gebhart/patrepeval huggingface dataset:
Solution Structure of a Novel Disintegrin, Salmosin, from<i>Agkistrondon halys</i>Venom<sup>,</sup> (2003)

Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. A new disintegrin, salmosin, isolated from the venom of the Korean snake Agkistrodon halys brevicaudus, has been characterized by mass spectrometry and NMR spectroscopy, and its in vitro biological activity has been assessed. The IC(50) value of the purified salmosin was determined to be 2.2 nM in an assay for the inhibition of glycoprotein IIb-IIIa/fibrinogen interaction. Salmosin also inhibited the bovine capillary endothelial cell proliferation induced by bFGF in a dose-dependent manner. The NMR solution structures were well converged with a root-mean-square deviation of 0.76 A for backbone atoms among the 20 lowest energy structures, except for the arginylglycylaspartic acid (RGD) loop. The structure revealed that the conserved RGD motif with an unusual finger shape is distal from the rigid core of the C-terminal domain. Furthermore, even though the RGD motif did not interact with the hydrophobic core of the protein, it was stabilized by a network of molecular contacts through a small antiparallel beta-sheet comprising residues of Ile46-Ala50 and Asp54-Tyr58. Last, the electrostatic charge distribution on the surface of salmosin differs dramatically from that of other disintegrin proteins in that there is a cluster of negatively charged residues in close proximity to the RGD loop.
Deep Neural Network-Based Phase-Recovery and Auto-Focusing Extend the Depth-of-Field in Digital Holography (2018)

A deep convolutional neural network simultaneously performs auto-focusing and phase-recovery using a single hologram intensity, and achieves >25-fold and >30-fold increase in depth-of-field and reconstruction speed of digital holographic imaging, respectively.
New fabrication approach to fine multifilamentary Nb/sub 3/(Al,Ge) superconductors using an intermediate rapid quenching technique (2003)

Drawability of Nb/Al-Ge composite has been improved by a reel-to-reel intermediate rapid quenching technique. The intermediate rapid quenching is performed at an early stage of the fabrication process of multifilamentary wires to convert the coarse Al-Ge core structure into very fine microstructure. Depending on the heat treatment condition, an Al-Ge nano-structure can be obtained in the core. The hardness of the Al-Ge core is balanced with that of the Nb matrix. This technique thus allows construction of multifilamentary structure easily. In addition, it also allows an easy increase of Ge content to 25 at% in the Al-Ge core and reduction of the nonsuperconducting matrix ratio to less than 1. By a diffusion reaction heat treatment at 1400/spl deg/C for the developed multifilamentary Nb/Al-Ge wire, non-Cu J/sub c/=75 A/mm/sup 2/ at 21 T, 4.2 K has been obtained so far.
Method and Circuit for In-Situ Health Monitoring of Solar Cells in Space (2010)

This innovation represents a method and circuit realization of a system designed to make in-situ measurements of test solar-cell operational parameters on orbit using readily available high-temperature and high-ionizing-radiation- tolerant electronic components. This innovation enables on-orbit in-situ solar-array health monitoring and is in response to a need recognized by the U.S. Air Force for future solar arrays for unmanned spacecraft. This system can also be constructed out of commercial-grade electronics and can be embedded into terrestrial solar power system as a diagnostics instrument. This innovation represents a novel approach to I-V curve measurement that is radiation and temperature hard, consumes very few system resources, is economical, and utilizes commercially available components. The circuit will also operate at temperatures as low as 55 C and up to +225 C, allowing it to reside close to the array in direct sunlight. It uses a swept mode transistor functioning as a resistive load while utilizing the solar cells themselves as the biasing device, so the size of the instrument is small and there is no danger of over-driving the cells. Further, this innovation utilizes nearly universal spacecraft bus resources and therefore can be readily adapted to any spacecraft bus allowing for ease of retrofit, or designed into new systems without requiring the addition of infrastructure. One unique characteristic of this innovation is that it effects the measurement of I-V curves without the use of large resistor arrays or active current sources normally used to characterize cells. A single transistor is used as a variable resistive load across the cell. This multi-measurement instrument was constructed using operational amplifiers, analog switches, voltage regulators, MOSFETs, resistors, and capacitors. The operational amplifiers, analog switches, and voltage regulators are silicon-on-insulator (SOI) technology known for its hardness to the effects of ionizing radiation. The SOI components used can tolerate temperatures up to 225 C, which gives plenty of thermal headroom allowing this circuit to perhaps reside in the solar cell panel itself where temperatures can reach over 100 C.
Synthesis, Characterization, and in vitro Testing of a Bacteria‐Targeted MR Contrast Agent (2012)

