bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Multicomponent Reactions of Amino Alcohols with CH2O and Dithiols in the Synthesis of 1,3,5‐Dithiazepanes and Macroheterocycles.
Authors: Khabibullina Guzel R. , Akhmetova Vnira R. , Abdullin Marat F. , Tyumkina Tatiana V. , Khalilov Leonard M. , Ibragimov Askhat G. , Dzhemilev Usein M.
Published: October 2014

A facile protocol allows the intermolecular three‐component cyclocondensation of dithiols, formaldehyde, and amines to give 1,3,5‐dithiazepanes and a wide variety of macroheterocycles.
ChemInform Abstract: Diversity‐Oriented Approach to Normuscopyridine and Its Analogues Through Ring‐Closing Metathesis.
Authors: Kotha Sambasivarao , Waghule Gopalkrushna T. , Shirbhate Mukesh E.
Published: October 2014

Two RCM‐based approaches to normuscopyridine (Va) and its analogues are explored.
ChemInform Abstract: Metal—Organic Framework Composites
Authors: Zhu Qi‐Long , Xu Qiang
Published: October 2014

Review: recent progress in designing and fabricating metal—organic framework composites for diverse functional applications; 419 refs.
ChemInform Abstract: Metal—Metalloporphyrin Frameworks: A Resurging Class of Functional Materials
Authors: Gao Wen‐Yang , Chrzanowski Matthew , Ma Shengqian
Published: October 2014

Review: 112 refs.
ChemInform Abstract: Substitution Reactions in Metal—Organic Frameworks and Metal—Organic Polyhedra
Authors: Han Yi , Li Jian‐Rong , Xie Yabo , Guo Guangsheng
Published: October 2014

Review: 256 refs.
ChemInform Abstract: Catalytic Formation of Monosaccharides: From the Formose Reaction Towards Selective Synthesis
Authors: Delidovich Irina V. , Simonov Alexandr N. , Taran Oxana P. , Parmon Valentin N.
Published: October 2014

Review: [110 refs.
ChemInform Abstract: Synthesis and Chemical Reactivity of 4‐Oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde
Authors: Sepay Nayim , Dey Sankar P.
Published: October 2014

Review: 89 refs.
ChemInform Abstract: On the Discovery and Development of Tandem 1,4‐ and 1,2‐Addition of Phosphites to 1‐Azadienes
Authors: Van Waes Frederik E. A. , Debrouwer Wouter , Heugebaert Thomas S. A. , Stevens Christian V.
Published: October 2014

Review: 55 refs.
ChemInform Abstract: Six‐Membered Ring Systems: With O and/or S Atoms
Authors: Santos Clementina M. M. , Silva Artur M. S.
Published: October 2014

Review: 361 refs.
ChemInform Abstract: Metal—Organic Frameworks for Artificial Photosynthesis and Photocatalysis
Authors: Zhang Teng , Lin Wenbin
Published: October 2014

Review: 107 refs.
Postnatal growth of the human pons: A morphometric and immunohistochemical analysis
Authors: Tate Matthew C. , Lindquist Robert A. , Nguyen Thuhien , Sanai Nader , Barkovich A. James , Huang Eric J. , Rowitch David H. , Alvarez‐Buylla Arturo
Published: October 2014

Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)‐based morphometric analyses of the postnatal human pons (0–18 years; n = 6–14/timepoint). Pons volume increased 6‐fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2‐based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67+ cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2+ was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67+ cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67+ cells observed throughout childhood. In addition, two populations of vimentin/nestin‐expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases. J. Comp. Neurol. 523:449–462, 2015. © 2014 Wiley Periodicals, Inc.
Cytogenesis in the adult monkey motor cortex: Perivascular NG2 cells are the major adult born cell type
Authors: Stanton Gregory B. , Kohler Shawn J. , Boklweski Jennifer , Cameron Judy L. , Greenough William T.
Published: October 2014

We used confocal microscopy and immunohistochemistry (IHC) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. Twenty‐four female Macaca fascicularis monkeys divided into groups by age (10–12 years, 15–17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (BrdU) to mark new cells. Sixteen monkeys survived 15 weeks (5 weeks postexercise) and 8 monkeys survived 27 weeks (12 weeks postexercise) after initial BrdU injections. Additionally, five Macaca mulatta female monkeys (∼5.5–7 years) received single injections of BrdU and survived 2 days, 2 weeks, and 6 weeks after BrdU injections. Neural and glial antibodies were used to identify new cell phenotypes and to look for changes in proportions of these cells with respect to time and experimental conditions. No BrdU+/DCx+ cells were found but about 7.5% of new cells were calretinin‐positive (Cr+). BrdU+/GABA+ (gamma‐aminobutyric acid) cells were also found but no new Cr+ or GABA+ cells colabeled with a mature neuron marker, NeuN or chondroitin sulfate antibody, NG2. The proportion of new cells that were NG2+ was about 85% for short and long survival monkeys of which two, newly described perivascular phenotypes (Pldv and Elu) and a small percentage of pericytes (2.5%) comprised 44% and 51% of the new NG2+ cells, respectively. Proportions of NG2+ phenotypes were affected by post‐BrdU survival periods, monkey age, and possibly a postexercise sedentary period but no direct effect of exercise was found. J. Comp. Neurol. 523:849–868, 2015. © 2014 Wiley Periodicals, Inc.
Three Dimensional Angular Distributions of X‐Rays in a 4 kJ Plasma Focus Device for Different Anode Tips Using TLD‐100 Dosimeters
Authors: Baharani M. D. , Habibi M. , Mohammadi Kh.
Published: October 2014

