gebhart/patrepeval huggingface dataset:
TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients (2011)

Abstract Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8+ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients.
An empirical analysis of sponsored search performance in search engine advertising (2008)

The phenomenon of sponsored search advertising - where advertisers pay a fee to Internet search engines to be displayed alongside organic (non-sponsored) web search results - is gaining ground as the largest source of revenues for search engines. Despite the growth of search advertising, we have little understanding of how consumers respond to contextual and sponsored search advertising on the Internet. Using a unique panel dataset of several hundred keywords collected from a large nationwide retailer that advertises on Google, we empirically model the relationship between different metrics such as click-through rates, conversion rates, bid prices and keyword ranks. Our paper proposes a novel framework and data to better understand what drives these differences. We use a Hierarchical Bayesian modeling framework and estimate the model using Markov Chain Monte Carlo (MCMC) methods. We empirically estimate the impact of keyword attributes on consumer search and purchase behavior as well as on firms' decision-making behavior on bid prices and ranks. We find that the presence of retailer-specific information in the keyword increases click-through rates, and the presence of brand-specific information in the keyword increases conversion rates. We also demonstrate that as suggested by anecdotal evidence, search engines like Google factor in both the auction bid price as well as prior click-through rates before allotting a final rank to an advertisement. To the best of our knowledge, this is the first study that uses real world data from an advertiser and jointly estimates the effect of sponsored search advertising at a keyword level on consumer search, click and purchase behavior in electronic markets
Early Failure of Minimally Invasive Unicompartmental Knee Arthroplasty Is Associated with Obesity (2005)

Prognostic study, Level IV-2 (case series). See the Guidelines for Authors for a complete description of levels of evidence.
Performance of Combined Constellation Rearrangement and Space-Time Block Coding Scheme for Multi-Level Modulation (2007)

In this paper, we present a combined constellation rearrangement and space-time block code scheme which is bandwidth- efficient and power-efficient and suitable for improving the performance of linear multi-level modulation schemes over multiple antenna transmission. Orthogonal transmit diversity with optimum signal combining can take full advantage of fading multi-path channels but for such a scheme the bandwidth efficiency decreases proportionally with the number of transmit branches. It will be shown that using different signal mapping constellations for each transmit branch improves the system performance. While keeping the same rate and complexity, both analytical and simulation results show a significant improvement of the system performance.
Synthesis of 2‐[(4‐[<sup>18</sup>F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione from 2‐hydroxymethyl 1,4‐naphthoquinone and 4‐[<sup>18</sup>F]fluorobenzoic acid using dicyclohexyl carbodiimide (2011)

2‐[(4‐[ 18 F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione ([ 18 F] 1 ) was synthesised as a putative hypoxia imaging agent from 2‐hydroxymethyl 1,4‐naphthoquinone ( 7 ) and 4‐[ 18 F]fluorobenzoic acid ([ 18 F] 8 ) using dicyclohexyl carbodiimide (DCC) to activate [ 18 F] 8 . This coupling reaction was fast and gave quantitative yields. Further investigations are warranted on the use of DCC as a coupling agent in Positron Emission Tomography. The synthesis including HPLC purification and reformulation has been fully automated on a modified FDG synthesiser with two reactor vials. [ 18 F] 1 was produced in a radiochemical yield of 27 ± 5%, with a radiochemical purity of 97.5% and a specific activity of 78.4–134.5 GBq/µmol at the end of synthesis ( n = 23). The total synthesis time including reformulation was 65 min. [ 18 F] 1 was found to be stable in plasma and saline, but underwent rapid metabolism in a phase 1 metabolite assay using rat S9 liver fractions. An in vivo evaluation of [ 18 F] 1 in transplanted, hypoxic SK‐RC‐52 tumour‐bearing BALB/c nude mice revealed the tumour‐to‐muscle ratio to be 2.4 ± 0.1 at 2 h post‐injection. Copyright © 2011 John Wiley & Sons, Ltd.
Efficient Transposition of the Retrotransposon Tnt1 in Cucumber (Cucumis sativus L.) (2018)

