gebhart/patrepeval huggingface dataset:
Mutations of CB<sub>1</sub> T210 Produce Active and Inactive Receptor Forms:  Correlations with Ligand Affinity, Receptor Stability, and Cellular Localization (2006)

Human cannabinoid receptor 1 (CB(1)) has attracted substantial interest as a potential therapeutic target for treating obesity and other obsessive disorders. An understanding of the mechanism governing the transition of the CB(1) receptor between its inactive and active states is critical for understanding how therapeutics can selectively regulate receptor activity. We have examined the importance of the Thr at position 210 in CB(1) in this transition, a residue predicted to be on the same face of the helix as the Arg of the DRY motif highly conserved in the G protein-coupled receptor superfamily. This Thr was substituted with Ile and Ala via mutagenesis, and the receptors, T210I and T210A, were expressed in HEK 293 cells. The T210I receptor exhibited enhanced agonist and diminished inverse agonist affinity relative to the wild type, consistent with a shift toward the active form. However, treatment with GTPgammaS to inhibit G protein coupling diminished the affinity change for the inverse agonist SR141716A. The decreased thermal stability of the T210I receptor and increased level of internalization of a T210I receptor-GFP chimera were also observed, consistent with constitutive activity. In contrast, the T210A receptor exhibited the opposite profile: diminished agonist and enhanced inverse agonist affinity. The T210A receptor was found to be more thermally stable than the wild type, and high levels of a T210A receptor-GFP chimera were localized to the cell surface as predicted for an inactive receptor form. These results suggest that T210 plays a key role in governing the transition between inactive and active CB(1) receptor states.
Pancreatic β‐cell imaging in humans: fiction or option? (2015)

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune-mediated destruction of insulin-secreting pancreatic β cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at β-cell restoration is still hampered by the absence of means to measure β-cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public-private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in β-cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.
HMG-CoA Reductase Inhibitors Reduce MMP-9 Secretion by Macrophages (1998)

-Macrophages secrete matrix metalloproteinases (MMPs) that may weaken the fibrous cap of atherosclerotic plaque, predisposing its fissuration. The 92-kDa gelatinase B (MMP-9) has been identified in abdominal aortic aneurysms and in atherosclerotic tissues. Fluvastatin, through the inhibition of the isoprenoid pathway, inhibits major processes of atherogenesis in experimental models (smooth muscle cell migration and proliferation and cholesterol accumulation in macrophages). We studied the effect of fluvastatin on the activity of MMP-9 in mouse and human macrophages in culture. Conditioned media of cells treated for 24 hours with fluvastatin were analyzed by gelatin zymography. In mouse macrophages, fluvastatin (5 to 100 micromol/L) significantly inhibited in a dose-dependent manner MMP-9 activity from 20% to 40% versus control. The drug, at a concentration as low as 5 micromol/L, inhibited MMP-9 activity ( approximately 30%) in human monocyte-derived macrophages as well. Phorbol esters (TPA, 50 ng/mL) stimulated MMP-9 activity by 50%, and fluvastatin inhibited this enhanced activity up to 50% in both mouse and human macrophages. The above results on the secretion of MMP-9 were confirmed by Western blotting and ELISA. The inhibitory effect of fluvastatin was overcome by the simultaneous addition of exogenous mevalonate (100 micromol/L), a precursor of isoprenoids. Fluvastatin's effect was fully reversible, and the drug did not cause any cellular toxicity. The statin did not block directly the in vitro activation of the secreted protease. Similar data were obtained with simvastatin. Altogether, our data indicate an inhibition of MMP-9 secretion by the drug. This effect is mediated by the inhibition of synthesis of mevalonate, a precursor of numerous derivatives essential for several cellular functions.
Haptic Interfaces for Wheelchair Navigation in the Built Environment (2004)

