gebhart/patrepeval huggingface dataset:
Molecular approaches to genome analysis: a strategy for the construction of ordered overlapping clone libraries (1987)

Here we describe progress on a series of molecular techniques designed to bridge the gap between genetic and molecular distances in mammals. This is an essential step in the molecular cloning of genes defined by mammalian mutations, and in the molecular analysis of large regions of mammalian genomes. We summarize approaches for the physical and molecular analysis of genetic distances and describe the experimental, statistical and computational basis of a new approach to create ordered libraries of overlapping clones from large genomes.
ADIABATIC HEATING OF CONTRACTING TURBULENT FLUIDS (2012)

Turbulence influences the behavior of many astrophysical systems, frequently by providing non-thermal pressure support through random bulk motions. Although turbulence is commonly studied in systems with constant volume and mean density, turbulent astrophysical gases often expand or contract under the influence of pressure or gravity. Here, we examine the behavior of turbulence in contracting volumes using idealized models of compressed gases. Employing numerical simulations and an analytical model, we identify a simple mechanism by which the turbulent motions of contracting gases "adiabatically heat," experiencing an increase in their random bulk velocities until the largest eddies in the gas circulate over a Hubble time of the contraction. Adiabatic heating provides a mechanism for sustaining turbulence in gases where no large-scale driving exists. We describe this mechanism in detail and discuss some potential applications to turbulence in astrophysical settings.
Dielectrophoretic approaches to sample preparation and analysis (2001)

Dielectrophoresis (DEP) has been used to manipulate cells in low-conductivity suspending media using AC electrical fields generated on micro-fabricated electrode arrays. This has created the possibility of performing automatically on a micro-scale more sophisticated cell processing than that currently requiring substantial laboratory equipment, reagent volumes, time, and human intervention. In this research the manipulation of aqueous droplets in an immiscible, low-permittivity suspending medium is described to complement previous work on dielectrophoretic cell manipulation. Such droplets can be used as carriers not only for air- and water-borne samples, contaminants, chemical reagents, viral and gene products, and cells, but also the reagents to process and characterize these samples. A long-term goal of this area of research is to perform chemical and biological assays on automated, micro-scaled devices at or near the point-of-care, which will increase the availability of modern medicine to people who do not have ready access to large medical institutions and decrease the cost and delays associated with that lack of access. In this research I present proofs-of-concept for droplet manipulation and droplet-based biochemical analysis using dielectrophoresis as the motive force. Proofs-of-concept developed for the first time in this research include: (1) showing droplet movement on a two-dimensional array of electrodes, (2) achieving controlled dielectric droplet injection, (3) fusing and reacting droplets, and (4) demonstrating a protein fluorescence assay using micro-droplets.
Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells. (2001)

RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective apoptotic agent for cancer cells but not normal cells. VES has been shown to inhibit the growth of a wide variety of tumor cells in cell culture and animal models. Studies addressing mechanisms of action of VES-induced apoptosis have identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the extracellular signal-regulated kinases (ERK), and the stress-activated protein kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates ERK1/2 and JNK both in level and duration of kinase activity. Expression of dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38 blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and inhibited VES-induced apoptosis. Increased phosphorylation and transactivation activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES-induced apoptosis based on antisense blockage experiments. Collectively, these results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced apoptosis of human MDA-MB-435 breast cancer cells.
Regulation of nitrogen metabolism in Bacillus subtilis: vive la différence! (1999)

Nitrogen metabolism genes of Bacillus subtilis are regulated by the availability of rapidly metabolizable nitrogen sources, but not by any mechanism analogous to the two-component Ntr regulatory system found in enteric bacteria. Instead, at least three regulatory proteins independently control the expression of gene products involved in nitrogen metabolism in response to nutrient availability. Genes expressed at high levels during nitrogen-limited growth are controlled by two related proteins, GlnR and TnrA, which bind to similar DNA sequences under different nutritional conditions. The TnrA protein is active only during nitrogen limitation, whereas GlnR-dependent repression occurs in cells growing with excess nitrogen. Although the nitrogen signal regulating the activity of the GlnR and TnrA proteins is not known, the wild-type glutamine synthetase protein is required for the transduction of this signal to the GlnR and TnrA proteins. Examination of GlnR- and TnrA-regulated gene expression suggests that these proteins allow the cell to adapt to growth during nitrogen-limited conditions. A third regulatory protein, CodY, controls the expression of several genes involved in nitrogen metabolism, competence and acetate metabolism in response to growth rate. The highest levels of CodY-dependent repression occur in cells growing rapidly in a medium rich in amino acids, and this regulation is relieved during the transition to nutrient-limited growth. While the synthesis of amino acid degradative enzymes in B. subtilis is substrate inducible, their expression is generally not regulated in response to nitrogen availability by GlnR and TnrA. This pattern of regulation may reflect the fact that the catabolism of amino acids produced by proteolysis during sporulation and germination provides the cell with substrates for energy production and macromolecular synthesis. As a result, expression of amino acid degradative enzymes may be regulated to ensure that high levels of these enzymes are present in sporulating cells and in dormant spores.
Study on the Faith Construction Issue under Economic Angel (2010)

