bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved base editing and functional screening in Leishmania via co-expression of the AsCas12a ultra variant, a T7 RNA polymerase, and a cytosine base editor
Authors: Herrmann May Nicole , Cao Anh , Schmid Annika , Link Fabian , Arias-del-Angel Jorge , Meiser Elisabeth , Beneke Tom
Published: June 2024

The ability to analyze the function of all genes in a genome is highly desirable, yet challenging in Leishmania due to a repetitive genome, limited DNA repair mechanisms, and lack of RNA interference in most species. While our introduction of a cytosine base editor (CBE) demonstrated potential to overcome these limitations (Engstler and Beneke, 2023), challenges remained, including low transfection efficiency, variable editing rates across species, parasite growth effects, and competition between deleterious and non-deleterious mutations. Here, we present an optimized approach addressing these issues. We identified a T7 RNAP promoter variant ensuring high editing rates across Leishmania species without compromising growth. A revised CBE single-guide RNAs (sgRNAs) scoring system was developed to prioritize STOP codon generation. Additionally, a triple-expression construct was created for stable integration of CBE sgRNA expression cassettes into a Leishmania safe harbor locus using AsCas12a ultra-mediated DNA double-strand breaks, increasing transfection efficiency by ~400-fold to 1 transfectant per 70 transfected cells. Using this improved system for a small-scale proof-of-principle pooled screen, we successfully confirmed the essential and fitness-associated functions of CK1.2, CRK2, CRK3, AUK1/AIRK, TOR1, IFT88, IFT139, IFT140, and RAB5A in Leishmania mexicana, demonstrating a significant improvement over our previous method. Lastly, we show the utility of co-expressing AsCas12a ultra, T7 RNAP, and CBE for hybrid CRISPR gene replacement and base editing within the same cell line. Overall, these improvements will broaden the range of possible gene editing applications in Leishmania species and will enable a variety of loss-of-function screens in the near future.
CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility
Authors: Wu Bingbing , Long Chenghong , Yang Yuzhuo , Zhang Zhe , Ma Shuang , Ma Yanjie , Wei Huafang , Li Jinghe , Jiang Hui , Li Wei , Liu Chao
Published: June 2024

The structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility. Further analysis revealed that CCDC113 could bind to CFAP57 and CFAP91, and function as an adaptor protein for the connection of radial spokes, nexin-dynein regulatory complex (N-DRC) and doublet microtubules (DMTs) in sperm axoneme. Moreover, CCDC113 was identified as a structural component of HTCA, collaborating with SUN5 and CENTELIN to connect sperm head to tail during spermiogenesis. Together, our studies reveal that CCDC113 serve as critical hub for sperm axoneme and HTCA stabilization, providing insights into the potential pathogenesis of infertility associated with human CCDC113 mutations.
Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses
Authors: Cuaya Heriberto Coatl , Martínez-Gallego Irene , Rodríguez-Moreno Antonio
Published: June 2024

The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic, and sensory and information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer’s disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections. We investigated whether spike timing-dependent long-term depression (t- LTD) exists at these two different EC-DG synaptic connections in mice, and whether they have different action mechanisms. We have found two different forms of t-LTD, at LPP- and MPP-GC synapses and characterised their cellular and intracellular mechanistic requirement. We found that both forms of t-LTD are expressed presynaptically and that whereas t-LTD at LPP-GC synapses does not require NMDAR, t-LTD at MPP-GC synapses requires ionotropic NMDAR containing GluN2A subunits. The two forms of t-LTD require different group I mGluR, mGluR5 LPP-GC synapses and mGluR1 MPP-GC synapses. In addition, both forms of t-LTD require postsynaptic calcium, eCB synthesis, CB1R, astrocyte activity, and glutamate. Thus, we discovered two novel forms of t-LTD that require astrocytes at EC-GC synapses.
Altered visual cortex excitatory/inhibitory ratio following transient congenital visual deprivation in humans
Authors: Pant Rashi , Pitchaimuthu Kabilan , Ossandón José , Shareef Idris , Lingareddy Sunitha , Finsterbusch Jürgen , Kekunnaya Ramesh , Röder Brigitte
Published: June 2024

