bluuebunny/crossref_metadata_2025 huggingface dataset:
circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA
Authors: Okholm Trine Line Hauge , Kamstrup Andreas Bjerregaard , Nielsen Morten Muhlig , Hollensen Anne Kruse , Graversgaard Mette Laugesen , Sørensen Matilde Helbo , Kristensen Lasse Sommer , Vang Søren , Park Samuel S , Yeo Eugene , Dyrskjøt Lars , Kjems Jørgen , Pedersen Jakob Skou , Damgaard Christian Kroun
Published: July 2024

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.
Optimizing road safety: integrated analysis of motorized vehicle using lattice ordered complex linear diophantine fuzzy soft set
Authors: Banu K. Ashma , Vimala J. , Kausar Nasreen , Stević Željko
Published: July 2024

In this manuscript, we delve into the realm of lattice ordered complex linear diophantine fuzzy soft set, which constitutes an invaluable extension to the existing Fuzzy set theories. Within this exploration, we investigate basic operations such as $\oplus$ and $\otimes$, together with their properties and theorems. This manuscript is more amenable in two ways, i.e., it enables real-life problems involving parametrization tool and applications with an existing order between the components of the parameter set based on the preference in the complex frame of reference. Adaptive cruise control (ACC) is a system designed for maintaining distance between two vehicles and to sustain a manually provided input speed. The purpose of cars with ACC is to avoid a collision that frequently happens nowadays, thereby improving road safety regulations amidst rising collision rates. The fundamental aim of this manuscript is to prefer an applicable car with ACC together with its latest model by defining a peculiar postulation of lattice ordered complex linear diophantine fuzzy soft set $\rm ( \widehat{LOCLDFSS} )$. Emphasizing real-life applicability, we illustrate the effectiveness and validity of our suggested methodology in tackling current automotive safety concerns, providing useful guidance on reducing challenges related to contemporary driving conditions.
piRNA-disease association prediction based on multi-channel graph variational autoencoder
Authors: Sun Wei , Guo Chang , Wan Jing , Ren Han
Published: July 2024

Piwi-interacting RNA (piRNA) is a type of non-coding small RNA that is highly expressed in mammalian testis. PiRNA has been implicated in various human diseases, but the experimental validation of piRNA-disease associations is costly and time-consuming. In this article, a novel computational method for predicting piRNA-disease associations using a multi-channel graph variational autoencoder (MC-GVAE) is proposed. This method integrates four types of similarity networks for piRNAs and diseases, which are derived from piRNA sequences, disease semantics, piRNA Gaussian Interaction Profile (GIP) kernel, and disease GIP kernel, respectively. These networks are modeled by a graph VAE framework, which can learn low-dimensional and informative feature representations for piRNAs and diseases. Then, a multi-channel method is used to fuse the feature representations from different networks. Finally, a three-layer neural network classifier is applied to predict the potential associations between piRNAs and diseases. The method was evaluated on a benchmark dataset containing 5,002 experimentally validated associations with 4,350 piRNAs and 21 diseases, constructed from the piRDisease v1.0 database. It achieved state-of-the-art performance, with an average AUC value of 0.9310 and an AUPR value of 0.9247 under five-fold cross-validation. This demonstrates the method’s effectiveness and superiority in piRNA-disease association prediction.
Resultados do IDEB e gestão escolar: implicações e reflexões
Authors: Ribeiro Oseny Amorim , Magalhães de Albuquerque Jader Cristiano , Sales Káthia Marise Borges , Almeida Itana Vieira , Cruz Agda Rocha , Silva Rosana Cruz Marques da
Published: July 2024

Este artigo surgiu a partir de pesquisa realizada durante o curso de Mestrado e tem o propósito de trazer à luz aspectos sobre a atuação da gestão escolar, a partir da dimensão pedagógica, em duas escolas municipais de Lauro de Freitas (BA) e se suas ações impactaram no resultado do IDEB – Índice de Desenvolvimento da Educação Básica, levando-as a obter as notas mais altas do município por sete edições consecutivas, no período de 2007-2019, e a figurar, em alguns anos, com nota mais alta que a do IDEB do próprio município. Para tanto, mapeamos as ações da gestão escolar, a fim de perceber se existe correlação entre elas e o desempenho da instituição consolidado pelo IDEB. Para obter os dados, foram realizados questionários e entrevistas com membros dos grupos de cada instituição. As informações obtidas através dos dados coletados foram analisadas seguindo a metodologia proposta e os resultados obtidos revelam que as práticas dos gestores entrevistados coadunam com o referencial teórico que guiou a pesquisa. Como recorte dos resultados, identificamos alguns achados que dizem muito acerca das práticas de gestão de ambas as escolas pesquisadas. A discussão é complexa e mais estudos são necessários para buscar mais dados que fortaleçam a discussão em torno do tema.
Atypical Haemolytic Uraemic Syndrome in an Infant with Ventricular Septal Defect: A Case Report
Authors: Paul Sheuli , Salunkhe Shradha Rahul , Patil Manojkumar G , Mane Shailaja V
Published: July 2024

