gebhart/patrepeval huggingface dataset:
General Strategy to Humanize a Camelid Single-domain Antibody and Identification of a Universal Humanized Nanobody Scaffold (2008)

Nanobodies, single-domain antigen-binding fragments of camelid-specific heavy-chain only antibodies offer special advantages in therapy over classic antibody fragments because of their smaller size, robustness, and preference to target unique epitopes. A Nanobody differs from a human heavy chain variable domain in about ten amino acids spread all over its surface, four hallmark Nanobody-specific amino acids in the framework-2 region (positions 42, 49, 50, and 52), and a longer third antigen-binding loop (H3) folding over this area. For therapeutic applications the camelid-specific amino acid sequences in the framework have to be mutated to their human heavy chain variable domain equivalent, i.e. humanized. We performed this humanization exercise with Nanobodies of the subfamily that represents close to 80% of all dromedary-derived Nanobodies and investigated the effects on antigen affinity, solubility, expression yield, and stability. It is demonstrated that the humanization of Nanobody-specific residues outside framework-2 are neutral to the Nanobody properties. Surprisingly, the Glu-49 --> Gly and Arg-50 --> Leu humanization of hallmark amino acids generates a single domain that is more stable though probably less soluble. The other framework-2 substitutions, Phe-42 --> Val and Gly/Ala-52 --> Trp, are detrimental for antigen affinity, due to a repositioning of the H3 loop as shown by their crystal structures. These insights were used to identify a soluble, stable, well expressed universal humanized Nanobody scaffold that allows grafts of antigen-binding loops from other Nanobodies with transfer of the antigen specificity and affinity.
Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder (2010)

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic diet.
The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells (2000)

Campath-1H, a humanized mAb undergoing clinical trials for treatment of leukemia, transplantation and autoimmune diseases, produces substantial lymphocyte depletion in vivo. The antibody binds to CD52, a highly glycosylated molecule attached to the membrane by a glycosylphosphatidylinositol anchor. Cross-linked Campath-1H is known to activate T cells in vitro. We have investigated the molecular basis for these effects by comparing the protein tyrosine phosphorylation signals induced by Campath-1H and the CD3 mAb OKT3 in primary T cells, and in CD45(+)TCR(+), CD45(-)TCR(+) and CD45(+)TCR(-) Jurkat subclones transfected with CD52. Our results show that Campath-1H triggers similar tyrosine phosphorylation events as OKT3 in both primary T cells and in the CD45(+)TCR(+) Jurkat sub-clone, albeit at quantitatively lower levels. However, no phospholipase C gamma 1 activation nor calcium signals were detected in response to CD52 ligation. The CD52-mediated induction of protein tyrosine phosphorylation was absolutely dependent upon the expression of both the TCR and the CD45 phosphotyrosine phosphatase at the cell surface. Cross-linking of Campath-1H was essential for signal transduction in all cells investigated. Fluorescence resonance energy transfer was used to demonstrate CD52 homo-association at the cell surface in Jurkat T cells in a TCR- and CD45-independent manner, and CD52-TCR association in CD45(+)TCR(+) cells. We propose a model to explain the activating effects of Campath-1H in which CD52 mAb cross-linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface, thereby inducing signals via the TCR by a process which depends on the CD45-mediated regulation of the p56(lck) and p59(fyn) tyrosine kinases.
Structure Determination and Synthesis of Fluoro Nissl Green: An RNA-Binding Fluorochrome (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure Determination and Synthesis of Fluoro Nissl Green: An RNA-Binding FluorochromeCraig A. Merlic, Soheil Motamed, and Bruce QuinnCite this: J. Org. Chem. 1995, 60, 11, 3365–3369Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/jo00116a020https://doi.org/10.1021/jo00116a020research-articleACS PublicationsRequest reuse permissionsArticle Views1505Altmetric-Citations75LEARN 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 optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Directional Discrete Cosine Transforms for Image Coding (2006)

