gebhart/patrepeval huggingface dataset:
Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem-like Cancer Cells in Melanoma (2015)

The basis for resistance to VEGF inhibition is not fully understood despite its clinical importance. In this study, we examined the adaptive response to VEGF-A inhibition by a loss-of-function analysis using plasmid-based shRNA. Tumor xenografts that initially responded to VEGF-A inhibition underwent an adaptation in vivo, leading to acquired resistance. VEGF-A blockade in tumors was associated with HIF1α expression and an increase in CD144(+) vasculogenic mimicry (VM), leading to formation of channels displaying Tie-1 and MMP-2 upregulation. CD133(+) and CD271(+) melanoma stem-like cells (MSLC) accumulated in the perivascular niche. Tumor xenografts of melanoma cell populations that were intrinsically resistant to VEGF-A blockade did not exhibit any of these features, compared with nontarget control counterparts. Thus, melanomas that are initially sensitive to VEGF-A blockade acquire adaptive resistance by adopting VM as an alternate angiogenic strategy, thereby enriching for deposition of MSLC in the perivascular niche through an HIF1α-dependent process. Conversely, melanomas that are intrinsically resistant to VEGF-A blockade do not show any evidence of compensatory survival mechanisms that promote MSLC accumulation. Our work highlights the potential risk of anti-VEGF treatments owing to a selective pressure for an adaptive resistance mechanism that empowers the development of stem-like cancer cells, with implications for how to design combination therapies that can improve outcomes in patients.
N-Linked Glycosylation of CXCR4 Masks Coreceptor Function for CCR5-Dependent Human Immunodeficiency Virus Type 1 Isolates (2000)

The chemokine receptors CXCR4 and CCR5 are the principal coreceptors for infection of X4 and R5 human immunodeficiency virus type 1 (HIV-1) isolates, respectively. Here we report on the unexpected observation that the removal of the N-linked glycosylation sites in CXCR4 potentially allows the protein to serve as a universal coreceptor for both X4 and R5 laboratory-adapted and primary HIV-1 strains. We hypothesize that this alteration unmasks existing common extracellular structures reflecting a conserved three-dimensional similarity of important elements of CXCR4 and CCR5 that are involved in HIV envelope glycoprotein (Env) interaction. These results may have far-reaching implications for the differential recognition of cell type-dependent glycosylated CXCR4 by HIV-1 isolates and their evolution in vivo. They also suggest a possible explanation for the various observations of restricted virus entry in some cell types and further our understanding of the framework of elements that represent the Env-coreceptor contact sites.
Formation of the extracellular mucous matrix of olfactory neuroepithelium: Identification of partially glycosylated and nonglycosylated precursors of olfactomedin (1993)

Olfactomedin is the major glycoprotein of the extracellular mucous matrix of frog olfactory neuroepithelium. It is responsible for the primary architecture of this extracellular matrix by forming via intermolecular disulfide bonds polymers, which are covered with evenly spaced carbohydrate groups. To study glycosylation of olfactomedin, we raised antibodies against the mature protein and antibodies against a region adjacent to an N-linked glycosylation site near its amino terminus. The latter antibodies cannot bind when this site is glycosylated and reveal precursors of olfactomedin in the perinuclear regions of Bowman's glands. In contrast, antiserum against the mature protein stains acinar regions of glands and the ciliary surface. Enzymatic deglycosylation of olfactomedin shows stepwise removal of carbohydrate and reveals a 51-kDa deglycosylated form. Our results indicate that, prior to secretion, most, if not all, of the six potential N-linked glycosylation sites of olfactomedin are glycosylated with carbohydrate moieties of about 8-10 sugar residues.
Loss of chromosome arm 8p loci in prostate cancer: Mapping by quantitative allelic imbalance (1994)