Atypical Haemolytic Uraemic Syndrome (aHUS) is a rare type of thrombotic microangiopathy that occurs without Shiga toxin producing bacteria. It is a condition related to complement regulation, which may be genetic or acquired. The complement system’s alternative pathway is commonly implicated, with around 6-10% of cases being caused by autoantibodies directed against factor H. While it typically affects children between 9 to 13-years-old, it can also occur in adults. Many patients do not have circulating Complement Factor H-related proteins 1 and 3 due to a homozygous deletion involving CFHR1 and CFHR3. Authors hereby report a case of a six-month-old female child who was diagnosed with Ventricular Septal Defect (VSD) at one and a half months of age. She presented with pneumonia and subsequently developed haemolytic anaemia with thrombocytopenia, oliguria, and acute kidney failure. She was diagnosed with Antifactor H antibody-mediated HUS. She was treated with plasma therapy, but the patient succumbed due to multiorgan dysfunction.
Evaluating the Application of the SIR Model to a Localized Population
Authors: Close Alexandra
Published: July 2024

Objective

Using data collected from the Johns Hopkins COVID-19 Repository, I investigated the reliability of the SIR (Susceptible-Infected-Removed) model.

Summary of Background Data

Modern pandemic responses have evolved into effective defenses when implemented correctly but present issues in epidemiological modeling efforts. Intervention strategies such as quarantining and masking limit population size (N), which affects the accuracy of modeling population-based rate systems especially in highly transmissible diseases.

Methods

I begin by reviewing the SIR model retroactively to the initial SARS-CoV-2 Wuhan strain. I compared the parameters available in the published literature (N = 2,717,000, β = 2, γ = 1/14) to the best-fitting SIR-yielded values by minimizing the root mean squared error function. Subsequently, I evaluated its predictive capabilities on the Delta variant using early surge data, which was later compared against a retroactive analysis.

Results

Using a least-squares error best-fit analysis allowed me to retroactively define remarkably accurate model parameters for the Wuhan waves. Parameters including N = 730, β = 0.46, γ = 0.043 in the first wave and N = 11,200, β = 0.198, γ = 0.07 in the second reflected effective intervention strategies. I show it is an effective predictive tool regarding the Delta variant, yielding parameters N = 50,900, β = 0.87, γ = 1/3.7 that proved accurate when compared with parameters from a full retroactive analysis (N = 60,000, β = 0.94, γ = 1/3.6).

Conclusion

The similarity of the yielded parameters in my results supports the SIR model’s utility in epidemiological monitoring of high-transmissibility, low-mortality outbreaks vis-à-vis various containment measures.
Toward robust and consistent regional CO2 flux estimates from in situ and spaceborne measurements of atmospheric CO2
Authors: Chevallier Frédéric , Palmer Paul I. , Feng Liang , Boesch Hartmut , O'Dell Christopher W. , Bousquet Philippe
Published: January 2014

We evaluate the robustness and consistency of global and regional posterior CO2 flux estimates for 2010 inferred from two versions of bias‐corrected CO2 column retrievals from the Japanese Greenhouse Gases Observing Satellite (GOSAT). Six satellite‐based inversions, generated from three atmospheric transport models and two independent Bayesian inference algorithms, facilitate a rigorous investigation of the uncertainty of the inverted fluxes. This ensemble shows hemispheric and regional differences in posterior flux estimates that are beyond 1 sigma uncertainties and in some regions are unrealistic. We recognize the importance of these satellite data in further understanding the contemporary carbon cycle but we argue that more resources should be invested in characterizing the errors of the prior fluxes, the systematic errors of the retrievals, and the systematic errors of the transport models, to improve confidence in the resulting posterior fluxes.
Estimating the ETAS model from an early aftershock sequence
Authors: Omi Takahiro , Ogata Yosihiko , Hirata Yoshito , Aihara Kazuyuki
Published: January 2014

Forecasting aftershock probabilities, as early as possible after a main shock, is required to mitigate seismic risks in the disaster area. In general, aftershock activity can be complex, including secondary aftershocks or even triggering larger earthquakes. However, this early forecasting implementation has been difficult because numerous aftershocks are unobserved immediately after the main shock due to dense overlapping of seismic waves. Here we propose a method for estimating parameters of the epidemic type aftershock sequence (ETAS) model from incompletely observed aftershocks shortly after the main shock by modeling an empirical feature of data deficiency. Such an ETAS model can effectively forecast the following aftershock occurrences. For example, the ETAS model estimated from the first 24 h data after the main shock can well forecast secondary aftershocks after strong aftershocks. This method can be useful in early and unbiased assessment of the aftershock hazard.
The spatial structure of Martian magnetic flux ropes recovered by the Grad‐Shafranov reconstruction technique
Authors: Hara Takuya , Seki Kanako , Hasegawa Hiroshi , Brain David A. , Matsunaga Kazunari , Saito Miho H.
Published: January 2014

