gebhart/patrepeval huggingface dataset:
Function and Structure of a Prokaryotic Formylglycine-generating Enzyme (2008)

Type I sulfatases require an unusual co- or post-translational modification for their activity in hydrolyzing sulfate esters. In eukaryotic sulfatases, an active site cysteine residue is oxidized to the aldehyde-containing C(alpha)-formylglycine residue by the formylglycine-generating enzyme (FGE). The machinery responsible for sulfatase activation is poorly understood in prokaryotes. Here we describe the identification of a prokaryotic FGE from Mycobacterium tuberculosis. In addition, we solved the crystal structure of the Streptomyces coelicolor FGE homolog to 2.1 A resolution. The prokaryotic homolog exhibits remarkable structural similarity to human FGE, including the position of catalytic cysteine residues. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. In addition, we generated a mutant M. tuberculosis strain lacking FGE. Although global sulfatase activity was reduced in the mutant, a significant amount of residual sulfatase activity suggests the presence of FGE-independent sulfatases in this organism.
Protein crystallography: a concise guide (2008)

The proteome remains a mysterious realm. Researchers have determined the structures of only a small fraction of the proteins encoded by the human genome. Crystallography continues to be the primary method used to determine the structures of the remaining unknown proteins. This imaging technique uses the diffraction of X-rays to determine a protein's three-dimensional molecular structure. Drawing on years of research and teaching experience, Eaton E. Lattman and Patrick J. Loll use clear examples and abundant illustrations to provide a concise and accessible primer on protein crystallography. Discussing the basics of diffraction, the behavior of two- and three-dimensional crystals, phase determination (including MIR and MAD phasing and molecular replacement), the Patterson function, and refinement, Lattman and Loll provide a complete overview of this important technique, illuminated by physical insights. The crisp writing style and simple illustrations will provide beginner crystallographers with a guide to the process of unraveling protein structure.
A case for virtual channel processors (2003)

Modern desktop and server computer systems use multiple processors: general purpose CPU(s), graphic processor (GPU), network processors (NP) on Network Interface Cards (NICs), RAID controllers, and signal processors on sound cards and modems. Some of these processors traditionally have been special purpose processors but there is a trend towards replacing some of these with embedded general purpose processors. At the same time main CPUs become more powerful; desktop CPUs start featuring Simultaneous Multi-Threading (SMT); and Symmetric Multi-Processing (SMP) systems are widely used in server systems. However, the structure of operating systems has not really changed to reflect these trends --- different types of processors evolve at different timescales (largely driven by market forces) requiring significant changes to operating systems kernels to reflect the appropriate tradeoffs.In this position paper we propose to re-vitalise the old idea of channel processors by encapsulating operating system I/O subsystems in Virtual Channel Processors (VCPs). VCPs perform I/O operations on behalf of an OS. They provide similar development, performance, and fault isolation as dedicated (embedded) I/O processors do while offering the flexibility to split functionality between the main processor(s) and dedicated processors without affecting the rest of the OS. If part of a VCP is executed on the main processor, we propose to make use of virtual machine technology and SMT/SMP features to isolate its performance from that of the rest of the system and to protect the system from faults within the VCP.
Short-Circuit Current Density Behavior of Dye-Sensitized Solar Cells (2005)

Short-circuit current densities ( J sc s) were measured on two kinds of dye-sensitized solar cells (DSCs). The dependences of J sc on the diffusion coefficient of I 3 - and the cell gap are discussed using relevant model equations for the DSC. In the lower diffusion coefficient region, the DSC operates under an I 3 - diffusion-limiting condition and, under this condition, narrowing the cell gap is a simple and effective way to increase the J sc . The J sc of a gel-type polymeric-electrolyte-based DSC with a cell gap of 20 µm is verified to be equal to that of a liquid electrolyte-based DSC.
Antibody‐based strategies for the detection of Luspatercept (ACE‐536) in human serum (2017)