Tnt1 is an active retrotransposon originally identified in tobacco (Nicotiana tabacum L.) (Grandbastien et al., 1989), but its transposition activity could be activated through tissue culture in other plant species. The insertions are stable and inheritable in the progeny, which has made it a valuable and versatile tool for developing insertional mutagenesis libraries in several plant species. Here, we explored its utility for mutagenesis in cucumber (Cucumis sativus L.). T3 Tnt1 transgenic cucumber plants were subjected to tissue culture to regenerate self-pollinated progeny. With PCR and analyses and Southern hybridization, we found regenerated plants maintained the original Tnt1 insertion and created new insertions suggesting characteristic re-transposition activity of Tnt1 during this process. Using genome walking, some flanking sequences of Tnt1 insertions were recovered in regenerated plants. The results demonstrated that Tnt1 could be stably inherited and re-transposable during tissue culture in cucumber and that it is feasible to use for developing an insertional mutagenesis library for cucumber.
Inositol 1,4,5-Trisphosphate (InsP3) and Calcium Interact to Increase the Dynamic Range of InsP3 Receptor-dependent Calcium Signaling (1997)

The inositol 1,4,5-trisphosphate (InsP3)-gated Ca channel in cerebellum is tightly regulated by Ca (Bezprozvanny, I., J. Watras, and B.E. Ehrlich. 1991. Nature (Lond.). 351:751-754; Finch, E.A., T. J. Turner, and S.M. Goldin. 1991. Science (Wash. DC). 252:443-446; Hannaert-Merah, Z., J.F. Coquil, L. Combettes, M. Claret, J.P. Mauger, and P. Champeil. 1994. J. Biol. Chem. 269:29642-29649; Iino, M. 1990. J. Gen. Physiol. 95:1103-1122; Marshall, I., and C. Taylor. 1994. Biochem. J. 301:591-598). In previous single channel studies, the Ca dependence of channel activity, monitored at 2 microM InsP3, was described by a bell-shaped curve (Bezprozvanny, I., J. Watras, and B.E. Ehrlich. 1991. Nature (Lond.). 351:751-754). We report here that, when we used lower InsP3 concentrations, the peak of the Ca-dependence curve shifted to lower Ca concentrations. Unexpectedly, when we used high InsP3 concentrations, channel activity persisted at Ca concentrations as high as 30 microM. To explore this unexpected response of the channel, we measured InsP3 binding over a broad range of InsP3 concentrations. We found the well-characterized high affinity InsP3 binding sites (with Kd < 1 and 50 nM) (Maeda, N., M. Niinobe, and K. Mikoshiba. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:61-67; Mignery, G., T.C. Sudhof, K. Takei, and P. De Camilli. 1989. Nature (Lond.). 342:192-195; Ross, C.A., J. Meldolesi, T.A. Milner, T. Satoh, S. Supattapone, and S.H. Snyder. 1989. Nature (Lond.). 339:468-470) and a low affinity InsP3 binding site (Kd = 10 microM). Using these InsP3 binding sites, we developed a new model that accounts for the shift in the Ca-dependence curve at low InsP3 levels and the maintained channel activity at high Ca and InsP3 levels. The observed Ca dependence of the InsP3-gated Ca channel allows the cell to abbreviate the rise of intracellular Ca in the presence of low levels of InsP3, but also provides a means of maintaining high intracellular Ca during periods of prolonged stimulation.
Recent advances in liposomal dry powder formulations: preparation and evaluation (2009)

Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well-designed inhalation toxicology studies to support these products, especially for chronic diseases.
Magnesium Adducts of Substituted Anthracenes – Preparation and Properties (1990)

