gebhart/patrepeval huggingface dataset:
The Influence of Cannabidiol and Δ9‐Tetrahydrocannabinol on Cobalt Epilepsy in Rats (1979)

The mechanisms of the anticonvulsant activity of cannabidiol (CBD) and the central excitation of delta 9-tetrahydrocannabinol (delta 9-THC) were investigated electrophysiologically with conscious, unrestrained cobalt epileptic rats. The well-known antiepileptics, trimethadione (TMO), ethosuximide (ESM), and phenytoin (PHT), were included as reference drugs. Direct measurements were made of spontaneously firing, epileptic potentials from a primary focus on the parietal cortex and convulsions were monitored visually. ESM and TMO decreased the frequency of focal potentials, but PHT and CBD exerted no such effect. Although CBD did not suppress the focal abnormality, it did abolish jaw and limb clonus; in contrast, delta 9-THC markedly increased the frequency of focal potentials, evoked generalized bursts of polyspikes, and produced frank convlusions. 11-OH-delta 9-THC, the major metabolite of delta 9-THC, displayed only one of the excitatory properties of the parent compound: production of bursts of polyspikes. In contrast to delta 9-THC and its 11-OH metabolite, CBD, even in very high doses, did not induce any excitatory effects or convulsions. The present study provides the first evidence that CBD exerts anticonvulsant activity against the motor manifestations of a focal epilepsy, and that the mechanism of the effect may involve a depression of seizure generation or spread in the CNS.
Association between both lipid and protein oxidation and the risk of fatal or non-fatal coronary heart disease in a human population (2008)

The role of oxidative damage in the aetiology of coronary disease remains controversial, as clinical trials investigating the effect of antioxidants have not generally been positive. In the present study, 227 coronary cases, identified from a cohort study, were matched, by age and gender, with 420 controls in a nested case-control design. Stored plasma samples were analysed for F2-isoprostanes by stable isotope dilution MS, and specifically oxidized forms of apoA-I (apolipoprotein A-I) by HPLC of HDL (high-density lipoprotein). Median values of F2-isoprostanes were higher in plasma samples that contained oxidized apoA-I compared with samples with undetectable oxidized apoA-I (1542 compared with 1165 pmol/l). F2-Isoprostanes were significantly correlated with variants of non-oxidized apoA-II (r=-0.15) and were associated with HDL-cholesterol (P<0.0001). F2-Isoprostanes in cases (median, 1146 pmol/l) were not different from controls (1250 pmol/l); the odds ratio (95% confidence interval) for a 1 S.D. increase in F2-isoprostanes was 1.08 (0.91-1.29). Similarly, there was no independent association between the presence of oxidized apoA-I, detected in approx. 20% of the samples, and coronary risk. In conclusion, we found no evidence of associations between markers of lipid (F2-isoprostanes) and protein (oxidized apoA-I) oxidation and the risk of fatal or non-fatal coronary heart disease in a general population. This may be due to a true lack of association or insufficient power.
The role of inflammation in vascular diseases (2000)

When the body responds to an infectious insult, it initiates an immune response to eliminate the pathogen. The hallmark of the immune response is an inflammatory cascade that can also do extensive damage to host tissues. Inflammation is a major contributing factor to many vascular events, including atherosclerotic plaque development and rupture, aortic aneurysm formation, angiogenesis, and ischemia/reperfusion damage. The immune response is mediated by both circulating and resident leukocytes and the cells with which they interact (e.g., vascular endothelium and smooth muscle cells). The process is orchestrated by the activity of a changing series of released and displayed mediators. These include the expression of adhesion molecules on leukocytes and underlying vascular endothelium and the release of cytokines, chemokines, and tissue-destructive metalloproteases and reactive oxygen species. This review focuses on the causes, the inflammatory processes involved, and possible strategies for decreasing vascular disease through regulation of the inflammatory response.
The viridin family of steroidal antibiotics (1995)

J. R. Hanson, Nat. Prod. Rep., 1995, 12, 381 DOI: 10.1039/NP9951200381
Plasma and Microwave Flash Sintering of a Tailored Silver Nanoparticle Ink, Yielding 60% Bulk Conductivity on Cost‐Effective Polymer Foils (2012)

A combination of plasma and microwave flash sintering is used to sinter an inkjet-printed and tailored silver nanoparticle formulation. By using two sintering techniques sequentially, the obtained conductivity is 60%, while keeping the processing temperature well below the glass transition temperature (T(g)) of the used polymer substrate. This approach leads to highly conductive features on cost-effective polymer substrates in relatively short times, which are compatible with roll-to-roll (R2R) production. An electroluminescence device is prepared as an example.
Effects of Sympathectomy on Skin and Muscle Microcirculation during Dorsal Column Stimulation: Animal Studies (1991)

