gebhart/patrepeval huggingface dataset:
Serial Determinations of Melanoma Tumor—Associated Antigen and Antibody in Patients With Stage I Melanoma (1986)

The correlation of circulating immune complexes (CICs) and the clinical course of malignant melanoma has not been consistent when using nonspecific assays for CIC. To improve predictability, serial serum samples from patients with pathologic stage I melanoma were analyzed for the presence of antimelanoma tumor-associated antigen (TAA) antibody by direct radioimmunoassay and for the presence of melanoma TAA in CIC by the antigen competition method. Immunochemically characterized TAA was isolated from the spent culture medium of a melanoma cell line. Seventy-five percent of patients with melanoma TAA-specific immune complex (IC) had recurrences, while 71% of patients without melanoma TAA-specific IC remained free of disease for prolonged periods (up to 14 years of follow-up). Anti-TAA antibody titers did not correlate with disease recurrence. Our results demonstrate a correlation with melanoma TAA-specific IC and disease recurrence. The absence of melanoma TAA-specific IC is associated with a low risk of recurrence. Fluctuations in melanoma TAA-specific IC levels indicate a dynamic tumor host immunobiology and the need for serial follow-up.
Interactions of Cbl with Grb2 and Phosphatidylinositol 3′-Kinase in Activated Jurkat Cells (1995)

T-cell receptor (TCR) cross-linking increases tyrosine phosphorylation of multiple proteins, only a few of which have been identified. One of the most rapidly tyrosine-phosphorylated polypeptides is the 120-kDa product of the proto-oncogene c-cbl, a cytosolic and cytoskeletal protein containing multiple proline-rich motifs that are potential binding sites for proteins containing Src homology 3 (SH3) domains. We report here that in cultured Jurkat T cells, Cbl is coprecipitated with antibody against the adapter protein Grb2. Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross-linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain. Grb2 antisera also precipitated p85 from serum-starved cells, while TCR activation increased p85 and tyrosine-phosphorylated Cbl but not Cbl protein in Grb2 immunocomplexes. Phosphatidylinositol (PI) 3-kinase activity was immunoprecipitated from serum-starved cells with Cbl and to a lesser extent with Grb2 antisera, and TCR cross-linking increased this activity severalfold. The PI 3-kinase activity associated with Cbl amounted to 5 to 10% of the total cellular activity that could be precipitated by p85 antisera. The Ras exchange factor Son-of-sevenless 1 (Sos-1) was not found in anti-Cbl immunoprecipitates from activated cells, and Cbl was not detectable in anti-Sos-1 precipitates, supporting the likelihood that Sos-Grb2 and Cbl-Grb2 are present as distinct complexes. Taken together, these data suggest that Cbl function in Jurkat T cells involves its constitutive association with Grb2 and its recruitment of PI 3-kinase in response to TCR activation.
Mutator activity induced by microRNA-155 ( miR-155 ) links inflammation and cancer (2011)

Infection-driven inflammation has been implicated in the pathogenesis of ~15-20% of human tumors. Expression of microRNA-155 (miR-155) is elevated during innate immune response and autoimmune disorders as well as in various malignancies. However, the molecular mechanisms providing miR-155 with its oncogenic properties remain unclear. We examined the effects of miR-155 overexpression and proinflammatory environment on the frequency of spontaneous hypoxanthine phosphoribosyltransferase (HPRT) mutations that can be detected based on the resistance to 6-thioguanine. Both miR-155 overexpression and inflammatory environment increased the frequency of HPRT mutations and down-regulated WEE1 (WEE1 homolog-S. pombe), a kinase that blocks cell-cycle progression. The increased frequency of HPRT mutation was only modestly attributable to defects in mismatch repair machinery. This result suggests that miR-155 enhances the mutation rate by simultaneously targeting different genes that suppress mutations and decreasing the efficiency of DNA safeguard mechanisms by targeting of cell-cycle regulators such as WEE1. By simultaneously targeting tumor suppressor genes and inducing a mutator phenotype, miR-155 may allow the selection of gene alterations required for tumor development and progression. Hence, we anticipate that the development of drugs reducing endogenous miR-155 levels might be key in the treatment of inflammation-related cancers.
Transdermal Testosterone Delivery Systems (1996)

