bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental Broader Autism Subphenotypes in ASD Affected Families: Relationship to Gender, Child's Symptoms, SSRI Treatment, and Platelet Serotonin
Authors: Levin‐Decanini Tal , Maltman Nell , Francis Sunday M. , Guter Steve , Anderson George M. , Cook Edwin H. , Jacob Suma
Published: August 2013

Relationships between parental broader autism phenotype (BAP) scores, gender, selective serotonin reuptake inhibitor (SSRI) treatment, serotonin (5HT) levels, and the child's symptoms were investigated in a family study of autism spectrum disorder (ASD). The Broader Autism Phenotype Questionnaire (BAPQ) was used to measure the BAP of 275 parents. Fathers not taking SSRIs (F‐SSRI; n = 115) scored significantly higher on BAP Total and Aloof subscales compared to mothers not receiving treatment (M‐SSRI; n = 136.) However, mothers taking SSRIs (M + SSRI; n = 19) scored higher than those not taking medication on BAP Total and Rigid subscales, and they were more likely to be BAPQ Total, Aloof, and Rigid positive. Significant correlations were noted between proband autism symptoms and parental BAPQ scores such that Total, Aloof, and Rigid subscale scores of F‐SSRI correlated with proband restricted repetitive behavior (RRB) measures on the ADOS, CRI, and RBS‐R. However, only the Aloof subscale score of M + SSRI correlated with proband RRB on the ADOS. The correlation between the BAPQ scores of mothers taking SSRIs and child scores, as well as the increase in BAPQ scores of this group of mothers, requires careful interpretation and further study because correlations would not withstand multiple corrections. As expected by previous research, significant parent–child correlations were observed for 5HT levels. However, 5HT levels were not correlated with behavioral measures. Study results suggest that the expression of the BAP varies not only across parental gender, but also across individuals using psychotropic medication and those who do not. Autism Res 2013, 6: 621–630. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Ex vivo cytokine production in peripheral blood mononuclear cells after their stimulation with dsRNA of natural origin
Authors: Veinalde Rūta , Petrovska Ramona , Brūvere Rūta , Feldmane Guna , Pjanova Dace
Published: August 2013

Double‐stranded RNA (dsRNA) is a pathogen‐associated molecular pattern, known for its ability to induce antiviral response and enhance communication between cells mediating innate and adaptive immune responses. The aim of this study was to characterize the effect of the dsRNA‐containing product Larifan on the production of a wide spectrum of cytokines and chemokines in ex vivo cultivated peripheral blood mononuclear cells. Concentrations of 29 different cytokines were detected by a Luminex® 200™ System using three Milliplex MAP Multiplex Assay Kits. Larifan caused strong induction of chemokine macrophage inflammatory protein 1, I‐309, and TARC, proinflammatory cytokines IL‐6, tumor necrosis factor ‐, granulocyte macrophage colony‐stimulating factor, anti‐inflammatory IL‐10, and cellular immunity mediating factors IL‐23 and interferon‐. Considerable suppression of IL‐16 and chemokine stromal cell‐derived factor 1 a+b and interferon gamma‐induced protein 10 was also observed. The network of molecules responding to the presence of Larifan revealed the pleiotropic effect this product exerts on immune response.
Expression of codon optimized human bone morphogenetic protein 4 in Pichia pastoris
Authors: Huang Yide , Zhen Binqiong , Lin Yao , Cai Yanhui , Lin Zhen , Deng Chunmei , Zhang Yanding
Published: August 2013

Bone morphogenetic proteins (BMPs) are TGF‐β family member proteins that have therapeutic potential. The amount of BMPs from natural resources is limited, and the production of biologically active BMPs in heterologous protein expression systems remains an obstacle for their clinical application. In this study, the DNA sequence of human BMP4 mature domain (hBMP4) was optimized according to the codon relative synonymous codon usage values in Pichia pastoris, and the A+T content in the sequence after optimization was within the range of 30% to 55%. In Pichia pastoris cultured in shake‐flask, the expression level of hBMP4 protein from the optimized sequence (48 mg/L) increased fourfold in comparison with that from the native sequence (12 mg/L). Recombinant hBMP4 protein was purified by SP Sepharose and heparin affinity chromatography. The biological activities of recombinant hBMP4 were examined by measuring proliferation stimulation in cells and induction of ectopic cartilage formation in mouse models. Our results demonstrated that the optimized DNA sequence could significantly enhance hBMP4 protein expression in Pichia pastoris compared with the native sequence and produce biologically active recombinant hBMP4; this indicates the potential of this optimized sequence for bulk production of hBMP4 protein in future clinical applications.
Enzymatic hydrolysis of pelletized AFEX™‐treated corn stover at high solid loadings
Authors: Bals Bryan D. , Gunawan Christa , Moore Janette , Teymouri Farzaneh , Dale Bruce E.
Published: August 2013

