gebhart/patrepeval huggingface dataset:
Mass Spectrometry Reveals Changes in MHC I Antigen Presentation After Lentivector Expression of a Gene Regulation System (2013)

The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I) molecules on transduced and wild-type (wt) cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.Molecular Therapy - Nucleic Acids (2013) 2, e75; doi:10.1038/mtna.2013.3; published online 12 February 2013.
Bacteremia in hematological and oncological children with febrile neutropenia: experience in a tertiary medical center in Taiwan. (2003)

A retrospective study of bacteremia in children with febrile neutropenia admitted to a medical center in Taiwan from January 1999 to December 1999 was performed. There were 190 episodes of febrile neutropenia during this period and 46 pathogens were isolated from blood specimens in 38 bacteremic episodes (7 mixed infections). Pseudomonas aeruginosa (17.4%), Staphylococcus aureus (10.9%), Klebsiella pneumoniae (10.9%), and Enterobacter cloacae (10.9%) were the most common isolates. Three of the 5 isolates of S. aureus were resistant to methicillin. Twenty-three episodes of bacteremia (four mixed infections) were associated with recent antibiotic use. Of the 23 bacteremic episodes with recent antibiotic use, P. aeruginosa (20%), methicillin-resistant S. aureus (10%), K. pneumoniae (10%), Escherichia coli (10%), and E. cloacae (10%) were isolated most often. Relapsed leukemia (odds ratio 3, 95% confidence interval 1.4-6.5) and recent antibiotic therapy (odds ratio 3.4, 95% confidence interval 1.7-7.7) were the independent risk factors of bacteremia. There were 9 mortality cases in patients with bacteremia, including 4 cases with mixed infections, and 5 cases with P. aeruginosa, E. coli, Klebsiella oxytoca, S. aureus, and Streptococcus mitis, respectively. Broad-spectrum antibiotics were necessary in febrile neutropenic children because of the high percentage of mixed infection.
Progestin regulation of alkaline phosphatase in the human breast cancer cell line T47D. (1991)

In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane-associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of the tissue-unspecific alkaline phosphatase was time and dose dependent. The protein synthesis inhibitor cycloheximide blocks the enzyme synthesis and tunicamycin blocks the enzyme activity, showing that the induction was new synthesis of protein in its complete glycosylated form and not activation of a preexisting enzyme. To our knowledge this is the first report of progesterone-induced expression of a tissue-unspecific alkaline phosphatase gene of such magnitude (about 30- to 100-fold) in a progesterone-responsive tissue.
Eight-channel p-i-n/HBT monolithic receiver array at 2.5 Gb/s per channel for WDM applications (1994)

We report a monolithic chip incorporating an eight channel p-i-n/HBT photoreceiver array designed for multichannel WDM applications. The p-i-n photodetectors are edge illuminated and centered at a 250 μm pitch for mating with either ribbon fiber connectors or waveguide demultiplexers. Each channel operates at 2.5 Gb/s with an electrical crosstalk of -20 dB between adjacent channels. The average sensitivity of each receiver in the array was measured to be (-20/spl plusmn/1) dBm for a bit error rate of 10/sup -9/ at a wavelength of 1.5 μm.
The cell biology of osteoclast function (2000)

Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.
MicroRNAs Modulate Hematopoietic Lineage Differentiation (2003)

MicroRNAs (miRNAs) are an abundant class of approximately 22-nucleotide regulatory RNAs found in plants and animals. Some miRNAs of plants, Caenorhabditis elegans, and Drosophila play important gene-regulatory roles during development by pairing to target mRNAs to specify posttranscriptional repression of these messages. We identify three miRNAs that are specifically expressed in hematopoietic cells and show that their expression is dynamically regulated during early hematopoiesis and lineage commitment. One of these miRNAs, miR-181, was preferentially expressed in the B-lymphoid cells of mouse bone marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue-culture differentiation assays and adult mice. Our results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.
Nucleation-dependent Tau Filament Formation (2008)

