gebhart/patrepeval huggingface dataset:
Therapeutic Potential of Adult Neural Stem Cells (2006)

The central nervous system (CNS) elicits limited capacity to recover from injury. Though considerable efforts and means have been deployed to find treatments for neurological diseases, disorders and injuries, there is still no cure for these ailments, and new alternatives for therapy must be explored. Because they generate the main phenotypes of the nervous system, neural stem cells (NSCs) hold the promise to cure a broad range of neurological diseases and injuries. With the confirmation that neurogenesis occurs in the adult brain and NSCs reside in the adult CNS, new treatments for neurological diseases and injuries are being considered. Particularly, the transplantation of adult-derived neural progenitor and stem cells to restore brain functions. In this manuscript, we will review the recent developments in adult neurogenesis and NSCs, and patent applications filed in relation to discoveries made in this new field of research.
Inhibition of PCSK9 (2012)

Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, UK Correspondence to Dr Sharmistha Roy Chowdhury, Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK. Tel: +44 2 92 074 3000; fax: +44 2 92 074 4581; e-mail: [email protected]
The emerging role of MRI in quantitative renal glomerular morphology (2013)

Techniques to measure morphological parameters, such as glomerular (and thereby nephron) number, glomerular size, and kidney volume, have been vital to understanding factors contributing to chronic kidney disease (CKD). These techniques have also been important to understanding the associations between CKD and other systemic and cardiovascular diseases and have led to the identification of developmental risk factors for these pathologies. However, existing techniques in quantitative kidney morphology are resource- and time-consuming and are destructive to the organ. This review discusses the emerging generation of techniques to study kidney morphology quantitatively using magnetic resonance imaging (MRI) using the intravenous injection of the superparamagnetic nanoparticle cationic ferritin, which binds to the glomerular basement membrane. A primary advantage of MRI over previously established techniques is the ability to quantify morphology in the intact organ with minimal sample preparation. We highlight areas of research where MRI-based morphological measurements will be helpful in animal models and possibly diagnostic clinical nephrology, discuss technical challenges in light of the progress in MRI techniques to date, and identify novel measurements that may be possible using MRI, both ex vivo and in vivo.
Synthesis of Polystyrene−Polylactide Bottlebrush Block Copolymers and Their Melt Self-Assembly into Large Domain Nanostructures (2009)

High molecular weight polystyrene−polylactide (PS−PLA) bottlebrush block copolymers have been shown to self-assemble into highly ordered lamellae structures with domain spacings as large as 163 nm, as identified by ultrasmall-angle X-ray scattering. Bottlebrush block copolymers were synthesized by a combination of living radical and ring-opening polymerizations. The backbone was prepared by RAFT block copolymerization of solketal methacrylate (SM) and 2-(bromoisobutyryl)ethyl methacrylate (BIEM). Polystyrene branches were grafted by ATRP from poly(BIEM) block, and PLA branches were grafted from the poly(SM) block after the removal of ketal groups. The investigation into the self-assembly of PS−PLA bottlebrush block copolymers with varying lengths of branches and backbones revealed a number of unusual trends, which were attributed to their dynamic, three-dimensional structure. The results suggest that in phase-separated melts the bottlebrush block copolymer backbone, while extended, still possesses a certain degree of flexibility to accommodate for different interfacial areas necessary to pack into lamellae microstructures.
The assessment of serum nontransferrin-bound iron in chelation therapy and iron supplementation (2000)

