bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentiometric Nanostructured Sensors
Authors: Andrade Francisco J. , Blondeau Pascal , Macho Santiago , Riu Jordi , Rius Francesc X.
Published: December 2014

The use of nanostructured materials has promoted a new impulse in the chemical sensors area. Electrochemical sensors have taken advantage of the new properties associated with the nanometer‐sized objects, and these properties have greatly influenced the performance and operational parameters of the sensing devices. This article provides an overview of the advantages and limitations of different nanomaterials used for the development of the potentiometric sensors. Different dimensional structures, from nanoparticles to graphene, have been used as elements in the recognition layer or the transducers of field‐effect transistors and potentiometric electrodes. Moreover, the introduction of nanomaterials has enabled the development of new miniaturized sensors that display good performance, rapid responses, and reduced cost and are easy to use. These sensors can be used in situ or incorporated in garments and other everyday life objects. That is, the era of wearable chemical sensors has started.
Current Electrospray Mass Spectrometry: An Overview. PartB. Analyte Charging
Authors: Verkerk Udo H.
Published: December 2014

Electrospray ionization(ESI) is an atomization and ionization method through which a solution‐phase analyte can be transferred into the gas‐phase as an ion via minute charged droplets. The second part of this two‐part review on electrospray mass spectrometry reviews the final part of the charged droplet trajectory and covers transfer into the gas‐phase and ionization of the analyte. The now customary separation into the ion evaporation model (for small analytes) and the charged residue model (for large analytes) is followed and reviewed. These models yield insight into the charging process, but observations made with newer atomization techniques and quantitation limitations imposed by ionization suppression (matrix effect) indicate that a complete understanding is not available yet. Deviations from expected charged residue or ion evaporation behavior will be indicated. Chemical and charge‐driven surfactancy is discussed in relation to small analyte ionization and quantitation, whereas hydration and kinetic trapping of protein conformers are treated as part of the charged residue model.
Perceptions of intimacy and friendship reciprocity moderate peer influence on aggression
Authors: Meter Diana J. , Casper Deborah M. , Card Noel A.
Published: December 2014

Previous research has shown that close friends’ influence can exacerbate adolescents’ aggressive behavior, but results of studies which examine whether friendships of greater or lesser qualities moderate peer influence effects are inconsistent. The present study tested whether the perception of the positive friendship quality of intimate exchange and friendship reciprocity moderated best friend influence on participant aggression over time. The 243 participants were approximately 12 years old and ethnically diverse. Neither intimate exchange nor reciprocity significantly moderated friend influence on aggression in a simple way, but the interaction of intimate exchange and friendship reciprocity predicted peer influence on participants’ aggression over time. Specifically, highly intimate, nonreciprocal best friendships and less intimate, reciprocal best friendships showed greatest influence when friends’ proportion of peer nominations for aggression was high. Reciprocity and intimacy should be considered when predicting peer influence on aggression. Aggr. Behav. 41:432–442, 2015. © 2014 Wiley Periodicals, Inc.
Multiple Layer‐by‐Layer Lipid‐Polymer Hybrid Nanoparticles for Improved FOLFIRINOX Chemotherapy in Pancreatic Tumor Models
Authors: Li Feng , Zhao Xiao , Wang Hai , Zhao Ruifang , Ji Tianjiao , Ren He , Anderson Gregory J. , Nie Guangjun , Hao Jihui
Published: December 2014

The FOLFIRINOX regimen, a combination of three chemotherapy agents (5‐fluorouracil, irinotecan, oxaliplatin) and folinic acid (a vitamin B derivatives reducing the side effect of 5‐fluorouracil), has proved to be effective in the treatment of pancreatic cancer, and is more efficacious than the long‐term reference standard, gemcitabine. However, the FOLFIRINOX is associated with high‐grade toxicity, which markedly limits its clinical application. Encapsulation of drugs in nanocarriers that selectively target cancer cells promises to be an effective method for co‐delivery of drug combinations and to mitigate the side effects of conventional chemotherapy. Here we reported the development of multiple layer‐by‐layer lipid‐polymer hybrid nanoparticles with targeting capability that show excellent biocompatibility and synergistically combine the favorable properties of liposomes and polymer nanoparticles. Relative to nanoparticles consisting of polymer alone, these novel nanocarriers have a long half‐life in vivo and a higher stability in serum. The nanocarriers were loaded with the three active antitumor constituents of FOLFIRINOX regimen. Little drugs were released from the nanoparticles in phosphate buffered saline (PBS) solution, but the cargoes were quickly released after the nanoparticles were taken up by tumor cells. These innovative drug‐loaded nanoparticles achieved higher antitumor efficacy and showed minimal side effects compared with the FOLFIRINOX regimen alone. Our study suggested that the multiple layer‐by‐layer hybrid nanoparticles have great potential for improving the chemotherapeutic efficacy for the patients with pancreatic cancer. This platform also provides new opportunities for tailored design of nanoparticles that may offer therapeutics benefits for a range of other tumors.
Porous Silicon Nanodiscs for Targeted Drug Delivery
Authors: Alhmoud Hashim , Delalat Bahman , Elnathan Roey , Cifuentes‐Rius Anna , Chaix Arnaud , Rogers Mary‐Louise , Durand Jean‐Olivier , Voelcker Nicolas H.
Published: December 2014

