gebhart/patrepeval huggingface dataset:
Recombinant soluble CD59 inhibits reactive haemolysis with complement. (1994)

Three soluble forms of membrane attack complex inhibitory factor (MACIF or CD59) were prepared using recombinant baculovirus-infected insect cells. They consisted of 70, 77 and 86 amino acids, starting from the amino terminus of naturally occurring CD59, and were designated recombinant (r) CD59 70, 77 and 86, respectively. All three rCD59 lacked a glycosyl-phosphatidylinositol (GPI) anchor, unlike membrane CD59 which has a GPI anchor at the anchor at the carboxyl terminus (77th amino acid). Their activities in inhibiting complement activation were assayed with C5b-7 intermediate cells and C8 and C9 components. The inhibitory activity of rCD59 70 was as high as that of rCD59 77 and twice that of rCD59 86. In addition, it was one-fourth and one-hundredth lower than the activities of urine and erythrocyte CD59, respectively. However, when assayed in the presence of human serum at a final concentration of 50% (v/v), the activities of both urine and erythrocyte CD59 were greatly decreased to to one-tenth of that of rCD59 70. Purified rCD59 70 molecules were all glycosylated, but rCD59 77 and 86 were mixtures of glycosylated and non-glycosylated molecules. The inhibitory activities of rCD59 77 and 86 were the same for the glycosylated and non-glycosylated forms. These results suggest that the soluble rCD59 provide a means for elucidating the biological roles of CD59.
In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis. (1994)

Human skin has an acid mantle of pH 4-6, contrasting with the almost neutral pH of the interior body and implying the existence of a pH gradient over the horny layer that might influence a variety of epidermal processes. In an attempt to characterize the pH gradient, we applied a glass electrode to the volar surface of the forearm before and after consecutive strippings with sello-tape. Before stripping, the surface pH (mean +/- SD) was 4.5 +/- 0.2 in men (n = 7) and 5.3 +/- 0.5 in women (n = 7), the values gradually increasing to pH 6.9 +/- 0.4 in men and 6.8 +/- 0.5 in women after about 100-120 tape strippings, which completely removed the stratum corneum. When plotted against the number of strippings, the pH values usually conformed to a sigmoid curve with inflection (50% change) after about 60 strippings, at a level corresponding histologically to the lower third of stratum corneum. Similar gradients were found also in skin of the abdomen and calf. Stripping with cyanoacrylate resin produced a similar gradient, even though this form of stripping was 10 times more effective. The healing process after tape stripping was studied by determining pH and transepidermal water loss in 5 persons over a period of 14 days. The importance of the re-established pH gradient is discussed in relation to the many pH-dependent enzymes operating in stratum corneum.
Extended half‐life clotting factor concentrates: results from published clinical trials (2016)

Extended half-life clotting factor concentrates have been recently introduced into the armamentarium of treatments for patients with haemophilia A and B. In general, the data from published studies have demonstrated these products to be safe with no inhibitors reported in previously treated patients and efficacious with the advantage of a longer half-life allowing for less frequent intravenous infusions of factor. This enhanced convenience has led to some patients not previously on prophylaxis to begin prophylaxis while for others, especially children, has led to the ability to provide prophylaxis with reduced use of central venous catheters. The extended half-life factor IX products are now allowing patients to dose every 1-2 weeks while maintaining higher trough levels while the extended half-life factor VIII products have reduced the frequency of administration for patients on prophylaxis to as infrequent as once per week for some patients and to twice per week for all patients including younger children. It is important to note that data from previously untreated patients have not been published yet and the incidence for inhibitors in this patient population is as of yet unknown. The era of extended half-life clotting factor products has begun and the challenge for the haemophilia community will be how to best integrate these products into haemophilia clinical practice.
The epitope spreading cascade during progression of experimental autoimmune encephalomyelitis and multiple sclerosis (1998)

We have made the following observations regarding self-recognition during the development and progression of murine experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS): 1) chronic progression of EAE is accompanied by a sequential, predictable cascade of neo-autoreactivity, commonly referred to as epitope spreading, presumably caused by endogenous self-priming during autoimmune-mediated tissue damage; 2) there is an invariant relationship between the progression of EAE and the emergence of epitope spreading; 3) progression of EAE can be inhibited by the induction of antigen-specific tolerance to spreading determinants after onset of initial neurologic symptoms; 4) CD4+ Th 1 cells responding to spreading determinants are autonomously encephalitogenic; 5) epitope spreading occurs during the development of MS and in some cases involves HLA-DP class II-restricted self-recognition; and 6) progression of both EAE and MS is accompanied by the decline of primary T-cell autoreactivity associated with disease onset and by the concurrent emergence of the epitope spreading cascade. Our studies directly challenge the traditional view that EAE and MS are initiated and maintained by autoreactivity directed against a single predominant myelin protein or determinant. Our results indicate that progression of EAE and MS involves a shifting of T-cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during disease progression.
Effects of Magnetic Thermoablation in Muscle Tissue Using Iron Oxide Particles (2000)

