gebhart/patrepeval huggingface dataset:
Transcending the prediction paradigm: novel applications of SHAPE to RNA function and evolution (2016)

Selective 2′‐hydroxyl acylation analyzed by primer extension ( SHAPE ) provides information on RNA structure at single‐nucleotide resolution. It is most often used in conjunction with RNA secondary structure prediction algorithms as a probabilistic or thermodynamic restraint. With the recent advent of ultra‐high‐throughput approaches for collecting SHAPE data, the applications of this technology are extending beyond structure prediction. In this review, we discuss recent applications of SHAPE data in the transcriptomic context and how this new experimental paradigm is changing our understanding of these experiments and RNA folding in general. SHAPE experiments probe both the secondary and tertiary structure of an RNA , suggesting that model‐free approaches for within and comparative RNA structure analysis can provide significant structural insight without the need for a full structural model. New methods incorporating SHAPE at different nucleotide resolutions are required to parse these transcriptomic data sets to transcend secondary structure modeling with global structural metrics. These ‘multiscale’ approaches provide deeper insights into RNA global structure, evolution, and function in the cell. WIREs RNA 2017, 8:e1374. doi: 10.1002/wrna.1374 This article is categorized under: RNA Structure and Dynamics &gt; RNA Structure, Dynamics, and Chemistry RNA Evolution and Genomics &gt; RNA and Ribonucleoprotein Evolution RNA Evolution and Genomics &gt; Computational Analyses of RNA
Expression of hepatocyte growth factor in growing and regenerating rat skeletal muscle (1993)

The expression of hepatocyte growth factor (HGF) was studied in rat skeletal muscle during postnatal growth and during regeneration after ischemic injury. By Northern blot analysis two RNA transcripts with estimated sizes of 6.0 and 3.1 kb, respectively, could be detected in immature skeletal muscle at 2, 4, and 10 days after birth, whereas no signal could be detected in adult skeletal muscle. In regenerating muscle, HGF mRNA was reexpressed, and a distinct signal was evident during the first days after the injury. One week after the injury only a weak signal was obtained. By in situ hybridization staining, HGF mRNA could be demonstrated in the immature muscle tissue of newborn rats but not in adult skeletal muscle. In regenerating muscle, the staining for HGF mRNA could be demonstrated in the regenerating muscle cells during the early phase of the regeneration. One week after the injury, only faint staining for HGF mRNA persisted in the regenerated fibers. It is concluded that HGF expression is developmentally regulated in skeletal muscle and that HGF is reexpressed in a transient manner during postischemic muscle regeneration.
Design of conducting redox polymers: A polythiophene‐Ru(bipy)3;n⊕Hybrid Material (1996)

The thiophene‐substituted Ru(L) complex shown in the Figure was synthesized and found to undergo polymerization when electrochemically oxidized. The electrochemical characteristics of the resultant polythiophene‐Ru(L) hybrid material were found to be a composite of those displayed by isolated Ru centers and the polymer prepared from the metal‐free ligand. This represents a promising approach to novel redox conductors. magnified image
A Method of Isolating Anucleated Yeast Protoplasts Unable to Synthesize the Glucan Fibrillar Component of the Wall (2000)

A mixture of nucleated and anucleated protoplasts was produced from log-phase Saccharomyces cerevisiae by the use of snail enzymes. The mixture was separated by centrifugation, and anucleated protoplasts were studied by means of light and electron microscopy. Anucleated protoplasts did not synthesize glucan fibrils even though they seemed to contain all other basic structures in their cytoplasm, and the structure of the plasma membrane was unchanged. This was in sharp contrast to ordinary nucleated protoplasts which synthesized glucan fibrils even after inhibition of protein synthesis by cycloheximide. The reason for this behaviour of anucleated protoplasts is not clear. Such anucleated yeast protoplasts represent the first example of uniform anucleated fungi produced by a reproducible method.
A Process for Capturing CO2 from the Atmosphere (2018)

We describe a process for capturing CO2 from the atmosphere in an industrial plant. The design captures ∼1 Mt-CO2/year in a continuous process using an aqueous KOH sorbent coupled to a calcium caustic recovery loop. We describe the design rationale, summarize performance of the major unit operations, and provide a capital cost breakdown developed with an independent consulting engineering firm. We report results from a pilot plant that provides data on performance of the major unit operations. We summarize the energy and material balance computed using an Aspen process simulation. When CO2 is delivered at 15 MPa, the design requires either 8.81 GJ of natural gas, or 5.25 GJ of gas and 366 kWhr of electricity, per ton of CO2 captured. Depending on financial assumptions, energy costs, and the specific choice of inputs and outputs, the levelized cost per ton CO2 captured from the atmosphere ranges from 94 to 232 $/t-CO2.
Crystal structure of the cyclophilin‐like domain from the parasitic nematode Brugia malayi (1998)

