bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between serum and salivary phenytoin drug metabolite levels to phenytoin influenced gingival overgrowth in adult male subjects. A prospective cohort study
Authors: Sridharan Srirangarajan , Priyanka S.
Published: July 2017

Background To correlate serum and salivary phenytoin drug metabolite levels in males to phenytoin influenced gingival overgrowth (PIGO).

Methods Thirty male patients who are to start with oral phenytoin therapy were recruited. Plaque index (PI), Gingival index (GI), and Oral hygiene index (OHI) were recorded. Basic periodontal therapy was performed. Patients were followed up at 3, 6, 9 and 12 months intervals. Based on the gingival status they were divided in to two groups; Group1 (responders) and Group 2 (non responders). Serum and Salivary samples were analyzed for the drug metabolite levels spectophotometrically.

Results The mean values of phenytoin drug metabolite levels in serum of group 1 and group 2 subjects were 14.5 ± 2.6 μg/ml and 14.2 ± 1.7 μg/ml respectively, with p value of 0.66. The corresponding mean values of phenytoin drug metabolite levels saliva were 1.42 ± 0.34 μg/ml and 1.38 ± 0.37 μg/ml with p value of 0.75. Correlation of phenytoin drug metabolite to PI, GI, and OHI in both the groups did not show any statistical significance. (R values ranging from −0.229 to 0.434). Correlation between the serum and salivary drug metabolites in both the responder and non responder group also did not show any statistically significant relationship.

Conclusion No correlation between the drug concentration in either the serum or saliva can be correlated to PIGO. Whole Saliva could be a useful tool in therapeutic drug monitoring of phenytoin.

Clinical relevance Scientific rationale: To assess and compare the drug metabolite levels in serum and saliva of a neurologic condition where therapeutic drug concentration is of key importance to minimize the side effects. Principle finding: Saliva could be as useful as serum in deciding the drug concentration of phenytoin. And PIGO is not related drug concentrations. Practical implication: Monitoring the drug dosage is of paramount importance for the success of antiepileptic therapy as well as control of its side effects. This longitudinal study confirms that saliva could be an effective alternative to serum for monitoring drug dosage of phenytoin.
Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis
Authors: Ovod Vitaliy , Ramsey Kara N. , Mawuenyega Kwasi G. , Bollinger Jim G. , Hicks Terry , Schneider Theresa , Sullivan Melissa , Paumier Katrina , Holtzman David M. , Morris John C. , Benzinger Tammie , Fagan Anne M. , Patterson Bruce W. , Bateman Randall J.
Published: July 2017

Introduction

Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid‐binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid β (Aβ) biomarker for central nervous system amyloid deposition.

Methods

We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma.

Results

Aβ isoforms have a half‐life of approximately 3 hours in plasma. Aβ38 demonstrated faster turnover kinetics compared with Aβ40 and Aβ42. Faster fractional turnover of Aβ42 relative to Aβ40 and lower Aβ42 and Aβ42/Aβ40 concentrations in amyloid‐positive participants were observed.

Discussion

Blood plasma Aβ42 shows similar amyloid‐associated alterations as we have previously reported in cerebrospinal fluid, suggesting a blood‐brain transportation mechanism of Aβ. The stability and sensitivity of plasma Aβ measurements suggest this may be a useful screening test for central nervous system amyloidosis.
The marketplace of ideology: “Elective affinities” in political psychology and their implications for consumer behavior
Authors: Jost John T.
Published: July 2017

An abundance of research in political psychology demonstrates that leftists and rightists (or liberals and conservatives) diverge from one another in terms of: (a) personality characteristics; (b) cognitive processing styles; (c) motivational interests and concerns; (d) the prioritization of personal values; and (e) neurological structures and physiological functions. In this article, I summarize these findings and discuss some of their implications for persuasion, framing, and advertising; consumer choice, judgment, decision‐making, and behavior; and customer satisfaction/dissatisfaction and politically motivated boycotts. I conclude that the theory and practice of consumer psychology will be enriched by taking into account ideological asymmetries and the ways in which human behavior both reflects and gives rise to left–right divergence in political orientation—not only in terms of beliefs, opinions, and values but also in terms of underlying psychological processes.
Taller para formación de instructores de Introducción a la Cirugía
Authors: Jiménez Corona José Luis , Peña Jiménez Carmen Magdalena , Santana Vargas Ángel Daniel , Millán Rosas Gabriela , Kim Koh Min Jeong , Argüero Sánchez Rubén
Published: July 2017

Introducción: La literatura reporta la importancia de enseñar a enseñar. Existen diversos estudios en los cuales se menciona que los estudiantes de medicina no suelen recibir instrucción formal para el desarrollo de competencias docentes. La formación docente ayuda a que los estudiantes sean mejores comunicadores y la enseñanza es un aspecto esencial de la relación médico-paciente.