Recently approved methods for testosterone delivery have provided increased options for men who require hormonal replacement therapy. Intramuscular administration of testosterone has classically been associated with early, high serum peaks in hormone followed by a gradual decline over the dosing interval. Transdermal patches are now available as an alternative. Testoderm® is applied to the scrotum; Androderm® is applied to nonscro-tal skin. Using either system, the majority of patients can achieve normal serum testosterone levels with a circadian variation and normal estradiol levels. Serum luteinizing hormone levels generally decrease but not to suppressed levels. Testoderm® use leads to an increase in plasma dihydrotestosterone. Clinical response in mood, energy level, and sexual function are improved with both systems and are generally comparable with intramuscular injection of testosterone. There are no clinically significant changes in laboratory parameters, including prostatic specific antigen, and prostate size did not increase to above normal. Skin reactions, however, are common and may require some patients to discontinue therapy. Patients with inadequate scrotal size may not have satisfactory results with Testoderm®. Patches are more costly than IM injections but do not require frequent office visits. Both the transscrotal and transdermal testosterone delivery systems offer a good alternative treatment for hypogonadal men who do not desire fertility during the treatment period.
Role of Endothelium in Doxorubicin-Induced Cardiomyopathy (2018)

The clinical use of doxorubicin in cancer is limited by cardiotoxic effects that can lead to heart failure. Whereas earlier work focused on the direct impact of doxorubicin on cardiomyocytes, recent studies have turned to the endothelium, because doxorubicin-damaged endothelial cells can trigger the development and progression of cardiomyopathy by decreasing the release and activity of key endothelial factors and inducing endothelial cell death. Thus, the endothelium represents a novel target for improving the detection, management, and prevention of doxorubicin-induced cardiomyopathy.
Optical path cross-connect system architecture suitable for large scale expansion (1996)

This paper proposes, for WPs (wavelength paths) and VWPs (virtual wavelength paths), a new OPXC (optical path cross-connect) architecture suitable for constructing large scale OPXC systems. The architecture is based on the multimodule concept and uses main modules and junction modules. The proposed OPXC is shown to provide triple the throughput of the conventional OPXC (delivery and coupling switch based) assuming state-of-the-art commercially available devices. It allows traffic demand increases to be supported with less OPXC switch hardware compared to the conventional OPXC architecture. The proposed architecture also keeps the advantages of the conventional architecture: a high level of expandability with regard to incoming/outgoing links and upgradability from a WP network to a VWP network. Thus the proposed OPXC architecture is highly flexible and allows minimum investment to encourage introduction while gracefully supporting future system scale expansion with incremental growth matching the traffic demand.
Overexpression and Mislocalization of a Tail‐Anchored GFP Redefines the Identity of Peroxisomal ER (2003)

Peroxisomal ascorbate peroxidase (APX) sorts indirectly via a subdomain of the ER (peroxisomal ER) to the boundary membrane of peroxisomes in tobacco Bright Yellow 2 cells. This novel subdomain characteristically appears as fluorescent reticular/circular compartments distributed variously in the cytoplasm. Further characterizations are presented herein. A peptide possessing the membrane targeting information for peroxisomal APX was fused to GFP (GFP-APX). Transiently expressed GFP-APX sorted to peroxisomes and to reticular/circular compartments; in both cases, the GFP moiety faced the cytosol. Of particular interest, both homotypic and heterotypic aggregates of peroxisomes, mitochondria, and/or plastids were formed. The latter two organelles comprised the circular portion of the reticular/circular compartments, apparently as a consequence of oligomerization (zippering) of the GFP moieties after insertion into the outer membranes of the affected organelles. These results, coupled with the accumulation of endogenous peroxisomal APX in cytoplasmic, noncircular compartment(s) following treatment with brefeldin A, indicate that authentic peroxisomal ER is composed only of a reticular compartment(s). Equally important, the data show that overexpressed, membrane-targeted GFP fusion proteins have a propensity to form organelle aggregates that may lead to misinterpretations of sorting pathways of trafficked proteins.
ITS2 and 18S rDNA sequence-structure phylogeny of Chlorella and allies (Chlorophyta, Trebouxiophyceae, Chlorellaceae) (2015)

In the last decade, the evolutionary diversity of Chlorella and allies has been discussed in a huge number of publications using internal transcribed spacer 2 (ITS2) and/or 18S ribosomal RNA gene sequences to infer the phylogenies. However, sister-group relations between different genera classified within the Chlorellaceae remained provisional, due to a lack of bootstrap support. In this study, using more than four hundred sequences, a comprehensive phylogenetic portrait of Chlorella and allies is presented and discussed; sixty key taxa are reconsidered by an analysis using primary sequences and their individual secondary structures simultaneously in inferring neighbor-joining, maximum parsimony and maximum likelihood trees, an approach most recently reviewed, with increasing robustness and accuracy of reconstructed phylogenies. While neighbor-joining and maximum parsimony analyses failed in inferring a robust phylogenetic tree, the maximum likelihood tree (in particular on a concatenated data set) provides a supported phylogeny preceding any taxonomic discussion.
Anonymous connections and onion routing (1998)

