bluuebunny/crossref_metadata_2025 huggingface dataset:
How Common Is the Common Core?
Authors: Thomas Amanda , Edson Alden J.
Published: November 2014

This article identifies major differences between NCTM's Principles and Standards for School Mathematics and the Common Core State Standards for Mathematics, including examples and implications for practice.
Solving Cubic Equations with Curly Roots
Authors: Kalman Dan , Burke Maurice
Published: November 2014

A nonstandard function, the curly root, is used in an alternative approach to solve cubic equations.
The Polymorphism of EME1 Gene is Associated with an Increased Risk of Lung Cancer: A Case-Control Study from Chinese Population
Authors: Jianwei Zhao  , Yongxiu Chen  , Xiaoxiao Lu  , Di Wu  , Jiansong Chen  , Zhihuang Chen  , Lin Liu  , Lei Yang  , Lan Zhang  , Yifeng Zhou  , Jiachun Lu
Published: November 2014

DNA double-strand breaks (DSBs) can lead to genomic instability and cancer susceptibility if unrepaired. EME1 is one of the key proteins that participate in the recognition and repair of DSBs in humans. We hypothesized that the exonic variants of EME1 are associated with lung cancer risk. In a two-stage case-control study of 1559 lung cancer patients and 1679 cancer-free controls, we genotyped two exonic variants of EME1(Glu69Asp: rs3760413T>G and Ile350Thr: rs12450550T>C) and analyzed their associations with risk of lung cancer. We found that the Asp variant genotypes conferred 1.35-folds risk of lung cancer compared to the Glu/Glu genotype (OR = 1.35, 95%CI = 1.18-1.56, P = 2.18 ƒ 10-5) in both stages. However, the SNP Ile350Thr was not confirmed to be associated with cancer risk in both stages. Moreover, by querying the gene expression database, we further found that the 69Asp variant genotypes confer a significantly lower mRNA expression of EME1 than the Glu/Glu genotype in 260 cases of lymphoblastoid cells (P=0.013). Our findings suggested that the SNP Glu69Asp of EME1 is associated with an increased risk of lung cancer, and may be a functional biomarker to predict lung cancer risk in Chinese. Validations in other ethnics are warranted.
Cancer Metastasis and Cancer Stem Cells
Authors: Huan Liu  , Haijuan Wang  , Haili Qian
Published: November 2014

Increasing amounts of evidence have indicated the important role of cancer stem cells (CSCs) in tumorigenesis and relapse. Metastasis is a key biological characteristic of malignant tumors. How cancer cells spread from the original tumor into the circulation and then infiltrate distant organs remains a topic of debate. Moreover, understanding the differences between metastasized and non-metastasized cancer cells is the key to develop strategies to block metastasis. In this review, we summarized the development of the CSC theory related to tumor metastasis over the last two decades.
Oxycodone Immediate Release for Cancer Pain Management in Turkey: Maximizing Value in Opioid Analgesics
Authors: Joseph V. Pergolizzi Jr  , Robert Taylor Jr  , Gianpietro Zampogna  , Fuat H. Demirelli  , Serdar Erdine  , Robert B. Raffa
Published: November 2014

Cancer pain can be severe, yet is often undertreated. In many parts of the world, there is a reluctance to prescribe narcotics for analgesia. Since the World Health Organization first published its pain ladder  treatment paradigm in 1988, cancer pain is usually treated initially with nonopioids, then weak opioids, and finally strong opioids along with adjuvant agents as the pain intensifies. When initiating opioid therapy for cancer patients, the clinician must consider whether the patient is opioid naƒ¯ve or opioid experienced. For naƒ¯ve patients, opioid therapy must be started slowly, at a low dose initially, with adverse events anticipated and treated proactively. In all cases, opioid titration involves a controlled, stepwise increase of opioid dose until adequate (but not necessarily 100%) analgesia is achieved. A variety of opioid products are available, including immediate-release and controlled-release formulations. Immediate-releaseformulations are designed for easy titration to adequate analgesia; their rapid onset of action also makes them appropriate for managing breakthrough pain. Although morphine has long been considered the gold standard of cancer analgesics, oral oxycodone is increasingly used and is similar to morphine in efficacy and safety for cancer patients. Indeed, about 75% of morphine-tolerant patients can be successfully rotated to oxycodone. Adverse events with oxycodone are similar or perhaps favorable compared to those of other strong opioids. Because cancer pain can be challenging to treat, the addition of oral oxycodone IR is an important new tool for clinicians to consider when trying to control cancer pain.
Le cadre juridique du paiement par carte de crédit et les moyens de défense du titulaire
Authors: Cumyn Michelle , Lalancette Lina
Published: November 2014