Objetivos: Evaluar el desempeño declarativo y procedimental de estudiantes del tercer año de la Licenciatura de Médico Cirujano con alto rendimiento académico, interesados en la enseñanza de la cirugía que cursaron el taller de formación para ayudantes de profesor de la asignatura de Introducción a la Cirugía.

Método: El taller se impartió al finalizar el segundo año de la licenciatura en el periodo interanual; comprendió 42 h teóricas y 54 prácticas, se revisaron 9 unidades temáticas y 16 prácticas, se aplicó un examen de selección y 4 exámenes teórico-prácticos.

Resultados: Durante el periodo de 2012-2016, 225 estudiantes solicitaron asistir al taller, de los cuales 111 estudiantes fueron seleccionados para cursarlo, con una composición de 67 mujeres (61%) y 44 hombres (39%); y fueron distinguidos 78 educandos, 45 mujeres y 33 hombres, para integrarse como instructores de la asignatura.

Conclusiones: Los estudiantes manifestaron que el taller cumple sus objetivos y expectativas, les proporciona estrategias de enseñanza-aprendizaje que promueven el trabajo en equipo, y se destaca la feminización en el taller.

Propuesta de futuro: Diseñar un programa académico complementario para los estudiantes interesados en ingresar a la residencia quirúrgica; implementar metodología de probada eficacia como el aprendizaje asistido por pares (PAL), que incluya la tutoría de un profesor del departamento con práctica quirúrgica y realizar un estudio cualitativo con la metodología de grupos focales para indagar las percepciones de los estudiantes a partir de su experiencia en el taller.
Standard Descriptive Vocabulary and Archaeology Digital Data Collection
Authors: Beebe Caroline
Published: July 2017

Archaeology has embraced the shift to digital technology for collecting, analyzing, and sharing data. Digital repositories are now recognized as essential for data stewardship and are setting standards for data deposition. These new technologies and systems support the scientific need for reproducible results through intra-cultural as well as cross-cultural hypothesis testing. Methods of digital data collection in the field, however, are often site specific, restricted by the limited availability of digital technologies, or not well suited for creating systems that support the requirements of the new digital information paradigm. As a small science project, the Chau Hiix Project in Belize will provide examples of the pitfalls in and insights about shifting to digital technology to make its primary data shareable and reusable. These experiences suggest the need for an international collaborative agenda that develops digital data description standards based on controlled vocabulary, facet analysis, and crosswalks implemented at the analog point of collection.
Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective
Authors: Burkholder David B. , Koehler Peter J. , Boes Christopher J.
Published: July 2017

Trigeminal neuralgia (TN) associated with multiple sclerosis (MS) was first described in Lehrbuch der Nervenkrankheiten für Ärzte und Studirende in 1894 by Hermann Oppenheim, including a pathologic description of trigeminal root entry zone demyelination. Early English-language translations in 1900 and 1904 did not so explicitly state this association compared with the German editions. The 1911 English-language translation described a more direct association. Other later descriptions were clinical with few pathologic reports, often referencing Oppenheim but citing the 1905 German or 1911 English editions of Lehrbuch. This discrepancy in part may be due to the translation differences of the original text.
Contrasted surface mass balances of debris-free glaciers observed between the southern and the inner parts of the Everest region (2007–15)
Authors: SHERPA SONAM FUTI , WAGNON PATRICK , BRUN FANNY , BERTHIER ETIENNE , VINCENT CHRISTIAN , LEJEUNE YVES , ARNAUD YVES , KAYASTHA RIJAN BHAKTA , SINISALO ANNA
Published: July 2017

Three debris-free glaciers with strongly differing annual glaciological glacier-wide mass balances (MBs) are monitored in the Everest region (central Himalaya, Nepal). The mass budget of Mera Glacier (5.1 km2in 2012), located in the southern part of this region, was balanced during 2007–15, whereas Pokalde (0.1 km2in 2011) and West Changri Nup glaciers (0.9 km2in 2013), ~30 km further north, have been losing mass rapidly with annual glacier-wide MBs of −0.69 ± 0.28 m w.e. a−1(2009–15) and −1.24 ± 0.27 m w.e. a−1(2010–15), respectively. An analysis of high-elevation meteorological variables reveals that these glaciers are sensitive to precipitation, and to occasional severe cyclonic storms originating from the Bay of Bengal. We observe a negative horizontal gradient of annual precipitation in south-to-north direction across the range (≤−21 mm km−1, i.e. −2% km−1). This contrasted mass-balance pattern over rather short distances is related (i) to the low maximum elevation of Pokalde and West Changri Nup glaciers, resulting in years where their accumulation area ratio is reduced to zero and (ii) to a steeper vertical gradient of MB for glaciers located in the inner arid part of the range.
Validity of the American College of Surgeons' National Surgical Quality Improvement Program risk calculator in South Australian glossectomy patients
Authors: Kao S S , Frauenfelder C , Wong D , Edwards S , Krishnan S , Ooi E H
Published: July 2017

Background:

Appropriate selection of tongue cancer patients considering surgery is critical in ensuring optimal outcomes. The American College of Surgeons' National Surgical Quality Improvement Program (‘ACS-NSQIP’) risk calculator was developed to assess patients' 30-day post-operative risk, providing surgeons with information to guide decision making.

