gebhart/patrepeval huggingface dataset:
Stability and Pharmacokinetic Characteristics of Oligonucleotides Modified at Terminal Linkages in Mice (1995)

To construct the strategy for delivery systems that can control in vivo disposition of antisense oligonucleotides, we studied the stability and basic pharmacokinetic characteristics of oligonucleotides. Decathymidylic acid (T10), a model oligodeoxynucleotide, and its derivatives, 5'-biotin-T10) and 3'-methoxyethylamine 5'-biotin-T10 (3'M5'B-T10), containing phosphoroamidate modification at 3'- and/or 5'-terminal internucleoside linkages, were synthesized. In phosphate-buffered saline (PBS, pH 7.4) containing 10% mouse serum, unmodified T10 was degraded with a half-life of 45 minutes; the degradation half-lives of 5'B-T10 and 3'M5'B-T10 were 11 and 30 h, respectively. In mouse whole blood, 3'M5'B-T10 was relatively stable, and 45% remained intact after 1 h incubation. After intravenous injection of [3H]3'M5'B-T10 into mice at a dose of 1 mg/kg, the radioactivity was rapidly cleared from plasma with a half-life of 2 minutes and accumulated in the kidney, liver, and gallbladder. About 30% of the dose was excreted in the urine within 60 minutes. A much more rapid degradation of [3H]3'M5'B-T10 was observed in vivo than expected from in vitro experiments: more than 90% of the radioactivity in plasma was degradation product at 2 minutes after injection. These results suggested that enzymatic degradation occurred in some compartments in addition to the blood pool. The apparent urinary excretion clearance of [3H]3'M5'B-T10 was close to that of inulin, whereas the apparent hepatic uptake clearance was much greater than that of inulin and comparable to that of dextran sulfate, which is taken up by the liver by scavenger receptors for polyanions.(ABSTRACT TRUNCATED AT 250 WORDS)
Toward Ubiquitous Blood Pressure Monitoring via Pulse Transit Time: Theory and Practice (2015)

Ubiquitous blood pressure (BP) monitoring is needed to improve hypertension detection and control and is becoming feasible due to recent technological advances such as in wearable sensing. Pulse transit time (PTT) represents a well-known potential approach for ubiquitous BP monitoring. The goal of this review is to facilitate the achievement of reliable ubiquitous BP monitoring via PTT. We explain the conventional BP measurement methods and their limitations; present models to summarize the theory of the PTT-BP relationship; outline the approach while pinpointing the key challenges; overview the previous work toward putting the theory to practice; make suggestions for best practice and future research; and discuss realistic expectations for the approach.
Power-optimized waveforms for improving the range and reliability of RFID systems (2009)

A major limitation in passive radio frequency identification (RFID) is the read range from the reader to tag, which is limited by the power available to the radio frequency integrated circuit (RFIC). The power-optimized waveform (POW) is a new type of multiple-tone carrier and modulation scheme that is designed to improve the read range and power efficiency of charge pump-based passive RFICs. This paper presents the POW concept, an estimation of effects on existing class 1 generation 2 RFID systems, several example POWs, simulation results, and measurement results of read range gains using a POW.
Hyperconserved CpG domains underlie Polycomb-binding sites (2007)

Comparative genomics of CpG dinucleotides, which are targets of DNA methyltransferases in vertebrate genomes, has been constrained by their evolutionary instability and by the effect of methylation on their mutation rates. We compared the human and chimpanzee genomes to identify DNA sequence signatures correlated with rates of mutation at CpG dinucleotides. The new signatures were used to develop robust comparative genomics of CpG dinucleotides in heterogeneous regions and to identify genomic domains that have anomalous CpG divergence rates. The data showed that there are approximately 200 genomic regions where CpG distributions are far more conserved than predicted. These hyperconserved CpG domains largely coincide with domains bound by Polycomb repressive complex 2 in undifferentiated human embryonic stem cells and are almost exclusively present near genes whose products are involved in the regulation of embryonic development. Several domains were experimentally shown to be unmethylated at different developmental stages. These data indicate that particular evolutionary patterns and distinct sequence properties on scales much larger than standard transcription factor-binding sites may play an important role in Polycomb recruitment and transcriptional regulation of key developmental genes.
THE HUMAN MIXED LYMPHOCYTE-ENDOTHELIUM CULTURE INTERACTION (1975)

