gebhart/patrepeval huggingface dataset:
Asymmetric synthesis and biological evaluation of .beta.-L-(2R,5S)- and .alpha.-L-(2R,5R)-1,3-oxathiolane-pyrimidine and -purine nucleosides as potential anti-HIV agents (1993)

In order to study the structure-activity relationships of L-oxathiolanyl nucleosides as potential anti-HIV agents, a series of enantiomerically pure L-oxathiolanyl pyrimidine and purine nucleosides were synthesized and evaluated for anti-HIV-1 activity in human peripheral blood mononuclear (PBM) cells. The key intermediate 8 was synthesized starting from L-gulose via 1,6-thioanhydro-L-gulopyranose. The acetate 8 was condensed with thymine, 5-substituted uracils and cytosines, 6-chloropurine, and 6-chloro-2-fluoropurine to give pyrimidine and purine nucleosides. Upon evaluation of these final nucleosides, the 5-fluorocytosine derivative 51 was found to be the most potent compound among those tested. In the case of 5-substituted cytosine analogues, the antiviral potency was found to be in the following decreasing order: cytosine (beta-isomer) > 5-iodocytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-methylcytosine (alpha-isomer) > 5-methylcytosine (beta-isomer) > 5-bromocytosine (beta-isomer) > 5-chlorocytosine (beta-isomer). Among the thymine, uracil, and 5-substituted uracil derivatives, thymine (alpha-isomer) and uracil (beta-isomer) derivatives exhibited moderate anti-HIV activity. In the purine series, the antiviral potency is found to be in the following decreasing order: adenine (beta-isomer) > 6-chloropurine (beta-isomer) > 6-chloropurine (alpha-isomer) > 2-NH2-6-Cl-purine (beta-isomer) > guanine (beta-isomer) > N6-methyladenine (alpha-isomer) > N6-methyladenine (beta-isomer). The cytotoxicity was also determined in human PBM cells as well as Vero cells. None of the synthesized nucleosides was toxic up to 100 microM in PBM cells.
Self-Assembled Inverted Micelles Prepared from a Dendrimer Template:  Phase Transfer of Encapsulated Guests (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSelf-Assembled Inverted Micelles Prepared from a Dendrimer Template: Phase Transfer of Encapsulated GuestsVictor Chechik, Mingqi Zhao, and Richard M. CrooksView Author Information Department of Chemistry, Texas A&M University P.O. Box 30012, College Station, Texas 77842-3012 Cite this: J. Am. Chem. Soc. 1999, 121, 20, 4910–4911Publication Date (Web):May 6, 1999Publication History Received11 February 1999Published online6 May 1999Published inissue 1 May 1999https://doi.org/10.1021/ja990445rCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1785Altmetric-Citations231LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (40 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Dendrons,Hydrocarbons,Metal nanoparticles,Solvents Get e-Alerts
“Cap-Tag”—Novel Methods for the Rapid Purification of Oligosaccharides Prepared by Automated Solid-Phase Synthesis Financial support from the donors of the Petroleum Research Fund, administered by the ACS (ACS-PRF 34649-G1), Merck (Predoctoral Fellowship for E.R.P.), Boehringer-Ingelheim (Predoctoral Fellowship for E.R.P.), and the NIH (Biotechnology Training Grant for M.C.H.) is gratefully acknowledged. Funding for the MIT-DCIF Inova 501 was provided by the NSF (Award CHE-9808061). Funding for the MIT-DCIF Avance (DPX) 400 was provided by the NIH (Award 1S10RR13886-01). We thank Silicycle (Quebec City, Canada) for the generous gift of fluorous silica gel and isocyanate silica gel scavenger resin. We thank Dr. O. Plante for helpful discussions and help with the automated oligosaccharide synthesizer. (2001)

React or get capped and tagged! Two capping reagents, designated A-Tag and F-Tag, mark unconverted oligosaccharides during automated synthesis for simple separation from the desired products. A-Tagged molecules are removed by an isocyanate scavenger resin after reduction to the amine, and those with an F-tag by filtration through fluorous silica gel. R=oligosaccharide. Supporting information for this article is available on the WWW under http://www.angewandte.com 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.
Sleep and Sleep Regulation in Normal and Prion Protein-Deficient Mice (1997)

