gebhart/patrepeval huggingface dataset:
Regulation of Gene Expression in Choriocarcinoma by Methotrexate and Hydroxyurea* (1991)

Choriocarcinoma, a highly malignant neoplasm of trophoblastic origin, is remarkable for its marked degree of sensitivity to chemotherapeutic agents. We treated two cell lines derived from choriocarcinoma patients with two antineoplastic agents, methotrexate and hydroxyurea (HU), both of which cause nucleotide depletion and have been previously shown to be effective against choriocarcinoma, and found pleiotropic regulation of several genes. Three genes, hCG alpha-subunit, beta-subunit, and placental alkaline phosphatase, were all strongly induced by methotrexate and HU. Expression of c-myc, an oncogene associated with proliferation, was reduced to nearly undetectable levels by the drug treatment, while expression of beta 2-microglobulin, a component of the class 1 major histocompatibility locus, was unchanged. In addition, the mechanism of induction by HU of one of these genes, the hCG alpha-subunit gene, was found to occur at the level of transcription. The similar effects of methotrexate and HU, two mechanistically unrelated antimetabolites, on the induction of specific gene expression in choriocarcinoma cells suggest that these effects are due to nucleotide pool alteration, rather than specific ligand effects. Furthermore, the hCG alpha-subunit promoter contains a transcriptionally regulated HU-responsive element.
Gadolinium-Encapsulating Iron Oxide Nanoprobe as Activatable NMR/MRI Contrast Agent (2012)

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.
Atmospheric-turbulence-effects correction factors for the laser range equation (2008)

The capability to detect an optical target using laser illumination is typically assessed using an equation commonly referred to as the laser range equation. In practice, however, the laser range equation often produces unreliable predictions when compared to actual results under field conditions. The lack of accuracy is due in large part to the failure of the range equation to account for the effects of atmospheric turbulence on the illuminating laser beam. Retrodirective reflections from a corner cube and a simple lens-mirror system, used as a surrogate for a lens-detector optical system, were studied using near-infrared laser illumination. Each optic was tested under a variety of atmospheric conditions in order to assess the effect of atmospheric turbulence on the returned power. Using established theory, a corrective term for use in the laser range equation that accounts for turbulence-induced beam spreading is developed and compared to experimental results. Additionally, a method for correcting the lab-measured optical cross section of a focused optical system in order to account for the defocusing effects of turbulence is developed. With these corrective terms, the laser range equation was modified to provide accurate return-power predictions under varied atmospheric conditions.
Envelope glycoprotein interactions in coronavirus assembly. (1995)

Coronaviruses are assembled by budding into smooth membranes of the intermediate ER-to-Golgi compartment. We have studied the association of the viral membrane glycoproteins M and S in the formation of the virion envelope. Using coimmunoprecipitation analysis we demonstrated that the M and S proteins of mouse hepatitis virus (MHV) interact specifically forming heteromultimeric complexes in infected cells. These could be detected only when the detergents used for their solubilization from cells or virions were carefully chosen: a combination of nonionic (NP-40) and ionic (deoxycholic acid) detergents proved to be optimal. Pulse-chase experiments revealed that newly made M and S proteins engaged in complex formation with different kinetics. Whereas the M protein appeared in complexes immediately after its synthesis, newly synthesized S protein did so only after a lag phase of > 20 min. Newly made M was incorporated into virus particles faster than S, which suggests that it associates with preexisting S molecules. Using the vaccinia virus T7-driven coexpression of M and S we also demonstrate formation of M/S complexes in the absence of other coronaviral proteins. Pulse-chase labelings and coimmunoprecipitation analyses revealed that M and S associate in pre-Golgi membranes because the unglycosylated form of M appeared in M/S complexes rapidly. Since no association of M and S was detected when protein export from the ER was blocked by brefeldin A, stable complexes most likely arise in the ER-to-Golgi intermediate compartment. Sucrose velocity gradient analysis showed the M/S complexes to be heterogeneous and of higher order, suggesting that they are maintained by homo- and heterotypic interactions. M/S complexes colocalized with alpha-mannosidase II, a resident Golgi protein. They acquired Golgi-specific oligosaccharide modifications but were not detected at the cell surface. Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein. Because coronaviruses bud at pre-Golgi membranes, this result implies that the envelope glycoprotein complexes do not determine the site of budding. Yet, the self-association of the MHV envelope glycoproteins into higher order complexes is indicative of its role in the sorting of the viral membrane proteins and in driving the formation of the viral lipoprotein coat in virus assembly.
Reduced perlecan in mice results in chondrodysplasia resembling Schwartz–Jampel syndrome (2007)