Cells separated from the wall of the umbilical cord vein by collagenase digestion could be identified as endothelial by their characteristic ultrastructure, their growth pattern in culture, and their microscopical morphology. These cells, both freshly explanted and after long-term culturing, were capable of stimulating allogeneic lymphocytes in vitro. Control experiments indicated that this stimulation was not attributable to contamination of the endothelial cell suspensions by foetal fibroblasts or passenger lymphocytes. The dose response characteristics and kinetics of the lymphoproliferative response using endothelial stimulating cells was similar to mixed lymphocyte cultures. Sera which were capable of inhibiting the mixed lymphocyte culture response were relatively ineffective in inhibiting the stimulation caused by endothelial cells.
Stimulation of Proliferation of a Human Osteosarcoma Cell Line by Exogenous Acidic Fibroblast Growth Factor Requires both Activation of Receptor Tyrosine Kinase and Growth Factor Internalization (1996)

U2OS Dr1 cells, originating from a human osteosarcoma, are resistant to the intracellular action of diphtheria toxin but contain toxin receptors on their surfaces. These cells do not have detectable amounts of fibroblast growth factor receptors. When these cells were transfected with fibroblast growth factor receptor 4, the addition of acidic fibroblast growth factor to the medium induced tyrosine phosphorylation, DNA synthesis, and cell proliferation. A considerable fraction of the cell-associated growth factor was found in the nuclear fraction. When the growth factor was fused to the diphtheria toxin A fragment, it was still bound to the growth factor receptor and induced tyrosine phosphorylation but did not induce DNA synthesis or cell proliferation, nor was any fusion protein recovered in the nuclear fraction. On the other hand, when the fusion protein was associated with the diphtheria toxin B fragment to allow translocation to the cytosol by the toxin pathway, the fusion protein was targeted to the nucleus and stimulated both DNA synthesis and cell proliferation. In untransfected cells containing toxin receptors but not fibroblast growth factor receptors, the fusion protein was translocated to the cytosol and targeted to the nucleus, but in this case, it stimulated only DNA synthesis. These data indicate that the following two signals are required to stimulate cell proliferation in transfected U2OS Dr1 cells: the tyrosine kinase signal from the activated fibroblast growth factor receptor and translocation of the growth factor into the cell.
Isolation and characterization of an inhibitor of neovascularization from scapular chondrocytes. (1992)

An inhibitor of neovascularization from the conditioned media of scapular chondrocytes established and maintained in serum-free culture has been isolated and characterized. To determine whether this chondrocyte-derived inhibitor (ChDI) was capable of inhibiting neovascularization in vivo, this protein was assayed in the chick chorioallantoic membrane assay. ChDI was a potent inhibitor of angiogenesis in vivo (4 micrograms = 87% avascular zones). This inhibitor is also an inhibitor of fibroblast growth factor-stimulated capillary endothelial cell (EC) proliferation and migration, as well as being an inhibitor of mammalian collagenase. ChDI significantly suppressed capillary EC proliferation in a dose-dependent, reversible manner with an IC50 (the inhibitory concentration at which 50% inhibition is achieved) of 2.025 micrograms/ml. Inhibition by ChDI of growth factor-stimulated capillary EC migration was also observed using a modified Boyden chamber assay (IC50 = 255 ng/ml). SDS-PAGE analysis followed by silver staining of ChDI purified to apparent homogeneity revealed a single band having an M(r) of 35,550. Gel elution experiments demonstrated that only protein eluting at this molecular weight was anti-angiogenic. These studies are the first demonstration that chondrocytes in culture can produce a highly enriched, potent inhibitor of neovascularization which also inhibits collagenase.
HTRA1 and TGF-β1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration (2017)

In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-β1.
Biotinylated fluorescent peptide substrates for the sensitive and specific determination of cathepsin D activity (2004)

Cathepsin D (CatD) is a member of the mammalian aspartic protease family and is involved in cellular protein degradation and in several pathological processes. A sensitive and specific assay for the determination of CatD activity in biological samples was developed. The peptide amide substrates Amca-EDKPILF downward arrowFRLGK(biotin)-CONH2 (I), Amca-EEKPIC(Acm)F downward arrowFRLGK(biotin)-CONH2 (II) and Amca-EEKPISF downward arrowFRLGK(biotin)-CONH2 (III) contain a CatD cleavage site (F downward arrowF) flanked by a N-terminal Amca-fluorophore (7-amino-4-methylcoumarin-3-acetic acid) and a C-terminal biotin moiety. Substrates II and III proved to be specific substrates containing only one cleavage site for CatD. After cleavage of the Phe-Phe bond by CatD all biotin conjugated peptides were removed with streptavidin-coated magnetic beads. The remaining fluorescent peptides in solution represent the amount of digested substrate. The versatility of this CatD digest and pull down assay was demonstrated by measuring the activity of CatD in different subcellular fractions of human EBV-transformed B cells and human monocytes. The described method based on the designed CatD substrates represents a valuable tool for routine assays.
ChemInform Abstract: New Cryptands with 1,3,5‐Triazines as Ring Building Blocks (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Biochemical Basis for Depressed Serum Retinol Levels in Transthyretin-deficient Mice (2001)

Transthyretin (TTR) acts physiologically in the transport of retinol in the circulation. We previously reported the generation and partial characterization of TTR-deficient (TTR(-)) mice. TTR(-) mice have very low circulating levels of retinol and its specific transport protein, retinol-binding protein (RBP). We have examined the biochemical basis for the low plasma retinol-RBP levels. Cultured primary hepatocytes isolated from wild type (WT) and TTR(-) mice accumulated RBP in their media to an identical degree, suggesting that RBP was being secreted from the hepatocytes at the same rate. In vivo experiments support this conclusion. For the first 11 h after complete nephrectomy, the levels retinol and RBP rose in the circulations of WT and TTR(-) mice at nearly identical rates. However, human retinol-RBP injected intravenously was more rapidly cleared from the circulation (t(12) = 0.5 h for TTR(-) versus t(12) >6 h for WT) and accumulated faster in the kidneys of TTR(-) compared with WT mice. The rate of infiltration of the retinol-RBP complex from the circulation to tissue interstitial fluids was identical in both strains. Taken together, these data indicate that low circulating retinol-RBP levels in TTR(-) mice arise from increased renal filtration of the retinol-RBP complex.
Role of the Rous Sarcoma Virus p10 Domain in Shape Determination of Gag Virus-Like Particles Assembled In Vitro and within Escherichia coli (2000)