We applied the Grad‐Shafranov (GS) reconstruction technique to Martian magnetic flux ropes observed by Mars Global Surveyor in order to estimate their spatial structures. This technique can provide a magnetic field map of their cross section from single spacecraft data, under the assumption that the structure is two‐dimensional, magnetohydrostatic, and time independent. We succeeded in recovering the spatial structure for 70 events observed between April 1999 and November 2006. The reconstruction results indicate that the flux rope axes were mostly oriented horizontal to the Martian surface and were randomly distributed with respect to the typical plasma streamline. A subset of events with duration longer than 240 s was observed at solar zenith angles larger than 75°. These events all occur downstream from strong crustal magnetic field in the southern hemisphere, indicating an association between the crustal fields and the detected flux ropes. Using the shape and size of the flux ropes obtained from the GS reconstruction, we estimate lower limits on their volume that span 2–3 orders of magnitude, with larger flux ropes observed downstream from strong crustal magnetic fields. Estimated ion escape rates associated with flux ropes are of the order of 1022–1023 ion/s, being approximately 10% of previously estimated escape rates during solar minimum.
Evaluation and improvement of a global land model against soil carbon data using a Bayesian Markov chain Monte Carlo method
Authors: Hararuk Oleksandra , Xia Jianyang , Luo Yiqi
Published: January 2014

Long‐term land carbon (C) cycle feedback to climate change is largely determined by dynamics of soil organic carbon (SOC). However, most evaluation studies conducted so far indicate that global land models predict SOC poorly. This study was conducted to evaluate predictions of SOC by the Community Land Model with Carnegie‐Ames‐Stanford Approach biogeochemistry submodel (CLM‐CASA'), investigate underlying causes of mismatches between model predictions and observations, and calibrate model parameters to improve the prediction of SOC. We compared modeled SOC to the SOC pools from a globally gridded observation data product and found that CLM‐CASA' on average underestimated SOC pools by 65% (r2= 0.28). We applied data assimilation to CLM‐CASA' to estimate SOC residence times, C partitioning coefficients among the pools, and temperature sensitivity of C decomposition. The model with calibrated parameters explained 41% of the global variability in the observed SOC, which was substantial improvement from the initial 27%. The SOC and litter C feedback to changing climate differed between models with original and calibrated parameters: after 95 years of climate change (2006–2100), soils released 48 Pg C less in the calibrated than in the noncalibrated model and litter released 6.5 Pg C less in the calibrated than the noncalibrated model. Thus, assimilating estimated soil carbon data into the model improved model performance and reduced the amount of C released under changing climate. To further reduce the uncertainty in the soil carbon prediction, we need to explore alternative model structures, improve representation of ecosystems, and develop additional global datasets for constraining model parameters.
A generalized global adaptive tracking control scheme for robot manipulators with bounded inputs
Authors: López‐Araujo Daniela J. , Zavala‐Río Arturo , Santibáñez Víctor , Reyes Fernando
Published: January 2014

In this work, a generalized adaptive scheme for the global motion control of robot manipulators with constrained inputs is proposed. It gives rise to various families of bounded adaptive controllers defined through a general class of saturation functions. Compared with adaptive tracking control algorithms previously developed in a bounded input context, the proposed adaptive approach guarantees the motion control objective for any initial condition, avoiding discontinuities throughout the scheme, preventing the inputs to reach their natural saturation bounds, and permitting innovation on the saturating structure through its generalized form, giving a wide range of possibilities for performance improvement. Experimental results corroborate the efficiency of the proposed scheme. Copyright © 2014 John Wiley & Sons, Ltd.
Aluminum–Iodoform Composite Reactive Material
Authors: Abraham Ani , Zhang Shasha , Aly Yasmine , Schoenitz Mirko , Dreizin Edward L.
Published: January 2014

Mechanically alloyed aluminum–iodoform composites were prepared with iodine concentration of 20 wt%. Ball milling at both room temperature and liquid nitrogen temperature was explored. Material characterization by electron microscopy and X‐ray diffraction showed no difference between samples milled at different temperatures. However, samples prepared at room temperature aged rapidly. Thermo‐gravimetric measurements quantifying release of iodine upon heating confirmed that cryogenic milling was necessary to stabilize iodoform in the Al‐matrix. Iodine was released upon heating in four distinct stages. The oxidation of the prepared materials was also studied using thermo‐gravimetric analysis and two main oxidation steps were detected. The ignition temperatures were determined for powders coated onto a metal filament heated electrically at 103–104 K min−1. The ignition temperatures of the prepared materials were noticeably lower compared to the Al · I2 composite prepared using a similar cryo‐milling approach. The combustion characteristics determined using constant volume explosions of aerosolized powders were found to be similar to those of Al · I2 composite. The maximum pressure and rate of pressure rise observed in the latter experiments were greater than for pure aluminum powders with comparable particle sizes.
Sustained Percolation in Stretched Silver Nanowire Networks for Stretchable Inter‐Connection Applications
Authors: Park Jae Sung , Rezaei Mohamad , Kim Woo Soo
Published: January 2014

Here we report a highly stretchable inter‐connection technology utilizing combination of the mechanical meander shape effect and silver nanowire (AgNW)‐based electrode's flexibility. Horseshoe‐shaped elastic materials, polydimethylsiloxanes, are used to embed the AgNW conductors for released stress concentration. Continuously maintained 2‐D percolation of stretchable AgNW networks overcome the rigid nature of Printed Circuit Board (PCB)'s restrictions. The horseshoe shaped inter‐connection maintains superior conductivity as well as repeating reliability under tensile strains upto 20 %, allowing the durable and practical stretchable PCB inter‐connecting applications.
Dendron‐Based Micelles for Topical Delivery of Endoxifen: A Potential Chemo‐Preventive Medicine for Breast Cancer
Authors: Yang Yang , Pearson Ryan M. , Lee Oukseub , Lee Chan‐Woo , Chatterton Robert T. , Khan Seema A. , Hong Seungpyo
Published: January 2014

Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen‐positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (‐NH2, ‐COOH, or ‐Ac) and into cationic liposomes as a control. End‐group modification significantly affects the drug loading, where the DM‐COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20‐fold) and human (up to 4‐fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM‐COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention.
Highly Asymmetric, Interfaced Dimers Made of Au Nanoparticles and Bimetallic Nanoshells: Synthesis and Photo‐Enhanced Catalysis
Authors: Hu Yongxing , Liu Yuzi , Li Zheng , Sun Yugang
Published: January 2014

Synthesis of a class of exotic interfaced dimers with high asymmetries in terms of composition, morphology, structure (solid versus hollow), and dimension of the individual nanoscale components in the dimers is successfully accomplished. Typical examples include the interfaced dimers made of solid Au nanoparticles and hollow bimetallic nanoshells with different compositions, such as Au/Ag, Pt/Ag, and Pd/Ag. The success of the synthesis relies on the combination of asymmetric overgrowth of Ag nanodomains on the partially passivated Au nanoparticles and a following galvanic replacement reaction between the Ag nanodomains and appropriate noble metal precursors. The entire synthesis is processed on the unique superparamagnetic colloidal substrates that offer many advantages, such as time‐efficiency, scalability, and high yield. The Au nanoparticle and the bimetallic nanoshell in each interfaced dimer are in direct contact, resulting in the possible strong coupling between them as well as novel properties that cannot be observed in either the nanoparticle or the nanoshell. For example, dimers made of Au nanoparticles and Pd/Ag nanoshells exhibit enhanced catalytic performance toward Suzuki coupling reactions under illumination of visible light because the strong surface plasmon resonances in the Au nanoparticles can influence the catalytic activity of the Pd/Ag nanoshells through coupling between the nanoparticles and the nanoshells.
25th Anniversary Article: Organic Field‐Effect Transistors: The Path Beyond Amorphous Silicon
Authors: Sirringhaus Henning
Published: January 2014

Over the past 25 years, organic field‐effect transistors (OFETs) have witnessed impressive improvements in materials performance by 3–4 orders of magnitude, and many of the key materials discoveries have been published in Advanced Materials. This includes some of the most recent demonstrations of organic field‐effect transistors with performance that clearly exceeds that of benchmark amorphous silicon‐based devices. In this article, state‐of‐the‐art in OFETs are reviewed in light of requirements for demanding future applications, in particular active‐matrix addressing for flexible organic light‐emitting diode (OLED) displays. An overview is provided over both small molecule and conjugated polymer materials for which field‐effect mobilities exceeding > 1 cm2 V–1 s–1 have been reported. Current understanding is also reviewed of their charge transport physics that allows reaching such unexpectedly high mobilities in these weakly van der Waals bonded and structurally comparatively disordered materials with a view towards understanding the potential for further improvement in performance in the future.
Cutting Short the Asymmetric Synthesis of the Ramatroban Precursor by Employing ω‐Transaminases
Authors: Busto Eduardo , Simon Robert C. , Grischek Barbara , Gotor‐Fernández Vicente , Kroutil Wolfgang
Published: January 2014

Starting from an adequate ketone precursor previous reports required three steps for the preparation of (R)‐2,3,4,9‐tetrahydro‐1H‐carbazol‐3‐amine, a key intermediate for the synthesis of the antiallergic drug ramatroban. A single biocatalytic step was sufficient to prepare the target amine with >97% ee (HPLC) via reductive amination of the corresponding ketone using an ω‐transaminase as biocatalyst. Since the ketone was barely soluble under the reaction conditions employed, it was provided as a solid and still the reaction went to completion within 4 h at 50 mM substrate concentration. Although 2‐propylamine is regarded as an ideal amine donor, it turned out to be detrimental for the specific ketone precursor leading to the formation of various side products. These could be avoided by using (R)‐1‐phenylethylamine as the best suited amine donor. An alternative work‐up was developed via freeze‐drying of the reaction mixture, enabling the isolation of the desired (R)‐amine in excellent yield (96%) and enantiopure form on a preparative scale (500 mg). No purification steps (e.g., column chromatography, crystallisation) were required.

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Production of aromatics by catalytic fast pyrolysis of cellulose in a bubbling fluidized bed reactor
Authors: Karanjkar Pranav U. , Coolman Robert J. , Huber George W. , Blatnik Michael T. , Almalkie Saba , de Bruyn Kops Stephen M. , Mountziaris Triantafillos J. , Conner William C.
Published: January 2014

Catalytic fast pyrolysis of cellulose was studied at 500°C using a ZSM‐5 catalyst in a bubbling fluidized bed reactor constructed from a 4.92‐cm ID pipe. Inert gas was fed from below through the distributor plate and from above through a vertical feed tube along with cellulose. Flowing 34% of the total fluidization gas through the feed tube led to the optimal mixing of the pyrolysis vapors into the catalyst bed, which experimentally corresponded to 29.5% carbon aromatic yield. Aromatic yield reached a maximum of 31.6% carbon with increasing gas residence time by changing the catalyst bed height. Increasing the hole‐spacing in the distributor plate was shown to have negligible effect on average bubble diameter and hence did not change the product distribution. Aromatic yields of up to 39.5% carbon were obtained when all studied parameters were optimized. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1320–1335, 2014
Modeling and control of solar‐grade silicon production in a fluidized bed reactor
Authors: Du Juan , Dutta Soham , Ydstie Birger Erik
Published: January 2014