Nontransferrin-bound iron (NTBI) appears in the serum of individuals with iron overload and in a variety of other pathologic conditions. Because NTBI constitutes a labile form of iron, it might underlie some of the biologic damage associated with iron overload. We have developed a simple method for NTBI determination, which operates in a 96-well enzyme-linked immunosorbent assay format with sensitivity comparable to that of previous assays. A weak ligand, oxalic acid, mobilizes the NTBI and mediates its transfer to the iron chelator deferoxamine (DFO) immobilized on the plate. The amount of DFO-bound iron, originating from NTBI, is quantitatively revealed in a fluorescence plate reader by the fluorescent metallosensor calcein. No NTBI is found in normal sera because transferrin-bound iron is not detected in the assay. Thalassemic sera contained NTBI in 80% of the cases (range, 0.9-12.8 micromol/L). In patients given intravenous infusions of DFO, NTBI initially became undetectable due to the presence of DFO in the sera, but reappeared in 55% of the cases within an hour of cessation of the DFO infusion. This apparent rebound was attributable to the loss of DFO from the circulation and the possibility that a major portion of NTBI was not mobilized by DFO. NTBI was also found in patients with end-stage renal disease who were treated for anemia with intravenous iron supplements and in patients with hereditary hemochromatosis, at respective frequencies of 22% and 69%. The availability of a simple assay for monitoring NTBI could provide a useful index of iron status during chelation and supplementation treatments. (Blood. 2000;95:2975-2982)
Fulvestrant for the treatment of endometrial cancer (2016)

Even if fulvestrant showed only marginal activity in two phase II trials, it shouldn't be abandoned but instead further developed in EC. Firstly, the dose of fulvestrant used in these trials was too low from today's point of view. Secondly, the available literature on other endocrine agents is full of limitations and does not provide a gold standard. Furthermore, given the activity of mTOR inhibitors in EC, there may also be synergistic effects, given the cross-regulation of ER and the PI3K/AKT/mTOR pathway. The authors suggest that a prospective, phase II trial in ER positive RMEC would help to further explore the efficacy and tolerability of fulvestrant together with a mTOR inhibitor.
The AVR9 Race-Specific Elicitor of Cladosporium fulvum Is Processed by Endogenous and Plant Proteases (1993)

The avirulence gene avr9 of the fungal tomato pathogen Cladosporium fulvum encodes a race-specific peptide elicitor that induces a hypersensitive response in tomato plants carrying the complementary resistance gene Cf9. The avr9 gene is highly expressed when C. fulvum is growing in the plant and the elicitor accumulates in infected leaves as a 28-amino acid (aa) peptide. In C. fulvum grown in vitro, the peptide elicitor is not produced in detectable amounts. To produce significant amounts of the AVR9 elicitor in vitro, the coding and termination sequences of the avr9 gene were fused to the constitutive gpd-promoter (glyceraldehyde 3-phosphate dehydrogenase) of Aspergillus nidulans. Transformants of C. fulvum were obtained that highly expressed the avr9 gene in vitro and produced active AVR9 peptide elicitors. These peptides were partially sequenced from the N terminus and appeared to consist of 32, 33, and 34 aa's, respectively, and are the precursors of the mature 28-aa AVR9 peptide. We demonstrated that plant factors process the 34-aa peptide into the mature 28-aa peptide. We present a model for the processing of AVR9 involving cleavage of a signal peptide during excretion and further maturation by fungal and plant proteases into the stable 28-aa peptide elicitor.
Experience with vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy in adults with refractory acute lymphocytic leukemia (1989)

Sixty-four adult patients with refractory acute lymphocytic leukemia (ALL) received salvage therapy with the vincristine, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and dexamethasone (VAD) regimen consisting of induction chemotherapy with the three agents followed by multiple-agent maintenance therapy for 2 years. Overall, 25 patients (39%) achieved complete remission. The median remission duration was 28 weeks with 20% of these patients remaining disease-free at 2 years. The median overall survival was 23 weeks. Prognostic factors associated with differences in remission rates included patient performance status, hemoglobin and platelet levels, and degree of peripheral and marrow blastosis. Factors related to differences in survival were patient age and performance status, hemoglobin and platelet levels, percentage of peripheral blasts, and albumin and bilirubin levels. The toxicity of the regimen was minimal, with 33% of patients requiring hospitalization because of febrile episodes of unknown origin (17%) or documented infections (16%). Therapy-related mortality occurred in four patients (6%). We conclude that the VAD program has significant antileukemic efficacy and acceptable toxicity in adult salvage ALL.
Adenovirus–Catheter Compatibility Increases Gene Expression After Delivery to Porcine Myocardium (2003)