Non-human animal models have indicated that the ratio of excitation to inhibition (E/I) in neural circuits is experience dependent and changes across development. Here, we assessed 3T Magnetic Resonance Spectroscopy (MRS) and electroencephalography (EEG) markers of cortical E/I ratio in ten individuals who had been treated for dense bilateral congenital cataracts, after an average of 12 years of blindness, to test for dependence of the E/I ratio in humans on early visual experience. First, participants underwent MRS scanning at rest with their eyes opened and eyes closed, to obtain visual cortex Gamma-Aminobutyric Acid (GABA+) concentration, Glutamate/Glutamine (Glx) concentration and the concentration ratio of Glx/GABA+, as measures of inhibition, excitation, and E/I ratio respectively. Subsequently, EEG was recorded to assess aperiodic activity (1-20 Hz) as a neurophysiological measure of the cortical E/I ratio, during rest with eyes open and eyes closed, and during flickering stimulation. Across conditions, congenital cataract-reversal individuals demonstrated a significantly lower visual cortex Glx/GABA+ ratio, and a higher intercept and steeper aperiodic slope at occipital electrodes, compared to age-matched sighted controls. In the congenital cataract-reversal group, a lower Glx/GABA+ ratio was associated with better visual acuity, and Glx concentration correlated positively with the aperiodic intercept in the conditions with visual input. We speculate that these findings result from an increased E/I ratio of the visual cortex as a consequence of congenital blindness, which might require commensurately increased inhibition in order to balance the additional excitation from restored visual input. The lower E/I ratio in congenital cataract-reversal individuals would thus be a consequence of homeostatic plasticity.
Predictive value of plasma ephrinB2 levels for amputation risk following endovascular revascularization in peripheral artery disease
Authors: Guo Pengcheng , Chen Lei , Yang Dafeng , Zhang Lei , Shu Chang , Li Huande , Zhu Jieting , Zhou Jienan , Li Xin
Published: June 2024

Background

The aim of this study is to investigate the expression levels of ephrinB2 in patients with lower extremity peripheral arterial disease (PAD) and explore its association with the severity of the disease and the risk of amputation after endovascular revascularization.

Methods

During the period from March 2021 to March 2023, this study collected blood samples and clinical data from 133 patients diagnosed with lower extremity PAD and 51 healthy volunteer donors. The severity of lower extremity PAD patients was classified using the Rutherford categories. The expression of ephrin-B2 in plasma samples was detected using the Western Blotting.

Results

Compared to the control group, the levels of serum ephrinB2 in patients were significantly elevated (p < 0.001). Moreover, the plasma EphrinB2 levels were positively correlated with white blood cell counts (r = 0.204, p = 0.018), neutrophil counts (r = 0.174, p = 0.045), and neutrophil-to-lymphocyte ratio (NLR) (r = 0.223, p = 0.009). Furthermore, the AUCs of plasma ephrinB2 level, NLR, and their combination as predictors for amputation events within 30 months after lower extremity PAD endovascular revascularization were 0.659, 0.730 and 0.811. In the high-ephrinB2 group, the incidence of amputation events within 30 months after endovascular revascularization was higher.

Conclusions

Plasma EphrinB2 levels may be linked to lower extremity PAD development, inflammation, and postoperative amputation. Combining EphrinB2 and NLR can improve amputation prediction accuracy after endovascular revascularization in lower extremity PAD patients.
Identifying the Factors of Export Competitiveness for Agricultural Products
Authors: Yadav Alok Kumar , Chattopadhyay Utpal
Published: June 2024

Recently, agriculture exports have been receiving a lot of attention from academicians, researchers, governments, and policymakers. However, India’s agri-products competitiveness is generally low, and the economic significance of agriculture has been declining over the years. This compels undertaking studies on the export competitiveness of agri-products. The purpose of this study is to explore the critical factors of India’s agri-product export competitiveness. The competitiveness research has put less than adequate attention on the agriculture sector as compared to other constituents of the economy, such as industries and services. Overall, the present study has successfully identified the key factors that affect India’s agri-products export competitiveness in the global market. Indian agriculture has a huge export potential in the world market, and this can be fully exploited if competitiveness issues are addressed properly. Therefore, by identifying the abovementioned influencing factors, this study may offer very useful insight to farmers, exporters, and the government on how to strengthen India’s agricultural exports in the global market. Further, the framework of the study also lays the foundation for undertaking econometric-aided empirical research on export competitiveness of selected agri-products or the entire agriculture sector.
Social transformation for development as second-order phase transitions
Authors:   Economic Research and Innovations, Zakir Zahid
Published: June 2024

The basic concepts, parameters and relationships of the model of social transformations as second-order phase transitions, when the level of symmetry of the system increases and long-range order appears, are considered. These are transitions from the K-model, where the quasi-elite dominates, to the E-model, where the elite dominates. It is shown that in countries that have successfully done such a phase transition, the quasi-elite, freed from general social functions, is transformed into corporations and develops with great success, and the elite creates the necessary assistance mechanisms for this. It is this process of contradictory cooperation between the elite and the quasi-elite that stimulates accelerated development.
Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors
Authors: Qian Lichuan , Krause Diane S. , Saltzman W. Mark
Published: September 2011

