bluuebunny/crossref_metadata_2025 huggingface dataset:
Politically‐Connected Boards and the Structure of Chief Executive Officer Compensation Packages in Taiwanese Firms*
Authors: Yu Hsin‐Yi
Published: September 2010

This paper examines the relationship between the level of political connection of the board and chief executive officer (CEO) equity‐based compensation. Using a sample of Taiwanese firms, the paper provides evidence that politically connected boards grant a lower proportion of equity‐based compensation to CEOs. Political intervention can reduce the proportion of equity‐based compensation and, thereby, can have negative consequences for the alignment between the interests of CEOs and shareholders in firms. The findings obtained in this paper could be useful to policy‐makers in emerging economies, where there is wide scope for political intervention.
Liquidity Commonality and its Causes: Evidence from the Korean Stock Market*
Authors: Choe Hyuk , Yang Cheol‐Won
Published: September 2010

This paper investigates the causes of liquidity commonality. We consider information asymmetry, volatility, utilitarian trading interest, style‐based trading, inventory cost, and investor sentiment as potential candidates. Our empirical analysis shows that greater information asymmetry causes higher liquidity commonality. The significant effect of the order imbalance beta supports our volatility hypothesis as a cause of liquidity commonality. Program trading and the KOSPI200 index dummy are positively related to liquidity commonality, which is consistent with the style‐based trading hypothesis. Higher individual trading is associated with higher liquidity commonality, which means that investor sentiment operates in the Korean market. However, volume beta and return beta, as proxies for the utilitarian trading effect and the inventory cost, respectively, are insignificantly related to liquidity commonality.
Hedge Ratio Stability and Hedging Effectiveness of Time‐Varying Hedge Ratios in Volatile Index Futures Markets: Evidence from the Asian Financial Crisis*
Authors: Wang Janchung , Hsu Hsinan
Published: September 2010

Hedge ratio stability is especially important because hedgers are likely to use the estimate of historical hedge ratios to hedge future positions of their portfolios. One main purpose of the present study is to examine hedge ratio stability during the Asian financial crisis and post‐crisis, periods characterized by high price volatility, using the Nikkei 225, Hang Seng, and KOSPI 200 index futures contracts. Empirical results from the Hang Seng and the KOSPI 200 futures markets indicate that during the two periods of high price volatility, hedge ratios appeared to be unstable. Additionally, both in‐sample and out‐of‐sample evidences indicate that, for hedging effectiveness, the time‐varying hedge ratios clearly outperform the constant hedge ratios for the Hang Seng and the KOSPI 200 index futures, consistent with the findings of hedge ratio instability. The comparison results of different time‐varying hedge ratios support the conclusion that the bivariate error correction generalized autoregressive conditional heteroskedastic (1,1) model enhances hedging effectiveness compared to other time‐varying hedge ratios. Finally, this study examines the impact of hedge duration on hedging effectiveness and hedge ratios. The empirical results indicate that hedging effectiveness improves with increasing hedge duration.
Idiopathic aseptic pericardial effusion with cardiac tamponade in a horse
Authors: Malalana F. , Bardell D. , McKane S.
Published: September 2010

This report describes the successful treatment of pericardial effusion and cardiac tamponade in a 10‐year‐old Hanoverian gelding. Pericarditis and pericardial effusion are uncommon conditions in horses. Although many potential causes for the effusion have been described most cases are classified as idiopathic. The most valuable diagnostic procedure for the detection of pericardial effusion is echocardiography. Pericardiocentesis and drainage of the fluid were carried out in this case. At one year follow‐up there were no clinical signs of recurrence and the horse has returned to his previous level of athletic performance.
How to Estimate Heat Spreading Effects in Practice
Authors: Lasance Clemens J. M.
Published: September 2010

The nontrivial issues associated with calculating the steady state heat spreading effects generated by a heat source on top of a multilayer assembly such as a printed circuit board are discussed. It is argued that problems arise with the interpretation of heat spreading effects due to a misconception about the meaning of often-quoted flux limits and especially the physical meaning of thermal resistance. The usefulness of a number of approaches that are generally in use to analyze heat spreading effects is discussed and it is shown that the popular series-resistance approach has severe limitations. A number of test cases are covered in detail and the results testify to this assertion.
Surface Roughening During Deformation of Polycrystalline Aluminum and Titanium Alloys
Authors: Zhou X. H. , Su X.
Published: September 2010

The surface topography of aluminum and titanium alloys after plastic deformation is investigated using white-light interferometry. The surface profiles of tensile samples in the longitudinal and transverse directions are analyzed. The surface develops self-affine roughness on length scales up to a correlation length that is of the same order of magnitude as the grain size in the two directions. The difference in correlation lengths between the two directions is large for aluminum alloy and small for titanium alloy. Initially, the roughness values in the two directions remain the same and then become different with strain increase. It is shown that the strains in the two directions influence the profile. The relationship between the 3D surface roughness parameter (Sq) and strain appears to be linear, and a linear relation is also observed between surface area increment and strain.
Evaluation of spherical fiducial localization in C‐arm cone‐beam CT using patient data
Authors: Yaniv Ziv
Published: September 2010

