gebhart/patrepeval huggingface dataset:
Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks (2002)

The architecture of membrane proteins in their native environment of the phospholipid bilayer is critical for understanding physiological function, but has been difficult to realize experimentally. In this communication we describe the incorporation of a membrane-anchored protein into a supported phospholipid bilayer. Cytochrome P450 2B4 solubilized and purified from the hepatic endoplasmic reticulum was incorporated into phospholipid bilayer nanostructures and oriented on a surface for visualization by atomic force microscopy. Individual P450 molecules were observed protruding from the bilayer surface. Problems associated with deformation of the protein by the atomic force microscopy probe were avoided by analyzing force-dependent height measurements to quantitate the height of the protein above the bilayer surface. Measurements of the atomic force microscopy cantilever deflection as a function of probe-sample separation reveal that the top of the P450 opposite the N-terminal membrane anchor region sits 3.5 nanometers above the phospholipid-water boundary. Models of the orientation of the enzyme are presented and discussed in relation to membrane interactions and interaction with cytochrome P450 reductase.
Regulation of mucosal immune responses in effector sites (2001)

In human disease and rodent models, immune responses in the intestinal mucosa can be damaging. Damage is characterised by villus atrophy, crypt hyperplasia and reduced ability to digest and absorb nutrients. In normal individuals active responses to harmless environmental antigens associated with food and commensal bacteria are controlled by the development of immunological tolerance. Similar pathological changes occur in piglets weaned early from their mothers. Active immune responses to food antigens are observed in these piglets, and we and others have hypothesised that the changes occur as a result of transient allergic immune responses to novel food or bacteria antigens. The normal mechanism for producing tolerance to food antigens may operate at induction (Peyer's patches and mesenteric lymph nodes) or at the effector stage (intestinal lamina propria). In our piglet studies immunological tolerance occurs despite the initial active response. Together with evidence from rodents, this observation suggests that active responses are likely to be controlled at the effector stage, within the intestinal lamina propria. Support for this mechanism comes from the observation that human and pig intestinal T-cells are susceptible to apoptosis, and that this process is accelerated by antigen. We suggest that the role of the normal mature intestinal lamina propria is a balance between immunological effector and regulatory function. In neonatal animals this balance develops slowly and is dependant on contact with antigen. Immunological insults such as weaning may tip the balance of the developing mucosal immune system into excessive effector or regulatory function resulting in transient or chronic allergy or disease susceptibility.
Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer (2016)

An LY2606368 dose of 105 mg/m(2) once every 14 days is being evaluated as the recommended phase II dose in dose-expansion cohorts for patients with SCC.
MET Exon 14 Skipping in Non-Small Cell Lung Cancer (2016)

MET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration.
IL-1β Scavenging by the Type II IL-1 Decoy Receptor in Human Neutrophils (2003)

IL-1 elicits its cellular effects by binding a heterodimeric receptor consisting of IL-1RI and the accessory protein, IL-1RAcPr. In addition, it binds to IL-1RII, which lacking signaling function has been ascribed a decoy role. The fate of the ligand following interaction with the decoy receptor was examined in human polymorphonuclear cells (PMN), which express predominantly (>90%) IL-1RII. Incubation of PMN with IL-1beta results in a rapid decrease in cell surface-associated ligand accompanied by a concomitant increase in internalized IL-1 with 50-60% of IL-1beta located intracellularly within 1 h at 37 degrees C. The use of blocking Abs revealed that IL-1 internalization is mediated exclusively by the decoy receptor. The results of inhibitor analysis demonstrate that internalization requires ATP synthesis and involves clathrin-mediated endocytosis. Following removal of the ligand, the receptor was rapidly re-expressed on the cell surface. Cyclohexamide, a protein synthesis inhibitor, had no effect upon the process, suggesting that the re-expressed receptor was recycled. In addition, human keratinocytes stably transfected with IL-1RII (HaCAT 811) also internalized the IL-1RII with 43% cell surface receptor internalized after 90 min. Immunofluorescence microscopy revealed colocalization of the internalized receptor with wheat germ agglutinin-labeled internalized glycoproteins and early endosome Ag-1, a protein associated with the early endosome compartments, indicative of cellular uptake of IL-1RII by endocytosis. In contrast, little or no internalization was observed in other cells of immune origin. These results suggest that the decoy receptor IL-1RII can act as a scavenger of IL-1, representing a novel autoregulatory mechanism of the IL-1 system.
A Self-Supervised Terrain Roughness Estimator for Off-Road Autonomous Driving (2012)

