gebhart/patrepeval huggingface dataset:
Inhibitory effects of antisense cathepsin B cDNA transfection on invasion and motility in a human osteosarcoma cell line. (1999)

Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by activating other matrix-degrading proteases like the urokinase-type plasminogen activator. To investigate the role of cathepsin B in bone tumor invasion, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense cDNA transcript of cathepsin B. Five stably transfected antisense cell clones, the control (vector) cell clones, and the parental cells were characterized. At first, the stable incorporation of the constructs was demonstrated by Southern blot analysis. In ELISA assays, all antisense clones showed a significant reduction at the cathepsin B antigen level (about 70%) as compared with the control cell clones and MNNG/HOS. Similar results were obtained for cathepsin B activity in the antisense-transfected cells. In the antisense cell clones, Northern blot analysis and reverse transcription-PCR revealed a considerable decrease of approximately 50% in the levels of cathepsin B mRNA. Expression of cathepsins L and K (sequence homologies) was not affected. The invasive potential and migration of untransfected and transfected tumor cell clones in vitro were analyzed in Transwell chambers. Antisense-transfected cells showed a markedly lower invasion and motility than did MNNG/HOS and the controls. Adhesion to collagen I and matrigel matrices was not affected. These results demonstrate that cathepsin B is involved in the complex proteolytic processes in invasive osteosarcomas.
Gene Transfer Using a Novel Fusion Protein, GAL4/Invasin (1997)

The delivery of DNA to target cells using simple, defined, nonviral systems has become an area of intense interest in gene therapy. We describe here the development and characterization of one such novel system. A recombinant, bifunctional, fusion protein was expressed and purified from Escherichia coli. This protein consists of the DNA-binding domain of the yeast transcription factor GAL4 fused to the cell binding, internalization domain of the Yersinia pseudotuberculosis inv gene product, invasin. This protein, GAL4/Inv, together with poly-L-lysine, formed complexes with a chloramphenicol acetyltransferase (CAT) reporter plasmid that contains eight repeats of the GAL4 consensus recognition sequence. These complexes were shown to transfect target cells in an invasin receptor-dependent manner, resulting in transient CAT expression. A simple, targeted DNA delivery vehicle, as we describe here, represents a viable approach to nonviral gene delivery.
α-Enolase, a Novel Strong Plasmin(ogen) Binding Protein on the Surface of Pathogenic Streptococci (1998)

The plasmin(ogen) binding property of group A streptococci is incriminated in tissue invasion processes. We have characterized a novel 45-kDa protein displaying strong plasmin(ogen) binding activity from the streptococcal surface. Based on its biochemical properties, we confirmed the identity of this protein as alpha-enolase, a key glycolytic enzyme. Dose-dependent alpha-enolase activity, immune electron microscopy of whole streptococci using specific antibodies, and the opsonic nature of polyclonal and monoclonal antibodies concluded the presence of this protein on the streptococcal surface. We, henceforth, termed the 45-kDa protein, SEN (streptococcal surface enolase). SEN is found ubiquitously on the surface of most streptococcal groups and serotypes and showed significantly greater plasmin(ogen) binding affinity compared with previously reported streptococcal plasminogen binding proteins. Both the C-terminal lysine residue of SEN and a region N-terminal to it play a critical role in plasminogen binding. Results from competitive plasminogen binding inhibition assays and cross-linking studies with intact streptococci indicate that SEN contributes significantly to the overall streptococcal ability to bind plasmin(ogen). Our findings, showing both the protected protease activity of SEN-bound plasmin and SEN-specific immune responses, provide evidence for an important role of SEN in the disease process and post-streptococcal autoimmune diseases.
Combinatorial androgen receptor targeted therapy for prostate cancer (2006)

Prostatic carcinogenesis is associated with changes in the androgen receptor (AR) axis converting it from a paracrine dependence upon stromal signaling to an autocrine-initiated signaling for proliferation and survival of prostatic cancer cells. This malignant conversion is due to gain of function changes in which the AR activates novel genomic (i.e. transcriptional) and non-genomic signaling pathways, which are not present in normal prostate epithelial cells. During further progression, additional molecular changes occur which allow these unique malignancy-dependent AR signaling pathways to be activated even in the low androgen ligand environment present following androgen ablation therapy. These signaling pathways are the result of partnering the AR with a series of other genomic (e.g. transcriptional co-activators) or non-genomic (e.g. steroid receptor co-activator (Src) kinase) signaling molecules. Thus, a combinatorial androgen receptor targeted therapy (termed CART therapy) inhibiting several points in the AR signaling cascade is needed to prevent the approximately 30,000 US males per year dying subsequent to failure of standard androgen ablation therapy. To develop such CART therapy, a series of agents targeted at specific points in the AR cascade should be used in combination with standard androgen ablative therapy to define the fewest number of agents needed to produce the maximal therapeutic anti-prostate cancer effect. As an initial approach for developing such CART therapy, a variety of new agents could be combined with luteinizing hormone-releasing hormone analogs. These include: (1) 5alpha-reductase inhibitors to inhibit the conversion of testosterone to the more potent androgen, dihydrotestosterone; (2) geldanamycin analogs to downregulate AR protein in prostate cancer cells, (3) 'bulky' steroid analogs, which can bind to AR and prevent its partnering with other co-activators/signaling molecules, and (4) small molecule kinase inhibitors to inhibit MEK, which is activated as part of the malignant AR signaling cascade.
Prognostic factors in aggressive non-Hodgkin's lymphoma: who has "high- risk" disease? (1994)

