gebhart/patrepeval huggingface dataset:
Mechanism and In Vitro Pharmacology of TAK1 Inhibition by (5Z)-7-Oxozeaenol (2012)

Transforming growth factor-β activated kinase-1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that regulates several signaling pathways including NF-κB signal transduction and p38 activation. TAK1 deregulation has been implicated in human diseases including cancer and inflammation. Here, we show that, in addition to its kinase activity, TAK1 has intrinsic ATPase activity, that (5Z)-7-Oxozeaenol irreversibly inhibits TAK1, and that sensitivity to (5Z)-7-Oxozeaenol inhibition in hematological cancer cell lines is NRAS mutation status and TAK1 pathway dependent. X-ray crystallographic and mass spectrometric studies showed that (5Z)-7-Oxozeaenol forms a covalent complex with TAK1. Detailed biochemical characterization revealed that (5Z)-7-Oxozeaenol inhibited both the kinase and the ATPase activity of TAK1 following a bi-phase kinetics, consistent with the irreversible inhibition mechanism. In DoHH2 cells, (5Z)-7-Oxozeaenol potently inhibited the p38 phosphorylation driven by TAK1, and the inhibition lasted over 6 h after withdrawal of (5Z)-7-Oxozeaenol. Profiling (5Z)-7-Oxozeaenol in a panel of hematological cancer cells showed that sensitive cell lines tended to carry NRAS mutations and that genes in TAK1 regulated pathways were enriched in sensitive cell lines. Taken together, we have elucidated the molecular mechanism of a TAK1 irreversible inhibitor and laid the foundation for designing next generation TAK1 irreversible inhibitors. The NRAS-TAK1-Wnt signaling network discerned in our study may prove to be useful in patient selection for TAK1 targeted agents in hematological cancers.
Neutral Amino Acid Transporter ASCT1 Is Preferentially Expressed in l-Ser-Synthetic/Storing Glial Cells in the Mouse Brain with Transient Expression in Developing Capillaries (2003)

Nonessential amino acid L-Ser plays an essential role in neuronal survival and differentiation, through preferential expression of the L-Ser biosynthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH), in particular in glial cells but not in neurons. To seek the molecular candidates responsible for glia-borne L-Ser transport, we performed histochemical analyses on amino acid transporter ASCT1, which prefers small neutral amino acids, such as Ala, Ser, Cys, and Thr, and mediates their obligatory exchange. At early developmental stages, neuroepithelial cells constituting the ventricular zone expressed ASCT1 mRNA and protein ubiquitously. Thereafter, ASCT1 expression was gradually downregulated in neuronal populations during the late embryonic and neonatal periods, whereas its high expression was transmitted to radial glial cells and then to astrocytes. High levels of ASCT1 were also detected in the olfactory ensheathing glia. The preferential glial expression of ASCT1 was consistent with that of 3PGDH, and their extensive colocalization was demonstrated at the cellular level. Moreover, high cellular contents of L-Ser were revealed in these glial cells by using a specific antibody to L-Ser. These results strongly suggest that a large amount of L-Ser is synthesized and stored in these glial cells and is released through ASCT1 in exchange for other extracellular substrates. In addition, we observed prominent expression of ASCT1 in capillary endothelial cells of embryonic and neonatal brains. Therefore, ASCT1 appears to be regulated to meet metabolic demands by differentiating and mature neurons through the transport of glia- and blood-borne small neutral amino acids.
Experimental results in range-only localization with radio (2004)

We present an early experimental result toward solving the localization problem with range-only sensors. We perform an experiment in which a mobile robot localizes using dead reckoning and range measurements to stationary radio-frequency beacons in its environment, incorporating the range measurements into the position estimate using a Kalman filter. This data set involves over 20,000 range readings to surveyed beacons while a robot moved continuously over a path for nearly 1 hour. Careful groundtruth accurate to a few centimeters was recorded during this motion. We show the improvement of the robot's position estimate over dead reckoning even when the range readings are very noisy. We extend this approach to the problem of simultaneous localization and mapping (SLAM), localizing both the robot and tag positions from noisy initial estimates.
Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice. (1994)

Tolerance to peripheral antigens is thought to result from the inability of parenchymal tissue to stimulate T cells--an inability that is believed to relate to the lack of expression of the costimulatory signal(s) required for T-cell activation. To test this model, we generated transgenic mice expressing costimulatory molecule B7-1 on the B cells of the pancreas. We find that islets from these transgenic mice are immunogenic for naive T cells in vitro and in vivo. Nonetheless, mice expressing the costimulator B7-1 specifically on beta cells do not develop diabetes, suggesting that expression of the B7-1 costimulator is not sufficient to abrogate the tolerance to peripheral antigens. We have reported that tumor necrosis factor alpha subunit (TNF-alpha) expressed by beta cells leads to a local inflammation but no islet destruction. Strikingly, however, the combination of a local inflammation due to the expression of the cytokine TNF-alpha and the expression of B7-1 results in tissue destruction and diabetes.
Accurate and efficient macromodel of submicron digital standard cells (1997)

