gebhart/patrepeval huggingface dataset:
VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment (2004)

Lymphangiogenesis, an important initial step in tumor metastasis and transplant sensitization, is mediated by the action of VEGF-C and -D on VEGFR3. In contrast, VEGF-A binds VEGFR1 and VEGFR2 and is an essential hemangiogenic factor. We re-evaluated the potential role of VEGF-A in lymphangiogenesis using a novel model in which both lymphangiogenesis and hemangiogenesis are induced in the normally avascular cornea. Administration of VEGF Trap, a receptor-based fusion protein that binds and neutralizes VEGF-A but not VEGF-C or -D, completely inhibited both hemangiogenesis and the outgrowth of LYVE-1(+) lymphatic vessels following injury. Furthermore, both lymphangiogenesis and hemangiogenesis were significantly reduced in mice transgenic for VEGF-A(164/164) or VEGF-A(188/188) (each of which expresses only one of the three principle VEGF-A isoforms). Because VEGF-A is chemotactic for macrophages and we demonstrate here that macrophages in inflamed corneas release lymphangiogenic VEGF-C/VEGF-D, we evaluated the possibility that macrophage recruitment plays a role in VEGF-A-mediated lymphangiogenesis. Either systemic depletion of all bone marrow-derived cells (by irradiation) or local depletion of macrophages in the cornea (using clodronate liposomes) prior to injury significantly inhibited both hemangiogenesis and lymphangiogenesis. We conclude that VEGF-A recruitment of monocytes/macrophages plays a crucial role in inducing inflammatory neovascularization by supplying/amplifying signals essential for pathological hemangiogenesis and lymphangiogenesis.
Animal models of inhibitors (2010)

Antibody responses to clotting factor concentrates remain a major treatment limitation. In conjucation with ongoing clinical studies, the pathogenesis and potential treatment of clotting factor immune responses is being evaluated in a variety of animal models.
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012)

Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
Trends in Antibody Sequence Changes during the Somatic Hypermutation Process (2006)

Probable germline gene sequences from thousands of aligned mature Ab sequences are inferred using simple computational matching to known V(D)J genes. Comparison of the germline to mature sequences in a structural region-dependent fashion allows insights into the methods that nature uses to mature Abs during the somatic hypermutation process. Four factors determine the residue type mutation patterns: biases in the germline, accessibility from single base permutations, location of mutation hotspots, and functional pressures during selection. Germline repertoires at positions that commonly contact the Ag are biased with tyrosine, serine, and tryptophan. These residue types have a high tendency to be present in mutation hotspot motifs, and their abundance is decreased during maturation by a net conversion to other types. The heavy use of tyrosines on mature Ab interfaces is thus a reflection of the germline composition rather than being due to selection during maturation. Potentially stabilizing changes such as increased proline usage and a small number of double cysteine mutations capable of forming disulfide bonds are ascribed to somatic hypermutation. Histidine is the only residue type for which usage increases in each of the interface, core, and surface regions. The net overall effect is a conversion from residue types that could provide nonspecific initial binding into a diversity of types that improve affinity and stability. Average mutation probabilities are approximately 4% for core residues, approximately 5% for surface residues, and approximately 12% for residues in common Ag-contacting positions, excepting the those coded by the D gene.
Role of Poloxamer 188 During Recovery from Ischemic Spinal Cord Injury: A Preliminary Study (1996)

Paraplegia following aortic surgery is not a common event. When it does occur it significantly alters the patient's outcome. Poloxamer 188 (P188) has been shown in the experimental animal to increase regional blood flow to ischemic areas. In order to investigate its protective effect during aortic cross-clamping, 23 animals were randomized to two groups (placebo n = 11, P188n = 12) and received an intravenous injection of placebo or P188 (200 mg/kg), and underwent occlusion of the thoracic aorta and both subclavian arteries for a period of 13 minutes. They were then connected to an intravenous pump delivering either placebo or P188 (250 mg/kg/hr at a rate of 0.942 ml/hour) for 48 hours. Hindlimb function was appraised, daily for 30 days, by a lesion score (0-15). Spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. Analysis of variance for repeated measures did not reveal significant difference between P188 and placebo groups (P = 0.66). Similarly, the mean histologic scores (placebo = 1.54 +/- 0.41 SE, P188 = 1.08 +/- 0.33 SE) did not differ (Wilcoxon, P = 0.43). We conclude that intravenous administration of P188 before, during, and for 48 hours after aortic cross-clamping does not prevent paraplegia or improve the long term neurologic outcome.
Cartilage Oligomeric Matrix Protein Shows High Affinity Zinc-dependent Interaction with Triple Helical Collagen (1998)

