gebhart/patrepeval huggingface dataset:
Antibodies to Macromolecular Platelet Factor 4-Heparin Complexes in Heparin-induced Thrombocytopenia: a Study of 44 Cases (1995)

As heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 < 0.3) and 35 patients with other causes of thrombocytopenia (A492 < 0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 +/- 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped < or = 100 x 10(9)/l only at days 11-12. Surprisingly, among 41 patients under heparin for > 7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.
SOX9 Is Expressed in Human Fetal Prostate Epithelium and Enhances Prostate Cancer Invasion (2008)

SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and was beta-catenin regulated. Here we report additional in vivo results showing that SOX9 is highly expressed during fetal prostate development by epithelial cells expanding into the mesenchyme, suggesting it may contribute to invasive growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced growth, angiogenesis, and invasion. Conversely, short hairpin RNA-mediated SOX9 suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results support important functions of SOX9 in both the development and maintenance of normal prostate, and indicate that these functions contribute to PCa tumor growth and invasion.
A Designed Heterotrimeric Coiled Coil (1995)

Principles that guide folding of coiled coils were tested by designing three peptides that preferentially associate with each other to form a heterotrimeric coiled coil. The core positions of the designed helices contained residues that promote formation of trimeric coiled coils. Ionic interactions were employed to mediate heterospecificity, and negative design was used to favor formation of the heterotrimer over alternative arrangements. A program was written to select sequences that maximized the number of attractive interhelical interactions in a parallel heterotrimer and the number of repulsive electrostatic interactions in alternative species. Solution studies indicate that an equimolar mixture of the three peptides forms a helical trimer with high specificity and stability. These results validate the principles used to guide the design and suggest that the heterotrimer may serve as a useful, autonomous trimerization domain.
Human skin wounds: A major and snowballing threat to public health and the economy (2009)

ABSTRACT In the United States, chronic wounds affect 6.5 million patients. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds and the burden is rapidly growing due to increasing health care costs, an aging population and a sharp rise in the incidence of diabetes and obesity worldwide. The annual wound care products market is projected to reach $15.3 billion by 2010. Chronic wounds are rarely seen in individuals who are otherwise healthy. In fact, chronic wound patients frequently suffer from "highly branded" diseases such as diabetes and obesity. This seems to have overshadowed the significance of wounds per se as a major health problem. For example, NIH's Research Portfolio Online Reporting Tool (RePORT; http://report.nih.gov/), directed at providing access to estimates of funding for various disease conditions does list several rare diseases but does not list wounds. Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.
Development of novel genetic cancer vaccines based on membrane‐attached β2 microglobulin (2013)

Cytotoxic T lymphocytes (CTLs) are the major effector arm of the immune system against tumors. Many tumor-associated antigens (TAAs), known today as potential rejection antigens, were identified by their ability to induce CTL responses. CTLs utilize their clonotypic T cell receptor (TCR) to recognize short antigenic peptides presented on major histocompatibility complex (MHC)-I proteins. These consist of a membrane-attached α heavy chain, which forms the peptide binding pocket, and a noncovalently associated β2m light chain, not anchored to the cell membrane. CTL activation requires that antigenic peptides be presented initially on professional antigen presenting cells (APCs), primarily dendritic cells (DCs). Autologous DCs are a powerful tool for the induction of antitumor responses and are thus widely explored as vehicles for cancer vaccines. Although encouraging evidence for the induction of tumor-specific CTLs by ex vivo-manipulated DCs came from numerous animal studies, reproducible objective clinical response in human trials is yet to be demonstrated.
Activation of Type IV Procollagenases by Human Tumor-associated Trypsin-2 (1997)

