gebhart/patrepeval huggingface dataset:
Cell mimetic lateral stabilization of outer cell mimetic bilayer on polymer surfaces by peptide bonding and their blood compatibility (2006)

The biological lipid bilayer membranes are stabilized laterally with the help of integral proteins. We have simulated this with an optimized ternary phospholipid/glycolipid/cholesterol system, and stabilized laterally on functionalized poly methyl methacrylate (PMMA) surfaces, using albumin, heparin, and polyethylene glycol as anchors. We have earlier demonstrated the differences due to orientation and packing of the ternary phospholipid monolayers in relation to blood compatibility (Kaladhar and Sharma, Langmuir 2004;20:11115-11122). The structure of albumin is changed here to expose its interior hydrophobic core by treating with organic solvent. The interaction between the hydrophobic core of the albumin molecule and the hydrophobic core of the lipid molecules is confirmed by incorporating the molecule into bilayer membranes. The secondary structure of the membrane incorporated albumin is studied by CD spectral analysis. The structure of the altered albumin molecule contains more beta-sheet as compared to the native albumin. This conformation is also retained in membranes. The partitioning of the different anchors based on its polarity and ionic interactions in the monolayer is studied from the pressure-area (pi-A) isotherm of the lipid monolayers at the air/water interface using Langmuir-Blodgett (LB) trough facility. Such two monolayers are deposited onto the functionalized PMMA surface using LB trough and crosslinked by carbodiimide chemistry. The structure of the deposited bilayer is studied by depth analysis using contact mode AFM in dry conditions. The stabilized bilayer shows stability up to 1 month by contact angle studies. Preliminary blood compatibility studies reveal that the calcification, protein adsorption, as well as blood-cell adhesion is significantly reduced after the surface modification. The reduced adsorption of ions, proteins, and cells to the modified surfaces may be due to the fluidity of the microenvironment along with the contribution of the mobile PEG groups at the surface and the phosphorylcholine groups of the phospholipids. The stability of the anchored bilayer under low shear stress conditions promises that the laterally stabilized supported bilayer system can be used for low shear applications like small diameter vascular graft and modification of biosensors, and so forth.
Review article: is non‐alcoholic fatty liver disease a spectrum, or are steatosis and non‐alcoholic steatohepatitis distinct conditions? (2012)

Although simple steatosis and non-alcoholic steatohepatitis are currently viewed as two histological subtypes of the unique spectrum of non-alcoholic fatty liver disease, the two conditions are likely distinct not only from a histological but also from a pathophysiological standpoint. Efforts to distinguish simple steatosis from non-alcoholic steatohepatitis using non-invasive modalities should be informed by the current pathophysiology of these two clinical entities.
High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases (2010)

We report here an efficient method for targeted mutagenesis of Arabidopsis genes through regulated expression of zinc finger nucleases (ZFNs)-enzymes engineered to create DNA double-strand breaks at specific target loci. ZFNs recognizing the Arabidopsis ADH1 and TT4 genes were made by Oligomerized Pool ENgineering (OPEN)-a publicly available, selection-based platform that yields high quality zinc finger arrays. The ADH1 and TT4 ZFNs were placed under control of an estrogen-inducible promoter and introduced into Arabidopsis plants by floral-dip transformation. Primary transgenic Arabidopsis seedlings induced to express the ADH1 or TT4 ZFNs exhibited somatic mutation frequencies of 7% or 16%, respectively. The induced mutations were typically insertions or deletions (1-142 bp) that were localized at the ZFN cleavage site and likely derived from imprecise repair of chromosome breaks by nonhomologous end-joining. Mutations were transmitted to the next generation for 69% of primary transgenics expressing the ADH1 ZFNs and 33% of transgenics expressing the TT4 ZFNs. Furthermore, approximately 20% of the mutant-producing plants were homozygous for mutations at ADH1 or TT4, indicating that both alleles were disrupted. ADH1 and TT4 were chosen as targets for this study because of their selectable or screenable phenotypes (adh1, allyl alcohol resistance; tt4, lack of anthocyanins in the seed coat). However, the high frequency of observed ZFN-induced mutagenesis suggests that targeted mutations can readily be recovered by simply screening progeny of primary transgenic plants by PCR and DNA sequencing. Taken together, our results suggest that it should now be possible to obtain mutations in any Arabidopsis target gene regardless of its mutant phenotype.
CBP/p300 TAZ1 Domain Forms a Structured Scaffold for Ligand Binding, (2004)

