gebhart/patrepeval huggingface dataset:
Heritable targeted mutagenesis in maize using a designed endonuclease (2009)

The liguleless locus (liguleless1) was chosen for demonstration of targeted mutagenesis in maize using an engineered endonuclease derived from the I-CreI homing endonuclease. A single-chain endonuclease, comprising a pair of I-CreI monomers fused into a single polypeptide, was designed to recognize a target sequence adjacent to the LIGULELESS1 (LG1) gene promoter. The endonuclease gene was delivered to maize cells by Agrobacterium-mediated transformation of immature embryos, and transgenic T(0) plants were screened for mutations introduced at the liguleless1 locus. We found mutations at the target locus in 3% of the T(0) plants, each of which was regenerated from independently selected callus. Plants that were monoallelic, biallelic and chimeric for mutations at the liguleless1 locus were found. Relatively short deletions (shortest 2 bp, longest 220 bp) were most frequently identified at the expected cut site, although short insertions were also detected at this site. We show that rational re-design of an endonuclease can produce a functional enzyme capable of introducing double-strand breaks at selected chromosomal loci. In combination with DNA repair mechanisms, the system produces targeted mutations with sufficient frequency that dedicated selection for such mutations is not required. Re-designed homing endonucleases are a useful molecular tool for introducing targeted mutations in a living organism, specifically a maize plant.
A fault tolerance approach to computer viruses (2003)

Extensions of program flow monitors and n-version programming can be combined to provide a solution to the detection and containment of computer viruses. The consequence is that a computer can tolerate both deliberate faults and random physical faults by one common mechanism. Specifically, the technique detects control flow errors due to physical faults as well as the presence of viruses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The AU-Rich Transcriptome: More Than Interferons and Cytokines, and Its Role in Disease (2005)

The AU-rich elements (AREs) are among the predominant cis-acting factors that exist primarily in the 3' untranslated region (3'-UTR) of messenger RNAs (mRNAs) and regulate mRNA stability. AREs were previously believed to be restricted to relatively few mRNAs, including those of interferons (IFNs) and cytokines, growth factors, and proto-oncogenes. Our recent analysis, however, showed that ARE mRNAs represent as much as 8% of mRNAs transcribed from human genes that encode functionally diverse proteins important in many transient biologic processes. Among those processes are cell growth and differentiation, immune responses, signal transduction, transcriptional and translational control, hematopoiesis, apoptosis, nutrient transport, and metabolism. Several recent studies examined signaling pathways that regulate ARE-mediated mRNA stability, notably the p38 mitogen-activated protein kinase (MAPK) pathway. In addition, several AU-rich binding proteins that regulate the ARE mRNA pathways have been characterized. Dysregulation of regulatory signaling pathways and regulatory proteins affecting ARE mRNA stability can lead to abnormalities in many critical cellular processes and to specific disease conditions. Thus, the heterogeneity in AREs, their signaling pathways, and effector proteins contribute to the functional diversity of the ARE gene family, which encompasses more than IFNs and cytokines.
Rat galactose-1-phosphate uridyltransferase coding sequence, transcription start site and genomic organization (1993)

Galactosemia is an inborn error of metabolism in humans due to deficient activity of the enzyme galactose-1-phosphate uridyl-transferase (GALT). Using a 1.3 kb Bam HI restriction fragment of the human GALT cDNA as a probe, three cDNAs, 786 bp, 265 bp and 1.4 kb were isolated from a rat liver cDNA library. The total rat GALT coding sequence obtained from these three clones was 1051 nt. Repeat cDNA library screening failed to isolate cDNA clones with additional 5'-coding sequence. Using the 786 bp cDNA as a probe, three genomic clones, RGG1, RGG2, and RGG3 were isolated from a rat genomic library. RGG2 and RGG3 contained additional 5'-coding sequence, missing from the cDNA clones, which was identified by comparison with the human cDNA sequence. The rat GALT sequence, from transcription start site to the polyadenylation tail, is 1254 nt and is divided into 11 exons which span over 3.5 kb of genomic sequence. Primer extension identified the transcription start site as 17 nt 5' to the translation start site. Rat GALT is 379 amino acids long, identical to human GALT, with a derived molecular weight of 43,312 Da similar to the 43,360 Da weight for human GALT. The derived rat amino acid sequence is 90% identical to the human sequence. The isolation of rat GALT genomic sequence will facilitate future investigations of the regulation of expression of the rat GALT gene.
Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells. (1988)

