gebhart/patrepeval huggingface dataset:
Phosphorylation of the Linker for Activation of T-Cells by Itk Promotes Recruitment of Vav (2002)

The linker for activation of T-cells (LAT) is a palmitoylated integral membrane adaptor protein that resides in lipid membrane rafts and contains nine consensus putative tyrosine phosphorylation sites, several of which have been shown to serve as SH2 binding sites. Upon T-cell antigen receptor (TCR/CD3) engagement, LAT is phosphorylated by protein tyrosine kinases (PTK) and binds to the adaptors Gads and Grb2, as well as to phospholipase Cgamma1 (PLCgamma1), thereby facilitating the recruitment of key signal transduction components to drive T-cell activation. The LAT tyrosine residues Y(132), Y(171), Y(191), and Y(226) have been shown previously to be critical for binding to Gads, Grb2, and PLCgamma1. In this report, we show by generation of LAT truncation mutants that the Syk-family kinase ZAP-70 and the Tec-family kinase Itk favor phosphorylation of carboxy-terminal tyrosines in LAT. By direct binding studies using purified recombinant proteins or phosphopeptides and by mutagenesis of individual tyrosines in LAT to phenylalanine residues, we demonstrate that Y(171) and potentially Y(226) are docking sites for the Vav guanine nucleotide exchange factor. Further, overexpression of a kinase-deficient mutant of Itk in T-cells reduced both the tyrosine phosphorylation of endogenous LAT and the recruitment of Vav to LAT complexes. These data indicate that kinases from distinct PTK families are likely responsible for LAT phosphorylation following T-cell activation and that Itk kinase activity promotes recruitment of Vav to LAT.
A Fluorescent-Based High-Throughput Screening Assay for Small Molecules That Inhibit the Interaction of MdmX with p53 (2012)

A fluorescent-based high-throughput screening (HTS) assay for small molecules that inhibit the interaction of MdmX with p53 was developed and applied to identify new inhibitors. The assay evaluated the MdmX-p53 interaction by detecting the quenching of the fluorescence of green fluorescent protein (GFP) fused to the MdmX protein, after its interaction with a p53 peptide labeled with a fluorescence quencher. In this report, the developed HTS assay was applied to about 40 000 compounds, and 255 hit compounds that abrogated the GFP quenching were selected. Next, the obtained hits were reevaluated by other assays. First, their effects on the diffusion time of a fluorescently-labeled p53 peptide after incubation with the MdmX protein were tested by measuring the diffusion time using fluorescence correlation spectroscopy, and six stable hit compounds with IC(50) values less than 5 µM were selected. Next, we further confirmed their inhibition of the MdmX-p53 interaction by surface plasmon resonance. To indicate the efficacy of the hit compound as a candidate anticancer drug, we showed that the hit compound triggered apoptosis after p53 and p21 accumulation in cultured MV4;11 leukemia cells. Thus, the new HTS assay is effective for obtaining novel MdmX-p53 interaction inhibitors that are valuable as candidate compounds for cancer treatment.
Characterization of a unique enzyme complex composed of S-adenosyl-L-methionine-tRNA-methyltransferase and aminoacyl-tRNA synthetase activities (1977)

S-adenosyl-L-methionine-tRNA methyltransferases of a murine leukemia cell line were found to exist in a high molecular weight enzyme complex. Aminoacyl-tRNA synthetase activity always co-chromatographed and co-sedimented with methyltransferase activity in evidence of a unique association of these two groups of enzymes. Molecular weight studies showed a probable molecular weight of 9 X 10(5) daltsons for the intact complex which dissociates to complexes of 6 X 10(5) and 3 X 10(5) daltons. The complexes contain discrete polypeptides of 25,000-90,000 daltons as determined from SDS-gel electrophoresis. High resolution fatty acid analysis showed that only very small amounts of saponifiable lipids were associated with the purified enzyme complex. Similarly very little protein-bound sugars was found within the complex indicating that neither lipids nor sugars were involved in the protein-protein interactions of the complex. Analysis of tRNA methylated in vitro indicated the presence of most methyltransferase activities in the purified complex. Of note was the absence from the complex of the methyltransferase responsible for the production of ribo Tp.
ChemInform Abstract: Heteroatom Assisted Isomerization of Epoxides: An Easy Access to Masked β‐Hydroxy Aldehydes. (1993)

