gebhart/patrepeval huggingface dataset:
An Essential E Box in the Promoter of the Gene Encoding the mRNA Cap-Binding Protein (Eukaryotic Initiation Factor 4E) Is a Target for Activation by c-myc (1996)

The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate limiting for protein synthesis. Overexpression of eIF4E transforms cells, and mutations in eIF4E arrest cells in G, in cdc33 mutants. In this work, we identified the promoter region of the gene encoding eIF4E, because we previously identified eIF4E as a potential myc-regulated gene. In support of our previous data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in cotransfections with c-myc. A direct role for myc in activating the eIF4E promoter was demonstrated by cotransfections with two dominant negative mutants of c-myc (MycdeltaTAD and MycdeltaBR) which equally suppressed promoter function. Furthermore, electrophoretic mobility shift assays demonstrated quantitative binding to the E box motifs that correlated with myc levels in the electrophoretic mobility shift assay extracts; supershift assays demonstrated max and USF binding to the same motif. cis mutations in the core or flank of the eIF4E E box simultaneously altered myc-max and USF binding and inactivated the promoter. Indeed, mutations of this E box inactivated the promoter in all cells tested, suggesting it is essential for expression of eIF4E. Furthermore, the GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but unlike other targets, it is located in the immediate promoter region. Its critical function in the eIF4E promoter coupled with the known functional significance of eIF4E in growth regulation makes it a particularly interesting target for c-myc regulation.
Lipid mediator networks in cell signaling: update and impact of cytokines 1 (1996)

Biomembranes serve barrier functions and serve as a store for precursors of rapidly generated, structurally diverse intracellular and extracellular lipid-derived mediators (LM). Cell activation is accompanied by remodeling of membrane components that appear to be essential in signal transduction. Phospholipases (PLA2, PLC, PLD, sphingomyelinase) are pivotal in the generation of these LM including eicosanoids, platelet activating factor (PAF), diacylglycerides, ceramide, and other newly discovered bioactive autacoids. Cytokines exert a dramatic multilevel impact both in regulating enzymes in individual LM pathways and in generating LM central to their action. Here, we provide an overview and update of recent progress in this area with emphasis on the effect of cytokines on LM networks. The generation of eicosanoids (prostaglandins, leukotrienes, and lipoxins), oxygenated lipids, and PAF remain the focus of rational drug design targets given their established roles in cell-cell communication and as mediators in inflammation and pathophysiologic events. Key enzymes in these pathways are cloned, sequenced, and their subcellular organization is investigated with surprising findings implicating involvement of the nuclear membrane at the functional level. Several LM receptors are identified and cloned, and results from transgenic animals have emerged for several key enzymes. Novel bioactive eicosanoids were discovered, including 15-epi-lipoxins, isoprostanes, and isoleukotrienes, that offered new concepts to consider in formation of LM and the actions of nonsteroidal anti-inflammatory drugs. Together, these findings indicate that LM play critical and essential roles in both signal transduction and cell-cell communication and will continue to be important pathways to be considered in novel therapeutic approaches.-Serhan, C. N., Haeggström, J. Z., Leslie, C. C. Lipid mediator networks in cell signaling: update and impact of cytokines.
Automating Request-based Software Distribution (2000)

Permission is granted for noncommercial reproduction of the work for educational or research purposes.
Z-Selective Metathesis Homocoupling of 1,3-Dienes by Molybdenum and Tungsten Monoaryloxide Pyrrolide (MAP) Complexes (2012)

Molybdenum or tungsten monoaryloxide pyrrolide (MAP) complexes that contain OHIPT as the aryloxide (hexaisopropylterphenoxide) are effective catalysts for homocoupling of simple (E)-1,3-dienes to give (E,Z,E)-trienes in high yield and with high Z selectivities. A vinylalkylidene MAP species was shown to have the expected syn structure in an X-ray study. MAP catalysts that contain OHMT (hexamethylterphenoxide) are relatively inefficient.
The adhesion molecule and cytokine profile of multiple sclerosis lesions (1995)