The transcriptional coactivator protein CBP and its paralog p300 each contain two homologous zinc-containing TAZ domains, which constitute the interaction sites for a number of transcription factors. Previous reports of the three-dimensional structures of TAZ1 in complex with binding partners and of the isolated CBP TAZ2 domain show a distinctive topology composed of four amphipathic helices, organized by three zinc-binding clusters with HCCC-type coordination. The isolated CBP TAZ2 domain forms a stable three-dimensional structure in solution, but a recent report [Dial, R., Sun, Z., and Freedman, S. J. (2003) Biochemistry 42, 9937] suggested that the isolated p300 TAZ1 domain lacks a well-defined structure and behaves like a molten globule, even in the presence of Zn(2+), and that the formation of a stable three-dimensional structure requires binding of a protein partner. In marked contrast to this result, we find that both the CBP and p300 TAZ domains in the presence of stoichiometric concentrations of Zn(2+) adopt a well-defined structure in solution in the absence of binding partners. We have determined the three-dimensional structure of the isolated CBP TAZ1 domain by NMR methods and show that it has the same structure in the presence and absence of binding partners. This is an important finding: whether the free TAZ1 domain forms a folded structure or behaves as a molten globule will have a significant bearing on the mechanism of protein-protein recognition. Although TAZ1 and TAZ2 share many structural similarities, there is a major structural difference: the fourth helix is oriented in opposite directions in the TAZ1 and TAZ2 domains. The structure of the free TAZ1 domain suggests that this difference is an inherent feature that determines binding specificity and facilitates discrimination between different subsets of transcription factors by the two TAZ domains.
Microwave switch using MEMS-technology (2002)

Integration of a Micro-sensor, Micro-actuator, Micro-electro-mechanical filter, RF switches, signal processing and intelligent control at one place that fit on to the surface of computer chip can provide a miniaturized systems and such devices go under different names, such as smart structure, smart sensors or micro-electro-mechanical systems (MEMS). These devices have numerous applications in medicine, aerospace, auto-motive and defense systems and the MEMS technology is starting to branch out into desperate application in the field of micro-wave components/systems. Much of the activity has been driven by the ability of MEMS to miniaturize, reduce the cost, and improve the performance of, transducers and actuators previously fabricated by hybrid techniques. Though some systems have been developed, most of them are in the development stage or conceptual stage. This paper presents a review of the MEMS design and development and describes a RF-switch at 26 GHz.
Structure-Based Drug Design: Combinatorial Chemistry and Molecular Modeling (1999)

Drug discovery efforts are shifting to include the rapid synthetic procedures of combinatorial chemistry and the elegance of rational library design. The wealth of computational methods which explore both the receptor structure and the ultimate pharmacophore complementarity, provide novel avenues for chemists to discover new lead compounds or design virtual libraries for screening prior to the synthetic stage. This mini-review provides an overview of a few current methodologies of library generation, highlighting docking procedures which have utility in both the discovery and optimization stages of drug development. Three specific examples of different approaches to the use of docking are provided. These describe the development of inhibitors to the human A3 adenosine receptor and HIV-1 protease, and the evaluation of the activity of novel inhibitors of the redox regulator protein, human thioredoxin.
Amperometric Assay for Aldolase Activity:  Antibody-Catalyzed Ferrocenylamine Formation (2005)

