gebhart/patrepeval huggingface dataset:
Learning interaction dynamics with coupledhidden Markovmodels (2000)

An analysis of interactions between different physiological control systems may only be possible with correlation functions if the signals have similar spectral distributions. Interactions between such signals can be modelled in state space rather than observation space, i.e. interactions are modelled after first translating the observations into a common domain. Coupled hidden Markov models (CHMM) are such state-space models. They form a natural extension to standard hidden Markov models. The authors perform CHMM parameter estimation under a Bayesian paradigm, using Gibbs sampling, and in a maximum likelihood framework, using the expectation maximisation algorithm. The performance differences between the estimators are demonstrated on simulated data as well as biomedical data. It is shown that the proposed method gives meaningful results when comparing two different signals, such as respiration and EEG.
Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases. (1989)

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.
Sorption Behavior of Aromatic Compounds in Water on β-Cyclodextrin Polyurethane Resins (1982)

Abstract The sorption behavior of aromatic compounds in water on β-cyclodextrin polyurethane resins was evaluated by batch and column procedures. The values of their sorption capacities obtained in the batch experiments were comparable to those of Amberlite XAD-2 and/or -7. In the column experiments, β-H6XDI-P-6.0-M showed a quantitative collection of the aromatic compounds at low concentrations, while Amberlite XAD-7 did not.
Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human T98G glioblastoma multiforme xenografts. (2001)

Although rare, the morbidity and mortality from brain tumors are significant. Chemotherapy has made only a small impact on these tumors. The human T98G glioblastoma multiforme cell line was used as a brain tumor model. The protein kinase Cbeta inhibitor 317615 x 2HCl was not highly cytotoxic toward T98G cells in culture and was additive in cytotoxicity with carmustine (BCNU). When nude mice bearing s.c. T98G tumors were treated with 317615 x 2HCl p.o. twice daily on days 14-30 after tumor cell implantation, the number of intratumoral vessels stained by CD31 was decreased to 37% of control, and the number of intratumoral vessels stained by CD105 was decreased to 50% of control. The compound 317615 x 2HCl was an active antitumor agent against s.c. growing T98G xenografts. A treatment regimen administering 317615 x 2HCl before, during, and after BCNU was compared with a treatment regimen administering 317615 x 2HCl sequentially after BCNU. In the tumor growth delay determination of the s.c. tumor, the sequential treatment regimen was more effective than the simultaneous treatment regimen. However, when the same treatments were administered to animals bearing intracranial T98G tumors, the survival of animals receiving the simultaneous treatment regimen increased from 41 days for those treated with BCNU alone to 102 days for animals treated with the combination, whereas animals receiving the sequential treatment regimen survived 74 days. Treatment with the protein kinase Cbeta inhibitor decreased T98G glioblastoma multiforme angiogenesis and improved treatment outcome with BCNU.
Studies on a mammalian hepatic binding protein specific for asialoglycoproteins. Evidence for receptor recycling in isolated rat hepatocytes. (1980)

Freshly isolated rat hepatocytes attained maximal ability to bind, internalize, and degrade 125I-asialo-orosomucoid after 5 h in suspension culture at 37 degrees C. Comparison of the number and distribution of the asialoglycoprotein binding sites of these cells revealed that 5% (6.7 x 10(4) receptors/cell) were on the external cell membrane with an average residency time of slightly less than 3 min. The remaining 95% were located intracellularly, as determined with detergent-solubilized hepatocytes. Binding of ligand (asialo-orosomucoid) was time-dependent, saturable, and dissociable. The dissociation constant for the single high affinity binding site was calculated to be 3.4 x 10(-8) M. The amount of asialo-orosomucoid metabolized by these cells over a period of 3 h at 37 degrees C was reduced 50% by the inclusion of 1 mM cycloheximide in the incubation medium. However, even in the absence of protein synthesis, 34 times more asialo-orosomucoid was metabolized than could be bound by the cell surface receptors, or twice the total capacity of the intact hepatocyte. These results provide clear evidence for the stability of the binding receptor under conditions where the ligand is being continually destroyed and support the previously proposed recycling hypothesis (Tanabe, T., Pricer, W.E., Jr., and Ashwell, G. (1979) J. Biol. Chem. 254, 1038-1043).
Physical mechanisms of cell damage in microcarrier cell culture bioreactors (1988)