The expression of the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and their respective receptors on leukocytes, very late activation antigen-4 (VLA-4) and lymphocyte function-associated antigen-1 (LFA-1), together with a selection of proinflammatory and immunomodulatory cytokines (interleukin [IL]-1, IL-2, IL-4, IL-10, tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], and interferon-gamma [IFN-gamma] was examined by immunocytochemistry in multiple sclerosis (MS) lesions of different ages and compared with central nervous system (CNS) tissue from other neurological diseases, both inflammatory and noninflammatory, and normal CNS tissue. These molecules play key roles in lymphocytic infiltration and interactions during tissue inflammation and are in large part normally not expressed by CNS cells. High levels of expression of all the molecules tested were found in MS, particularly in chronic active lesions. Positivity for all molecules was also seen in other neurological diseases, even in noninflammatory conditions. There was some suggestion that the VCAM-1/VLA-4 adhesion pathway was expressed at higher levels in chronic MS lesions, while ICAM-1/LEA-1 was used more uniformly in lesions of all ages. Of the cytokines examined, there was increased expression of TNF-alpha and IL-4 in MS; this was found to be statistically significant when compared with noninflammatory neurological diseases. The expression of most adhesion molecules and some cytokines was negligible in normal CNS tissue although low-level reactivity for ICAM-1 TGF-beta, IL-4, TNF-alpha, and IL-10 was detected, perhaps indicative of immunoregulatory mechanisms. Microglial cells and astrocytes were the major CNS cell types expressing cytokines. The results indicate a potential in the CNS for widespread induced expression of molecules involved in the inflammatory cascade. No adhesion or cytokine molecule or pattern of expression unusual for MS was apparent.
Autophagy Counterbalances Endoplasmic Reticulum Expansion during the Unfolded Protein Response (2006)

The protein folding capacity of the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR senses unfolded proteins in the ER lumen and transmits that information to the cell nucleus, where it drives a transcriptional program that is tailored to re-establish homeostasis. Using thin section electron microscopy, we found that yeast cells expand their ER volume at least 5-fold under UPR-inducing conditions. Surprisingly, we discovered that ER proliferation is accompanied by the formation of autophagosome-like structures that are densely and selectively packed with membrane stacks derived from the UPR-expanded ER. In analogy to pexophagy and mitophagy, which are autophagic processes that selectively sequester and degrade peroxisomes and mitochondria, the ER-specific autophagic process described utilizes several autophagy genes: they are induced by the UPR and are essential for the survival of cells subjected to severe ER stress. Intriguingly, cell survival does not require vacuolar proteases, indicating that ER sequestration into autophagosome-like structures, rather than their degradation, is the important step. Selective ER sequestration may help cells to maintain a new steady-state level of ER abundance even in the face of continuously accumulating unfolded proteins.
Cloning and characterization of the gene coding for cytoplasmic seryl-tRNA synthetase fromSaccharomyces cerevisiae (1987)

We have screened a Saccharomyces cerevisiae expression library with antibodies against seryl-tRNA synthetase (SerRS) from baker's yeast. In this way we obtained clones which contain serS, the structural gene for seryl-tRNA synthetase. Genomic Southern blots show that the serS gene resides on a 5.0 kb SalI fragment. Nucleotide sequence analysis of the genes revealed a single open reading frame from which we deduced the amino acid sequence of the enzyme consistent with that of two peptides isolated from SerRS. The enzyme is comprised of 462 amino acids consistent with earlier determinations of its molecular weight. The codon usage of serS is typical of abundant yeast proteins. Nuclease S1 analysis of serS mRNA defined the RNA initiation site 20-40 bases downstream from an AT rich sequence containing the TATA box and 21-39 nucleotides upstream of the translation initiation codon. Yeast strains transformed with the cloned gene overproduce seryl-tRNA synthetase in vivo.
Extensive Diversity of Ionizing-Radiation-Resistant Bacteria Recovered from Sonoran Desert Soil and Description of Nine New Species of the GenusDeinococcusObtained from a Single Soil Sample (2005)

