gebhart/patrepeval huggingface dataset:
Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor (2019)

Atrial natriuretic peptide (ANP) is a peptide hormone that in response to atrial stretch is secreted from atrial myocytes into the circulation, where it stimulates vasodilatation and natriuresis. ANP is an important biomarker of heart failure where low plasma concentrations exclude cardiac dysfunction. ANP is a member of the natriuretic peptide (NP) family, which also includes the B-type natriuretic peptide (BNP) and the C-type natriuretic peptide. The proforms of these hormones undergo processing to mature peptides, and for proBNP, this process has previously been demonstrated to be regulated by <i>O-</i>glycosylation. It has been suggested that proANP also may undergo post-translational modifications. Here, we conducted a targeted <i>O-</i>glycoproteomics approach to characterize <i>O-</i>glycans on NPs and demonstrate that all NP members can carry <i>O-</i>glycans. We identified four <i>O-</i>glycosites in proANP in the porcine heart, and surprisingly, two of these were located on the mature bioactive ANP itself. We found that one of these glycans is located within a conserved sequence motif of the receptor-binding region, suggesting that <i>O</i>-glycans may serve a function beyond intracellular processing and maturation. We also identified an <i>O</i>-glycoform of proANP naturally occurring in human circulation. We demonstrated that site-specific <i>O</i>-glycosylation shields bioactive ANP from proteolytic degradation and modifies potency at its cognate receptor <i>in vitro</i> Furthermore, we showed that ANP <i>O</i>-glycosylation attenuates acute renal and cardiovascular ANP actions <i>in vivo</i> The discovery of novel glycosylated ANP proteoforms reported here significantly improves our understanding of cardiac endocrinology and provides important insight into the etiology of heart failure.
Role of the Pyrrolidine Ring of Proline in Determining the Substrate Specificity of cdc2 Kinase or cdk5 (1997)

To examine structural features of proline which are essential for the proline-directed phosphorylation by cdc2 kinase or cdk5, we prepared the peptide representing the cdc2 kinase phosphorylation site at Ser-55 in vimentin [Ser-Leu-Tyr-Ser-Ser-Ser55-Pro56-Gly-Gly58-Ala-Tyr-NH2], the peptide containing arginine in place of Gly-58, and their derivatives containing various N-methylamino acids or proline homologs in place of Pro-56, and tested them as substrates for the kinases. While substitution of the proline by proline homologs (L-pipecolic acid or L-azetidine-2-carboxylic acid) increased the K(m) value 2- to 4-fold at utmost, substitution by N-methylamino acids (sarcosine, L-N-methylalanine, L-N-methylvaline, or L-N-methylleucine) increased the K(m) value 7- to 40-fold for cdc2 kinase. For cdk5, these substitutions led to parallel effects on the K(m) value to those found for cdc2 kinase; cdk5 recognized the peptides with a proline specificity similar to that for cdc2 kinase. These results suggest that the pyrrolidine ring of proline is important for substrate recognition by cdc2 kinase or cdk5. Molecular dynamics and molecular mechanics simulations indicated that the pyrrolidine ring of proline is optimal to stabilize a beta-turn at the phosphorylation site and that the K(m) values of the peptides for the enzymes might be related to the probability of the turn structure. The results obtained here also suggest that the pyrrolidine ring of proline is required to maintain a high V(max) value for cdc2 kinase or especially for cdk5. These will aid in designing specific substrates or inhibitors for cdc2 kinase or cdk5.
Laser ablation-combustion-GC-IRMS--a new method for online analysis of intra-annual variation of  13C in tree rings (2004)