Endomyocardial injection of adenoviral gene vectors enables localized delivery to comprised myocardial tissue. However, many materials used in endomyocardial delivery catheters may not be compatible with adenoviral gene vectors. In this study, a series of catheter-based endocardial and epicardial (direct visualization) procedures were performed to assess catheter-adenovirus compatibility in an in vivo model. A standard Nitinol-stainless steel (Ni-SS) catheter was compared with a novel Stiletto catheter designed for improved biocompatibility. In 4 animals 40 endocardial injections of adenovirus encoding beta-galactosidase (beta-Gal) were performed with the 2 catheters. After sectioning of the hearts only 8 of 20 Ni-SS beta-Gal+ sites could be identified (40% retrieval) whereas 16 of the 20 Stiletto injection sites were identified (80%). Within these areas successful transfection was observed (12.2 +/- 4.0 beta-Gal+ cells/high-power field [HPF] in the Ni-SS group vs. 30.1 +/- 6.8 beta-Gal+ cells/HPF in the Stiletto group; p = 0.03). After epicardial delivery to distinct areas of the myocardium adenoviral delivery as assayed by beta-galactosidase protein activity was >21 +/- 16-fold (range, 5 to >43-fold) greater than after Stiletto delivery. In conclusion, this study highlights the importance of adenovirus-material compatibility in gene delivery to the myocardium. Efficiency was greater when using the catheter designed to enhance biocompatibility.
Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo (2004)

Silencing gene expression by siRNAs is rapidly becoming a powerful tool for the genetic analysis of mammalian cells. However, the rapid degradation of siRNA and the limited duration of its action call for an efficient delivery technology. Accordingly, we describe here that Atelocollagen complexed with siRNA is resistant to nucleases and is efficiently transduced into cells, thereby allowing long-term gene silencing. Site-specific in vivo administration of an anti-luciferase siRNA/Atelocollagen complex reduced luciferase expression in a xenografted tumor. Furthermore, Atelocollagen-mediated transfer of siRNA in vivo showed efficient inhibition of tumor growth in an orthotopic xenograft model of a human non-seminomatous germ cell tumor. Thus, for clinical applications of siRNA, an Atelocollagen-based non-viral delivery method could be a reliable approach to achieve maximal function of siRNA in vivo.
Inhibition of Calcium–Calmodulin-Dependent Kinase II Suppresses Cardiac Fibroblast Proliferation and Extracellular Matrix Secretion (2010)

Calcium-calmodulin-dependent protein kinase II (CaMKII) is one of the main protein kinases mediating intracellular Ca changes. It is also involved in the process of cardiac diseases, such as cardiac hypertrophy, but its effects on myocardial fibrosis remain unclear. The present study investigates whether CaMKII is involved in cardiac fibroblast proliferation and extracellular matrix (ECM) secretion induced by angiotensin II (AngII) or electrical field stimulation (EFS) in cultured neonatal rat cardiac fibroblasts. Cardiac fibroblast proliferation was assessed by a cell survival assay (MTT) and manual cell enumeration. Cellular matrix production was demonstrated by matrix metalloproteinases (MMP) 1, 2, 9, and collagen I/III messenger RNA expression, MMP-2, 9 protein expression, and secretion of transforming growth factor beta1 and tumor necrosis factor alpha. Either AngII or EFS promoted cardiac fibroblast proliferation and ECM secretion, while also up-regulating expression of CaMKII deltaB and deltaC. More importantly, CaMKII inhibitors, autocamtide-2-related inhibitory peptide (AIP 5 microM) or KN93 (0.5 microM), suppressed cardiac fibroblast proliferation, inhibited the excretion of transforming growth factor beta1 and tumor necrosis factor alpha, decreased the messenger RNA expression of MMP-1, 2, 9 and collagen I/III, and decreased the protein expression of MMP-2, 9. These results suggest that CaMKII mediates cardiac fibroblast proliferation and ECM secretion induced by either AngII or EFS.
The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth (2000)