Ammonia fiber expansion (AFEX™) pretreatment can be performed at small depots, and the pretreated biomass can then be pelletized and shipped to a centralized refinery. To determine the feasibility of this approach, pelletized AFEX‐treated corn stover was hydrolyzed at high (18–36%) solid loadings. Water absorption and retention by the pellets was low compared to unpelletized stover, which allowed enzymatic hydrolysis slurries to remain well mixed without the need for fed‐batch addition. Glucose yields of 68% and xylose yields of 65% were obtained with 20 mg enzyme/g glucan and 18% solid loading after 72 h, compared to 61% and 59% for unpelletized corn stover. Pelletization also slightly increased the initial rate of hydrolysis compared to unpelletized biomass. The ease of mixing and high yields obtained suggests that pelletization after AFEX pretreatment could have additional advantages beyond improved logistical handling of biomass. Biotechnol. Bioeng. 2014;111: 264–271. © 2013 Wiley Periodicals, Inc.
A novel software framework for teaching aircraft dynamics and control
Authors: Shankar Praveen , Chung Wen‐Ting , Husman Jenefer , Wells Valana
Published: August 2013

Aircraft dynamics and control (ADC) is a core course requirement for an undergraduate program in aeronautical engineering. This article presents an undertaking that reconfigures the instruction of fundamental concepts in ADC by replacing traditional problem‐solving approach with a method that relies on a simulation framework comprising of Matlab, USAF DATCOM, and flight simulation software. The typical challenges experienced by students including their inability to visualize complicated, multi‐modal aircraft were overcome by the new method thus enhancing the student's learning experience. The implemented approach improved students' motivational belief and its calibration, their use of active learning strategies and actual performance. © 2013 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:63–71, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21579
Characterization of a Cyclic Nucleotide‐Activated K+ Channel and its Lipid Environment by Using Solid‐State NMR Spectroscopy
Authors: Cukkemane Abhishek , Baldus Marc
Published: August 2013

Voltage‐gated ion channels are large tetrameric multidomain membrane proteins that play crucial roles in various cellular transduction pathways. Because of their large size and domain‐related mobility, structural characterization has proved challenging. We analyzed high‐resolution solid‐state NMR data on different isotope‐labeled protein constructs of a bacterial cyclic nucleotide‐activated K+ channel (MlCNG) in lipid bilayers. We could identify the different subdomains of the 4×355 residue protein, such as the voltage‐sensing domain and the cyclic nucleotide binding domain. Comparison to ssNMR data obtained on isotope‐labeled cell membranes suggests a tight association of negatively charged lipids to the channel. We detected spectroscopic polymorphism that extends beyond the ligand binding site, and the corresponding protein segments have been associated with mutant channel types in eukaryotic systems. These findings illustrate the potential of ssNMR for structural investigations on large membrane‐embedded proteins, even in the presence of local disorder.
Effect of Organic Capping Agents on Ruthenium‐Nanoparticle‐Catalyzed Aqueous‐Phase Fischer–Tropsch Synthesis
Authors: Quek Xian‐Yang , Pestman Robert , van Santen Rutger A. , Hensen Emiel J. M.
Published: August 2013

The influence of organic capping agents on the performance of Ru nanoparticles in aqueous‐phase Fischer–Tropsch (FT) synthesis was investigated. Three organic capping agents were used: trimethyl(tetradecyl)ammonium bromide (TTAB), polyvinylpyrrolidone (PVP), and sodium 3‐mercapto‐1‐propanesulfonate (SMPS). To exclude the effects of particle size, the capping agents were placed onto carbon‐nanofiber‐supported Ru nanoparticles of size 3.4 nm. The activity in the FT reaction increased in the order: Ru‐SMPS≪Ru‐PVP<Ru‐TTAB<Ru. Kinetic data suggest that the FT mechanism was largely unaffected by the presence of capping agents; thus, their binding to active centers explains activity trends. Replacing water with n‐hexadecane as the solvent results in an increase in the rate of formation and a decrease in the chain‐growth probability for hydrocarbons, whereas the production of oxygenates is unaffected. This trend is consistent with the proposal that hydrocarbons are formed on reaction centers that involve facile CO dissociation and that termination is the rate‐determining step. For oxygenates, CO dissociation is proposed to be the rate‐determining step.
Electronic Structure Trends in N‐Heterocyclic Carbenes (NHCs) with Varying Number of Nitrogen Atoms and NHCTransition‐Metal Bond Properties
Authors: Bernhammer Jan C. , Frison Gilles , Huynh Han Vinh
Published: August 2013

Carbenes derived from five‐membered heterocycles with different numbers of nitrogen atoms ranging from two to four lead formally either to normal N‐heterocyclic or mesoionic carbenes with, in some cases, the same skeletal structure. The electronic structures of fourteen of these compounds were examined by means of DFT calculations at the B3LYP/aug‐cc‐pVTZ level. The examined parameters include the energies of the σ‐lone pair at Ccarbene and the π‐HOMO of the protonated form, which are correlated to the first and second proton affinities. The singlet–triplet energy gap was used as a measure of the stability of the N‐heterocyclic carbene (NHC) towards dimerisation. Natural population analysis provided insight into the variation of the pπ population and the natural charge at Ccarbene with NHC structure. Additionally, the transition metalNHC bond in L‐AuCl and L‐TiCl4 and the nature of the orbital interactions between the NHC and the transition‐metal fragment were analysed in detail by the extended transition state–natural orbitals for chemical valence (ETS–NOCV) approach at the BP86/TZ2P level. Similarities and differences between the NHCgold and the NHCtitanium bond are discussed, and trends in key bonding properties can be traced back to the variation of the electronic parameters of the NHC.
Use of Sulfated Cyclofructan 6 and Sulfated Cyclodextrins for the Chiral Separation of Four Basic Pharmaceuticals by Capillary Electrophoresis
Authors: Zhang Yi Jun , Huang Ming Xian , Zhang Yu Ping , Armstrong Daniel Wayne , Breitbach Zachary S. , Ryoo Jae Jeong
Published: August 2013

