gebhart/patrepeval huggingface dataset:
Compendium of Organic Synthetic Methods (1974)

Preface vii Introduction ix Index, Monofunctional Compounds xvii Index, Difunctional Compounds xix Abbreviations xxi About the Author xxv 1 Preparation of Alkynes 1 2 Preparation of Acid Derivatives 13 3 Preparation of Acohols 21 4 Preparation of Aldehydes 75 5 Preparation of Alkyls, Methylenes, and Arkyls 89 6 Preparation of Amides 225 7 Preparation of Amines 259 8 Preparation of Esters 303 9 Preparation of Ethers, Epoxides, and Thioethers 325 10 Preparation of Halides and Sulfonates 351 11 Preparation of Hydrides 365 12 Preparation of Ketones 371 13 Preparation of Nitriles 399 14 Preparation of Alkenes 409 15 Preparation of Oxides 433 16 Preparation of Difunctional Compounds 445 Author Index 629
A New Facile Route for the Preparation of Single-Source Precursors for Bulk, Thin-Film, and Nanocrystallite I−III−VI Semiconductors (2003)

We report a new simplified synthetic procedure for commercial manufacture of ternary single-source precursors (SSPs). This new synthetic process has been successfully implemented to fabricate known SSPs on bulk scale and the first liquid SSPs to the semiconductors CuInSe(2) and AgIn(x)S(y). Single crystal X-ray determination reveals the first unsolvated ternary AgInS SSP. SSPs prepared via this new route have successfully been used in a spray assisted chemical vapor deposition (CVD) process to deposit polycrystalline thin films, and for preparing ternary nanocrystallites.
Deep Brain Stimulation of the Center Median-Parafascicular Complex of the Thalamus Has Efficient Anti-Parkinsonian Action Associated with Widespread Cellular Responses in the Basal Ganglia Network in a Rat Model of Parkinson's Disease (2010)

The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.
Heat and moisture exchangers with bacterial filters: a laboratory evaluation (1992)

Six commercially available heat-moisture exchanger (HME) humidifiers with built-in bacterial filtration were evaluated by laboratory tests. Physical characteristics, humidification efficiency, resistance to flow and filtration capability were investigated. The resistance was comparable for all units and did not change notably with exposure to humidity. Deadspace values were in the range 55-92 ml and weight values between 34-55 g. The humidification efficiency of two units (Group 1) was clearly less (54%-63% at 11 tidal volume), than for the other four devices (Group 2) (77%-82%). This corresponds to an average humidification output of 22.0 g/m3 for Group 1 as compared to an output of 29.9 g/m3 for Group 2. The average filtration capability of Group 1 was 99.9998%, which is somewhat higher than the 99.9973% obtained for Group 2. There are significant differences between the humidification efficiency and deadspace of different units, with the Pall Conserve device having the least satisfactory performance. All units exhibit good filtering properties, with the Pall Conserve device performing best in this respect.
Images of a set via two channels and their role in multi-user communication (1977)

A technique is presented to determine the region of achievable rates for some source and channel networks. This technique is applied to the solution of a source:network problem that seems to be the simplest illustration of a new typical difficulty in coding for source networks: namely, when the same encoding of a source is required to meet the conflicting demands of 1) supplying side-information to the decoder of another source, and 2) providing direct-information to its own decoder in company with other side-information.
知识、道德和希望:乔姆斯基的社会思想 (1992)

概括说来,乔姆斯基的社会政治思想包括以下四个主要观点:1)人生来是道德性的和渴望自由的,2)一种自由社会主义的理想是符合人的本质的,3)人类的自由渴望和道德本质有助于说明现实社会制度的某些重要特点,如使用欺骗或暴力手段维护非正义状况等,4)并使我们有理由希望社会秩序关系在道德上会有所进步。人类似乎生来就是道德性的,惯于使用道德术
Discovery of ML314, a Brain Penetrant Nonpeptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor (2013)

