gebhart/patrepeval huggingface dataset:
Evolution of distinct EGF domains with specific functions (2005)

EGF domains are extracellular protein modules cross-linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three-disulfides, human EGF-like (hEGF) domains and complement C1r-like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C-termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern-based method represents a significant advancement over the currently available sequence detection techniques. We re-annotated EGF sequences in the latest release of Swiss-Prot looking for functional relationships that might correlate with EGF type. We show that important post-translational modifications of three-disulfide EGFs, including unusual forms of glycosylation and post-translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three-disulfide bonds and comparison to laminin and integrin-like EGF domains with an additional inter-domain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four-disulfide ancestor by selective loss of different cysteine residues.
Trench storage node technology for gigabit DRAM generations (2002)

The two mainstream technologies for DRAMs today are based on stacked capacitors and trench capacitors. While topography limitations require development of high /spl epsiv/ dielectric materials and complex capacitor structures for the stacked capacitor approach, ultra high aspect ratio deep trench structures allow the extension of conventional process technologies. Key points for trench storage node technology are reactive ion etching (RIE) of trench structures with a high rate and very tight taper angle control limits as well as the formation of reliable ultra thin nitride-oxide (NO) dielectric films. In this work we show to what degree these factors can be controlled and optimized focusing on a new dipole ring magnetron (DRM) reactor for deep trench etching and a new fast thermal processor (FTP) for node dielectric formation.
Improved Secretion of Native Human Insulin-Like Growth Factor 1 from gas1 Mutant Saccharomyces cerevisiae Cells (2000)

We studied the secretion of recombinant human insulin-like growth factor 1 (rhIGF-1) from transformed yeast cells. The hIGF-1 gene was fused to the mating factor alpha prepro- leader sequence under the control of the constitutive ACT1 promoter. We found that the inactivation of the GAS1 gene in the host strain led to a supersecretory phenotype yielding a considerable increase, from 8 to 55 mg/liter, in rhIGF-1 production.
Overexpression of ADAM9 in Non-Small Cell Lung Cancer Correlates with Brain Metastasis (2004)

The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines. To elucidate the role of ADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a full-length ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha 3 and beta 1 subunits. Administration of the anti-beta 1 monoclonal antibody attenuated this increase in invasive and adhesive activity. Intravenous administration of ADAM9-overexpressing A549 cells to mice resulted in micrometastatic foci in the brain and multiple metastatic colonies in the lungs. In contrast, administration of parent and mock-transfected A549 cells to mice resulted in lung tumors without brain metastasis. These results suggest that ADAM9 overexpression enhances cell adhesion and invasion of non-small cell lung cancer cells via modulation of other adhesion molecules and changes in sensitivity to growth factors, thereby promoting metastatic capacity to the brain.
EuGene: maximizing synthetic gene design for heterologous expression (2012)

EuGene is freely available for non-commercial use, at http://bioinformatics.ua.pt/eugene.
A Single Amino Acid Determines Lysophospholipid Specificity of the S1P1 (EDG1) and LPA1 (EDG2) Phospholipid Growth Factor Receptors (2001)

The phospholipid growth factors sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are ligands for the related G protein-coupled receptors S1P(1)/EDG1 and LPA(1)/EDG2, respectively. We have developed a model of LPA(1) that predicts interactions between three polar residues and LPA. One of these, glutamine 125, which is conserved in the LPA receptor subfamily (LPA(1)/EDG2, LPA(2)/EDG4, and LPA(3)/EDG7), hydrogen bonds with the LPA hydroxyl group. Our previous S1P(1) study identified that the corresponding glutamate residue, conserved in all S1P receptors, ion pairs with the S1P ammonium. These two results predict that this residue might influence ligand recognition and specificity. Characterization of glutamate/glutamine interchange point mutants of S1P(1) and LPA(1) validated this prediction as the presence of glutamate was required for S1P recognition, whereas LPA recognition was possible with either glutamine or glutamate. The most likely explanation for this dual specificity behavior is a shift in the equilibrium between the acid and conjugate base forms of glutamic acid due to other amino acids surrounding that position in LPA(1), producing a mixture of receptors including those having an anionic glutamate that recognize S1P and others with a neutral glutamic acid that recognize LPA. Thus, computational modeling of these receptors provided valid information necessary for understanding the molecular pharmacology of these receptors.
Resolution of apoptosis in atherosclerotic plaque by dietary modification and statin therapy. (2005)

Dietary modification and statin therapy in atherosclerosis lead to a reduction in apoptosis and contribute to plaque stabilization. It can be hypothesized that a reduction in apoptosis is a favorable process in atherosclerotic disease.
Cohort Study of Internal Malignancy in Genetic Hemochromatosis and Other Chronic Nonalcoholic Liver Diseases<xref ref-type="fn" rid="FN2">2</xref> (1985)