A bacteria-targeted MR contrast agent, Zn-<b>1</b>, consisting of two Zn-dipicolylamine (Zn-dpa) groups conjugated to a Gd<sup>III</sup> chelate has been synthesized and characterized. In vitro studies with <i>S. aureus</i> and <i>E. coli</i> show that Zn-<b>1</b> exhibits a significant improvement in bacteria labeling efficiency vs. control. Studies with a structural analogue, Zn-<b>2</b>, indicate that removal of one Zn-dpa moiety dramatically reduces the agent's affinity for bacteria. The ability of Zn-<b>1</b> to significantly reduce the <i>T</i><sub>1</sub> of labeled vs. unlabeled bacteria, resulting in enhanced MR image contrast, demonstrates its potential for visualizing bacterial infections in vivo.
Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody (1991)

A human monoclonal antibody designated 15e is reactive with the envelope glycoprotein (gp120) of multiple isolates of human immunodeficiency virus type 1 (HIV-1). Antibody 15e also neutralizes HIV-1 with broad specificity and blocks gp120 binding to CD4. Characterization of the 15e epitope shows that it is conformation dependent and is distinct from previously recognized functional domains of gp120, suggesting that this epitope represents a novel site important for HIV-1 neutralization and CD4 binding. These findings have implications for the development of a vaccine for AIDS.
P2‐105: IDENTIFYING MARKERS OF MICROGLIA ACTIVATION IN CSF FROM PATIENTS WITH ALZHEIMER'S DISEASE USING A NOVEL MASS SPECTROMETRY APPROACH (2014)

We hypothesise that an early event in neurodegenerative pathology involves activation of microglial cells that will secrete distinct proteins into the brain and thence into CSF and ultimately plasma. The challenge is how to find these molecules in a readily available biofluid. Traditional unbiased proteomic approaches have struggled to detect low abundance markers due to the high dynamic range of plasma and CSF proteins, and the predominance of plasma albumin and other hyper-abundant proteins. To improve biomarker discovery in peripheral fluids, we developed TMTcalibrator Plus; a novel MS workflow. Here the use of isobaric Tandem Mass Tags (TMT) allows tissue samples to be labelled and mixed into equivalently labelled samples of peripheral biofluids at a concentration sufficient to ensure the vast majority of MS/MS acquisitions are made on tissue-derived peptides In the present study we initially compared a non-activated and activated microglial cell-line in culture and then subsequently used these activated cell samples as surrogates for Alzheimer's disease (AD) brain tissue. Using isobaric TMTs, peptide preparations from activated microglial cells were labelled to form a standard reference peptide mix. Similarly, CSF samples from three patients with clinically and biomarker defined AD, and three non-AD controls were digested and labelled with the remaining members of the isobaric mass tag set. All labelled digests were pooled together to form the TMTcalibrator Plus analytical sample. The combined samples were analysed by LC-MS/MS on an LTQ-Orbitrap Velos mass spectrometer (Thermo Scientific, USA). By comparing the levels of each TMT reporter ion generated upon fragmentation, we can determine which activated microglial proteins are also found in CSF and which, if any, are differentially expressed in AD compared to individuals with normal cognitive function. From our preliminary study, we have identified 33 peptides, representing 30 proteins originating from microglia, that appear to be up-regulated at least 2-fold in the CSF of AD patients compared to controls. Application of our pioneering TMTcalibrator Plus MS approach has allowed the identification of multiple up-regulated peptides from microglia proteins in the CSF of AD patients. These proteins warrant further investigation as they may represent early events in the disease process.
Donor-Acceptor Complexes in Copolymerization. XXXVII. Alternating Diene-Dienophile Copolymers. 5. Formation of Conjugated Diene-Maleic Anhydride Copolymers through Retrograde Dissociation of Furan-Maleic Anhydride Diels-Alder Adduct (1972)

