gebhart/patrepeval huggingface dataset:
Breaking the one antibody–one target axiom (2006)

Studies at the interface of chemistry and biology have allowed us to develop an immunotherapeutic approach called chemically programmed antibodies (cpAbs), which combines the merits of traditional small-molecule drug design with immunotherapy. In this approach, a catalytic antibody catalyzes the covalent conjugation of a small molecule or peptide to the active site of the antibody, effectively recruiting the binding specificity of the conjugated molecule to the antibody. In essence, this technology provides the tools for breaking the "one antibody-one target axiom" of immunochemistry. Our studies in this area have focused on using the chemistry of the well studied aldolase catalytic antibodies of which mAb 38C2 is a member. Previously, we explored reversible assembly of cpAbs available through diketone chemistry. In this article, we explore a unique proadapter assembly strategy wherein an antibody 38C2-catalyzed transformation unveils a reactive tag that then reacts to form a stable covalent bond with the antibody. An integrin alpha(v)beta 3 antagonist was synthesized with the designed proadapter and studied using human breast cancer cell lines MDA-MB-231 and MDA-MB-435. We demonstrate that this approach allows for (i) the effective assembly of cpAbs in vitro and in vivo, (ii) selective retargeting of 38C2 to integrin alpha(v)beta 3 expressing breast cancer cell lines, (iii) intracellular delivery of cpAbs into cells, (iv) dramatically increased circulatory half-life, and (v) substantial enhancement of the therapeutic effect over the peptidomimetic itself in animal models of breast cancer metastasis. We believe that this technology possesses potential for the treatment and diagnosis of disease.
EL PROYECTO GRAN SÍMIO ESPAÑOL (2013)

O projeto do Grande Símio Espanhol (PGSE) foi organizado&lt;br /&gt;para salvar as diversas espécies de grandes símios, principalmente na&lt;br /&gt;Espanha e outros países, e visa evitar os maus-tratos, abusos sexuais,&lt;br /&gt;exploração em laboratórios, circos e tantas outras práticas horríveis&lt;br /&gt;realizadas com frequencia contra estes animais. Os relatórios mostram&lt;br /&gt;dados assustadores, e a atuação deste projeto é uma forma indispensável&lt;br /&gt;para garantir a integridade e liberdade dessas espécies.
Extraction-free whole transcriptome gene expression analysis of FFPE sections and histology-directed subareas of tissue (2019)

We describe the use of a ligation-based targeted whole transcriptome expression profiling assay, TempO-Seq, to profile formalin-fixed paraffin-embedded (FFPE) tissue, including H&E stained FFPE tissue, by directly lysing tissue scraped from slides without extracting RNA or converting the RNA to cDNA. The correlation of measured gene expression changes in unfixed and fixed samples using blocks prepared from a pellet of a single cell type was R2 = 0.97, demonstrating that no significant artifacts were introduced by fixation. Fixed and fresh samples prepared in an equivalent manner produced comparable sequencing depth results (+/- 20%), with similar %CV (11.5 and 12.7%, respectively), indicating no significant loss of measurable RNA due to fixation. The sensitivity of the TempO-Seq assay was the same whether the tissue section was fixed or not. The assay performance was equivalent for human, mouse, or rat whole transcriptome. The results from 10 mm2 and 2 mm2 areas of tissue obtained from 5 μm thick sections were equivalent, thus demonstrating high sensitivity and ability to profile focal areas of histology within a section. Replicate reproducibility of separate areas of tissue ranged from R2 = 0.83 (lung) to 0.96 (liver) depending on the tissue type, with an average correlation of R2 = 0.90 across nine tissue types. The average %CVs were 16.8% for genes expressed at greater than 200 counts, and 20.3% for genes greater than 50 counts. Tissue specific differences in gene expression were identified and agreed with the literature. There was negligible impact on assay performance using FFPE tissues that had been archived for up to 30 years. Similarly, there was negligible impact of H&E staining, facilitating accurate visualization for scraping and assay of small focal areas of specific histology within a section.
Gaussian Processes for Machine Learning (2005)

A comprehensive and self-contained introduction to Gaussian processes, which provide a principled, practical, probabilistic approach to learning in kernel machines.
Motion regularization for model-based head tracking (1996)

