gebhart/patrepeval huggingface dataset:
Signaling by insulin-like growth factors in paralyzed skeletal muscle: rapid induction of IGF1 expression in muscle fibers and prevention of interstitial cell proliferation by IGF-BP5 and IGF-BP4 (1994)

In the absence of muscle activity, muscle fibers, muscle interstitial cells, and intramuscular nerves display characteristic reactions presumably aimed at restoring a functioning neuromuscular system and avoiding degenerative events. In partially denervated muscle these include proliferation of interstitial cells, followed by nerve sprouting. The same reactions can be induced in intact muscle by elevation of intramuscular insulin-like growth factor (IGF) levels. To determine whether IGFs may participate in the initiation of restorative reactions in inactivated muscle we analyzed the expression of IGF1 and IGF2 mRNA in botulinum toxin-paralyzed and in denervated rat skeletal muscle, and interfered with the activity of IGFs by locally applying the IGF-binding proteins IGF-BP5 and IGF-BP4. To obtain a resolution of the in situ hybridization signals at the cellular level, a nonradioactive method based on digoxigenin-labeled probes was applied. We found that muscle fiber IGF1 mRNA increased rapidly and transiently in inactivated muscle. The time course of this response was similar to that reported for ACh receptor subunits and myogenins. A similar behavior was observed for the corresponding IGF1 protein. The IGF1 response coincided with the transient muscle interstitial cell proliferation reaction. Local application of recombinant IGF-BP5 or IGF-BP4, which are endogenous and specific extracellular ligands of IGFs, prevented the stimulation of interstitial cell proliferation in paralyzed muscle. Our data demonstrate the elevated production of the growth factor IGF1 among early reactions in electrically inactive skeletal muscle fibers and indicate that muscle IGFs are required for the induction of intramuscular interstitial cell proliferation. These findings support the hypothesis that in the neuromuscular system IGF1 plays an important role in initiating cellular reactions in the vicinity of inactive muscle fibers.
Engineered cyanobacteria: Teaching an old bug new tricks (2011)

Cyanobacteria have played an important role in the development of the Earth and have long been studied as model organisms for photosynthesis and the circadian rhythm. Recent developments have led to increased interest in the use of engineered cyanobacteria for the production of protein and chemical products. This review highlights the genetic tools and strategies for manipulation of cyanobacteria as well as previous accomplishments in the development of engineered cyanobacteria for applied use. Particular attention is given to the engineering of cyanobacteria for biofuel production, including both hydrocarbon and hydrogen fuels. Genetic engineering efforts to enhance cyanobacterial fitness are reviewed with an emphasis on physiological improvements for large-scale production. Lastly, a future outlook on engineered cyanobacteria is presented, highlighting the future areas of focus and technical challenges in this field. With the uncertainty of future energy security, it is an exciting time in applied cyanobacterial research, but we must take the time to learn from these past accomplishments before we can capitalize on the potential of these photosynthetic microorganisms.
Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin (1999)

Evidence suggests that nerve growth factor (NGF) is an important mediator in inflammatory pain states: NGF levels increase in inflamed tissue, and neutralization of endogenous NGF prevents the hyperalgesia which normally develops during inflammation of the skin. Here we asked whether NGF contributes to sensitization of primary afferent nociceptors, which are an important component of pain and hyperalgesia in inflamed tissue. An in vitro skin nerve preparation of the rat was used to directly record the receptive properties of thin myelinated (Adelta) and unmyelinated (C) nociceptors innervating normal hairy skin, carrageenan-inflamed skin and carrageenan-inflamed skin where endogenous NGF had been neutralized by application of a trkA-IgG (tyrosine kinase Aimmunoglobulin G) fusion molecule. Following carrageenan inflammation, there was a marked increase in the proportion of nociceptors which displayed ongoing activity (50% of nociceptors developed spontaneous activity compared to 4% of nociceptors innervating normal uninflamed skin), and this was reflected in a significant increase in the average ongoing discharge activity. Spontaneously active fibres were sensitized to heat and displayed a more than twofold increase in their discharge to a standard noxious heat stimulus. Furthermore, the number of nociceptors responding to the algesic mediator bradykinin increased significantly from 28% to 58%. By contrast, the mechanical threshold of nociceptive afferents did not change during inflammation. When the NGF-neutralizing molecule trkA-IgG was coadministered with carrageenan at the onset of the inflammation, primary afferent nociceptors did not sensitize and displayed essentially normal response properties, although the inflammation as evidenced by tissue oedema developed normally. We therefore conclude that NGF is a crucial component for the sensitization of primary afferent nociceptors associated with tissue inflammation.
Asthma phenotypes identified by latent class analysis in the ISAAC phase II Spain study (2012)