Purpose:

C‐arm based cone‐beam CT (CBCT) has been recently introduced as anin‐situ 3D soft tissue imaging modality. When combined with image‐guided navigation, it provides a streamlined clinical workflow with, potentially, improved interventional accuracy. A key component in these systems is image to patient registration. The most common registration method relies on fiducial markers placed on the patient's skin. The fiducials are localized in the volumetric image and in the interventional environment. When using C‐arm CBCT, the small spatial extent of the volumetric reconstruction makes this registration approach challenging, as the volume must include both the anatomy of interest and the fiducials. The authors have previously proposed a semiautomatic localization approach that addresses this challenge, with evaluation carried out using anthropomorphic phantoms. To truly evaluate the algorithm's utility, the evaluation must be carried out using clinical data. In this article, the authors extend the evaluation of the approach to data sets acquired in a clinical trial.

Methods:

Nine CBCT data sets were obtained in three interventional radiology procedures as part of a clinical trial evaluating a commercial navigation system. Fiducials were localized in the volumetric coordinate system directly from the projection images using the evaluated localization approach. Localization was assessed using two quality measures fiducial registration error to quantify precision and fiducial localization error to quantify accuracy. The fiducials used in this study are 6 mm spheres embedded in a custom registration phantom used by the navigation system.

Results:

In all cases, the proposed approach was able to localize all five fiducial markers embedded in the registration phantom. The approach's mean (std) fiducial registration error was 0.29 (0.13) mm. The mean (std) localization difference as compared to direct volumetric localization was 0.82 (0.34) mm.

Conclusions:

Based on the current evaluation using data from clinical cases, the authors conclude that the localization approach is sufficiently accurate for use in thoracic‐abdominal interventions, and that it can simplify the current workflow while reducing cumulative radiation to the patient due to repeated CBCT scans.
A support vector machine (SVM) for predicting preferred treatment position in radiotherapy of patients with breast cancer
Authors: Zhao Xuan , Wong Edward K. , Wang Yao , Lymberis Stella , Wen Bixiu , Formenti Silvia , Chang Jenghwa
Published: September 2010

Purpose:

NYU 05‐181 protocol compared the CT simulation in both supine and prone positions for 400 patients with breast cancer (200 left‐breast and 200 right‐breast) to identify which setup is better at sparing heart and lung involvement in the treatment process. The results demonstrated that all right‐breast patients benefited from the prone treatment position, while for left‐breast patients, 85% were better treated prone and 15% were better treated supine. Using the clinical data collected from this protocol, the authors aimed at developing an automated tool capable of identifying which of the left‐breast cancer patients are better treated supine without obtaining a second CT scan in the supine position.

Methods:

Prone CT scans from 198 of the 200 left‐breast cancer patients enrolled in NYU 05‐181 protocol were deidentified and exported to a dedicated research planning workstation. Three‐dimensional geometric features of the organs at risk and tumor bed were extracted. A two‐stage classifier was used to classify patients into the prone class or the supine class. In the first stage, the authors use simple thresholding to divide the patients into two groups based on their in‐field heart volume. For patients with in‐field heart volume, the prone position was chosen as the preferred treatment position. Patients with in‐field heart volume will be further classified in the second stage by a weighted support vector machine (SVM). The weight parameters of the SVM were adjusted to maximize the specificity at the cost of lowering but still maintaining reasonable sensitivity . The authors used ‐fold cross validations to test the performance of the SVM classifier. A feature selection algorithm was also used to identify features that give the best classification performance.

Results:

After the first stage, 49 of the 198 left‐breast cancer patients were found to have of in‐field heart volume. The three geometric features of heart orientation, distance between heart and tumor, and in‐field lung were selected by the feature selection algorithm in the second stage of the two‐stage classifier to give the best predefined weighted accuracy. The overall sensitivity and specificity of the proposed method were found to be 90.4% and 99.3%, respectively. Using two‐stage classification, the authors reduced the proportion of prone‐treated patients that need a second supine CT scan down to 16.3/170 or 9.6%, as compared to 21/170 or 12.4% when the authors use only the first stage (thresholding) for classification.

Conclusions:

The authors’ study showed that a feature‐based classifier is feasible for predicting the preferred treatment position, based on features extracted from prone CT scans. The two‐stage classifier achieved very high specificity at an acceptable expense of sensitivity.
Noninvasive mapping of spontaneous fluctuations in tumor oxygenation using MRI
Authors: Magat J. , Jordan B. F. , Cron G. O. , Gallez B.
Published: September 2010

Purpose:

Acute hypoxia (transient cycles of hypoxia‐reoxygenation) is known to occur in solid tumors and may be a poorly appreciated therapeutic problem as it can be associated with resistance to radiation therapy, impaired delivery of chemotherapeutic agents, or metastasis development. The objective of the present study was to use MR relaxometry maps to analyze the spontaneous fluctuations of partial pressure of oxygen over time in experimental tumors.