We present a machine learning approach for estimating the second derivative of a drivable surface, its roughness. Robot perception generally focuses on the first derivative, obstacle detection. However, the second derivative is also important due to its direct relation (with speed) to the shock the vehicle experiences. Knowing the second derivative allows a vehicle to slow down in advance of rough terrain. Estimating the second derivative is challenging due to uncertainty. For example, at range, laser readings may be so sparse that significant information about the surface is missing. Also, a high degree of precision is required in projecting laser readings. This precision may be unavailable due to latency or error in the pose estimation. We model these sources of error as a multivariate polynomial. Its coefficients are learned using the shock data as ground truth -- the accelerometers are used to train the lasers. The resulting classifier operates on individual laser readings from a road surface described by a 3D point cloud. The classifier identifies sections of road where the second derivative is likely to be large. Thus, the vehicle can slow down in advance, reducing the shock it experiences. The algorithm is an evolution of one we used in the 2005 DARPA Grand Challenge. We analyze it using data from that route.
Fibers from Regenerated Collagen (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFibers from Regenerated CollagenWarren C. Schimpf and Ferdinand RodriguezCite this: Ind. Eng. Chem. Prod. Res. Dev. 1977, 16, 1, 90–92Publication Date (Print):March 1, 1977Publication History Published online1 May 2002Published inissue 1 March 1977https://pubs.acs.org/doi/10.1021/i360061a018https://doi.org/10.1021/i360061a018research-articleACS PublicationsRequest reuse permissionsArticle Views152Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis delta-endotoxin. (1992)

Receptor binding studies were performed with 125I-labeled trypsin-activated insecticidal toxins, CryIA(a) and CryIA(c), from Bacillus thuringiensis on brush-border membrane vesicles (BBMV) prepared from Bombyx mori larval midgut. Bioassays were performed by gently force feeding B. mori with diluted toxins. CryIA(a) toxin (LD50; 0.002 micrograms) was 200 times more active against B. mori larvae than CryIA(c) toxin (LD50; 0.421 micrograms) and showed high-affinity saturable binding. The Kd and the binding site concentration for CryIA(a) toxin were 3.5 nM and 7.95 pmol/mg, respectively. CryIA(c) toxin (Kd, 50.35 nM; Bmax, 2.85 pmol/mg) did not demonstrate high-affinity binding to B. mori BBMV. Control experiments with CryIA(a) and CryIA(c) toxins revealed no binding to mouse small intestine BBMV and nonspecific binding to pig kidney BBMV. These data provide evidence that binding to a specific receptor on the membrane of midgut epithelial cells is an important determinant with respect to differences in insecticidal spectrum of insecticidal crystal proteins. To locate a B. mori receptor binding region on the CryIA(a) toxin, homologous and heterologous competition binding studies were performed with a set of mutant proteins which had previously been used to define the B. mori "specificity domain" on this toxin (Ge, A. Z., Shivarova, N. I., and Dean, D. H. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4037-4041). These mutant proteins have had regions of their genes reciprocally exchanged with the cryIA(c) gene. A B. mori receptor binding region on CryIA(a) toxin includes the amino-terminal portion of the hypervariable region, amino acids 332-450, which is identical to the previously described B. mori specificity determining region. These data provide direct evidence that delta-endotoxins contain a tract of amino acids that comprise a binding region and as a results determines the specificity of a toxin.
The cardiac effects of mitoxantrone: do the benefits in multiple sclerosis outweigh the risks? (2006)