LCA on reported symptoms in a cross-sectional survey allowed different subgroups with meaningful clinical correlates to be defined. It remains to be investigated to what extent these groups also have different aetiologies, prognoses and therapeutic needs.
Statistical considerations for digital approaches to non-invasive fetal genotyping (2010)

With this in mind, we have undertaken a statistical modeling of three contemporary (digital) analytical methods in the context of prenatal diagnosis using cell free DNA for monogenic diseases that segregate in a recessive mendelian fashion. We provide an experimental framework for the future development of diagnostic methods in this context that should be considered when designing molecular assays that seek to establish proof of concept in this field.
Characterization of the Binding of Different Conformational Forms of Plasminogen Activator Inhibitor-1 to Vitronectin (1997)

Plasminogen activator inhibitor type 1 (PAI-1), the primary physiologic inhibitor of plasminogen activation, is associated with the adhesive glycoprotein vitronectin (Vn) in plasma and the extracellular matrix. In this study we examined the binding of different conformational forms of PAI-1 to both native and urea-purified vitronectin using a solid-phase binding assay. These results demonstrate that active PAI-1 binds to urea-purified Vn with approximately 6-fold higher affinity than to native Vn. In contrast, inactive forms of PAI-1 (latent, elastase-cleaved, synthetic reactive center loop peptide-annealed, or complexed to plasminogen activators) display greatly reduced affinities for both forms of adsorbed Vn, with relative affinities reduced by more than 2 orders of magnitude. Structurally, these inactive conformations all differ from active PAI-1 by insertion of an additional strand into beta-sheet A, suggesting that it is the rearrangement of sheet A that results in reduced Vn affinity. This is supported by the observation that PAI-1 associated with beta-anhydrotrypsin, which does not undergo rearrangement of beta-sheet A, shows no such decrease in affinity, whereas PAI-1 complexed to beta-trypsin, which does undergo sheet A rearrangement, displays reduced affinity for Vn similar to PAI-1.plasminogen activator complexes. Together these data demonstrate that the interaction between PAI-1 and Vn depends on the conformational state of both proteins and suggest that the Vn binding site on PAI-1 is sensitive to structural changes associated with loss of inhibitory activity.
Transactivation of the grp78 promoter by Ca2+ depletion. A comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin (1993)

The calcium ionophore A23187 has been shown to induce the expression of a set of glucose-regulated protein (GRP) genes through the depletion of Ca2+ from the intracellular Ca2+ stores. Here we demonstrate that thapsigargin, which inhibits specifically the endoplasmic reticulum Ca(2+)-ATPase and causes a discharge of the intracellular Ca2+ store, is able to induce the transcription of two grp genes (grp78/BiP and grp94) with kinetics and magnitude similar to that of A23187. The induction of the grp genes by both reagents requires several hours of sustained treatment, in contrast to the rapid induction previously described for c-jun and c-fos. The transactivation of the rat grp78 promoter by A23187 is mediated through sequences spanning -154 to -130 and -99 to -90. Further, simultaneous mutation of two 10-base pair regions, spanning -139 to -130 and -99 to -90, severely reduced the A23187 response. The induction by thapsigargin is also partially mediated through these same promoter elements, without the involvement of the TRE and CRE-like elements of the grp78 promoter. The Ca2+ response elements are further defined by their ability to confer Ca2+ stress inducibility to a heterologous promoter. We show that subdomains of the grp78 promoter are capable of conferring the Ca2+ stress response. In particular, two copies of a 50-base pair region spanning -159 to -110, when cloned in either orientation, can confer a 5- and 9-fold induction by A23187 and thapsigargin, respectively. Our results lend support to the hypothesis that the induction of grp78 by A23187 and thapsigargin following ER Ca2+ discharge acts through a novel pathway in which a Ca2+ signal is transduced through redundant elements containing CCAAT box-like motifs flanked by GC-rich regions.
Classification of Serotonin Receptors (1987)