Le paiement par carte de crédit est une opération soit tripartite, soit quadripartite. Pour en rendre compte adéquatement, il importe de travailler à partir du modèle plus complexe qui est celui de la carte quadripartite. Celui-ci met en présence quatre acteurs principaux, soit le titulaire, le commerçant, l’institution financière du commerçant et l’institution financière émettrice. Trois des quatre rapports d’obligation intervenant entre ces parties font l’objet de notre étude : l’obligation initiale du titulaire de payer une somme d’argent au commerçant et celles, qui lui sont substituées, du titulaire de payer cette somme à l’institution financière émettrice et de l’institution financière du commerçant de payer ce dernier. C’est la manipulation de la carte qui opère le remplacement de la première dette par les deux autres. Le titulaire est immédiatement libéré envers le commerçant, car ce dernier bénéficie dès lors d’une garantie de paiement. Parmi les qualifications généralement proposées du paiement par carte de crédit (mandat, subrogation légale, cession de créance, délégation et novation), c’est la qualification de novation qui doit être retenue. En vertu du droit commun, le titulaire peut invoquer à l’encontre de l’institution financière émettrice soit l’invalidité du paiement, soit la nullité absolue ou relative du contrat conclu avec le commerçant. Le titulaire consommateur bénéficie d’une protection additionnelle en vertu des articles 118 à 130 de la Loi sur la protection du consommateur. Les articles 103 et 116 L.p.c, pour leur part, ne s’appliquent pas au paiement par carte de crédit. À la différence du Québec, plusieurs pays, comme les États-Unis et le Royaume-Uni, accordent depuis de nombreuses années au titulaire consommateur la possibilité de faire valoir contre l’institution financière émettrice des moyens de défense issus de son contrat avec le commerçant, ce qui semble aller à l’encontre de l’opinion selon laquelle une telle mesure constituerait un fardeau trop lourd pour les institutions financières. Les institutions financières canadiennes acceptent d’ailleurs le plus souvent de donner suite à une contestation qui leur est présentée par un titulaire insatisfait d’un bien ou d’un service acquis avec sa carte de crédit. L’adoption d’un cadre légal présenterait l’avantage de cristalliser cette procédure actuellement appliquée sur une base discrétionnaire, et dont seuls les titulaires très bien informés sont susceptibles de tirer profit.
El nuevo debate sobre el populismo y sus raíces en la transición democrática: el caso argentino
Authors: Aboy Carlés Gerardo
Published: November 2014

This paper examines the concerns which have led to the new wave of studies on populism in Argentina, focusing more on the debate surrounding the establishment of a new institutional framework typical of the 1980s than on the proliferation of 21st-century popular governments in South America. The typical characteristics and problems encountered in these studies are explained, and the defining features of the populist experience in 20th-century Argentina are analyzed by drawing comparisons with other populist processes in the region. Finally, the paper analyzes how certain features persist in the new political order, while others have gone through complete transformations since it was established in 1983.
Populismo en América Latina: desde la teoría hacia el análisis político. Discurso, sujeto e inclusión en el caso argentino
Authors: Retamozo Martín
Published: November 2014

The current processes have reignited the debate surrounding populism in Latin America; however, the category‘s theoretical status is far from being clarified. In this context, the article suggests that populism could contribute to political theory, starting from the open perspective of Ernesto Laclau, while also drawing on the definition of functional fields in its political analysis: populism as discourse; as a construction of a political subject; and as promoting the inclusion of all that has been excluded in the social order. Starting from these developments, the second part of the article uses these contributions to analyze the current political process in Argentina, and specifically the phenomenon of kirchnerism.
Encontrar la cultura: estrategias de indagación para el análisis sociopolítico
Authors: Fernández de Mosteyrín Laura , Luz Morán María
Published: November 2014

This paper is intended to explore modes of inquiry into culture and public discourse. To this end, the first part of the paper is devoted to situating discourses and practices within a broad notion of culture, a notion which goes beyond the cultural turn and focuses on culture in action, as well as on the dynamic dialogue between structure and action. In order to advance in a methodological proposal, the paper examines four different studies that propose differentiated strategies for making the concept of culture operational.
Relaciones entre dispositivos administrativos y arreglos familiares en la gestión de la infancia “con derechos vulnerados”. Una aproximación etnográfica
Authors: Barna Agustín
Published: November 2014

This article is part of an ethnographic study that explores processes of social intervention relating to children “with violated rights” in a state device in the metropolitan area of Buenos Aires, Argentina. I focus on the actions of institutional agents and their interactions with the “beneficiaries”, which constitute the most common dimension of the “policy of comprehensive protection of the rights of children”. Here I explore some implications of the new forms of relations between the administrative devices and the families and adults “responsible” for the children’s immediate environment. This reconfiguration is characterized by an asymmetric complementarity between administrators and those they administer to, which is constitutive of the modes of managing childhood in contemporary times.
Vivienda/violencia: intersecciones de la vivienda y la violencia intrafamiliar en Ciudad Bolívar, Bogotá
Authors: Lemaitre Ripoll Julieta , García Jaramillo Sandra , Ramírez Rodríguez Hernán
Published: November 2014