Time and energy integrated measurements of the 3‐D angular distribution of X‐rays emission within the chamber of a 4 kJ Mather‐type plasma focus is investigated employing four different anode shapes and using nitrogen as the filling gas by the TLD‐100 thermoluminescence dosimeters. The distributions of X‐ray radiation in the energy range of 5 keV to several hundred keV were bimodal for all of the anode tips, peaked approximately at ±15°. The intensity of X‐rays decreased abruptly along the central axis of the device where the quasi cylindrical plasma pinch was formed. High intensity of X‐ray was observed in the case of a tapered ?at‐end anode, whereas less was obtained with the cylindrical hollow‐end anode. The maximum nitrogen X‐rays were for the tapered flat‐end anode at 4.5 mbar and 13 kV. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spatial Uniformity of Atmospheric Pressure Discharges: A Simulation Study
Authors: Iqbal M. M. , Turner M. M.
Published: October 2014

Spatial uniformity is important in most applications of dielectric barrier discharges operating at atmospheric pressure. However, such uniformity is not easily achieved. Under many conditions, a filamentary structure usually develops. In this paper, we employ a two‐dimensional self‐consistent fluid model to explore the influence of several factors on the evolution of spatial structure of dielectric barrier discharges. In particular, we contrast the behavior of discharges in pure helium and He‐N2 gas mixture, which represent the reduction in breakdown voltage of gas during the evolvement of uniform glow discharge plasma. The transformation from filamentary to uniform mode of discharge plasma is analyzed by the phenomenon of coalescence of filaments and we investigate the effect of several external discharge parameters, such as driving frequency and effect of overvoltage, and the dielectric constant of the barrier material for the uniform and filamentary discharge plasmas. This simulation study is useful to describe the spatio‐temporal profiles of electron density in different phases of the filamentary, uniform Townsend and glow discharge regimes under various constraints. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Plasma Diagnostics Using K‐Line Emission Profiles of Silicon
Authors: Chen Y. , Sengebusch A. , Reinholz H. , Röpke G.
Published: October 2014

Modifications of K‐line profiles due to a warm dense plasma environment are a suitable tool for plasma diagnostics. We focus on Si Kα emissions due to an electron transfer from 2P to 1S shell. Besides 2P fine structure effects we also consider the influence of excited and higher ionized emitters. Generally spoken, a plasma of medium temperature and high density (warm dense matter) is created from bulk Si the greater part of atoms is ionized. The high energy of Kα x‐rays is necessary to penetrate and investigate the Si sample. The plasma effect influences the many‐particle system resulting in an energy shift due to electron‐ion and electron‐electron interaction. In our work we focus on pure Si using LS coupling. Non‐perturbative wave functions are calculated as well as ionization energies, binding energies and relevant emission energies using the chemical ab initio code Gaussian 03. The plasma effect is considered within a perturbative approach to the Hamiltonian. Using Roothaan‐Hartree‐Fock wave functions we calculate the screening effect within an ion‐sphere model. The different excitation and ionization probabilities of the electronic L‐shell and M‐shell lead to a charge state distribution. Using this distribution and a Lorentz profile convolution with a Gaussian instrument function we calculate spectral line profiles depending on the plasma parameters. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Designing Non‐uniform Wafer Micro‐topography for Macroscopic Uniformity in Multi‐scale CVD Processes
Authors: Kallikounis Nikolaos , Kokkoris George , Cheimarios Nikolaos , Boudouvis Andreas G.
Published: October 2014

The potential of an additional degree of freedom (DOF) in the effort to meet film or deposition rate uniformity along the wafer in CVD processes is investigated. The investigation applies to cases of deposition on a wafer with micro‐topography where the common practice is a uniform density of patterns or features (e.g., trenches or holes), with the additional DOF as the feature density along the wafer. A non‐uniform density is designed with the objective of improving the uniformity; as a consequence, the differences in the profiles of the deposited films in all the features on the wafer will be compensated. A multi‐scale modeling framework is utilized for the design. The case study is aluminum metal‐organic (MO)CVD from dimethylethylamine alane under conditions of low macroscopic uniformity. Compared to a uniform density of the same number of trenches, the multi‐scale computations predict that the designed density of features, namely trenches, induces a remarkable improvement of both the macroscopic uniformity and the number of trenches on the wafer where the uniformity exceeds 0.95. The methodology is applied to features, i.e., the simplest unit cell of topography on a wafer, even if practical implementation of the variation of feature density is difficult. The same methodology can be applied to design the density of a cluster of features comprising a single device, or a die on the wafer.
Bauphysikalische und mechanische Aspekte von Mauerwerk nach Flutkatastrophen
Authors: Alfes Christoph , Schäfers Martin
Published: October 2014

Hochwasserereignisse treten in Deutschland immer wieder auf. Gebäude werden dabei bisweilen bis ins Obergeschoss überflutet. Der Beitrag geht auf die Trocknung von Mauerwerk mit unterschiedlichen Trocknungsmethoden ein und es wird erörtert, wie Trocknungszeiten durch maschinelle Unterstützung verkürzt werden können. Weiterhin wird gezeigt, wie sich mechanische Eigenschaften von Mauerwerk bei Durchfeuchtung sowie nach anschließender Trocknung darstellen. Abschließend wird auf die Möglichkeit eines Schutzes durch geeignete Abdichtungssysteme hingewiesen.

