gebhart/patrepeval huggingface dataset:
High affinity binding sites for the Wilms’ tumour suppressor protein WT1 (1995)

The Wilms' tumour suppressor protein (WT1) is a putative transcriptional regulatory protein with four zinc fingers, the last three of which have extensive sequence homology to the early growth response-1 (EGR-1) protein. Although a peptide encoding the zinc finger domain of WT1[-KTS] can bind to a consensus 9 bp EGR-1 binding site, current knowledge about the mechanisms of zinc finger-DNA interactions would predict a more extended recognition site for WT1. Using a WT1[-KTS] zinc finger peptide (WT1-ZFP) and the template oligonucleotide GCG-TGG-GCG-NNNNN in a binding site selection assay, we have determined that the highest affinity binding sites for WT1[-KTS] consist of a 12 bp sequence GCG-TGG-GCG-(T/G)(G/A/T)(T/G). The binding of WT1-ZFP to a number of the selected sequences was measured by a quantitative nitrocellulose filter binding assay, and the results demonstrated that these sequences have a 4-fold higher affinity for the protein than the nonselected sequence GCG-TGG-GCG-CCC. The full length WT1 protein regulates transcription of reporter genes linked to these high affinity sequences. A peptide lacking the first zinc finger of WT1[-KTS], but containing the three zinc fingers homologous to EGR-1 failed to select any specific sequences downstream of the GCG-TGG-GCG consensus sequence in the binding site selection assay. DNA sequences in the fetal promoter of the insulin-like growth factor II gene that confer WT1 responsiveness in a transient transfection assay bind to the WT1-ZFP with affinities that vary according to the number of consensus bases each sequence possesses in the finger 1 subsite.
Constructive solid geometry for polyhedral objects (1986)

Constructive Solid Geometry (CSG) is a powerful way of describing solid objects for computer graphics and modeling. The surfaces of any primitive object (such as a cube, sphere or cylinder) can be approximated by polygons. Being abile to find the union, intersection or difference of these objects allows more interesting and complicated polygonal objects to be created. The algorithm presented here performs these set operations on objects constructed from convex polygons. These objects must bound a finite volume, but need not be convex. An object that results from one of these operations also contains only convex polygons, and bounds a finite volume; thus, it can be used in later combinations, allowing the generation of quite complicated objects. Our algorithm is robust and is presented in enough detail to be implemented.
A novel mutation within a transmembrane helix of the bile salt export pump (BSEP,ABCB11) with delayed development of cirrhosis (2013)

The novel mutation p.G374S impairs transport function without disabling membrane localization of BSEP. While all other known BSEP mutations within transmembrane helices are associated with PFIC-2, the new p.G374S mutation causes a transitional phenotype between BRIC-2 and PFIC-2.
Regioselective Glucosylation of Aromatic Compounds: Screening of a Recombinant Glycosyltransferase Library to Identify Biocatalysts (2006)

A novel whole-cell screen for the identification of new glucosyltransferase (GT) biocatalysts within a recombinant enzyme library was developed. Following biotransformation, levels of D-glucose were used as a measure of biocatalysis. Twenty five enzymes that transfer D-glucose to trans-resveratrol were identified that have the regioselectivity shown in the picture. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z504505_s.pdf or from the author. 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.
Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1 (1996)

Lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is involved in leukocyte adhesion during cellular interactions essential for immunologic responses and inflammation. mAbs against LFA-1 have been shown to inhibit several T cell-dependent immune functions in vitro and prevent graft failure after bone marrow transplantation in vivo. A murine anti-human CD11a mAb, MHM24, has been humanized and shown to prevent adhesion of human T cells to human keratinocytes and the proliferation of T cells in response to nonautologous leukocytes in the mixed lymphocyte response assay. However, of the nonhuman primate CD11a that we tested, the murine and humanized mAbs cross-reacted only with chimpanzee CD11a. To have a mAb available for preclinical studies in rhesus monkeys, the humanized mAb was reengineered to bind to rhesus CD11a by changing four residues in one of the complementarity-determining regions, CDR-H2, in the variable heavy domain. Cloning and molecular modeling of rhesus CD11a I-domain suggested that the changes from Lys197 and/or Arg189 in human CD11a I-domain to Glu197 and Gln189 in rhesus CD11a I-domain may be the reason that rhesus CD11a does not bind to the murine and humanized mAbs.
Human coronary laser recanalization (1984)