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.
Scientific principles of anesthesia (1998)

Cellular Signal Transduction. Physics Principles Important in Anesthesiology. Pharmacokinetic and Pharmacodynamic Principles. Autonomic Nervous System. Cardiovascular Physiology and Pharmacology. Respiratory Physiology, Including Hyperbaria and Hypobaria. Cerebral Physiology. Neuromuscular Transmission. Coagulation. Injury and Inflammation. Mechanisms of Pain Transmission. Molecular Biology Principles in Anesthesia. Mechanisms of Anesthetic Action. Pharmacology and Physiology of Inhaled Anesthetic Agents. Pharmacology and Physiology of Intravenous Anesthetic Agents. Mechanism of Local Anesthetic Action Hardware Requirements: Macintosh 68030, 68040, Power PC. System 7.0. 8 MB RAM. Windows 386SX 25 Mhz Processor. Windows 0 3.1 or Higher, Running in 386 Enhanced Mode. 8 MB RAM (16 MB Preferred). 9.5 MB Free Hard Disk Space. Mouse. Sound Card. Double-Speed CD-ROM Drive. VGA Monitor
Andrographolide Stimulates Neurogenesis in the Adult Hippocampus (2015)

Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.
A‐kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA synthesis (2015)

The RNA polymerase I transcription apparatus acquires and integrates the combined information from multiple cellular signalling cascades to regulate ribosome production essential for cell growth and proliferation. In the present study, we show that a subpopulation of A-kinase anchoring protein 95 (AKAP95) targets the nucleolus during interphase and is involved in regulating rRNA production. We show that AKAP95 co-localizes with the nucleolar upstream binding factor, an essential rRNA transcription factor. Similar to other members of the C2 H2 -zinc finger family, we show, using systematic selection and evolution of ligands by exponential enrichment and in vitro binding analysis, that AKAP95 has a preference for GC-rich DNA in vitro, whereas fluorescence recovery after photobleaching analysis reveals AKAP95 to be a highly mobile protein that exhibits RNA polymerase I and II dependent nucleolar trafficking. In line with its GC-binding features, chromatin immunoprecipitation analysis revealed AKAP95 to be associated with ribosomal chromatin in vivo. Manipulation of AKAP95-expression in U2OS cells revealed a reciprocal relationship between the expression of AKAP95 and 47S rRNA. Taken together, our data indicate that AKAP95 is a novel nucleolus-associated protein with a regulatory role on rRNA production.
Resource Tuning in a Multipath Superscalar Architecture (1999)

This paper presents the resource tuning in a multipath superscalar architecture model. The main goal of this model is to provide a high bandwidth for superscalar architectures that need a high instruction throughput. This architecture has an aggressive fetch mechanism to increase the number of instructions available to the execution stage of the pipeline, allowing a high number of instructions to be executed per cycle. To achieve this, instructions from multiple paths are fetched in the same clock cycle. The model results in a reduction of the occurrence of breaks in the flow. A more detailed study into the resource distribution throughout the architecture is needed. Simply increasing the number of resources to support throughput is not recommended, given the prohibitive implementation costs. The resource tuning of this superscalar architecture is then an important focus of research, to balance resource requirements and to tune them.
Optical and Electronic Ion Channel Monitoring from Native Human Membranes (2020)