Polysialic acid-containing glycoproteins consisting of extended chains of at least 55 sialyl residues (DP55, where DP represents degree of polymerization) are expressed on human neuroblastoma cells, CHP-134. The strategy used for detecting these unique carbohydrate structures was based on the use of two highly specific prokaryotic-derived enzyme systems and an anti-polysialosyl antibody (H.46). These probes were developed for the detection of polysialic acid on neural cell adhesion molecules (Troy, F. A., Hallenbeck, P. C., McCoy, R. D., and Vimr, E. R. (1987) Methods Enzymol. 138, 169-185). Proof for the presence of long chain multimers of sialic acid was based on two types of experiments which utilized: 1) a glycopeptide fraction of CHP-134 cells, labeled metabolically with D-[3H]GlcN and 2) a membrane fraction from CHP-134 cells which served as an exogenous acceptor of [14C] NeuNAc residues in an Escherichia coli K1 sialyltransferase assay. In vitro, this enzyme CMP-NeuNAc:poly-alpha-2,8-sialosyl sialyltransferase catalyzes the transfer of [14C]NeuNAc from CMP-[14C]NeuNAc to exogenous acceptors containing at least 3 sialyl residues. In the first series of experiments, endo-N-acetylneuraminidase (Endo-N), a bacteriophage-derived enzyme specific for hydrolyzing poly-alpha-2,8-sialosyl chains containing a minimum of 5 sialyl residues was used. Limit Endo-N digestion of the 3H-glycopeptides from the [3H] GlcN-labeled cells released short [3H]sialyl oligomers [( 3H]DP1-6) which were degraded to [3H]NeuNAc by exosialidase. Partial Endo-N digestion released a series of [3H]sialyl oligomers extending up to DP55. The longer (DP20-55) and intermediate sized (DP10-20) oligomers were isolated and converted to short oligomers ((3H]DP1-6) by retreating with Endo-N, thus confirming their identity as homo-oligomers of alpha-2,8-linked [3H]NeuNAc residues. In the second series of experiments, a membrane fraction of CHP-134 cells was radiolabeled in vitro with [14C]NeuNAc by E. coli K1 sialyltransferase. The membrane fraction had a major portion of radioactivity that was high Mr and polydisperse (Mr 100,000-250,000) as demonstrated in sodium dodecyl sulfate-polyacrylamide gels. Using Western blotting, pre-existing material of similar size was shown to react with antibody H.46.(ABSTRACT TRUNCATED AT 400 WORDS)
Reducing moment method storage from order N 2 to order N (1989)

Previously, integral equation-based calculations of electromagnetic scattering and radiation (e.g. moment method calculations) have required a full N × N matrix when there are N unknowns. However, in the letter novel basis and testing functions are presented, for which the resulting matrix is approximately sparse. That is, nearly all of its elements are nearly zero. This kind of technique is expected to reduce typical storage and execution time requirements by orders of magnitude.
Armed Therapeutic Viruses – A Disruptive Therapy on the Horizon of Cancer Immunotherapy (2014)

For the past 150 years cancer immunotherapy has been largely a theoretical hope that recently has begun to show potential as a highly impactful treatment for various cancers. In particular, the identification and targeting of immune checkpoints have given rise to exciting data suggesting that this strategy has the potential to activate sustained antitumor immunity. It is likely that this approach, like other anti-cancer strategies before it, will benefit from co-administration with an additional therapeutic and that it is this combination therapy that may generate the greatest clinical outcome for the patient. In this regard, oncolytic viruses are a therapeutic moiety that is well suited to deliver and augment these immune-modulating therapies in a highly targeted and economically advantageous way over current treatment. In this review, we discuss the blockade of immune checkpoints, how oncolytic viruses complement and extend these therapies, and speculate on how this combination will uniquely impact the future of cancer immunotherapy.
Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein (1990)