A number of countries have recently introduced legislation aimed at ending discrimination against disabled people; in the United Kingdom the Disability Discrimination Act (1995) provides the disabled community with new employment and access rights. The intention of the act is to help those who rely on wheelchairs for mobility and who frequently find that not all buildings provide conditions suited to easy access. Central to these new rights will be an obligation for employers and organizations to provide premises that do not disadvantage the disabled. This work reports on the development of instrumentation that allows wheelchair navigation within virtual buildings and can assist architects in identifying the needs of wheel-chair users at an early design stage. Central to this project has been the need to provide a platform that can accommodate a range of wheelchair types and will map intended wheelchair motion into a virtual space. This interface must have the capacity to provide feedback to the user reflecting constraints present in the physical world, including changes in floor surface characteristics, gradients, and collisions. Integrating visual and nonvisual sensory feedback correlating to the physical effort of wheelchair propulsion has been found to augment the perception of self-motion within the virtual world and so can create an effective instrument for use in the study of wheelchair accessibility within the built environment. This project represents a collaborative effort between architects and bioengineers engaged in research related to platform design, construction, and interfacing, while testing and evaluation has been accomplished with the assistance of user groups.
Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved (2011)

Many plastic products are mischaracterized as being EA free if extracted with only one solvent and not exposed to common-use stresses. However, we can identify existing compounds, or have developed, monomers, additives, or processing agents that have no detectable EA and have similar costs. Hence, our data suggest that EA-free plastic products exposed to common-use stresses and extracted by saline and ethanol solvents could be cost-effectively made on a commercial scale and thereby eliminate a potential health risk posed by most currently available plastic products that leach chemicals having EA into food products.
KINETIC STUDY OF METHANOL TO PROPYLENE PROCESS ON HIGH SILICA H-ZSM5 CATALYST (2013)

A series of experiments were carried out by mixture of methanol and water as feed of the methanol to propylene (MTP) process in temperature range of 623-823 K. The HZSM5 catalyst with the Si/Al ratio of 200 was applied for carrying out the experiments. A novel lumped kinetic scheme was proposed for methanol to propylene (MTP) process. The reactor was mathematically modeled by assumptions of being isothermal, fixed bed, plug flow and the hybrid genetic algorithm was applied for estimating the kinetic parameters. The temperature dependency of the kinetic parameters was determined, using the modified Arrhenius relation. A good agreement was observed between the experimental and the calculated data. Effect of temperature on propylene and ethylene selectivity was investigated. It was found that the propylene selectivity increases with temperature until 773.15 K, but after that it decreases.
Sol-gel-derived thick coatings and their thermomechanical and optical properties (1992)

The preparation of crackfree and transparent SiO2 coatings on soda lime glass with thicknesses of about 8 µm after densification at 500°C is presented. The high thickness can be obtained by using on 80:20 mixture of methyltriethoxysilane and tetraethyl orthosilicate as alkoxide precursors in combination with an aqueous colloidal SiO2 sol with particle sizes of about 7 nm. This principle of synthesis is also applied to ZrO2 containing coatings yielding to thickness of about 3 µm. Refractive index measurements indicate that the coatings are nearly completely densified. At higher temperatures tensile stresses appear within the layers and are transmitted to the substrate, increasing its thermal stability.
<i>Alternaria alternata</i> Flower Blight of <i>Zinnia acerosa</i> in Texas (2001)

