bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro
,
In Vivo
, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions
Authors: Flanagan S. , Bartizal K. , Minassian S. L. , Fang E. , Prokocimer P. 
Published: April 2013

ABSTRACT

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.
In vitro
, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC
50
) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR
30
) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR
30
/tedizolid phosphate TYR
30
) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B
in vitro
. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at
www.clinicaltrials.gov
as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).
High-Throughput Analysis of Antimalarial Susceptibility Data by the WorldWide Antimalarial Resistance Network (WWARN)
In Vitro
Analysis and Reporting Tool
Authors: Woodrow Charles J. , Dahlström Sabina , Cooksey Richard , Flegg Jennifer A. , Le Nagard Hervé , Mentré France , Murillo Claribel , Ménard Didier , Nosten François , Sriprawat Kanlaya , Musset Lise , Quashie Neils B. , Lim Pharath , Fairhurst Rick M. , Nsobya Sam L. , Sinou Veronique , Noedl Harald , Pradines Bruno , Johnson Jacob D. , Guerin Philippe J. , Sibley Carol H. , Le Bras Jacques 
Published: April 2013

ABSTRACT

Assessment of
in vitro
susceptibility is a fundamental component of antimalarial surveillance studies, but wide variations in the measurement of parasite growth and the calculation of inhibitory constants make comparisons of data from different laboratories difficult. Here we describe a Web-based, high-throughput
in vitro
analysis and reporting tool (IVART) generating inhibitory constants for large data sets. Fourteen primary data sets examining laboratory-determined susceptibility to artemisinin derivatives and artemisinin combination therapy partner drugs were collated from 11 laboratories. Drug concentrations associated with half-maximal inhibition of growth (IC
50
s) were determined by a modified sigmoid
E
max
model-fitting algorithm, allowing standardized analysis of 7,350 concentration-inhibition assays involving 1,592 isolates. Examination of concentration-inhibition data revealed evidence of apparent paradoxical growth at high concentrations of nonartemisinin drugs, supporting amendment of the method for calculating the maximal drug effect in each assay. Criteria for defining more-reliable IC
50
s based on estimated confidence intervals and growth ratios improved correlation coefficients for the drug pairs mefloquine-quinine and chloroquine-desethylamodiaquine in 9 of 11 and 8 of 8 data sets, respectively. Further analysis showed that maximal drug inhibition was higher for artemisinins than for other drugs, particularly in ELISA (enzyme-linked immunosorbent assay)-based assays, a finding consistent with the earlier onset of action of these drugs in the parasite life cycle. This is the first high-throughput analytical approach to apply consistent constraints and reliability criteria to large, diverse antimalarial susceptibility data sets. The data also illustrate the distinct biological properties of artemisinins and underline the need to apply more sensitive approaches to assessing
in vitro
susceptibility to these drugs.
Ex Vivo
Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger
Authors: Issaka Mariama , Salissou Adamou , Arzika Ibrahim , Guillebaud Julia , Maazou Abani , Specht Sabine , Zamanka Halima , Fandeur Thierry 
Published: April 2013

ABSTRACT

Little is known about resistance of
Plasmodium falciparum
to antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease in
P. falciparum
susceptibilities to these antimalarials.
Aqueous Inorganic Salt Solutions at High Temperatures
Authors: Keevil N. B. 
Published: April 2013

ContentsPageTable 151. Composition and vapor pressure of saturated solutions2162. Properties of 1 gram of saturated solution (KCl + H2O)2203. Freezing-point curves for three-phase silicate-water systems2214. Solubility of water in silicate melts at high temperatures and pressures (two-phase equilibrium)222
This section presents the limited amount of information, some of it still unpublished, regarding solubility and vapor pressure in aqueous solutions at temperatures above 100°C. No attempt is made to cover the wealth of data which exists for temperatures below 100°C., and which is exhaustively tabulated in other places (Int. Crit. Tables, Vol. IV; Handbook of Chemistry and Physics, Chemical Rubber Publishing Co.).
Solubility determinations from the cryohydric point to the triple point of the salt have been carried out for sodium and potassium nitrates (m.p. 308°C. and 334°C., resp.) and for boric oxide (m.p. 450°C.), but for higher-melting salts only parts of certain binary systems with water as one component have been investigated. The experimental methods, in order of decreasing accuracy, are:
(1) Heating water and excess salt in a closed thermostated system, with some device for sampling a portion of the saturated solution for analysis [2, 3];
(2) Heating known weights of salt and water in a closed glass system, and observing the temperature at which the last portion of salt passes into solution [4, 5];
(3) For glass-forming solutes, quenching charges of glass after treatment with excess water in a closed bomb [6, 10];
(4) Observing the discontinuity of . . .
Elasticity (Except Compressibility)
Authors: Birch Francis 
Published: April 2013