Methods:

The maps were generated after direct intratumoral administration of a fluorine compound (hexafluorobenzene) whose relaxation rate is proportional to the % . The authors used a SNAP inversion‐recovery sequence at 4.7 T to acquire parametric images of the relaxation time with a high spatial and temporal resolution. Homemade routines were developed to perform regions of interest analysis, as well as pixel by pixel analysis of over time.

Results:

The authors were able to quantify and probe the heterogeneity of spontaneous fluctuations in tumor: (i) Spontaneous fluctuations in occurred regardless of the basal oxygenation state (i.e., both in oxygenated and in hypoxic regions) and (ii) spontaneous fluctuations occurred at a rate of 1 cycle/12–47 min. For validation, the analysis was performed in dead mice for which acute changes did not occur. The authors thereby demonstrated that MRI technique is sensitive to acute change in in tumors.

Conclusions:

This is the first approach that allows quantitative minimally invasive measurement of the spontaneous fluctuations of tumor oxygenation using a look‐locker approach (e.g., SNAP IR). This approach could be an important tool to characterize the phenomenon of tumor acute hypoxia, to understand its physiopathology, and to improve therapies.
Clinical development of a failure detection‐based online repositioning strategy for prostate IMRT—Experiments, simulation, and dosimetry study
Authors: Liu Wu , Qian Jianguo , Hancock Steven L. , Xing Lei , Luxton Gary
Published: September 2010

Purpose:

To implement and evaluate clinic‐ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as‐needed use of on‐board kV.

Methods:

The authors examine the two‐step decision‐making strategy: (1) Use cine‐MV imaging and online‐updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV‐kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field‐by‐field based motion correction for present‐day linacs and (2) instantaneous repositioning for new‐generation linacs with capabilities of simultaneous MV‐kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients.

Results:

Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the marker's projected position on the MV imager, the field‐by‐field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV‐kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage , the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to ) if the MLC blockage problem were relieved. The information acquired for repositioning using combined MV‐kV images was found to have submillimeter accuracy.

Conclusions:

This work demonstrated with a current clinical setup that substantial reduction of adverse targeting effects of intrafraction prostate motion can be realized. The proposed adaptive imaging strategy incurs minimal imaging dose to the patient as compared to other stereoscopic imaging techniques.
Validation for photon beams in the energy range of 20–1000 keV
Authors: Terribilini Dario , Fix Michael K. , Frei Daniel , Volken Werner , Manser Peter
Published: September 2010

Purpose:

In high energy teletherapy,is known to be a very accurate and efficient Monte Carlo (MC) code. In principle, the MC method is also a powerful dose calculation tool in other areas in radiation oncology, e.g., brachytherapy or orthovoltage radiotherapy. However,is not validated for the low‐energy range of such applications. This work aims in the validation of theMC code for photon beams in the energy range between 20 and 1000 keV.

Methods:

Dose calculations were performed in differentphantoms of different materials. Dose distributions of monoenergetic (ranging from 20 to 1000 keV)andparallel beams were calculated. Voxel sizes ofandwere used for the dose calculations. The resulting dose distributions were compared to those calculated using EGSnrc, which is used as a golden standard in this work.

Results:

At energies between 100 and 1000 keV, EGSnrc andcalculated dose distributions agree within the statistical uncertainty of about 1%. At energies, dose differences of up to 1.6% (in % of) occur whenand EGSnrc are compared. Turning off Rayleigh scattering, binding effects for Compton scattering, and the atomic relaxation after photoelectric absorption in EGSnrc (all not implemented in) leads to an agreement between both MC codes within statistical uncertainty. Further, using the KERMA approximation feature implemented inleads to very efficient simulations in the energy range between 20 and 1000 keV.

Conclusions:

Further improvements for very low energies in accuracy ofcould be achieved by implementing Rayleigh scattering, binding effects for Compton scattering, and the atomic relaxation after photoelectric absorption. Implementation intoof KERMA approximation has been validated.
Regularized antenna profile adaptation in online hyperthermia treatment
Authors: Ranneberg Maximilian , Weiser Martin , Weihrauch Mirko , Budach Volker , Gellermann Johanna , Wust Peter
Published: September 2010

Purpose:

Online optimization of annular‐phased‐array hyperthermia (HT) is based on planning tools and magnetic resonance (MR) thermometry. Until now, the method has been validated in phantoms. Further developments and extensions are required for clinical purposes. In particular, the problem of deducing the electric field distribution inside the patient from MR thermometry is ill‐posed, which leads to an amplification of measurement errors. A method to overcome this difficulty is proposed.

Methods:

The authors utilized a regularized Gauß–Newton algorithm with a fast bioheat transfer equation (BHTE) approximation to identify the field parameters. To evaluate the method, simulations with patient models are conducted and a treatment data set obtained from a heat treatment performed in the hybrid HT‐MR system at the Charité Medical School is used to visualize the error amplification.

Results:

The regularization leads to a significantly improved accuracy of the predicted electric fields and temperatures compared to an unregularized approach. The BHTE approximation enables highly accurate temperature predictions in real‐time.