Zinnia acerosa (D.C.) Gray, is a Southwest native flowering plant frequently observed in the Trans-Pecos desert and desert grasslands of Arizona, Texas, and New Mexico. The plant is valued for producing an abundance of distinctive 2.0 cm diameter white flowers on greenish and sparsely leaved stems. Selections of Z. acerosa from West Texas are under evaluation as a water conserving plant species for use in arid landscapes of the Southwest. During April through June, Z. acerosa plants in TAMU, Dallas field plots were observed with small, brown flower spots that enlarged to include whole petals, causing conspicuous flower blighting. Microscopic examination of lesions from infected flower blossoms demonstrated the presence of short beaked, cylindrical spores near the smaller lesions on flower petals. Isolations from symptomatic flower petals consistently yielded cultures of an Alternaria sp. with long chains of conidia. Typical conidia contained 3 to 5 transverse walls and 1 to 2 longitudinal walls and measured 43 μm length by 15 μm width. The fungus was identified as A. alternata (Fries) Keissler consistent with the description in Ellis (1). Pathogenicity tests were conducted on plants maintained on a greenhouse bench by spraying spore suspensions obtained from 16-day-old A. alternata cultures on potato-dextrose agar. Inoculations produced light brown lesions on blossoms typical of field disease symptoms of the disease. This disease is important as a flower blight, however, infections on the leaves are also apparent but limited. Outbreaks of the disease are frequently observed during periods of rainfall during the summer months. This is the first report of Alternaria alternata causing a floral blight on Z. acerosa. References: (1) M. B. Ellis. 1971. Dematiaceous Hyphomycetes. Commonwealth Mycological Institute, Kew, Surrey, England.
Visualizing Changes in Cytosolic-Free Ca 2+ during the Response of Stomatal Guard Cells to Abscisic Acid (1992)

Martin R. McAinsh, Colin Brownlee, Alistair M. Hetherington, Visualizing Changes in Cytosolic-Free Ca2+ during the Response of Stomatal Guard Cells to Abscisic Acid, The Plant Cell, Vol. 4, No. 9 (Sep., 1992), pp. 1113-1122
A protocol for satellite access via use of spot-beams (1993)

In this paper, we develop a new protocol for multiple access to a GEO-satellite that utilizes an electronically-switched spot-beam. The emphasis is on an integrated voice/data protocol which takes advantage of the propagation latency and which offers centralized control with excellent delay and throughput characteristics. The protocol also allows full exploitation of the advantages of a hopping beam satellite, such as smaller earth stations and frequency re-use.
Generating Topical Poetry (2016)

We describe Hafez, a program that generates any number of distinct poems on a usersupplied topic. Poems obey rhythmic and rhyme constraints. We describe the poetrygeneration algorithm, give experimental data concerning its parameters, and show its generality with respect to language and poetic form.
Adaptable design: Concepts, methods, and applications (2009)

Increasing competition in the global marketplace demands products with better functionality, higher quality, lower cost, shorter delivery lead time, and increased environmental friendliness. Although advanced manufacturing technologies can partially address these challenges, advanced design technologies are considered critical, since most design and manufacturing properties of a product are influenced by the design decisions made in the early design stages. This paper provides a comprehensive review on a new design paradigm — adaptable design — that aims at developing adaptable products to satisfy the various requirements of customers. The topics discussed in this review include the fundamental concepts, objectives, methodologies, and applications. The paper also presents the differences between adaptable design and other design methods, such as modular design, platform design, and product customization. The focus is on mechanical product design; however, potential applications of adaptable design in other disciplines are also briefly mentioned.
Semi-blind signal estimation for smart antennas using subspace tracking (2003)

We discuss a semi-blind algorithm for smart antennas that utilises user identifiers that are available in existing cellular systems in addition to some structural signal properties. Our algorithm estimates, first, the row span of the adequately composed data matrix. In this part we gain a factor of up to 70 in computational complexity by employing subspace tracking algorithms. After that we project the obtained basis vectors iteratively to the finite alphabet constellation. We call the projection part of our algorithm DILSF (decoupled iterative least-squares with subspace fitting). Assuming two co-channel users in a GSM-like TDMA system and a Rayleigh fading channel with finite angular spread, we obtained a BER<10/sup -3/ with only 3 antennas, spaced 10/spl lambda/ apart. We also investigate the effect of the rank estimation accuracy on the performance and find the algorithm insensitive to minor rank estimation errors.
Evaluation of extraction kits and RT-qPCR systems adapted to high-throughput platform for circulating miRNAs (2015)