Mice are the preferred mammalian species for genetic investigations of the role of proteins. The normal function of the prion protein (PrP) is unknown, although it plays a major role in the prion diseases, including fatal familial insomnia. We investigated its role in sleep and sleep regulation by comparing baseline recordings and the effects of sleep deprivation in PrP knockout mice (129/SV) and wild-type controls (129/SV x C57BL/6), which are the mice used for most gene targeting experiments and whose behavior is not well characterized. Although no difference was evident in the amount of vigilance states, the null mice exhibited a larger degree of sleep fragmentation than the wild-type with almost double the amount of short waking episodes. As in other rodents, cortical temperature closely reflected the time course of waking. The increase of slow-wave activity (SWA; mean EEG power density in the 0.25-4.0 Hz range) at waking to nonrapid eye movement (NREM) sleep transitions was faster and reached a lower level in the null mice than in the wild-type. The contribution of the lower frequencies (0.25-5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance states, and the distinction between NREM sleep and REM sleep was most marked in the theta band. After the sleep deprivation, SWA was increased, but the changes in EEG power density and SWA were more prominent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.
Calcium alginate beads as a slow‐release system for delivering angiogenic molecules In Vivo and In Vitro (1992)

A method previously used in this laboratory for entrapment of tumor cells in alginate beads has been extended to provide a slow release delivery system for growth factors with known in vivo angiogenic activity. Protein growth factors were entrapped in alginate beads in amounts sufficient to cause incorporation of 3H-thymidine by COMMA-D cells in vitro, and in vivo neovascularization when injected subcutaneously into Balb/c mice. Entrapment of 125I-labelled growth factors showed that the amount of molecule entrapped in alginate beads may vary with the charge of the molecule. In vitro cell proliferation studies showed that entrapment in alginate beads may provide a slow-release system or a stabilizing environment for the protein. In some cases biological activity of the growth factor in solution was increased by the presence of control alginate beads. When alginate-entrapped growth factors were injected into Balb/c mice, induction of new blood vessels could be monitored qualitatively by macroscopic photography and assessed quantitatively by measuring the pooling of radiolabelled red blood cells at the experimental site. Subcutaneous injection of purified angiogenic factors not entrapped in alginate beads did not cause neovascularization. Diffusion of 125I-labelled growth factors from alginate beads in the animal showed that release in vivo may depend on the charge of the protein molecule. These results indicate that injection of purified molecules entrapped in alginate beads provides an effective localized and slow-release delivery of biologically active molecules. This delivery system may extend the time of effectiveness of biologically active molecules in vivo compared to direct injection without alginate entrapment. The method of entrapment and injection has potential for identifying active factors in tumor-induced angiogenesis and testing new compounds as modulators of neovascularization.
Structural order in conjugated oligothiophenes and its implications on opto-electronic devices (2000)

Over the last ten years, conjugated oligothiophenes have emerged as one of the largest families of organic semiconductors with potential applications in electronics devices. Thin film transistors (TFTs), photovoltaic solar cells, light-emitting diodes (LEDs), light modulators, photochromic switches and laser microcavities are some examples of devices that have been fabricated with oligothiophenes as the active materials. The key advantage of well-defined oligomers over their parent polymers is the high degree of molecular and crystalline ordering they can achieve. Polycrystalline and highly oriented thin films can be easily prepared from solution or by vacuum deposition. In many cases it has even been possible to grow single crystals and elucidate their X-ray structure. The aim of this review is to describe the structure of oligothiophene crystals and thin films and to explore its implications on the performances of various electronic devices.
ChemInform Abstract: Synthesis and Biological Activity of Certain Nicotinic Acid Derivatives. (1986)

Abstract Eine vereinfachte und reproduzierbare Synthese für das Pyridon (III) wird vorgestellt.
Interactions between acidic proteins and crystals: stereochemical requirements in biomineralization. (1985)

Acidic matrix macromolecules are intimately involved in biological crystal growth. In vitro experiments, in which crystals of calcium dicarboxylate salts were grown in the presence of aspartic acid-rich proteins, revealed a stereochemical property common to all the interacting faces. Calcite crystals are nucleated on stereochemically analogous faces when proteins are adsorbed onto a rigid substrate. The importance of this property in biomineralization is discussed.
Autonomous Vehicles: Disengagements, Accidents and Reaction Times (2016)

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems.
IMPLEMENTING REAL-TIME PARTITIONED CONVOLUTION ALGORITHMS ON CONVENTIONAL OPERATING SYSTEMS (2011)

We describe techniques for implementing real-time partitioned convolution algorithms on conventional operating systems using two different scheduling paradigms: time-distributed (cooperative) and multi-threaded (preemptive). We discuss the optimizations applied to both implementations and present measurements of their performance for a range of impulse response lengths on a recent high-end desktop machine. We find that while the time-distributed implementation is better suited for use as a plugin within a host audio application, the preemptive version was easier to implement and significantly outperforms the time-distributed version despite the overhead of frequent context switches.
Probe for Measuring Soil Specific Heat Using A Heat‐Pulse Method (1991)