In this paper a new analytic gate delay modelingtechnique is presented that allows to accuratelyreproduce the timing behavior of deep submicron digitalstandard cells for a large range of operating conditions.The proposed technique sensibly improves the accuracyof the existing analytic delay models and it usuallyrequires less simulations for the cell characterization.Moreover it is compatible with the most advanced interconnectdelay models that have been recently proposed inthe literature.
The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop (2011)

Silent information regulator 1 (SIRT1) represents an NAD(+)-dependent deacetylase that inhibits proapoptotic factors including p53. Here we determined whether SIRT1 is downstream of the prototypic c-MYC oncogene, which is activated in the majority of tumors. Elevated expression of c-MYC in human colorectal cancer correlated with increased SIRT1 protein levels. Activation of a conditional c-MYC allele induced increased levels of SIRT1 protein, NAD(+), and nicotinamide-phosphoribosyltransferase (NAMPT) mRNA in several cell types. This increase in SIRT1 required the induction of the NAMPT gene by c-MYC. NAMPT is the rate-limiting enzyme of the NAD(+) salvage pathway and enhances SIRT1 activity by increasing the amount of NAD(+). c-MYC also contributed to SIRT1 activation by sequestering the SIRT1 inhibitor deleted in breast cancer 1 (DBC1) from the SIRT1 protein. In primary human fibroblasts previously immortalized by introduction of c-MYC, down-regulation of SIRT1 induced senescence and apoptosis. In various cell lines inactivation of SIRT1 by RNA interference, chemical inhibitors, or ectopic DBC1 enhanced c-MYC-induced apoptosis. Furthermore, SIRT1 directly bound to and deacetylated c-MYC. Enforced SIRT1 expression increased and depletion/inhibition of SIRT1 reduced c-MYC stability. Depletion/inhibition of SIRT1 correlated with reduced lysine 63-linked polyubiquitination of c-Myc, which presumably destabilizes c-MYC by supporting degradative lysine 48-linked polyubiquitination. Moreover, SIRT1 enhanced the transcriptional activity of c-MYC. Taken together, these results show that c-MYC activates SIRT1, which in turn promotes c-MYC function. Furthermore, SIRT1 suppressed cellular senescence in cells with deregulated c-MYC expression and also inhibited c-MYC-induced apoptosis. Constitutive activation of this positive feedback loop may contribute to the development and maintenance of tumors in the context of deregulated c-MYC.
ChemInform Abstract: Peptide Nucleic Acids (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Inferring Descriptions and Similarity for Music from Community Metadata (2002)

We propose methods for unsupervised learning of text profiles for music from unstructured text obtained from the web. The profiles can be used for classification, recommendation, and understanding, and may be used in conjunction with existing methods such as audio analysis and collaborative filtering to improve performance. A formal method for analyzing the quality of the learned profiles is given, and results indicate that they perform well when used to find similar artists. 1
The melt anisotropy of ultrahigh‐molecular‐weight polyethylene (1983)

Abstract In the course of melt‐flow crystallization studies with ultrahigh‐molecular‐weight polyethylene (UHMWPE), we observed that the melt of UHMWPE is highly anisotropic above its equilibrium melting point and has a tendency to fibrillate. An examination of the melt anisotropy of UHMWPE by optical, Thermal, and x‐ray analysis indicates that the melt anisotropy persists at 345°C, i.e., the temperature at which the polymer degrades under nitrogen, and appears similar to a smectic liquid‐crystalline phase.
Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3 (2008)

Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G beta-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.
Research on the axis shape of an active catheter (2008)

An active catheter prototype has been designed using the theory presented in this paper. Utilizing a vascular model, the active catheter-based invasive surgery was simulated. The experiment confirmed that the large deflection theory calculation method can be used to guide the design of the active catheter.
Organic light-emitting diodes formed by soft contact lamination (2004)