The negative effects of excessive agitation on tissue cells in microcarrier culture have often been ascribed to "shear." Analysis of the fluid mechanics occurring suggests that there are actually three potential damage mechanisms: collisions of a cell-covered microcarrier with other beads, collisions with parts of the reactor (primarily the impeller), and interaction with turbulent eddies the size of the microcarrier beads. Review of the available quantitative information on agitation effects in cell cultures does not establish which mechanism is predominant; the range of experimental variables reported emphasizes power input over the other reactor and impeller parameters. The bead-bead collision model is tentatively supported by the available data, but the other mechanisms may still be significant in some systems. The formation of bead aggregates by cellular bridging provides a parallel means of damaging cells. Breaking of these bridges by any of the three means identified earlier can cause cell destruction and/or the net transfer of cells to formerly bare beads. High concentrations of bridges are favored by lower agitation rates, presumably because the bridges are not as quickly destroyed after formation.
Reviews in Food and Nutrition Toxicity, Volume 2 (2004)

This second volume of Reviews in Food and Nutrition Toxicity follows on directly from the successes of the first volume published last year. This series disseminates important data pertaining to food and nutrition safety and toxicology that is relevant to humans. Chapters in this series extend from the introduction of toxins in the manufacture or p
5-Nitroimidazoles. II: Unexpected reactivity of ronidazole and dimetridazole with thiols (1993)

Ronidazole and dimetridazole, two important veterinary drugs, were found to react readily in the presence of cysteine, under neutral aqueous conditions, leading to the formation of 5-S-cysteinyl-1-methylimidazole-2-methanol carbamate and 5-S-cysteinyl-1,2-dimethylimidazole respectively through nitro displacement. The reaction products were identified by spectroscopic techniques. The rate of reaction was accelerated by increasing the pH of the medium and was accompanied by a slight change in the product distribution. The reaction was also observed, albeit at a slower rate than that of cysteine, with glutathione, another ubiquitous thiol substrate found in biological systems. While this type of nucleophilic reaction has previously been observed for suitably substituted nitrobenzene derivatives, to the best of our knowledge its occurrence with nitro-heteroaromatics has never been reported. The ready reaction of the parent nitro drugs under such mild aqueous conditions suggests that this may be an alternative path for the formation of nonextractable bound residues in tissues.
Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. (1988)

Prostaglandin G/H synthase (8,11,14-icosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1) catalyzes the first step in the formation of prostaglandins and thromboxanes, the conversion of arachidonic acid to prostaglandin endoperoxides G and H. This enzyme is the site of action of nonsteroidal anti-inflammatory drugs. We have isolated a 2.7-kilobase complementary DNA (cDNA) encompassing the entire coding region of prostaglandin G/H synthase from sheep vesicular glands. This cDNA, cloned from a lambda gt 10 library prepared from poly(A)+ RNA of vesicular glands, hybridizes with a single 2.75-kilobase mRNA species. The cDNA clone was selected using oligonucleotide probes modeled from amino acid sequences of tryptic peptides prepared from the purified enzyme. The full-length cDNA encodes a protein of 600 amino acids, including a signal sequence of 24 amino acids. Identification of the cDNA as coding for prostaglandin G/H synthase is based on comparison of amino acid sequences of seven peptides comprising 103 amino acids with the amino acid sequence deduced from the nucleotide sequence of the cDNA. The molecular weight of the unglycosylated enzyme lacking the signal peptide is 65,621. The synthase is a glycoprotein, and there are three potential sites for N-glycosylation, two of them in the amino-terminal half of the molecule. The serine reported to be acetylated by aspirin is at position 530, near the carboxyl terminus. There is no significant similarity between the sequence of the synthase and that of any other protein in amino acid or nucleotide sequence libraries, and a heme binding site(s) is not apparent from the amino acid sequence. The availability of a full-length cDNA clone coding for prostaglandin G/H synthase should facilitate studies of the regulation of expression of this enzyme and the structural features important for catalysis and for interaction with anti-inflammatory drugs.
A prognostic model of Alzheimer's disease relying on multiple longitudinal measures and time‐to‐event data (2018)

The prognostic model was improved by incorporating multiple longitudinal markers. It is useful for monitoring disease and identifying patients for clinical trial recruitment.
VEGF administration in chronic myocardial ischemia in pigs (1998)

Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.
FLT3 ligand causes autocrine signaling in acute myeloid leukemia cells (2003)

