gebhart/patrepeval huggingface dataset:
Immunohistochemical localization of amyloid in Finnish hereditary amyloidosis with antibodies to gelsolin peptides. (1991)

The amyloid fibril protein in the Finnish type of familial amyloid polyneuropathy was recently identified as a fragment of gelsolin, a cytoskeletal and plasma protein with actin-modulating properties. Antibodies to three synthetic peptides of various parts of gelsolin were raised in rabbits and used in immunocytochemistry. The P-3 dodecapeptide, corresponding to the C-terminal region of the amyloid protein, elicited the best immunologic response and the P-3 antibodies were found suitable for use in immunohistochemistry and enzyme immunoassay. The P-3 antibodies specifically stained the amyloid deposits in various tissues including the skin, kidney, heart, thyroid gland, salivary gland, and rectum in patients with Finnish familial amyloid polyneuropathy. The staining was completely abolished by absorption of the antiserum with the synthetic dodecapeptide used for immunization, but not by a peptide of another region of the gelsolin molecule. The antibodies did not stain the amyloid of secondary amyloid A or of the myeloma-associated amyloid light chain. The results provide evidence for the relation between the amyloid deposited in the systemic tissues of patients with Finnish familial amyloid polyneuropathy and gelsolin, and demonstrate the utility of these anti-gelsolin antibodies in diagnostic immunohistochemistry.
How to Measure the Diagnostic Accuracy of Noninvasive Liver Fibrosis Indices: The Area Under the ROC Curve Revisited (2008)

We recommend using the Obuchowski measure for assessing the diagnostic accuracy of noninvasive indices of fibrosis.
Essential fatty acids in perspective. (1984)

There are two families of essential fatty acids, the linoleic and linolenic. Linoleic acid (C18:2n-6), found mainly in vegetable seed oils, is desaturated and elongated in the body, forming arachidonic acid (C20:4n-6). Linolenic acid (C18:3n-3), the main dietary source of which is leaves, is desaturated and elongated, forming two fatty acids that are prevalent in fish oils: timnodonic (C20:5n-3) and clupanodonic (C22:6n-3). EFA are very easily peroxidized in air, but vitamin E protects against this. There are three functions of EFA. The most important is as part of phospholipids in all animal cellular membranes: in deficiency of EFA faulty membranes are formed. A second is in the transport and oxidation of cholesterol: EFA tend to lower plasma cholesterol. A third function is as precursors of prostanoids which are only formed from EFA. Deficiency of EFA in experimental animals causes lesions mainly attributable to faulty cellular membranes: sudden failure of growth, lesions of skin and kidney and connective tissue, erythrocyte fragility, impaired fertility, uncoupling of oxidation and phosphorylation. In man pure deficiency of EFA has been studied particularly in persons fed intravenously. A relative deficiency (that is, a low ratio in the body of EFA to long-chain saturated fatty acids and isomers of EFA) is common on Western diets and plays an important part in the causation of atherosclerosis, coronary thrombosis, multiple sclerosis, the triopathy of diabetes mellitus, hypertension and certain forms of malignant disease. Various factors affect the dietary requirement of EFA.
Cellular transfer of macromolecules across the developing choroid plexus of Monodelphis domestica (2009)

Choroid plexus epithelial cells secrete cerebrospinal fluid (CSF) and transfer molecules from blood into CSF. Tight junctions between choroidal epithelial cells are functionally effective from early in development: the route of transfer is suggested to be transcellular. Routes of transfer for endogenous and exogenous plasma proteins and dextrans were studied in Monodelphis domestica (opossum). Pups at postnatal (P) days 1-65 and young adults were injected with biotinylated dextrans (3-70 kDa) and/or foetal protein fetuin. CSF, plasma and brain samples were collected from terminally anaesthetized animals. Choroid plexus cells containing plasma proteins were detected immunocytochemically. Numbers of plasma protein-positive epithelial cells increased to adult levels by P28, but their percentage of plexus cells declined. Numbers of cells positive for biotinylated probes increased with age, while their percentage remained constant. Colocalization studies showed specificity for individual proteins in some epithelial cells. Biotinylated probes and endogenous proteins colocalized in about 10% of cells in younger animals, increasing towards 100% by adulthood. Injections of markers into the ventricles demonstrated that protein is transferred only from blood into CSF, whereas dextrans pass in both directions. These results indicate that protein and lipid-insoluble markers are transferred by separate mechanisms present in choroid plexuses from the earliest stage of brain development, and transfer of proteins from plasma across choroid plexus epithelial cells contributes to the high protein concentration in CSF in the immature brain.
Symbian OS C++ for Mobile Phones (2003)

