gebhart/patrepeval huggingface dataset:
Old and new tools to dissect calcineurin's role in pressure-overload cardiac hypertrophy (2002)

In the last several years, a number of experiments have implicated a pivotal role of the calcium/calmodulin-calcineurin dependent pathway as a final common signaling mechanism by which diverse hypertrophic stimuli converge to mediate hypertrophic responses in cardiomyocytes. Calcineurin inhibitors, i.e. cyclosporine A (CsA) and FK506, can interrupt the pathway, thereby preventing cardiac hypertrophy. The data that convincingly support this novel hypothesis were derived either from in vitro studies in cultured cardiomyocytes or from in vivo studies in transgenic mice. However, when the hypothesis was tested in clinically relevant animal models of cardiac hypertrophy, controversial results and conclusions emerged. In conventional models of cardiac hypertrophy, two questions remain to be answered: (1) whether calcineurin is activated in hypertrophied cardiac muscle, and (2) whether calcineurin inhibitors prevent cardiac hypertrophy. In addition, clinical observations have revealed that calcineurin inhibitors appear to exert pro-hypertrophic effects in organ transplant recipients. The controversies suggest that current calcineurin inhibitors are blunt tools for testing the hypothesis in pressure-overload hypertrophy in vivo, because there are so many confounding effects that are associated with systemic administration of the drugs. As such, new genetic approaches may overcome some of the problems associated with pharmacological inhibitors. This invited review will focus on the controversies surrounding the ability of calcineurin inhibition to prevent conventional (pressure-overload) cardiac hypertrophy and the new genetic approaches to address the question.
The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains (2016)

An expanded GGGGCC hexanucleotide in <i>C9ORF72</i> (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It has been proposed that expanded transcripts adopt G-quadruplex (G-Q) structures and associate with proteins, but whether this occurs and contributes to disease is unknown. Here we show first that the protein that predominantly associates with GGGGCC repeat RNA in vitro is the splicing factor hnRNP H, and that this interaction is linked to G-Q formation. We then show that G-Q RNA foci are more abundant in C9 ALS patient fibroblasts and astrocytes compared to those without the expansion, and more frequently colocalize with hnRNP H. Importantly, we demonstrate dysregulated splicing of multiple known hnRNP H-target transcripts in C9 patient brains, which correlates with elevated insoluble hnRNP H/G-Q aggregates. Together, our data implicate C9 expansion-mediated sequestration of hnRNP H as a significant contributor to neurodegeneration in C9 ALS/FTD.
Modeling of laser thermoelastic generation of ultrasound in an orthotropic medium (1994)

We present a numerical model that calculates the surface displacements generated by the absorption of a laser pulse by an orthotropic medium. This model solves the heat and acoustic wave equations using temporal Laplace and spatial two-dimensional Fourier transformations. This model allows us to calculate the normal and in-plane displacements on the front or back surface of an orthotropic plate over a complete area and for virtually any time and beam profiles of the laser excitation. Numerical simulations are compared to experimental results obtained on an aluminum sample and on a graphite-epoxy plate. The experimental and numerical results are in good agreement.
Topographical and Conformational Epitopes of Bovine Papillomavirus Type 1 Defined by Monoclonal Antibodies<xref ref-type="fn" rid="FN2">2</xref> (1987)

Monoclonal antibodies (MAbs) were generated against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (BPV-1). When screened by enzyme-linked immunosorbent assay (ELISA) on intact and disrupted BPV-1, -2, and deer papillomavirus, three patterns of reactivity were defined: reactivity only with intact virus, with both intact and disrupted virus, and only with disrupted virus. On the basis of ELISA results, the topographical location and requirement for conformation for immunoreactivity of epitopes was defined as external conformational, external linear, and internal linear. Cross-reactivity of MAbs with other papillomavirus types was analyzed by immunofluorescence on warts from different species. Type-specific, BPV-1 and/or -2 cross-reactive, broadly cross-reactive, and genus-specific MAbs were identified. MAb reactivity with structural polypeptides of BPV-1 was analyzed by Western blot. MAbs reactive with epitopes defined as conformational by ELISA did not react in Western blot. All MAbs reactive in Western blot reacted with the major capsid protein (MCP) [55 kilodalton (kDa)], demonstrating that the MCP carries both type-specific and cross-reactive epitopes. Most MAbs reactive with the MCP were cross-reactive with structural polypeptides of 48 and 96 kDa, demonstrating the immunologic relatedness of these three polypeptides.
Psychiatric comorbidity in patients with generalized anxiety disorder (1993)

These results support previous findings of high rates of psychiatric comorbidity in generalized anxiety disorder and validate the usefulness of generalized anxiety disorder as a separate diagnostic entity.
Crystal engineering of binary metal imidazolate and triazolate frameworks (2006)

