gebhart/patrepeval huggingface dataset:
Regulation of carbachol‐ and histamine‐induced inositol phospholipid hydrolysis in a human oligodendroglioma (1992)

A stable cell line derived from a human oligodendroglioma (HOG) was used to study the regulation of muscarinic- and histamine receptor-mediated phosphoinositide hydrolysis. Both carbachol and histamine increased inositol monophosphate (InsP) accumulation in a dose- and time-dependent manner in the presence of lithium and the effect of simultaneous addition of carbachol and histamine was additive, implying independent signal transduction pathways. Homologous desensitization of muscarinic, but not histamine receptors, could be demonstrated although neither receptor type appeared to be heterologously desensitized. [3H]InsP accumulation in HOG cells was also stimulated by fluoride, suggesting guanosine triphosphate (GTP)-binding protein involvement, but phosphoinositide (PtdIns) hydrolysis was not sensitive to pertussis toxin. Phorbol ester-activation of protein kinase C (PKC) inhibited both muscarinic and histamine receptor-stimulated InsP release but did not attenuate either the fluoride-induced release of InsP nor beta-adrenergic receptor-mediated stimulation of adenylate cyclase activity. Taken together, we conclude that muscarinic and histamine receptors are differentially regulated through both PKC-dependent and -independent mechanisms, and that feedback inhibition of PtdIns turnover occurs proximal to the GTP binding proteins.
Ristocetin-dependent reconstitution of binding of von Willebrand factor to purified human platelet membrane glycoprotein Ib-IX complex (1988)

Whether the human platelet membrane glycoprotein (GP) Ib-IX complex is the receptor for ristocetin-dependent binding of von Willebrand factor (vWF) has been examined by reconstitution with the purified components using a solid-phase bead assay. Purified GP Ib-IX complex was bound and orientated on the beads via a monoclonal antibody, FMC 25, directed against the membrane-associated region of the complex. Specific binding of 125I-labeled vWF to the GP Ib-IX complex coated beads was strictly ristocetin dependent with maximal binding occurring at ristocetin concentrations greater than or equal to 1 mg/mL. Ristocetin-dependent specific binding of 125I-labeled vWF was saturable. The observed binding was specific to the interaction between vWF and the GP Ib-IX complex since there was no ristocetin-dependent specific binding of vWF if the physicochemically related platelet membrane glycoprotein, GP IIb, was substituted for the GP Ib-IX complex in a corresponding bead assay. Further, neither bovine serum albumin nor other adhesive glycoproteins, such as fibrinogen or fibronectin, specifically bound to the GP Ib-IX complex in the presence of ristocetin. Ristocetin-dependent binding of vWF to platelets and to GP Ib-IX complex coated beads was inhibited by monoclonal antibodies against a 45,000 molecular weight N-terminal region of GP Ib but not by monoclonal antibodies directed against other regions of the GP Ib-IX complex. Similar correspondence between platelets and purified GP Ib-IX complex with respect to the ristocetin-dependent binding of vWF was obtained with anti-vWF monoclonal antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promoters (1994)

We have studied tolerance induction in transgenic CBA mice expressing H-2Kb genes under the influence of guinea-pig alpha-lactalbumin (KAL) or human beta-globin gene promoter (K beta). KAL radio-resistant cells, but not bone marrow derived cells, induce tolerance to H-2Kb in chimeric mice. In contrast, bone marrow derived and radio-resistant cells of K beta mice induce tolerance. Although appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and K beta mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In addition, dendritic cells and macrophages express H-2Kb molecules when K beta, but not when KAL bone marrow is cultured in vitro. The mode of tolerance induction was examined in double transgenic mice by mating KAL or K beta mice to mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8-independent cytotoxic T cell clone. In both cases, a large number of Tg-TCR+ CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fail to appear suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and CD8-CD4+ Tg-TCR+ T cells develop in double transgenic mice and respond to activation through their TCR-CD3 complex in vitro, although no responses to stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction in KAL and K beta mice proceeds via a deletional mechanism that is inefficient due either to low numbers of H-2Kb expressing thymic cells or to the low levels of H-2Kb expressed by thymic cells, or to a combination of these factors.
Chemokine-Like Receptor-1 Expression by Central Nervous System-Infiltrating Leukocytes and Involvement in a Model of Autoimmune Demyelinating Disease (2009)

