gebhart/patrepeval huggingface dataset:
Experimental Evidence for Bone Marrow as a Source of Nonhematopoietic Endometrial Stromal and Epithelial Compartment Cells in a Murine Model1 (2013)

Human endometrium has the remarkable ability to regenerate all cellular compartments with every menstrual cycle; the cellular source remains unknown. The objective of the present study was to determine whether the bone marrow (BM) is a source of multiple endometrial cell types using a murine BM transplant model. BM cells were harvested from transgenic donor mice that ubiquitously express green fluorescent protein (GFP) and were injected into lethally irradiated, syngeneic female recipient mice. Recipients with successful hematopoietic reconstitution were sacrificed at 3, 5, 9, and 12 mo posttransplant, after which hysterectomy was performed. Numbers of GFP-positive, CD45-positive, and CD45-negative cells in the endometrial stromal and epithelial compartments were determined. In the stromal compartment, BM-derived cells (BMDCs) were detectable as early as 3 mo posttransplant, and the BM remained a long-term contributor of nonhematopoietic endometrial cells. Nonhematopoietic endometrial cells comprised 47.3%-72.2% of total BMDCs in the stromal compartment at 12 mo posttransplant. In contrast, BMDCs were not detected in the glandular or luminal epithelial compartments until 12 mo posttransplant. These data demonstrate that the BM is a significant source of nonhematopoietic endometrial stromal compartment cells and contributes to a much lesser extent to the epithelial compartments. That BM is a source of nonhematopoietic cells in the endometrial stromal and epithelial compartments provides a potential mechanism by which monthly regeneration of the endometrium may occur.
A novel modular mosaic of cell adhesion motifs in the extracellular domains of the neurogenic trk and trkB tyrosine kinase receptors. (1991)

The extracellular domains of the human trk protooncogene and the closely homologous murine trkB share two highly conserved regions as well as several invariant cysteines which are supposed to be important for ligand recognition. Detailed comparative sequence analyses have now revealed the presence of a novel combination of distinct cell adhesion motifs corresponding precisely with these conserved regions. The N-terminal part consists of an array of three tandem leucine-rich motifs of 24 amino acids which is flanked by two distinct cysteine clusters. Significantly homologous structural features are found in the toll gene product of Drosophila, a transmembrane protein mediating specific cell adhesion events involved in the dorsoventral embryonic pattern formation. Directly adjacent to these structures we additionally identified two repeats of the immunoglobulin-like C2 type, which are significantly similar to repeats found in the neural cell adhesion molecules (N-CAMs) and in the platelet-derived growth factor receptor (PDGFR)-like tyrosine kinase receptor family. Our findings indicate that the trk/trkB protein tyrosine kinase receptors are involved in the transmembrane signalling of growth factor binding as well as of specific cell adhesion events during neuronal development. Additionally, we propose that the specifically expressed truncated forms of the trkB receptor, lacking the tyrosine kinase domain, are functioning as neural cell adhesion molecules. The knowledge of this domain structure will facilitate the elucidation of the molecular reasons why alterations in the extracellular region lead to oncogenic activation of the human trk proto-oncogene, which is a major cause of papillary thyroid carcinoma.
High‐efficiency protein expression mediated by enterovirus 71 internal ribosome entry site (2005)

An internal ribosome entry site (IRES) has been used to facilitate the expression of more than one protein in a single transcript. In this study, we examined the translational activities of several IRES elements derived from different RNA viruses. The protein expression of encephalomyocarditis virus (EMCV) IRES is similar to that of hepatitis C virus (HCV) IRES in mammalian cells. Notably, the protein expression of enterovirus 71 (EV71) IRES was 23-fold higher than the efficiency of EMCV IRES following normalization of mRNA transcriptional level. Thus, expression of the secreted alkaline phosphatase (SEAP) reporter protein in mammalian cells may be controlled at desirable levels by using appropriate IRES in the expression vector.
Optimization of Electroporation Parameters for the Intramuscular Delivery of Plasmids in Pigs (2003)

