gebhart/patrepeval huggingface dataset:
Concurrent operation of Bluetooth low energy and ANT wireless protocols with an embedded controller (2011)

With the introduction of low-power wireless technologies, new applicationsin the healthcare, fitness and home entertainment markets emergethrough the use of ultra low-power sensors. These devices are designed torun for years on a single coin-cell battery.ANT and Bluetooth Low Energy are two low-power protocols that emergeas competitors in this market. The ability to combine these in a single systemnot only takes away the element of choice from the manufacturers, but alsoprovides compatibility between the two protocols. An ANT-enabled devicecan be coupled to a Bluetooth network, with the benefit of connecting tonon-ANT central devices, such as smartphones, tablets and laptops.In this thesis, the co-existence of these two protocols is discussed. Animplementation with two distinct radios for each protocol, controlled by asingle embedded microcontroller, is presented. The implementation is testedwith regards to packet loss with a simple test application. Test results showthat the obtained packet loss cannot be correlated to the co-existence of thetwo protocols.
Complete genomic sequence of Pasteurella multocida ,Pm70 (2001)

We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged approximately 270 million years ago and the gamma subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for approximately 1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and whole-genome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen.
Structural Characterization of the 1918 Influenza Virus H1N1 Neuraminidase (2008)

Influenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 "Spanish flu" (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-A and 1.45-A resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147 to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza.
The Natural History of Recurrent Herpes Simplex Labialis (1977)

We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.
Presence of a carboxy-terminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau’s interaction with microtubules in axon-like processes (2016)

A current challenge of cell biology is to investigate molecular interactions in subcellular compartments of living cells to overcome the artificial character of in vitro studies. To dissect the interaction of the neuronal microtubule (MT)-associated protein tau with MTs in axon-like processes, we used a refined fluorescence decay after photoactivation approach and single-molecule tracking. We found that isoform variation had only a minor influence on the tau-MT interaction, whereas the presence of a C-terminal pseudorepeat region (PRR) greatly increased MT binding by a greater-than-sixfold reduction of the dissociation rate. Bioinformatic analysis revealed that the PRR contained a highly conserved motif of 18 amino acids. Disease-associated tau mutations in the PRR (K369I, G389R) did not influence apparent MT binding but increased its dynamicity. Simulation of disease-like tau hyperphosphorylation dramatically diminished the tau-MT interaction by a greater-than-fivefold decrease of the association rate with no major change in the dissociation rate. Apparent binding of tau to MTs was similar in axons and dendrites but more sensitive to increased phosphorylation in axons. Our data indicate that under the conditions of high MT density that prevail in the axon, tau's MT binding and localization are crucially affected by the presence of the PRR and tau hyperphosphorylation.
Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. (1992)

Subtractive hybridization, selecting for mRNAs expressed in normal human mammary epithelial cells (NMECs) but not in mammary tumor cell lines (TMECs), led to the cloning of the human gap junction gene connexin 26 (Cx26), identified by its sequence similarity to the rat gene. Two Cx26 transcripts derived from a single gene are expressed in NMECs but neither is expressed in a series of TMECs. Northern analysis using rat Cx probes showed that Cx43 mRNA is also expressed in the normal cells, but not in the tumor lines examined. Connexin genes Cx31.1, Cx32, Cx33, Cx37, and Cx40 are not expressed in either normal cells or the tumor lines examined. In cell-cell communication studies, the normal cells transferred Lucifer yellow, while tumor cells failed to show dye transfer. Both Cx26 and Cx43 proteins were immunolocalized to membrane sites in normal cells but were not found in tumor cells. Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up-regulated in late S and G2, as shown with lovastatin-synchronized NMECs. Cx43, on the contrary is constitutively expressed at a uniform low level throughout the cell cycle. Treatment of normal and tumor cells with a series of drugs: 5dB-cAMP, retinoic acid, okadaic acid, estradiol, or TGFb had no connexin-inducing effect in tumor cells. However, PMA induced re-expression of the two Cx26 transcripts but not of Cx43 in several TMECs. Thus Cx26 and Cx43 are both downregulated in tumor cells but respond differentially to some signals. Modulation of gap-junctional activity by drug therapy may have useful clinical applications in cancer.
SK&F 96365, a novel inhibitor of receptor-mediated calcium entry (1990)

