gebhart/patrepeval huggingface dataset:
Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems (2009)

Selenocysteine and pyrrolysine, known as the 21st and 22nd amino acids, are directly inserted into growing polypeptides during translation. Selenocysteine is synthesized via a tRNA-dependent pathway and decodes UGA (opal) codons. The incorporation of selenocysteine requires the concerted action of specific RNA and protein elements. In contrast, pyrrolysine is ligated directly to tRNA(Pyl) and inserted into proteins in response to UAG (amber) codons without the need for complex re-coding machinery. Here we review the latest updates on the structure and mechanisms of molecules involved in Sec-tRNA(Sec) and Pyl-tRNA(Pyl) formation as well as the distribution of the Pyl-decoding trait.
Studies on the Degradation Mechanisms of Proteins and Their Derivatives in the Foods (1960)

Cysteine mercaptals and mercaptoles were prepared by the reactions of L-cysteine with formal-dehyde, acetaldehyde, n-butyraldehyde, benzaldehyde, furfural, pyruvic acid and levulinic acid in 6 N hydrochloric or sulfuric acid. Hydrogen sulfide released from cysteine mercaptals and mercaptoles in heated aqueous solutions (oil bath:120°C) was determined. Although a small amount of hydrogen sulfide was liberated from L-cystine on one hour heating, its amount increased suddenly after three hours. Among these compounds L-cysteine mercaptal of furfural was most unstable and a large amount of hydrogen sulfide was produced.
Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease (2015)

The NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease (DKD). However, a mechanistic understanding of the downstream effects of NOX4 remains to be established. We report that podocyte-specific induction of NOX4 in vivo was sufficient to recapitulate the characteristic glomerular changes noted with DKD, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, albuminuria, and podocyte dropout. Intervention with a NOX1/NOX4 inhibitor reduced albuminuria, glomerular hypertrophy, and mesangial matrix accumulation in the F1 Akita model of DKD. Metabolomic analyses from these mouse studies revealed that tricarboxylic acid (TCA) cycle-related urinary metabolites were increased in DKD, but fumarate levels were uniquely reduced by the NOX1/NOX4 inhibitor. Expression of fumarate hydratase (FH), which regulates urine fumarate accumulation, was reduced in the diabetic kidney (in mouse and human tissue), and administration of the NOX1/NOX4 inhibitor increased glomerular FH levels in diabetic mice. Induction of Nox4 in vitro and in the podocyte-specific NOX4 transgenic mouse led to reduced FH levels. In vitro, fumarate stimulated endoplasmic reticulum stress, matrix gene expression, and expression of hypoxia-inducible factor-1α (HIF-1α) and TGF-β. Similar upregulation of renal HIF-1α and TGF-β expression was observed in NOX4 transgenic mice and diabetic mice and was attenuated by NOX1/NOX4 inhibition in diabetic mice. In conclusion, NOX4 is a major mediator of diabetes-associated glomerular dysfunction through targeting of renal FH, which increases fumarate levels. Fumarate is therefore a key link connecting metabolic pathways to DKD pathogenesis, and measuring urinary fumarate levels may have application for monitoring renal NOX4 activity.
Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine (2010)

Clinicaltrials.gov NCT00252148.
Genetically engineered proinsulin constitutively processed and secreted as mature, active insulin. (1994)

The conversion of human proinsulin to insulin occurs only in specialized cells which contain the appropriate processing enzymes. To allow proinsulin processing to occur in a wide variety of cell types, we engineered human proinsulin to be cleaved in the constitutive secretory pathway. Using site-directed mutagenesis, we have introduced furin consensus cleavage sequences (Arg-X-Lys-Arg) into the human proinsulin cDNA. These mutations allowed for efficient proteolytic maturation of human proinsulin to insulin within cells containing only a constitutive pathway of secretion. Additionally, a naturally occurring mutation (histidine B10 to aspartic acid) yields a form of human insulin which accumulates 10- to over 100-fold more mature insulin when compared to the mutants lacking this change. Engineering furin-specific cleavage sites into each junction of the human proinsulin cDNA results in the secretion of peptides that display the expected molecular weights for the A and B chains of insulin. The accumulation of mature, processed, human insulin was measured in the supernatants by radioimmunoassay, and the bioactivity of this molecule was measured by its ability to stimulate autophosphorylation of the insulin receptor. Our results suggest that any cell type might be engineered to produce mature, active, and stable insulin in the constitutive pathway of secretion.
Pentacene thin film transistors and inverter circuits (2002)

