gebhart/patrepeval huggingface dataset:
Porous Metal–Organic Frameworks for Heterogeneous Biomimetic Catalysis (2014)

Metalloporphyrins are the active sites in monooxygenases that oxidize a variety of substrates efficiently and under mild conditions. Researchers have developed artificial metalloporphyrins, but these structures have had limited catalytic applications. Homogeneous artificial metalloporphyrins can undergo catalytic deactivation via suicidal self-oxidation, which lowers their catalytic activity and sustainability relative to their counterparts in Nature. Heme molecules in protein scaffolds can maintain high efficiency over numerous catalytic cycles. Therefore, we wondered if immobilizing metalloporphyrin moieties within porous metal-organic frameworks (MOFs) could stabilize these structures and facilitate the molecular recognition of substrates and produce highly efficient biomimetic catalysis. In this Account, we describe our research to develop multifunctional porphyrinic frameworks as highly efficient heterogeneous biomimetic catalysts. Our studies indicate that porous porphyrinic frameworks provide an excellent platform for mimicking the activity of biocatalysts and developing new heterogeneous catalysts that effect new chemical transformations under mild conditions. The porous structures and framework topologies of the porphyrinic frameworks depend on the configurations, coordination donors, and porphyrin metal ions of the metalloporphyrin moieties. To improve the activity of porous porphyrinic frameworks, we have developed a two-step synthesis that introduces the functional polyoxometalates (POMs) into POM-porphyrin hybrid materials. To tune the pore structures and the catalytic properties of porphyrinic frameworks, we have designed metalloporphyrin M-H8OCPP ligands with four m-benzenedicarboxylate moieties, and introduced the secondary auxiliary ligands. The porphyrin metal ions and the secondary functional moieties that are incorporated into porous metal-organic frameworks greatly influence the catalytic properties and activities of porphyrinic frameworks in different reactions, such as the oxidation of alkylbenzenes, olefins, and hexane and the photo-oxygenation of 1,5-dihydroxynaphthalene and sulfides. The porphyrin metal ions and the secondary auxiliary sites in the pores can work together synergistically to enhance the catalytic activities of porphyrinic frameworks. Compared with their homogeneous counterparts, the activities and stabilities of the heterogeneous porphyrinic frameworks are remarkable: the immobilization of metalloporphyrins onto the pore surfaces of MOFs not only prevents their suicidal self-oxidation but also allows them to activate inert substrate molecules, such as cyclohexane. Moreover, because the bulky molecules cannot easily access the active sites inside the pores of porphyrinic frameworks, these porous materials demonstrate interesting size-selective catalytic properties toward substrates.
Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells (2008)

We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications.
Copper metallization for ULSL and beyond (1995)

Abstract The investigation of copper for use as an interconnection metal in the ultra large-scale integration (ULSI) era of silicon integrated circuits has accelerated in the past several years. The obvious advantages for using copper to replace currently used Al are related to its lower resistivity (1.7 μΩ-cm vs. 2.7 μω-cm for Al) and its higher electromigration resistance (several orders of magnitude higher compared with Al). The goal of this review is to examine the properties of copper and its applicability as the interconnection metal. A comparison of electromigration behavior of various possible interconnection metal in standard “bulk” state is made. This is followed by a review of the calculations made comparing (a) the RC (resistance × capacitance) time constants of various material systems and (b) the joule heating of the interconnection materials. A comparative study of various metal systems for the application as the interconnect metal is then made. These discussions will clearly establish the superiority of copper over other metals despite certain limitations of copper. We then review the properties, both physical and chemical, and materials science of copper. The concept of using alloys of copper with a minimal sacrifice on resistivity to gain reliability is also discussed. This is followed by the review of the deposition, pattern definition and etching. passivation, need of the diffusion barrier (DB) and adhesion promoter (AP), planarization and dual damascene process using chemical mechanical planarization, and reliability. This review shows that copper will satisfy the needs of the future integrated circuits and provide high performance and reliability as long as we provide an appropriate barrier to diffusion in the underlying devices and the dielectric.
Immunomodulatory spherical nucleic acids (2015)

Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.
Efficacy of a New Cream Formulation of Mupirocin: Comparison with Oral and Topical Agents in Experimental Skin Infections (2000)