Electric stimulation of the dorsal spinal cord (DCS) in the treatment of pain in peripheral vascular disease is known to enhance peripheral circulation, but the mechanisms are still obscure. An earlier study has provided indirect evidence that the vasodilator effect is dependent upon alteration of sympathetic vasomotor activity. In the present study, surgical interruption of sympathetic pathways was performed to define the role of the sympathetic system for the stimulation-induced vasodilation. Three groups of normal rats were used: one group subjected to lumbar sympathectomy, one group sham-operated about 1 week before performing spinal cord stimulation, and a third group, without pretreatment, serving as a second control. Stimulation was applied to one dorsal column at the thoracolumbar junction, and peripheral microcirculation was recorded in hind limb skin and muscle by laser Doppler technique. The stimulation parameters were chosen to correspond with those used clinically in man. A cold test with monitoring of cold-induced changes in peripheral blood flow was used to assess the completeness of the sympathectomy. The preoperative cold test induced a reciprocal response, vasoconstriction in the skin and vasodilation in muscle. DCS with clinical parameters did not produce this reciprocity in the control and sham-operated rats, but induced a vasodilation in both skin and muscle. After complete sympathectomy, defined as postoperative disappearance of the vasomotor responses to cold, the vasodilation in skin and muscle in response to DCS was abolished; however, the vasodilatory response to high-intensity stimulation (approximately 10 times the motor threshold) was not affected. Incomplete sympathetic denervation in some animals resulted in partial preservation of a vasodilatory response to DCS. The results indicate a major contribution of the sympathetic system to DCS-induced peripheral vasodilation and explains why the method can be clinically effective also after chemical or surgical sympathectomy. It is likely that sympathetic vasoconstrictor activity is depressed by stimulation-induced activation of spinal inhibitory mechanisms, and that this constitutes a major component of the vasodilatory effect of DCS. (Neurosurgery 29:874-879, 1991)
Musical understanding at the beat level: real-time beat tracking for audio signals (1998)

This paper presents the main issues and our solutions to the problem of understanding musical audio signals at the beat level, issues which are common to more general auditory scene analysis. Previous beat tracking systems were not able to work in realistic acoustic environments. We built a real-time beat tracking system that processes audio signals that contain sounds of various instruments. The main features of our solutions are: (1) To handle ambiguous situations, our system manages multiple agents that maintain multiple hypotheses of beats. (2) Our system makes a context-dependent decision by leveraging musical knowledge represented as drum patterns. (3) All processes are performed based on how reliable detected events and hypotheses are, since it is impossible to handle realistic complex signals without mistakes. (4) Frequency-analysis parameters are dynamically adjusted by interaction between low-level and high-level processing. In our experiment using music on commercially distributed compact discs, our system correctly tracked beats in 40 out of 42 popular songs in which drums maintain the beat.
Structures of PD-1 with its ligands: Sideways and dancing cheek to cheek (2008)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Expression of two related nonstructural proteins of bluetongue virus (BTV) type 10 in insect cells by a recombinant baculovirus: production of polyclonal ascitic fluid and characterization of the gene product in BTV-infected BHK cells (1989)

In vitro translation of bluetongue virus (BTV) double-stranded RNA in the rabbit reticulocyte lysate system has shown segment 10 (S10) to code for two related proteins, NS3 and NS3A. The presence of both products in vivo, however, has remained unconfirmed owing to the very low level of synthesis of the S10 gene product(s) in BTV-infected BHK cells. In the present work, a cDNA copy of BTV type 10 (BTV-10) S10 RNA was inserted into Autographa californica nuclear polyhedrosis baculovirus (AcNPV) in lieu of the 5' coding region of the AcNPV polyhedrin gene. Spodoptera frugiperda cells infected with the recombinant baculovirus synthesized two polypeptides, which were shown to represent NS3 and NS3A by Western blot (immunoblot) and peptide map analysis. Antibodies raised to the expressed NS3 by immunization of mice detected both NS3 and NS3A in BTV-10-infected BHK cells but not in purified BTV-10 virus particles. In contrast to in vitro translation of BTV S10 RNA in which NS3 and NS3A are synthesized in equimolar amounts, NS3 was the principle product both in the baculovirus expression system and in vivo in BTV-infected cells. The results indicate the caution which should be exercised when using the rabbit reticulocyte lysate system to predict the pattern of protein synthesis from a gene with alternative start codons. The expressed NS3 and NS3A proteins reacted strongly with sera from sheep infected with homologous and heterologous BTV serotypes, suggesting that the S10 gene products are highly conserved group-specific antigens.
Polynomial texture maps (2001)