Onion routing is an infrastructure for private communication over a public network. It provides anonymous connections that are strongly resistant to both eavesdropping and traffic analysis. Onion routing's anonymous connections are bidirectional, near real-time, and can be used anywhere a socket connection can be used. Any identifying information must be in the data stream carried over an anonymous connection. An onion is a data structure that is treated as the destination address by onion routers; thus, it is used to establish an anonymous connection. Onions themselves appear different to each onion router as well as to network observers. The same goes for data carried over the connections they establish. Proxy-aware applications, such as Web browsers and e-mail clients, require no modification to use onion routing, and do so through a series of proxies. A prototype onion routing network is running between our lab and other sites. This paper describes anonymous connections and their implementation using onion routing. This paper also describes several application proxies for onion routing, as well as configurations of onion routing networks.
Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids. (1997)

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.
Antibodies Against G-Protein Coupled Receptors: Novel Uses in Screening and Drug Development (2008)

Antibodies are components of the body's humoral immune system that are generated in response to foreign pathogens. Modern biomedical research has employed these very specific and efficient molecules designed by nature in the diagnosis of diseases, localization of gene products as well as in the rapid screening of targets for drug discovery and testing. In addition, the introduction of antibodies with fluorescent or enzymatic tags has significantly contributed to advances in imaging and microarray technology, which are revolutionizing disease research and the search for effective therapeutics. More recently antibodies have been used in the isolation of dimeric G protein-coupled receptor (GPCR) complexes. In this review, we discuss antibodies as powerful research tools for studying GPCRs, and their potential to be developed as drugs themselves.
Side Chain Contributions to the Stability of Alpha-Helical Structure in Peptides (1990)

Short peptides that contain significant alpha-helical structure in aqueous solution allow the investigation of the role of amino acid side chains in stabilizing or destabilizing alpha-helix structure. A host-guest system of soluble synthetic peptides was designed that consisted of chains with the block sequence TyrSerGlu4Lys4X3Glu4Lys4, denoted EXK, in which X represents any "guest" amino acid residue. Circular dichroism spectroscopy indicates that the extent of helicity of these peptides follows the order Ala greater than Leu greater than Met greater than Gln greater than Ile greater than Val greater than Ser greater than Thr greater than Asn greater than Gly. This order differs from both host-guest copolymer values (Met greater than Ile greater than Leu greater than Ala greater than Gln greater than Val greater than Thr greater than Asn greater than Ser greater than Gly) and the tendencies of these amino acids to occur in helices in globular proteins (Ala greater than Met greater than Leu greater than Gln greater than Ile greater than Val greater than Asn, Thr greater than Ser greater than Gly), but matches the order found in a series of synthetic coiled-coil alpha helices, except for Ser. Proton nuclear magnetic resonance analysis of several EXK peptides indicates that these peptides are partially helical, with the helical residues favoring the amino terminus.
Kabat Database and its applications: 30 years after the first variability plot (2000)

The Kabat Database was initially started in 1970 to determine the combining site of antibodies based on the available amino acid sequences at that time. Bence Jones proteins, mostly from human, were aligned, using the now-known Kabat numbering system, and a quantitative measure, variability, was calculated for every position. Three peaks, at positions 24-34, 50-56 and 89-97, were identified and proposed to form the complementarity determining regions (CDR) of light chains. Subsequently, antibody heavy chain amino acid sequences were also aligned using a different numbering system, since the locations of their CDRs (31-35B, 50-65 and 95-102) are different from those of the light chains. CDRL1 starts right after the first invariant Cys 23 of light chains, while CDRH1 is eight amino acid residues away from the first invariant Cys 22 of heavy chains. During the past 30 years, the Kabat database has grown to include nucleotide sequences, sequences of T cell receptors for antigens (TCR), major histocompatibility complex (MHC) class I and II molecules and other proteins of immunological interest. It has been used extensively by immunologists to derive useful structural and functional information from the primary sequences of these proteins. An overall view of the Kabat Database and its various applications are summarized here. The Kabat Database is freely available at http://immuno.bme.nwu.edu
Deconvolution and phase retrieval with use of zero sheets (1995)

Recent developments in the application of zeros (of the analytically continued spectrum of a compact two-dimensional image) in solving deconvolution and phase retrieval problems are reviewed. New algorithms for use in the presence of noise are described and demonstrated. These include algorithms for deconvolution where the point-spread function is approximately known, for ensemble blind deconvolution (such as is required for ensembles of astronomical speckle images), and for phase retrieval (itself a special case of blind deconvolution). Many of the ideas embodied in the algorithms were foreshadowed by Bates et al. [ J. Opt. Soc. Am. A7, 468 ( 1990)]. Simulated images are employed in the examples shown, except for phase retrieval, where successful recovery of the phase error in the aperture of a radio telescope is demonstrated.
Enhanced growth capacity of neonatal pulmonary artery smooth muscle cells in vitro: Dependence on cell size, time from birth, insulin‐like growth factor I, and auto‐activation of protein Kinase C (1994)