Filamentous inclusions composed of the microtubule-associated protein tau are found in Alzheimer disease and other tauopathic neurodegenerative diseases, but the mechanisms underlying their formation from full-length protein monomer under physiological conditions are unclear. To address this issue, the fibrillization of recombinant full-length four-repeat human tau was examined in vitro as a function of time and submicromolar tau concentrations using electron microscopy assay methods and a small-molecule inducer of aggregation, thiazine red. Data were then fit to a simple homogeneous nucleation model with rate constant constraints established from filament dissociation rate, critical concentration, and mass-per-unit length measurements. The model was then tested by comparing the predicted time-dependent evolution of length distributions to experimental data. Results indicated that once assembly-competent conformations were attained, the rate-limiting step in the fibrillization pathway was tau dimer formation. Filament elongation then proceeded by addition of tau monomers to nascent filament ends. Filaments isolated at reaction plateau contained approximately 2 tau protomers/beta-strand spacing on the basis of mass-per-unit length measurements. The model suggests four key steps in the aggregation pathway that must be surmounted for tau filaments to form in disease.
Detection of anthrax simulants with microcalorimetric spectroscopy: Bacillus subtilis and Bacillus cereus spores (2003)

Recent advances in the development of ultrasensitive micromechnical thermal detectors have led to the advent of novel subfemtojoule microcalorimetric spectoscopy (CalSpec). On the basis of principles of photothermal IR spectroscopy combined with efficient thermomechanical transduction, CalSpec provides acquisition of vibrational spectra of microscopic samples and absorbates. We use CalSpec as a method of identifying nanogram quantities of biological micro-organisms. Our studies focus on Bacillus subtilis and Bacillus cereus spores as simulants for Bacillus anthracis spores. Using CalSpec, we measured IR spectra of B. subtilis and B. cereus spores present on surfaces in nanogram quantities (approximately 100-1,000 spores). The spectra acquired in the wavelength range of 690-4000 cm(-1) (2.5-14.5 microm) contain information-rich vibrational signatures that reflect the different ratios of biochemical makeup of the micro-organisms. The distinctive features in the spectra obtained for the two types of microorganism can be used to distinguish between the spores of the Bacillus family. As compared with conventional IR and Fourier-transform IR microscopic spectroscopy techniques, the advantages of the present technique include significantly improved sensitivity (at least a full order of magnitude), absence of expensive IR detectors, and excellent potential for miniaturization.
Interactions between single-stranded DNA binding protein and oligonucleotide analogs with different backbone chemistries (1997)

Chemical modification of backbone structures has been an important strategy in designing oligonucleotides capable of improved antisense effects. However, altered backbone chemistry may also affect the binding of oligonucleotides to key cellular proteins, and thus may impact on the overall biological action of antisense agents. In this study we have examined the binding of oligonucleotides having four different backbone chemistries to single-strand binding protein (SSB), a protein having a key role in DNA repair and replication. The oligomers tested had the same sequence, while the internucleoside linkages were phosphodiester (PO), phosphorothioate (PS), phosphorodithioate (PS2), or methylphosphonate (MP). We found that both PS and PS2 oligomers bound to SSB with higher affinity than PO oligonucleotides, while MP oligonucleotides did not bind appreciably at the concentrations tested. Oligonucleotide length was also an important factor in binding to SSB, but sequence was less critical. These observations indicate that backbone chemistry is an important factor in interactions between oligonucleotides and critical cellular proteins, and thus may be a key determinant of the biological effects of antisense oligonucleotides.
'Disappearing Sensor'-Textile Based Sensor for Monitoring Breathing (2011)

Textile based sensors were developed and used for remote monitoring of breathing. The breathing is simulated by using a new cyclic tester device. In the simulated a cyclic force is applied along the length of the textile sensor. However due to the morphology of human body, in real situation the sensor is not only under stretching but also under a certain degree of bending. A prototype garment with the sensor situated on the chest area was made. The prototype was worn by 10 persons, and breathing was recorded as the persons were sitting still, walking and jogging. Deep breathing in the supine position and breathing with a method called athletic breathing were used to evaluate the sensor. A testing circuit and a Labview program were made for preliminary test. The sensor is wearable, washable and comfortable. Sensor construction is totally 'disappearing' and visualize as printed pattern onto the surface of garment.
Hypergastrinaemia in Helicobacter Pylori Infection: In Vitro Effects of H. Pylori Products and Inflammatory Cytokines on Gastrin Release (1996)

