gebhart/patrepeval huggingface dataset:
Characterization of engineered anti-p185HER-2 (scFv-CH3)2 antibody fragments (minibodies) for tumor targeting (2004)

An engineered antibody fragment (minibody; scFv-C(H)3gamma(1) dimer, M(r) 80 000) specific for carcinoembryonic antigen (CEA) has previously demonstrated excellent tumor targeting coupled with rapid clearance in vivo. In this study, variable (V) genes from the anti- p185(HER-2) 10H8 antibody were similarly assembled and expressed. Four constructs were made: first, the V genes were assembled in both orientations (V(L)-linker-V(H) and V(H)-linker-V(L)) as single chain Fvs (scFvs). Then each scFv was fused to the human IgG1 C(H)3 domain, either by a two amino acid linker (ValGlu) that resulted in a non-covalent, hingeless minibody, or by IgG1 hinge and a GlySer linker peptide to produce a covalent, hinge-minibody. The constructs, expressed in NS0 mouse myeloma cells at levels of 20-60 mg/l, demonstrated binding to the human p185(HER-2) overexpressing breast cancer cell line, MCF7/HER2. Binding affinities (K(D) approximately 2-4 nM) were equivalent to that for the parental 10H8 mAb (K(D) approximately 1.6 nM). Radioiodinated 10H8 hinge-minibody was evaluated in athymic mice, bearing MCF7/HER2 xenografts. Maximum tumor uptake was 5.6 (+/-1.65)% injected dose/g (ID/g) at 12 h, which was lower than that of the anti-CEA minibody, whereas the blood clearance (beta-phase, 5.62 h) was similar. Thus, minibodies with different specificities display similar pharmacokinetics, while tumor uptake may vary depending on the antigen-antibody system.
Sortase A as a tool for high‐yield histatin cyclization (2011)

Cyclic peptides are highly valued tools in biomedical research. In many cases, they show higher receptor affinity, enhanced biological activity, and improved serum stability. Technical difficulties in producing cyclic peptides, especially larger ones, in appreciable yields have precluded a prolific use in biomedical research. Here, we describe a novel and efficient cyclization method that uses the peptidyl-transferase activity of the Staphylococcus aureus enzyme sortase A to cyclize linear synthetic precursor peptides. As a model, we used histatin 1, a 38-mer salivary peptide with motogenic activity. Chemical cyclization of histatin 1 resulted in ≤ 3% yields, whereas sortase-mediated cyclization provided a yield of >90%. The sortase-cyclized peptide displayed a maximum wound closure activity at 10 nM, whereas the linear peptide displayed maximal activity at 10 μM. Circular dichroism and NMR spectroscopic analysis of the linear and cyclic peptide in solution showed no evidence for conformational changes, suggesting that structural differences due to cyclization only became manifest when these peptides were located in the binding domain of the receptor. The sortase-based cyclization technology provides a general method for easy and efficient manufacturing of large cyclic peptides.
Dysgraphia in a Patient with Bilateral Opercular Syndrome. (1998)

周産期障害で生じた両側弁蓋部障害を呈する小児の文字表出障害について報告した.4年間の言語訓練の中で, 読字や読解力の向上は良好なのに書字能力が劣るという解離が認められた.書字の誤りを分析した結果, 時間的な要因によって強まる語音認知障害と, 音韻の再構成障害が考えられ, 脳の病巣との関連が示唆された.
Highly Immunostimulatory CpG-Free Oligodeoxynucleotides for Activation of Human Leukocytes (2002)

Synthetic oligodeoxynucleotides (ODNs) bearing CpG dinucleotides can mimic the immunostimulatory effects of bacterial DNA in vertebrates. Besides the known CpG motifs, no other sequence motif has been shown to have independent immunostimulatory effects. Several past investigators have demonstrated that the nucleotide content or the phosphorothioate (PS) backbone may have effects independently of the sequence. However, the effect of both nucleotide content and PS backbone to stimulate human leukocytes is not well understood. We investigated the immunostimulatory activity of 34 PS-ODNs with different nucleotide contents, lengths, and methylation status on human leukocytes. The thymidine content showed strong CpG-independent contribution to immunostimulation. In contrast, ODNs rich in other nucleotides (guanosine, cytosine, or adenosine) induced no or much lower levels of immunostimulation. The observed effects were highly dependent on the PS backbone chemistry. In addition to the base content and the backbone chemistry, the length of the PS-ODN was directly related to the magnitude of its stimulatory effects, especially on B cells. In addition, methylation of CpG dinucleotides did not always cause an abrogation of the immunostimulation. Immunostimulatory effects could be observed with methylated CpG ODNs, specifically as the ODN length was increased from 18 to 24 or more nucleotides (nt). In contrast, PS-ODNs with inverted CpG dinucleotides showed some but only weak immunostimulation. Our results demonstrate that non-CpG ODNs rich in thymidine or ODNs with methylated CpG motifs have length-dependent immunostimulatory effects. Such ODNs can induce effects similar to those seen with CpG ODNs but are much less efficient in stimulating human immune cells.
Linear amplification technique for digital mobile communications (2003)

