gebhart/patrepeval huggingface dataset:
Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis (2012)

MLN4924, a newly discovered small molecule inhibitor of NEDD8-activating enzyme (NAE), inactivates Cullin-RING E3 ubiquitin Ligases (CRLs) by blocking cullin neddylation. As a result, MLN4924 causes accumulation of several key substrates of CRLs and effectively suppresses tumor cell growth by inducing apoptosis and senescence. However, the role of MLN4924 in induction of autophagy and its biological significance are totally unknown. Here we showed that MLN4924 effectively induces autophagy in both time- and dose-dependent manners in multiple human cancer lines, indicating a general phenomenon. Mechanistically, by inactivating CRLs, MLN4924 causes accumulation of DEPTOR and HIF1α. The siRNA knockdown and gene KO studies showed that DEPTOR and the HIF1-REDD1-TSC1 axis are responsible for MLN4924-induced autophagy via inhibiting mTORC1. Biologically, autophagy is a survival signal to tumor cells, and blockage of autophagy via siRNA knockdown, gene KO and small molecule inhibitor remarkably enhanced MLN4924-induced apoptosis. Our study reveals an uncharacterized mechanism of MLN4924 action and provides the proof-of-concept evidence for strategic drug combination of MLN4924 with an autophagy inhibitor for maximal killing of tumor cells via enhancing apoptosis.
Lipid transport systems : some recent aspects in swine, cattle and trout during development (1985)

Lipids such as triacylglycerols, free and esterified cholesterol and phospholipids are essentially insoluble in water; lipoproteins, which are complex macromolecules of pseudomicellar structure, have evolved to ensure their efficient transport in the vascular system of vertebrates. Plasma lipoproteins are operationally classified according to their relative lipid and protein contents and thus according to density. The protein components, i.e. apolipoproteins, have a highly specialized structure contributing to particle stability and metabolism. The chemistry and structure of plasma lipoproteins and apoproteins is discussed and their biosynthesis, intravascular metabolism and cellular degradation briefly considered. Circulating concentrations of lipoproteins are under complex control, involving hormonal, nutritional and genetic factors; changes occurring in lipoprotein levels in pigs (Sus domesticus), cattle (Bos sp.) and rainbow trout (Salmo gairdnerii) during development are discussed. In pigs and calves, LDL predominate at the fetal stage and VLDL are absent. During suckling, this pattern is rapidly modified with HDL becoming the major class and low levels of VLDL appearing. These changes in part reflect high levels of exogenous triglyceride lipolysis consequent to the ingestion of fat-rich, maternal milk. With further growth, HDL predominate in both adult pigs and steers, although the LDL:HDL ratio is considerably lower in the latter (0.5-0.8 and approximately 0.2, respectively). Our studies in pigs suggest that the intestinal secretion of lipoproteins commences rapidly after birth since proteins akin to human apo-B48 and apo-B100 are detectable in plasma VLDL some 2-3 h after parturition. Although the trout is an oviparous vertebrate, LDL is also preponderate at the juvenile stage. With sexual maturity, LDL and VLDL levels diminish progressively, plasma HDL attaining concentrations as high as 1,500 mg/dl in adults. Our knowledge of the biochemical mechanisms at the origin of these developmental changes in lipid transport in both mammals and fish remains largely incomplete.
Linearly polarised 121W output from a diode-pumped Nd: YALO laser (2000)

We demonstrated a compact, CW, diode-pumped Nd: YALO laser with 121W at 1079nm and 60W at 1341nm. Lasing and non-lasing thermal lensing data are presented.
Managing mine road maintenance interventions using mine truck on-board data (2008)

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Impulsivity and Emotional Dysregulation Predict Choice Behavior During a Mixed-Strategy Game in Adolescents With Borderline Personality Disorder (2022)

Impulsivity and emotional dysregulation are two core features of borderline personality disorder (BPD), and the neural mechanisms recruited during mixed-strategy interactions overlap with frontolimbic networks that have been implicated in BPD. We investigated strategic choice patterns during the classic two-player game, Matching Pennies, where the most efficient strategy is to choose each option randomly from trial-to-trial to avoid exploitation by one's opponent. Twenty-seven female adolescents with BPD (mean age: 16 years) and twenty-seven age-matched female controls (mean age: 16 years) participated in an experiment that explored the relationship between strategic choice behavior and impulsivity in both groups and emotional dysregulation in BPD. Relative to controls, BPD participants showed marginally fewer reinforcement learning biases, particularly decreased lose-shift biases, increased variability in reaction times (coefficient of variation; CV), and a greater percentage of anticipatory decisions. A subset of BPD participants with high levels of impulsivity showed higher overall reward rates, and greater modulation of reaction times by outcome, particularly following loss trials, relative to control and BPD participants with lower levels of impulsivity. Additionally, BPD participants with higher levels of emotional dysregulation showed marginally increased reward rate and increased entropy in choice patterns. Together, our preliminary results suggest that impulsivity and emotional dysregulation may contribute to variability in mixed-strategy decision-making in female adolescents with BPD.
Efficacy, Safety, and Tolerability of Low-Dose Hormone Therapy in Managing Menopausal Symptoms (2009)

Use of the lowest clinically effective dose of postmenopausal hormone therapy conforms to current recommendations and good clinical practice. Although accumulating evidence demonstrates the efficacy and tolerability of low hormone therapy doses, data about their use are limited by a lack of long-term, randomized studies. This review evaluates current evidence on the efficacy, safety, and tolerability of these preparations and their role in menopausal management.
Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation (2009)

Human APOBEC3 (A3) proteins form part of the intrinsic immunity to retroviruses. Carrying 1 or 2 copies of a cytidine deaminase motif, A3s act by deamination of retroviral genomes during reverse transcription. HIV-1 overcomes this inhibition by the Vif protein, which prevents incorporation of A3 into virions. In this study we modeled and probed the structure of APOBEC3C (A3C), a single-domain A3 with strong antilentiviral activity. The 3-dimensional protein model was used to predict the effect of mutations on antiviral activity, which was tested in a Deltavif simian immunodeficiency virus (SIV) reporter virus assay. We found that A3C activity requires protein dimerization for antiviral activity against SIV. Furthermore, by using a structure-based algorithm for automated pocket extraction, we detected a putative substrate binding pocket of A3C distal from the zinc-coordinating deaminase motif. Mutations in this region diminished antiviral activity by excluding A3C from virions. We found evidence that the small 5.8S RNA specifically binds to this locus and mediates incorporation of A3C into virus particles.
An encapsulated dipole shaped beam array for air traffic control (1992)

An encapsulated dipole array has been developed for use as an aircraft beacon interrogator antenna, the high gain open planar array. The interrogator antenna provides a highly shaped beam which provides elevation coverage to greater than 50 degrees elevation over the frequency range of 1026.5 to 1095 MHz. In addition, three channels of performance are provided (sum, difference and sidelobe suppression). The design procedure and resulting performance are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cell Cycle–Targeted Cancer Therapies (2016)

A cardinal feature of cancer cells is the deregulation of cell cycle controls. Targeted drug therapy is designed to take advantage of specific genetic alterations that distinguish tumor cells from their normal counterparts. Mutated oncogenes and inactivated tumor suppressors can increase the dependency of cancer cells on G 1 -phase cyclin-dependent kinases, augment replication stress and DNA damage during S phase, and dismantle checkpoints that monitor progression through S/G 2 /M. These acquired defects generate cancer cell–specific vulnerabilities that provide a window of opportunity for targeted cancer treatments. We review the basic principles underlying the design of targeted therapies with emphasis on two main features: oncogene addiction and synthetic lethality. We discuss how traditional cytotoxic agents may depend, with relatively less specificity, on these same features and then point to examples of the successful application of newly developed, targeted therapeutic agents that offer reduced, dose-limiting toxicities to normal cells.
Feature issue introduction: optical materials for flat panel displays (2014)

This feature issue on “Optical Materials for Flat Panel Displays” of Optical Materials Express spotlights recent advances in optical materials for information display applications. It comprises 12 papers primarily on liquid-crystal and light-emitting materials and their devices. It is hoped that the present special theme issue encourages and stimulates further research endeavors into novel optical materials with improved optical or electro-optical properties, their mechanisms of operation, and their promoted device performance for potential flat-panel-display applications.
Transcriptome analysis in switchgrass discloses ecotype difference in photosynthetic efficiency (2016)

The gene ontology (GO) analysis of the transcriptome indicated lowland ecotype had significantly higher representation for cellular components associated with photosynthesis machinery controlling carbon fixation. In addition, using the transcriptome data, SNP markers were detected, which were distributed throughout the genome. The differentially expressed genes and SNP markers detected in this study would be useful resources for traits mapping and gene transfer across ecotypes in switchgrass breeding for increased biomass yield for biofuel conversion.
Yttrium-90 zur Schmerztherapie von Knochenmetastasen (1981)

Im fortgeschrittenen Tumorstadium hat sich bei Ausbildung von schmerzhaften Skelettmetastasen die Applikation von betastrahlenden knochenaffinen Isotopen bewährt. Die Anwendung von 89Sr bietet aufgrund der langen physikalischen Halbwertzeit erhebliche Strahlenschutzprobleme. Durch tierexperimentelle Untersuchungen mit Yttrium konnte nachgewiesen werden, daß bei Verwendung eines Y-Zitratkomplexes eine hohe Knochenaffinität besteht und Y sich damit kalziumähnlidh verhält. 90Y läßt sich nach dem beschriebenen Verfahren mit hoher Reinheit trägerfrei von einer 90Sr-Säule eluieren. Retentionsmessungen mit einem Ganzkörperzähler ergaben bei Tumorpatienten mit ausgedehnten Knochenmetastasen eine Gesamtretention von Yttrium von über 80%. Die ersten Ergebnisse therapeutischer Anwendung bei der Knochenmetastasenbehandlung zeigen den gleichen analgetischen Effekt wie 89Sr, wobei aufgrund der kurzen Halbwertzeit von 64 Std. die Strahlenschutzprobleme gering sind. Auch kostenmäßig bietet die Anwendung von 90Y gegenüber 89Sr Vorteile.
A η4‐Dithio‐para‐benzoquinone Metal Complex (2006)

Endlich geschafft: Ein rationales Syntheseverfahren führte zur Isolierung des ersten stabilen η4-Dithio-para-benzochinon-Komplexes (2; Cp*=C5Me5). Seine röntgenographisch ermittelte Molekülstruktur bestätigt die η4-Koordination des nicht fassbaren Intermediats 1. Rechnungen zufolge spielt das {Cp*Ir}-Fragment bei der Stabilisierung dieses reaktiven Intermediats eine entscheidende Rolle.
Medicinal Azides. Part 3. The Metabolism of the Investigational Antitumour Agent Meta-Azidopyrimethamine in Mouse Tissuein vitro (1988)

1. The experimental antitumour agent meta-azidopyrimethamine is deactivated by reduction of the azide moiety to yield meta-aminopyrimethamine. This reaction was followed by h.p.l.c. subsequent to incubation of the drug with homogenates prepared from liver, kidney, spleen, intestine and heart of mice. Reducing activity was highest in liver homogenate and was time dependent. Following the incubation of 530 nmol meta-azidopyrimethamine with liver homogenate equivalent to 1 g liver for 30 min under air, 84% of the agent was reduced to meta-aminopyrimethamine. 2. Reducing activity was markedly lower in incubations containing subcellular fractions obtained from liver homogenate. Under aerobic conditions the 700 g and 12,500 g supernatant fractions were able to reduce 57% and 23%, respectively, of the amount of meta-azidopyrimethamine initially present. The respective pellets possessed weak reducing ability, but on reconstitution of the supernatants with their corresponding pellets most of the reducing activity as observed in the whole homogenate was recovered. 3. Microsomes and mitochondria reduced the drug only when incubations were performed in the presence of nitrogen but not under air. 4. A fraction of the reducing activity measured in the tissue homogenates was non-enzymatic, as heat-inactivated homogenates retained less than 10% of the activity exhibited by the untreated homogenates. Neither bovine serum albumin nor glutathione could reduce meta-azidopyrimethamine under the conditions of the tissue incubations, whereas dithiothreitol was a powerful reductant. The mixed enzymatic and non-enzymatic nature, the tissue distribution and the diffuse subcellular localisation of meta-azidopyrimethamine reducing activity resemble features of the bioreduction of N-oxides.
Biochemical procedure for production of small deletions in simian virus 40 DNA. (1975)

A simple biochemical procedure for producing small deletions (15 to 50 base pairs) at virtually any location in simian virus 40 DNA has been developed. The steps involved are: cleavage of the closed-circular DNA to produce a linear structure followed by 5'-exonuclease digestion to expose a short single-stranded segment at each 3' end of the molecule. Mutants containing deletions at the site of the cleavage are obtained by infecting permissive monkey kidney cells with the exonuclease-treated DNA in the presence or absence of a helper DNA (depending upon whether or not the site of cleavage and therefore the deletion occurred in a gene required for vegetative multiplication). In this paper viable mutants with deletions at the HpaII endonuclease cleavage site (0.735 map position) and defective trans-complementable mutants with deletions at the EcoRI endonuclease cleavage site (0/1.0 map position) were isolated.
<b>Inhibition of a mite protease (Df-protease) by synthetic </b><b>inhibitors </b> (1994)

A protease (Df-protease) from house dust mites (Dermatophagoidesfarinae), which is closely related to mite-induced allergic diseases, catalyzes the activation of kallikrein-kinin system in plasma (3, 6, 12). Df-protease was competitively inhibited by guanidine and amidine derivatives with low-molecular weight. The kinetic study revealed that the Ki values of 1-[p-(p-amidinophenoxycarbonyl)benzoyl]-D-proline benzyl ester acetate and N-[p-(2-methoxycarbonyl-4-amidinophenoxycarbonyl)benzoyl]-N-phenylglycine ethyl ester acetate were 5 >< 10-9 M and 6>< 10-9 M, respectively.
Flow and atomization in flashing injectors (1985)

Flashing injection involves expanding a fluid through an injector until a supersaturated state is reached, causing a portion of the fluid to flash to a vapor. This investigation considered the flow, atomization and spreading properties of flashing injectors with flowing liquids containing dissolved gases (Jet A/air) as well as superheated liquids (Freon-11). The use of a two-stage expansion process, separated by an expansion chamber, was found to be beneficial for good atomization properties of flashing injection - particularly for dissolved gas systems. Both locally homogeneous and separated flow models provided good predictions of injector flow properties. Conventional correlations for drop sizes from pressure and airblast injectors were successfully modified, using the separated flow model to prescribe injector exit conditions, and to correlate drop size measurements. Additional experimental results are provided for spray angles of sprays from flashing injectors.
Progression of Watermelon Bud Necrosis Virus Infection in Its Vector, Thrips palmi (2021)

Thrips are important pests of agricultural, horticultural, and forest crops worldwide. In addition to direct damages caused by feeding, several thrips species can transmit diverse tospoviruses. The present understanding of thrips-tospovirus relationships is largely based on studies of tomato spotted wilt virus (TSWV) and Western flower thrips (<i>Frankliniella occidentalis</i>). Little is known about other predominant tospoviruses and their thrips vectors. In this study, we report the progression of watermelon bud necrosis virus (WBNV) infection in its vector, melon thrips (<i>Thrips palmi</i>). Virus infection was visualized in different life stages of thrips using WBNV-nucleocapsid protein antibodies detected with FITC-conjugated secondary antibodies. The anterior midgut was the first to be infected with WBNV in the first instar larvae. The midgut of <i>T. palmi</i> was connected to the principal salivary glands (PSG) via ligaments and the tubular salivary glands (TSG). The infection progressed to the PSG primarily through the connecting ligaments during early larval instars. The TSG may also have an ancillary role in disseminating WBNV from the midgut to PSG in older instars of <i>T. palmi</i>. Infection of WBNV was also spread to the Malpighian tubules, hindgut, and posterior portion of the foregut during the adult stage. Maximum virus-specific fluorescence in the anterior midgut and PSG indicated the primary sites for WBNV replication. These findings will help to better understand the thrips-tospovirus molecular relationships and identify novel potential targets for their management. To our knowledge, this is the first report of the WBNV dissemination path in its vector, <i>T. palmi</i>.
Use of Weather Radar Data for Site Diversity Predictions and Impact of Rain Field Advection (2008)