This paper describes a method for the robust tracking of rigid head motion from video. This method uses a 3D ellipsoidal model of the head and interprets the optical flow in terms of the possible rigid motions of the model. This method is robust to large angular and translational motions of the head and is not subject to the singularities of a 2D model. The method has been successfully applied to heads with a variety of shapes, hair styles, etc. This method also has the advantage of accurately capturing the 3D motion parameters of the head. This accuracy is shown through comparison with a ground truth synthetic sequence (a rendered 3D animation of a model head). In addition, the ellipsoidal model is robust to small variations in the initial fit, enabling the automation of the model initialization. Lastly, due to its consideration of the entire 3D aspect of the head, the tracking is very stable over a large number of frames. This robustness extends even to sequences with very low frame rates and noisy camera images.
IgM and IgA anti-erythrocyte autoantibodies induce anemia in a mouse model through multivalency-dependent hemagglutination but not through complement activation (2007)

By generating IgM and IgA switch variants of the 34-3C IgG2a anti-red blood cell (RBC) autoantibody, we evaluated the pathogenic activity of these 2 isotypes in view of the Fc-associated effector functions (ie, complement activation and polyvalency-dependent agglutination). We found that polymeric forms of 34-3C IgM and IgA anti-RBC autoantibody were as pathogenic as IgG2a, which was the most pathogenic among 4 different IgG subclasses, whereas their monomeric variants completely lacked pathogenic effects. Histological examination showed that 34-3C IgM and IgA autoantibodies caused anemia as a result of multivalency-dependent hemaggultination and subsequent sequestration of RBC in the spleen, in contrast to Fc receptor- and complement receptor-mediated erythrophagocytosis by Kupffer cells with IgG isotypes. In addition, the development of anemia induced by IgM and IgA isotypes of 34-3C antibody and by 2 additional IgM anti-RBC monoclonal autoantibodies was not inhibited at all in C3-deficient mice, indicating the lack of involvement of complement activation in the pathogenesis of IgM- and IgA-induced anemia. Our data demonstrate a remarkably high pathogenic potential of polymeric forms of IgM and IgA anti-RBC autoantibodies due to their ability to induce hemagglutination but completely independent of complement activation.
Squamous cell carcinoma of the oral cavity in patients younger than 40 years (1997)

Squamous cell carcinoma of the head and neck has been regarded as a disease affecting the elderly. Several etiologic factors have been demonstrated, such as tobacco and alcohol use and premalignant lesions, whereas others have been suspected, such as genetic or immunodeficiency disorders. Recently, some reports have addressed a tendency toward an increase in the incidence of squamous cell carcinoma in young patients. In recent years we have observed an increase in the number of squamous cell carcinomas in patients younger than 40 years. Therefore we retrospectively reviewed our clinical experience of cancer in those patients younger than 40 years. After screening 505 clinical charts, 294 patients met the criteria to enter our study. Twenty-four (8.2%) patients were aged 40 years or younger. Data collected included the history of premalignant lesions, etiologic factors, TNM stages, treatment modalities, and histopathologic issues. Statistical analysis with Kaplan-Meier survival rates and log-rank tests between various variables were applied. A significant association in survival was observed between patterns of recurrence (p = 0.031) and presence of neoplastic cells 5 mm or closer to the specimen margin. On the other hand, a lack of association was assessed in carcinogenic-related habits and in premalignant lesions. Likewise, although men showed a slightly worse prognosis than women, statistically no significant differences were found (p = 0.27).
Specific binding sites for 3,3′‐diiodo‐l‐thyronine (3,3′‐T2) in rat liver mitochondria (1994)

Specific binding sites for 3,3'-T2 can be detected in swollen and osmotically treated mitochondria (OTM) from normal and hypothyroid rat liver. In hypothyroid animals, maximal values of binding were obtained at 0 degrees C while values were lower at 37 degrees C and no specific binding could be observed at 60 degrees C. Binding was maximal at pH 6.4 and the mean values for the apparent association constant (Ka) and the binding capacity were on average 0.5 x 10(8) M-1 and 2.4 pmol/mg mitochondrial protein, respectively. No differences were observed between normal and hypothyroid rats with the exception of the capacity that was higher in normal animals (5.5 pmol/mg mitochondrial protein). The specificity of 3,3'-T2 binding, examined in competition studies, followed this order: 3,3'-T2 > 3,5-T2 > rT3. The other iodothyronines (3',5'-T2, T3, T4, 3-T1, 3'-T1, 3,5-Diac and 3,3'-Diac) showed only a small competition or none at all.
A Role for Kinesin in Insulin-stimulated GLUT4 Glucose Transporter Translocation in 3T3-L1 Adipocytes (2001)