Richard Harrisons existing books are the bestsellers in the Press Portfolio. His latest book, co-written with Mark Shackman is the successor to Symbian OS C++ for Mobile Phones Volumes One and Two. Written in the same style as the two previous volumes, this is set to be another gem in the series. The existing material from the volumes will be combined, with explanations and example code updated to reflect the introduction of OS v9. New and simplified example application will be introduced, which will be used throughout the book. The reference and theory section in particular sets this book apart from the competition and complements other books being proposed at this time. Anyone looking for a thorough insight into OS C++ before moving onto specialize on particular OS phones need this book! It will not teach people how to program in C++, but it will reinforce the techniques behind developing applications in OS C++, and more. This innovative new book covers OS fundamentals, core concepts and UI. Key highlights include: A quick guide to Kernel Platform security Publishing Applications View Architecture Multi-User games
Triple-helix formation of DNA oligomers with methylthiourea-linked nucleosides (DNmt): A kinetic and thermodynamic analysis (1999)

Complementary short-strand DNA homooligomers and methylthiourea-linked homonucleosides associate and form triplexes in solution. The melting temperatures, Tm, the association and dissociation kinetic and thermodynamic parameters, and activation energies were determined by UV thermal analysis for the triplexes of short-strand DNA homooligomers [d(pA)10-d(pA)23] and poly(dA) with the methylthiourea-linked nucleoside [5'-NH3+-d(Tmt)4-T-OH [DNmt5]]. Circular dichroism studies show evidence of triple-helical association dependent on the length of the target homooligomer. The melting and cooling curves exhibit hysteresis behavior in the temperature range of 10-95 degrees C at 0.13 deg/min thermal rate. From these curves, the rate constants and the energies of activation for association (kon, Eon) and dissociation (koff, Eoff) were obtained. Tm decreases with the ionic strength and increases with increase in length of the monomers. The rate constants kon and koff at a given temperature (288 K-310 K) are dependent on the DNA strand length and also decrease and increase respectively with the ionic strength. The energies of activation for the association and dissociation processes are in the range of -18 to -38 kcal/mol and 3 to 18 kcal/mol, respectively. The equilibrium constant for the formation of the triplexes [5'-NH3+-d(Tmt)4-T-OH)2.d(pA)x, x = 10-23] is several orders of magnitude greater when compared with the triplexes of DNA. The number of base triplets in the nucleus of the DNmt2.DNA triple-helix (nucleation-zipping model) increases with decreased DNA oligomer length and with increased ionic strength. The values of DeltaH degrees calculated from the activation parameters are between -30 and -50 kcal/(mol base) and the values of DeltaG degrees are between -6 and -11 kcal/(mol base) for short-strand DNA.
Peripheral and Cerebrovascular Actions of Ethanol, Acetaldehyde, and Acetate: Relationship to Divalent Cations (1987)