This article summarizes the recent advances in the crystal growth, structural control strategies and diverse structures of the binary metal imidazolate and triazolate frameworks, which are the simplest systems for crystal engineering of two-, three- and four-connected coordination polymers.
Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors (2014)

Cancer diagnosis is typically delayed to the late stages of disease due to the asymptomatic nature of cancer in its early stages. Cancer screening offers the promise of early cancer detection, but most conventional diagnostic methods are invasive and remain ineffective at early detection. Breath analysis is, however, non-invasive and has the potential to detect cancer at an earlier stage by analyzing volatile biomarkers in exhaled breath. This paper summarizes breath sampling techniques and recent developments of various array-based sensor technologies for breath analysis. Significant advancements were made by a number of different research groups in the development of nanomaterial-based sensor arrays, and the ability to accurately distinguish cancer patients from healthy controls based on the volatile organic compounds (VOCs) in exhaled breath has been demonstrated. Optical sensors based on colorimetric sensor array technology are also discussed, where preliminary clinical studies suggest that metabolic VOC profiles could be used to accurately diagnose various forms of lung cancer. Recent studies have demonstrated the potential of using metabolic VOCs for cancer detection, but further standardization and validation is needed before breath analysis can be widely adopted as a clinically useful tool.
Distributed photoacoustic system for cure monitoring of composites (2001)

In this paper we describe a laser ultrasonic system for real-time monitoring of the degree of cure of a graphite-epoxy composite part during manufacturing. The system is integrated with a Resin-Transfer Molding (RTM) machine, and contains (i) a fiberized laser ultrasonic source, and (ii) an embedded ultrasonic sensor based on an intrinsic fiber optic Sagnac interferometer. Bulk ultrasonic waves generated by the laser source are transmitted into the composite structure and are subsequently detected by the embedded ultrasonic sensor. The degree of cure can be obtained from measurements of ultrasonic velocity and attenuation in the composite part. The use of an optical switch in the fiber optic delivery system of the laser ultrasonic source allows ultrasonic generation at several locations of the composite part. In this paper we discuss the design of the laser ultrasonic source and the sensor optimized for cure monitoring applications, and their integration with the RTM mold. The results of ultrasonic measurements during manufacturing of a composite specimen are presented. Our results show that laser ultrasonics offer distinct advantages for manufacturing of modern composite structures including the ability to operate in a high temperature and high pressure environment and provide distributed sensing that can cover critical areas of a component.
Effects of salt bridges on protein structure and design (1998)

Theoretical calculations (Hendsch ZS & Tidor B, 1994, Protein Sci 3:211-226) and experiments (Waldburger CD et al., 1995, Nat Struct Biol 2:122-128; Wimley WC et al., 1996, Proc Natl Acad Sci USA 93:2985-2990) suggest that hydrophobic interactions are more stabilizing than salt bridges in protein folding. The lack of apparent stability benefit for many salt bridges requires an alternative explanation for their occurrence within proteins. To examine the effect of salt bridges on protein structure and stability in more detail, we have developed an energy function for simple cubic lattice polymers based on continuum electrostatic calculations of a representative selection of salt bridges found in known protein crystal structures. There are only three types of residues in the model, with charges of -1, 0, or + 1. We have exhaustively enumerated conformational space and significant regions of sequence space for three-dimensional cubic lattice polymers of length 16. The results demonstrate that, while the more highly charged sequences are less stable, the loss of stability is accompanied by a substantial reduction in the degeneracy of the lowest-energy state. Moreover, the reduction in degeneracy is greater due to charges that pair than for lone charges that remain relatively exposed to solvent. We have also explored and illustrated the use of ion-pairing strategies for rational structural design using model lattice studies.
Differential Tag Clouds: Highlighting Particular Features in Documents (2009)

This paper introduces the concepts of “summary tag cloud” and “differential tag cloud”. A summary tag cloud is a unique tag cloud that summarizes the contents of all the documents in a set. A differential tag cloud is a tag cloud that highlights the particular features of each document with regard to the summary tag cloud. We also present a general abstract procedure to automatically generate tag clouds and a specific implementation that exemplifies our ideas
DNA Sequences That Activate Isocitrate Lyase Gene Expression during Late Embryogenesis and during Postgerminative Growth (1996)