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.
Dasatinib suppresses TGFβ-induced epithelial mesenchymal transition and inhibits pulmonary fibrosis (2014)

[Background] Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been reported that imatinib attenuated bleomycin (BLM)-induced fibrosis in mice. Dasatinib (DAS) is tyrosine kinase inhibitor against platelet derived growth factor receptor as well as imatinib. However, there have been no studies on the effects of DAS on pulmonary fibrosis. [Aim] Our aim is to investigate the effect of DAS on TGFβ-induced EMT in human alveolar epithelial cells in vitro and to evaluate the efficacy of DAS on lung fibrosis in vivo. [Materials and Methods] A549 cells were stimulated with TGFβ and treated with or without DAS. We analyzed epithelial and mesenchymal markers by quantitative real time PCR and western blot and cell motility by wound healing assay. We developed a mouse model for pulmonary fibrosis by intravenous injection of BLM. Either DAS or vehicle was administered by oral gavage, and mice were sacrificed on day 22. We evaluated pathological findings and measured the collagen contents in the lungs of the mice. [Results] In vitro , TGFβ-induced expression of mesenchymal proteins and transcriptional factors were significantly suppressed by the treatment with DAS. Furthermore, DAS markedly inhibited TGFβ-induced cell motility. In vivo, treatment with DAS significantly attenuated BLM-induced lung fibrosis and collagen contents in the lungs. [Conclusion] These findings suggest that DAS inhibits pulmonary fibrosis by suppressing TGFβ-induced EMT. DAS may be a promising and novel anti-fibrotic agent for the prevention of IPF.
Synthesis of congeners of adenosine resistant to deamination by adenosine deaminase (1989)

V. Nair, D. F. Purdy and T. B. Sells, J. Chem. Soc., Chem. Commun., 1989, 878 DOI: 10.1039/C39890000878
Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells. (2002)

The monoclonal antibody trastuzumab (Herceptin) directed against the human epidermal growth factor receptor 2 (HER2) results in tumor regressions when administered to patients with HER2-overexpressing breast cancer. One of the underlying mechanisms of this antibody-induced tumor regression is based on the internalization and degradation of HER2 by tumor cells on interaction with trastuzumab, subsequently inhibiting signal transduction pathways. As antibody-induced degradation of HER2 is likely to be accompanied with increased numbers of HER2 peptides presented with MHC, we asked whether trastuzumab-treated tumor cells were more susceptible to CTL-mediated lysis. Here we show that the cytolytic activity of human, HER2-specific CD8(+) CTLs is augmented by anti-HER2 antibody trastuzumab. HER2-reactive CTL clones lyse class I-matched, HER2-overexpressing tumor cells more efficiently after treatment with trastuzumab. The potentially synergistic activity of HER2-specific antibody and CTL encourages the development of an HER2-targeted immunotherapy using a combination of inhibitory antibodies and CTLs for patients with HER2-overexpressing tumors.
Integrated micro-coaxial passive components for millimeter-wave antenna front ends (2007)

Miniature 250 to 700-μm tall copper air-filled rectangular coaxial line with inner conductor supported by periodic dielectric straps is demonstrated. The measured loss is as low as 0.08dB/cm at 37GHz, while the isolation between two parallel lines with center-to-center separation of 350μm is better than 60dB. A number of quasi-planar components are designed to be fabricated on the same 6-inch wafer using a sequential micro-fabrication process with 5 to 10 layers of copper. This paper presents an overview of several components that have been demonstrated in the air-micro-coax technology: low-loss densely-packed lines with a range of characteristic impedances; patch-type antenna elements; branch-line hybrids; cavity resonators; a Buttler matrix beamforming network. In addition to these components, the paper also discusses dividers/combiners and broadband hybrids, with an overview of the limitations and advantages of the technology.
Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis. (1994)