Conclusions:

Regularization proves to be necessary to identify electromagnetic field parameters. The proposed method is able to reproduce measurements without overfitting to the noise in the MR measurements and results in an improved treatment planning.
Virtual eversion and rotation of colon based on outer surface centerline
Authors: Zhang Danfeng , Zhao Jun , Lu Lin , Li Lei , Wang Zhizhong
Published: September 2010

Purpose:

Virtual eversion turns the colon's inner surface to its outside while maintaining the original colon path. The virtually everted colon allows both global and local views of the mucosal surface for observation. However, the conventional colon's inner surface centerline commonly used in virtual colonoscopy and virtual flattening is not suitable for virtual eversion. Therefore, the colon's outer surface centerline is introduced for virtual eversion to produce a more accurate representation.

Methods:

An improved level set segmentation method is presented for generating the colon's outer surface. To achieve eversion with fewer errors, the centerline of the colon's outer surface is employed in the proposed virtual eversion method instead of the inner surface centerline. A hybrid sampling method is designed to accelerate the eversion. Virtual rotation is introduced to visualize the lateral and rear views of the colon better. The gathered structures in the high curvature regions can be separated by virtual rotation.

Results:

The proposed methods were validated using two three‐dimensional phantoms and 87 CT data sets. A study on the observation performance of the everted data showed that the reading times were (63% of time reduction for phantom A, 65% of time reduction for phantom B, and 77% of time reduction for CT data) less than those using virtual colonoscopy, while maintaining the sensibility. The incidence of improperly everted regions in the virtual eversion based on the outer surface centerline was 71% less than that based on the inner surface centerline.

Conclusions:

The virtual eversion based on the outer surface centerline is more accurate than the one based on the inner surface centerline whether the colon's inner surface is smooth or ragged. The time required for polyp detection using the virtual eversion is considerably less than that using the conventional virtual endoscopy. Virtual eversion and virtual rotation are promising methods for the rapid location of colonic polyps. Together with virtual colonoscopy and virtual flattening, virtual eversion and virtual rotation can be integrated to produce a powerful system for diagnosing colonic lesions.
Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau
Authors: Matsuura Taeko , Egashira Yusuke , Nishio Teiji , Matsumoto Yoshitaka , Wada Mami , Koike Sachiko , Furusawa Yoshiya , Kohno Ryosuke , Nishioka Shie , Kameoka Satoru , Tsuchihara Katsuya , Kawashima Mitsuhiko , Ogino Takashi
Published: September 2010

Purpose:

Respiration‐gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10–100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence.

Methods:

HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose‐averaged LET was, and at the plateau, where it was . After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared.

Results:

No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was at the Bragg peak and at the plateau. On the other hand, Bragg peak/plateau RBE ratio was for UDR and for CDR.

Conclusions:

Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required.
Response to Comment on “The Human K-Complex Represents an Isolated Cortical Down-State”
Authors: Cash Sydney S. , Halgren Eric , Dehghani Nima , Rossetti Andrea O. , Thesen Thomas , Wang ChunMao , Devinsky Orrin , Kuzniecky Ruben , Doyle Werner , Madsen Joseph R. , Erőss Loránd , Halász Péter , Karmos George , Csercsa Richárd , Wittner Lucia , Ulbert István
Published: September 2010

Our study confirmed the hypothesis of Amzica and Steriade that the human K-complex (KC) shares neural mechanisms with so-called slow oscillation between periods of intense neuronal firing and silence, but found that the KC can occur independently of this oscillatory activity. We agree with Amzica that the KC often has multiple components but contend that the major component is surface-negative and corresponds to the cortical down-state.
The CRAC Channel Activator STIM1 Binds and Inhibits L-Type Voltage-Gated Calcium Channels
Authors: Park Chan Young , Shcheglovitov Aleksandr , Dolmetsch Ricardo
Published: September 2010

Channel STIMulation

The STIM1 protein functions as a calcium sensor and regulates entry of calcium into cells across the plasma membrane. When cell surface receptors are stimulated and cause release of calcium from internal stores in the endoplasmic reticulum (ER), STIM proteins in the ER membrane interact with the Orai channel pore protein in the plasma membrane to allow calcium entry from the outside of the cell (see the Perspective by

Cahalan

).

Park
et al.

(p.
101
) and

Wang
et al.

(p.
105
) now show that STIM also acts to suppress conductance by another calcium channel—the voltage-operated Ca
V
1.2 channel. STIM1 appeared to interact directly with Ca
V
1.2 channels in multiple cell types, including vascular smooth muscle cells, neurons, and cultured cells derived from T lymphocytes. The interaction inhibited opening of the Ca
V
1.2 channels and caused depletion of the channel from the cell surface.
Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in
Escherichia coli
Authors: Ajikumar Parayil Kumaran , Xiao Wen-Hai , Tyo Keith E. J. , Wang Yong , Simeon Fritz , Leonard Effendi , Mucha Oliver , Phon Too Heng , Pfeifer Blaine , Stephanopoulos Gregory
Published: September 2010

Toward Microbial Taxol

Taxol, a minor chemical constituent of yew tree bark, has provided a potent cancer treatment. Production methods presently rely on plant cell cultures.

Ajikumar
et al.