Cartilage and tendon extracellular matrices are composed of collagens, proteoglycans, and a number of noncollagenous proteins. Cartilage oligomeric matrix protein (COMP) is a prominent such protein, structurally related to the thrombospondins. We found that native COMP binds to collagen I/II and procollagen I/II and that the interaction is dependent on the divalent cations Zn2+ or Ni2+, whereas Ca2+, Mg2+, and Mn2+ did not promote binding. Using a solid phase assay, Scatchard analysis identified one class of binding site with a dissociation constant (Kd) close to 1.5 nM in the presence of Zn2+. The results were confirmed by studies using surface plasmon resonance. Furthermore, metal chelate chromatography demonstrated that COMP bound Zn2+ and Ni2+. Electron microscopy showed that the interaction occurred at four defined sites on the 300-nm collagen and procollagen molecules. Two were located close to each end, and two at 126 and 206 nm, respectively, from the C-terminal. COMP interacted via its C-terminal globular domain and significantly only in the presence of Zn2+.
PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy (2014)

p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer.
Site-Specific Deuteration of Polyunsaturated Alkenes (2017)

Selective deuteration of drugs and biologically relevant molecules is becoming increasingly important in the pharmaceutical industry. Site-selective isotopic reinforcement of polyunsaturated fatty acids (PUFAs) at their bis-allylic sites has been identified as a unique approach in preventing oxidative damage in these molecules, which had been linked to neuronal and retinal diseases, atherosclerosis, and aging. Typical methods for preparation of site-selectively deuterated PUFAs require rather long, laborious, and expensive syntheses. In this report, we disclose a very efficient catalytic protocol for site-specific deuteration of PUFAs and analogous poly-alkenes under exceptional kinetic control. Deuterium oxide (D<sub>2</sub>O) has been identified not only as a deuterium source but also as a crucial component in the overall reaction mechanism responsible for averting the formation of thermodynamically favored side-products.
Selective medium for isolation of Clostridium botulinum from human feces (1981)

A selective medium, Clostridium botulinum isolation (CBI) agar, was developed for the isolation of C. botulinum from human feces. This medium contains cycloserine (250 microgram/ml), sulfamethoxazole (76 microgram/ml), and trimethoprim (4 microgram/ml) as selective inhibitory agents. Qualitative tests indicated complete recovery of C. botulinum types A, B, F, and G on CBI medium. It was more difficult to recognize type G colonies on the medium because of their lack of lipase activity. Except for a few species of Clostridium, the growth of other obligate anaerobes and of the facultative anaerobes tested on CBI medium was suppressed. Quantitative studies of C. botulinum on the selective medium yielded counts comparable to those obtained on egg yolk agar control plates. Isolation of C. botulinum types A, B, and F from seeded fecal specimens was easily achieved with CBI medium. The use of CBI agar should aid the rapid isolation of C. botulinum from fecal specimens associated with foodborne and infant botulism.
Kinetic studies of carrier transport and recombination at the n-silicon methanol interface (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic studies of carrier transport and recombination at the n-silicon methanol interfaceMary L. Rosenbluth and Nathan S. LewisCite this: J. Am. Chem. Soc. 1986, 108, 16, 4689–4695Publication Date (Print):August 1, 1986Publication History Published online1 May 2002Published inissue 1 August 1986https://pubs.acs.org/doi/10.1021/ja00276a001https://doi.org/10.1021/ja00276a001research-articleACS PublicationsRequest reuse permissionsArticle Views535Altmetric-Citations77LEARN 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 Get e-Alerts
Precision genome editing: A small revolution for glycobiology (2014)

