gebhart/patrepeval huggingface dataset:
Mutational Analysis of mRNA Capping Enzyme Identifies Amino Acids Involved in GTP Binding, Enzyme-Guanylate Formation, and GMP Transfer to RNA (1995)

Vaccinia virus mRNA capping enzyme is a multifunctional protein with RNA triphosphatase, RNA guanylyltransferase, RNA (guanine-7) methyltransferase, and transcription termination factor activities. The protein is a heterodimer of 95- and 33-kDa subunits encoded by the vaccinia virus D1 and D12 genes, respectively. The capping reaction entails transfer of GMP from GTP to the 5'-diphosphate end of mRNA via a covalent enzyme-(lysyl-GMP) intermediate. The active site is situated at Lys-260 of the D1 subunit within a sequence element, KxDG (motif I), that is conserved in the capping enzymes from yeasts and other DNA viruses and at the active sites of covalent adenylylation of RNA and DNA ligases. Four additional sequence motifs (II to V) are conserved in the same order and with similar spacing among the capping enzymes and several ATP-dependent ligases. The relevance of these common sequence elements to the RNA capping reaction was addressed by mutational analysis of the vaccinia virus D1 protein. Nine alanine substitution mutations were targeted to motifs II to V. Histidine-tagged versions of the mutated D1 polypeptide were coexpressed in bacteria with the D12 subunit, and the His-tagged heterodimers were purified by Ni affinity and phosphocellulose chromatography steps. Whereas each of the mutated enzymes retained triphosphatase, methyltransferase, and termination factor activities, six of nine mutant enzymes were defective in some aspect of transguanylylation. Individual mutations in motifs III, IV, and V had distinctive effects on the affinity of enzyme for GTP, the rate of covalent catalysis (EpG formation), or the transfer of GMP from enzyme to RNA. These results are concordant with mutational studies of yeast RNA capping enzyme and suggest a conserved structural basis for covalent nucleotidyl transfer.
The role of fatty aldehyde dehydrogenase in epidermal structure and function (2011)

The epidermal water barrier resides in the stratum corneum (SC) and is dependent on a highly organized network of multi-lamellar membranes comprised of a critical lipid composition. The SC membranes are formed from precursor membranes packaged in cytoplasmic lamellar bodies in the stratum granulosum and delivered to the SC by exocytosis. An abnormal lipid composition of the SC membranes often results in a disrupted water barrier and the clinical appearance of ichthyosis. This cutaneous feature is characteristic of Sjögren-Larsson syndrome (SLS), an inborn error of lipid metabolism caused by deficiency of fatty aldehyde dehydrogenase (FALDH). The contribution of FALDH to normal epidermal function has become increasingly evident with the recognition that this enzyme has an essential role in metabolism of several lipids, including fatty aldehydes and alcohols, ether glycerolipids, isoprenoid alcohols and certain lipids that undergo ω-oxidation, such as leukotriene B4 and very long-chain fatty acids. In the absence of FALDH, the skin produces lamellar bodies that are empty, lack their surrounding vesicle membranes or contain granular contents rather then the usual cargo membranes. These defective organelles also have impaired exocytosis, which results in structurally abnormal, deficient multi-lamellar membranes in the SC and a leaky water barrier. Although the exact biochemical mechanism for the cutaneous pathology is still unclear, studies in SLS demonstrate the critical importance of FALDH for normal epidermal structure and function.
Human oscillatory brain activity near 40 Hz coexists with cognitive temporal binding. (1994)

Spontaneous oscillatory electrical activity at a frequency near 40 Hz in the human brain and its reset by sensory stimulation have been proposed to be related to cognitive processing and to the temporal binding of sensory stimuli. These experiments were designed to test this hypothesis and to determine specifically whether the minimal interval required to identify separate auditory stimuli correlates with the reset of the 40-Hz magnetic signal. Auditory clicks were presented at varying times, while magnetic activity was recorded from awake human subjects. Experimental and modeling results indicate a stimulus-interval-dependent response with a critical interval of 12-15 ms. At shorter intervals only one 40-Hz response, to the first stimulus, was observed. With longer intervals, a second 40-Hz wave abruptly appeared, which coincided with the subject's perception of a second distinct auditory stimulus. These results indicate that oscillatory activity near 40 Hz represents a neurophysiological correlate to the temporal processing of auditory stimuli. It also supports the view that 40-Hz activity not only relates to primary sensory processing, but also could reflect the temporal binding underlying cognition.
Impaired Eukaryotic Translation Initiation Factor 2B Activity Specifically in Oligodendrocytes Reproduces the Pathology of Vanishing White Matter Disease in Mice (2014)