This article explores the impact of self-owned versus rented housing on violence against women in Ciudad Bolívar, Bogota. We used a mixed methods approach based on semi-structured interviews in the locality as well as on observation of domestic violence cases in the locality, between 2011 and 2012. We also analyzed the statistical data of the National Health and Demography Survey for 2010, with representative data for the locality. We concluded that self-owned housing has a protective impact because it reduces economic stress, increases women’s status and facilitates solutions to domestic conflict. Furthermore, according to the statistical data, this protective effect is associated, at both the national and local level, to a significantly lower level of violence, regardless of wealth.
Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post–transfer refinement
Authors: Michener Joshua K , Camargo Neves Aline A , Vuilleumier Stéphane , Bringel Françoise , Marx Christopher J
Published: November 2014

When microbes acquire new abilities through horizontal gene transfer, the genes and pathways must function under conditions with which they did not coevolve. If newly-acquired genes burden the host, their utility will depend on further evolutionary refinement of the recombinant strain. We used laboratory evolution to recapitulate this process of transfer and refinement, demonstrating that effective use of an introduced dichloromethane degradation pathway required one of several mutations to the bacterial host that are predicted to increase chloride efflux. We then used this knowledge to identify parallel, beneficial mutations that independently evolved in two natural dichloromethane-degrading strains. Finally, we constructed a synthetic mobile genetic element carrying both the degradation pathway and a chloride exporter, which preempted the adaptive process and directly enabled effective dichloromethane degradation across diverse Methylobacterium environmental isolates. Our results demonstrate the importance of post–transfer refinement in horizontal gene transfer, with potential applications in bioremediation and synthetic biology.
Antibiotic genes spread far and wide
Authors: Catchpole Ryan J , Poole Anthony M
Published: November 2014

The genes responsible for antibiotics can spread between the three domains of life—Archaea, Bacteria and Eukaryotes.
Response Assessment in Locally Advanced Head and Neck Cancer Based on RECIST and Volume Measurements Using Cone Beam CT Images
Authors: Hou Jidong , Guerrero Mariana , Suntharalingam Mohan , D’Souza Warren D.
Published: November 2014

The purpose of this work was to find potential trends in RECIST measurements and volume regressions obtained from weekly cone-beam computed tomography images and to evaluate their relationship to clinical outcomes in locally advanced head and neck cancer. We examined thirty head and neck cancer patients who underwent a pre-treatment planning CT and weekly cone-beam computed tomography (CBCT) during the 5-7 week treatment period. The gross tumor volume (GTV) and lymph nodes were manually contoured on the treatment planning CT. The regions of interest enclosed by delineated contours were converted to binary masks and warped to weekly CBCT images using the 3D deformation field obtained by deformable image registration. The RECIST diameters and volumes were measured from these warped masks. Different predictor variables based on these measurements were calculated and correlated with clinical outcomes, based on a clinical exam and a PET imaging study. We found that there was substantial regression of the gross tumor volume over the treatment course (average gross tumor volume regression of 25%). Among the gross tumor volume predicators, it was found that the early regression of gross tumor volume showed a marginal statistical significance (p = 0.045) with complete response and non-complete response treatment outcomes. RECIST diameter measurements during treatment varied very little and did not correlate with clinical outcomes. We concluded that regression of the gross tumor volume obtained from weekly CBCT images is a promising predictor of clinical outcomes for head and neck patients. A larger sample is needed to confirm its statistical significance.
Enhancement in vertical fluxes at a front by mesoscale‐submesoscale coupling
Authors: Ramachandran Sanjiv , Tandon Amit , Mahadevan Amala
Published: November 2014

Oceanic frontal instabilities are of importance for the vertical exchange of properties in the ocean. Submesoscale, O(1) Rossby number, dynamics are particularly relevant for inducing the vertical (and lateral) flux of buoyancy and tracers in the mixed layer, but how these couple with the stratified pycnocline is less clear. Observations show surface fronts often persist beneath the mixed layer. Here we use idealized, three‐dimensional model simulations to show how surface fronts that extend deeper into the pycnocline invoke enhanced vertical fluxes through the coupling of submesoscale and mesoscale instabilities. We contrast simulations in which the front is restricted to the mixed layer with those in which it extends deeper. For the deeper fronts, we examine the effect of density stratification on the vertical coupling. Our results show deep fronts can dynamically couple the mixed layer and pycnocline on time scales that increase with the peak stratification beneath the mixed layer. Eddies in the interior generate skew fluxes of buoyancy and tracer oriented along isopycnals, thus providing an adiabatic pathway for the interior to interact with the mixed layer at fronts. The vertical enhancement of tracer fluxes through the mesoscale‐submesoscale coupling described here is thus relevant to the vertical supply of nutrients for phytoplankton in the ocean. A further implication for wind‐forced fronts is that the vertical structure of the stream function characterizing the exchange between the interior and the mixed layer exhibits significant qualitative differences compared to a linear combination of existing parameterizations of submesoscale eddies in the mixed layer and mesoscale eddies in the interior. The discrepancies are most severe within the mixed layer suggesting a potential role for Ekman‐layer dynamics absent in existing submesoscale parameterizations.
The daytime cycle in dust aerosol direct radiative effects observed in the central Sahara during the Fennec campaign in June 2011
Authors: Banks Jamie R. , Brindley Helen E. , Hobby Matthew , Marsham John H.
Published: November 2014