Transmembrane proteins represent a major target for modulating cell activity, both in terms of therapeutics drugs and for pathogen interactions. Work on screening such therapeutics or identifying toxins has been severely limited by the lack of available methods that would give high content information on functionality (ideally multimodal) and that are suitable for high-throughput. Here, we have demonstrated a platform that is capable of multimodal (optical and electronic) screening of ligand gated ion-channel activity in human-derived membranes. The TREK-1 ion-channel was expressed within supported lipid bilayers, formed <i>via</i> vesicle fusion of blebs obtained from the HEK cell line overexpressing TREK-1. The resulting reconstituted native membranes were confirmed <i>via</i> fluorescence recovery after photobleaching to form mobile bilayers on top of films of the polymeric electroactive transducer poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS). PEDOT:PSS electrodes were then used for quantitative electrochemical impedance spectroscopy measurements of ligand-mediated TREK-1 interactions with two compounds, spadin and arachidonic acid, known to suppress and activate TREK-1 channels, respectively. PEDOT:PSS-based organic electrochemical transistors were then used for combined optical and electronic measurements of TREK-1 functionality. The technology demonstrated here is highly promising for future high-throughput screening of transmembrane protein modulators owing to the robust nature of the membrane integrated device and the highly quantitative electrical signals obtained. This is in contrast with live-cell-based electrophysiology assays (<i>e</i>.<i>g</i>., patch clamp) which compare poorly in terms of cost, usability, and compatibility with optical transduction.
Impact of Changing the Core in Tetrapyrrolic Dendrimers Designed for Oxygen Sensitization: New Fluorescent Phthalocyanine-Based Dendrimers with High Two-Photon Absorption Cross-sections (2021)

In the continuation of our sustained interest for porphyrin-based dendrimers and their use as luminescent photosensitizers for two-photon photodynamic therapy (2P-PDT), we wondered about the effect of changing the central porphyrin core for a phthalocyanine core in these macromolecular structures. Thus, related phthalocyanine-based dendrimers possessing up to 16 conjugated 9,9-dibutyl-2-fluorenyl endgroups at their periphery were now prepared and studied. As for porphyrin analogues, it was found that an efficient energy transfer occurs from the peripheral fluorenyl units toward the central phthalocyanine unit of these compounds, leading to intense red light emission and photosensitization of oxygen. While the linear optical properties of these new dendrimers are only slightly improved compared to those of their porphyrin-cored analogues for PDT and fluorescence imaging, their two-photon absorption (2PA) cross-sections are much more significantly boosted, evidencing the key role played by the central tetrapyrrolic unit in this respect. The impact of this structural change in relation with the impact resulting from the change in dendrimer generations is then discussed with the help of DFT and molecular dynamic calculations.
Transmission of 96 $\,\times\,$100-Gb/s Bandwidth-Constrained PDM-RZ-QPSK Channels With 300% Spectral Efficiency Over 10610 km and 400% Spectral Efficiency Over 4370 km (2010)

We demonstrated that simple pre-filtering at the transmitter to constrain the channel bandwidth together with a maximum a posteriori probability (MAP) detection algorithm can significantly improve spectral efficiency (SE). 96 × 100-Gb/s bandwidth-constrained polarization-division-multiplexing return- to-zero-QPSK channels were transmitted with 300% SE over 10 610 km using 52-km spans of 150-μ m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> fiber and simple single-stage erbium-doped fiber amplifiers without any Raman amplification. We also achieved 400% SE over 4370 km using similar techniques.
A novel multi-target detection algorithm for automotive FMCW radar (2018)

In automotive radar systems resolution of each target in multi-target environment is necessary. A conventional FMCW radar which transmits and receives triangular waves, does not effectively remove the ghost-targets which arise in the process of Doppler-range localization process. Using a sophisticated waveform design can help removing the ghost-targets, however, there remains many of them. In this paper, we propose a novel ghost-target removal algorithm using the inter-relationship between the upbeat and downbeat frequency after the Fast Fourier Transform(FFT).
Modeling Polysiloxane Volume and Viscosity Variations With Molecular Structure and Thermodynamic State (2013)