Rev is an essential regulatory protein of the human immunodeficiency virus type 1 (HIV-1) that affects the transport and half-life of certain viral mRNAs. Rev exerts its function via a unique element, the Rev-responsive element (RRE), located within the env region of HIV-1. It has been previously demonstrated that Rev affects the relative levels of RRE-containing and RRE-lacking mRNAs. We have studied the effects of Rev on the expression of the three different groups of small, multiply spliced mRNAs that lack the RRE sequence and encode the regulatory proteins Tat, Rev, and Nef. To monitor the tat, rev, and nef mRNAs we generated specific S1 nuclease mapping probes that distinguish among them. Analysis of all the mRNA species producing Tat, Rev, and Nef revealed that their levels are coordinately regulated by Rev. They are increased in the absence of Rev protein and are down regulated in the presence of Rev. The corresponding proteins were measured by immunoprecipitations, and their levels are in agreement with the RNA levels. These results verify the model proposing that Rev is a general regulator indirectly affecting all the multiply spliced mRNAs to a similar extent. Therefore, Rev down regulates its own expression and the expression of Tat and Nef.
Direct Hydrocarbon Solid Oxide Fuel Cells (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect Hydrocarbon Solid Oxide Fuel CellsSteven McIntosh and Raymond J. GorteView Author Information Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Cite this: Chem. Rev. 2004, 104, 10, 4845–4866Publication Date (Web):July 21, 2004Publication History Received31 October 2003Published online21 July 2004Published inissue 1 October 2004https://pubs.acs.org/doi/10.1021/cr020725ghttps://doi.org/10.1021/cr020725gresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views7321Altmetric-Citations804LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Electrodes,Electrolytes,Fuels,Hydrocarbons,Oxides Get e-Alerts
PROTEIN CRYSTALLIZATION (1996)

Crystallization is necessary to obtain the three-dimensional structure of proteins and nucleic acids; it often represents the bottleneck in structure determination. Our understanding of crystallization mechanisms is still incomplete. In this review, we emphasize fundamental aspects of the crystallization process. Protein-protein contacts in crystals are complex, involving a delicate balance of specific and nonspecific interactions. Depending on solution conditions, these interactions can lead to nucleation of crystals or to amorphous aggregation; this stage of crystallization has been successfully studied by light scattering. Post-nucleation crystal growth may proceed by mechanisms involving crystal defects or two-dimensional nucleation, as observed by atomic force and interference microscopy. Cessation of growth has been observed but remains incompletely understood. Impurities may play important roles during all stages of crystallization. Phase diagrams can guide optimization of conditions for nucleation and subsequent crystal growth; a theoretical understanding relating these to the intermolecular interactions is beginning to develop.
The Donor‐Acceptor‐Acceptor Purine Analog: Transformation of 5‐aza‐7‐deaza‐1H‐isoguanine (=4‐aminoimidazo‐[1,2‐a]‐1,3,5‐triazin‐2(1H)‐one) to 2′‐deoxy‐5‐aza‐7‐deaza‐isoguanosine using purine nucleoside phosphorylase (1993)

Abstract A new synthesis is reported for 4‐aminoimidazo[1,2‐ a ]‐1,3,5‐triazin‐2(1 H )‐one ( =5‐aza‐7‐deaza‐isoguanosine; 8 ), a purine analog that, when incorporated into an oligonucleotide chain, presents a H‐bond donor‐acceptor‐acceptor pattern to a complementary pyrimidine analog. A protected ribose derivative was coupled to 8 to yield 4‐amino‐8‐(β‐ D ‐ribofuranosyl)imidazo[1,2‐ a ]‐1,3,5‐triazin‐2(8 H )‐one ( =5‐aza‐7‐deaza‐isoguanosine; 11 ) after deprotection, Alternatively, direct synthesis of both the ribo derivative 11 and the corresponding deoxyribo derivative 17 as the β‐ D ‐anomers was achieved using the enzyme purine nucleoside phosphorylase in a one‐pot reaction. This adapts a known synthetic approach to yield a new strategy for obtaining diastereoisomerically pure deoxyribonucleoside analogs on 1‐gram scales.
A Peptide Binding Motif for HLA-DQA1*0102/DQB1*0602, the Class II MHC Molecule Associated with Dominant Protection in Insulin-Dependent Diabetes Mellitus (1998)