The subdivision of serotonin (5-HT) receptors into three classes, designated 5-HT1, 5-HT2, and 5-HT3, has been based on radioligand binding studies and experiments in isolated tissues. As a result of radioligand binding studies, two types of 5-HT recognition sites have been postulated. One site specifically labeled by [3H]5-HT was termed 5-HT1, and the other one labeled by [3H]spiperone or [3H]ketanserin was designated 5-HT2. The pharmacological properties of the latter sites are obviously identical to those of the majority of the classical "D" receptors, whereas a smaller proportion of "D" receptors resemble the 5-HT1 type. Hence, according to the current definition, 5-HT1 and 5-HT2 receptors mediate effects previously ascribed to "D" receptors. Three subtypes of 5-HT1 binding sites, designated 5-HT1A, 5-HT1B, and 5-HT1C, can now be distinguished by improved binding assay with rather selective radioligands. The identity of a given 5-HT binding site with a 5-HT receptor was suggested by correlating the agonists' and antagonists' affinities for the binding site with their potencies to produce certain effects. This was further confirmed by the development of rather selective agonists and antagonists. A third class of 5-HT receptors, the "M" receptors, which are now designated 5-HT3 in order to distinguish them from muscarinic cholinoceptors, were identified in functional in vitro experiments. They are present on terminals of sympathetic and parasympathetic nerves and on afferent nerve fibers. All three receptor classes are involved in cardiovascular regulation.
Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra‐cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum (2007)

The omentum is a major site of ovarian cancer metastasis. Our goal was to establish a three-dimensional (3D) model of the key components of the omental microenvironment (mesothelial cells, fibroblasts and extracellular matrices) to study ovarian cancer cell adhesion and invasion. The 3D model comprised of primary human fibroblasts extracted from normal human omentum, mixed with ECM and covered by a layer of primary human mesothelial cells, also from normal human omentum. After addition of ovarian cancer cells, the histological appearance of the 3D culture mimicked microscopic metastases to the omentum from patients with ovarian cancer. When ovarian cancer cells, SKOV3ip.1 and HeyA8, were applied to the 3D omental culture, 60% and 68% of all cells attached, respectively, but only 18% and 25% were able to invade. Ovarian cancer cells preferentially adhered to and invaded collagen I, followed by binding to collagen IV, fibronectin, vitronectin, laminin 10 and 1. Omental mesothelial cells significantly inhibited ovarian cancer cell adhesion and invasion, while omental fibroblasts induced adhesion and invasion. This effect is clearly mediated by direct cell-cell contact, since conditioned medium from mesothelial cells or fibroblasts has a minimal, or no, effect on ovarian cancer cell adhesion and invasion. In summary, we have established a 3D model to study the early steps of ovarian cancer metastasis to the human omentum, and found that omental mesothelial cells inhibit, while omental fibroblasts and the ECM enhance, the attachment and invasion of ovarian cancer cells.
Data Compression of Large Document Data Bases (1975)