We examined the involvement of chemokine-like receptor-1 (CMKLR1) in experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Upon EAE induction by active immunization with myelin oligodendrocyte glycoprotein amino acids 35-55 (MOG(35-55)), microglial cells and CNS-infiltrating myeloid dendritic cells expressed CMKLR1, as determined by flow cytometric analysis. In addition, chemerin, a natural ligand for CMKLR1, was up-regulated in the CNS of mice with EAE. We found that CMKLR1-deficient (CMKLR1 knockout (KO)) mice develop less severe clinical and histologic disease than their wild-type (WT) counterparts. CMKLR1 KO lymphocytes proliferate and produce proinflammatory cytokines in vitro, yet MOG(35-55)-reactive CMKLR1 KO lymphocytes are deficient in their ability to induce EAE by adoptive transfer to WT or CMKLR1 KO recipients. Moreover, CMKLR1 KO recipients fail to fully support EAE induction by transferred MOG-reactive WT lymphocytes. The results imply involvement of CMKLR1 in both the induction and effector phases of disease. We conclude that CMKLR1 participates in the inflammatory mechanisms of EAE and represents a potential therapeutic target in multiple sclerosis.
Prostate-specific antigen triggers transformation of seminal α2-macroglobulin (α2-M) and its binding to α2-macroglobulin receptor/low-density lipoprotein receptor-related protein (α2-M-R/LRP) on human spermatozoa (1998)

PSA, the main proteinase in seminal fluid, is responsible for the transformation of alpha2-M and for its binding to alpha2-M-R/LRP present on spermatozoa. The binding of alpha2-M-PSA complexes to the spermatozoa receptor may exert an impact on normal sperm-cell functions.
Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study (2010)

Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
Articulated models from video (2004)

Past research on model-based tracking of articulated targets has neglected to address the problems of model-acquisition and initialization. However, for model-based approaches to ever become practical and autonomous, these important issues need to be addressed Towards this goal, this paper-presents a model-acquisition framework for acquiring articulated models directly from monocular video. Both structure, shape, and appearance of articulated models are estimated In addition, the initialization problem is solved by estimating pose information for at least one frame of a sequence, allowing subsequent model-based tracking. The presented work is based on basic assumptions and hence not restricted towards specific types of targets. It has in particular the ability to process human as well as non-human targets and makes no assumptions with respect to the structure of the kinematic tree or complexity. This work hence presents a set of systematic solutions to the problems of model-acquisition and initialization that bridge the gap between state of the art model-based tracking approaches and practical applications.
Estimating phoneme class conditional probabilities from raw speech signal using convolutional neural networks (2013)

In hybrid hidden Markov model/artificial neural networks (HMM/ANN) automatic speech recognition (ASR) system, the phoneme class conditional probabilities are estimated by first extracting acoustic features from the speech signal based on prior knowledge such as, speech perception or/and speech production knowledge, and, then modeling the acoustic features with an ANN. Recent advances in machine learning techniques, more specifically in the field of image processing and text processing, have shown that such divide and conquer strategy (i.e., separating feature extraction and modeling steps) may not be necessary. Motivated from these studies, in the framework of convolutional neural networks (CNNs), this paper investigates a novel approach, where the input to the ANN is raw speech signal and the output is phoneme class conditional probability estimates. On TIMIT phoneme recognition task, we study different ANN architectures to show the benefit of CNNs and compare the proposed approach against conventional approach where, spectral-based feature MFCC is extracted and modeled by a multilayer perceptron. Our studies show that the proposed approach can yield comparable or better phoneme recognition performance when compared to the conventional approach. It indicates that CNNs can learn features relevant for phoneme classification automatically from the raw speech signal.
Renewed debate over postnatal oogenesis in the mammalian ovary (2004)