A multiscale model predicts silicon production yield and powder loss in a fluidized bed reactor for solar silicon production. The reaction module calculates the silicon vapor deposition and powder scavenging rates. A computational fluid dynamics model predicts temperature and bed density. A population balance model calculates the particle‐mass distribution functions on silicon yield. The model results are validated against industrial data. Furthermore, we conduct a sensitivity analysis to investigate the effect of gas flow rate and inlet silane concentration. Finally, a control strategy is proposed to maintain the process at the desired operating point. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1740–1751, 2014
BRAF kinase domain mutations are present in a subset of chronic myelomonocytic leukemia with wild‐type RAS
Authors: Zhang Liping , Singh Rajesh R. , Patel Keyur P. , Stingo Francesco , Routbort Mark , You M. James , Miranda Roberto N. , Garcia‐Manero Guillermo , Kantarjian Hagop M. , Medeiros L. Jeffrey , Luthra Rajyalakshmi , Khoury Joseph D.
Published: January 2014

The frequency of RAS mutations in chronic myelomonocytic leukemia (CMML) suggests that activation of the MAPK pathway is important in CMML pathogenesis. Accordingly, we hypothesized that mutations in other members of the MAPK pathway might be overrepresented in RASwt CMML. We performed targeted next generation sequencing analysis on 70 CMML patients with known RAS mutation status. The study group included 37 men and 33 women with a median age of 67.8 years (range, 28–86 years). Forty patients were RASwt and 30 were RASmut; the latter included KRAS = 17; NRAS = 12; KRAS + NRAS = 1. Five patients (7.1% of total group; 12.5% of RASwt group) with RASwt had kinase domain BRAF mutations. The BRAF mutations were of missense type and involved exon 11 in one patient and exon 15 in four patients. All BRAFmut patients had CMML‐1 with low‐risk cytogenetic findings. Two (40%) of the five patients with BRAFmut patients transformed to acute myeloid leukemia during follow‐up. In summary, we demonstrate that a subset of patients with RASwt CMML harbors BRAF kinase domain mutations that are potentially capable of activating the MAPK signaling pathway. Am. J. Hematol. 89:499–504, 2014. © 2014 Wiley Periodicals, Inc.
Zwitterionische Polymere mit antimikrobiellen und Nonfouling‐Eigenschaften
Authors: Mi Luo , Jiang Shaoyi
Published: January 2014

Zwitterionische Polymere werden im Allgemeinen als eine neue Klasse von abweisenden “Nonfouling”‐Materialien angesehen. Sie verfügen über eine breitere chemische Diversität als entsprechende Polyethylenglycole (PEG) und eine größere Freiheit hinsichtlich des Moleküldesigns. Dieser Kurzaufsatz stellt neueste mikrobiologische Anwendungen zwitterionischer Polymere und ihrer Derivate in den Mittelpunkt, wobei verschiedene molekulare Strategien hervorgehoben werden, die antimikrobielle und Nonfouling‐Eigenschaften integrieren. Ferner werden Erkenntnisse über die Bakterienbewuchshemmung durch zwitterionische Polymere sowie ein Beispiel für die technische Verwendung zwitterionischer Polymerderivate als antimikrobielle Wundauflagen diskutiert.
Chinone als Dienophile in der Diels‐Alder‐Reaktion – historische Entwicklung und Anwendungen in der Totalsynthese
Authors: Nawrat Christopher C. , Moody Christopher J.
Published: January 2014

Im Repertoire an Reaktionen, das dem Organiker in der Totalsynthese zur Verfügung steht, gehört die Diels‐Alder‐Reaktion zu den wirksamsten und am besten verstandenen. Ihre Fähigkeit, komplexe Molekülstrukturen rasch durch die gleichzeitige Bildung von zwei Kohlenstoff‐Kohlenstoff‐Bindungen aufzubauen, ist nahezu unerreicht. Das spiegelt sich in der Vielzahl von Anwendungen der Reaktion wider, die in der Literatur beschrieben wurden. Im historischen Zusammenhang ist die Verwendung von Chinonen als Dienophile von großer Bedeutung, da sie das allererste Beispiel bildeten, das von Diels und Alder untersucht wurde. Dieser Aufsatz gibt einen Überblick über die Anwendung der Diels‐Alder‐Reaktion von Chinonen in der Totalsynthese von Naturstoffen. Die behandelten Beispiele stammen aus einem Zeitraum von etwa 60 Jahren: von den bahnbrechenden Synthesen von Morphin 1952 durch Gates und von Reserpin 1956 durch Woodward bis hin zu aktuellen Beispielen wie den Tetracyclinen.
One‐Pot Semisynthesis of Exon 1 of the Huntingtin Protein: New Tools for Elucidating the Role of Posttranslational Modifications in the Pathogenesis of Huntington’s Disease
Authors: Ansaloni Annalisa , Wang Zhe‐Ming , Jeong Jae Sun , Ruggeri Francesco Simone , Dietler Giovanni , Lashuel Hilal A.
Published: January 2014