(p.
70
; see the Perspective by

Liu and Khosla

) engineered
Escherichia coli
cells to produce a key taxol precursor, in which the polycyclic carbon skeleton is intact. The approach relied on optimizing the relative activity of two pathways, the first of which synthesized isoprenoid building blocks that were then stitched together with the second pathway. Accumulation of indole as a by-product inhibited the isoprenoid pathway—an insight that should facilitate more efficient engineered biosynthesis of a wide range of commercially important isoprenoid derivatives.
Sequencing of
Culex quinquefasciatus
Establishes a Platform for Mosquito Comparative Genomics
Authors: Arensburger Peter , Megy Karine , Waterhouse Robert M. , Abrudan Jenica , Amedeo Paolo , Antelo Beatriz , Bartholomay Lyric , Bidwell Shelby , Caler Elisabet , Camara Francisco , Campbell Corey L. , Campbell Kathryn S. , Casola Claudio , Castro Marta T. , Chandramouliswaran Ishwar , Chapman Sinéad B. , Christley Scott , Costas Javier , Eisenstadt Eric , Feschotte Cedric , Fraser-Liggett Claire , Guigo Roderic , Haas Brian , Hammond Martin , Hansson Bill S. , Hemingway Janet , Hill Sharon R. , Howarth Clint , Ignell Rickard , Kennedy Ryan C. , Kodira Chinnappa D. , Lobo Neil F. , Mao Chunhong , Mayhew George , Michel Kristin , Mori Akio , Liu Nannan , Naveira Horacio , Nene Vishvanath , Nguyen Nam , Pearson Matthew D. , Pritham Ellen J. , Puiu Daniela , Qi Yumin , Ranson Hilary , Ribeiro Jose M. C. , Roberston Hugh M. , Severson David W. , Shumway Martin , Stanke Mario , Strausberg Robert L. , Sun Cheng , Sutton Granger , Tu Zhijian (Jake) , Tubio Jose Manuel C. , Unger Maria F. , Vanlandingham Dana L. , Vilella Albert J. , White Owen , White Jared R. , Wondji Charles S. , Wortman Jennifer , Zdobnov Evgeny M. , Birren Bruce , Christensen Bruce M. , Collins Frank H. , Cornel Anthony , Dimopoulos George , Hannick Linda I. , Higgs Stephen , Lanzaro Gregory C. , Lawson Daniel , Lee Norman H. , Muskavitch Marc A. T. , Raikhel Alexander S. , Atkinson Peter W.
Published: September 2010

Closing the Vector Circle

The genome sequence of
Culex quinquefasciatus
offers a representative of the third major genus of mosquito disease vectors for comparative analysis. In a major international effort,

Arensburger
et al.

(p.
86
) uncovered divergences in the
C. quinquefasciatus
genome compared with the representatives of the other two genera
Aedes aegypti
and
Anopheles gambiae
. The main difference noted is the expansion of numbers of genes, particularly for immunity, oxidoreductive functions, and digestive enzymes, which may reflect specific aspects of the
Culex
life cycle.

Bartholomay
et al.

(p.
88
) explored infection-response genes in
Culex
in more depth and uncovered 500 immune response-related genes, similar to the numbers seen in
Aedes
, but fewer than seen in
Anopheles
or the fruit fly
Drosophila melanogaster
. The higher numbers of genes were attributed partly to expansions in those encoding serpins, C-type lectins, and fibrinogen-related proteins, consistent with greater immune surveillance and associated signaling needed to monitor the dangers of breeding in polluted, urbanized environments. Transcriptome analysis confirmed that inoculation with unfamiliar bacteria prompted strong immune responses in
Culex
. The worm and virus pathogens that the mosquitoes transmit naturally provoked little immune activation, however, suggesting that tolerance has evolved to any damage caused by replication of the pathogens in the insects.
Human Adaptation and Plant Use in Highland New Guinea 49,000 to 44,000 Years Ago
Authors: Summerhayes Glenn R. , Leavesley Matthew , Fairbairn Andrew , Mandui Herman , Field Judith , Ford Anne , Fullagar Richard
Published: September 2010

New Guinea's Ancient Colonies

Isolated by water, Australia and New Guinea were some of the last major parts of the world colonized by modern humans.

Summerhayes
et al.

(p.
78
; see the Perspective by

Gosden

) describe an archaeological site in the highlands of New Guinea that sheds light on this migration. The record extends back to nearly 50,000 years ago and thus represents one of the earliest known records. Nuts and yams were widely consumed, and the variety of stone tools discovered implies that the early humans may have cleared forest patches to promote the growth of useful plants.
Identifying the Driver of Pulsating Aurora
Authors: Nishimura Y. , Bortnik J. , Li W. , Thorne R. M. , Lyons L. R. , Angelopoulos V. , Mende S. B. , Bonnell J. W. , Le Contel O. , Cully C. , Ergun R. , Auster U.
Published: September 2010

Auroral Chorus

Energetic particles that arrive from near-Earth space produce photon emissions—the aurora—as they bombard the atmosphere in the polar regions. The pulsating aurora, which is characterized by temporal intensity variations, is thought to be caused by modulations in electron precipitation possibly produced by resonance with electromagnetic waves in Earth's magnetosphere.