We analyzed DNA sequences that regulate the expression of an isocitrate lyase gene from Brassica napus L. during late embryogenesis and during postgerminative growth to determine whether glyoxysomal function is induced by a common mechanism at different developmental stages. beta-Glucuronidase constructs were used both in transient expression assays in B. napus and in transgenic Arabidopsis thaliana to identify the segments of the isocitrate lyase 5' flanking region that influence promoter activity. DNA sequences that play the principal role in activating the promoter during post-germinative growth are located more than 1,200 bp upstream of the gene. Distinct DNA sequences that were sufficient for high-level expression during late embryogenesis but only low-level expression during postgerminative growth were also identified. Other parts of the 5' flanking region increased promoter activity both in developing seed and in seedlings. We conclude that a combination of elements is involved in regulating the isocitrate lyase gene and that distinct DNA sequences play primary roles in activating the gene in embryos and in seedlings. These findings suggest that different signals contribute to the induction of glyoxysomal function during these two developmental stages. We also showed that some of the constructs were expressed differently in transient expression assays and in transgenic plants.
Validation of the Female Sexual Distress Scale-Revised for Assessing Distress in Women with Hypoactive Sexual Desire Disorder (2007)

Consistent with the FSDS, the FSDS-R demonstrated good discriminant validity, high test-retest reliability, and a high degree of internal consistency in measuring sexually related personal distress in women with HSDD. FSDS-R item 13 alone also demonstrated good discriminant validity and test-retest reliability.
The Molecular Physiology of Hepatic Nuclear Factor 3 in the Regulation of Gluconeogenesis (2000)

Glucocorticoids stimulate gluconeogenesis by increasing the rate of transcription of genes that encode gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase. Previous studies have shown that hepatic nuclear factor 3 (HNF3) is required as an accessory factor for several glucocorticoid-stimulated genes, including PEPCK. Here, we show that adenovirus-mediated expression of an HNF3beta protein with a deleted C-terminal transactivation domain (HNF3betaDeltaC) reduces the glucocorticoid-induced expression of the PEPCK and glucose-6-phosphatase genes in H4IIE hepatoma cells. Furthermore, expression of this truncated HNF3 protein results in a proportionate reduction of glucocorticoid-stimulated glucose production from lactate and pyruvate in these cells. The expression of HNF3betaDeltaN, in which the N-terminal transactivation domain is deleted, does not exhibit any of these effects. These results provide direct evidence that members of the HNF3 family are required for proper regulation of hepatic gluconeogenesis. Modulation of the function of the HNF3 family of proteins might be used to reduce the excessive hepatic production of glucose that is an important pathophysiologic feature of diabetes mellitus.
Mapping the Determinants of the CCR5 Amino-Terminal Sulfopeptide Interaction with Soluble Human Immunodeficiency Virus Type 1 gp120-CD4 Complexes (2001)

CD4 and CCR5 mediate fusion and entry of R5 human immunodeficiency virus type 1 (HIV-1) strains. Sulfotyrosine and other negatively charged residues in the CCR5 amino-terminal domain (Nt) are crucial for gp120 binding and viral entry. We previously showed that a soluble gp120-CD4 complex specifically binds to a peptide corresponding to CCR5 Nt residues 2 to 18, with sulfotyrosines in positions 10 and 14. This sulfopeptide also inhibits soluble gp120-CD4 binding to cell surface CCR5 as well as infection by an R5 virus. Here we show that residues 10 to 18 constitute the minimal domain of the CCR5 Nt that is able to specifically interact with soluble gp120-CD4 complexes. In addition to sulfotyrosines in positions 10 and 14, negatively charged residues in positions 11 and 18 participate in this interaction. Furthermore, the CCR5 Nt binds to a CD4-induced surface on gp120 that is composed of conserved residues in the V3 loop stem and the C4 domain. Binding of gp120 to cell surface CCR5 is further influenced by residues in the crown of the V3 loop, C1, C2, and C3. Our data suggest that gp120 docking to CCR5 is a multistep process involving several independent regions of the envelope glycoprotein and the coreceptor.
One-Bead–Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2 (2017)

Identification of molecular ligands that recognize peptides or proteins is significant but poses a fundamental challenge in chemical biology and biomedical sciences. Development of cyclic peptidomimetic library is scarce, and thus discovery of cyclic peptidomimetic ligands for protein targets is rare. Herein we report the unprecedented one-bead-two-compound (OBTC) combinatorial library based on a novel class of the macrocyclic peptidomimetics γ-AApeptides. In the library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound to EphA2 (K<sub>d</sub> = 81 nM) and potently antagonized EphA2-mediated signaling. This new approach of macrocyclic peptidomimetic library may lead to a novel platform for biomacromolecular surface recognition and function modulation.
Inactivation of Interleukin-1.beta. Converting Enzyme by Peptide (Acyloxy)methyl Ketones (1994)

