gebhart/patrepeval huggingface dataset:
Caveolin‐mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo (1998)

The p42/44 mitogen-activated protein (MAP)-kinase cascade is a well-established signal transduction pathway that is initiated at the cell surface and terminates within the nucleus. More specifically, receptor tyrosine kinases can indirectly activate Raf, which in turn leads to activation of MEK and ERK and ultimately phosphorylation of Elk, a nuclear transcription factor. Recent reports have suggested that some members of p42/44 MAP kinase cascade can be sequestered within plasmalemmal caveolae in vivo. For example, morphological studies have directly shown that ERK-1/2 is concentrated in plasma membrane caveolae in vivo using immunoelectron microscopy. In addition, constitutive activation of the p42/44 MAP kinase cascade is sufficient to reversibly down-regulate caveolin-1 mRNA and protein expression. However, the functional relationship between the p42/44 MAP kinase cascade and caveolins remains unknown. Here, we examine the in vivo role of caveolins in regulating signaling along the MAP kinase cascade. We find that co-expression with caveolin 1 dramatically inhibits signaling from EGF-R, Raf, MEK-1 and ERK-2 to the nucleus. Using a variety of caveolin-1 deletion mutants, we mapped this in vivo inhibitory activity to caveolin-1 residues 32-95. Peptides derived from this region of caveolin 1 also inhibit the in vitro kinase activity of purified MEK-1 and ERK-2. Thus, we show here that caveolin-1 expression can inhibit signal transduction from the p42/44 MAP kinase cascade both in vitro and in vivo. Taken together with previous data, our results also suggest that a novel form of reciprocal negative regulation exists between p42/44 MAP kinase activation and caveolin-1 protein expression, i.e. up-regulation of caveolin-1 protein expression down-modulates p42/44 MAP kinase activity (this report) and up-regulation of p42/44 MAP kinase activity down-regulates caveolin-1 mRNA and protein expression.
Knowledge discovery from users Web-page navigation (2002)

The authors propose to detect users' navigation paths to the advantage of Web site owners. First, they explain the design and implementation of a profiler which captures a client's selected links and page order, accurate page viewing time and cache references, using a Java based remote agent. The information captured by the profiler is then utilized by a knowledge discovery technique to cluster users with similar interests. They introduce a novel path clustering method based on the similarity of the history of user navigation. This approach is capable of capturing the interests of the user which could persist through several subsequent hypertext link selections. Finally, they evaluate their path clustering technique via a simulation study on a sample WWW site. They show that, depending on the level of inserted noise, they can recover the correct clusters by 10%-27% of average error margin.
Technologies for an Autonomous Wireless Home Healthcare System (2009)

We present a design study highlighting our recent technological developments that will enable the implementation of autonomous wireless sensor networks for home healthcare monitoring systems. We outline the power requirements for a commercially available implantable glucose sensor which transmits measurements to an external wireless sensor node embedded in the home. A network of these sensor nodes will relay the data to a base station, such as a computer with internet connection, which will record and report this data to the user. We explore the feasibility of powering these sensors using energy scavenging from both body temperature gradients and vibrations in the home, and discuss our developments in energy storage and low power consuming hardware.
Structure-Function Relationships of the Raloxifene-Estrogen Receptor-α Complex for Regulating Transforming Growth Factor-α Expression in Breast Cancer Cells (2002)

