gebhart/patrepeval huggingface dataset:
Structure-Activity Relationship of Colistins. (1967)

1) Purified samples of polymyxin group antibiotics were shown to be remarkable antimicrobial agents as colistin against E. coli. 2) Removal of the C9-fatty acid from the colistin molecule resulted in the decrease of the activity. 3) The side chain moiety itself showed no antimicrobial activity. 4) The cyclic peptide moiety showed an antimicrobial activity although it was less active than the parent antibiotic. These results indicate that the "active"structure responsible for the antimicrobial activity is the"cyclic peptide moiety"in colistin molecule.
The cave and the digital wire frame (2004)

In this essay, a connection is made between the imagery of 1990's liquid architecture, designed with the help of the computer, and the 1960's fascination with prehistoric caves. This comparison allows one to pinpoint a contemporary notion of historical valuation and continuity. This response to difference does not lie primarily in possible resemblances of compared forms, but relates primarily rather to the construction of imagination: The cultural premises of design.
Mechanistic studies of sequential injection of cationic liposome and plasmid DNA (2005)

We previously reported that sequential injection of cationic liposome and plasmid DNA leads to notably reduced inflammatory toxicity and improved transfection in the lung (Y. Tan et al., 2001, Mol. Ther. 3, 673-682). The purpose of the current study was to explore the mechanism involved in sequential injection. It was observed that sequential injection resulted in dramatically lower DNA uptake by the liver and higher DNA levels in the lung than the lipoplex injection. In vitro experiments with macrophage cells further showed that sequential addition of liposomes and DNA could diminish the cellular uptake of DNA by these cells. The contributions of serum to the enhanced bioactivity and decreased toxicity were examined by injecting mice with samples of premixed liposome with serum and then DNA (LSD sample), and the resulting activities were compared to those obtained with injection of lipoplex-serum mixtures (LDS sample). LSD yielded 80% lower TNF-alpha levels and over 10-fold higher transfection than lipoplex, which is consistent with the reported findings with sequential injection. In contrast, LDS resulted in the same TNF-alpha levels and comparable transfection with lipoplex. Thus, the results suggest that the primary interaction of serum with liposome is a critical factor contributing to the superior activity and reduced toxicity of sequential injection. Studies on the interaction between mouse serum, liposomes, and DNA showed that DNA could bind negatively charged liposome-serum complex to form a ternary complex, which has a density similar to that of the ternary complex formed between lipoplex with serum. Further in vitro tests showed that LSD and LDS were similar in particle size and protein content, but different in protein composition as observed by 2-D gel electrophoresis. In addition, DNA in LSD was more readily displaced by dextran sulfate, an anionic polymer, than in LDS. The above findings suggest that the inhibition of opsonin protein binding on the particle surface with the sequential injection may contribute to the reduced macrophage uptake and cytokine induction and that the high ability of DNA release from the particles formed after sequential injection may contribute to the improved lung gene transfection.
Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study (2006)

Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517-525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches.
P1‐068: Environmental enrichment “sessions” are sufficient to provide cognitive benefit to impaired Alzheimer's transgenic mice without affecting brain or plasma Aβ levels (2008)

Environmental enrichment (EE) studies using AD mouse models have involved either EE sessions or continuous EE housing. These two EE paradigms, employed separately by different laboratories, are a potential variable that may explain some of the divergent results thus far reported with EE in AD mouse models. Moreover, only our initial study (Neuroreport 15:1751, 2004) investigated the potential of EE to cognitively benefit aged, impaired APPsw transgenic (Tg) mice, with that study showing that continuous EE improves cognitive performance in aged Tg mice. If, however, cognitive stimulation/rehabilitation is to be utilized therapeutically in AD patients, cognitive stimulation “sessions”, given several times weekly, would be the most likely paradigm. Beginning at 10 months of age, APPsw mice were placed in one of four different complex environments (on a rotating basis) for one hour sessions, three times weekly for two months. Additional APPsw mice were placed in continuous EE housing or maintained in standard individual cages for the two month period. A comprehensive behavioral test battery was then administered. Tg mice given EE sessions or continuous EE exhibited similarly-enhanced cognitive performance versus Tg controls in a variety of tasks testing various cognitive domains (e.g., the circular platform task of spatial learning/memory, the platform recognition task of switching from a spatial to a recognition strategy). In the radial arm water maze task of working memory, Tg mice given continuous EE and those given EE sessions also benefited similarly in performing much better than Tg controls and identical to non-transgenic controls. Evaluation of plasma and hippocampal Aβ1–40 and Aβ1–42 (both soluble and insoluble) revealed no effects of either EE sessions or continuous EE in Tg mice versus Tg controls. Thus, EE “sessions” provided cognitive benefits in aged APPsw mice that were similar to those resulting from continuous EE, with neither paradigm impacting Aβ levels. We conclude that EE sessions are sufficient to provide cognitive benefit to aged Tg mice through Aβ independent mechanisms, suggesting that frequent and long-term cognition stimulation/rehabilitation sessions could be of substantial cognitive benefit to AD patients irrespective of their brain Aβ burdens.
Reply to Dr Nielsen: Pericapsular Nerve Group (PENG) block for hip fracture (2019)

