gebhart/patrepeval huggingface dataset:
Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory (2013)

Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2(nd)-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how systems biology tools coupled with directed evolution and selection allows non-intuitive, rapid and substantial re-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals.
A hierarchy of SSB protomers in replication protein A. (1996)

Replication Protein A (RPA) is a heterotrimeric single-stranded DNA-binding protein (SSB) found in all eukaryotic cells. RPA is known to be required for many of the same reactions catalyzed by the homotetrameric SSB of bacteria, but its origin, subunit functions, and mechanism of binding remain a mystery. Here we show that the three subunits of yeast RPA contain a total of four domains with weak sequence similarity to the Escherichia coli SSB protomer. We refer to these four regions as potential ssDNA-binding domains (SBDs). The p69 subunit, which is known to bind ssDNA on its own, contains two SBDs that together confer stable binding to ssDNA. The p36 and p13 subunits each contain a single SBD that does not bind stably, but corresponds to the minimal region required for viability in yeast. Photocross-linking of recombinant protein to ssDNA indicates that an SBD consists of approximately 120 amino acids with two centrally located aromatic residues. Mutation of these aromatic residues inactivates ssDNA binding and is a lethal event in three of the four domains. Finally, we present evidence that the p36 subunit binds ssDNA, as part of the RPA complex, in a salt-dependent reaction similar to the wrapping of ssDNA about E. coli SSB. The results are consistent with the notion that RPA arose by duplication of an ancestral SSB gene and that tetrameric ssDNA-binding domains and higher order binding are essential features of cellular SSBs.
A Deeper Look into Comet—Implementation and Features (2015)

The Comet database search software was initially released as an open source project in late 2012. Prior to that, Comet existed as the University of Washington's academic version of the SEQUEST database search tool. Despite its availability and widespread use over the years, some details about its implementation have not been previously disseminated or are not well understood. We address a few of these details in depth and highlight new features available in the latest release. Comet is freely available for download at http://comet-ms.sourceforge.net or it can be accessed as a component of a number of larger software projects into which it has been incorporated. Graphical Abstract ᅟ.
Current transport in metal/hafnium oxide/silicon structure (2002)

Based on the experimental results of the temperature dependence of gate leakage current and Fowler-Nordheim tunneling characteristics at 77 K, we have extracted the energy band diagrams and current transport mechanisms for metal/HfO/sub 2//Si structures. In particular, we have obtained the following quantities that will be useful for modeling and simulation: i) HfO/sub 2//Si conduction band offset (or barrier height): 1.13 /spl plusmn/ 0.13 eV; ii) Pt/HfO/sub 2/ barrier height: /spl sim/ 2.48 eV; iii) Al/HfO/sub 2/ barrier height: /spl sim/ 1.28 eV; iv) electron effective mass in HfO/sub 2/: 0.1 m/sub o/, where m/sub o/ is the free electron mass and v) a trap level at 1.5 /spl plusmn/ 0.1 eV below the HfO/sub 2/ conduction band which contributes to Frenkel-Poole conduction.
Two mutations affecting the transport and maturation of lysosomal α-glucosidase in an adult case of glycogen storage disease type II (1993)

The autosomal recessive glycogen storage disease type II is associated with a deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the mutations in the lysosomal alpha-glucosidase alleles of an adult patient. A G-1927 to A transition was discovered in exon 14 causing the substitution of Gly-643 by Arg and a second C-2173 to T transition in exon 15 resulting in the substitution of Arg-725 by Trp. Each of the mutations was located in a different allele. The mutations were introduced in the wild-type lysosomal alpha-glucosidase cDNA and expressed in COS cells. Both mutations had a similar effect. The synthesis of the mutant enzyme precursors was not disturbed but the intracellular transport and maturation were impaired. As a result there was an overall deficiency of catalytic activity.
Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling. (1986)

Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles from multidrug-resistant cells were exposed to two analogs of vinblastine, N-(p-azido-[3,5-3H]benzoyl)-N'-(beta-aminoethyl)vindesine and N-(p-azido-[3-125I]salicyl)-N'-(beta-aminoethyl)vindesine, that could be photoactivated. Our studies show the specific labeling of a 150- to 170-kDa protein in membrane vesicles from two independently selected multidrug-resistant KB cell lines, which was not seen in drug-sensitive parental or revertant cell lines. The labeling of the high molecular weight protein was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at about 1 microM. Photolabeling was also inhibited by 100 microM vincristine or 100 microM verapamil but not by 100 microM colchicine or 100 microM dexamethasone. The data suggest that the 150- to 170-kDa protein may play an important role in the multidrug-resistance phenotype.
Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF (2009)

CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8+ T-cells. Two major MDSC subsets were recently shown to play an equal role in MDSC-induced immune dysfunctions: monocytic- and granulocytic-like. We isolated three fractions of MDSC, i.e. CD11b+/Gr-1high, CD11b+/Gr-1int, and CD11b+/Gr-1low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b+/Gr-1int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8+ T-cell activation, while CD11b+/Gr-1high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b+/Gr-1int but not CD11b+/Gr-1high cells were also immunosuppressive in vivo following adoptive transfer. CD11b+/Gr-1low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM-CSF was necessary to induce preferential expansion of both CD11b+/Gr-1int and CD11b+/Gr-1low subsets in the spleen of tumor-bearing mice and mediate tumor-induced tolerance whereas G-CSF, which preferentially expanded CD11b+/Gr-1high cells, did not create such immunosuppressive environment. GM-CSF also acted on granulocyte-macrophage progenitors in the bone marrow inducing local expansion of CD11b+/Gr-1low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor-released GM-CSF.
Optimizing splinted ligation of highly structured small RNAs (2005)

The synthesis of highly structured small RNAs containing nonstandard nucleotides is of high interest for structural and functional investigations. A general approach is the joining, by T4 DNA ligase-mediated splinted ligation, of two or more RNA fragments, each of which may contain its own set of modified nucleotides. The RNA fragments hybridize with a complementary DNA splint to form a ternary ligation-competent-complex (LCC), which is then turned over by the DNA ligase. We studied the formation of the LCC and its precursors using size exclusion chromatography combined with a fluorescence detector. The spatial proximity of two cyanine-dye-labeled RNA fragments in LCCs was detected by monitoring FRET. An observed correlation of LCC formation and ligation yields suggests the use of long splints to stabilize LCCs. Splint oligos of increasing length, which in general appear to reduce the number of different hybridization intermediate species found in a reaction mixture, were applied to the synthesis by T4-DNA-ligation of two highly structured target molecules, one a 73 mer tRNA, the other a 49 mer synthetic ribozyme. A stable LCC could be isolated and turned over with>95% ligation efficiency. In conclusion, the use of long splints presents a generally applicable means to overcome the low propensity of highly structured RNAs for hybridization, and thus to significantly improve ligation efficiencies.
Realeza y concejos versus ladrones y malfechores: la lucha contra la delincuencia en la Asturias Medieval (siglos XII-XIV) (2006)

espanolDurante la Edad Media Asturias se nos presenta como un territorio de limitados recursos economicos, con un debil nivel de urbanizacion y una numerosa y turbulenta poblacion de caballeros propicia a todo tipo de desafueros, que encuentra un facil aliado en la accidentada geografia. Estos factores constituyeron un caldo de cultivo especialmente favorable para la existencia de una endemica situacion de desorden publico. En este trabajo prestaremos atencion a los protagonistas de esas malfetrias, a las manifestaciones mas caracteristicas de esa generalizada conducta perturbadora de la paz publica y a los mecanismos coactivos puestos en funcionamiento por el poder politico para restaurar el orden juridico y lograr el mantenimiento de una paz publica. EnglishDuring the Middle Ages Asturias was a territory of limited economic resources, with a weak level of urbanization and a numerous and turbulent knights who made all kinds of outrages, helped by an uneven geography. These factors favored an endemic situation of public disorder. In this work we will give attention to the protagonists of these malfetrias, to the most typical manifestations of that behavior that perturbs the public peace and to the coercive mechanisms that are articulated by the public power to restore the juridical order and to keep the public peace. francaisPendant le Moyen âge Asturias apparait nous comme un territoire de ressources economiques limitees, avec un niveau faible d'urbanisation et une population nombreuse et turbulente de seigneurs favorable a toutes les sortes d'atrocites, a ce qu'il aide une accidentee geographie. Ces facteurs ont constitue un moyen particulierement favorable pour l'existence d'une situation endemique de desordre public. Dans ce travail nous preterons attention aux protagonistes de ces malfetrias, aux manifestations les plus typiques de cette conduite inquietante repandue de la paix publique et aux mecanismes coercitifs mis dans le fonctionnement pour le pouvoir politique de retablir l'ordre juridique et realiser la maintenance d'une paix publique. euskaraErdi Aroan, Asturias baliabide ekonomiko mugatuko lurraldea zen; hirigintza-maila baxua eta geografia malkartsua kide hartuta, edozein lege-hauste egiteko prest zegoen zaldun-populazio kopurutsu eta asaldatua zituen. Faktore horiek desordena publikoko egoera endemikoa gerta zedin baldintza ezin hobeak ziren. Lan honetan, arreta berezia eskaini diegu malfetria edo gaiztakeria horien protagonistei, bake publikoa nahasten zuen portaera orokor haren adierazpen esanguratsuenei eta botere politikoak, ordena juridikoa berrezarri eta bake publikori eustea lortzeko, abian jarritako mekanismo hertsagarriei.
Miniaturized pH Sensors Based on Zinc Oxide Nanotubes/Nanorods (2009)

