gebhart/patrepeval huggingface dataset:
Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ (2020)

Skeletal muscle atrophy is a highly-prevalent and debilitating condition that remains poorly understood at the molecular level. Previous work found that aging, fasting, and immobilization promote skeletal muscle atrophy via expression of activating transcription factor 4 (ATF4) in skeletal muscle fibers. However, the direct biochemical mechanism by which ATF4 promotes muscle atrophy is unknown. ATF4 is a member of the basic leucine zipper transcription factor (bZIP) superfamily. Because bZIP transcription factors are obligate dimers, and because ATF4 is unable to form highly-stable homodimers, we hypothesized that ATF4 may promote muscle atrophy by forming a heterodimer with another bZIP family member. To test this hypothesis, we biochemically isolated skeletal muscle proteins that associate with the dimerization- and DNA-binding domain of ATF4 (the bZIP domain) in mouse skeletal muscle fibers <i>in vivo</i> Interestingly, we found that ATF4 forms at least five distinct heterodimeric bZIP transcription factors in skeletal muscle fibers. Furthermore, one of these heterodimers, composed of ATF4 and CCAAT enhancer-binding protein β (C/EBPβ), mediates muscle atrophy. Within skeletal muscle fibers, the ATF4-C/EBPβ heterodimer interacts with a previously unrecognized and evolutionarily conserved ATF-C/EBP composite site in exon 4 of the <i>Gadd45a</i> gene. This three-way interaction between ATF4, C/EBPβ, and the ATF-C/EBP composite site activates the <i>Gadd45a</i> gene, which encodes a critical mediator of muscle atrophy. Together, these results identify a biochemical mechanism by which ATF4 induces skeletal muscle atrophy, providing molecular-level insights into the etiology of skeletal muscle atrophy.
Fundamental superstrate (cover) effects on printed circuit antennas (1984)

The fundamental effects of superstrate (cover) materials on printed circuits antennas are investigated. Substrate-superstrate resonance conditions are established which maximize antenna gain, radiation resistance, and radiation efficiency. Criteria are determined for material properties and dimensions for which surface waves are eliminated and a radiation efficiency due to substrate-superstrate effects of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">e_{s} = 100</tex> percent is obtained. Criteria for nearly omnidirectional <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\bar{H}</tex> -plane patterns and nearly omnidirctional <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\bar{E}</tex> -plane patterns are presented. Finally, a general criterion is given for choosing a superstrate to optimize efficiency for the important case of nonmagnetic layers with the antenna at the interface.
Pain without Nociceptors? Nav1.7-Independent Pain Mechanisms (2014)

Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive nociceptors. Thus, similar pain phenotypes arise through distinct cellular and molecular mechanisms. Therefore, rational analgesic drug therapy requires patient stratification in terms of mechanisms and not just phenotype.
Multi-Resolution Sound Rendering (2004)

Point-based multi-resolution representations have been used successfully for rendering highly complex three dimensional scenes in real-time. In this paper, we apply this paradigm to sound rendering: A hierarchy of stochastic sample sound sources is used to approximate complex sound environments (containing a large number of sound sources, such as a football stadium), allowing for interactive real-time walkthroughs. Additionally, the proposed technique can be used for observer-dependent auralizations of simple approximations of global sound propagation. Typical applications of the technique are in virtual reality and computer games, especially to complement established output-sensitive algorithms for rendering visual content.
Intracellular localization of antigens recognized by anti-vimentin monoclonal antibodies (mAbs): cross-reactivities of anti-vimentin mAbs with other cellular components. (1996)