We present a new, rapid method for high-resolution online determination of delta13C in tree rings, combining laser ablation (LA), combustion (C), gas chromatography (GC) and isotope ratio mass spectrometry (IRMS) (LA-C-GC-IRMS). Sample material was extracted every 6 min with a UV-laser from a tree core, leaving 40-microm-wide holes. Ablated wood dust was combusted to CO2 at 700 degrees C, separated from other gases on a GC column and injected into an isotope ratio mass spectrometer after removal of water vapor. The measurements were calibrated against an internal and an external standard. The tree core remained intact and could be used for subsequent dendrochronological and dendrochemical analyses. Cores from two Scots pine trees (Pinus sylvestris spp. sibirica Lebed.) from central Siberia were sampled. Inter- and intra-annual patterns of delta13C in whole-wood and lignin-extracted cores were indistinguishable apart from a constant offset, suggesting that lignin extraction is unnecessary for our method. Comparison with the conventional method (microtome slicing, elemental analysis and IRMS) indicated high accuracy of the LA-C-GC-IRMS measurements. Patterns of delta13C along three parallel ablation lines on the same core showed high congruence. A conservative estimate of the precision was +/- 0.24 per thousand. Isotopic patterns of the two Scots pine trees were broadly similar, indicating a signal related to the forest stand's climate history. The maximum variation in delta13C over 22 years was about 5 per thousand, ranging from -27 to -22.3 per thousand. The most obvious pattern was a sharp decline in delta13C during latewood formation and a rapid increase with spring early growth. We conclude that the LA-C-GC-IRMS method will be useful in elucidating short-term climate effects on the delta13C signal in tree rings.
The Effect of Sr Substitution on Phase Formation and Magnetic Properties of Y‐type Hexagonal Ferrite (2005)

The effect of Sr substitution in Y‐type hexagonal ferrite of composition Ba 2– x Sr x Zn 1.2 Co 0.4 Cu 0.4 Fe 12 O 22 was investigated. x varied from 0 to 2.0. The samples were prepared by the solid‐state reaction method. Phase formation was characterized by powder X‐ray diffraction. The microstructure was observed via scanning electron microscopy and magnetic properties were measured using an impedance analyzer and vibrating sample magnetometer (VSM). Results reveal that Sr 2+ cannot completely substitute for Ba 2+ ions in Y‐type hexagonal ferrites. The maximum solubility of Sr in the Y‐type ferrite is about 1.8. With Sr above 1.8, the lattice mismatch induced by the difference in ionic radii of Ba 2+ and Sr 2+ ions prevents the formation of Y‐type phase. While Sr content is equal or less than 1.0, the magnetic properties may be enhanced. As x >1.0, because of the internal stress resulting from the lattice mismatch, demagnetizing field significantly degrades initial permeability.
Synthesis and in vitro antiproliferative activity of new benzothiazole derivatives (2008)

A series of benzothiazole bearing piperazino-arylsulfonamides (5a-k), and arylthiol analogues (6a-j) as well as substituted benzothiazoles having sulfonamides (9b, 9l-n and 10) have been synthesized. All compounds were evaluated, in vitro, for their antiproliferative activity against a large panel of human tumor-derived cell lines. Compounds 5c, 5d, 5j, 6b, 6c and 6j were the most potent analogues in this series, showing activity against both cell lines derived from haematological and solid tumors (CC 50 range = 8-24 M), only 5d was found to be selective and not cytotoxic to normal human tissues.
Prefoldin 5 Is Required for Normal Sensory and Neuronal Development in a Murine Model (2010)

Molecular chaperones and co-chaperones are crucial for cellular development and maintenance as they assist in protein folding and stabilization of unfolded or misfolded proteins. Prefoldin (PFDN), a ubiquitously expressed heterohexameric co-chaperone, is necessary for proper folding of nascent proteins, in particular, tubulin and actin. Here we show that a genetic disruption in the murine Pfdn5 gene, a subunit of prefoldin, causes a syndrome characterized by photoreceptor degeneration, central nervous system abnormalities, and male infertility. Our data indicate that a missense mutation in Pfdn5, may cause these phenotypes through a reduction in formation of microtubules and microfilaments, which are necessary for the development of cilia and cytoskeletal structures, respectively. The diversity of phenotypes demonstrated by models carrying mutations in different PFDN subunits suggests that each PFDN subunit must confer a distinct substrate specificity to the prefoldin holocomplex.
High-Dose Dipyridamole and Gated Sestamibi SPECT Imaging Provide Diagnostic Resting and Stress Ejection Fractions Useful for Predicting Extent of Coronary Artery Disease (2002)

