gebhart/patrepeval huggingface dataset:
The three heavy-chain precursors for the inter-α-inhibitor family in mouse: new members of the multicopper oxidase protein group with differential transcription in liver and brain (1995)

The inter-alpha-inhibitor (I alpha I) family is comprised of the plasma protease inhibitors I alpha I, inter-alpha-like inhibitor (I alpha LI), pre-alpha-inhibitor (P alpha I) and bikunin. I alpha I, I alpha LI and P alpha I are distinct assemblies of bikunin with one of three heavy (H) chains designated H1, H2 and H3. These H chains and bikunin are respectively encoded by a set of three H genes and an alpha 1-microglobulin/bikunin precursor (AMBP) gene. All four gene products undergo maturation steps from precursor polypeptides. The full-length cDNAs for the H1-, H2- and H3-chain precursors were cloned from a mouse liver cDNA library and sequenced. Extensive searches of amino acid sequence similarities to other proteins in databanks revealed (i) a highly significant similarity of the C-terminal sequence in the three H-chain precursors to the multicopper-binding domain in the group of multicopper oxidase proteins and (ii) the presence of von Willebrand type-A domains in the mature H chains. Amino acid sequence comparisons between the three mouse H1-, H2- and H3-chain precursors and their human counterparts allowed us to appraise the timing and order of occurrence of the three H-chain genes from a shared ancestor during mammalian evolution. Owing to a multiple alignment of the six mouse and human nucleotide sequences for these H-chain precursors, a reverse transcriptase PCR assay with degenerate oligonucleotides was designed, allowing us to (i) present evidence that no mRNAs for further H genes exist in mouse liver and (ii) demonstrate a previously undescribed transcription of the H2- and H3-chain mRNAs in mouse brain, which contrasts with the expression of all four, H1, H2, H3 and AMBP, mRNAs in liver.
Chlorate-induced inhibition of tyrosine sulfation on bone sialoprotein synthesized by a rat osteoblast-like cell line (UMR 106-01 BSP). (1994)

Bone sialoprotein (BSP) is a major noncollagenous, RGD-containing glycoprotein found in the extracellular matrix of bone. The RGD sequence is flanked by two tyrosine-rich regions, which fit the established consensus requirements for tyrosine sulfation. Tyrosine sulfation is suggested to be important in the regulation of protein secretion and function. The role of this post-translational modification on the cell attachment activity and secretion of a highly sulfated form of BSP isolated from a rat osteoblast-like cell line (UMR 106-01 BSP) was investigated by inhibiting sulfation with chlorate. [35S]Sulfate, [3H]glucosamine, and [3H]tyrosine were used as metabolic precursors to monitor biosynthetic products. Chlorate was effective in inhibiting total [35S]sulfate incorporation by 90% without altering overall protein synthesis and secretion in cultures up to 72 h under serum-free conditions. Isolated proteoglycans and purified BSP were analyzed for sulfate incorporation. Proteoglycans isolated from the medium of cells treated with chlorate displayed a difference in the hydrodynamic properties of the molecules as compared with control cultures. An increase in the specific activity of proteoglycans labeled with [3H]glucosamine isolated from chlorate-treated cells was also observed suggesting a change in hexosamine metabolism induced by chlorate. BSP purified from the medium of chlorate-treated cells contained approximately 7% of the 35S incorporation as compared with nontreated control cultures. Quantification of sulfate incorporation into glycoconjugates versus tyrosine sulfate of BSP indicates that the amount of sulfate associated with N- and O-linked oligosaccharides was reduced by approximately 97%, while that on tyrosine residues was reduced by approximately 90%. Using normal human bone cells, the cell attachment activity of the reduced sulfate form of BSP was nearly equivalent to that of the fully sulfated product.
SYNTHESIS OF TRICYCLIC COMPOUNDS WITH THIOPYRIDONE RINGS (1989)

Abstract Reaction of 3,4-trimethylene-6-amino-5-ethoxycarbonylthiopyrane-2-thione (1) with hydrazine hydrate gave the corresponding o-diaminocyclopentapyridine-2-thione (2). Ring closure of 2 with some reagents, namely, formic acid, aromatic aldehydes, carbon disulphide. phenacyl bromide, ethyl chloroformate, ethyl chloroacetate, nitrosylsulfuric acid, and pyruvic acid gave tricyclic compounds (2–14) by direct or indirect pathways, respectively.
Electrostatic Potential in a Bent Piezoelectric Nanowire. The Fundamental Theory of Nanogenerator and Nanopiezotronics (2007)