The neurotensin 1 receptor (NTR1) is an important therapeutic target for a range of disease states including addiction. A high throughput screening campaign, followed by medicinal chemistry optimization, led to the discovery of a non-peptidic β-arrestin biased agonist for NTR1. The lead compound, 2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)- piperazin-1-yl)quinazoline, <b>32</b> (<b>ML314</b>), exhibits full agonist behavior against NTR1 (EC<sub>50</sub> = 2.0 μM) in the primary assay and selectivity against NTR2. The effect of <b>32</b> is blocked by the NTR1 antagonist SR142948A in a dose dependent manner. Unlike peptide based NTR1 agonists, compound <b>32</b> has no significant response in a Ca<sup>2+</sup> mobilization assay and is thus a biased agonist that activates the β-arrestin pathway rather than the traditional G <sub><i>q</i></sub> coupled pathway. This bias has distinct biochemical and functional consequences that may lead to physiological advantages. Compound <b>32</b> displays good brain penetration in rodents, and studies examining its <i>in vivo</i> properties are underway.
Self-assembly and application of diphenylalanine-based nanostructures (2010)

Micro- and nanostructures fabricated from biological building blocks have attracted tremendous attention owing to their potential for application in biology and in nanotechnology. Many biomolecules, including peptides and proteins, can interact and self-assemble into highly ordered supramolecular architectures with functionality. By imitating the processes where biological peptides or proteins are assembled in nature, one can delicately design and synthesize various peptide building blocks composed of several to dozens of amino acids for the creation of biomimetic or bioinspired nanostructured materials. This tutorial review aims to introduce a new kind of peptide building block, the diphenylalanine motif, extracted with inspiration of a pathogenic process towards molecular self-assembly. We highlight recent and current advances in fabrication and application of diphenylalanine-based peptide nanomaterials. We also highlight the preparation of such peptide-based nanostructures as nanotubes, spherical vesicles, nanofibrils, nanowires and hybrids through self-assembly, the improvement of their properties and the extension of their applications.
Introduction and General Overview of Cyclodextrin Chemistry (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntroduction and General Overview of Cyclodextrin ChemistryJózsef SzejtliView Author Information CYCLOLAB, Cyclodextrin Research and Development Laboratory, Budapest, Hungary Cite this: Chem. Rev. 1998, 98, 5, 1743–1754Publication Date (Web):June 9, 1998Publication History Received17 October 1997Revised28 January 1998Published online9 June 1998Published inissue 30 July 1998https://pubs.acs.org/doi/10.1021/cr970022chttps://doi.org/10.1021/cr970022cresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views27203Altmetric-Citations4176LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cadmium sulfide,Macrocyclic compounds,Molecules,Oligosaccharides Get e-Alerts
Infectious Complications of Dental and Periodontal Diseases in the Elderly Population (2002)

Retention of teeth into advanced age makes caries and periodontitis lifelong concerns. Dental caries occurs when acidic metabolites of oral streptococci dissolve enamel and dentin. Dissolution progresses to cavitation and, if untreated, to bacterial invasion of dental pulp, whereby oral bacteria access the bloodstream. Oral organisms have been linked to infections of the endocardium, meninges, mediastinum, vertebrae, hepatobiliary system, and prosthetic joints. Periodontitis is a pathogen-specific, lytic inflammatory reaction to dental plaque that degrades the tooth attachment. Periodontal disease is more severe and less readily controlled in people with diabetes; impaired glycemic control may exacerbate host response. Aspiration of oropharyngeal (including periodontal) pathogens is the dominant cause of nursing home-acquired pneumonia; factors reflecting poor oral health strongly correlate with increased risk of developing aspiration pneumonia. Bloodborne periodontopathic organisms may play a role in atherosclerosis. Daily oral hygiene practice and receipt of regular dental care are cost-effective means for minimizing morbidity of oral infections and their nonoral sequelae.
Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways (2011)

A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a therapeutic target in human disease. We carried out a high-throughput screen to identify inhibitors of p97 ATPase activity. Dual-reporter cell lines that simultaneously express p97-dependent and p97-independent proteasome substrates were used to stratify inhibitors that emerged from the screen. N2,N4-dibenzylquinazoline-2,4-diamine (DBeQ) was identified as a selective, potent, reversible, and ATP-competitive p97 inhibitor. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7. Our results provide a rationale for targeting p97 in cancer therapy.
Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. (1992)

Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training. Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF, including abnormalities in autonomic balance.
Induction of proteins in response to low temperature in Escherichia coli (1987)

When the growth temperature of an exponential culture of Escherichia coli is abruptly decreased from 37 to 10 degrees C, growth stops for several hours before a new rate of growth is established. During this growth lag the number of proteins synthesized is dramatically reduced, and at one point only about two dozen proteins are made; 13 of these are made at differential rates that are 3 to 300 times increased over the rates at 37 degrees C. The protein with the highest rate of synthesis during the lag is not detectably made at 37 degrees C. The identities of several of these cold shock proteins correlate with previous observations that indicate a block in translation initiation at low temperatures.
Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds (2010)

Biomatrix scaffolds can be used for biological and pharmaceutical studies of lineage-restricted stem cells, for maintenance of mature cells, and, in the future, for implantable, vascularized engineered tissues or organs.
Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain (2007)

The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.
Ultrasensitive Detection of Botulinum Neurotoxins and Anthrax Lethal Factor in Biological Samples by ALISSA (2011)

Both botulinum neurotoxins (BoNTs) and anthrax lethal factor, a component of anthrax toxin, exhibit zinc metalloprotease activity. The assay detailed here is capable of quantitatively detecting these proteins by measuring their enzymatic functions with high sensitivity. The detection method encompasses two steps: (1) specific target capture and enrichment and (2) cleavage of a fluorogenic substrate by the immobilized active target, the extent of which is quantitatively determined by differential fluorometry. Because a critical ingredient for the target enrichment is an immobilization matrix made out of hundreds of thousands of microscopic, antibody-coated beads, we have termed this detection method an assay with a large immuno-sorbent surface area (ALISSA). The binding and reaction surface area in the ALISSA is approximately 30-fold larger than in most microtiter plate-based enzyme-linked immunosorbent assays (ELISAs). ALISSA reaches atto (10(-18)) to femto (10(-15)) molar sensitivities for the detection of BoNT serotypes A and E and anthrax lethal factor. In addition, ALISSA provides high specificity in complex biological matrices, such as serum and liquid foods, which may contain various other proteases and hydrolytic enzymes. This methodology can potentially be expanded to many other enzyme targets by selecting appropriate fluorogenic substrates and capture antibodies. Important requirements are that the enzyme remains active after being immobilized by the capture antibody and that the substrate is specifically converted by the immobilized enzyme target at a fast conversion rate.A detailed protocol to conduct ALISSA for the detection and quantification of BoNT serotypes A and E and anthrax lethal factor is described.
Freeze-Drying of Proteins in Glass Solids Formed by Basic Amino Acids and Dicarboxylic Acids (2009)

The purpose of this study was to produce and characterize glass-state amorphous solids containing amino acids and organic acids that protect co-lyophilized proteins. Thermal analysis of frozen solutions containing a basic amino acid (e.g., L-arginine, L-lysine, L-histidine) and a hydroxy di- or tricarboxylic acid (e.g., citric acid, L-tartaric acid, DL-malic acid) showed glass transition of maximally freeze-concentrated solute at temperatures (T'g) significantly higher than those of the individual solute solutions. Mixing of the amino acid with some dicarboxylic acids (e.g., oxalic acid) also suggested an upward shift of the transition temperature. Contrarily, combinations of the amino acid with monocarboxylic acids (e.g., acetic acid) had T'gs between those of the individual solute solutions. Co-lyophilization of the basic amino acids and citric acid or L-tartaric acid resulted in amorphous solids that have glass transition temperatures (Tg) higher than the individual components. Mid- and near-infrared analysis indicated altered environment around the functional groups of the consisting molecules. Some of the glass-state excipient combinations protected an enzyme (lactate dehydrogenase, LDH) from inactivation during freeze-drying. The glass-state excipient combinations formed by hydrogen-bonding and electrostatic interaction network would be potent alternative to stabilize therapeutic proteins in freeze-dried formulations.
Developmental Silencing of Human ζ-Globin Gene Expression Is Mediated by the Transcriptional Repressor RREB1 (2010)