Siloxane-based polymers (polysiloxanes) exhibit a range of volume, viscosity, and pressure-viscosity behaviors that are strongly influenced by the macromolecular structure. In this report, a combination of extant rheological models is applied to develop a molecular-rheological modeling formalism that predicts polysiloxane rheological properties, such as specific volume, which means density, viscosity, and pressure-viscosity index variations with macromolecular structure, pressure, and temperature. Polysiloxane molecular features are described in terms of alkyl branch length L, pendant type J, density of branch functional monomers Q, and degree of polymerization DP. Both new and published data are used for model parameter determination and validation. Several siloxane-based polymers with alkyl, aryl, alkyl-aryl, cycloalkyl, and halogenated branches were synthesized to examine the modeled relationship between their molecular structures and rheological behaviors.
The Design and Development of a Particulate In-Situ Sampler (PARISS) (1987)

The accurate determination of concentrations of particulate matter in the deep ocean is complicated by the fact that such concentrations are extremely low. Consequently, considerable quantities of water must be filtered to obtain significant results. This paper describes a device which is designed to operate on a standard CTD cable to obtain insitu samples of particulate matter by filtering large measured quantities of sea water at moderate flow rates. The unit includes six banks of filters which can be sequentially engaged on command from the surface. This allows multiple samples to be collected from a single depth, or sampling at multiple depths from a single cast. The sampler is remotely powered and controlled from the surface, with information being transferred to and from the instrumentation package and the ship via a single wire. Test results indicate correct electro-mechanical operation to 2000 m however, some discrepancy with concentrations measured by conventional systems is noted.
TAL Effector Specificity for base 0 of the DNA Target Is Altered in a Complex, Effector- and Assay-Dependent Manner by Substitutions for the Tryptophan in Cryptic Repeat –1 (2013)

TAL effectors are re-targetable transcription factors used for tailored gene regulation and, as TAL effector-nuclease fusions (TALENs), for genome engineering. Their hallmark feature is a customizable central string of polymorphic amino acid repeats that interact one-to-one with individual DNA bases to specify the target. Sequences targeted by TAL effector repeats in nature are nearly all directly preceded by a thymine (T) that is required for maximal activity, and target sites for custom TAL effector constructs have typically been selected with this constraint. Multiple crystal structures suggest that this requirement for T at base 0 is encoded by a tryptophan residue (W232) in a cryptic repeat N-terminal to the central repeats that exhibits energetically favorable van der Waals contacts with the T. We generated variants based on TAL effector PthXo1 with all single amino acid substitutions for W232. In a transcriptional activation assay, many substitutions altered or relaxed the specificity for T and a few were as active as wild type. Some showed higher activity. However, when replicated in a different TAL effector, the effects of the substitutions differed. Further, the effects differed when tested in the context of a TALEN in a DNA cleavage assay, and in a TAL effector-DNA binding assay. Substitution of the N-terminal region of the PthXo1 construct with that of one of the TAL effector-like proteins of Ralstonia solanacearum, which have arginine in place of the tryptophan, resulted in specificity for guanine as the 5' base but low activity, and several substitutions for the arginine, including tryptophan, destroyed activity altogether. Thus, the effects on specificity and activity generated by substitutions at the W232 (or equivalent) position are complex and context dependent. Generating TAL effector scaffolds with high activity that robustly accommodate sites without a T at position 0 may require larger scale re-engineering.
Clinical Application of Patient Specific Virtual Realistic Surgical Simulator (2013)

Training systems on commercial basis for laparoscopic surgery are useful for basic training, but are not suitable for specific training corresponding to the patient’s condition. We, therefore, have developed a unique training system, a patient-specific type simulator for laparoscopic surgery. When specific data of each individual patient is entered, this system facilitates surgeons to perform a “rehearsal” operation. We applied this technique in laparoscopic surgery on the basis of volume data obtained by multislice computed tomography imaging. We underwent surgical simulations before laparoscopic surgeries and compared them. Simulation was helpful because we could obtain information about the complicated vessel network and “rehearse” the procedure. Our simulator allows surgeons to perform a sham operation with different perspectives and tactile sensations and has received favorable reviews from users.
New multi-rod linear actuator for direct-drive, wide mechanical band pass applications (2003)