Fetal liver epithelial cells (FLEC) are valuable for liver cell therapy and tissue engineering, but methods for culture and characterization of these cells are not well developed. This work explores the influence of multiple soluble factors on FLEC, with the long‐term goal of developing an optimal culture system to generate functional liver tissue. Our comparative analysis suggests hepatocyte growth factor (HGF) is required throughout the culture period. In the presence of HGF, addition of oncostatin M (OSM) at culture initiation results in concurrent growth and maturation, while constant presence of protective agents like ascorbic acid enhances cell survival. Study observations led to the development of a culture medium that provided optimal growth and hepatic differentiation conditions. FLEC expansion was observed to be approximately twofold of that under standard conditions, albumin secretion rate was 2–3 times greater than maximal values obtained with other media, and the highest level of glycogen accumulation among all conditions was observed with the developed medium. Our findings serve to advance culture methods for liver progenitors in cell therapy and tissue engineering applications.
Crystallization processes at the surface of polylactic acid—bioactive glass composites during immersion in simulated body fluid
Authors: Ginsac Nathalie , Chenal Jean‐Marc , Meille Sylvain , Pacard Elodie , Zenati Rachid , Hartmann Daniel J. , Chevalier Jérôme
Published: September 2011

We report on the crystallization processes occurring at the surface of PDLLA‐Bioglass® composites immersed in simulated body fluid. Composites manufactured by injection molding and containing different amounts (0, 20, 30, and 50 wt %) of 45S5 Bioglass® particles were tested for durations up to 56 days and compared with Bioglass® particles alone. Crystallization processes were followed by visual inspection, X‐ray diffraction (with Rietveld analysis) and scanning electron microscopy. Both calcite and hydroxyapatite were formed at the surface of all materials, but their relative ratio was dependent on the Bioglass® content and immersion time. Hydroxyapatite was always the major phase after sufficient immersion time, insuring bioactivity of such composites especially for Bioglass® content higher than 30 wt %. A scenario of crystallization is proposed. Rapid degradation of the composites with 50 wt % was also observed during immersion. Therefore, composites with 30 wt % of Bioglass® particles seem to exhibit the best balance between bioactivity and stability at least during the first weeks of immersion in contact with body fluids. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Late Holocene environmental conditions in Coronation Gulf, southwestern Canadian Arctic Archipelago: evidence from dinoflagellate cysts, other non‐pollen palynomorphs, and pollen
Authors: Pieńkowski Anna J. , Mudie Peta J. , England John H. , Smith John N. , Furze Mark F. A.
Published: September 2011

Boxcore 99LSSL‐001 (68.095° N, 114.186° W; 211 m water depth) from Coronation Gulf represents the first decadal‐scale marine palynology and late Holocene sediment record for the southwestern part of the Northwest Passage. The record was studied for organic‐walled microfossils (dinoflagellate cysts, non‐pollen palynomorphs), pollen, terrestrial spores, and sediment characteristics. 210Pb, 137Cs, and three accelerator mass spectrometry 14C dates constrain the chronology. Three prominent palaeoenvironmental zones were identified. During the interval AD 1470–1680 (Zone I), the climate was warmer and wetter than at present, and environmental conditions were more favourable to biological activity and northward boreal forest migration, with reduced sea‐ice and a longer open‐water (growing) season. The interval AD 1680–1940 (Zone II) records sea‐ice increase, and generally cool, polar conditions during the Little Ice Age. During AD 1940–2000 (Zone III), organic microfossils indicate an extended open‐water season and decreased sea‐ice, with suggested amelioration surpassing that of Zone I. Although more marine studies are needed to place this record into an appropriate context, the succession from ameliorated (Zone I) to cooler, sea‐ice influenced conditions (Zone II) and finally to 20th‐century warming (Zone III) corresponds well with several terrestrial climatic records from the neighbouring mainland and Victoria Island, and with lower‐resolution marine records to the west. Copyright © 2011 John Wiley & Sons, Ltd.
A CPW‐fed slot antenna with embedded ring‐type strip for dual‐frequency operation
Authors: Chiang Meng‐Ju , Wei Chia‐Yen , Bor Sheau‐Shong
Published: September 2011

The coplanar waveguide‐fed planar slot antenna with the embedded ring‐type strip for dual‐frequency operation is investigated and experimentally explores in this letter. The prototype, which is implemented on the 0.8‐mm FR‐4 substrate with εr = 4.4, indicates that the embedded ring‐type strip offers extended path for the electric current flow, achieving 45.1% size reduction of the fundamental resonant mode. The ratio of the center frequencies of the first two resonant bands can be tuned within a range wider than 1.81 by increasing the radius and line width of ring‐type strip. Furthermore, the fundamental resonant mode can be shifted to the higher frequency to combine with the second resonant mode of the circular slot, indicating the wideband operation with the bandwidth of 1332 MHz (40.5%). © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2882–2887, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26370
Design of miniaturized broadband and high gain metamaterial patch antenna
Authors: Liu Tao , Cao Xiang‐Yu , Gao Jun , Yang Qun , Li Wen‐Qiang
Published: September 2011