Mitoxantrone, an immunosuppressant agent with potent anti-inflammatory activity, has been used to treat patients with multiple sclerosis (MS) who have worsening relapsing-remitting (RRMS) or secondary progressive multiple sclerosis (SPMS) despite prior therapy with interferons or glatiramer acetate. From previous experience of treating cancer with mitoxantrone, it was expected that cardiotoxic effects and occasional malignancy would develop in some patients treated with this agent. From the earliest trials, reduction of left ventricular ejection fraction (LVEF) was seen in 2-3% of cases, and in some this effect may persist and less commonly there can be congestive heart failure and even death. There are also occasional reports of leukaemia developing in MS patients treated with this agent. Mitoxantrone has been shown to reduce relapses, the number of new lesions visualised on magnetic resonance imaging and stop or reduce the progression of the disease in many patients treated. The drug has found a place in MS therapy because in this progressing group of MS patients who are failing on the disease-modifying therapies with interferons or glatiramer acetate, trials have shown that mitoxantrone may arrest or even improve many patients. Recognising the risks, mitoxantrone therapy is a reasonable option for MS patients with RRMS and SPMS who are progressing despite current disease-modifying therapy.
Isolation of the epidermal growth factor from the shrew submaxillary gland (1985)

The epidermal growth factor (EGF) from the submaxillary glands of the Chinese Shrew ( Suncus murinus ) is purified to apparent homogeneity by using a sequence of four chromatographic steps, viz. gel filtration on Sephacryl S‐200, affinity chromatography on immobilized Ni, hydrophobic interaction on phenyl‐Sepharose CL‐4B and reverse‐phase HPLC. An 800‐fold increase in specific activity and an overal recovery of 46% were achieved. The most effective step in its purification is the successful use of immobilized metal ion affinity chromatography (IMAC). This method was very selective, reproducible and requires a minimum of sample pre‐treatment prior to chromatography.
Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms (2013)

Key Points Recurrent U2AF1 mutations are associated with missplicing in the specific genes. U2AF1 mutant protein might identify the specific sequence signals at the splice sites.
A bacterial model system for chromosomal targeting (1991)

A system that permits efficient site-specific chromosomal targeting of foreign DNA on the Escherichia coli chromosome has been developed, using the FLP site-specific recombination system derived from the yeast 2µ plasmld. The system demonstrates the feasibility of using site-specific recombination for this purpose, and provides a means to gather information on parameters that may affect chromosomal targeting to guide efforts to establish similar systems in higher eukaryotes. In this model system, the efficiency of integration of foreign DNA is affected by the location of the target site in the chromosome, and the structure of the recombination sites.
Abstract 2943: Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient ovarian cancer (2015)