2‐Methyl‐, 1,4‐dimethyl‐, 9‐methyl‐, 9‐ethyl‐, 9,10‐dimethyl‐, and 9‐phenylanthracene ( 1a – f ) react with magnesium in THF at room temperature to afford the corresponding substituted magnesium anthracenes 2a ‐ i . 9,10‐Diphenylanthracene ( 1g ), however, reacts with magnesium under the same conditions to produce the deep‐blue magnesium bis(9,10‐diphenylanthracenide) · 6 THF ( 4g ). Upon heating to 60°C in THF, 4g reversibly dissociated to give magnesium 9,10‐diphenylanthracene · 3 THF ( 2g ) and 1g , while prolonged heating at 60°C causes decomposition of 2g to active magnesium (Mg * ) and 1g . In THF 2a – c , e , and f exhibit temperature‐dependent equilibria with 1a – c , e , and f and magnesium. Compared with magnesium anthracene · 3 THF ( 2 ), these equilibria are strongly shifted toward substituted anthracenes and magnesium, and only at 0°C high conversions are achieved. The magnesium exchange between 2 and the substituted anthracenes 1a,b , and f in THF has been experimentally verified. 2a,e , and f react with organic halides in the same way as 2 , however, in the case of allyl, propargyl, and benzyl chloride the yields of Grignard compounds are lower than for 2 ; with bromobenzene, the tendency for the radical transfer reaction is stronger than for 2 . Magnesium 9,10‐dimethylanthracene ( 2e ) reacts with ethyl acetate to give the bicyclic tertiary alcohol 9 by an intramolecular C–C coupling reaction.
Impediments to Secretion of Green Fluorescent Protein and Its Fusion from <i>Saccharomyces cerevisiae</i> (2002)

While it has been demonstrated that GFP-tagged proteins were transported to their correct cellular compartments in most cells, attempts to secrete GFP/GFP-fusion through the default secretory pathway have not been as successful. In an attempt to induce secretion of GFP and Hexokinase (HXK)-GFP fusion in Saccharomycescerevisiae, we have cloned constructs that employed four different yeast secretion signal sequences, i.e., INU1, SUC2, PHO5, and MEL1. The expression is under the control of the galactose-inducible GAL1 promoter. Our results showed that all eight constructs entered the secretory pathway successfully, and the signal peptides were all cleaved off. However, none of the eight constructs were able to lead to secretion into the culture media or the periplasmic space. The expression levels of the eight constructs differ dramatically, depending on both the signal peptide and whether GFP was fused with HXK. Confocal microscopy studies revealed that the eight constructs also led to very different localization patterns. Among them, two constructs targeted GFP to the vacuole partially or exclusively, whereas others were mostly retained in the ER/Golgi compartments. Our efforts, together with those of others, seem to suggest that the signal peptide itself is not enough to lead to secretion of GFP from S. cerevisiae, although it has been successful in some other organisms. Nonetheless, the advantage of GFP's in vivo detection makes it a powerful tool for investigating protein localization events.
Capsules of <i>Streptococcus pneumoniae</i> and Other Bacteria: Paradigms for Polysaccharide Biosynthesis and Regulation (2010)

Capsular polysaccharides and exopolysaccharides play critical roles in bacterial survival strategies, and they can have important medical and industrial applications. An immense variety of sugars and glycosidic linkages leads to an almost unlimited diversity of potential polysaccharide structures. This diversity is reflected in the large number of serologically and chemically distinct polysaccharides that have been identified among both gram-positive and gram-negative bacteria. Despite this diversity, however, the genetic loci and mechanisms responsible for polysaccharide biosynthesis exhibit conserved features and can be classified into a small number of groups. In Streptococcus pneumoniae, capsule synthesis occurs by one of two distinct mechanisms that involve the polymerization of either individual sugars in a processive reaction (synthase dependent) or discrete repeat units in a nonprocessive reaction (Wzy dependent). Characterization of these systems has provided novel insights that are applicable to polymers synthesized by many gram-positive and gram-negative bacteria, as well as eukaryotes.
Synthesis of New Analogues of the Tetraponerines (2009)