The mammalian embryonic zeta-globin genes, including that of humans, are expressed at the early embryonic stage and then switched off during erythroid development. This autonomous silencing of the zeta-globin gene transcription is probably regulated by the cooperative work of various protein-DNA and protein-protein complexes formed at the zeta-globin promoter and its upstream enhancer (HS-40). We present data here indicating that a protein-binding motif, ZF2, contributes to the repression of the HS-40-regulated human zeta-promoter activity in erythroid cell lines and in transgenic mice. Combined site-directed mutagenesis and EMSA suggest that repression of the human zeta-globin promoter is mediated through binding of the zinc finger factor RREB1 to ZF2. This model is further supported by the observation that human zeta-globin gene transcription is elevated in the human erythroid K562 cell line or the primary erythroid culture upon RNA interference (RNAi)(2) knockdown of RREB1 expression. These data together suggest that RREB1 is a putative repressor for the silencing of the mammalian zeta-globin genes during erythroid development. Because zeta-globin is a powerful inhibitor of HbS polymerization, our experiments have provided a foundation for therapeutic up-regulation of zeta-globin gene expression in patients with severe hemoglobinopathies.
Novel approaches to retinal drug delivery (2007)

Research into treatment modalities affecting vision is rapidly progressing due to the high incidence of diseases such as diabetic macular edema, proliferative vitreoretinopathy, wet and dry age-related macular degeneration and cytomegalovirus retinitis. The unique anatomy and physiology of eye offers many challenges to developing effective retinal drug delivery systems. Historically, drugs have been administered to the eye as liquid drops instilled in the cul-de-sac. However retinal drug delivery is a challenging area. The transport of molecules between the vitreous/retina and systemic circulation is restricted by the blood-retinal barrier, which is made up of retinal pigment epithelium and endothelial cells of the retinal blood vessels. An increase in the understanding of drug absorption mechanisms into the retina from local and systemic administration has led to the development of various drug delivery systems, such as biodegradable and non-biodegradable implants, microspheres, nanoparticles and liposomes, gels and transporter-targeted prodrugs. Such diversity in approaches is an indication that there is still a need for an optimized noninvasive or minimally invasive drug delivery system to the eye. A number of large molecular weight compounds (i.e., oligonucleotides, RNA aptamers, peptides and monoclonal antibodies) have been and continue to be introduced as new therapeutic entities. However, for high molecular weight polar compounds the mechanism of epithelial transport is primarily through the tight junctions in the retinal pigment epithelium, as these agents undergo limited transcellular diffusion. Delivery and administration of these new drugs in a safe and effective manner is still a major challenge facing pharmaceutical scientists. In this review article, the authors discuss various drug delivery strategies, devices and challenges associated with drug delivery to the retina.
n–3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored (2004)

Long chain n-3 PUFAs (polyunsaturated fatty acids) are found in fatty fish and in fish oils. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, fatty fish and long-chain n-3 PUFAs reduces the risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 PUFAs in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality, with an especially potent effect on sudden death. Long-chain n-3 PUFAs have been shown to decrease blood triacylglycerol (triglyceride) concentrations, to decrease production of chemoattractants, growth factors, adhesion molecules, inflammatory eicosanoids and inflammatory cytokines, to lower blood pressure, to increase nitric oxide production, endothelial relaxation and vascular compliance, to decrease thrombosis and cardiac arrhythmias and to increase heart rate variability. These mechanisms most likely explain the primary and secondary cardiovascular protection afforded by long-chain n-3 PUFA consumption. A recent study suggests that long-chain n-3 PUFAs might also act to stabilize advanced atherosclerotic plaques, perhaps through their anti-inflammatory effects. As a result of the robust evidence in their favour, a number of recommendations to increase intake of long-chain n-3 PUFAs have been made.
Carbon Nanotube Arrays Encapsulated into Freely Suspended Flexible Films (2005)

We demonstrated the fabrication of a carbon nanotube (CNT) array with microscopic spacing encapsulated into freely suspended flexible films with a nanoscale thickness. This result implies that freely suspended carbon nanotube arrays embedded in nanoscale polymer films can be assembled providing access from both sides and helping to tune micromechanical elastic properties.