Inasmuch as ethanol is thought to exert its major effects in the autonomic and central nervous systems, it is important to determine whether acute versus chronic ingestion of this abused substance exerts any direct actions on peripheral and cerebral blood vessels. Since the chronic effects of ethanol on the cardiovascular system appear to be pivotal in the etiology of hypertension, coronary heart disease, and strokelike events, it is important to elucidate and understand the effects of chronic ethanol abuse and its mechanism(s) of action on the peripheral and cerebral blood vessels. Data are reviewed which suggest that the peripheral vasodilation and hypotension which result from acute ingestion (or administration) of ethanol may, in large part, be a consequence of its direct actions on vascular smooth muscle cells, both at the macro- and microcirculatory levels. At least two mechanisms appear to contribute to this vasodilator effect: inhibition of the normal rhythm or vasomotion (spontaneous mechanical activity) of vascular smooth muscle, and depression of the contractile responses to endogenous neurohumoral substances that play a role in maintaining vascular tone and regulation of blood flow. The data acquired so far suggest that the dilator actions are related causally to interference with movement and/or translocation of Ca2+ across the vascular membranes. In addition, these actions appear to resemble the peripheral vascular effects of general anesthetics. Evidence is also reviewed which indicate that ethanol, in contrast to acting as a vasodilator in the splanchnic vasculature, is often a potent and concentration-dependent constrictor of arterioles and venules in the skeletal muscle vasculature. Direct in situ observations on the rat brain, using high resolution, quantitative TV image-intensification microscopy, indicates that administration of ethanol, irrespective of the route of administration (e.g., perivascularly, intraarterially, or systemically), produces graded concentration-dependent spasms of arterioles and venules. Concentrations of ethanol approximately equal to greater than 250 mg/dl produce intense spasms resulting in rupture of these vessels. Recent in situ studies in conscious dogs, using radiolabeled microspheres, also indicate that ethanol can produce deficits in regional brain blood flow. Studies with isolated canine middle cerebral and basilar arteries clearly demonstrate that low concentrations of ethanol (e.g., less than 10 mM) can produce concentration-dependent spasms by a direct vascular action.(ABSTRACT TRUNCATED AT 400 WORDS)
Protein kinase C beta 1 and protein kinase C beta 2 activate p57 mitogen-activated protein kinase and block differentiation in colon carcinoma cells. (1996)

When HD3 colon carcinoma cells differentiate to fluid-transporting, enterocytic-like cells, they down-regulate their protein kinase C (PKC) beta levels 5-10-fold and lose two responses to basic fibroblast growth factor (FGF): proliferation and the ability to activate p57 mitogen-activated protein (MAP) kinase. HD3 cells were transfected with expression plasmids for the splice variants PKC-beta 1 and PKC-beta 2 and the empty vector for a control. Each of two PKC-beta 1 and each of two PKC-beta 2 transfectant clones exhibited elevated levels of Ca(2+)-and phosphatidylserine-dependent PKC activity. Both PKC-beta 1 transfectant clones had elevated levels of PKC-beta 1 protein compared with the PKC-beta 2 transfectants or controls, whereas both PKC-beta 2 transfectant clones had elevated levels of PKC-beta 2 protein compared with PKC-beta 1 transfectants. Control transfectants had no detectable PKC-beta 2 protein. Similar levels of PKC-alpha were found in all lines. Each PKC-beta transfectant was less differentiated than the parental line and had regained proliferative response to basic FGF. Increased growth rates in athymic mice were seen for PKC-beta 2 and PKC-beta 1 transfectant cells. Immunocytochemistry of the sectioned tumors showed enhanced protein levels of PKC-beta 2 and PKC-beta 1, correlating increased levels of these isonzymes with increased growth. Increased myelin-basic protein (MBP) kinase activities of M(r) 44,000, 57,000, 63,000, 110,000, and 130,000 by in-gel kinase assay characterized each PKC-beta transfectant. Both Western blotting and immunoprecipitation studies from 35S-prelabeled cells with a pan-erk antibody showed no increase in protein abundance of MAP kinases of M(r) 44,000, 57,000, and 63,000, suggesting that elevated PKC-beta levels led to activation of the smaller three MAP and MBP kinases. Activation of p57 MAP kinase in each PKC-beta transfectant was demonstrated by immunoprecipitation with an antiphosphotyrosine monoclonal antibody and then by assay of the immunoprecipitates by in-gel kinase assay on MBP. p57 MAP kinase was distinguished from the M(r) 54,000 stress-activated protein kinases, which migrated more rapidly on SDS gels and could be detected by in-gel kinase assay on MBP only after cellular stress. Thus, expression of elevated levels of PKC-beta 1 and PKC-beta 2 in differentiated HD3 colon carcinoma cells blocked their differentiation, enabled them to proliferate in response to basic FGF like undifferentiated cells, increased their growth rate in athymic mice, and activated several MBP kinases, among them, p57 MAP kinase.
Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids (1996)

The parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described. Parameters for both torsional and nonbonded energetics have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER all-atom force field. The torsional parameters were determined by fitting to rotational energy profiles obtained from ab initio molecular orbital calculations at the RHF/6-31G*//RHF/6-31G* level for more than 50 organic molecules and ions. The quality of the fits was high with average errors for conformational energies of less than 0.2 kcal/mol. The force-field results for molecular structures are also demonstrated to closely match the ab initio predictions. The nonbonded parameters were developed in conjunction with Monte Carlo statistical mechanics simulations by computing thermodynamic and structural properties for 34 pure organic liquids including alkanes, alkenes, alcohols, ethers, acetals, thiols, sulfides, disulfides, aldehydes, ketones, and amides. Average errors in comparison with experimental data are 2% for heats of vaporization and densities. The Monte Carlo simulations included sampling all internal and intermolecular degrees of freedom. It is found that such non-polar and monofunctional systems do not show significant condensed-phase effects on internal energies in going from the gas phase to the pure liquids.
Differential Expression of Aggrecanase and Matrix Metalloproteinase Activity in Chondrocytes Isolated from Bovine and Porcine Articular Cartilage (1998)

The release of aggrecan catabolites from cartilage is an early event in the pathogenesis of degenerative joint diseases. The enzymes involved in this process are unknown, controversial, and the subject of intense investigation. In this paper we have utilized a recombinant substrate containing the interglobular domain (IGD) of aggrecan to study specifically aggrecanase versus matrix metalloproteinase (MMP) catabolism in this domain of aggrecan. Our studies have shown that (i) there are species differences in the expression of latent versus active MMP activity on the aggrecan IGD; (ii) interleukin-1alpha exposure induces both aggrecanase and MMP activities, whereas retinoic acid induces only aggrecanase activity and inhibits the MMP activity on the aggrecan IGD; (iii) activators of latent MMP activity (p-aminophenylmercuric acetate and trypsin) significantly reduce aggrecanase activity; (iv) the time course of the appearance of aggrecanase versus the MMP catabolism of aggrecan IGD differs; (v) aggrecanase is a protease with metalloprotease characteristics; however (vi) the physiological (tissue) inhibitors of MMPs show weak inhibition (TIMP-1) or no inhibition (TIMP-2) of aggrecanase activity. Collectively, these studies show that aggrecanase and MMP catabolism of the aggrecan IGD are independent and uncoupled.
High-Performance Nanowire Electronics and Photonics and Nanoscale Patterning on Flexible Plastic Substrates (2005)

The introduction of an ambient-temperature route for integrating high-mobility semiconductors on flexible substrates could enable the development of novel electronic and photonic devices with the potential to impact a broad spectrum of applications. Here we review our recent studies demonstrating that high-quality single-crystal nanowires (NWs) can be assembled onto flexible plastic substrates under ambient conditions to create FETs and light-emitting diodes. We also show that polymer substrates can be patterned through the use of a room temperature nanoimprint lithography technique for the general fabrication of hundred-nanometer scale features, which can be hierarchically patterned to the millimeter scale and integrated with semiconductor NWs to make high-performance FETs. The key to our approach is the separation of the high-temperature synthesis of single-crystal NWs from room temperature solution-based assembly, thus enabling fabrication of single-crystal devices on virtually any substrate. Silicon NW FETs on plastic substrates display mobilities of 200 cm/sup 2/-V/sup -1/-s/sup -1/, rivaling those of single-crystal silicon and exceeding those of state-of-the-art amorphous silicon and organic transistors currently used for flexible electronics. Furthermore, the generality of this bottom-up assembly approach suggests the integration of diverse nanoscale building blocks on a variety of substrates, potentially enabling far-reaching advances in lightweight display, mobile computing, and information storage applications.
Continuous Analytics: Rethinking Query Processing in a Network-Effect World (2009)

www.truviso.com Modern data analysis applications driven by the Network Effect are pushing traditional database and data warehousing technologies beyond their limits due to their massively increasing data volumes and demands for low latency. To address this problem, we advocate an integrated query processing approach that runs SQL continuously and incrementally over data before that data is stored in the database. Continuous Analytics technology is seamlessly integrated into a full-function database system, creating a powerful and flexible system that can run SQL over tables, streams, and combinations of the two. A continuous analytics system can run many orders of magnitude more efficiently than traditional store-first-query-later technologies. In this paper, we describe the Continuous Analytics approach and outline some of the key technical arguments behind it. 1.
Absence of Vascular Dementia in an Autopsy Series from a Dementia Clinic (1998)