Sulfated cyclofructan 6 (S‐CF6) and sulfated cyclodextrins (S‐α‐, β‐, γ‐CDs) are highly selective chiral selectors for the enantioseparation of basic solutes. In this study, S‐CF6 was introduced for the enantiomeric separation of four basic pharmaceuticals (including tamsulosin, tiropramide, bupivacaine, and norephedrine) by capillary electrophoresis (CE), and the enantiomeric separation performance was compared with S‐α‐, β‐, γ‐CDs. The effects of the chiral selector type, chiral selector concentration, operating voltage, and column temperature were examined and optimized. Excellent resolutions were obtained for all solutes on these chiral selectors. Chirality 25:735–742, 2013. © 2013 Wiley Periodicals, Inc.
Numerical simulation of spouting of cylindroid particles in a spouted bed
Authors: Ren Bing , Zhong Wenqi , Jiang Xiaofeng , Jin Baosheng , Yuan Zhulin
Published: August 2013

The hydrodynamic behaviours of cylindroid particles in a spouted bed are studied by three‐dimensionally coupled computational fluid dynamic (CFD) and discrete element method (DEM) model. The cylindroid particles are constructed by multi‐sphere method. The drag coefficient model for non‐spherical particles is employed which shows higher accuracy by comparing the calculated flow pattern and pressure drop distribution data with the experimental measurements and the predicted results with the traditional drag coefficient model for spherical particles. Peak pressure drop, flow pattern, spout diameter and geometry of the fountain are discussed in detail.
Interactions of the Multidrug Resistance Modulators Tariquidar and Elacridar and their Analogues with P‐glycoprotein
Authors: Pajeva Ilza K. , Sterz Katja , Christlieb Matthias , Steggemann Kerstin , Marighetti Federico , Wiese Michael
Published: August 2013

Tariquidar and elacridar are among the most potent inhibitors of the multidrug resistance transporter P‐glycoprotein (P‐gp), but how they interact with the protein is yet unknown. In this work, we describe a possible way in which these inhibitors interact with P‐gp. We rely on structure–activity relationship analysis of a small group of tariquidar and elacridar analogues that was purposefully selected, designed, and tested. Structural modifications of the compounds relate to the presence or absence of functional groups in the tariquidar and elacridar scaffolds. The activity of the compounds was evaluated by their effects on the accumulation of P‐gp substrates rhodamine 123 and Hoechst 33342 in resistant tumor cells. The data allow estimation of the ability of the compounds to interact with the experimentally proposed R‐ and H‐sites to which rhodamine 123 and Hoechst 33342 bind, respectively. Using an inward‐facing homology model of human P‐gp based on the crystallographic structure of mouse P‐gp, we demonstrate that these binding sites may overlap with the binding sites of the QZ59 ligands co‐crystallized with mouse P‐gp. Based on this SAR analysis, and using flexible alignment and docking, we propose possible binding modes for tariquidar and elacridar. Our results suggest the possibility for the studied compounds to bind to sites that coincide or overlap with the binding sites of rhodamine 123 and Hoechst 33342. These results contribute to further understanding of structure–function relationships of P‐gp and can help in the design of selective and potent P‐gp inhibitors with potential clinical use.
Targets, Structures, and Recent Approaches in Malignant Melanoma Chemotherapy
Authors: Matos Ana Marta , Francisco Ana Paula
Published: August 2013

Malignant metastatic melanoma is one of the oncologic diseases with the worst clinical prognosis, due primarily to resistance phenomena against chemotherapeutic agents in current use. However, over the last few years, characterization of the molecular mechanisms involved in the development and progression of the disease has contributed to elucidation of the main pathways by which tissue invasion and metastasis can occur. More importantly, the identification of abnormalities in signaling cascades in melanoma cells has facilitated new therapeutic approaches against malignant melanoma through the design of highly potent and selective drugs with low associated toxicity. Ultimately, recognition of the restricted applicability of new chemotherapies in certain genetic contexts has led to significant improvements in the results of clinical trials, anticipating the existing need for investment in personalized therapies, and taking into account the molecular alterations observed in tumors. Although significant advances have been made in terms of extending the median overall survival rate and improving the quality of life for patients, the mechanisms that compromise in vivo drug efficacy remain poorly understood, particularly those concerning therapeutic resistance phenomena. This review summarizes recently validated targets from the perspective of the medicinal chemistry carried out in the design of the most promising structures.
A Conformational Mimetic Approach for the Synthesis of Carbocyclic Nucleosides as Anti‐HCV Leads
Authors: Kasula Mohan , Balaraju Tuniki , Toyama Massaki , Thiyagarajan Anandarajan , Bal Chandralata , Baba Masanori , Sharon Ashoke
Published: August 2013