Abstract To evaluate the influences of the tetraponerine alkyl chains and tricyclic ring systems on their cytotoxic activities, we have prepared a series of alkyl derivatives ( 3a , 3b and 4a – f ) of the non‐natural tricyclic skeletons decahydro‐2 H ,6 H ‐dipyrido[1,2‐ a :1′,2′‐ c ]pyrimidine ( 3 , 6–6–6 skeleton) and dodecahydro‐2 H ‐1,8a‐diazaphenanthrene ( 4 , iso‐6–6–6 skeleton). In this study, two ways to synthesise the 6–6–6 analogues have been developed and compared. One is based on the condensation of α‐tripiperideine with diethyl malonate (DEM) in water at pH 11. This yielded oxo ester 11 , precursor of the amino nitrile 8 , but only in moderate yield. In the second pathway, the key intermediate 8 was more efficiently synthesised by starting from 2‐(2‐piperidyl)ethanol. Treatment of 8 with alkyl Grignard reagents led to the 6–6–6 analogues 3a and 3b . When the one‐pot reaction between α‐tripiperideine and DEM was performed in water at pH 8, the lactam 12 , precursor of the iso‐6–6–6 skeleton, was obtained in a yield of 76 %. The same lactam was also obtained in a yield of 86 % by treatment of tetrahydroanabasine 14 with DEM in water at pH 8. Lactam 12 was transformed into the iso‐6–6–6 analogues 4a – 4f . The cytotoxic activities of the 6–6–6 and iso‐6–6–6 analogues against HT29 cancer cells were compared with those of the 5–6–5 and 6–6–5 tetraponerines and with those of solenopsin analogues. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
On-line spectroscopic monitoring of metal ions for environmental and space applications using photodiode array spectrometry (1990)

A photodiode-array spectrometry characterized by fast data acquisition, simultaneous readings at multiple wavelengths, reproducibility, a wide dynamic range, and enhanced accuracy due to a low instrument drift is considered for on-line real-time monitoring of the trace levels of metal ions in water solutions for environmental, power plant, and space applications. An experimental application for NASA's Controlled Ecological Life Support System is outlined along with nuclear-plant monitoring applications. Steps involved in the developing of an algorithm for on-line multicomponent analyses in absorption spectrometry are presented, and a photodiode-array spectrometer used in the described experimental investigations is detailed.
Race-free state assignments for synthesizing large-scale asynchronous sequential logic circuits (1993)

A state assignment technique is introduced for synthesizing large-scale asynchronous sequential logic circuits (ASLCs). It provides a systematic and efficient approach for generating race-free state assignments. A race condition is classified as being either an intrinsic race (IR) or or a generated race. Intrinsic races decompose into two subclassifications: visible intrinsic races and hidden intrinsic races. Algorithms have been developed to identify and eliminate these races. A graph, referred to as a Node-Weight Diagram, facilitates the process of making state assignments and guarantees that no races are generated. Moreover, it provides a convenient and efficient method for investigating the implications of selecting from an allowed set of alternative race-free state assignments. The state assignment technique described adds cycles and states, as needed, to avoid IRs and always attempts to use the minimum or near-minimum number of state variables and states. This technique has been implemented and incorporated into an ASLC design automation system. Experimental results show that it provides significantly better results than other approaches in terms of the computation time required to make the assignments and the number of state variables required to achieve race-free ASLCs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Templated Formation of Binuclear Macrocycles via Hemilabile Ligands (1999)