The natural enzymes involved in regulating many of the posttranslational modifications (PTMs) within the first 17 residues (Nt17) of Huntingtin exon 1 (Httex1) remain unknown. A semisynthetic strategy that allows the site‐specific introduction of PTMs within Nt17 by using expressed protein ligation (EPL) was developed. This strategy was used to produce untagged wild‐type (wt) and T3‐phosphorylated (pT3) Httex1 containing 23 glutamine residues (Httex1‐23Q). Our studies show that pT3 significantly slows the oligomerization and fibrillization of Httex1‐23Q and that Httex1 variants containing polyQ repeats below the pathogenic threshold readily aggregate and form fibrils in vitro. These findings suggest that crossing the polyQ pathogenic threshold is not essential for Httex1 aggregation. The ability to produce wt or site‐specifically modified tag‐free Httex1 should facilitate determining its structure and the role of N‐terminal PTMs in regulating the functions of Htt in health and disease.
Single‐Layered Ultrasmall Nanoplates of MoS2 Embedded in Carbon Nanofibers with Excellent Electrochemical Performance for Lithium and Sodium Storage
Authors: Zhu Changbao , Mu Xiaoke , van Aken Peter A. , Yu Yan , Maier Joachim
Published: January 2014

The preparation and electrochemical storage behavior of MoS2 nanodots—more precisely single‐layered ultrasmall nanoplates—embedded in carbon nanowires has been studied. The preparation is achieved by an electrospinning process that can be easily scaled up. The rate performance and cycling stability of both lithium and sodium storage were found to be outstanding. The storage behavior is, moreover, highly exciting from a fundamental point of view, as the differences between the usual storage modes—insertion, conversion, interfacial storage—are beneficially blurred. The restriction to ultrasmall reaction domains allows for an almost diffusion‐less and nucleation‐free “conversion”, thereby resulting in a high capacity and a remarkable cycling performance.
Multifunctional Core–Shell Silica Nanoparticles for Highly Sensitive 19F Magnetic Resonance Imaging
Authors: Matsushita Hisashi , Mizukami Shin , Sugihara Fuminori , Nakanishi Yosuke , Yoshioka Yoshichika , Kikuchi Kazuya
Published: January 2014

19F magnetic resonance imaging (19F MRI) is useful for monitoring particular signals from biological samples, cells, and target tissues, because background signals are missing in animal bodies. Therefore, highly sensitive 19F MRI contrast agents are in great demand for their practical applications. However, we have faced the following challenges: 1) increasing the number of fluorine atoms decreases the solubility of the molecular probes, and 2) the restriction of the molecular mobility attenuates the 19F MRI signals. Herein, we developed novel multifunctional core–shell nanoparticles to solve these issues. They are composed of a core micelle filled with liquid perfluorocarbon and a robust silica shell. These core–shell nanoparticles have superior properties such as high sensitivity, modifiability of the surface, biocompatibility, and sufficient in vivo stability. By the adequate surface modifications, gene expression in living cells and tumor tissue in living mice were successfully detected by 19F MRI.
Identification of Living Legionella pneumophila Using Species‐Specific Metabolic Lipopolysaccharide Labeling
Authors: Mas Pons Jordi , Dumont Audrey , Sautejeau Grégory , Fugier Emilie , Baron Aurélie , Dukan Sam , Vauzeilles Boris
Published: January 2014

Legionella pneumophila is a pathogenic bacterium involved in regular outbreaks characterized by a relatively high fatality rate and an important societal impact. Frequent monitoring of the presence of this bacterium in environmental water samples is necessary to prevent these epidemic events, but the traditional culture‐based detection and identification method requires up to 10 days. Reported herein is a method allowing identification of Legionella pneumophila by metabolic lipopolysaccharide labeling which targets, for the first time, a precursor to monosaccharides that are specifically present within the O‐antigen of the bacterium. This new approach allows easy detection of living Legionella pneumophila, while other Legionella species are not labeled.
Atom‐Economic, Regiodivergent, and Stereoselective Coupling of Imidazole Derivatives with Terminal Allenes
Authors: Xu Kun , Thieme Niels , Breit Bernhard
Published: January 2014

New Rh‐ and Pd‐catalyzed regiodivergent and stereoselective intermolecular coupling reactions of imidazole derivatives with mono‐substituted allenes are herein reported. Using a RhI/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a PdII/dppf system gave linear products with high regioselectivities and high E/Z selectivities. This method permits the atom economic synthesis of valuable branched and linear allylic imidazole derivatives.
Photoresponsive Hybrid Raspberry‐Like Colloids Based on Cucurbit[8]uril Host–Guest Interactions
Authors: Lan Yang , Wu Yuchao , Fox Athan , Scherman Oren A.
Published: January 2014

