gebhart/patrepeval huggingface dataset:
The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives (2017)

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient. The breakthrough of the technology to generate autologous-induced pluripotent stem cells (iPSCs) by nuclear reprogramming of patient's somatic cells raised the possibility that autologous iPSC-derived cells can be transplanted into the patients without the concern of immune rejection. However, accumulating data indicate that certain iPSC-derived cells can be immunogenic. In addition, the genomic instability associated with iPSCs raises additional safety concern to use iPSC-derived cells in human cell therapy. In this review, we will discuss the mechanism underlying the immunogenicity of the pluripotent stem cells and recent progress in developing immune tolerance strategies of human pluripotent stem cell (hPSC)-derived allografts. The successful development of safe and effective immune tolerance strategy will greatly facilitate the clinical development of hPSC-based cell therapy.
Biomolecular interactions by Surface Plasmon Resonance technology. (2005)

The Surface Plasmon Resonance (SPR) technique makes it possible to measure biomolecular interactions in real-time with a high degree of sensitivity and without the need of label. The information obtained is both qualitative and quantitative and it is possible to obtain the kinetic parameters of the interaction. This new technology has been used to study a diverse set of interaction partners of biological interest, such as protein-protein, protein-lipids, protein- nucleic acids or protein and low molecular weight molecules such as drugs, substrates and cofactors. In addition to basic biomedical research, the SPR biosensor has recently been used in food analysis, proteomics, immunogenicity and drug discovery.
Calcium dobesilate combined with a heparinoid in the topical treatment of chronic venous insufficiency : a double-blind study (1990)

Three gels, containing [1] calcium dobesilate alone, [2] the heparinoid compound potassium hydrodextransulphate alone and [3] the two compounds together were applied locally for four weeks in a double-blind experiment to 21, 20, and 29 patients respectively with chronic venous insufficiency in the legs. The results were significantly better with the combined preparation than with dobesilate alone or with heparinoid alone. Tolerance was good and there were no local or systemic side effects
Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast (2015)

There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used high-throughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant α-amylase. Efficient secretion was genetically stable in the selected clones. We performed whole-genome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole-genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories.
Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors (2010)

CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells, indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment. In vivo, daratumumab was highly active and interrupted xenograft tumor growth at low dosing. Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms. These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.
Automated Analysis of Deformable Structure in Groups of Images (2007)

We describe an approach for automated analysis of deformable objects which extracts structure information from groups of images containing different examples of the object with a particular application to human imaging. The proposed analysis framework simultaneously segments and registers a set of images, incrementally constructing a model of the composition of the object. By fitting an appropriate intensity distribution model to the image we obtain a soft segmentation which allows us to explicitly model the construction of each pixel from constituent image segments, rather than its expected intensity. This effectively decouples the model from the effects of the imaging system and varying statistics in different examples. When estimating the optimal deformation field for each example, the original image is compared to a reconstruction, generated using the composition model and its intensity distribution parameters for each segment (i.e. an estimate of how the model would appear given the imaging conditions for that image). In the paper we describe the algorithm in detail and show results of applying it to two sets of medical images of different anatomies taken with different imaging modalities. We present quantitative results demonstrating that the proposed algorithm is more powerful than current state of the art methods at extracting structural information such as spatial correspondences across groups of images with varying statistics.
A local ensemble Kalman filter for atmospheric data assimilation (2004)

In this paper, we introduce a new, local formulation of the ensemble Kalman filter approach for atmospheric data assimilation. Our scheme is based on the hypothesis that, when the Earth’s surface is divided up into local regions of moderate size, vectors of the forecast uncertainties in such regions tend to lie in a subspace of much lower dimension than that of the full atmospheric state vector of such a region. Ensemble Kalman filters, in general, take the analysis resulting from the data assimilation to lie in the same subspace as the expected forecast error. Under our hypothesis the dimension of the subspace corresponding to local regions is low. This is used in our scheme to allow operations only on relatively low-dimensional matrices. The data assimilation analysis is performed locally in a manner allowing massively parallel computation to be exploited. The local analyses are then used to construct global states for advancement to the next forecast time. One advantage, which may take on more importance as ever-increasing amounts of remotely-sensed satellite data become available, is the favorable scaling of the computational cost of our method with increasing data size, as compared to other methods that assimilate data sequentially. The method, its potential advantages, properties, and implementation requirements are illustrated by numerical experiments on the Lorenz-96 model. It is found that accurate analysis can be achieved at a cost which is very modest compared to that of a full global ensemble Kalman filter.
Macromol. Chem. Phys. 16/2007 (2007)