The direct clear‐sky radiative effect (DRE) of atmospheric mineral dust is diagnosed over the Bordj Badji Mokhtar (BBM) supersite in the central Sahara during the Fennec campaign in June 2011. During this period, thick dust events were observed, with aerosol optical depth values peaking at 3.5. Satellite observations from Meteosat‐9 are combined with ground‐based radiative flux measurements to obtain estimates of DRE at the surface, top‐of‐atmosphere (TOA), and within the atmosphere. At TOA, there is a distinct daytime cycle in net DRE. Both shortwave (SW) and longwave (LW) DRE peak around noon and induce a warming of the Earth‐atmosphere system. Toward dusk and dawn, the LW DRE reduces while the SW effect can switch sign triggering net radiative cooling. The net TOA DRE mean values range from −9 Wm−2 in the morning to heating of +59 Wm−2 near midday. At the surface, the SW dust impact is larger than at TOA: SW scattering and absorption by dust results in a mean surface radiative cooling of 145Wm−2. The corresponding mean surface heating caused by increased downward LW emission from the dust layer is a factor of 6 smaller. The dust impact on the magnitude and variability of the atmospheric radiative divergence is dominated by the SW cooling of the surface, modified by the smaller SW and LW effects at TOA. Consequently, dust has a mean daytime net radiative warming effect on the atmosphere of 153Wm−2.
Anscombe,FrancisJohn
Authors: Brillinger David R.
Published: November 2014

This entry provides a short biography of Francis John Anscombe who made pioneering contributions to the analysis of outliers, Bayesian statistics, biometrics, quality control, residual analysis, sequential analysis, and statistical computing.
Improving the Quality of Care of Patients With Rheumatic Disease Using Patient‐Centric Electronic Redesign Software
Authors: Newman Eric D. , Lerch Virginia , Billet Jon , Berger Andrea , Kirchner H. Lester
Published: November 2014

Objective

Electronic health records (EHRs) are not optimized for chronic disease management. To improve the quality of care for patients with rheumatic disease, we developed electronic data capture, aggregation, display, and documentation software.

Methods

The software integrated and reassembled information from the patient (via a touchscreen questionnaire), nurse, physician, and EHR into a series of actionable views. Core functions included trends over time, rheumatology‐related demographics, and documentation for patient and provider. Quality measures collected included patient‐reported outcomes, disease activity, and function. The software was tested and implemented in 3 rheumatology departments, and integrated into routine care delivery. Post‐implementation evaluation measured adoption, efficiency, productivity, and patient perception.

Results

Over 2 years, 6,725 patients completed 19,786 touchscreen questionnaires. The software was adopted for use by 86% of patients and rheumatologists. Chart review and documentation time trended downward, and productivity increased by 26%. Patient satisfaction, activation, and adherence remained unchanged, although pre‐implementation values were high. A strong correlation was seen between use of the software and disease control (weighted Pearson's correlation coefficient 0.5927, P = 0.0095), and a relative increase in patients with low disease activity of 3% per quarter was noted.

Conclusion

We describe innovative software that aggregates, stores, and displays information vital to improving the quality of care for patients with chronic rheumatic disease. The software was well‐adopted by patients and providers. Post‐implementation, significant improvements in quality of care, efficiency of care, and productivity were demonstrated.
A convex optimization approach to adaptive stabilization of discrete‐time LTI systems with polytopic uncertainties
Authors: Lee Dong Hwan , Joo Young Hoon , Tak Myung Hwan
Published: November 2014

This paper suggests a simple convex optimization approach to state‐feedback adaptive stabilization problem for a class of discrete‐time LTI systems subject to polytopic uncertainties. The proposed method relies on estimating the uncertain parameters by solving an online optimization at each time step, such as a linear or quadratic programming, and then, on tuning the control law with that information, which can be conceptually viewed as a kind of gain‐scheduling or indirect adaptive control. Specifically, an admissible domain of stabilizing state‐feedback gain matrices is designed offline by means of linear matrix inequality problems, and based on the online estimation of the uncertain parameters, the state‐feedback gain matrix is calculated over the set of stabilizing feedback gains. The proposed stabilization algorithm guarantees the asymptotic stability of the overall closed‐loop control system. An example is given to show the effectiveness of the proposed approach. Copyright © 2014 John Wiley & Sons, Ltd.
Ancient DNA from the Schild site in Illinois: Implications for the Mississippian transition in the Lower Illinois River Valley
Authors: Reynolds Austin W. , Raff Jennifer A. , Bolnick Deborah A. , Cook Della C. , Kaestle Frederika A.
Published: November 2014