Several decades of basic and clinical research have demonstrated that there is an association between the insulin-like growth factors (IGFs) and neoplasia. We begin with a brief discussion of the function and regulation of expression of the IGFs, their receptors and the IGF-binding proteins (IGFBPs). A number of investigational interventional strategies targeting the GH or IGFs are then reviewed. Finally, we have assembled the available scientific knowledge about this relationship for each of the major tumor types. The tumors have been grouped together by organ system and for each of the major tumors, various key elements of the relationship between IGFs and tumor growth are discussed. Specifically these include the presence or absence of autocrine IGF-I and IGF-II production; presence or absence of IGF-I and IGF-II receptor expression; the expression and functions of the IGFBPs; in vitro and in vivo experiments involving therapeutic interventions; and available results from clinical trials evaluating the effect of GH/IGF axis down-regulation in various malignancies.
Paramyxovirus V Proteins Interact with the RNA Helicase LGP2 To Inhibit RIG-I-Dependent Interferon Induction (2012)

RIG-I and mda-5 are activated by viral RNA and stimulate type I interferon production. Laboratory of genetics and physiology 2 (LGP2) shares homology with RIG-I and mda-5 but lacks the CARD domains required for signaling. The V proteins of paramyxoviruses limit interferon induction by binding mda-5 and preventing its activation; however, they do not bind RIG-I and have not been considered inhibitors of RIG-I signaling. Here we uncover a novel mechanism of RIG-I inhibition in which the V protein of parainfluenzavirus type 5 (PIV5; formerly known as simian virus type 5 [SV5]) interacts with LGP2 and cooperatively inhibits induction by RIG-I ligands. A complex between RIG-I and LGP2 is observed in the presence of PIV5-V, and we propose that this complex is refractory to activation by RIG-I ligands. The V proteins from other paramyxoviruses also bind LGP2 and demonstrate LGP2-dependent inhibition of RIG-I signaling. This is significant, because it demonstrates a general mechanism for the targeting of the RIG-I pathway by paramyxoviruses.
Cloning, Expression, and Gene Structure of a G Protein-Coupled Glutamate Receptor from Rat Brain (1991)

A complementary DNA encoding a G protein-coupled glutamate receptor from rat brain, GluGR, was cloned by functional expression in Xenopus oocytes. The complementary DNA encodes a protein of 1199 amino acids containing a seven-transmembrane motif, flanked by large amino- and carboxyl-terminal domains. This receptor lacks any amino acid sequence similarity with other G protein-coupled receptors, suggesting that it may be a member of a new subfamily. The presence of two introns flanking the central core suggests that GluGR may have evolved by exon shuffling. Expressed in oocytes, GluGR is activated by quisqualate greater than glutamate greater than ibotenate greater than trans-1-aminocyclopentyl-1,3-dicarboxylate, and it is inhibited by 2-amino-3-phosphonopropionate. Activation is blocked by Bordella pertussis toxin. These properties are typical of some metabotropic glutamate receptors.
Nanometer‐Range Communication of Stereochemical Information by Reversible Switching of Molecular Helicity (2010)

A long-distance call: The inversion of configuration at a stereogenic center led to a detectable switch in the position of a 13C stereochemical probe 40 bonds (2.5 nm) away. Information was relayed between the sites by an inversion of screw sense in the intervening helix as illustrated (13C NMR signals were read as output). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Automatic Implantable Cardioverter Defibrillator: T Wave Sensing in the Newest Generation (1988)

The AICD uses an automatic gain control amplifier for detecting the small electrograms during ventricular fibrillation. The latest generation of the AICD appears to have a more sensitive lock on gain amplifier, as 6 of 76 patients implanted with the new AICD had double counting of the QRS-T wave complex resulting in asymptomatic discharges. Solutions to the problem of limiting these asymptomatic discharges are difficult and include slowing of the heart rate with beta blockers, changing the lead system, or replacement of the device. One of the six patients was treated with beta blockers. Three patients had their device changed, two patients requested the inactivation of their device until a rate programmable unit was available. The potential for T wave sensing in a lock on gain amplifier represents the unique dilemma between detecting small electrograms of ventricular fibrillation, and detecting diastolic events which occur shortly after the QRS complex.
Inside dropbox (2012)