Cover: Dynamics of laser‐induced alignment and surface grating formation of azobenzene polymer were examined in relation to the photoisomerization pathway of the excited states. Further details can be found in the Full Paper by M. J. Kim * , J. D. Lee, C. Chun, D. Y. Kim, S. Higuchi, and T. Nakayama on page 1753.
Characterization of EBV‐genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non‐Hodgkin lymphoma (1977)

Abstract Sixty‐two explants from peripheral blood, bone marrow and cerebral fluid of children with acute lymphoblastic leukemia (ALL) and leukemic transformed non‐Hodgkin lymphoma (NHL) were cultivated for at least 8 weeks. Although lymphatic cells persisted up to 16 weeks in tissue culture, no proliferation was observed in 54 cultures. From the remaining cultures, eight permanently growing cell lines were obtained. Five of these were EBNA (Epstein‐Barr virus‐specific nuclear antigen)‐positive. Three, however, were EBNA‐negative and lacked Epstein‐Barr virus genomes. Two cell lines (KM‐3 and SH‐2) expressed neither B nor T cell characteristics. One line (JM) expressed T cell characteristics and complement receptors. The growing lymphatic cells represented leukemic cells, since the pattern of cytochemical staining and that of membrane receptors of lymphoblasts from the same donor prior to cultivation were identical. All leukemic cell lines were derived from patients in relapse. In contrast, no proliferation of leukemic cells occurred in explants from patients revealing the first manifestation of the disease. These results suggest enhanced growth potential of lymphoblasts resisting antileukemic therapy.
The dimerization domain of the HIV‐1 capsid protein binds a capsid protein‐derived peptide: A biophysical characterization (2004)

The type 1 HIV presents a conical capsid formed by approximately 1500 units of the capsid protein, CA. Homodimerization of CA via its C-terminal domain, CA-C, constitutes a key step in virion assembly. CA-C dimerization is largely mediated by reciprocal interactions between residues of its second alpha-helix. Here, we show that an N-terminal-acetylated and C-terminal-amidated peptide, CAC1, comprising the sequence of the CA-C dimerization helix plus three flanking residues at each side, is able to form a complex with the entire CA-C domain. Thermal denaturation measurements followed by circular dichroism (CD), NMR, and size-exclusion chromatography provided evidence of the interaction between CAC1 and CA-C. The apparent dissociation constant of the heterocomplex formed by CA-C and CAC1 was determined by several biophysical techniques, namely, fluorescence (using an anthraniloyl-labeled peptide), affinity chromatography, and isothermal titration calorimetry. The three techniques yielded similar values for the apparent dissociation constant, in the order of 50 microM. This apparent dissociation constant was only five times higher than was the dissociation constant of both CA-C and the intact capsid protein homodimers (10 microM).
Improvement in health-related quality of life in systemic lupus erythematosus patients enrolled in a randomized clinical trial comparing LJP 394 treatment with placebo (2003)

In a 76-week, randomized controlled trial, patients received 100 mg LJP 394 or placebo weekly for 16 weeks followed by three 12-week treatment cycles of 50 mg LJP 394 or placebo weekly each separated by eight-week periods when no therapy was administered. Health-related quality of life (HRQOL) was assessed using SF-36 at baseline, 16 weeks and every 12 weeks thereafter. Analyses populations included intent to treat (ITT) (n = 179) and patients with high-affinity anti-dsDNA antibody binding (HA): 157/179; 85% active, 90% placebo. In the ITT population, there were improvements in role emotional (RE) (+7.3 versus -8.2), social functioning (SF) (+4.3 versus +0.7), and role physical (RP) (+11.3 versus +6.0) domains in the active treatment group when compared with placebo, with similar changes observed in the HA population. In 37 patients with data pre- and post-renal flares, those receiving LJP 394 reported stabilization or improvement in all but one domain compared with deterioration in all domains with placebo. Changes in RE domain scores following a flare differed by 22.7 points between the two treatment groups, favouring LJP 394 treatment. Patients receiving LJP 394 reported stable or improved HRQOL with active treatment following renal flares compared with deterioration in placebo. Differences between treatment groups in RE and SF domains are clinically important and were replicated irrespective of the protocol population analysed.
Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison (2014)