In this article, a new multi-rod linear actuator is presented. This actuator has been developed for high thrust density and wide mechanical band pass applications. The multi-airgap concept is first illustrated and explained. Its advantages are highlighted thanks to finite element method optimizations. Next, the multi-rod prototype technology is discussed. Lastly, experimental measurements for prototype forces are provided.
Dual-Modality Immuno-PET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer Using an Anti–Prostate Stem Cell Antigen Cys-Diabody (2018)

Pancreatic cancer has a high mortality rate due to late diagnosis and the tendency to invade surrounding tissues and metastasize at an early stage. A molecular imaging agent that enables both presurgery antigen-specific PET (immuno-PET) and intraoperative near-infrared fluorescence (NIRF) guidance might benefit diagnosis of pancreatic cancer, staging, and surgical resection, which remains the only curative treatment. <b>Methods:</b> We developed a dual-labeled probe based on A2 cys-diabody (A2cDb) targeting the cell-surface prostate stem cell antigen (PSCA), which is expressed in most pancreatic cancers. Maleimide-IRDye800CW was site-specifically conjugated to the C-terminal cys-tag (A2cDb-800) without impairing integrity or affinity (half-maximal binding, 4.3 nM). Direct radioiodination with <sup>124</sup>I (<sup>124</sup>I-A2cDb-800) yielded a specific activity of 159 ± 48 MBq/mg with a radiochemical purity exceeding 99% and 65% ± 4.5% immunoreactivity (<i>n</i> = 3). In vivo <i>s</i>pecificity for PSCA-expressing tumor cells and biodistribution of the dual-modality tracer were evaluated in a prostate cancer xenograft model and compared with single-labeled <sup>124</sup>I-A2cDb. Patient-derived pancreatic ductal adenocarcinoma xenografts (PDX-PDACs) were grown subcutaneously in NSG mice and screened for PSCA expression by immuno-PET. Small-animal PET/CT scans of PDX-PDAC-bearing mice were obtained using the dual-modality <sup>124</sup>I-A2cDb-800 followed by postmortem NIRF imaging with the skin removed. Tumors and organs were analyzed ex vivo to compare the relative fluorescent signals without obstruction by other organs. <b>Results:</b> Specific uptake in PSCA-positive tumors and low nonspecific background activity resulted in high-contrast immuno-PET images. Concurrent with the PET studies, fluorescent signal was observed in the PSCA-positive tumors of mice injected with the dual-tracer <sup>124</sup>I-A2cDb-800, with low background uptake or autofluorescence in the surrounding tissue. Ex vivo biodistribution confirmed comparable tumor uptake of both <sup>124</sup>I-A2cDb-800 and <sup>124</sup>I-A2cDb. <b>Conclusion:</b> Dual-modality imaging using the anti-PSCA cys-diabody resulted in high-contrast immuno-PET/NIRF images of PDX-PDACs, suggesting that this imaging agent might offer both noninvasive whole-body imaging to localize PSCA-positive pancreatic cancer and fluorescence image-guided identification of tumor margins during surgery.
Transformation of rat fibroblast cells with early mutants of polyoma (tsa) and simian virus 40 (tsA30): occurrence of either A or N transformants depends on the multiplicity of infection (1980)

Infection of rat fibroblasts with early mutants of polyoma virus (tsa) or simian virus 40 (tsA30) leads to the establishment of either temperature-independent A transformants or N transformants temperature-sensitive for the expression of the transformed phenotype. The choice between the A- and N-transformed states is not only dependent, as we reported previously (Rassoulzadegan et al., j. Virol., 28:421-426, 1978), on the growth conditions after infection, but is also a function of the multiplicity of infection (MOI); high MOI led to the predominant occurrence of A derivatives, and lower MOI led to that of N transformants.