Organic thin film transistors and simple electronic circuits have been fabricated using the fused-ring small-molecule aromatic hydrocarbon pentacene as the active material. Carrier field-effect mobilities greater than 0.2 cm/sup 2//V-s were obtained for thin film transistors fabricated on glass using low-temperature ion-beam deposited silicon dioxide as the gate dielectric and thermally evaporated pentacene as the active material. Using similar transistors, integrated voltage inverters with voltage gain large enough to be useful for the fabrication of electronic circuits have been fabricated.
Phenylalanine ammonia‐lyase immobilized in semipermeable microcapsules for enzyme replacement in phenylketonuria (1985)

Phenylalanine ammonia-lyase immobilized within semipermeable microcapsules has an assayed enzyme activity which is 20% +/- 4% of the enzyme in free solution. The Km for the immobilized enzyme remained the same as that of the free enzyme. The pH optimum also remained unchanged at pH 8.5 +/- 1.0. At the lower pH range, enzyme activity is higher for the immobilized enzyme. Daily oral administration of microencapsulated phenylalanine ammonia-lyase to phenylketonuric rats decreased the systemic phenylalanine level by 35 +/- 8% in 2 days (P less than 0.05) and by 75 +/- 8% in 7 days (P less than 0.001).
An efficient recombination system for chromosome engineering in Escherichia coli (2000)

A recombination system has been developed for efficient chromosome engineering in Escherichia coli by using electroporated linear DNA. A defective lambda prophage supplies functions that protect and recombine an electroporated linear DNA substrate in the bacterial cell. The use of recombination eliminates the requirement for standard cloning as all novel joints are engineered by chemical synthesis in vitro and the linear DNA is efficiently recombined into place in vivo. The technology and manipulations required are simple and straightforward. A temperature-dependent repressor tightly controls prophage expression, and, thus, recombination functions can be transiently supplied by shifting cultures to 42 degrees C for 15 min. The efficient prophage recombination system does not require host RecA function and depends primarily on Exo, Beta, and Gam functions expressed from the defective lambda prophage. The defective prophage can be moved to other strains and can be easily removed from any strain. Gene disruptions and modifications of both the bacterial chromosome and bacterial plasmids are possible. This system will be especially useful for the engineering of large bacterial plasmids such as those from bacterial artificial chromosome libraries.
Decreased Cyclic AMP in the Epidermis of Lesions of Psoriasis (1972)

Previously we suggested that incomplete differentiation, accelerated proliferation and glycogen accumulation in epidermis of psoriatic lesions might be due to deficient adenosine 3',5'-monophosphate (cyclic AMP) in epidermis of the lesion. Therefore, we measured endogenous cyclic AMP in involved and uninvolved epidermis of 25 psoriasis patients and normal epidermis of 25 control subjects. A statistically significant decrease in cyclic AMP was found in involved psoriatic epidermis when compared with uninvolved psoriatic and control epidermis. Because cyclic AMP regulates glycogen metabolism and promotes differentiation of cancer cells in culture while limiting their proliferation, the cyclic AMP deficiency may play a pathophysiological role in the rapid epidermal cell cycle kinetics of psoriasis. Therefore, topical application of cyclic AMP analogues or agents which promote cyclic AMP synthesis or retard its hydrolysis might be used therapeutically to either normalize psoriatic differentiation or prevent psoriasis from occurring.
On feed-forward and feedback timing recovery for digital magnetic recording systems (1991)