Purified retrovirus Gag proteins can assemble in vitro into virus-like particles (VLPs) in the presence of RNA. It was shown previously that a Rous sarcoma virus Gag protein missing only the protease domain forms spherical particles resembling immature virions lacking a membrane but that a similar protein missing the p10 domain forms tubular particles. Thus, p10 plays a role in spherical particle formation. To further study this shape-determining function, we dissected the p10 domain by mutagenesis and examined VLPs assembled within Escherichia coli or assembled in vitro from purified proteins. The results identified a minimal contiguous segment of 25 amino acid residues at the C terminus of p10 that is sufficient to restore efficient spherical assembly to a p10 deletion mutant. Random and site-directed mutations were introduced into this segment of polypeptide, and the shapes of particles formed in E. coli were examined in crude extracts by electron microscopy. Three phenotypes were observed: tubular morphology, spherical morphology, or no regular structure. While the particle morphology visualized in crude extracts generally was the same as that visualized for purified proteins, some tubular mutants scored as spherical when tested as purified proteins, suggesting that a cellular factor may also play a role in shape determination. We also examined the assembly properties of smaller Gag proteins consisting of the capsid protein-nucleocapsid protein (CA-NC) domains with short N-terminal extensions or deletions. Addition of one or three residues allowed CA-NC to form spheres instead of tubes in vitro, but the efficiency of assembly was extremely low. Deletion of the N-terminal residue(s) abrogated assembly. Taken together, these results imply that the N terminus of CA and the adjacent upstream 25 residues play an important role in the polymerization of the Gag protein.
Fibroblast growth factor mediated alterations in drug resistance, and evidence of gene amplification. (1994)

We have investigated the drug resistance and gene amplification potential of NIH3T3 cells transfected with sequences coding for K-FGF, a known oncogene product, or bFGF, a non-oncogene member of the fibroblast growth factor family. Resistance to methotrexate, N-(phosphonacetyl)-L-aspartate and hydroxyurea was observed with K-fgf transfectants, due to amplification of dihydrofolate reductase, CAD or ribonucleotide reductase R2 genes, respectively. In keeping with the increase in gene amplification frequency, cells transfected with the K-fgf gene also exhibited a marked increase in CAD gene amplification rate, as determined by fluctuation analysis in the presence of N-(phosphonacetyl)-L-aspartate. Cells transfected with bFGF encoding cDNA also exhibited a significant elevation in N-(phosphonacetyl)-L-aspartate resistance, and CAD gene amplification. Treatment with suramin, which interferes with the interaction of fibroblast growth factors with their cell surface receptors, did not decrease the drug resistance properties of K-fgf transfected cells. These observations with suramin and the findings with bFGF, which lacks a conventional signal sequence for secretion, suggests that the growth factor-mediated effects on drug resistance and gene amplification occur through an intracellular as opposed to autocrine mode of action. The finding that aberrant growth factor expression regulates gene amplification opens up new possibilities for investigating intracellular mechanisms relevant to this process and also describes new functions for the altered expression of K-FGF and bFGF, which are relevant to mechanisms of malignant progression.
Designing Efficient Inductive Power Links for Implantable Devices (2007)

Due to limited battery life and size limitations, many implantable biomedical devices must be powered inductively. Because of weak coupling between implanted and external coils, obtaining high power efficiency is a challenge. Previous authors have addressed the issue of optimizing power efficiency in these systems. In this paper, we further this analysis for the case of planar spiral "pancake" coils at low RF frequencies (100 kHz -10 MHz). We consider practical design constraints such as component variation, power amplifier limitations, and coil voltage limits. We introduce a new, complete expression for total power link efficiency.
Internalisation and recycling of the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) receptor on a murine myelomonocytic leukemia (1987)

Radioiodinated granulocyte-macrophage colony-stimulating factor (125I-GM-CSF) binds to specific receptors (molecular weight approximately 50,000 daltons) on the murine myelomonocytic leukemia, WEHI-3BD+. At 4 degrees C 125I-GM-CSF remains on the surface of the cells and can be eluted by washing the cells with acidified isotonic buffer. When the cells are warmed to 37 degrees C, the 125I-GM-CSF is internalized rapidly (t 1/2: 7 min). The internalisation appears to be entirely receptor mediated and is independent of energy sources inhibited by sodium azide. This GM-CSF-mediated internalisation is not due to a general increase in the turnover of cell surface molecules as the specific binding of 125I-transferrin is not affected by incubation of WEHI-3BD+ cells with GM-CSF. The initial 125I released when the cells are warmed to 37 degrees C appears to be intact 125I-GM-CSF; however, after 2 h 80% of the 125I released was not precipitable with trichloroacetic acid and presumably represented degraded 125I-GM-CSF. Ammonium chloride or monensin reduced the release of 125I-GM-CSF from the cells, suggesting that the receptor-bound ligand was processed through the lysosomes. A considerable proportion of the internalised GM-CSF receptors were recycled to the surface and were available for ligand binding. Synthesis of new GM-CSF receptors contributed to the re-expression of GM-CSF receptors after down-regulation and it is possible that the GM-CSF enhances the synthesis of its own receptors.
Wafer sawing process characterization for thin die (75micron) applications (2004)