Abstract As the above-mentioned cellular and molecular parameters and newly identified biologic features are evaluated in larger numbers of patients with aggressive NHL, the biologic heterogeneity of this disease will be better appreciated. With a more complete understanding of the disease, it is likely that we will substitute biologic variables for clinical surrogate features in our prognostic factor models and target these biologic variables for therapy in specific subsets of patients. In the meantime, widely accepted clinical models such as the International Index and the age-adjusted index will aid in the identification of specific patient risk groups and the ongoing comparison of different therapeutic approaches. Early restaging with sensitive techniques like Ga-67 citrate scans may also identify patients with suboptimal responses to induction therapy at timepoints when additional therapeutic alternatives may be most effective.
Insights in the rational design of synthetic multivalent glycoconjugates as lectin ligands (2010)

Much effort has been made during the last decade to design lectin inhibitors as therapeutics against viral and bacterial adhesion or to control biological functions. The chemical strategy adopted generally consists in the tethering of several binding epitopes on a common scaffold. The resulting multivalent glycoconjugates often display a much higher binding affinity for their targets compared to their monovalent counterparts, a phenomenon designed as the "cluster" or "multivalent effect". Hundreds of multimeric architectures have been designed so far and some of the compounds displayed impressive gains in binding affinity or in vivo efficiency. Progress in this area is, however, hampered by the difficulty to predict the potency of the new multimeric inhibitors. This review presents the recent efforts to probe the important structural features of the synthetic multivalent glycoconjugates for a tight binding with specific lectins. We hope that the reported examples will aid the reader to design efficient multivalent ligands in a more predictable way.
Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis rat. The utility of a class II binding motif in selecting self-reactive peptides. (1994)

Cardiac myosin (CM) has been implicated as an autoantigen in the induction of experimental allergic myocarditis (EAM). At the present time no myocarditogenic peptides of CM have been identified. To identify CM peptides with myocarditogenic properties we have made use of a putative binding motif for the MHC class II molecule RT1.BI in the rat. The amino acid sequence of CM alpha-chain was scanned and found to contain nine peptides that contain this binding motif, three peptides found only in the cardiac form of myosin were chosen for further study. This manuscript describes the identification of two CM peptides capable of inducing EAM in the Lewis rat. In doing so this study demonstrates the utility of an MHC class II binding motif to (correctly) predict pathogenic, autoimmunity inducing, peptides. Peptides, CM 1, and CM 2 are the first peptides described that are capable of inducing EAM in rats. The utilization of CM 2 peptide has permitted the establishment of a long term, Ag specific cell line capable of adoptively transferring EAM. Moreover, the establishment of CM 2 specific T lymphocyte lines has permitted the description of a detailed proliferative response of a myocarditogenic cell line to a specific cardiac Ag. The identification of CM 1 and 2 formally proves that CM, and not a co-purified contaminant, is an Ag in EAM. Finally, this report documents that experimentally induced giant cell myocarditis is not a separate disease entity arising from a distinct cardiac Ag or CM epitope from regular myocarditis.
Induction of acetylcholine receptors on cultured skeletal muscle by a factor extracted from brain and spinal cord. (1979)

Extracts of chicken brain and spinal cord increase the total number of acetylcholine receptors and the number of acetylcholine receptors and the number of receptor clusters on uninnervated skeletal myotubes in culture. The active component in these extracts may be unique to neural tissue. Spinal cord cells grown in culture contain the active factor and they secrete it into the medium. Most of the activity is associated with a small molecule possibly a peptide. Such a factor may be responsible for the clustering of receptors at newly formed nerve-muscle synapses.
In Vitro Induction of Trophoblast from Human Embryonic Stem Cells (2005)