Abstract The equimolar, alternating copolymer of isoprene, as well as other conjugated dienes, and maleic anhydride is formed by the radical catalyzed reaction of the conjugated diene with maleic anhydride in the presence of furan as well as with the furan-maleic anhydride Diels-Alder adduct. The retrograde dissociation of the cyclic adduct above 60°C regenerates furan and maleic anhydride which in the presence of isoprene forms the isoprene-maleic anhydride ground state complex. The latter yields the corresponding cyclic adduct in the absence of a radical catalyst and undergoes excitation and homopolymerization in the presence of a catalyst.
Structural and Functional Analysis of SFT, a Stimulator of Fe Transport (1998)

Previous studies demonstrated that SFT (Stimulator of Fe Transport) facilitates both transferrin and nontransferrin-bound iron uptake in HeLa cells (Yu, J., and Wessling-Resnick, M. (1998) J. Biol. Chem. 273, 6909-6915). To further characterize the structure and function of SFT, we studied this human factor in rodent BHK cells. Kyte-Doolittle analysis suggests that SFT has six transmembrane-spanning segments. This transport protein also displays an REXXE motif resembling domains involved in iron binding by ferritin and in iron uptake mediated by the yeast transporter Ftr1. Using N- and C-terminal epitope tags, we have identified that modification of either protein terminus does not interfere with SFT function in nontransferrin-bound iron uptake. The N- and C-terminal domains are intracellularly disposed since antibodies against these epitopes fail to recognize expressed proteins unless BHK cells are solubilized with detergents. To define the topology of two large extramembranous loop domains, anti-peptide antibodies were employed; anti-loop 4 antibodies show no immunoreactivity unless cells are permeabilized but anti-loop 5 antibodies recognize and bind surface SFT. Thus, loop 4 must be intracellular while loop 5 is extracellular. These topological studies situate the putative iron-binding REXXE domain on the cytosolic face of the plasma membrane. However, 55Fe-binding studies reveal that the ability of SFT to bind and mediate transport of extracellular iron is defective in mutants with Glu --> Ala conversions in this motif. Curiously, we also find that depletion of intracellular iron by desferrioxamine impairs SFT transport and iron-binding functions. These observations lead to the speculation that the REXXE motif may play an important role in regulating SFT activity through interaction with intracellular iron and demonstrate that iron transport mediated by SFT is itself an iron-dependent process.
A phase 1 study of MSC-1, a humanized anti-LIF monoclonal antibody, in patients with advanced solid tumors. (2018)