Cyclophilins are a family of proteins that exhibit peptidyl-prolyl cis-trans isomerase activity and bind the immunosuppressive agent cyclosporin A (CsA). Brugia malayi is a filarial nematode parasite of humans, for which a cyclophilin-like domain was identified at the N-terminal of a protein containing 843 amino acid residues. There are two differences in sequence in the highly conserved CsA binding site: A histidine and a lysine replace a tryptophan and an alanine, respectively. The crystal structure of this domain has been determined by the molecular replacement method and refined to an R-factor of 16.9% at 2.15 A resolution. The overall structure is similar to other cyclophilins; however, major differences occur in two loops. Comparison of the CsA binding site of this domain with members of the cyclophilin family shows significant structural differences, which can account for the reduced sensitivity of the Brugia malayi protein to inhibition by CsA.
Hyaluronic Acid Oligosaccharides Suppress TLR3-Dependent Cytokine Expression in a TLR4-Dependent Manner (2013)

The release of endogenous molecules from the skin after injury has been proposed to influence inflammation. Recent studies have found that pro-inflammatory signals can be generated by damaged endogenous self-RNA, and this event is detected by TLR3. Conversely, release of endogenous fragments of hyaluronic acid (HA) after injury has been proposed to inhibit LPS induced inflammation driven by TLR4. In this study we investigated if HA oligomers could also influence inflammation mediated by TLR3. A tetramer form of HA (oligo-HA) was added to MH-S cells (mouse alveolar macrophage cell line) that were then activated by poly(I:C). ELISA analysis of culture supernatants showed that the presence of oligo-HA suppressed the poly(I:C) induced release of IL-6 and TNFα. IL-6 mRNA expression was also suppressed as measured by quantitative RT-PCR. To determine the mechanism of action for oligo-HA to inhibit poly(I:C), macrophages derived from wild-type (WT), Tlr2-/- or Tlr4-/- mice were treated with oligo-HA and poly(I:C). Similar to WT cells, Tlr2-/- macrophages were inhibited by oligo-HA and retained suppression of cytokine release. In contrast, Tlr4-/- macrophages lost the capacity to be suppressed by oligo-HA. An increase in Traf1 (TLR negative regulator) mRNA was observed after oligo-HA treatment of WT but not in Tlr4-/- macrophages, and oligo-HA did not suppress cytokine responsiveness in Traf1-/- macrophages. These results show that oligo-HA acts through TLR4 and TRAF1 to inhibit TLR3-dependent inflammation. This observation illustrates the complex immunomodulatory action of endogenous products released after injury.
An empirical study of low-power wireless (2010)

We present empirical measurements of the packet delivery performance of the latest sensor platforms: Micaz and Telos motes. In this article, we present observations that have implications to a set of common assumptions protocol designers make while designing sensornet protocols—specifically—the MAC and network layer protocols. We first distill these common assumptions in to a conceptual model and show how our observations support or dispute these assumptions. We also present case studies of protocols that do not make these assumptions. Understanding the implications of these observations to the conceptual model can improve future protocol designs.
Activation of HIV-specific ribozyme activity by self-cleavage (1993)

A hammerhead ribozyme designed to cleave in trans the R region of HIV-1 RNA was inserted into a eukaryotic expression vector. This ribozyme was studied in vitro using the T3 RNA polymerase promoter located upstream of the eukaryotic promoter. The ribozyme showed no activity against its specific target sequence under any condition tested. To decrease the influence of potential cis inhibitory sequences in such a ribozyme transcript, a specific target sequence was inserted upstream of the ribozyme-coding sequence. This insertion allowed the release by cis cleavage of a short RNA bearing ribozyme activity and able to cleave in trans an external RNA target. The cis cleavage reaction generated two RNA molecules: the shorter RNA species, which included the catalytic domain, showed a trans cleavage reaction. This self-cleavable ribozyme was active in vitro at 37 degrees C against three distinct HIV-1 transcripts sharing the specific target sequence. Ribozyme activity was thus attained by self-cleavage of the ribozyme-containing sequence from the longer vector transcript.
Negatively Thermoresponsive Membranes with Functional Gates Driven by Zipper‐Type Hydrogen‐Bonding Interactions (2005)

Open the gate: Thermoresponsive gating membranes based on interpenetrating polymer networks composed of polyacrylamide (PAAM) and poly(acrylic acid) (PAAC) have inverse gating characteristics, with opening of the membrane pores induced by a decrease rather than an increase in temperature (see picture; UCST=upper critical solution temperature). The membranes provide a new mode of phase-transition behavior for thermoresponsive “smart” membrane actuators. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462687_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses (2007)