HLA-DQA1*0102/DQB1*0602 (DQ0602) is observed at a decreased frequency in insulin-dependent diabetes mellitus in different ethnic groups, suggesting a protective role for DQ0602. Analysis of overlapping peptides from human insulin found that insulin B(1-15) bound well to DQ0602 and exhibited a high degree of allelic specificity. Truncation analysis of insulin B(1-15) identified insulin B(5-15) as the minimal peptide for DQ0602 binding. Insulin B(5-15) bound to DQ0602 with an apparent KD of 0.7 to 1.0 microM and peptide binding reached equilibrium at 96 h. Single arginine substitutions at each position of the insulin B(5-15) peptide identified amino acids 6, 8, 9, 11, and 14 (relative positions P1, P3, P4, P6, and P9) as important for binding. Extensive substitutions for each of these amino acids revealed that amino acids 11 and 14 (P6 and P9) exhibited the highest specificity. Amino acid 11 (P6) preferred large aliphatic amino acids, while amino acid 14 (P9) preferred smaller aliphatic and hydroxyl amino acids. Binding of an overlapping series of peptides from a randomly chosen protein, the herpes simplex virus-2 tegument protein UL49, correlated completely with the presence or absence of the DQ0602 peptide binding motif. Peptides 11 amino acids long were selected from GAD65, IA-2, and proinsulin, that contained the DQ0602 peptide binding motif. Of these, 79% (19 of 24) were able to bind DQ0602. This study identifies a peptide binding motif for DQ0602 and peptides from insulin-dependent diabetes mellitus autoantigens that bind DQ0602 in vitro.
Linear controller design: limits of performance via convex optimization (1990)

In this tutorial, an approach to the analysis and design of linear control systems based on numerical convex optimization over closed-loop maps is presented. Convexity makes numerical solution effective: it is possible to determine whether or not there is a controller that achieves a given set of specifications. Thus, the limit of achievable performance can be computed. To provide a context for the material presented, a brief overview of control engineering is given. A broad outline of various approaches to control design for linear and time-invariant systems is presented, including their advantages and disadvantages, for purposes of comparison with the approach presented. It is shown that many performance specifications have natural and useful geometric interpretations, and the notion of a closed-loop convex design specification is defined. The performance requirement that the closed-loop system be stable is discussed. It is shown that many performance specifications can be expressed as convex constraints on closed-loop performance specifications, and how some of these can be expressed as convex constraints on closed-loop transfer matrices is examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Incorporation of Lysozyme into Liposomes (1970)

Abstract To define a model for enzyme latency in vitro, the capture was studied of egg white lysozyme by liposomes (phospholipid spherules in the smectic mesophase). Gel filtration resolved liposomes formed in the absence of enzyme from free enzyme when both were chromatographed immediately after mixing. In contrast, if liposomes were swollen in the presence of lysozyme, subsequent chromatography disclosed two peaks of enzyme activity: one associated with liposomes, the other emerging as free lysozyme. The activity of lysozyme associated with liposomes was latent; i.e. there was little or no activity on substrate (Micrococcus lysodeikticus cell walls) unless the spherules were disrupted by Triton X-100, amphotericin B, or nystatin. Lysozyme unassociated with lipid was as available to substrate in the absence of detergent or polyenes as in their presence. Charge-induced associations were not crucial for enzyme capture since both positively (lecithin-stearylamine-cholesterol) and negatively charged liposomes (lecithin-dicetylphosphate-cholesterol) captured lysozyme in latent form. As a measure of their integrity, liposomes could also be shown to capture a marker molecule (glucose), the bulk of which was released together with lysozyme from liposomes by detergent or polyenes. As the aqueous interspaces of positively charged liposomes were increased by incremental incorporation of stearylamine, capture of both glucose and lysozyme was increased proportionally. For these and other reasons it was considered likely that the liposomes had captured lysozyme in the interspaces between lipid lamellae.
地域素材を活用した地学の学習(3) : 西条層を対象とした地層観察の視点について (2011)

