bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Testing: a Genetic Counselor's Personal Reflection on Three Years of Consenting and Testing
Authors: Wynn Julia
Published: August 2015

Whole exome sequencing (WES) is increasingly used in research and clinical genetics as the cost of sequencing decreases and the interpretation improves. Genetic counselors need to be prepared to counsel a diverse patient population for this complex test. This commentary is a reflection of one genetic counselor's experiences in counseling, consenting, and returning results for clinical and research WES for over 120 participants and patients. She reflects on how she overcame the initial challenges and concerns of counseling for WES and how her counseling evolved from a teaching based counseling model to an interactive patient‐center counseling model. Her insights are offered to prepare other genetic counselors for the growing use of genomic testing.
Fatty Acid and Lipid Profiles with Emphasis on n‐3 Fatty Acids and Phospholipids from Ciona intestinalis
Authors: Zhao Yadong , Wang Miao , Lindström Mikael E. , Li Jiebing
Published: August 2015

In order to establish Ciona intestinalis as a new bioresource for n‐3 fatty acids‐rich marine lipids, the animal was fractionated into tunic and inner body tissues prior to lipid extraction. The lipids obtained were further classified into neutral lipids (NL), glycolipids (GL) and phospholipids (PL) followed by qualitative and quantitative analysis using GC‐FID, GC–MS, 1H NMR, 2D NMR, MALDI‐TOF‐MS and LC–ESI–MS methods. It was found that the tunic and inner body tissues contained 3.42–4.08 % and 15.9–23.4 % of lipids respectively. PL was the dominant lipid class (42–60 %) irrespective of the anatomic fractions. From all lipid fractions and classes, the major fatty acids were 16:0, 18:1n‐9, C20:1n‐9, C20:5n‐3 (EPA) and C22:6n‐3 (DHA). The highest amounts of long chain n‐3 fatty acids, mainly EPA and DHA, were located in PL from both body fractions. Cholestanol and cholesterol were the dominant sterols together with noticeable amounts of stellasterol, 22 (Z)‐dehydrocholesterol and lathosterol. Several other identified and two yet unidentified sterols were observed for the first time from C. intestinalis. Different molecular species of phosphatidylcholine (34 species), sphingomyelin (2 species), phosphatidylethanolamine (2 species), phosphatidylserine (10 species), phosphatidylglycerol (9 species), ceramide (38 species) and lysophospholipid (5 species) were identified, representing the most systematic PL profiling knowledge so far for the animal. It could be concluded that C. intestinalis lipids should be a good alternative for fish oil with high contents of n‐3 fatty acids. The lipids would be more bioavailable due to the presence of the fatty acids being mainly in the form of PL.
Mobilitätsdynamiken und Wissensarbeit – zum Wandel berufsbedingter zirkulärer Mobilität
Authors: Strambach Simone , Kohl Hendrik
Published: August 2015

An increasing importance of mobile and com- plex forms of working and living has been noticed in re- cent mobility research. These developments are closely linked to the socio-economic structural change toward a knowledge economy and to changes in the organization of employment. So far only few empirical results indicate that knowledge workers are more mobile than other em- ployees. However, the relationship between knowledge-in- tensive activities and job-related—especially the so-called circular—mobility has not been systematically examined in-depth. Merging interdisciplinary mobility research with the spatial innovation and knowledge science seems to be a promising approach for utilizing synergy potentials that allow a more differentiated analysis of the fluid, spatiotem- poral connection between knowledge work and its complex implications for the job-related circular mobility.
Oligomerization state and pigment binding strength of the peridinin‐Chla‐protein
Authors: Jiang Jing , Zhang Hao , Lu Xun , Lu Yue , Cuneo Matthew J. , O'Neill Hugh M. , Urban Volker , Lo Cynthia S. , Blankenship Robert E.
Published: August 2015

The peridinin‐chlorophylla‐protein (PCP) is one of the major light harvesting complexes (LHCs) in photosynthetic dinoflagellates. We analyzed the oligomeric state of PCP isolated from the dinoflagellateSymbiodinium, which has received increasing attention in recent years because of its role in coral bleaching. Size‐exclusion chromatography (SEC) and small angle neutron scattering (SANS) analysis indicated PCP exists as monomers. Native mass spectrometry (native MS) demonstrated two oligomeric states of PCP, with the monomeric PCP being dominant. The trimerization may not be necessary for PCP to function as a light‐harvesting complex.
Inventory record inaccuracy: Causes and labor effects
Authors: Chuang Howard Hao‐Chun , Oliva Rogelio
Published: August 2015