Human embryonic stem (ES) cells can proliferate without a known limit and can form advanced derivatives of all three embryonic germ layers. What is less widely appreciated is that human ES cells can also form the extra-embryonic tissues that differentiate from the embryo before gastrulation. The use of human ES cells to derive early human trophoblast is particularly valuable, because it is difficult to obtain from other sources and is significantly different from mouse trophoblast. Here we describe a method by using bone morphogenetic protein (BMP)4, a member of the transforming growth factor (TGF)-beta superfamily, to induce the differentiation of human ES cells to trophoblast. Immunoassays (as well as DNA microarray and reverse-transcription polymerase chain reaction analyses--data not shown) demonstrate that the differentiated cells express a range of trophoblast markers and secrete placental hormones. When plated at low density, the BMP4-treated cells form syncytia that express chorionic gonadotrophin (CG). This technique underscores fundamental differences between human and mouse ES cells, which differentiate poorly, if at all, to trophoblast. Human ES cells thus provide a tool for studying the differentiation and function of early human trophoblast and could provide a new understanding of some of the earliest differentiation events of human postimplantation development.
A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants (2012)

Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.
Development of anti-p185HER2 immunoliposomes for cancer therapy. (1995)

The product of the HER2 protooncogene, p185HER2, represents an attractive target for cancer immunotherapies. We have prepared anti-p185HER2 immunoliposomes in which Fab' fragments of a humanized anti-p185HER2 monoclonal antibody with antiproliferative properties (rhuMAb-HER2) were conjugated to either conventional or sterically stabilized liposomes. These immunoliposomes bind specifically to p185HER2-overexpressing breast cancer cells (SK-BR-3 and BT-474). High-affinity binding of anti-p185HER2 immunoliposomes is comparable to that of free rhuMAbHER2-Fab' or the intact antibody. Empty immunoliposomes inhibit the culture growth of p185HER2-overexpressing breast cancer cells, and this antiproliferative effect is superior to that of free rhuMAbHER2-Fab', indicating that liposomal anchoring of these anti-p185HER2 Fab' fragments enhances their biological activity. Efficient internalization of anti-p185HER2 immunoliposomes, demonstrated by light and electron microscopy, occurs by receptor-mediated endocytosis via the coated pit pathway and also possibly by membrane fusion. Doxorubicin-loaded anti-p185HER2 immunoliposomes are markedly and specifically cytotoxic against p185HER2-overexpressing tumor cells in vitro. Anti-p185HER2 immunoliposomes administered in vivo in Scid mice bearing human breast tumor (BT-474) xenografts can deliver doxorubicin to tumors. These results indicate that anti-p185HER2 immunoliposomes are a promising therapeutic vehicle for the treatment of p185HER2-overexpressing human cancers.
Biomechanical Pulping of Loblolly Pine Chips with Selected White-Rot Fungi (1993)

Abstracting & Indexing
Functional Analysis of Bacillus anthracis Protective Antigen by Using Neutralizing Monoclonal Antibodies (2004)

Protective antigen (PA) is central to the action of the lethal and edema toxins produced by Bacillus anthracis. It is the common cell-binding component, mediating the translocation of the enzymatic moieties (lethal factor [LF] and edema factor) into the cytoplasm of the host cell. Monoclonal antibodies (MAbs) against PA, able to neutralize the activities of the toxins in vitro and in vivo, were screened. Two such MAbs, named 7.5 and 48.3, were purified and further characterized. MAb 7.5 binds to domain 4 of PA and prevents the binding of PA to its cell receptor. MAb 48.3 binds to domain 2 and blocks the cleavage of PA into PA63, a step necessary for the subsequent interaction with the enzymatic moieties. The epitope recognized by this antibody is in a region involved in the oligomerization of PA63; thus, MAb 48.3 does not recognize the oligomer form. MAbs 7.5 and 48.3 neutralize the activities of anthrax toxins produced by B. anthracis in mice. Also, there is an additive effect between the two MAbs against PA and a MAb against LF, in protecting mice against a lethal challenge by the Sterne strain. This work contributes to the functional analysis of PA and offers immunotherapeutic perspectives for the treatment of anthrax disease.
Mach–Zehnder interferometer as a spectral analyzer for molecular Doppler wind lidar (2001)

The theoretical performance of a Mach-Zehnder interferometer used as a spectral analyzer for wind-speed measurement by direct-detection Doppler lidar is presented. The interferometer is optimized for measurement of wind velocity from the signal backscattered by the molecules. Two arrangements are proposed, involving two detection channels (DMZ) or four detection channels (QMZ). Using the assumption of a pure molecular signal with a Gaussian spectral profile, we derive an analytic expression for the standard deviation of the measurement error for each arrangement. They are then compared with the ideal spectral analyzer (ISA) and with the double-edge Fabry-Perot (DFP) in the case of a shot-noise-limited signal. The DMZ measurement error is shown to be only 1.65 times that of the ISA and is 1.4 times lower than that given by the DFP. The QMZ arrangement provides a measurement that is insensitive to the aerosol scattering contribution but gives a measurement error that is 1.4 times higher than that of the DMZ.
Gene Expression Profiling by DNA Microarrays and Metabolic Fluxes in Escherichia coli (2000)