Method:

A retrospective review of 30-day actual mortality and morbidity of tongue cancer patients was undertaken to investigate the validity of this tool for South Australian patients treated from 2005 to 2015.

Results:

One hundred and twenty patients had undergone glossectomy. Predicted length of stay using the risk calculator was significantly different from actual length of stay. Predicted mortality and other complications were found to be similar to actual outcomes.

Conclusion:

The American College of Surgeons' National Surgical Quality Improvement Program risk calculator was found to be effective in predicting post-operative complication rates in South Australian tongue cancer patients. However, significant discrepancies in predicted and actual length of stay may limit its use in this population.
Infanticide attacks and associated epimeletic behaviour in free-ranging common bottlenose dolphins (Tursiops truncatus)
Authors: Díaz López Bruno , López Alfredo , Methion Séverine , Covelo Pablo
Published: July 2017

Infanticide is considered a conspicuous expression of sexual conflict amongst mammals, including bottlenose dolphins. Although reported previously in this species, confirmed cases of infanticide and associated epimeletic behaviour are very rare and their socio-behavioural context remains poorly understood. Here, we provide evidence of epimeletic and infanticide behaviours in free-ranging bottlenose dolphins in Galicia, NW Spain. After describing the observed events, we include a complete description of the post-mortem examinations (where the carcasses were recovered) in order to confirm the cause of death. With evidences of blunt trauma in two of the presented cases, we confirm that the calves were intentionally killed by adult individuals. The aggressive interaction between adult individuals and the neonates together with the observed ante-mortem injuries bore a strong resemblance to the behaviours and traumatic injuries described in other cases of violent dolphin interactions in other parts of the world. The circumstances under which these infanticides occurred at our site fit the conditions proposed under the sexual selection hypothesis. The difficulties for researchers to observe this type of behaviour in the field and to find carcasses in good enough condition to determine the cause of death, emphasizes the importance of this type of study.
The interaction between nutrition and exercise for promoting health and performance
Authors: Witard Oliver C. , Ball Derek
Published: July 2017

The theme of The Nutrition Society Spring Conference 2017 was on the interaction between nutrition and exercise for promoting healthy ageing, maintaining cognitive function and improving the metabolic health of the population. The importance of this theme is highlighted by the public health issues surrounding obesity, diabetes and the age-related loss of skeletal muscle mass (sarcopenia). The opening symposium provided a historical perspective of both invasive and non-invasive methodologies for measuring exercise energetics and energy balance. Data derived from these techniques underpin current understanding regarding the metabolic response to nutrition and exercise. Further symposia examined the importance of skeletal muscle for healthy ageing in older men and postmenopausal women. From a nutritional perspective, the potential for animal- v. plant-based protein sources to offset the age-related decline in muscle mass was discussed. The day concluded by discussing the link(s) between nutrition, exercise and brain function. Day 2 commenced with examples of applied equine research illustrating the link between nutrition/exercise and insulin resistance to those of a human model. The final symposium examined the combined role of nutrition and exercise in reducing risk of type 2 diabetes and dyslipidaemia. The overall conclusion from the meeting was that the interaction between diet and physical activity confers greater benefits to human health and performance than either component alone.
Parasites as prey: the effect of cercarial density and alternative prey on consumption of cercariae by four non-host species
Authors: WELSH JENNIFER E. , LIDDELL CAROLINE , VAN DER MEER JAAP , THIELTGES DAVID W.
Published: July 2017

In parasites with complex life cycles the transmission of free-living infective stages can be influenced by ambient community diversity, in particular via predation. Here, we experimentally investigated whether parasite density and the presence of alternative prey can alter predation rates on free-living cercarial stages of a marine trematode by several non-host predators. All four predator species consumed increasing numbers of cercariae with an increase in cercarial density, indicating that the removal of cercariae by predators is effective over a range of natural densities as well as in the presence of alternative prey for a number of predators typical of marine ecosystems. However, the relative removal rates and the effects of cercarial density and alternative prey differed among predator species. In barnacles and shrimps, significant interactive effects of cercarial density and alternative prey on cercarial predation occurred while in oysters and crabs cercarial removal rates were unaffected by both factors. As changes in cercarial densities directly translate into changes in infection levels in down-stream hosts in this parasite–host system, the observed predator-specific responses suggest that cercarial predation effects on disease risks will depend on the specific species composition of ambient communities and not on non-host biodiversity per se.
Ecological outcomes and popular perceptions of urban restored forests in Rio de Janeiro, Brazil
Authors: MULER ANA ELENA , PRIETO PABLO VIANY , RICHARDS RYAN C. , BRANCALION PEDRO H. S. , BRAGA JOÃO MARCELO ALVARENGA
Published: July 2017