The ionizing-radiation-resistant fractions of two soil bacterial communities were investigated by exposing an arid soil from the Sonoran Desert and a nonarid soil from a Louisiana forest to various doses of ionizing radiation using a (60)Co source. The numbers of surviving bacteria decreased as the dose of gamma radiation to which the soils were exposed increased. Bacterial isolates surviving doses of 30 kGy were recovered from the Sonoran Desert soil, while no isolates were recovered from the nonarid forest soil after exposure to doses greater than 13 kGy. The phylogenetic diversities of the surviving culturable bacteria were compared for the two soils using 16S rRNA gene sequence analysis. In addition to a bacterial population that was more resistant to higher doses of ionizing radiation, the diversity of the isolates was greater in the arid soil. The taxonomic diversity of the isolates recovered was found to decrease as the level of ionizing-radiation exposure increased. Bacterial isolates of the genera Deinococcus, Geodermatophilus, and Hymenobacter were still recovered from the arid soil after exposure to doses of 17 to 30 kGy. The recovery of large numbers of extremely ionizing-radiation-resistant bacteria from an arid soil and not from a nonarid soil provides further ecological support for the hypothesis that the ionizing-radiation resistance phenotype is a consequence of the evolution of other DNA repair systems that protect cells against commonly encountered environmental stressors, such as desiccation. The diverse group of bacterial strains isolated from the arid soil sample included 60 Deinococcus strains, the characterization of which revealed nine novel species of this genus.
Activation of a Rel-A/CEBP-?-related transcription factor heteromer by PGG-Glucan in a murine monocytic cell line (2000)

PGG-Glucan is a soluble beta-glucan immunomodulator that enhances a variety of leukocyte microbicidal activities without activating inflammatory cytokines. Although several different cell surface receptors for soluble (and particulate) beta-glucans have been described, the signal transduction pathway(s) used by these soluble ligands have not been elucidated. Previously we reported that PGG-Glucan treatment of mouse BMC2.3 macrophage cells activates a nuclear factor kappa-B-like (NF-kappaB) transcription factor complex containing subunit p65 (rel-A) attached to an unidentified cohort. In this study, we identify the cohort to be a non-rel family member: a CCAAT enhancer-binding protein-beta (C/EBP-beta)-related molecule with an apparent size of 48 kDa, which is a different protein than the previously identified C/EBP-beta p34 also present in these cells. C/EBP-beta is a member of the bZIP family whose members have previously been shown to interact with rel family members. This rel/bZIP heteromer complex activated by PGG-Glucan is different from the p65/p50 rel/rel complex induced in these cells by lipopolysaccharide (LPS). Thus, our data demonstrate that PGG-Glucan uses signal transduction pathways different from those used by LPS, which activates leukocyte microbicidal activities and inflammatory cytokines. We further show that heteromer activation appears to use protein kinase C (PKC) and protein tyrosine kinase (PTK) pathways, but not mitogen-activated protein kinase p38. Inhibitor kappa-B-alpha (IkappaB-alpha) is associated with the heteromer; this association decreases after PGG-Glucan treatment. These data are consistent with a model whereby treatment of BMC2.3 cells with PGG-Glucan activates IkappaB-alpha via PKC and/or PTK pathways, permitting translocation of the rel-A/CEBP-beta heteromer complex to the nucleus and increases its DNA-binding affinity.
Antagonistic Properties of Centrally Truncated Analogs of [d-Trp32]NPY (1996)

