gebhart/patrepeval huggingface dataset:
Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis. (1983)

A protein with properties of laminin has been isolated from human placental extracts by using monoclonal antibodies. Placental tissue was extracted with 0.5 M NaCl and high molecular weight proteins were isolated from the extract by salt precipitation and gel filtration on Sepharose 6B. The resulting protein fraction which contained material cross-reactive with anti-sera to rat laminin was used as immunogen to prepare hybridomas. Thirteen hybrids produced antibodies which reacted with basement membrane-associated antigens in indirect immunofluorescence of tissues. One of these, 4E10, was characterized in detail. This monoclonal antibody reacted with human laminin as shown by several lines of evidence. Immunoprecipitation from metabolically labeled culture media of a human amniotic epithelial cell line with the 4E10 antibody followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed polypeptides with Mr similar to those of rat laminin. Immunochromatography of placental extracts obtained by limited pepsin digestion yielded material with main polypeptides at 160 and 130 kilodaltons in sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction. These peptic fragments cross-reacted with rat laminin in immunodiffusion and enzyme immunoassay, and a polyclonal antiserum against the fragments reacted with basement membranes in tissues in a manner identical with the 4E10 antibody. Electron microscopic images of the human peptic fragments showed structures similar to the cross-shaped images of murine laminins, although the short arms were truncated to various degrees or even absent. The isolated peptic fragments also displayed biological activity similar to that of murine laminins in that the outgrowth of neurites by neuronal cells was promoted on plates coated with the fragments.
Scaling-up production of recombinant AAV vectors for clinical applications. (2000)

Recombinant adeno-associated virus (AAV)-based vectors capable of expressing therapeutic gene products in vivo have shown significant promise for human gene therapy. A major challenge for these applications is the development of processes to enable production of large quantities of AAV vectors and purification of material that is well characterized and appropriate for parenteral administration. Several cell culture systems have been developed for AAV vector production, and a limited number of these demonstrate the potential to generate AAV vectors at concentrations compatible with cost-effective large-scale production. Vector purification protocols, in particular those based on the use of scalable column chromatography, have concurrently been developed that demonstrate the potential to provide highly purified AAV vector preparations with high yield. These advances support the potential for AAV vectors as therapeutic agents for gene therapy.
Transmission Lines and Networks (1950)

Transmission lines and networks , Transmission lines and networks , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Trehalose 6,6′-Dimycolate (Cord Factor) Enhances Neovascularization through Vascular Endothelial Growth Factor Production by Neutrophils and Macrophages (2000)

Trehalose 6,6'-dimycolate (TDM) plays important roles in the development of granulomatous inflammation during infection with Mycobacterium spp., Rhodococcus spp., etc. To reveal the augmenting effect of TDM on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granulomatous tissue air pouches induced by Rhodococcus sp. strain 4306 TDM dissolved in Freund's incomplete adjuvant (FIA), comparing them to pouches treated with FIA alone. Histologically, granulomatous tissue and new vessel formation, which reached a maximum at day 7, was greatly enhanced by treatment with TDM. At day 1, VEGF-positive neutrophils accumulated in the pouch wall with frequency of 95% of total infiltrating cells, adhering to TDM-containing micelles. By day 3, granulomatous tissue and new vessels started to develop, and VEGF-positive macrophages appeared in a small number and gradually increased in number thereafter. The pouch contents of VEGF, interleukin-1beta, tumor necrosis factor alpha, and transforming growth factor beta were significantly elevated in TDM-treated pouches, with peaks at days 1, 0.5, 1, and 3, respectively, compared to those of control pouches, while that of basic fibroblast growth factor showed no significant increase. Treatment with anti-VEGF antibody inhibited TDM-induced granulomatous tissue formation and neovascularization, and administration of recombinant VEGF into pouches treated with FIA alone induced neovascularization comparable to that in the TDM-treated pouches. Incubation of neutrophils and macrophages on TDM-coated plastic dishes increased the VEGF release. The present results indicate that TDM augments VEGF production by neutrophils and macrophages and induces neovascularization in the granulomatous tissue.
Directed Assembly of Lamellae‐ Forming Block Copolymers by Using Chemically and Topographically Patterned Substrates (2007)

Lamellae-forming polystyrene-block-poly(methyl methacrylate) films were directed to assemble with perpendicularly oriented domains and long-range order in confining grooves (see figure), with preferential and neutral wetting in sidewalls and bottoms, respectively. The assembled films were highly amenable for pattern transfer by reactive-ion etching.
Signaling of Human Ciliary Neurotrophic Factor (CNTF) Revisited (2003)