A miniaturized broad bandwidth and high‐gain patch antenna was designed and fabricated using the metamaterial concept via the pattern‐etched upper patch and bottom ground plane in this article. Due to the left‐handed transmission characteristics, the wave propagation along the patch induces the strongest radiation in horizontal direction instead of the vertical direction of the conventional patch antenna. It is shown to have great impact on the antenna performance enhancement in terms of the resonant center frequency obviously reduced about 36.4%, the bandwidth significantly broadened from about 2.9% to about 39.9%, and also in terms of low voltage standing wave ratio. Experimental data show a reasonably good agreement between the simulation and measured results. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2893–2896, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26383
Microwave transmission characteristics of electromagnetic crystals with modified diamond lattice
Authors: Yuan Zhi‐Hui , Li Di‐Chen
Published: September 2011

Microwave transmission characteristics of electromagnetic crystals with normal and stretched sphere diamond lattice structures were investigated experimentally. Three‐dimensional stretched structures were designed using a CAD program to form band‐gaps in the GHz range. Diamond lattices were stretched linearly and nonlinearly in the direction 〈100〉. Electromagnetic crystals with lattice modification were fabricated by means of stereolithography (SL) and gelcasting process using aluminum‐oxide ceramic successfully and their microwave properties were measured by network analyzer and a rectangular waveguide system. Compared with the normal diamond structure, the microwave properties of the electromagnetic crystals containing stretched lattices have some regular changes depending on the stretched structures and the material filling ratio. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2809–2811, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26384
A compact broadband MIMO antenna for mobile handset applications
Authors: Zhou Xiang , Li RongLin , Jin Guiping , Tentzeris M. M.
Published: September 2011

A compact planar broadband multiple‐input multiple‐output (MIMO) antenna, which has a good performance under MIMO situations with low mutual coupling (<−11 dB) and low correlation coefficient (≤−15 dB) is presented. The antenna operates a very wide band with good impedance matching (S11 <−10 dB), covering the LTE band 33–37 and 39–40. The elements are mounted on the same side of ground plane with the inter‐element space of 32 mm. The total size of the array is compact (50 mm × 67.2 mm × 0.254 mm), suitable for mobile handset applications. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2773–2776, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26386
A spice model for multiconductor microstrip lines excited by an incident plane wave
Authors: Zhang Wei , Du Zhengwei
Published: September 2011

This article presents a SPICE model to analyze the terminal response of multiconductor microstrip lines excited by an incident plane wave. The analysis is based on multiconductor transmission line equations with the quasi‐TEM propagation mode approximation on microstrip lines and an accurate calculation of electromagnetic fields in the air/dielectric medium. The proposed SPICE model can be directly used for both the time‐domain and frequency‐domain analyzes and allows incorporating nonlinear and time‐varying loads. Several cases with an arbitrary plane wave incidence are simulated by using the proposed SPICE model. The results are in good agreement with those obtained using the Baum‐Liu‐Tesche equations model and full‐wave analysis simulator (by CST Microwave Studio Software). © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2754–2761, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26396
Design of dualband antenna for IEEE 802.11 a/b/g/n applications
Authors: Zhang Yabin
Published: September 2011

This letter provides a design of 2.4–2.5 GHz/5–6 GHz dualband antenna for IEEE 802.11 a/b/g/n applications. The antenna has ultra small planar structure and dimension is 25 × 10 × 1 mm3. For verifying the proposed design, the prototype antenna was fabricated and measured. The measured data indicate that the design is successful and applicable. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 2890–2893, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26399
A method to improve radiation efficiency by using a slot on a ground plane
Authors: Lee Seung‐Jun , Seo Jae‐Min , Kim Young‐Sik
Published: September 2011

In this letter, a planar inverted‐F antenna with a slot on a ground is proposed to improve the antenna radiation efficiency at the CDMA band of 824–894 MHz. In this configuration, the electric fields are more confined to the inverted‐F section and the end‐point of the ground. The measured results show that the radiation efficiencies of the proposed antenna are improved by up to 16.8% and that the radiation patterns are similar to those of the antenna without a slot. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:3001–3003, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26401
Modified cylindrical dielectric resonators excited with loaded fork monopole antenna
Authors: Khalily M. , Rahim M. K. A. , Kamarudin M. R.
Published: September 2011

A novel hybrid dielectric resonator antenna (DRA) excited by a printed monopole antenna is proposed and implemented. This new microstrip‐fed fork‐like stepped monopole antenna is designed to obtain a wide impedance bandwidth from 2 to 6 GHz. A quad‐band characteristic is achieved by incorporating two modified cylindrical dielectric resonators with a high dielectric constant of 80, on top of the monopole exciter. Measured results demonstrated that the proposed DRA can be used in multiband wireless operations, covering GSM, PCS, UMTS, WLAN, and WiMax systems, from 1.75 to 5.85 GHz. Experimental and simulation results show a good agreement. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2887–2890, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26407
Compact monopole antenna with two bands—notched characteristic for ultra‐wideband applications
Authors: Naser‐Moghadasi M. , Gotolo S.Faraji , Dadashzadeh G.
Published: September 2011