ZnO nanotubes and nanorods grown on gold thin film were used to create pH sensor devices. The developed ZnO nanotube and nanorod pH sensors display good reproducibility, repeatability and long-term stability and exhibit a pH-dependent electrochemical potential difference versus an Ag/AgCl reference electrode over a large dynamic pH range. We found the ZnO nanotubes provide sensitivity as high as twice that of the ZnO nanorods, which can be ascribed to the fact that small dimensional ZnO nanotubes have a higher level of surface and subsurface oxygen vacancies and provide a larger effective surface area with higher surface-to-volume ratio as compared to ZnO nanorods, thus affording the ZnO nanotube pH sensor a higher sensitivity. Experimental results indicate ZnO nanotubes can be used in pH sensor applications with improved performance. Moreover, the ZnO nanotube arrays may find potential application as a novel material for measurements of intracellular biochemical species within single living cells.
Clinical pharmacology of hepatic arterial chemotherapy. (1983)

The techniques now exist to deliver drug infusions reliably through the hepatic artery to infuse the entire liver and tumor within the liver. Drug selection for use in these systems should be rational and include agents with short half-lives (high total body clearance) and some evidence of activity against the tumor type in question. Hepatic extraction and metabolism of the drug will in turn decrease systemic exposure or allow more drug to be given per set amount of systemic exposure. The dose-limiting toxicity of appropriate drug programs may well be regional and not systemic. Further pharmacokinetic studies and controlled clinical trials are needed to evaluate existing regimens and to design new regimens. Future advances are likely to involve the combination of effective drugs and the use of therapeutic microspheres to improve selectivity based on tumor microcirculation.
Expression of Epidermal Growth Factor in Transgenic Mice Causes Growth Retardation (2000)

The epidermal growth factor (EGF) family of peptides signals through the erbB family of receptor tyrosine kinases and plays important roles in development and tumorigenesis. Both EGF and transforming growth factor (TGF)-alpha only bind to erbB1 and activate it. The precursor of EGF is distinct from that of TGF-alpha in having eight additional EGF-like repeats. We have recently shown that the EGF precursor without these repeats is biologically active and leads to hypospermatogenesis in transgenic mice. Here we present evidence that the growth of transgenic mice widely expressing this engineered EGF precursor is also stunted. These mice were consistently born at half the normal weight and reached almost 80% of normal weight at adulthood. The mechanism involved a reduction of serum insulin-like growth factor-binding protein-3. Chondrocyte development in the growth plate was affected, and osteoblasts accumulated in the endosteum and periosteum. Besides these novel findings on the in vivo effects of EGF on bone development, we observed no sign of tumor formation in our transgenic animals. In contrast to previous reports on TGF-alpha transgenic mice, we show that the biological functions of EGF and TGF-alpha are clearly distinct.
Croissance épitaxique de composés semiconducteurs par évaporation-diffusion en régime isotherme (1966)

On présente un nouveau procédé permettant de réaliser l'épitaxie de composés semiconducteurs tels HgTe, GeTe, GaSb, ... en régime isotherme, presque à l'équilibre thermodynamique. Des couches monocristallines d'épaisseur 1 à 200 µ ont été obtenues. Le phénomène de transport consiste en une évaporation de matière de la source au substrat, couplée à une diffusion dans le substrat des atomes transférés. Les paramètres de préparation étudiés sont la distance de la source au substrat, la durée et la température du traitement. La variation de l'épaisseur du dépôt avec la température fait apparaître, aux hautes températures, une énergie d'activation de 29 kc/mole en bon accord avec les prévisions théoriques.
Low Temperature Synthesis of Complex Refractory Oxide Powders From Molten Salts (2007)