Although tremendous progress has been made in organic light-emitting diodes (OLEDs), with few exceptions they are fabricated in the standard way by sequentially depositing active layers and electrodes onto a substrate. Here we describe a different approach for building OLEDs, which is based on physical lamination of thin metal electrodes supported by an elastomeric layer against an electroluminescent organic. This method relies only on van der Waals interactions to establish spatially homogeneous, intimate contacts between the electrodes and the organic. We find that devices fabricated in this manner have better performance than those constructed with standard processing techniques. The lamination approach avoids forms of disruption that can be introduced at the electrode/organic interface by metal evaporation and has a reduced sensitivity to pinhole or partial pinhole defects. In addition, because this form of "soft" contact lamination is intrinsically compatible with the techniques of soft lithography, it is easy to build patterned OLEDs with feature sizes into the nanometer regime. This method provides a new route to OLEDs for applications ranging from high performance displays to storage and lithography systems that rely on subwavelength light sources.
Fully depleted dual-gated thin-film SOI P-MOSFETs fabricated in SOI islands with an isolated buried polysilicon backgate (1996)

P-channel dual-gated thin-film silicon-on-insulator (DG-TFSOI) MOSFETs have been fabricated with an isolated buried polysilicon backgate in an SOI island formed by epitaxial lateral overgrowth (ELO) of silicon. This structure allows individual operation of both the top and back gates rather than the conventional common backgate structure. When fully-depleted, the buried gate is used to individually shift the top gate threshold voltage (V/sub T/). A linear shift of /spl Delta/V/sub T,top///spl Delta/V/sub G,back/ of 0.5 V/V was achieved with a thin buried oxide. The effective density of interface traps (D/sub it/) for the backgate polysilicon-oxide SOI interface was measured to be 1.8/spl times/10/sup 11/ #/cm/sup 2//spl middot/eV as compared to the substrate-oxide of 1.1/spl times/10/sup 11/ #/cm/sup 2//spl middot/eV.
Stimulation of butyrate production through the metabolic interaction among lactic acid bacteria, Lactobacillus acidophilus, and lactic acid‐utilizing bacteria, Megasphaera elsdenii, in porcine cecal digesta (2006)

ABSTRACT In this study, we examined the potential of Megasphaera elsdenii as a probiotic agent in combination with sodium gluconate. We also examined the combination of M. elsdenii with probiotic lactic acid bacteria (LAB), Lactobacillus acidophilus , to enhance butyrate production in the large intestine using a pig cecal in vitro model under the presence of sodium gluconate. Compared to the uninoculated control culture (with only diluted cecal digesta), the addition of M. elsdenii and LAB to the culture stimulated significantly the production of n‐butyrate (60% increase) and n‐valerate (50% increase) after 24 h incubation. n‐Butyrate is regarded as the most important short‐chain fatty acid in the large intestine because it stimulates the proliferation of epithelial cells, mucus release and water and mineral absorption. Therefore, lactate‐utilizing butyrate producers such as M. elsdenii play a significant role in supporting the health‐beneficial effects of lactogenic prebiotics and probiotics LAB. The potential of M. elsdenii as a probiotic was also suggested.
Multiple Peptide Synthesis Methods and Their Applications. New Synthetic Methods (87) (1992)

Abstract Rapid developments in the biotechnology of new proteins, as well as advances in immunology and the development of pharmaceuticals based on inhibitors and antagonists, have led to immense demands for synthetic peptides. Simultaneous preparation of 100–150 completely different peptides, having chain lengths of up to 20 amino acids can nowadays be achieved using multiple synthesis methods. The yields and qualities of the peptides so obtained are high enough to permit reliable in vivo and in vitro screening for biological activities. Moreover, it is possible to optimize synthetic conditions and to carry out comparative studies on the secondary structures and conformational mapping of proteins. Special multiple synthesis methods facilitate the epitope mapping of larger peptides for diagnostic purposes and for the development of vaccines based on a few hundreds of free or rod‐bound peptides that are useful for immunoassays. Multiple methods of peptide synthesis also enable the preparation of so‐called peptide libraries which could comprise hundreds of thousands of peptides, and by which new perspectives for the screening of lead structures will be opened up. Peptide synthesis using a combination of photolabile protecting groups and photolithographic procedures enables the assembling of peptide libraries on small plates for use in miniature immunoassays. Furthermore, lipopeptide‐antigen conjugates allow both the preparation of peptide‐specific and monoclonal antibodies as well as a complete screening of epitopes of B‐, T‐helper and T‐killer cells. Applications in the areas of AIDS diagnosis, the development of vaccines, and screening for the hormone analogues, demonstrate just some of the possibilities that have been opened up by multiple peptide synthesis methods.
Incisional Wound Healing: A Controlled Study of Low and High Dose Ultrasound (1993)