Two different timing recovery techniques, namely, feedforward and feedback, for digital magnetic recording systems are compared. The feedforward approach uses nonlinear filtering to derive the timing information, whereas the feedback approach relies on detected symbols from a suitably equalized signal. The steady-state performance of these timing recovery methods is compared under the same operating conditions. It is shown that the feedforward method provides superior performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Block copolymers as bilevel resists (1985)

A bilayer resist system is demonstrated using chlorinated polymethylstyrene-polydimethylsiloxane (CPMS/DMS) block copolymers. The copolymers are prepared using anionic polymerization techniques and are subsequently sensitized to electron beam, and 250–300 nm radiation by preferential chlorination of the polymethylstyrene block. The electron lithographic performance of a block copolymer containing 15.5 wt. % silicon, 0.58 chlorines per methylstyrene unit (total M̄w=8.7×104) and polydispersity=1.3 was determined to exhibit a sensitivity (D0.5g)=0.9 μC/cm2, and contrast=1.3. The etch ratio compared to the HPR-204 planarizing layer was 13.5 : 1 with an observed resolution range of 0.75 to 1.0 μm. These results derive from the intrinsic behavior of block copolymers, which provides for the synergistic combination of inherently distinct polymer species while avoiding macroscopic phase separation prevalent in homopolymer blends. The concept of utilizing block copolymers as resists is general and may be extended to positive tone resists as well.
Chronic phantom and stump pain among american veterans: results of a survey (1984)

Questions concerning stump, phantom and other pain problems as well as demographic data were mailed to 5000 Americans whose amputations were connected with military service. Fifty-five percent responded and of these, 78% reported phantom pain. No predisposing factors, other than presence of stump pain, correlated with the presence or severity of phantom pain. Of those receiving treatment, only 1% reported lasting benefits from any of a multitude of treatments attempted.
Why targeted therapy hasn’t worked in advanced cancer (2007)

In this issue of the JCI, Nissen et al. report that a reciprocal interaction exists between the growth factors FGF2 and PDGF-BB, causing tumors to exhibit increased angiogenesis and metastatic potential. Both FGF2 and PDGF-BB signal through tyrosine kinase receptors, which have been the target of tyrosine kinase inhibitors for cancer therapies. These inhibitors are usually small molecules that inhibit the kinase activity of a receptor or nonreceptor tyrosine kinase, preventing downstream signaling. The results of this study shed light on why tyrosine kinase inhibitors have been useful for the treatment of only a small number of advanced cancers. Currently, a major focus of pharmaceutical companies is to develop ever more potent and specific tyrosine kinases. The results presented here suggest that this approach may not be successful.
Driver Workload Effects of Cell Phone, Music Player, and Text Messaging Tasks with the Ford SYNC Voice Interface versus Handheld Visual-Manual Interfaces (2009)

&lt;div class="htmlview paragraph"&gt;A fixed-base driving simulator study was conducted to compare driver performance and eye glance behavior effects of tasks performed using the voice interface in Ford Motor Company’s SYNC® system versus handheld operation of portable music players and cellular phones. Data were analyzed from a sample of 25 test participants. All test participants were regular SYNC users (but not SYNC developers), though they varied in their familiarity with SYNC functions. During a car-following scenario at highway speeds on the simulator, the participants performed 7 tasks using SYNC’s voice interface and those same 7 tasks with their own handheld music player and cellular phone. The seven tasks under test were: dial a 10-digit number; call a specific person from a phonebook; receive a call while driving; play a specific song; play songs from a specific artist; review (listen to or read) a text message; and select a reply from a list or type a reply to a text message. Task-level paired comparisons are reported for total eyes-off-road time, standard deviation of lane position, percentage of trials with one or more lane exceedances, speed variability, and response time to a visual detection task. Consistent with prior voice interface literature, driving distraction potential for most tasks was minimized when the SYNC voice interface was used as compared to the visual-manual interfaces of the handheld devices.&lt;/div&gt;
<title>Image-based modeling of objects and human faces</title> (2000)