Ecological restoration is suggested as a tool to mitigate environmental problems caused by urbanization, but its utility may be hampered by conflict between ecological design and neighbouring communities’ needs. We explore this issue by comparing vegetation diversity and structure in a 21-year-old urban reforestation project in Rio de Janeiro city, Brazil, with a nearby reference forest, and we assessed popular perceptions about the project. Overall, density and basal area of canopy trees in the restoration plantation reached 73% and 46%, respectively, of the values found in the reference forest, but ground cover by exotic grasses was substantially higher in the planted forest. Rarefied species richness was similarly high in the plantation forest (59 species) and in the remnant forest (69 species), but species composition was markedly different. The human legacy on restoration diminished with time, reflected in the higher proportion of species and individuals of late-successional, native and not-planted species in the seedling community of the plantation forest. While community perceptions of reforestation were positive and both use and non-use values were reported, interviewees reported little involvement in the development of the project, which could have contributed to synergies between ecological and social outcomes.
The seed ecology of Agriophyllum squarrosum, a pioneer sand dune annual in Central Asia, with particular reference to seed germination
Authors: Fan Shugao , Baskin Carol C. , Baskin Jerry M. , Wang Yanrong
Published: July 2017

In central Asia, Agriophyllum squarrosum is the first species to become established during natural succession on sand dunes. However, low germination percentages and thus poor stand establishment greatly inhibit the use of this key species in the stabilization of dunes. The aim of this review is to critically analyse published information on the seed biology of A. squarrosum with particular reference to identifying the factors limiting germination of seeds sown in the field. A conceptual model is used to illustrate the complexities of factors as well as the unknowns we found about the seed/seedling stage of the life cycle of this sand dune annual. A major result of this review is that we now know that high germination percentages can be obtained by storing freshly collected seeds dry at room temperatures for 2 to 3 months to allow dormancy break to occur via afterripening, and then storing them dry at low (e.g. 4–5°C) temperature to prevent them from entering secondary dormancy. Non-dormant seeds should be sown in the field in late spring when wind-blown sand will cover them, thus ensuring that they are in darkness, which promotes germination, at the time summer rains occur.
Syllabus of Plant Families. A. Engler’s Syllabus der Pflanzenfamilien, 13th edition. Part 2/1: Photoautotrophic Eukaryotic Algae. Glaucocystophyta, Cryptophyta, Dinophyta/Dinozoa, Haptophyta, Heterokontophyta/Ochrophyta, Chlorarachniophyta/ Cercozoa
Authors: Mann David G.
Published: July 2017

..
Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions
Authors: Davies M. J. , Rumbold A. R. , Moore V. M.
Published: July 2017

The use of assisted reproductive technologies (ART) for the treatment of infertility has grown exponentially over the last 20 years, and now accounts for 4% of all births in Australia, and over 1 m births annually around the globe. There is consistent reporting of increased risk of adverse perinatal outcomes and birth defects following infertility treatment. However, change in practice has been stymied by critical knowledge gaps with regards to (a) the relative contribution of patient and treatment factors to adverse outcomes, (b) the independent contribution of specific contemporary treatments and treatment combinations to outcomes, (c) the impact of innovations in laboratory and clinical practice on treatment success and observed risk and (d) changes over time in patient characteristics. Here we summarize key findings from the South Australian Birth Cohort, which is a whole-of-population cohort of over 300,000 births from 1986 to 2002. Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn [odds ratio (OR)=1.82; 95% confidence interval (CI) 1.34–2.48], while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (OR=2109 g; 95% CI 2129–289), very low birth weight (OR=2.74; 95% CI 2.19–3.43), very preterm birth (OR=2.30; 95% CI 1.82–2.90) and neonatal death (OR=2.04; 95% CI 1.27–3.26). Major birth defects, including cardiac, urogenital and musculoskeletal defects are doubled after fresh ICSI cycles, which is a particular concern as ICSI now accounts for 70% of all treatment cycles globally. Future study is needed to provide contemporary, precise evidence to inform patient and clinic decision making, and generate knowledge for future innovation in ART laboratory methods and clinical practice, thereby optimizing treatment and health outcomes while reducing adverse events.
Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures
Authors: Shin Kwangsoo , Choi Jin Woo , Ko Giho , Baik Seungmin , Kim Dokyoon , Park Ok Kyu , Lee Kyoungbun , Cho Hye Rim , Han Sang Ihn , Lee Soo Hong , Lee Dong Jun , Lee Nohyun , Kim Hyo-Cheol , Hyeon Taeghwan
Published: July 2017