There is a strong demand for techniques that allow the fabrication of biocompatible porous nanoparticles for drug delivery applications. In this work, a new method to fabricate size‐ and shape‐controlled porous silicon (pSi) nanodiscs is described. The process relies on a combination of colloidal lithography and metal‐assisted chemical etching. Height and diameter of the pSi nanodiscs can be easily adjusted. The nanodiscs are degradable in physiological milieu and are nontoxic to mammalian cells. In order to highlight the potential of the pSi nanodiscs in drug delivery, an in vitro investigation that involved loading of nanodiscs with the anticancer agent camptothecin and functionalization of the nanodisc periphery with an antibody that targets receptors on the surface of neuroblastoma cells is carried out. The thus‐prepared nanocarriers are found to selectively attach to and kill cancer cells.
Self‐Powered Trace Memorization by Conjunction of Contact‐Electrification and Ferroelectricity
Authors: Chen Xiangyu , Iwamoto Mitsumasa , Shi Zhemin , Zhang Limin , Wang Zhong Lin
Published: December 2014

Triboelectric nanogenerator (TENG) is a newly invented technology that can effectively harvest ambient mechanical energy from various motions with promising applications in portable electronics, self‐powered sensor networks, etc. Here, by coupling TENG and a thin film of ferroelectric polymer, a new application is designed for TENG as a self‐powered memory system for recording a mechanical displacement/trace. The output voltage produced by the TENG during motion can polarize the dipole moments in the ferroelectric thin film. Later, by applying a displacement current measurement to detect the polarization density in the ferroelectric film, the motion information of the TENG can be directly read. The sliding TENG and the single‐electrode TENG matrix are both utilized for realizing the memorization of the motion trace in one‐dimensional and two‐dimensional space, respectively. Currently, the ferroelectric thin film with a size of 3.1 mm2 can record a minimum area changing of 30 mm2 and such resolution can still be possibly improved. These results prove that the ferroelectric polymer is an effective memory material to work together with TENG and thereby the fabricated memory system can potentially be used as a self‐powered displacement monitor.
Graphene Foam with Switchable Oil Wettability for Oil and Organic Solvents Recovery
Authors: Zhu Haiguang , Chen Dongyun , Li Najun , Xu Qingfeng , Li Hua , He Jinghui , Lu Jianmei
Published: December 2014

One of the most pervasive environmental issues is water contaminated with oil or organic solvents; this global challenge calls for emerging materials that could effectively separate oil or organic solvents from water. Here, such a material is presented by integrating 3D porous graphene foam (GF) with a smart pH‐responsive surface, showing switchable superoleophilic and superoleophobic properties in response to the medium pH. The key chemistry applied in this study is to modify the 3D porous GF with an amphiphilic copolymer containing a block of poly(2‐vinylpyridine) and polyhexadecyl acrylate (P2VP‐b‐PHA), resulting in a smart GF (ss‐GF) with an either superoleophilic or superoleophobic surface at different medium pH. The as‐designed ss‐GF can effectively absorb oil or organic solvents from the aqueous media by using its superoleophilic surface at pH of 7.0, and it can also completely release the adsorbates when the pH is switched to 3.0 (and the surface of ss‐GF is therefore shifted to superoleophobic); with a continuous operation of many cycles (e.g., >10). Furthermore, the as‐designed ss‐GF shows superior absorption capacity for oil and organic solvent, with a high capacity of ≈196 times of the weight relative to that of the pristine ss‐GF. The present work suggests encouraging applications of the ss‐GF to water–oil and water–organic solvent separation.
A unified theoretical model for breakup of bubbles and droplets in turbulent flows
Authors: Xing Chutian , Wang Tiefeng , Guo Kunyu , Wang Jinfu
Published: December 2014

Pressure has a significant effect on bubble breakup, and bubbles and droplets have very different breakup behaviors. This work aimed to propose a unified breakup model for both bubbles and droplets including the effect of pressure. A mechanism analysis was made on the internal flow through the bubble/droplet neck in the breakup process, and a mathematical model was obtained based on the Young–Laplace and Bernoulli equations. The internal flow behavior strongly depended on the pressure or gas density, and based on this mechanism, a unified breakup model was proposed for both bubbles and droplets. For the first time, this unified breakup model gave good predictions of both the effect of pressure or gas density on the bubble breakup rate and the different daughter size distributions of bubbles and droplets. The effect of the mother bubble/droplet diameter, turbulent energy dissipation rate and surface tension on the breakup rate, and daughter bubble/droplet size distribution was discussed. This bubble breakup model can be further used in a population balance model (PBM) to study the effect of pressure on the bubble size distribution and in a computational fluid dynamics‐population balance model (CFD‐PBM) coupled model to study the hydrodynamic behaviors of a bubble column at elevated pressures. © 2014 American Institute of Chemical Engineers AIChE J, 61: 1391–1403, 2015
Prenatal hormones in first‐time expectant parents: Longitudinal changes and within‐couple correlations
Authors: Edelstein Robin S. , Wardecker Britney M. , Chopik William J. , Moors Amy C. , Shipman Emily L. , Lin Natalie J.
Published: December 2014

Objectives

Expectant mothers experience marked hormone changes throughout the transition to parenthood. Although similar neuroendocrine pathways are thought to support maternal and paternal behavior, much less is known about prenatal hormone changes in expectant fathers, especially in humans.

Methods

We examined longitudinal changes in salivary testosterone, cortisol, estradiol, and progesterone in 29 first‐time expectant couples (N = 58). Couples were assessed up to four times throughout the prenatal period, at approximately weeks 12, 20, 28, and 36 of pregnancy. We also examined within‐couple correlations in hormones. Data were analyzed using dyadic growth curve modeling.

