gebhart/patrepeval huggingface dataset:
Enhanced and prolonged cross‐presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles (2005)

CD8(+) T-cell responses are critical in the immunological control of tumours and infectious diseases. To prime CD8(+) T cells against these cell-associated antigens, exogenous antigens must be cross-presented by professional antigen-presenting cells (APCs). While cross-presentation of soluble antigens by dendritic cells is detectable in vivo, the efficiency is low, limiting the clinical utility of protein-based vaccinations. To enhance the efficiency of presentation, we generated nanoparticles from a biodegradable polymer, poly(D,L-lactide-co-glycolide) (PLGA), to deliver antigen into the major histocompatibility complex (MHC) class I antigen presentation pathway. In primary mouse bone marrow-derived dendritic cells (BMDCs), the MHC class I presentation of PLGA-encapsulated ovalbumin (OVA) stimulated T cell interleukin-2 secretion at 1000-fold lower concentration than soluble antigen and 10-fold lower than antigen-coated latex beads. The microparticles also served as an intracellular antigen reservoir, leading to sustained MHC class I presentation of OVA for 72 hr, decreasing by only 20% after 96 hr, a time at which the presentation of soluble and latex bead-associated antigens was undetectable. Cytosol extraction demonstrated that antigen delivery via PLGA particles increased the amount of protein that escaped from endosomes into the cytoplasm, thereby increasing the access of exogenous antigen to the classic MHC class I loading pathway. These data indicate that the unique properties of PLGA particle-mediated antigen delivery dramatically enhance and sustain exogenous antigen presentation by MHC class I, potentially facilitating the clinical use of these particles in vaccination.
Substituted 2-Imino-5-arylidenethiazolidin-4-one Inhibitors of Bacterial Type III Secretion (2008)

Diverse species of pathogenic Gram-negative bacteria use secretion systems to export a variety of protein toxins and virulence factors that help establish and maintain infection. Disruption of such secretion systems is a potentially effective therapeutic strategy. We developed a high-throughput screen and identified a tris-aryl substituted 2-imino-5-arylidenethiazolidin-4-one, compound 1, as an inhibitor of the type III secretion system. Expansion of this chemotype enabled us to define the essential pharmacophore for type III secretion inhibition by this structural class. A synthetic diversity set helped us identify N-3 as the most permissive locus and led to the design of a panel of novel N-3-dipeptide-modified congeners with improved activity and physiochemical properties. We now report on the synthesis of these compounds, including a novel solid phase approach to the rapid generation of the dipeptide-thiazolidinone hybrids, and their in vitro characterization as inhibitors of type III secretion in Salmonella enterica serovar Typhimurium.
Genetic background modifies neurodegeneration and neuroinflammation driven by misfolded human tau protein in rat model of tauopathy: implication for immunomodulatory approach to Alzheimer's disease (2010)

These results show that the immune response represents a pivotal and genetically variable modifying factor that is able to influence vulnerability to neurodegeneration. Therefore, targeted immunomodulation could represent a prospective therapeutic approach to Alzheimer's disease.
Type‐C Natriuretic Peptide Prevents Development Of Experimental Atherosclerosis In Rabbits (2000)

1. We investigated the effect of local administration of type-C natriuretic peptide (CNP) on the endothelial dysfunction and development of an atheroma-like neointima induced by a peri-arterial collar in rabbits. 2. Peri-arterial collars were placed on both common carotid arteries allowing local treatment of the collared region with either CNP (10 micromol/L) or saline. After 7 days, uncollared (control) and collared sections were taken from both arteries for pharmacological and morphological analysis. 3. Application of the collar markedly attenuated (P < 0.05) endothelium-dependent vasorelaxation induced by acetylcholine (ACh); inhibition of 5-hydroxytryptamine contraction was 80+/-5% in control sections compared with 44+/-4% in collared sections from the same arteries. Local infusion of CNP (10 micromol/L) into the collar restored ACh-induced vasorelaxation (74+/-3% from collared arteries + CNP vs 77+/-2% from control sections from the same arteries). 4. Type-C natriuretic peptide treatment also reduced (P < 0.05) intimal thickening compared with contralateral collared arteries (intima/media ratio 0.06+/-0.01 vs 0.16+/-0.01). 5. These results provide evidence that locally administered CNP is effective in preventing the endothelial dysfunction and development of a neointima in this model.
Imperialism and Colonialism – Essays on the History of European ExpansionH. W. Wesseling Greenwood Press, Westport, Connecticut, USA1997 (x + 212 pages) £47.50, hardback, ISBN 0-313-30431-9. Distributed by the European Group, London. (1999)