Human ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that exerts a neuroprotective effect in multiple sclerosis and amyotrophic lateral sclerosis. Clinical application of human CNTF, however, was prevented by high toxicity at higher dosages. Human CNTF elicits cellular responses by induction of a receptor complex consisting of the CNTF alpha-receptor (CNTFR), which is not involved in signal transduction, and the beta-receptors gp130 and leukemia inhibitory factor receptor (LIFR). Previous studies with rat CNTF demonstrated that rat CNTF is unable to interact with the human interleukin-6 alpha-receptor, whereas at high concentrations, it can directly induce a signaling heterodimer of human gp130 and human LIFR in the absence of the CNTF receptor. Here, we demonstrate that human CNTF cannot directly induce a heterodimer of human gp130 and LIFR. However, human CNTF can use both the membrane-bound and the soluble human IL-6R as a substitute for its cognate alpha-receptor and thus widen the target spectrum of human CNTF. Engineering a CNTFR-specific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF.
A series of anti-CEA/anti-DOTA bispecific antibody formats evaluated for pre-targeting: comparison of tumor uptake and blood clearance (2012)

A series of anti-tumor/anti-chelate bispecific antibody formats were developed for pre-targeted radioimmunotherapy. Based on the anti-carcinoembryonic antigen humanized hT84.66-M5A monoclonal antibody and the anti-DOTA C8.2.5 scFv antibody fragment, this cognate series of bispecific antibodies were radioiodinated to determine their tumor targeting, biodistribution and pharmacokinetic properties in a mouse xenograft tumor model. The in vivo biodistribution studies showed that all the bispecific antibodies exhibited specific high tumor uptake but the tumor targeting was approximately onehalf of the parental anti-CEA mAb due to faster blood clearance. Serum stability and FcRn studies showed no apparent reason for the faster blood clearance. A dual radiolabel biodistribution study revealed that the 111 In-DOTA bispecific antibody had increased liver and spleen uptake, not seen for the 125 I-version due to metabolism and release of the radioiodine from the cells. These data suggest increased clearance of the antibody fusion formats by the mononuclear phagocyte system. Importantly, a pre-targeted study showed specific tumor uptake of 177 Lu-DOTA and a tumor : blood ratio of 199 : 1. This pretargeted radiotherapeutic and substantial reduction in the radioactive exposure to the bone marrow should enhance the therapeutic potential of RIT.
Design ofN-SpiroC2-Symmetric Chiral Quaternary Ammonium Bromides as Novel Chiral Phase-Transfer Catalysts:  Synthesis and Application to Practical Asymmetric Synthesis of α-Amino Acids (2003)

A series of C(2)-symmetric chiral quaternary ammonium bromides 10 and 11 have been designed as a new, purely synthetic chiral phase-transfer catalyst, and readily prepared from commercially available optically pure 1,1'-bi-2-naphthol as a basic chiral unit. The details of the synthetic procedures of each requisite chiral binaphthyl subunit have been disclosed, and the structures of the assembled N-spiro chiral quaternary ammonium bromides 11a and 11f were unequivocally determined by single-crystal X-ray diffraction analysis. The reactivity and selectivity of these chiral ammonium bromides as chiral phase-transfer catalysts have been evaluated in the asymmetric alkylation of the benzophenone Schiff base of glycine ester 7 under mild liquid-liquid phase-transfer conditions, and the optimization of the reaction variables (solvent, base, and temperature) has also been conducted. Further, the scope and limitations of this asymmetric alkylation have been thoroughly investigated with a variety of alkyl halides, in which the advantage of the unique N-spiro structure of 11 and dramatic effect of the steric as well as the electronic properties of the aromatic substituents on the 3,3'-position of one binaphthyl moiety have been particularly emphasized. Finally, the potential synthetic utility of the present method for the practical asymmetric synthesis of structurally diverse natural and unnatural alpha-amino acids has been demonstrated by its successful application to the facile asymmetric syntheses of (S)-N-acetylindoline-2-carboxylate, a key intermediate in the synthesis of the ACE inhibitor, and l-Dopa (l-3,4-dihydroxyphenylalanine) ester and its analogue.
Characterization of Peptide YY Receptors in the Brain (1989)