Computer‐aided approaches coupled with medicinal chemistry were used to explore novel carbocyclic nucleosides as potential anti‐hepatitis C virus (HCV) agents. Conformational analyses were carried out on 6‐amino‐1H‐pyrazolo[3,4‐d]pyrimidine (6‐APP)‐based carbocyclic nucleoside analogues, which were considered as nucleoside mimetics to act as HCV RNA‐dependent RNA polymerase (RdRp) inhibitors. Structural insight gained from the modeling studies revealed the molecular basis behind these nucleoside mimetics. The rationally chosen 6‐APP analogues were prepared and evaluated for anti‐HCV activity. RdRp SiteMap analysis revealed the presence of a hydrophobic cavity near C7 of the nucleosides; introduction of bulkier substituents at this position enhanced their activity. Herein we report the identification of an iodinated compound with an EC50 value of 6.6 μM as a preliminary anti‐HCV lead.
Cytologic subtyping of lung adenocarcinoma by using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) adenocarcinoma classification
Authors: Rodriguez Erika F. , Monaco Sara E. , Dacic Sanja
Published: August 2013

BACKGROUND

The significance of histologic subtyping of surgically resected lung adenocarcinoma (ADC) was recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. Approximately 70% of lung cancer patients present with advanced disease, and small biopsies or cytology specimens are frequently the only available diagnostic material. It is uncertain whether proposed morphologic subtyping of ADC can be applied to small specimens. The objective of this study was to assess the applicability of morphologic subtyping of ADC on cytologic specimens.

METHODS

Consecutive, newly diagnosed primary lung ADC specimens from patients with matched surgical resection and cytology specimens (n = 66) were selected for the study. The dominant morphologic pattern was determined according to the IASLC/ATS/ERS classification. The number and percentage of malignant cells in cytology specimens were also evaluated.

RESULTS

Concordant subtyping of ADC between the dominant pattern on resection and cytology specimens was observed in 26 cases (40%), and was discordant in 32 cases (48%). Concordance increased in specimens that had >200 cells and when correlating with the primary or secondary histologic pattern. The acinar pattern was the most common in concordant cases, whereas discordant cases had a predominantly solid pattern.

CONCLUSIONS

Application of the IASLC/ATS/ERS ADC classification to cytologic specimens is challenging and depends on the sufficient cellularity of cytologic preparations. The identification of solid and micropapillary patterns is prognostically important but may be unreliable and difficult on cytology specimens. Future studies are needed to establish reproducible cytologic criteria for the precise subtyping of lung ADC on small specimens. Cancer (Cancer Cytopathol) 2013;121:629–37. © 2013 American Cancer Society.
Effect of Vortioxetine on Cardiac Repolarization in Healthy Adult Male Subjects: Results of a Thorough QT/QTc Study
Authors: Wang Ying , Nomikos George G. , Karim Aziz , Munsaka Melvin , Serenko Michael , Liosatos Maggie , Harris Stuart
Published: August 2013

This double‐blind, randomized, placebo‐ and positive‐controlled, parallel‐group study evaluated the effect of vortioxetine (Lu AA21004), an investigational multimodal antidepressant, on QT interval in accordance with current guidelines of the International Conference on Harmonisation (ICH‐E14). A total of 340 healthy men were randomized to receive 1 of 4 treatments for 14 days: (1) vortioxetine 10 mg once daily (QD), (2) vortioxetine 40 mg QD, (3) placebo QD, or (4) placebo QD on Days 1 through 13 followed by a single dose of moxifloxacin 400 mg (positive control). The primary endpoint was the largest time‐matched, baseline‐adjusted least‐squares (LS) mean difference for the individual‐corrected QT interval (QTcNi [linear]) between vortioxetine and placebo. Alternative QT correction formulas (i.e., Fredericia [QTcF], Bazett [QTcB], Framingham [QTcFm], and QTcNi [nonlinear]) were used as secondary endpoints. The upper bound of the 2‐sided 90% confidence interval around the LS mean difference from placebo for baseline‐adjusted QTcNi (linear), QTcF, QTcB, QTcFm, and QTcNi (nonlinear) did not exceed 10 ms at any time point after multiple doses of vortioxetine 10 mg (therapeutic) or 40 mg (supratherapeutic). Overall, the study results indicate that vortioxetine is unlikely to affect cardiac repolarization in healthy subjects.
Pharmacokinetics of Single‐Dose Dolutegravir in HIV‐Seronegative Subjects With Moderate Hepatic Impairment Compared to Healthy Matched Controls
Authors: Song Ivy H. , Borland Julie , Savina Paul M. , Chen Shuguang , Patel Parul , Wajima Toshihiro , Peppercorn Amanda F. , Piscitelli Stephen C.
Published: August 2013

This study evaluated dolutegravir pharmacokinetics (PK) in subjects with moderate hepatic impairment compared to matched, healthy controls. In this open‐label, parallel‐group study, eight adult subjects with moderate hepatic impairment (Child‐Pugh Score 7–9) and eight healthy subjects matched for gender, age, and body mass index received a single dolutegravir 50‐mg dose. Following dosing, 72‐hour PK sampling was performed to determine total and unbound dolutegravir concentrations. PK parameters were calculated using non‐compartmental analysis. Geometric least squares mean ratios (GMR) and 90% confidence intervals (CIs) in subjects with hepatic impairment versus healthy subjects were generated by analysis of variance. Results showed that PK parameters of total plasma dolutegravir were similar between subject groups. The unbound fraction was higher in subjects with moderate hepatic impairment than in healthy subjects with GMR (90% CI) of 2.20 (1.62, 2.99) for unbound fraction at 3 hours post‐dose and 1.76 (1.23, 2.51) for unbound fraction at 24 hours post‐dose; this correlated with lower serum albumin concentrations and was not considered clinically significant. Dolutegravir was well tolerated in both groups; all adverse events were reported as minor. Although free fraction was increased, no dose adjustment is required for patients treated with dolutegravir who have mild to moderate hepatic impairment.
Number Density of Liquid Inclusions Formed in Frozen Aqueous Electrolyte
Authors: Hashimoto Takuya , Harada Makoto , Nojima Shuichi , Okada Tetsuo
Published: August 2013