The author proposes a novel predistortion linearizer which can meet the power-amplification requirements of digital mobile radio systems with high power efficiency and low out-of-band emission. This method can be used for narrowband mobile radio systems. It has been shown that the linearizer can achieve low-out-of-band emission under frequent changes of the amplifier nonlinearity. It is indicated that the hardware volume and the power consumption can be reduced sufficiently to make this predistortion linearizer applicable to mobile station transmitters. Nearly -60dB out-of-band emission and 33% power efficiency were obtained, which is comparable to corresponding results for a class C amplifier.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A compliant Corethane/Dacron composite vascular prosthesis. Comparison with 4-mm ePTFE grafts in a canine model. (1994)

We have developed a composite vascular prosthesis with the inner blood interfacing layer made of a porous elastomeric membrane of spun Corethane fibers (10-15 microns in diameter, pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp knitted Dacron sheath. Forty-eight Corethane/Dacron composite (CDC) vascular grafts, 4 mm in diameter and 5 cm in length, and 48 expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar size were implanted bilaterally as end to end interposition grafts on opposite sides in the carotid and femoral arteries in dogs on low dose (162 mg/day) aspirin. Patency at 3 months was 37/48 (77%) for the ePTFE grafts and 44/48 (91.7%) for the CDC grafts. Fisher's exact test (two-tailed comparison) indicates the probability of superior CDC graft patency to be 95.5%. In the seven pairs of grafts in which one graft was occluded and the contralateral graft of another type was patent, the CDC graft was patent and the ePTFE graft was occluded in every instance. Explant histology and scanning electron microscopy showed greater collagenization, less residual platelet-fibrin and red blood cell deposits, and more frequent mid-graft endothelialization in the CDC grafts than in the ePTFE grafts.
Immunoreactivity for interleukin 3 and 5 and granulocyte/macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma. (1995)

T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.
Overexpression of the Anti-Adhesin Podocalyxin Is an Independent Predictor of Breast Cancer Progression (2004)

Podocalyxin is a CD34-related cell surface molecule with anti-adhesive qualities. We probed a tissue microarray (n = 272) linked to long-term outcome data and found that podocalyxin was highly overexpressed in a distinct subset of invasive breast carcinomas (n = 15; 6%). Univariate disease-specific (P < 0.01) and multivariate regression (P < 0.0005) analyses indicated that this overexpression is an independent indicator of poor outcome. Forced podocalyxin expression perturbed cell junctions between MCF-7 breast carcinoma cells, and it caused cell shedding from confluent monolayers. Therefore, podocalyxin overexpression is a novel predictor of breast cancer progression that may contribute to the process by perturbing tumor cell adhesion.
Three-Dimensional Corrective Osteotomy for Malunited Diaphyseal Forearm Fractures Using Custom-Made Surgical Guides Based on Computer Simulation (2012)

IndicationsContraindicationsPitfalls & Challenges.
High-brightness source for ion and electron beams (invited) (1998)

By controlled formation of nanoprotrusions on single-crystal tips of tungsten and iridium extremely bright beams of both ions and electrons were obtained. Specific brightness values range up to 1 TA/cm2 srd eV which are considerably higher than those of previous source systems for charged particle emission. The physical mechanisms involved in the generation of these supertips will be outlined. The basic source properties were used to estimate the limiting image size and the obtainable target current-densities. Some of the most important applications of ion and electron beams are considered for materials modification and analysis.
The leapfrog principle: a rule for electron counts of carbon clusters (1987)

Pseudospherical carbon clusters Cn with n= 60 + 6k and k equal either to zero or to any integer greater than one are expected to have closed electronic shells; a simple rule predicts the symmetries of the bonding orbitals of these ‘leapfrog’ clusters.
Molecular imaging for the diagnosis of high-risk plaque. (2003)

Despite advances in our understanding of the pathogenesis of atherosclerosis and new therapeutic modalities, the absence of an adequate method for early detection limits the prevention and treatment of the disease. High-resolution magnetic resonance has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor progression. This review of plaque imaging focuses on the most recent technique: "molecular imaging", which uses specific contrast agents targeted to plaque components, and may allow for better stratification of "high-risk" plaque and "high-risk" patients.
Theoretical and measured performance of a DFE modem on a fading multipath channel (1977)