Abstract Temperature rise, measured a short distance from a line heat source, can be used to determine the volumetric specific heat of soil and other materials. Volumetric specific heat is linearly related to the inverse of the temperature rise. The purpose of this note is to describe the construction and performance of a device for measuring specific heat using the line source method. The device was constructed from two hypodermic needles, 0.813 mm in diam. and 28 mm long, and spaced 6 mm apart. One needle contained a heater and the other a thermocouple. The temperature rise from heat pulses given to the heater were measured with the thermocouple. The coefficientof variation (CV) of specific heat on replicate samples was around 1%. Since water is the main variable component of the specific heat in nonswelling soil, changes in water content might be resolved to 0.01 or better in nonswelling soils.
Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats (2012)

Rats with chronic inhibition of GABA synthesis by infusion of l-allyglycine, a glutamic acid decarboxylase inhibitor, into their dorsomedial/perifornical hypothalamus are anxious and exhibit panic-like cardio-respiratory responses to treatment with intravenous (i.v.) sodium lactate (NaLac) infusions, in a manner similar to what occurs in patients with panic disorder. We previously showed that either NMDA receptor antagonists or metabotropic glutamate receptor type 2/3 receptor agonists can block such a NaLac response, suggesting that a glutamate mechanism is contributing to this panic-like state. Using this animal model of panic, we tested the efficacy of CBiPES and THIIC, which are selective group II metabotropic glutamate type 2 receptor allosteric potentiators (at 10-30 mg/kg i.p.), in preventing NaLac-induced panic-like behavioral and cardiovascular responses. The positive control was alprazolam (3mg/kg i.p.), a clinically effective anti-panic benzodiazepine. As predicted, panic-prone rats given a NaLac challenge displayed NaLac-induced panic-like cardiovascular (i.e. tachycardia and hypertensive) responses and "anxiety" (i.e. decreased social interaction time) and "flight" (i.e. increased locomotion) -associated behaviors; however, systemic injection of the panic-prone rats with CBiPES, THIIC or alprazolam prior to the NaLac dose blocked all NaLac-induced panic-like behaviors and cardiovascular responses. These data suggested that in a rat animal model, selective group II metabotropic glutamate type 2 receptor allosteric potentiators show an anti-panic efficacy similar to alprazolam.
Asymmetric titanium-catalysed Michael addition of O-benzylhydroxylamine to αβ-unsaturated carbonyl compounds: synthesis of β-amino acid precursors (1996)

A new titanium-catalysed Michael type addition of O-benzylhydroxylamine to αβ-unsaturated N-acylated 1,3-oxazolidinones giving β-amino acid precursors has been developed. The reaction is catalysed by TiX2–TADDOLate and TiCl2–BINOLate complexes and good conversions with enantiomeric excesses up to 42% were obtained with the application of 10 mol% of the catalyst. In order to determine the absolute stereochemistry of the enriched enantiomer one of the products, 3-(3-benzyloxyaminobutanoyl)-1,3-oxazolidin-2-one, was converted into methyl 3-benzoylaminobutanoate. Based on the absolute stereochemistry of the Michael type addition product the mechanism for the addition step is discussed, as well as the structure of the active intermediate.
Algorithms for sleep–wake identification using actigraphy: a comparative study and new results (2009)

The aim of this study was to investigate two new scoring algorithms employing artificial neural networks and decision trees for distinguishing sleep and wake states in infants using actigraphy and to validate and compare the performance of the proposed algorithms with known actigraphy scoring algorithms. The study employed previously recorded longitudinal physiological infant data set from the Collaborative Home Infant Monitoring Evaluation (CHIME) study conducted between 1994 and 1998 [http://dccwww.bumc.bu.edu/ChimeNisp/Main_Chime.asp; Sleep26 (1997) 553] at five clinical sites around the USA. The original CHIME data set contains recordings of 1079 infants <1 year old. In our study, we used the overnight polysomnography scored data and ankle actimeter (Alice 3) raw data for 354 infants from this data set. The participants were heterogeneous and grouped into four categories: healthy term, preterm, siblings of SIDS and infants with apparent life-threatening events (apnea of infancy). The selection of the most discriminant actigraphy features was carried out using Fisher's discriminant analysis. Approximately 80% of all the epochs were used to train the artificial neural network and decision tree models. The models were then validated on the remaining 20% of the epochs. The use of artificial neural networks and decision trees was able to capture potentially nonlinear classification characteristics, when compared to the previously reported linear combination methods and hence showed improved performance. The quality of sleep-wake scoring was further improved by including more wake epochs in the training phase and by employing rescoring rules to remove artifacts. The large size of the database (approximately 337,000 epochs for 354 patients) provided a solid basis for determining the efficacy of actigraphy in sleep scoring. The study also suggested that artificial neural networks and decision trees could be much more routinely utilized in the context of clinical sleep search.
A Soybean Transcript Map: Gene Distribution, Haplotype and Single-Nucleotide Polymorphism Analysis (2007)