Insulin regulates glucose uptake in adipocytes and muscle by stimulating the movement of sequestered glucose transporter 4 (GLUT4) proteins from intracellular membranes to the cell surface. Here we report that optimal insulin-mediated GLUT4 translocation is dependent upon both microtubule and actin-based cytoskeletal structures in cultured adipocytes. Depolymerization of microtubules and F-actin in 3T3-L1 adipocytes causes the dispersion of perinuclear GLUT4-containing membranes and abolishes insulin action on GLUT4 movements to the plasma membrane. Furthermore, heterologous expression in 3T3-L1 adipocytes of the microtubule-binding protein hTau40, which impairs kinesin motors that move toward the plus ends of microtubules, markedly delayed the appearance of GLUT4 at the plasma membrane in response to insulin. The hTau40 protein had no detectable effect on microtubule structure or perinuclear GLUT4 localization under these conditions. These results are consistent with the hypothesis that both the actin and microtubule-based cytoskeleton, as well as a kinesin motor, direct the translocation of GLUT4 to the plasma membrane in response to insulin.
Decreased Expression of Membrane IL-5 Receptor α on Human Eosinophils: II. IL-5 Down-Modulates Its Receptor Via a Proteinase-Mediated Process (2002)

In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Ralpha expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Ralpha is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Ralpha mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Ralpha, which in turn contributes to the presence of sIL-5Ralpha. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Ralpha was accompanied by an increase in sIL-5Ralpha in the supernatant. IL-5 had no ligand-specific effect on mIL-5Ralpha or sIL-5Ralpha mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Ralpha, suggesting that sIL-5Ralpha may be produced by proteolytic cleavage of mIL-5Ralpha. IL-5 transiently reduced surface expression of beta-chain, but had no effect on the expression of GM-CSFRalpha. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Ralpha rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Ralpha and release sIL-5Ralpha in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.
Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1 (2006)

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes.
Robust and flexible mixed-initiative dialogue for telephone services (1999)

In this work, we present an experimental analysis of a Dialogue System for the automatization of simple telephone services. Starting from the evaluation of a preliminar version of the system we conclude the necessity to desing a robust and flexible system suitable to have to have different dialogue control strategies depending on the characteristics of the user and the performance of the speech recognition module. Experimental results following the PARADISE framework show an important improvement both in terms of task success and dialogue cost for the proposed system.
Bending to Kinetic Energy Transfer in Adhesive Peel Front Microinstability (2019)

We report an extensive experimental study of a detachment front dynamics instability, appearing at microscopic scales during the peeling of adhesive tapes. The amplitude of this instability scales with its period as A_{mss}∝T_{mss}^{1/3}, with a prefactor evolving slightly with the peel angle θ, and increasing systematically with the bending modulus B of the tape backing. Establishing a local energy budget of the detachment process during one period of this microinstability, our theoretical model shows that the elastic bending energy stored in the portion of tape to be peeled is converted into kinetic energy, providing a quantitative description of the experimental scaling law.
A Gallium-67/68–Labeled Antibody Fragment for Immuno-SPECT/PET Shows Low Renal Radioactivity Without Loss of Tumor Uptake (2018)

<b>Purpose:</b> This study was undertaken to evaluate the renal radioactivity levels of a newly designed <sup>67</sup>Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule.<b>Experimental Design:</b><sup>67</sup>Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (<sup>67</sup>Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and <sup>67</sup>Ga-NOTA-Met is excreted from the kidney into the urine. The enzymatic recognition of the linkage was evaluated with a low-molecular-weight <sup>67</sup>Ga-NOTA-Met-Val-Lys derivative. Biodistribution of radioactivity after injection of <sup>67</sup>Ga-NOTA-MVK-Fab into mice was compared with <sup>67</sup>Ga-NOTA-conjugated Fab fragments through a Met-Ile linkage that liberates <sup>67</sup>Ga-NOTA-Met (<sup>67</sup>Ga-NOTA-MI-Fab) or a conventional thiourea linkage (<sup>67</sup>Ga-NOTA-Fab).<b>Results:</b> The MVK linkage remained stable in plasma and was recognized by enzymes on renal BBM to liberate <sup>67</sup>Ga-NOTA-Met. When injected into mice, all three <sup>67</sup>Ga-labeled Fab exhibited similar blood clearance rates and tumor accumulation. Significant differences were observed in the kidney where <sup>67</sup>Ga-NOTA-MVK-Fab registered the lowest renal radioactivity levels from early postinjection time (<i>P</i> < 0.05), followed by <sup>67</sup>Ga-NOTA-MI-Fab, which was well reflected in the SPECT/CT images.<b>Conclusions:</b> These findings indicated that our proposal of liberating a radiolabeled compound to urinary excretion from antibody fragments at the renal BBM to reduce the renal radioactivity levels was applicable to <sup>67/68</sup>Ga-labeled antibody fragments. Because antibody fragments and constructs share similar metabolic fates in the kidney, the present labeling procedure would also apply to a variety of antibody fragments and constructs of interest. <i>Clin Cancer Res; 24(14); 3309-16. ©2018 AACR</i>.
Biomarkers in Cervical Cancer Screening (2007)