Nishimura
et al.

(p.
81
) present a detailed study of an event that showed a good correlation between the temporal changes in auroral luminosity and chorus emission—a type of electromagnetic wave occurring in Earth's magnetosphere. The results points to chorus waves as the driver of the pulsating aurora.
Reactivity of the Gold/Water Interface During Selective Oxidation Catalysis
Authors: Zope Bhushan N. , Hibbitts David D. , Neurock Matthew , Davis Robert J.
Published: September 2010

Indirect Oxidation by Oxygen

Partial oxidation of alcohols to aldehydes and ketones must avoid complete oxidation to carbon dioxide and water.

Zope
et al.

(p.
74
) examined the partial oxidation of ethanol and glycerol to acids in alkaline aqueous solvents over gold and platinum catalysts. Conversions were highest for gold supported on titania, but studies with isotopically labeled molecular oxygen showed that oxygen incorporated into the acid comes from hydroxide ions. Direct incorporation of oxygen did not occur even for the platinum catalysts, despite the fact that oxygen can dissociate on this metal. Instead, molecular oxygen appeared to regenerate hydroxide ions at the metal surface through the formation of peroxide intermediates.
How to STIMulate Calcium Channels
Authors: Cahalan Michael D.
Published: September 2010

Two studies reveal the reciprocal regulation of two different calcium channels.
George C. Williams (1926–2010)
Authors: Dawkins Richard
Published: September 2010

The clear and wide-ranging vision of a great biologist enlightened our understanding of natural selection and adaptation.
When the Guardian Looks Away
Authors: Morozov Alexei
Published: September 2010

The same single-nucleotide polymorphism in the p53 regulator MDM2 increases cancer risk in mice but is a marker of less aggressive prostate cancer in humans.
Protection of Sheep against Rift Valley Fever Virus and Sheep Poxvirus with a Recombinant Capripoxvirus Vaccine
Authors: Soi Reuben K. , Rurangirwa Fred R. , McGuire Travis C. , Rwambo Paul M. , DeMartini James C. , Crawford Timothy B.
Published: September 2010

Rift Valley fever (RVF) is an epizootic viral disease of sheep that can be transmitted from sheep to humans, particularly by contact with aborted fetuses. A capripoxvirus (CPV) recombinant virus (rKS1/RVFV) was developed, which expressed the Rift Valley fever virus (RVFV) Gn and Gc glycoproteins. These expressed glycoproteins had the correct size and reacted with monoclonal antibodies (MAb) to native glycoproteins. Mice vaccinated with rKS1/RVFV were protected against RVFV challenge. Sheep vaccinated with rKS1/RVFV twice developed neutralizing antibodies and were significantly protected against RVFV and sheep poxvirus challenge. These findings further document the value of CPV recombinants as ruminant vaccine vectors and support the inclusion of RVFV genes encoding glycoproteins in multivalent recombinant vaccines to be used where RVF occurs.
Identification, Characterization, and Application of a Recombinant Antigen for the Serological Investigation of Feline Hemotropic Mycoplasma Infections
Authors: Wolf-Jäckel Godelind A. , Jäckel Christian , Museux Kristina , Hoelzle Katharina , Tasker Séverine , Lutz Hans , Hofmann-Lehmann Regina
Published: September 2010

In felids, three hemotropic mycoplasma species (hemoplasmas) have been described:Mycoplasma haemofelis, “CandidatusMycoplasma haemominutum,” and “CandidatusMycoplasma turicensis.” In particular,M. haemofelismay cause severe, potentially life-threatening hemolytic anemia. No routine serological assays for feline hemoplasma infections are available. Thus, the goal of our project was to identify and characterize anM. haemofelisantigen (DnaK) that subsequently could be applied as a recombinant antigen in a serological assay. The gene sequence of this protein was determined using consensus primers and blood samples from two naturallyM. haemofelis-infected Swiss pet cats, an experimentallyM. haemofelis-infected specific-pathogen-free cat, and a naturallyM. haemofelis-infected Iberian lynx (Lynx pardinus). TheM. haemofelisDnaK gene sequence showed the highest identity to an analogous protein of a porcine hemoplasma (72%).M. haemofelisDnaK was expressed recombinantly in anEscherichia coliDnaK knockout strain and purified using Ni affinity, size-exclusion, and anion-exchange chromatography. It then was biochemically and functionally characterized and showed characteristics typical for DnaKs (secondary structure profile, thermal denaturation, ATPase activity, and DnaK complementation). Moreover, its immunogenicity was assessed using serum samples from experimentally hemoplasma-infected cats. In Western blotting or enzyme-linked immunosorbent assays, it was recognized by sera from cats infected withM. haemofelis, “Ca.Mycoplasma haemominutum,” and “Ca.Mycoplasma turicensis,” respectively, but not from uninfected cats. This is the first description of a full-length purified recombinant feline hemoplasma antigen that can readily be applied in future pathogenesis studies and may have potential for application in a diagnostic serological test.
Phenotypic and Genotypic Characterization of Group B Streptococcal Isolates in Southern Brazil
Authors: Palmeiro Jussara K. , Dalla-Costa Libera M. , Fracalanzza Sérgio E. L. , Botelho Ana C. N. , da Silva Nogueira Keite , Scheffer Mara C. , de Almeida Torres Rosângela S. L. , de Carvalho Newton Sérgio , Cogo Laura Lúcia , Madeira Humberto M. F.
Published: September 2010