Tissue adhesives have emerged as an alternative to sutures and staples for wound closure and reconnection of injured tissues after surgery or trauma. Owing to their convenience and effectiveness, these adhesives have received growing attention particularly in minimally invasive procedures. For safe and accurate applications, tissue adhesives should be detectable via clinical imaging modalities and be highly biocompatible for intracorporeal procedures. However, few adhesives meet all these requirements. Herein, we show that biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) exhibit not only high contrast effects for real-time imaging but also strong adhesive properties. Furthermore, the biocompatible TSNs cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (that is, a mixture of cyanoacrylate and Lipiodol). Because of their multifunctional imaging and adhesive property, the TSNs are successfully applied as a hemostatic adhesive for minimally invasive procedures and as an immobilized marker for image-guided procedures.
Universality and chaoticity in ultracold K+KRb chemical reactions
Authors: Croft J. F. E. , Makrides C. , Li M. , Petrov A. , Kendrick B. K. , Balakrishnan N. , Kotochigova S.
Published: July 2017

A fundamental question in the study of chemical reactions is how reactions proceed at a collision energy close to absolute zero. This question is no longer hypothetical: quantum degenerate gases of atoms and molecules can now be created at temperatures lower than a few tens of nanokelvin. Here we consider the benchmark ultracold reaction between, the most-celebrated ultracold molecule, KRb and K. We map out an accurate ab initio ground-state potential energy surface of the K2Rb complex in full dimensionality and report numerically-exact quantum-mechanical reaction dynamics. The distribution of rotationally resolved rates is shown to be Poissonian. An analysis of the hyperspherical adiabatic potential curves explains this statistical character revealing a chaotic distribution for the short-range collision complex that plays a key role in governing the reaction outcome.
Highly-conducting molecular circuits based on antiaromaticity
Authors: Fujii Shintaro , Marqués-González Santiago , Shin Ji-Young , Shinokubo Hiroshi , Masuda Takuya , Nishino Tomoaki , Arasu Narendra P. , Vázquez Héctor , Kiguchi Manabu
Published: July 2017

Aromaticity is a fundamental concept in chemistry. It is described by Hückel’s rule that states that a cyclic planar π-system is aromatic when it shares 4n+2 π-electrons and antiaromatic when it possesses 4n π-electrons. Antiaromatic compounds are predicted to exhibit remarkable charge transport properties and high redox activities. However, it has so far only been possible to measure compounds with reduced aromaticity but not antiaromatic species due to their energetic instability. Here, we address these issues by investigating the single-molecule charge transport properties of a genuinely antiaromatic compound, showing that antiaromaticity results in an order of magnitude increase in conductance compared with the aromatic counterpart. Single-molecule current–voltage measurements and ab initio transport calculations reveal that this results from a reduced energy gap and a frontier molecular resonance closer to the Fermi level in the antiaromatic species. The conductance of the antiaromatic complex is further modulated electrochemically, demonstrating its potential as a high-conductance transistor.
Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami
Authors: Rubin Charles M. , Horton Benjamin P. , Sieh Kerry , Pilarczyk Jessica E. , Daly Patrick , Ismail Nazli , Parnell Andrew C.
Published: July 2017

The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami.
High-energy mid-infrared sub-cycle pulse synthesis from a parametric amplifier
Authors: Liang Houkun , Krogen Peter , Wang Zhou , Park Hyunwook , Kroh Tobias , Zawilski Kevin , Schunemann Peter , Moses Jeffrey , DiMauro Louis F. , Kärtner Franz X. , Hong Kyung-Han
Published: July 2017

High-energy phase-stable sub-cycle mid-infrared pulses can provide unique opportunities to explore phase-sensitive strong-field light–matter interactions in atoms, molecules and solids. At the mid-infrared wavelength, the Keldysh parameter could be much smaller than unity even at relatively modest laser intensities, enabling the study of the strong-field sub-cycle electron dynamics in solids without damage. Here we report a high-energy sub-cycle pulse synthesiser based on a mid-infrared optical parametric amplifier and its application to high-harmonic generation in solids. The signal and idler combined spectrum spans from 2.5 to 9.0 µm. We coherently synthesise the passively carrier-envelope phase-stable signal and idler pulses to generate 33 μJ, 0.88-cycle, multi-gigawatt pulses centred at ~4.2 μm, which is further energy scalable. The mid-infrared sub-cycle pulse is used for driving high-harmonic generation in thin silicon samples, producing harmonics up to ~19th order with a continuous spectral coverage due to the isolated emission by the sub-cycle driver.
A room temperature continuous-wave nanolaser using colloidal quantum wells
Authors: Yang Zhili , Pelton Matthew , Fedin Igor , Talapin Dmitri V. , Waks Edo
Published: July 2017