A decline in ejection fraction at stress compared with rest images has been associated with increased severity of coronary artery disease (CAD) and suggests a poorer prognosis. Myocardial perfusion imaging (MPI) using high-dose dipyridamole (HDD) has been shown to more accurately detect CAD than either standard dose dipyridamole (SDD) or exercise-induced stress (EST), but has not been looked at to determine its usefulness in detecting changes in stress and rest ejection fractions. To determine the relationship between changes in left ventricular ejection fraction (LVEF) and the severity of CAD, 36 Individuals underwent gated single photon emission computed tomography (SPECT) MPI using HDD. In each case resting and stress LVEFs were determined along with MPI results. Subjects with single-vessel CAD demonstrated an increase in LVEF from 77.8% (sd +/-8.8%) to 85.6% (sd +/-8.4%) resulting in a statistically significant increase in LVEF of 7.8% (p = 0.009). Patients with two-vessel disease showed a smaller increase from 73.2% (sd + 8.3%) to 79.8% (sd + 9.8%) following HDD stress. This increase was statistically (p = 0.008) significant. Patients with triple-vessel CAD showed a reduction in LVEF from 67.4% (sd +/-14.07) to 65.1% (sd +/-16.5%) which represented a decrease in LVEF of 2.7% and approached (p = 0.25) but did not reach statistical significance. Both the resting and stress LVEFs were statistically lower (p<0.05) in patients with triple-vessel CAD. Changes in resting LVEF (REF) and HDD pharmacologically induced stress LVEF (SEF) provide a valuable diagnostic marker as to the number of significantly diseased coronary arteries and can be acquired from gated SPECT sestamibi images.
A file comparison program (1985)

Abstract This paper presents a simple method for computing a shortest sequence of insertion and deletion commands that converts one given file to another. The method is particularly efficient when the difference between the two files is small compared to the files' lengths. In experiments performed on typical files, the program often ran four times faster than the UNIX diff command.
Low Salinity Cyclic Water Floods for Enhanced Oil Recovery on Alaska North Slope (2013)

Abstract With low salinity waterflooding already implemented, cyclic waterflooding is under extensive research for increased oil recovery than conventional waterflooding. Low salinity cyclic water injection (CWI) is an interesting combination that offers the effects of both, with notably high oil recovery and less usage of water. Careful evaluation might promote the application of cyclic injection in the fields, especially on Alaska North Slope (ANS). Two phase flow experiments were conducted on representative sandstone cores. After establishing initial water saturation, Amott-Harvey Wettability tests were performed with spontaneous and forced displacement of the fluids by one another. Cyclic water floods were conducted to calculate oil recovery from the volume of produced fluids. Pulsed cyclic floods were programmed in the injection pump. The experiments were repeated with cores of different permeability and lab reconstituted brines of 22000, 11000 and 5500 ppm salinity. Results were compared with available data from continuous injection performed on the same cores. Cyclic floods were also tested for two symmetric on-off time intervals. With the dead oil experiments, it is observed that residual oil saturation (Sor) is achieved as early as 3-4 pore volumes (PV) of injected water in cyclic injection as compared to 6-7 PV’s in continuous injection. Additional oil recovery is observed in cyclic injection’s idle time, when the already flooded water spreads smoothly within the pores to displace oil out of the core. Better recovery was obtained with lower salinity brines. Within cyclic injection, shorter pulse intervals yielded better results. To conclude, low salinity CWI with shorter pulse intervals yield better oil recovery and early Sor. This is an attractive option for ANS operators.
Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3 (2006)

The mechanisms of malignant cell transformation mediated by the oncogenic, chimeric nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) tyrosine kinase remain only partially understood. Here we report that the NPM/ALK-carrying T cell lymphoma (ALK+TCL) cells secrete IL-10 and TGF-beta and express FoxP3, indicating their T regulatory (Treg) cell phenotype. The secreted IL-10 suppresses proliferation of normal immune, CD3/CD28-stimulated peripheral blood mononuclear cells and enhances viability of the ALK+TCL cells. The Treg phenotype of the affected cells is strictly dependent on NPM/ALK expression and function as demonstrated by transfection of the kinase into BaF3 cells and inhibition of its enzymatic activity and expression in ALK+TCL cells. NPM/ALK, in turn, induces the phenotype through activation of its key signal transmitter, signal transducer and activator of transcription 3 (STAT3). These findings identify a mechanism of NPM/ALK-mediated oncogenesis based on induction of the Treg phenotype of the transformed CD4(+) T cells. These results also provide an additional rationale to therapeutically target the chimeric kinase and/or STAT3 in ALK+TCL.
Wavelength-Dependent Photodissociation of [Fe(bpy)<sub>3</sub>·(CH<sub>3</sub>OH)<sub><i>n</i></sub>]<sup>2+</sup> Clusters, <i>n</i> = 2−6, Triggered by Excitation of the Metal-to-Ligand Charge-Transfer Transition (1997)