Perlecan knock-in mice were developed to model Schwartz -Jampel syndrome (SJS), a skeletal disease resulting from decreased perlecan. Two mouse strains were generated: those carrying a C-to-Y mutation at residue 1532 and the neomycin cassette (C1532Yneo) and those harboring the mutation alone (C1532Y). Immunostaining, biochemistry, size measurements, skeletal studies and histology revealed Hspg2 transcriptional changes in C1532Yneo mice, leading to reduced perlecan secretion and a skeletal disease phenotype characteristic of SJS patients. Skeletal disease features include smaller size, impaired mineralization, misshapen bones, flat face and joint dysplasias reminiscent of osteoarthritis and osteonecrosis. Moreover, C1532Yneo mice displayed transient expansion of hypertrophic cartilage in the growth plate concomitant with radial trabecular bone orientation. In contrast, C1532Y mice, harboring only the mutation associated with SJS, displayed a mild phenotype, inconsistent with SJS. These studies question the C1532Y mutation as the sole causative factor of SJS in the human family harboring this alteration and imply that transcriptional changes leading to perlecan reduction may represent the disease mechanism for SJS.
Formation of porous PLGA scaffolds by a combining method of thermally induced phase separation and porogen leaching (2008)

Abstract A novel method for the fabrication of porous poly( L ‐lactide‐ co ‐glycolide) (PLGA) scaffolds by combining thermally induced phase separation and porogen leaching is presented in this article. Big pores with about 75–400 μm diameters in the obtained scaffolds were generated by the porogen, sucrose particles, while small pores with diameters less than 20 μm induced via phase separation. Extraction of the solvent, chloroform by ethanol at cool temperatures could reduce the scaffold toxicity. Effects of PLGA concentration, freezing temperature, volume fraction of porogen, and introduction of β‐tricalcium phosphate (β‐TCP) on morphology, porosity, and compressive properties of the scaffolds were systematically discussed. Results showed that the size of small pores decreased by decreasing the polymer concentration and reducing the freezing temperature, whereas the interconnectivity of the scaffolds was improved by increasing the porogen fraction. The compressive modulus and strength were significantly lowered by increasing the scaffold porosity, that is, by increasing porogen fraction, or decreasing the polymer concentration, or reducing the freezing temperature. Addition of β‐TCP into the scaffolds did not influence the compressive modulus significantly but tended to decrease the compressive strength. The obtained scaffolds with diverse pore sizes would be potentially used in bone tissue engineering. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Material modeling and high-speed machining process (1982)

Orthogonal machining experiments have been conducted at moderate speeds with 6061-T6 aluminum and Ti-6Al-4V titanium alloys to measure strain distributions in the deformed chip, using a grid technique. While the aluminum alloy displayed large uniform strain within continuous chips, the titanium alloy exhibited highly nonuniform strain distributions within segmented chips, a feature known to occur under high-speed machining. Concurrently, a set of simple constitutive equations are formulated in order to describe the plastic flow behavior of materials over wide ranges of strain, strain rate and temperature. Based on experimental data, the proposed form of constitutive equation is capable of simulating stress-strain-strain rate relationships of 6061-T6 aluminum and Ti-6Al-4V over the range of strain rates applicable to the high-speed machining process. Given the constitutive relations, analytical problems that will be encountered in modeling the localized shear process are outlined based on the experimental observations of chip formation. As a step toward modeling the high-speed machining process, a partially successful finite element analysis of a simplified, continuous chip orthogonal machining process was made using the ADINA code. Some of the relevant analytical and experimental results that have been obtained for the aluminum and titanium alloys are examined. 47 references, 14 figures.
Novel Antibody-Lectin Enzyme-Linked Immunosorbent Assay That Distinguishes Prion Proteins in Sporadic and Variant Cases of Creutzfeldt-Jakob Disease (2005)