Colloidal semiconductor nanocrystals have emerged as promising active materials for solution-processable optoelectronic and light-emitting devices. In particular, the development of nanocrystal lasers is currently experiencing rapid progress. However, these lasers require large pump powers, and realizing an efficient low-power nanocrystal laser has remained a difficult challenge. Here, we demonstrate a nanolaser using colloidal nanocrystals that exhibits a threshold input power of less than 1 μW, a very low threshold for any laser using colloidal emitters. We use CdSe/CdS core-shell nanoplatelets, which are efficient nanocrystal emitters with the electronic structure of quantum wells, coupled to a photonic-crystal nanobeam cavity that attains high coupling efficiencies. The device achieves stable continuous-wave lasing at room temperature, which is essential for many photonic and optoelectronic applications. Our results show that colloidal nanocrystals are suitable for compact and efficient optoelectronic devices based on versatile and inexpensive solution-processable materials.
Ubiquitin-specific protease 21 stabilizes BRCA2 to control DNA repair and tumor growth
Authors: Liu Jinping , Kruswick Alex , Dang Hien , Tran Andy D. , Kwon So Mee , Wang Xin Wei , Oberdoerffer Philipp
Published: July 2017

Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of DNA damage associated with excessive cell division. Modulating repair factor function, thus, provides a promising strategy to manipulate malignant growth. Here, we identify the ubiquitin-specific protease USP21 as a positive regulator of BRCA2, a key mediator of DNA repair by homologous recombination. USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks. As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival. Importantly, BRCA2 overexpression partially restores the USP21-associated survival defect. Moreover, we show that USP21 is overexpressed in hepatocellular carcinoma, where it promotes BRCA2 stability and inversely correlates with patient survival. Together, our findings identify deubiquitination as a means to regulate BRCA2 function and point to USP21 as a potential therapeutic target in BRCA2-proficient tumors.
Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis
Authors: Gao Yun-Rong , Li De-Feng , Fleming Joy , Zhou Ya-Feng , Liu Ying , Deng Jiao-Yu , Zhou Lin , Zhou Jie , Zhu Guo-Feng , Zhang Xian-En , Wang Da-Cheng , Bi Li-Jun
Published: July 2017

MarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high affinity. Subsequent determination and analysis of Rv2887 crystal structures in apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion of helix α4 into the major groove. Ligand binding triggers rotation of the wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene Rv0560c. The structures provided here lay a foundation for the design of small molecules that target Rv2887, a potential new approach for the development of anti-mycobacterials.
Fragment optimization for GPCRs by molecular dynamics free energy calculations: Probing druggable subpockets of the A
2A
adenosine receptor binding site
Authors: Matricon Pierre , Ranganathan Anirudh , Warnick Eugene , Gao Zhan-Guo , Rudling Axel , Lambertucci Catia , Marucci Gabriella , Ezzati Aitakin , Jaiteh Mariama , Dal Ben Diego , Jacobson Kenneth A. , Carlsson Jens
Published: July 2017

Fragment-based lead discovery is becoming an increasingly popular strategy for drug discovery. Fragment screening identifies weakly binding compounds that require optimization to become high-affinity leads. As design of leads from fragments is challenging, reliable computational methods to guide optimization would be invaluable. We evaluated using molecular dynamics simulations and the free energy perturbation method (MD/FEP) in fragment optimization for the A2A adenosine receptor, a pharmaceutically relevant G protein-coupled receptor. Optimization of fragments exploring two binding site subpockets was probed by calculating relative binding affinities for 23 adenine derivatives, resulting in strong agreement with experimental data (R2 = 0.78). The predictive power of MD/FEP was significantly better than that of an empirical scoring function. We also demonstrated the potential of the MD/FEP to assess multiple binding modes and to tailor the thermodynamic profile of ligands during optimization. Finally, MD/FEP was applied prospectively to optimize three nonpurine fragments, and predictions for 12 compounds were evaluated experimentally. The direction of the change in binding affinity was correctly predicted in a majority of the cases, and agreement with experiment could be improved with rigorous parameter derivation. The results suggest that MD/FEP will become a powerful tool in structure-driven optimization of fragments to lead candidates.
High diversity of the Ganzhou Oviraptorid Fauna increased by a new “cassowary-like” crested species
Authors: Lü Junchang , Li Guoqing , Kundrát Martin , Lee Yuong-Nam , Sun Zhenyuan , Kobayashi Yoshitsugu , Shen Caizhi , Teng Fangfang , Liu Hanfeng
Published: July 2017