Archaeologists have long debated whether rapid cultural change in the archaeological record is due to in situ developments, migration of a new group into the region, or the spread of new cultural practices into an area through existing social networks, with the local peoples adopting and adapting practices from elsewhere as they see fit (acculturation). Researchers have suggested each of these explanations for the major cultural transition that occurred at the beginning of the Mississippian period (AD 1050) across eastern North America. In this study, we used ancient DNA to test competing hypotheses of migration and acculturation for the culture change that occurred between the Late Woodland (AD 400–1050) and Mississippian (AD 1050–1500) periods in the Lower Illinois River Valley. We obtained sequences of the first hypervariable segment of the mitochondrial genome (mtDNA) from 39 individuals (17 Late Woodland, 22 Mississippian) interred in the Schild cemetery in western Illinois, and compared these lineages to ancient mtDNA lineages present at other sites in the region. Computer simulations were used to test a null hypothesis of population continuity from Late Woodland to Mississippian times at the Schild site and to investigate the possibility of gene flow from elsewhere in the region. Our results suggest that the Late Woodland to Mississippian cultural transition at Schild was not due to an influx of people from elsewhere. Instead, it is more likely that the transition to Mississippian cultural practices at this site was due to a process of acculturation. Am J Phys Anthropol 156:434–448, 2015. © 2014 Wiley Periodicals, Inc.
Mitochondrial DNA perspective of Serbian genetic diversity
Authors: Davidovic Slobodan , Malyarchuk Boris , Aleksic Jelena M. , Derenko Miroslava , Topalovic Vladanka , Litvinov Andrey , Stevanovic Milena , Kovacevic‐Grujicic Natasa
Published: November 2014

Although south‐Slavic populations have been studied to date from various aspects, the population of Serbia, occupying the central part of the Balkan Peninsula, is still genetically understudied at least at the level of mitochondrial DNA (mtDNA) variation. We analyzed polymorphisms of the first and the second mtDNA hypervariable segments (HVS‐I and HVS‐II) and informative coding‐region markers in 139 Serbians to shed more light on their mtDNA variability, and used available data on other Slavic and neighboring non‐Slavic populations to assess their interrelations in a broader European context. The contemporary Serbian mtDNA profile is consistent with the general European maternal landscape having a substantial proportion of shared haplotypes with eastern, central, and southern European populations. Serbian population was characterized as an important link between easternmost and westernmost south‐Slavic populations due to the observed lack of genetic differentiation with all other south‐Slavic populations and its geographical positioning within the Balkan Peninsula. An increased heterogeneity of south Slavs, most likely mirroring turbulent demographic events within the Balkan Peninsula over time (i.e., frequent admixture and differential introgression of various gene pools), and a marked geographical stratification of Slavs to south‐, east‐, and west‐Slavic groups, were also found. A phylogeographic analyses of 20 completely sequenced Serbian mitochondrial genomes revealed not only the presence of mtDNA lineages predominantly found within the Slavic gene pool (U4a2a*, U4a2a1, U4a2c, U4a2g, HV10), supporting a common Slavic origin, but also lineages that may have originated within the southern Europe (H5*, H5e1, H5a1v) and the Balkan Peninsula in particular (H6a2b and L2a1k). Am J Phys Anthropol 156:449–465, 2015. © 2014 Wiley Periodicals, Inc.
Stereospezifische Kupplungen von sekundären und tertiären Boronsäureestern
Authors: Leonori Daniele , Aggarwal Varinder K.
Published: November 2014

In diesem Kurzaufsatz werden die Fortschritte bei der Suzuki‐ Miyaura‐Kreuzkupplung von sekundären Borreagentien für die Erzeugung von C‐C‐Bindungen mit kontrollierter Stereochemie aufgezeigt. Des Weiteren wird die übergangsmetallfreie Kupplung von sekundären und tertiären Boronsäureestern an elektronenreiche Arene behandelt.
Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G‐Quadruplex
Authors: Yangyuoru Philip M. , Di Antonio Marco , Ghimire Chiran , Biffi Giulia , Balasubramanian Shankar , Mao Hanbin
Published: November 2014

In investigating the binding interactions between the human telomeric RNA (TERRA) G‐quadruplex (GQ) and its ligands, it was found that the small molecule carboxypyridostatin (cPDS) and the GQ‐selective antibody BG4 simultaneously bind the TERRA GQ. We previously showed that the overall binding affinity of BG4 for RNA GQs is not significantly affected in the presence of cPDS. However, single‐molecule mechanical unfolding experiments revealed a population (48 %) with substantially increased mechanical and thermodynamic stability. Force‐jump kinetic investigations suggested competitive binding of cPDS and BG4 to the TERRA GQ. Following this, the two bound ligands slowly rearrange, thereby leading to the minor population with increased stability. Given the relevance of G‐quadruplexes in the regulation of biological processes, we anticipate that the unprecedented conformational rearrangement observed in the TERRA‐GQ–ligand complex may inspire new strategies for the selective stabilization of G‐quadruplexes in cells.
A Preloaded Amorphous Calcium Carbonate/Doxorubicin@Silica Nanoreactor for pH‐Responsive Delivery of an Anticancer Drug
Authors: Zhao Yang , Luo Zhong , Li Menghuan , Qu Qiuyu , Ma Xing , Yu Shu‐Hong , Zhao Yanli
Published: November 2014