Monoclonal antibodies were raised against immunoaffinity-purified fusion regulatory protein (FRP)-1 complex from membrane fraction of HeLa cells. Immunoblotting and immunoprecipitation studies showed all ten antibodies reacted with a 55 kDa band of cell lysate and purified vimentin. Interestingly, one of the antibodies (mAb57) cross-reacted with purified tropomyosin and myosin. Further analyses using vimentin chemically cleaved by 2-nitro-5-thio-cyanobenzoic acid, and lambda gt 11 cDNA which encoded a partial sequence of vimentin indicated that six mAbs recognized epitopes between amino acids 1 and 313 and the other four mAbs recognized epitopes in the area between residues 314 and 326. Indirect immunofluorescence microscopy using 3% formalin-fixed, 0.1% Triton X-100 treated HeLa cells revealed that seven antibodies stained various intracellular components other than vimentin, while three antibodies stained vimentin filaments alone. Furthermore, flow cytometric analysis showed one of the antibodies (mAb25) clearly stained the surface of unfixed HeLa cells. All immunofluorescent findings were the same when HeLa, baby hamster kidney (BHK) and murine L229 cells were examined. These results indicate that we could obtain unique anti-vimentin mAbs which show cross-reactivities with previously undescribed cell surface and intracellular molecules including tropomyosin and myosin. Taken together, there are two possibilities that explain our findings: (1) The unknown molecules may have structural similarity to vimentin. (2) Our anti-vimentin mAbs can react specifically with structurally distinct epitopes present on both unknown molecules and vimentin. In either case, our cross-reactive mAbs, which recognized undescribed epitopes on vimentin, maybe provide useful tools for studying intermediate filaments and related cellular components.
Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. (1989)

We asked this question: in normal humans, is either a normal dietary intake or normal serum concentration of phosphorus a determinant of the serum concentration of 1,25(OH)2D? In seven normal men whose dietary phosphorus was decreased from 2,300 to 625 mg/d, each intake for 8-9 d, under strictly controlled, normal metabolic conditions, we measured serum concentrations of 1,25(OH)2D daily, and concentrations of phosphorus hourly throughout a 24-h period, before and after restriction. Decreasing dietary phosphorus induced: (a) a 58% increase in serum levels of 1,25(OH)2D; (b) a 35% decrease in serum levels of phosphorus measured in the afternoon; (c) a 12% decrease in the 24-h mean serum level of phosphorus; but, (d) no decrease in morning fasting levels of phosphorus. Serum concentrations of 1,25(OH)2D varied inversely and significantly with 24-h mean concentrations of phosphorus (r = -0.77, P less than 0.001). When these data are combined with those of our prior study in which dietary phosphorus was varied over an extreme range, the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P less than 0.001). In the aggregate, the results demonstrate that in normal men, dietary phosphorus throughout a normal range and beyond, can finely regulate the renal production and serum concentration of 1,25(OH)2D, and provide evidence that this regulation is mediated by fine modulation of the serum concentration of phosphorus.
Role of oxidants in microbial pathophysiology (1997)

Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical, hypohalous acid, and nitric oxide) are involved in many of the complex interactions between the invading microorganism and its host. Regardless of the source of these compounds or whether they are produced under normal conditions or those of oxidative stress, these oxidants exhibit a broad range of toxic effects to biomolecules that are essential for cell survival. Production of these oxidants by microorganisms enables them to have a survival advantage in their environment. Host oxidant production, especially by phagocytes, is a counteractive mechanism aimed at microbial killing. However, this mechanism may be contribute to a deleterious consequence of oxidant exposure, i.e., inflammatory tissue injury. Both the host and the microorganism have evolved complex adaptive mechanisms to deflect oxidant-mediated damage, including enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the formation of reactive oxidant species in vivo and how they mediate many of the processes involved in the complex interplay between microbial invasion and host defense.
Engagement of NKG2D by Cognate Ligand or Antibody Alone Is Insufficient to Mediate Costimulation of Human and Mouse CD8+ T Cells (2005)