Precise and stable gene editing in mammalian cell lines has until recently been hampered by the lack of efficient targeting methods. While different gene silencing strategies have had tremendous impact on many biological fields, they have generally not been applied with wide success in the field of glycobiology, primarily due to their low efficiencies, with resultant failure to impose substantial phenotypic consequences upon the final glycosylation products. Here, we review novel nuclease-based precision genome editing techniques enabling efficient and stable gene editing, including gene disruption, insertion, repair, modification and deletion. The nuclease-based techniques comprised of homing endonucleases, zinc finger nucleases, transcription activator-like effector nucleases, as well as the RNA-guided clustered regularly interspaced short palindromic repeat/Cas nuclease system, all function by introducing single or double-stranded breaks at a defined genomic sequence. We here compare and contrast the different techniques and summarize their current applications, highlighting cases from the field of glycobiology as well as pointing to future opportunities. The emerging potential of precision gene editing for the field is exemplified by applications to xenotransplantation; to probing O-glycoproteomes, including differential O-GalNAc glycoproteomes, to decipher the function of individual polypeptide GalNAc-transferases, as well as for engineering Chinese Hamster Ovary host cells for production of improved therapeutic biologics.
Purification of the major species of human leucocyte interferon with the help of a monoclonal antibody. (1984)

A mouse hybridoma cell line has been isolated, which secretes a monoclonal antibody (HBA) specific of human leucocyte (alpha) interferon. This monoclonal antibody neutralizes biological activities (cellular and antiviral) of most of the molecular species of alpha interferon produced by human leucocytes. Bound to Sepharose, it has been used as an immunoadsorbent (HBA-Sepharose) to purify human leucocyte interferon. Human leucocyte interferon can be purified to homogeneity by a two-step chromatography on the immunoadsorbent. A high recovery (70-90%) of purified leucocyte interferon is obtained from crude or partially purified preparations, with a specific activity of 2,8 X 10(8) IU/mg of protein. Analysis of the purified proteins by SDS-gel electrophoresis and silver staining shows that the purified human leucocyte interferon consists of three species of molecular weight: 18 000-21 000 and 27 000. This simple and rapid technique can be applied for the preparation of homogeneous leucocyte interferon on a large scale.
Adenosine, Adenosine Receptors and the Actions of Caffeine * (1995)

Of the known biochemical actions of caffeine, only inhibition of adenosine receptors occurs at concentrations achieved during normal human consumption of the drug. Under normal physiological conditions, adenosine is present in sufficient concentrations to activate A1 and A2a receptors. Via actions on A1 receptors, adenosine decreases neuronal firing and the release of neurotransmitters. The exact mechanisms are not known, but several possibilities are discussed. Via actions on A2a receptors, adenosine--and hence caffeine--can influence dopaminergic neurotransmission. Caffeine can induce rapid changes in gene expression and, somewhat later, marked adaptive changes. These include antiepileptic and neuroprotective changes. Thus, caffeine has a number of central effects directly or indirectly related to adenosine receptors. Some of these are potentially useful, and drug development based on the actions of caffeine should be interesting.
An improved method for deriving water‐bottom reflectivities for processing dual‐sensor ocean‐bottom cable data (1995)

PreviousNext No AccessSEG Technical Program Expanded Abstracts 1995An improved method for deriving water‐bottom reflectivities for processing dual‐sensor ocean‐bottom cable dataAuthors: Josef PaffenholzFred J. BarrJosef PaffenholzWestern Geophysical and Fred J. BarrWestern Geophysicalhttps://doi.org/10.1190/1.1887432 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Permalink: https://doi.org/10.1190/1.1887432FiguresReferencesRelatedDetailsCited byApplying wavelet transform to suppress ghost in ocean-bottom node dual-sensor technology17 February 2022 | Marine Geophysical Research, Vol. 43, No. 1Seismic receiver coupling to the seafloor15 March 2019 | Geophysical Prospecting, Vol. 67, No. 6References14 March 2018References24 May 2016References29 April 2013Crossline wavefield reconstruction from multicomponent streamer data: Part 2 — Joint interpolation and 3D up/down separation by generalized matching pursuitAli Özbek, Massimiliano Vassallo, Kemal Özdemir, Dirk-Jan van Manen, and Kurt Eggenberger22 December 2010 | GEOPHYSICS, Vol. 75, No. 6Receiver function decomposition of OBC data: theoryGeophysical Journal International, Vol. 177, No. 3Detector coupling corrections for vector infidelity of multicomponent OBC dataJames E. Gaiser6 April 2007 | GEOPHYSICS, Vol. 72, No. 3OBC multiple suppression with the Texas two‐stepMax Deffenbaugh and Ramesh Neelamani7 December 2005References21 March 201211. Reservoir Geophysics21 March 2012On unified dual fields and Einstein deconvolutionDan Loewenthal and Enders A. Robinson7 February 2012 | GEOPHYSICS, Vol. 65, No. 1Suppression of downcoming waves at the ocean bottom with a scalar combination of hydrophone and geophone dataChanpen Silawongsawat and Gary F. Margrave4 January 2005 SEG Technical Program Expanded Abstracts 1995ISSN (print):1052-3812 ISSN (online):1949-4645Copyright: 1995 Pages: 1566 publication data© 1995 Copyright © 1995 Society of Exploration GeophysicistsPublisher:Society of Exploration Geophysicists HistoryPublished Online: 10 Feb 2005 CITATION INFORMATION Josef Paffenholz and Fred J. Barr, (1995), "An improved method for deriving water‐bottom reflectivities for processing dual‐sensor ocean‐bottom cable data," SEG Technical Program Expanded Abstracts : 987-990. https://doi.org/10.1190/1.1887432 Plain-Language Summary PDF DownloadLoading ...
Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death (2000)