A novel inhibitor of receptor-mediated calcium entry (RMCE) is described. SK&F 96365 (1-(beta-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl)-1H- imidazole hydrochloride) is structurally distinct from the known 'calcium antagonists' and shows selectivity in blocking RMCE compared with receptor-mediated internal Ca2+ release. Human platelets, neutrophils and endothelial cells were loaded with the fluorescent Ca2(+)-indicator dyes quin2 or fura-2, in order to measure Ca2+ or Mn2+ entry through RMCE as well as Ca2+ release from internal stores. The IC50 (concn. producing 50% inhibition) for inhibition of RMCE by SK&F 96365 in platelets stimulated with ADP or thrombin was 8.5 microM or 11.7 microM respectively; these concentrations of SK&F 96365 did not affect internal Ca2+ release. Similar effects of SK&F 96365 were observed in suspensions of neutrophils and in single endothelial cells. SK&F 96365 also inhibited agonist-stimulated Mn2+ entry in platelets and neutrophils. The effects of SK&F 96365 were independent of cell type and of agonist, as would be expected for a compound that modulates post-receptor events. Voltage-gated Ca2+ entry in fura-2-loaded GH3 (pituitary) cells and rabbit ear-artery smooth-muscle cells held under voltage-clamp was also inhibited by SK&F 96365; however, the ATP-gated Ca2(+)-permeable channel of rabbit ear-artery smooth-muscle cells was unaffected by SK&F 96365. Thus SK&F 96365 (unlike the 'organic Ca2+ antagonists') shows no selectivity between voltage-gated Ca2+ entry and RMCE, although the lack of effect on ATP-gated channels indicates that it discriminates between different types of RMCE. The effects of SK&F 96365 on functional responses of cells thought to be dependent on Ca2+ entry via RMCE were also studied. Under conditions where platelet aggregation is dependent on stimulated Ca2+ entry via RMCE, the response was blocked by SK&F 96365 with an IC50 of 15.9 microM, which is similar to the IC50 of 8-12 microM observed for inhibition of RMCE. Adhesion and chemotaxis of neutrophils were also inhibited by SK&F 96365. SK&F 96365 is a useful tool to distinguish RMCE from internal Ca2+ release, and to probe the role of RMCE in mediating functional responses of cells. However, SK&F 96365 is not as potent (IC50 around 10 microM) or selective (also inhibits voltage-gated Ca2+ entry) as would be desirable, so caution must be exercised when using this compound.
Synthesis and Use of Mechanism-Based Protein-Profiling Probes for Retaining β-d-Glucosaminidases Facilitate Identification of Pseudomonas aeruginosa NagZ (2007)

The NagZ class of retaining exo-glucosaminidases play a critical role in peptidoglycan recycling in Gram-negative bacteria and the induction of resistance to beta-lactams. Here we describe the concise synthesis of 2-azidoacetyl-2-deoxy-5-fluoro-beta-d-glucopyranosyl fluoride as an activity-based proteomics probe for profiling these exo-glycosidases. This active-site directed reagent covalently inactivates this class of retaining N-acetylglucosaminidases with exquisite selectivity by stabilizing the glycosyl-enzyme intermediate. Inactivated Vibrio cholerae NagZ can be elaborated with biotin or a FLAG-peptide epitope using the Staudinger ligation or the Sharpless-Meldal click reaction and detected at nanogram levels. This ABPP enabled the profiling of the Pseudomonas aeruginosa proteome and identification at endogenous levels of a tagged protein with properties consistent with those of PA3005. Cloning of the gene encoding this hypothetical protein and biochemical characterization enabled unambiguous assignment of this hypothetical protein as a NagZ. The identification and cloning of this NagZ may facilitate the development of strategies to circumvent resistance to beta-lactams in this human pathogen. As well, this general strategy, involving such 5-fluoro inactivators, may prove to be of general use for profiling proteomes and identifying glycoside hydrolases of medical importance or having desirable properties for biotechnology.
Spectral Responses of the Human Circadian System Depend on the Irradiance and Duration of Exposure to Light (2010)

In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.
Picosecond Time-Resolved FRET in the Fluorescent Protein from Discosoma Red (wt-DsRed) (2001)