The drive for package thickness reduction has created new processing challenges with regards to thin wafer handling. While back-grinding and die attach film (DAF) lamination are now established procedures, sawing DAF-laminated wafers with wafer thickness 3 mils and below is still a significant challenge. The need is for a suitable saw process that meets the following criteria: less than 1 mil wafer chipping, low cost and high throughput. This paper elaborates work that evaluated different saw parameters and their effects on wafer chipping. 8" wafers with varied die sizes and 2 in 1 DAF-dicing material sets were used during this evaluation. The work evaluated both single and dual pass saw processes. The effects of saw parameters-feed speed, RPM and blade types are also elucidated. The results show that for thin die a dual pass saw process gives better results than a conventional single pass process. Results also show that using non-optimized saw process parameters for a given DAF material set combination could adversely affect the yield consequent assembly processes like die attach and wirebond.
Assessing residual reasoning ability in overtly non-communicative patients using fMRI (2012)

It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple auditory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cognition, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition.
Excision of Reprogramming Transgenes Improves the Differentiation Potential of iPS Cells Generated with a Single Excisable Vector (2009)

The residual presence of integrated transgenes following the derivation of induced pluripotent stem (iPS) cells is highly undesirable. Here we demonstrate efficient derivation of iPS cells free of exogenous reprogramming transgenes using an excisable polycistronic lentiviral vector. A novel version of this vector containing a reporter fluorochrome allows direct visualization of vector excision in living iPS cells in real time. We find that removal of the reprogramming vector markedly improves the developmental potential of iPS cells and significantly augments their capacity to undergo directed differentiation in vitro. We further propose that methods to efficiently excise reprogramming transgenes with minimal culture passaging, such as those demonstrated here, are critical since we find that iPS cells may acquire chromosomal abnormalities, such as trisomy of chromosome 8, similar to embryonic stem cells after expansion in culture. Our findings illustrate an efficient method for the generation of transgene-free iPS cells and emphasize the potential beneficial effects that may result from elimination of integrated reprogramming factors. In addition, our results underscore the consequences of long-term culture that will need to be taken into account for the clinical application of iPS cells.
A tag-based approach for the design and composition of information processing applications (2008)

In the realm of component-based software systems, pursuers of the holy grail of automated application composition face many significant challenges. In this paper we argue that, while the general problem of automated composition in response to high-level goal statements is indeed very difficult to solve, we can realize composition in a restricted context, supporting varying degrees of manual to automated assembly for specific types of applications. We propose a novel paradigm for composition in flow-based information processing systems, where application design and component development are facilitated by the pervasive use of faceted, tag-based descriptions of processing goals, of component capabilities, and of structural patterns of families of application. The facets and tags represent different dimensions of both data and processing, where each facet is modeled as a finite set of tags that are defined in a controlled folksonomy. All data flowing through the system, as well as the functional capabilities of components are described using tags. A customized AI planner is used to automatically build an application, in the form of a flow of components, given a high-level goal specification in the form of a set of tags. End-users use an automatically populated faceted search and navigation mechanism to construct these high-level goals. We also propose a novel software engineering methodology to design and develop a set of reusable, well-described components that can be assembled into a variety of applications. With examples from a case study in the Financial Services domain, we demonstrate that composition using a faceted, tag-based application design is not only possible, but also extremely useful in helping end-users create situational applications from a wide variety of available components.