Increased transgene expression after plasmid transfer to the skeletal muscle is obtained with electroporation in many species, but optimum conditions are not well defined. Using a plasmid with a muscle-specific secreted embryonic alkaline phosphatase (SEAP) gene, we have optimized the electroporation conditions in a large mammal (pig). Parameters tested included electric field intensity, number of pulses, lag time between plasmid injection and electroporation, and plasmid delivery volume. Electric pulses, between 0.4 and 0.6 Amp constant current, applied 80 sec after the injection of 0.5 mg SEAP-expressing plasmid in a total volume of 2 mL produced the highest levels of expression. Further testing demonstrated that electroporation of a nondelineated injection site reduces the levels of SEAP expression. These results demonstrate that electroporation parameters such as amperage, lag time, and the number of pulses are able to regulate the levels of reporter gene expression in pigs.
A ubiquitous protein is the source of naturally occurring peptides that are recognized by a CD8+ T-cell clone. (1993)

We previously isolated from mouse spleen an octapeptide (LSPFPFDL) that in association with the class I major histocompatibility complex protein Ld is recognized by the antigen-specific receptor of an alloreactive CD8+ T-cell clone (2C). Guided by an assay dependent upon the same 2C T-cell receptor, we have now isolated from the same source another naturally occurring peptide. The second peptide (VAITRIEQLSPFPFDL) includes the entire octapeptide sequence and preliminary evidence suggests that it may be a natural precursor of the octapeptide. On finding extensive sequence homology between the 16-mer and part of human 2-oxoglutarate dehydrogenase, we determined the cDNA sequence of mouse 2-oxoglutarate dehydrogenase and found that the deduced amino acid sequence matches precisely the two naturally occurring peptides, indicating their origin by cellular processing of this ubiquitous self protein.
The role of iron in doxorubicin-induced cardiomyopathy. (1998)

Doxorubicin participates in a wide range of free radical reactions. The drug can undergo one electron reduction to the corresponding semiquinone, leading the generation of superoxide and hydrogen peroxide. Additionally, the drug causes the disappearance of cardiac glutathione peroxidase, leaving the heart with no means of disposing of the hydrogen peroxide thus generated. Doxorubicin also is a powerful iron chelator and the resultant iron-drug complex is an efficient catalyst of the conversion of hydrogen peroxide to the highly reactive hydroxyl radical. Without the drug-iron complex, little or no cardiac production of hydroxyl radical occurs and heart damage does not occur.
Characterisation of the metal‐ion–GDP complex at the active sites of transforming and nontransforming p21 proteins by observation of the 17O‐Mn superhyperfine coupling and by kinetic methods (1987)

Kinetic studies on the interaction of three Ha-ras-encoded p21 proteins with GDP and MgGDP have yielded values for the association (10(6)-10(7) M-1 s-1) and dissociation (10(-3)-10(-5) s-1) rate constants at 0 degrees C. Dramatic differences in the rate constants were not observed for the three proteins. Under non-physiological conditions (absence of Mg2+), the rate constant for GDP release was an order of magnitude faster for the viral protein p21v than for the cellular form p21c or the T24 mutant p21t, but this was reduced to a factor of about 3 in the presence of Mg2+. In all cases, there was an increase of about one order of magnitude in the rate of GDP release on removing magnesium. The binding affinities ranged from 5.7 X 10(10) M-1 for p21c to 1.3 X 10(11) M-1 for p21v. Electron paramagnetic resonance (EPR) measurements on Mn2+ bound together with stereospecifically 17O-labelled GDP showed direct coordination of a beta-phosphate oxygen to the metal ion with a superhyperfine coupling constant of 0.16-0.22 mT, but no interaction with the alpha-phosphate oxygens at the active site of all three proteins. The association constant of Mn(II) to p21 proteins in the absence of nucleotides was estimated to be greater than 10(5) M-1. In agreement with the EPR results, experiments on the metal ion dependence of the binding of thiophosphate analogs of GDP provided further evidence for the absence of direct coordination of the metal ion to the alpha-phosphate group. These results have been used to construct a model for the interactions of Mg X GDP with the active site of p21 proteins.
Marburg virus infection in nonhuman primates: Therapeutic treatment by lipid-encapsulated siRNA (2014)