The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.
Large-Angle, Multifunctional Metagratings Based on Freeform Multimode Geometries (2017)

We show that silicon-based metagratings capable of large-angle, multifunctional performance can be realized using inverse freeform design. These devices consist of nonintuitive nanoscale patterns and support a large number of spatially overlapping optical modes per unit area. The quantity of modes, in combination with their optimized responses, provides the degrees of freedom required to produce high-efficiency devices. To demonstrate the power and versatility of our approach, we fabricate metagratings that can efficiently deflect light to 75° angles and multifunctional devices that can steer beams to different diffraction orders based on wavelength. A theoretical analysis of the Bloch modes supported by these devices elucidates the spatial mode profiles and coupling dynamics that make high-performance beam deflection possible. This approach represents a new paradigm in nano-optical mode engineering and utilizes different physics from the current state-of-the-art, which is based on the stitching of noninteracting waveguide structures. We envision that inverse design will enable new classes of high-performance photonic systems and new strategies toward the nanoscale control of light fields.
Characterization of a Rat C6 Glioma‐Secreted Follistatin‐Related Protein (FRP) (1994)

A protein was isolated from rat C6 glioma-conditioned medium and was biochemically characterized. The heparin-binding protein has a native molecular mass of 55-75,000 Da, a molecular mass of 40-48,000 Da under denaturing conditions, and a pI of 5.0-6.0. Based on the determined partial amino acid sequences, the full lenght cDNA encoding the rat and human proteins were cloned. The cDNA sequences identified the isolated rat and human protein as the homologue of a recently reported mouse osteoblast-transforming-growth-factor-beta 1-inducible protein, encoded by the TSC-36 gene [Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T. & Nose, K. (1993) Eur. J. Biochem. 217, 13-19]. Analysis of the human, rat and mouse amino acid sequences indicates that these proteins are highly conserved (> 92% sequence identity). Sequence similarities with follistatin and the follistatin-like domain of agrin are revealed. The relationship with follistatin and agrin points to possible common functions for the cloned follistatin-related proteins (FRP). The protein has no effect on the inhibitory action of transforming growth factor-beta 1, on CCl-64 cell growth.
COMP–Angiopoietin-1 Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Model (2006)

Injury to the renal microvasculature may be a major factor in the progression of renal disease; therefore, protection of endothelial cells (EC) in renal vasculature may have a therapeutic role in renal fibrosis. Recently, a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, was developed. The contribution of COMP-Ang1 in renal interstitial fibrosis, however, remains to be clarified. This study investigated the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the renal fibrogenic process that is triggered by unilateral ureteral obstruction. COMP-Ang1 preserved renal platelet-EC adhesion molecule-1-and Tie2-positive EC. Morphologic examination indicated less tubular injury and tubulointerstitial fibrosis in mice that received COMP-Ang1 than vehicle-treated mice. Interstitial type I collagen and myofibroblast accumulation were significantly suppressed by COMP-Ang1 treatment. COMP-Ang1 increased Tie2 and Akt phosphorylation in ureteral obstructed kidneys. Renal surface microvasculature and renal blood flow were higher after treatment with COMP-Ang1 than with vehicle. COMP-Ang1 treatment decreased monocyte/macrophage infiltration, tissue levels of TGF-beta1, and Smad 2/3 phosphorylation and increased Smad 7 in the obstructed kidney. These results demonstrate that COMP-Ang1 treatment can decrease the progression of renal fibrosis in unilateral ureteral obstruction. COMP-Ang1 may be an endothelium-specific therapeutic modality in fibrotic renal disease.
Lumbar sympathetic nerve activity and hindquarter blood flow during REM sleep in rats (2004)

The present study aimed to investigate the response of lumbar sympathetic nerve activity (LSNA) to the onset of rapid eye movement (REM) sleep and its contribution to the regulation of muscle blood flow during REM sleep in rats. Electrodes for the measurements of LSNA, electroencephalogram, electromyogram and electrocardiogram and a Doppler flow cuff for the measurements of blood flow in the common iliac and mesenteric arteries, also catheters for the measurements of systemic arterial and central venous pressures were implanted chronically. REM sleep resulted in a step increase in LSNA, by 22 +/- 9% (mean +/-S.E.M., P < 0.05), a reduction of iliac vascular conductance, by -16 +/- 3% (P < 0.05) and a gradual increase in systemic arterial pressure, reaching a maximum value of 8.1 +/- 2.0 mmHg (P < 0.05) at 89 s after onset of REM sleep, while mesenteric vascular conductance increased simultaneously by 5 +/- 2% (P < 0.05). There was a significant (Pearson's correlation coefficient = 0.94, P < 0.05) inverse linear relationship between LSNA and the iliac blood flow. Unilateral lumbar sympathectomy blunted the reduction of iliac blood flow induced by the onset of REM sleep. The present observations suggest that the onset of REM sleep appears to be associated with a vasodilation in viscera and a vasoconstriction in skeletal muscle, such that systemic arterial pressure increases during REM sleep in rats.
The ABI1 and ABI2 protein phosphatases 2C act in a negative feedback regulatory loop of the abscisic acid signalling pathway (2001)