Building physical und mechanical aspects of masonry after flood disaster. Flood incidences appear in Germany from time to time. Buildings were occasionally flooded up to the first floor. The contribution assumes drying of masonry, drying methods and how drying periods can be shortened by applying technical equipment. Furtheron it is pointed out, how mechanical properties chance during moisture penetration und perform after subsequent drying. Concluding, possibilities of protecting masonry by suitable sealing systems are indicated.
Estimates of direct and indirect effects for early juvenile survival in captive populations maintained for conservation purposes: the case of Cuvier's gazelle
Authors: Ibáñez Belén , Cervantes Isabel , Gutiérrez Juan P. , Goyache Félix , Moreno Eulalia
Published: October 2014

Together with the avoidance of any negative impact of inbreeding, preservation of genetic variability for life‐history traits that could undergo future selective pressure is a major issue in endangered species management programmes. However, most of these programmes ignore that, apart from the direct action of genes on such traits, parents, as contributors of offspring environment, can influence offspring performance through indirect parental effects (when parental genotype and phenotype exerts environmental influences on offspring phenotype independently of additive genetic effects). Using quantitative genetic models, we estimated the additive genetic variance for juvenile survival in a population of the endangered Cuvier's gazelle kept in captivity since 1975. The dataset analyzed included performance recording for 700 calves and a total pedigree of 740 individuals. Results indicated that in this population juvenile survival harbors significant additive genetic variance. The estimates of heritability obtained were in general moderate (0.115–0.457) and not affected by the inclusion of inbreeding in the models. Maternal genetic contribution to juvenile survival seems to be of major importance in this gazelle's population as well. Indirect genetic and indirect environmental effects assigned to mothers (i.e., maternal genetic and maternal permanent environmental effects) roughly explain a quarter of the total variance estimated for the trait analyzed. These findings have major evolutionary consequences for the species as show that offspring phenotypes can evolve strictly through changes in the environment provided by mothers. They are also relevant for the captive breeding programme of the species. To take into account, the contribution that mothers have on offspring phenotype through indirect genetic effects when designing pairing strategies might serve to identify those females with better ability to recruit, and, additionally, to predict reliable responses to selection in the captive population.
The Brazilian Cerrado: assessment of water and soil degradation in catchments under intensive agricultural use
Authors: Hunke Philip , Mueller Eva Nora , Schröder Boris , Zeilhofer Peter
Published: October 2014

The Brazilian Cerrado is recognized as one of the most threatened biomes in the world, as the region has experienced a striking change from natural Cerrado vegetation to intense cash crop production. This paper reviews the history of land conversion in the Cerrado and the development of soil properties and water resources under past and ongoing land use. We compared soil and water quality parameters from different land uses considering 80 soil and 18 water studies conducted in different regions across the Cerrado to provide quantitative evidence of soil and water alterations from land use change.

Following the conversion of native Cerrado, significant effects on soil pH, bulk density and available P and K for croplands and less‐pronounced effects on pastures were evident. Soil total N did not differ between land uses because most of the sites classified as croplands were nitrogen‐fixing soybeans, which are not artificially fertilized with N. In contrast, water quality studies showed nitrogen enrichment in agricultural catchments, indicating fertilizer impacts and potential susceptibility to eutrophication. Regardless of the land use, P is widely absent because of the high‐fixing capacities of deeply weathered soils and the filtering capacity of riparian vegetation. Pesticides, however, were consistently detected throughout the entire aquatic system. In several case studies, extremely high‐peak concentrations exceeded Brazilian and European Union (EU) water quality limits, which were potentially accompanied by serious health implications. Land use intensification is likely to continue, particularly in regions where less annual rainfall and severe droughts are projected in the northeastern and western Cerrado. Thus, the leaching risk and displacement of agrochemicals are expected to increase, particularly because the current legislation has caused a reduction in riparian vegetation. We conclude that land use intensification is likely to seriously limit the Cerrado's future regarding both agricultural productivity and ecosystem stability. Because only limited data are available, we recommend further field studies to understand the interaction between terrestrial and aquatic systems. This study may serve as a valuable database for integrated modelling to investigate the impact of land use and climate change on soil and water resources and to test and develop mitigation measures for the Cerrado. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐term follow‐up in optimally treated and stable heart failure patients: primary care vs. heart failure clinic. Results of the COACH‐2 study
Authors: Luttik Marie Louise A. , Jaarsma Tiny , van Geel Peter Paul , Brons Maaike , Hillege Hans L. , Hoes Arno W. , de Jong Richard , Linssen Gerard , Lok Dirk J.A. , Berge Marjolein , van Veldhuisen Dirk J.
Published: October 2014

Aims

It has been suggested that home‐based heart failure (HF) management in primary care may be an alternative to clinic‐based management in HF patients. However, little is known about adherence to HF guidelines and adherence to the medication regimen in these home‐based programmes. The aim of the current study was to determine whether long‐term follow‐up and treatment in primary care is equally effective as follow‐up at a specialized HF clinic in terms of guideline adherence and patient adherence, in HF patients initially managed and up‐titrated to optimal treatment at a specialized HF clinic.