Amino acid Asp-351 in the ligand binding domain of estrogen receptor alpha (ERalpha) plays an important role in regulating the estrogen-like activity of selective estrogen receptor modulator-ERalpha complexes. 4-Hydroxytamoxifen is a full agonist at a transforming growth factor alpha target gene in situ in MDA-MB-231 human breast cancer cells stably transfected with the wild-type ERalpha. In contrast, raloxifene (Ral), which is also a selective estrogen receptor modulator, is a complete antiestrogen in this system. Because D351G ERalpha allosterically silences activation function-1 activity in the 4-hydroxytamoxifen-ERalpha complex with the complete loss of estrogen-like activity, we examined the converse interaction of amino acid 351 and the piperidine ring of the antiestrogen side chain of raloxifene to enhance estrogen-like action. MDA-MB-231 cells were either transiently or stably transfected with Asp-351 (the wild type), D351E, D351Y, or D351F ERalpha expression vectors. Profound differences in the agonist and antagonist actions of Ralcenter dotERalpha complexes were noted only in stable transfectants. The agonist activity of the Ralcenter dotERalpha complex was enhanced with D351E and D351Y ERalpha, but raloxifene lost its agonist activity with D351F ERalpha. The distance between the piperidine nitrogen of raloxifene and the negative charge of amino acid 351 was critical for estrogen-like actions. The role of the piperidine ring in neutralizing Asp-351 was addressed using compound R1h, a raloxifene derivative replacing the nitrogen on its piperidine ring with a carbon to form cyclohexane. The derivative was a potent agonist with wild type ERalpha. These results support the concept that the side chain of raloxifene shields and neutralizes the Asp-351 to produce an antiestrogenic ERalpha complex. Alteration of either the side chain or its relationship with the negative charge at amino acid 351 controls the estrogen-like action at activating function 2b of the selective estrogen receptor modulator ERalpha complex.
Superoxide and hydrogen peroxide induce CD18-mediated adhesion in the postischemic heart (1996)

A burst of endothelial derived oxidants including hydrogen peroxide (H2O2) and superoxide (.O2-) occurs on reperfusion of ischemic tissues that directly causes injury; however, it is not known if this also triggers further injury due to subsequent leukocyte adhesion and adhesion molecule expression. Therefore, studies were performed in an isolated heart model developed to enable study of the role of isolated cellular and humoral factors in the mechanism of postischemic injury. Isolated rat hearts were subjected to 20 min of 37 degrees C-global ischemia followed by reperfusion with polymorphonuclear leukocytes (PMNs) and plasma in the presence or absence of superoxide dismutase (SOD), 200 U/ml, or catalase, 500 U/ml. Measurements of contractile function, coronary flow, high-energy phosphates, free radical generation, and PMN accumulation were performed. Adhesion molecule expression was measured on the surface of effluent PMNs by fluorescence flow cytometry and within the tissue using immunohistochemistry. SOD or catalase treatment resulted in 2- to 3-fold higher recoveries of contractile function, coronary flow, and high energy phosphates. EPR spin trapping measurements demonstrated that SOD totally quenched the free radical generation observed upon reperfusion while catalase prevented the formation of hydroxyl and alkyl radicals derived from superoxide. SOD or catalase treatment decreased PMN accumulation in the reperfused heart and prevented the marked upregulation of CD18 expression seen after reperfusion. These experiments demonstrate that in addition to their direct antioxidative actions, SOD and catalase each decrease PMN adhesion and CD18 expression resulting in marked suppression of PMN-mediated injury in the postischemic heart. Thus, endothelial derived H2O2 and .O2- further amplify postischemic injury by triggering CD18 expression on the surface of PMNs leading to increased PMN adhesion within the heart.
Biological Evaluation of Chitosan Nanofiber Membrane for Guided Bone Regeneration (2005)

The biocompatibility of the chitosan nanofiber membrane was confirmed, with enhanced bone regeneration and no evidence of an inflammatory reaction. This experiment shows that the novel biodegradable chitosan nanofiber membrane may be useful as a tool for guided bone regeneration.
Light field image sensors based on the Talbot effect (2009)

We present a pixel-scale sensor that uses the Talbot effect to detect the local intensity and incident angle of light. The sensor comprises two local diffraction gratings stacked above a photodiode. When illuminated by a plane wave, the upper grating generates a self-image at the half Talbot depth. The second grating, placed at this depth, blocks or passes light depending upon incident angle. Several such structures, tuned to different incident angles, are sufficient to extract local incident angle and intensity. Furthermore, arrays of such structures are sufficient to localize light sources in three dimensions without any additional optics.
Audio-driven facial animation by joint end-to-end learning of pose and emotion (2017)

