gebhart/patrepeval huggingface dataset:
Direct demonstration in intestinal secretions of an IgA memory response to orally administered Shigella flexneri antigens. (1982)

Abstract In the present studies our previously characterized, isolated intestinal loop model in rabbits was used to follow kinetically the local IgA immune response of the intestine and to determine whether a local (IgA) memory response could be elicited after peroral immunization with S. flexneri antigens. Nineteen rabbits received 1010 live S. flexneri strain X16 (hybrid of S. flexneri and E. coli) orally on the day after surgical creation of the isolated ileal loop. The isolated intestinal loops were never exposed directly to the shigella antigens, and shigella were not cultured from these loops. The kinetics of the local IgA response (detected by enzyme-linked immunosorbent assay) in daily secretions from these isolated loops paralleled the IgA responses we described previously when the isolated loops were directly immunized with S. flexneri strain X16. These findings are consistent with the known recirculation of sensitized gut-associated lymphoid cells to other (not directly stimulated) mucosal surfaces. A group of 10 rabbits that did not have chronically isolated ileal loops were given three weekly peroral doses of 1010 live S. flexneri strain X16 and then were allowed to rest for 60 days after the third oral immunization. At this point, chronically isolated loops were created, and a single oral challenge with 1010 live S. flexneri strain X16 was given. A striking IgA memory response was found in secretions from this group of rabbits. No such memory response was seen when killed shigella were used to prime and challenge the rabbits. These studies provide conclusive data that peroral immunization will produce a local IgA anamestic response.
Selective N-alkylation of anilines in ionic liquids (2005)

A simple and efficient method for the preparation of N-monoalkyl-substituted anilines employing ionic liquids (ILs) as the solvent is presented. The reactions have been performed in several ionic liquids using differently substituted anilines as substrates and alkyl, allyl and benzyl halides as alkylating agents in order to establish the factors that affect the reactivity and the chemoselectivity of the N-alkylation process.
Whole-Genome Analysis of the Methyl tert -Butyl Ether-Degrading Beta-Proteobacterium Methylibium petroleiphilum PM1 (2006)

Methylibium petroleiphilum PM1 is a methylotroph distinguished by its ability to completely metabolize the fuel oxygenate methyl tert-butyl ether (MTBE). Strain PM1 also degrades aromatic (benzene, toluene, and xylene) and straight-chain (C(5) to C(12)) hydrocarbons present in petroleum products. Whole-genome analysis of PM1 revealed an approximately 4-Mb circular chromosome and an approximately 600-kb megaplasmid, containing 3,831 and 646 genes, respectively. Aromatic hydrocarbon and alkane degradation, metal resistance, and methylotrophy are encoded on the chromosome. The megaplasmid contains an unusual t-RNA island, numerous insertion sequences, and large repeated elements, including a 40-kb region also present on the chromosome and a 29-kb tandem repeat encoding phosphonate transport and cobalamin biosynthesis. The megaplasmid also codes for alkane degradation and was shown to play an essential role in MTBE degradation through plasmid-curing experiments. Discrepancies between the insertion sequence element distribution patterns, the distributions of best BLASTP hits among major phylogenetic groups, and the G+C contents of the chromosome (69.2%) and plasmid (66%), together with comparative genome hybridization experiments, suggest that the plasmid was recently acquired and apparently carries the genetic information responsible for PM1's ability to degrade MTBE. Comparative genomic hybridization analysis with two PM1-like MTBE-degrading environmental isolates (approximately 99% identical 16S rRNA gene sequences) showed that the plasmid was highly conserved (ca. 99% identical), whereas the chromosomes were too diverse to conduct resequencing analysis. PM1's genome sequence provides a foundation for investigating MTBE biodegradation and exploring the genetic regulation of multiple biodegradation pathways in M. petroleiphilum and other MTBE-degrading beta-proteobacteria.
Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray. (2001)

Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS.
Upregulated NLRP3 Inflammasome Activation in Patients With Type 2 Diabetes (2012)

Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients. In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-naïve patients with newly diagnosed type 2 diabetes. Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). Mitochondrial reactive oxygen species and NLRP3 were required for IL-1β synthesis in MDMs. Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1β in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation. Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.
Innovative Therapeutic Strategies for Cystic Fibrosis: Moving Forward to CRISPR Technique (2018)

One of the most revolutionary technologies in recent years in the field of molecular biology is CRISPR-Cas9. CRISPR technology is a promising tool for gene editing that provides researchers the opportunity to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases. Cystic fibrosis (CF) is one of the most common lethal genetic diseases caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Although CF is an old acquaintance, there is still no effective/resolutive cure. Life expectancy has improved thanks to the combination of various treatments, but it is generally below average. Recently, a significant number of additional key medications have become licensed in Europe for the CF treatment including CFTR modulators. But innovative genomically-guided therapies have begun for CF and it is predictable that this will lead to rapid improvements in CF clinical disease and survival in the next decades. In this way, CRISPR-Cas9 approach may represent a valid tool to repair the CFTR mutation and hopeful results were obtained in tissue and animal models of CF disease.
Vitamin K epoxide reductase significantly improves carboxylation in a cell line overexpressing factor X (2005)