This paper presents the analysis on two weather radar datasets, collected at Spino d'Adda (Italy) and Bordeaux (France), for the simulation and the performance evaluation of a site diversity system. Results from the two locations are compared and the impact of different factors such as baseline and link orientation is assessed and related to the local climatologic and topographic characteristics. A link is then established between the preferable baseline orientation and the predominant direction of the rain field advection. The rain field displacement is finally shown to be well approximated by the wind speed and direction at the 700 hPa pressure level extracted from the ECMWF ERA-40 meteorological database.
Heterologous rhamnolipid biosynthesis by P. putida KT2440 on bio-oil derived small organic acids and fractions (2019)

In many cases in industrial biotechnology, substrate costs make up a major part of the overall production costs. One strategy to achieve more cost-efficient processes in general is to exploit cheaper sources of substrate. Small organic acids derived from fast pyrolysis of lignocellulosic biomass represent a significant proportion of microbially accessible carbon in bio-oil. However, using bio-oil for microbial cultivation is a highly challenging task due to its strong adverse effects on microbial growth as well as its complex composition. In this study, the suitability of bio-oil as a substrate for industrial biotechnology was investigated with special focus on organic acids. For this purpose, using the example of the genetically engineered, non-pathogenic bacterium Pseudomonas putida KT2440 producing mono-rhamnolipids, cultivation on small organic acids derived from fast pyrolysis of lignocellulosic biomass, as well as on bio-oil fractions, was investigated and evaluated. As biosurfactants, rhamnolipids represent a potential bulk product of industrial biotechnology where substitution of traditional carbon sources is of conceivable interest. Results suggest that maximum achievable productivities as well as substrate-to-biomass yields are in a comparable range for glucose, acetate, as well as the mixture of acetate, formate and propionate. Similar yields were obtained for a pretreated bio-oil fraction, which was used as reference real raw material, although with significantly lower titers. As such, the reported process constitutes a proof-of-principle for using bio-oil as a potential cost-effective alternative carbon source in a future bio-based economy.
Dry etching of copper film with hexafluoroacetylacetone via oxidation process (1999)

Dry etching of Cu film was achieved via oxidation process using oxidizing agents such as O2 plasma, O3, or O3 plasma, followed by the removal process of the copper oxides (CuOx) by reaction with hexafluoroacetylacetone [H(hfac)] to form volatile copper compound, [bis-hexafluoroacetylacetonate: Cu(hfac)2] and H2O. The etching rate was increased with the increase of etchant [H(hfac) and O3] flow rate, plasma power, and substrate temperature. Oxygen radical concentration is the highest in the plasma generated with ozone, which leads to the highest etching rate up to 1400 Å/min. The etch rate dependence on the substrate temperature showed the activation energy of about 7 kcal/mol and gas phase transport seems to be the rate controlling step.
Metabolic Detoxification of 2-Oxobutyrate by Remodeling Escherichia coli Acetate Bypass (2021)

2-Oxobutyrate (2-OBA), as a toxic metabolic intermediate, generally arrests the cell growth of most microorganisms and blocks the biosynthesis of target metabolites. In this study, we demonstrated that using the acetate bypass to replace the pyruvate dehydrogenase complex (PDHc) in <i>Escherichia coli</i> could recharge the intracellular acetyl-CoA pool to alleviate the metabolic toxicity of 2-OBA. Furthermore, based on the crystal structure of pyruvate oxidase (PoxB), two candidate residues in the substrate-binding pocket of PoxB were predicted by computational simulation. Site-directed saturation mutagenesis was performed to attenuate 2-OBA-binding affinity, and one of the variants, PoxB<sup>F112W</sup>, exhibited a 20-fold activity ratio of pyruvate/2-OBA in substrate selectivity. PoxB<sup>F112W</sup> was employed to remodel the acetate bypass in <i>E. coli</i>, resulting in l-threonine (a precursor of 2-OBA) biosynthesis with minimal inhibition from 2-OBA. After metabolic detoxification of 2-OBA, the supplies of intracellular acetyl-CoA and NADPH (nicotinamide adenine dinucleotide phosphate) used for l-threonine biosynthesis were restored. Therefore, 2-OBA is the substitute for pyruvate to engage in enzymatic reactions and disturbs pyruvate metabolism. Our study makes a straightforward explanation of the 2-OBA toxicity mechanism and gives an effective approach for its metabolic detoxification.