Conference Abstract| February 01 1996 Hypergastrinaemia in Helicobacter Pylori Infection: In Vitro Effects of H. Pylori Products and Inflammatory Cytokines on Gastrin Release ILP Beales; ILP Beales *∞ Vanderbilt University, TN, USA#Department of Gastroenterology, RPMS, London Search for other works by this author on: This Site PubMed Google Scholar M Blaser; M Blaser *∞ Vanderbilt University, TN, USA Search for other works by this author on: This Site PubMed Google Scholar L Post; L Post *University of Michigan, Ann Arbor, USA Search for other works by this author on: This Site PubMed Google Scholar J Park; J Park *University of Michigan, Ann Arbor, USA Search for other works by this author on: This Site PubMed Google Scholar T Yamada; T Yamada *University of Michigan, Ann Arbor, USA Search for other works by this author on: This Site PubMed Google Scholar J Del Valle; J Del Valle *University of Michigan, Ann Arbor, USA Search for other works by this author on: This Site PubMed Google Scholar J Calam J Calam #Department of Gastroenterology, RPMS, London Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1996) 90 (s34): 1P. https://doi.org/10.1042/cs090001P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation ILP Beales, M Blaser, L Post, J Park, T Yamada, J Del Valle, J Calam; Hypergastrinaemia in Helicobacter Pylori Infection: In Vitro Effects of H. Pylori Products and Inflammatory Cytokines on Gastrin Release. Clin Sci (Lond) 1 February 1996; 90 (s34): 1P. doi: https://doi.org/10.1042/cs090001P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1996 The Biochemical Society and the Medical Research Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
Kohlenhydratmimetika: ein neuer Lösungsansatz für das Problem der kohlenhydratvermittelten biologischen Erkennung (1999)

Zahlreiche nützliche Strategien für das Design von Molekülen, die Kohlenhydrate nachahmen, wurden in den letzten Jahren entwickelt. Mimetika der Targets können neue funktionelle Gruppen und/oder neue Gerüste enthalten (in der schematischen Darstellung ist der natürliche Ligand links und der modifizierte rechts gezeigt). Es liegen bislang viele Beispiele für Kohlenhydratmimetika vor, die Zucker-Protein- und Zucker-Nucleinsäure-Wechselwirkungen effizient stören.
Molecular Dissection of the α-Dystroglycan- and Integrin-binding Sites within the Globular Domain of Human Laminin-10 (2004)

The adhesive interactions of cells with laminins are mediated by integrins and non-integrin-type receptors such as alpha-dystroglycan and syndecans. Laminins bind to these receptors at the C-terminal globular domain of their alpha chains, but the regions recognized by these receptors have not been mapped precisely. In this study, we sought to locate the binding sites of laminin-10 (alpha5beta1gamma1) for alpha(3)beta(1) and alpha(6)beta(1) integrins and alpha-dystroglycan through the production of a series of recombinant laminin-10 proteins with deletions of the LG (laminin G-like) modules within the globular domain. We found that deletion of the LG4-5 modules did not compromise the binding of laminin-10 to alpha(3)beta(1) and alpha(6)beta(1) integrins but completely abrogated its binding to alpha-dystroglycan. Further deletion up to the LG3 module resulted in loss of its binding to the integrins, underlining the importance of LG3 for integrin binding by laminin-10. When expressed individually as fusion proteins with glutathione S-transferase or the N-terminal 70-kDa region of fibronectin, only LG4 was capable of binding to alpha-dystroglycan, whereas neither LG3 nor any of the other LG modules retained the ability to bind to the integrins. Site-directed mutagenesis of the LG3 and LG4 modules indicated that Asp-3198 in the LG3 module is involved in the integrin binding by laminin-10, whereas multiple basic amino acid residues in the putative loop regions are involved synergistically in the alpha-dystroglycan binding by the LG4 module.
Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. (1994)

(1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.
The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease (1993)