Frozen aqueous chlorides (≤50 mM) are characterized by using confocal fluorescence microscopy and small angel X‐ray scattering (SAXS). The former method allows us to determine the size of a liquid inclusion formed in the ice matrix at temperatures above the eutectic point of the system (teu). Isolated liquid inclusions of a uniform size are formed when the temperature of a frozen electrolyte increases past teu. The size of the liquid inclusions depends on the observation temperature as well as on the concentration (csalt) and type of salt dissolved in the original unfrozen solution. However, the number density of liquid inclusions is almost constant and independent of these experimental parameters, particularly when an electrolyte is frozen in liquid nitrogen. Salt accumulation can then occur at the imperfections of the ice crystals. The occurrence probability of the imperfections is independent of the nature of an incorporated salt. The amount of a salt confined in each inclusion ranges from 7 to 240 fmol, depending on csalt. SAXS measurements provide information on the size of individual salt crystals formed at temperatures below teu. The radius of gyration of a salt crystal ranges from 2 to 2.8 nm, and does not depend significantly on csalt. Thus, each inclusion is formed from 106–109 nanocrystals, which can act as seeds. When doped ice is prepared at higher temperatures, for example −16 °C, the isolation of liquid inclusions is not sufficient and coalescence occurs more easily upon an increase in temperature or csalt. However, when csalt is lower than 10 mM, the number density of liquid inclusions is almost constant, irrespective of the freezing temperature.
Comparison of Force Fields on the Basis of Various Model Approaches—How To Design the Best Model for the [CnMIM][NTf2] Family of Ionic Liquids
Authors: Köddermann Thorsten , Reith Dirk , Ludwig Ralf
Published: August 2013

In this contribution, we present two new united‐atom force fields (UA‐FFs) for 1‐alkyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide [CnMIM][NTf2] (n=1, 2, 4, 6, 8) ionic liquids (ILs). One is parametrized manually, and the other is developed with the gradient‐based optimization workflow (GROW). By doing so, we wanted to perform a hard test to determine how researchers could benefit from semiautomated optimization procedures. As with our already published all‐atom force field (AA‐FF) for [CnMIM][NTf2] (T. Köddermann, D. Paschek, R. Ludwig, ChemPhysChem­ 2007, 8, 2464), the new force fields were derived to fit experimental densities, self‐diffusion coefficients, and NMR rotational correlation times for the IL cation and for water molecules dissolved in [C2MIM][NTf2]. In the manual force field, the alkyl chains of the cation and the CF3 groups of the anion were treated as united atoms. In the GROW force field, only the alkyl chains of the cation were united. All other parts of the structures of the ions remained unchanged to prevent any loss of physical information. Structural, dynamic, and thermodynamic properties such as viscosity, cation rotational correlation times, and heats of vaporization calculated with the new force fields were compared with values simulated with the previous AA‐FF and the experimental data. All simulated properties were in excellent agreement with the experimental values. Altogether, the UA‐FFs are slightly superior for speed‐up reasons. The UA‐FF speeds up the simulation by about 100 % and reduces the demanded disk space by about 78 %. More importantly, real time and efforts to generate force fields could be significantly reduced by utilizing GROW. The real time for the GROW parametrization in this work was 2 months. Manual parametrization, in contrast, may take up to 12 months, and this is, therefore, a significant increase in speed, though it is difficult to estimate the duration of manual parametrization.
The Semiempirical Quantum Mechanical Scoring Function for In Silico Drug Design
Authors: Lepšík Martin , Řezáč Jan , Kolář Michal , Pecina Adam , Hobza Pavel , Fanfrlík Jindřich
Published: August 2013

This Minireview discusses the latest developments in modern quantum mechanics (QM)‐based computer‐aided drug design, especially using semiempirical QM (SQM) methods. It first tackles biochemical and biophysical quantities and the approaches to their measurements. Protein–ligand affinities are determined mostly by noncovalent interactions. The text thus illustrates how these can be accurately treated with SQM methods. Next, a construction of a modern SQM‐based scoring function is presented and its applications listed. In summary, SQM‐based scoring is a promising modern efficient strategy to be exploited in computer‐aided drug design.
Recover, Recycle, and Reuse: Prove‐Out of Pyrotechnic Illuminants Containing Demilitarized Magnesium
Authors: Sabatini Jesse J. , Moretti Jared D. , Hall Derrick R. , Robert Leon L.
Published: August 2013

The development and prove‐out of yellow‐light‐emitting pyrotechnic illuminants based on recover, recycle, and reuse (R3) technology is described. Magnesium used in this investigation was recovered from four different illuminating pyrotechnic munitions by means of an environmentally friendly demilitarization process. Despite significant differences in the particle size and purity between the four lots of recovered magnesium, the performance of each lot—on evaluation in the M127A1 US Army yellow‐light‐emitting illuminant configuration—exceeded the military requirement and performance of the virgin magnesium‐containing control. All formulations were found to have low sensitivities to various ignition stimuli and possessed high thermal onset temperatures. In addition to the military significance, this demonstrated “green” pyrotechnics technology of using recycled magnesium in illuminating pyrotechnics may also be of interest to the civilian fireworks community.
Interference with Ca2+ release activated Ca2+ (CRAC) channel function delays T‐cell arrest in vivo
Authors: Waite Janelle C. , Vardhana Santosh , Shaw Patrick J. , Jang Jung‐Eun , McCarl Christie‐Ann , Cameron Thomas O. , Feske Stefan , Dustin Michael L.
Published: August 2013

Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca2+]i) elevation. TCR activation triggers increased [Ca2+]i and can arrest T‐cell motility in vitro. However, the requirement for [Ca2+]i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca2+ release‐activated Ca2+ (CRAC) channel pathway required for [Ca2+]i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant‐negative ORAI1 channel subunit (ORAI1‐DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4+ T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1‐DN lacked TCR activation induced [Ca2+]i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen‐specific ORAI1‐DN T cells had a twofold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest.
Chemistry of Heterocyclic 2‐Thiones: In Situ Generation of 3‐(2‐Thiazolin‐2‐yl)thiazolidine‐2‐thione and 1,1′‐Dimethyl‐2,2′‐diimidazolyl Sulfide and Their Coordination to CuI and CuII
Authors: Lobana Tarlok S. , Sultana Razia , Butcher Ray J. , Castineiras Alfonso , Akitsu Takashiro , Fernandez Francisco J. , Vega M. Cristina
Published: August 2013

The chemical reactivity of copper(I) chloride/copper(I) bromide, [CuI(NCCH3)4](BF4), and copper(II) nitrate towards a series of heterocyclic‐2‐thiones under aerobic conditions is described. Thiazolidine‐2‐thione (NC3H5S2) in CH3CN in the presence of copper(I) chloride/bromide and [CuI(NCCH3)4](BF4) was transformed into 3‐(2‐thiazolin‐2‐yl)thiazolidine‐2‐thione (C3H4S2N‐C3H4SN) through C–S bond cleavage and the formation of a C–N bond between two heterocyclic rings. This new thio ligand (C3H4S2N‐C3H4SN) chelates to CuI through N,S‐donor atoms, and the third site is occupied by the halogen atoms (Cl, Br), which leads to the formation of three‐coordinate CuI complexes, [CuIX(κ2‐N,S‐C3H4S2N‐C3H4SN)] [X = Cl (1), Br (2)], and a four‐coordinate N,S‐chelated complex, [CuI(κ2‐N,S‐C3H4S2N‐C3H4SN)2](BF4) (3), is obtained in the presence of BF4–. In each case, the formation of CuSO4·5H2O was also observed. Upon reaction of 1‐methylimidazoline‐2‐thione (N2C4H6S) with [CuI(NCCH3)4](BF4) or copper(II) nitrate in CH3CN or CH3CN/MeOH, respectively, the thio ligand is converted into 1,1′‐dimethyl‐2,2′‐diimidazolyl sulfide (N2C4H5)2S (a thioether), which prefers to bind to CuII (in situ formed) to yield six‐coordinate N,N‐chelated octahedral complexes, namely, {CuII[κ2‐N,N‐(N2C4H5)2S]2(κ1‐OH2)2}X2 [X = BF4 (6), NO3 (7)], with water in the axial positions. The transformation of the thio ligand into 1,1′‐dimethyl‐2,2′‐diimidazolyl sulfide is also observed in its copper(I) chloride reaction in acetonitrile, which yields an N,N‐chelated chloro‐bridged dimer, {CuII2[κ2‐N,N‐(N2C4H5)2S]2(μ‐Cl)2Cl2} (5). Reaction of copper(I) iodide with thiazolidine‐2‐thione and 1‐methylimidazolidine‐2‐thione (N2C4H8S) in acetonitrile yields an iodo‐bridged dimer, [Cu2(κ1‐S‐NC3H5S2)4(μ‐I)2] (4), and a novel polymer, [Cu4(μ3‐I)2(μ‐I)2(μ‐S‐N2C4H8S)2(κ1‐S‐N2C4H8S)]n (8), respectively.
Bis(aryl)acenaphthenequinonediimine Substituent Effect on the Properties and Coordination Environment of Ligands and Their Bis‐Chelate AgI Complexes
Authors: Papanikolaou Panagiotis A. , Gdaniec Maria , Wicher Barbara , Akrivos Pericles D. , Tkachenko Nikolai V.
Published: August 2013

The reaction of a series of Ar–BIAN ligands (Ar = o‐Ph, m‐Cl, m‐CF3, p‐Cl, p‐MeO, and p‐Me–C6H4) with AgNO3 results in the formation of the corresponding bis‐chelate complexes. Substituent groups on the aryl rings seem to offer tunability of the electronic properties of the diimines, also affecting the metal coordination environment through the mono‐coordination or chelation of the nitrate anion as promoted by the substituents p‐MeO, p‐Me, and m‐CF3. The enhanced absorption capacity of the complexes in the visible region in combination with the well‐known redox activity of the ligands and their ability to potentially accommodate a fifth coordinated ligand on the metal center opens a route for the preparation of new silver species of high propensity for catalytic, photocatalytic, and biological applications.
Numerical solution of large and sparse continuous time algebraic matrix Riccati and Lyapunov equations: a state of the art survey
Authors: Benner Peter , Saak Jens
Published: August 2013