Since the tourism faith default of China’s tourism industry has become a fiercely harmful problem, strengthening the faith construction becomes an inevitable choice and the urgent issue. Seen from the economic angle, the tourism industry faith default in China is caused by three reasons. These are the asymmetrical information among the economic main bodies, limited gaming in this industry, and “the government failure”. Therefore, the tourism enterprises, the government, and tourism industry associations should joint efforts to develop the tourism faith construction and build a good faithful environment. Key words: Tourism Faith, Faith Default, Faith Construction Resume: Actuellement, un serieux probleme du manque de l’honnetete s' apparait dans le tourisme, c’est un certain choix et une obligation pressante d’intensifier l’edification de l’honnetete du tourisme en vue de realiser nos developpements dans ce domaine. Au point de vue d’economie, la cause principale de ce probleme est des informations asymetriques et des concurrences restreintes entre les parties principales d’economie dans le tourisme, ainsi que “le sans controle du gouvernement”. Il faut que les entreprise touristiques, le gouvernement, les associations touristiques travaillent ensemble de pratiquer la construction de l’honnetete du tourisme et de bâtir l’environnement honnete. Mots-Cles: l’honnetete du tourisme , le manque de l’honnetete , l’edification de l’honnetete
Glyphosate selection of gene amplification in suspension cultures of 3 plant species (2001)

Stepwise selection was carried out with increasing glyphosate concentrations to produce suspension cultures of Medicago sativa L. (alfalfa), Glycine max L. (Merr.) (soybean) and Nicotiana tabacum L. (tobacco) (two lines) that were at least 100-fold more resistant than the original culture as measured by the I50. The selection process required from 8 to 11 transfers to fresh medium over a total period from 161 to 312 days. The alfalfa and soybean lines contained 62- and 21-fold higher activity levels of the glyphosate target enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), respectively. The tobacco lines had EPSPS enzyme activity levels more than 800-times higher than the original cultures. The EPSPS gene copy number and mRNA were increased in all of the lines as measured by southern and northern hybridization, respectively. Thus, as has been found before with most glyphosate-resistant suspension cultures, the resistance is caused by high EPSPS enzyme activity due to EPSPS gene amplification. Alfalfa and soybean EPSPS gene amplification and the very high EPSPS enzyme activity increases found in the tobacco cultures have not been reported before. These studies show that EPSPS gene amplification can occur in many plant species to confer glyphosate tolerance.
Controlled delivery of inductive proteins, plasmid DNA and cells from tissue engineering matrices (1999)

It has been estimated that half the annual health care budget in the United States is spent on patients suffering from tissue loss and late stage organ failure. Critical limitations inherent in traditional therapies call for novel tissue and organ replacement strategies. This paper discusses development of biomaterials for conductive, inductive and cell-based tissue replacement strategies. Biodegradable polymer scaffolds can be used as space-filling matrices for tissue development and barriers to migration of epithelial cells in tissue conductive approaches. Inductive approaches involve sustained delivery of bioactive factors, such as protein growth factors and DNA, to alter cell function in localized regions. Factors can be released from highly porous polymer scaffolds to allow factor delivery and tissue development to occur in concert. Cell-based approaches involve seeding of cells onto polymeric scaffolds in vitro and subsequent transplantation of the scaffold. New scaffold materials are being developed that address specific tissue engineering design requirements, and in some cases attempt to mimic natural extracellular matrices. These strategies together offer the possibility of predictably forming specific tissue structures, and may provide solutions to problems such as periodontal ligament detachment, alveolar bone resorption and furcation defects.
The Role of TLR4 in Photoreceptor αA Crystallin Upregulation during Early Experimental Autoimmune Uveitis (2010)