We present a machine learning technique for driving 3D facial animation by audio input in real time and with low latency. Our deep neural network learns a mapping from input waveforms to the 3D vertex coordinates of a face model, and simultaneously discovers a compact, latent code that disambiguates the variations in facial expression that cannot be explained by the audio alone. During inference, the latent code can be used as an intuitive control for the emotional state of the face puppet. We train our network with 3--5 minutes of high-quality animation data obtained using traditional, vision-based performance capture methods. Even though our primary goal is to model the speaking style of a single actor, our model yields reasonable results even when driven with audio from other speakers with different gender, accent, or language, as we demonstrate with a user study. The results are applicable to in-game dialogue, low-cost localization, virtual reality avatars, and telepresence.
In Vivo Biosynthesis of Endogenous and of Human C1 Inhibitor in Transgenic Mice: Tissue Distribution and Colocalization of Their Expression (2002)

We have produced transgenic mice expressing human C1 inhibitor mRNA and protein under the control of the human promoter and regulatory elements. The transgene was generated using a minigene construct in which most of the human C1 inhibitor gene (C1NH) was replaced by C1 inhibitor cDNA. The construct retained the promoter region extending 1.18 kb upstream of the transcription start site, introns 1 and 2 as well as a stretch of 2.5 kb downstream of the polyadenylation site, and therefore carried all known elements involved in transcriptional regulation of the C1NH gene. Mice with high serum levels of human C1 inhibitor, resulting from multiple tandem integrations of the C1 inhibitor transgene, were selected. Immunohistochemistry in combination with in situ hybridization was applied to localize the sites of C1 inhibitor biosynthesis and to demonstrate its local production in brain, spleen, liver, heart, kidney, and lung. The distribution of human C1 inhibitor-expressing cells was qualitatively indistinguishable from that of its mouse counterpart, but expression levels of the transgene were significantly higher. In the spleen, production of C1 inhibitor was colocalized with that of a specific marker for white pulp follicular dendritic cells. This study demonstrates a stringently regulated expression of both the endogenous and the transgenic human C1 inhibitor gene and reveals local biosynthesis of C1 inhibitor at multiple sites in which the components of the macromolecular C1 complex are also produced.
Performance of low-complexity RAKE reception in a realistic UWB channel (2003)

We evaluate the link performance of an ultra-wide band (UWB) system using reduced-complexity RAKE receivers, which are based on either partial combining (called PRAKE) or selective combining (called SRAKE). The first is suboptimum and combines the first arriving multipath components, while the second combines the strongest multipath components. We use a statistical tapped-delay-line channel model that is based on extensive measurement campaigns, and reflects both small-scale and large-scale variations of the channel. Through semi-analytical evaluations of the bit error probability, we show that the simpler PRAKE receiver is almost as good as the SRAKE even for a small number of fingers. We show how this behavior can be related to the channel characteristics.
Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI‐1 antigen in obese men during the fasting and postprandial state (2004)

Abstract Background In obese subjects, chronic low‐grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti‐inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. Material and methods Eleven obese men (BMI: 30–35 kg m −2 ) received daily fish oil (1·35 g n‐3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9·4 kg. At the end of each experimental period a postprandial study was performed. Results Relative to fasting concentrations, interleukin‐6 (IL‐6) levels increased by 75% 2 h and by 118% 4 h after the meal ( P &lt; 0·001), when subjects consumed the control capsules. In contrast, C‐reactive protein (C‐RP) concentrations decreased slightly by 0·7% and 6·6% ( P = 0·046), and those of plasminogen activator inhibitor‐1 (PAI‐1) antigen by, respectively, 26% and 53% ( P &lt; 0·001). Tumour necrosis factor‐α (TNF‐α; P = 0·330) and soluble TNF‐receptor concentrations (sTNF‐R55 and sTNF‐R75; P = 0·451 and P = 0·108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL‐6, C‐RP, sTNF‐R55, sTNF‐R75, and PAI‐1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. Conclusion For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low‐grade inflammatory state as weight reduction.
Nonuniform Nighttime Distribution of Acute Cardiac Events (1997)

Nocturnal myocardial infarction, sudden cardiac death, and AICD discharge exhibit nonuniform distributions. This finding is consistent with the hypothesis that sleep-state dependent fluctuations in autonomic nervous system activity may trigger the onset of major cardiovascular events and provides further impetus for more directly testing this hypothesis at population, individual, and mechanistic levels. A better understanding of nocturnal triggers may make it possible to reduce the incidence of myocardial infarction, ventricular tachyarrhythmias, and sudden cardiac death during the nocturnal period.
Splicing of Messenger RNA Precursors (1987)