In this paper we present a new form of texture mapping that produces increased photorealism. Coefficients of a biquadratic polynomial are stored per texel, and used to reconstruct the surface color under varying lighting conditions. Like bump mapping, this allows the perception of surface deformations. However, our method is image based, and photographs of a surface under varying lighting conditions can be used to construct these maps. Unlike bump maps, these Polynomial Texture Maps (PTMs) also capture variations due to surface self-shadowing and interreflections, which enhance realism. Surface colors can be efficiently reconstructed from polynomial coefficients and light directions with minimal fixed-point hardware. We have also found PTMs useful for producing a number of other effects such as anisotropic and Fresnel shading models and variable depth of focus. Lastly, we present several reflectance function transformations that act as contrast enhancement operators. We have found these particularly useful in the study of ancient archeological clay and stone writings.
Phase I and pharmacokinetic studies of DON. (1982)

DON, a glutamine antagonist, was administered iv to 26 patients with advanced cancer either once every 3 wks or daily for 3 days every 3 wks to determine toxicity and to look for evidence of therapeutic effect. Total doses ranged from 150 to 600 mg/m2. The single-day schedule produced intolerable nausea and vomiting and no evidence of cytotoxicity at 450-550 mg/m2 given over 10 mins or over 4 hrs. On the 3-day schedule, patients had tolerable gastrointestinal toxic effects at total doses up to 480 mg/m2 given in three equally divided doses by 10-min infusion. This dose also produced cytotoxic activity manifested as transient mild leukopenia and, rarely, thrombocytopenia. No objective responses were seen. Analysis of the plasma elimination of DON demonstrated dose-dependent pharmacokinetic behavior. The parent compound was not detectable in the urine of any patient, indicating extensive metabolism of the drug.
Flow Effects on Prostacyclin Production by Cultured Human Endothelial Cells (1985)

Endothelial cell functions, such as arachidonic acid metabolism, may be modulated by membrane stresses induced by blood flow. The production of prostacyclin by primary human endothelial cell cultures subjected to pulsatile and steady flow shear stress was measured. The onset of flow led to a sudden increase in prostacyclin production, which decreased to a steady rate within several minutes. The steady-state production rate of cells subjected to pulsatile shear stress was more than twice that of cells exposed to steady shear stress and 16 times greater than that of cells in stationary culture.
Acute and Impaired Wound Healing (2012)

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed.
Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. (1989)

We collected a total of 78 tissue specimens, including primary colorectal carcinoma, normal colonic mucosa, and liver metastases of colon carcinoma, to examine whether the extracts of these tissues inhibited the binding of a monoclonal antibody FH6, specific for sialyl-dimeric LeX antigen. The results of inhibition assays demonstrated that: (a) contents of FH6-reactive molecules were greater in carcinoma tissues than in normal colonic mucosa; (b) metastatic foci in livers contained more FH6-reactive molecules than primary tumors; (c) primary tumors from Dukes' stage B1 patients contained less FH6-reactive molecules than primary tumors from Dukes' stage D patients. The inhibitory activity of these tumor tissue extracts against the binding of a monoclonal antibody FH6 to cultured colon carcinoma cells was eliminated by prior treatment of the extracts with sialidase, confirming that the FH6-reactive materials were sialyl-dimeric LeX antigen. Electrophoretic separation of tumor tissue extracts on 3% polyacrylamide gels followed by direct staining with monoclonal antibody FH6 revealed that very high molecular weight glycoproteins, presumably mucins, contained sialyl-dimeric LeX antigen.
Multiview camera-calibration framework for nonparametric distortions removal (2005)

This paper proposes a technique that uses a planar calibration object and projective constraints to calibrate parametric and nonparametric distortions. An iterative surface fitting is first used to constrain a B-spline distortion model by fusing the corrective distortion maps obtained from multiple views. The model is then refined within the whole camera-calibration process.
Purification of Bovine α-Lactalbumin by Immobilized Metal Ion Affinity Chromatography (1997)

The milk protein alpha-lactalbumin was isolated from bovine whey protein concentrate solution by immobilized metal ion affinity chromatography (IMAC) using Cu(II)-Chelating Sepharose Fast Flow. Stepwise pH (5.5-3.8) changes in sodium acetate buffer were used to elute the protein selectively, at which time it was concentrated and reapplied to an uncharged Chelating Sepharose Fast Flow column to remove the contaminating Cu(II) ions. A purity of 90% and recovery of 80% was achieved. The described method appears to be suitable for isolation of alpha-lactalbumin in a form adequate for milk formula engineering.
Vampire Bats Yield Potent Clot Buster for Ischemic Stroke (2004)