TPS2602 Background: Leukemia Inhibitory Factor (LIF) is a pleiotropic cytokine involved in many physiological and pathological processes. LIF is highly expressed in a subset of tumors across multiple tumor types and shown to correlate with poor prognosis. LIF is hypothesized to contribute to tumor growth and progression by acting on multiple aspects of cancer biology, including immunosuppression of the tumor microenvironment (TME), and is a key regulator of cancer initiating cells (CICs), which are thought to underpin tumor growth, metastasis, and resistance to therapy. MSC-1, a first-in-class humanized IgG1 monoclonal antibody, is a potent and selective inhibitor of LIF. MSC-1 leads to robust STAT3 inhibition by disrupting the LIF signaling through the LIF receptor (LIFR). Blocking LIF with MSC-1 decreased tumor growth in multiple mouse tumor models and drove reprogramming of the TME through differentiation of immunosuppressive macrophages and modulation of several immune cell types. These findings form the basis of a robust therapeutic hypothesis, whereby MSC-1 treatment may lead to clinical activity in multiple cancer indications. Methods: The Phase 1 study of MSC-1 will enroll patients with advanced relapsed/refractory solid tumors. The study will employ an accelerated 3+3 escalation design to explore the safety, PK, immuno-regulatory activity and preliminary anti-tumor activity of MSC-1. Patients will receive treatment with MSC-1 intravenously once every three-weeks until confirmed disease progression or intolerable toxicity. Four tumor specific expansion cohorts will be initiated once dose and schedule are established from dose escalation and include NSCLC, ovarian cancer, pancreatic cancer and a basket of advanced solid tumors; enrollment will be restricted to patients with LIF-High expression in their tumors using a diagnostic selection assay. Response will be assessed every 6 weeks per RECIST v1.1.
MVA Vectors Expressing Conserved Influenza Proteins Protect Mice against Lethal Challenge with H5N1, H9N2 and H7N1 Viruses (2014)

MVA vectors expressing influenza NP protect mice against lethal challenge with H5N1, H7N1 and H9N2 viruses by a mechanism involving influenza-specific CD4(+) and CD8(+) T cell responses.
A novel synthesis of (+)-4-demethoxydaunomycinone (1990)

W. Cabri, S. De Bernardinis, F. Francalanci and S. Penco, J. Chem. Soc., Perkin Trans. 1, 1990, 428 DOI: 10.1039/P19900000428
Keynote Address: Blueprint of the Breast and Colorectal Cancer Genomes (2007)

KN-01 It is widely accepted that human cancer is a genetic disease caused by accumulation of mutations in oncogenes and tumor suppressor genes. These tumor-specific mutations provide clues to the cellular processes underlying tumorigenesis and have proven useful for diagnostic and therapeutic purposes. To date, however, only a small fraction of the genes has been analyzed and the number and type of alterations responsible for the development of common tumor types are unknown. The determination of the human genome sequence coupled with improvements in sequencing and bioinformatic approaches have now made it possible, in principle, to examine the cancer cell genome in a comprehensive and unbiased manner. We have begun a systematic study of the cancer genome through examination of gene families involved in signal transduction. These efforts have identified frequent activating mutations in a number of different kinases and phosphatases not previously linked to human cancer. For example, we have found genetic alterations in the PIK3CA gene encoding the p110 alpha phosphatidylinositol 3-kinase in ~30% of colon and breast cancers, providing a rational target for therapy in a large fraction of common malignancies. These studies have recently been extended to genome-wide analyses of the protein coding genes in breast and colorectal cancer. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.
A new method of measuring field distribution using NMR images (1985)

This paper analyzes several factors that degrade accuracy in field distributions measured using a method proposed by the authors. It is shown that phase errors resulting from a misadjusted pulse-sequence can be removed by using two sets of complex nuclear magnetic resonance (NMR) images. We also show that the distortion of a measured distribution, which can seriously affect the accuracy of the measurements in an inhomogeneous field, can be corrected, and the limitation and effectiveness of this correction are discussed. Noise transfer through the calculation of a field distribution is also analyzed. It is pointed out that the time difference, which causes phase shifts proportional to the field inhomogeneity, needs to be set at a value as large as possible, so as to obtain a maximum signal-to-noise ratio in a calculated distribution.
W-Sb-Te phase-change material: A candidate for the trade-off between programming speed and data retention (2012)

W-Sb-Te phase-change material has been proposed to improve the performance of phase-change memory (PCM). Crystallization temperature, crystalline resistance, and 10-year data retention of Sb2Te increase markedly by W doping. The Wx(Sb2Te)1−x films crystallize quickly into a stable hexagonal phase with W uniformly distributing in the crystal lattice, which ensures faster SET speed and better operation stability for the application in practical device. PCM device based on W0.07(Sb2Te)0.93 shows ultrafast SET operation (6 ns) and good endurance (1.8 × 105 cycles). W-Sb-Te material is a promising candidate for the trade-off between programming speed and data retention.
5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology (2017)