Ultrafast, intra-oligomer fluorescence resonance energy transfer (FRET) between an immature green-emitting GFP-like chromophore to the mature red-emitting chromophore is found in the novel red fluorescent protein wt-DsRed (the picture shows the steady-state absorption (solid line) and emission (dotted) spectra). Since FRET is by its very nature a short range process, it represents a highly suitable method to probe oligomerization. This work describes a method preferentially applicable to the efficient screening of protein variants with mutagenetically altered surface docking sites.
Clostridium perfringens Iota-Toxin: Structure and Function (2009)

Clostridium perfringens iota-toxin is composed of the enzyme component (Ia) and the binding component (Ib). Ib binds to receptor on targeted cells and translocates Ia into the cytosol of the cells. Ia ADP-ribosylates actin, resulting in cell rounding and death. Comparisons of the deduced amino acid sequence from the gene and three-dimensional structure of Ia with those of ADP-ribosylating toxins (ARTs) suggests that there is striking structural similarity among these toxins. Our objectives are to review the recent advances in the character, structure-function, and the mode of action of iota-toxin by consideration of the findings about ARTs.
Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research (2018)

Stroke represents a severe medical condition that causes stroke survivors to suffer from long-term and even lifelong disability. Over the past several decades, a vast majority of stroke research targets neuroprotection in the acute phase, while little work has been done to enhance stroke recovery at the later stage. Through reviewing current understanding of brain plasticity, stroke pathology, and emerging preclinical and clinical restorative approaches, this review aims to provide new insights to advance the research field for stroke recovery. Lifelong brain plasticity offers the long-lasting possibility to repair a stroke-damaged brain. Stroke impairs the structural and functional integrity of entire brain networks; the restorative approaches containing multi-components have great potential to maximize stroke recovery by rebuilding and normalizing the stroke-disrupted entire brain networks and brain functioning. The restorative window for stroke recovery is much longer than previously thought. The optimal time for brain repair appears to be at later stage of stroke rather than the earlier stage. It is expected that these new insights will advance our understanding of stroke recovery and assist in developing the next generation of restorative approaches for enhancing brain repair after stroke.
A programming system for the dynamic manipulation of temporally sensitive data (1994)

In computer-participative multimedia applications, the computer not only manipulates media, but also digests it and performs independent actions based on media content. In this report I discuss an approach to the design of environments to support the development of computer-participative multimedia applications and I describe the implementation of the VuSystem, a computer-participative multimedia system built using this approach. The system is unique in that it combines the programming techniques of visualization systems and the temporal sensitivity of multimedia systems. I report measurements made of the performance of the VuSystem, which demonstrate its practicality. I conclude with a brief summary of users&amp;apos; experiences with the VuSystem, and suggests future directions for research in this area.
Use and applications of nucleic acid probes in the clinical laboratory. (1989)

The use and availability of nucleic acid probes are significantly greater than they were three to five years ago. This increased utilization has resulted because of numerous changes in molecular genetic procedures. First, the sources of probes have shifted from cloned genomic and cDNA fragments to single-strand oligonucleotides and RNA or "riboprobes." These newer probes offer defined composition and capability to create separate sense and anti-sense strands. Second, an increased variety of labeling techniques provide more ways to incorporate isotopic and nonisotopic species into these nucleic acid fragments than before. Third, the advent of nucleic acid amplification forecasts the ability to detect sub-attomol quantities of target nucleic acids, which could not be detected by classical hybridization methods. Fourth, more-sensitive signaling systems (e.g., chemiluminescence) now available will also contribute to the lowering of detection limits. Fifth, alternative sample-processing methods will shorten the time required to perform these assays. Finally, coupling these newer molecular probe procedures with automation will lead to improved precision and reliability and promote their introduction into the clinical laboratory as routine procedures. Additional factors such as clinical correlation, cost analysis, etc. will stimulate clinical laboratory personnel to participate further in development and use of these procedures.
The nature of topogenic sequences determines the transport competence of topological mutants of neutral endopeptidase-24.11 (1995)