Increased production of proteinases, such as matrix metalloproteinases (MMPs), is a characteristic feature of malignant tumors. Some human cancers and cell lines derived from them also express trypsinogen, but the function of the extrapancreatic trypsin has remained unclear. In this study we cloned and sequenced trypsinogen-2 cDNA from human COLO 205 colon carcinoma cells and characterized the ability of the enzyme to activate latent human type IV procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino acid sequencing, the amino acid sequence of tumor-associated trypsin-2 is identical to that of pancreatic trypsin-2. We found that both pancreatic trypsin-2 and tumor cell-derived trypsin-2 are efficient activators of proMMP-9 and are capable of activating proMMP-9 at a molar ratio of 1:1000, the lowest reported so far. Human trypsin-2 was a more efficient activator than widely used bovine trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not fragmented further. The single peptide bond cleaved by trypsin-2 in proMMP-9 was Arg87-Phe88. The generation of the 77-kDa species coincided with the increase in specific activity of MMP-9. In contrast, trypsin-2 only partially activated proMMP-2. Trypsin-2 cleaved the Arg99-Lys100 peptide bond of proMMP-2 generating 62-65-kDa MMP-2 species. Trypsin-2-induced proMMP-2 and -9 conversions were inhibited by tumor-associated trypsin inhibitor added either prior to or during activation indicating that proMMPs were not activated autocatalytically. Trypsin-2 also activated proMMPs associated with tissue inhibitor of matrix metalloproteinases, the complexes of which are thought to be the major MMP forms in vivo. The ability of human tumor cell-derived trypsin-2 to activate latent MMPs suggests a role for trypsin-2 in initiating the proteinase cascade that mediates tumor invasion and metastasis formation.
Replicating plasmids in Schizosaccharomyces pombe: improvement of symmetric segregation by a new genetic element. (1986)

We characterized a number of widely used yeast-Escherichia coli shuttle vectors in the fission yeast Schizosaccharomyces pombe. The 2 micron vectors pDB248 and YEp13 showed high frequency of transformation, intermediate mitotic and low meiotic stability, and a low copy number in S. pombe, analogous to their behavior in [cir0] strains of Saccharomyces cerevisiae. The S. cerevisiae integration vectors pLEU2 and pURA3 transformed S. pombe at very low frequencies but, surprisingly, in a nonintegrative fashion. Instead, they replicated autonomously, and they showed very high copy numbers (up to 150 copies per plasmid-containing cell). This could reflect a lack of sequence specificity for replication of plasmid DNA in S. pombe. pFL20, an S. pombe ars vector, and a series of plasmids derived from it were studied to analyze the unusually high stability of this plasmid. Mitotic stability and partitioning of the plasmids was measured by pedigree analysis of transformed S. pombe cells. An S. pombe DNA fragment (stb) was identified that stabilizes pFL20 by improvement of plasmid partitioning in mitosis and meiosis.
Critical Variables in the Radioimmunoassay of Serum Insulin Using the Double Antibody Technic (1965)

An adaptation of the double antibody radioimmunoassay for insulin originally presented by Morgan and Lazarow is described. These studies have confirmed the presence of an inhibitor in serum and plasma (heparin) which delays the rate at which the insulin-insulin antibody complex is rendered insoluble by rabbit serum containing antibodies to guinea pig globulin. Serum dilution reduces the effect of the inhibitor but increases dilutional error. Heparin similarly reduces the effect of the inhibitor, but excess heparin produces falsely low values for immunoreactive insulin (IRI). Data are presented for serum which show that if sufficient time (72 hrs.) is allowed to elapse after the addition of the precipitating antibody (rabbit, anti-guinea pig globulin, serum), the precipitating system reaches equilibrium. Employing this modification, additional data are presented, showing excellent recovery of human insulin added to serum, good duplication of respective serum IRI values in repeat assays, and constancy of fasting serum IRI in any one individual on repeated sampling. Normal adults exhibit fasting values of serum IRI from 1 to 20 μU./ml. with a mean of 8.4 μU./ml., and after rapid intravenous glucose, serum IRI usually reaches maximum levels in one to two minutes.
Directed Self-Assembly of Metallosupramolecular Polymers at the Polymer–Polymer Interface (2012)

Directed self-assembly of a metallosupramolecular polymer is achieved at the interface between two polymer films by simple melt pressing. Blends of a 2,6-bis(<i>N</i>-methylbenzimidazolyl)pyridine (MeBip) side-chain functionalized polystyrene in a polystyrene matrix and Zn(NTf<sub>2</sub>)<sub>2</sub> in a poly(methyl methacrylate) matrix were pressed together above the <i>T</i><sub>g</sub> of the matrix polymers resulting in diffusion of the components and subsequent self-assembly of the metallosupramolecular polymer at the polymer-polymer interface. The formation of the metallosupramolecular polymer was monitored by spectroscopy and microscopy and it was found that the interfacial self-assembly occurs at the processing temperatures (ca. 210 °C) within 5 min. It was further shown that this materials system resulted in robust films that exhibited a new emergent property, namely, phosphorescence, which is not exhibited by any of the individual components nor the metallosupramolecular polymer itself.
The collagenous lesion scar--an obstacle for axonal regeneration in brain and spinal cord injury. (2001)