Marburg virus (MARV) and the closely related filovirus Ebola virus cause severe and often fatal hemorrhagic fever (HF) in humans and nonhuman primates with mortality rates up to 90%. There are no vaccines or drugs approved for human use, and no postexposure treatment has completely protected nonhuman primates against MARV-Angola, the strain associated with the highest rate of mortality in naturally occurring human outbreaks. Studies performed with other MARV strains assessed candidate treatments at times shortly after virus exposure, before signs of disease are detectable. We assessed the efficacy of lipid nanoparticle (LNP) delivery of anti-MARV nucleoprotein (NP)-targeting small interfering RNA (siRNA) at several time points after virus exposure, including after the onset of detectable disease in a uniformly lethal nonhuman primate model of MARV-Angola HF. Twenty-one rhesus monkeys were challenged with a lethal dose of MARV-Angola. Sixteen of these animals were treated with LNP containing anti-MARV NP siRNA beginning at 30 to 45 min, 1 day, 2 days, or 3 days after virus challenge. All 16 macaques that received LNP-encapsulated anti-MARV NP siRNA survived infection, whereas the untreated or mock-treated control subjects succumbed to disease between days 7 and 9 after infection. These results represent the successful demonstration of therapeutic anti-MARV-Angola efficacy in nonhuman primates and highlight the substantial impact of an LNP-delivered siRNA therapeutic as a countermeasure against this highly lethal human disease.
Antifreeze proteins from the sea raven, Hemitripterus americanus. Further evidence for diversity among fish polypeptide antifreezes. (1981)

The antifreeze proteins of the sea raven, Hemitripterus americanus, were isolated and compared with other fish antifreeze proteins. The sea raven contains one major protein of molecular weight 14,000-16,000 with little or no carbohydrate. Except for its similar seasonal appearance, the sea raven antifreeze protein differs from other polypeptide antifreeze in its amino acid composition, secondary structure, and immunological specificity. Amino acid analysis of sea raven antifreeze showed that it contains a high amount of half-cystine, hydrophilic amino acids, and only an average amount of alanine. In contrast, all other fish antifreeze proteins contain approximately 60% alanine and no half-cystine residues. Furthermore, the sea raven antifreeze protein is sensitive to sulfhydryl reagents. The antifreeze activity was decreased by 67% in the presence of 0.01 M dithiothreitol. Circular dichroism studies indicated the absence of significant amounts of alpha-helix and the possible presence of beta-structure. Antibodies raised against the antifreeze protein did not cross-react with the known polypeptide antifreeze from the winter flounder and shorthorn sculpin (Hew, C. L., Fletcher, G. L., and Ananthanarayanan, V. S. (1980) Can. J. Biochem. 58, 377-383). A specific radioimmunoassay was developed for the sea raven antifreeze protein and was used to quantitate the protein concentration in the fish. The seasonal profile obtained by radioimmunoassay was compatible with the antifreeze activity determined with a freezing point osmometer.
Left-handed media and homogenization of photonic crystals (2005)

Using homogenization theory, we derive the effective permittivity and permeability of a wire-mesh photonic crystal from first principles. We show that this structure does not lead to a left-handed medium when it is embedded in a matrix with a negative mu, but that resonators in a medium with a negative epsilon do form a left-handed medium in the correct range of frequencies.
A randomized trial of cerclage vs. 17 α-hydroxyprogesterone caproate for treatment of short cervix (2009)

Objective: To determine pregnancy outcome in patients with short cervix on transvaginal ultrasound between 16 and 24 weeks' gestation treated with McDonald cerclage compared to weekly intramuscular injections of 17 α-hydroxyprogesterone caproate (17OHP-C). Methods: From November 2003 through December 2006, asymptomatic, singleton pregnancies were screened with transvaginal ultrasound between 16-24 weeks' gestation. Patients with a cervical length (CL) <25 mm were offered enrollment. Patients were randomly assigned to treatment with McDonald cerclage or weekly intramuscular injections of 17OHP-C. The primary outcome was spontaneous preterm birth (PTB) prior to 35 weeks' gestation. Results: Seventy-nine patients met inclusion criteria; 42 were randomly assigned to the cerclage and 37 to 17OHP-C. Spontaneous PTB prior to 35 weeks' gestation occurred in 16/42 (38.1 %) of the cerclage group and in 16/37 (43.2%) of the 17OHP-C group (relative risk, 1.14 95% Cl, 0.67, 1.93). A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB <35 weeks between groups. A similar analysis of patients with a CL<15 mm showed a reduction in spontaneous PTB <35 weeks in the cerclage group (relative risk 0.48, 0.24-0.97). Conclusion: Women with CL ≤25 mm in the second-trimester appear to have similar risks of delivering prior to 35 weeks' gestation when treated with 17OHP-C or McDonald cerclage. However, cerclage may be more effective in preventing spontaneous PTB in women with CL≤15 mm.
A Unique Platform for Materials Design (2008)