Imperialism and Colonialism – Essays on the History of European ExpansionH. W. Wesseling Greenwood Press, Westport, Connecticut, USA1997 (x + 212 pages) £47.50, hardback, ISBN 0-313-30431-9. Distributed by the European Group, London. - Volume 7 Issue 1
Measurement of ligand-receptor interactions. (1991)

One distinguishing feature of "life" is that the physical forces between biological molecules and membrane surfaces are often highly specific, in contrast to nonspecific interactions such as van der Waals, hydrophobic, and electrostatic (Coulombic) forces. We have used the surface-forces-apparatus technique to study the specific "lock and key" or "ligand-receptor" interaction between two model biomembrane surfaces in aqueous solution. The membranes were lipid bilayers supported on mica surfaces; one carrying streptavidin receptors, the other exposing biotin ligand groups. We found that, although no unusual or specific interaction occurs between two avidin or two biotin surfaces, an avidin and a biotin surface exhibit a very strong, very short-range (less than 1 nm) attraction and that the binding mechanism involves equally specific molecular rearrangements. The results also show that highly specific biological interactions such as are involved in immunological recognition and cell-cell contacts may be studied at the molecular level and in real time by the surface-forces-apparatus technique.
Increased expression of interleukin 17 in inflammatory bowel disease (2002)

IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.
Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). (1990)

Adhesive interactions between lymphocyte cell-surface receptors and components of the vascular endothelium and the extracellular matrix play an important role in the control of lymphocyte migration and homing. To investigate whether lymphocyte adhesion molecules involved in the migration of normal lymphocytes, i.e., CD44 homing receptor, LFA-1 (CD11a/18), and ICAM-1 (CD54), also play a role in the spread and hence in the disease course of non-Hodgkin's lymphomas (NHL), expression of these molecules was examined in 78 cases of diffuse large-cell lymphoma. Other potential risk factors considered in this study were sex, age, primary tumor localization, lineage (T cell vs. B cell), and histopathological subtype. 27 of 53 (51%) patients with a lymphoma having a high CD44 antigen expression showed tumor spread beyond stage II at diagnosis while this was the case in only three of 25 (12%) patients with lymphomas that were CD44 low/negative (chi-square 25.4, p less than 0.001). Similarly, poor response to treatment, i.e., absence of remission or relapse, and or death from lymphoma, was more common among patients with lymphomas expressing high levels of CD44; actuarial survival among patients with CD44 high and low lymphomas was 47% and 91%, respectively (Mantel-Cox 6.1, p = 0.02). Neither LFA-1 nor ICAM-1 expression showed a significant correlation to lymphoma dissemination or disease course. Of the other factors considered, T cell phenotype was associated with an unfavorable prognosis while nodal localization was a risk factor for dissemination. Taken together, our findings suggest that CD44 antigen expression plays an important role in the dissemination of NHL and via this mechanism exerts an unfavorable prognostic influence.
Development of anti-MUC1 DNA aptamers for the imaging and radiotherapy of breast cancer (2006)

Background Epidemiological studies have shown that only about 20% of the familial clustering of breast cancer is explained by the known highly penetrant mutations in BRCA1 and BCRA2. We have set out to search for the genes for the remaining 80%. Twin studies indicate a predominant role of shared genes rather than a shared environment; the patterns of occurrence of breast cancer in families are consistent with a major polygenic component. Methods We have assembled a population based set of 5,000 breast cancer cases and 5,000 controls from the East Anglian population. We have simple clinical and epidemiological information, including family history, and samples of blood and paraffin embedded tumour. We have used association studies based on single nucleotide polymorphisms, first with candidate genes and then in a genome-wide scan of 266,000 single nucleotide polymorphisms, to search for the putative predisposing genes. We have as yet searched only for common variants (frequency >5%).
Pharmaceutical Particle Engineering via Spray Drying (2007)

This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based on a better understanding of particle formation in the spray drying process. Microparticles with nanoscale substructures can now be designed and their functionality has contributed significantly to stability and efficacy of the particulate dosage form. The review provides concepts and a theoretical framework for particle design calculations. It reviews experimental research into parameters that influence particle formation. A classification based on dimensionless numbers is presented that can be used to estimate how excipient properties in combination with process parameters influence the morphology of the engineered particles. A wide range of pharmaceutical application examples -- low density particles, composite particles, microencapsulation, and glass stabilization -- is discussed, with specific emphasis on the underlying particle formation mechanisms and design concepts.
PROGRAMA EXTERNO DE MAESTRIA EN ADMINISTRACION (1984)