A decision-feedback equalizer (DFE) is the basis of a recent development of a quadruple diversity troposcatter modem which can operate up to a data rate of 12.6 Mbit/s in a 99% bandwidth of 15 MHz. In this paper a theoretical approach is developed for the calculation of average bit error rate (ABER), including the effects of intersymbol interference due to multipath and the finiteness of the transversal filters used to realize the DFE. By omitting the intersymbol interference effect, the calculation provides a lower bound which can be used to assess the intersymbol interference penalty for a particular DFE structure. The paper includes calculations of a DFE configuration which has a three tap forward filter with tap spacing equal to one-half a symbol interval. Measured performance results from fading channel simulator tests of a three tap forward filter DFE are presented for data rates from 1.5 to 12.6 Mbit/s and for a wide range of multipath statistical conditions. The results for this DFE configuration show (1) excellent agreement between calculated and measured ABER, (2) a small intersymbol interference penalty when the 2σ multipath spread is less than approximnately one-half the data symbol interval, and (3) successful operation at values of multipath spread up to twice the data symbol interval. In a sequel to this paper, the results of a field test of the DFE modem are presented. These live links test results are consistent with both the calculated and simulator measured data presented here.
High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45 (2012)

Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert Opin Ther Targets 10:157-177]. Here we developed a method to monitor tyrosine phosphatase activity at the single-cell level and applied it to the identification of cell-permeable inhibitors. The method takes advantage of the fluorogenic properties of phosphorylated coumaryl amino propionic acid (pCAP), an analog of phosphotyrosine, which can be incorporated into peptides. Once delivered into cells, pCAP peptides were dephosphorylated by protein tyrosine phosphatases, and the resulting cell fluorescence could be monitored by flow cytometry and high-content imaging. The robustness and sensitivity of the assay was validated using peptides preferentially dephosphorylated by CD45 and T-cell tyrosine phosphatase and available inhibitors of these two enzymes. The assay was applied to high-throughput screening for inhibitors of CD45, an important target for autoimmunity and infectious diseases [Hermiston ML, et al. (2003) Annu Rev Immunol 21:107-137]. We identified four CD45 inhibitors that showed activity in T cells and macrophages. These results indicate that our assay can be applied to primary screening for inhibitors of CD45 and of other protein tyrosine phosphatases to increase the yield of biologically active inhibitors.
Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation (1997)

Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.
Nicotinic Acid Adenine Dinucleotide Phosphate Analogues Containing Substituted Nicotinic Acid: Effect of Modification on Ca2+ Release (2010)

Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of the nicotinic acid resulted in the loss of agonist potency for release of Ca(2+)-ions from sea urchin egg homogenates and in potency for competition ligand binding assays using [(32)P]NAADP. In contrast, several 5-substituted NAADP derivatives showed high potency for binding and full agonist activity for Ca(2+) release. 5-Azido-NAADP was shown to release calcium from sea urchin egg homogenates at low concentration and to compete with [(32)P]NAADP in a competition ligand binding assay with an IC(50) of 18 nM, indicating that this compound might be a potential photoprobe useful for specific labeling and identification of the NAADP receptor.
Dendritic Cell Immunotherapy for Malignant Gliomas (2008)

The prognosis for patients with malignant gliomas remains poor despite advances in surgical technique, chemotherapy and radiation therapy. Median survival for glioblastoma multiforme, the most aggressive and deadliest form of brain cancer, remains only fifteen months even after optimal treatment with surgical resection followed by chemoradiation therapy. The grim prognosis can be attributed to the infiltrative nature of the disease, a central nervous system microenvironment that can escape immune surveillance and resistance of the tumor to chemotherapy. In recent trials, dendritic cells have demonstrated an ability to promote an effective anti-tumor immune response and sensitize glioma cells to chemotherapy. This review will discuss the results of dendritic-cell based immunotherapy clinical trials for the treatment of malignant gliomas and explore the future strategies of DC vaccines for glioma immunotherapy.
Long-Term Benefit of Adeno-Associated Virus/Antisense-Mediated Exon Skipping in Dystrophic Mice (2008)

Many mutations and deletions in the dystrophin gene, responsible for Duchenne muscular dystrophy (DMD), can be corrected at the posttranscriptional level by skipping specific exons. Here we show that long-term benefit can be obtained in the dystrophic mouse model through the use of adeno-associated viral vectors expressing antisense sequences: persistent exon skipping, dystrophin rescue, and functional benefit were observed 74 weeks after a single systemic administration. The therapeutic benefit was sufficient to preserve the muscle integrity of mice up to old age. These results indicate a possible long-term gene therapy treatment of the DMD pathology.
Effect of lanthanum loading in Fe-K/La-Al2O3 catalysts for CO2 hydrogenation to hydrocarbons (2000)