This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes, either as monotherapy or combination therapy.
LOW POWER LASER THERAPY: A NONINVASIVE HIGHLY EFFECTIVE THERAPEUTIC MODALITY. (1997)

Over the past 15 years the author and his colleagues have treated over 1500 patients wit a wide range of pathological conditions using a variety of low power lasers (LPL) with different wavelengths and incident energy densities. The results have, however, been very good independent of these parameters. In the present study the authors offers his hypotheses as to why this should be, drawing on the physical characteristics of light and specific laser/tissue interaction models, and presents some clinical studies as examples of his experiences.
Studies of Nuclear 3,5,3′-Triiodothyronine Binding in Primary Cultures of Rat Brain* (1985)

Primary cultures of enzymatically dispersed cells from 17-day-old fetal rat cerebral hemispheres were used to detect the presence of nuclear T3 receptors. Cells grown in Minimum Essential Medium supplemented with 10% fetal bovine serum were grown in parallel with cytosine-arabinoside (ARA-C)-treated counterparts which had been exposed to the antimetabolite for 18 h on culture days 3 and 5 or 4 and 6. Five days after the second ARA-C treatment, phase contrast photomicrographs showed substantial loss of the proliferating basal cells, corresponding to an 85% decrease in cell number. Immunocytochemical studies using antiglial fibrillary acidic protein (anti-GFAP) and antineurofilament (anti-NF) antisera demonstrated loss of GFAP-positive cells (astrocytes) and preservation of NF-positive cells (neurons), the latter considered to be a nondividing population under the culture conditions. Nuclei obtained from the brain cell cultures at this time by Triton washing bound T3 with properties similar to those observed in vivo. Scatchard analysis showed a single, high affinity, limited capacity nuclear T3 receptor with a maximal binding capacity (MBC) of 0.53 +/- 0.10 ng T3/mg DNA and a Kd of 0.19 +/- 0.02 nM (+/- SE; n = 4). ARA-C treatment resulted in a mean decrease in DNA per culture dish of 54%, with an accompanying 2-fold enrichment of the MBC, and no change in the Kd. In untreated cultures grown for 20 days, DNA per dish increased until day 14 and subsequently remained stable at approximately 100 micrograms/dish. The MBC also increased from days 0 to 7, and remained stable until day 14. On day 20, the MBC had declined by approximately 60% to 0.21 ng T3/mg DNA, at which time the neuron population was decreased. The extracted nuclear receptor from brain cell cultures had a sedimentation coefficient of 3.6S. The relative binding affinities of the nuclear receptor for T3 and several analogs were identical to those found in vivo, making significant contamination of the nuclei with cytosolic or serum binding proteins very unlikely. Nuclei isolated from long term, neuron-free glial cell cultures failed to show any consistent high affinity saturable T3 binding.(ABSTRACT TRUNCATED AT 400 WORDS)
A Novel Process for Demulsification of Water-in-Crude Oil Emulsions by Dense Carbon Dioxide (2003)

CO2 was used to break several water-in-crude oil and water-in-model oil emulsions stabilized by asphaltenic films. The stability of asphaltenic films in model oils having varying H/C ratios (aromaticities) was also studied upon contact with liquid or supercritical CO2. The efficacy and kinetics of demulsification appeared to be enhanced with increased CO2 density and mole fraction. The proposed mechanism by which CO2 destabilizes water-in-crude oil emulsions involves asphaltene flocculation and precipitation. The emulsions break by flocculating the adsorbed asphaltenes, leading to film defects, film thinning, film rupture, and water coalescence. The various factors influencing asphaltene precipitation and emulsion destabilization were studied in model solvent systems containing asphaltenes and resins. Increasing CO2 pressure, residence time, temperature, and degree of mixing were found to increase the rate of asphaltene precipitation. Asphaltene precipitation by CO2 was found to increase in the presence of water as compared to precipitation from water-free systems. It is apparent that CO2 preferentially precipitates the most surface-active portion of asphaltenes, leading to a substantial weakening of the viscoelastic asphaltenic film built around the dispersed water droplets in the emulsion. The rate of the demulsification process was greatly enhanced when the emulsion was injected under pressure into compressed CO2 as a result of the enhanced CO2/emulsion volume ratio and mass transfer rates.
Effects of pH and urea on the conformational properties of subtilisin DY (1982)