CD8+ T cells require a signal through a costimulatory receptor in addition to TCR engagement to become activated. The role of CD28 in costimulating T cell activation is well established. NKG2D, a receptor found on NK cells, CD8+ alphabeta-TCR+ T cells, and gammadelta-TCR+ T cells, has also been implicated in T cell costimulation. In this study we have evaluated the role of NKG2D in costimulating mouse and human naive and effector CD8+ T cells. Unexpectedly, in contrast to CD28, NKG2D engagement by ligand or mAb is not sufficient to costimulate naive or effector CD8+ T cell responses in conventional T cell populations. While NKG2D did not costimulate CD8+ T cells on its own, it was able to modify CD28-mediated costimulation of human CD8+ T cells under certain contitions. It is, therefore, likely that NKG2D acts as a costimulatory molecule only under restricted conditions or requires additional cofactors.
Chemotherapeutic agents, XXI: Synthesis of π‐deficient pyrimidines as leishmanicides (1991)

Synthesis of 5-cyano-6-(3-pyridyl)-2-thiouracil (1) has been described from 3-pyridinecarboxaldehyde, thiourea, and ethyl cyanoacetate. Alkylation of 1 with mono- and dihaloalkanes under different conditions, provided 2a,b, 3a,b, and 4a-i. Halogenation of 4g with POCl3 yielded 5 which underwent nucleophilic substitution with amines to give 6a-g. Fusion of 4a with aromatic and heterocyclic amines at 160 degrees C gave the substitution products 7a-c. Some of the compounds were screened for antileishmanial activity but only one of them (6d) demonstrated very significant activity.
Small nucleolar RNA interference induced by antisense or double-stranded RNA in trypanosomatids (2003)

In trypanosomes the C/D- and H/ACA-like small nucleolar RNAs (snoRNAs) are clustered and repeated in the genome. The snoRNAs studied to date are transcribed as polycistronic transcripts by RNA polymerase II and then processed, resulting in mature snoRNAs. In this study we demonstrated that snoRNA genes can be silenced in three trypanosomatid species: Leptomonas collosoma, Leishmania major, and Trypanosoma brucei. Silencing was achieved in L. collosoma and L. major by the expressing of an antisense transcript complementary to the snoRNA gene and was accompanied by the accumulation of small interfering RNA. Silencing eliminated the mature snoRNA but not its precursor and abolished the specific 2'-O-methylation guided by the snoRNA. In T. brucei, silencing was achieved by using the inducible synthesis of double-stranded RNA from T7 opposing promoters. Silencing varied between the different snoRNA genes, which may reflect the accessibility of small interfering RNA to the target RNAs. This study suggests that RNA interference can degrade snoRNAs. This study has further implications in elucidating the function of nucleolar RNAs and specific modifications guided by these RNAs in trypanosomatids and perhaps in other eukaryotes as well.
Genetic Interactions of DNA Repair Pathways in the PathogenNeisseria meningitidis (2007)

The current increase in the incidence and severity of infectious diseases mandates improved understanding of the basic biology and DNA repair profiles of virulent microbes. In our studies of the major pathogen and model organism Neisseria meningitidis, we constructed a panel of mutants inactivating genes involved in base excision repair, mismatch repair, nucleotide excision repair (NER), translesion synthesis, and recombinational repair pathways. The highest spontaneous mutation frequency among the N. meningitidis single mutants was found in the MutY-deficient strain as opposed to mutS mutants in Escherichia coli, indicating a role for meningococcal MutY in antibiotic resistance development. Recombinational repair was recognized as a major pathway counteracting methyl methanesulfonate-induced alkylation damage in the N. meningitidis. In contrast to what has been shown in other species, meningococcal NER did not contribute significantly to repair of alkylation-induced DNA damage, and meningococcal recombinational repair may thus be one of the main pathways for removal of abasic (apurinic/apyrimidinic) sites and strand breaks in DNA. Conversely, NER was identified as the main meningococcal defense pathway against UV-induced DNA damage. N. meningitidis RecA single mutants exhibited only a moderate decrease in survival after UV exposure as opposed to E. coli recA strains, which are extremely UV sensitive, possibly reflecting the lack of a meningococcal SOS response. In conclusion, distinct differences between N. meningitidis and established DNA repair characteristics in E. coli and other species were identified.
A 200-mW, 3.3-V, CMOS color camera IC producing 352×288 24-b video at 30 frames/s (1998)