A general mechanism for the splicing of nuclear messenger RNA precursors in eukaryotic cells has been widely accepted. This mechanism, which generates lariat RNAs possessing a branch site, seems related to the RNA-catalyzed reactions of self-splicing introns. The splicing of nuclear messenger RNA precursors involves the formation of a multicomponent complex, the spliceosome. This splicing body contains at least three different small nuclear ribonucleoprotein particles (snRNPs), U2, U5, and U4 + U6. A complex containing precursor RNA and the U2 snRNP particle is a likely intermediate in the formation of the spliceosome.
Synthesis and Quantitative Structure−Activity Relationship of a Novel Series of Small Conductance Ca2+-Activated K+ Channel Blockers Related to Dequalinium (1996)

The synthesis, pharmacological testing, and quantitative structure-activity relationship studies of a novel series of bisquinolinium small conductance Ca(2+)-activated K+ channel blockers (23) related to dequalinium are described. In this series, two quinolinium rings are linked via the 4-position to an alpha, omega-diamino alkylene chain and the ring N atom is quaternized with a methyl or benzyl group. The exocyclic N atom can be replaced by O, S, or CH2 but with some loss of potency. The quinoline groups do not have to be quaternized for blocking activity, as long as they are basic enough to be protonated at the site of action. For the quaternary compounds, there is considerable steric tolerance for the group R attached to the ring N atom of the quinoline; a benzyl group gave the optimum potency in this series. Moreover, and in contrast to previously reported results for dequalinium analogues, there is no correlation of activity to previously reported results for dequalinium analogues, there is no correlation of activity with N1 charge or EHOMO. On the other hand, a good correlation was obtained between the blocking potency of the compounds and ELUMO [pEMR = 1.16(+/-0.26)ELUMO + 5.33(+/-01.29)(n = 11, r= 0.83, s = 0.243)]. It has been possible to combine this equation with the previously reported ELUMO correlation for a series of dequalinium analogues to include all the compounds of both series [pEMR = 1.17(+/-0.15)ELUMO +5.33(+/-0.76)(n =24, r = 0.85, s = 0.249)]. A possible physical meaning for the ELUMO correlation based upon the principle of maximum hardness is discussed.
Granulocyte-mediated injury to herpes simplex virus-infected human endothelium. (1989)

Some endothelial-injury syndromes, including atherosclerosis, may involve herpes simplex virus (HSV) infection. Examining the mechanism of injury, we found adherence of unstimulated granulocytes to HSV infected endothelium to be twice that to uninfected endothelium (34.8 +/- 1.1 versus 18.8 +/- 0.5%; mean +/- SEM; p less than 0.001) which further increased in the presence of anti-HSV antibodies. Enhanced adhesion was accompanied by excessive granulocyte-mediated lysis of 51Cr-labeled, HSV-infected endothelium (16.4 +/- 0.9%, HSV-infected versus 0.9 +/- 4.5% for uninfected endothelium; p less than 0.01). HSV infection also increased granulocyte-mediated endothelial cell detachment from its substratum (14.7 +/- 1.7% versus 3.3 +/- 0.3% for uninfected endothelium; p less than 0.001), which further increased (p less than 0.01) in the presence of immune complexes (IgG-sensitized erythrocytes). This suggests that neo-Fc receptors of infected endothelium bind IgG-coated particles, which, in turn, attract and stimulate granulocytes. In support, granulocyte-mediated detachment was not enhanced by immune complexes if endothelium was infected with a mutant HSV strain (E3/3) that does not produce glycoprotein E, the viral glycoprotein having Fc-receptor activity. Exaggerated endothelial detachment correlated with poor binding of infected endothelial cells to the substratum matrix protein, fibronectin. Resuspended, virus-infected endothelial cells bound significantly less well to tissue-culture wells coated with both low (p less than 0.001) and high (p less than 0.05) concentrations of fibronectin as compared with uninfected endothelial cells, a dichotomy further worsened in the presence of granulocyte-released elastase. We conclude that HSV-infected human endothelium is vulnerable to granulocyte-mediated injury by opposing alterations in its adhesive properties: its increased binding of granulocytes and its weakened tethering to matrix fibronectin, particularly when exposed to secreted granulocyte proteases, such as elastase.
A novel chemokine, macrophage inflammatory protein-related protein-2, inhibits colony formation of bone marrow myeloid progenitors (1995)