Screening of new catalysts for aldolase activity is a major task in bioorganic chemistry. For this purpose, fast and convenient methods are required for the detection of the catalysts. We have developed the first amperometric assay for aldol or retro-aldol catalytic activity. A new ferrocene-aldol derivative was synthesized with redox activity significantly different from that of ferrocenylamine. It was shown that the reaction between aldolase antibody 38C2 and a ferrocene-aldol substrate generated free ferrocenylamine, which could be detected and quantified by simple electrochemical measurement. The amperometric assay was applied to perform a Michaelis-Menten analysis of catalytic antibody 38C2 in order to determine the enzymatic kinetic parameters.
국내 의류산업의 물류 아웃소싱 결정시 고려요인에 관한 연구 (2002)

Recently, companies have pursued innovative management techniques and concepts to cope with and increasingly competitive environment. Companies have especially focused on the logistics of outsourcing. This has become and increasing trend because companies are focusing on the concept of core competence. The most important aspect of the clothing industry is a sound logistical system. Thus logistics outsourcing is an important strategy in this industry. The purpose of this study is to contribute to the establishment of a strategy for logistical outsourcing.
Fate of Water in the Soft Contact Lens Immediately After Lens Placement onto the Cornea (1991)

Soft contact lenses presoaked in D2O or H2(17)O were used to examine the movement of water immediately after their placement onto the eye. Two experiments were conducted: (1) the rate of D2O loss from these soft lenses was determined by assaying residual D2O with nuclear magnetic resonance spectroscopy; and (2) the movement of water into/inside the eye was followed by tracking the path of H2(17)O using magnetic resonance imaging. D2O dissipation occurred in two phases: an initial rapid washout (1.25 ml/h) followed by a slower phase (0.13 ml/h). The latter was eliminated by previous contact lens wear. The H2(17)O study showed that once water entered the anterior chamber, it rapidly exchanged with water in the ocular (predominantly iris) circulation (flow rate constant = 0.1/min). It appears that exogenous water, in this case water from the soft lens, ultimately interacts with the ocular circulation. This is one aspect of cornea-soft lens interaction previously unreported.
Ion channel drug potency assay with an artificial bilayer chip (2012)

The potency of pharmaceutical compounds acting on ion channels can be determined through measurements of ion channel conductance as a function of compound concentration. We have developed an artificial lipid bilayer chip for simple, fast, and high-yield measurement of ion channel conductance with simultaneous solution perfusion. Here we show the application of this chip to the measurement of the mammalian cold and menthol receptor TRPM8. Ensemble measurements of TRPM8 as a function of concentration of menthol and 2-aminoethoxydiphenyl borate (2-APB) enabled efficient determination of menthol's EC(50) (111.8 μM ± 2.4 μM) and 2-APB's IC(50) (4.9 μM ± 0.2 μM) in agreement with published values. This validation, coupled with the compatibility of this platform with automation and parallelization, indicates significant potential for large-scale pharmaceutical ion channel screening.
A new sinusoidal modelling approach for parametric speech and audio coding (2004)

In this paper we propose a new approach based on energy-adaptive matching pursuits to improve sinusoidal modelling for parametric speech and audio coding. To reduce the complexity of the algorithm, an over-complete dictionary composed of complex exponentials is used. An analysis-synthesis windows scheme that avoids overlapping is proposed. For efficient quantization of sinusoidal model parameters, a new algorithm that largely reduces the side information required by the decoder is described. Experimental results show evidence of the advantages of the proposed method to be integrated into multi-pans models for parametric speech/audio coding.
Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease (1992)

Asymptomatic intracranial aneurysms appear to be more frequent in people with polycystic kidney disease than in the general population, although our 95 percent confidence interval includes the possibility of no difference. Because cerebral angiography is associated with increased morbidity in people with polycystic kidney disease, we recommend high-resolution CT as a screening test.
Sympathetic control of white adipose tissue in lean and obese humans (2003)

The present review summarizes evidence for a direct neuronal influence on lipolysis in humans.
Non-small-cell lung carcinoma: role of the Notch signaling pathway (2015)