Results

As expected, women showed large prenatal increases in all four hormones. Men showed significant prenatal declines in testosterone and estradiol, but there were no detectable changes in men's cortisol or progesterone. Average levels of cortisol and progesterone were significantly positively correlated within couples.

Conclusions

The current study represents one of the most extensive investigations to date of prenatal hormones in expectant couples. It is also the first study to demonstrate prenatal testosterone changes in expectant fathers and within‐couple correlations in progesterone. We discuss implications of these findings for parental behavior and adjustment. Am. J. Hum. Biol. 27:317–325, 2015. © 2014 Wiley Periodicals, Inc.
Adjunctive traditional Chinese medicine therapy for patients with chronic rhinosinusitis: a population‐based study
Authors: Yen Hung‐Rong , Sun Mao‐Feng , Lin Cheng‐Li , Sung Fung‐Chang , Wang Chen‐Chi , Liang Kai‐Li
Published: December 2014

Background

Chronic rhinosinusitis (CRS) is a chronic illness with a high prevalence worldwide. The purpose of this study was to investigate the characteristics of adjunctive traditional Chinese medicine (TCM) use in patients with CRS.

Methods

Data were retrieved from a dataset made available by the Taiwan National Health Insurance Research Database (NHIRD) containing the medical records of 1,000,000 randomly sampled beneficiaries insured in the year 2000. Patients newly diagnosed with CRS in the year 2000 were enrolled, and their medical records during the period 2000 to 2011 were collected and analyzed.

Results

A total of 14,806 CRS subjects were enrolled in this study: 10,512 were non‐TCM users and 4294 were TCM users. TCM group had a significantly higher proportion of females, were younger, and a greater proportion lived in urban areas compared with the non‐TCM group (all p < 0.0001). Ninety‐seven percent (97%) of the TCM users received herbal remedies. The most common Chinese herbal formula used was Xin‐Yi‐Qing‐Fei‐Tang and the most commonly used single herb was Baizhi. The hazard ratio (HR) for functional endoscopic sinus surgery (FESS) was 0.17 for TCM users (95% confidence interval [CI], 0.15 to 0.20) compared with non‐TCM users after adjusting for age, sex, urbanization, and comorbidities.

Conclusion

Our investigation found that 29% of CRS patients used TCM in addition to Western medical treatment. A lower proportion of patients in the TCM group underwent ESS compared with that in the non‐TCM group. These findings may be of value in further studies evaluating the efficacy and safety of TCM use in CRS patients.
Totalsynthese des Aglykons von Tiacumicin B (Lipiarmycin A3/ Fidaxomicin)
Authors: Glaus Florian , Altmann Karl‐Heinz
Published: December 2014

Tiacumicin B (Lipiarmycin A3, Fidaxomicin) ist ein atypisches Makrolidantibiotikum, das klinisch zur Behandlung von Infektionen mit Clostridium difficile eingesetzt wird. Tiacumicin B ist auch ein potenter Hemmer von Mycobacterium tuberculosis, kann jedoch infolge seiner unzureichenden oralen Bioverfügbarkeit nicht zur systemischen Therapie eingesetzt werden. Mit dem Ziel, eine Grundlage für Struktur‐Aktivitäts‐Studien und die mögliche Entwicklung verbesserter Tiacumicin Varianten zu schaffen, haben wir eine effiziente Synthese des Tiacumicin‐B‐Aglykons entwickelt, die auf dem Ringschluss zum Makrocyclus mittels einer hocheffizienten Suzuki‐Kreuzkupplung basiert. Weitere Schlüsselschritte waren eine hochselektive Corey‐Peterson‐Olefinierung und eine En‐Dien‐Kreuzmetathese. Die abschließende Entschützung lieferte in Abhängigkeit von den gewählten Reaktionsbedingungen entweder das vollständig entschützte Aglykon oder, alternativ, teilweise entschützte Varianten davon.
CO‐Extrusion in der homogenen Gold‐Katalyse: Reaktivität von Goldacyl‐Spezies, erzeugt durch Wasser‐Addition an Goldvinylidene
Authors: Bucher Janina , Stößer Tim , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: December 2014

Eine neue Gold‐katalysierte decarbonylierende Inden‐Synthese wird beschrieben. Synergistische σ,π‐Aktivierung von Diin‐Substraten führt zu Goldvinyliden‐Intermediaten, die nach der Addition von Wasser in Goldacyl‐Spezies übergehen – ein Typ von Organogold‐Verbindung, über den bisher nur sehr selten berichtet wurde. Für diese Spezies beweisen wir eine Extrusion von CO, einen in der homogenen Gold‐Katalyse bislang unbekannten Elementarschritt. Durch gezielte Wahl der elektronischen und sterischen Eigenschaften des Edukt‐Diins konnte diese neue Reaktivität für die Synthese von Inden‐Derivaten in hohen Ausbeuten genutzt werden.
Cystobactamide: Topoisomerase‐Inhibitoren aus Myxobakterien mit hoher antibakterieller Aktivität
Authors: Baumann Sascha , Herrmann Jennifer , Raju Ritesh , Steinmetz Heinrich , Mohr Kathrin I. , Hüttel Stephan , Harmrolfs Kirsten , Stadler Marc , Müller Rolf
Published: December 2014