By combining ionic liquids with block polymers, a virtually unlimited range of composite materials can be prepared.
Synthesis and Characterization of Acetalated Dextran Polymer and Microparticles with Ethanol as a Degradation Product (2012)

In the field of drug delivery, pH-sensitive polymeric microparticles can be used to release therapeutic payloads slowly in extracellular conditions (pH 7.4) and faster in more acidic areas in vivo, such as sites of inflammation, tumors, or intracellular conditions. Our group currently uses and is further developing the pH-sensitive polymer acetalated dextran (Ac-DEX), which is a biodegradable polymer with highly tunable degradation kinetics. Ac-DEX has displayed enhanced delivery of vaccine and drug components to immune and other cells, making it an extremely desirable polymer for immune applications. Currently, one of the degradation products of Ac-DEX is methanol, which may cause toxicity issues if applied at high concentrations with repeated doses. Therefore, in this manuscript we report the first synthesis and characterization of an Ac-DEX analog which, instead of a methanol degradation product, has a much safer ethanol degradation product. We abbreviate this ethoxy acetal derivatized acetalated dextran polymer as Ace-DEX, with the 'e' to indicate an ethanol degradation product. Like Ac-DEX, Ace-DEX microparticles have tunable degradation rates at pH 5 (intracellular). These rates range from hours to several days and are controlled simply by reaction time. Ace-DEX microparticles also show minimal cytotoxicity compared to commonly used poly(lactic-co-glycolic acid) (PLGA) microparticles when incubated with macrophages. This study aims to enhance the biocompatibility of acetalated dextran-type polymers to allow their use in high volume clinical applications such as multiple dosing and tissue engineering.
Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain (1995)

Abstract CD97 is a monomeric glycoprotein of 75 to 85 kDa that is induced rapidly on the surface of most leukocytes upon activation. We herein report the isolation of a cDNA encoding human CD97 by expression cloning in COS cells. The 3-kb cDNA clone encodes a mature polypeptide chain of 722 amino acids with a predicted molecular mass of 79 kDa. Within the C-terminal part of the protein, a region with seven hydrophobic segments was identified, suggesting that CD97 is a seven-span transmembrane molecule. Sequence comparison indicates that CD97 is the first leukocyte Ag in a recently described superfamily that includes the receptors for secretin, calcitonin, and other mammalian and insect peptide hormones. Different from these receptors, CD97 has an extended extracellular region of 433 amino acids that possesses three N-terminal epidermal growth factor-like domains, two of them with a calcium-binding site, and a single Arg-Gly-Asp (RGD) motif. The existence of structural elements characteristic for extracellular matrix proteins in a seven-span transmembrane molecule makes CD97 a receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. The gene encoding CD97 is localized on chromosome 19 (19p13.12-13.2).
Imparting Temperature Sensitivity and Attenuation in Ferrets to A/Puerto Rico/8/34 Influenza Virus by Transferring the Genetic Signature for Temperature Sensitivity from Cold-Adapted A/Ann Arbor/6/60 (2003)

The four temperature-sensitive (ts) loci identified in the PB1 and PB2 gene segments of cold-adapted A/Ann Arbor/6/60 influenza virus, the master donor virus for influenza A virus (MDV-A) FluMist vaccines, were introduced into a divergent A/Puerto Rico/8/34 influenza virus strain. Recombinant A/Puerto Rico/8/34 virus with these four introduced ts loci exhibited both ts and att phenotypes similar to those of MDV-A, which could be used as a donor virus for manufacturing large quantities of inactivated influenza virus vaccine against potential pandemic strains.
A single molecule array for digital targeted molecular analyses (2008)

We present a new random array format together with a decoding scheme for targeted multiplex digital molecular analyses. DNA samples are analyzed using multiplex sets of padlock or selector probes that create circular DNA molecules upon target recognition. The circularized DNA molecules are amplified through rolling-circle amplification (RCA) to generate amplified single molecules (ASMs). A random array is generated by immobilizing all ASMs on a microscopy glass slide. The ASMs are identified and counted through serial hybridizations of small sets of tag probes, according to a combinatorial decoding scheme. We show that random array format permits at least 10 iterations of hybridization, imaging and dehybridization, a process required for the combinatorial decoding scheme. We further investigated the quantitative dynamic range and precision of the random array format. Finally, as a demonstration, the decoding scheme was applied for multiplex quantitative analysis of genomic loci in samples having verified copy-number variations. Of 31 analyzed loci, all but one were correctly identified and responded according to the known copy-number variations. The decoding strategy is generic in that the target can be any biomolecule which has been encoded into a DNA circle via a molecular probing reaction.
Bladder wall grafting in rats using salt‐modified and collagen‐coated polycaprolactone scaffolds: Preliminary report (2007)