Inventory record inaccuracy (IRI) is a pervasive problem in retailing and causes non‐trivial profit loss. In response to retailers’ interest in identifying antecedents and consequences of IRI, we present a study that comprises multiple modeling initiatives. We first develop a dynamic simulation model to compare and contrast impacts of different operational errors in a continuous (Q,R) inventory system through a full‐factorial experimental design. While backroom and shelf shrinkage are found to be predominant drivers of IRI, the other three errors related to recording and shelving have negligible impacts on IRI. Next, we empirically assess the relationships between labor availability and IRI using longitudinal data from five stores in a global retail chain. After deriving a robust measure of IRI through Bayesian computation and estimating panel data models, we find strong evidence that full‐time labor reduces IRI whereas part‐time labor fails to alleviate it. Further, we articulate the reinforcing relationships between labor and IRI by formally assessing the gain of the feedback loop based on our empirical findings and analyzing immediate, intermediate, and long‐term impacts of IRI on labor availability. The feedback modeling effort not only integrates findings from simulation and econometric analysis but also structurally explores the impacts of current practices. We conclude by discussing implications of our findings for practitioners and researchers.
Intervención educativa en médicos residentes para el dominio de lectura crítica de reportes de investigación
Authors: Cabrera-Pivaral Carlos Enrique , González-Pérez Guillermo Julián , Vega-López María Guadalupe , Recinos-Girón Juan José , Zavala-González Marco Antonio , Alonso-Álvarez María Angelica
Published: August 2015

Objetivo: Determinar el efecto de una intervención educativa en el dominio de lectura crítica de reportes de investigación clínica originales en médicos residentes.
Método: Se realizó un cuasi experimento en el que se estudió una muestra por conveniencia tomada a partir de un universo de 156 médicos residentes de un hospital de Guatemala, en la que se incluyeron a quienes aceptaron participar y concluyeron el proceso de intervención.Se incluyeron las variables: edad, sexo y año de residencia, además del dominio de lectura crítica pre- y postintervención; esta última fue evaluada mediante un instrumento estructurado previamente validado. La intervención consistió en 72 horas de sesiones de lectura comentada y discusión de artículos de investigación original, distribuidas en una sesión semanal de 90 minutos durante 12 meses, en las que además se trataron contenidos temáticos alusivos a la metodología de cada artículo. Los resultados pre- y postintervención fueron comparados mediante estadística inferencial no paramétrica. La información fue sistematizada y analizada usando Epi Info© 6 para Windows©.
Resultados: Se incluyeron 156 médicos residentes, con una edad media de 27±3 años, 55% de sexo femenino, 60% cursando el tercer año de su especialidad. La mediana del dominio grupal de lectura crítica preintervención fue de 53 en un intervalo de 26-78, y postintervención fue de 78.5 en un intervalo de 24-89, con diferencia estadísticamente significativa (p<0.05).
Conclusiones: Una intervención educativa participativa, centrada en la reflexión, confrontación y discusión grupal de reportes de investigación, fomenta significativamente la construcción del propio conocimiento.
Comparación de factores sociales asociados al estatus académico en estudiantes de Medicina
Authors: Gómez López Víctor Manuel , Rosales Gracia Sandra , Maldonado Vigil Martha Patricia
Published: August 2015

Introducción: Una de las metas de los directivos de las escuelas y facultades de Medicina debe ser el lograr que los alumnos de esta carrera adquieran las competencias suficientes para poder desempeñarse de manera eficiente en la práctica clínica. Sin embargo, hay que reconocer que en el proceso educativo son fundamentales ciertas características del alumno para poder alcanzar el propósito de la formación en Medicina, así como de las competencias docentes.
Objetivo: Comparar la asociación que existe de algunos factores sociales entre alumnos de la carrera de Medicina, de acuerdo con su estatus académico. 
Método: Durante el ciclo académico 2013-02 se realizó un estudio observacional, prolectivo y comparativo, en donde se incluyeron 336 alumnos de la licenciatura de Medicina de una escuela del sector privado del sur de Tamaulipas, los cuales en ese momento estaban inscritos entre el segundo y el séptimo semestre y que aceptaron participar en el estudio contestando un cuestionario acerca de los factores sociales relacionados con el rendimiento académico. Para el análisis estadístico de las variables cuantitativas se utilizaron promedios y desviación estándar, y para las variables cualitativas, porcentajes. Para comparar la frecuencia de los diferentes factores estudiados en los grupos se utilizó la Ji cuadrado con un nivel de significación de 0.05. 
Resultados: Existió una mayor frecuencia de ser alumno irregular en el género femenino (52.4% vs. 47.6%). El nivel educativo de los padres no mostró asociación estadísticamente significativa con el hecho de ser alumno regular o irregular.
Conclusiones: Existe una asociación positiva entre el hecho de vivir con ambos padres y ser alumno regular. La satisfacción de la función familiar percibida por los estudiantes no tiene asociación con el hecho de ser alumno regular.
¿Qué tan libres somos cuando enseñamos medicina?
Authors: Sánchez-Mendiola Melchor
Published: August 2015

¿De qué tanta libertad gozamos en el salón de clase o en el servicio hospitalario para enseñar y aprender la medicina, tanto estudiantes como docentes? Reflexione el lector sobre nuestros diversos escenarios educativos.
AMS-dated mollusks in beach ridges and berms document Holocene sea-level and coastal changes in northeastern Kuwait Bay
Authors: Reinink-Smith Linda M.
Published: August 2015