Die Entwicklung neuer Antibiotika befindet sich in einer ernsthaften Krise, die unter anderem dadurch begründet ist, dass kaum innovative chemische Grundstrukturen mit Aktivität gegen Gram‐negative und multiresistente Bakterien gefunden werden. Hier berichten wir über die Entdeckung neuer hochwirksamer Antibiotika aus Myxobakterien, den Cystobactamiden 1–3, die aus Cystobacter sp. isoliert wurden und minimale Hemmkonzentrationen im niedrigen μg mL−1‐Bereich aufweisen. Wir beschreiben die Aufreinigung und Strukturaufklärung von drei Derivaten und die Identifizierung und Annotation des dazugehörigen Biosynthesegenclusters. Die molekularen Zielstrukturen der Cystobactamide konnten über die Analyse des Eigenresistenzmechanismus des Produzentenstammes als bakterielle Typ‐IIa‐Topoisomerasen identifiziert werden. Da die Optimierungsmöglichkeiten von Chinolonen als Basis für neue Inhibitoren der Typ‐II‐Topoisomerasen weitgehend ausgereizt sind, erscheinen die Cystobactamide als hochinteressante Alternativen, die durch Medizinalchemie und biosynthetisches Engineering der Entwicklung neuartiger Antibiotika dienen können.
Tuning the Colloidal Crystal Structure of Magnetic Particles by External Field
Authors: Pal Antara , Malik Vikash , He Le , Erné Ben H. , Yin Yadong , Kegel Willem K. , Petukhov Andrei V.
Published: December 2014

Manipulation of the self‐assembly of magnetic colloidal particles by an externally applied magnetic field paves a way toward developing novel stimuli responsive photonic structures. Using microradian X‐ray scattering technique we have investigated the different crystal structures exhibited by self‐assembly of core–shell magnetite/silica nanoparticles. An external magnetic field was employed to tune the colloidal crystallization. We find that the equilibrium structure in absence of the field is random hexagonal close‐packed (RHCP) one. External field drives the self‐assembly toward a body‐centered tetragonal (BCT) structure. Our findings are in good agreement with simulation results on the assembly of these particles.
Highly Regio‐ and Enantioselective Synthesis of γ,δ‐Unsaturated Amido Esters by Catalytic Hydrogenation of Conjugated Enamides
Authors: Gao Min , Meng Jing‐jing , Lv Hui , Zhang Xumu
Published: December 2014

An efficient and highly regio‐ and enantioselective catalytic asymmetric hydrogenation of α,γ‐dienamido esters to γ,δ‐unsaturated amido esters has been achieved using Rh/TangPhos as the catalyst. A series of γ,δ‐unsaturated amido acids were furnished in excellent yields with up to 99 % ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor.
Effect of MWNTs concentration and cooling rate on the morphological, structural, and electrical properties of non‐isothermally crystallized PEN/MWNT nanocomposites
Authors: Espinoza‐Martínez Adriana B. , Ávila‐Orta Carlos A. , Cruz‐Delgado Víctor J. , Medellín‐Rodríguez Francisco J. , Bueno‐Baqués Darío , Mata‐Padilla José M.
Published: December 2014

The effect of multiwall carbon nanotubes (MWNT) concentration and cooling rate on the morphological, structural and electrical properties of non‐isothermally crystallized Poly(ethylene naphthalate) nanocomposites (PEN/MWNT) was studied. PEN/MWNT nanocomposites containing 1 and 2 wt % of nanotubes were prepared by melt blending in a mini twin screw extruder. Nanocomposite samples with different degree of crystallinity (Xc) were obtained via non‐isothermally crystallization at cooling rates of 2, 10, 20, and 300°C min−1. In this study it was demonstrated that carbon nanotubes and cooling rate strongly influence morphological and structural characteristics of PEN. Calorimetric results showed that the peak crystallization temperature (Tc) of PEN nanocomposites was increased ∼9° through heterogeneous nucleation with respect to pure PEN. X‐ray diffraction revealed that carbon nanotubes modify the crystalline structure of PEN favoring the formation of β‐crystals, and this effect increases with the nanotubes content. On the basis of X‐ray scattering analysis, the variation of lamellar thickness revealed that nanotubes promote the formation of lamellar crystals with average thickness of 20 nm at different cooling rates. These structural and morphological changes play an important role on the electrical properties of nanocomposites. It was found that higher concentration of nanotubes and crystallinity promotes electrical conductivity of nanocomposites in the order of semiconductors (until 1 × 10−4 S cm−1) as well as permittivity of 20 at different tested frequencies. This may due to the interconnected networks of nanotubes throughout the crystalline structure formed in PEN nanocomposites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41765.
Clinical and Immunologic Predictors of Scleroderma Renal Crisis in Japanese Systemic Sclerosis Patients With Anti–RNA Polymerase III Autoantibodies
Authors: Hamaguchi Yasuhito , Kodera Masanari , Matsushita Takashi , Hasegawa Minoru , Inaba Yuki , Usuda Toshikazu , Kuwana Masataka , Takehara Kazuhiko , Fujimoto Manabu
Published: December 2014

Objective

To identify predictive factors for scleroderma renal crisis (SRC) in patients with anti–RNA polymerase III (anti–RNAP III) antibodies.

Methods

A total of 583 adult Japanese patients with systemic sclerosis (SSc) were screened for anti–RNAP III using a commercially available enzyme‐linked immunosorbent assay (ELISA) kit. RNAP subsets were further identified by immunoprecipitation (IP) assays. The association of clinical and immunologic factors with SRC was examined by logistic analyses.