Presynaptic ionotropic glutamate receptors are emerging as key players in the regulation of synaptic transmission. Here we identify GluR7, a kainate receptor (KAR) subunit with no known function in the brain, as an essential subunit of presynaptic autoreceptors that facilitate hippocampal mossy fiber synaptic transmission. GluR7(-/-) mice display markedly reduced short- and long-term synaptic potentiation. Our data suggest that presynaptic KARs are GluR6/GluR7 heteromers that coassemble and are localized within synapses. We show that recombinant GluR6/GluR7 KARs exhibit low sensitivity to glutamate, and we provide evidence that presynaptic KARs at mossy fiber synapses are likely activated by high concentrations of glutamate. Overall, from our data, we propose a model whereby presynaptic KARs are localized in the presynaptic active zone close to release sites, display low affinity for glutamate, are likely Ca(2+)-permeable, are activated by single release events, and operate within a short time window to facilitate the subsequent release of glutamate.
Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease (2000)

The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.
Reduced percolation thresholds of immiscible conductive blends (1999)

The DC conductivity of polymer blends composed of poly(ethylene-co-vinyl acetate) (EVA) and high density polyethylene (HDPE), where a conductive carbon black (CB) had been preferentially blended into the HDPE, were investigated to establish the percolation characteristics. The blends exhibited reduced percolation thresholds and enhanced conductivities above that of the individually carbon filled HDPE and EVA. The percolation threshold of the EVA/HDPE/CB composites was between 3.6 and 4.2 wt % carbon black, where the volume resistivity changed by 8 orders of magnitude. This threshold is at a significantly lower carbon content than the individually filled HDPE or EVA. At a carbon black loading of 4.8 wt %, the EVA/HDPE/CB composite exhibits a volume resistivity which is approximately 14 and 11 orders of magnitude lower than the HDPE/CB and EVA/CB systems, respectively, at the same level of incorporated carbon black. The dielectric response of the ternary composites, at a temperature of 23°C and frequency of 1 kHz, exhibited an abrupt increase of ca. 252% at a carbon concentration of 4.8 wt %, suggesting that the percolation threshold is somewhat higher than the range predicted from DC conductivity measurements. Percolating composites with increasing levels of carbon black exhibit significantly greater relative permittivity and dielectric loss factors, with the composite containing 6 wt % of carbon black having a value of ϵ′ ≈ 79 and ϵ″ ≈ 14. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1899–1910, 1999
Reactive aluminium in UK surface waters (1998)

The determination of chemically reactive forms of aluminium in 20 major UK rivers is reported. The reaction of aluminium with 8-hydroxyquinoline followed by a 15 second extraction of chelated forms into an organic solvent is used to separate reactive low molecular weight forms of the metal from more inert aluminium species. Concentrations of reactive aluminium are found to lie in the range 0 to 50 μg l−1. Data are presented on the performance of the speciation method and the stability of the determinand. The observed levels of reactive aluminium are discussed in relation to river quality.
Monozygotic Twins With Age-Related Macular Degeneration (1988)

This clinical study, to the best of our knowledge, is the first report of severe age-related macular degeneration in both identical twins, documented as monozygotic by genetic testing. This suggests that genetic factors may be of primary importance in certain cases of age-related macular degeneration.
Mitigation of susceptibility‐induced signal loss in neuroimaging using localized shim coils (2005)

Correction of magnetic field distortions is essential for obtaining accurate brain blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) activation maps. The present work introduces an active shimming method that utilizes the magnetic field generated by resistive shim coils placed in the mouth to locally homogenize the magnetic field in the inferior portion of the frontal lobe, where the field is most seriously distorted. The shimming field can be optimized in situ patient by patient for the region of interest of the scanner operator's choice. The method at 1.5 T is shown to be effective in reducing field inhomogeneity and in recovery of fMRI signal. For example, in a region of interest approximately of 149 cm3, a coil of simple geometry can reduce the root mean square of the magnetic field by more than 50% and the recovered signal increases the extent of activation detected in a breath-holding fMRI experiment.
Structural chemistry of polycyclic heteroaromatic compounds. Part 4. Electronic structures of angular dithienopyridines (1994)

The Hel photoelectron spectra of nine isomeric [b,d]-annellated dithienopyridines (5–13) are reported and discussed including those of some closely related compounds such as phenanthridine (2), dithieno[3,4-a: 3′,4′-c]benzene (4) and its tetrahydro derivative 3. The ionization potentials are assigned to molecular orbitals using the results of MNDO, AM1 and PM3 calculations. The ability of PE spectroscopy as an analytical method in the analysis of the isomers 5–13 is investigated. From the spectra as well as from the theoretical results, the isomers can be divided into two groups, depending on the mode of annellation. The crystal and molecular structures of one member of each group (isomers 9 and 12) are determined by X-ray diffraction. The mode of annellation is also reflected in the bond lengths of the pyridine and thiophene rings.
Transgene Loss and Changes in the Promoter Methylation Status as Determinants for Expression Duration in Nonviral Gene Transfer for Factor IX (2010)