In northeastern Kuwait, ancient beach ridges and associated berms are separated from the present shoreline by a 4–6 km-wide sabkha. A diverse mollusk fauna in the beach ridges attests to a former open marine environment. A total of 21 AMS dates were obtained in this study. Thirteen mollusk samples from beach ridges yielded AMS dates ranging from ~ 6990 cal yr BP in the southeast to ~ 3370 cal yr BP in the northwest, suggesting a southeast to northwest age progression during the Holocene transgression. In contrast, four samples from berms throughout the study area yielded AMS dates of 5195–3350 cal yr BP showing no age progression; these berms consist largely ofConomurex persicusgastropods that aggregated by storms during a highstand at ~ 5000–3500 cal yr BP. The berms are presently at ~ + 6 m above sea level, 2–3 m above the beach ridges. Human settlements were common on the ridge crests before and after the highstand. Regression to present-day sea level commenced after the highstand, which is when the sabkha began forming. A landward, marine-built terrace, which yielded AMS dates > 43,50014C yr BP, probably formed during Marine Oxygen Isotope Stage 5e and hence is not genetically related to the beach ridges.
Learning Experiences in Return to Work Among Workplace Actors
Authors: Tjulin Åsa , Müssener Ulrika , Selander John , Ekberg Kerstin
Published: August 2015

Purpose: The objective of this article was to investigate how individual learning emerges among workplace actors during the return-to-work process, and whether the prerequisites for collective learning at the workplace are present and managed by the actors. Learning in this context is viewed as a change in the preconceptions, experience or competence of the individual as a result of interactions in the workplace due to the return-to-work process. Method: A qualitative method was used, consisting of open-ended interviews with 19 individuals across 11 workplaces in the public and private sector. Inductive content analysis was performed. Results: The key findings from this study are that individual learning emerges in the return-to-work process due to previous experience, communication with other workplace actors, or insights into what works for the individual. However, the individual learning that occurs in the return-to-work process is not carried over into workplace learning due to barriers in understanding the needs and opportunities that may be present in the process. Conclusion: Our findings suggest that individual learning occurs within social practices through social interaction between the actors involved (workers on sickness absence supervisors and colleagues) and individual experiences. A greater knowledge of the factors that contribute to workplace learning could facilitate biopsychosocial and ecological return-to-work interventions, which allow workplace actors to draw on previous experiences from one return-to-work process to another.
Pervasiveness of Dominant General Factors in Organizational Measurement
Authors: Ree Malcolm James , Carretta Thomas R. , Teachout Mark S.
Published: August 2015

General factors are found in the measurement of many human traits. The concept of dominant general factors (DGFs) is introduced to represent the magnitude of general factors within numerous content domains. DGFs are defined as coming from the largest sources of reliable variance and influencing every variable measuring the construct. Although these factors are most frequently found in measures of cognitive ability, they are not limited to cognitive abilities. Examples are provided for a variety of construct and content domains along with estimates of their DGF percentages, ranging from 38% to 92%. Several reasons for these results are offered, and a call for concerted research is made. Research that ignores DGFs by treating specific factors or constructs within a domain as if they were distinct and uncorrelated can lead to errors in interpretation.
Wentzel–Kramers–Brillouin approximation for atmospheric waves
Authors: Godin Oleg A.
Published: August 2015

Ray and Wentzel–Kramers–Brillouin (WKB) approximations have long been important tools in understanding and modelling propagation of atmospheric waves. However, contradictory claims regarding the applicability and uniqueness of the WKB approximation persist in the literature. Here, we consider linear acoustic–gravity waves (AGWs) in a layered atmosphere with horizontal winds. A self-consistent version of the WKB approximation is systematically derived from first principles and compared toad hocapproximations proposed earlier. The parameters of the problem are identified that need to be small to ensure the validity of the WKB approximation. Properties of low-order WKB approximations are discussed in some detail. Contrary to the better-studied cases of acoustic waves and internal gravity waves in the Boussinesq approximation, the WKB solution contains the geometric, or Berry, phase. The Berry phase is generally non-negligible for AGWs in a moving atmosphere. In other words, knowledge of the AGW dispersion relation is not sufficient for calculation of the wave phase.
Editorial
Authors: The Australian Journal of Indigenous Education
Published: August 2015

The challenge for any research journal today is how to continue to make the work we publish relevant, contemporary and innovative for the research groups, educational organisations, and Indigenous communities locally and globally that we serve. At the same time, we recognise it is important for us to continue our work in The Australian Journal of Indigenous Education within the critical pedagogical agenda in which it began; that is, the empowerment of Aboriginal and Torres Strait Islander peoples through education, combined with a concern to critique and challenge the national and international colonial contexts in which Indigenous education is positioned today.
Preparing Preservice Teachers for Inclusive Classrooms: Does Completing Coursework on Managing Challenging Behaviours Increase Their Classroom Management Sense of Efficacy?
Authors: O’Neill Sue C.
Published: August 2015

Preservice teacher education courses provide an opportunity for the development of knowledge, skills, and confidence in classroom and behaviour management. This study reports the change in classroom management sense of efficacy (CMSE) of a small cohort of Australian preservice primary teachers at 4 time points (precoursework, preprofessional experience, postprofessional experience, and postcoursework), during a semester-long course focused on managing challenging behaviours in the inclusive classroom. CMSE increased between the time points, significantly so, pre–post course. The sources of efficacy information available and the learning activities completed during each intervening time point are explored as possible explanations for the changes in CMSE reported. Issues in measuring preservice teachers’ efficacy related to coursework are discussed.
Fine Water: A Hedonic Pricing Approach
Authors: Capehart Kevin W.
Published: August 2015