After CNS trauma a sheet-like, collagen type IV (Coll IV) immunopositive basement membrane (BM) develops in the lesion zone as well as at newly formed blood vessels. The basic scaffold of this BM is composed of Coll IV, laminin and nidogen but numerous other proteins some of which are discussed to be inhibitory for axonal regeneration, i.e. chondroitin- and heparansufate-proteoglycans, are associated with BM. This review will focus on the collagenous wound healing scar, discuss its composition and summarize the experimental results that demonstrate its role in the failure of axonal regeneration in the injured mammalian CNS.
Excavations at Hann River 1, Central Cape York Peninsula (1995)

The excavations at Hann River 1, central Cape York Peninsula, have provided the first evidence for Aboriginal prehistory in the region. The reconnaissance fieldwork has included a general survey of local sandstone scraps and the recording of rock art sites.
The thioredoxin system—From science to clinic (2003)

The thioredoxin system-formed by thioredoxin reductase and its characteristic substrate thioredoxin-is an important constituent of the intracellular redox milieu. Interactions with many different metabolic pathways such as DNA-synthesis, selenium metabolism, and the antioxidative network as well as significant species differences render this system an attractive target for chemotherapeutic approaches in many fields of medicine-ranging from infectious diseases to cancer therapy. In this review we will present and evaluate the preclinical and clinical results available today. Current trends in drug development are emphasized.
The sensitivity of the hepatic glycogenolytic mechanism to stimulation of the splanchnic nerves (1972)

1. The sensitivity of the hepatic glycogenolytic mechanism to splanchnic nerve stimulation at relatively low frequencies has been investigated in adrenalectomized calves, dogs and cats.2. In young calves the hyperglycaemic response to splanchnic nerve stimulation at 1.0 c/s for 5 min increased steadily during the first 2 weeks after birth.3. The hyperglycaemic response to splanchnic nerve stimulation for 5 min was directly related to frequency of stimulation within the range 0.5-4.0 c/s in calves tested 2-5 weeks after birth. Pronounced rises in plasma glucose concentration also occurred in calves of this age in response to maximal stimulation (20 c/s) for shorter periods (30 sec) whereas occlusion of the portal vein for the same period produced no comparable effect.4. The effects of splanchnic nerve stimulation for prolonged periods were also investigated in 2- to 5-week-old calves. Under these conditions increased concentrations of glucose in the plasma were maintained for periods of up to 90 min and fell towards the initial values when stimulation was discontinued.5. Prolonged stimulation of the peripheral ends of both splanchnic nerves at either 2.0 or 4.0 c/s produced a transient reversal of hypoglycaemia in calves pretreated with large doses of insulin; both the extent and duration of these responses were related to frequency of stimulation.6. The hyperglycaemic response to bilateral splanchnic nerve stimulation was directly related to frequency of stimulation within the range 0.5-4.0 c/s in adrenalectomized dogs. Comparable responses were obtained in adrenalectomized cats in response to stimulation at 2.0 c/s, but stimulation at 1.0 c/s produced no rise in mean plasma glucose concentration in these animals.7. The sensitivity of the hepatic glycogenolytic mechanism has been assessed in relation to the associated changes in haematocrit and mean aortic blood pressure under the same conditions.8. The results of these experiments support the contention that tonic changes in sympathetic efferent activity are associated with variations in the rate at which glucose is released from the liver under physiological conditions.
Asymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone system (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone systemR. B. Woodward, B. W. Au-Yeung, P. Balaram, L. J. Browne, D. E. Ward, B. W. Au-Yeung, P. Balaram, L. J. Browne, P. J. Card, and C. H. ChenCite this: J. Am. Chem. Soc. 1981, 103, 11, 3213–3215Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://pubs.acs.org/doi/10.1021/ja00401a050https://doi.org/10.1021/ja00401a050research-articleACS PublicationsRequest reuse permissionsArticle Views3636Altmetric-Citations158LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Interaction of HIV-1 and human salivary mucins. (1994)