A previous study of 18 primary or metastatic prostate cancers showed loss of genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim USR et al. (1991) Genes Chromosom Cancer 3:215-220]. The small size and infiltrative nature of primary prostatic tumors have hindered efforts to assess allelic losses by traditional restriction fragment length polymorphism (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of this analysis in early prostate cancer, we have amplified polymorphic microsatellite repeats by polymerase chain reaction (PCR), and have quantitated allelic imbalances with phosphor imaging technology. In this study, 63 primary prostate tumors and matched benign tissues obtained by radical prostatectomy were examined at 28 genetic loci on chromosome 8, all but five of which were located on the short arm. Twenty-nine (46%) of the 63 cases showed loss of at least one locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22, were lost in 28 cases. In 10 of these, losses were observed at all informative loci on the p arm. In another 15 tumors, losses were restricted to subregions of the p arm by loci retained either distally toward the p terminus or proximally at the 8p12-8p21 border, or both. In three tumors, two discrete regions of loss were observed within 8p, separated by several retained loci. Allelic loss of 8p loci was associated with higher tumor grade. These data are complementary to previous reports of allelic deletions in colorectal, hepatocellular, and non-small cell lung cancers and suggest the existence of one or more pleotropic tumor suppressor genes on 8p.
Chlamydial nucleic acids in synovium in osteoarthritis: what are the implications? (2001)

C. trachomatis and C. pneumoniae nucleic acids can be present in joints in some cases of apparently classical OA. Whether chlamydial or other difficult to culture bacterial presence is associated with complications is suggested, but remains to be determined. Simple presence of C. trachomatis by PCR does not define a clinical syndrome or disease course.
Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. (1982)

The immunogenicity of long-surviving, enhanced (AS X AUG)F1 renal allografts retransplanted into secondary AS recipients was restored by the injection of small numbers of donor strain dendritic cells derived from afferent lymph. Whereas 1 X 10(4) to 5 X 10(4) dendritic cells were able to trigger an acute rejection response, neither the passenger volume of donor strain blood nor 5 X 10(6) T or B lymphocytes were able to do so, thereby demonstrating more than a 100-fold difference in immunogenic potency. It is concluded that intrarenal dendritic cells provide the major immunogenic stimulus of a kidney allograft. These results suggest that the antigenic strength of major histocompatibility complex-incompatible tissue correlates with the content of donor strain dendritic cells. They also provide further evidence that antigens of the major histocompatibility complex behave like conventional antigens unless they are on the surface of allogeneic dendritic cells.
Dimensional metrology with scanning probe microscopes (1993)

We review the application of scanning probe microscopes to dimensional measurement of topographic features. Probe microscopes show great promise as metrology tools because they produce three-dimensional data over almost all solids in a wide range of ambients. Even though these microscopes readily achieve atomic resolution, there are several aspects of their behavior that can cause them to exhibit large measurement errors. The actuators that drive the probe exhibit hysteresis and creep, so they must be independently monitored. In addition, the geometry of an extended probe moving across the surface makes probe-sample interaction intrinsically nonlinear. Forces on the probe that cause it to flex are another source of inaccuracy. Probe fabrication and characterization are, consequently, important issues. We describe present understanding of these problems and the techniques being developed to solve them.
Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection (2014)

Mother-to-child transmission (MTCT) of cytomegalovirus (CMV) occurs transplacentally (congenital infection), during birth and through breast milk, although the latter 2 modes of transmission are not associated with the central nervous system sequelae that occur with congenital infection. CMV persists indefinitely in its human host, and MTCT can occur if the mother was infected in the past or during the current pregnancy. The goal of efforts to prevent MTCT of CMV is to prevent congenital infection, an important cause of disability due to hearing loss, impaired vision, cognitive impairment, and neuromotor deficits. Vaccines for prevention of maternal and congenital CMV infection are being developed but will not likely be available for at least a decade. Rather than waiting for an effective vaccine to solve the problem, more effort must be devoted to defining the potential for public health measures to prevent congenital CMV infection by reducing rates of maternal infection during pregnancy.
Technique for detecting serial topographic changes in the optic disc and peripapillary retina using scanning laser tomography. (2000)

This technique has a high level of sensitivity to detect changes in the optic disc while maintaining a high level of specificity.
Functional expression in yeast of the Escherichia coli plasmid gene coding for chloramphenicol acetyltransferase. (1980)

The Escherichia coli R factor-derived chloramphenicol resistance (camr) gene is functionally expressed in the yeast Saccharomyces cerevisiae. the gene was introduced by transformation into yeast cells as part of a chimeric plasmid, pYT11-LEU2, constructed in vitro. The plasmide vector consists of the E. coli plasmid pBR325 (carrying the camr gene), the yeast 2-micron DNA plasmid, and the yeast LEU2 structural gene. Yeast cells harboring pYT11-LEU2 acquire resistance to chloramphenicol and cell-free extracts prepared from such cells contain chloramphenicol acetyltransferase (acetyl-CoA: chloramphenicol 3-O-acetyltransferase, EC 2.3.1.28), the enzyme specified by the camr gene in E. coli. Resistance to chloramphenicol and the presence of chloramphenicol acetyltransferase activity segregate with the yeast marker LEU2, carried by the transforming plasmid, during both mitotic growth and meiotic division.
Short Alkylated Peptoid Mimics of Antimicrobial Lipopeptides (2010)