Nearly all block-based transform schemes for image and video coding developed so far choose the 2-D discrete cosine transform (DCT) of a square block shape. With almost no exception, this conventional DCT is implemented separately through two 1-D transforms, one along the vertical direction and another along the horizontal direction. In this paper, we develop a new block-based DCT framework in which the first transform may follow a direction other than the vertical or horizontal one, while the second transform is arranged to be a horizontal one. Compared to the conventional DCT, the resulting directional DCT framework is able to provide a better coding performance for image blocks that contain directional edges - a popular scenario in many image signals. By choosing the best from all directional DCT's (including the conventional DCT as a special case) for each image block, we will demonstrate that the rate-distortion coding performance can be improved remarkably.
Mast cells (1997)

Mast cells are found resident in tissues throughout the body, particularly in association with structures such as blood vessels and nerves, and in proximity to surfaces that interface the external environment. Mast cells are bone marrow-derived and particularly depend upon stem cell factor for their survival. Mast cells express a variety of phenotypic features within tissues as determined by the local environment. Withdrawal of required growth factors results in mast cell apoptosis. Mast cells appear to be highly engineered cells with multiple critical biological functions. They may be activated by a number of stimuli that are both Fc epsilon RI dependent and Fc epsilon RI independent. Activation through various receptors leads to distinct signaling pathways. After activation, mast cells may immediately extrude granule-associated mediators and generate lipid-derived substances that induce immediate allergic inflammation. Mast cell activation may also be followed by the synthesis of chemokines and cytokines. Cytokine and chemokine secretion, which occurs hours later, may contribute to chronic inflammation. Biological functions of mast cells appear to include a role in innate immunity, involvement in host defense mechanisms against parasitic infestations, immunomodulation of the immune system, and tissue repair and angiogenesis.
ML estimation of a stochastic linear system with the EM algorithm and its application to speech recognition (1993)

A nontraditional approach to the problem of estimating the parameters of a stochastic linear system is presented. The method is based on the expectation-maximization algorithm and can be considered as the continuous analog of the Baum-Welch estimation algorithm for hidden Markov models. The algorithm is used for training the parameters of a dynamical system model that is proposed for better representing the spectral dynamics of speech for recognition. It is assumed that the observed feature vectors of a phone segment are the output of a stochastic linear dynamical system, and it is shown how the evolution of the dynamics as a function of the segment length can be modeled using alternative assumptions. A phoneme classification task using the TIMIT database demonstrates that the approach is the first effective use of an explicit model for statistical dependence between frames of speech.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reduction of aerobic acetate production by Escherichia coli (1997)

Acetate excretion by Escherichia coli during aerobic growth on glucose is a major obstacle to enhanced recombinant protein production. We report here that the fraction of carbon flux through the anaplerotic pathways is one of the factors influencing acetate excretion. Flux analysis of E. coli central metabolic pathways predicts that increasing the fraction of carbon flux through the phosphoenolpyruvate carboxylase (PPC) pathway and the glyoxylate bypass reduces acetate production. We tested this prediction by overexpressing PPC and deregulating the glyoxylate bypass by using a fadR strain. Results show that the acetate yield by the fadR strain with PPC overexpression is decreased more than fourfold compared to the control, while the biomass yield is relatively unaffected. Apparently, the fraction of carbon flux through the anaplerotic pathways is one of the factors that influence acetate excretion. These results confirm the prediction of our flux analysis and further suggest that E. coli is not fully optimized for efficient utilization of glucose.
Inhibitors of HCV NS5A: From Iminothiazolidinones to Symmetrical Stilbenes (2011)