We have applied the perturbation theory for calculating the piezoelectric potential distribution in a nanowire (NW) as pushed by a lateral force at the tip. The analytical solution given under the first-order approximation produces a result that is within 6% from the full numerically calculated result using the finite element method. The calculation shows that the piezoelectric potential in the NW almost does not depend on the z-coordinate along the NW unless very close to the two ends, meaning that the NW can be approximately taken as a "parallel plated capacitor". This is entirely consistent to the model established for nanopiezotronics, in which the potential drop across the nanowire serves as the gate voltage for the piezoelectric field effect transistor. The maximum potential at the surface of the NW is directly proportional to the lateral displacement of the NW and inversely proportional to the cube of its length-to-diameter aspect ratio. The magnitude of piezoelectric potential for a NW of diameter 50 nm and length 600 nm is approximately 0.3 V. This voltage is much larger than the thermal voltage ( approximately 25 mV) and is high enough to drive the metal-semiconductor Schottky diode at the interface between atomic force microscope tip and the ZnO NW, as assumed in our original mechanism for the nanogenerators.
Design and Performance of an Instrument for Soft Landing of Biomolecular Ions on Surfaces (2007)

A new ion deposition apparatus was designed and constructed in our laboratory. Our research objectives were to investigate interactions of biomolecules with hydrophilic and hydrophobic surfaces and to carry out exploratory experiments aimed at highly selective deposition of spatially defined and uniquely selected biological molecules on surfaces. The apparatus includes a high-transmission electrospray ion source, a quadrupole mass filter, a bending quadrupole that deflects the ion beam and prevents neutral molecules originating in the ion source from impacting the surface, an ultrahigh vacuum (UHV) chamber for ion deposition by soft landing, and a vacuum lock system for introducing surfaces into the UHV chamber without breaking vacuum. Ex situ analysis of surfaces following soft landing of mass-selected peptide ions was performed using 15 keV Ga+ time-of-flight secondary ion mass spectrometry and grazing incidence infrared reflection-absorption spectroscopy. It is shown that these two techniques are highly complementary methods for characterization of surfaces prepared with a range of doses of mass-selected biomolecular ions. We also demonstrated that soft landing of peptide ions on surfaces can be utilized for controlled preparation of peptide films of known coverage for fundamental studies of matrix effects in SIMS.
Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development (2008)

During mouse development, the sophisticated vascular network of the lung is established from embryonic day (E) approximately 10.5 and continues to develop postnatally. This network is composed of endothelial cells enclosed by vascular smooth muscle, pericytes, and other mesenchymal cells. Recent in vivo lineage labeling studies in the developing heart and intestine suggest that some of the vascular smooth muscle cells arise from the surface mesothelium. In the developing lung, the Wilm's tumor 1 gene (Wt1) is expressed only in the mesothelial cells. Therefore, we lineage-labeled the mesothelium in vivo by using a Wt1-Cre transgene in combination with either Rosa26R(lacZ), Rosa26R(CAG-hPLAP), or Rosa26R(EYFP) reporter alleles. In all three cases, cells derived from lineage-labeled mesothelium are found inside the lung and as smooth muscle actin (SMA) and PDGF receptor-beta positive cells in the walls of pulmonary blood vessels. To corroborate this finding, we used 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate, succinimidyl ester "mixed isomers" (CCFSE) dye to label mesothelial cells on the surface of the embryonic lung. Over the course of 72-h culture, dye-labeled cells also appear within the lung mesenchyme. Together, our data provide evidence that mesothelial cells serve as a source of vascular smooth muscle cells in the developing lung and suggest that a conserved mechanism applies to the development of blood vessels in all coelomic organs.
Rapid microfabrication of solvent-resistant biocompatible microfluidic devices (2008)

This paper presents a rapid, simple, and low-cost fabrication method to prepare solvent resistant and biocompatible microfluidic devices with three-dimensional geometries. The devices were fabricated in thiolene and replicated from PDMS master with high molding fidelity. Good chemical compatibility for organic solvents allows volatile chemicals in synthesis and analysis applications. The surface can be processed to be hydrophobic or hydrophilic for water-in-oil and oil-in-water emulsions. Monodisperse organic solvent droplet generation is demonstrated to be reproducible in thiolene microchannels without swelling. The thiolene surface prevents cell adhesion but normal cell growth and adhesion on glass substrates is not affected by the adjacent thiolene patterns.
Sox9 in Testis Determination (2005)