Several variants of the beta amyloid protein, differing only at their carboxy terminus (beta 1-39, beta 1-40, beta 1-42, and beta 1-43), have been identified as the major components of the cerebral amyloid deposits which are characteristic of Alzheimer's disease. Kinetic studies of aggregation by three naturally occurring beta protein variants (beta 1-39, beta 1-40, beta 1-42) and four model peptides (beta 26-39, beta 26-40, beta 26-42, beta 26-43) demonstrate that amyloid formation, like crystallization, is a nucleation-dependent phenomenon. This discovery has practical consequences for studies of the beta amyloid protein. The length of the C-terminus is a critical determinant of the rate of amyloid formation ("kinetic solubility") but has only a minor effect on the thermodynamic solubility. Amyloid formation by the kinetically soluble peptides (e.g., beta 1-39, beta 1-40, beta 26-39, beta 26-40) can be nucleated, or "seeded", by peptides which include the critical C-terminal residues (beta 1-42, beta 26-42, beta 26-43, beta 34-42). These results suggest that nucleation may be the rate-determining step of in vivo amyloidogenesis and that beta 1-42 and/or beta 1-43, rather than beta 1-40, may be the pathogenic protein(s) in AD.
Are contemporary methods for somatic gene therapy suitable for clinical applications? (1993)

Clinical trials involving the introduction of recombinant genes into human subjects began in 1989 after a decade of earnest debate concerning the technical, social, and ethical implications of somatic gene therapy. The initial trials involved the introduction of recombinant genes into peripheral blood lymphocytes to study the characteristics of tumor infiltrating lymphocytes, enhance immunotherapy for cancer, and treat severe combined immunodeficiency due to adenosine deaminase deficiency. Additional clinical trials involving the introduction of genes into bone marrow, hepatocytes, and tumor cells are underway. Are these clinical trials premature? This article reviews basic methods for somatic gene therapy and the clinical trials which have been proposed or performed to date. This clinical experience suggests that gene therapy can be performed in select clinical trials safely and with public acceptance. Clinical trials have provided essential data concerning the feasibility and safety of gene transfer in human subjects. These trials have also brought a clinical focus to the assessment of technologies currently being used in experimental models. While there will certainly be significant advances in somatic gene therapy in the future, existing methods may be employed fairly in clinical trials.
DeepTox: Toxicity Prediction using Deep Learning (2016)

The Tox21 Data Challenge has been the largest effort of the scientific community to compare computational methods for toxicity prediction. This challenge comprised 12,000 environmental chemicals and drugs which were measured for 12 different toxic effects by specifically designed assays. We participated in this challenge to assess the performance of Deep Learning in computational toxicity prediction. Deep Learning has already revolutionized image processing, speech recognition, and language understanding but has not yet been applied to computational toxicity. Deep Learning is founded on novel algorithms and architectures for artificial neural networks together with the recent availability of very fast computers and massive datasets. It discovers multiple levels of distributed representations of the input, with higher levels representing more abstract concepts. We hypothesized that the construction of a hierarchy of chemical features gives Deep Learning the edge over other toxicity prediction methods. Furthermore, Deep Learning naturally enables multi-task learning, that is, learning of all toxic effects in one neural network and thereby learning of highly informative chemical features.In order to utilize Deep Learning for toxicity prediction, we have developed the DeepTox pipeline. First, DeepTox normalizes the chemical representations of the compounds. Then it computes a large number of chemical descriptors that are used as input to machine learning methods. In its next step, DeepTox trains models, evaluates them, and combines the best of them to ensembles. Finally, DeepTox predicts the toxicity of new compounds. In the Tox21 Data Challenge, DeepTox had the highest performance of all computational methods winning the grand challenge, the nuclear receptor panel, the stress response panel, and six single assays (teams ``Bioinf@JKU''). We found that Deep Learning excelled in toxicity prediction and outperformed many other computational approaches like naive Bayes, support vector machines, and random forests.
Characterization of the Nucleocytoplasmic Shuttle of the Matrix Protein of Influenza B Virus (2014)

This study expands our understanding of the life cycle of influenza B virus by defining the dynamic mechanism of the nucleocytoplasmic shuttle of BM1 and could provide a scientific basis for the development of antiviral medication.