The data demonstrate the applicability of local magnetic thermoablation for therapy of muscle lesions in the long term.
Ion- and electron-assisted gas-surface chemistry—An important effect in plasma etching (1979)

The extent to which gas-surface chemical reactions can be enhanced by energetic radiation (primarily ions and electrons) incident on the surface is described. Emphasis is placed on chemical systems which lead to volatile reaction products. In particular, the reactions of Si, SiO2, and Si3N4 with XeF2, F2, and Cl2 are examined experimentally. Possible mechanisms for the radiation-induced enhancement are discussed and some technological implications of this process in plasma etching technology and lithography are considered.
Guide to Receptors and Channels, 1st Edition (2005 revision) (2005)

The great proliferation of drug targets in recent years has driven the need to organise and condense the information in a logical way. This is the underlying reason for this Guide to Receptors and Channels, distributed with the British Journal of Pharmacology and Nature Reviews Drug Discovery. Our intent is to produce an authoritative but user-friendly publication, which allows a rapid overview of the key properties of a wide range of established or potential pharmacological targets. The aim is to provide information succinctly so that a newcomer to a particular target group can identify the main elements ''at a glance''. It is not our goal to produce all-inclusive reviews of the targets presented; references to these are included in the Further Reading sections of the entries. The Guide to Receptors and Channels presents each entry, typically a circumscribed target class family, on a single page so as to allow easy access and rapid oversight. Targets have been selected for inclusion where there is sufficient pharmacological information to allow clear definition or where, in our view, there is clear interest in this molecular class from the pharmacological community. Our philosophy has been to present data on human receptors wherever possible, both in terms of structural information and pharmacology. To this end, the Ensembl ID allows rapid access through a free online database (http://www.ensembl.org/) to several other species, including mouse and rat. From this database, links are also provided to structural information in a number of formats. Where structural or pharmacological information is not available for human targets, we have used data from other species. A priority in constructing these tables was to present agents which represent the most selective and which are available by donation or from commercial sources, now or in the near future. The Guide is divided into seven sections, which comprise pharmacological targets of similar structure/function. These are 7TM receptors, transmitter-gated channels, ion channels, catalytic receptors, nuclear receptors, cell-surface transmitter transporters and second messenger metabolising enzymes. The Editors of the Guide have compiled the individual records, taking advice from many Consultants (listed on page ii). With each record, an indication is given of the status of the nomenclature as proposed by Nomenclature Committees of the International Pharmacological Congress (NC-IUPHAR), published in Pharmacological Reviews. Where this guidance is lacking, advice from several prominent, independent experts has been obtained to produce an authoritative consensus, which attempts to fit in within the general guidelines from IUPHAR (Vanhoutte et al., 1996). Tabulated data provide ready comparison of selective agents and we recommend that any citations to information in the guide be presented in the following format: e.g. Histamine receptors, in Guide to Receptors and Channels, radioligands within a family of targets and additional commentary highlights whether species differences or ligand metabolism are potential confounding factors.
Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis (2004)

Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells ( approximately 500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer.
Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily (1997)

The insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate the actions of the insulin-like growth factors in endocrine, paracrine, and autocrine settings. Additionally, some IGFBPs appear to exhibit biological effects that are IGF independent. The six high-affinity IGFBPs that have been characterized to date exhibit 40-60% amino acid sequence identity overall, with the most conserved sequences in their NH2 and COOH termini. We have recently demonstrated that the product of the mac25/IGFBP-7 gene, which shows significant conservation in the NH2 terminus, including an "IGFBP motif' (GCGCCXXC), exhibits low-affinity IGF binding. The closely related mammalian genes connective tissue growth factor (CTGF) gene, nov, and cyr61 encode secreted proteins that also contain the conserved sequences and IGFBP motifs in their NH2 termini. To ascertain if these genes, along with mac25/IGFBP-7, encode a family of low-affinity IGFBPs, we assessed the IGF binding characteristics of recombinant human CTGF (rhCTGF). The ability of baculovirus-synthesized rhCTGF to bind IGFs was demonstrated by Western ligand blotting, affinity cross-linking, and competitive affinity binding assays using 125I-labeled IGF-I or IGF-II and unlabeled IGFs. CTGF, like mac25/IGFBP-7, specifically binds IGFs, although with relatively low affinity. On the basis of these data, we propose that CTGF represents another member of the IGFBP family (IGFBP-8) and that the CTGF gene, mac25/IGFBP-7, nov, and cyr61 are members of a family of low-affinity IGFBP genes. These genes, along with those encoding the high-affinity IGFBPs 1-6, together constitute an IGFBP superfamily whose products function in IGF-dependent or IGF-independent modes to regulate normal and neoplastic cell growth.
Three-dimensional structure of murine anti-p-azophenylarsonate Fab 36-71. 1. X-ray crystallography, site-directed mutagenesis, and modeling of the complex with hapten (1991)