Previously we reported that we could increase the fraction of carboxylated factor X by reducing the affinity of the propeptide for its binding site on human gamma glutamyl carboxylase. We attributed this to an increased turnover rate. However, even with the reduced affinity propeptide, when sufficient overproduction of factor X is achieved, there is still a significant fraction of uncarboxylated recombinant factor X. We report here that the factor X of such a cell line was only 52% carboxylated but that the fraction of carboxylated factor X could be increased to 92% by coexpressing the recently identified gene for vitamin K epoxide reductase. Because vitamin K is in excess in both the untransfected and vitamin K epoxide reductase (VKOR)-transfected cells, the simplest explanation for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition to its mechanistic relevance, this observation has practical implications for overproducing recombinant vitamin K-dependent proteins for therapeutic use.
A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B (1997)

There is compelling evidence that members of the caspase (interleukin-1beta converting enzyme/CED-3) family of cysteine proteases and the cytotoxic lymphocyte-derived serine protease granzyme B play essential roles in mammalian apoptosis. Here we use a novel method employing a positional scanning substrate combinatorial library to rigorously define their individual specificities. The results divide these proteases into three distinct groups and suggest that several have redundant functions. The specificity of caspases 2, 3, and 7 and Caenorhabditis elegans CED-3 (DEXD) suggests that all of these enzymes function to incapacitate essential homeostatic pathways during the effector phase of apoptosis. In contrast, the optimal sequence for caspases 6, 8, and 9 and granzyme B ((I/L/V)EXD) resembles activation sites in effector caspase proenzymes, consistent with a role for these enzymes as upstream components in a proteolytic cascade that amplifies the death signal.
Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities (2001)

Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.
NMDA Receptor Losses in Putamen from Patients with Huntington's Disease (1988)

N-Methyl-D-aspartate (NMDA), phencyclidine (PCP), and quisqualate receptor binding were compared to benzodiazepine, gamma-aminobutyric acid (GABA), and muscarinic cholinergic receptor binding in the putamen and cerebral cortex of individuals with Huntington's disease (HD). NMDA receptor binding was reduced by 93 percent in putamen from HD brains compared to binding in normal brains. Quisqualate and PCP receptor binding were reduced by 67 percent, and the binding to other receptors was reduced by 55 percent or less. Binding to these receptors in the cerebral cortex was unchanged in HD brains. The results support the hypothesis that NMDA receptor-mediated neurotoxicity plays a role in the pathophysiology of Huntington's disease.
Bonding Organics to Ti Alloys:  Facilitating Human Osteoblast Attachment and Spreading on Surgical Implant Materials (2002)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Bonding Organics to Ti Alloys: Facilitating Human Osteoblast Attachment and Spreading on Surgical Implant MaterialsEllen S. Gawalt, Michael J. Avaltroni, Michael P. Danahy, Brett M. Silverman, Eric L. Hanson, Kim S. Midwood, Jean E. Schwarzbauer, and Jeffrey SchwartzView Author Information Department of Chemistry, Princeton University, Princeton, New Jersey 08544-1009, and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014 Cite this: Langmuir 2003, 19, 1, 200–204Publication Date (Web):December 4, 2002Publication History Received10 April 2002Revised20 August 2002Published online4 December 2002Published inissue 1 January 2003https://pubs.acs.org/doi/10.1021/la0203436https://doi.org/10.1021/la0203436brief-reportACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views1140Altmetric-Citations108LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cell physiology,Crystals,Organophosphorus compounds,Oxides,Thin films Get e-Alerts
Two Cellobiohydrolase-Encoding Genes from Aspergillus niger Require d -Xylose and the Xylanolytic Transcriptional Activator XlnR for Their Expression (1999)

Two cellobiohydrolase-encoding genes, cbhA and cbhB, have been isolated from the filamentous fungus Aspergillus niger. The deduced amino acid sequence shows that CbhB has a modular structure consisting of a fungus-type cellulose-binding domain (CBD) and a catalytic domain separated by a Pro/Ser/Thr-rich linker peptide. CbhA consists only of a catalytic domain and lacks a CBD and linker peptide. Both proteins are homologous to fungal cellobiohydrolases in family 7 of the glycosyl hydrolases. Northern blot analysis showed that the transcription of the cbhA and cbhB genes is induced by D-xylose but not by sophorose and, in addition, requires the xylanolytic transcriptional activator XlnR.
Total Parenteral Nutrition Induced Liver Pathology: An Autopsy Series of 24 Newborn Cases (2004)

Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale-New Haven Children's Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher's exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes ( n = 16), and the group with moderate-to-severe liver changes ( n = 8). On the other hand, DTPN was significantly different between these two groups ( P = 0.008). Also, patients small for gestational age ( P = 0.003) and patients with bronchopulmonary dysplasia ( P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings ( P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.
Meningococcal lipopolysaccharides: virulence factor and potential vaccine component (1993)

Lipopolysaccharides (LPS) are surface components of the outer membrane of Neisseria meningitidis. Today, 12 different types of meningococcal LPS (immunotypes) are known, of which 3 are prevalent in the western world. The differences between these immunotypes are in the oligosaccharide part of the LPS molecule and consist of small differences in the oligosaccharide structure, the amount and location of phosphoethanolamine groups, and the degree of O acetylation of individual monosaccharides. Although the differences between the various immunotypes are small, they have a profound influence on the immunochemical and immunological properties of these molecules. Furthermore, each individual strain synthesizes a number of different LPS molecules. The expression of the various components (protective epitopes) is influenced by growth conditions and growth phase. Meningococci can endogenously sialyate their LPS, which constitutes one of the mechanisms by which N. meningitidis can evade the response of the human host. Meningococcal LPS play a key role in the induction of septic shock and can probably enhance the invasiveness of meningococcal strains and shield protective epitopes. Therefore, incorporation of (detoxified) LPS or oligosaccharide components derived therefrom might be very beneficial for the efficacy of a vaccine against group B meningococci. An overview of the development of vaccines against group B meningococci is given, and the status and potential of meningococcal LPS-derived (synthetic) oligosaccharide-protein conjugate vaccines are discussed.
Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell Transplantation (2000)

Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.
Whole-Body Subcellular Multicolor Imaging of Tumor-Host Interaction and Drug Response in Real Time (2007)

To noninvasively image cancer cell/stromal cell interaction in the tumor microenvironment and drug response at the cellular level in live animals in real time, we developed a new imageable three-color animal model. The model consists of green fluorescent protein (GFP)-expressing mice transplanted with dual-color cancer cells labeled with GFP in the nucleus and red fluorescent protein in the cytoplasm. The Olympus IV100 Laser Scanning Microscope, with ultra-narrow microscope objectives ("stick objectives"), is used for three-color whole-body imaging of the two-color cancer cells interacting with the GFP-expressing stromal cells. In this model, drug response of both cancer and stromal cells in the intact live animal is also imaged in real time. Various in vivo phenomena of tumor-host interaction and cellular dynamics were imaged, including mitotic and apoptotic tumor cells, stromal cells interacting with the tumor cells, tumor vasculature, and tumor blood flow. This new model system enables the first cellular and subcellular images of unperturbed tumors in the live intact animal. New visible real-time targets for novel anticancer agents are provided in this model, including the color-coded interacting cancer and stromal cells, tumor vasculature, and blood flow. This imageable model should lead to many new insights of in vivo cancer cell biology and to novel drug discovery.
SimICS/sun4m: a virtual workstation (1998)

Annual Technical Conference. all rights reserved. System level simulators allow computer architects and system software designers to recreate an accurate and complete replica of the program behavior of a target system, regardless of the availability, existence, or instrumentation support of such a system. Applications include evaluation of architectural design alternatives as well as software engineering tasks such as traditional debugging and performance tuning. We present an implementation of a simulator acting as a virtual workstation fully compatible with the sun4m architecture from Sun Microsystems. Built using the system-level SPARC V8 simulator SimICS, SimICS/sun4m models one or more SPARC V8 processors, supports user-developed modules for data cache and instruction cache simulation and execution profiling of all code, and provides a symbolic and performance debugging environment for operating systems. SimICS/sun4m can boot unmodified operating systems, including Linux 2.0.30 and Solaris 2.6, directly from snapshots of disk partitions. To support essentially arbitrary code, we implemented binary-compatible simulators for several devices, including SCSI, console, interrupt, timers, EEPROM, and Ethernet. The Ethernet simulation hooks into the host and allows the virtual workstation to appear on the local network with full services available (NFS, NIS, rsh, etc). Ethernet and console traffic can be recorded for future playback. The performance of SimICS/sun4m is sufficient to run realistic workloads, such as the database benchmark TPC-D, scaling factor 1/100, or an interactive network application such as Mozilla. The slowdown in relation to native hardware is in the range of 25 to 75 (measured using SPECint95). We also demonstrate some applications, including modeling an 8-processor sun4m version (which does not exist), modeling future memory hierarchies, and debugging an operating system.