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclinical characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations. No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound's safety profile, identifies 1 as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.
A fast algorithm to cluster high dimensional basket data (2002)

Clustering is a data mining problem that has received significant attention by the database community. Data set size, dimensionality and sparsity have been identified as aspects that make clustering more difficult. The article introduces a fast algorithm to cluster large binary data sets where data points have high dimensionality and most of their coordinates are zero. This is the case with basket data transactions containing items, that can be represented as sparse binary vectors with very high dimensionality. An experimental section shows performance, advantages and limitations of the proposed approach.
<title>Visual masking in wavelet compression for JPEG-2000</title> (2000)

We describe a nonuniform quantization scheme for JPEG2000 that leverages the masking properties of the visual system, in which visibility to distortions declines as image energy increases. Derivatives of contrast transducer functions convey visual threshold changes due to local image content (i.e. the mask). For any frequency region, these functions have approximately the same shape, once the threshold and mask contrast axes are normalized to the frequency's threshold. We have developed two methods that can work together to take advantage of masking. One uses a nonlinearity interposed between the visual weighting and uniform quantization stage at the encoder. In the decoder, the inverse nonlinearity is applied before the inverse transform. The resulting image- adaptive behavior is achieved with only a small overhead (the masking table), and without adding image assessment computations. This approach, however, underestimates masking near zero crossings within a frequency band, so an additional technique pools coefficient energy in a small local neighborhood around each coefficient within a frequency band. It does this in a causal manner to avoid overhead. The first effect of these techniques is to improve the image quality as the image becomes more complex, and these techniques allow image quality increases in applications where using the visual system's frequency response provides little advantage. A key area of improvement is in low amplitude textures, in areas such as facial skin. The second effect relates to operational attributes, since for a given bitrate, the image quality is more robust against variations in image complexity.
Simple Approach for Selective Crystal Growth of Intermetallic Clathrates (2011)

We report on a new method for the synthesis of single-crystal inter-metallic clathrates. Alkali-metal is slowly removed from an alkali-silicide precursor by reaction of the vapor phase with spatially separated graphite, in a closed volume under uniaxial pressure, to form single-crystals of the binary intermetallic clathrates Na8Si46 and Na24Si136. Single-crystal structure refinement for Na8Si46 is reported for the first time. For both Na8Si46 and Na24Si136, full occupation of all Si framework sites as well as full Na occupancy in both polyhedra was observed. In addition to comprising a simple method for selective, phase-pure crystal growth of clathrates such as Na8Si46 or Na24Si136 which was previously challenging to achieve, this or similar approaches are applicable in the preparation of new compositions from different alkali-metal precursors.
Experimental Demonstration of Inserting Phase-Locked Lines into Kerr Combs using Electro-Optical Modulation (2016)

We experimentally demonstrate the flexibility of inserting one or two lines into Kerr combs. The effect of the spacing between two sidebands (260 KHz and 770 KHz) from EO modulation on the communication system is studied.
A New Small-Molecule Antagonist Inhibits Graves' Disease Antibody Activation of the TSH Receptor (2010)

NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera.
Off-axis interferometric phase microscopy with tripled imaging area (2014)

We present an interferometric approach, referred to as interferometry with tripled-imaging area (ITIA), for tripling the quantitative information that can be collected in a single camera exposure while using off-axis interferometric imaging. ITIA enables optical multiplexing of three off-axis interferograms onto a single camera sensor without changing the imaging-system characteristics, such as magnification and spatial resolution, or losing temporal resolution (no scanning is involved). This approach is useful for many applications in which interferometric and holographic imaging are used. Our experimental demonstrations include quantitative phase microscopy of a transparent U.S. Air Force 1951 test target, thin diatom shells, and live human cancer cells.