MicroRNAs regulate gene expression at the post-transcriptional level. Differential expression of miRNAs can potentially be used as biomarkers for early diagnosis and prediction for outcomes. Failure in validation of miRNA profiles is often caused by variations in experimental parameters. In this study, the performance of five extraction kits and three RT-qPCR systems were evaluated using BioMark high-throughput platform and the effects of different experimental parameters on circulating miRNA levels were determined. Differences in the performance of extraction kits as well as varying accuracy, sensitivity and reproducibility in qPCR systems were observed. Normalisation of RT-qPCR data to spike-in controls can reduce extraction bias. However, the extent of correlation for different qPCR systems varies in different assays. At different time points, there was no significant fold change in eight of the plasma miRNAs that we evaluated. Higher level of miRNAs was detected in plasma as compared to serum of the same cohort. In summary, we demonstrated that high-throughput RT-qPCR with pre-amplification step had increased sensitivity and can be achieved with accuracy and high reproducibility through stringent experimental controls. The information provided here is useful for planning biomarker validation studies involving circulating miRNAs.
Vectorology and Factor Delivery in Induced Pluripotent Stem Cell Reprogramming (2014)

Induced pluripotent stem cell (iPSC) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10-30 days). Conventional iPSC reprogramming was achieved using lentiviral or simple retroviral vectors. Retroviral reprogramming has flaws of insertional mutagenesis, uncontrolled silencing, residual expression and re-activation of transgenes, and immunogenicity. To overcome these issues, various technologies were explored, including adenoviral vectors, protein transduction, RNA transfection, minicircle DNA, excisable PiggyBac (PB) transposon, Cre-lox excision system, negative-sense RNA replicon, positive-sense RNA replicon, Epstein-Barr virus-based episomal plasmids, and repeated transfections of plasmids. This review provides summaries of the main vectorologies and factor delivery systems used in current reprogramming protocols.
A resurrected mammalian <i>hAT</i> transposable element and a closely related insect element are highly active in human cell culture (2012)

Chromosome structure and function are influenced by transposable elements, which are mobile DNA segments that can move from place to place. hAT elements are a superfamily of DNA cut and paste elements that move by excision and integration. We have characterized two hAT elements, TcBuster and Space Invaders (SPIN), that are members of a recently described subfamily of hAT elements called Buster elements. We show that TcBuster, from the red flour beetle Tribolium castaneum, is highly active in human cells. SPIN elements are currently inactive elements that were recently highly active in multiple vertebrate genomes, and the high level of sequence similarity across widely diverged species and patchy phylogenetic distribution suggest that they may have moved between genomes by horizontal transfer. We have generated an intact version of this element, SPIN(ON), which is highly active in human cells. In vitro analysis of TcBuster and SPIN(ON) shows that no proteins other than transposase are essential for recombination, a property that may contribute to the ability of SPIN to successfully invade multiple organisms. We also analyze the target site preferences of de novo insertions in the human genome of TcBuster and SPIN(ON) and compare them with the preferences of Sleeping Beauty and piggyBac, showing that each superfamily has a distinctive pattern of insertion. The high-frequency transposition of both TcBuster and SPIN(ON) suggests that these transposon systems offer powerful tools for genome engineering. Finally, we describe a Saccharomyces cerevisiae assay for TcBuster that will provide a means for isolation of hyperactive and other interesting classes of transposase mutants.
Identification and Characterization of a Poliovirus Capsid Mutant with Enhanced Thermal Stability (2018)