In the rat model, we have successfully demonstrated the applicability of collagen coated and salt-modified PCL in reconstruction of the partial cystectomized bladder.
Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23) (2012)

X-linked retinitis pigmentosa (XLRP) is genetically heterogeneous with two causative genes identified, RPGR and RP2. We previously mapped a locus for a severe form of XLRP, RP23, to a 10.71 Mb interval on Xp22.31-22.13 containing 62 genes. Candidate gene screening failed to identify a causative mutation, so we adopted targeted genomic next-generation sequencing of the disease interval to determine the molecular cause of RP23. No coding variants or variants within or near splice sites were identified. In contrast, a variant deep within intron 9 of OFD1 increased the splice site prediction score 4 bp upstream of the variant. Mutations in OFD1 cause the syndromic ciliopathies orofaciodigital syndrome-1, which is male lethal, Simpson-Golabi-Behmel syndrome type 2 and Joubert syndrome. We tested the effect of the IVS9+706A>G variant on OFD1 splicing in vivo. In RP23 patient-derived RNA, we detected an OFD1 transcript with the insertion of a cryptic exon spliced between exons 9 and 10 causing a frameshift, p.N313fs.X330. Correctly spliced OFD1 was also detected in patient-derived RNA, although at reduced levels (39%), hence the mutation is not male lethal. Our data suggest that photoreceptors are uniquely susceptible to reduced expression of OFD1 and that an alternative disease mechanism can cause XLRP. This disease mechanism of reduced expression for a syndromic ciliopathy gene causing isolated retinal degeneration is reminiscent of CEP290 intronic mutations that cause Leber congenital amaurosis, and we speculate that reduced dosage of correctly spliced ciliopathy genes may be a common disease mechanism in retinal degenerations.
Alumina etch masks for fabrication of high-aspect-ratio silicon micropillars and nanopillars (2009)

We introduce using sputtered aluminum oxide (alumina) as a resilient etch mask for fluorinated silicon reactive ion etches. Achieving selectivity of 5000:1 for cryogenic silicon etching and 68:1 for SF(6)/C(4)F(8) silicon etching, we employ this mask for fabrication of high-aspect-ratio silicon micropillars and nanopillars. Nanopillars with diameters ranging from below 50 nm up to several hundred nanometers are etched to heights greater than 2 microm. Micropillars of 5, 10, 20, and 50 microm diameters are etched to heights of over 150 microm with aspect ratios greater than 25. Processing and characterization of the sputtered alumina is also discussed.
Family 4 Glycosidases Carry Out Efficient Hydrolysis of Thioglycosides by an α,β‐Elimination Mechanism (2006)

Thioglycosides are widely used as competitive inhibitors of glycosidases. The first glycosidase capable of hydrolyzing unactivated thioglycosides—BglT, a 6-phospho-β-glucosidase from glucosidase family 4—has been found. The efficient cleavage of the thioglycosidic linkage is a consequence of the α,β-elimination mechanism used by GH4 enzymes, in contrast to the nucleophilic displacement mechanisms of “classical” glycosidases.
In Vitro Activities of CB-183,315, Vancomycin, and Metronidazole against 556 Strains of Clostridium difficile, 445 Other Intestinal Anaerobes, and 56 Enterobacteriaceae Species (2011)

MICs of CB-183,315, a novel lipopeptide antibiotic, vancomycin, and metronidazole were determined for intestinal anaerobes and Enterobacteriaceae. The MIC(90)s for Gram-negative anaerobes were >8,192, 8,192, and 4 μg/ml for CB-183,315, vancomycin, and metronidazole, respectively. Against Enterobacteriaceae, the MIC(90)s were >8,192 μg/ml, 1,024 μg/ml, and 1,024 μg/ml, respectively. The CB-183,315 MIC(90) for Clostridium difficile was 0.5 μg/ml. Its lack of activity against normal fecal organisms makes it a promising new agent for treating C. difficile.