Bottles of water vary in price with some priced as if they were bottles of fine wine. This article attempts to explain price differences between over 100 bottled waters included in a guidebook to fine waters by drawing on the hedonic pricing approach, which has been used to try to explain price differences among bottles of wine. As part of that approach, the price of each bottled water is regressed against various characteristics, including those related to its water. Water-related characteristics explain only a small part of the price differences among the bottled waters. Thus, to a large extent, the premium that consumers pay for a more expensive bottled water does not seem to be a premium for its water. (JEL Classifications: C21, Q25)
First abundance estimate of the Antillean manatee (Trichechus manatus manatus) in Brazil by aerial survey
Authors: Alves Maria Danise , Kinas Paul Gerhard , Marmontel Miriam , Borges João Carlos Gomes , Costa Alexandra Fernandes , Schiel Nicola , Araújo Maria Elisabeth
Published: August 2015

We estimated the abundance of Antillean manatees (Trichechus manatus manatus) through a large-scale project conducted in 2010 in north-eastern Brazil and evaluated the efficacy of an aerial survey for conservation purposes. Two observers conducted the survey via flights that maintained an altitude of 150 m and an air speed of 140 km h−1, covering over 2590.2 km2of the coastline. Strip transects were flown in a zigzag pattern. A total of 67 manatees (on- and off-effort) were recorded in 55 sightings. Historical published records of occurrence were formally incorporated using a Bayesian approach. We estimated the manatee population for north-eastern Brazil in the form of a posterior distribution with a mean of 1104 individuals and a 95% posterior probability interval ranging from 485 to 2221 individuals, which indicates high uncertainty. More large-scale studies in the region are warranted to understand temporal trends, in addition to further studies in hotspot areas, with smaller spatial scales, to reduce the coefficient of variation and to allow the use of improved techniques for monitoring the manatees. A greater emphasis on species-specific characteristics and methods to enhance detection probability (e.g. dual observers) are also recommended. The conditions prevailing along the study area were not conducive to aerial surveillance; thus, the results are not a precise estimate of the manatee population. However, these highlight the importance of conservation efforts for the Antillean manatee, considered the most endangered aquatic mammal in Brazil.
Philosophical Arminianism: a breakthrough in the foreknowledge controversy?
Authors: HASKER WILLIAM
Published: August 2015

Jonathan Kvanvig has proposed a novel approach to the topics of divine foreknowledge and providence, a view he terms ‘Philosophical Arminianism’. This article expounds and assesses the view; it is maintained that there are at least two major difficulties that have yet to be addressed.
Iberian Nationality Legislation and Sephardic Jews
Authors: Jessurun d’Oliveira Hans Ulrich
Published: August 2015

Proposal to grant Spanish nationality to Sephardic Jews – History of Sephardic Jews in Iberia – Sephardim and the Portuguese nationality code – The EU and the nationality laws of the member states – Impact of Union law on the acquisition of Iberian nationalities by Sephardic Jews – European Convention on Nationality – Sephardim from third countries –Micheletti – Nottebohm
The Relocation of the Legality Principle by the European Courts’ Case Law
Authors: Lupo Nicola , Piccirilli Giovanni
Published: August 2015

Rule of law and the legality principle – Legality principle in the Italian legal system – ‘Prescribed by law’ – Legality in supranational dimension – ‘Democratic disconnect’ – Margin of appreciation – Concepts of ‘law’ and ‘legislation’ – Democracy-based legislation – Quality of legislation – ‘Political constitutionalism’ versus ‘legal constitutionalism’
EU Regulatory Policy and World Trade
Authors: Perišin Tamara
Published: August 2015

Divergent regulatory practices in WTO compliance and external trade effects – The regulatory policy of EU ‘legislative’ institutions – The (de)regulatory policy of the ECJ – Explaining diverging regulatory practices – Policies behind diverging regulatory practices – Different institutional interaction in diverging regulatory practices – Should all EU institutions care what the world thinks?
A brief overview of legal interoperability challenges for NATO arising from the interrelationship between IHL and IHRL in light of the European Convention on Human Rights
Authors: Abbott Kirby
Published: August 2015

This article briefly overviews some of the current and future challenges to NATO legal interoperability arising from the relationship between international humanitarian law (IHL) and international human rights law generally and between IHL and the European Convention on Human Rights in particular.
Arithmetic Fact Retrieval
Authors: Busch Jenny , Schmidt Claudia , Grube Dietmar
Published: August 2015