Abstract Ovarian cancer (OC) is initially chemoresponsive but the majority of patients relapse after first line platinum-, taxane-based chemotherapy. Recurrence has been shown to be associated with increased DNA damage response (DDR) mediated by poly-(ADP)-ribose polymerase 1/2 (PARP1/2), which can be therapeutically targeted by PARP inhibitors (PARPi). Although PARPi are indicated for platinum-responsive, BRCA-mutated OC, most OC patients have BRCA-proficient disease. Based on our previous studies supporting a role for DNA methylation in chemoresistant OC, mediated by the enzyme DNA methyltransferase 1 (DNMT1), and reports on a functional role for DNMT1 in DNA double strand break repair mediated by BRCA1/2, we hypothesized that combining DNMTi and PARPi will impair BRCA-mediated DDR, resulting in cytotoxicity in OC cells. A panel of OC cell lines, including A2780 (platinum sensitive, BRCA-wild type (wt)), A2780-cp and HeyC2 (platinum resistant, BRCA-wt) and Kuramochi (platinum resistant, BRCA2 mutant) were examined for cell growth using colony formation assays after treatment with DNMTi SGI-110 (5, 20, or 100nM) and PARPi talazoparib (1 or 10nM), alone or in combination. Combination treatment schemas consisted of: 1) “priming”: SGI-110 for three days, 24 hour recovery, then talazoparib treatment on Day 5 or 2) “co-administration”: talazoparib administration on day 1 and SGI-110 treatment on days 1-3. Colony formation was inhibited by talazoparib alone in all cell lines but in a dose-dependent manner. Decreased colony formation after SGI-110 alone (20 or 100 nM) was observed only in Kuramochi cells. Combination drug treatments resulted in significant reductions in colony formation. For example, regardless of BRCA and platinum sensitivity status, co-administration of SGI-110 and talazoparib reduced (P&amp;lt;0.05) cell survival, albeit%survival was dependent on drug dose and OC cell line. In general, priming with SGI-110 prior to treatment with talazoparib reduced (P&amp;lt;0.05) survival of A2780, Kuramochi and HeyC2 (majority of combinations tested); however, decreased (P&amp;lt;0.05) survival of A2780-cp was observed only after priming with 100 nM SGI-110. In summary, talazoparib combined with SGI-110 displayed effective cytotoxicity in OC cell lines harboring either wt- or mutant-BRCA, indicating that this DNMTi-PARPi drug combination impairs BRCA-mediated DDR and may represent an effective treatment regimen for OC. Citation Format: Nicholas Pulliam, Pietro Taverna, John Lyons, Kenneth P. Nephew. Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2943. doi:10.1158/1538-7445.AM2015-2943
Semi-Closed Gas Turbine/Combined Cycle With Water Recovery and Extensive Exhaust Gas Recirculation (1996)

This innovative gas turbine cycle can offer several advantages over conventional cycles from the point of view of environmental friendship. The basic idea of SCGT/CC (Semi-Closed Gas Turbine/Combined Cycle with water recovery) is to cool down the exhaust temperatures to allow full condensation of the water vapor, and recirculate a large part of the exhaust gases to the compressor. The condensed water can then be reinjected by means of a pump at compressor delivery. The working gas composition is thus close to that corresponding to stoichiometric combustion, which opens the possibility of applying techniques for CO2 recycling and general exhaust gas treatment. An increase in work output is connected to water injection, while a high level of efficiency is maintained as the compressor work is reduced and the cycle parameters are tuned for the exhaust of this turbine.
Helicenes from Diarylmaleimides (2014)

Perkin condensations of arylglyoxylic acids with arylacetic acids, followed by the addition of alkylamine, yield diarylmaleimides in a one-pot procedure. The arylglyoxylic acids are obtained by arene acylation with ClCOCO2Et and reduced with NaI and hypophosphorous acid to the arylacetic acids. With 2,7-di-tert-butyl-pyren-4-yl or chrysen-6-yl as the aryl, photocyclodehydrogenation of the diarylmaleimides yields substituted helicenes which can be reduced to stable anions. The helicenes combine bathochromically shifted absorption with hypsochromically shifted fluorescence with respect to their precursors.
Transmembrane Domains 4 and 7 of the M1Muscarinic Acetylcholine Receptor Are Critical for Ligand Binding and the Receptor Activation Switch (2001)

Activation of the muscarinic acetylcholine receptors requires agonist binding followed by a conformational change, but the ligand binding and conformation-switching residues have not been completely identified. Systematic alanine-scanning mutagenesis has been used to assess residues 142-164 in transmembrane helix 4 and 402-421 in transmembrane helix 7 of the M(1) muscarinic acetylcholine receptor. Several inward-facing amino acid side chains in the exofacial parts of transmembrane helices 4 and 7 contribute to acetylcholine binding. Alanine substitution of the aromatic residues in this group reduced signaling efficacy, suggesting that they may form part of a charge-stabilized aromatic cage, which triggers rotation and movement of the transmembrane helices. The mutation of adjacent residues modulated receptor activation, either reducing signaling or causing constitutive activation. In the buried endofacial section of transmembrane helix 7, alanine substitution mutants of the conserved NSXXNPXXY motif displayed strongly reduced signaling efficacy, despite having increased or unchanged acetylcholine affinity. These residues may have dual functions, forming intramolecular contacts that stabilize the receptor in the inactive ground state, but that are broken, allowing them to form new intramolecular bonds in the activated state. This conformational rearrangement is critical to produce a G protein binding site and may represent a key mechanism of receptor activation.
Occurrence and Distribution of Aphis glycines on Soybeans in Illinois in 2000 and Its Potential Control (2001)