We have previously shown that [d-Trp32]NPY can competitively antagonize NPY-induced feeding in rats (Balasubramaniam et al. J. Med. Chem. 1994, 37, 811−815). This peptide, however, did not bind to SK-N-MC cells with Y-1 receptors. Since centrally truncated NPY analogs have been shown to bind Y-1 receptors, we synthesized similar analogs of [d-Trp32]NPY and investigated their Y-1 (SK-N-MC) and Y-2 (SK-N-BE2) receptor affinities and their properties in human erythroleukemia (HEL) cells. None of the analogs with d-Trp32 mobilized intracellular calcium, [Ca2+]i, in HEL cells. Although Des-AA6-24[Aoc6]NPY and the corresponding d-Trp32 analog exhibited no affinity to Y-1 receptors, Des- AA7-24[Aoc6,d-Trp32]NPY (6) exhibited weak binding. Replacing Pro5 in 6 with d-Ala to stabilize the central chain reversal, and hence the antiparallel alignment of the N- and C-terminal regions known to be important for Y-1 binding, resulted in an analog, Des-AA7-24[d-Ala5,Aoc6,d-Trp32]NPY (7), which exhibited moderate antagonist potency in attenuating NPY effects on cAMP and [Ca2+]i in SK-N-MC and HEL cells, respectively. This analog also shifted the dose−response curve of NPY on blood pressure in anesthetized rats. Deletion of only the 7−17 and/or the incorporation of N-Me-Ala5, a superior β-turn stabilizer, in 7 did not improve the Y-1 receptor affinity. Des-AA7-24[d-Ala5,Gly6,d-Trp32]NPY exhibited an affinity similar to that of 7, suggesting that a long spacer arm is not necessary for efficient Y-1 receptor interaction. Locking the antiparallel alignment via a 2/26 or 2/27 lactam bridge did not improve the binding. Finally, replacement of d-Ala5 in 7 with d-Trp dramatically increased both the binding and the antagonistic potencies. Modeling based on the avian pancreatic polypeptide X-ray structure suggested that analogs which have the N- and C-terminal regions in close proximity might exhibit good binding, and that the d-Trp32 substitution may induce a β-turn that could be important for exhibiting antagonism. A systematic investigation has resulted in the development of relatively potent Y-1 receptor antagonists. Further structure−activity studies with these compounds and those previously reported by us and other investigators should result in the development of long-acting and receptor selective antagonists.
Receptor Mechanisms Mediating Non-Genomic Actions of Sex Steroids (2007)

Sex steroid hormones, including estrogen, progesterone, and androgen, mediate their biological effects on cell proliferation, differentiation, and homeostasis through their respective nuclear receptors. In addition to functioning as ligand-activated nuclear transcription factors to regulate gene transcription, these receptors also have been shown to mediate rapid activation of non-genomic signaling pathways independent of their transcriptional activity. Despite the fact that non-genomic effects of sex steroids have been observed since more than three decades ago, the receptor mechanisms mediating these rapid effects still are not well understood. A subpopulation of nuclear steroid receptors localized to the cell membrane or cytoplasm has been proposed to mediate steroid hormone activation of signaling pathways; however, novel membrane receptors unrelated to nuclear receptors have also been implicated. This review focuses on recent advances in our understanding of the nature of the receptors and mechanisms responsible for rapid non-genomic signaling actions of sex steroids, including novel membrane receptors and interactions of nuclear steroid receptors with membrane and cytoplasmic signaling molecules such as adapter proteins, G proteins, ion channels, and protein kinases. A better definition of receptor mechanisms involved in mediating activation of non-genomic signaling pathways is important to our overall understanding of the biology of steroid hormones.
Experimental study and analytical model of deformation of magnetostrictive films as applied to mirrors for x-ray space telescopes (2014)

The desire for continuously gaining new knowledge in astronomy has pushed the frontier of engineering methods to deliver lighter, thinner, higher quality mirrors at an affordable cost for use in an x-ray observatory. To address these needs, we have been investigating the application of magnetic smart materials (MSMs) deposited as a thin film on mirror substrates. MSMs have some interesting properties that make the application of MSMs to mirror substrates a promising solution for making the next generation of x-ray telescopes. Due to the ability to hold a shape with an impressed permanent magnetic field, MSMs have the potential to be the method used to make light weight, affordable x-ray telescope mirrors. This paper presents the experimental setup for measuring the deformation of the magnetostrictive bimorph specimens under an applied magnetic field, and the analytical and numerical analysis of the deformation. As a first step in the development of tools to predict deflections, we deposited Terfenol-D on the glass substrates. We then made measurements that were compared with the results from the analytical and numerical analysis. The surface profiles of thin-film specimens were measured under an external magnetic field with white light interferometry (WLI). The analytical model provides good predictions of film deformation behavior under various magnetic field strengths. This work establishes a solid foundation for further research to analyze the full three-dimensional deformation behavior of magnetostrictive thin films.
Natural Language Processing (almost) from Scratch (2011)