The central dogma of female reproductive biology has long held that oogenesis ceases prior to birth in mammals. During the first half of the last century, there was much debate about whether this was the case or whether oogenesis continued in the postnatal ovary. A report in 1951 effectively put an end to this debate and laid the foundation for the dogma. A new paper by Johnson et al. (2004) resurrects the debate over whether postnatal oogenesis occurs in the mammalian ovary. If confirmed, this would have tremendous impact on issues related to female fertility and reproductive longevity.
Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy (2009)

Increased Th1 serum cytokines (IL-2, IL-12 and interferon-gamma) and IL-1ra levels are associated with AA regardless of disease severity or the presence of atopy.
Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters (2000)

It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolemic subjects consuming prepared diets each over 21 d using a cross-over design. Diets contained either i) margarine (M), ii) margarine with phytosterol esters (MSE) (1.84 g/d), or iii) margarine with phytostanol esters (MSA) (1.84 g/d). Cholesterol absorption was measured using the ratio of [(13)C]cholesterol(oral):D(7)-cholesterol(IV); biosynthesis using D incorporation from D(2)O and turnover by D(7)-cholesterol(IV) decay rates. Plasma total cholesterol level at d 21/22 was lower (P < 0. 05) for MSE (13.4%) but not MSA (10.2%) versus M (6.0%) diets. Plasma low density lipoprotein-cholesterol (LDL-C) mean reductions at d 21/22 were larger (P < 0.05) for MSE (12.9%) and MSA (7.9%) compared with M (3.9%). Plasma TG and high density lipoprotein-cholesterol (HDL-C) levels did not differ across diets. Cholesterol absorption was reduced (P < 0.05) 36.2 and 25.9% at d 21 for MSE and MSA versus M, while cholesterol biosynthesis was reciprocally increased (P < 0.05) 53.3 and 37.8% for MSE and MSA versus M, respectively. Cholesterol turnover was not influenced by diet. These data indicate that plant sterol and stanol esters differentially lower circulating total and LDL cholesterol levels by suppression of cholesterol absorption in hypercholesterolemic subjects.
Dynamic path planning for a mobile automaton with limited information on the environment (1986)

The problem of path planning is studied for the case of a mobile robot moving in an environment filled with obstacles whose shape and positions are not known. Under the accepted model, the automaton knows its own and the target coordinates, and has a "sensory" feedback which provides it with local information on its immediate surroundings. Ibis information is shown to be sufficient to guarantee reaching a global objective (the target), while generating reasonable (if not optimal) paths. A lower bound on the length of paths generated by any algorithm operating with uncertainty is formulated, and two nonheuristic path planning algorithms are described. In the algorithms, motion planning is done continuously (dynamically), based on the automaton's current position and on its feedback. The effect of additional sources of information (e.g., from a vision sensor) on the outlined approach is discussed.
Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism (2008)

Myogenic Akt signaling coordinates blood vessel recruitment with normal tissue growth. Here, we investigated the role of Follistatin-like 1 (Fstl1) in the regulation of endothelial cell function and blood vessel growth in muscle. Transgenic Akt1 overexpression in skeletal muscle led to myofiber growth that was coupled to an increase in muscle capillary density. Myogenic Akt signaling or ischemic hind limb surgery led to the induction of Fstl1 in muscle and increased circulating levels of Fstl1. Intramuscular administration of an adenoviral vector expressing Fstl1 (Ad-Fstl1) accelerated flow recovery and increased capillary density in the ischemic hind limbs of wild-type mice, and this was associated with an increase in endothelial nitric oxide synthase (eNOS) phosphorylation at residue Ser-1179. In cultured endothelial cells, Ad-Fstl1 stimulated migration and differentiation into network structures and inhibited apoptosis under conditions of serum deprivation. These cell responses were associated with the activating phosphorylation of Akt and eNOS. Conversely, transduction with dominant-negative Akt or LY294002 blocked Fstl1-stimulated eNOS phosphorylation and inhibited Fstl1-stimulated cellular responses. Treatment with the eNOS inhibitor N(G)-nitro-L-arginine methyl ester also reduced endothelial cell migration and differentiation induced by Ad-Fstl1. The stimulatory effect of Ad-Fstl1 on ischemic limb reperfusion was abolished in mice lacking eNOS. These data indicate that Fstl1 is a secreted muscle protein or myokine that can function to promote endothelial cell function and stimulates revascularization in response to ischemic insult through its ability to activate Akt-eNOS signaling.
Molecular Target Class Is Predictive of In vitro Response Profile (2010)