Clinicians should maintain a high index of suspicion of AD or other neurodegenerative process in older patients whose presenting complaint is dementia, even in the presence of well documented cerebrovascular disease.
Augmented Antitumor Activity against B-Cell Lymphoma by a Combination of Monoclonal Antibodies Targeting TRAIL-R1 and CD20 (2007)

Mapatumumab induces apoptosis, cell growth arrest, ADCC, and CMC. The combination of mapatumumab plus rituximab is more effective in controlling lymphoma growth in vivo than either antibody. Rituximab and mapatumumab warrant further evaluation against B-cell lymphoma.
TOSO, the Fcμ Receptor, Is Highly Expressed on Chronic Lymphocytic Leukemia B Cells, Internalizes upon IgM Binding, Shuttles to the Lysosome, and Is Downregulated in Response to TLR Activation (2011)

TOSO/FAIM3 recently has been identified as the long-sought-after FcR for IgM (FcμR). FcμR is expressed on human CD19(+) B cells, CD4(+)/CD8(+) T cells, and CD56(+)/CD3(-) NK cells and has been shown to be overexpressed in chronic lymphocytic leukemia (CLL) cells. CLL is a malignancy of mature IgM(+) B lymphocytes that display features of polyreactive, partially anergized B cells related to memory B cells. In this article, we report that FcμR is O-glycosylated in its extracellular domain and identify the major sites of O-glycosylation. By using immunofluorescence confocal microscopy, we found that FcμR localized to the cell membrane but also found that large pools of FcμR accumulate in the trans-Golgi network. Aggregation of FcμR on CLL cells by IgM prompted rapid internalization of both IgM and FcμR, reaching half-maximal internalization of cell-bound IgM within 1 min. Upon internalization, FcμR transported IgM through the endocytic pathway to the lysosome, where it was degraded. Using a series of FcμR deletion mutants, we identified a proline-rich domain essential for cell surface expression of FcμR and a second domain, containing a YXXΦ motif, that controls internalization. Although it has been reported that BCR activation increases FcμR expression, we found that activation of TLRs strongly downregulated FcμR at both the mRNA and protein levels. Through internalization of IgM bound immune complexes, FcμR may play a role in immune surveillance and contribute to B cell activation. In addition, FcμR deserves study as a potential pathway for the delivery of therapeutic Ab-drug conjugates into CLL cells.
Functional Analysis of the Putative Integrin Recognition Motif on Adeno-associated Virus 9 (2014)

Adeno-associated viruses (AAVs) display a highly conserved NGR motif on the capsid surface. Earlier studies have established this tripeptide motif as being essential for integrin-mediated uptake of recombinant AAV serotype 2 (AAV2) in cultured cells. However, functional attributes of this putative integrin recognition motif in other recombinant AAV serotypes displaying systemic transduction in vivo remain unknown. In this study, we dissect the biology of an integrin domain capsid mutant derived from the human isolate AAV9 in mice. The AAV9/NGA mutant shows decreased systemic transduction in mice. This defective phenotype was accompanied by rapid clearance of mutant virions from the blood circulation and nonspecific sequestration by the spleen. Transient vascular hyperpermeability, induced by histamine coinjection, exacerbated AAV9/NGA uptake by the spleen but not the liver. However, such treatment did not affect AAV9 virions, suggesting a potential entry/post-entry defect for the mutant in different tissues. Further characterization revealed modestly decreased cell surface binding but a more pronounced defect in the cellular entry of mutant virions. These findings were corroborated by the observation that blocking multiple integrins adversely affected recombinant AAV9 transduction in different cell types, albeit with variable efficiencies. From a structural perspective, we observed that the integrin recognition motif is located in close proximity to the galactose binding footprint on AAV9 capsids and postulate that this feature could influence cell surface attachment, cellular uptake at the tissue level, and systemic clearance by the reticuloendothelial system.