To the Editor: We would like to thank Dr Nielsen and Bendtsen[1][1] for the interest in our work.[2][2] This group is well respected for their novel work in regional anesthesia. Subsequent to our work in the innervation of hip joint and the sonoanatomy described in that article,[3][3] we expected
Antigen Receptor Allelic Exclusion: An Update and Reappraisal (2010)

Most lymphocytes express cell surface Ag receptor chains from single alleles of distinct Ig or TCR loci. Since the identification of Ag receptor allelic exclusion, the importance of this process and the precise molecular mechanisms by which it is achieved have remained enigmatic. This brief review summarizes current knowledge of the extent to which Ig and TCR loci are subject to allelic exclusion. Recent progress in studying and defining mechanistic steps and molecules that may control the monoallelic initiation and subsequent inhibition of V-to-(D)-J recombination is outlined using the mouse TCRβ locus as a model with frequent comparisons to the mouse IgH and Igκ loci. Potential consequences of defects in mechanisms that control Ag receptor allelic exclusion and a reappraisal of the physiologic relevance of this immunologic process also are discussed.
A new intracellular serine protease inhibitor expressed in the rat pituitary gland complexes with granzyme B (1998)

We have cloned a novel serpin (raPIT5a) from a rat pituitary cDNA library which is structurally related to members of the ovalbumin subfamily of serine protease inhibitors. This new cDNA encodes a 374-amino acid protein, designated raPIT5a. raPIT5a was expressed in specific cells in the intermediate and anterior lobes of the pituitary. Recombinant raPIT5a was not secreted suggesting raPIT5a functions to inhibit intracellular proteases. Recombinant raPIT5a formed an SDS-stable complex with human granzyme B, a serine protease which induces apoptosis by activating members of the caspase enzyme family. These data suggest raPIT5a may have a role in regulating granzyme B or related enzymes and apoptosis in the pituitary gland.
Successful Topical Respiratory Tract Immunization of Primates against Ebola Virus (2007)

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.
Techniques for characterization of charge carrier mobility in organic semiconductors (2012)

Abstract The charge transport characteristics of organic semiconductors are one of the key attributes that impacts the performance of organic electronic and optoelectronic devices in which they are utilized. For improved performance in organic photovoltaic cells, light‐emitting diodes, and field‐effect transistors (FETs), efficient transport of the charge carriers within the organic semiconductor is especially critical. Characterization of charge transport in these organic semiconductors is important both from scientific and technological perspectives. In this review, we shall mainly discuss the techniques for measuring the charge carrier mobility and not the theoretical underpinnings of the mechanism of charge transport. Mobility measurements in organic semiconductors and particularly in conjugated polymers, using space‐charge‐limited current, time of flight, carrier extraction by linearly increasing voltage, double injection, FETs, and impedance spectroscopy are discussed. The relative merits, as well as limitations for each of these techniques are reviewed. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Effect of Cation on Physical Properties and CO2 Solubility for Phosphonium-Based Ionic Liquids with 2-Cyanopyrrolide Anions (2015)

A series of tetraalkylphosphonium 2-cyanopyrrolide ([Pnnnn][2-CNPyr]) ionic liquids (ILs) were prepared to investigate the effect of cation size on physical properties and CO2 solubility. Each IL was synthesized in our laboratory and characterized by NMR spectroscopy. Their physical properties, including density, viscosity, and ionic conductivity, were determined as a function of temperature and fit to empirical equations. The density gradually increased with decreasing cation size, while the viscosity decreased noticeably. In addition, the [Pnnnn][2-CNPyr] ILs with large cations exhibited relatively low degrees of ionicity based on analysis of the Walden plots. This implies the presence of extensive ion pairing or formation of aggregates resulting from van der Waals interactions between the long hydrocarbon substituents. The CO2 solubility in each IL was measured at 22 °C using a volumetric method. While the anion is typically known to be predominantly responsible for the CO2 capture reaction, the [Pnnnn][2-CNPyr] ILs with shorter alkyl chains on the cations exhibited slightly stronger CO2 binding ability than the ILs with longer alkyl chains. We attribute this to the difference in entropy of reaction, as well as the variation in the relative degree of ionicity.
Simulation globaler und hemisphärischer Temperaturvariationen und Signalanalyse mit Hilfe neuronaler Netzwerke (1998)