DNA microarray technology was applied to detect differential transcription profiles of a subset of the Escherichia coli genome. A total of 111 E. coli genes, including those in central metabolism, key biosyntheses, and some regulatory functions, were cloned, amplified, and used as probes for detecting the level of transcripts. An E. coli strain was grown in glucose, acetate, and glycerol media, and the transcript levels of the selected genes were detected. Despite extensive studies on E. coli physiology, many new features were found in the regulation of these genes. For example, several genes were unexpectedly up-regulated, such as pps, ilvG, aroF, secA, and dsbA in acetate and asnA and asnB in glycerol, or down-regulated, such as ackA, pta, and adhE in acetate. These genes were regulated with no apparent reasons by unknown mechanisms. Meanwhile, many genes were regulated for apparent purposes but by unknown mechanisms. For example, the glucose transport genes (ptsHI, ptsG, crr) in both acetate and glycerol media were down-regulated, and the ppc, glycolytic, and biosynthetic genes in acetate were also down-regulated because of the reduced fluxes. However, their molecular mechanisms remain to be elucidated. Furthermore, a group of genes were regulated by known mechanisms, but the physiological roles of such regulation remain unclear. This group includes pckA and aspA, which are up-regulated in glycerol, and gnd and aspA, which are down- and up-regulated, respectively, in acetate. The DNA microarray technology demonstrated here is a powerful yet economical tool for characterizing gene regulation and will prove to be useful for strain improvement and bioprocess development.
Lumped Elements for RF and Microwave Circuits (2003)

Due to the unprecedented growth in wireless applications over the past decade, development of low-cost solutions for RF and microwave communication systems has become of great importance. This practical new book is the first comprehensive treatment of lumped elements, which are playing a critical role in the development of the circuits that make these cost-effective systems possible. The books offers you an in-depth understanding of the different types of RF and microwave circuit elements, including inductors, capacitors, resistors, transformers, via holes, airbridges, and crossovers. Support
Changes in Plasma Lipoprotein Cholesterol Levels by Antisense Oligodeoxynucleotides against Cholesteryl Ester Transfer Protein in Cholesterol-fed Rabbits (1996)

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apoB-containing lipoproteins and also affects the low density lipoprotein metabolism. On the other hand, the liver is the major tissue responsible for the production of CETP (CETP mRNA) in rabbits. To test the hypothesis that a reduction of CETP mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect the plasma lipoprotein cholesterol levels, we intravenously injected antisense ODNs against rabbit CETP coupled with asialoglycoprotein carrier molecules, which serve as an important method to regulate liver gene expression, to cholesterol-fed rabbits via their ear veins. All rabbits were fed a standard rabbit chow supplement with 0.1% cholesterol for 10 weeks before and throughout the experiment. After injecting rabbits with antisense ODNs, the plasma total cholesterol concentrations and plasma CETP activities all decreased at 24, 48, and 96 h, whereas the plasma HDL cholesterol concentrations increased at 48 h. A reduction in the hepatic CETP mRNA was also observed at 6, 24, and 48 h after the injection with antisense ODNs. However, in the rabbits injected with sense ODNs, the plasma total and HDL cholesterol concentrations and the plasma CETP activities did not significantly change, and the hepatic CETP mRNA did not change either throughout the experimental period. Although the exact role of CETP in the development of atherosclerosis remains to be clarified, these findings showed for the first time that the intravenous injection with antisense ODNs against CETP coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma CETP activity and, as a result, could induce a decrease in the plasma low density lipoprotein and very low density lipoprotein cholesterol and an increase in the plasma HDL cholesterol in cholesterol-fed rabbits.
An Investigation of Missing Data Methods for Classification Trees (2006)

There are many different missing data methods used by classification tree algorithms, but few studies have been done comparing their appropriateness and performance. This paper provides both analytic and Monte Carlo evidence regarding the effectiveness of six popular missing data methods for classification trees. We show that in the context of classification trees, the relationship between the missingness and the dependent variable, rather than the standard missingness classification approach of Little and Rubin (2002) (missing completely at random (MCAR), missing at random (MAR) and not missing at random (NMAR)), is the most helpful criterion to distinguish different missing data methods. We make recommendations as to the best method to use in various situations. The paper concludes with discussion of a real data set related to predicting bankruptcy of a firm.
Impaired Fas Response and Autoimmunity in Pten +/− Mice (1999)

Inactivating mutations in the PTEN tumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown that Pten heterozygous (Pten+/-) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten+/- mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. Phosphatidylinositol (PI) 3-kinase inhibitors restored Fas responsiveness in Pten+/- cells. These results indicate that Pten is an essential mediator of the Fas response and a repressor of autoimmunity and thus implicate the PI 3-kinase/Akt pathway in Fas-mediated apoptosis.