Results

In this cohort, 37 patients (6%) were positive for anti–RNAP III, as determined by anti–RNAP III–specific ELISA. Further IP assays revealed that 19 patients were positive for anti–RNAP I/III, 17 for anti–RNAP I/II/III, and 1 for anti‐RNAP III. SRC occurred in a total of 17 (2.9%) of 583 patients, with a significantly higher frequency in anti–RNAP III–positive SSc patients (9 of 37 [24%]) than those without anti–RNAP III (8 of 546 [1%]) (odds ratio [OR] 21.6 [95% confidence interval (95% CI) 7.8–60.3], P < 0.00001). Our multivariate analyses using the Cox proportional hazards regression model revealed that anti–RNAP I/II/III positivity (OR 11.0 [95% CI 1.6–222.8], P = 0.0118) and an ELISA index for anti–RNAP III of ≥157 (OR 2.4 × 109 [95% CI 2.1–uncalculated], P = 0.0093) were independent factors associated with the development of SRC.

Conclusion

Our findings indicate that anti–RNAP III is associated with SRC, as reported previously. In addition, the presence of anti–RNAP II in combination with anti–RNAP I/III (anti–RNAP I/II/III) and a higher ELISA index for anti–RNAP III may be associated with the development of SRC in SSc patients with anti–RNAP III.
Mast Cell Promotion of T Cell–Driven Antigen‐Induced Arthritis Despite Being Dispensable for Antibody‐Induced Arthritis in Which T Cells Are Bypassed
Authors: Schubert Nadja , Dudeck Jan , Liu Peng , Karutz Anna , Speier Stephan , Maurer Marcus , Tuckermann Jan , Dudeck Anne
Published: December 2014

Objective

The function of mast cells (MCs) in autoimmune disorders has been a subject of controversy recently. MC‐deficient KitW/W‐v mice were found to be resistant to K/BxN serum–transfer arthritis, whereas KitW‐sh/W‐sh mice and a genetic model of MC deficiency independent of the Kit mutation were found to be fully susceptible. This debate might lead to the assumption that MCs are dispensable in autoimmunity in general. Thus, the purpose of this study was to examine the relevance of MCs to arthritis using a genetic model of inducible MC deficiency without compromised Kit signaling.

Methods

We compared MC functions in K/BxN serum–induced arthritis and in collagen‐induced arthritis (CIA) in a mouse model of inducible MC deficiency by analyzing joint inflammation, parameters of cartilage degradation and bone erosion, and the autoreactive adaptive immune response.

Results

We observed a redundant role of MCs in K/BxN serum–induced arthritis, where joint inflammation is triggered by cartilage‐bound immune complexes independently of T cells. In contrast, we found MCs to be critically relevant in CIA, which is provoked by two arms of autoimmune attack: autoreactive antibodies and effector T cells. In addition to diminished joint inflammation in the absence of MCs, we found a dramatic loss of T cell expansion upon immunization, accompanied by reduced T cell cytokine responses.

Conclusion

In this analysis of an arthritis model in which the cellular arm of adaptive immunity was not bypassed, we identified MCs as important promoters of T cell–conditioned autoimmune disorders and, consequently, as potential therapeutic targets in rheumatoid arthritis.
Functional Anti‐CD94/NKG2A and Anti‐CD94/NKG2C Autoantibodies in Patients With Systemic Lupus Erythematosus
Authors: Hagberg Niklas , Theorell Jakob , Hjorton Karin , Spee Pieter , Eloranta Maija‐Leena , Bryceson Yenan T. , Rönnblom Lars
Published: December 2014

Objective

Recently we serendipitously identified a patient with systemic lupus erythematosus (SLE) who was positive for autoantibodies to CD94/natural killer receptor group 2A (NKG2A). The present study was undertaken to investigate the occurrence and function of autoantibodies targeting lectin‐like NK cell receptors in SLE.

Methods

Sera from 203 SLE patients and 90 healthy individuals were analyzed, by flow cytometry, for Ig binding to Ba/F3 cells transfected with CD94/NKG2A, CD94/NKG2C, or NKG2D. Autoantibodies identified were characterized with regard to interference with HLA–E binding, effect on NK cell activation in response to HLA–E‐transfected K562 cells, and capacity to facilitate antibody‐dependent cell‐mediated cytotoxicity (ADCC). Levels of autoantibodies were determined in longitudinally sampled sera, and correlations with disease activity (SLE Disease Activity Index 2000) and severity (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were investigated.

Results

Anti‐CD94/NKG2A autoantibodies were identified in 7 SLE patients. The autoantibodies from 6 patients inhibited binding of HLA–E to CD94/NKG2A, whereas those from the seventh patient augmented this binding. Autoantibodies from 2 patients also reacted with the activating receptor CD94/NKG2C, with inhibition of the binding of HLA–E to CD94/NKG2C observed in 1 case and enhancement of this binding in the other. None of the sera contained anti‐NKG2D autoantibodies. The levels of anti‐CD94/NKG2A and anti‐CD94/NKG2C autoantibodies correlated with disease activity and with a more severe SLE phenotype. Mechanistically, anti‐CD94/NKG2A and anti‐CD94/NKG2C autoantibodies both interfered with HLA–E‐mediated regulation of NK cell activation and facilitated the elimination of target cells expressing CD94/NKG2A or CD94/NKG2C through ADCC.