In this article, we present a novel small ultra‐wideband microstrip‐fed planar monopole antenna composed of a hexagonal patch, a truncated stub, a step ground structure, and a conductor back plane in the shape of a window. Impedance bandwidth of the proposed antenna is ∼136% with voltage‐standing wave ratio <2 in the frequency range of 2.7–14.3 GHz over an UWB frequency range that satisfies FCC's requirements for an antenna. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2817–2821, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26409
Design of a compact patch antenna using split‐ring resonator embedded substrate
Authors: Zhao Xing , Lee Youngki , Choi Jaehoon
Published: September 2011

In this article, a compact patch antenna using split‐ring resonators (SRRs) is proposed.To reduce the size of a conventional patch antenna, the SRRs are inserted between the main patch and ground. The size reduction is achieved by utilizing the high equivalent permeability characteristics of the proposed structure. The resonance frequency of the antenna shifts from 6.6 to 4.67 GHz without changing the fractional bandwidth and the gain characteristic. A size reduction of 29.3% is achieved, and a maximum gain of 4.84 dBi is obtained. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2786–2790, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26411
Configurable ink‐jet‐printed RFID tag on paper substrate for low cost and green applications
Authors: Shao Botao , Chen Qiang , Liu Ran , Zheng Li‐Rong
Published: September 2011

The letter presents the design, fabrication, and measurement of a configurable radio frequency identification (RFID) tag based on time‐domain reflections. The tag circuit contains a microstrip line (ML) that propagates radio frequency (RF) signals, and a group of capacitors that introduce impedance discontinuities to encode binary codes. The configurability of the tag circuit is allowed by connecting the nearby‐placed capacitors with the ML. Ink‐jet printing technology is employed to implement the layout of the proposed tag on paper substrate. To overcome the limitations of printed metallic tracks, a linearly tapering technique is proposed. With this technique, a four‐bit configurable passive chipless RFID tag is realized. Both time‐domain reflectometry (TDR) measurements and ultrawideband (UWB) characterizations were conducted for the proposed tag, and the results are in good consistence with the simulation ones from the circuit simulator advanced design system (ADS). Owing to its low cost fabrication and environmentally friendly nature, the proposed tag has great potential to be widely employed in low‐end RFID applications. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2781–2786, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26412
On the design of inscribed pentagonal‐cut fractal antenna for ultra wideband applications
Authors: Kumar Raj , Chaubey Prem Narayan
Published: September 2011

The article presents the CPW‐feed inscribed pentagonal‐cut fractal antenna. This planar monopole antenna has been designed on low cost FR4 substrate of εr = 4.3 and thickness h = 1.53 mm. The proposed antenna has been fabricated with optimized dimension. The experimental result of this antenna exhibits the ultra wideband from 2.5 to 15 GHz. The antenna has been simulated using EM simulator based on finite element method. The experimental and simulated results are in good agreement. The radiation patterns of this antenna are omnidirectional in H‐plane and bidirectional in E‐plane, respectively. The measured group delay is almost flat throughout the band. This antenna can be useful for UWB system, microwave imaging and vehicular radar. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2828–2830, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26415
Optical amplification based on slow light effects in the photonic crystal waveguide
Authors: Zhang Yejin , Zheng Wanhua , Qi Aiyi , Qu Hongwei , Chen Lianghui
Published: September 2011

Optical amplification is demonstrated in a slab photonic crystal waveguide (PCW). Nonlinear dispersive gain FDTD and traveling‐wave rate equation method (TWRE) are used to design a photonic crystal semiconductor optical amplifier (PC‐SOA). Optical amplification based on slow light of PCW can be obtained not only in theory but also in experiment. In the C band, the gain of more than 10 dB is obtained in a 20‐μm long PC‐SOA sample. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2997–3001, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26419
Wide‐locking range ÷3 active‐inductor injection‐locked frequency divider using the push–push oscillator
Authors: Chang Chia‐Wei , Jang Sheng‐Lyang , Hsieh Chao‐Wei
Published: September 2011

A new wide locking range active‐inductor divide‐by‐3 injection‐locked frequency divider (ILFD) using a standard 0.18‐μm CMOS process is presented.The push–push ILFD circuit is realized with a push–push cross‐coupled n‐core MOS LC‐tank oscillator. The core power consumption of the ILFD core is 7.41 mW. The divider's free‐running frequency is tunable from 1.39 to 3.18 GHz by tuning the varactor's control bias, and at the incident power of 0 dBm the maximum locking range is 2.9 GHz (43.6%), from the incident frequency 5.2 to 8.1 GHz. The operation range is 5.9 GHz (80.27%), from 4.4 to 10.3 GHz. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2771–2773, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26426
Modeling and imaging of biomechanical properties of breast using microwave pulses
Authors: Abbosh A. M.
Published: September 2011