When diagnosing children with learning disorders (as per ICD-10), their scholastic performance has to be significantly below the level of intelligence. Although this discrepancy criterion has received much criticism in the field of literacy, few researchers in mathematics have examined it. We used a two (mathematical performance) by two (intelligence) factorial design to analyze the arithmetic fact retrieval of low-performing children in mathematics who met the criterion (developmental dyscalculia) or did not (mathematical difficulties) and of two groups of average-achieving children matched for intelligence. The four groups (each n = 27 third-graders) were matched for their attention span and their literacy skills. Children solved addition verification tasks with numbers up to 10 and 20 under standard and under dual task conditions requiring further working memory capacity to evaluate the potential use of counting strategies. Performance in addition tasks proved to be associated with mathematical achievement especially in the higher number range, whereas dual task performance did not point to the use of counting strategies among low performers in mathematics. No interaction between mathematics and intelligence was identified, which would have confirmed the discrepancy criterion. These results illustrate that stable knowledge of arithmetic facts is essential for mathematical achievement, regardless of whether the discrepancy criterion is met.
Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2
Authors: Carter Megan , Jemth Ann-Sofie , Hagenkort Anna , Page Brent D. G. , Gustafsson Robert , Griese Julia J. , Gad Helge , Valerie Nicholas C. K. , Desroses Matthieu , Boström Johan , Warpman Berglund Ulrika , Helleday Thomas , Stenmark Pål
Published: August 2015

Deregulated redox metabolism in cancer leads to oxidative damage to cellular components including deoxyribonucleoside triphosphates (dNTPs). Targeting dNTP pool sanitizing enzymes, such as MTH1, is a highly promising anticancer strategy. The MTH2 protein, known as NUDT15, is described as the second human homologue of bacterial MutT with 8-oxo-dGTPase activity. We present the first NUDT15 crystal structure and demonstrate that NUDT15 prefers other nucleotide substrates over 8-oxo-dGTP. Key structural features are identified that explain different substrate preferences for NUDT15 and MTH1. We find that depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT17 and NUDT18 were also profiled and found to have far less activity than MTH1 against oxidized nucleotides. We show that NUDT15 is not a biologically relevant 8-oxo-dGTPase, and that MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date.
Droplets move over viscoelastic substrates by surfing a ridge
Authors: Karpitschka S. , Das S. , van Gorcum M. , Perrin H. , Andreotti B. , Snoeijer J. H.
Published: August 2015

Liquid drops on soft solids generate strong deformations below the contact line, resulting from a balance of capillary and elastic forces. The movement of these drops may cause strong, potentially singular dissipation in the soft solid. Here we show that a drop on a soft substrate moves by surfing a ridge: the initially flat solid surface is deformed into a sharp ridge whose orientation angle depends on the contact line velocity. We measure this angle for water on a silicone gel and develop a theory based on the substrate rheology. We quantitatively recover the dynamic contact angle and provide a mechanism for stick–slip motion when a drop is forced strongly: the contact line depins and slides down the wetting ridge, forming a new one after a transient. We anticipate that our theory will have implications in problems such as self-organization of cell tissues or the design of capillarity-based microrheometers.
Non-plasmonic nanoantennas for surface enhanced spectroscopies with ultra-low heat conversion
Authors: Caldarola Martín , Albella Pablo , Cortés Emiliano , Rahmani Mohsen , Roschuk Tyler , Grinblat Gustavo , Oulton Rupert F. , Bragas Andrea V. , Maier Stefan A.
Published: August 2015

Nanoplasmonics has recently revolutionized our ability to control light on the nanoscale. Using metallic nanostructures with tailored shapes, it is possible to efficiently focus light into nanoscale field ‘hot spots’. High field enhancement factors have been achieved in such optical nanoantennas, enabling transformative science in the areas of single molecule interactions, highly enhanced nonlinearities and nanoscale waveguiding. Unfortunately, these large enhancements come at the price of high optical losses due to absorption in the metal, severely limiting real-world applications. Via the realization of a novel nanophotonic platform based on dielectric nanostructures to form efficient nanoantennas with ultra-low light-into-heat conversion, here we demonstrate an approach that overcomes these limitations. We show that dimer-like silicon-based single nanoantennas produce both high surface enhanced fluorescence and surface enhanced Raman scattering, while at the same time generating a negligible temperature increase in their hot spots and surrounding environments.
Time reversal and charge conjugation in an embedding quantum simulator
Authors: Zhang Xiang , Shen Yangchao , Zhang Junhua , Casanova Jorge , Lamata Lucas , Solano Enrique , Yung Man-Hong , Zhang Jing-Ning , Kim Kihwan
Published: August 2015

A quantum simulator is an important device that may soon outperform current classical computations. A basic arithmetic operation, the complex conjugate, however, is considered to be impossible to be implemented in such a quantum system due to the linear character of quantum mechanics. Here, we present the experimental quantum simulation of such an unphysical operation beyond the regime of unitary and dissipative evolutions through the embedding of a quantum dynamics in the electronic multilevels of a 171Yb+ ion. We perform time reversal and charge conjugation, which are paradigmatic examples of antiunitary symmetry operators, in the evolution of a Majorana equation without the tomographic knowledge of the evolving state. Thus, these operations can be applied regardless of the system size. Our approach offers the possibility to add unphysical operations to the toolbox of quantum simulation, and provides a route to efficiently compute otherwise intractable quantities, such as entanglement monotones.
A search for synergy in the binding kinetics of Trastuzumab and Pertuzumab whole and F(ab) to Her2
Authors: Lua Wai-Heng , Gan Samuel Ken-En , Lane David Philip , Verma Chandra Shekhar
Published: August 2015