Methods and results

We conducted a multicentre, randomized, controlled study in 189 HF patients (62% male, age 72 ± 11 years), who were assigned to follow‐up either in primary care (n = 97) or in a HF clinic (n = 92). After 12 months, no differences between guideline adherence, as estimated by the Guideline Adherence Indicator (GAI‐3), and patient adherence, in terms of the medication possession ratio (MPR), were found between treatment groups. There was no difference in the number of deaths (n = 12 in primary care and n = 8 in the HF clinic; P = 0.48), and hospital readmissions for cardiovascular (CV) reasons were also similar. The total number of unplanned non‐CV hospital readmissions, however, tended to be higher in the primary care group (n = 22) than in the HF clinic group (n = 10; P = 0.05).

Conclusions

Patients discharged after initial management in a specialized HF clinic can be discharged to primary care for long‐term follow‐up with regard to maintaining guideline adherence and patient adherence. However, the complexity of the HF syndrome and its associated co‐morbidities requires continuous monitoring. Close collaboration between healthcare providers will be crucial in order to provide HF patients with optimal, integrated care.
The Geomorphological Context of Medieval Juslibol Castle in the Middle Reaches of the River Ebro, Spain
Authors: Peña‐Monné José L. , Rubio‐Fernández Virginia , Longares‐Aladrén Luis A. , Gutiérrez‐González Francisco J. , Pérez‐Lambán Fernando , Laliena‐Corbera Carlos
Published: October 2014

An interdisciplinary non‐invasive research strategy combining the analysis of archival documents, detailed geomorphological mapping, Quaternary stratigraphic studies, analysis of ceramics, and radiocarbon dating was designed to reconstruct the evolution of the Mezimegeer–Juslibol Castle, northeastern Spain. This fortress had great strategic importance in the siege and conquest of the nearby Islamic city of Saraqusta by the Christians in A.D. 1118. The castle and moat complex was built in the mid‐10th century. In the mid‐12th century, its rapid degradation began, as it is shown by this geoarchaeological study of the sediments in the moats. Its present state of decay is due to later erosion that is promoted by the unstable bedrock of Miocene gypsum, highly deformed gravels that form a Pleistocene fluvial terrace, and the environmental aridity.
Primitive Ordovician (Floian) echinoderms from Sandu, Guizhou Province, South China, and their significance
Authors: Paul Christopher R. C. , Donovan Stephen K. , Muir Lucy A. , Botting Joseph P. , Lin Jih‐Pai , Zhang Yuandong
Published: October 2014

Pelmatozoans diversified primarily during the Middle and Late Ordovician Period, with Early Ordovician records being much more limited, resulting in many gaps in our knowledge of the early stages of their diversification. Dissociated pelmatozoan ossicles have been found abundantly in one section in the Tonggao Formation (Tetragraptus approximatus Biozone, Floian, Early Ordovician). Most of the ossicles are thecal plates and stem ossicles from hemicosmitoid and glyptocystitoid cystoids. Thecal plates of ‘Cheirocrinus’ sp., Polycosmites sp., and other plates of uncertain affinity are described. A different ossicle type, Pentagonopentagonalis (col.), may represent crinoid remains; this would be one of the earliest occurrences of the class. The thecal ossicles and columnals are all considered, as both sets of data are desirable to determine the most complete estimate of generic diversity. The echinoderm ossicles may have been transported in from shallower water palaeoenvironments and clusters of ossicles may represent coprolites or regurgitates. Estimates of Early Ordovician palaeogeography that place this site at 30°S or near the palaeoequator are supported by the physiological requirements of the primitive echinoderms described herein. Copyright © 2014 John Wiley & Sons, Ltd.
Trends in Managed Care Cost Containment: An Analysis of the Managed Care Backlash
Authors: Dugan Jerome
Published: October 2014

Consumer dissatisfaction with the quality and limitations of managed health care led to rapid disenrollment from managed care plans and demands for regulation between 1998 and 2003. Managed care organizations, particularly health maintenance organizations (HMOs), now face quality and coverage mandates that restrict them from using their most aggressive strategies for managing costs. This paper examines the effect of this backlash on managed care's ability to contain costs among short‐term, non‐federal hospitals between 1998 and 2008. The results show that the impact of increased HMO penetration on inpatient costs reversed over the study period, but HMOs were still effective at containing outpatient costs. These findings have important policy implications for understanding the continuing role that HMOs should play in cost containment policy and for understanding how effective the latest wave of cost containment institutions may perform in heavily regulated markets. Copyright © 2014 John Wiley & Sons, Ltd.
Signal transducer and activator of transcription 5b drives malignant progression in a PDGFB‐dependent proneural glioma model by suppressing apoptosis
Authors: Gressot Loyola V. , Doucette Tiffany A. , Yang Yuhui , Fuller Gregory N. , Heimberger Amy B. , Bögler Oliver , Rao Arvind , Latha Khatri , Rao Ganesh
Published: October 2014