The FLT3 receptor tyrosine kinase is highly expressed in most acute leukemias and frequently mutated in acute myeloid leukemia (AML). The mutated form of the receptor is constitutively activated and known to play an important role in AML, but the activation state of the overexpressed wild-type (wt) receptor is, at present, unknown. In this study, we examined the activation state of the wild-type receptor in AML. We found that the wild-type receptor was constitutively phosphorylated/activated in 8 of 12 primary AML samples and 4 of 13 leukemia cell lines. To explain why wtFLT3 is often activated, we investigated the expression of its ligand, FL, by these same cells. Coexpression of FL with FLT3 was a universal finding in both primary AML samples and leukemic-derived cell lines. To further prove that autocrine signaling was accounting for the activation, we showed that conditioned media but not fresh media was able to activate FLT3. In addition, an antibody that blocks binding of ligand to the receptor blocks FLT3 activation. Finally, depletion of FL from conditioned media is able to block the activation of FLT3. Taken together, these findings represent strong evidence that wtFLT3 is often constitutively activated in AML and thus, like its mutated form, might contribute to the altered signaling that characterizes leukemogenesis.
Physical Interaction between TBX5 and MEF2C Is Required for Early Heart Development (2009)

TBX5 is a transcription factor which plays important roles in the development of the heart and upper limbs. Mutations in this gene produce the inherited disorder Holt-Oram syndrome. Here, we report a physical interaction between TBX5 and MEF2C leading to a synergistic activation of the alpha-cardiac myosin heavy chain (MYH6). Mutants of TBX5, TBX5G80R, and TBX5R279X that produce severe cardiac phenotypes impair the synergy. Using fluorescence resonance energy transfer, we demonstrate the interaction of TBX5 and MEF2C in living cells. We also show that they physically associate through their DNA-binding domains to form a complex on the MYH6 promoter. Morpholino-mediated knockdowns of Tbx5 and Mef2c in zebrafish suggest that the genetic interaction of these proteins is not only required for MYH6 expression but also essential for the early stages of heart development and survival. This is the first report of a functional interaction between a T-box protein and a MADS box factor that may be crucial in cardiomyocyte differentiation.
A comparison of the thrombolytic and hemorrhagic effects of tissue-type plasminogen activator and streptokinase in rabbits. (1985)

Tissue-type plasminogen activator (t-PA) is a promising thrombolytic agent because it can produce thrombolysis without inducing a plasma proteolytic state. It is uncertain if this potentially important feature renders t-PA less hemorrhagic than other plasminogen activators. We have compared the hemorrhagic and thrombolytic effects of t-PA and streptokinase in rabbits. Streptokinase, 4000 U/kg/hr over 4 hr, failed to produce significant thrombolysis and 8000 U/kg/hr streptokinase over 4 hr produced only 28 +/- 6% thrombolysis. Both streptokinase regimens were associated with a plasmin-mediated plasma proteolytic state and both streptokinase regimens produced a significant increase in hemorrhage that was evident within 15 min of beginning the infusion and was progressive over the 4 hr of drug administration. In contrast, t-PA in a dose of 7500 U/kg/hr produced 35 +/- 6% thrombolysis, but it did not produce a plasmin-mediated plasma proteolytic state or a significant increase in hemorrhage over the 4 hr of infusion. t-PA in a dose of 15,000 U/kg/hr produced 85 +/- 4% thrombolysis but was associated with a plasmin-mediated proteolytic state and produced significant bleeding which, in contrast to streptokinase-induced bleeding, was delayed in onset. Therefore, t-PA induced less hemorrhage than streptokinase at doses that produced more effective thrombolysis. Bleeding with both thrombolytic agents was associated with a plasmin-mediated proteolytic state.
Dietary fibre in infancy and childhood (2003)

There is very little evidence for the effects of dietary fibre in young children and current dietary guidelines are based on assumptions and data extrapolated from studies in adults. The first years of life may be critical for the establishment of a healthy colonic microflora, as well as good eating habits. The lack of clear and well-founded guidelines for the intake of dietary fibre in childhood may hinder both factors. The fears that a high-fibre diet in children < 5 years of age will lead to growth faltering and mineral imbalance are not well supported in the literature, especially for children in the developed world. Indeed, with the rising levels of obesity, fibre intake may be of benefit in reducing energy intake. A low-fibre diet may also be implicated in the aetiology of childhood constipation and appendicitis. The latest proposals for the definition of dietary fibre include oligosaccharides, which may act as prebiotics. There are potential health benefits of including oligosaccharides in the diets of infants and children, but more research is needed to consider the long-term effects. The immature intestine of the infant may also result in a greater amount of starch entering the colon during weaning, and this starch would now be considered dietary fibre under the new definitions. Much new research is needed to allow adequate recommendations for the intake of dietary fibre in childhood based on data collected in appropriate age-groups.
Responsive Gels Based on a Dynamic Covalent Trithiocarbonate Cross-Linker (2010)