A new oviraptorid dinosaur from the Late Cretaceous of Ganzhou, bringing oviraptrotid diversity of this region to seven taxa, is described. It is characterized by a distinct cassowary-like crest on the skull, no pleurocoels on the centra from the second through fourth cervical vertebrae, a neck twice as long as the dorsal vertebral column and slightly longer than the forelimb (including the manus). Phylogenetic analysis recovers the new oviraptorid taxon, Corythoraptor jacobsi, as closely related to Huanansaurus from Ganzhou. Osteochronology suggests that the type specimen of Corythoraptor had not reached stationary growth stage but died while decreasing growth rates. The histology implies that it would correspond to an immature individual approximately eight years old. We hypothesize, based on the inner structure compared to that in modern cassowaries, that the prominent casque of Corythoraptor was a multifunction-structure utilized in display, communication and probably expression of the fitness during mating seasons.
Match between soaring modes of black kites and the fine-scale distribution of updrafts
Authors: Santos Carlos D. , Hanssen Frank , Muñoz Antonio-Román , Onrubia Alejandro , Wikelski Martin , May Roel , Silva João P.
Published: July 2017

Understanding how soaring birds use updrafts at small spatial scales is important to identify ecological constraints of movement, and may help to prevent conflicts between wind-energy development and the conservation of wildlife. We combined high-frequency GPS animal tracking and fine-spatial-scale uplift modelling to establish a link between flight behaviour of soaring birds and the distribution of updrafts. We caught 21 black kites (Milvus migrans) and GPS-tracked them while flying over the Tarifa region, on the Spanish side of the Strait of Gibraltar. This region has a diverse topography and land cover, favouring a heterogeneous updraft spatial distribution. Bird tracks were segmented and classified into flight modes from motion parameters. Thermal and orographic uplift velocities were modelled from publically available remote-sensing and meteorological data. We found that birds perform circular soaring in areas of higher predicted thermal uplift and linear soaring in areas of higher predicted orographic uplift velocity. We show that updraft maps produced from publically available data can be used to predict where soaring birds will concentrate their flight paths and how they will behave in flight. We recommend the use of this methodological approach to improve environmental impact assessments of new wind-energy installations.
Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging
Authors: Shah N. J. , Arrubla J. , Rajkumar R. , Farrher E. , Mauler J. , Kops E. Rota , Tellmann L. , Scheins J. , Boers F. , Dammers J. , Sripad P. , Lerche C. , Langen K. J. , Herzog H. , Neuner I.
Published: July 2017

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography – electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain’s default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition – excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and β–1, but not with β–2 and β–3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.
Lactate oxidation facilitates growth of Mycobacterium tuberculosis in human macrophages
Authors: Billig Sandra , Schneefeld Marie , Huber Claudia , Grassl Guntram A. , Eisenreich Wolfgang , Bange Franz-Christoph
Published: July 2017

Mycobacterium tuberculosis (Mtb) uses alveolar macrophages as primary host cells during infection. In response to an infection, macrophages switch from pyruvate oxidation to reduction of pyruvate into lactate. Lactate might present an additional carbon substrate for Mtb. Here, we demonstrate that Mtb can utilize L-lactate as sole carbon source for in vitro growth. Lactate conversion is strictly dependent on one of two potential L-lactate dehydrogenases. A knock-out mutant lacking lldD2 (Rv1872c) was unable to utilize L-lactate. In contrast, the lldD1 (Rv0694) knock-out strain was not affected in growth on lactate and retained full enzymatic activity. On the basis of labelling experiments using [U-13C3]-L-lactate as a tracer the efficient uptake of lactate by Mtb and its conversion into pyruvate could be demonstrated. Moreover, carbon flux from lactate into the TCA cycle, and through gluconeogenesis was observed. Gluconeogenesis during lactate consumption depended on the phosphoenolpyruvate carboxykinase, a key enzyme for intracellular survival, showing that lactate utilization requires essential metabolic pathways. We observed that the ΔlldD2 mutant was impaired in replication in human macrophages, indicating a critical role for lactate oxidation during intracellular growth.
Eternal non-Markovianity: from random unitary to Markov chain realisations
Authors: Megier Nina , Chruściński Dariusz , Piilo Jyrki , Strunz Walter T.
Published: July 2017

The theoretical description of quantum dynamics in an intriguing way does not necessarily imply the underlying dynamics is indeed intriguing. Here we show how a known very interesting master equation with an always negative decay rate [eternal non-Markovianity (ENM)] arises from simple stochastic Schrödinger dynamics (random unitary dynamics). Equivalently, it may be seen as arising from a mixture of Markov (semi-group) open system dynamics. Both these approaches lead to a more general family of CPT maps, characterized by a point within a parameter triangle. Our results show how ENM quantum dynamics can be realised easily in the laboratory. Moreover, we find a quantum time-continuously measured (quantum trajectory) realisation of the dynamics of the ENM master equation based on unitary transformations and projective measurements in an extended Hilbert space, guided by a classical Markov process. Furthermore, a Gorini-Kossakowski-Sudarshan-Lindblad (GKSL) representation of the dynamics in an extended Hilbert space can be found, with a remarkable property: there is no dynamics in the ancilla state. Finally, analogous constructions for two qubits extend these results from non-CP-divisible to non-P-divisible dynamics.
Optical Band Gap Alteration of Graphene Oxide via Ozone Treatment
Authors: Hasan Md Tanvir , Senger Brian J. , Ryan Conor , Culp Marais , Gonzalez-Rodriguez Roberto , Coffer Jeffery L. , Naumov Anton V.
Published: July 2017