A digital color camera has been monolithically realized in a standard 0.8-/spl mu/m CMOS technology. The chip integrates a 353/spl times/292 photogate sensor array with a unity-gain column circuit, a hierarchical column multiplexer, a switched-capacitor programmable-gain amplifier, and an 8-b flash analog/digital converter together with digital circuits performing color interpolation, color correction, computation of image statistics, and control functions. The 105-mm/sup 2/ chip produces 24-b RGB video at 30 frames/s. The sensor array achieves a conversion gain of 40 /spl mu/V/electron and a monochrome sensitivity of 7 V/lux/spl middot/s. For a 33-ms exposure time, the camera chip achieves a dynamic range of 65 dB and peak-to-peak fixed pattern noise that is 0.3% of saturation. Digital switching noise coupling into the analog circuits is shown to be data independent and therefore has no effect on image quality. Total power dissipation is less than 200 mW from a 3.3 V supply.
A Cluster Separation Measure (1979)

A measure is presented which indicates the similarity of clusters which are assumed to have a data density which is a decreasing function of distance from a vector characteristic of the cluster. The measure can be used to infer the appropriateness of data partitions and can therefore be used to compare relative appropriateness of various divisions of the data. The measure does not depend on either the number of clusters analyzed nor the method of partitioning of the data and can be used to guide a cluster seeking algorithm.
Influence of sapphire nitridation on properties of gallium nitride grown by metalorganic chemical vapor deposition (1996)

The properties of 1.2 μm thick GaN films were found to be significantly influenced by the duration of exposing the sapphire substrate to ammonia prior to the GaN growth initiation. The different nitridation schemes of sapphire strongly affect the dislocation structure of GaN films resulting in a decrease of the dislocation density from 2×1010 to 4×108 cm−2 for shorter NH3 preflow times. Room- and low-temperature electron transport characteristics of these films are specifically affected by the dislocation structure. A 300 K electron mobility as high as 592 cm2/V s was obtained for a short ammonia preflow whereas a long nitridation caused the mobility to drop to 149 cm2/V s. Additionally, the photoluminescence quality deteriorates for samples with a long sapphire nitridation time.
Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels (2007)

SCN(-) (thiocyanate) is an important physiological anion involved in innate defense of mucosal surfaces. SCN(-) is oxidized by H(2)O(2), a reaction catalyzed by lactoperoxidase, to produce OSCN(-) (hypothiocyanite), a molecule with antimicrobial activity. Given the importance of the availability of SCN(-) in the airway surface fluid, we studied transepithelial SCN(-) transport in the human bronchial epithelium. We found evidence for at least three mechanisms for basolateral to apical SCN(-) flux. cAMP and Ca(2+) regulatory pathways controlled SCN(-) transport through cystic fibrosis transmembrane conductance regulator and Ca(2+)-activated Cl(-) channels, respectively, the latter mechanism being significantly increased by treatment with IL-4. Stimulation with IL-4 also induced the strong up-regulation of an electroneutral SCN(-)/Cl(-) exchange. Global gene expression analysis with microarrays and functional studies indicated pendrin (SLC26A4) as the protein responsible for this SCN(-) transport. Measurements of H(2)O(2) production at the apical surface of bronchial cells indicated that the extent of SCN(-) transport is important to modulate the conversion of this oxidant molecule by the lactoperoxidase system. Our studies indicate that the human bronchial epithelium expresses various SCN(-) transport mechanisms under resting and stimulated conditions. Defects in SCN(-) transport in the airways may be responsible for susceptibility to infections and/or decreased ability to scavenge oxidants.
Receptor Activity-Modifying Proteins: RAMPing up Adrenomedullin Signaling (2006)