Previous studies have suggested that salivary secretions may act as inhibitors of HIV-1 replication in vitro. This inhibitory activity was determined to be associated mainly with secretions obtained from the human submandibular-sublingual glands, and subsequent electron micrographs revealed the association of viral particles with the salivary sediment. Fractionation of human submandibular-sublingual (HSMSL) saliva by size-exclusion chromatography was initiated, and resulting fractions were tested for their ability to modulate the replication of HIV-1 using a plaque assay on HeLa CD4+ cell monolayers. Results indicated that the filtration-sensitive inhibitory activity was primarily associated with the mucin-rich fractions, and the inhibitory activity was found to reduce the number of infectious units by 75%. To determine the identity of the salivary components involved, adsorption experiments involving the interaction of HIV particles with immobilized salivary components were performed. Immunological counter staining revealed an interaction of HIV particles as well as recombinant gp120 with the lower-molecular-weight mucin. Electron microscopic examination of the mucin-rich fractions-HIV incubates revealed the aggregation of virus particles by salivary components. These results suggest that human salivary mucins may have a role in modulating the infectivity of HIV-1.
Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268. (2002)

The selective estrogen receptor modulator arzoxifene and the rexinoid LG 100268 were active not only as single agents for prevention and treatment of breast cancer in the rat model that uses nitrosomethylurea as the carcinogen but also showed striking synergy, both preventively and therapeutically, in a series of six experiments with a total of 465 rats. Mechanistic studies in cell culture reported here suggest that enhancement of stromal-epithelial interactions may contribute to this synergy. The possible clinical use of the combination of arzoxifene and LG 100268 for prevention of breast cancer in women at high risk, for treatment of women in the adjuvant setting, or for treatment of end-stage disease should now be considered.
Immune checkpoint blockade immunotherapy to activate anti‐tumour T‐cell immunity (2013)

The tumour microenvironment plays a dual role in cancer: it can promote tumour progression by establishing pro-tumour survival conditions but can also suppress tumour progression by killing cancer cells or inhibiting their outgrowth. These dynamically interconnected processes are under intense investigation to better understand cancer pathophysiology and allow identification of new therapeutic approaches. The ability of cancer cells to evade anti-tumour T-cell activity in the microenvironment has recently been accepted as a hallmark of cancer progression. This review will highlight the most promising therapeutic approach aimed at activating anti-tumour T-cell immunity in the cancer microenvironment: blocking inhibitory immune regulatory proteins (immune checkpoint ligands and receptors). There is emerging evidence that haematological tumours co-opt immune checkpoints as a major immune resistance mechanism. Pre-clinical findings indicate that targeted therapies and blockade of immune checkpoints could be combined to promote therapeutic synergy and long-term anti-tumour immunity to improve clinical outcomes for cancer patients.
Spam! (1998)

article Free Access Share on Spam! Authors: Lorrie Faith Cranor AT&T Labs, Florham Park, NJ AT&T Labs, Florham Park, NJView Profile , Brian A. LaMacchia Microsoft Corp., Redmond, WA Microsoft Corp., Redmond, WAView Profile Authors Info & Claims Communications of the ACMVolume 41Issue 8Aug. 1998 pp 74–83https://doi.org/10.1145/280324.280336Published:01 August 1998Publication History 179citation5,728DownloadsMetricsTotal Citations179Total Downloads5,728Last 12 Months269Last 6 weeks40 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids (1985)

Lubricin was isolated from bovine ankle, metacarpophalangeal and knee and human knee synovial fluids. The lubricins isolated from the bovine joint fluids had the same amino acid and carbohydrate compositions, but differences were observed in the relative molecular masses. The Mr values of bovine metacarpophalangeal and ankle lubricin determined by light-scattering measurements were about 200 000, whereas values of 132 000 and 143 000 were obtained for the bovine knee lubricin. The human knee lubricin had a similar carbohydrate composition to bovine knee lubricin except for the higher glucosamine content, and the amino acid composition differed slightly. The human sample had a lower glutamic acid content and a leucine/isoleucine ratio of 2:1 compared with 1:1 in the bovine. The Mr value of the human knee lubricin (166 000) was also lower than that of the bovine metacarpophalangeal and ankle samples. The Mr value of the bovine knee lubricin determined by sedimentation-equilibrium measurements was 171 000. The length measurements determined by electron microscopy and also the sedimentation measurements showed considerable polydispersity and indicate that the degree of extension of lubricin molecules can vary. Friction measurements showed that the human knee synovial-fluid lubricin had equivalent lubricating ability in a test system in vitro to that observed for lubricin isolated from normal bovine synovial fluids. The lubricating ability of lubricin was concentration-dependent, and each lubricin sample was able to act as a lubricant in vitro in an equivalent manner to whole synovial fluid at concentrations that are thought to occur in vivo.