The Arabidopsis ABI1 and ABI2 genes encode two protein serine/threonine phosphatases 2C (PP2C). These genes have been originally identified by the dominant mutations abi1--1 and abi2--1, which reduce the plant's responsiveness to the hormone abscisic acid (ABA). However, recessive mutants of ABI1 were recently shown to be supersensitive to ABA, which demonstrated that the ABI1 phosphatase is a negative regulator of ABA signalling. We report here the isolation and characterisation of the first reduction-of-function allele of ABI2, abi2--1R1. The in vitro phosphatase activity of the abi2--1R1 protein is approximately 100-fold lower than that of the wild-type ABI2 protein. Abi2--1R1 plants displayed a wild-type ABA sensitivity. However, doubly mutant plants combining the abi2--1R1 allele and a loss-of-function allele at the ABI1 locus were more responsive to ABA than each of the parental single mutants. These data indicate that the wild-type ABI2 phosphatase is a negative regulator of ABA signalling, and that the ABI1 and ABI2 phosphatases have overlapping roles in controlling ABA action. Measurements of PP2C activity in plant extracts showed that the phosphatase activity of ABI1 and ABI2 increases in response to ABA. These results suggest that ABI1 and ABI2 act in a negative feedback regulatory loop of the ABA signalling pathway.
Glycerol utilization by Rhizobium leguminosarum requires an ABC transporter and affects competition for nodulation (2012)

Plasmid curing has shown that the ability to use glycerol as a carbon source is plasmid-encoded in Rhizobium leguminosarum. We isolated the locus responsible for glycerol utilization from plasmid pRleVF39c in R. leguminosarum bv. viciae VF39. This region was analyzed by DNA sequencing and mutagenesis. The locus encompasses a gene encoding GlpR (a DeoR regulator), genes encoding an ABC transporter, and genes glpK and glpD, encoding a kinase and dehydrogenase, respectively. All the genes except the regulatory gene glpR were organized into a single operon, and were required for growth on glycerol. The glp operon was strongly induced by both glycerol and glycerol 3-phosphate, as well as by pea seed exudate. GlpR repressed the operon in the absence of inducer. Mutation of genes encoding the ABC transporter abolished all transport of glycerol in transport assays using radiolabelled glycerol. This confirms that, unlike in other organisms such as Escherichia coli and Pseudomonas aeruginosa, which use facilitated diffusion, glycerol uptake occurs by an active process in R. leguminosarum. Since the glp locus is highly conserved in all sequenced R. leguminosarum and Rhizobium etli strains, as well as in Sinorhizobium spp. and Agrobacterium spp. and other alphaproteobacteria, this process for glycerol uptake is probably widespread. Mutants unable to use glycerol were deficient in competitiveness for nodulation of peas compared with the wild-type, suggesting that glycerol catabolism confers an advantage upon the bacterium in the rhizosphere or in the infection thread.
„V/Q mismatch“ bei sekundärer pulmonaler Hypertonie – Riociguat im Vergleich (2011)

Etablierte Therapien der pulmonal-arteriellen Hypertonie (PAH) scheiterten bisher bei sekundären Formen der pulmonalen Hypertonie (PH) aufgrund von Entsättigungseffekten mit Hypoxämie. Ziel dieses Projekts war es, ein Tiermodell zu etablieren, um unterschiedliche Vasodilatatoren unter experimentell induzierter heterogener Ventilation im Hinblick auf ihr Entsättigungspotenzial vergleichend zu untersuchen.
Lignin Biosynthesis and Structure (2010)

Lignin is the generic term for a large group of aromatic polymers resulting from the oxidative combinatorial coupling of 4-hydroxyphenylpropanoids ([Boerjan et al., 2003][1]; [Ralph et al., 2004][2]). These polymers are deposited predominantly in the walls of secondarily thickened cells, making them
RACE, SEARCH, AND MY BABY-SELF: REFLECTIONS OF A TRANSRACIAL ADOPTEE (1997)