DURANTE LA CEREMONIA EN QUE SE LLEVO AL CABO LA ENTREGA DE RECONOCIMIENTOS A LA PRIMERA GENERACION DE ALUMNOS QUE TERMINARON SUS ESTUDIOS DE MAESTRIA EN ADMINISTRACION, EL CP ALFREDO ADAM ADAM, DIRECTOR DE LA FACULTAD DE CONTADURIA Y ADMINISTRACION, MANIFESTO QUE EL PROGRAMA EXTERNO DE MAESTRIA EN ADMINISTRACION ES UNO DE LOS AMBICIOSOS PLANES QUE SE HA PROPUESTO LA UNAM. LO ANTERIOR FUE LOGRADO GRACIAS A LA COLABORACION ENTRE ESTA CASA DE ESTUDIOS Y LA SECRETARIA DE PROGRAMACION Y PRESUPUESTO, ACTO QUE FUE PRESIDIDO POR LA LICENCIADA MARCELA GONZALEZ PETRICCIOLI, OFICIAL MAYOR DE LA SPP; EL LICENCIADO RICARDO VARELA, JEFE DE LA DIVISION DE ESTUDIOS DE POSGRADO DE LA FCA; EL LICENCIADO PABLO BEDOLLO LOPEZ, DIRECTOR DE PLANEACION Y DESAROLLO DE LA SPP, Y EL INGENIERO ANTONIO RODRIGUEZ, DIECTOR GENERAL DEL PERSONAL DE ESA DEPENDENCIA. LA CELEBRACION SE REALIZO EL PASADO 9 DE DICIEMBRE EN EL SALON EL GENERALITO, ANTIGUO EDIFICIO DE SAN ILDEFONSO.
The severity of dependence score correlates with medication overuse in persons with secondary chronic headaches. The Akershus study of chronic headache (2010)

The objective was to compare the Severity of Dependence Scale (SDS) score and pattern of medication use in persons with secondary chronic headache (>or= 15 days/month for at least 3 months) in a cross-sectional epidemiological survey. A posted questionnaire screened for chronic headache. Neurological residents interviewed those with self-reported chronic headache. The International Classification of Headache Disorders was used. Split file methodology was employed for data analysis. People with secondary chronic headaches were identified in an age and gender stratified sample of 30,000 30-44 year olds from the general population. The interviews and examinations were conducted at the Akershus University Hospital, Oslo, Norway. The main outcome measure was the SDS score in those with and without medication overuse. Fifty-five (49%) of the 113 persons with secondary chronic headaches were found to have medication overuse. Fifty-eight percent overused simple analgesics and 31% overused combination analgesics. The SDS score was significantly higher among those with than without medication overuse (5.5 vs. 1.9). The sensitivity, specificity, positive and negative predictive values were 0.82, 0.82, 0.82 and 0.83, respectively. Thus the SDS score correlates with medication overuse, and a high SDS score suggests dependency-like behaviour in persons with secondary chronic headache. The use of SDS score in subjects with frequent pain episodes may contribute to the detection of medication overuse and better management of this group of patients.
Entry and uncoating of enveloped viruses (1994)

Research Article| September 01 1994 Entry and uncoating of enveloped viruses M Lanzrein; M Lanzrein *Institute for Cancer Research, Department of Biochemistry, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway Search for other works by this author on: This Site PubMed Google Scholar A Schlegel; A Schlegel †University of Colorado at Boulder, Department of Molecular, Cellular and Developmental Biology, Campus Box 347, Boulder, CO 80309-0347, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar C Kempf C Kempf ‡Institute of Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland§Central Laboratory, Blood Transfusion Service, Swiss Red Cross, Wankdorfstrasse 10, 3000 Bern 22, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1994) 302 (2): 313–320. https://doi.org/10.1042/bj3020313 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 M Lanzrein, A Schlegel, C Kempf; Entry and uncoating of enveloped viruses. Biochem J 1 September 1994; 302 (2): 313–320. doi: https://doi.org/10.1042/bj3020313 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 JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1994 The Biochemical Society, London1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Ink-jet printed nanoparticle microelectromechanical systems (2002)