Purpose. Previous studies indicate that the upregulation of alphaA crystallin prevents photoreceptor mitochondrial oxidative stress-mediated apoptosis in experimental autoimmune uveitis (EAU). In this study, the role of TLR4 was investigated in the upregulation of alphaA crystallin in the retinas of animals with EAU. Methods. TLR4(-/-), iNOS(-/-), TNF-alpha(-/-), MyD88(-/-), wild-type (WT) control (C57BL/6), and nude mice (B6.Cg-Foxn1(nu)) were immunized with IRBP mixed with complete Freund's adjuvant; eyes were enucleated on day 7 after immunization. Real-time polymerase chain reaction was first used to detect upregulated inflammatory cytokines and alphaA crystallin in retinas with EAU; confirmed with Western blot analysis, and the site of upregulation was localized by immunohistochemistry. Oxidative stress was localized using 8-OHdG, and TUNEL staining was used to detect apoptosis. Results. In early EAU, increased expression of TNF-alpha, iNOS, and alphaA crystallin genes were detected in the retinas of WT mice, whereas such upregulation was absent in TLR4-deficient mice (P < 0.001). alphaA Crystallin was not elevated in MyD88(-/-), TNF-alpha(-/-), and iNOS(-/-) mice with EAU. Immunostaining revealed TNF-alpha, iNOS, and alphaA crystallin localization in the photoreceptor inner segments and outer plexiform layer in the WT controls with EAU; but such staining was absent in TLR4-deficient mice with EAU. 8-OHdG staining showed oxidative stress in the photoreceptors in WT mice with EAU and there was no apoptosis. Conclusions. TLR4 plays an important role in the upregulation of alphaA crystallin through the interaction of MyD88 and the subsequent generation of TNF-alpha and iNOS in the EAU retina. Such crystallin upregulation may prevent oxidative stress-mediated apoptosis of photoreceptors in uveitis.
Reaktionen von Diazoalkanen mit α‐Diketonen und Chinonen, XII. Ringerweiterung von 1.1‐Dimethyl‐indandion‐(2.3) (1969)

Abstract Die Umsetzung von 1.1‐Dimethyl‐indandion‐(2.3) ( 1 ) mit Diazomethan liefert als Hauptprodukt stets das β‐Diketon 5a ; als Nebenprodukt entsteht in Abwesenheit von Alkali das α‐Diketon 2a , in Gegenwart von Alkali das isomere α‐Diketon 3a . Ein in der Literatur als 5a angesprochenes Produkt erwies sich als 3a . Mit Tosylazid gibt 5a das Diazodiketon 6 bzw. die Azoverbindung 8 . Auch mit Diazoäthan und Phenyldiazomethan bildet 1 in Gegenwart von Alkali als Hauptprodukt das β‐Diketon 5b bzw. 5c , als Nebenprodukt das α‐Diketon 3b bzw. 3c . Die Konstitution von 5b und 5c wird u.a. durch Japp‐Klingemann‐Spaltung ihrer Azo‐Kupplungsprodukte ( 7 → 9 ) bestätigt. Diazoessigester und Diazoacetophenon reagieren mit 1 ohne Katalysator sehr langsam; bei Zusatz von Bortrifluorid bzw. Zinkchlorid wurden der Diketo‐Ester 5d bzw. das Triketon 5e erhalten.
Carving fiber-top cantilevers with femtosecond laser micromachining (2008)

We present a new fabrication method to carve fiber-top cantilevers from single-mode optical fibers. The procedure, which is entirely based on a two-step femtosecond laser micromachining technique, is faster and more convenient with respect to what has been reported so far in the literature, and should be well adaptable to automatization and, thus, to series production. © 2008 IOP Publishing Ltd.
Presence on a human melanoma of multiple antigens recognized by autologous CTL (1989)

We derived from blood lymphocytes of a melanoma patient a large number of cytolytic T-cell clones directed against a cell line of the autologous tumor. Three distinct groups of antigens were recognized by these CTL on the autologous melanoma cells: group A consisted of stable antigens present on all sublines, whereas antigens B and C appeared unstable and were expressed by distinct sublines. In vitro immunoselections with various anti-A CTL clones were applied to the melanoma cells and variants resistant to 3 different CTL clones were obtained. These variants remained sensitive to other anti-A CTL clones, indicating that group A comprises at least 4 different antigens (D, E, F and A'). From a total of 76 CTL clones obtained from lymphocytes collected from the patient at various times, we found that 45 were anti-B, 17 were anti-C, 2 were anti-D, 9 were anti-E, 2 were anti-F and I was anti-A'. It is therefore likely that the 6 antigens identified by these CTL clones represent all or nearly all the transplantation antigens recognized by autologous CTL on this human melanoma.
On the Kinetics and Mechanism of Enoate Reductase (1982)