We propose a unified neural network architecture and learning algorithm that can be applied to various natural language processing tasks including: part-of-speech tagging, chunking, named entity recognition, and semantic role labeling. This versatility is achieved by trying to avoid task-specific engineering and therefore disregarding a lot of prior knowledge. Instead of exploiting man-made input features carefully optimized for each task, our system learns internal representations on the basis of vast amounts of mostly unlabeled training data. This work is then used as a basis for building a freely available tagging system with good performance and minimal computational requirements.
Mutations in the SMAD4/DPC4 Gene in Juvenile Polyposis (1998)

Familial juvenile polyposis is an autosomal dominant disease characterized by a predisposition to hamartomatous polyps and gastrointestinal cancer. Here it is shown that a subset of juvenile polyposis families carry germ line mutations in the gene SMAD4 (also known as DPC4), located on chromosome 18q21.1, that encodes a critical cytoplasmic mediator in the transforming growth factor-beta signaling pathway. The mutant SMAD4 proteins are predicted to be truncated at the carboxyl-terminus and lack sequences required for normal function. These results confirm an important role for SMAD4 in the development of gastrointestinal tumors.
A novel organic solvent‐based coupling method for the preparation of covalently immobilized proteins on gold (1996)

A novel organic solvent-based coupling method has been developed for the covalent immobilization of biological material to gold surfaces. The method employs the polar organic solvent anhydrous 2,2,2-trifluoroethanol as the reaction medium and involves dissolution of the protein (catalase) in the solvent allowing protein coupling to proceed under basic conditions in a dry organic environment. The advantage of this method is that protein attachment is favored over hydrolysis of the coupling reagent. We have shown qualitatively and quantitatively that following attachment to the gold surface a significant proportion of the enzyme catalase remains catalytically active (at least 20-31%).
Tissue Transglutaminase Expression and Activity in Normal and Glaucomatous Human Trabecular Meshwork Cells and Tissues (2008)

This study demonstrated that both NTM and GTM cells express TGM2. In addition, TGM2 protein levels and enzyme activities were elevated in GTM cells. There was also an increase in colocalization of FN and GGEL protein in GTM tissues. These results indicate that TGM2 may play an important role in the pathogenesis of glaucoma by cross-linking ECM proteins such as FN and thus making the ECM more resistant to degradation.
Crystallographic and Magnetic Properties of Solid Solutions of the Phosphides M2P, M = Cr, Mn, Fe, Co, and Ni (1969)

Several phosphides with the chemical formula M2P crystallize in a hexagonal structure: Mn2P, Fe2P, and Ni2P. The structure of Co2P is orthorhombic. These two structures are related via an identical elementary subcell consisting of a tetrahedral-site and a pyramidal-site M-atom pair. This investigation shows that solid solutions between two hexagonal end members, such as Fe2P or Ni2P with Mn2P, may exhibit orthorhombic structures at intermediate compositions. Fe2P shows complete solid solubility with Ni2P. Curiously, hexagonal and orthorhombic symmetries alternate with decreasing number of 3d electrons, Ni2P(hex) -Co2P(ortho) -Fe2P(hex) -FeMnP(ortho) -Mn2P(hex). Lattice parameter variations with composition and Mössbauer studies reveal atomic ordering in the mixed systems, Mn and Cr substituting for pyramidal-site iron in FeMnP and FeCrP while Ni and Co substitute preferentially for tetrahedralsite iron in FeCoP and FeNiP. While neither Co2P nor Mn2P are ferromagnetic, intermediate phases are, the Curie temperature and magnetization reaching the maximum values 310°C and 3.03 μB/molecule for MnCoP. Metamagnetism appears for a range of compositions about (Mn0.7Co0.3)2P. The Co2P-Fe2P system is also ferromagnetic with a maximum Curie temperature near FeCoP. This system shows a sharp discontinuity in magnetization, but only a small discontinuity in Curie temperature, across the phase transition. Sensitivity to stoichiometry in the magnetization of Fe2-εP is attributed to an electron/atom ratio near that for the appearance of metamagnetism.