gebhart/patrepeval huggingface dataset:
Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers (2009)

Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.
Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast (2016)

We demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates.
High Endothelial Cells of Postcapillary Venules Express the Scavenger Receptor in Human Peripheral Lymph Nodes (1995)

The macrophage scavenger receptor (MSR) is a multipotent receptor that mediates uptake of macromolecules with clustered negative charges, such as endotoxins and oxidized proteins and lipoproteins. It may also serve as an adhesion molecule for monocytes and macrophages. We have analysed MSR expression in human peripheral lymph nodes and show, by reverse transcription-PCR, that the type I isoform of MSR is abundantly expressed in this tissue. With the use of a new set of isoform-specific peptide antibodies, both isoforms of MSR were detected in the cuboidal endothelium of high-endothelial venules (HEV). MSR antibodies also stained macrophages and follicular dendritic cells of germinal centres. These data indicate that the MSR gene is expressed in HEV endothelium in vivo. It is suggested that MSR expression may be important for antigen uptake and leucocyte adhesion to HEV in the lymph node.
Identification of the Kv2.1 K+Channel as a Major Component of the Delayed Rectifier K+Current in Rat Hippocampal Neurons (1999)

Molecular cloning studies have revealed the existence of a large family of voltage-gated K+ channel genes expressed in mammalian brain. This molecular diversity underlies the vast repertoire of neuronal K+ channels that regulate action potential conduction and neurotransmitter release and that are essential to the control of neuronal excitability. However, the specific contribution of individual K+ channel gene products to these neuronal K+ currents is poorly understood. We have shown previously, using an antibody, "KC, " specific for the Kv2.1 K+ channel alpha-subunit, the high-level expression of Kv2.1 protein in hippocampal neurons in situ and in culture. Here we show that KC is a potent blocker of K+ currents expressed in cells transfected with the Kv2.1 cDNA, but not of currents expressed in cells transfected with other highly related K+ channel alpha-subunit cDNAs. KC also blocks the majority of the slowly inactivating outward current in cultured hippocampal neurons, although antibodies to two other K+ channel alpha-subunits known to be expressed in these cells did not exhibit blocking effects. In all cases the blocking effects of KC were eliminated by previous incubation with a recombinant fusion protein containing the KC antigenic sequence. Together these studies show that Kv2.1, which is expressed at high levels in most mammalian central neurons, is a major contributor to the delayed rectifier K+ current in hippocampal neurons and that the KC antibody is a powerful tool for the elucidation of the role of the Kv2.1 K+ channel in regulating neuronal excitability.
Electrical Stimulation of Neural Stem Cells Mediated by Humanized Carbon Nanotube Composite Made with Extracellular Matrix Protein (2008)

One of the key challenges to engineering neural interfaces is to minimize their immune response toward implanted electrodes. One potential approach is to manufacture materials that bear greater structural resemblance to living tissues and by utilizing neural stem cells. The unique electrical and mechanical properties of carbon nanotubes make them excellent candidates for neural interfaces, but their adoption hinges on finding approaches for "humanizing" their composites. Here we demonstrated the fabrication of layer-by-layer assembled composites from single-walled carbon nanotubes (SWNTs) and laminin, which is an essential part of human extracellular matrix. Laminin-SWNT thin films were found to be conducive to neural stem cells (NSC) differentiation and suitable for their successful excitation. We observed extensive formation of functional neural network as indicated by the presence of synaptic connections. Calcium imaging of the NSCs revealed generation of action potentials upon the application of a lateral current through the SWNT substrate. These results indicate that the protein-SWNT composite can serve as materials foundation of neural electrodes with chemical structure better adapted with long-term integration with the neural tissue.
Collaborative computational anatomy: An MRI morphometry study of the human brain via diffeomorphic metric mapping (2008)

This article describes a large multi-institutional analysis of the shape and structure of the human hippocampus in the aging brain as measured via MRI. The study was conducted on a population of 101 subjects including nondemented control subjects (n = 57) and subjects clinically diagnosed with Alzheimer's Disease (AD, n = 38) or semantic dementia (n = 6) with imaging data collected at Washington University in St. Louis, hippocampal structure annotated at the Massachusetts General Hospital, and anatomical shapes embedded into a metric shape space using large deformation diffeomorphic metric mapping (LDDMM) at the Johns Hopkins University. A global classifier was constructed for discriminating cohorts of nondemented and demented subjects based on linear discriminant analysis of dimensions derived from metric distances between anatomical shapes, demonstrating class conditional structure differences measured via LDDMM metric shape (P < 0.01). Localized analysis of the control and AD subjects only on the coordinates of the population template demonstrates shape changes in the subiculum and the CA1 subfield in AD (P < 0.05). Such large scale collaborative analysis of anatomical shapes has the potential to enhance the understanding of neurodevelopmental and neuropsychiatric disorders.
microRNA expression in the aging mouse lung (2007)