Dimethacrylate trithiocarbonate was synthesized and used as a dynamic covalent cross-linker to prepare PMMA and PSt gels via radical polymerization. The swelling properties of the PMMA gels were studied and showed that in the presence of radicals the gels reorganize to accommodate forces generated by the swelling processes. This reshuffling of the cross-link network yields an increase in the swelling ratio (up to 300% increase) of the PMMA gels. Two different radical generators, a thermal initiator and a CuI/L complex, were successfully used to trigger the reorganization of the gels. To illustrate the broad utility of the procedure, three discrete pieces of gels were fused into one single piece to demonstrate that dynamic covalent cross-linkers can be used to prepare materials that can be reprocessed and/or undergo self-repair.
Angiogenesis Protocols (2001)

Although angiogenesis-the formation of new blood vessels from pre-existing ones-has emerged as an exciting new target for the treatment of many varied disorders, fundamental aspects of this important biological process remain poorly understood. To address the needs of those working in such a dramatically advancing area, Cliff Murray and a panel of experienced investigators have brought together in Angiogenesis Protocols a comprehensive collection of key techniques for assessing the formation of new blood vessels in both whole tissues and cell culture. These readily reproducible methods range from low-cost in vitro assays to cutting-edge in vivo models, such as the dorsal window chamber, which demands high levels of surgical skill as well as relatively expensive, custom-made equipment. The authors have also included details of the associated techniques for the isolation, identification, and culture of microvessel endothelial cells from human adipose tissues and for the transfection and transduction of primary human endothelial cells. Timely and highly practical, Angiogenesis Protocols is a gold-standard resource for today's angiogenesis investigator, providing easy access to a wide variety of proven assays suitable for laboratories with greatly differing technical expertise, materials, and financial resources
Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle (1981)

Spontaneous discharge of norepinephrine-containing locus coeruleus (NE-LC) neurons was examined during the sleep-walking cycle (S-WC) in behaving rats. Single unit and multiple unit extracellular recordings yielded a consistent set of characteristic discharge properties. (1) Tonic discharge co-varied with stages of the S-WC, being highest during waking, lower during slow wave sleep, and virtually absent during paradoxical sleep. (2) Discharge anticipated S-WC stages as well as phasic cortical activity, such as spindles, during slow wave sleep. (3) Discharge decreased within active waking during grooming and sweet water consumption. (4) Bursts of impulses accompanied spontaneous or sensory-evoked interruptions of sleep, grooming, consumption, or other such ongoing behavior. (5) These characteristic discharge properties were topographically homogeneous for recordings throughout the NE-LC. (6) Phasic robust activity was synchronized markedly among neurons in multiple unit populations. (7) Field potentials occurred spontaneously in the NE-LC and were synchronized with bursts of unit activity from the same electrodes. (8) Field potentials became dissociated from unit activity during paradoxical sleep, exhibiting their highest rates in the virtual absence of impulses. These results are generally consistent with previous proposals that the NE-LC system is involved in regulating cortical and behavioral arousal. On the basis of the present data and those described in the following report (Aston-Jones, G., and F. E. Bloom (1981) J. Neurosci.1: 887-900), we conclude that these neurons may mediate a specific function within the general arousal framework. In brief, the NE-LC system may globally bias the responsiveness of target neurons and thereby influence overall behavioral orientation.
Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin (1997)

Mice deficient for plasminogen exhibit a variety of pathologies, all of which examined to date are reversed when the animals are also made fibrin(ogen) deficient. These results suggested that the predominant, and perhaps exclusive, physiological role of plasminogen is clearance of fibrin. Plasminogen-deficient mice also display resistance to excitotoxin-induced neurodegeneration, in contrast with wild-type mice, which are sensitive. Based on the genetic interaction between plasminogen and fibrinogen, we investigated whether resistance to neuronal cell death in the plasminogen-deficient mice is dependent on fibrin(ogen). Unexpectedly, mice lacking both plasminogen and fibrinogen are resistant to neurodegeneration to levels comparable to plasminogen-deficient mice. Therefore, plasmin acts on substrates other than fibrin during experimental neuronal degeneration, and may function similarly in other pathological settings in the central nervous system.
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release (1996)

Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.