Ultrasound is commonly used by physical therapists, but there is no consensus regarding the most effective therapeutic dose for accelerating healing of open or closed wounds. A controlled, single-blind, posttest experimental study was carried out to compare differences in wound breaking strength and collagen deposition [hydroxyproline (HoPro)]. Forty-eight incisions were surgically induced in three mini Yucatan pigs. Each incision was randomly assigned to a control or an ultrasound treatment group with the sonated incisions further randomly assigned to 5 or 10 days of ultrasound treatment with either high dose ultrasound (HUS) (1.5 W/cm2, continuous mode, 1 MHz, 5 minutes) or low dose ultrasound (LUS) (0.5 W/cm2, pulsed mode, 20% duty cycle, 1 MHz, 5 minutes). Using the nonparametric two-sample Wilcoxon test, the breaking strength was found to be significantly higher in the sonated incisions compared with the control incisions (p < or = 0.02), but there were no significant differences in HoPro. For all groups, the level of HoPro measured the second week was significantly higher (an average of 60%) than measured the first week (p < or = 0.001). A significant interaction was found between the number of days of treatment and the dose of ultrasound. Hydroxyproline was significantly higher in the LUS group compared with the HUS group after 5 days of ultrasound. Both the wound breaking strength and the HoPro levels were significantly higher in the LUS group compared with the HUS group after 10 days of treatment (p < or = 0.02 and 0.01, respectively). The findings from this study suggest that physical therapists can use either LUS or HUS for approximately 1 week to enhance wound breaking strength in an acute incisional wound. However, if the goal is to continue to facilitate collagen deposition and wound strength, then a low dose of ultrasound should be used when treatment is continued for 2 weeks or more.
Does adipose tissue influence bioelectric impedance in obese men and women? (1998)

Bioelectric-impedance analysis overestimates fat-free mass in obese people. No clear hypotheses have been presented or tested that explain this effect. This study tested the hypothesis that adipose tissue affects measurements of resistance by using data for whole body and body segment resistance and by using muscle, adipose tissue, and bone volumes from magnetic resonance imaging for 86 overweight and obese men and women (body mass index > 27 kg/m2; age 38.5 +/- 10.2 yr). In multiple-regression analysis, muscle volumes had strong associations with resistance, confirming that the electric currents are conducted primarily in the lean soft tissues. Subcutaneous adipose tissue had a slight but statistically significant effect in women, primarily for the leg, suggesting that adipose tissue can affect measured resistance when the volume of adipose tissue is greater than muscle volume, as may occur in obese women in particular. This resulted in a slight overestimation of fat-free mass (e.g., +3 kg) when a bioelectric-impedance-analysis equation calibrated for nonobese female subjects was applied.
Engineering an Obligate Domain-Swapped Dimer of Cyanovirin-N with Enhanced Anti-HIV Activity (2002)

The anti-HIV cyanobacterial protein cyanovirin-N can undergo domain swapping to form an intertwined dimer. The dimeric form is stable at low pH and millimolar concentrations. By deleting an amino acid from the hinge linker about which domain swapping occurs, we have constructed an obligate domain-swapped dimer of cyanovirin-N that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values. This obligate dimer displays enhanced anti-HIV activity relative to the wild-type cyanovirin-N monomer with an observed 3.5-fold decrease in IC(50) (9nM for the dimer vs 32 nM for the monomer) for inhibition of HIV-1 envelope-mediated cell fusion and, when expressed in Escherichia coli, can be rapidly obtained in >98% purity in a single chromatographic step.
Redox Properties of CytochromecAdsorbed on Self-Assembled Monolayers: A Probe for Protein Conformation and Orientation (2002)

The redox behavior of cytochrome c (cyt c) adsorbed to gold electrodes modified with self-assembled monolayers (SAMs) depends on the SAM. This paper examines SAMs generated from alkanethiols terminating in trimethylammonium (1), sulfonate (2), methyl (3), amine (4), and carboxylic acid (5) groups and from an aromatic thiol (6). The redox potentials of cyt c adsorbed on SAMs of 1 and 5 are relatively close to the formal potential of native cyt c measured in solution. The redox potentials of cyt c adsorbed on SAMs of 3, 4, and 6 are significantly shifted from the formal potential, and a reduction peak at about 0.5 V more negative than the formal potential (that is, a value corresponding to a more difficult reduction) was observed in all three cases. These observations suggest that cyt c changes its conformation significantly on adsorption on these surfaces. No redox peaks were observed for cyt c adsorbed on SAMs of 2, although surface plasmon resonance (SPR) studies indicate that the SAMs of 2 irreversibly adsorbed approximately a double layer of cyt c. Mixed SAMs were also studied. Most interestingly, cyt c adsorbed on mixed SAMs formed from the combinations of 1 and 2 exhibited significantly slower electron transfer (0.3−1.2 s-1) than cyt c adsorbed on a homogeneous SAM of 1 (45 s-1). These observations suggest changes in protein orientation due to the presence of the sulfonate groups at the interface. This study suggests that electrochemical measurement can be a useful probe for the conformation and orientation of protein adsorbed on surfaces.