This paper reports the first investigation of the energetics of charge transfer in a coordination complex containing a divalent transition-metal ion as a function of the extent of solvation and provides a detailed description of the first instrument designed for spectroscopic characterization of gas-phase ions and clusters produced by electrospray ionization. Metal-to-ligand charge transfer (MLCT) is probed by laser photofragmentation mass spectrometry in clusters of the complex tris(2,2‘-bipyridyl)iron(II), [Fe(bpy)3]2+, with methanol prepared by electrospray ionization. Excitation of the MLCT transition in [Fe(bpy)3]2+ triggers evaporation of methanol solvent molecules from these clusters, permitting indirect detection of absorption. Measurement of ion beam depletion and/or production of charged photofragments as a function of photon energy yields the red edge of the MLCT band for [Fe(bpy)3·(CH3OH)n]2+ clusters, n = 2−6. Increasing the number of methanol molecules in the clusters shifts the onset of the MLCT band to lower energies, reflecting preferential solvation of the MLCT excited state of [Fe(bpy)3]2+ relative to its ground state. A measurable fraction of mass-selected [Fe(bpy)3·(CH3OH)n]2+ clusters also lose methanol molecules through metastable decomposition between primary mass selection and secondary mass analysis. Application of the evaporative ensemble model with RRK rate constants for metastable decomposition permits estimation of sequential methanol binding energies and internal temperatures for [Fe(bpy)3·(CH3OH)n]2+ clusters prepared by electrospray ionization.
Far-field superlens for nanolithography (2010)

A far-field optical lithography is developed in this paper. By designing the structure of a far-field optical superlens, lithographical resolution can be improved by using a conventional UV light source. The finite different time domain numerical studies indicate that the lithographic resolution at 50 nm line width is achievable with the structure shown in this paper by using 365 nm wavelength light, and the light can be transferred to a far distance in the photoresist.
FKBP12 Binds the Inositol 1,4,5-Trisphosphate Receptor at Leucine-Proline (1400–1401) and Anchors Calcineurin to this FK506-like Domain (1997)

The immunophilin FKBP12 is one of the most abundant and conserved proteins in biology. It is the primary receptor for the immunosuppressant actions of the drug FK506 in whose presence FKBP12 binds to and inhibits calcineurin, disrupting interleukin formation in lymphocytes. The physiologic functions of FKBP12 are less clear, although the protein has been demonstrated to physiologically interact with the inositol 1,4,5-trisphosphate receptor (IP3R), the ryanodine receptor, and the type 1 transforming growth factor beta receptor. We now report that FKBP12 binds the IP3R at residues 1400-1401, a leucyl-prolyl dipeptide epitope that structurally resembles FK506. We further demonstrate that binding to IP3R at this site enables FKBP12 to interact with calcineurin, presumably to anchor the phosphatase to IP3R and modulate the receptor's phosphorylation status. We propose that FK506 promotes an FKBP12-calcineurin interaction by mimicking structurally similar dipeptide epitopes present within proteins that use FKBP12 to anchor calcineurin to the appropriate physiologic substrates.
Porcine Somatostatin Receptor 2 Displays Typical Pharmacological sst2 Features but Unique Dynamics of Homodimerization and Internalization (2006)

Somatostatin (SRIF) exerts its multiple actions, including inhibition of GH secretion and of tumoral growth, through a family of five receptor subtypes (sst1-sst5). We recently reported that an sst2-selective agonist markedly decreases GH release from pig somatotropes, suggesting important roles for this scarcely explored receptor, psst2. Here, functional expression of psst2 in Chinese hamster ovary-K1 and human embryonic kidney-293-AD cell lines was employed to determine its pharmacological features and functional ability to reduce cAMP, and to examine its homodimerization and internalization dynamics in real time in single living cells. Results show that psst2 is a high-affinity receptor (dissociation constant = 0.27 nM) displaying a typical sst2 profile (nM affinity for SRIF-14> or =SRIF-28>cortistatin>MK678>octreotide) and high selectivity (EC(50) = 1.1 nM) for the sst2 agonist l-779,976, but millimolar or undetectable affinity to other sst-specific agonists (sst3>sst1>sst5>>>sst4). Accordingly, SRIF dose-dependently inhibited forskolin-stimulated cAMP with high potency (EC(50) = 6.55 pm) and modest efficacy (maximum 29.1%) via psst2. Cotransfection of human embryonic kidney-293 and Chinese hamster ovary-K1 cells with two receptor constructs modified with distinct fluorescent tags (psst2-YFP/psst2-CFP) enabled fluorescence resonance energy transfer measurement of physical interaction between psst2 receptors and also receptor internalization in single living cells. This revealed that under basal conditions, psst2 forms constitutive homodimers/homomultimers, which dissociate immediately (11 sec) upon SRIF binding. Interestingly, contrary to human sst2, psst2 rapidly reassociates (110.5 sec) during a subsequent process that temporally overlaps with receptor internalization (half-maximal = 95.1 sec). Therefore, psst2 is a potent inhibitory receptor displaying a unique set of interrelated dynamic features of agonist-dependent dimerization, dissociation, internalization, and reassociation, a cascade of events that might be critical for receptor function.
A flat-panel TV display system in monochrome and color (1975)