ContentsPageTable 51. Elasticity of single crystals661.1. Extreme values of Young’s modulus and of rigidity in certain metal single crystals691.2. Effect of temperature on the elasticity of quartz702. Elasticity of polycrystalline metals at ordinary pressure and temperature; effect of pressure on rigidity713. Effect of temperature on the elasticity of polycrystalline metals724. Elastic constants of rocks at ordinary pressure and temperature735. Effect of stress on Young’s modulus of rocks786. Effect of stress on Young’s modulus and on σ in granite.797. Effect of moisture upon velocity in Amherst sandstone798. Elastic parameters of certain rocks at 4,000 kg.cm−2 and 30°C809. Rigidity and velocity of shear waves, in rocks, as function of pressure8110. Effect of temperature on the velocity of shear waves in rocks at high pressure8311. Elasticity of glass and glassy rocks; effect of pressure upon rigidity8412. Effect of temperature on elasticity of glasses8513. Elasticity of rocks from seismic determinations86
(For compressibility, see Section 4.)
(For velocities determined in the field, see Section 7.)
For sufficiently small stresses, two elastic “constants” are necessary and sufficient to determine the elastic behavior of a homogeneous, isotropic, elastic solid. Various pairs of constants are in common use; those usually measured in the laboratory are Young’s modulus E, the modulus of rigidity or the shear modulus G, Poisson’s ratio σ, and the compressibility β or its. . . .
Interacting with social networks of intelligent things and people in the world of gastronomy
Authors: Console Luca , Antonelli Fabrizio , Biamino Giulia , Carmagnola Francesca , Cena Federica , Chiabrando Elisa , Cuciti Vincenzo , Demichelis Matteo , Fassio Franco , Franceschi Fabrizio , Furnari Roberto , Gena Cristina , Geymonat Marina , Grimaldi Piercarlo , Grillo Pierluige , Likavec Silvia , Lombardi Ilaria , Mana Dario , Marcengo Alessandro , Mioli Michele , Mirabelli Mario , Perrero Monica , Picardi Claudia , Protti Federica , Rapp Amon , Simeoni Rossana , Dupré Daniele Theseider , Torre Ilaria , Toso Andrea , Torta Fabio , Vernero Fabiana 
Published: April 2013

This article introduces a framework for creating rich augmented environments based on a social web of intelligent things and people. We target outdoor environments, aiming to transform a region into a smart environment that can share its cultural heritage with people, promoting itself and its special qualities. Using the applications developed in the framework, people can interact with things, listen to the stories that these things tell them, and make their own contributions. The things are intelligent in the sense that they aggregate information provided by users and behave in a socially active way. They can autonomously establish social relationships on the basis of their properties and their interaction with users. Hence when a user gets in touch with a thing, she is also introduced to its social network consisting of other things and of users; she can navigate this network to discover and explore the world around the thing itself. Thus the system supports serendipitous navigation in a network of things and people that evolves according to the behavior of users. An innovative interaction model was defined that allows users to interact with objects in a natural, playful way using smartphones without the need for a specially created infrastructure.
The framework was instantiated into a suite of applications called WantEat, in which objects from the domain of tourism and gastronomy (such as cheese wheels or bottles of wine) are taken as testimonials of the cultural roots of a region. WantEat includes an application that allows the definition and registration of things, a mobile application that allows users to interact with things, and an application that supports stakeholders in getting feedback about the things that they have registered in the system. WantEat was developed and tested in a real-world context which involved a region and gastronomy-related items from it (such as products, shops, restaurants, and recipes), through an early evaluation with stakeholders and a final evaluation with hundreds of users.
Nrf2 Prevents Initiation but Accelerates Progression through the Kras Signaling Pathway during Lung Carcinogenesis
Authors: Satoh Hironori , Moriguchi Takashi , Takai Jun , Ebina Masahito , Yamamoto Masayuki 
Published: April 2013