Preclinical cellular response profiling of tumor models has become a cornerstone in the development of novel cancer therapeutics. As efforts to predict clinical efficacy using cohorts of in vitro tumor models have been successful, expansive panels of tumor-derived cell lines can recapitulate an "all comers" efficacy trial, thereby identifying which tumors are most likely to benefit from treatment. The response profile of a therapy is most often studied in isolation; however, drug treatment effect patterns in tumor models across a diverse panel of compounds can help determine the value of unique molecular target classes in specific tumor cohorts. To this end, a panel of 19 compounds was evaluated against a diverse group of cancer cell lines (n = 311). The primary oncogenic targets were a key determinant of concentration-dependent proliferation response, as a total of five of six, four of four, and five of five phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, insulin-like growth factor-I receptor (IGF-IR), and mitotic inhibitors, respectively, clustered with others of that common target class. In addition, molecular target class was correlated with increased responsiveness in certain histologies. A cohort of PI3K/AKT/mTOR inhibitors was more efficacious in breast cancers compared with other tumor types, whereas IGF-IR inhibitors more selectively inhibited growth in colon cancer lines. Finally, specific phenotypes play an important role in cellular response profiles. For example, luminal breast cancer cells (nine of nine; 100%) segregated from basal cells (six of seven; 86%). The convergence of a common cellular response profile for different molecules targeting the same oncogenic pathway substantiates a rational clinical path for patient populations most likely to benefit from treatment. Cancer Res; 70(9); 3677-86. (c)2010 AACR.
Current Status of Melanoma Vaccines (1997)

Melanoma vaccines are relatively safe immunotherapeutic modalities for the management of malignant melanoma. The clinical effectiveness of melanoma vaccines is unclear and adequately controlled studies need yet to be performed. Current melanoma vaccines manipulate antigen presentation networks and combine the best cellular and antibody antitumor immune response effective in mediating tumor protective immunity; these combination vaccines hold the most promise. The ideal melanoma vaccine will ultimately prevent melanoma.
Total Synthesis of Distamycin A and 2640 Analogues:  A Solution-Phase Combinatorial Approach to the Discovery of New, Bioactive DNA Binding Agents and Development of a Rapid, High-Throughput Screen for Determining Relative DNA Binding Affinity or DNA Binding Sequence Selectivity (2000)

The development of a solution-phase synthesis of distamycin A and its extension to the preparation of 2640 analogues are described. Thus, solution-phase synthesis techniques with reaction workup and purification employing acid/base liquid−liquid extractions were used in the multistep preparation of distamycin A (8 steps, 40% overall yield) and a prototypical library of 2640 analogues providing intermediates and final products that are ≥95% pure on conventional reaction scales. The complementary development of a simple, rapid, and high-throughput screen for DNA binding affinity based on the loss of fluorescence derived from displacement of prebound ethidium bromide is disclosed which is applicable for assessing relative or absolute binding affinity to DNA homopolymers or specific sequences (hairpin oligonucleotides). Using hairpin oligonucleotides, this method permits the screening of a library of compounds against a single predefined sequence to identify high affinity binders, or the screening of a single compound against a full library of individual hairpin oligionucleotides to define its sequence selectivity. The combination permits the establishment of the complete DNA binding profile of each member of a library of compounds. Screening the prototypical library provided compounds that are 1000 times more potent than distamycin A in cytotoxic assays (67, IC50 = 29 nM, L1210), that bind to poly[dA]−poly[dT] with comparable affinity, and that exhibit an altered DNA binding sequence selectivity. Several candidates were identified which bound the five-base-pair AT-rich site of the PSA-ARE-3 sequence, and one (128, K = 3.2 × 106 M-1) maintained the high affinity binding (K = 4.5 × 106 M-1) to the ARE-consensus sequence containing a GC base-pair interrupted five-base-pair AT-rich site suitable for inhibition of gene transcription initiated by hormone insensitive androgen receptor dimerization and DNA binding characteristic of therapeutic resistant prostate cancer.
Clinical Articles Low Prevalence of Chlamydia pneumoniae in Atherectomy Specimens from Patients with Coronary Heart Disease (1999)