We used different anti-prion protein (anti-PrP) monoclonal antibodies to capture either full-length or truncated PrP species and then used biotinylated lectin to compare the nature of the glycans on bound PrP species present in control, sporadic Creutzfeldt-Jakob disease (sCJD), or variant CJD (vCJD) brains. When full-length PrP species in these three groups were compared, no significant difference in the binding of concanavalin A or Aleuria aurantia lectin was detected. However, the binding of Ricinus communis agglutinin I (RCA) to sCJD and vCJD samples was significantly increased. In contrast, when only truncated PrP species were compared, only vCJD samples had more RCA binding activity. Therefore, while most of the RCA binding activity in sCJD is restricted to the full-length PrP species, the RCA binding activity in vCJD is associated with truncated and full-length PrP species. Furthermore, the RCA binding activity in sCJD and vCJD samples is mostly associated with proteinase K-resistant PrP species, a known signature of infectious prion. Therefore, PrP species in sCJD and vCJD have dissimilar lectin immunoreactivity, which reflects differences in their N-linked glycans. These differences may account for the distinct phenotypes of sCJD and vCJD.
Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung (2008)

Vascular endothelial growth factor (VEGF) is known to have a pivotal role in lung development and in a variety of pathologic conditions in the adult lung. Our earlier studies have shown that NO is a critical mediator of VEGF-induced vascular and extravascular effects in the adult murine lung. As significant differences have been reported in the cytokine responses in the adult versus the neonatal lung, we hypothesized that there may be significant differences in VEGF-induced alterations in the developing as opposed to the mature lung. Furthermore, nitric oxide (NO) mediation of these VEGF-induced effects may be developmentally regulated. Using a novel externally regulatable lung-targeted transgenic murine model, we found that VEGF-induced pulmonary hemorrhage was mediated by NO-dependent mechanisms in adults and newborns. VEGF enhanced surfactant production in adults as well as increased surfactant and lung development in newborns, via an NO-independent mechanism. While the enhanced survival in hyperoxia in the adult was partly NO-dependent, there was enhanced hyperoxia-induced lung injury in the newborn. In addition, human amniotic fluid VEGF levels correlated positively with surfactant phospholipids. Tracheal aspirate VEGF levels had an initial spike, followed by a decline, and then a subsequent rise, in human neonates with an outcome of bronchopulmonary dysplasia or death. Our data show that VEGF can have injurious as well as potentially beneficial developmental effects, of which some are NO dependent, others NO independent. This opens up the possibility of selective manipulation of any VEGF-based intervention using NO inhibitors for maximal potential clinical benefit.
Sorting and processing of secretory proteins (1994)

Research Article| April 01 1994 Sorting and processing of secretory proteins P A Halban; P A Halban 1Laboratoires de Recherche Louis Jeantet, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland Search for other works by this author on: This Site PubMed Google Scholar J C Irminger J C Irminger 1Laboratoires de Recherche Louis Jeantet, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1994) 299 (1): 1–18. https://doi.org/10.1042/bj2990001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation P A Halban, J C Irminger; Sorting and processing of secretory proteins. Biochem J 1 April 1994; 299 (1): 1–18. doi: https://doi.org/10.1042/bj2990001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1994 The Biochemical Society, London1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Exploiting ICN for Efficient Content Dissemination in CDNs (2016)

The Content Delivery Network (CDN) has become an important element in the Internet, which uses applicationlayer caches to improve user experience and reduce network/server load. However, CDNs face efficiency issues due to the following two reasons: 1) they are not aware of the network status, and 2) the underlying location-centric network (IP) does not understand content. At the same time, the Information-Centric Network (ICN) has been developed to address these issues: they use content identities as routing labels and support functions such as multi-source, multicast and in-network caching. While these in-network caches can help improve the content delivery performance, they are unaware of applicationspecific characteristics like policy and popularity. As a result, we believe application-layer CDN solutions are still beneficial in ICN. They can take advantage of ICN content delivery capabilities while having access to application-level details, therefore getting the best from both worlds. In this paper, we propose a CDN architecture over Mobility-First - a representative example of ICN - to show the benefit of such a design. The solution uses self-certifying names that can enable efficient content validation in CDNs, an applicationlayer CDN design that can maximize the utility of caches, and a pushing mechanism that allows content providers cache content proactively. Through a prototype, we show the feasibility and efficiency of the architecture.
Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. (1995)