Abstract
Nrf2 (Nfe2l2) governs cellular defenses against oxidative and electrophilic stresses and protects against chemical carcinogenesis. However, many cancers have been found to accumulate NRF2 protein, raising questions of precisely how Nrf2 contributes to carcinogenesis. In this report, we explored such questions in an established urethane-induced multistep model of lung carcinogenesis. Consistent with earlier observations, Nrf2-deficient (Nrf2−/−) mice exhibited a relative increase in tumor foci by 8 weeks after urethane administration. However, after 16 weeks, we observed a relative reduction in the number of tumors with more malignant characteristics in Nrf2−/− mice. Furthermore, all Nrf2+/+ tumors harbored activated mutations in Kras, whereas Nrf2−/− tumors were rarely associated with similar Kras mutations. Overall, our results established that Nrf2 has two roles during carcinogenesis, one of which is preventive during tumor initiation and the second that promotes malignant progression. These findings establish Nrf2 inhibitors as rational tools to prevent malignant progression in lung cancer, whereas Nrf2 activators are more suited for lung cancer prevention. Cancer Res; 73(13); 4158–68. ©2013 AACR.
“We Are the Ones We Have Been Waiting For”
Authors: Motta Sara C. 
Published: April 2013

An autonomist Marxist feminist analysis of the narratives of three women participants in Venezuela’s Bolivarian Revolution—women linked by their participation in the urban land committees of La Vega, a Caracas shantytown—stresses the fundamental significance of women’s struggles in this revolutionary process. By focusing on the realities of women in movement we can begin to grasp the complexity of the feminized political subjectivities being formed and the contradictions and tensions in this process. This reading seeks to rewrite, in solidarity with women in movement, the dominant patriarchal script of politics by placing their agency and rationality at the center of Venezuela’s revolution. There is an urgent need to recognize a feminization of resistance that is historically distinctive and challenges masculinist conceptualizations of political and social transformation. Un análisis marxista feminista autonomista de los relatos de tres mujeres que participaron en la Revolución Bolivariana de Venezuela—las mujeres unidas por su participación en los comités de tierras urbanas de La Vega, un rancho de Caracas—destaca la importancia fundamental de las luchas de las mujeres en este proceso revolucionario. Al centrarse en las realidades de las mujeres en movimiento, podemos empezar a comprender la complejidad de las subjetividades políticas feminizadas que se están formando y las contradicciones y tensiones en este proceso. Esta lectura pretende reescribir, en solidaridad con las mujeres en el movimiento, el texto patriarcal dominante de la política mediante la colocación de su agencia y racionalidad en el centro de la revolución de Venezuela. Hay una necesidad urgente de reconocer una feminización de la resistencia que es históricamente distintivo y desafía conceptualizaciones masculinistas de transformación política y social.
Anatomic Double-Bundle Reconstruction Techniques Result in Graft Obliquities That Closely Mimic the Native Anterior Cruciate Ligament Anatomy
Authors: Kyung Bong Soo , Kim Jae Gyoon , Chang Minho , Jang Ki-Mo , Lee Sung Sahn , Ahn Jin Hwan , Wang Joon Ho 
Published: April 2013

Background: It has been reported previously that single-bundle anterior cruciate ligament (ACL) reconstruction with more accurate restoration of the footprint of the native ACL fails to restore the graft obliquity of the native ACL in the coronal plane. Whether double-bundle ACL reconstruction restores the graft obliquity of each bundle of the native ACL has not yet been determined. Hypothesis: Anatomic double-bundle ACL reconstruction using transportal (TP) and outside-in (OI) techniques can restore the graft obliquities of both anteromedial (AM) and posterolateral (PL) bundles in the native ACL in both sagittal and coronal planes. Study Design: Cohort study; Level of evidence, 2. Methods: Seventy-six patients underwent anatomic double-bundle ACL reconstruction. Patients were randomized to 2 groups to undergo either TP or OI tibial tunnel–independent anatomic ACL reconstruction. All participants underwent postoperative magnetic resonance imaging of both knees, and the native ACL obliquity was determined using the participant’s contralateral knee. Graft obliquities were determined by measuring the angles between the center line of the graft and the surface line of the tibial plateau, and the obliquities of paired knees were compared. Graft obliquities were analyzed in each group. Results: In the sagittal plane, the mean AM graft obliquity was 54.2° on the operated side and 54.6° on the nonoperated side, and the difference between sides was not statistically significant ( P = .352). The mean PL graft obliquity in the sagittal plane was 54.1° on the operated side and 53.0° on the nonoperated side, and the difference between sides was also not statistically significant ( P = .228). In the coronal plane, the mean AM graft obliquity was 73.8° on the operated side and 73.4° on the nonoperated side, and the mean PL graft obliquity was 65.5° on the operated side and 66.4° on the nonoperated side. There were no statistically significant differences between sides ( P = .418 for AM graft; P = .328 for PL graft). Differences in the paired graft obliquities in each group were also statistically insignificant between the TP and OI groups. Conclusion: Both TP and OI anatomic double-bundle reconstruction techniques can result in graft obliquities in both bundles that resemble the native ACL in both sagittal and coronal planes. Clinical Relevance: Double-bundle ACL reconstruction techniques might more closely restore the normal kinematics of the native ACL by restoring the normal obliquity of both ACL bundles.
Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice
Authors: Nijagal Amar , Derderian Chris , Le Tom , Jarvis Erin , Nguyen Linda , Tang Qizhi , MacKenzie Tippi C. 
Published: April 2013