Hybrid raspberry‐like colloids (HRCs) were prepared by employing cucurbit[8]uril (CB[8]) as a supramolecular linker to assemble functional polymeric nanoparticles onto a silica core. The formed HRCs are photoresponsive and can be reversibly disassembled upon light irradiation. This facile supramolecular approach provides a platform for the synthesis of colloids with sophisticated structures and properties.
Flavoenzyme‐Catalyzed Formation of Disulfide Bonds in Natural Products
Authors: Scharf Daniel H. , Groll Michael , Habel Andreas , Heinekamp Thorsten , Hertweck Christian , Brakhage Axel A. , Huber Eva M.
Published: January 2014

Nature provides a rich source of compounds with diverse chemical structures and biological activities, among them, sulfur‐containing metabolites from bacteria and fungi. Some of these compounds bear a disulfide moiety that is indispensable for their bioactivity. Specialized oxidoreductases such as GliT, HlmI, and DepH catalyze the formation of this disulfide bridge in the virulence factor gliotoxin, the antibiotic holomycin, and the anticancer drug romidepsin, respectively. We have examined all three enzymes by X‐ray crystallography and activity assays. Despite their differently sized substrate binding clefts and hence, their diverse substrate preferences, a unifying reaction mechanism is proposed based on the obtained crystal structures and further supported by mutagenesis experiments.
Pseudilins: Halogenated, Allosteric Inhibitors of the Non‐Mevalonate Pathway Enzyme IspD
Authors: Kunfermann Andrea , Witschel Matthias , Illarionov Boris , Martin René , Rottmann Matthias , Höffken H. Wolfgang , Seet Michael , Eisenreich Wolfgang , Knölker Hans‐Joachim , Fischer Markus , Bacher Adelbert , Groll Michael , Diederich François
Published: January 2014

The enzymes of the non‐mevalonate pathway for isoprenoid biosynthesis have been identified as attractive targets with novel modes of action for the development of herbicides for crop protection and agents against infectious diseases. This pathway is present in many pathogenic organisms and plants, but absent in mammals. By using high‐throughput screening, we identified highly halogenated marine natural products, the pseudilins, to be inhibitors of the third enzyme, IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis thaliana and Plasmodium vivax was determined in photometric and NMR‐based assays. Cocrystal structures revealed that pseudilins bind to an allosteric pocket by using both divalent metal ion coordination and halogen bonding. The allosteric mode of action for preventing cosubstrate (CTP) binding at the active site was elucidated. Pseudilins show herbicidal activity in plant assays and antiplasmodial activity in cell‐based assays.
Syntheses, toxicity and biodistribution of CO‐releasing molecules containing M(CO)5 (M = Mo, W and Cr)
Authors: Liu Huapeng , Wang Pengpeng , Zhao Quanyi , Chen Yonglin , Liu Bin , Zhang Baoping , Zheng Qian
Published: January 2014

A series of CO‐releasing molecules M(CO)5 L (M = Mo, W and Cr), (1, 2, 3, L = glycine methyl ester; 4, 5, 6, N‐methylimidazole; 7, 8, 9, 2‐aminopyridine; 10, 11, 12, 3‐aminopyridine; 13, 14, 15, 4‐aminopyridine), were synthesized. All complexes have been characterized by NMR, IR and electrospray ionization mass spectroscopy; the octahedral structures of 14 and 15 were also established by X‐ray crystallography. Furthermore, all complexes were evaluated for toxicity, pharmacokinetics and metabolic processes. Cytotoxic effects on the proliferation of fibroblast cell line were assayed by MTT. Among the complexes, Mo complex 1 showed the lowest cytotoxicity (IC50 = 597 µmol l−1) and W complex 2 showed a remarkable toxic effect, with IC50 = 52 µmol l−1. With the same ligand, the toxic effects of the complexes increase in the order of metal element W < Cr < Mo. For the same central metal element, the complexes containing imidazole showed lower toxic effects than those containing amino acid ester or aminopyridine. In accordance with the results from cytotoxicity, the complexes also showed corresponding toxic effects in animal models. The biodistributions of the complexes were established by inductively coupled plasma–atomic emission spectroscopy, measuring metal in tissues and organs. The results show that the complexes were gradually absorbed and unevenly distributed in vivo. The complexes containing imidazole entered tissues and organs faster than those containing amino acid ester. The complexes containing W atom were absorbed and distributed more slowly than those containing Mo or Cr atoms. Copyright © 2014 John Wiley & Sons, Ltd.
Pd‐catalyzed homocoupling of arylhydrazines via C―N cleavage under O2
Authors: Yao Peng
Published: January 2014

An efficient and simple synthetic method for biaryl synthesis was developed using Pd(OAc)2 as catalyst from aryl hydrazides under O2. Various biaryls were synthesized in good yields, offering an expedient protocol for the synthesis of symmetrical biaryl molecules via C―N cleavage. The reactions were performed in component solvent of toluene and acetone without using any pro‐oxidant. Copyright © 2014 John Wiley & Sons, Ltd.
Postsynthetic modification of IRMOF‐3 with a copper iminopyridine complex as heterogeneous catalyst for the synthesis of 2‐aminobenzothiazoles
Authors: Liu Jie , Zhang Xiaobin , Yang Jin , Wang Lei
Published: January 2014