Conclusion

Anti‐CD94/NKG2A and anti‐CD94/NKG2C autoantibodies occur in a subset of patients with clinically active SLE. Given their capacity to deplete certain NK cell subsets and interfere with particular NK cell function, such autoantibodies may promote the pathogenesis of SLE.
tris‐Heteroleptic Cyclometalated Iridium(III) Complexes with Ambipolar or Electron Injection/Transport Features for Highly Efficient Electrophosphorescent Devices
Authors: Xu Xianbin , Yang Xiaolong , Wu Yong , Zhou Guijiang , Wu Chao , Wong Wai‐Yeung
Published: December 2014

A series of tris‐heteroleptic phosphorescent cyclometalated IrIII complexes with two different cyclometalating ligands and one ancillary ligand was synthesized. Through manipulation of the electronic features of individual cyclometalating ligands, not only the emission color and electrochemical properties of these IrIII complexes can be tuned, but also unique charge carrier injection and transport traits can be conferred to them. Owing to the enhanced electron injection/transport and ambipolar characters associated with these tris‐heteroleptic structures, these IrIII emitters showed very impressive electroluminescent performance with a maximum external quantum efficiency of 20.20 %, luminance efficiency of 69.41 cd A−1 and power efficiency of 35.15 Lm W−1. These results provide a new outlet to design and synthesize highly efficient electrophosphors for phosphorescent organic light‐emitting diodes.
A Novel Robust MM Filter against Outliers
Authors: Liu Yong , Liang Yan , Liu Zhun‐Ga , Pan Quan
Published: December 2014

An Interacting Multiple Model (IMM) filter suppresses outliers by integrating model‐conditioned estimation and model mode recognition through adaptive mode switches based on a Bayesian probability update. However, it may face significant outlier‐caused peak errors, which are undesirable or even impermissible in many applications, for example, target tracking. This paper considers that, from the view of the Dempster‐Shafer Theory, the IMM filter actually fuses the Bayesian beliefs of the model mode with Dempster's Rule of Combination, which can deal with uncertainties instead of the evidence conflicts that may exist as outliers appear. Therefore, we propose the adaptive robust multiple model (RMM) filter through introducing practical expert knowledge in the belief function framework, which runs online to reduce outlier‐caused peak errors. In RMM, the Likelihood Temporal Ratio (LTR) is incorporated to provide extra information on the tendency of mode switching. Moreover, expert rules are introduced to construct adaptive belief functions using discount techniques and to select the combination rule that better deals with evidence conflicts when outliers appear. The simulations in target tracking scenarios show that the proposed RMM filter significantly reduces outlier‐caused peak errors and hence obtains a lower rate of track loss in the cluttered environment.
On measures of dissimilarity between point patterns: Classification based on prototypes and multidimensional scaling
Authors: Mateu Jorge , Schoenberg Frederic P. , Diez David M. , González Jonatan A. , Lu Weipeng
Published: December 2014

This paper presents a collection of dissimilarity measures to describe and then classify spatial point patterns when multiple replicates of different types are available for analysis. In particular, we consider a range of distances including the spike‐time distance and its variants, as well as cluster‐based distances and dissimilarity measures based on classical statistical summaries of point patterns. We review and explore, in the form of a tutorial, their uses, and their pros and cons. These distances are then used to summarize and describe collections of repeated realizations of point patterns via prototypes and multidimensional scaling. We also show a simulation study to evaluate the performance of multidimensional scaling with two types of selected distances. Finally, a multivariate spatial point pattern of a natural plant community is analyzed through various of these measures of dissimilarity.
On stability issues in deriving multivariable regression models
Authors: Sauerbrei Willi , Buchholz Anika , Boulesteix Anne‐Laure , Binder Harald
Published: December 2014

In many areas of science where empirical data are analyzed, a task is often to identify important variables with influence on an outcome. Most often this is done by using a variable selection strategy in the context of a multivariable regression model. Using a study on ozone effects in children (n= 496, 24 covariates), we will discuss aspects relevant for deriving a suitable model. With an emphasis on model stability, we will explore and illustrate differences between predictive models and explanatory models, the key role of stopping criteria, and the value of bootstrap resampling (with and without replacement). Bootstrap resampling will be used to assess variable selection stability, to derive a predictor that incorporates model uncertainty, check for influential points, and visualize the variable selection process. For the latter two tasks we adapt and extend recent approaches, such as stability paths, to serve our purposes. Based on earlier experiences and on results from the example, we will argue for simpler models and that predictions are usually very similar, irrespective of the selection method used. Important differences exist for the corresponding variances, and the model uncertainty concept helps to protect against serious underestimation of the variance of a predictor‐derived data dependently. Results of stability investigations illustrate severe difficulties in the task of deriving a suitable explanatory model. It seems possible to identify a small number of variables with an important and probably true influence on the outcome, but too often several variables are included whose selection may be a result of chance or may depend on a small number of observations.
Geographic origin is not supported by the genetic variability found in a large living collection of Jatropha curcas with accessions from three continents
Authors: Maghuly Fatemeh , Jankowicz‐Cieslak Joanna , Pabinger Stephan , Till Bradley J. , Laimer Margit
Published: December 2014

