: tonic, which fire comparatively slowly but continuously throughout stimulation; phasic, which fire a high frequency burst of variable duration; delayed onset, which fire irregularly and with a marked delay to the first spike; and single spike, which typically fire only one action potential even when strongly depolarised. Classification by spiking pattern was further refined by identification of characteristic stimulus-response curves and quantification of several response parameters. Objectivity of the classification was confirmed by cluster analysis. Responses to stimulus trains and synaptic input as well as the kinetics of spontaneous synaptic events revealed differences in the signal processing characteristics of the cell types: tonic and delayed onset cells appeared to act predominantly as integrators whereas phasic and single spike cells acted as coincidence detectors. Intracellular labelling revealed a significant correlation between morphological and physiological cell types: tonic cells were typically fusiform, phasic cells were pyramidal, and delayed onset and single spike cells were multipolar. Thus, there are multiple physiological cells types in lamina I with specific morphological correlates and distinctive signal processing characteristics that confer significant differences in the transduction of input into spike trains.
Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats. (2001)

It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.
In vivo mitogenic action of HGF on lung epithelial cells: pulmotrophic role in lung regeneration (1996)

Hepatocyte growth factor (HGF) has mitogenic, morphogenic, and motogenic activities on epithelial cells and plays important roles in regeneration of the liver and the kidney. We previously found that the expression of HGF gene is rapidly induced in the lung after acute lung injury in experimental animals and that HGF levels are elevated in blood of patients with lung diseases. To search for a possible pulmotrophic function of HGF in lung regeneration, we examined the mitogenic activity of HGF on tracheal epithelial cells in vitro and evaluated the efficacy of HGF-administration on lung regeneration after acute lung injury in mice. HGF markedly stimulated proliferation and DNA synthesis of rat tracheal epithelial cells in primary culture in a dose-dependent manner. The intravenous injection of human recombinant HGF (10 micrograms.mouse-1.day-1) into mice with acute lung injury induced by the intratracheal infusion of 10 mM HCI stimulated DNA synthesis of airway epithelial cells to levels threefold higher than those in mice with no HGF-injections, but it did not stimulate DNA synthesis of alveolar epithelial cells. However, HGF injection at higher dose (100 micrograms.mouse-1.day-1) stimulated DNA synthesis of alveolar epithelial cells in vivo. These results indicate that HGF is a potent mitogen for airway epithelial cells and alveolar epithelial cells in vivo as well as in vitro. HGF may act as pulmotrophic factor responsible for airway and alveolar regeneration during lung regeneration after acute lung injury.
Delayed adverse reactions to total‐dose intravenous iron polymaltose (2009)

The rate of infusion reactions to total-dose intravenous iron polymaltose is very low, but the frequency and severity of adverse reactions following the infusion are unknown. In 50 consecutive patients, adverse reactions developed up to 2 days after the infusion in 26% and lasted 1-8 days (median 4). Severe systemic reactions occurred in 8%. Patients should be warned of the chance of delayed reactions and an alternative iron preparation should be considered if parenteral iron is again indicated.