One-hundred sixty-eight group B streptococcal (GBS) isolates from a Brazilian hospital were phenotypically and genotypically characterized. Isolates were recovered from human sources from April 2006 to May 2008 and classified as either invasive, noninvasive, or colonizing isolates. Classical methods for serotyping and antibiotic resistance profiling were employed. Clonal groups were also defined by pulsed-field gel electrophoresis (PFGE). Results showed that susceptibility to beta-lactam antimicrobials was predominant among the isolates. Only 4.7% were resistant to erythromycin and clindamycin. The
erm
(B) gene was widely detected in our GBS isolates, according to our phenotypic results (constitutive macrolide-lincosamide-streptogramin B [cMLS
B
] resistance phenotype), and the
erm
(A) gene was also detected in some isolates. MLS
B
resistance was restricted to strains isolated from patients with noninvasive infections and carriers. Serotype Ia was predominant (38.1%), serotype IV isolates were found at a high frequency (13.1%), and few isolates of serotype III were identified (3%). Pulsed-field gel electrophoresis results revealed a variety of types, reflecting the substantial genetic diversity among GBS strains, although a great number of isolates could be clustered into two major groups with a high degree of genetic relatedness. Three main PFGE clonal groups were found, and isolates sharing the same PFGE type were grouped into different serotypes. Furthermore, in a few cases, isolates from the same patients and possessing the same PFGE type were of different serotypes. These findings could be related to the occurrence of capsular switching by horizontal transfer of capsular genes.
Candida bracarensis
Bloodstream Infection in an Immunocompromised Patient
Authors: Warren Thomas A. , McTaggart Lisa , Richardson Susan E. , Zhang Sean X.
Published: September 2010

Candida bracarensis
is a recently described
Candida
species which is phenotypically similar to
Candida glabrata
. A case of
C. bracarensis
bloodstream infection in a bone marrow transplant patient is described and confirms this organism as an opportunistic human pathogen. The organism can be distinguished from
C. glabrata
by its white color on CHROMagar and by DNA sequence analysis using D1/D2 and internal transcribed spacer (ITS) primers.
Nonhealing Wound Due toRhodococcus equiin an Apparently Immunocompetent Patient, Revealing CD8+T-Lymphocyte Deficiency
Authors: Denes Eric , Peignon-Orsoni Dominique , Terrade François-Xavier
Published: September 2010

We describe a case of a nonhealing wound due toRhodococcus equi. Failure of the wound to heal led to immunological investigations and the discovery of a previously unknown CD8+T-lymphocyte deficit responsible for the chronic infection. The infection was cured after a 3-month course of a combination of antibiotics.
Molecular Characterization of Clinical Methicillin-Resistant
Staphylococcus aureus
Isolates in South Africa
Authors: Moodley A. , Oosthuysen W. F. , Dusé A. G. , Marais E.
Published: September 2010

Eighty-two percent of 320 clinical methicillin-resistant
Staphylococcus aureus
(MRSA) isolates from various infection sites collected throughout South Africa were separated into five major globally prevalent clusters by SmaI pulsed-field gel electrophoresis,
spa
, and SCC
mec
typing. Only one Panton-Valentine leukocidin-positive isolate was detected. This is the first detailed MRSA epidemiology study for the whole country.
gyrB
Multiplex PCR To Differentiate between
Acinetobacter calcoaceticus
and
Acinetobacter
Genomic Species 3
Authors: Higgins Paul G. , Lehmann Marlene , Wisplinghoff Hilmar , Seifert Harald
Published: September 2010

A previously established multiplex PCR that identifies to the species level
Acinetobacter baumannii
and
Acinetobacter
genomic species 13TU (GS13TU) was expanded to include
Acinetobacter calcoaceticus
and
Acinetobacter
genomic species 3.
Interaction of Decay-Accelerating Factor with Echovirus 7
Authors: Plevka Pavel , Hafenstein Susan , Harris Katherine G. , Cifuente Javier O. , Zhang Ying , Bowman Valorie D. , Chipman Paul R. , Bator Carol M. , Lin Feng , Medof M. Edward , Rossmann Michael G.
Published: September 2010