Sox9 is an Sry-box-containing gene that encodes a transcriptional activator. During mouse gonadogenesis, Sox9 is detected in the male gonad at 11.5 days postcoitus (dpc). At 12.5 dpc, testicular cords form, morphologically distinguishing the male gonad from the ovary. From this stage onwards, Sox9 expression is restricted to the Sertoli cell lineage and persists in the adult. Humans with heterozygous mutations in SOX9 develop a skeletal syndrome known as campomelic dysplasia. Furthermore, most XY SOX9 heterozygotes show variable male-to-female sex reversal, implicating SOX9 in testis development. Sox9 heterozygous knockout mice die at birth with a syndrome similar to that of human campomelic dysplasia. In contrast to humans, XY Sox9+/- mice form normal appearing testes. Germ-line knockout of Sox9 using a conditional null allele provides a tool for generating Sox9-/- mice by simple genetic crosses. However, Sox9-/- mice die soon after 11.5 dpc because of cardiovascular defects. In vitro culture of the urogenital ridges of XY Sox9-/- results in gonads lacking testicular cords and Sertoli cell marker expression, but with the expression of ovarian-specific markers. Therefore, Sox9 is essential for diverting an intrinsically ovarian program of organogenesis toward testis formation.
In vivo performance of a sol–gel glass‐coated collagen (2006)

Synthetic bioactive materials offer possibilities to repair large tissue defects. It is well known that bioactivity, angiogenesis, and inflammation are key events in implant incorporation. Using glass-coated and glass-free collagen as potential bone graft substitutes, we carried out in vitro bioactivity and an in vivo angiogenesis and inflammation studies. The in vitro study showed bioactivity when the glass-coated samples were left in SBF for 5 days. This was confirmed by FTIR results, which presented P--O vibration bands characteristic of hydroxyapatite close to 1060 cm(-1) and 600 cm(-1). The in vivo response was evaluated following subcutaneous implantation of the biomaterial in the mouse dorsa. Angiogenesis, as determined by hemoglobin content extracted from implants 7 and 14 days after implantation, increased progressively in both glass-coated and glass-free collagen implants. However, vascularization was higher in the glass-coated collagen implants 14 days after implantation (mug Hb per mg wet tissue 6.0 +/- 0.3) compared with the glass-free group (1.6 +/- 0.1). The inflammatory process, determined by the levels of myeloperoxidase and N-acetylglucosaminidase, was similar for both implants. This study shows that glass-coated collagen implants hold osteogenic and angiogenic potential and may be used in clinical conditions requiring improvement of these biological processes.
Small Molecule STAT5-SH2 Domain Inhibitors Exhibit Potent Antileukemia Activity (2011)

A growing body of evidence shows that Signal Transducer and Activator of Transcription 5 (STAT5) protein, a key member of the STAT family of signaling proteins, plays a pivotal role in the progression of many human cancers, including acute myeloid leukemia and prostate cancer. Unlike STAT3, where significant medicinal effort has been expended to identify potent direct inhibitors, Stat5 has been poorly investigated as a molecular therapeutic target. Thus, in an effort to identify direct inhibitors of STAT5 protein, we conducted an in vitro screen of a focused library of SH2 domain binding salicylic acid-containing inhibitors (∼150) against STAT5, as well as against STAT3 and STAT1 proteins for SH2 domain selectivity. We herein report the identification of several potent (K(i) < 5 μM) and STAT5 selective (>3-fold specificity for STAT5 cf. STAT1 and STAT3) inhibitors, BP-1-107, BP-1-108, SF-1-087, and SF-1-088. Lead agents, evaluated in K562 and MV-4-11 human leukemia cells, showed potent induction of apoptosis (IC(50)'s ∼ 20 μM) which correlated with potent and selective suppression of STAT5 phosphorylation, as well as inhibition of STAT5 target genes cyclin D1, cyclin D2, C-MYC, and MCL-1. Moreover, lead agent BP-1-108 showed negligible cytotoxic effects in normal bone marrow cells not expressing activated STAT5 protein. Inhibitors identified in this study represent some of the most potent direct small molecule, nonphosphorylated inhibitors of STAT5 to date.
Structural color via layer-by-layer deposition: layered nanoparticle arrays with near-UV and visible reflectivity bands (2009)