The structure of the antigen-binding fragment (Fab) of an anti-p-azophenylarsonate monoclonal antibody, 36-71, bearing a major cross-reactive idiotype of A/J mice has been refined to an R factor of 24.8% at a resolution of 1.85 A. The previously solved partial structure of this Fab at a resolution of 2.9 A (Rose et al., 1990) was used as an initial model for refinement against the high-resolution data. The complex with hapten has been modeled by docking the small-molecule crystal structure of phenylarsonic acid into the structure of the native Fab on the basis of a low-resolution electron density map of the complex. In this model, residue Arg-96 in the light chain and residues Asn-35, Trp-47, and Ser-99 in the heavy chain contact the arsonate moiety of the hapten; an additional bond is found between the arsonate group and a tightly bound water molecule. The phenyl moiety of the hapten packs against two tyrosine side chains at positions 50 and 106 in the heavy chain. Residue Arg-96 in the light chain had been implicated as involved in hapten binding on the basis of previous experiments, and indeed, this residue appears to play a crucial role in this model. Experiments employing site-directed mutagenesis directly support this conclusion. The heavy-chain complementarity-determining regions have novel conformations not previously observed in immunoglobulins except for the recently solved anti-p-azophenylarsonate Fab R 19.9 (Lascombe et al., 1989).
The functional relevance of somatic synonymous mutations in melanoma and other cancers (2015)

Recent technological advances in sequencing have flooded the field of cancer research with knowledge about somatic mutations for many different cancer types. Most cancer genomics studies focus on mutations that alter the amino acid sequence, ignoring the potential impact of synonymous mutations. However, accumulating experimental evidence has demonstrated clear consequences for gene function, leading to a widespread recognition of the functional role of synonymous mutations and their causal connection to various diseases. Here, we review the evidence supporting the direct impact of synonymous mutations on gene function via gene splicing; mRNA stability, folding, and translation; protein folding; and miRNA-based regulation of expression. These results highlight the functional contribution of synonymous mutations to oncogenesis and the need to further investigate their detection and prioritization for experimental assessment.
Complete primary structure of bovine plasma fibronectin (1986)

The primary structure of the 2265 residues of bovine plasma fibronectin has been completed. The new sequences reported in this paper are residues 600-868 (269 residues), 1138-1217 (80 residues), 1518-1599 (82 residues) and 1868-2061 (194 residues). These sequences constitute six type III homology units and two non-homologous connecting strands. Thus, there are fifteen type III homology units in plasma fibronectin. Evidence for two of the three splice variants found in rat liver cells [Schwarzbauer et al. (1983) Cell 35, 421-431] was obtained. No indication of the 'extra' type III domain present in some human fibroblast fibronectins [Kornblihtt et al. (1984) EMBO J. 3, 221-226] was found. Three carbohydrate groups (two glucosamine-based and one galactosamine-based) were identified, giving a total of eight carbohydrate groups in the longest splice variant of bovine plasma fibronectin. A second free sulfhydryl group (cysteine) was identified. This cysteine, like the first, is in a type III homology unit. HPLC patterns of peptides obtained from the C-terminal 6-kDa fragment suggested that the interchain bridge pattern of fibronectin is antiparallel. The bovine plasma fibronectin sequence is highly homologous to the human cellular fibronectin sequence deduced from the cDNA sequence [Kornblihtt et al. (1985) EMBO J. 4, 1755-1759].
A [Pd]-mediated ω-alkynone cycloisomerization approach for the central tetrahydropyran unit and the synthesis of C(31)–C(48) fragment of aflastatin A (2011)

A concise assembly of the central tetrahydropyran unit of aflastatin A featuring a Pd-mediated alkynone cycloisomerization to provide a glycal and its subsequent stereoselective hydroboration to deliver the requisite stereochemistry at C(33) and C(34) centers is documented.
The impact of non-endotoxin LAL-reactive materials on Limulus amebocyte lysate analyses. (1997)