Signal transducer and activator of transcription 5b (STAT5b) is likely the relevant STAT5 isoform with respect to the process of malignant progression in gliomas. STAT5b is a latent cytoplasmic protein involved in cell signaling through the modulation of growth factors, apoptosis, and angiogenesis. Previous in vitro studies have shown increased STAT5b expression in glioblastomas relative to low‐grade tumors and normal brain. We recently demonstrated that phosphorylated STAT5b associates with delta epidermal growth factor receptor in the nucleus and subsequently binds the promoters of downstream effector molecules, including aurora kinase A. Analysis of TCGA dataset reveals that STAT5b is predominantly expressed in proneural (PN) gliomas relative to mesenchymal and neural gliomas. Here, we modeled ectopic expression of STAT5b in vivo using a platelet‐derived growth factor subunit B (PDGFB)‐dependent mouse model of PN glioma to determine its effect on tumor formation and progression. We showed that coexpression of STAT5b and PDGFB in mice yielded a significantly higher rate of high‐grade gliomas than PDGFB expression alone. We also observed shorter survival in the combined expression set. High‐grade tumors from the STAT5b + PDGFB expression set were found to have a lower rate of apoptosis than those from PDGFB alone. Furthermore, we showed that increased expression of STAT5b + PDGFB led to increased expression of downstream STAT5b targets, including Bcl‐xL, cyclin D1 and aurora kinase A in high‐grade tumors when compared to tumors derived from PDGFB alone. Our findings show that STAT5b promotes the malignant transformation of gliomas, particularly the PN subtype, and is a potential therapeutic target.
Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients
Authors: Madic Jordan , Kiialainen Anna , Bidard Francois‐Clement , Birzele Fabian , Ramey Guillemette , Leroy Quentin , Frio Thomas Rio , Vaucher Isabelle , Raynal Virginie , Bernard Virginie , Lermine Alban , Clausen Inga , Giroud Nicolas , Schmucki Roland , Milder Maud , Horn Carsten , Spleiss Olivia , Lantz Olivier , Stern Marc‐Henri , Pierga Jean‐Yves , Weisser Martin , Lebofsky Ronald
Published: October 2014

Circulating tumor DNA (ctDNA) is a new circulating tumor biomarker which might be used as a prognostic biomarker in a way similar to circulating tumor cells (CTCs). Here, we used the high prevalence of TP53 mutations in triple negative breast cancer (TNBC) to compare ctDNA and CTC detection rates and prognostic value in metastatic TNBC patients. Forty patients were enrolled before starting a new line of treatment. TP53 mutations were characterized in archived tumor tissues and in plasma DNA using two next generation sequencing (NGS) platforms in parallel. Archived tumor tissue was sequenced successfully for 31/40 patients. TP53 mutations were found in 26/31 (84%) of tumor samples. The same mutation was detected in the matched plasma of 21/26 (81%) patients with an additional mutation found only in the plasma for one patient. Mutated allele fractions ranged from 2 to 70% (median 5%). The observed correlation between the two NGS approaches (R2 = 0.903) suggested that ctDNA levels data were quantitative. Among the 27 patients with TP53 mutations, CTC count was ≥1 in 19 patients (70%) and ≥5 in 14 patients (52%). ctDNA levels had no prognostic impact on time to progression (TTP) or overall survival (OS), whereas CTC numbers were correlated with OS (p = 0.04) and marginally with TTP (p = 0.06). Performance status and elevated LDH also had significant prognostic impact. Here, absence of prognostic impact of baseline ctDNA level suggests that mechanisms of ctDNA release in metastatic TNBC may involve, beyond tumor burden, biological features that do not dramatically affect patient outcome.
PRACTICAL TOOLS FOR POLICY ANALYSIS IN DSGE MODELS WITH MISSING SHOCKS
Authors: Caldara Dario , Harrison Richard , Lipińska Anna
Published: October 2014

In this paper we analyze the propagation of shocks originating in sectors that are not present in a baseline dynamic stochastic general equilibrium (DSGE) model. Specifically, we proxy the missing sector through a small set of factors that feed into the structural shocks of the DSGE model to create correlated disturbances. We estimate the factor structure by either matching impulse responses of the augmented DSGE model to those generated by an auxiliary model or by using Bayesian techniques. We apply this methodology to track the effects of oil shocks and housing demand shocks in models without energy or housing sectors. Copyright © 2014 John Wiley & Sons, Ltd.
An Empirical Test of Pricing Kernel Monotonicity
Authors: Beare Brendan K. , Schmidt Lawrence D. W.
Published: October 2014

A large class of asset pricing models predicts that securities which have high payoffs when market returns are low tend to be more valuable than those with high payoffs when market returns are high. More generally, we expect the projection of the stochastic discount factor on the market portfolio—that is, the discounted pricing kernel evaluated at the market portfolio—to be a monotonically decreasing function of the market portfolio. Numerous recent empirical studies appear to contradict this prediction. The non‐monotonicity of empirical pricing kernel estimates has become known as the pricing kernel puzzle. In this paper we propose and apply a formal statistical test of pricing kernel monotonicity. We apply the test using 17 years of data from the market for European put and call options written on the S&P 500 index. Statistically significant violations of pricing kernel monotonicity occur in a substantial proportion of months, suggesting that observed non‐monotonicities are unlikely to be the product of statistical noise. Copyright © 2014 John Wiley & Sons, Ltd.
Enhanced sampling simulations of DNA step parameters
Authors: Karolak Aleksandra , van der Vaart Arjan
Published: October 2014

A novel approach for the selection of step parameters as reaction coordinates in enhanced sampling simulations of DNA is presented. The method uses three atoms per base and does not require coordinate overlays or idealized base pairs. This allowed for a highly efficient implementation of the calculation of all step parameters and their Cartesian derivatives in molecular dynamics simulations. Good correlation between the calculated and actual twist, roll, tilt, shift, and slide parameters is obtained, while the correlation with rise is modest. The method is illustrated by its application to the methylated and unmethylated 5′‐CATGTGACGTCACATG‐3′ double stranded DNA sequence. One‐dimensional umbrella simulations indicate that the flexibility of the central CG step is only marginally affected by methylation. © 2014 Wiley Periodicals, Inc.
Failure to observe untested derived stimulus relations in extinction: Implications for understanding stimulus‐equivalence formation
Authors: Doughty Adam H. , Leake Lesley W. , Stoudemire M. Lee
Published: October 2014

Wilson and Hayes (1996) and Doughty, Kastner, and Bismark (2011) observed resurgence of past equivalence relations when newer equivalence relations were punished or extinguished, respectively. Their findings support the notion that deriving stimulus relations is a form of operant behavior. Although there is consensus regarding the operant nature of deriving untrained stimulus relations, the necessary and sufficient conditions that establish these relations remain unclear. For example, in the aforementioned work, the resurgent equivalence relations were tested earlier in each study. The present research investigated whether this resurgence of equivalence relations requires their initial testing. In Experiment 1, college students received arbitrary matching‐to‐sample training in Phase 1. After these baseline discriminations were established, equivalence testing was omitted. In Phase 2, four 4‐member equivalence classes were established that were inconsistent with the Phase‐1 training. These Phase‐2 relations then were extinguished to test whether the equivalence relations consistent with Phase‐1 training would occur. Unlike in earlier research, these untested relations did not occur reliably. This finding was replicated in Experiment 2, and additional tests of stimulus relatedness did not reveal any evidence of derived stimulus relations consistent with the Phase‐1 training. The present research extends other findings suggesting that the equivalence‐testing context helps establish these stimulus classes.
Increased tumor distribution and expression of histidine‐rich plasmid polyplexes
Authors: Leng Qixin , Chou Szu‐Ting , Scaria Puthupparampil V. , Woodle Martin C. , Mixson A. James
Published: October 2014

Background

Selecting nonviral carriers for in vivo gene delivery is often dependent on determining the optimal carriers from transfection assays in vitro. The rationale behind this in vitro strategy is to cast a net sufficiently wide to identify the few effective carriers of plasmids for in vivo studies. Nevertheless, many effective in vivo carriers may be overlooked by this strategy because of the marked differences between in vitro and in vivo assays.

Methods

After solid‐phase synthesis of linear and branched histidine/lysine (HK) peptides, the two peptide carriers were compared for their ability to transfect MDA‐MB‐435 tumor cells in vitro and then in vivo.

Results

By contrast to their transfection activity in vitro, the linear H2K carrier of plasmids was far more effective in vivo compared to the branch H2K4b. Surprisingly, negatively‐charged polyplexes formed by the linear H2K peptide gave higher transfection in vivo than did those with a positive surface charge. To examine the distribution of plasmid expression within the tumor from H2K polyplexes, we found widespread expression by immunohistochemical staining. With a fluorescent tdTomato expressing‐plasmid, we confirmed a pervasive distribution and gene expression within the tumor mediated by the H2K polyplex.

Conclusions

Although mechanisms underlying the efficiency of gene expression are probably multifactorial, unpacking of the H2K polyplex within the tumor appears to have a significant role. Further development of these H2K polyplexes represents an attractive approach for plasmid‐based therapies of cancer. © 2014 The Authors. The Journal of Gene Medicine published by John Wiley & Sons, Ltd.
Ultrastructure of spermatozoa of orsolobidae (Haplogynae, Araneae) with implications on the evolution of sperm transfer forms in Dysderoidea
Authors: Lipke Elisabeth , Ramírez Martín J. , Michalik Peter
Published: October 2014

Cover illustration. Haplogynae are highly diverse group of spiders with respect to the primary male genital system and sperm characteristics. Within this group, different sperm transfer forms evolved, i.e., individually transferred sperm (cleistospermia), sperm conjugates (primary and secondary sperm conjugates). In this issue of the Journal of Morphology, Lipke et al. (pp. 1238–1257 10.1002/jmor.20298) study the evolution of sperm transfer forms in Orsolobidae by using histology, TEM and X‐ray microscopy. The cover image shows a 3D‐reconstruction of a sperm conjugate of Tasmanoonops alipes comprising two spermatozoa that are arranged opposed to each other.
Glucose and glycerol concentrations and their tracer enrichment measurements using liquid chromatography tandem mass spectrometry
Authors: Bornø Andreas , Foged Lene , van Hall Gerrit
Published: October 2014

The present study describes a new liquid chromatography tandem mass spectrometry method for high‐throughput quantification of glucose and glycerol in human plasma using stable isotopically labeled internal standards and is suitable for simultaneous measurements of glucose and glycerol enrichments in connection to in vivo metabolic studies investigating glucose turnover and lipolytic rate. Moreover, in order to keep up with this new fast analysis, simple derivatization procedures have been developed.