We studied the pharmacological and structural characteristics of peptide YY (PYY) receptors in porcine brain. PYY and neuropeptide Y (NPY) bound with high affinity to crude membrane preparations from the hippocampus, but their C-terminal fragments bound with 30- to 450-fold lower affinity Guanine nucleotides, especially the nonhydrolyzable GTP analog GTP gammas inhibited the binding of [125I]PYY, but other transmitters, hormones, and central nervous system-acting drugs did not, except for gangliosides at high concentrations. These results suggest that PYY receptor binding resides in the N-terminal part of the PYY molecule and is coupled to a guanine nucleotide regulatory protein. To elucidate PYY receptor structure, we used the cross-linking reagent disuccinimidyl suberate to covalently attach [125I]PYY to its receptors in the hippocampus membrane. Gel electrophoresis followed by autoradiography revealed a band centered at the mol wt of 50,000. Competitive inhibition of binding by unlabeled PYY resulted in a parallel inhibition of labeling of the 50,000 mol wt protein. The reducing agent 2-mercaptoethanol did not affect the appearance of this band, suggesting that the PYY receptor does not have subunits connected by sulfhydryl bonds. Furthermore, cross-linking [125I]NPY to its receptors in the porcine hippocampus produced the same 50,000 mol wt band regardless of 2-mercaptoethanol. The identity in the size of NPY and PYY receptors together with their similarities in binding properties including regional distribution and peptide specificity, indicate that NPY and PYY regulate brain function through interaction at a common receptor site.
Syndecan-1 regulates αvβ3 and αvβ5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor (2009)

Syndecan-1 (Sdc1) is a matrix receptor shown to associate via its extracellular domain with the alpha(v)beta(3) and alpha(v)beta(5) integrins, potentially regulating cell adhesion, spreading, and invasion of cells expressing these integrins. Using Sdc1 deletion mutants expressed in human mammary carcinoma cells, we identified the active site within the Sdc1 core protein and derived a peptide inhibitor called synstatin (SSTN) that disrupts Sdc1's interaction with these integrins. Because the alpha(v)beta(3) and alpha(v)beta(5) integrins are critical in angiogenesis, a process in which a role for Sdc1 has been uncertain, we used human vascular endothelial cells in vitro to show that the Sdc1 regulatory mechanism is also required for integrin activation on these cells. We found Sdc1 expressed in the vascular endothelium during microvessel outgrowth from aortic explants in vitro and in mouse mammary tumors in vivo. Moreover, we show that SSTN blocks angiogenesis in vitro or when delivered systemically in a mouse model of angiogenesis in vivo, and impairs mammary tumor growth in an orthotopic mouse tumor model. Thus, Sdc1 is a critical regulator of these two important integrins during angiogenesis and tumorigenesis, and is inhibited by the novel SSTN peptide.
Potential of p38 MAP kinase inhibitors in the treatment of cancer (2003)

The involvement of chronic inflammation in tumor development and progression is reviewed. Based on the natural history of certain diseases and epidemiology studies, a strong association has been established between particular chronic inflammatory conditions and eventual tumor appearance. Solid tumors require a stroma for their growth and recruit macrophages to synthesize essential growth and angiogenic factors that they do not have the capacity to produce. The microenvironment of the local host tissue appears to be an active participant in exchanging cytokines and enzymes with tumor cells that modify the local extracellular matrix, stimulate migration, and promote tumor angiogenesis, proliferation and survival. The role of p38 MAP kinase as a therapeutic target for treating cancer is discussed.
Retroregulation of the int gene of bacteriophage lambda: control of translation completion. (1981)

Bacteriophage lambda regulates the integration--excision reaction as a crucial aspect of the choice of pathway during lysogenic or lytic viral development. This control involves differential expression of the tightly linked, partially overlapping int and xis genes from two promoter sites: pI, positively regulated by cII/cIII proteins, and pL, positively regulated by N protein. After lambda infection, Int is synthesized from the pI transcript under cII regulation; however, very little Int is produced from the pL RNA because of the existence of a cis-acting regulatory element, sib, on the opposite side of the int gene from the pL promoter. Presumably sib serves to prevent unwanted synthesis of Int protein during the lytic response; the Int protein necessary for excisive recombination from a prophage can be supplied by pL transcription because sib is separated from int by prophage insertion. We have studied the effect of sib on nearby lambda genes by means of gel electrophoresis of labeled proteins from infected cells. Deletion of the sib region greatly enhances production of Int protein without substantial effect on Xis production; thus, sib regulation normally is highly specific for Int. When the sib region is moved past int and xis by deletion, regulation of the adjacent gene for the protein Ea22 occurs, suggesting that sib regulation can work on other genes. Although synthesis of wild-type Int is severely inhibited by sib, shorter Int protein fragments generated by nonsense mutations escape sib regulation, indicating that the regulation is translational and occurs near the completion stage of protein synthesis. Regulation by sib thus exhibits novel regulatory features: distal location, recombinational control, and regulation of the completion of protein synthesis. Because Int and Ea22 control is lost in a RNase III- host, we suggest that sib regulation might involve RNase III cleavage of a RNA duplex region that includes sib and the regulatory target (normally the int gene). We note such a potential site within int.
ChemInform Abstract: β1‐SELECTIVE ADRENOCEPTOR ANTAGONISTS: EXAMPLES OF THE 2‐(4‐(3‐(SUBSTITUTED‐AMINO)‐2‐HYDROXYPROPOXY)PHENYL)IMIDAZOLE CLASS (1983)