For many years, the Saijo Formation widely distributed in Higashi-Hiroshima has been used to observe strata in science classes. We reconsider viewpoints of observation of the Saijo Formation on the basis of its sedimentological features. The proposal of the viewpoints were discrimination of the sedimentary facies and consideration of the relation between features of strata and function of running water. We also selected an outcrop which a teacher can use as a teaching material with consideration for the viewpoints, and we proposed a learning program to observe the Saijo Formation on the outcrop. The program was carried out in a science class of an elementary school. In consequence, we found that some students achieved the object of the program.
Dimethyl sulfoxide (DMSO): a review. (1986)

Dimethyl sulfoxide (DMSO) is a very simple compound that has stimulated much controversy in the scientific and popular literature. Fig. 1 It is an aprotic solvent. Therapeutic and toxic agents that are not soluble in water are often soluble in DMSO. DMSO has a very strong affinity for water; on exposure to air, pure DMSO is rapidly diluted. DMSO's physiologic and pharmacologic properties and effects are incompletely understood. Properties that are considered to be particularly important to its therapeutic and toxic effects include: its own rapid penetration and enhanced penetration of other substances across biologic membranes; free radical scavenging; effects on coagulation; anticholinesterase activity; and DMSO-induced histamine release by mast cells. DMSO's systemic toxicity is considered to be low. Combinations of DMSO with other toxic agents probably constitute its greatest toxic potential. The scientific literature is reviewed with particular attention to mechanisms underlying DMSO's reported therapeutic and toxic effects. Currently approved, veterinary applications of DMSO are limited. DMSO's potential value in specific, approved and unapproved veterinary applications is discussed.
Direct Interaction of the Rho GDP Dissociation Inhibitor with Ezrin/Radixin/Moesin Initiates the Activation of the Rho Small G Protein (1997)

The Rho GDP dissociation inhibitor (GDI) forms a complex with the GDP-bound form of the Rho family small G proteins and inhibits their activation. The GDP-bound form complexed with Rho GDI is not activated by the GDP/GTP exchange factor for the Rho family members, suggesting the presence of another factor necessary for this activation. We have reported that the Rho subfamily members regulate the ezrin/radixin/moesin (ERM)-CD44 system, implicated in reorganization of actin filaments. Here we report that Rho GDI directly interacts with ERM, initiating the activation of the Rho subfamily members by reducing the Rho GDI activity. These results suggest that ERM as well as Rho GDI and the Rho GDP/GTP exchange factor are involved in the activation of the Rho subfamily members, which then regulate reorganization of actin filaments through the ERM system.
Application of the Luminex LabMAP in Rapid Screening for Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Gene: A Pilot Study (2000)

Cystic fibrosis (CF) is an autosomal recessive disorder that occurs in ∼1 in 2500 Caucasians (1)(2)(3). CF can result from combinations of >750 known mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and in certain populations, as many as 1 person in 25 is a carrier (1)(2)(3). To date, screening methods have either been narrow, requiring multiple methodologies to be brought to bear for comprehensive coverage, or are cost prohibitive (1)(4). This study describes the Luminex LabMAPTM system and its potential for simultaneous, rapid, sensitive, and specific screening for mutations in the CFTR gene.

The LabMAP system incorporates polystyrene microspheres that are internally dyed with two spectrally distinct fluorochromes. Using precise ratios of these fluorochromes, an array is created consisting of 100 different microsphere sets with specific spectral addresses. Each microsphere set can possess a different reactant on its surface. Because microsphere sets can be distinguished by their spectral addresses, they can be combined, allowing up to 100 different analytes to be measured simultaneously in a single reaction vessel. A third fluorochrome coupled to a reporter molecule quantifies the biomolecular interaction that has occurred at the microsphere surface. Microspheres are interrogated individually in a rapidly flowing fluid stream as they pass by two separate lasers in the Luminex100 analyzer. High-speed digital …