A new approach to synthesizing binuclear metallomacrocycles is reported. This approach utilizes flexible bisphosphine alkyl−aryl ether hemilabile ligands which complex Rh(I) to form “condensed” macrocycles held together by a series of both strong and weak links of the following type: [(κ2:μ2:κ2-(1,4-(Ph2PCH2CH2O)2-2,3,5,6-((CH3)4C6)))2Rh2][BF4]2 (5a) or [(μ2,η1:η6:η1-(1,4-(Ph2P(CH2)nO)2-X))2Rh2][BF4]2 (5b, n = 2, X = 2,3,5,6-((CH3)4C6); 6, n = 3, X = 2,3,5,6-((CH3)4C6); 7, n = 2, X = C6H4; 8, n = 2, X = C6H4−C6H4). Introduction of ligands that will bind to Rh(I) more strongly than either the Rh−η6-aryl or Rh−η1-ether weak links of 5a−8 results in the breaking of the weak links to form a series of 26−34-membered macrocyclic ring structures such as [(μ2-(1,4-(Ph2P(CH2)nO)2X))2(L1)m(L2)oRh2][BF4]2 (9, n = 2, X = 2,3,5,6-((CH3)4C6)), L1 = CO, m = 6, L2 = none; 10, n = 2, X = C6H4, L1 = CO, m = 6, L2 = none; 11, n = 2, X= C6H4−C6H4; L1 = CO, m = 6, L2 = none; 12, n = 2, X = 2,3,5,6-((CH3)4C6)), L1 = CO, m = 2, L2 = CH3CN, o = 2; 13, n = 3, X = 2,3,5,6-((CH3)4C6)), L1 = CO, m = 2, L2 = CH3CN, o = 2; 14, n = 2, X = C6H4, L1 = CO, m = 2, L2 = CH3CN, o = 2; 15, n = 2, X = C6H4−C6H4, L1 = CO, m = 2, L2 = CH3CN, o = 2). These homobimetallic macrocycles can be used to sequester bifunctional aromatic molecules to form host−guest structures such as [(μ2-(1,4-(Ph2PCH2CH2O)2-2,3,5,6-((CH3)4C6)))2(CO)2(μ2-1,4-(−NC)2C6H4)Rh2][BF4]2 (16) and [(μ2-(1,4-(Ph2PCH2CH2O)2-2,3,5,6-((CH3)4C6)))2(CH3CN)2(μ2-1,4-(−CN)2C6H4)Rh2][BF4]2 (17). The synthetic methods described within this article represent a powerful new way of making binuclear macrocycles from flexible ligands in nearly quantitative yields. Moreover, the macrocycles are highly tailorable with respect to cavity size and hydrophobicity and the metals' steric and electronic environments. Solid-state structures as determined by single-crystal X-ray diffraction studies are presented for compounds 5a, 6, 7, 9, 10, 12, and 17.
The reactions of oligoalcohols with arsenic, arsenous, boric and germanic acids (1980)

The reactions of sorbitol, mannitol, adonitol, dulcitol, glucose and glycerol with H 3 AsO 4 , H 3 AsO 3 , H 3 BO 3 and GeO 2 acids in dilute aqueous solutions were studied by potentiometric neutralization titrations. The formation of the following chelates was demonstrated: As(V)L 3 - , As(III)L(OH) 2 - , HAs(III)L(OH) 2 , BL 2 - , GeL 2 (OH) - and GeL 3 2- and the equilibrium constants for their formation were found. Conditions for formation of these chelates of organic oligohydroxy compounds are discussed.
Linear Phase-gradient Imaging with Asymmetric Illumination based Differential Phase Contrast (AIDPC) (2009)

This paper demonstrates how one could engineer the transfer function of AIDPC, a novel optical thickness (phase) gradient measurement method suitable for live cell imaging, for linear imaging of the specimen phase-gradient.
Molecular Nuclear imaging of Angiogenesis (2004)

Fifty-five patients with presumptive macular amyloidosis were investigated for the presence of amyloid in dermal tissue. In twenty-six of these patients the diagnosis could be confirmed by the demonstration of amyloid deposits by optical and/or electron microscopy. In this paper attention is called to the frequency of oligosymptomatic forms of macular amyloidosis, which are often overlooked in spite of the usual existence of itching. These inconspicuous forms are termed "minor macular amyloidosis", and they consist of tenuous brown macules on the upper back, irregularly interspersed with the normal skin and with speckles of whitish discoloration. The diagnosis must be verified by the finding of dermal deposits of amyloid. For that purpose the electron microscopy is a much more reliable procedure than conventional methods or thioflavine T.
Focal spot size and scatter suppression in magnification mammography (1979)

The improved image quality using magnification in film-screen mammography is related to a complicated interplay between focal spot size, x-ray tube output, detector resolution and sensitivity, air gap size, and target dimensions. Preliminary clinical evaluation of magnification mammography indicates that accuracy of diagnosis has been considerably enhanced. Additional technical and clinical evaluations are continuing, as suggested by mathematical modeling, in order to determine the best possible magnification protocols. While a small focal spot (less than 300 micrometers) is highly recommended for both contact and magnification with the film-screen systems, the smallest focal spot sizes (150 micrometers and smaller) may neither be necessary nor the best in all situations of reduced dose magnification mammography.