SUMMARY The procedure of molten salt synthesis (MSS) could be potentially used to synthesize a range of complex oxides used by the refractory industry. Two reaction mechanisms, “template-growth” and “dissolution-precipitation”, are involved in MSS. The former functions when one reactant is soluble but another much less-soluble in the salt, whereas the latter functions when the two reactants are both soluble in the salt. In the former, the more soluble reactant dissolves in the salt, diffuses onto the surface of the less soluble reactant, and then reacts to form the product particles which retain the morphologies and sizes of the less soluble reactant, whereas in the latter, the product phases precipitate from the salt oversaturated with the two reactants, and often show different morphologies and sizes from those of the reactants. By using appropriate morphologies/size of raw materials and salt assemblies, complex refractory oxides with desirable morphologies and sizes could be prepared at much lowered temperatures up to 1000 o C lower than those used by the Conventional Mixed Oxide Synthesis (CMOS).
Molecular Cloning of Porcine Interleukin-1 beta Converting Enzyme and Differential Gene Expression of IL-1 beta Converting Enzyme, IL-1 beta, and IL-18 in Porcine Alveolar Macrophages (1999)

We have cloned and sequenced a cDNA that contains the coding sequence of porcine interleukin-1beta (IL-1beta) converting enzyme (ICE). Using degenerate oligonucleotide primers based on the amino acid sequences of the human, murine, and rat ICE, we performed the reverse transcription polymerase chain reaction (RT-PCR) with total RNA prepared from porcine alveolar macrophages stimulated with lipopolysaccharide (LPS) to clone the cDNA of porcine ICE. The open reading frame (ORF) of the porcine ICE cDNA is 1215 base pairs (bp) in length and encodes 404 amino acids. The predicted amino acid sequence is 72.5%, 62.6%, and 64.1% homologous to the human, murine, and rat amino acid sequences, respectively. The kinetics of mRNA expression of ICE, IL-1beta, and IL-18 in porcine alveolar macrophages after LPS stimulation revealed that ICE transcripts were weakly expressed in nonstimulated condition and upregulated after LPS stimulation. Moreover, IL-1beta and IL-18 transcripts were differently expressed after LPS stimulation.
Measurement of antigen–antibody interactions with biosensors (1998)

The introduction in 1990 of a new biosensor technology based on surface plasmon resonance has revolutionized the measurement of antigen-antibody binding interactions. In this technique, one of the interacting partners is immobilized on a sensor chip and the binding of the other is followed by the increase in refractive index caused by the mass of bound species. The following immunochemical applications of this new technology will be described: (1) functional mapping of epitopes and paratopes by mutagenesis; (2) analysis of the thermodynamic parameters of the interaction; (3) measurement of the concentration of biologically active molecules; (4) selection of diagnostic probes.
Automated interferometric synthetic aperture microscopy and computational adaptive optics for improved optical coherence tomography (2016)

In this paper, we introduce an algorithm framework for the automation of interferometric synthetic aperture microscopy (ISAM). Under this framework, common processing steps such as dispersion correction, Fourier domain resampling, and computational adaptive optics aberration correction are carried out as metrics-assisted parameter search problems. We further present the results of this algorithm applied to phantom and biological tissue samples and compare with manually adjusted results. With the automated algorithm, near-optimal ISAM reconstruction can be achieved without manual adjustment. At the same time, the technical barrier for the nonexpert using ISAM imaging is also significantly lowered.
Isolation of quelling-defective ( qde ) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa (1997)

We report the isolation of 15 Neurospora crassa mutants defective in "quelling" or transgene-induced gene silencing. These quelling-defective mutants (qde) belonging to three complementation groups have provided insights into the mechanism of posttranscriptional gene silencing in N. crassa. The recessive nature of the qde mutations indicates that the encoded gene products act in trans. We show that when qde genes are mutated in a transgenic-induced silenced strain containing many copies of the transgene, the expression of the endogenous gene is maintained despite the presence of transgene sense RNA, the molecule proposed to trigger quelling. Moreover, the qde mutants failed to show quelling when tested with another gene, suggesting that they may be universally defective in transgene-induced gene silencing. As such, qde genes may be involved in sensing aberrant sense RNA and/or targeting/degrading the native mRNA. The qde mutations may be used to isolate the genes encoding the first components of the quelling mechanism. Moreover, these quelling mutants may be important in applied and basic research for the creation of strains able to overexpress a transgene.
Effect of Calorie Restriction on Change in Lacrimal Gland With Age (2011)

Rapid growth in the number of dry eye syndrome patients has been observed worldwide. Increased life span is considered to be at least part of the reason for this because there is a close association between aging and decreased secretory function in the lacrimal gland. Recent advances have led to a new way of thinking about intervention in the aging process. Calorie restriction (CR) is believed to retard functional decline in various organs with age. We hypothesized that CR could prevent age-related lacrimal dysfunction. In this paper, we begin by reviewing the epidemiology of dry eye syndrome and explaining how aging affects lacrimal gland function. We then introduce a possible therapeutic approach to this problem, intervention by means of CR. Finally, suggestions are made for further prospective research that would elucidate the molecular mechanisms by which CR maintains lacrimal gland function.