In this paper, provided is an overview of our project on 3D object and face modeling from images taken by a free-moving camera. We strive to advance the state of the art in 3D computer vision, and develop flexible and robust techniques for ordinary users to gain 3D experience from a ste of casually collected 2D images. Applications include product advertisement on the Web, virtual conference, and interactive games. We briefly cover the following topics: camera calibration, stereo rectification, image matching, 3D photo editing, object modeling, and face modeling. Demos on the last three topics will be shown during the conference.
Theory of Josephson effects in anisotropic superconductors (1997)

An analytical formula for the dc Josephson current in anisotropic singlet superconductor/insulator/anisotropic singlet superconductor junctions is presented. The formula is applicable for junctions with arbitrary insulating-potential height and thickness and with any symmetries including $d$-wave superconductors. In contrast to the formulas for conventional $s$-wave superconductors, the formula includes two additional effects. One is the intrinsic phase of the pair potential originating from the pairing symmetry in anisotropic superconductors. The other is the formation of localized states around the insulator. Using this formula, the Josephson current is calculated in $s$-wave superconductor/insulator/${d}_{{x}^{2}\ensuremath{-}{y}^{2}}$-wave superconductor $(s/I/d)$ and ${d}_{{x}^{2}\ensuremath{-}{y}^{2}}$-wave superconductor/insulator/${d}_{{x}^{2}\ensuremath{-}{y}^{2}}$-wave superconductor $(d/I/d)$ junction configurations. In the case of the $(d/I/d)$ junction, the anomalous temperature dependence of the maximum Josephson current is calculated. This behavior is completely different from that expected for $s$-wave superconductors. The validity of a phenomenological theory by Sigrist and Rice [J. Phys. Soc. Jpn. 61, 4283 (1992)] is also discussed.
An ordered addition, essential activation model of the tissue factor pathway of coagulation: evidence for a conformational cage (1986)

One way in which coagulation may be initiated is by the action of factor VIIa (a plasma serine protease) and tissue factor (a membrane-bound lipid-dependent glycoprotein). We show that in the absence of either factor VIIa or tissue factor, the activation of the natural coagulation substrates, factors IX and X, is not detectable; i.e., tissue factor is an essential activator. We propose that the reaction is fully ordered; that is, the enzyme-activator complex picks up substrate to form a ternary product forming species. Our model precludes the formation of enzyme-substrate and activator-substrate complexes. We have derived equations for the two possible variations of this model: one in which product formation is accompanied by the release of the enzyme-activator complex and the other in which product, free enzyme, and free activator are formed with each catalytic cycle. Our data support only the former which is consistent with both steady-state and rapid equilibrium assumptions. The model is supported by experiments using a monoclonal anti-tissue factor antibody, which affects only the Km app, and a modified form of factor VIIa, which, depending on the sequence in which reagents are added to the reaction, either decreases the Vmax or increases the Km app. We present equations describing the initial velocity of these reactions. Utilizing dilution-jump experiments, we show that the system is hysteretic and suggest that this phenomenon is due to a slow release of enzyme from activator. However, the kinetically determined dissociation constant of enzyme and activator, previously found to be 4.5 nM under equilibrium conditions, was estimated to be 0.04-0.09 nM. Accordingly, we examined other essential activation models in which the product-forming species consists of a complex of enzyme, activator, and substrate at a molar ratio of 1:1:1; none could account for the apparent tight binding of enzyme and activator. We therefore postulate an ordered addition, essential activation model in which the enzyme undergoes two conformational transformations: one as a consequence of binding to tissue factor, resulting in a species which binds to and hydrolyzes its natural substrates. The other conformational change in the enzyme is induced by substrate, resulting in a species which binds more tightly to its activator. Thus, we hypothesize a "conformational cage" which precludes the dissociation of enzyme from activator while significant concentrations of substrate are present.
Directed Assembly of Nucleic Acid-Based Polymeric Nanoparticles from Molecular Tetravalent Cores (2015)