Biomedical applications of nontoxic amorphous calcium carbonate (ACC) nanoparticles have mainly been restricted because of their aqueous instability. To improve their stability in physiological environments while retaining their pH‐responsiveness, a novel nanoreactor of ACC–doxorubicin (DOX)@silica was developed for drug delivery for use in cancer therapy. As a result of its rationally engineered structure, this nanoreactor maintains a low drug leakage in physiological and lysosomal/endosomal environments, and responds specifically to pH 6.5 to release the drug. This unique ACC–DOX@silica nanoreactor releases DOX precisely in the weakly acidic microenvironment of cancer cells and results in efficient cell death, thus showing its great potential as a desirable chemotherapeutic nanosystem for cancer therapy.
Direct Surface‐Enhanced Raman Scattering Analysis of DNA Duplexes
Authors: Guerrini Luca , Krpetić Željka , van Lierop Danny , Alvarez‐Puebla Ramon A. , Graham Duncan
Published: November 2014

The exploration of the genetic information carried by DNA has become a major scientific challenge. Routine DNA analysis, such as PCR, still suffers from important intrinsic limitations. Surface‐enhanced Raman spectroscopy (SERS) has emerged as an outstanding opportunity for the development of DNA analysis, but its application to duplexes (dsDNA) has been largely hampered by reproducibility and/or sensitivity issues. A simple strategy is presented to perform ultrasensitive direct label‐free analysis of unmodified dsDNA with the means of SERS by using positively charged silver colloids. Electrostatic adhesion of DNA promotes nanoparticle aggregation into stable clusters yielding intense and reproducible SERS spectra at nanogram level. As potential applications, we report the quantitative recognition of hybridization events as well as the first examples of SERS recognition of single base mismatches and base methylations (5‐methylated cytosine and N6‐methylated Adenine) in duplexes.
Partitioning Solvophobic and Dispersion Forces in Alkyl and Perfluoroalkyl Cohesion
Authors: Adam Catherine , Yang Lixu , Cockroft Scott L.
Published: November 2014

Fluorocarbons often have distinct miscibility properties compared to their nonfluorinated analogues. These differences may be attributed to van der Waals dispersion forces or solvophobic effects, but their contributions are notoriously difficult to separate in molecular recognition processes. Here, molecular torsion balances were used to compare cohesive alkyl and perfluoroalkyl interactions in a range of solvents. A simple linear regression enabled the energetic partitioning of solvophobic and van der Waals forces in the self‐association of apolar chains. The contributions of dispersion interactions in apolar cohesion were found to be strongly attenuated in solution compared to the gas phase, but still play a major role in fluorous and organic solvents. In contrast, solvophobic effects were found to be dominant in driving the association of apolar chains in aqueous solution. The results are expected to assist the computational modelling of van der Waals forces in solution.
Design and Synthesis of High‐Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors
Authors: Maric Hans Michael , Kasaragod Vikram Babu , Haugaard‐Kedström Linda , Hausrat Torben Johann , Kneussel Matthias , Schindelin Hermann , Strømgaard Kristian
Published: November 2014

Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor‐derived minimal gephyrin‐binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220‐fold enhancement of the gephyrin affinity (KD=6.8 nM). In X‐ray crystal structures we visualized the simultaneous dimer‐to‐dimer binding in atomic detail, revealing compound‐specific binding modes. Thus, we defined the molecular basis of the affinity‐enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin–receptor interplay.
Synthesis and Structure of LaSc2N@Cs(hept)‐C80 with One Heptagon and Thirteen Pentagons
Authors: Zhang Yang , Ghiassi Kamran B. , Deng Qingming , Samoylova Nataliya A. , Olmstead Marilyn M. , Balch Alan L. , Popov Alexey A.
Published: November 2014

The synthesis and single‐crystal X‐ray structural characterization of the first endohedral metallofullerene to contain a heptagon in the carbon cage are reported. The carbon framework surrounding the planar LaSc2N unit in LaSc2N@Cs(hept)‐C80 consists of one heptagon, 13 pentagons, and 28 hexagons. This cage is related to the most abundant Ih‐C80 isomer by one Stone–Wales‐like, heptagon/pentagon to hexagon/hexagon realignment. DFT computations predict that LaSc2N@Cs(hept)‐C80 is more stable than LaSc2N@D5h‐C80, and suggests that the low yield of the heptagon‐containing endohedral fullerene may be caused by kinetic factors.
Enantiotopos‐selektive CH‐Oxygenierung mit einem supramolekularen Ruthenium‐Katalysator
Authors: Frost James R. , Huber Stefan M. , Breitenlechner Stefan , Bannwarth Christoph , Bach Thorsten
Published: November 2014