Notch signaling plays a pivotal role during embryogenesis. It regulates three fundamental processes: lateral inhibition, boundary formation, and lineage specification. During post-natal life, Notch receptors and ligands control critical cell fate decisions both in compartments that are undergoing differentiation and in pluripotent progenitor cells. First recognized as a potent oncogene in certain lymphoblastic leukemias and mesothelium-derived tissue, the role of Notch signaling in epithelial, solid tumors has been far more controversial. The overall consequence of Notch signaling and which form of the Notch receptor drives malignancy in humans is deeply debated. Most likely, this is due to the high degree of context-dependent effects of Notch signaling. More recently, it has been discovered that Notch (especially Notch-1) can exert different, even opposite effects in the same tissue under differing microenvironmental conditions. Further complicating the understanding of Notch receptors is the recently discovered role for non-canonical Notch signaling. Additionally, the most frequent Notch signaling antagonists used in biological systems have been inhibitors of the transmembrane protease complex γ-secretase, which itself processes a plethora of class one transmembrane proteins and thus cannot be considered a Notch-specific upstream regulator. Here we review the available empirical evidence gathered in recent years concerning Notch receptors and ligands in non-small-cell lung carcinoma (NSCLC). Although an overview of the field reveals seemingly contradicting results, we propose that Notch signaling can be exploited as a therapeutic target in NSCLC and represents a promising complement to the current arsenal utilized to combat this malignancy, particularly in targeting NSCLC tissues under specific environmental conditions, such as hypoxia.
Docosahexaenoic Acid Complexed to Albumin Elicits High-Grade Ischemic Neuroprotection (2004)

The high-grade neuroprotection afforded by the DHA-albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.
A GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB (2015)

No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease due to defect in α-N-acetylglucosaminidase (NAGLU). In preparation for a clinical trial, we performed an IND-enabling GLP-toxicology study to assess systemic rAAV9-CMV-hNAGLU gene delivery in WT C57BL/6 mice at 1 × 10(14) vg/kg and 2 × 10(14) vg/kg (n = 30/group, M:F = 1:1), and non-GLP testing in MPS IIIB mice at 2 × 10(14) vg/kg. Importantly, no adverse clinical signs or chronic toxicity were observed through the 6 month study duration. The rAAV9-mediated rNAGLU expression was rapid and persistent in virtually all tested CNS and somatic tissues. However, acute liver toxicity occurred in 33% (5/15) WT males in the 2 × 10(14) vg/kg cohort, which was dose-dependent, sex-associated, and genotype-specific, likely due to hepatic rNAGLU overexpression. Interestingly, a significant dose response was observed only in the brain and spinal cord, whereas in the liver at 24 weeks postinfection (pi), NAGLU activity was reduced to endogenous levels in the high dose cohort but remained at supranormal levels in the low dose group. The possibility of rAAV9 germline transmission appears to be minimal. The vector delivery resulted in transient T-cell responses and characteristic acute antibody responses to both AAV9 and rNAGLU in all rAAV9-treated animals, with no detectable impacts on tissue transgene expression. This study demonstrates a generally safe and effective profile, and may have identified the upper dosing limit of rAAV9-CMV-hNAGLU via systemic delivery for the treatment of MPS IIIB.
Human cortical glial tumors contain neural stem‐like cells expressing astroglial and neuronal markers in vitro (2002)

Neural stem cells from neurogenic regions of mammalian CNS are clonogenic in an in vitro culture system exploiting serum and anchorage withdrawal in medium supplemented with methyl cellulose and the pleiotropic growth factors EGF, FGF2, and insulin. The aim of this study was to test whether cortical glial tumors contain stem-like cells capable, under this culture system, of forming clones showing intraclonal heterogeneity in the expression of neural lineage-specific proteins. The high frequencies of clone-forming cells (about 0.1-10 x 10(-3)) in clinical tumor specimens with mutated p53, and in neurogenic regions of normal human CNS, suggest that the ability to form clones in this culture system is induced epigenetically. RT-PCR analyses of populations of normal brain- and tumor-derived sister clones revealed transcripts for nestin, neuron-specific enolase, and glial fibrillary acidic protein (GFAP). However, the tumor-derived clones were different from clones derived from neurogenic regions of normal brain in the expression of transcripts specific for genes associated with neural cell fate determination via the Notch-signaling pathway (Delta and Jagged), and cell survival at G2 or mitotic phases (Survivin). Moreover, the individual glioma-derived clones contain cells immunopositive separately for GFAP or neuronal beta-III tubulin, as well as single cells coexpressing both glial and neuronal markers. The data suggest that the latent critical stem cell characteristics can be epigenetically induced by growth conditions not only in cells from neurogenic regions of normal CNS but also in cells from cortical glial tumors. Moreover, tumor stem-like cells with genetically defective responses to epigenetic stimuli may contribute to gliomagenesis and the developmental pathological heterogeneity of glial tumors.
Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290 (2012)