Limulus amebocyte lysate (LAL) is activated by bacterial endotoxins and certain glucans (beta-D-glucan, LAL-RM). The potential for conflicting inter-laboratory results for LAL tests exists because commercial LAL reagents are highly variable in response to LAL-reactive glucans. The nature of beta-D-glucan activation of LAL and means for rendering LAL non-responsive to glucan are reviewed to provide a background for resolving conflicting data. Kinetic LAL methods are particularly useful for screening materials potentially contaminated with glucan. The presence of beta-D-glucan in parenterals is uncommon and is likely limited to products exposed to microbial or cellulosic materials. A scheme is suggested for identifying LAL-reactive glucans and for LAL release-testing without glucan interference.
A Bispecific Antibody-IFNα2b Immunocytokine Targeting CD20 and HLA-DR Is Highly Toxic to Human Lymphoma and Multiple Myeloma Cells (2010)

The short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα to a tumor-targeting monoclonal antibody (MAb-IFNα) can enhance potency due to increased tumor localization and improved pharmacokinetics. We report the generation and characterization of the first bispecific MAb-IFNα, designated 20-C2-2b, which comprises two copies of IFNα2b and a stabilized F(ab)(2) of hL243 (humanized anti-HLA-DR; IMMU-114) site-specifically linked to veltuzumab (humanized anti-CD20). In vitro, 20-C2-2b inhibited each of four lymphoma and eight myeloma cell lines, and was more effective than monospecific CD20-targeted MAb-IFNα or a mixture comprising the parental antibodies and IFNα in all but one (HLA-DR(-)/CD20(-)) myeloma line, suggesting that 20-C2-2b should be useful in the treatment of various hematopoietic malignancies. 20-C2-2b displayed greater cytotoxicity against KMS12-BM (CD20(+)/HLA-DR(+) myeloma) compared with monospecific MAb-IFNα, which targets only HLA-DR or CD20, indicating that all three components in 20-C2-2b could contribute to toxicity. Our findings indicate that a given cell's responsiveness to MAb-IFNα depends on its sensitivity to IFNα and the specific antibodies, as well as the expression and density of the targeted antigens.
Attosecond timing jitter actively modelocked semiconductor fiber ring laser with normal net cavity dispersion (2007)

We report the generation of optical pulse trains with timing jitter of 770 attosecond (1 Hz -10 MHz) and 17.5 fs (extrapolated to Nyquist frequency) from a modelocked laser, using slab coupled optical waveguide amplifier.
A cell-penetrating antibody inhibits human RAD51 via direct binding (2017)

RAD51, a key factor in homology-directed repair (HDR), has long been considered an attractive target for cancer therapy, but few specific inhibitors have been found. A cell-penetrating, anti-DNA, lupus autoantibody, 3E10, was previously shown to inhibit HDR, sensitize tumors to radiation, and mediate synthetic lethal killing of BRCA2-deficient cancer cells, effects that were initially attributed to its affinity for DNA. However, as the molecular basis for its ability to inhibit DNA repair, we report that 3E10 directly binds to the N-terminus of RAD51, sequesters RAD51 in the cytoplasm, and impedes RAD51 binding to DNA. Further, we generate separation-of-function mutations in the complementarity-determining regions of 3E10 revealing that inhibition of HDR tracks with binding to RAD51 but not to DNA, whereas cell penetration is linked to DNA binding. The consequences of these mutations on putative 3E10 interactions with RAD51 and DNA are correlated with in silico molecular modeling. Taken together, the results identify 3E10 as a novel inhibitor of RAD51 by direct binding, accounting for its ability to suppress HDR and providing the molecular basis to guide pre-clinical development of 3E10 as an anti-cancer agent.
Effectiveness and security of CT-guided percutaneous implantation of125I seeds in pancreatic carcinoma (2014)

The CT-guided percutaneous implantation of (125)I seeds in unresectable pancreatic cancer showed highly successful rates without serious complications.
Prediction of the binding energy for small molecules, peptides and proteins (1999)

A fast and reliable evaluation of the binding energy from a single conformation of a molecular complex is an important practical task. Knowledge-based scoring schemes may not be sufficiently general and transferable, while molecular dynamics or Monte Carlo calculations with explicit solvent are too computationally expensive for many applications. Recently, several empirical schemes using finite difference Poisson-Boltzmann electrostatics to predict energies for particular types of complexes were proposed. Here, an improved empirical binding energy function has been derived and validated on three different types of complexes: protein-small ligand, protein-peptide and protein-protein. The function uses the boundary element algorithm to evaluate the electrostatic solvation energy. We show that a single set of parameters can predict the relative binding energies of the heterogeneous validation set of complexes with 2.5 kcal/mol accuracy. We also demonstrate that global optimization of the ligand and of the flexible side-chains of the receptor improves the accuracy of the evaluation.