Vanishing white matter disease (VWMD) is an inherited autosomal-recessive hypomyelinating disease caused by mutations in eukaryotic translation initiation factor 2B (eIF2B). eIF2B mutations predominantly affect the brain white matter, and the characteristic features of VWMD pathology include myelin loss and foamy oligodendrocytes. Activation of pancreatic endoplasmic reticulum kinase (PERK) has been observed in oligodendrocytes in VWMD. PERK activation in response to endoplasmic reticulum stress attenuates eIF2B activity by phosphorylating eIF2α, suggesting that impaired eIF2B activity in oligodendrocytes induced by VWMD mutations or PERK activation exploit similar mechanisms to promote selective white matter pathology in VWMD. Using transgenic mice that allow for temporally controlled activation of PERK specifically in oligodendrocytes, we discovered that strong PERK activation in oligodendrocytes during development suppressed eIF2B activity and reproduced the characteristic features of VWMD in mice, including hypomyelinating phenotype, foamy oligodendrocytes, and myelin loss. Notably, impaired eIF2B activity induced by PERK activation in oligodendrocytes of fully myelinated adult mice had minimal effects on morphology or function. Our observations point to a cell-autonomous role of impaired eIF2B activity in myelinating oligodendrocytes in the pathogenesis of VWMD.
Oligomerized grape seed proanthocyanidins ameliorates isoproterenol‐induced cardiac remodeling in rats: role of oxidative stress (2010)

The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics, cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1 (ASK1) and nuclear factor-κB (NF-κB) cascades in isoproterenol (Iso)-induced cardiac remodelling (CR) rat model were investigated, in addition, the serum SOD activities and MDA content were assayed. Rats were treated with Iso to induce CR and were given distilled water or GSP for 1 week. Control rats received vehicle instead of Iso. Administration of GSP markedly alleviated the elevation of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in the heart, and improved the haemodynamic index. Meanwhile, treatment with GSP significantly ameliorated oxidative stress by improving SOD activities and decreasing MDA formation. Moreover, GSP apparently inhibited the expression ASK1, NF-κB and its targeted gene - COX-2. These findings suggest that administration of GSP has the potential to attenuate Iso-induced CR by repressing oxidative stress and inhibiting the activation of the cellular signaling cascades involving the ASK1 and NF-κB pathways, at least in part, providing a molecular mechanism for the cardioprotective effect of GSP.
Smoothing of diamond-turned substrates for extreme ultraviolet illuminators (2004)

Condenser optics in extreme ultraviolet lithography (EUVL) systems are subjected to frequent replacement as they are positioned close to the illumination source, where increased heating and contamination occur. In the case of aspherical condenser elements made by optical figuring/finishing, their replacement can be very expensive (several hundred thousand dollars). One approach to this problem would be to manufacture inexpensive illuminator optics that meet all required specifications and could be replaced at no substantial cost. Diamond-turned metal substrates are a factor of 100 less expensive than conventional aspherical substrates but have insufficient finish, leading to unacceptably low EUV reflectance after multilayer coating. We show that by applying a smoothing film prior to multilayer coating, the high-spatial-frequency roughness of a diamond-turned metal substrate is reduced from 1.76 to 0.27 nm root mean square (rms), while the figure slope error is maintained at acceptable levels. Metrology tests performed at various stages of the fabrication of the element demonstrate that it satisfies all critical figure and finish specifications as an illuminator. Initial experimental results on the stability and performance of the optic in a real EUVL plasma source environment show no accelerated degradation when compared to conventional substrates.
VIRUS-CELL AND CELL-CELL FUSION (1996)

Significant progress has been made in elucidating the mechanisms of viral membrane fusion proteins; both those that function at low, as well as those that function at neutral, pH. For many viral fusion proteins evidence now suggests that a triggered conformational change that exposes a previously cryptic fusion peptide, along with a rearrangement of the fusion protein oligomer, allows the fusion peptide to gain access to the target bilayer and thus initiate the fusion reaction. Although the topologically equivalent process of cell-cell fusion is less well understood, several cell surface proteins, including members of the newly described ADAM gene family, have emerged as candidate adhesion/fusion proteins.
Importance of Urinary Interleukin-18 in Intravesical Immunotherapy with Bacillus Calmette-Guérin for Superficial Bladder Tumors (2005)

Our results clearly show the predominant importance of IL-18 followed by increases in Th1 cytokines, such as IL-2 and IFN-gamma, in the mechanisms of intravesical immunotherapy with BCG.
Real-time control of a servosystem using the inverter-fed power lines to communicate sensor feedback (1999)