A closed‐form theoretical model for the biomechanical properties of breast tissues under the influence of external pressure is derived and validated. That model is employed in a microwave imaging method that aims at extracting the three‐dimensional biomechanical properties of breast. The high contrast in the biomechanical properties between healthy and malignant tissues represents the basis of the presented imaging method. In this method, the breast is inserted in an enclosure that has an array of ultrawideband (UWB) antennas embedded in the upper movable plate of the enclosure. Each of those antennas transmits an UWB pulse towards the breast and measure the backscattered pulse before and after compressing the breast by a controlled force applied at the top of the movable plate. A sliding‐window cross‐correlation is used to get a three‐dimensional strain image of the breast. As lesion tissue is much stiffer than the normal breast tissues the regions of zero strain indicate areas of suspected tumor. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2761–2765, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26440
Printed Yagi–Uda array for on‐body communication channels at 60 GHz
Authors: Wu X. Y. , Akhoondzadeh‐Asl L. , Hall P. S.
Published: September 2011

A novel low‐profile high‐gain, end‐fire Yagi–Uda antenna array designed for an on‐body communication link at 60 GHz is described. The antenna consists of four single Yagi antennas, which is composed of a driven dipole, 18 directors, and a reflector. Simulation and measurement in free space show a good agreement, and 15 dBi gain is achieved. Measurements with a body tissue phantom have been done to investigate the antenna's performance in close proximity to the human body. Results show that the reflection coefficient changes a little, whereas the radiation pattern in the H plane is affected. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:2728–2730, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26443
Considerations on what constitutes a ‘qualified statistician’ in regulatory guidelines
Authors: Gerlinger Christoph , Edler Lutz , Friede Tim , Kieser Meinhard , Nakas Christos T , Schumacher Martin , Seldrup Jørgen , Victor Norbert
Published: September 2011

International regulatory guidelines require that a ‘qualified statistician’ takes responsibility for the statistical aspects of a clinical trial used for drug licensing. No consensus on what constitutes a ‘qualified statistician’ appears to have been developed so far.

The International Society for Clinical Biostatistics is issuing this reflection paper in order to stimulate a discussion on the concept. Copyright © 2011 John Wiley & Sons, Ltd.
Analyses of longitudinal, hospital clinical laboratory data with application to blood glucose concentrations
Authors: Schildcrout Jonathan S. , Haneuse Sebastien , Peterson Josh F. , Denny Joshua C. , Matheny Michael E. , Waitman Lemuel R. , Miller Randolph A.
Published: September 2011

Electronic medical record (EMR) systems afford researchers with opportunities to investigate a broad range of scientific questions. In contrast to purposeful study designs, however, EMR data acquisition procedures typically do not align with any specific hypothesis. Subsequent investigations therefore require detailed characterization of clinical procedures and protocols that underlie EMR data, as well as careful consideration of model choice. For example, many intensive care units currently implement insulin infusion protocols to better control patients’ blood glucose levels. The protocols use prior glucose levels to determine, in part, how to adjust the infusion rate. Such feedback loops introduce time‐dependent confounding into longitudinal analyses even though they may not always be evident to the analyst. In this paper, we review commonly used longitudinal model specifications and interpretations and show how these are particularly important in the presence of hospital‐based clinical protocols. We show that parameter relationships among various models can be used to identify and characterize the impact of time‐dependent confounding and therefore help explain seemingly incongruous conclusions. We also review important estimation challenges in the presence of time‐dependent confounding and show how certain model specifications may be more or less susceptible to bias. To illustrate these points, we present a detailed analysis of the relationship between blood glucose levels and insulin doses on the basis of data from an intensive care unit. Copyright © 2011 John Wiley & Sons, Ltd.
Optimum threshold estimation based on cost function in a multistate diagnostic setting
Authors: Skaltsa Konstantina , Jover Lluís , Fuster David , Carrasco Josep Lluís
Published: September 2011

In the diagnostic area, the usual setting considers two populations: nondiseased and diseased. The use of the standard ROC analysis methodology is well established. Sometimes, however, diagnostic problems inherently include more than two classification states. For example, ‘yes, uncertain, no’ or ‘low, normal, high’. Here we consider a three‐normal distribution setting and derive estimators for the optimum thresholds between states based on a cost function. These estimators can be extended for clinical contexts with more than three states. This approach is well known for the two‐state setting and its advantage lies in the fact that it accounts for the specific context's properties, such as disease prevalence and classification costs. Here we calculated the variance of the estimators by the use of parametric methods on nonlinear equations and we constructed confidence intervals accounting for possible uncertainty in the threshold estimation. We conducted a simulation study to assess the performance of these estimators and the confidence intervals. Comparisons with the naive threshold estimation method of joining the distributions two‐by‐two and applying standard ROC techniques proved that the latter method is not reliable for all parameter combinations and should be avoided. Copyright © 2011 John Wiley & Sons, Ltd.
Statechartable Petri nets
Authors: Eshuis Rik
Published: September 2011