A copper iminopyridine complex has been immobilized on to a metal–organic framework (MOF) through postsynthetic modification of IRMOF‐3. The modified MOFs were fully demonstrated by using a variety of methods, and the structural integrity of the modified MOFs has been confirmed by powder X‐ray diffraction (XRD). Furthermore, it was shown that the modified IRMOF‐3 can act as an efficient solid catalyst for the synthesis of 2‐aminobenzothiazoles via the reaction of 2‐iodoanilines with isothiocyanates in a heterogeneous manner. Moreover, the catalyst could be facilely separated from the reaction mixture and reused for six consecutive cycles without significant degradation in catalytic activity. Copyright © 2014 John Wiley & Sons, Ltd.
Detecting and interpreting clusters of economic activity in rural areas using scan statistic and LISA under a unified framework
Authors: Bersimis S. , Chalkias C. , Anthopoulou T.
Published: January 2014

The primary aim of this paper is to expose the use and the value of spatial statistical analysis in business and especially in designing economic policies in rural areas. Specifically, we aim to present under a unified framework, the use of both point and area‐based methods, in order to analyze in‐depth economic data, as well as, to drive conclusions through interpreting the analysis results. The motivating problem is related to the establishment of women‐run enterprises in a rural area of Greece. Moreover, in this article, the spatial scan statistic is successfully applied to the spatial economic data at hand, in order to detect possible clusters of small women‐run enterprises in a rural mountainous and disadvantaged region of Greece. Then, it is combined with Geographical Information System based on Local Indicator of Spatial Autocorrelation scan statistic for further exploring and interpreting the spatial patterns. The rejection of the random establishment of women‐run enterprises and the interpretation of the clustering patterns are deemed necessary, in order to assist government in designing policies for rural development. Copyright © 2014 John Wiley & Sons, Ltd.
Statistical learning for variable annuity policyholder withdrawal behavior
Authors: Zhu Zhe , Welsch Roy E.
Published: January 2014

The variable annuity product has many desirable features for retirement saving purposes, such as stock‐linked growth potential, protection against losses in the investment, and guarantees of minimum payout amount at annuitization. Therefore, it is of great interest to study this product for designing next generation retirement solutions. Policyholder behavior is one of the most important profit or loss factors for the variable annuity product, and insurance companies generally do not have sophisticated models at the current time. This paper will discuss a new approach using modern statistical learning techniques to model policyholder withdrawal behavior with promising results. Copyright © 2014 John Wiley & Sons, Ltd.
Inference concerning a common dispersion of several treatment groups in the analysis of over/underdispersed count data
Authors: Saha Krishna K.
Published: January 2014

Over/underdispersed count data arise in many biostatistical practices in which a number of different treatment groups are compared in an experiment. In the analysis of several treatment groups of such count data, a very common statistical inference problem is to test whether these data come from the same population. The usual practice for testing homogeneity of several treatment groups in terms of means and dispersions is first to test the equality of dispersions and then to test the equality of the means based on the result of the test for equality of dispersions. Previous studies reported test procedures for testing the homogeneity of the means of several treatment groups with an assumption of equal or unequal dispersions. This article develops test procedures for testing the validity of the equal or unequal dispersions assumption of several treatment groups in the analysis of over/underdispersed count data. We consider thetest based on the maximum likelihood (ML) method using the negative binomial model as well as the three othertests based on the method of moments, extended quasi‐likelihood, and double extended quasi‐likelihood using the models specified by the first two moments of counts. Monte Carlo simulations are then used to study the comparative behavior of thesetests along with the likelihood ratio test in terms of size and power. The simulation results demonstrate that all four statistics hold the nominal level reasonably well in most of the data situations studied here, and thetest based on ML shows some edge in power over the other threetests. Finally, applications to biostatistical practices are analyzed.
Comparison of monovalent and divalent ion distributions around a DNA duplex with molecular dynamics simulation and a Poisson‐Boltzmann approach
Authors: Robbins Timothy J. , Ziebarth Jesse D. , Wang Yongmei
Published: January 2014

The ion atmosphere created by monovalent (Na+) or divalent (Mg2+) cations surrounding a B‐form DNA duplex were examined using atomistic molecular dynamics (MD) simulations and the nonlinear Poisson‐Boltzmann (PB) equation. The ion distributions predicted by the two methods were compared using plots of radial and two‐dimensional cation concentrations and by calculating the total number of cations and net solution charge surrounding the DNA. Na+ ion distributions near the DNA were more diffuse in PB calculations than in corresponding MD simulations, with PB calculations predicting lower concentrations near DNA groove sites and phosphate groups and a higher concentration in the region between these locations. Other than this difference, the Na+ distributions generated by the two methods largely agreed, as both predicted similar locations of high Na+ concentration and nearly identical values of the number of cations and the net solution charge at all distances from the DNA. In contrast, there was greater disagreement between the two methods for Mg2+ cation concentration profiles, as both the locations and magnitudes of peaks in Mg2+ concentration were different. Despite experimental and simulation observations that Mg2+ typically maintains its first solvation shell when interacting with nucleic acids, modeling Mg2+ as an unsolvated ion during PB calculations improved the agreement of the Mg2+ ion atmosphere predicted by the two methods and allowed for values of the number of bound ions and net solution charge surrounding the DNA from PB calculations that approached the values observed in MD simulations. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 834–848, 2014.
Lessons learned in breast cancer surgery
Authors: Fentiman I S
Published: January 2014

Changes in a professional life time