In industrialized countries, population wide cytological screening programs using the Pap test have led to a substantial reduction of the incidence of cervical cancer. Despite this evident success, screening programs that rely on Pap-stained cytological samples have several limitations. First, a number of equivocal or mildly abnormal test results require costly work up by either repeated retesting or direct colposcopy and biopsy, since a certain percentage of high grade lesions that require immediate treatment hide among these unclear test results. This work up of mildly abnormal or equivocal cytological tests consumes a large amount of the overall costs spent for cervical cancer screening. Improved triage of these samples might substantially reduce the costs. Cervical cancer is induced by persistent infections with oncogenic human papilloma viruses (HPV). While HPV infection is an indispensable factor, it is not sufficient to cause cancer. The majority of acute HPV infections induce low grade precursor lesions that are cleared spontaneously after several months in more than 90% of cases, and less than 10% eventually progress to high grade lesions or invasive cancer. Progression is characterized by the deregulated expression of the viral oncogenes E6 and E7 in infected basal and parabasal cells. Novel biomarkers that allow monitoring these essential molecular events in histological or cytological specimens are likely to improve the detection of lesions that have a high risk of progression in both primary screening and triage settings. In this review, we will discuss potential biomarkers for cervical cancer screening with a focus on the level of clinical evidence that supports their application as novel markers in refined cervical cancer screening programs.
Creating the Virtual Store: Taking Your Web Site from Browsing to Buying (1996)

Introducing the Virtual Store Planning the Virtual Store Designing The Shopping Experience Getting to Know Your Virtual Customers Advertising and Promoting Your Virtual Store Accepting Virtual Payments: Selecting Methods that are Right for You Understanding Virtual Legality Preparing for the Future Epilogue Appendices References Index.
Inter-peptide interaction and delocalization of amide I vibrational excitons in myoglobin and flavodoxin (2002)

The amide I vibrational normal-mode analyses of two globular proteins, myoglobin and flavodoxin, were carried out and the spatial delocalization and phase correlation of each normal mode was studied. The Hessian matrix in the restricted space constructed by the N peptides was obtained by using both ab initio quantum chemistry calculation results and empirical transition dipole coupling model. For both of the two proteins, the amide I normal modes are fairly delocalized and on average about 15% of the polypeptides in myoglobin and flavodoxin are participated in the formation of each amide I normal mode. The analysis of vibrational phase correlation of myoglobin reveals that the high-frequency amide I normal modes are mostly (symmetric) A-mode like, whereas the low-frequency ones are (antisymmetric) E-mode like. For flavodoxin, among the three distinct bands at 1653, 1636, and 1628 cm−1, the high-frequency modes are found to be fairly localized in the four α helices, the low-frequency modes around 1628 cm−1 are strictly localized in the five β sheets, and the midfrequency modes around 1636 cm−1 are delocalized in both the α helices and β sheets. Effects of the diagonal disorder on the amide I band of both proteins were studied. We found that the sharp peak at 1628 cm−1 in the resolution enhanced amide I infrared spectrum of flavodoxin is a direct signature that the through-space interactions between two different β sheets exist.
Low-resistance bandgap-engineered W/Si/sub 1-x/Ge/sub x//Si contacts (1996)

Bandgap-engineered W/Si/sub 1-x/Ge/sub x//Si junctions (p/sup +/ and n/sup +/) with ultra-low contact resistivity and low leakage have been fabricated and characterized. The junctions are formed via outdiffusion from a selectively deposited Si/sub 0.7/Ge/sub 0.3/ layer which is implanted and annealed using RTA. The Si/sub 1-x/Ge/sub x/ layer can then be selectively thinned using NH/sub 4/OH/H/sub 2/O/sub 2//H/sub 2/O at 75/spl deg/C with little change in characteristics or left as-deposited. Leakage currents were better than 1.6/spl times/10/sup -9/ A/cm/sup 2/ (areal), 7.45/spl times/10/sup -12/ A/cm (peripheral) for p/sup +//n and 3.5/spl times/10/sup -10/ A/cm/sup 2/ (peripheral) for n/sup +//p. W contacts were formed using selective LPCVD on Si/sub 1-x/Ge/sub x/. A specific contact resistivity of better than 3.2/spl times/10/sup -8/ /spl Omega/ cm/sup 2/ for p/sup +//n and 2.2/spl times/10/sup -8/ /spl Omega/ cm/sup 2/ for n/sup +//p is demonstrated-an order of magnitude n/sup +/ better than current TiSi/sub 2/ technology. W/Si/sub 1-x/Ge/sub x//Si junctions show great potential for ULSI applications.
Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease (2009)

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe.