gebhart/patrepeval huggingface dataset:
Nuclear ERK: Mechanism of Translocation, Substrates, and Role in Cancer (2019)

The extracellular signal-regulated kinases 1/2 (ERK) are central signaling components that regulate stimulated cellular processes such as proliferation and differentiation. When dysregulated, these kinases participate in the induction and maintenance of various pathologies, primarily cancer. While ERK is localized in the cytoplasm of resting cells, many of its substrates are nuclear, and indeed, extracellular stimulation induces a rapid and robust nuclear translocation of ERK. Similarly to other signaling components that shuttle to the nucleus upon stimulation, ERK does not use the canonical importinmechanism of nuclear translocation. Rather, it has its own unique nuclear translocation signal (NTS) that interacts with importin7 to allow stimulated shuttling via the nuclear pores. Prevention of the nuclear translocation inhibits proliferation of B-Raf- and N/K-Ras-transformed cancers. This effect is distinct from the one achieved by catalytic Raf and MEK inhibitors used clinically, as cells treated with the translocation inhibitors develop resistance much more slowly. In this review, we describe the mechanism of ERK translocation, present all its nuclear substrates, discuss its role in cancer and compare its translocation to the translocation of other signaling components. We also present proof of principle data for the use of nuclear ERK translocation as an anti-cancer target. It is likely that the prevention of nuclear ERK translocation will eventually serve as a way to combat Ras and Raf transformed cancers with less side-effects than the currently used drugs.
ATR Inhibition Induces CDK1–SPOP Signaling and Enhances Anti–PD-L1 Cytotoxicity in Prostate Cancer (2021)

This work provides a molecular mechanistic rationale for combining ATR-targeted agents with immune checkpoint blockade for patients with CRPC. Multiple early-phase clinical trials of this combination are underway.
Novel Donor p-Acceptor Conjugates-Functionalized Zinc Phthalocyanines Application in Dye-Sensitized Solar Cells (2014)

New zinc phthalocyanines [2-(N,N-bisacetic acid amino)-9,16,23-(N,N-bisethylamino)zinc phthalocyanine (SPC), 2-(N,N-bisacetic acid amino)-9,16,23-(N,N-bispropyl-amino)zinc phthalocyanine (TPC), 2-(N,N-bisacetic acid amino)-9,16,23-(N,N-bisbutylamino)zinc phthalocyanine (FPC)], functionalized with donor--acceptor conjugates were synthesized, The new compounds were characterized using FTIR, UV-visible, 1 H NMR, cyclic voltammetry, differential pulse voltammetry and elemental analysis. From the reduction and oxidation behaviour, it is proved that SPC, TPC, FPC have negative LUMO levels and positive HOMO levels, satisfying the energy gap rule, they can be employed as sensitizers for dye-sensitized solar cells and their optical, electrochemical and photovoltaic properties were also studied. They exhibited broad absorption adsorbed onto a 6 m thick TiO films. The photovoltaic devices produced short circuit current densities of 1.53, 2.07, 1.89 mA/cm 2 , the open circuit voltage of 0.48, 0.55, 0.56 V and power conversion efficiency of 1.42, 1.67, 1.64 % respectively under AM1.5G illumination.
Opposing responses of apoptosis and autophagy to moderate compression in skeletal muscle (2010)

These data demonstrate the opposing responses of apoptosis and autophagy to moderate compression in muscle. Moreover, our findings suggest that cellular changes in apoptosis and autophagy have already taken place in the very early stage in which apparent histopathology has yet to develop in the process of compression-induced muscle pathology.
Arachidonic acid metabolism among human mononuclear leukocytes. Lipoxygenase-related pathways. (1984)

Human peripheral blood mononuclear cells were isolated and assessed for the presence of contaminating polymorphonuclear leukocytes and platelets. Incubations of these cell isolates were performed in the presence or absence of the calcium ionophore A23187 and/or 1-14C-labeled or unlabeled arachidonic acid. Using reverse phase high pressure liquid chromatography with simultaneous monitoring of ultraviolet light absorption at 229 and 280 nm and, where appropriate, of radioactivity, our studies reveal that human peripheral blood mononuclear cells generate leukotrienes C4 and B4 (LTC4 and LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) following stimulation with A23187. The ratio of LTC4 to LTB4 was approximately 10-fold greater among the mononuclear cells than among similar incubations of polymorphonuclear leukocytes. Furthermore, the mononuclear cells failed to metabolize LTB4 into the omega-hydroxy or omega-carboxy derivatives that were always present in, and very characteristic of incubations of polymorphonuclear leukocytes. Depletion of monocytes from the mononuclear cells by double adherence resulted in virtual loss of the generation of 5-lipoxygenase-derived products by the remaining nonadherent cells, supporting the conclusion that the monocytes and not the lymphocytes were the source of LTC4, LTB4, and 5-HETE. The presence of both 12-HETE and the cyclooxygenase-derived 12-hydroxyheptadecatrienoic acid correlated with the degree of platelet contamination, suggesting that the platelets account for the presence of these compounds.
Xpertfinder - message analysis for the recommendation of contact persons within defined topics (2003)

Personal acquaintance represents an essential basis for the exchange of information between employees. Recommendation of contact persons is a method that fosters the build-up of acquaintanceship in order to support the exchange of information. The subject of the present paper is a new recommendation technique, which automatically and continuously detects contact persons within relevant topics and represents them anonymously. For the detection of contact persons, various indicators are drawn up, e.g. authorship for the source of textual information and addresses for contact information. The emphasis of the paper is on the description of the data processing concept using Latent Semantic Analysis as well as the effectiveness of that method for document classification.
Somatotropin and β-adrenergic agonists: Their efficacy and mechanisms of action (1991)

This review discusses the efficacy and biological mechanisms by which somatotropin (ST) and β-adrenergic agonists improve growth performance. These metabolism modifiers increase growth rate, improve productive efficiency (feed efficiency), and increase carcass leanness. The ST-dependent reduction in adipose tissue accretion is the result of remarkable decreases in glucose transport, lipogenesis, and the ability of insulin to stimulate these processes in the adipocyte. Lipolysis is not affected by pST. The effects of ST are chronic in nature rather than acute, as was previously believed. This temporal profile may reflect a ST-dependent decrease in the transcription of important regulatory genes such as the glucose transporter(s) and key lipogenic enzymes. The effects of ST on cell proliferation are mediated by insulin-like growth factor I (IGF-I). A number of IGF binding proteins (IGFBP) are found in serum and are produced locally in a wide variety of tissues. The IGFBP have been shown to modulate the biological effects of IGF-I. The effects observed (either stimulatory or inhibitory) depend on the IGFBP used and the tissue studied. The significance of IGFBP-dependent modulation of IGF-I action remains to be established. β-adrenergic agonists (clenbuterol, cimaterol, and ractopamine) also alter growth rate and carcass composition of growing meat animals. β-adrenergic agonists seem to decrease carcass fat content by decreasing lipogenesis and stimulating lipolysis. The increase in muscle growth observed in animals treated with β-adrenergic agonists is associated with an enhancement of satellite cell proliferation, stimulation of myofibrillar protein synthesis, and depression of myofibrillar protein degradation.
Stimuli That Activate MSK in Cells and the Molecular Mechanism (2012)

The mitogen‑ and stress‑activated kinases‑1 and ‑2 (MSK1 and MSK2) are ubiquitous serine/ threonine kinases that mediate intracellular signal transduction by mitogen‑activated protein kinases (MAPKs) of the p38 and ERK1/2 families. The structure of MSK is complex, featuring a substrate‑phosphorylating N‑terminal kinase domain, a regulatory C‑terminal kinase domain as well as many regulatory phosphorylation sites and motifs. Here we review all aspects of the structure‑function and mechanism of activation of MSK. First, we summarize the numerous and diverse environmental stimuli, ranging from physiological signaling molecules to cellular stresses that activate ERK1/2, p38a or both to effect activation of MSK in cells. Next is described the series of sequential phosphorylation events that first activates the C‑terminal kinase domain and finally the N‑terminal kinase domain of MSK in an activation mechanism that can be divided into four stages. We proceed by detailing the activation mechanism from a 3‑dimensional perspective, focusing on the roles of each of the phosphorylation events. Throughout, parallels are drawn to similarities with activation mechanisms of the kinase super family in general and with kinases of the AGC and CaMK groups in particular, to which the N‑ and C‑terminal kinase domains, respectively, belong. Finally, topics like MSK interactions with MAPK docking sites, MSK substrate specificity, monitoring of MSK activity in cells and mutant MSK as research tools are discussed.
Note: Design and characterization of an optical light source based on mixture of white and near-ultraviolet light emitting diode spectra (2011)

An optical light source based on a solid-state lighting technology is designed. Main components of the light source are a phosphor-converted white and a near-ultraviolet (near-UV) light emitting diodes (LEDs), the spectral power distributions (SPDs) of which are mixed using a fiber optic combiner. The near-UV LED is used for improving insufficient SPDs of the white LED at shorter wavelengths of the visible radiation. Stable direct current power supplies are also designed and used to operate each of the LED separately. Three steps of the driving current can be selected by means of serial resistors altered with a commutator at nominal current values of ∼40%, ∼50%, and ∼69%. The light source can be used for many characteristic measurements within the scope of photometry and colorimetry.
Search for the molecular basis of morphological variation in Mycobacterium avium (1994)

Isolates of Mycobacterium avium exhibit three different colonial variations: smooth domed (SmD), smooth transparent (SmT), and rough (Rg). Because the discrimination between morphotypes is founded on morphological rather than molecular principles and because of the absence of consensus over the relevance of morphology to pathogenesis and drug sensitivity, a comparative study at the protein level was undertaken. By direct immunization of BALB/c mice with the soluble sonicate of one of the morphotypes of M. avium serovar 2, eight monoclonal antibodies (MAbs) were identified, of which one was M. avium specific. Cross immunization of syngeneic mice with serum-absorbed antigens allowed the generation of 15 further MAbs; 11 were M. avium or M. avium complex specific, but none of them was morphotype specific. Subcellular fractions analyzed by electrophoresis showed similar profiles, with the exception of a cytosolic protein with a relative molecular mass of ca. 66 kDa (protein SmT 66), which was most highly expressed in SmT variants of M. avium serotypes 2 and 4. Because a well-known, ubiquitous stress-heat shock protein (hsp65) has a similar molecular mass, protein SmT 66 was compared with hsp65. Western blot (immunoblot) analyses using several cross-reacting MAbs and N-terminal amino acid sequencing established that this protein was not the ubiquitous stress protein. Thus, SmT 66 is the first product to be described which might be associated with the SmT morphotype.
Mitochondrial proton leak in brown adipose tissue mitochondria ofUcp1-deficient mice is GDP insensitive (1999)

Mice deficient in mitochondrial uncoupling protein (UCP) 1 are cold sensitive, despite abundant expression of the homologues, Ucp2 and Ucp3 (S. Enerbäck, A. Jacobsson, E. M. Simpson, C. Guerra, H. Yamashita, M.-E. Harper, and L. P. Kozak. Nature 387: 90-94, 1997). We have analyzed characteristics of mitochondrial proton leak from brown adipose tissue (BAT) of Ucp1-deficient mice and normal controls and conducted the first top-down metabolic control analysis of oxidative phosphorylation in BAT mitochondria. Because purine nucleotides inhibit UCP1 and because UCP2 and the long form of UCP3 have putative purine nucleotide-binding regions, we predicted that proton leak in BAT mitochondria from Ucp1-deficient mice would be sensitive to GDP. On the contrary, although control over mitochondrial oxygen consumption and proton leak reactions at state 4 are strongly affected by 1 mM GDP in mitochondria from normal mice, there is no effect in UCP1-deficient mitochondria. In the presence of GDP, the overall kinetics of proton leak were not significantly different between Ucp1-deficient mice and controls. In its absence, state 4 respiration in normal BAT mitochondria was double that in its presence. Leak-dependent oxygen consumption was higher over a range of membrane potentials in its absence than in its presence. Thus proton leak, potentially including that through UCP2 and UCP3, is GDP insensitive. However, our measurements were made in the presence of albumin and may not allow for the detection of any fatty acid-induced UCP-mediated leak; this possibility requires investigation.
Robust vision-based indoor localization (2015)

Vision-based positioning has proven to be highly successful and popular in mobile robotics and computer vision applications. These methods have, however, not enjoyed the same popularity in the field of indoor localization.
Animal models of ??anxiety??: where next? (1997)

Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically designed to study defensive reactions (e.g. rat and mouse defence test batteries) or which incorporate a more detailed knowledge of defence into established procedures (e.g. ethological plus-maze and defensive burying paradigms). Furthermore, recent evidence also suggests that drugs with proved clinical efficacy in panic attacks/panic disorder have reliably stronger effects on flight responses than other components of the defensive repertoire. It is concluded that a focus on defensive behaviour patterns improves test validity (predictive/face/construct), offers a more rational basis for test selection in drug development programmes, and provides a firmer theoretical framework for future methodological and therapeutic advance.
Dating the Siple Dome (Antarctica) ice core by manual and computer interpretation of annual layering (2004)

Abstract The Holocene portion of the Siple Dome (Antarctica) ice core was dated by interpreting the electrical, visual and chemical properties of the core. The data were interpreted manually and with a computer algorithm. The algorithm interpretation was adjusted to be consistent with atmospheric methane stratigraphic ties to the GISP2 (Greenland Ice Sheet Project 2) ice core, 10 Be stratigraphic ties to the dendrochronology 14 C record and the dated volcanic stratigraphy. The algorithm interpretation is more consistent and better quantified than the tedious and subjective manual interpretation.
At what Pressure Shall CO2 Be Transported by Ship? An in-Depth Cost Comparison of 7 and 15 Barg Shipping (2021)

The pipeline has historically been the preferred means to transport CO2 due to its low cost for short distances and opportunities for economies of scale. However, interest in vessel-based transport of CO2 is growing. While most of the literature has assumed that CO2 shipping would take place at low pressure (at 7 barg and −46 °C), the issue of identifying best transport conditions, in terms of pressure, temperature, and gas composition, is becoming more relevant as ship-based carbon capture and storage chains move towards implementation. This study focuses on an in-depth comparison of the two primary and relevant transport pressures, 7 and 15 barg, for annual volumes up to 20 MtCO2/year and transport distances up to 2000 km. We also address the impact of a number of key factors on optimal transport conditions, including (a) transport between harbours versus transport to an offshore site, (b) CO2 pressure prior to conditioning, (c) the presence of impurities and of purity constraints, and (d) maximum feasible ship capacities for the 7 and 15 barg options. Overall, we have found that 7 barg shipping is the most cost-efficient option for the combinations of distance and annual volume where transport by ship is the cost-optimal means of transport. Furthermore, 7 barg shipping can enable significant cost reductions (beyond 30%) compared to 15 barg shipping for a wide range of annual volume capacities.
Non-Thermal Radio Frequency Stimulation Inhibits the Tryptophan Synthase Beta Subunit in the Algae &lt;i&gt;Chlamydomonas reinhardtii&lt;/i&gt; (2017)

To demonstrate the ability of the Nativis signal transduction technology (Butters et al. 2014) to modulate the expression of algae mRNA and protein, we tested if we can alter specific enzyme levels in Chlamydomonas reinhardtii. We inhibited the synthesis of the enzyme tryptophan synthase beta subunit (MAA7) by applying the signal derived from a published siRNA (Zhao et al. 2009). With lower levels of MAA7, Chlamydomonas reinhardtii can grow in the presence of the prodrug 5-Fluoroindole (5-FI), because less 5-Fluoroin-dole can be converted to the toxic 5-Fluoro-L-tryptophan (5-FT). We find a 24% (±5%) increase of growth with the signal versus no signal. To see if that effect was due to the reduction of the amount of mRNA encoding MAA7, we used Real-Time Quantitative PCR (RT-QPCR) to measure the levels of MAA7 mRNA. To normalize the MAA7 mRNA level, we compared them to the levels of a mRNA that is not affected by the signal (G protein beta subunit-like polypeptide, Cblp). Two conditions increase the effectiveness of the signal. One can either treat the cell cultures during the logarithmic growth phase (starting the cultures at density of 0.104 OD at 750 nm). Or one can treat the cultures at a later stage of the logarithmic growth, but treating them for a longer time (8.7% versus 3.5% of the culture time). Under these conditions we found around a 50% decrease in the mRNA levels for MAA7. Treating the cultures at the earlier growth phase or at a later growth phase is less effective, with only a 20% effect.
Mechanistic Characterization of the HDV Genomic Ribozyme:  Assessing the Catalytic and Structural Contributions of Divalent Metal Ions within a Multichannel Reaction Mechanism (2001)

Hepatitis delta virus (HDV) uses genomic and antigenomic ribozymes in its replication cycle. We examined ribozyme self-cleavage over eight orders of magnitude of Mg(2+) concentration, from approximately 10(-9) to 10(-1) M. These experiments were carried out in 1 M NaCl to aid folding of the ribozyme and to control the ionic strength. The concentration of free Mg(2+) ions was established using an EDTA-Mg(2+) buffered system. Over the pH range of 5-9, the rate was independent of Mg(2+) concentration up to 10(-7) M, and of the addition of a large excess of EDTA. This suggests that in the presence of 1 M NaCl, the ribozyme can fold and cleave without using divalent metal ions. Brønsted analysis under these reaction conditions suggests that solvent and hydroxide ions may play important roles as general base and specific base catalysts. The observed rate constant displayed a log-linear dependence on intermediate Mg(2+) concentration from approximately 10(-7) to 10(-4) M. These data combined with the shape of the pH profile under these conditions are consistent with the binding of at least one structural divalent metal ion that does not participate in catalysis and binds tighter at lower pH. No evidence for a catalytic role for Mg(2+) was found at low or intermediate Mg(2+) concentrations. Addition of Mg(2+) to physiological and higher concentrations, from 10(-3) to 10(-1) M, revealed a second saturable divalent metal ion which binds tighter at high pH. The shape of the pH profile is inverted relative to that at low Mg(2+) concentrations, consistent with a general acid-base catalysis mechanism in which a cytosine (C75) acts as the general acid and a hydroxide ion from the divalent metal ion, or possibly from solvent, acts as the base. Overall, the data support a model in which the HDV ribozyme can self-cleave by multiple divalent ion-independent and -dependent channels, and in which the contribution of Mg(2+) to catalysis is modest at approximately 25-fold. Surface electrostatic potential maps were calculated on the self-cleaved form of the ribozyme using the nonlinear Poisson-Boltzmann equation. These calculations revealed several patches of high negative potential, one of which is present in a cleft near N4 of C75. These calculations suggest that distinct catalytic and structural metal ion sites exist on the ribozyme, and that the negative potential at the active site may help shift the pK(a) for N3 of C75 toward neutrality.