Enteric viruses, including poliovirus, are spread by the fecal-oral route. In order to persist and transmit to a new host, enteric virus particles must remain stable once they are in the environment. Environmental stressors such as heat and disinfectants can inactivate virus particles and prevent viral transmission. It has been previously demonstrated that bacteria or bacterial surface glycans can enhance poliovirus virion stability and limit inactivation from heat or bleach. While investigating the mechanisms underlying bacterially enhanced virion thermal stability, we identified and characterized a poliovirus (PV) mutant with increased resistance to heat inactivation. The M132V mutant harbors a single amino acid change in the VP1 capsid coding that is sufficient to confer heat resistance but not bleach resistance. Although the M132V virus was stable in the absence of bacteria or feces at most temperatures, M132V virus was stabilized by feces at very high temperatures. M132V PV had reduced specific infectivity and RNA uncoating compared with those of wild-type (WT) PV, but viral yields in HeLa cells were similar. In orally inoculated mice, M132V had a slight fitness cost since fecal titers were lower and 12.5% of fecal viruses reverted to the WT. Overall, this work sheds light on factors that influence virion stability and fitness.<b>IMPORTANCE</b> Viruses spread by the fecal-oral route need to maintain viability in the environment to ensure transmission. Previous work indicated that bacteria and bacterial surface polysaccharides can stabilize viral particles and enhance transmission. To explore factors that influence viral particle stability, we isolated a mutant poliovirus that is heat resistant. This mutant virus does not require feces for stability at most temperatures but can be stabilized by feces at very high temperatures. Even though the mutant virus is heat resistant, it is susceptible to inactivation by treatment with bleach. This work provides insight into how viral particles maintain infectivity in the environment.
Metagenomic Characterization of Chesapeake Bay Virioplankton (2007)

Viruses are ubiquitous and abundant throughout the biosphere. In marine systems, virus-mediated processes can have significant impacts on microbial diversity and on global biogeocehmical cycling. However, viral genetic diversity remains poorly characterized. To address this shortcoming, a metagenomic library was constructed from Chesapeake Bay virioplankton. The resulting sequences constitute the largest collection of long-read double-stranded DNA (dsDNA) viral metagenome data reported to date. BLAST homology comparisons showed that Chesapeake Bay virioplankton contained a high proportion of unknown (homologous only to environmental sequences) and novel (no significant homolog) sequences. This analysis suggests that dsDNA viruses are likely one of the largest reservoirs of unknown genetic diversity in the biosphere. The taxonomic origin of BLAST homologs to viral library sequences agreed well with reported abundances of cooccurring bacterial subphyla within the estuary and indicated that cyanophages were abundant. However, the low proportion of Siphophage homologs contradicts a previous assertion that this family comprises most bacteriophage diversity. Identification and analyses of cyanobacterial homologs of the psbA gene illustrated the value of metagenomic studies of virioplankton. The phylogeny of inferred PsbA protein sequences suggested that Chesapeake Bay cyanophage strains are endemic in that environment. The ratio of psbA homologous sequences to total cyanophage sequences in the metagenome indicated that the psbA gene may be nearly universal in Chesapeake Bay cyanophage genomes. Furthermore, the low frequency of psbD homologs in the library supports the prediction that Chesapeake Bay cyanophage populations are dominated by Podoviridae.
Direct visual-inertial odometry with stereo cameras (2016)

We propose a novel direct visual-inertial odometry method for stereo cameras. Camera pose, velocity and IMU biases are simultaneously estimated by minimizing a combined photometric and inertial energy functional. This allows us to exploit the complementary nature of vision and inertial data. At the same time, and in contrast to all existing visual-inertial methods, our approach is fully direct: geometry is estimated in the form of semi-dense depth maps instead of manually designed sparse keypoints. Depth information is obtained both from static stereo - relating the fixed-baseline images of the stereo camera - and temporal stereo - relating images from the same camera, taken at different points in time. We show that our method outperforms not only vision-only or loosely coupled approaches, but also can achieve more accurate results than state-of-the-art keypoint-based methods on different datasets, including rapid motion and significant illumination changes. In addition, our method provides high-fidelity semi-dense, metric reconstructions of the environment, and runs in real-time on a CPU.