Coronary atherectomy specimens from 50 patients with coronary heart disease were examined for the presence of Chlamydia pneumoniae by two different methods of polymerase chain reaction (PCR) and by in situ hybridization. C. pneumoniae DNA was detected by PCR in atherosclerotic plaques of four patients (8%). Two patients' coronary atheromas were positive, both by a single-step 16S rRNA-based PCR and by an omp1-based nested PCR. The other two patients' specimens were positive only by the nested PCR. In contrast, C. pneumoniae was not detected by in situ hybridization in any of the cardiovascular tissues tested. Of three patients with evidence of C. pneumoniae in coronary atheromas, two had an antibody titer of 1:32 and the third had no specific antibodies detectable. Results of this study demonstrate a low prevalence of C. pneumoniae DNA in coronary atheromas. These findings do not support the hypothesis that the organism plays a major role in atherogenesis.
Selective Matrix Metalloproteinase Inhibition Reduces Left Ventricular Remodeling but Does Not Inhibit Angiogenesis After Myocardial Infarction (2002)

MMP inhibition attenuates left ventricular remodeling even when the dominant collagenase MMP-1 is not inhibited; furthermore, this selective MMP inhibition appears to increase rather than decrease neovascularization in the subendocardium.
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Polygalloyl Polyflavan-3-ols in Grape Seed Extract (2000)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was employed to characterize the polygalloyl polyflavan-3-ols (PGPF) in grape seed extracts. Masses corresponding to a series of PGPF units inclusive of nonamers were observed in the positive-ion reflectron mode. Masses of PGPF inclusive of undecamers were observed in the positive-ion linear mode, providing the first known evidence of PGPF of this size. Soluble PGPF of grape seed extracts were precipitated by complexation with Yb(3+). The PGPF were then recovered by dissolving the precipitate in water and removing the Yb(3+) by a weakly acidic cation-exchange resin (Amberlite IRP-64). Comparisons of HPLC chromatograms of the crude grape seed extract prior to precipitation with Yb(3+) and after recovery of the PGPF indicated that 96% of the phenolic compounds were precipitated and 99% of the precipitated PGPF were recovered by cation-exchange resin. These results indicate that MALDI-TOF MS is able to determine the mass distribution of complex mixtures of oligomeric PGPF and that precipitation of PGPF by Yb(3+) is useful for isolation and quantification.
Virtual distributed environments in a shared infrastructure (2005)

We have developed a middleware system that integrates and extends virtual machine and virtual network technologies to support mutually isolated virtual distributed environments in shared infrastructures like the grid and the PlanetLab overlay infrastructure. Integrating virtual network and on-demand virtual machine creation and customization technologies makes virtual distributed environments a reality. The Violin-based middleware system integrates and enhances such technologies to create virtual distributed environments.
Use of Simulation Technology in Dental Education (2001)

Simulation is becoming very beneficial in the area of health care education. Dentistry has used various types of simulation in preclinical education for some time. This article discusses the impact of the current simulation laboratories on dental education and reviews advanced technology simulation that has recently become available or is in the developmental stage. The abilities of advanced technology simulation, its advantages and disadvantages, and its potential to affect dental education are addressed.