In Gegenwart eines katalytisch aktiven, chiralen Ruthenium‐Porphyrin‐Komplexes (1 Mol‐%) gehen spirocyclische Oxindole eine enantioselektive Oxygenierungsreaktion ein (neun Beispiele; e.r. bis zu 97:3). Der Katalysator weist einen Lactamring auf, der für die Substratassoziation über Wasserstoffbrücken verantwortlich ist, und verfügt über ein Ruthenium‐Zentrum, das sich in einer definierten räumlichen Beziehung zum Substrat der Oxygenierung befindet. DFT‐Rechnungen illustrieren die perfekte Anordnung des aktiven Zentrums mit der reaktiven C‐H‐Bindung und deuten – in Übereinstimmung mit dem kinetischen Isotopeneffekt – auf einen Sauerstoff‐Rebound‐Mechanismus für die Reaktion hin.
Direct Dehydroxytrifluoromethylthiolation of Alcohols Using Silver(I) Trifluoromethanethiolate and Tetra‐n‐butylammonium Iodide
Authors: Liu Jian‐Bo , Xu Xiu‐Hua , Chen Zeng‐Hao , Qing Feng‐Ling
Published: November 2014

An unprecedented reaction for the direct trifluoromethylthiolation and fluorination of alkyl alcohols using AgSCF3 and nBu4NI has been developed. The trifluoromethylthiolated compounds and alkyl fluorides were selectively formed by changing the ratio of AgSCF3/nBu4NI. This protocol is tolerant of different functional groups and might be applicable to late‐stage trifluoromethylthiolation of alcohols.
Transformation of Cell‐Derived Microparticles into Quantum‐Dot‐Labeled Nanovectors for Antitumor siRNA Delivery
Authors: Chen Gang , Zhu Jun‐Yi , Zhang Zhi‐Ling , Zhang Wei , Ren Jian‐Gang , Wu Min , Hong Zheng‐Yuan , Lv Cheng , Pang Dai‐Wen , Zhao Yi‐Fang
Published: November 2014

Cell‐derived microparticles (MPs) have been recently recognized as critical intercellular information conveyors. However, further understanding of their biological behavior and potential application has been hampered by the limitations of current labeling techniques. Herein, a universal donor‐cell‐assisted membrane biotinylation strategy was proposed for labeling MPs by skillfully utilizing the natural membrane phospholipid exchange of their donor cells. This innovative strategy conveniently led to specific, efficient, reproducible, and biocompatible quantum dot (QD) labeling of MPs, thereby reliably conferring valuable traceability on MPs. By further loading with small interference RNA, QD‐labeled MPs that had inherent cell‐targeting and biomolecule‐conveying ability were successfully employed for combined bioimaging and tumor‐targeted therapy. This study provides the first reliable and biofriendly strategy for transforming biogenic MPs into functionalized nanovectors.
Synthesis and Characterization of Fluorodinitroamine, FN(NO2)2
Authors: Christe Karl O. , Wilson William W. , Bélanger‐Chabot Guillaume , Haiges Ralf , Boatz Jerry A. , Rahm Martin , Prakash G. K. Surya , Saal Thomas , Hopfinger Mathias
Published: November 2014

NF3 and N(NO2)3 are known compounds, whereas the mixed fluoronitroamines, FN(NO2)2 and F2NNO2, have been unknown thus far. One of these, FN(NO2)2, has now been prepared and characterized by multinuclear NMR and Raman spectroscopy. FN(NO2)2 is the first known example of an inorganic fluoronitroamine. It is a thermally unstable, highly energetic material formed by the fluorination of the dinitramide anion using NF4+ salts as the preferred fluorinating agent.
Brief Report: No Excess Risks in Offspring With Paternal Preconception Exposure to Disease‐Modifying Antirheumatic Drugs
Authors: Wallenius Marianne , Lie Elisabeth , Daltveit Anne K. , Salvesen Kjell Å. , Skomsvoll Johan F. , Kalstad Synøve , Lexberg Åse S. , Mikkelsen Knut , Kvien Tore K. , Østensen Monika
Published: November 2014

Objective

To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease‐modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population.

Methods

Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease‐Modifying Antirheumatic Drug [NOR‐DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis.

Results

A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group.

Conclusion

Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.
To What Extent Is the Familial Risk of Rheumatoid Arthritis Explained by Established Rheumatoid Arthritis Risk Factors?
Authors: Jiang Xia , Frisell Thomas , Askling Johan , Karlson Elizabeth W. , Klareskog Lars , Alfredsson Lars , Källberg Henrik
Published: November 2014

Objective

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors.

Methods

History of RA among first‐degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case–control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single‐nucleotide polymorphisms [SNPs]).

Results

Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE‐adjusted OR 3.72, SNP‐adjusted OR 3.46, and SE and SNP–adjusted OR 3.35).

