gebhart/patrepeval huggingface dataset:
The Integration of Medicinal Chemistry, Drug Metabolism, and Pharmaceutical Research and Development in Drug Discovery and Development (2006)

ConclusionHistory tells us that when given a reasonably active lead compound, medicinal chemists usually are able to increase the potency of the lead structure to a useful degree. The critical challenge for developing a clinically useful therapeutic agent is to improve oral bioavailability of the compounds to a practical level. Despite a wide variety of structural modifications to an early HIV-1 protease inhibitor lead, no general solution has emerged for the poor bioavailability that is characteristic of this molecular class. However, we have developed a series of potent inhibitors with increased polarity incorporated into the inhibitor backbone that led to an increase in aqueous solubility without compromising potency. Pharmacokinetic studies in dog showed an improvement in bioavailability from less than 5% for most previous inhibitors to greater than 20% for an initial analogue. Further development of this series led to the discovery of Crixivan®, which has now gained widespread use in the treatment of AIDS.Although pharmacokinetics and molecular biochemistry have advanced greatly in recent years, it is not yet possible to predict all of the pharmacokinetic and metabolic parameters of a drug in human from animal studies or from in vitro studies. Nevertheless, under certain well-defined conditions, it may be possible to make reasonably good predictions as in the examples described in this chapter. Moreover, these examples illustrate the integration of drug metabolism in drug discovery and development.
Изучение диффузионно-транспортных свойств поликомплексных матричных систем, образованных хитозаном и эудрагитом L100 (2005)

With a view to the development of new oral controlled drug delivery systems, the formation of interpolyelectrolyte complexes (IPEC) between chitosan (CS) and Eudragit L100 (EL-100) has been studied. The structure of the IPEC is such that two maxima are observed in the swelling curves in the media with different pH values. The release of a model drug (ibuprofen) from IPEC based tablets is significantly retarded, and this delay can be controlled by changing the molecular weight of CS component in the IPEC.
Synthesis and activity of 3-(1-alkylaminoalkylidene)-2H-pyran-2,4(3H)-diones as new photosynthetic electron transport inhibitors. (1987)

A series of 3-(1-alkylaminoalkylidene)-6-methyl-2H-pyran-2, 4(3H)-diones was newly synthesized, and they were assayed as photosynthetic electron transport (PET) inhibitors because of their structural resemblance to cyanoacrylates and 2-alkylaminoalkylidene-l, 3-cyclohexanedione derivatives, which are potent PET inhibitors. Some of the compounds synthesized here showed very high PET inhibition.
Effect of defensins on interleukin-8 synthesis in airway epithelial cells (1997)

Neutrophils play an important role in inflammatory processes in the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils also release small nonenzymatic and cationic polypeptides termed defensins. The aim of the present study was to investigate whether defensins induce interleukin (IL)-8 expression in cells of the A549 lung epithelial cell line and in human primary bronchial epithelial cells (PBEC). Supernatants of defensin-treated A549 cells contained increased neutrophil chemotactic activity (16-fold) that was inhibited by antibodies against IL-8. Concurrently, within 3 and 6 h, defensins significantly increased the IL-8 levels in supernatants of both A549 cells (n = 6, P < 0.05 and P < 0.01, respectively) and PBEC (n = 4, P < 0.001 and P < 0.001, respectively). This defensin-induced increase was fully inhibited by the serine proteinase inhibitor alpha 1-proteinase inhibitor. In addition, defensins also increased IL-8 mRNA levels (12-fold); this increase was dependent on de novo mRNA synthesis and did not require protein synthesis. Furthermore, defensins did not affect IL-8 mRNA stability, indicating that the enhanced IL-8 expression was due to increased transcription. Our findings suggest that defensins, released by stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and thus may mediate the recruitment of additional neutrophils into the airways.
Reduction Method for Pulse Noises Using Statistical t-Test (1985)