Increasing economic interest in Jatropha curcas requires a major research focus on the genetic background and geographic origin of this non‐edible biofuel crop. To determine the worldwide genetic structure of this species, amplified fragment length polymorphisms, inter simple sequence repeats, and novel single nucleotide polymorphisms (SNPs) were employed for a large collection of 907 J. curcas accessions and related species (RS) from three continents, 15 countries and 53 regions. PCoA, phenogram, and cophenetic analyses separated RS from two J. curcas groups. Accessions from Mexico, Bolivia, Paraguay, Kenya, and Ethiopia with unknown origins were found in both groups. In general, there was a considerable overlap between individuals from different regions and countries. The Bayesian approach using STRUCTURE demonstrated two groups with a low genetic variation. Analysis of molecular varience revealed significant variation among individuals within populations. SNPs found by in silico analyses of Δ12 fatty acid desaturase indicated possible changes in gene expression and thus in fatty acid profiles. SNP variation was higher in the curcin gene compared to genes involved in oil production. Novel SNPs allowed separating toxic, non‐toxic, and Mexican accessions. The present study confirms that human activities had a major influence on the genetic diversity of J. curcas, not only because of domestication, but also because of biased selection.
Isothermal microcalorimetry accurately detects bacteria, tumorous microtissues, and parasitic worms in a label‐free well‐plate assay
Authors: Braissant Olivier , Keiser Jennifer , Meister Isabel , Bachmann Alexander , Wirz Dieter , Göpfert Beat , Bonkat Gernot , Wadsö Ingemar
Published: December 2014

Isothermal microcalorimetry is a label‐free assay that allows monitoring of enzymatic and metabolic activities. The technique has strengths, but most instruments have a low throughput, which has limited their use for bioassays. Here, an isothermal microcalorimeter, equipped with a vessel holder similar to a 48‐well plate, was used. The increased throughput of this microcalorimeter makes it valuable for biomedical and pharmaceutical applications. Our results show that the sensitivity of the instrument allows the detection of 3 × 104 bacteria per vial. Growth of P. mirabilis in Luria Broth medium was detected between 2 and 9 h with decreasing inoculum. The culture released 2.1J with a maximum thermal power of 76 μW. The growth rate calculated using calorimetric and spectrophotometric data were 0.60 and 0.57 h–1, respectively. Additional insight on protease activities of P. mirabilis matching the last peak in heat production could be gathered as well. Growth of tumor microtissues releasing a maximum thermal power of 2.1 μW was also monitored and corresponds to a diameter increase of the microtissues from ca. 100 to 428 μm. This opens new research avenues in cancer research, diagnostics, and development of new antitumor drugs. For parasitic worms, the technique allows assessment of parasite survival using motor and metabolic activities even with a single worm.
Tethered ribozyme ligation enables detection of molecular proximity in homogeneous solutions
Authors: Katzman Bella , Vyazmensky Maria , Press Olga , Volokita Micha , Engel Stanislav
Published: December 2014

In contemporary drug discovery, bulk selection represents an important alternative to time consuming and expensive high‐throughput screening. The selection methods, however, generally rely on affinity separation, a step that limits overall selection process efficiency. To overcome common drawbacks of conventional methods, we exploited the unique catalytic properties of an artificial enzyme, ribozyme ligase, to develop a selection methodology in which the entire detection process takes place in a homogeneous solution, thus eliminating the need for affinity separation. A molecular target is associated with the ribozyme, and library compounds are attached to a barcoded oligonucleotide that is a substrate for the ribozyme ligase. Spatial proximity resulting from specific target‐compound interactions increases the probability of ribozyme ligation to the oligo‐substrate, thus differentiating the interacting species from the bulk mixture. The covalent link formed between the ribozyme and target‐interacting compounds diminishes the mass‐action effect on the efficiency with which low‐affinity and rare active species are detected. In addition, the magnitude of the detection signal associated with the interaction event renders the methodology an efficient platform for identifying inhibitors of intermolecular interactions. The proposed solution‐based tethered ribozyme‐ligation proximity detection method may facilitate the discovery of target‐interacting compounds using both library selection and high‐throughput screening approaches.
Engineering connectivity by multiscale micropatterning of individual populations of neurons
Authors: Albers Jonas , Toma Koji , Offenhäusser Andreas
Published: December 2014

Functional networks are the basis of information processing in the central nervous system. Essential for their formation are guided neuronal growth as well as controlled connectivity and information flow. The basis of neuronal development is generated by guiding cues and geometric constraints. To investigate the neuronal growth and connectivity of adjacent neuronal networks, two‐dimensional protein patterns were created. A mixture of poly‐L‐lysine and laminin was transferred onto a silanized glass surface by microcontact printing. The structures were populated with dissociated primary cortical embryonic rat neurons. Triangular structures with diverse opening angles, height, and design were chosen as two‐dimensional structures to allow network formation with constricted gateways. Neuronal development was observed by immunohistochemistry to pursue the influence of the chosen structures on the neuronal outgrowth. Neurons were stained for MAP2, while poly‐L‐lysine was FITC labeled. With this study we present an easy‐to‐use technique to engineer two‐dimensional networks in vitro with defined gateways. The presented micropatterning method is used to generate daisy‐chained neuronal networks with predefined connectivity. Signal propagation among geometrically constrained networks can easily be monitored by calcium‐sensitive dyes, providing insights into network communication in vitro.
Optomagnetic read‐out enables easy, rapid, and cost‐efficient qualitative biplex detection of bacterial DNA sequences
Authors: Bejhed Rebecca S. , Zardán Gómez de la Torre Teresa , Svedlindh Peter , Strömberg Mattias
Published: December 2014