Enoate reductases from Clostridium spec. La 1 and Clostridium kluyveri show a rather broad substrate specificity i.e. many alpha,beta-unsaturated carboxylates are reduced in a NADH-dependent reaction. The relative rates for different substrates are different for both reductases. The Km value of NADH for the reductase from C. spec. La 1 is about 12 muM. The transhydrogenase activity (reduction of N-acetylpyridine adenine dinucleotide) with NADH shows a maximum at pH 8 which is about 2 units higher than that for the reduction of enoates. Results of initial rate studies can be best explained by a Bi Bi ping pong mechanism. No back reaction and no proton exchange from 2(-3)H-labelled acylates could be demonstrated. NAD+ is a mixed-type inhibitor. The product inhibition constant Ki = 0.84mM and the dissociation constant for the dead-end inhibition complex 4.8mM. Aliphatic acylates show no measurable inhibition when they are applied in concentrations at the 100-fold Km values of the corresponding enoates. Measurable inhibitions can be observed with phenyl group-containing acylates. 3-Phenylpropionate (38mM) shows about 86% inhibition. Fumarate which is not a substrate inhibits the reduction of enoates by NADH as well as by reduced methylviologen. However, the reduction of NAD+ by reduced methylviologen as well that of acetylpyridine adenine dinucleotide by NADH is not inhibited by fumarate. On the other hand inhibitors such as morin or dicoumarol which probably bind to the flavin domain do not impair the reduction of enoates by reduced methylviologen however, all reductions with NADH are inhibited. These results are indicative for three binding domains: one for NADH which can be blocked by dicoumarol or morin, another for enoates which can be occupied by fumarate and a third one for reduced methylviologen. Enoate reductase splits off exclusively the (4S)-hydrogen atom from NADH. There is no direct hydrogen transfer from NADH to the products. Depending on the substrate concentration the isotope effect of the reduction of (E)-2-methyl-2-butenoate with (4S)-[4(-3)H]NADH varies from 6.8 to 1.3. The presence of NAD+ decreases the isotope effect.
Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder (1999)

A single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder.
Common Superficial Fungal Infections in Patients with AIDS (1996)

Superficial mycotic infections such as seborrheic dermatitis, tinea pedis, tinea corporis, and onychomycosis are common in patients infected with human immunodeficiency virus (HIV). In communities where HIV infections are frequent, some of these clinical presentations serve as markers of the stage of HIV infection. The diagnosis of superficial fungal infection in HIV-positive patients may be difficult because of atypical clinical manifestations. Therefore, to ensure a correct diagnosis, skin scrapings should be collected for potassium hydroxide preparations and cultures. Most forms of dermatophytosis in HIV-positive patients respond well to many topical antifungal agents, such as azoles, terbinafine, and ciclopirox olamine. If the disease is chronic and extensive, then ketoconazole, fluconazole, and itraconazole are each effective.
Storage of platelet concentrates using ion exchange resin charged with dibasic phosphate. (1981)

Platelet concentrates were prepared at twice the normal concentration and stored at room temperature for 7 days in either standard bags (controls) or bags to which 1 or 2 g of Amberlite resin beads charged with dibasic phosphate had been added. The resin beads served as a buffer system by providing a “slow release” form of phosphate ions as well as by binding CO2 produced during platelet metabolism. Control platelets demonstrated rapid falls in pH, ATP content, morphology score, and thrombin-induced nucleotide release after 24 hr of storage with a fall in pH to less than 6.0 by day 3. Profound ultrastructural changes and a rise in pO2, suggesting loss of platelet viability, accompanied these changes. In contrast, the resin-stored platelets remained near normal after 24 hr of storage, with preservation of discoid morphology, 95% of ATP levels, excellent ultrastructural appearance, and evidence of continued oxygen consumption after 3 days of storage. Even after 7 days of storage, ATP levels remained greater than 50% of baseline and ultrastructurally intact platelets were seen. In the 1-g resin bags the pH remained at baseline levels (6.9–7.0), while there was a rise in pH in the 2-g resin bags. These results demonstrate the beneficial effects of maintaining a higher pH during platelet storage and provide a new approach to studying the metabolic changes that occur during longer term storage.
Novel IBX-Mediated Processes for the Synthesis of Amino Sugars and Libraries Thereof (2000)

The cyclization of N-arylcarbamates onto olefins, orchestrated by IBX, is a new synthetic method for the preparation of diverse arrays of amino sugar building blocks (see scheme for an example). A revised proposal for the mechanism of this novel reaction is also disclosed, which leads to the discovery of a remarkable interaction of IBX and glycals. The new reactions have potential in the production of libraries for biological screening. IBX=o-iodoxybenzoic acid = 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide.
The Processive Degradation of Individual Polyribonucleotide Chains (1968)

Abstract The experiments reported here suggest that Escherichia coli ribonuclease II, an exonuclease, hydrolyzes a given polyribonucleotide chain to completion before releasing a small, resistant oligonucleotide and initiating hydrolysis of another chain. Investigation of the products of hydrolysis of oligo- and polyribonucleotides indicates that enzymatic degradation starts at that end of the chain bearing a 3'-hydroxyl group. The enzyme shows a strong preference for long polymers as substrates, although oligonucleotides are hydrolyzed if present at sufficiently high concentration.