Overall, these results show that miRNA transcription is unchanged during lung aging and suggests that stable expression of miRNAs might instead buffer age related changes in the expression of protein-encoding genes.
Favorable response to crizotinib in three patients with echinoderm microtubule‐associated protein‐like 4–anaplastic lymphoma kinase fusion‐type oncogene‐positive non‐small cell lung cancer (2011)

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) is a recently identified fusion-type oncoprotein that exists in approximately 5% of non-small cell lung cancer (NSCLC). It has been demonstrated that NSCLC driven by EML4-ALK is strongly addicted to this fusion-type oncokinase. A clinical trial of crizotinib (PF-02341066) sponsored by Pfizer has proven this oncogene addiction in humans by demonstrating a high response rate to inhibition of ALK kinase activity. In the present study, we report on three cases harboring EML4-ALK rearrangement who were enrolled in the trial (A8081001, NCT00585195). All three patients showed favorable responses to the ALK-specific tyrosine kinase inhibitor.
An Effective Solvation Term Based on Atomic Occupancies for Use in Protein Simulations (1993)

Abstract Several approaches to the treatment of solvent effects based on continuum models are reviewed and a new method based on occupied atomic volumes (occupancies) is proposed and tested. The new method describes protein-water interactions in terms of atomic solvation parameters, which represent the solvation free energy per unit of volume. These parameters were determined for six different atoms types, using experimental free energies of solvation. The method was implemented in the GROMOS and PRESTO molecular simulation program suites. Simulations with the solvation term require 20-50% more CPU time than the corresponding vacuum simulations and are approximately 20 times faster than explicit water simulations. The method and parameters were tested by carrying out 200 ps simulations of BPTI in water, in vacuo, and with the solvation term. The performance of the solvation term was assessed by comparing the structures and energies from the solvation simulations with the equivalent quantities derived from several BPTI crystal structures and from the explicit water and vacuum simulations. The model structures were evaluated in terms of exposed total surface, buried and exposed polar surfaces, secondary structure preservation, number of hydrogen bonds, energy contributions, and positional deviations from BPTI crystal structures. Vacuum simulations produced unrealistic structures with respect to all criteria applied. The structures resulting from the simulations with explicit water were closer to the 5PTI crystal structure, although part of the secondary structure dissolved. The simulations with the effective solvation term produce structures that are normal according to all evaluations and in most respects are remarkably similar to the 5PTI crystal structure despite considerable positional fluctuations during the simulations. The segments where the model and crystal structures differ are known to be flexible and the observed difference may be physically realistic. The effective solvation term based on occupancies is not only very efficient in terms of computer time but also results in meaningful structural properties for BPTI. It may therefore be generally useful in molecular dynamics of macromolecules.
Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390). (1989)

Brequinar sodium is a 4-quinolinecarboxylic acid analogue that inhibits dihydroorotate dehydrogenase and subsequent de novo pyrimidine biosynthesis. It has shown dose-dependent antineoplastic activity against several mouse and human tumor models. This trial evaluated Brequinar given as a single daily i.v. bolus over a 5-day period repeated every 28 days. One hundred seven courses of treatment at dosages ranging from 36 to 300 mg/m2/day x 5 were administered to 45 patients (31 male and 14 female) with refractory solid tumors; median age was 58 years (range 30-74); median Southwest Oncology Group performance status was 1 (range, 0-3). Thirty patients had prior cytotoxic chemotherapy. Dose-limiting toxicities were thrombocytopenia and a severe desquamative maculopapular dermatitis. Two of 5 good risk patients at 300 mg/m2 and 3 of 6 poor risk patients at 170 mg/m2 developed a platelet count less than 25 x 10(3)/microliters. Two of 5 good risk patients at 300 mg/m2 and 1 of 6 poor risk patients at 170 mg/m2 developed a severe desquamative dermatitis. Moderate to severe mucositis was usually associated with the thrombocytopenia and/or the dermatitis. Nonhematological drug-related toxicities included nausea and vomiting, malaise, anorexia, diarrhea, phlebitis, reversible transaminase elevation, and mucositis. Other hematological toxicities were anemia, granulocytopenia, and leukopenia. There were no drug-related deaths. There were no objective tumor responses. Plasma and urine levels of Brequinar were quantified by high pressure liquid chromatography in 28 patients. Plasma levels and areas under the curve increased proportionally with increased dose. Brequinar had a harmonic mean terminal t1/2 of 8.1 +/- 3.6 h with a model-independent determined apparent volume of distribution at steady state of 9.0 +/- 2.9 liters/m2 and a total body clearance of 19.2 +/- 7.7 ml/min/m2. Renal excretion was a minor route of elimination for Brequinar. The maximally tolerated dose of Brequinar on a daily x 5 i.v. schedule was 250 mg/m2 for good risk patients. For the daily x 5 i.v. schedule, the recommended dose of Brequinar for phase II evaluation is 250 mg/m2 for good risk patients and 135 mg/m2 for poor risk patients.
Spectrophotometric Determination of Freshwater pH Using Bromocresol Purple and Phenol Red (2001)