Type II integral membrane proteins are anchored by a signal-peptide/membrane-anchor domain (SA domain) located near their N-terminus, whereas type I membrane proteins are anchored by stop-transfer sequences usually located near the C-terminus. In this study we have attempted to transform neutral endopeptidase-24.11 (EC 3.4.24.11; NEP), a type II membrane protein, into a type I membrane protein. Three type I mutant proteins were constructed by fusion of topogenic sequences to the C-terminus of SecNEP, a soluble form of NEP. The first two type I mutants, SecNEP-TMC and SecNEP-TMIC, were constructed by fusing in frame the cytosolic and SA domains of NEP to the C-terminus of SecNEP. These two fusion proteins differ only in the orientation of the cytosolic tail. The third type I mutant, SecNEP-ACE, was constructed by fusing in frame the stop-transfer and cytosolic domains of angiotensin I-converting enzyme (EC 3.4.15.1; ACE) to the C-terminus of SecNEP. Our results suggest that: (1) the NEP ectodomain can be anchored with a type I topology in the endoplasmic reticulum (ER) membrane by both NEP and ACE topogenic sequences; (2) SecNEP-TMC and SecNEP-TMIC were transport-incompetent and needed proteolytic cleavage in the C-terminal region to leave the ER, whereas SecNEP-ACE was transported out of the ER as a type I membrane protein. Therefore we concluded that the nature of topogenic sequences determines the transport-competence of topological mutants of neutral endopeptidase-24.11.
An Analysis of Taxation Theory in Medieval England (2007)

Influenced by the lord-vassal system,a king of medieval England had dual identities:supreme lord and monarch.As a supreme lord,the king shouldlive on his own,that is,he should live on his ordinary income derived from crown lands.But the ordinary income was often hard to sufficiently satisfy his needs.Hence,the king levied personal taxes on his subjects on the pretence of common goodand common needso as to meet with ever increasing administrative and military expenditures.The Parliament seized the power to authorize moveable taxes by acting as the judge of common good,thus facilitating the constitutional development of medieval England.
Comparison of Various Expression Plasmids for the Induction of Immune Response by DNA Immunization (1997)

Intramuscular injection of plasmid DNA is an efficient method to introduce a foreign gene into a live animal. We investigated several factors affecting the gene transfer efficiency and the following immune response by intramuscular injection of plasmid DNA. When the strength of several highly efficient viral promoters was compared in muscle by using the chloramphenicol acetyltransferase (CAT) gene as an indicator, cytomegalovirus (CMV) immediate early promoter was found to be stronger than any other viral promoters including Rous sarcoma virus (RSV), murine leukemia virus (SL3-3) and simian virus 40 (SV40) early promoters. Inclusion of adenovirus tripartite leader (TPL) sequences and a synthetic intron in the 5' untranslated region of mRNA moderately stimulated the CAT expression. On the other hand, the expression of encephalomyocarditis virus (EMCV) VP1 gene was greatly enhanced by the TPL sequences and an intron. The level of humoral immune response by intramuscular injection of various VP1 expression plasmids was compared. The seroconversion rate was highly dependent on the strength of the expression vector. However, the ratio of IgG1 and IgG2a immune response was not significantly variable depending on the strength of the expression vector. Also, the efficiency of the sindbis virus-based DNA vector was examined for the gene expression and immune response. Although a high level of CAT expression was obtained in muscle by using this system, VP1 was not produced as much as the conventional expression vectors. Furthermore, little humoral immune response was elicited by intramuscular injection of VP1-expressing sindbis vector, suggesting that this system was not superior to the conventional vector for DNA immunization.
Adenovirus-Mediated Transfer of a Recombinant α1-Antitrypsin Gene to the Lung Epithelium in Vivo (1991)

The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis. A replication-deficient adenoviral vector (Ad-alpha 1AT) containing an adenovirus major late promoter and a recombinant human alpha 1AT gene was used to infect epithelial cells of the cotton rat respiratory tract in vitro and in vivo. Freshly isolated tracheobronchial epithelial cells infected with Ad-alpha 1AT contained human alpha 1AT messenger RNA transcripts and synthesized and secreted human alpha 1AT. After in vivo intratracheal administration of Ad-alpha 1AT to these rats, human alpha 1AT messenger RNA was observed in the respiratory epithelium, human alpha 1AT was synthesized and secreted by lung tissue, and human alpha 1AT was detected in the epithelial lining fluid for at least 1 week.