Efficient numerical algorithms for the solution of large and sparse matrix Riccati and Lyapunov equations based on the low rank alternating directions implicit (ADI) iteration have become available around the year 2000. Over the decade that passed since then, additional methods based on extended and rational Krylov subspace projection have entered the field and proved to be competitive alternatives. In this survey we sketch both types of methods and discuss their advantages and drawbacks. We focus on the continuous time case here, but corresponding results for discrete time problems can for most results be found in the available literature. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theory and applications of compressed sensing
Authors: Kutyniok Gitta
Published: August 2013

Compressed sensing is a novel research area, which was introduced in 2006, and since then has already become a key concept in various areas of applied mathematics, computer science, and electrical engineering. It surprisingly predicts that high‐dimensional signals, which allow a sparse representation by a suitable basis or, more generally, a frame, can be recovered from what was previously considered highly incomplete linear measurements by using efficient algorithms. This article shall serve as an introduction to and a survey about compressed sensing. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The geography of semidiurnal mode‐1 internal‐tide energy loss
Authors: Kelly S. M. , Jones N. L. , Nash J. D. , Waterhouse A. F.
Published: August 2013

The semidiurnal mode‐1 internal tide receives 0.1–0.3 TW from the surface tide and is capable of propagating across ocean basins. The ultimate fate of mode‐1 energy after long‐distance propagation is poorly constrained by existing observations and numerical simulations. Here, global results from a two‐dimensional semi‐analytical model indicate that topographic scattering is inefficient at most locations deeper than 2500 m. Next, results from a one‐dimensional linear model with realistic topography and stratification create a map of mode‐1 scattering coefficients along the continental margins. On average, mode‐1 internal tides lose about 60% of their energy upon impacting the continental margins: 20% transmits onto the continental shelf, 40% scatters to higher modes, and 40% reflects back to the ocean interior. These analyses indicate that the majority of mode‐1 energy is likely lost at large topographic features (e.g., continental slopes, seamounts, and mid‐ocean ridges), where it may drive elevated turbulent mixing.
Medullary thyroid cancer diagnosis: An appraisal
Authors: Trimboli Pierpaolo , Giovanella Luca , Crescenzi Anna , Romanelli Francesco , Valabrega Stefano , Spriano Giuseppe , Cremonini Nadia , Guglielmi Rinaldo , Papini Enrico
Published: August 2013

Since its first description in 1951, a timely diagnosis of medullary thyroid carcinoma (MTC) may represent a diagnostic challenge in clinical practice. Several contributions have been addressed to the treatment and follow‐up of MTC, but review articles focused on the diagnostic problems of this cancer in clinical practice are sparse. As a delayed diagnosis and an inadequate initial treatment may severely affect the prognosis of this thyroid malignancy, the appropriate use and the correct interpretation of the available diagnostic tools for MTC are of crucial importance. The purpose of the present article is to provide an easy‐to‐use guide reviewing the main issues of MTC diagnosis: (1) basal serum calcitonin; (2) stimulated serum calcitonin; (3) additional serum markers for MTC; (4) ultrasound and other imaging techniques; (5) fine‐needle aspiration (FNA) cytology; (6) calcitonin measurement on FNA washout; (7) rearranged during transfection (RET) mutations; and (8) scope of the problem. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1216–1223, 2014
Hydrograph separation to improve understanding of Dissolved Organic Carbon Dynamics in Headwater catchments
Authors: Chaplot V. , Ribolzi O.
Published: August 2013

Dissolved organic carbon (DOC) is a key component of the global carbon cycle, but, to date, large uncertainties still exist on its source and fate in first‐order streams. In a 23 ha rangeland and steep‐slope headwater of South Africa, our aim was to quantify the contribution of overland flow (OF), soil water (SW) and ground water (GW) to DOC fluxes (DOCF), and to interpret the results in terms of DOC sources and fate. The average 2010–2011 DOC concentration (DOCC) at the catchment outlet was 4.7 mg C l−1 with a standard error of ±2.5 mg C l−1, which was significantly lower than in SW (15.2 ± 1.6 mg C l−1) and OF (11.9 ± 0.8 mg C l−1), but higher than in GW (2.3 ± 0.6 mg C l−1). Based on end‐member mixing using Si and Na concentration in the water compartments, the average SW contribution to DOCF was 66.4%, followed by OF (30.0%) and GW (3.6%). The resulting estimated DOCF at the catchment outlet was 8.05 g C m2 y−1. This was much higher than the observed value of 2.80 g C m2 y−1, meaning that 5.25 g C m2 y−1 or 65% of the DOC is lost during its downslope and/or downstream transport to the catchment outlet. Complementary investigations revealed that the DOCC in SW dropped from 15.2 ± 1.6 to 2.6 ± 0.3 mg C l−1 during its downslope transport to the river system, which corresponded to a net loss of 5.10 g C m2 y−1, or 97% of the catchment DOC losses. These results on DOC sources and potential fate in headwaters are expected to improve our understanding of the impact of hydrology on the global C‐cycle. Copyright © 2013 John Wiley & Sons, Ltd.
ROC‐based calibration of flood inundation models
Authors: Schumann G. J.‐P. , Vernieuwe H. , De Baets B. , Verhoest N. E. C.
Published: August 2013