An algorithm for reduction of pulse noises in a scanner (1-dimensional) data is proposed. It is assumed that there is no pulse signal in the data. The algorithm consists of two procedures, that is, noise ‘detection’ and noise ‘reduction’ procedures. The former is based on the fact that the mean value of the data including pulse noises is different from that without them. The difference (therefore the noise) is detected by the statistical t-test on the null hypothesis that the mean values of two sets of data are equal. The criterion for the detection is derived from the statistics for the t-test.Two kinds of non-linear adaptive noise reduction procedures are proposed here. They are adaptive because they are applied only if the noise is detected. In addition, one of them applies an averaging or a median filter adaptively to the property of the signal, also.The validity of the algorithm is experimentally confirmed by simulation. The application of the the algorithm to 2-dimensional data is also shown.
Mechanism of photochemical ring expansion reactions of cyclic ketones (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of photochemical ring expansion reactions of cyclic ketonesNicholas J. Turro and Douglas R. MortonCite this: J. Am. Chem. Soc. 1971, 93, 10, 2569–2571Publication Date (Print):May 1, 1971Publication History Published online1 May 2002Published inissue 1 May 1971https://pubs.acs.org/doi/10.1021/ja00739a054https://doi.org/10.1021/ja00739a054research-articleACS PublicationsRequest reuse permissionsArticle Views110Altmetric-Citations18LEARN 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 Get e-Alerts
MALNUTRITION IN THE WORLD'S CHILDREN (1969)

Protein-Calorie malnutrition coupled with infection is the greatest killer of infants and young children and the major cause of retarded child growth and development in today world. It has been estimated that by 1968 there would be 276,000,000 child victims of serious malnutrition in 29 developing countries. Its greatest toll is during the weaning period and in children below the age of 2 years. Some of these young children will die. Others, who survive severe disease, may sustain brain damage which impairs learning, limits achievement, and condemns them to the fate of their parents, thus perpetuating a cycle which interferes with national development itself. The occurrence of protein-calorie malnutrition is not limited to developing countries, particular ethnic groups, or tropical climates. This affliction is found in the United States, although less frequently and rarely in extreme degree when compared to developing countries. More accurate information about its prevalence in the United States will soon be available. The causes of protein-calorie malnutrition can be described within a variety of different conceptual frameworks: political, economic, educational, socio-cultural, agricultural, industrial, and medical-nutritional. The interrelation of the size of the world population and its food supply is so vital a factor that inadequate programs of family planning increase the likelihood of malnutrition. Programs to eliminate malnutrition must be delineated within these different frameworks, and each must be brought into appropriate collaboration with the others. Obviously, no statement of ours can cover this multiplicity of factors completely. We can speak only as pediatricians to whom any degree of malnutrition is unacceptable.
Simultane (18F) FDG PET/MRT bei Patienten mit Kopf-Hals-Tumoren (2013)

Ziele: Evaluierung des klinischen Einsatzes der neuen Methode der simultanen (18F)FDG PET/MRT bei Patienten mit Kopf-Hals Tumoren. Methode: 15 konsekutive Patienten mit histologisch gesicherten Tumoren der Kopf-Hals-Region wurden direkt im Anschluss an eine (18F) FDG PET-CT mit der simultanen (18F) FDG PET/MRT (Siemens MMR Biograph) untersucht. Das Sequenzprotokoll bestand aus einer STIR-Sequenz, nativen T1-gewichteten Sequenzen in coronaler und transversaler Schichtführung, nativen T2 gewichteten Sequenzen transversal, T1-gewichteten Sequenzen nach Kontrastmittel mit Fettsättigung transversal und coronal sowie einer diffusionsgewichteten Sequenz. Die simultane Akquisition der PET-Daten erfolgte mit LSO basierten AP-Dioden und einem FoV von 25,8 cm. Ergebnis: Alle Bilddatensätze waren von diagnostischer Qualität. Die simultane Akquisition der PET-Daten war in allen untersuchten Patienten störungsfrei möglich und zeigte eine sehr hohe Übereinstimmung mit den PET-Daten der vorher durchgeführten PET/CT. Die Nachverarbeitung inklusive Fusionierung erlaubte eine exakte anatomische Korrelation eines erhöhten Glukosemetabolismus. Schlussfolgerung: Die neue Methode der simultanen (18F) FDG PET/MRT von Kopf/Hals Tumoren eignet sich für den klinischen Routinebetrieb und erlaubt eine detaillierte anatomische Einordnung sowie Abgrenzung von Primärtumoren und Lymphknoten mit pathologischem Glukosemetabolismus.
Stable Transduction of the Interleukin-2 Gene Into Human Natural Killer Cell Lines and Their Phenotypic and Functional Characterization In Vitro and In Vivo (1998)