Reports a method to additively build three-dimensional (3-D) microelectromechanical systems (MEMS) and electrical circuitry by ink-jet printing nanoparticle metal colloids. Fabricating metallic structures from nanoparticles avoids the extreme processing conditions required for standard lithographic fabrication and molten-metal-droplet deposition. Nanoparticles typically measure 1 to 100 nm in diameter and can be sintered at plastic-compatible temperatures as low as 300/spl deg/C to form material nearly indistinguishable from the bulk material. Multiple ink-jet print heads mounted to a computer-controlled 3-axis gantry deposit the 10% by weight metal colloid ink layer-by-layer onto a heated substrate to make two-dimensional (2-D) and 3-D structures. We report a high-Q resonant inductive coil, linear and rotary electrostatic-drive motors, and in-plane and vertical electrothermal actuators. The devices, printed in minutes with a 100 /spl mu/m feature size, were made out of silver and gold material with high conductivity,and feature as many as 400 layers, insulators, 10:1 vertical aspect ratios, and etch-released mechanical structure. These results suggest a route to a desktop or large-area MEMS fabrication system characterized by many layers, low cost, and data-driven fabrication for rapid turn-around time, and represent the first use of ink-jet printing to build active MEMS.
Improving the usability of the hierarchical file system (2003)

Whether you are interested in improving the usability of Linux, Macintosh or Windows, there is one restriction you cannot escape -- the hierarchical file storage system. The notion of files and folders has been with us for so long that it almost seems axiomatic. In this paper we look at the effects on users of forcing a hierarchical classification of files. We also consider how some of the resultant problems can be tackled with a new piece of file browsing software based on the ideas of relational database systems.
Chitinase-like Proteins are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury (2012)

Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36-48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI.
Differential Effects of AAV.BDNF and AAV.Ntf3 in the Deafened Adult Guinea Pig Ear (2015)

Cochlear hair cell loss results in secondary regression of peripheral auditory fibers (PAFs) and loss of spiral ganglion neurons (SGNs). The performance of cochlear implants (CI) in rehabilitating hearing depends on survival of SGNs. Here we compare the effects of adeno-associated virus vectors with neurotrophin gene inserts, AAV.BDNF and AAV.Ntf3, on guinea pig ears deafened systemically (kanamycin and furosemide) or locally (neomycin). AAV.BDNF or AAV.Ntf3 was delivered to the guinea pig cochlea one week following deafening and ears were assessed morphologically 3 months later. At that time, neurotrophins levels were not significantly elevated in the cochlear fluids, even though in vitro and shorter term in vivo experiments demonstrate robust elevation of neurotrophins with these viral vectors. Nevertheless, animals receiving these vectors exhibited considerable re-growth of PAFs in the basilar membrane area. In systemically deafened animals there was a negative correlation between the presence of differentiated supporting cells and PAFs, suggesting that supporting cells influence the outcome of neurotrophin over-expression aimed at enhancing the cochlear neural substrate. Counts of SGN in Rosenthal's canal indicate that BDNF was more effective than NT-3 in preserving SGNs. The results demonstrate that a transient elevation in neurotrophin levels can sustain the cochlear neural substrate in the long term.
Rate-distortion speech coding with a minimum discrimination information distortion measure (1981)

An information theory approach to the theory and practice of linear predictive coded (LPC) speech compression systems is developed. It is shown that a traditional LPC system can be viewed as a minimum distortion or nearest-neighbor system where the distortion measure is a minimum discrimination information between a speech process model and an observed frame of actual speech. This distortion measure is used in an algorithm for computer-aided design of block source codes subject to a fidelity criterion to obtain a 750-bits/s speech compression system that resembles an LPC system but has a much lower rate, a larger memory requirement, and requires no on-line LPC analysis. Quantitative and informal subjective comparisons are made among our system and LPC systems.
Inflammation and Coagulation: Implications for the Septic Patient (2003)

Sepsis with acute organ dysfunction (severe sepsis) is common, frequently fatal, and associated with a significant national health/economic burden. In addition to standard care, investigators have focused on interrupting the inflammatory and anti-inflammatory cascade associated with this disease. Unfortunately, despite promising preclinical results, interventions directed at the inflammatory elements have not reduced the morbidity and mortality associated with this disease. Inflammation and coagulation are tightly linked. In fact, sepsis-associated coagulopathy is almost universal in patients with severe sepsis. Preclinical observations indicate that antithrombotic-targeted therapy has the potential to reduce morbidity and mortality in patients with this disease. Treatment with recombinant human activated protein C (drotrecogin alpha [activated]) was the first antithrombotic-targeted therapy to significantly reduce 28-day all-cause mortality in patients with severe sepsis. The pathophysiological and clinical significance of this evidence and the relationship of coagulation to inflammation are discussed, as are positive and negative results of clinical trials of antithrombotic therapy.
Genome Architecture and Its Roles in Human Copy Number Variation (2014)

Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.