Petri nets and statecharts can model concurrent systems in a succinct way. While translations from statecharts to Petri nets exist, a well-defined translation from Petri nets to statecharts is lacking. Such a translation should map an input net to a corresponding statechart, having a structure and behaviour similar to that of the input net. Since statecharts can only model a restricted form of concurrency, not every Petri net has a corresponding statechart. We identify a class of Petri nets, called statechartable nets, that can be translated to corresponding statecharts. Statechartable Petri nets are structurally defined using the novel notion of an area. We also define a structural translation that maps each statechartable Petri net to a corresponding statechart. The translation is proven sound and complete for statechartable Petri nets.
Kinetic Analysis of Lecithin:Cholesterol Acyltransferase Activity Toward Discoidal HDL
Authors: Dergunov Alexander D.
Published: September 2011

The kinetics of lecithin:cholesterol acyltransferase(LCAT, EC 2.3.1.43)‐catalyzed generation of cholesteryl ester in discoidal high density lipoproteins (HDL) was analyzed in terms of initial binding of LCAT to the disc surface followed by a three‐state reaction of the hydrolysis of phosphatidylcholine sn‐2 ester bond and acyl‐enzyme formation. Cholesterol was considered as alcoholic nucleophile that increases the solvolysis rate of acyl‐LCAT. The raw kinetic data of Sparks et al. (J Biol Chem 270:5151–5157, 1995) for four preparations of reconstituted discoidal HDL with a constant level of apolipoprotein A‐I and palmitoyloleoylphosphatidylcholine per disc but with cholesterol in a lipid phase continuously increasing from 2.1 to 12.5 mol%, were analyzed in terms of the kinetic equation and a complete set of rate constants was obtained. Data at high cholesterol content do not indicate a saturation phenomenon, thus giving no evidence for a binding of cholesterol to the enzyme. This analysis may be used in the study of LCAT activation by exchangeable apolipoproteins and contribution of the HDL structure.
Microfluidics Enables Small-Scale Tissue-Based Drug Metabolism Studies with Scarce Human Tissue
Authors: van Midwoud Paul M. , Merema Marjolijn T. , Verpoorte Elisabeth , Groothuis Geny M.M.
Published: September 2011

Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither are ideal predictors of drug behavior in humans. Improving in vitro systems for preclinical studies both from a technological and biological model standpoint thus remains a major challenge. This article describes how microfluidics can be exploited to come closer to this goal in combination with precision-cut liver slices (PCLS) as an improved organomimetic system. Recently, we developed a novel microfluidic-based system incorporating a microchamber for slice perifusion to perform drug metabolism studies with mammalian PCLS under continuous flow. In the present study, the viability and metabolism of human PCLS were assessed by the measurement of the leakage of liver-specific enzymes and metabolism of four different substrates: lidocaine, 7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone. All experiments were verified with well plates, an excellent benchmark for these experiments. Clearly, however, human tissue is not readily available, and it is worth considering how to perform a maximum number of informative experiments with small amounts of material. In one approach, the microfluidic system was coupled to an HPLC system to allow on-line monitoring and immediate detection of unstable metabolites, something that is generally not possible with conventional well-plate systems. This novel microfluidic system also enables the in vitro measurement of interorgan interactions by connecting microchambers containing different organ slices in series for sequential perfusion. This versatile experimental system has the potential to yield more information about the metabolic profiles of new drug candidates in human and animal tissues in an early stage of development compared with well plates alone.
Emerging Clinical Applications of Microchip-Based Acoustophoresis
Authors: Lenshof A. , Laurell T.
Published: September 2011

Acoustophoresis is currently in a state of transition from the academic laboratories, moving into the biomedical laboratories and industries. Clear areas of interest are seen in clinical diagnostics and therapeutics, where new approaches to cell handling and purification are emphasized as highly potent areas. This article outlines some of the basic unit operations of acoustophoresis, where applications as cell washing, binary separation, free-flow acoustophoresis, and affinity acoustophoresis are highlighted. The most recent steps to move acoustophoresis into clinical and preclinical applications are also presented.
Uncontrolled Study Assessing the Impact of a Psyllium-Enriched Extruded Dry Diet on Faecal Consistency in Cats with Constipation
Authors: Freiche Valerie , Houston Doreen , Weese Heather , Evason Michelle , Deswarte Géraldine , Ettinger Gérald , Soulard Yannick , Biourge Vincent , German Alexander J
Published: September 2011

Two field trials, involving 66 cats (15 trial 1; 51 trial 2) were conducted to assess the efficacy of a psyllium-enriched diet for management of constipation in cats. After investigations and faecal evacuation (by enema if required), all cats were fed on a moderate fibre, psyllium-enriched, dry extruded diet. Additional therapy was either not used (trial 1), or initially allowed but was subsequently withdrawn if possible (trial 2). The diet was well tolerated, and palatability was excellent. Most cases improved after initial therapy (at 2 months; trial 1: 14/15 [93%]; trial 2: 42/51 [82%]), and faecal consistency improved significantly in both trials ( P < 0.001). Use of cisapride and lactulose decreased significantly in trial 2 ( P < 0.001 for both). The diets used in these pilot studies were efficient in the management of recurrent feline constipation. Randomised control trials are now recommended to examine whether a clinical benefit can be proven.
The Chinese version of the Severity of Dependence Scale as a screening tool for benzodiazepine dependence in Taiwan
Authors: Tsai Jui‐Hsiu , Tang Tze‐Chun , Yeh Yi‐Chun , Yang Yi‐Hsin , Yeung Tsang Hin , Wang Shing‐Yaw , Chen Cheng‐Chung
Published: September 2011