A variety of strategies have been attempted in the past to stably transduce natural killer (NK) cells with cytokine or other cellular genes. Here, we demonstrate the successful delivery of the interleukin-2 (IL-2) gene into two human NK cell lines, IL-2–dependent NK-92 and IL-2–independent YT, by retroviral transduction. An MuLV-based retroviral vector expressing human IL-2 andneor markers from a polycistronic message was constructed and transduced into a CRIP packaging cell line. By coincubation of NK cells with monolayers of CRIP cells or by using retrovirus-containing supernatants in a flow-through method, 10% to 20% of NK cells were stably transduced. Upon selection in the presence of increasing G418 concentrations, transduced NK cells were able to proliferate independently of IL-2 for more than 5 months and to secrete up to 5.5 ng/106 cells/24 h of IL-2. IL-2 gene-transduced NK-92 cells had an in vitro cytotoxicity against tumor targets that was significantly higher than that of parental cells and secreted interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) in addition to IL-2. Moreover, the in vivo antitumor activity of IL-2 gene-transduced NK-92 cells against established 3-day liver metastases in mice was greater than that of parental nontransduced NK cells. Stable expression of the IL-2 transgene in NK cells improved their therapeutic potential in tumor-bearing hosts. Thus, transduced NK cells secreted sufficient quantities of bioactive IL-2 to proliferate in vitro and mediated the antitumor effects both in vitro and in vivo in the absence of exogenous IL-2. These results suggest that genetic modification of NK cells ex vivo could be useful for clinical cancer therapy in the future.
The Fluid Mechanics of Capsule Pipelines : 1st Report, Analysis of the Required Pressure Drop for Hydraulic and Pneumatic Capsules (1986)

This paper presents a study on the flow characteristics of capsule transportation. Especially, a method is presented for predicting the pressure drop required to move cylindrical solid capsules steadily and to suspend them freely in pipeline. For this prediction, an analytical method based on a study of multi-phase mixtures is proposed and it is confirmed that the present method is very useful for both hydraulic and pneumatic capsules. During the experimental and theoretical work, we can derive a general formula of the required pressure drop which has an inherent value for each of various conditions of capsule pipelining. In this paper, a detailed comparison of capsule transport with hydraulic transport of solids is also made.
Computer Logic Testing by Simulation (1962)

With the advent of high-speed computers having large memory capacities, it has become possible to automate one of the more difficult and time-consuming areas of computer developmental work; namely, that of checking the logical design. This paper describes one such method which utilizes an IBM 704 to simulate the logical equivalent of a specific computer under development by Nortronics Division of Northrop Corporation. Such logic testing before fabrication and checkout of the first computer eliminates much of the expensive checkout time usually required. The method employed by this simulation technique can readily be adapted to other types of digital equipment.
Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression<i>in vitro</i> (1996)

A marked suppression of immune function has long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. As a hallmark of measles virus (MV)-induced immunosuppression, peripheral blood lymphocytes (PBLs) isolated from patients exhibit a significantly reduced capacity to proliferate in response to mitogens, allogens, or recall antigens. In an in vitro system we show that proliferation of naive PBLs [responder cells (RCs)] in response to a variety of stimuli was significantly impaired after cocultivation with MV-infected, UV-irradiated autologous PBLs [presenter cells (PCs)]. We further observed that a 50% reduction in proliferation of RCs could still be observed when the ratio of PC to RC was 1:100. The effect was completely abolished after physical separation of the two populations, which suggests that soluble factors were not involved. Proliferative inhibition of the RCs was observed after short cocultivation with MV-infected cells, which indicates that surface contact between one or more viral proteins and the RC population was required. We identified that the complex of both MV glycoproteins, F and H, is critically involved in triggering MV-induced suppression of mitogen-dependent proliferation, since the effect was not observed ( i ) using a recombinant MV in which F and H were replaced with vesicular stomatitis virus G or ( ii ) when either of these proteins was expressed alone. Coexpression of F and H, however, lead to a significant proliferative inhibition in the RC population. Our data indicate that a small number of MV-infected PBLs can induce a general nonresponsiveness in uninfected PBLs by surface contact, which may, in turn, account for the general suppression of immune responses observed in patients with acute measles.
Degradation of 3,4‐Dichloro‐ and 3,4‐Difluoroaniline by<i>Pseudomonas fluorescens</i>26‐K (2003)