Five patients undergoing distal saphenous vein bypass had an attempt at intraoperative laser vaporization of a proximal coronary stenosis. Laser treatment of three patients was technically successful. One patient's successfully treated native vessel was competing with the graft at angiographic restudy 25 days after the procedure. This first human intraoperative laser recanalization trial generated questions regarding the energy source, power parameters, and catheter modifications required for satisfactory clinical laser therapy. The trial is directing future experiments toward more efficient and complete laser vaporization of atherosclerotic plaques in the human coronary vasculature.
Growth factor- and dexamethasone-induced proteins in Swiss 3T3 cells. Relationship to DNA synthesis. (1985)

Dexamethasone synergistically enhances the stimulation of DNA synthesis in quiescent Swiss 3T3 cells by cartilage-derived growth factor (CDGF) while having no consistent effect when added with platelet-derived growth factor (PDGF) or serum. We examined the hypothesis that this difference might be attributed to selective synthesis of individual proteins early in the G1 phase of the cell cycle. Swiss 3T3 cells were treated with CDGF, PDGF, and fetal bovine serum for 3 h, with or without dexamethasone, and [35S]methionine-labeled proteins were separated by two-dimensional electrophoresis on giant gels. Over 3300 proteins could be distinguished; 34 of these were consistently induced more than 3-fold by all three factors, while an additional 30 inductions were variably present. Dexamethasone by itself induced 8 other proteins, and at least 9 growth factor inductions were synergistically enhanced by addition of the hormone. To identify proteins intimately associated with growth control, we looked for inductions that reflected the dexamethasone synergy with CDGF on DNA synthesis and lack of such an effect with PDGF. The induction of only one group of proteins, the Band 1 isoforms (44-46 kDa, pI 6.1-5.9) displayed such selective synergy. The majority of the other growth factor inductions were inhibited by dexamethasone, even in the context of maximal DNA synthesis, implying that their increased synthesis is not required for growth. When 3T3 cells were treated with increasing doses of CDGF with and without dexamethasone, autoradiographic densities of induced proteins varied in a dose-responsive fashion. However, only levels of the Band 1 proteins bore a constant linear relationship to DNA synthesis, suggesting that they play an important role in early control of the cell cycle.
α-Glucosidase and Ν-Acetyl-α-D-glucosaminidase Isoenzymes in Serum (1992)

Using different conditions for incubation and fluorometry with 4-methylumbelliferylglycosides as substrates, we demonstrated the presence of acid alpha-glucosidase, "renal" alpha-glucosidase, N-acetyl-beta-D-glucosaminidase A, and N-acetyl-beta-D-glucosaminidase B in freshly drawn normal human serum. The acid alpha-glucosidase enzymatic activity was determined at pH 4.0 in 0.1 mol/L Tris reagent, whereas the renal isoenzyme activity was determined at pH 5.6 in presence of 0.05 mol/L turanose reagent. N-Acetyl-beta-D-glucosaminidases A and B were determined by their different behaviors on heating. The corresponding reference intervals for each enzyme were calculated from results for 40 controls: acid alpha-glucosidase (0.024 +/- 0.010 U/L), renal alpha-glucosidase (0.035 +/- 0.012 U/L), N-acetyl-beta-D-glucosaminidase A (10.2 +/- 2.9 U/L), and N-acetyl-beta-D-glucosaminidase B (4.4 +/- 2.1 U/L).
Molecular Mechanisms of 4-Hydroxy-2-nonenal and Acrolein Toxicity: Nucleophilic Targets and Adduct Formation (2009)

Acrolein and 4-hydroxy-2-nonenal (HNE) are byproducts of lipid peroxidation and are thought to play central roles in various traumatic injuries and disease states that involve cellular oxidative stress, for example, spinal cord trauma, diabetes, and Alzheimer's disease. In this review, we will discuss the chemical attributes of acrolein and HNE that determine their toxicities. Specifically, these aldehydes are classified as type 2 alkenes and are characterized by an alpha,beta-unsaturated carbonyl structure. This structure is a conjugated system that contains mobile pi-electrons. The carbonyl oxygen atom is electronegative and can promote the withdrawal of mobile electron density from the beta-carbon atom causing regional electron deficiency. On the basis of this type of electron polarizability, both acrolein and HNE are considered to be soft electrophiles that preferentially form 1,4-Michael type adducts with soft nucleophiles. Proteomic, quantum mechanical, and kinetic data will be presented, indicating that cysteine sulfhydryl groups are the primary soft nucleophilic targets of acrolein and HNE. This is in contrast to nitrogen groups on harder biological nucleophiles such as lysine or histidine residues. The toxicological outcome of adduct formation is not only dependent upon residue selectivity but also the importance of the targeted amino acid in protein function or structure. In attempting to discern the toxicological significance of a given adduct, we will consider the normal roles of cysteine, lysine, and histidine residues in proteins and the relative merits of corresponding adducts in the manifestations of diseases or toxic states. Understanding the molecular actions of acrolein and HNE could provide insight into many pathogenic conditions that involve initial cellular oxidative stress and could, thereby, offer new efficacious avenues of pharmacological defense.
An estrogen receptor repressor induces cataract formation in transgenic mice (2002)

Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER Delta , a dominant-negative form of ER alpha that inhibits ER alpha function. In the ER Delta 3 transgenic mice, cortical cataracts spontaneously form in ER Delta 3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER Delta 3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DES-induced cataracts in ER Delta 3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER Delta 3 repressor. Evidence of DES-induced cataracts in the ER Delta 3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER Delta 3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens.
The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin Potency Testing (2010)

An Expert Meeting on The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin (BoNT) Potency Testing was organised by the Centre for Documentation and Evaluation of Alternatives to Animal Experiments (ZEBET) at the Federal Institute for Risk Assessment (BfR), and took place on 27–28 April 2009, in Berlin, Germany. The goal of ZEBET is to promote primarily the replacement of legally required animal experiments with valid alternative test methods, to reduce the numbers of test animals used to the absolutely necessary level, and to alleviate their pain and suffering. ZEBET’s tasks are the documentation, assessment and promotion of alternative methods to animal experiments on a national and international level, and the initiation of research and development, including the funding of smaller research projects. The Expert Meeting on alternative methods for Botulinum neurotoxin (BoNT) potency testing was held at the BfR as the result of a decree from the German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV), after it was informed by German state authorities about an increase in animal numbers being used in the LD50 potency test in mice for the purposes of BoNT potency testing. Ethical concerns have been raised in both Europe and the United States about the animal suffering involved in this type of testing, especially in the context of BoNT’s aesthetic applications. There had been increased public pressure on the German Government, due to successful campaigning by animal welfare/anti-vivisectionist organisations on the issue of BoNT animal testing. As a result, the BMELV asked ZEBET to assess the status of the different alternative methods to the BoNT LD50 potency test that are cited in the European Pharmacopoeia (EP) 6.0, Monograph 2113, Botulinum Toxin Type The Current Scientific and Legal Status of Alternative Methods to the LD50 Test for Botulinum Neurotoxin Potency Testing
On the Role of PKG for Proxy Re-encryption in Identity Based Setting. (2008)

Abstract. In 1998, Blaze, Bleumer, and Strauss proposed a kind of cryptographic primitive called proxy re-encryption[3]. In proxy re-encryption, a proxy can transform a ciphertext computed under Alice’s public key into one that can be opened under Bob’s decryption key. In 2007, Matsuo proposed the concept of four types of proxy re-encryption schemes: CBE(Certificate Based Public Key Encryption) to IBE(Identity Based Encryption)(type 1), IBE to IBE(type 2), IBE to CBE (type 3), CBE to CBE (type 4)[29]. Now CBE to IBE and IBE to IBE proxy re-encryption schemes are being standardized by IEEEP1363.3 working group[31]. In this paper, based on [29] we pay attention to the role of PKG for proxy re-encryption in identity based setting. We find that if we allow the PKG to use its master-key in the process of generating re-encryption key for proxy re-encryption in identity based setting, many open problems can be solved. Our main results are as following: We construct the first proxy re-encryption scheme from CBE to IBE which can resist malicious PKG attack, the first proxy re-encryption scheme from IBE to CBE, the second proxy re-encryption scheme based on a variant of BB1 IBE 1, the first proxy re-encryption scheme based on BB2 IBE, the first proxy re-encryption scheme based on SK IBE, we also prove their security in their corresponding security models. 1
A Framework for Multimedia Communication in a General-Purpose Distributed System (1989)