During August of the 2000 growing season, Aphis glycines Matsumura, an aphid native to Asia, was found colonizing soybean plants in Illinois. Accepted for publication 1 February 2001. Published 5 February 2001.
An unusual isopentenyl diphosphate isomerase found in the mevalonate pathway gene cluster from Streptomyces sp. strain CL190 (2001)

A gene cluster encoding five enzymes of the mevalonate pathway had been cloned from Streptomyces sp. strain CL190. This gene cluster contained an additional ORF, orfD, encoding an unknown protein that was detected in some archaebacteria and some Gram-positive bacteria including Staphylococcus aureus. The recombinant product of orfD was purified as a soluble protein and characterized. The molecular mass of the enzyme was estimated to be 37 kDa by SDS-polyacrylamide gel electrophoresis and 155 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a tetramer. The purified enzyme contained flavin mononucleotide (FMN) with the amount per tetramer being 1.4 to 1.6 mol/mol. The enzyme catalyzed the isomerization of isopentenyl diphosphate (IPP) to produce dimethylallyl diphosphate (DMAPP) in the presence of both FMN and NADPH. The Escherichia coli plasmid expressing orfD could complement the disrupted IPP isomerase gene in E. coli. These results indicate that orfD encodes an unusual IPP isomerase showing no sequence similarity to those of IPP isomerases identified to date. Based on the difference in enzymatic properties, we classify the IPP isomerases into two types: Type 2 for FMN- and NAD(P)H-dependent enzymes, and type 1 for the others. In view of the critical role of this isomerase in S. aureus and of the different enzymatic properties of mammalian (type 1) and S. aureus (type 2) isomerases, this unusual enzyme is considered to be a suitable molecular target for the screening of antibacterial drugs specific to S. aureus.
A VL single-domain antibody library shows a high-propensity to yield non-aggregating binders (2012)

A synthetic human V(L) phage display library, created by the randomization of all complementarity-determining regions (CDRs) in a V(L) scaffold, was panned against three test antigens to determine the propensity of the library to yield non-aggregating binders. A total of 22 binders were isolated against the test antigens and the majority (20) were monomeric. Thus, human V(L) repertoires provide an efficient source of non-aggregating binders and represent an attractive alternative to human V(H) repertoires, which are notorious for containing high proportions of aggregating species. Moreover, the solubility of V(L)s, in contrast to V(H)s, appears much less CDR dependent.
Adaptive Modulation and Coding for Free-Space Optical Channels (2010)

Adaptive modulation and coding can provide robust and spectrally efficient transmission over terrestrial free-space optical channels. Three adaptive modulation schemes are considered in this paper: (i) variable-rate variable-power adaptation, (ii) channel inversion, and (iii) truncated channel inversion schemes. It is shown that a simple channel inversion scheme performs comparable to a variable-rate variable-power adaptation scheme in the weak turbulence regime but faces significant performance degradation in the strong turbulence regime. We further study adaptive coding based on large-girth quasi-cyclic low-density parity-check- (LDPC-) coded modulation. It is shown by simulation that deep fades of the order of 30 dB and above in the regime of strong turbulence can be tolerated with the proposed scheme. It is demonstrated that communication in the saturation regime is possible with the proposed adaptive LDPC-coded modulation. We also determine the spectral efficiencies for the proposed adaptive modulation and adaptive coding schemes.