In these two works, Susan Harris gives voice to the realities of her experiences as a transracial adoptee and the experiences of other persons of color adopted into white families. "Can You Imagine?" is a narrative of stories pieced together and drawn from the stories of transracial adoptees whom Harris has met, counseled, and known. It unmasks the unique complexities of race and racism, so often ignored, in the lives of transracial adoptees, and challenges adoptive families and adoption professionals to honestly confront the role of race in the adoption process. In "Come Celebrate My First Birthday," Harris discusses the painful and joyous revelations of her search for information regarding the first fourteen months of her life-when her "baby-self' spent this "holding period" in foster care. During this search for her baby-self, Harris discovers that her baby-self was very likely the victim of some of the many types of racial assault depicted in "Can You Imagine?" In her telling of her story, Harris points out the need for increased attention to adoptive searches which target the holding period, an area of exploration crucial to an adoptee's understanding of herself.
The lipocalin protein family: A role in cell regulation (1994)

The lipocalins, a large, diverse, but relatively poorly understood family of small extracellular proteins, are characterized by the ability to bind small hydrophobic molecules, such as retinol, and by their binding to specific cell surface receptors. These general properties suggest such proteins as appropriate transporters transferring biologically hazardous molecules in a safe and controlled manner between cells. Moreover, many lipocalins have been implicated in the regulation of cell homeostasis: apolipoprotein D, quiescience specific protein, purpurin, alpha-1-microglobulin, and NGAL. This combination of direct and indirect evidence suggests that the lipocalin protein family may be involved, in a quite general way, in the mediation of cell regulation and that many presently functionless family members might act in this way.
Binding or Bending: Distinction of Allosteric Abl Kinase Agonists from Antagonists by an NMR-Based Conformational Assay (2010)

Allosteric inhibitors of Bcr-Abl have emerged as a novel therapeutic option for the treatment of CML. Using fragment-based screening, a search for novel Abl inhibitors that bind to the myristate pocket was carried out. Here we show that not all myristate ligands are functional inhibitors, but that the conformational state of C-terminal helix_I is a structural determinant for functional activity. We present an NMR-based conformational assay to monitor the conformation of this crucial helix_I and show that myristate ligands that bend helix_I are functional antagonists, whereas ligands that bind to the myristate pocket but do not induce this conformational change are kinase agonists. Activation of c-Abl by allosteric agonists has been confirmed in a biochemical assay.
Regulatory Oversight and Safety of Probiotic Use (2010)

Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. For dietary supplements, premarketing demonstration of safety and efficacy and approval by the Food and Drug Administration are not required; only premarket notification is required. Saccharomyces boulardii is a probiotic regulated as a dietary supplement intended for use by the general healthy population, not as a drug to prevent, treat, or mitigate disease. However, since recent increases in incidence and severity of Clostridium difficile infection, probiotics have been used to treat recurrent and/or refractory disease in hospitalized patients. Saccharomyces fungemia secondary to use of the probiotic has been described for patients who are critically ill, are receiving nutrition enterally, or have a central venous catheter. Before use of a probiotic is considered for hospitalized patients, careful assessment of risk versus benefit must be made. To ensure patient safety, probiotics should be properly handled during administration.
Nonsense mutations in the human β-globin gene lead to unexpected levels of cytoplasmic mRNA accumulation (2000)

Generally, nonsense codons 50 bp or more upstream of the 3′-most intron of the human β-globin gene reduce mRNA abundance. In contrast, dominantly inherited β-thalassemia is frequently associated with nonsense mutations in the last exon. In this work, murine erythroleukemia (MEL) cells were stably transfected with human β-globin genes mutated within each of the 3 exons, namely at codons 15 (TGG→TGA), 39 (C→T), or 127 (C→T). Primer extension analysis after erythroid differentiation induction showed codon 127 (C→T) mRNA accumulated in the cytoplasm at approximately 20% of the normal mRNA level. Codon 39 (C→T) mutation did not result in significant mRNA accumulation. Unexpectedly, codon 15 (TGG→TGA) mRNA accumulated at approximately 90%. Concordant results were obtained when reticulocyte mRNA from 2 carriers for this mutation was studied. High mRNA accumulation of codon 15 nonsense-mutated gene was revealed to be independent of the type of nonsense mutation and the genomic background in which this mutation occurs. To investigate the effects of other nonsense mutations located in the first exon on the mRNA level, nonsense mutations at codons 5, 17, and 26 were also cloned and stably transfected into MEL cells. After erythroid differentiation induction, mRNAs with a mutation at codon 5 or 17 were detected at high levels, whereas the mutation at codon 26 led to low mRNA levels. These findings suggest that nonsense-mediated mRNA decay is not exclusively dependent on the localization of mutations relative to the 3′-most intron. Other factors may also contribute to determine the cytoplasmic nonsense-mutated mRNA level in erythroid cells.
Electrochemical Saccharide Recognition by a Phenylboronic Acid-Terminated Redox Active Self-Assembled Monolayer on a Gold Electrode (2000)

Abstract Phenylboronic acid-terminated viologen-carrying alkyl disulfide (1) and a reference compound 2 were designed and synthesized. Self-assembled monolayers of 1 on gold electrodes were found to function as a highly sensitive saccharide sensor in aqueous solution.