The concept of neural network models is a statistical strategy which can be used if a superposition of any forcing mechanisms leads to any effects and if a sufficient related observational data base is available. In comparison to multiple regression analysis, the main advantages are that neural network models are an appropriate tool also in the case of non-linear cause-effect relations and that interactions of the forcing mechanisms are allowed. In comparison to more sophisticated methods like general circulation models, the main advantage is that details of the physical background, like feedbacks, can be unknown. Neural networks learn from observations which reflect feedbacks implicity. The disadvantage, of course, is that the physical background is neglected. In addition, the results prove to be sensitively dependent from the network architecture like the number of hidden neurons or the initialisation of learning parameters. We used a supervised learning backpropagationnetworkwith three neuron layers, as well as an unsupervised learning counterpropagation network. This latter network architecture consists of a so-called Kohonen layer, where the internal features of the data set in question are "learned", which is followed by a so-called Grossberg layer, where the "learned" internal representations are adjusted to the observed time series to be simulated. Both concepts (backpropagation, counterpropagation) are tested in respect to their ability to simulate the observed global as well as hemispheric mean surface air temperature annual variations 1874-1993 if parameter time series of the following forcing mechanisms are incorporated: equivalent CO2 concentrations, tropospheric sulfate aerosol concentrations (both anthropogenic), volcanism, solar activity, and ENSO (all natural). It arises that in this way up to 83 % of the observed temperature variance can be explained, significantly more than by multiple regression analysis. The implication of the North Atlantic Oscillation does not improve these results. On a global average, the greenhouse gas signal so far is assessed to be 0.9-1.3 K (warming), the sulfate signal 0.2-0.4 K (cooling), results which are in close similarity to the GCM findings published in the recent IPCC Report. The related signals of the natural forcing mechanisms considered cover amplitudes of 0.1-0.3 K.
Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors (2001)

Cytochrome P450 14α-sterol demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes. CYP51 removes the 14α-methyl group from sterol precursors such as lanosterol, obtusifoliol, dihydrolanosterol, and 24(28)-methylene-24,25-dihydrolanosterol. Inhibitors of CYP51 include triazole antifungal agents fluconazole and itraconazole, drugs used in treatment of topical and systemic mycoses. The 2.1- and 2.2-Å crystal structures reported here for 4-phenylimidazole- and fluconazole-bound CYP51 from Mycobacterium tuberculosis (MTCYP51) are the first structures of an authentic P450 drug target. MTCYP51 exhibits the P450 fold with the exception of two striking differences—a bent I helix and an open conformation of BC loop—that define an active site-access channel running along the heme plane perpendicular to the direction observed for the substrate entry in P450BM3. Although a channel analogous to that in P450BM3 is evident also in MTCYP51, it is not open at the surface. The presence of two different channels, with one being open to the surface, suggests the possibility of conformationally regulated substrate-in/product-out openings in CYP51. Mapping mutations identified in Candida albicans azole-resistant isolates indicates that azole resistance in fungi develops in protein regions involved in orchestrating passage of CYP51 through different conformational stages along the catalytic cycle rather than in residues directly contacting fluconazole. These new structures provide a basis for rational design of new, more efficacious antifungal agents as well as insight into the molecular mechanism of P450 catalysis.
Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease (2016)

The elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features.
Straightforward Access to Protected syn α‐Amino‐β‐hydroxy Acid Derivatives (2008)

Titanium stability: syn α-Amino-β-hydroxy acid derivatives were prepared in excellent diastereoselectivities by an aldol reaction with chiral N-(azidoacetyl)thiazolidin-2-thione derivatives (see scheme; NMP=N-methylpyrrolidinone). Titanium enolates of these derivatives are stable and provide a new and efficient method to access chiral amino acids. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z800860_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.
Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription (2009)

Retroviral reverse transcriptases possess both a DNA polymerase and an RNase H activity. The linkage with the DNA polymerase activity endows the retroviral RNases H with unique properties not found in the cellular counterparts. In addition to the typical endonuclease activity on a DNA/RNA hybrid, cleavage by the retroviral enzymes is also directed by both DNA 3' recessed and RNA 5' recessed ends, and by certain nucleotide sequence preferences in the vicinity of the cleavage site. This spectrum of specificities enables retroviral RNases H to carry out a series of cleavage reactions during reverse transcription that degrade the viral RNA genome after minus-strand synthesis, precisely generate the primer for the initiation of plus strands, facilitate the initiation of plus-strand synthesis and remove both plus- and minus-strand primers after they have been extended.
Contrast-enhanced NMR imaging: animal studies using gadolinium-DTPA complex (1984)

Gadolinium (Gd)-DTPA complex was assessed as a nuclear magnetic resonance (NMR) contrast-enhancing agent by experimentally imaging normal and diseased animals. After intravenous injection, Gd-DTPA, a strongly paramagnetic complex by virtue of unpaired electrons, was rapidly excreted into the urine of rats, producing an easily observable contrast enhancement on NMR images in kidney parenchyma and urine. Spin-echo intensity of urine within the renal pelvis increased from 2263 to 4414 units; intensity of renal parenchyma increased from 2901 to 3893 after administration of 0.1 mmol/kg Gd-DTPA. Sterile soft-tissue abscesses demonstrated an obvious rim pattern of enhancement. A focus of radiation-induced brain damage in a canine model was only faintly detectable on spin-echo NMR images before contrast administration; after 0.5 mmol/kg Gd-DTPA administration, the lesion intensity increased from 3867 to 5590. In comparison, the normal brain with an intact blood-brain barrier remained unchanged in NMR characterization. Gd-DTPA is a promising new NMR contrast enhancer for the clinical assessment of renal function, of inflammatory lesions, and of focal disruption of the blood-brain barrier.