Consideration is given to a document data base that is structured for information retrieval purposes by means of an inverted index and term dictionary. Vocabulary characteristics of various fields are described, and it is shown how the data base may be stored in a compressed form by use of restricted variable length codes that produce a compression not greatly in excess of the optimum that could be achieved through use of Huffman codes. The coding is word oriented. An alternative scheme of word fragment coding is described. It has the advantage that it allows the use of a small dictionary, but is less efficient with respect to compression of the data base.
Semisynthetic Enzymes in Asymmetric Synthesis:  Enantioselective Reduction of Racemic Hydroperoxides Catalyzed by Seleno-Subtilisin (1999)

The serine protease subtilisin was chemically converted into the peroxidase-active seleno-subtilisin. This semisynthetic enzyme catalyzes the enantioselective reduction of racemic hydroperoxides in the presence of thiophenols to yield optically active hydroperoxides and alcohols on the semipreparative scale. The kinetic parameters and enantioselectivities of seleno-subtilisin-catalyzed reduction of various chiral hydroperoxides were determined. The catalytic efficiency of this semisynthetic enzyme is comparable to that of the native horseradish peroxidase. The sense in the enantioselectivity of the seleno-subtilisin is opposite to the natural enzymes previously used in the synthesis of optically active hydroperoxides. Consequently, the semisynthetic enzyme seleno-subtilisin complements the naturally available peroxidases for the asymmetric synthesis of both enantiomers.
Structure and binding kinetics of three different human CD1d–α-galactosylceramide–specific T cell receptors (2006)

Invariant human TCR Valpha24-Jalpha18+/Vbeta11+ NKT cells (iNKT) are restricted by CD1d-alpha-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d-alpha-GalCer-specific Vbeta11+ TCRs that use different TCR Valpha chains. The results were similar to those previously reported for MHC-peptide-specific TCRs, illustrating the versatility of the TCR platform. Docking TCR and CD1d-alpha-GalCer structures provided plausible insights into their interaction. The model supports a diagonal orientation of TCR on CD1d and suggests that complementarity determining region (CDR)3alpha, CDR3beta, and CDR1beta interact with ligands presented by CD1d, whereas CDR2beta binds to the CD1d alpha1 helix. This docking provides an explanation for the dominant usage of Vbeta11 and Vbeta8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-alpha-GalCer.
Growth anisotropy and self-shadowing: A model for the development of in-plane texture during polycrystalline thin-film growth (1997)

The development of a preferred crystallographic orientation in the plane of growth, an in-plane texture, is addressed in a model that incorporates anisotropic growth rates of a material and self-shadowing. Most crystalline materials exhibit fast growth along certain crystallographic directions and slow growth along others. This crystallographic growth anisotropy, which may be due to differences in surface free energy and surface diffusion, leads to the evolution of specific grain shapes in a material. In addition, self-shadowing due to an obliquely incident deposition flux leads to a variation in in-plane grain growth rates, where the “fast” growth direction is normal to the plane defined by the substrate normal and the incident flux direction. This geometric growth anisotropy leads to the formation of elongated grains in the plane of growth. Neither growth anisotropy alone can explain the development of an in-plane texture during polycrystalline thin-film growth. However, whenever both are present (i.e., oblique incidence deposition of anisotropic materials), an in-plane texture will develop. Grains that have “fast” crystallographic growth directions aligned with the “fast” geometric growth direction overgrow grains that do not exhibit this alignment. Furthermore, the rate of texturing increases with the degree of each anisotropy. This model was used to simulate in-plane texturing during thin-film deposition. The simulation results are in excellent quantitative agreement with recent experimental results concerning the development of in-plane texture in sputter deposited Mo films.
Neurotensin Receptor 1 Determines the Outcome of Non–Small Cell Lung Cancer (2010)

NTSR1 expression was identified as a potential new prognostic biomarker for surgically resected stage I lung adenocarcinomas, as NTSR1 activation was shown to participate in lung cancer progression.
Advancing polymer process understanding in package and board applications through molecular modeling (2002)