Therapeutic efficacy resulting from combining Trastuzumab and Pertuzumab in the treatment of Her2 overexpressing breast cancer patients has been shown to increase patient survival. This is thought to arise from inhibition of receptor dimerization and the immune tagging of the cancer cells; however, the underlying molecular mechanisms have remained enigmatic. Previously, a molecular modeling study suggested that this resulted from colocalization of the two antibodies on to the extracellular domain of Her2. We report here the experimental characterization of this interaction by measuring the binding kinetics of these two whole antibodies and their F(ab)s to the extracellular domain of Her2 in solution. We found that both antibodies (the whole antibodies and the fragments) colocalized on to Her2, but did not augment the binding of each other.
A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment
Authors: Fu Wei , Zhu Pengyu , Wang Chenguang , Huang Kunlun , Du Zhixin , Tian Wenying , Wang Qin , Wang Huiyu , Xu Wentao , Zhu Shuifang
Published: August 2015

Digital PCR has developed rapidly since it was first reported in the 1990s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.
USP18 negatively regulates NF-κB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms
Authors: Yang Zhifen , Xian Huifang , Hu Jiajia , Tian Shuo , Qin Yunfei , Wang Rong-Fu , Cui Jun
Published: August 2015

Nuclear factor κB (NF-κB) is a key transcription factor in inflammatory immune responses and cell survival. Multiple types of ubiquitination play critical roles in the activation of NF-κB signaling, yet the molecular mechanisms responsible for their reversible deubiquitination are still poorly understood. In this study, we identified a member of the deubiquitinases family, ubiquitin-specific protease 18 (USP18), as a novel negative regulator in Toll-like receptor (TLR)-mediated NF-κB activation in human macrophages. USP18 is an interferon inducible gene, which is also upregulated by various TLR ligands in human monocytes and macrophages. Knockdown of USP18 enhanced the phosphorylation of IKK, the degradation of IκB and augmented the expression of pro-inflammatory cytokines. Furthermore, USP18 interacted with TAK1-TAB1 complex and IKKα/β-NEMO complex, respectively. USP18 cleaved the K63-linked polyubiquitin chains attached to TAK1 in a protease-dependent manner. Moreover, USP18 targeted the IKK complex through the regulatory subunit NEMO of IKK and specifically inhibited K63-linked ubiquitination of NEMO. Mutation analysis revealed direct binding of USP18 to the UBAN motif of NEMO. Our study has identified a previously unrecognized role for USP18 in the negative regulation of NF-κB activation by inhibiting K63-linked ubiquitination of TAK1 and NEMO through distinct mechanisms.
N-myc is a key switch regulating the proliferation cycle of postnatal cerebellar granule cell progenitors
Authors: Ma Ming , Wu Wenting , Li Qing , Li Jinya , Sheng Zhejin , Shi Jiahao , Zhang Mengjie , Yang Hua , Wang Zhugang , Sun Ruilin , Fei Jian
Published: August 2015

N-myc plays an important role in early cerebellar development; however, the role of N-myc in postnatal cerebellar development is still unknown. In this study, inducible and reversible N-myc mouse models (NmycTRE/TRE:tTS and NmycEGFP/TRE:tTS) are used to regulate and track the expression of endogenous N-myc in vivo. Loss of N-myc at the neonatal stage results in reduced proliferation of granule cell precursors (GCPs) and reduced cerebellar volume/mass. Restoration of N-myc expression no later than postnatal day 4 can rescue the cerebellar developmental defect caused by the absence of N-myc after birth. During cerebellar postnatal development, N-myc acts as a key switch, regulating the proliferation cycle of postnatal granule cell progenitors. Loss of N-myc significantly impairs the Sonic hedgehog signalling pathway and disrupts the expression of cell cycle effectors with a significant reduction of Ccnd2. More importantly, N-myc negatively regulates the expression of microRNA-9 during postnatal cerebellar development. Our findings demonstrate that over-expression of miR-9 can inhibit the proliferation of GCPs. The regulation of these factors by N-myc is at least partly responsible for the switch role of N-myc in the proliferation cycle of GCPs.
Interface Engineering through Atomic Layer Deposition towards Highly Improved Performance of Dye-Sensitized Solar Cells
Authors: Lu Hao , Tian Wei , Guo Jun , Li Liang
Published: August 2015

A composite photoanode comprising ultralong ZnO nanobelts and TiO2 nanoparticles was prepared and its performance in dye-sensitized solar cells (DSSCs) was optimized and compared to the photoanode consisting of conventional TiO2 nanoparticles. The ultralong ZnO nanobelts were synthesized in high yield by a facile solution approach at 90 oC followed by annealing at 500 oC. The effect of the ratio of ZnO nanobelts to TiO2 nanoparticles on the light scattering, specific surface area and interface recombination were investigated. An optimum amount of ZnO nanobelts enhanced the photon-conversion efficiency by 61.4% compared to that of the conventional TiO2 nanoparticles. To further reduce the recombination rate and increase the carrier lifetime, Atomic Layer Deposition (ALD) technique was utilized to coat a continuous TiO2 film surrounding the ZnO nanobelts and TiO2 nanoparticles, functioning as a barrier-free access of all electrons to conductive electrodes. This ALD treatment improved the interface contact within the whole photoanode system, finally leading to significant enhancement (137%) in the conversion efficiency of DSSCs.
HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response
Authors: Lim Key-Hwan , Park Jang-Joon , Gu Bon-Hee , Kim Jin-Ock , Park Sang Gyu , Baek Kwang-Hyun
Published: August 2015

HAUSP (herpes virus-associated ubiquitin specific protease, known as ubiquitin specific protease 7), one of DUBs, regulates the dynamics of the p53 and Mdm2 network in response to DNA damage by deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Its concerted action increases the level of functional p53 by preventing proteasome-dependent degradation of p53. However, the protein substrates that are targeted by HAUSP to mediate DNA damage responses in the context of the HAUSP-p53-Mdm2 complex are not fully identified. Here, we identified nucleolin as a new substrate for HAUSP by proteomic analysis. Nucleolin has two HAUSP binding sites in its N- and C-terminal regions and the mutation of HAUSP interacting peptides on nucleolin disrupts their interaction and it leads to the increased level of nucleolin ubiquitination. In addition, HAUSP regulates the stability of nucleolin by removing ubiquitin from nucleolin. Nucleolin exists as a component of the HAUSP-p53-Mdm2 complex and both Mdm2 and p53 are required for the interaction between HAUSP and nucleolin. Importantly, the irradiation increases the HAUSP-nucleolin interaction, leading to nucleolin stabilization significantly. Taken together, this study reveals a new component of the HAUSP-p53-Mdm2 complex that governs dynamic cellular responses to DNA damage.
Sensitivity of mRNA Translation
Authors: Poker Gilad , Margaliot Michael , Tuller Tamir
Published: August 2015

Using the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, elongation and termination rates along the mRNA strand on the steady-state protein translation rate. We show that the sensitivity of mRNA translation is equal to the sensitivity of the maximal eigenvalue of a symmetric, nonnegative, tridiagonal and irreducible matrix. This leads to new analytical results as well as efficient numerical schemes that are applicable for large-scale models. Our results show that in the usual endogenous case, when initiation is more rate-limiting than elongation, the sensitivity of the translation rate to small mutations rapidly increases towards the 5′ end of the ORF. When the initiation rate is high, as may be the case for highly expressed and/or heterologous optimized genes, the maximal sensitivity is with respect to the elongation rates at the middle of the mRNA strand. We also show that the maximal possible effect of a small increase/decrease in any of the rates along the mRNA is an increase/decrease of the same magnitude in the translation rate. These results are in agreement with previous molecular evolutionary and synthetic biology experimental studies.
Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients
Authors: Ho Li-chun , Yen Chung-Jen , Chao Chia-Ter , Chiang Chih-Kang , Huang Jenq-Wen , Hung Kuan-Yu
Published: August 2015

Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.
CACUL1/CAC1 Regulates the Antioxidant Response by Stabilizing Nrf2
Authors: Kigoshi Yu , Fukuda Tomomi , Endo Tomoyuki , Hayasaka Nami , Iemura Shun-ichiro , Natsume Toru , Tsuruta Fuminori , Chiba Tomoki
Published: August 2015

Nrf2 is the pre-dominant transcription activator responsible for coordinated up-regulation of ARE-driven antioxidant and detoxification genes. The activity of Nrf2 is tightly regulated at basal levels through its ubiquitination by Cul3-Keap1 and consequential degradation. Upon exposure to stress, the Cul3-Keap1 ligase is inhibited, leading to Nrf2 stabilization and activation. Here we describe CACUL1/CAC1 as a positive regulator of the Nrf2 pathway. We found that CACUL1 is up-regulated by Nrf2-activating oxidative stresses in cells and in mice. The association of CACUL1 with the Cul3-Keap1 complex led to a decrease in Nrf2 ubiquitination levels at non-stressed as well as stressed conditions and sensitized cells for higher Nrf2 activation. Furthermore, CACUL1 knock-down led to a decrease in Nrf2 activity and cell viability under stress. Our results show that CACUL1 is a regulator of Nrf2 ubiquitination, adding another regulatory layer to the Nrf2 antioxidant stress response.
A Surface-Enhanced Raman Scattering Sensor Integrated with Battery-Controlled Fluidic Device for Capture and Detection of Trace Small Molecules
Authors: Zhou Qitao , Meng Guowen , Zheng Peng , Cushing Scott , Wu Nianqiang , Huang Qing , Zhu Chuhong , Zhang Zhuo , Wang Zhiwei
Published: August 2015

For surface-enhanced Raman scattering (SERS) sensors, one of the important issues is the development of substrates not only with high SERS-activity but also with strong ability to capture analytes. However, it is difficult to achieve the two goals simultaneously especially when detecting small molecules. Herein a compact battery-controlled nanostructure-assembled SERS system has been demonstrated for capture and detection of trace small molecule pollutants in water. In this SERS fluidic system, an electrical heating constantan wire covered with the vertically aligned ZnO nanotapers decorated with Ag-nanoparticles is inserted into a glass capillary. A mixture of thermo-responsive microgels, Au-nanorods colloids and analyte solution is then filled into the remnant space of the capillary. When the system is heated by switching on the battery, the thermo-responsive microgels shrink, which immobilizes the analyte and drives the Au-nanorod close to each other and close to the Ag-ZnO nanotapers. This process has also created high-density “hot spots” due to multi-type plasmonic couplings in three-dimensional space, amplifying the SERS signal. This integrated device has been successfully used to measure methyl parathion in lake water, showing a great potential in detection of aquatic pollutants.
Correction: Synthetic enzyme supercomplexes: co-immobilization of enzyme cascades
Authors: Kazenwadel F. , Franzreb M. , Rapp B. E.
Published: August 2015