3,4-Dichloro- and 3,4-difluoroanilines were degraded by Pseudomonas fluorescens 26-K under aerobic conditions. In the presence of glucose strain degraded 170 mg/L of 3,4-dichloroaniline (3,4-DCA) during 2-3 days. Increasing of toxicant concentration up to 250 mg/L led to degradation of 3,4-DCA during 4 days and its intermediates during 5-7 days. Without cosubstrate and nitrogen source degradation of 3,4-DCA took place too, but more slowly--about 40% of toxicant at initial concentration 75 mg/L was degraded during 15 days. 3,4-Difluoroaniline (3,4-DFA) (initial concentration 170 mg/L) was degraded by Pseudomonas fluorescens 26-K during 5-7 days. The strain was able to completely degrade up to 90 mg/L of 3,4-DFA, without addition of cosubstrate and nitrogen during 15 days. Degradation of fluorinated aniline was accompanied by intensive defluorination. Activity of catechol 2,3-dioxygenase (C2,3DO) (0.230 micromol/min/mg of protein) was found in the culture liquid of the strain, grown with 3,4-DCA and glucose. This fact, as well as, the presence of 3-chloro-4-hydroxyaniline as a metabolite suggested that 3,4-DCA degradation pathway includes dehalogenation and hydroxylation of aromatic ring followed by its subsequent cleaving by C2,3DO. On the contrary, activity of catechol 1,2-dioxygenase (C1,2DO) (0.08 micromol/min/mg of protein) was found in the cell-free extract of biomass grown on 3,4-DFA. 3-Fluoro-4-hydroxyaniline as intermediate was found in this cell-free extract.
Molecular Complexes of Pyromellitic Dianhydride<sup>1</sup> (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Complexes of Pyromellitic Dianhydride1L. L. Ferstandig, W. G. Toland, and C. D. HeatonCite this: J. Am. Chem. Soc. 1961, 83, 5, 1151–1155Publication Date (Print):March 1, 1961Publication History Published online1 May 2002Published inissue 1 March 1961https://pubs.acs.org/doi/10.1021/ja01466a035https://doi.org/10.1021/ja01466a035research-articleACS PublicationsRequest reuse permissionsArticle Views137Altmetric-Citations21LEARN 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 Get e-Alerts
Importance relative du fer et de l'aluminimum dans les sols sableux des landes de Gascogne (1965)

National audience
Controllable Grid Interface for Testing Ancillary Service Controls and Fault Performance of Utility-Scale Wind Power Generation: Preprint (2017)

The rapid expansion of wind power has led many transmission system operators to demand modern wind power plants to comply with strict interconnection requirements. Such requirements involve various aspects of wind power plant operation, including fault ride-through and power quality performance as well as the provision of ancillary services to enhance grid reliability. During recent years, the National Renewable Energy Laboratory (NREL) of the U.S. Department of Energy has developed a new, groundbreaking testing apparatus and methodology to test and demonstrate many existing and future advanced controls for wind generation (and other renewable generation technologies) on the multimegawatt scale and medium-voltage levels. This paper describes the capabilities and control features of NREL's 7-MVA power electronic grid simulator (also called a controllable grid interface, or CGI) that enables testing many active and reactive power control features of modern wind turbine generators -- including inertial response, primary and secondary frequency responses, and voltage regulation -- under a controlled, medium-voltage grid environment. In particular, this paper focuses on the specifics of testing the balanced and unbalanced fault ride-through characteristics of wind turbine generators under simulated strong and weak medium-voltage grid conditions. In addition, this paper provides insights on the power hardware-in-the-loop feature implemented in the CGI to emulate (in real time) the conditions that might exist in various types of electric power systems under normal operations and/or contingency scenarios. Using actual test examples and simulation results, this paper describes the value of CGI as an ultimate modeling validation tool for all types of 'grid-friendly' controls by wind generation.
Beam Hardening Correction for Middle-Energy (2006)

In this paper, a new beam hardening correction (BHC) method for middle-energy industrial computerized tomog- raphy (CT) is presented. Our method is derived from linearization and is straightforward without iteration involved. The lineariza- tion is commonly used as a preprocessing method in BHC. Conventionally, only one-material objects can be conveniently corrected by linearization. In industrial CT, two-material objects, especially cylinders with high-Z material outside and low-Z mate- rial inside are frequently encountered. Our approach focuses on this kind of objects. The new method works well as long as the two-material object meets the conditions that the thickness of the outer material (usually wall) is thick enough and the second-order item of the Taylor expansion of the linearization is relatively small. We pointed out and proved that there is an approximately constant scaling factor difference between our linearization step and an ideal correction based on prior knowledge of objects. The scaling factor magnifies the attenuation coefficient of the inner material after reconstruction. Therefore, a weighting function is introduced into our algorithm as a restoration. To sum up, there are three steps in our method: 1) correct raw projections by the mapping function of the outer material; 2) reconstruct the cross-section image from the modified projections; 3) scale the image by a weighting function. With this method, the beam hardening arti- facts are greatly reduced and the overall attenuation coefficients are accurately obtained. We also presented a compensation step to remove the countercupping artifacts in case that the conditions are not fully met. Our method is well verified in both numerical simulations and practical experiments on a 450-KeV CT system. Index Terms—Beam hardening correction, cupping artifacts, in- dustrial computerized tomography, linearization.