There is an increasing need to develop novel bioassay methods for low‐cost, rapid, and easy‐to‐use multiplex detection of pathogens in various fields ranging from human infectious disease diagnosis, drinking water quality control, to food safety applications. Due to their unique advantages, magnetic and optomagnetic bioassay principles are particularly promising for biodetection platforms that will be used in developing countries. In this paper, an optomagnetic method for rapid and cost‐efficient qualitative biplex detection of bacterial DNA sequences is demonstrated. Within less than two hours, the assay gives an answer to whether none, both, or only one of the bacterial DNA sequences is present in the sample. The assay relies on hybridization of oligonucleotide‐functionalized magnetic nanobeads of two different sizes to rolling circle amplification (RCA) products originating from two different bacterial targets. The different bead sizes are equipped with different oligonucleotide probes, complementary to only one of the RCA products, and the read‐out is carried out in the same sample volume. In an optomagnetic setup, the frequency modulation of transmitted laser light in response to an applied AC magnetic field is measured. The presented methodology is potentially interesting for low‐cost screening of pathogens relating to both human and veterinary medicine in resource‐poor regions of the world.
Recreation and procreation: A critical view of sex in the human female
Authors: Levin Roy J
Published: December 2014

This review deals critically with many aspects of the functional genital anatomy of the human female in relation to inducing sexual arousal and its relevance to procreation and recreation. Various controversial problems are discussed including: the roles of clitorally versus coitally induced arousal and orgasm in relation to the health of women, the various sites of induction of orgasm and the difficulty women find in specifically identifying them because of “'ambiguity problems” and “genital site pareidolia,” the cervix and sexual arousal, why there are so many sites for arousal, why multiple orgasms occur, genital reflexes and coitus, the sites of arousal and their representation in the brain, and identifying aspects and functions of the genitalia with appropriate new nomenclature. Clin. Anat. 28:339–354, 2015. © 2014 Wiley Periodicals, Inc.
Know what to consider when partnering with outside legal counsel
Authors: Sievert Justin P. , Thomas Kaitlyn R.
Published: December 2014

The relationship between outside legal counsel and colleges and universities has always been a delicate one. This is especially true when institutions are involved in the National Collegiate Athletic Association enforcement process due to an alleged NCAA violation.
Mobility impaired users respond differently than healthy users in virtual environments
Authors: Guo Rongkai , Samaraweera Gayani , Quarles John
Published: December 2014

Virtual environments (VEs) have been shown to be beneficial in physical rehabilitation, increasing motivation and the range of exercises that can be safely performed. However, little is known about how disabilities may impact a user's responses to a VE, which could affect rehabilitation motivation. Thus, the primary objective of this research is to understand how VEs affect users with mobility impairments (MI). Specifically, we investigate the influence of full body avatars that have canes. To begin investigating this, we designed a VE that included a range of multimodal feedback to induce a strong sense of presence and was novel to the participants. Using this VE, we conducted a study with two different populations: eight persons with MI and eight healthy persons as a control. The healthy participants were of similar demographics (e.g., age, weight, height, and previous VE experience) to the participants with MI who walked with a cane (i.e., on the basis of strict selection criteria to maintain homogeneity). This is one of the first studies to investigate how a VE can affect the gait of the users with MI, physiological response, presence, behavior, and the influence of avatars. Results of the study suggest generalizable guidelines for the design of VEs for users with MI. Copyright © 2014 John Wiley & Sons, Ltd.
Genome Mining‐Directed Activation of a Silent Angucycline Biosynthetic Gene Cluster in Streptomyces chattanoogensis
Authors: Zhou Zhenxing , Xu Qingqing , Bu Qingting , Guo Yuanyang , Liu Shuiping , Liu Yu , Du Yiling , Li Yongquan
Published: December 2014

Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway‐specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads.
Interoperator and intraoperator (in)accuracy of stent selection based on visual estimation
Authors: Campbell Paul T. , Mahmud Ehtisham , Marshall J. Jeffrey
Published: December 2014

Objectives

The objectives of this study were to evaluate the ability of interventional cardiologists to accurately measure lesion length and select appropriate stents.

Background

Inaccurate measurement of lesion length during percutaneous coronary intervention (PCI) increases the risk of restenosis.

Methods

Interventional cardiologists (n = 40) evaluated 25 matched orthogonal angiographic images that were prescored using quantitative coronary angiography (QCA) by a core laboratory. Visual estimates of lesion length and stent length selection were compared to the maximum QCA value. A 2–4 mm stent overlap of both the proximal and distal lesion edges was considered to be optimal. Based on optimal stent overlap, accurate lesion lengths were those measured from −1 to +4 mm from the QCA. Likewise, appropriate stent lengths were those that measured between +4 mm to +8 mm from the QCA value. Five images were repeated to assess intrarater variability.

Results

Lesion length measurements were short and long for 51.1% (95% CI 47.6–54.6%) and 19.0% (95% CI 16.3–21.9%) of the images, respectively. Stent length selections that were short and long were recorded for 55.0% (95% CI 51.5–58.5%) and 22.8% (95% CI 19.9–25.8%) of the images, respectively. Intrarater variability evaluation indicated that 38.5% (95% CI 31.7–45.6%) of lesion length measurements and 37.5% (95% CI 30.8–44.6%) of stent length selections were >3 mm different between the first and second evaluation of repeated images.

Conclusions

Visual estimation of coronary lesion length has a high degree of variability, which may lead to inappropriate stent selection. Improving the accuracy of lesion length measurement may improve patient outcomes. © 2015 Wiley Periodicals, Inc.