The same near-ultraviolet (NUV) (300–400 nm) light that facilitates photo-degradation in polymers is also a key component in animal communication, particularly in insects and birds. We developed a nature-inspired 1D photonic crystal structure that has simultaneous narrow stop bands in the NUV and visible wavelength range, resulting in a NUV reflector with tunable structural color in the visible region of the spectrum. The samples were prepared by high precision deposition of alternating stacks of SiO2 and more densely packed TiO2nanoparticlesvia aqueous layer-by-layer (LbL) deposition. Multilayer thin films with eleven stacks achieved up to 75% reflectance with a 50 nm bandwidth and 65% reflectance with a 100 nm bandwidth for structural colors centered at 500 nm and 690 nm, respectively. Despite UV absorbance of the TiO2nanoparticles and the supporting glass substrate, all samples exhibited a narrow NUV stop-band centered in the 300–400 nm range with a reflectance over 65%. Upon introduction of a defect mode, we also demonstrated the creation of a narrow reflectance dip associated with a localized state in the photonic band gap. Multilayer-based structural colors with NUV reflectivity can be used as pigments that can promote prevention of photo-degradation in coatings, in addition to bird and insect repelling functionality.
Cholesterol trafficking is required for mTOR activation in endothelial cells (2010)

Mammalian target of rapamycin (mTOR) constitutes a nodal point of a signaling network that regulates cell growth and proliferation in response to various environmental cues ranging from growth factor stimulation to nutrients to stress. Whether mTOR is also affected by cholesterol homeostasis, however, has remained unknown. We report that blockade of cholesterol trafficking through lysosome by a newly identified inhibitor of angiogenesis, itraconazole, leads to inhibition of mTOR activity in endothelial cells. Inhibition of mTOR by itraconazole but not rapamycin can be partially restored by extracellular cholesterol delivered by cyclodextrin. Moreover, other known inhibitors of endosomal/lysosomal cholesterol trafficking as well as siRNA knockdown of Niemann-Pick disease type C (NPC) 1 and NPC2 also cause inhibition of mTOR in endothelial cells. In addition, both the accumulation of cholesterol in the lysosome and inhibition of mTOR caused by itraconazole can be reversed by thapsigarin. These observations suggest that mTOR is likely to be involved in sensing membrane sterol concentrations in endothelial cells, and the cholesterol trafficking pathway is a promising target for the discovery of inhibitors of angiogenesis.
Hiding distribution in distributed systems (1991)

The author focuses on the evolution of transparency in distributed systems, that is, the provision of logically centralized system facilities on distributed system architectures. The author proposes a comparison between the virtues and faults of centralized and distributed architectures, and reviews the evolution of distributed systems. The notion of transparency is described in detail with some examples. The main features of new technologies used to build transparent subsystems on distributed architectures are discussed. >
Receptors and Transmembrane Signaling (1992)

Receptors were recognized as a cell-surface phenomenon long before they were recognized as protein molecules located in a membrane. This phenomenon was the ability of an organism or cell to recognize a specific stimulus from the outside environment and to use the information to initiate a signal transduction pathway, producing changes in the organism's behavior or metabolism that usually improve the organism's chances for survival or affect a cell's interactions with its immediate environment. An increased understanding of receptors led to the generalization that receptors are in fact protein molecules which could process information from outside a cell to specific signal transduction pathways within the cell. The crucial link in that process is the ability of a protein molecule to be influenced by a stimulus—a chemical, light, mechanical compression, or even heat—and to deliver that information across the membrane to the inside of the cell, where the signal is amplified...
Clinical development of valbenazine for tics associated with Tourette syndrome (2021)