Adrenomedullin (AM) is a 52-amino-acid multifunctional peptide that circulates in the plasma in the low picomolar range and can exert a multitude of biological effects through an autocrine/paracrine mode of action. The mechanism by which AM transduces its signal represents a novel and pharmacologically tractable paradigm in G protein-coupled receptor signaling. Since its discovery in 1993, the study of AM has emerged into a new field of research with nearly 1800 publications that rivals the renown of other common factors like angiopoetin (1015 publications) and ghrelin (1550 publications). Despite the tremendous strides made in recent years toward unveiling the biochemical and cellular functions of AM, we are still lagging in our understanding of the essential roles of AM in normal and disease physiology. As discussed in this current review, a concerted effort to combine information from clinical, genomic, biochemical, and genetic mouse model sources can provide a focused view to help define the physiological functions of AM. Specifically, we find that certain conditions, such as pregnancy, cardiovascular disease, and sepsis, are associated with robust and dynamic changes in the expression of AM and AM receptor proteins, which together represent an elegant mechanism for altering the physiological responsiveness or function of AM. Thus, the modulation of AM signaling may be further exploited for therapeutic strategies in the management and treatment of human disease.
Factors that influence tadpole narcosis. An LFER analysis (1995)

Application of the new solvation equation to the results of Overton on tadpole narcosis yield the correlation given by eqn. (a), where Cnar is the narcotic concentration of solute in mol dm–3 and the log (1/Cnar)= 0.579 + 0.824R2– 0.334π2H– 2.871Σβ2o+ 3.097Vx(a) descriptors are R2 the solute excess molar refraction, π2H the solute dipolarity/polarizability, Σβ2o the solute hydrogen-bond basicity and Vx the solute volume. For 84 solutes, the correlation coefficient, ρ, is 0.9730 and the standard deviation, sd, is 0.246 log units. The above equation shows that the two main factors that influence tadpole narcosis are solute hydrogen-bond basicity that decreases toxicity and solute volume that increases toxicity. Solute hydrogen-bond acidity has no effect at all.The use of water–octanol partition coefficients as log P(oct) leads to the regression equation [eqn. (b)] log (1/Cnar)= 1.129 + 0.833log P(oct)(b) where ρ= 0.9212 and sd = 0.407 for the same 84 solutes. This equation is not improved by addition of [log P(oct)]2 as a descriptor, but it is if Vx is included [eqn. (c)]. Now ρ= 0.9400 and sd = 0.359 log (1/Cnar)= 0.621 + 0.743log P(oct)+ 0.668Vx(c) log units. When additional data are added to the Overton set, similar equations to the above are obtained for 114 varied solutes, showing that tadpole narcosis is a general phenomenon.Results on the narcosis of α,ω-diols and cycloalkanols can be interpreted using the analysis of Franks and Lieb. It is suggested that the anaesthetic binding site on the primary protein target is a large or flexible pocket, extending inward from the external water-facing surface, that is rather aqueous and of limited hydrophobicity.
Pyroglutamyl-aprotinin, a New Aprotinin Homologue from Bovine Lungs - Isolation, Properties, Sequence Analysis and Characterization Using1H Nuclear Magnetic Resonance in Solution (1987)

A new Kunitz-inhibitor, which is different from aprotinin was extracted from bovine lungs with methanol, further purified by affinity chromatography on trypsin-Sepharose CL-6B and by repeated cation exchange chromatography on CM-Sephadex C-25. The inhibitor, which is less basic than aprotinin was characterized by polyacrylamide gel electrophoresis and ion-exchange HPLC. The N-terminus is blocked by pyroglutamic acid (Glu-1). After enzymatic removal of this residue with pyroglutamate aminopeptidase, complete identity with the primary structure of aprotinin was established by sequencing the inhibitor, which had been oxidized with performic acid, and by sequencing a tryptic fragment. The occurrence of the inhibitor, which can be denoted as pyroglutamyl-aprotinin or Glu-1-aprotinin, but which cannot be distinguished from aprotinin regarding its inhibitory specificity, is obviously the result of a different proteolytic processing of the bovine aprotinin precursor. By using CD and NMR-techniques it was shown that the N-terminus of the inhibitor is blocked, and that the conformation and the internal mobility correspond with those of aprotinin.