Graphene oxide (GO) is a graphene derivative that emits fluorescence, which makes GO an attractive material for optoelectronics and biotechnology. In this work, we utilize ozone treatment to controllably tune the band gap of GO, which can significantly enhance its applications. Ozone treatment in aqueous GO suspensions yields the addition/rearrangement of oxygen-containing functional groups suggested by the increase in vibrational transitions of C-O and C=O moieties. Concomitantly it leads to an initial increase in GO fluorescence intensity and significant (100 nm) blue shifts in emission maxima. Based on the model of GO fluorescence originating from sp2 graphitic islands confined by oxygenated addends, we propose that ozone-induced functionalization decreases the size of graphitic islands affecting the GO band gap and emission energies. TEM analyses of GO flakes confirm the size decrease of ordered sp2 domains with ozone treatment, whereas semi-empirical PM3 calculations on model addend-confined graphitic clusters predict the inverse dependence of the band gap energies on sp2 cluster size. This mod﻿el explains ozone-induced increase in emission energies yielding fluorescence blue shifts and helps develop an understanding of the origins of GO fluorescence emission. Furthermore, ozone treatment provides a versatile approach to controllably alter GO band gap for optoelectronics and bio-sensing applications.
CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and Neurons
Authors: Pardo Luis , Valor Luis Miguel , Eraso-Pichot Abel , Barco Angel , Golbano Arantxa , Hardingham Giles E. , Masgrau Roser , Galea Elena
Published: July 2017

The cyclic AMP response element binding protein (CREB) is a primary hub of activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are unknown despite the fact that the astrocytic CREB is also activity-driven and neuroprotective. Herein we identified the transcriptional programs regulated by CREB in astrocytes as compared to neurons using, as study materials, transcriptome databases of astrocyte exposed to well-known activators of CREB-dependent transcription as well as publicly available transcriptomes of neuronal cultures. Functional CREB signatures were extracted from the transcriptomes using Gene Ontology, adult-brain gene lists generated by Translating Ribosome Affinity Purification (TRAP) and CREB-target gene repositories. We found minimal overlap between CREB signatures in astrocytes and neurons. In astrocytes, the top triad of functions regulated by CREB consists of ‘Gene expression’, ‘Mitochondria’, and ‘Signalling’, while in neurons it is ‘Neurotransmission’, ‘Signalling’ and ‘Gene expression’, the latter two being represented by different genes from those in astrocytes. The newly generated databases will provide a tool to explore novel means whereby CREB impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptional cascades in astrocytes.
Modeling of an Inverted Drift Tube for Improved Mobility Analysis of Aerosol Particles
Authors: Nahin Minal , Oberreit Derek , Fukushima Nobuhiko , Larriba-Andaluz Carlos
Published: July 2017

A new mobility particle analyzer, which has been termed Inverted Drift Tube, has been modeled analytically as well as numerically and proven to be a very capable instrument. The basis for the new design have been the shortcomings of the previous ion mobility spectrometers, in particular (a) diffusional broadening which leads to degradation of instrument resolution and (b) inadequate low and fixed resolution (not mobility dependent) for large sizes. To overcome the diffusional broadening and have a mobility based resolution, the IDT uses two varying controllable opposite forces, a flow of gas with velocity v
gas
, and a linearly increasing electric field that opposes the movement. A new parameter, the separation ratio Λ = v
drift
/v
gas
, is employed to determine the best possible separation for a given set of nanoparticles. Due to the system’s need to operate at room pressure, two methods of capturing the ions at the end of the drift tube have been developed, Intermittent Push Flow for a large range of mobilities, and Nearly-Stopping Potential Separation, with very high separation but limited only to a narrow mobility range. A chromatography existing concept of resolving power is used to differentiate between peak resolution in the IDT and acceptable separation between similar mobility sizes.
Transformation-induced changes in the DNA-nuclear matrix interface, revealed by high-throughput analysis of DNA halos
Authors: Wilson Rosemary H. C. , Coverley Dawn
Published: July 2017

In higher eukaryotic nuclei, DNA is periodically anchored to an extraction-resistant protein structure, via matrix attachment regions. We describe a refined and accessible method to non-subjectively, rapidly and reproducibly measure both size and stability of the intervening chromatin loops, and use it to demonstrate that malignant transformation compromises the DNA-nuclear matrix interface.