Echovirus 7 (EV7) belongs to theEnterovirusgenus within the familyPicornaviridae. Many picornaviruses use IgG-like receptors that bind in the viral canyon and are required to initiate viral uncoating during infection. However, in addition, some of the enteroviruses use an alternative or additional receptor that binds outside the canyon. Decay-accelerating factor (DAF) has been identified as a cellular receptor for EV7. The crystal structure of EV7 has been determined to 3.1-Å resolution and used to interpret the 7.2-Å-resolution cryo-electron microscopy reconstruction of EV7 complexed with DAF. Each DAF binding site on EV7 is near a 2-fold icosahedral symmetry axis, which differs from the binding site of DAF on the surface of coxsackievirus B3, indicating that there are independent evolutionary processes by which DAF was selected as a picornavirus accessory receptor. This suggests that there is an advantage for these viruses to recognize DAF during the initial process of infection.
The Innate Immune Adaptor Molecule MyD88 Restricts West Nile Virus Replication and Spread in Neurons of the Central Nervous System
Authors: Szretter Kristy J. , Daffis Stephane , Patel Jigisha , Suthar Mehul S. , Klein Robyn S. , Gale Michael , Diamond Michael S.
Published: September 2010

Type I interferons (IFN-α/β) control viral infection by triggering the expression of genes that restrict transcription, translation, replication, and assembly. Many viruses induce IFN responses after recognition by cytoplasmic or endosomal RNA sensors (RIG-I-like RNA helicases [RLR] and Toll-like receptors [TLR]), which signal through the cognate adaptor signaling molecules IPS-1, TRIF, and MyD88. Recent studies have demonstrated that IPS-1-dependent induction of IFN-α/β downstream of RLR recognition restricts West Nile virus (WNV) infection in many cell types, whereas TRIF-dependent TLR3 signaling limits WNV replication in neurons. Here, we examined the contribution of MyD88 signaling to the control of WNV by evaluating IFN induction and virus replication in genetically deficient cells and mice.
MyD88
−
/
−
mice showed increased lethality after WNV infection and elevated viral burden primarily in the brain, even though little effect on the systemic type I IFN response was observed. Intracranial inoculation studies corroborated these findings, as WNV spread more rapidly in the central nervous system of
MyD88
−
/
−
mice, and this phenotype preceded the recruitment of inflammatory leukocytes.
In vitro
, increased WNV replication was observed in
MyD88
−
/
−
macrophages and subsets of neurons but not in myeloid dendritic cells. MyD88 had an independent effect on recruitment of monocyte-derived macrophages and T cells into the brain that was associated with blunted induction of the chemokines that attract leukocytes. Our experiments suggest that MyD88 restricts WNV by inhibiting replication in subsets of cells and modulating expression of chemokines that regulate immune cell migration into the central nervous system.
Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus
Authors: Kayamuro Hiroyuki , Yoshioka Yasuo , Abe Yasuhiro , Arita Shuhei , Katayama Kazufumi , Nomura Tetsuya , Yoshikawa Tomoaki , Kubota-Koketsu Ritsuko , Ikuta Kazuyoshi , Okamoto Shigefumi , Mori Yasuko , Kunisawa Jun , Kiyono Hiroshi , Itoh Norio , Nagano Kazuya , Kamada Haruhiko , Tsutsumi Yasuo , Tsunoda Shin-Ichi
Published: September 2010

A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficientW/Wvmice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.
RNA Structures Facilitate Recombination-Mediated Gene Swapping in HIV-1
Authors: Simon-Loriere Etienne , Martin Darren P. , Weeks Kevin M. , Negroni Matteo
Published: September 2010

Many viruses, including retroviruses, undergo frequent recombination, a process which can increase their rate of adaptive evolution. In the case of HIV, recombination has been responsible for the generation of numerous intersubtype recombinant variants with epidemiological importance in the AIDS pandemic. Although it is known that fragments of genetic material do not combine randomly during the generation of recombinant viruses, the mechanisms that lead to preferential recombination at specific sites are not fully understood. Here we reanalyze recent independent data defining (i) the structure of a complete HIV-1 RNA genome and (ii) favorable sites for recombination. We show that in the absence of selection acting on recombinant genomes, regions harboring RNA structures in the NL4-3 model strain are strongly predictive of recombination breakpoints in the HIV-1
env
genes of primary isolates. In addition, we found that breakpoints within recombinant HIV-1 genomes sampled from human populations, which have been acted upon extensively by natural selection, also colocalize with RNA structures. Critically, junctions between genes are enriched in structured RNA elements and are also preferred sites for generating functional recombinant forms. These data suggest that RNA structure-mediated recombination allows the virus to exchange intact genes rather than arbitrary subgene fragments, which is likely to increase the overall viability and replication success of the recombinant HIV progeny.
Intrinsic Cytoskeleton-Dependent Clustering of Influenza Virus M2 Protein with Hemagglutinin Assessed by FLIM-FRET
Authors: Thaa Bastian , Herrmann Andreas , Veit Michael
Published: September 2010

The hemagglutinin (HA) of influenza virus organizes the virus bud zone, a domain of the plasma membrane enriched in raft lipids. Using fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET), a technique that detects close colocalization of fluorescent proteins in transfected cells, we show that the viral proton channel M2 clusters with HA but not with a marker for inner leaflet rafts. The FRET signal between M2 and HA depends on the raft-targeting signals in HA and on an intact actin cytoskeleton. We conclude that M2 contains an intrinsic signal that targets the protein to the viral bud zone, which is organized by raft-associated HA and by cortical actin.