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a high incidence of colon cancer. Dysplasia is a precursor to carcinoma and a predictor of malignant potential; epithelia containing high-grade or severe dysplasia is most likely to develop cancer. The cellular oncogene c-src and its viral homologue v-src (the transforming gene of Rous sarcoma virus) encode 60-kD cytoplasmic, membrane-associated protein tyrosine kinases. For the viral protein or transforming mutants of the cellular protein (Src), a close correlation exists between elevated tyrosine kinase activity and malignant transformation of cells. Previously, we and others observed elevated Src activity in sporadic colon carcinomas and benign adenomas at greatest risk for developing cancer (those with large size, villous architecture, and/or severe dysplasia). Here we report that Src activity and protein abundance are also elevated in neoplastic UC epithelia. Activity is highest in malignant and severely dysplastic epithelia, and 6-10-fold higher in mildly dysplastic than in nondysplastic epithelia. Thus, Src activity is elevated in premalignant UC epithelia, which is at greatest risk for developing cancer. The data suggest that activation of the src proto-oncogene is an early event in the genesis of UC colon cancer.
Fibrillation of the Major Curli Subunit CsgA under a Wide Range of Conditions Implies a Robust Design of Aggregation (2011)

The amyloid fold is usually considered a result of protein misfolding. However, a number of studies have recently shown that the amyloid structure is also used in nature for functional purposes. CsgA is the major subunit of Escherichia coli curli, one of the most well-characterized functional amyloids. Here we show, using a highly efficient approach to prepare monomeric CsgA, that in vitro fibrillation of CsgA occurs under a wide variety of environmental conditions and that the resulting fibrils exhibit similar structural features. This highlights how fibrillation is "hardwired" into amyloid that has evolved for structural purposes in a fluctuating extracellular environment and represents a clear contrast to disease-related amyloid formation. Furthermore, we show that CsgA polymerization in vitro is preceded by the formation of thin needlelike protofibrils followed by aggregation of the amyloid fibrils.
Retroviral‐Fibronectin Interactions in Transduction of Mammalian Cells (1999)

Hematopoiesis occurs in a complex environment in the medullary cavity in close proximity to stromal cells, fibroblasts, endothelial cells and matrix molecules. Hematopoietic cell interactions in this environment appear to involve both integrin and proteoglycan-mediated cell-cell and cell-matrix interactions. Genetic transduction of hematopoietic stem cells via retroviral vectors has been hampered by low efficiency of gene transfer. Recently, hematopoietic stem cell adhesion to the extracellular matrix molecule fibronectin has been shown to increase transduction of these target cells using retrovirus vectors. The mechanism of increased transduction appears to involve colocalization of virus particles and target cells. These data are reviewed in this paper.
Comparison of Different Aspect Ratio Cooling Channel Designs for a Liquid Propellant Rocket Engine (2007)

High combustion temperatures and long operation durations require the use of cooling techniques in liquid propellant rocket engines. For high-pressure and high-thrust rocket engines with long operation times, regenerative cooling is the most preferred cooling method. In regenerative cooling, a coolant flows through passages formed either by constructing the chamber liner from tubes or by milling channels in a solid liner. Traditionally, approximately square cross sectional channels have been used. However, recent studies have shown that by increasing the coolant channel height-to-width aspect ratio, the rocket combustion chamber hot-gas-side wall temperature can be reduced significantly. In this study, the regenerative cooling of a liquid propellant rocket engine has been numerically simulated. The engine has been modeled to operate on a LOX/GH <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> mixture at a chamber pressure of 68 atm and LH <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (liquid-hydrogen) is considered as the coolant. A numerical investigation was performed to determine the effect of different aspect ratio cooling channels and different coolant mass flow rates on hot-gas-side wall temperature and coolant pressure drop. The variables considered in the cooling channel design were the number of cooling channels and the cooling channel cross-sectional geometry along the length of the combustion chamber.
Robust Vehicle and Traffic Information Extraction for Highway Surveillance (2005)

A robust vision-based traffic monitoring system for vehicle and traffic information extraction is developed in this research. It is challenging to maintain detection robustness at all time for a highway surveillance system. There are three major problems in detecting and tracking a vehicle: (1) the moving cast shadow effect, (2) the occlusion effect, and (3) nighttime detection. For moving cast shadow elimination, a 2D joint vehicle-shadow model is employed. For occlusion detection, a multiple-camera system is used to detect occlusion so as to extract the exact location of each vehicle. For vehicle nighttime detection, a rear-view monitoring technique is proposed to maintain tracking and detection accuracy. Furthermore, we propose a method to improve the accuracy of background extraction, which usually serves as the first step in any vehicle detection processing. Experimental results are given to demonstrate that the proposed techniques are effective and efficient for vision-based highway surveillance.
Thermally Rearrangeable PIM-Polyimides for Gas Separation Membranes (2014)