In this paper we will discuss two molecular modeling methods which have been developed and applied at Honeywell to help predict material behavior from the process engineer's standpoint. Both stress cycling and process analyses have been used to trend the probable behavior of material types in order to provide advanced intelligence on possible failure mechanisms. For instance, we have found that there are similarities in the response trends to strain and the number of cycles which suggests a link exists between the molecular-scale mechanism and engineering theories of reliability. That is, the cycling response on a molecular scale appears to be Coffin-Manson-like. On a similar scale, the molecular response of polymer chains to process stress induced either thermally or mechanically has shown to give insight to the response from actual processed parts.
Complexes formed by (pyrimidine)n·(purine)nDNAs on lowering the pH are three-stranded (1979)

(Pyrimidine)n . (purine)n DNAs of repeating sequences form a distinctive complex on lowering the pH below 6. Previously this complex was thought to be tetra-stranded. The present work is inconsistent with this view, and four lines of evidence show that the complex consists of a triplex together with a poly d(purine) possessing secondary structure. Formula: (see text). (a) S1 nuclease digestion leads to degradation of 50% of the poly d(purine) content of the pH 5-induced complex. (b) Buoyant density studies demonstrate that there is no interaction between the triplex and added free poly d(purine) and also that the complex formed from duplex DNA contained poly d(purine) which is free to form a triplex on addition of an appropriate poly d(pyrimidine) in the correct stoichiometry. (c) The hyperchromic shifts of the triplex and poly d(purine), upon melting, are mutually independent. (d) The circular dichroism spectrum of the complex is simply the weighted average of a triplex together with a free poly d(purine). The triplexes have tm's approximately 20 degrees higher than the corresponding duplexes under comparable conditions and they are extremely resistant to various deoxyribonucleases; properties which may prove useful for their isolation from natural sources.
WebSifter: an ontology-based personalizable search agent for the Web (2002)

The World Wide Web provides access to a great deal of information on a vast array of subjects. In a typical Web search a vast amount of information is retrieved. The quantity can be overwhelming, and much of the information may be marginally relevant or completely irrelevant to the user's request. We present a methodology, architecture, and proof-of-concept prototype for query construction and results analysis that provides the user with a ranking of choices based on the user's determination of importance. The user initially designs the query with assistance from the user's profile, a thesaurus, and previously constructed queries acting as a taxonomy of the information requirements. After the query has returned its results, decision analytic methods and information source reliability information are used in conjunction with the expanded taxonomy to rank the solution candidates.
Identification of an Enhancer Sequence within the First Intron Required for Cartilage-specific Transcription of the α2(XI) Collagen Gene (2000)

Type XI collagen, a heterotrimer composed of alpha1(XI), alpha2(XI) and alpha3(XI), is primarily synthesized by chondrocytes in cartilage and is also present in some other tissues. Type XI collagen plays a critical role in collagen fibril formation and skeletal morphogenesis. We investigated a tissue-specific transcriptional enhancer in the first intron of the alpha2(XI) collagen gene (Col11a2). Transient transfection assays using reporter gene constructs revealed that a 60-base pair (bp) segment within intron 1 increased promoter activity of Col11a2 in rat chondrosarcoma cells but not in either BalB/3T3 cells or undifferentiated ATDC5 cells, suggesting that it contained cell type-specific enhancer activity. In transgenic mice, this 60-bp fragment was also able to target beta-galactosidase expression to cartilage including the limbs and axial skeleton, with similar localization specificity as the full-length intron 1 fragment. Competition experiments in gel shift assays using mutated oligonucleotides showed that recombinant Sox9 bound to a 7-bp sequence, CTCAAAG, within the 60-bp segment. Anti-Sox9 antibodies supershifted the complex of the 60-bp segment with recombinant Sox9 or with rat chondrosarcoma cell extracts, confirming the binding of Sox9 to the enhancer. Moreover, a site-specific mutation within the 7-bp segment resulted in essentially complete loss of the enhancer activity in chondrosarcoma cells and transgenic mice. These results suggest that the 7-bp sequence within intron 1 plays a critical role in the cartilage-specific enhancer activity of Col11a2 through Sox9-mediated transcriptional activation.