Interleukin-1 beta converting enzyme (ICE) is a cysteine protease in monocytes that is essential for the proteolytic activation of interleukin-1 beta, an important mediator of inflammation. Peptide (acyloxy)methyl ketones designed with the appropriate peptide recognition sequence (Ac-Tyr-Val-Ala-Asp-CH2-OC(O)Ar) are potent, competitive, irreversible inhibitors. Mass spectrometry and sequence analysis indicate that inactivation proceeds through expulsion of the carboxylate leaving group to form a thiomethyl ketone with the active site Cys285. The second-order inactivation rate is independent of leaving group pKa, with an approximate value of 1 x 10(6) M-1 s-1. This rate constant is directly proportional to the reaction macroviscosity, indicating that the rate-limiting step in inactivation is association of enzyme and inhibitor, rather than any bond-forming reactions. Affinity labeling of THP.1 monocytic cell cytosol with a biotinylated tetrapeptide (acyloxy)methyl ketone for 28 half-lives resulted in labeling of only ICE, demonstrating the selectivity of these inhibitors. These inhibitors are relatively inert toward other bionucleophiles such as glutathione (< 5 x 10(-4) M-1 s-1), making them excellent candidates for in vivo studies of enzyme inhibition.
The axonal repellent, Slit2, inhibits directional migration of circulating neutrophils (2009)

In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals are provided by many different chemotactic molecules, such that blockade of one may not prevent neutrophil recruitment effectively. The Slit family of secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows that by inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit migration of other cell types toward a variety of chemotactic factors in vitro and in vivo. The role of Slit2 in inflammation, however, has been largely unexplored. We isolated primary neutrophils from human peripheral blood and mouse bone marrow and detected Robo-1 expression. Using video-microscopic live cell tracking, we found that Slit2 selectively impaired directional migration but not random movement of neutrophils toward fMLP. Slit2 also inhibited neutrophil migration toward other chemoattractants, namely C5a and IL-8. Slit2 inhibited neutrophil chemotaxis by preventing chemoattractant-induced actin barbed end formation and cell polarization. Slit2 mediated these effects by suppressing inducible activation of Cdc42 and Rac2 but did not impair activation of other major kinase pathways involved in neutrophil migration. We further tested the effects of Slit2 in vivo using mouse models of peritoneal inflammation induced by sodium periodate, C5a, and MIP-2. In all instances, Slit2 reduced neutrophil recruitment effectively (P<0.01). Collectively, these data demonstrate that Slit2 potently inhibits chemotaxis but not random motion of circulating neutrophils and point to Slit2 as a potential new therapeutic for preventing localized inflammation.
Growth and Carotenoid Production ofThraustochytriumsp. CHN-1 Cultured under Superbright Red and Blue Light-emitting Diodes (2004)

Isomers of astaxanthin produced by Thraustochytrium sp. CHN-1 are identified as (3S,3S')-trans-astaxanthin, (3R,3R')-trans-astaxanthin and (3S,3S')-cis-astaxanthin by chirality column HPLC, and 1H and 13C NMR. We studied the effects of light generated by superbright blue, red and near-red LEDs on the growth and carotenoid production of Thraustochytrium sp. CHN-1. Thraustochytrium sp. CHN-1 responded to blue LEDs light: It produced carotenoid pigments (astaxanthin)
Memory characteristics of Pt nanocrystals self-assembledfrom reduction of an embedded PtOx ultrathin film in metal-oxide-semiconductor structures (2004)

The nonvolatile memory characteristics of metal-oxide-semiconductor structures containing Pt nanocrystals in SiO2 gate oxide were studied. The Pt nanocrystals of 2–3nm in diameter were self-assembled from reduction of an ultrathin PtOx layer embedded in the SiO2 by vacuum annealing at 425°C. A large hysteresis loop was found in the capacitance–voltage (C–V) relation indicating this significant memory effect. However, two different charge storage mechanisms were found for the Pt nanocrystals in devices with different tunnel oxide thickness. A counterclockwise C–V hysteresis was induced from substrate injection for the devices made with a thin tunnel oxide layer 2.5–5.0nm thick. Contrast, a clockwise behavior attributed to the electron transfer from charged defects in the gate oxide was found for the devices having a tunnel oxide layer 7.5nm thick. The relatively stable memory characteristics of Pt nanocrystals resulted from substrate injection were also demonstrated.
Electrically tunable polymer stabilized liquid-crystal lens (2005)

A tunable focal lens using flat electro-optical liquid-crystal cell with uniform pixel-free electrodes is developed. The lenslike gradient refractive index profile is created in the cell via the spatially distributed polymer network obtained by photopolymerization using a spatially nonuniform laser beam. The conditions of the polymer network generation are optimized to improve the optical quality of the lens and its focusing properties. Low optical loss (scattering) is achieved for a focal length smoothly tunable from infinity to 0.8m. Obtained results can be applied to develop lenses that have no moving parts and allow the electro-optical zooming.