Advances in delivery techniques and in expression construct design have renewed interest in nonviral gene transfer. Here, we test plasmid or bacterial backbone free minicircle vectors for factor IX (FIX) expression by hydrodynamic liver-directed delivery. Both constructs are driven by a hepatic control region, the human α(1)-antitrypsin promoter, which results in long-term expression in FIX knockout mice. However, levels of expression were higher and expression loss over time was reduced when using minicircles. Even at the highest expression levels (>700% of normal) FIX was fully functional. Transgene loss was the main determinant for expression loss over time for both vector types. A significant effect of gene silencing was observed only for the plasmid, not for the minicircle vector. To determine the influence of promoter methylation, we performed bisulfite-mediated conversion and sequencing of vector DNA on days 14 and 100 after gene transfer. We determined a higher frequency of methyl-protected cytosines in CpGs and a lower degree of demethylation at bacterial Dcm methylation sequences near transcription factor-binding sites in the α(1)-antitrypsin promoter in plasmid compared with minicircle mice on day 100. Therefore, the methylation status might reflect differences in the levels and durability of expression. Judging from the high levels of functional FIX obtained, small fractions of liver or single liver segments should be sufficient to reach therapeutic efficacy in translating hydrodynamic delivery to humans. However, transgene loss remains to be addressed to further guarantee sustained expression over time.
Novel Retinoic Acid Metabolism Blocking Agents Endowed with Multiple Biological Activities Are Efficient Growth Inhibitors of Human Breast and Prostate Cancer Cells in Vitro and a Human Breast Tumor Xenograft in Nude Mice (2004)

Novel retinoic acid metabolism blocking agents (RAMBAs) have been synthesized and characterized. The synthetic features include introduction of nucleophilic ligands at C-4 of all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid, and modification of terminal carboxylic acid group. Most of our compounds are powerful inhibitors of hamster liver microsomal ATRA metabolism enzyme(s). The most potent compound is methyl (2E,4E,6E,8E)-9-(3-imidazolyl-2,6,6-trimethylcyclohex-1-enyl)-3,7-dimethylnona-2,4,6,8-tetraenoate (5) with an IC(50) value of 0.009 nM, which is 666,667 times more potent than the well-known RAMBA, liarozole (Liazal, IC(50) = 6000 nM). Quite unexpectedly, there was essentially no difference between the enzyme inhibitory activities of the two enantiomers of compound 5. In MCF-7 cell proliferation assays, the RAMBAs also enhance the ATRA-mediated antiproliferative activity in a concentration dependent manner. The novel atypical RAMBAs, in addition to being highly potent inhibitors of ATRA metabolism in microsomal preparations and in intact human cancer cells (MCF-7, T47D, and LNCaP), also exhibit multiple biological activities, including induction of apoptosis and differentiation, retinoic acid receptor binding, and potent antiproliferative activity on a number of human cancer cells. Following subcutaneous administration to mice bearing human breast MCF-7 tumor xenografts, 6 (VN/14-1, the free carboxylic acid of 5) was well-tolerated and caused significant tumor growth suppression ( approximately 85.2% vs control, p = 0.022). Our RAMBAs represent novel anticancer agents with unique multiple mechanisms of action. The most potent compounds are strong candidates for development as therapeutic agents for the treatment of a variety of cancers.
Neurobiological foundations of neurologic music therapy: rhythmic entrainment and the motor system (2015)

Entrainment is defined by a temporal locking process in which one system's motion or signal frequency entrains the frequency of another system. This process is a universal phenomenon that can be observed in physical (e.g., pendulum clocks) and biological systems (e.g., fire flies). However, entrainment can also be observed between human sensory and motor systems. The function of rhythmic entrainment in rehabilitative training and learning was established for the first time by Thaut and colleagues in several research studies in the early 1990s. It was shown that the inherent periodicity of auditory rhythmic patterns could entrain movement patterns in patients with movement disorders (see for a review: Thaut et al., 1999). Physiological, kinematic, and behavioral movement analysis showed very quickly that entrainment cues not only changed the timing of movement but also improved spatial and force parameters. Mathematical models have shown that anticipatory rhythmic templates as critical time constraints can result in the complete specification of the dynamics of a movement over the entire movement cycle, thereby optimizing motor planning and execution. Furthermore, temporal rhythmic entrainment has been successfully extended into applications in cognitive rehabilitation and speech and language rehabilitation, and thus become one of the major neurological mechanisms linking music and rhythm to brain rehabilitation. These findings provided a scientific basis for the development of neurologic music therapy.