A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel1a melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel1b melatonin receptor. The Mel1b receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel1a receptor. Transient expression of the Mel1b receptor in COS-1 cells results in high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel1a melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel1b melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel1b melatonin receptor is expressed in retina and, to a lesser extent, brain. PCR analysis of human-rodent somatic cell hybrids maps the Mel1b receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel1b melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals.
A transprecision floating-point platform for ultra-low power computing (2018)

In modern low-power embedded platforms, the execution of floating-point (FP) operations emerges as a major contributor to the energy consumption of compute-intensive applications with large dynamic range. Experimental evidence shows that 50% of the energy consumed by a core and its data memory is related to FP computations. The adoption of FP formats requiring a lower number of bits is an interesting opportunity to reduce energy consumption, since it allows to simplify the arithmetic circuitry and to reduce the memory bandwidth required to transfer data between memory and registers by enabling vectorization. From a theoretical point of view, the adoption of multiple FP types perfectly fits with the principle of transprecision computing, allowing fine-grained control of approximation while meeting specified constraints on the precision of final results. In this paper we propose an extended FP type system with complete hardware support to enable transprecision computing on low-power embedded processors, including two standard formats (binary32 and binary16) and two new formats (binary8 and binary16alt). First, we introduce a software library that enables exploration of FP types by tuning both precision and dynamic range of program variables. Then, we present a methodology to integrate our library with an external tool for precision tuning, and experimental results that highlight the clear benefits of introducing the new formats. Finally, we present the design of a transprecision FP unit capable of handling 8-bit and 16-bit operations in addition to standard 32-bit operations. Experimental results on FP-intensive benchmarks show that up to 90% of FP operations can be safely scaled down to 8-bit or 16-bit formats. Thanks to precision tuning and vectorization, execution time is decreased by 12% and memory accesses are reduced by 27% on average, leading to a reduction of energy consumption up to 30%.
Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release (2017)

Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors.
A rechargeable aluminum-ion battery utilizing a copper hexacyanoferrate cathode in an organic electrolyte (2015)

Reversible aluminum intercalation/deintercalation from an organic electrolyte into copper hexacyanoferrate is presented. Evidence suggest that an aluminum-solute complex is the intercalating species. The system shows initial discharge capacities as high as 60 mA h g(-1) and reversible capacities between 5 and 14 mA h g(-1), with capacity typically fading after 10 to 15 cycles.
Bacterial and fungal core microbiomes associated with small grain silages during ensiling and aerobic spoilage (2017)

Next Generation Sequencing was successfully used to describe bacterial communities and the first record of fungal communities throughout the process of ensiling and utilization. Adequately describing the microbial ecology of silages could lead to improved ensiling practices and the selection of silage inoculants that act synergistically with the natural forage microbiome.
Energy of Crowded Molecules:  3,4,5-Trimethoxybenzoic Acid (2001)

The enthalpy of combustion and enthalpy of sublimation of 3,4,5-trimethoxybenzoic acid (2) were measured, and the gas-phase enthalpy of formation at 298.15 K was calculated. Ab initio energies at the B3LYP/ 6-311+G(d,p) level were calculated for this compound, some mono- and dimethoxybenzoic acids, and a similar series of methyl-substituted benzoic acids. Intramolecular interaction (called the buttressing effect) of the groups COOH and OCH3 (or CH3) was defined in terms of isodesmic homodesmotic reactions. Steric crowding raises the energy of 2 in relation to monomethoxybenzoic acids, but no further effect is observed in comparison with 3,4-dimethoxybenzoic acid, on either calculated or experimental values. Similar results were obtained with 3,4,5-trimethylbenzoic acid (1); a previous claim of interaction of remote groups in the meta position was based on inaccurate enthalpies of formation of reference compounds.