Key PointsTolerance induction after in utero hematopoietic cell transplantation involves both direct and indirect antigen presentation. Tolerance is achieved by deletion of effector T cells, which results in Treg enrichment without de novo Treg induction.
Carriers of a novel frame-shift insertion in WNT16a possess elevatedpancreatic expression of TCF7L2
Authors: Howard Eric W , Been Latonya F , Lerner Megan , Brackett Daniel , Lightfoot Stan , Bullen Elizabeth C , Sanghera Dharambir K 
Published: April 2013

AbstractBackgroundThe discovery ofTCF7L2as a global type 2 diabetes (T2D) gene hassparked investigations to explore the clinical utility of its variants forguiding the development of new diagnostic and therapeutic strategies.However, interpreting the resulting associations into function still remainsunclear. Canonical Wnt signaling regulates β-catenin and its bindingwith TCF7L2, which in turn is critical for the production of glucagon-likepeptide-1 (GLP-1). This study examines the role of a novel frame-shiftinsertion discovered in a conserved region ofWNT16a, and it isproposed that this mutation affects T2D susceptibility in conjunction withgene variants inTCF7L2.ResultsOur results predicted that the insertion would convert the upstream openreading frame in the Wnt16a mRNA to an alternative, in-frame translationinitiation site, resulting in the prevention of nonsense-mediated decay,leading to a consequent stabilization of the mutated WNT16a message. Toexamine the role of Wnt16a in the Wnt signaling pathway, DNA and serumsamples from 2,034 individuals (48% with T2D) from the Sikh Diabetes Studywere used in this investigation. Prevalence of Wnt16a insertion did notdiffer among T2D cases (33%) and controls (32%). However, there was a 3.2fold increase in Wnt16a mRNA levels in pancreatic tissues from the insertioncarriers and a significant increase (70%, p < 0.0001) in luciferaseactivity in the constructs carrying the insertion. The expression of TCF7L2mRNA in pancreas was also elevated (~23-fold) among the insertion carriers(p=0.003).ConclusionsOur results suggest synergistic effects ofWNT16ainsertion and theat-risk ‘T’ allele of TCF7L2 (rs7903146) for elevating theexpression ofTCF7L2in human pancreas which may affect theregulation of downstream target genes involved in the development of T2Dthrough Wnt/β-catenin/TCF7L2 signaling pathway. However, furtherstudies would be needed to mechanistically link the two definitively.
Six novel Y chromosome genes in Anophelesmosquitoes discovered by independently sequencing males and females
Authors: Hall Andrew Brantley , Qi Yumin , Timoshevskiy Vladimir , Sharakhova Maria V , Sharakhov Igor V , Tu Zhijian 
Published: April 2013

Abstract

Background
Y chromosomes are responsible for the initiation of male development, male fertility, and other male-related functions in diverse species. However, Y genes are rarely characterized outside a few model species due to the arduous nature of studying the repeat-rich Y.

Results
The chromosome quotient (CQ) is a novel approach to systematically discover Y chromosome genes. In the CQ method, genomic DNA from males and females is sequenced independently and aligned to candidate reference sequences. The female to male ratio of the number of alignments to a reference sequence, a parameter called the chromosome quotient (CQ), is used to determine whether the sequence is Y-linked. Using the CQ method, we successfully identified known Y sequences from Homo sapiens and Drosophila melanogaster. The CQ method facilitated the discovery of Y chromosome sequences from the malaria mosquitoes Anopheles stephensi and An. gambiae. Comparisons to transcriptome sequence data with blastn led to the discovery of six Anopheles Y genes, three from each species. All six genes are expressed in the early embryo. Two of the three An. stephensi Y genes were recently acquired from the autosomes or the X. Although An. stephensi and An. gambiae belong to the same subgenus, we found no evidence of Y genes shared between the species.

Conclusions
The CQ method can reliably identify Y chromosome sequences using the ratio of alignments from male and female sequence data. The CQ method is widely applicable to species with fragmented genome assemblies produced from next-generation sequencing data. Analysis of the six Y genes characterized in this study indicates rapid Y chromosome evolution between An. stephensi and An. gambiae. The Anopheles Y genes discovered by the CQ method provide unique markers for population and phylogenetic analysis, and opportunities for novel mosquito control measures through the manipulation of sexual dimorphism and fertility.