Complementary tetrahedral small molecule-DNA hybrid (SMDH) building blocks have been combined to form nucleic acid-based polymeric nanoparticles without the need for an underlying template or scaffold. The sizes of these particles can be tailored in a facile fashion by adjusting assembly conditions such as SMDH concentration, assembly time, and NaCl concentration. Notably, these novel particles can be stabilized and transformed into functionalized spherical nucleic acid (SNA) structures through the incorporation of capping DNA strands conjugated with functional groups. These results demonstrate a systematic, efficient strategy for the construction and surface functionalization of well-defined, size-tunable nucleic acid particles from readily accessible molecular building blocks. Furthermore, because these nucleic acid-based polymeric nanoparticles exhibited enhanced cellular internalization and resistance to DNase I compared to free synthetic nucleic acids, they should have a plethora of applications in diagnostics and therapeutics.
Protein kinase C isoenzymes: divergence in signal transduction? (1993)

Research Article| April 15 1993 Protein kinase C isoenzymes: divergence in signal transduction? H Hug; H Hug 1Institute of Molecular Cell Biology, University of c/o Gödecke AG, Mooswaldallee 1-9, 7800 Freiburg, Freiburg, Federal Republic of Germany. Search for other works by this author on: This Site PubMed Google Scholar T F Sarre T F Sarre 1Institute of Molecular Cell Biology, University of c/o Gödecke AG, Mooswaldallee 1-9, 7800 Freiburg, Freiburg, Federal Republic of Germany. Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1993) 291 (2): 329–343. https://doi.org/10.1042/bj2910329 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation H Hug, T F Sarre; Protein kinase C isoenzymes: divergence in signal transduction?. Biochem J 15 April 1993; 291 (2): 329–343. doi: https://doi.org/10.1042/bj2910329 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1993 The Biochemical Society, London1993 Article PDF first page preview Close Modal You do not currently have access to this content.
Use of hybridization kinetics for differentiating specific from non-specific binding to oligonucleotide microarrays (2002)

Hybridization kinetics were found to be significantly different for specific and non-specific binding of labeled cRNA to surface-bound oligonucleotides on microarrays. We show direct evidence that in a complex sample specific binding takes longer to reach hybridization equilibrium than the non- specific binding. We find that this property can be used to estimate and to correct for the hybridization contributed by non-specific binding. Useful applications are illustrated including the selection of superior oligonucleotides, and the reduction of false positives in exon identification.
Carrier-linked primaquine in the chemotherapy of malaria (1986)

The antimalarial effect of intravenously administered primaquine (PQ) can be improved and its toxicity diminished by linking it to a macromolecular carrier protein. A thiol-containing primaquine derivative 8-[[4-(2-amino-3-mercaptopropionamido)-1-methylbutyl]amino]-6- methoxyquinoline was synthesized. This compound could readily be linked via a disulfide bond to a carrier protein containing (pyridyldithio)propionate groups. The derivative was coupled to serum albumin as well as to serum albumin that contained covalently linked lactose residues. The protein-drug conjugates were tested for their antimalarial activity in mice inoculated with Plasmodium berghei. The causal prophylactic activity of the conjugate with the lactosaminated serum albumin was 2 times higher than that of the free drug; the mean causal prophylactic doses (CPD50) were 6 and 13 mg of primaquine base/kg, respectively. Moreover, its acute lethal toxicity had decreased at least 6.5-fold (mean lethal dose (LD50) greater than 85 mg of primaquine base/kg). The therapeutic index of this conjugate was at least 12 times higher than that of the free drug. This allowed the administration of a dose that cured 100% of the animals (17.5 mg of primaquine base/kg), in a single injection. With unmodified serum albumin the conjugate showed an increased therapeutic efficacy (the CPD50 was approximately 10 mg of primaquine base/kg) and a strongly reduced lethal toxicity.