Abstract : Next-generation distributed computer systems will support network communication of digital multimedia (audio and video) traffic. Evolving hardware technology will provide the necessary performance. However, difficult design issues arise in the software structure of such a system. We consider three related issues: 1) What basic IPC abstractions can accommodate the likely range of traffic types? 2) How can IPC functions such as security and flow control be optimally assigned to system layers? 3) How can host resources such as CPU time and memory be optimally allocated? In response to these questions, we have defined channels, an IPC abstraction with security, reliability, and performance parameters. The channel abstraction underpins the network communication architecture of DASH, an experimental distributed system. In DASH, IPC functions are dynamically assigned to the layer in which they can be performed most efficiently, and the allocation policies for kernel resources are dictated by the performance needs of IPC. All IPC (local and request/reply as well as multimedia) is handled in a single framework.
Dynamic Removal of Replication Protein A by Dna2 Facilitates Primer Cleavage during Okazaki Fragment Processing in Saccharomyces cerevisiae (2008)

Eukaryotic Okazaki fragments are initiated by a RNA/DNA primer, which is removed before the fragments are joined. Polymerase delta displaces the primer into a flap for processing. Dna2 nuclease/helicase and flap endonuclease 1 (FEN1) are proposed to cleave the flap. The single-stranded DNA-binding protein, replication protein A (RPA), governs cleavage activity. Flap-bound RPA inhibits FEN1. This necessitates cleavage by Dna2, which is stimulated by RPA. FEN1 then cuts the remaining RPA-free flap to create a nick for ligation. Cleavage by Dna2 requires that it enter the 5'-end and track down the flap. Because Dna2 cleaves the RPA-bound flap, we investigated the mechanism by which Dna2 accesses the protein-coated flap for cleavage. Using a nuclease-defective Dna2 mutant, we showed that just binding of Dna2 dissociates the flap-bound RPA. Facile dissociation is specific to substrates with a genuine flap, and will not occur with an RPA-coated single strand. We also compared the cleavage patterns of Dna2 with and without RPA to better define RPA stimulation of Dna2. Stimulation derived from removal of DNA folding in the flap. Apparently, coordinated with its dissociation, RPA relinquishes the flap to Dna2 for tracking in a way that does not allow flap structure to reform. We also found that RPA strand melting activity promotes excessive flap elongation, but it is suppressed by Dna2-promoted RPA dissociation. Overall, results indicate that Dna2 and RPA coordinate their functions for efficient flap cleavage and preparation for FEN1.
Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes (2016)

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.
Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. (1982)

A human hepatoma cell line, HuH-7, which was established from a hepatocellular carcinoma, was found to replicate continuously in a chemically defined medium when the medium was supplemented with Na2SeO3. The cells grew better in this medium than in serum-containing medium without any adaptation period. Other established human hepatoma and hepatoblastoma cell lines, HuH-6 cl-5, PLC/PRF/5, huH-1, and huH-4, also grew in the defined medium. Although HLEC-1 cells failed to proliferate continuously with Na2SeO3 alone, they grew if a cell-free conditioned medium from HuH-7 cells was added to the medium. These cell lines, except the HLEC-1 cell line, produced the following human plasma proteins among those examined: albumin, prealbumin, alpha 1-antitrypsin, ceruloplasmin, fibrinogen, fibronectin, haptoglobin, hemopexin, beta-lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, Complement Components 3 and 4, and alpha 1-fetoprotein. Beside plasma proteins, the media from HuH-7, HuH-6 cl-5, PLC/PRF/5, and huH-1 contained anti-carcinoembryonic antigen-reactive proteins, and those from PLC/PRF/5, huH-1, and huH-4 medium contained hepatitis B surface antigen. These proteins were detected during periods of serial cultivation over 9 months under the above culture conditions. The hepatoma cell lines grown in the fully defined synthetic medium may provide a new approach for investigating the growth and metabolism of human hepatoma cells in vitro.
Noble metal nanoparticle@metal oxide core/yolk–shell nanostructures as catalysts: recent progress and perspective (2014)

Controllable integration of noble metals (e.g., Au, Ag, Pt, and Pd) and metal oxides (e.g., TiO₂, CeO₂, and ZrO₂) into single nanostructures has attracted immense research interest in heterogeneous catalysis, because they not only combine the properties of both noble metals and metal oxides, but also bring unique collective and synergetic functions in comparison with single-component materials. Among many strategies recently developed, one of the most efficient ways is to encapsulate and protect individual noble metal nanoparticles by a metal oxide shell of a certain thickness to generate the core-shell or yolk-shell structure, which exhibits enhanced catalytic performance compared with conventional supported catalysts. In this review article, we summarize the state-of-the art progress in synthesis and catalytic application of noble metal nanoparticle@metal oxide core/yolk-shell nanostructures. We hope that this review will help the readers to obtain better insight into the design and application of well-defined nanocomposites in both the energy and environmental fields.