A new member of the beta-chemokine family, macrophage inflammatory protein (MIP)-related protein-2 (MRP-2) was isolated from a murine macrophage cell line, RAW 264.7. MRP-2 is composed of 122 amino acids of which the first 21 residues constitute a putative signal sequence. The putative mature protein is composed of 101 amino acids with a molecular weight of 11,600. MRP-2 is structurally similar to MIP-related protein-1 (MRP-1) (C10) and MIP-1 alpha. MRP-2 shows a 50.8% sequence identity at the protein level to MRP-1 and 46.3% identity to MIP-1 alpha. MRP-2 detects approximately 1.3 kilobase mRNA from monocyte and macrophage cell lines but does not detect the mRNA from T and B cells. The MRP-2 gene termed Scya9 was mapped to the central region of mouse chromosome 11 near the Scya1 and Scya2 genes, which are also members of the beta-chemokine superfamily. The Scya gene cluster was located between neurofibromatosis type 1 (Nf1) and myeloperoxidase (Mpo). rMRP-2 significantly suppressed colony formation by murine and human bone marrow granulocyte-macrophage (CFU-granulocyte-macrophage), erythroid (burst-forming unit-E), and multipotential (CFU-granulocyte-erythroid-macrophage-megakaryocyte) progenitor cells stimulated by combinations of growth factors.
GGAPs, a New Family of Bifunctional GTP-Binding and GTPase-Activating Proteins (2003)

G proteins are molecular switches that control a wide variety of physiological functions, including neurotransmission, transcriptional activation, cell migration, cell growth. and proliferation. The ability of GTPases to participate in signaling events is determined by the ratio of GTP-bound to GDP-bound forms in the cell. All known GTPases exist in an inactive (GDP-bound) and an active (GTP-bound) conformation, which are catalyzed by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs), respectively. In this study, we identified and characterized a new family of bifunctional GTP-binding and GTPase-activating proteins, named GGAP. GGAPs contain an N-terminal Ras homology domain, called the G domain, followed by a pleckstrin homology (PH) domain, a C-terminal GAP domain, and a tandem ankyrin (ANK) repeat domain. Expression analysis indicates that this new family of proteins has distinct cell localization, tissue distribution, and even message sizes. GTPase assays demonstrate that GGAPs have high GTPase activity through direct intramolecular interaction of the N-terminal G domain and the C-terminal GAP domain. In the absence of the GAP domain, the N-terminal G domain has very low activity, suggesting a new model of GGAP protein regulation via intramolecular interaction like the multidomain protein kinases. Overexpression of GGAPs leads to changes in cell morphology and activation of gene transcription.
Structure/Processing/Properties Relationships in Nanoporous Nanoparticles As Applied to Catalysis of the Cathodic Oxygen Reduction Reaction (2012)

We present a comprehensive experimental study of the formation and activity of dealloyed nanoporous Ni/Pt alloy nanoparticles for the cathodic oxygen reduction reaction. By addressing the kinetics of nucleation during solvothermal synthesis we developed a method to control the size and composition of Ni/Pt alloy nanoparticles over a broad range while maintaining an adequate size distribution. Electrochemical dealloying of these size-controlled nanoparticles was used to explore conditions in which hierarchical nanoporosity within nanoparticles can evolve. Our results show that in order to evolve fully formed porosity, particles must have a minimum diameter of ∼15 nm, a result consistent with the surface kinetic processes occurring during dealloying. Nanoporous nanoparticles possess ligaments and voids with diameters of approximately 2 nm, high surface area/mass ratios usually associated with much smaller particles, and a composition consistent with a Pt-skeleton covering a Ni/Pt alloy core. Electrochemical measurements show that the mass activity for the oxygen reduction reaction using carbon-supported nanoporous Ni/Pt nanoparticles is nearly four times that of commercial Pt/C catalyst and even exceeds that of comparable nonporous Pt-skeleton Ni/Pt alloy nanoparticles.