The dissociation constants (KI = [H+][I2-]/[HI-]) of two sulfonephthalein indicators (bromocresol purple and phenol red) were determined as function of temperature (10-30 degrees C) at zero ionic strength. Freshwater pH, on the free hydrogen ion concentration scale (molal units), can be precisely calculated from measurements of indicator absorbance ratios (lambda2A/lambda1A) using the following equations: pH = pKI + log((R - e1)/(e2 - Re3)) and pKI = pKI(degrees) - AdeltaZ2(mu1/2 /(1 + mu1/2) - 0.3 mu), where R = lambda2A/lambda1A, pKI = -log KI, mu is the ionic strength, deltaZ2 = 4, and values of A for 283 < or = T < or = 303 can be estimated from the equation: A = 0.5092 + (T-298.15) x 8.5 x 10(-4). For bromocresol purple (lambda1 = 432 nm, lambda2 = 589 nm), pKI(degrees) = 5.226 + 378.1/T, e1 = 0.00387, e2 = 2.858, and e3 = 0.0181. For phenol red (lambda1 = 433 nm, lambda2 = 558 nm), pKI(degrees) = 5.798 + 666.7/T, e1 = 0.00244, e2= 2.734, and e3 = 0.1075. These two indicators can be used to make accurate pH measurements of freshwaters (river water, lake water, groundwater, rainwater, etc) within the range 4.5 < or =pH < or =8.5. The precision of pH measurements using phenol red in well-buffered freshwaters is on the order of +/-0.001 or better.
Performance of a Heat Exchanger Based on Enhanced Heat Diffusion in Fluids by Oscillation: Experiment (1990)

The results of a study on the performance of a heat exchanger that takes advantage of enhanced heat diffusion in oscillated fluids are presented. In this heat exchanger, the fluid occupies a bundle of capillary tubes that connects two reservoirs at different temperatures; a piston in each reservoir drives the oscillation. The experimental findings are compared with predictions based on the assumptions that (a) a capillary tube does not exchange heat with the neighboring tubes, (b) the pressure in the reservoirs undergoes an ideal sinusoidal motion, and (c) each reservoir has an infinite heat capacity such that the fluid entering the tubes is at a constant temperature. Good agreement has been found between the actual performance of the heat exchanger and the idealized analysis for low and high frequencies. However, around the frequency corresponding to optimum performance, i.e., where the thermal boundary layers occupy the entire cross section of the capillary tubes, agreement is only fair. The measurements show that there is a temperature variation across the bundle and that the fluid entering the tubes has a nonsteady temperature due to weak, nonuniform mixing within the reservoirs (therefore, a spatial/temporal average was taken). This lateral and temporal variation in the temperature distribution appears to be the leading cause of the difference between the experimental and predicted results. As with any heat pipe, the reduction in the resistance to heat flow in the pipe must be accompanied by a similar ease of heat flow to and away from the ends of the pipe. Therefore, the reservoir fluid dynamics is of paramount importance in these heat exchangers. Some numerical modeling of the fluid flow in the reservoirs, as well as some velocity measurements (using a laser-Doppler anemometer), are also presented.
Field Experiments on Ultimate Frequency Efficiency Exceeding 30 Bit/Second/Hz Using MLD Signal Detection in MIMO-OFDM Broadband Packet Radio Access (2007)