Luspatercept (ACE-536, ACVR2B-Fc), a fusion protein consisting of the extracellular domain of ActRIIB receptor and the Fc-part of human immunoglobulin G1 (IgG1), is currently under clinical development (Phase III). It stimulates the formation of red blood cells and hence may be misused by athletes for doping purposes in the future. Several antibody-based strategies for the detection of Luspatercept and other ACVR2B-Fc fusion proteins in human serum were evaluated (ELISA; IEF-, SDS-, and SAR-PAGE followed by Western blotting; immunoprecipitation). Two methods led to useful results: a commercial "soluble" ACTR-IIB ELISA, which also detected Luspatercept and other ACVR2B-Fc's, but showed no cross-reactivity with Sotatercept/ACVR2A-Fc's. The ELISA might be applied as fast screening tool (100 μL serum; limit of detection (LOD) ca 15.6 ng/mL). The second method uses a polyclonal ACVR2B-antibody for immunoprecipitation followed by SAR-PAGE and Western blotting with a monoclonal detection antibody (50 μL serum; LOD ca 1.0 ng/mL). It can be used for initial as well as for confirmatory testing. Due to the high doses (mg/kg) and long serum half-life of Luspatercept, both strategies may be useful in anti-doping control in the future. Copyright © 2017 John Wiley & Sons, Ltd.
Nonisotopic probing, blotting, and sequencing (1995)

Labels, Labelling, Analytical Strategies and Applications. Nonradioactive Labelling Methods for Nucleic Acids. Detection of Alkaline Phosphatase Labels By Time-Resolved Fluorescence. Detection of Alkaline Phosphatase By Bioluminescence. Detection of DNA on Membranes with Alkaline Phosphatase Labelled Probes and Chemiluminescence Cspdr Substrate. Detection of Alkaline Phosphatase By Colorimetry. Detection of Alkaline Phosphatase By Chemiluminescence Using NADP, Ascorbate and Indoxyl Phosphates. Detection of Horseradish Peroxidase By Enhanced Chemiluminescence. Dtection of Horseradish Peroxidase By Colorimetry. Detection of Glucose 6-Phosphate Dehydrogenase By Bioluminescence. Detection of Xanthine Oxidase By Enhanced Chemiluminescence. Electrochemiluminescent Detection of PCR-Derived Nucleic Acids. Detection of Phosphors By Phosphorescence. Detection of Europium Cryptates By Fluorescence. Detection of Lanthanid Chelates By Time-Resolved Fluorescence. Detection of Lanthanide Chelates and Multiple Labelling Strategies Based on Time-Resolved Fluorescence. Detection of Acridinium Esters By Chemiluminescence. Detection of Energy Transfer and Fluorescence Quenching. DNA Sequencing By Nonisotopic Methods. Chemiluminescent DNA Sequencing with 1, 2-Dioxetanes.
Differential Patterns of Intracellular Metabolism of 2′,3′-Didehydro-2′,3′-dideoxythymidine and 3′-Azido-2′,3′-dideoxythymidine, Two Potent Anti-human Immunodeficiency Virus Compounds (1989)

3'-Azido-2',3'-dideoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) are potent and selective inhibitors of human immunodeficiency virus replication in MT-4 and ATH8 cells. They are also inhibitory to the replication of murine retroviruses, i.e. Moloney murine sarcoma virus-induced transformation of C3H cells. In MT-4 cells AZT is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monophosphate. D4T is phosphorylated in MT-4 cells to its 5'-monophosphate at a 300-600-fold lower extent than AZT. The phosphorylation of AZT in the thymidine kinase-deficient cell line (Raji/TK-) is severely depressed, while D4T phosphorylation is only slightly diminished in Raji/TK- as compared to Raji/0 cells. D4T has a 10-fold lower affinity for phosphorylation by crude MT-4 cell extracts than AZT (Km, 142 and 14 microM, respectively), and the Vmax for phosphorylation of D4T is only 5% that of AZT. D4T is phosphorylated by MT-4 cell extracts about 180-fold less efficiently than AZT (Vmax/Km, 0.06 for D4T, as compared to 11 for AZT), and this is consistent with the differences found in the amounts of phosphorylated products of D4T and AZT formed in intact MT-4 cells. The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus.
Interaction of fibrinogen with its platelet receptor. Differential effects of alpha and gamma chain fibrinogen peptides on the glycoprotein IIb-IIIa complex. (1988)