Prior to analysis, glucose and glycerol were derivatized using benzoyl chloride in order to form benzoylated derivatives via new simplified fast procedures. For glucose, two internal standards were evaluated, [U‐13C6]glucose and [U‐13C6, D7]glucose, and for glycerol, [U‐13C3, D8]glycerol was used. The method was validated by means of calibration curves, quality control samples, and plasma samples spiked with [6,6‐D2]glucose, [U‐13C6]glucose, and [1,1,2,3,3‐D5]glycerol in order to test accuracy, precision, and recovery of the method. Moreover, post preparative and freeze‐thaw sample stability were tested.

The correlation of calibration curves for the glucose concentration were r2 = 0.9998 for [U‐13C6]glucose and r2 = 0.9996 for [U‐13C6, D7]glucose, and r2 = 0.9995 for the glycerol concentration. Interday accuracy for glucose using [U‐13C6]glucose and glycerol determined in spiked plasma were respectively 103.5% and 106.0%, and the coefficients of variation were 2.0% and 9.7%, respectively. After derivatization, plasma samples were stable for at least 14 days.

In conclusion, we have developed and validated a novel, accurate, and sensitive high‐throughput liquid chromatography tandem mass spectrometry method for simultaneous determination of glucose and glycerol concentrations and enrichment of infused tracers most commonly used in human metabolic kinetic studies. Copyright © 2014 John Wiley & Sons, Ltd.
Conformational changes of ubiquitin during electrospray ionization as determined by in‐ESI source H/D exchange combined with high‐resolution MS and ECD fragmentation
Authors: Kostyukevich Yury , Kononikhin Alexey , Popov Igor , Nikolaev Eugene
Published: October 2014

In the paper, we have demonstrated the possibility of performing hydrogen/deuterium (H/D) exchange of proteins in the region of gas‐phase ion formation in an electrospray ion source by saturating the electrospray ionization source with vapors of a deuterating agent (D2O or MeOD). In this region, charged droplets are shrinking and the protein ions transfer into the gas phase. As a model protein, we have used ubiquitin whose ion mobility spectrometry and gas‐phase H/D exchange in the vacuum part of a mass spectrometer demonstrated the presence of gas‐phase conformers with different cross sections and H/D exchange rates. In our experiments, we observed monomodal deuterium distributions for all solvents, charge states, desolvating capillary temperature and types of deuterating agent. Also, we found that the number of H/D exchanges increases with an increasing desolvating capillary temperature and decreasing charge state. We observed that solution composition (49 : 50 : 1 H2O : MeOH : formic acid or 99 : 1 H2O : formic acid) influences the charge‐state distribution but did not change the degree of H/D exchange for the same charge state. Electron‐capture dissociation fragmentation shows that higher charge states contain a segment that is protected from access by the deuterating agent. Copyright © 2014 John Wiley & Sons, Ltd.
Approach to the study of flavone di‐C‐glycosides by high performance liquid chromatography‐tandem ion trap mass spectrometry and its application to characterization of flavonoid composition in Viola yedoensis
Authors: Cao Jie , Yin Chengle , Qin Yan , Cheng Zhihong , Chen Daofeng
Published: October 2014

The mass spectrometric (MS) analysis of flavone di‐C‐glycosides has been a difficult task due to pure standards being unavailable commercially and to that the reported relative intensities of some diagnostic ions varied with MS instruments. In this study, five flavone di‐C‐glycoside standards from Viola yedoensis have been systematically studied by high performance liquid chromatography‐electrospray ionization‐tandem ion trap mass spectrometry (HPLC‐ESI‐IT‐MSn) in the negative ion mode to analyze their fragmentation patterns. A new MS2 and MS3 hierarchical fragmentation for the identification of the sugar nature (hexoses or pentoses) at C‐6 and C‐8 is presented based on previously established rules of fragmentation. Here, for the first time, we report that the MS2 and MS3 structure‐diagnostic fragments about the glycosylation types and positions are highly dependent on the configuration of the sugars at C‐6 and C‐8. The base peak (0,2X10,2X2− ion) in MS3 spectra of di‐C‐glycosides could be used as a diagnostic ion for flavone aglycones. These newly proposed fragmentation behaviors have been successfully applied to the characterization of flavone di‐C‐glycosides found in V. yedoensis. A total of 35 flavonoid glycosides, including 1 flavone mono‐C‐hexoside, 2 flavone 6,8‐di‐C‐hexosides, 11 flavone 6,8‐di‐C‐pentosides, 13 flavone 6,8‐C‐hexosyl‐C‐pentosides, 5 acetylated flavone C‐glycosides and 3 flavonol O‐glycosides, were identified or tentatively identified on the base of their UV profiles, MS and MSn (n = 5) data, or by comparing with reference substances. Among these, the acetylated flavone C‐glycosides were reported from V. yedoensis for the first time. Copyright © 2014 John Wiley & Sons, Ltd.
In‐time and in‐space tandem mass spectrometry to determine the metabolic profiling of flavonoids in a typical sweet cherry (Prunus avium L.) cultivar from Southern Italy
Authors: Crupi Pasquale , Genghi Rosalinda , Antonacci Donato
Published: October 2014