Personal cloud storage services are gaining popularity. With a rush of providers to enter the market and an increasing offer of cheap storage space, it is to be expected that cloud storage will soon generate a high amount of Internet traffic. Very little is known about the architecture and the performance of such systems, and the workload they have to face. This understanding is essential for designing efficient cloud storage systems and predicting their impact on the network.
Polymeric Complements to the Alzheimer's Disease Biomarker β-Amyloid Isoforms Aβ1–40 and Aβ1–42 for Blood Serum Analysis under Denaturing Conditions (2011)

Treatment of Alzheimer's diesease (AD) is plagued by a lack of practical and reliable methods allowing early diagnosis of the disease. We here demonstrate that robust receptors prepared by molecular imprinting successfully address current limitations of biologically derived receptors in displaying affinity for hydrophobic peptide biomarkers for AD under denaturing conditions. C-terminal epitope-imprinted polymers showing enhanced binding affinity for Aβ1–42 were first identified from a 96-polymer combinatorial library. This information was then used to synthesize molecularly imprinted polymers for both of the β-amyloid (Aβ) isoforms and a corresponding nonimprinted polymer. A solid-phase extraction method was developed to be compatible with sample loading under conditions of complete protein denaturation. This resulted in a method capable of quantitatively and selectively enriching a shorter C-terminal peptide corresponding to the sequences Aβ33–40 and Aβ33–42 as well as the full-length sequence Aβ1–40 and Aβ1–42 from a 4 M guanidinum chloride solution. Application of the method to serum allowed selective, high-recovery extraction of both biomarkers at spiking levels marginally higher than clinically relevant concentrations found in cerebrospinal fluid.
Surface Modification of Nanoporous Alumina Surfaces with Poly(ethylene glycol) (2004)

Nanoporous alumina surfaces have a variety of applications in biosensors, biofiltration, and targeted drug delivery. However, the fabrication route to create these nanopores in alumina results in surface defects in the crystal lattice. This results in inherent charge on the porous surface causing biofouling, that is, nonspecific adsorption of biomolecules. Poly(ethylene glycol) (PEG) is known to form biocompatible nonfouling films on silicon surfaces. However, its application to alumina surfaces is very limited and has not been well investigated. In this study, we have covalently attached PEG to nanoporous alumina surfaces to improve their nonfouling properties. A PEG-silane coupling technique was used to modify the surface. Different concentrations of PEG for different immobilization times were used to form PEG films of various grafting densities. X-ray photoelectron spectroscopy (XPS) was used to verify the presence of PEG moieties on the alumina surface. High-resolution C1s spectra show that with an increase in concentration and immobilization time, the grafting density of PEG also increases. Further, a standard overlayer model was used to calculate the thickness of PEG films formed using the XPS intensities of the Al2p peaks. The films formed by this technique are less than 2.5 nm thick, suggesting that such films will not clog the pores which are in the range of 70-80 nm.
Damping Performance of Cocured Graphite/Epoxy Composite Laminates with Embedded Damping Materials (1999)

Cocuring viscoelastic damping materials in composites has been shown to be successful in greatly increasing the damping of composite structures. The damping performance, however, is often not as high in cocured composites as in secondarily bonded composites, where the damping material does not undergo the laminate cure cycle. The reason for the discrepancy in damping between the cocured and secondarily bonded samples was found to be resin penetration into the damping material. Samples with a barrier layer between the damping material and the epoxy resin had a 15.7% to 92.3% higher effective loss factor (depending on the frequency) than cocured FasTape™ 1125 samples without the barrier and at least 168% higher effective loss factor than cocured ISD 112 samples without the barrier. These higher damping values are very close to the values achieved by secondarily bonding. Viscoelastic damping materials typically have maximum recommended temperatures below that of the composite cure cycles. The effect of cure temperature on viscoelastic damping materials was also studied and it was determined that most damping materials are marginally affected by cure cycle temperature.