We have developed two compact flat TV sets and a full-color prototype model, using thin matrix dc gas-discharge panels of novel structure. The display panel is ¼ in thick, has a 7-in diagonal picture size, and contains 60 000 elements. The monochrome version has a peak luminance of 25 fL, a contrast ratio of 40:1, and 32 digitized gray levels, while the full-color set has a luminance of 5 fL, a 20:1 contrast ratio, and 48 levels. Luminance control is performed by varying the magnitude as well as the duration of the display current. All signals are digitized and all circuits consist of TTL IC's, with the exception of the drive transistors. We have constructed two types of experimental monochrome model sets: one for desk-top use packaged in a 300 × 350 × 80 mm housing which includes tuner, A/D converter, and all TV circuits with the exception of a power supply, the other for wall hanging. A full-color flat display panel has also been developed using a similar panel structure and circuitry.
On the mapping between logical and physical topologies (2009)

Network graphs, in general, successfully model a wide variety of interactions and relationships among entities, including both physical and logical connections. In this work, we study the problem of mapping a logical network on to a physical network; such a problem arises in various scenarios, for example, assignment of virtual machines on to physical servers in cloud computing, assignment of services on to physical devices in wireless/wire-line environments and physical resource assignment based on social networks. Specifically, in this paper, a logical network is a set of nodes with edges that denote the communication/bandwidth requirement between them, while a physical network denotes a set of physical nodes with edges that represent the available physical resources. The goal is to map the logical nodes on to the physical nodes and find physical resource allocation to meet the logical network demands, subject to physical network constraints. Towards this end, we propose a two-step approach to the problem, provide a set of novel feasibility checks for node assignment which are proved to be necessary and sufficient, and finally present a simple and fast algorithm that achieves a feasible logical to physical mapping with high probability. Illustrative simulation results are also presented to highlight the efficiency of the proposed algorithms.
<i>Fgf8</i>is required for anterior heart field development (2006)

In the mouse embryo, the splanchnic mesodermal cells of the anterior heart field (AHF) migrate from the pharynx to contribute to the early myocardium of the outflow tract (OT) and right ventricle (RV). Recent studies have attempted to distinguish the AHF from other precardiac populations, and to determine the genetic and molecular mechanisms that regulate its development. Here, we have used an Fgf8lacZ allele to demonstrate that Fgf8 is expressed within the developing AHF. In addition, we use both a hypomorphic Fgf8 allele (Fgf8neo) and Cre-mediated gene ablation to show that Fgf8 is essential for the survival and proliferation of the AHF. Nkx2.5Cre is expressed in the AHF, primary heart tube and pharyngeal endoderm, while TnT-Cre is expressed only within the specified heart tube myocardium. Deletion of Fgf8 by Nkx2.5Cre results in a significant loss of the Nkx2.5Cre lineage and severe OT and RV truncations by E9.5, while the remaining heart chambers (left ventricle and atria) are grossly normal. These defects result from significant decreases in cell proliferation and aberrant cell death in both the pharyngeal endoderm and splanchnic mesoderm. By contrast, ablation of Fgf8 in the TnT-Cre domain does not result in OT or RV defects, providing strong evidence that Fgf8 expression is crucial in the pharyngeal endoderm and/or overlying splanchnic mesoderm of the AHF at a stage prior to heart tube elongation. Analysis of downstream signaling components, such as phosphorylated-Erk and Pea3, identifies the AHF splanchnic mesoderm itself as a target for Fgf8 signaling.