This paper presents indoor and field experimental results on extremely high-speed packet transmissions of 4.92 Gbps in a 100-MHz channel bandwidth, i.e., the frequency efficiency of approximately 50 bit/second/Hz, in the downlink orthogonal frequency division multiplexing (OFDM) radio access. The required received signal-to-noise power ratio (SNR) is less than 30 dB, which approaches the almost upper limit in cellular environments near a cell site even with a light channel load, with the aim of the application to future universal broadband packet radio access. We apply 12-by-12 MIMO multiplexing using the maximum likelihood detection employing QR decomposition and the M-algorithm (QRM-MLD) with adaptive selection of the surviving symbol replica candidates (ASESS), 64QAM data modulation, and turbo coding with the coding rate of R = 8/9 to achieve an extremely high frequency efficiency level. In the field experiments conducted in the Yokosuka Research Park (YRP) district of Yokosuka city, we show that the measured throughput of 4.92 Gbps is achieved at the average received SNR per receiver antenna of approximately 28.0 and 28.5 dB when the receiver antenna spacing is 40 cm (6.2lambda), and 10 cm (1.5lambda) at the average speed of 10 km/h, respectively.
Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP (2000)

Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, with advancing age, an increased incidence of hematologic malignancies. The latter are characterized, at least in some cases, by loss of heterozygosity (LOH) at the CBP locus. No such pathology was observed in wild-type or p300 heterozygous null mice of the same age and genetic background. Thus, a full complement of CBP, but not p300, is required for normal hematopoietic differentiation. These results also provide the first experimental evidence for the hypothesis that CBP has tumor-suppressing activity.
Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts. (1983)

The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult beta-like globin gene domains were evaluated in greater than or equal to 90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-wk gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic epsilon chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult beta chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic leads to fetal and fetal leads to adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-alpha gene cluster, thus leading to a 5' leads to 3' activation of globin genes in a balanced fashion.
Vaults and Telomerase Share a Common Subunit, TEP1 (1999)

Vaults are large cytoplasmic ribonucleoprotein complexes of undetermined function. Mammalian vaults have two high molecular mass proteins of 193 and 240 kDa. We have identified a partial cDNA encoding the 240-kDa vault protein and determined it is identical to the mammalian telomerase-associated component, TEP1. TEP1 is the mammalian homolog of the Tetrahymena p80 telomerase protein and has been shown to interact specifically with mammalian telomerase RNA and the catalytic protein subunit hTERT. We show that while TEP1 is a component of the vault particle, vaults have no detectable telomerase activity. Using a yeast three-hybrid assay we demonstrate that several of the human vRNAs interact in a sequence-specific manner with TEP1. The presence of 16 WD40 repeats in the carboxyl terminus of the TEP1 protein is a convenient number for this protein to serve a structural or organizing role in the vault, a particle with eight-fold symmetry. The sharing of the TEP1 protein between vaults and telomerase suggests that TEP1 may play a common role in some aspect of ribonucleoprotein structure, function, or assembly.
Neural stem cell migration toward gliomas in vitro (2005)

Various in vivo studies demonstrated a migration tendency of neural stem cells (NSCs) toward gliomas, making these cells a potential carrier for delivery of therapeutic genes to disseminated glioma cells. We analyzed which factors determine NSC migration and invasion in vitro. Conditioned media prepared from 10 different human glioma cell lines, as well as 13 different tumor-associated growth factors, were analyzed for their chemotactic effects on murine C17.2 NSCs. The growth factor receptor status was analyzed by reverse transcriptase-polymerase chain reaction. Invasion of NSCs into multicellular tumor spheroids generated from 10 glioma cell lines was quantified. NSCs displayed a heterogeneous migration pattern toward glioma spheroids as well as toward glioma-cell-conditioned medium. Chemotactic migration was stimulated up to fivefold by conditioned medium as compared to controls. In coculture assays, NSC invasion varied from single cell invasion into glioma spheroids to complete dissemination of NSCs into glioma spheroids of different cell lines. Among 13 different growth factors, scatter factor/hepatocyte growth factor (SF/HGF) was the most powerful chemoattractant for NSCs, inducing a 2.5-fold migration stimulation. An antibody against SF/HGF inhibited migratory stimulation induced by conditioned media. NSC migration can be stimulated by various growth factors, similar to glioma cell migration. The extent to which NSCs infiltrate three-dimensional glioma cell aggregates appears to depend on additional factors, which are likely to include cell-to-cell contacts and interaction with extracellular matrix proteins.
Reactions of some 4‐methylene‐4H‐pyran derivatives with primary and secondary amines (1970)

Abstract 4‐Dicyanomethylene‐4 H ‐pyrans react with secondary amines to give 2‐aminopyridine and 2‐pyridone derivatives which, in turn, have been used to prepare copyrine derivatives. These pyrans and primary amines gave copyrine and iminopyridone derivatives in addition to the dicyanomethylene‐1,4‐dihydropyridines, which had been reported previously. Reaction of cyanocarbamoylmethylene‐4 H ‐pyrans with secondary amines gave 2‐pyrones, and with primary amines, gave copyrines and 1,4‐dihydropyridine derivatives.