The development of an instrument to estimate the incidence, characteristics, and risk factors of benzodiazepine (BZD) dependence broadly in Taiwan is an important task. This study assessed the validity of the Chinese version of the Severity of Dependence Scale (SDS[Ch]) among regular BZD users in Taiwan (n = 228). A positive correlation was shown between SDS[Ch] and Mini‐International Neuropsychiatric Interview diagnosed of BZD dependence. Thirty‐six percent of the users received a Mini‐International Neuropsychiatric Interview diagnosis of current BZD dependence. The dependent users tended to be divorced/widowed; not schizophrenic; and have higher SDS[Ch] scores, a longer duration of use, and multiple‐BZD use. The SDS[Ch] for BZD dependence was shown to have high diagnostic utility (area under the receiver operating characteristic curve = 0.779), a sensitivity of 80.5%, and a specificity of 85.7%, with a cutoff point of 7. The findings support that the SDS[Ch] is a valid brief self‐reported questionnaire for the assessment of BZD dependence among chronic users in Taiwan.
The inter- and intra-individual variance in descending pain modulation evoked by different conditioning stimuli in healthy men
Authors: Oono Yuka , Nie Hongling , Matos Renata Lima , Wang Kelun , Arendt-Nielsen Lars
Published: September 2011

Background and purpose

Conditioned pain modulation (CPM) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation. It is not known how the experimental condition affects the magnitude of the CPM response and the inter-and intra-individual variations. It is important to get the information of the test–retest reliability and inter–individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds. This study evaluated (1) the magnitude of CPM, (2) the inter-individual coefficient of variation (inter-CV) and (3) the intra-individual coefficient of variation (intra-CV) to (A) different stimulus modalities to evoke CPM and (B) different assessment sites.

Methods

Twelve healthy men (age 19–38 years) participated in this study. Cold pressor pain (CPP) (immersing the hand into cold water), tourniquet pain (cuff around the upper arm) and mechanical pressure pain (craniofacial region) were used in randomized order as conditioning stimuli (CS). The test stimulus (TS) was pressure pain applied to the right masseter muscle, left forearm and leg (bilateral tibialis anterior: TA). The responses were pressure pain thresholds (PPT), pressure pain tolerance (PPTol) thresholds and the pain intensity which was assessed on a visual analogue scale (VAS, 0–10 cm) following 1.4 and 1.6 × PPT applied to TA. The TS was applied before, during and 10 min after the CS. The intra-individual CV was estimated between different days.

Results

CPP induced the most powerful CPM on PPT (66.3 ± 10.0% increase), VAS ratings (41.5 ± 5.3% reduction) and PPTol (32.6±4.6% increase), especially at TA, and resulted in the smallest inter-CV (41.4–60.1%). Independently of the CS, the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg. The smallest intra-CV value was obtained in pain ratings with CPP (27.0%).

Conclusions

This study suggests that (1) the CPP evokes the largest CPM, (2) the leg as the assessment site results in the largest CPM responses and (3) the CPP causes the smallest inter- and intra-CV.

Implication

The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds.
The Cambridge Companion to the Literature of London
Authors: Manley Lawrence
Published: September 2011

London has provided the setting and inspiration for a host of literary works in English, from canonical masterpieces to the popular and ephemeral. Drawing upon a variety of methods and materials, the essays in this volume explore the London of Langland and the Peasants' Rebellion, of Shakespeare and the Elizabethan stage, of Pepys and the Restoration coffee house, of Dickens and Victorian wealth and poverty, of Conrad and the Empire, of Woolf and the wartime Blitz, of Naipaul and postcolonial immigration, and of contemporary globalism. Contributions from historians, art historians, theorists and media specialists as well as leading literary scholars exemplify current approaches to genre, gender studies, book history, performance studies and urban studies. In showing how the tradition of English literature is shaped by representations of London, this volume also illuminates the relationship between the literary imagination and the society of one of the world's greatest cities.
Dynamic bifurcations and pattern formation in melting-boundary convection
Authors: Vasil G. M. , Proctor M. R. E.
Published: September 2011

We consider weakly nonlinear convection in a fluid layer with a melting top boundary. This leads us to derive a new set of non-autonomous envelope equations as a dynamic generalization to the well-known Ginzburg–Landau equation. However, this new system possesses a number of interesting properties not found in systems close to a traditional dynamic bifurcation, because it involves the interaction of two destabilizing mechanisms. We investigate the system both analytically and numerically; specifically, we find the robust ‘locking in’ of spatially complex patterns, and show this is a general feature of systems of this nature.