It is shown that the pulsewidth modulation inverter-fed power line is a feasible medium for the transmission of modulated digital information at data rates of over 40 kb/s and that this transmission path provides a suitable alternative to the sensor cabling between the actuator and the controller of an encoder-based servosystem. The encoder data is modulated and transmitted from the actuator to the controller, over the inverter-fed power cable. The data is modulated using frequency-shift keying, based on a center frequency of 5 MHz. Specialized magnetics design techniques are outlined for the coupling and decoupling circuits which transfer the modulated digital information to and from the power lines. A software observer is employed to improve the velocity derived from the received position information, and this velocity is used in the motion control algorithm to generate a reference torque signal for the controller.
Broadband silica fibre Raman amplifiers at 1.3 μm and 1.5 μm (2002)

High power fibre lasers operating at 1.24 /spl mu/m and 1.42 /spl mu/m respectively have been used to provide broad band Raman gain around 1.3 /spl mu/m and 1.5 /spl mu/m in compact, efficient, silica fibre-amplifier configurations. The gain and noise performance of these broad band amplifiers are described as well the mechanism to further increase and flatten the operational bandwidths.
B29: a member of the immunoglobulin gene superfamily exclusively expressed on beta-lineage cells. (1988)

A number of the glycoproteins identified on the surfaces of cells of the immune response belong to the immunoglobulin superfamily. We have isolated and characterized cDNA clones and the complete genomic gene encoding a B-cell-specific member of the immunoglobulin superfamily called "B29." This isolate is expressed at all stages in B-cell development beginning with the earliest precursor B cells undergoing immunoglobulin heavy chain gene diversity region----joining region gene (DH----JH) rearrangements. The protein sequence predicted by the B29 coding region contains a leader sequence and a single extracellular immunoglobulin-like domain, followed by a hydrophobic transmembrane segment and a charged intracytoplasmic domain. The immunoglobulin-like domain contains cysteines and other conserved amino acids characteristic of light chain variable and joining regions, but overall the sequence is only distantly related to immunoglobulins. Each of these domains is encoded in separate exons in the B29 gene, in analogy to other members of the immunoglobulin superfamily. The conserved structural features of the immunoglobulin-like domain in the B29 gene product resemble those of other members of the immunoglobulin superfamily involved in cell recognition and adhesion.
Virtual Notepad: handwriting in immersive VR (2002)

We present Virtual Notepad, a collection of interface tools that allows the user to take notes, annotate documents and input text using a pen, while still immersed in virtual environments (VEs). Using a spatially-tracked, pressure-sensitive graphics tablet, pen and handwriting recognition software, Virtual Notepad explores handwriting as a new modality for interaction in immersive VEs. This paper reports details of the Virtual Notepad interface and interaction techniques, discusses implementation and design issues, reports the results of initial evaluation and overviews possible applications of virtual handwriting.
The new Health in Pregnancy Grant. (2008)

From April 2009, pregnant women throughout the UK will be eligible for the Health in Pregnancy Grant. This is a one-off, non-means-tested payment of pounds 190 to support the general health and well-being of women in the later stages of pregnancy, for example through a healthy lifestyle and diet, and help with some of the costs before the birth. The grant is part of a Government strategy to reduce health inequalities and improve pregnancy outcomes. A midwife or doctor will be required to sign the claim form, and health professionals will therefore have an essential role in ensuring women receive the grant.
Directed changes in the number of double-stranded RNA genomic segments in bacteriophage Φ6 (1998)

Bacteriophage Phi6 has a genome of three segments of double-stranded RNA. The segments are designated S, M, and L. Each segment has a unique packaging site, pac, near the 5' end of the plus strand. The plus strands of the segments are normally packaged in the order S, M, L. Chimeras of segment M and S in which segment M is at the 5' end of the plus strand can be stably incorporated into the virion; however, an independent segment S must be included along with normal segment L, even if it contains no active genes. A chimera of segment M and S in which segment S is at the 5' end of the plus strand can be stably incorporated into the virion along with normal segment L to form a two-segment genome. A chimera of segments S, M, and L in which the packaging sequence is that of S can also form a stable nonsegmented genome. These findings are consistent with a model that we have proposed for the packaging of the Phi6 genome.
Electrostatic and Steric Contributions to Block of the Skeletal Muscle Sodium Channel by μ-Conotoxin (2002)