While tissue-type plasminogen activator (tPA) is currently the standard "clot-busting" drug used to treat patients with acute ischemic stroke, another new option for treatment is now under clinical study. Desmodus rotundus plasminogen activator (DSPA), an enzyme found in the saliva of vampire bats, may offer another therapeutic option instead of tPA, a current therapy for stroke. Animal research indicates that tPA may mediate neuronal death as well as increase systemic plasminogen consumption and fibrinogenolysis. Conversely, DSPA's activity is dependent on the presence of fibrin and therefore has not been associated with the systemic plasminogen consumption and fibrinogenolysis that potentially may occur in those receiving tPA. In animal studies, tPA was found to exhibit "inherent neurotoxic properties" not seen with DSPA. In addition, DSPA may be administered up to 9 hours after the onset of symptoms, unlike tPA, which cannot be given after 3 hours without potential risk of additional brain injury. Phase II clinical trials have demonstrated a positive result in human subjects. Phase III trials are currently under way in stroke populations.
Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. (1993)

Extracellular signal-regulated protein kinases (ERK) 1 and 2 and mutants of each were expressed in bacteria with a hexahistidine tag and purified using nickel-chelate chromatography. Basal activity of wild type ERK2 was approximately 2 nmol/min/mg. Self-catalyzed phosphorylation occurred in vitro on the major physiological site of tyrosine phosphorylation in an intramolecular reaction. Rabbit muscle ERK activator activated ERK2 500-1000-fold up to a specific activity (approximately 2 mumol/min/mg) approximating that of ERK1 purified from stimulated cells (Boulton, T.G., Gregory, J.S., and Cobb, M.H. (1991) Biochemistry 30, 278-286). ERK1 could also be activated by the ERK activator to the same extent. Mutants lacking the major site of tyrosine phosphorylation were autophosphorylated at a greatly reduced rate and were no longer highly activated by the ERK kinase. Mutants lacking the major site of threonine phosphorylation were autophosphorylated at the same or an enhanced rate, but the kinase activity of these mutants depended on the residue used to replace the threonine. Replacement by glutamate rendered the kinase capable of being activated by ERK activator, while replacement by alanine did not. Thus, the carboxyl group of glutamate can provide at least some of the features introduced by phosphothreonine in activated ERKs.
Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity. (1990)

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.
Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. (1994)

We investigated the influence of organ microenvironment on the angiogenic phenotype in human renal cell carcinoma (HRCC) cells. HRCC line SN12C was established in vitro from a surgical specimen, and metastatic line SN12PM6 was isolated from a lung metastasis produced by parental cells implanted into the kidney of nude mice. SN12C (low metastasis) and SN12PM6 (high metastasis) cells were injected into the kidney or subcutis of nude mice. The kidney tumors were highly vascularized (as revealed by immunohistochemistry using antibodies against factor VIII), and metastatic, whereas the subcutaneous tumors were not. The expression of mRNA for basic fibroblast growth factor (bFGF) in kidney tumors was 10 to 20 times that found in subcutaneous tumors. Similar data were obtained at the protein level by using fluorescence activated cell sorting, immunohistochemistry, and enzyme-linked immunosorbent assay. bFGF was detected in the urine of mice with tumors in the kidney but not subcutaneous tumors. The level of bFGF in the serum of mice with kidney tumors was two to three times that in mice with subcutaneous tumors. The changes in bFGF expression in the tumors was transient. Collectively, these data indicate that the organ microenvironment can influence the expression level of bFGF in HRCC.
The role of mTOR in memory CD8+ T‐cell differentiation (2010)

The mammalian target of rapamycin (mTOR) is an intracellular kinase that regulates cell growth and metabolism. Its specific inhibitor rapamycin is currently used in transplant recipients as an immunosuppressive drug to prevent allograft rejection. Studies have shown complex and diverse mechanisms for the immunosuppressive effects of rapamycin. The drug has been reported to inhibit T-cell proliferation, induce anergy, modulate T-cell trafficking, promote regulatory T cells, and also prevent maturation of dendritic cells as well as production of type I interferon. However, several other studies have paradoxically demonstrated immunostimulatory effects of rapamycin by improving antigen presentation and regulating cytokine production from macrophages and myeloid dendritic cells. Recently, it has been shown that rapamycin also exhibits immunostimulatory effects on memory CD8(+) T-cell differentiation. The drug improved both quantity and quality of memory CD8(+) T cells induced by viral infection and vaccination, showing that mTOR is a major regulator of memory CD8(+) T-cell differentiation. These discoveries have implications for the development of novel vaccine regimens. Here, we review the role of mTOR in memory CD8(+) T-cell differentiation and compare the effect of rapamycin among CD8(+) T cells, CD4(+) T cells, and dendritic cells. Also, we discuss potential application of these findings in a clinical setting.