This paper presents a comprehensive analytical methodology, based on ‘in‐time’ and ‘in‐space’ tandem mass spectrometry (MS) techniques, to identify and quantify flavonoid compounds in a typical Italian sweet cherry cultivar (cv. Ferrovia). Five anthocyanins, four flavan‐3‐ols and nine flavonols were determined by means of hyphenated high‐performance liquid chromatography – multi‐stage MS (HPLC‐MSn) analyses (MSn up to MS4), among which quercetin‐3‐O‐rutinoside‐7‐O‐glucoside, kaempferol‐3‐O‐rutinoside‐7‐O‐glucoside, quercetin‐3‐O‐galactosyl‐rhamnoside and quercetin‐3‐O‐coumaroylglucoside were tentatively identified in sweet cherries for the first time. Ultrafast HPLC and tandem MS (UHPLC‐MS/MS) analyses through multiple reaction monitoring experiments showed that cyanidin‐3‐O‐rutinoside and cyanidin‐3‐O‐glucoside were the main anthocyanins of cv. Ferrovia at maturity. Moreover, consistent levels of catechin and epicatechin as well as quercetin‐3‐O‐rutinoside and kaempferol‐3‐O‐rutinoside were also found. Because flavonoids have been ascribed as potential health‐promoting compounds, gathered findings provide new insight into the knowledge of the quali‐quantitative profile of these phytochemicals into a widespread fruit such as sweet cherry. Copyright © 2014 John Wiley & Sons, Ltd.
Projected changes in extreme precipitation characteristics for Central Eastern Germany (21st century, model‐based analysis)
Authors: Schwarzak Susann , Hänsel Stephanie , Matschullat Jörg
Published: October 2014

Changes in frequency, duration and/or intensity of extreme precipitation events, such as heavy precipitation or drought, profoundly impact both society and the natural environment. Regional climate models are valuable tools to assess any future progress of such events, and to complement the development of regional and local adaptation and mitigation strategies – here for the model region Dresden within the REGKLAM project. Multi‐model approaches may alleviate some of the problems related to uncertainties of projected changes.

The bandwidth of future climate conditions in Central Eastern Germany has been estimated, using 12 regional climate projections in daily resolution as simulated within the EU‐project ENSEMBLES (emission scenario A1B). Validation of the model runs against an observation data set displayed significant difficulties of the models to describe the regional precipitation characteristics. Shortcomings are particularly obvious in realistically simulating dry period characteristics, likely due to an overestimation of precipitation totals. Most models agree in the projection of more frequent and longer‐lasting drought events during summer, while wet phase frequency and persistence is projected to increase in winter. Extreme precipitation events (99th percentile) are likely to increase by the end of the 21st century in most seasons – even in summer, despite projected decreasing average precipitation.

The suggested display of all individual model results allows comparing the characteristics and the trend behaviour of the individual regional climate projections. This supports selecting the suitable model(s) for specific impact modelling demands.
Multi‐dataset comparison of gridded observed temperature and precipitation extremes over China
Authors: Yin Hong , Donat Markus G. , Alexander Lisa V. , Sun Ying
Published: October 2014

Five gridded datasets containing measures of temperature and precipitation extremes over the past five decades over China are compared. Time series, spatial averages and trends in China's coldest and warmest days and nights and wettest days are estimated from these datasets that vary in their station network density, interpolation procedures and the order in which extremes are calculated. We find that country‐wide trends in temperature extremes are coherent irrespective of dataset choice although actual values are generally smaller in the dataset in which indices are calculated from daily interpolated grids rather than from station points. There are also some regional differences in trends especially over regions with sparse data networks, e.g. the Tibetan Plateau. Averaged across China, trends calculated over the period 1961–2009 vary from a minimum of 0.13 °C decade−1(hottest day) to 0.65 °C decade−1(coldest night). The coldest day and night have tended to warm faster than the warmest day and night. Trends in precipitation extremes are much less coherent spatially and can be positive or negative depending on the choice of dataset. The length of station record chosen is also vital to eliminate spurious trends. The results have important implications for detection and attribution and model evaluation studies.
Salting‐out assisted liquid–liquid extraction coupled to dispersive liquid–liquid microextraction for the determination of chlorophenols in wine by high‐performance liquid chromatography
Authors: Fan Yingying , Hu Shibin , Liu Shuhui
Published: October 2014

A novel procedure of sample preparation combined with high‐performance liquid chromatography with diode array detection is introduced for the analysis of highly chlorinated phenols (trichlorophenols, tetrachlorophenols, and pentachlorophenol) in wine. The main features of the proposed method are (i) low‐toxicity diethyl carbonate as extraction solvent to selectively extract the analytes without matrix effect, (ii) the combination of salting‐out assisted liquid–liquid extraction and dispersive liquid–liquid microextraction to achieve an enrichment factor of 334–361, and (iii) the extract is analyzed by high‐performance liquid chromatography to avoid derivatization. Under the optimum conditions, correlation coefficients (r) were >0.997 for calibration curves in the range 1–80 ng/mL, detection limits and quantification limits ranged from 0.19 to 0.67 and 0.63 to 2.23 ng/mL, respectively, and relative standard deviation was <8%. The method was applied for the determination of chlorophenols in real wines, with recovery rates in the range 82–104%.