Conclusion

Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA.
Study of a Class of Almost‐controllable Discrete‐time Bilinear Systems
Authors: Shen Jinzhong , Zhu Yuanguo
Published: November 2014

This paper studies the controllability of a class of time‐invariant discrete‐time bilinear systems. Although the system is not controllable in the whole space, there is a very large region where control is effective. Results show that the uncontrollable region of this kind of bilinear system has a Lebesgue measure of zero. In other words, for almost any initial state and any terminal state in the state space, the former can be transferred to the latter. Further, a necessary condition for near controllability is presented. Therefore, the results in this paper unify and generalize the corresponding conclusions in the literature. ©2014 Chinese Automatic Control Society and Wiley Publishing Asia Pty Ltd
A Measurement‐Based Approach for Designing Fixed‐Order Controllers for Unknown Closed‐Loop Architecture
Authors: Khadraoui Sofiane , Nounou Hazem N. , Nounou Mohamed N. , Datta Aniruddha , Bhattacharyya Shankar P.
Published: November 2014

This paper presents a new technique to design fixed‐structure controllers for linear unknown systems using a set of measurements. In model‐based approaches, the measured data are used to identify a model of the plant for which a suitable controller can be designed. Due to the fact that real processes cannot be described perfectly by mathematical models, designing controllers using such models to guarantee some desired closed‐loop performance is a challenging task. Hence, a possible alternative to model‐based methods is to directly utilize the measured data in the design process. We propose an approach to designing structured controllers using a set of closed‐loop frequency‐domain data. The principle of such an approach is based on computing the parameters of a fixed‐order controller for which the closed‐loop frequency response fits a desired frequency response that describes some desired performance indices. This problem is formulated as an error minimization problem, which can be solved to find suitable values of the controller parameters. The main feature of the proposed control methodology is that it can be applied to stable and unstable plants. Additionally, the design process depends on a pre‐selected controller structure, which allows for the selection of low‐order controllers. An application of the proposed method to a DC servomotor system is presented to experimentally validate and demonstrate its efficacy.
Exposure to electromagnetic fields in households—Trends from 2006 to 2012
Authors: Tomitsch Johannes , Dechant Engelbert
Published: November 2014

This article is a follow‐up study of extremely low‐frequency electric and magnetic fields (ELF‐EFs, ELF‐MFs) and radiofrequency electromagnetic fields (RF‐EMFs) using data collected in 2012 following earlier data sets from 2006 and 2009. Measurements were conducted in 219 bedrooms in Lower Austria. Out of these rooms 113 measurements were done in the same households in 2006, 2009 and 2012, and 106 were conducted in neighbouring buildings added in 2009 and newly recruited buildings in mainly urban areas in 2012. In revisited places the median of the ELF‐EFs decreased from 23.20 V/m in 2006 to 13.90 V/m in 2012. The median of all‐night measurements of ELF‐MFs at 50 Hz decreased from 13.50 to 11.37 nT. The median of total RF‐EMFs increased from 28.13 to 52.16 µW/m2. Highest increases were found for universal mobile telecommunication system (UMTS) and wireless local area networks (WLAN). The analysis of all households showed higher total RF‐EMFs in urban (median = 117.73 µW/m2) than in rural (median = 34.52 µW/m2) areas. Long‐term evolution (LTE) in the 2600 MHz frequency range was detected at 17 locations with a maximum of 38.20 µW/m2. Indoor RF‐EMF sources resulted in decreased exposure in the frequency range of digital enhanced cordless telecommunications telephones (DECT) and increased exposure in the frequency range of WLAN. Bioelectromagnetics. 35:77–85, 2015. © 2014 Wiley Periodicals, Inc.
Support and Reluctance in the Pre‐substantive Phase of Alleged Child Abuse Victim Investigative Interviews: Revised versus Standard NICHD Protocols
Authors: Ahern Elizabeth C. , Hershkowitz Irit , Lamb Michael E. , Blasbalg Uri , Winstanley Alice
Published: November 2014

Children's unwillingness to report abuse places them at risk for re‐victimization, and interviewers who do not respond sensitively to that unwillingness may increase the likelihood that victims will not disclose abuse. Interviewer support and children's reluctance were examined on a turn‐by‐turn basis using sequential analyses in 199 forensic interviews of 3‐ to 13‐year‐olds who alleged maltreatment. Half of the children were interviewed using the Revised Protocol that emphasized rapport‐building (RP), the others using the Standard National Institute of Child Health and Human Development Protocol (SP). When using the RP, interviewers provided proportionally more support than when using the SP, but even when using the RP they did not specifically provide support when children expressed reluctance. The RP promoted immediate cooperation when reluctant utterances were met with support, however, suggesting that supportive statements were valuable. The findings enhance our understanding of children's willingness to participate in investigative interviews and the means through which interviewers can foster the comfort and well‐being of young witnesses. Copyright © 2014 John Wiley & Sons, Ltd.
Polymer Enzyme Conjugates as Chiral Ligands for Sharpless Dihydroxylation of Alkenes in Organic Solvents
Authors: Konieczny Stefan , Leurs Melanie , Tiller Joerg C.
Published: November 2014

Conjugates of enzymes and poly(2‐methyloxazoline) were used as organosoluble amphiphilic polymer nanocontainers for dissolving osmate, thereby converting the enzymes into organosoluble artificial metalloenzymes. These were shown to catalyze the dihydroxylation of different alkenes with high enantioselectivity. The highest selectivities, found for osmate complexed with laccase polymer–enzyme conjugates (PECs), even exceed those of classical Sharpless catalysts.