We report the creation of alkylated poly-N-substituted glycine (peptoid) mimics of antimicrobial lipopeptides with alkyl tails ranging from 5 to 13 carbons. In several cases, alkylation significantly improved the selectivity of the peptoids with no loss in antimicrobial potency. Using this technique, we synthesized an antimicrobial peptoid only 5 monomers in length with selective, broad-spectrum antimicrobial activity as potent as previously reported dodecameric peptoids and the antimicrobial peptide pexiganan.
Identifying the vulnerable plaque: A review of invasive and non-invasive imaging modalities (2008)

Atherosclerotic cardiovascular disease is the current leading cause of death in industrialized countries. The vast majority of acute cardiovascular events (50e70%) are ascribed to thrombosis following rupture of a vulnerable plaque. Therefore there is an urgent need to discern vulnerable, unstable plaques from stable plaques. A variety of imaging modalities, both invasive and non-invasive, have been developed for the assessment of visualization and quantification of atherosclerosis. In this review, we discuss the advantages and limitations of the available imaging techniques, and their clinical potential for assessment of plaque vulnerability.
Hepatocellular Injury in a Patient Receiving Rosiglitazone: A Case Report (2000)

Rosiglitazone may be associated with hepatocellular injury. We believe that patients receiving rosiglitazone should have liver enzyme levels monitored earlier and more frequently than initially recommended.
Development of growth factor fusion proteins for cell‐triggered drug delivery (2001)

ABSTRACT The goal of this research was to develop an approach to growth factor delivery that would allow the stable incorporation of growth factors within a cell in‐growth matrix in a manner such that local enzymatic activity associated with tissue regeneration could trigger growth factor release. We investigated this approach in the context of peripheral nerve regeneration by designing modified beta‐nerve growth factor (β‐NGF) fusion proteins and testing their ability to promote neurite extension. Fibrin was selected as the cell in‐growth matrix, and the transglutaminase activity of factor XIIIa was utilized to covalently incorporate β‐NGF fusion proteins within fibrin matrices. Novel β‐NGF fusion proteins, which contained an exogenous factor XIIIa substrate to allow incorporation into fibrin matrices, were expressed recombinantly. An intervening plasmin substrate domain was placed between the factor XIIIa substrate and the NGF domain to allow cell‐mediated growth factor release in response to plasmin, which is generated by invading cells. Immobilized NGF fusion protein with an intervening functional plasmin cleavage sequence enhanced neurite extension from embryonic chick dorsal root ganglia by 50% relative to soluble native β‐NGF and by 350% relative to the absence of NGF. These results suggest that this novel approach to growth factor delivery, in which the factor is delivered upon cellular demand, could enhance nerve regeneration and may be useful in tissue engineering.
Towards Exclusion - Evaluating the Relationship between Employer Negativity and Recruitment Inhibition as a Premise for the Governments Proposed Exemption of Small Businesses from Federal Unfair Dismissal Obligations (2006)

The article examines the attitudes of the small business sector towards the unfair dismissal regime and evaluates the legitimacy of the sources of any negative sentiments to determine whether the sectors experience of the regime justifies perceptions or whether a 'perception gap' has evolved as a consequence of Government rhetoric. The article considers whether the sectors attitudes form an objective basis for legislative reform via a consideration of the extent to which attitudes have influenced recruitment practices within the sector. The credibility of projected job growth statistics in the event of the introduction of a small business exemption will also be appraised.
Development of Degenerative Spondylosis of the Lumbar Spine After Partial Discectomy (1995)

The increased incidence of spondyloarthrosis with the posterior approach suggests that minimally invasive posterolateral extradural procedures should be considered for the decompression of a compromised lumbar nerve root.
Equivalences induced by n-self-cotilting comodules (2010)