Membrane gas separations require materials with high permeability and good selectivity. For glassy polymers, the gas transport properties depend strongly on the amount and distribution of free volume, which may be enhanced either by engineering the macromolecular backbone to frustrate packing in the solid state or by thermal conversion of a soluble precursor to a more rigid structure of appropriate topology. The first approach gives polymers of intrinsic microporosity (PIMs), while the second approach is used in thermally rearranged (TR) polymers. Recent research has sought to combine these approaches, and here a new range of thermally rearrangeable PIM-polyimides are reported, derived from dianhydrides incorporating a spiro center. Hydroxyl-functionalized polyimides were prepared using two different diamines: 2,2-bis(3-amino-4-hydroxyphenyl) hexafluoropropane (bisAPAF) and 4,6-diaminoresorcinol (DAR). Thermal treatment at 450 °C under N2 for 1 h yielded polybenzoxazole (PBO) polymers, which showed increased permeability, compared to the precursor, in membrane gas permeation experiments. A polymer based on DAR (PIM-PBO-3) exhibited a CO2/N2 selectivity of 30 as prepared, higher than the values of 21-23 obtained for polymers derived from bisAPAF with the same dianhydride (PIM-PBO-1). © 2014 American Chemical Society.
New Allele at the Fan Locus in the Soybean Line A5 (1991)

The soybean [ Glycine max (L.) Merr.] line A5 has a low content of linolenic acid in the seed oil. Our objective was to determine if alleles at the Fan locus were influencing this trait in A5. To reduce environmental influences, the study was conducted indoors. Crosses were made between A5 and the low linolenic acid lines C1640 ( fan/fan ) and N78‐2245 ( Fan/Fan ). The F 2 progeny of A5 ✕ N78‐2245, N78‐2245 ✕ A5, and N78‐2245 ✕ C1640 segregated in bimodal patterns for linolenic acid content, each consistent with a 3:1 ratio. The F 2 patterns were confirmed by assays of F 3 progeny. There was no segregation for linolenic acid content in the F 2 progeny of A5 ✕ C1640. These observations indicated that A5 ✕ N78‐2245, and N78‐2245 ✕ A5 segregated for alleles at the Fan locus. The pattern of low linolenic acid content showed that the Fan and Idh2 loci were linked at distances of 25.2 ± 3.5 units for A5 ✕ N78‐2245, 24.3 ± 3.4 for N78‐2245 ✕ AS, and 24.7 ± 3.5 for N78‐2245 ✕ C1640. These results were all consistent with an allele at the Fan locus being the primary factor responsible for the low linolenic acid content in A5. The allele in A5 has been designated fan (AS). The fan (AS) allele appeared to be in two F 4 lines from A5 ✕ N78‐2245 that were characterized by a mean linolenic acid content &lt;25 g kg −1 when grown under 16 h daylength at 28/22°C day/night. The complete genetic basis of this phenotype is receiving further study.
The human cystatin C gene promoter: Functional analysis and identification of heterogeneous mRNA (1995)

Human cystatin C is a low molecular weight protein involved in the control of human cysteine proteinase activity as well as microbial cysteine proteinase activity threatening the integrity of tissues. The gene for cystatin C is located on the short arm of chromosome 20, spans 6.5 kb and has three exons. To understand the mechanisms for the expression of cystatin C at the transcriptional level we mapped the 5' boundary of mRNA transcripts and studied the 5'-region of the cystatin C gene in a transient expression system with chimeric constructs utilizing various fragments of 1.1 kb of the 5'-flanking region coupled to the gene for human growth hormone. Mapping of the 5'-end of human cystatin C mRNA from placenta and seminal vesicles (low to medium versus high cystatin C expression, respectively) identified three major transcription initiation sites (positions -75, -78 and -80, A of initiation ATG as +1) and three minor sites (positions -98, -101 and -103). The relative amounts of different mRNA species were approximately the same in these two tissues. Functional analysis of the 5'-region in cultured HeLa cells revealed one region (positions -279 to -156) with a strong positive effect on transcription and comprising three identical tandemly arranged GC-rich sequences.