Subtilisin DY is very resistant to the denaturing action of urea: the conformational properties are not affected up to 4.5 M-urea, and even in the presence of 8 M-urea there is only a slow loss of ordered structure and caseinolytic activity. C.d. and fluorescence-emission studies also show that this proteinase is stable in the 5.5-10.0 pH range, whereas below pH 5.5 a sharp denaturation occurs that is complete at pH 4.5. Protein denaturation leads to a change of the emission quantum yield; in particular, in the native protein, indole fluorescence is quenched by some amino groups. Moreover, subtilisin DY possesses two classes of tyrosine residues: one class of exposed residues titrates normally, with pKapp. = 10.24, whereas one class of partially buried or hydrogen-bonded residues ionizes with pKapp. = 11.58. In general, such conformational properties resemble those of other subtilisins. However, some differences occur: e.g., subtilisin DY is less stable at acidic pH values and its tyrosine residues are more accessible to the solvent. Such differences are probably due to small variations of the three-dimensional structure; e.g., subtilisin DY has a slightly lower alpha-helix content.
Chromosome abnormalities in human non-small cell lung cancer. (1992)

Clonal cytogenetic abnormalities found in 30 non-small cell lung carcinomas (NSCLC), including 28 newly diagnosed primary tumor specimens, are summarized. Multiple chromosome alterations were identified in every case, and 19 of 30 tumors had near-triploid or near-tetraploid karyotypes. Polysomy 7 and partial gains of 7p, including 7p11-p13 (site of the EGFR gene), were particularly frequent, occurring alone or in combination in 26 tumors. Recurrent losses involving 1p, 3p, 6q, 9p, 11p, 15p, and 17p (where the TP53 gene is located) were each seen in 16-25 cases. Five tumors exhibited double minutes, which were associated with amplified MYC1 (1 case) and EGFR (1 case), as determined by Southern analysis. The cytogenetic data were compiled from either short term cultures of tumor tissue harvested within 1-9 days (18 cases) or later harvests performed on long term cultures or cell lines (6 cases); in the other 6 cases results were obtained from both short term and long term cultures. Two studies were performed to validate the use of long term culture for cytogenetic analysis of solid lung tumors. First, in order to determine whether cytogenetic results from cultures are representative of the original tumor, the modal chromosome number of 13 specimens placed into culture was compared to the DNA index of the original tumor tissue, as measured by flow cytometry. The DNA indices of the solid tumor biopsies agreed with the degree of aneuploidy observed by cytogenetic analysis in every case. Second, in 6 cases we performed direct comparisons of karyotypes obtained from cells cultured by both methods. Identical chromosome abnormalities were detected in short term cultures and later harvests of the same specimen. Overall, our findings indicate that tumorigenesis in NSCLC is characterized by the accumulation of multiple chromosome alterations. Furthermore, these data demonstrate that recurrent cytogenetic changes can be identified in NSCLC and that detailed karyotypes from long term cultures are relevant to the original tumor. Chromosome abnormalities detected by these techniques may have clinical and biological significance. However, the complex pattern of karyotypic changes seen in newly diagnosed NSCLC emphasizes the need for future investigations of premalignant bronchial lesions in order to identify primary genetic changes important for early detection and intervention in this aggressive neoplasm.
Analytical Study of the Rotation Spreading Matrix of Block Spread OFDM with MMSE Equalization (2008)

This paper presents an analytical study on the new spreading matrix for block spread OFDM known as the rotation spreading matrix and simulates the BER performance in the MMSE equation. In (I. Raad et al., 2006) a new spreading matrix was presented for block spread OFDM (BSOFDM) known as the rotation spreading matrix. It was shown to greatly improve on the existing spreading matrices such as the Hadamard and the rotated Hadamard matrices in frequency selective channels such as the ultra wide band and slow fading channels. This paper studies the effect of increasing the block size in BSOFDM using this new matrix.
Design of a Bio-Inspired 3D Orientation Coordinate System and Application in Robotised Tele-Sonography (2011)

frame Fusion and mental representation in mental frame Aim Trajectory planning in mental frame Current state Generation of a reference trajectory in sensorimotor frame Integration in sensorymotor system (cortex) Kinesthetic proprioception Variation encoding Variation encoding Variation encoding Coordinates updating in proprioceptive frame muscles activation Target visual variation Variation encoding in visual frame Target variation Variation encoding in proprioceptive frame