We give the definitions of n-self-cotilting comodules and n-cotilting comodules in comodule categories. We also obtain that n-self-cotilting comodules and n-cotilting comodules can induce equivalences between categories of comodules.
Measurement of Hemostatic Factors in EDTA Plasma (2008)

This study determined whether immunoassays of factors VII (FVII) and VIII (FVIII) and von Willebrand factor (vWF) in EDTA-anticoagulated plasma samples are comparable to bioassays and immunoassays of these factors in citrate-anticoagulated plasma. Blood from 40 healthy volunteers was collected in EDTA- and citrate-anticoagulant tubes and assayed using immunoassays (EDTA and citrate) and clotting assays (citrate). Linear regression analyses were performed and Pearson correlation coefficients recorded. The correlation coefficients (95% confidence intervals [CIs]) between levels in EDTA- and citrate-anticoagulated plasma samples were 0.893 (0.806-0.943) for FVII antigen (ag), 0.930 (0.870-0.962) for FVIIIag, 0.990 (0.981-0.995) for vWFag, and 0.949 (0.906-0.973) for vWF activity. Coefficients (CIs) were 0.811 (0.668-0.896) for FVII coagulant activity (c) in citrate and FVIIag in EDTA and 0.608 (0.366-0.774) for FVIIIc in citrate and FVIIIag in EDTA. Measurements of FVII, FVIII, and vWF antigens in EDTA-anticoagulated plasma samples give values comparable to similar measurements in citrate-anticoagulated samples. Clotting activity, especially of FVIII, is less well correlated. Although antigen assays using EDTA are not recommended for patients with coagulopathies, they may be suitable for population-based studies.
Utility of Exit Block for Identifying Electrical Isolation of the Pulmonary Veins (2002)

Identification of exit block after ostial PV ablation provides a clear endpoint for electrical isolation of the PVs. Isolation of the PVs can be performed during sustained AF without the need to apply excess RF lesions. Applying a 20-minute waiting period after electrical isolation will identify reconnection in approximately 10% of PVs.
Direct visualization of nanopatterns by single-molecule imaging (2005)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Erwen Mei, Alexey Sharonov, James H. Ferris, Robin M. Hochstrasser; Direct visualization of nanopatterns by single-molecule imaging. Appl. Phys. Lett. 24 January 2005; 86 (4): 043102. https://doi.org/10.1063/1.1850608 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 ContentAIP Publishing PortfolioApplied Physics Letters Search Advanced Search |Citation Search
New Ulcerative Colitis Model Induced by Sulfhydryl Blockers in Rats and the Effects of Antiinflammatory Drugs on the Colitis. (1997)

We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.
The Lymphocytic Infiltration in Calcific Aortic Stenosis Predominantly Consists of Clonally Expanded T Cells (2007)

Valve lesions in degenerative calcific aortic stenosis (CAS), a disorder affecting 3% of those older than 75 years, are infiltrated by T lymphocytes. We sought to determine whether the alphabeta TCR repertoire of these valve-infiltrating lymphocytes exhibited features either of a polyclonal nonselective response to inflammation or contained expanded clones suggesting a more specific immune process. TCR beta-chain CDR3-length distribution analysis using PCR primers specific for 23 Vbeta families performed in eight individuals with CAS affecting tri- or bileaflet aortic valves revealed considerable oligoclonal T cell expansion. In five cases, beta-chain nucleotide sequencing in five selected Vbeta families showed that an average of 92% of the valve-infiltrating T cell repertoire consisted of expanded T cell clones, differing markedly in composition from the relatively more polyclonal peripheral CD8 or CD4 T cell subsets found even in this elderly population. Twenty-four of the valve-infiltrating T cell clones also had the same clone identified in blood, some of which were highly expanded. Interestingly, 22 of these 24 shared clones were CD8 in lineage (p = 1.5 x 10(-12)), suggesting a possible relationship to the expanded CD8(+)CD28(-) T cell clones frequently present in the elderly. Additionally, the sequences of several TCR beta-chain CDR3 regions were homologous to TCR beta-chains identified previously in allograft arteriosclerosis. We infer that these findings are inconsistent with a nonselective secondary response of T cells to inflammation and instead suggest that clonally expanded alphabeta T cells are implicated in mediating a component of the valvular injury responsible for CAS.
A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression. (1990)

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.
SIGNALLING BY RECEPTOR TYROSINE KINASES (1993)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More