The iminothiazolidinone BMS-858 (2) was identified as a specific inhibitor of HCV replication in a genotype 1b replicon assay via a high-throughput screening campaign. A more potent analogue, BMS-824 (18), was used in resistance mapping studies, which revealed that inhibitory activity was related to disrupting the function of the HCV nonstructural protein 5A. Despite the development of coherent and interpretable SAR, it was subsequently discovered that in DMSO 18 underwent an oxidation and structural rearrangement to afford the thiohydantoin 47, a compound with reduced HCV inhibitory activity. However, HPLC bioassay fractionation studies performed after incubation of 18 in assay media led to the identification of fractions containing a dimeric species 48 that exhibited potent antiviral activity. Excision of the key elements hypothesized to be responsible for antiviral activity based on SAR observations reduced 48 to a simplified, symmetrical, pharmacophore realized most effectively with the stilbene 55, a compound that demonstrated potent inhibition of HCV in a genotype 1b replicon with an EC50 = 86 pM.
Conservation of signal transduction mechanisms via the human Fc epsilon RI alpha after transfection into a rat mast cell line, RBL 2H3 (1992)

The high affinity receptor for IgE (Fc epsilon RI) is present on mast cells and basophils, and the aggregation of IgE-occupied receptors by Ag is responsible for the release of allergic mediators. The Fc epsilon RI is composed of at least three different subunits, alpha, beta, and gamma, with the alpha subunit binding IgE. The series of biochemical events linking receptor aggregation to the release of mediators has not been fully delineated. As a step towards understanding these processes, and for the development of functional cell lines, we have transfected the human Fc epsilon RI alpha subunit into the rat mast cell line RBL 2H3. These human Fc epsilon RI alpha-transfected cell lines have been characterized with respect to the association of the human alpha subunit with endogenous rat beta and gamma subunits and the ability of aggregated Fc epsilon RI alpha subunits to mediate a variety of biochemical events. The signal transduction events monitored include phosphoinositide hydrolysis, Ca2+ mobilization, tyrosine phosphorylation, histamine release, and arachidonic acid metabolism. In all cases, the events mediated by aggregating human Fc epsilon RI alpha subunits were indistinguishable from those produced via the rat Fc epsilon RI alpha. These results demonstrate that the human Fc epsilon RI alpha subunit can functionally substitute for the rat Fc epsilon RI alpha subunit during signal transduction. The availability of this cell line will provide a means of evaluating potential Fc epsilon RI antagonists.
Hydrodynamic Lubrication in Wavy Contacting Face Seals—A Two Dimensional Model (1981)

The role of circumferential surface waviness in contacting mechanical face seals is examined. First, a two dimensional model is developed. The model considers waviness amplitude, surface roughness, asperity contact, hydrodynamic and hydrostatic pressures, and fluid cavitation. Given waviness, roughness, number of waves, geometry, and sealed fluid, the model predicts the fraction of load supported by fluid pressure, the relative wear rate, friction coefficient, and leakage rate. A numerical method for solving this problem is presented. Using this model, the effects of waviness amplitude, roughness, number of waves, face width, and sealed pressure on seal performance are examined. Based on these results, certain conclusions are reached concerning the role of waviness in commercial face seals. Finally, using the model, it is shown how waviness can be applied to advantage to reduce seal friction and wear rates.
Autologous Bone Marrow Transplantation in Patients with Acute Nonlymphocytic Leukemia, Using ex Vivo Marrow Treatment with 4-Hydroperoxycyclophosphamide (1986)

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.
Autoantibody responses in the cerebrospinal fluid of guinea pigs with chronic relapsing experimental allergic encephalomyelitis (1988)

We report the use of the ELISA technique to measure IgG specific for whole cord, myelin, myelin basic protein and Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) of Strain 13 guinea pigs in different stages of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Specific antibody levels to all 4 antigen preparations were related to the severity of clinical signs, with the highest levels of IgG in the CSF of guinea pigs in relapse or in stable chronic disease. Total IgG levels in the CSF, though elevated throughout the course of CR-EAE, did not show any association with the category of disease. Control animals inoculated with complete Freund's adjuvant (CFA) alone showed CSF IgG levels specific for M. tuberculosis that were not significantly different from those in animals with chronic EAE, indicating that CFA may itself induce a late-acting increase in blood-brain barrier permeability.
Deep sub-micron stud-via technology for superconductor VLSI circuits (2014)