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal degeneration, with an onset in the first year of life. The most frequent mutation that causes LCA, present in at least 10% of individuals with LCA from North-American and Northern-European descent, is an intronic mutation in CEP290 that results in the inclusion of an aberrant exon in the CEP290 mRNA. Here, we describe a genetic therapy approach that is based on antisense oligonucleotides (AONs), small RNA molecules that are able to redirect normal splicing of aberrantly processed pre-mRNA. Immortalized lymphoblastoid cells of individuals with LCA homozygously carrying the intronic CEP290 mutation were transfected with several AONs that target the aberrant exon that is incorporated in the mutant CEP290 mRNA. Subsequent RNA isolation and reverse transcription-PCR analysis revealed that a number of AONs were capable of almost fully redirecting normal CEP290 splicing, in a dose-dependent manner. Other AONs however, displayed no effect on CEP290 splicing at all, indicating that the rescue of aberrant CEP290 splicing shows a high degree of sequence specificity. Together, our data show that AON-based therapy is a promising therapeutic approach for CEP290-associated LCA that warrants future research in animal models to develop a cure for this blinding disease.
Functional Domains of Human Endothelin Receptor (1993)

The ligand binding site to the ETA receptor was investigated by substitution of each 5-amino acid sequence located in the second extracellular (B) region of the ETA receptor with the cognate sequences of the beta 2-adrenergic receptor. A 5-amino acid sequence (140-KLLAG-144) in the B-loop region was implicated as the most important element required for ligand binding. In addition, both the third and the fourth extracellular regions (C- and D-loops), including the flanking transmembrane regions, were found to play an important role in ligand selection. As for the biological significance of the intracellular regions of the ETA receptor, we have found that the C-terminal 8-amino acid residues located in close proximity to the seventh transmembrane region and the C-terminal 16-amino acid residues in the third intracellular loop are important for the binding of ET-1. Therefore, the intracellular third loop and C-terminal domains seem to contribute to the three-dimensional structure of the ligand binding site located in the extracellular domains. The same lines of experiment showed that the ETA receptor requires > 13 amino acid residues at the proximal cytoplasmic tail and 10 amino acid residues in the C-terminal region of the third intracellular loop to induce an ET-1-dependent increase in [Ca2+]i. Both regions are possibly involved in the interaction with G-protein.
Imaging and Quantification of Isotachophoresis Zones Using Nonfocusing Fluorescent Tracers (2009)

We present a novel method for visualizing isotachophoresis (ITP) zones. We introduce negligibly small concentrations of a fluorophore that is not focused by isotachophoresis. This nonfocusing tracer (NFT) migrates through multiple isotachophoresis zones. As it enters each zone, the NFT concentration adapts to the local electric field in each zone. ITP zones can then be visualized with a point detector or camera. The method can be used to detect, identify, and quantify unknown analyte zones and can visualize complex and even transient electrophoresis processes. This visualization technique is particularly suited to microfluidic and laboratory-on-a-chip applications, as typical fluorescence microscopes and charge-coupled device (CCD) cameras can provide high-resolution spatiotemporal data. We present a theoretical description, a methodology for identifying analytes, and experimental validation. We also visualize and analyze a complex, transient DNA ITP preconcentration and separation.