Correction for ‘Synthetic enzyme supercomplexes: co-immobilization of enzyme cascades’ by F. Kazenwadel et al., Anal. Methods, 2015, 7, 4030–4037.
Pt(ii)-Catalyzed photosynthesis for H2 evolution cycling between singly and triply reduced species
Authors: Yamamoto Keiya , Kitamoto Kyoji , Yamauchi Kosei , Sakai Ken
Published: August 2015

A platinum(ii)-based single-component molecular photocatalyst for hydrogen evolution from water cycling between the singly and triply reduced forms is reported.
Plasmon-induced spatial electron transfer between single Au nanorods and ALD-coated TiO2: dependence on TiO2 thickness
Authors: Zheng Zhaoke , Tachikawa Takashi , Majima Tetsuro
Published: August 2015

The interfacial electron transfer between single Au nanorods and TiO2 coated by ALD was investigated by single-particle photoluminescence measurements.
Thermotropic interface and core relaxation dynamics of liquid crystals in silica glass nanochannels: a dielectric spectroscopy study
Authors: Całus Sylwia , Borowik Lech , Kityk Andriy V. , Eich Manfred , Busch Mark , Huber Patrick
Published: August 2015

We report dielectric relaxation spectroscopy experiments on two rod-like liquid crystals of the cyanobiphenyl family (5CB and 6CB) confined in tubular nanochannels with 7 nm radius and 340 micrometer length in a monolithic, mesoporous silica membrane.
Energy dissipative photoprotective mechanism of carotenoid spheroidene from the photoreaction center of purple bacteria Rhodobacter sphaeroides
Authors: Arulmozhiraja Sundaram , Nakatani Naoki , Nakayama Akira , Hasegawa Jun-ya
Published: August 2015

Triplet energy dissipation mechanism of a carotenoid: just bond twisting and stretching lead to minimum energy intersystem crossing point.
PRESTO polarization transfer to quadrupolar nuclei: implications for dynamic nuclear polarization
Authors: Perras Frédéric A. , Kobayashi Takeshi , Pruski Marek
Published: August 2015

We show both experimentally and numerically that in experiments involving transfer of magnetization from 1H to the quadrupolar nuclei under MAS, the PRESTO technique consistently outperforms the traditionally used CP method, affording more quantitative intensities, improved lineshapes, better sensitivity, and easier optimization.
Biodegradation of ionic liquids – a critical review
Authors: Jordan Andrew , Gathergood Nicholas
Published: August 2015

The importance of biodegradation data as part of the design of safer chemicals is presented using ionic liquids (ILs) as a model study.
Ethylene oligomerization promoted by chromium complexes bearing pyrrolide–imine–amine/ether tridentate ligands
Authors: Pinheiro A. C. , Roisnel T. , Kirillov E. , Carpentier J.-F. , Casagrande Osvaldo L.
Published: August 2015

Chromium complexes bearing pyrrolide–imino-amine/ether tridentate ligands have been synthesized and their catalytic behavior in ethylene oligomerization has been investigated. Drastic changes in selectivity have been observed upon slight variation of the MAO-to-Cr ratio.
A novel solid-state Li–O2 battery with an integrated electrolyte and cathode structure
Authors: Zhu X. B. , Zhao T. S. , Wei Z. H. , Tan P. , Zhao G.
Published: August 2015

A novel solid-state lithium–air battery allows a thin electrolyte layer to reduce RΩ and a highly porous cathode (enhanced TPBs).
Room temperature seed mediated growth of gold nanoparticles: mechanistic investigations and life cycle assesment
Authors: Leng Weinan , Pati Paramjeet , Vikesland Peter J.
Published: August 2015

In this study, we report the first room temperature seed-mediated synthesis of gold nanoparticles (AuNPs) in the presence of citrate and gold salt.
An efficient metal-free pathway to vinyl thioesters with calcium carbide as the acetylene source
Authors: Rodygin Konstantin S. , Ananikov Valentine P.
Published: August 2015

Acetylene was replaced with calcium carbide and utilized for the synthesis of practically useful vinyl thioesters in a simple and environmentally benign procedure.
Integrated in silico and experimental methods revealed that Arctigenin inhibited angiogenesis and HCT116 cell migration and invasion through regulating the H1F4A and Wnt/β-catenin pathway
Authors: Zhang Shouyue , Li Jie , Song Sicheng , Li Jing , Tong Rongsheng , Zang Zhihe , Jiang Qinglin , Cai Lulu
Published: August 2015

The proteomic analysis integrated signalling network analysis suggested that the Wnt/β-catenin signalling pathway was a novel target of Arctigenin.