Lanthanum-modified alumina supports prepared by the impregnation method have been used as supports for potassium-promoted iron catalysts in CO2 hydrogenation. The catalysts have been characterized by X-ray diffraction, CO2 chemisorption, temperature-programmed reduction (TPR) and temperature-programmed decarburization (TPDC) techniques. The selectivity towards total hydrocarbons and lower olefins (C2–C4) was found to increase with increase in lanthanum content up to 4 wt% in Fe–K/La–Al2O3 catalysts and to decrease above this lanthanum content. The TPR profiles of the catalysts of lanthanum-modified Al2O3 shows the reduction of Fe2O3 to iron(0) follows a three-stage reduction mechanism through formation of the FeO phase. The TPDC profiles show the formation of three types of carbide species on the catalysts during the reaction. The activities of the catalysts are correlated with physico-chemical characteristics of the catalysts. Copyright © 2000 John Wiley & Sons, Ltd.
Optimal phase conflict removal for layout of dark field alternating phase shifting masks (2000)

We describe new, efficient algorithms for layout modification and phase assignment for dark field alternating-type phase shifting masks in the single exposure regime. We make the following contributions. First, we suggest new two-coloring and compaction approach that simultaneously optimizes layout and phase assignment which is based on planar embedding of an associated conflict graph. We also describe additional approaches to cooptimization of layout and phase assignment for alternating PSM. Second, we give optimal and fast algorithms to minimize the number of phase conflicts that must be removed to ensure two colorability of the conflict graph. We reduce this problem to the T-join problem which asks for a minimum weight edge set A such that a node u is incident to an odd number of edges of A if u belongs to a given node subset T of a weighted graph. Third, we suggest several practical algorithms for the T-join problem. In sparse graphs, our algorithms are faster than previously known methods. Computational experience with industrial VLSI layout benchmarks shows the advantages of the new algorithms.
Analysis of the dynamic Bacillus subtilis Ser/Thr/Tyr phosphoproteome implicated in a wide variety of cellular processes (2006)

The physiological role of proteins phosphorylated on serine/threonine/tyrosine (Ser/Thr/Tyr) residues or the identity of the corresponding kinases and phosphatases is generally poorly understood in bacteria. As a first step in analysing the importance of such phosphorylation, we sought to establish the nature of the Ser/Thr/Tyr phosphoproteome in Bacillus subtilis, using in vivo labelling with [(32)P]-orthophosphate, one-unit pH 2-DE, combined with MS. Highly reproducible 2-D profiles of phosphoproteins were obtained with early stationary-phase cells. The 2-D profiles contained at least 80 clearly labelled spots in the pH range 4-7. Forty-six spots were analysed by MS (confirmed in most cases by LC-MS/MS), identifying a total of 29 different proteins, with 19 identified for the first time as bacterial phosphoproteins. These phosphoproteins are implicated in a wide variety of cellular processes, including carbon and energy metabolism, transport, stress and development. Significant changes to the profiles were obtained as a result of cold, heat or osmotic shock, demonstrating that, in stationary-phase cells, the phosphoproteome is dynamic. An initial comparative study indicated that at least 25 [(32)P]-labelled spots were also stained by Pro-Q Diamond, with apparently six additional phosphoproteins uniquely detected by Pro-Q.
Från stav till stav : Utvecklingen till elit inom svenskt skidskytte (2010)

Seniorlandalaget 2009 utgjorde elitgruppen och som samtliga gatt pa riksidrottsgymnasium (RIG). Kontrollgruppen - likaledes fran RIG - matchades parvis i variablerna alder, kon och presterade resul ...
Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol (1991)

The interaction of high density lipoproteins (HDL) with the HDL receptor stimulates the translocation of cholesterol from intracellular pools to the plasma membrane where the cholesterol becomes available for removal by appropriate acceptors. The role of signal transduction through protein kinase C in HDL receptor-dependent cholesterol translocation and efflux was examined using cholesterol-loaded cultured human skin fibroblasts. Treatment of cells with HDL3 activated protein kinase C, demonstrated by a transient increase in membrane associated kinase activity. Kinase activation appeared to be dependent on binding of HDL3 to the HDL receptor, since tetranitromethane-modified HDL3, which does not bind to the receptor, was without effect. Translocation of intracellular sterol to the plasma membrane was stimulated by treatment of cells with the protein kinase C activators, dioctanoylglycerol and phorbol myristic acetate, and the calcium ionophore A23187. Conversely, treatment of cells with sphingosine, a protein kinase C inhibitor, reduced HDL3-mediated translocation and efflux of intracellular sterols. However, sphingosine had no effect on efflux of labeled cholesterol derived from the plasma membrane. Down-regulation of cellular protein kinase C activity by long term incubation with phorbol esters also inhibited HDL3-mediated efflux of intracellular sterols and abolished the ability of sphingosine to further inhibit HDL3-mediated efflux. These studies support the conclusion that HDL receptor-mediated translocation and efflux of intracellular cholesterol occurs through activation of protein kinase C.