The platelet membrane glycoprotein IIb-IIIa complex (GPIIb-IIIa) recognizes peptides containing the amino acid sequence Arg-Gly-Asp, a sequence present at two locations in the alpha chain of fibrinogen. GPIIb-IIIa also interacts with peptides containing the carboxyl-terminal 10-15 residues of the fibrinogen gamma chain. We found that the alpha chain tetrapeptide, Arg-Gly-Asp-Ser (RGDS), and the gamma chain peptide, Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (LGGAKQAG-DV), each inhibited fibrinogen binding to ADP-stimulated platelets with Ki values of 15.6 +/- 2.7 and 46.2 +/- 8.2 microM, respectively. Furthermore, the inhibitory effect of the peptides was additive, indicating that they interact with GPIIb-IIIa in a mutually exclusive manner. Mutually exclusive binding suggests that either the alpha and gamma chain peptides bind to identical or overlapping sites on the GPIIb-IIIa complex or that one peptide induces a change in the complex that excludes the other. To differentiate between these possibilities, we compared the ability of RGDS and LGGAKQAGDV to inhibit the binding of fibrinogen and two GPIIb-IIIa complex-specific monoclonal antibodies, A2A9 and PAC-1, to ADP-stimulated platelets. A2A9 and PAC-1 appear to bind to different sites on GPIIb-IIIa because A2A9 binds to both stimulated and unstimulated platelets while PAC-1 only binds to stimulated platelets. RGDS specifically inhibited fibrinogen and PAC-1 binding with nearly identical Ki values of 15.6 +/- 2.7 and 20.2 +/- 3.5 microM, respectively. In contrast, LGGAKQAGDV had a differential effect on fibrinogen and PAC-1 binding, inhibiting PAC-1 binding with a Ki of 116.1 +/- 12.9 microM and fibrinogen binding with a Ki of 46.2 +/- 8.2 microM (p less than 0.005). Furthermore, while RGDS had no effect on the binding of the monoclonal antibody A2A9, LGGAKQAGDV was a partial inhibitor of A2A9 binding to activated platelets. These results suggest that the bindings sites for RGDS and LGGAKQAGDV are spatially distinct. They also suggest that ligand-induced changes in GPIIb-IIIa conformation are likely to be responsible for the mutually exclusive nature of alpha and gamma chain peptide binding.
Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke (2016)

We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.
An Extension of the String-to-String Correction Problem (1975)

The string-to-string correction problem asks for a sequence S of "edit operations" of minimal cost such that ~(A) = B, for given strings A and B. The edit operations previously investigated allow changing one symbol of a string into another single symbol, deleting one symbol from a string, or inserting a single symbol into a string. This paper extends the set of allowable edit operations to include the operation of interchanging the positions of two adjacent characters Under certain restrictions on edit-operation costs, it is shown that the extended problem can still be solved in time proportional to the product of the lengths of the given strings.
The Advisors: Oppenheimer, Teller, and the Superbomb (1977)

First Page
Circulating Tumor Cells: A Novel Prognostic Factor for Newly Diagnosed Metastatic Breast Cancer (2005)

Detection of CTCs before initiation of first-line therapy in patients with MBC is highly predictive of PFS and OS. This technology can aid in appropriate patient stratification and design of tailored treatments.
Is there a role for mast cells in psoriasis? (2008)

Mast cells have traditionally been considered as effector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential effectors in the development of skin inflammation. Besides promoting inflammation, mast cells may attempt in some circumstances to suppress the inflammation and epidermal growth but the regulation between suppressive and proinflammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inflammation where tryptase- and chymase-positive MC(TC) mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inflammation the role of mast cells in psoriasis is discussed in this review.
A 6.3 µW 20 bit Incremental Zoom-ADC with 6 ppm INL and 1 µV Offset (2013)

A 20-bit incremental ADC for battery-powered sensor applications is presented. It is based on an energy-efficient zoom ADC architecture, which employs a coarse 6-bit SAR conversion followed by a fine 15-bit ΔΣ conversion. To further improve its energy efficiency, the ADC employs integrators based on cascoded dynamic inverters for extra gain and PVT tolerance. Dynamic error correction techniques such as auto-zeroing, chopping and dynamic element matching are used to achieve both low offset and high linearity. Measurements show that the ADC achieves 20-bit resolution, 6 ppm INL and 1 μV offset in a conversion time of 40 ms, while drawing only 3.5 μA current from a 1.8 V supply. This corresponds to a state-of-the-art figure-of-merit (FoM) of 182.7 dB. The 0.35 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> chip was fabricated in a standard 0.16 μm CMOS process.
Radius of Gyration of Polymer Chains. II. Segment Density and Excluded Volume Effects (1962)

The segment density ρ(r) at a distance r from the center of mass is evaluated for chains constrained to have a large specified radius of gyration R. It is found that ρ(r)≅(N/2π2)[r2(2R2−r2)12]−1H(2R2−r2),where N is the number of segments and H( ) is the step function. It is argued that this conditional distribution takes better account of large excluded volume effects than a simple scaling of the random flight ρ(r).
Cellular Composition of the Nipple Aspirate Specimen of Breast Fluid: II. Abnormal Findings (1975)

Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions.
Ceramic‐reinforced polymers and polymer‐modified ceramics (1996)

Abstract The composites discussed in this review are prepared using techniques similar to those used in the new sol‐gel approach to ceramics. Organometallis such as silicates, titanates, and aluminates are hydrolyzed in the presence of polymer chains (for example polysiloxanes and polyimides) that typically contain hydroxyl or amino groups. The functional groups are used to bond the polymer chains onto the silica, titania, or alumina being formed in the hydrolysis, thus forming organic‐inorganic composites. When the polymer chains are present in excess, they constitute the continuous phase, with the ceramic‐type material appearing as reinforcing particles. When present in smaller amounts, the polymer is dispersed in the continuous ceramic phase, to give a polymer‐modified ceramic. Under some conditions, bicontinuous systems are obtained. The composites thus prepared are characterized by electron microscopy, X ray, and neutron scattering intensities, density determinations, and stress‐strain and impact‐strength measurements.
Characterization of Fas (Apo-1, CD95)-Fas Ligand Interaction (1997)

The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). When human soluble FasL (sFasL, containing the extracellular portion) was expressed in human embryo kidney 293 cells, the three N-linked glycans of each FasL monomer were found to be essential for efficient secretion. Based on the structure of the closely related lymphotoxin alpha-tumor necrosis factor receptor I complex, a molecular model of the FasL homotrimer bound to three Fas molecules was generated using knowledge-based protein modeling methods. Point mutations of amino acid residues predicted to affect the receptor-ligand interaction were introduced at three sites. The F275L mutant, mimicking the loss of function murine gld mutation, exhibited a high propensity for aggregation and was unable to bind to Fas. Mutants P206R, P206D, and P206F displayed reduced cytotoxicity toward Fas-positive cells with a concomitant decrease in the binding affinity for the recombinant Fas-immunoglobulin Fc fusion proteins. Although the cytotoxic activity of mutant Y218D was unaltered, mutant Y218R was inactive, correlating with the prediction that Tyr-218 of FasL interacts with a cluster of three basic amino acid side chains of Fas. Interestingly, mutant Y218F could induce apoptosis in murine, but not human cells.
Stochastic language generation for spoken dialogue systems (2000)

The two current approaches to language generation, template-based and rule-based (linguistic) NLG, have limitations when applied to spoken dialogue systems, in part because they were developed for text generation. In this paper, we propose a new corpus-based approach to natural language generation, specifically designed for spoken dialogue systems.
Haptic based walking stick for visually impaired people (2013)

This paper proposes a new product concept of an electronic travelling aid with haptic perception for the visually impaired people. The device is much similar to the conventional white cane in appearance and it is fabricated using ultrasonic sensors, a vibrator motor scheme, a controller and a power unit inside the walking stick. The sensor system comprises of three ultrasonic sensors to acquire obstacle distance measurements and the user can interpret the distance information as a tactile sensation. The sonar sensors are fired with a sequential firing mechanism to avoid crosstalk. Distance is felt by the user in terms of the vibration intensity change. This device was tested with blind school students and results are presented.
Perspectives on antisense therapy for the prevention of restenosis. (2001)

One of the potential clinical applications of antisense therapy is the prevention or treatment of restenosis following coronary interventions. Inhibition of several cellular proto-oncogenes have been shown to inhibit smooth muscle cell proliferation in vitro and to reduce neointimal thickening in vivo. The clinical applicability of antisense technology, however, remains limited due to a relative lack of specificity, slow uptake across the cell membrane and rapid intracellular degradation of the oligonucleotide. The one study in humans with c-myc antisense yielded a negative result with respect to restenosis after stent implantation. Recent studies have introduced phosphorothioate morpholino oligomers (PMO), which represent an unusual DNA chemistry with a six-membered morpholino ring instead of a deoxyribose sugar. In addition, the charged phosphodiester internucleotide linkage is replaced by an uncharged phosphorothioate. The PMOs are resistant to serum nucleases found in serum and exhibit a high degree of specificity and efficacy in both in vitro and cell-free translation studies. In vivo studies in four different animal models of restenosis demonstrated significant reduction of myointimal response. The combination of enhanced efficacy and greater specificity introduced by the PMO chemistry led us to re-examine the potential efficacy of a neutrally charged c-myc antisense approach for the prevention of restenosis. Clinical studies are underway to investigate safety and efficacy of local delivery of this latest generation of antisense to reduce restenosis after coronary stenting.