<b>Introduction</b>: Significant need exists for effective, well-tolerated pharmacologic treatments for Tourette syndrome (TS). Medications that inhibit vesicular monoamine transporters (i.e. VMAT2 inhibitors) downregulate presynaptic packaging and release of dopamine into the neuronal synapse and are effective in treating hyperkinetic movement disorders such as Huntington's chorea and tardive dyskinesia (TD); thus, they may be useful in treating TS.<b>Areas covered</b>: This review describes the clinical program evaluating the safety and efficacy of valbenazine in the treatment of involuntary tics associated with TS in adult and pediatric subjects. While there was a trend in the 6 completed trials toward greater improvement in valbenazine-treated versus placebo subjects on the primary efficacy endpoint (Yale Global Tic Severity Scale Total Tic Score), this difference did not reach statistical significance. Valbenazine was generally well-tolerated in the studies, and treatment-emergent adverse events were consistent with valbenazine studies in TD.<b>Expert opinion</b>: Due to the failure to meet the primary endpoint in these trials, further investigation of valbenazine for TS is unlikely. Given the need for safe and effective TS therapies and the key role of VMAT2 in modulating dopaminergic activity, it is reasonable for future studies to investigate other VMAT2 inhibitors as potential treatments for TS.
Dispersions or solutions? A mechanism for certain thickening agents (1974)

Abstract Hydrolyzed starch–polyacrylonitrile (H‐SPAN) graft copolymers form highly viscoelastic mixtures with water, even at concentrations less than 1% by weight. In many ways these mixtures behave like ordinary polyelectrolyte solutions, but dilution experiments revealed that linear reduced viscosity–concentration plots could not be obtained even under ostensibly isoionic dilution conditions. This result, combined with a determination of gel content from centrifugation studies, led to the conclusion that high viscosity H‐SPAN water mixtures consist of swollen, deformable gel particles closely packed in intimate contact. Under high dilution or at high ionic strength conditions, the gel particles no longer are tightly packed, solvent is present in excess, the viscosity drops precipitously, and the thickening action effectively disappears. For comparative purposes, a commercial thickening agent (Carbopol 941) was examined and found to act in the same way. All reduced viscosity‐concentration curves obtained by dilution, either with salt solutions or water, can be shifted to a single normalized reduced viscosity plot. This shift is done by using as the concentration variable the quantity cQ , where c is the polyelectrolyte concentration and Q is the swelling which the gel particles undergo in an excess of solvent at the corresponding total ionic strength of the solution of concentration c .
CD25+ Regulatory T Cell Depletion Augments Immunotherapy of Micrometastases by an IL-21-Secreting Cellular Vaccine (2006)

IL-21 is an IL-2-like cytokine, signaling through a specific IL-21R and the IL-2R gamma-chain. Because the TS/A mammary adenocarcinoma cells genetically modified to secrete IL-21 (TS/A-IL-21) are strongly immunogenic in syngeneic mice, we analyzed their application as vaccine. In mice bearing TS/A-parental cell (pc) micrometastases, vaccination with irradiated TS/A-IL-21 cells significantly increased the animal life span, but cured only 17% of mice. Spleen cells from cured mice developed CTL activity and produced IFN-gamma in response to stimulation by the AH1 epitope of the gp70env Ag of TS/A-pc. We tested whether the low therapeutic outcome might be due to CD4+CD25+ regulatory T cells (Treg) present in TS/A-pc tumors and draining lymph nodes and whether IL-21 had any effect on these cells. Indeed, CD4+CD25+ cells suppressed IFN-gamma production by splenocytes from immune mice in response to stimulation by the AH1 peptide. Low concentrations of IL-21 (10 ng/ml) failed to reverse the inhibitory activity of CD4+CD25+ cells in an allogeneic MLR, whereas 60 ng/ml rIL-21 partially restored responder T cell proliferation. IL-21R expression on CD25- lymphocytes suggested that IL-21 could be more effective in mice depleted of CD25+ cells. Depletion of Treg cells by a single dose of anti-CD25 mAb combined with TS/A-IL-21 cell vaccine cured >70% of mice bearing micrometastases, whereas anti-CD25 mAb treatment alone had no effect. Successful combined immunotherapy required NK cells, CD8+ T cells, and IFN-gamma. In conclusion, immunotherapy of micrometastases by an IL-21-based cellular vaccine is strongly potentiated by CD25+ cell depletion.
A working spatio-temporal model of the human visual system for image restoration and quality assessment applications (2002)

This paper describes a spatio-temporal model of the human visual system (HVS) for video imaging applications, predicting the response of the neurons of the primary visual cortex. The model simulates the behavior of the HVS with a three-dimensional filter bank which decomposes the data into perceptual channels, each one being tuned to a specific spatial frequency, orientation and temporal frequency. It further accounts for contrast sensitivity, inter-stimuli masking and spatio-temporal interaction. The free parameters of the model have been estimated by psychophysics. The model can then be used as the basis for many applications. As an example, a quality metric for coded video sequences is presented.