A fabrication process has been developed for fully planarized Nb-based superconducting inter-layer connections (vias) with minimum size down to 250 nm for superconductor very large scale integrated (VLSI) circuits with 8 and 10 superconducting layers on 200-mm wafers.Instead of single Nb wiring layers, it utilizes Nb/Al/Nb trilayers for each wiring layer to form Nb pillars (studs) providing vertical connections between the wires etched in the bottom layer of the trilayer and the next wiring layer that is also deposited as a Nb/Al/Nb trilayer.This technology makes possible a dramatic increase in the density of superconducting digital circuits by reducing the area of interconnects with respect to presently utilized etched contact holes between superconducting layers and by enabling the use of stacked vias.Results on the fabrication and size dependence of electric properties of Nb studs with dimensions near the resolution limit of 248-nm photolithography are presented.Superconducting critical current density in the fabricated stud-vias is about 0.3 A/µm 2 and approaches the depairing current density of Nb films.
Evidence for the nitration of γ-tocopherol in vivo: 5-nitro-γ-tocopherol is elevated in the plasma of subjects with coronary heart disease (2002)

This study investigated the hypothesis that nitration of gamma-tocopherol may be an important mechanism for the detoxification of reactive nitrogen oxide species in vivo. Using liquid chromatography-tandem MS we have shown that gamma-tocopherol can be nitrated in vivo to form 5-nitro-gamma-tocopherol and that concentrations of this compound are elevated in the plasma of subjects with coronary heart disease. In addition, we demonstrate in carotid-artery atherosclerotic plaque that nitration of gamma-tocopherol is also evident at levels similar to that seen in the plasma of subjects with coronary heart disease.
A kinetic description of antifreeze glycoprotein activity. (1986)

The antifreeze glycoproteins (AFGP) of polar fish have the ability to depress the freezing temperature of water approximately 500 times the amount expected based on the number of AFGP molecules in solution; yet AFGP solutions have a purely colligative melting point depression. The difference of solution melting and freezing temperatures is the antifreeze activity of AFGP. One characteristic of AFGP activity that requires further examination is the effect of concentration on antifreeze activity, especially whether the activity saturates at high concentrations or the measured activity increases ad infinitum. This study first surveys the activity of the various antifreeze components from both Pagothenia borchgrevinki and the Arg-containing antifreeze glycoprotein from Eleginus gracilis (EgAF). It was found that all AFGP components examined have a plateau in activity at high concentration, but the actual value of the plateau activity differs between the different length AFGP components and between AFGP and EgAF. While the low molecular weight components of both AFGP and EgAF lose activity at deep supercooling, at high concentration activity is restored. The activity data is then shown to fit a reversible kinetic model of AFGP activity, and the coefficients obtained are used to compare the activity differences between AFGP components and between AFGP and EgAF. The model is also shown to describe the activity of the antifreeze protein of the fish Pseudopleuronectes americanus and the thermal hysteresis protein of the insect, Tenebrio molitor.
Adaptive pulse compression for transform-limited 15-fs high-energy pulse generation (2000)

We demonstrate the use of a deformable-mirror pulse shaper, combined with an evolutionary optimization algorithm, to correct high-order residual phase aberrations in a 1-mJ, 1-kHz, 15-fs laser amplifier. Frequency-resolved optical gating measurements reveal that the output pulse duration of 15.2 fs is within our measurement error of the theoretical transform limit. This technique significantly reduces the pulse duration and the temporal prepulse energy of the pulse while increasing the peak intensity by 26%. It is demonstrated, for what is believed to be the first time, that the problem of pedestals in laser amplifiers can be addressed by spectral-domain correction.