The use of spatial patterns of flood inundation (often obtained from remotely sensed imagery) to calibrate flood inundation models has been widespread over the last 15 years. Model calibration is most often achieved by employing one or even several performance measures derived from the well‐known confusion matrix based on a binary classification of flooding. However, relatively early on, it has been recognized that the use of commonly reported performance measures for calibrating flood inundation models (such as the F measure) is hampered because the calibration procedure commonly utilizes only one possible solution of a wet/dry classification of a remote sensing image [most often acquired by a synthetic aperture radar (SAR)] to calibrate or validate models and are biased towards either over‐prediction or under‐prediction of flooding. Despite the call in several studies for an alternative statistic, to this date, very few, if any, unbiased performance measure based on the confusion matrix has been proposed for flood model calibration/validation studies. In this paper, we employ a robust statistical measure that operates in the receiver operating characteristics (ROC) space and allows automated model calibration with high identifiability of the best model parameter set but without the need of a classification of the SAR image. The ROC‐based method for flood model calibration is demonstrated using two different flood event test cases with flood models of varying degree of complexity and boundary conditions with varying degree of accuracy. Verification of the calibration results and optional SAR classification is successfully performed with independent observations of the events. We believe that this proposed alternative approach to flood model calibration using spatial patterns of flood inundation should be employed instead of performance measures commonly used in conjunction with a binary flood map. © 2013 California Institute of Technology. Hydrological Processes © 2013 John Wiley & Sons, Ltd.
Promoting Positive Mother–Infant Relationships: A Randomized Trial of Community Doula Support For Young Mothers
Authors: Hans Sydney L. , Thullen Matthew , Henson Linda G. , Lee Helen , Edwards Renee C. , Bernstein Victor J.
Published: August 2013

Doulas, whose traditional role is to support women during labor and delivery, are being increasingly utilized within community‐based programs where a primary goal is supporting mother–infant relationships. The present study investigated the effect of doula services on parenting among young, low‐income mothers. A total of 248 pregnant women were randomly assigned to receive either doula services or routine medical and social services. The doulas provided prenatal home visitation, support during labor and delivery, and 3 months of postpartum home visitation. Parenting was assessed through video recordings of mother–infant interaction at 4, 12, and 24 months of child age and maternal report of parenting attitudes and stress. Intent‐to‐treat analyses showed that mothers who had received doula services endorsed more child‐centered parenting values, showed more positive engagement with their infants, and were more likely to respond to infant distress at 4 months. Their infants were less likely to show visible upset during observed interactions. Most effects of the program on parent and child behavior faded over time. Community doula intervention is a promising practice for supporting parenting and parent–infant interaction. Integration of doulas into longer term home‐visiting models might sustain the early impact of doula services and enhance parenting services offered by traditional home‐visiting programs.
How is radiating leg pain defined in randomized controlled trials of conservative treatments in primary care? A systematic review
Authors: Lin C.‐W.C. , Verwoerd A.J.H. , Maher C.G. , Verhagen A.P. , Pinto R.Z. , Luijsterburg P.A.J. , Hancock M.J.
Published: August 2013

Many terms exist to describe radiating leg pain or symptoms associated with back pain (e.g., sciatica or radiculopathy) and it appears that these terms are used inconsistently. We examined the terms used to describe, and the eligibility criteria used to define, radiating leg pain in randomized controlled trials of conservative treatments, and evaluated how the eligibility criteria compared to an international pain taxonomy. Eligible studies were identified from two systematic reviews and an updated search of their search strategy. Studies were included if they recruited adults with radiating leg pain associated with back pain. Two independent reviewers screened the studies and extracted data. Studies were grouped according to the terms used to describe radiating leg pain. Thirty‐one of the seventy‐seven included studies used multiple terms to describe radiating leg pain; the most commonly used terms were sciatica (60 studies) and disc herniation (19 studies). Most studies that used the term sciatica included pain distribution in the eligibility criteria, but studies were inconsistent in including signs (e.g., neurological deficits) and imaging findings. Similarly, studies that used other terms to describe radiating leg pain used inconsistent eligibility criteria between studies and to the pain taxonomy, except that positive imaging findings were required for almost all studies that used disc herniation to describe radiating leg pain. In view of the varying terms to describe, and eligibility criteria to define, radiating leg pain, consensus needs to be reached for each of communication and comparison between studies.
Concurrent schedules: Discriminating reinforcer‐ratio reversals at a fixed time after the previous reinforcer
Authors: Cowie Sarah , Elliffe Douglas , Davison Michael
Published: August 2013

Six pigeons worked on concurrent exponential variable‐interval schedules in which the relative frequency of food deliveries for responding on the two alternatives reversed at a fixed time after each food delivery. Across conditions, the point of food–ratio reversal was varied from 10 s to 30 s, and the overall reinforcer rate was varied from 1.33 to 4 per minute. The effect of rate of food delivery and food–ratio‐reversal time on choice and response rates was small. In all conditions, postfood choice was toward the locally richer key, regardless of the last‐food location. Unlike the local food ratio which changed in a stepwise fashion, local choice changed according to a decelerating monotonic function, becoming substantially less extreme than the local food ratio soon after food delivery. This deviation in choice appeared to result from the birds' inaccurate discrimination of the time of food deliveries; local choice was described well by a model that assumed that log response ratios matched food ratios that were redistributed across surrounding time bins with mean time t and a constant coefficient of variation. We suggest that local choice is controlled by the likely availability of food in time, and that choice matches the discriminated log of the ratio of food rates across time since the last food delivery.