Pore-blocking toxins are valuable probes of ion channels that underlie electrical signaling. To be effective inhibitors, they must show high affinity and specificity and prevent ion conduction. The 22-residue sea snail peptide, mu-conotoxin GIIIA, blocks the skeletal muscle sodium channel completely. Partially blocking peptides, derived by making single or paired amino acid substitutions in mu-conotoxin GIIIA, allow a novel analysis of blocking mechanisms. Replacement of one critical residue (Arg-13) yielded peptides that only partially blocked single-channel current. These derivatives, and others with simultaneous substitution of a second residue, were used to elucidate the structural basis of the toxin's blocking action. The charge at residue-13 was the most striking determinant. A positive charge was necessary, though not sufficient, for complete block. Blocking efficacy increased with increasing residue-13 side chain size, regardless of charge, suggesting a steric contribution to inhibition. Charges grouped on one side of the toxin molecule at positions 2, 12, and 14 had a weaker influence, whereas residue-16, on the opposite face of the toxin, was more influential. Most directly interpreted, the data suggest that one side of the toxin is masked by close apposition to a binding surface on the pore, whereas the other side, bearing Lys-16, is exposed to an aqueous cavity accessible to entering ions. Strong charge-dependent effects emanate from this toxin surface. In the native toxin, Arg-13 probably presents a strategically placed electrostatic barrier rather than effecting a complete steric occlusion of the pore. This differs from other well-described channel inhibitors such as the charybdotoxin family of potassium channel blockers and the sodium channel-blocking guanidinium toxins (tetrodotoxin and saxitoxin), which appear to occlude the narrow part of the pore.
Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome (1991)

The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of a single CpG island, at or very near the fragile site. Probes adjacent to this island detected very localized DNA rearrangements that constituted the fragile X mutations, and whose target was a 550-base pair GC-rich fragment. Normal transmitting males had a 150- to 400-base pair insertion that was inherited by their daughters either unchanged, or with small differences in size. Fragile X-positive individuals in the next generation had much larger fragments that differed among siblings and showed a generally heterogeneous pattern indicating somatic mutation. The mutated allele appeared unmethylated in normal transmitting males, methylated only on the inactive X chromosome in their daughters, and totally methylated in most fragile X males. However, some males had a mosaic pattern. Expression of the fragile X syndrome thus appears to result from a two-step mutation as well as a highly localized methylation. Carriers of the fragile X mutation can easily be detected regardless of sex or phenotypic expression, and rare apparent false negatives may result from genetic heterogeneity or misdiagnosis.
Bacterial toxins and virulence factors in disease (1995)

Biosynthesis and targeting of pertussis toxin diphthamide - the toxin target in protein synthesis elogation factor 2 leukocidines heat-stable enterotoxin of escherichia coli therapeutic effects of botulinum toxins endotoxin - a mediator of and potential therapeutic target zot and ace toxins of vibrio cholerae ADP-ribosylation factors - a family of guanine nucleotide-binding proteins that activate cholera toxin and regulate vesicular transport liposomes and vehicles for vaccines GTP-binding proteins as the substrate of pertussis toxin-catalyzed ADP-ribosylation modification of actin and rho proteins by clostridial ADP-ribosylating toxins muramyl peptides as exotoxins - bordetella tracheal cytotoxin adenylyl cyclase toxin from bordetella pertussis clostridium difficile and its toxins structure and function of e. coli heat labile enterotoxin and cholera toxin B-pentamer anthrax toxins the diphtheria toxin receptor bacterial ADP-ribosyltransferases bordetella pertussis - determinants of virulence shiga and shiga-like (vero) toxins cholera toxin and related enterotoxins of gram-negative bacteria.
Multiple aggregations over data streams (2005)

Monitoring aggregates on IP traffic data streams is a compelling application for data stream management systems. The need for exploratory IP traffic data analysis naturally leads to posing related aggregation queries on data streams, that differ only in the choice of grouping attributes. In this paper, we address this problem of efficiently computing multiple aggregations over high speed data streams, based on a two-level LFTA/HFTA DSMS architecture, inspired by Gigascope.Our first contribution is the insight that in such a scenario, additionally computing and maintaining fine-granularity aggregation queries (phantoms) at the LFTA has the benefit of supporting shared computation. Our second contribution is an investigation into the problem of identifying beneficial LFTA configurations of phantoms and user-queries. We formulate this problem as a cost optimization problem, which consists of two sub-optimization problems: how to choose phantoms and how to allocate space for them in the LFTA. We formally show the hardness of determining the optimal configuration, and propose cost greedy heuristics for these independent sub-problems based on detailed analyses. Our final contribution is a thorough experimental study, based on real IP traffic data, as well as synthetic data, to demonstrate the effectiveness of our techniques for identifying beneficial configurations.