Sphingosine and sphingosine-1-phosphate (SPP) are interconvertible sphingolipid metabolites with opposing effects on cell growth and apoptosis. Based on sequence homology with LBP1, a lipid phosphohydrolase that regulates the levels of phosphorylated sphingoid bases in yeast, we report here the cloning, identification, and characterization of a mammalian SPP phosphatase (mSPP1). This hydrophobic enzyme, which contains the type 2 lipid phosphohydrolase conserved sequence motif, shows substrate specificity for SPP. Partially purified Myc-tagged mSPP1 was also highly active at dephosphorylating SPP. When expressed in yeast, mSPP1 can partially substitute for the function of LBP1. Membrane fractions from human embryonic kidney HEK293 cells transfected with mSPP1 markedly degraded SPP but not lysophosphatidic acid, phosphatidic acid, or ceramide-1-phosphate. Enforced expression of mSPP1 in NIH 3T3 fibroblasts not only decreased SPP and enhanced ceramide levels, it also markedly diminished survival and induced the characteristic traits of apoptosis. Collectively, our results suggest that SPP phosphohydrolase may regulate the dynamic balance between sphingolipid metabolite levels in mammalian cells and consequently influence cell fate.
Towards an automated approach for protein identification in proteome projects (1998)

The development of automated, high throughput technologies for the rapid identification of proteins is essential for large-scale proteome projects. While a degree of automation already exists in some stages of the protein identification process, such as automated acquisition of matrix assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectra, efficient interfaces between different stages are still lacking. We report the development of a highly automated, integrated system for large scale identification of proteins separated by two-dimensional gel electrophoresis (2-DE), based on peptide mass fingerprinting. A prototype robotic system was used to image and excise 288 protein spots from an amido black stained polyvinylidene difluoride (PVDF) blot. Protein samples were enzymatically digested with a commercial automated liquid handling system. MALDI-TOF mass spectrometry was used to acquire mass spectra automatically, and the data analysed with novel automated peptide mass fingerprinting database interrogation software. Using this highly automated system, we were able to identify 95 proteins on the basis of peptide mass fingerprinting, isoelectric point and molecular weight, in a period of less than ten working days. Advantages, problems, and future developments in robotic excision systems, liquid handling, and automated database interrogation software are discussed.
Gap junctions: structure and function (Review) (2002)

Gap junctions are plasma membrane spatial microdomains constructed of assemblies of channel proteins called connexins in vertebrates and innexins in invertebrates. The channels provide direct intercellular communication pathways allowing rapid exchange of ions and metabolites up to approximately 1 kD in size. Approximately 20 connexins are identified in the human or mouse genome, and orthologues are increasingly characterized in other vertebrates. Most cell types express multiple connexin isoforms, making likely the construction of a spectrum of heteromeric hemichannels and heterotypic gap junctions that could provide a structural basis for the charge and size selectivity of these intercellular channels. The precise nature of the potential signalling information traversing junctions in physiologically defined situations remains elusive, but extensive progress has been made in elucidating how connexins are assembled into gap junctions. Also, participation of gap junction hemichannels in the propagation of calcium waves via an extracellular purinergic pathway is emerging. Connexin mutations have been identified in a number of genetically inherited channel communication-opathies. These are detected in connexin 32 in Charcot Marie Tooth-X linked disease, in connexins 26 and 30 in deafness and skin diseases, and in connexins 46 and 50 in hereditary cataracts. Biochemical approaches indicate that many of the mutated connexins are mistargeted to gap junctions and/or fail to oligomerize correctly into hemichannels. Genetic ablation approaches are helping to map out a connexin code and point to specific connexins being required for cell growth and differentiation as well as underwriting basic intercellular communication.