Based on the unique susceptibility of the neonatal pulmonary circulation to hypoxia-induced structural alteration in vivo, we hypothesized that pulmonary artery (PA) smooth muscle cells (SMC) from the neonate would demonstrate enhanced growth capacity in vitro compared to adult cells. To test this hypothesis, matched neonatal and adult bovine SMC were tested for differences in size, serum-stimulated proliferation, susceptibility to senescence, resistance to serum withdrawal, autocrine growth capacity, and responsiveness to a locally important growth factor (insulin-like growth factor I; IGF-I) and an activator of protein kinase C (PKC) (phorbol 12-myristate 13-acetate; PMA). Neonatal PA SMC were smaller, grew faster, reached a higher plateau density, and were less susceptible to senescence. They were more resistant to serum withdrawal, had spontaneous autocrine growth capacity, and were more responsive to IGF-I, PMA, and the combination. Acquisition of increased growth factor responsiveness occurred between d5 and d14 after birth. Increased neonatal growth to IGF-I was associated with reduced IGF-I binding activity, implicating a post-receptor mechanism in enhanced responsiveness. Increased membrane-bound PKC catalytic activity was found in serum-deprived neonatal SMC. This basal increase was equal to that stimulated by 1 nM PMA in adult SMC, a pretreatment that caused these cells to become as responsive to IGF-I as untreated neonatal ones. We conclude that neonatal bovine PA SMC have marked enhancement of growth capacity in vitro, the acquisition of which is dependent on time from birth and is associated with auto-activation of PKC, These increased growth properties detected in vitro may contribute to the striking hyperplasia of neonatal PA SMC found in vivo following hypoxic exposure.
Targeting lymphangiogenesis to prevent tumour metastasis (2006)

Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involves the secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3) localised on the surface of lymphatic endothelial cells. In this review, we discuss the evidence supporting a role for this signalling system in the spread of cancer and potential approaches for blocking this system to prevent tumour metastasis.
Projections to the spinal cord from medullary somatosensory relay nuclei (1977)

Abstract Descending projections to the spinal card from the dorsal column nuclei were studied in the cat, rat and monkey with the retrograde horseradish peroxidase (HRP) technique, and in the cat with the autoradiographic anterograde axonal transport technique. Retrogradely labeled neurons were seen in the dorsal column nuclei after HRP injections at all levels of the spinal cord and additionally in the magnocellular division of the spinal caudalis nucleus of the trigeminal nerve after injections into cervical spinal segments in all three species. HRP‐positive neurons were predominantly located along the middle of the rostro‐caudal axis of the dorsal column nuclei and amongst the fusiform, triangular and polygonal cells that surround, especially ventrally, the cell nest zone containing thalamic relay neurons. The labeled neurons are densely concentrated in those portions of the dorsal column nuclei where most corticofugal and non‐primary afferent projections terminate and where the terminal distribution of primary afferent fibers is overlapping and diffuse. Previous studies have shown that most neurons in this middle and ventral region do not project to the thalamus or cerebellum. The majority of the cells in the dorsal column nuclei with descending axons or axon collaterals project by way of the ipsilateral dorsal columns, but some fibers project into the dorsolateral funiculus; the descending trigeminal fibers course in the dorsolateral funiculus. The terminal fields for these fibers in the cervical spinal cord include the lateral cervical nucleus, laminae IV and V, and possibly lamina I. These results indicate that the dorsal column nuclei may contribute to a feedback mechanism regulating the flow of sensory information ascending along other somatosensory spinal pathways.
Bulk amorphous alloys with high mechanical strength and good soft magnetic properties in Fe–TM–B (TM=IV–VIII group transition metal) system (1997)

New bulk amorphous alloys exhibiting a wide supercooled liquid region before crystallization were found in Fe–(Co,Ni)–(Zr,Nb,Ta)–(Mo,W)–B systems. The Tg is as high as about 870 K and the supercooled liquid region reaches 88 K. The high thermal stability of the supercooled liquid enabled the production of bulk amorphous alloys with diameters up to 6 mm. These bulk amorphous alloys exhibit a high compressive strength of 3800 MPa, high Vickers hardness of 1360, and high corrosion resistance. Besides, the amorphous alloys exhibit a high magnetic-flux density of 0.74–0.96 T, low coercivity of 1.1–3.2 A/m, high permeability exceeding 1.2×104 at 1 kHz, and low magnetostriction of about 12×10−6.