Abstract Ausgehend von den Phenolen (I) erhält man über die Epoxide (III) die Aminoalkohole (IV).
Polymeric particles conjugated with a ligand to VCAM‐1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis (2008)

The increased expression of VCAM-1 on endothelial segments within plaque regions could be used as a target to deliver polymeric drug carriers selectively to sites of atherosclerosis. We probed the hypothesis that polymeric particles conjugated with a ligand for VCAM-1 exhibit selective and avid adhesion to sites of atherosclerosis. Particles made from polystyrene or the biodegradable polymer poly(sebacic acid)-block-polyethylene glycol (PSA-PEG) were conjugated with an antibody to VCAM-1 (alpha-VCAM-1) or IgG (negative control). The particles were injected into the jugular vein of ApoE(-/-) (a murine model of atherosclerosis) or wild type mice and their adhesion to the aorta determined. alpha-VCAM-1 particles exhibited significantly greater adhesion to ApoE(-/-) mouse aorta [32 +/- 5 (mean +/- SEM) particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles] compared to the level of adhesion to wild type mouse aorta (18 +/- 1 particles/mm(2) for polystyrene particles and 6 +/- 1 particles/mm(2) for PSA-PEG particles). Within ApoE(-/-) mice, the alpha-VCAM-1 particles exhibited significantly greater adhesion to the aorta (32 +/- 5 particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles) compared to the adhesion of IgG particles (1 +/- 1 particles/mm(2) for polystyrene particles and 2 +/- 1 particles/mm(2) for PSA-PEG particles). Detailed analysis of the adhesion revealed that alpha-VCAM-1 particles exhibited focal adhesion to plaque regions, in particular the periphery of the plaques, within the ApoE(-/-) mouse aorta. Combined the data demonstrate that polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid and focal adhesion to sites of atherosclerosis providing strong evidence that VCAM-1 ligand bearing polymeric particles could be used for targeting drugs selectively to atherosclerotic tissue.
Hormones and Cancer (1996)

This text discusses fundamental concepts in molecular genetics, endocrinilogy and cancer, including clinical research results.
A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA (2015)

Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.
Tobacco : production, chemistry, and technology (1999)

Preface List of Contributors Acknowledgements Seed to smoke Breeding and genetics Biotechnology: uses and applications in tobacco improvement Agronomy and physiology Production practices Major tobacco diseases Tobacco insect pests Lead chemistry Physical properties of leaf tobacco Marketing processing and storage Cigarette manufacture Smoke chemistry Cigars and cigarillos Smokeless tobacco Index.
Clonal anergy of memory B cells in epitope-specific regulation. (1990)

Immunization of carrier (keyhole limpet hemocyanin (KLH)) primed mice with the hapten-carrier TNP-KLH induces specific suppression for the IgG anti-TNP-response without interfering with the response to epitopes on the carrier molecule. To examine the status of hapten-specific memory B cells from suppressed mice, highly enriched populations of TNP-specific memory B cells were purified from the spleen of TNP-KLH (control) or KLH/TNP-KLH (suppressed) immunized mice and tested in vitro for their ability to respond to TD or TI (TNP-KLH, TNP-LPS) antigenic challenge in presence of a KLH-specific Th cell line. Similar numbers of TNP-specific B cells with the characteristics of memory B cells were obtained from control and suppressed mice. TNP-specific B cells from suppressed mice could be triggered to IgG production by TNP-LPS but had an impaired ability to differentiate into IgG-secreting cells in response to TNP-KLH. This impaired IgG response to TNP-KLH was not due to an active suppression by a subset of TNP-specific B cells, or to an impedence of memory cells to a class switching but to an intrinsic memory B cell defect. TNP-specific B cells from suppressed mice were as efficient as memory B cells from control mice to present TNP-KLH to KLH-specific Th cells and to proliferate in response to T cell help. Our data support the view that the effector mechanism of epitope specific regulation does not interfere with the development of hapten-specific memory B cells but that these cells have an intrinsic defect that prevents their differentiation into active IgG antibody secreting cells in response to a T-dependent antigenic challenge.