The first genetic transcript map of the soybean genome was created by mapping one SNP in each of 1141 genes in one or more of three recombinant inbred line mapping populations, thus providing a picture of the distribution of genic sequences across the mapped portion of the genome. Single-nucleotide polymorphisms (SNPs) were discovered via the resequencing of sequence-tagged sites (STSs) developed from expressed sequence tag (EST) sequence. From an initial set of 9459 polymerase chain reaction primer sets designed to a diverse set of genes, 4240 STSs were amplified and sequenced in each of six diverse soybean genotypes. In the resulting 2.44 Mbp of aligned sequence, a total of 5551 SNPs were discovered, including 4712 single-base changes and 839 indels for an average nucleotide diversity of Theta= 0.000997. The analysis of the observed genetic distances between adjacent genes vs. the theoretical distribution based upon the assumption of a random distribution of genes across the 20 soybean linkage groups clearly indicated that genes were clustered. Of the 1141 genes, 291 mapped to 72 of the 112 gaps of 5-10 cM in the preexisting simple sequence repeat (SSR)-based map, while 111 genes mapped in 19 of the 26 gaps >10 cM. The addition of 1141 sequence-based genic markers to the soybean genome map will provide an important resource to soybean geneticists for quantitative trait locus discovery and map-based cloning, as well as to soybean breeders who increasingly depend upon marker-assisted selection in cultivar improvement.
Abstract A07: Plinabulin: Evidence for an immune-mediated mechanism of action (2016)

Abstract The purpose of this study was to investigate the evidence for an immune-mediated mechanism of action for plinabulin. Plinabulin, a novel compound for use in oncology, is an inhibitor of tubulin polymerization, induces direct tumor cell apoptosis (Nicholson et al, 2006), inhibits angiogenesis and activates the JNK pathway (Singh et al, 2011) and is in Phase 3 trials for NSCLC (Bazhenova, 2015). The methods for the in vitro and in vivo studies performed are described by Martin et al (2014) and Müller et al (2014). Recent data from in vitro studies demonstrate that plinabulin enhances immune responses as (1) it increases dendritic cell maturation as evidenced by elevated levels of CD40, MHCII, CD80 and CD86 and (2) the release of pro-inflammatory cytokines such as IL-1beta, IL-6 and IL12p40. These increases were similar to those observed with LPS. Paclitaxel and etoposide were inactive in these assays. In the MC-38 syngeneic colon tumor model in the C57BL/6 immunocompetent mouse, plinabulin (7.5 mg/kg, IP, BIW) significantly enhanced the therapeutic effect of combined PD-1/CTLA-4 inhibition on tumor volume, with a maximal effect occurring between days 13-20 after initiation of treatment. When tumor weight was measured at necropsy, plinabulin significantly enhanced the effect of both PD-1 inhibition and combined PD-1 + CTLA-4 inhibition. In this regard, evidence has been provided that agents which interfere with tubulin polymerization (e.g. ansamytocin-P3, dolastatin-10), but not microtubule stabilizing agents (e.g. docetaxel, paclitaxel) promote anti-tumor immunity as demonstrated by dendritic cell maturation and enhanced T-cell activation both in vitro and in vivo. In addition, the microtubule depolymerizing agents act synergistically with immune checkpoint inhibitors (Martin et al, 2014, Müller et al, 2014). These data indicate an immune mediated mechanism of action of plinabulin and provide the basis for initiating a clinical trial of plinabulin with the PD-1 mAb Nivolumab in metastatic NSCLC (Yeh et al, 2015). Citation Format: George Kenneth Lloyd, Philipp Mueller, ALfred Zippelius, Lan Huang. Plinabulin: Evidence for an immune-mediated mechanism of action. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A07.
Synapse Formation and Function Is Modulated by the Amyloid Precursor Protein (2006)

The amyloid precursor protein (APP) is critical in the pathogenesis of Alzheimer's disease. The question of its normal biological function in neurons, in which it is predominantly located at synapses, is still unclear. Using autaptic cultures of hippocampal neurons, we demonstrate that hippocampal neurons lacking APP show significantly enhanced amplitudes of evoked AMPA- and NMDA-receptor-mediated EPSCs. The size of the readily releasable synaptic vesicle pool was also increased in neurons lacking APP, whereas the release probability was not affected. In addition, the analysis of spontaneous miniature synaptic currents revealed an augmented frequency in neurons lacking APP, whereas the amplitude of miniature synaptic currents was not found to be altered. Together, these findings strongly indicate that lack of APP increases the number of functional synapses. This hypothesis is further supported by morphometric immunohistochemical analysis revealing an increase of synaptophysin-positive puncta per cultured APP knock-out neuron. In conclusion, lack of APP affects synapse formation and transmission in cultured hippocampal neurons.