bluuebunny/crossref_metadata_2025 huggingface dataset:
Pricing and power control for energy‐efficient radio resource management in cognitive femtocell networks
Authors: An Chunyan , Xie Renchao , Ji Hong , Li Yi
Published: December 2013

Cognitive femtocell has been considered as a promising technique that can improve the capacity and the utilization of spectrum efficiency in wireless networks because of the short transmission distance and low transmit power. In this paper, we study the win–win solution of energy‐efficient radio resource management in cognitive femtocell networks, where the macrocell tries to maximize its revenue by adjusting spectrum utilization price while the femtocells try to maximize their revenues by dynamically adjusting the transmit power. When the spectrum utilization price is given by macrocell, we formulate the power control problem of standalone femtocells as an optimization problem and introduce a low‐complexity iteration algorithm based on gradient‐assisted binary search algorithm to solve it. Besides, non‐cooperative game is used to formulate the power control problem between collocated femtocells in a collocated femtocell set, and then low complexity and widely used gradient‐based iteration algorithm is applied to obtain the Nash‐equilibrium solution. Specially, asymptotic analysis is applied to find the approximate spectrum utilization price in macrocell, which can greatly reduce the computational complexity of the proposed energy‐efficient radio resource management scheme. Finally, extensive simulation results are presented to verify our theoretical analysis and demonstrate the performance of the proposed scheme. Copyright © 2013 John Wiley & Sons, Ltd.
Hoarding severity predicts functional disability in late‐life hoarding disorder patients
Authors: Ayers Catherine R. , Ly Princeton , Howard Ian , Mayes Tina , Porter Ben , Iqbal Yasmeen
Published: December 2013

Objective

Late‐life hoarding is a serious psychiatric condition with significant implications in health and functioning. Geriatric hoarding patients show greater impairment in activities of daily living and have a greater number of medical conditions compared with same‐aged nonhoarders. This study examined the relationship between geriatric hoarding severity and functional disability severity.

Methods

Sixty‐five subjects age 60 or older with hoarding disorder (HD) participated in the current study. Participants were assessed with measures of hoarding severity, psychiatric symptoms, and general disability. Hierarchical regression was used to test the unique association of hoarding symptoms with functional disability beyond the effects of demographic factors, anxiety, and depression.

Results

When controlling for demographics (age and gender) and psychiatric symptoms (anxiety and depression), hoarding severity predicts functional disability severity. Analyses also show that clinician‐administered measures of hoarding are stronger predictors of disability than patient self‐report measures.

Conclusions

When treating older adults with HD, clinicians must consider symptom impact on daily life. A multidisciplinary team must be utilized to address the wide‐ranging consequences of hoarding symptoms. Future work should examine how psychiatric treatment of HD affects functional disability. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of multitasking‐training on gray matter structure and resting state neural mechanisms
Authors: Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Hashizume Hiroshi , Sekiguchi Atsushi , Kotozaki Yuka , Nakagawa Seishu , Miyauchi Carlos Makoto , Sassa Yuko , Kawashima Ryuta
Published: December 2013

Multitasking (MT) constitutes engaging in two or more cognitive activities at the same time. MT‐training improves performance on untrained MT tasks and alters the functional activity of the brain during MT. However, the effects of MT‐training on neural mechanisms beyond MT‐related functions are not known. We investigated the effects of 4 weeks of MT‐training on regional gray matter volume (rGMV) and functional connectivity during rest (resting‐FC) in young human adults. MT‐training was associated with increased rGMV in three prefrontal cortical regions (left lateral rostral prefrontal cortex (PFC), dorsolateral PFC (DLPFC), and left inferior frontal junction), the left posterior parietal cortex, and the left temporal and lateral occipital areas as well as decreased resting‐FC between the right DLPFC and an anatomical cluster around the ventral anterior cingulate cortex (ACC). Our findings suggest that participation in MT‐training is as a whole associated with task‐irrelevant plasticity (i.e., neural changes are not limited to certain specific task conditions) in regions and the network that are assumed to play roles in MT as well as diverse higher‐order cognitive functions. We could not dissociate the effects of each task component and the diverse cognitive processes involved in MT because of the nature of the study, and these remain to be investigated. Hum Brain Mapp 35:3646–3660, 2014. © 2013 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.
Regorafenib (BAY 73‐4506): Antitumor and antimetastatic activities in preclinical models of colorectal cancer
Authors: Schmieder Roberta , Hoffmann Jens , Becker Michael , Bhargava Ajay , Müller Tina , Kahmann Nicole , Ellinghaus Peter , Adams Robert , Rosenthal André , Thierauch Karl‐Heinz , Scholz Arne , Wilhelm Scott M. , Zopf Dieter
Published: December 2013

Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and to assess its potential in combination therapy. Regorafenib was tested alone and in combination with irinotecan in patient‐derived (PD) CRC models and a murine CRC liver metastasis model. Mechanism of action was investigated using in vitro functional assays, immunohistochemistry and correlation with CRC‐related oncogenes. Regorafenib demonstrated significant inhibition of growth‐factor‐mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3 autophosphorylation, and intracellular VEGFR3 signaling in human umbilical vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of seven PD xenograft models. Combination of regorafenib with irinotecan significantly delayed tumor growth after extended treatment in four xenograft models. Reduced CD31 staining indicates that the antiangiogenic effects of regorafenib contribute to its antitumor activity. Finally, regorafenib significantly delayed disease progression in a murine CRC liver metastasis model by inhibiting the growth of established liver metastases and preventing the formation of new metastases in other organs. In addition, our results suggest that regorafenib displays antimetastatic activity, which may contribute to its efficacy in patients with metastatic CRC. Combination of regorafenib and irinotecan demonstrated an increased antitumor effect and could provide a future treatment option for CRC patients.
Big Data: New Opportunities for M&A
Authors: Fanning Kurt , Drogt Emily
Published: December 2013

Big data is one of the hottest areas in information technology (IT). So it's not surprising that big data also affects the world of M&As. The authors look at recent and future possible big data M&A targets, and discuss how to use big data to identify potential M&A targets. © 2014 Wiley Periodicals, Inc.
New Antibribery Guidelines for M&A Deals
Authors: Byington J. Ralph , McGee Jo Ann
Published: December 2013

Management traditionally tries to increase shareholder wealth with M&A deals. But there are risks. These days, the buyer's due diligence should be especially cautious about possible bribery existing in a target company. So the authors discuss some important new guidelines issued by the U.S. Department of Justice (DOJ) and the U.S. Securities and Exchange Commission (SEC). These guidelines cover procedures to avoid liability and reduce the risk of civil and criminal action with the Foreign Corrupt Practices Act (FCPA). © 2014 Wiley Periodicals, Inc.
How to Predict the Market's Reaction When You Announce an Acquisition
Authors: Jansen Ivo Ph. , Stuart Nathan V.
Published: December 2013

Successful M&A activity depends on carefully integrating the target firm into the acquirer. But it is also im‐portant that CEOs, CFOs, and top financial officers be prepared for the stock market's immediate reaction to an M&A announcement. This reaction is not always positive. But what factors actually determine the stock market's reaction? The authors of this article reveal what they are‐because executives who know what to expect will be better prepared to answer questions from the media, analysts, and investors. © 2014 Wiley Periodicals, Inc.
Relational coherence in ambiguous and unambiguous relational networks
Authors: Quinones Jennifer L. , Hayes Steven C.
Published: December 2013

Clinical theories often appeal to general cognitive styles in explaining psychopathology, but without describing in detail how the patterns are formed. In the present investigation, two experiments were conducted to examine how individuals respond to ambiguous relational networks. In both experiments, the participants learned two 3‐stimulus networks (A1 LESS THAN B1, A1 GREATER THAN C1 and A2 GREATER THAN B2, C2 LESS THAN A2). Participants were presented with test trials to examine if they classified the combinatorial relations (B1 ↔ C1 and B2 ↔ C2) as SAME or DIFFERENT and as GREATER THAN or LESS THAN. Although the B–C combinatorial relation in Network 1 is derivable in a readily coherent way (B1 GREATER THAN C1 and thus also B1 DIFFERENT C1), in Network 2 the combinatorial relation is ambiguous. When participants were required to specify the Network 2 B–C relation as either SAME or DIFFERENT, those who chose DIFFERENT, also consistently chose B2 as either GREATER THAN or LESS THAN C2. Conversely, those who classified the B–C relation as SAME were inconsistent within themselves in choosing B2 as GREATER THAN or LESS THAN C2. In Experiment 2, nonarbitrary multiple exemplar pretraining was used to bias SAME versus DIFFERENT as a response for ambiguous combinatorial relations. In accord with the pattern seen in Experiment 1, those biased toward DIFFERENT consistently chose a comparative relation between B2 and C2 while those biased toward SAME were inconsistent in their comparative choices. The findings provide support for the importance of history and coherence in establishing patterns of responding to ambiguous relational networks, providing a beginning behavioral model of cognitive styles and errors.
Leader self‐awareness: An examination and implications of women's under‐prediction
Authors: Sturm Rachel E. , Taylor Scott N. , Atwater Leanne E. , Braddy Phillip W.
Published: December 2013

Self‐awareness represents an important aspect of leadership. However, past research on leader self‐awareness has focused on one component of self‐awareness, self versus others' ratings, leaving the second component, the ability to anticipate the views of others, largely neglected. We examined this second component of self‐awareness by focusing on women leaders who have been found to under‐predict how others rate them. In two studies, we measured how women leaders anticipate the views of their bosses in regard to their leadership. In Study 1, 194 leaders rated their leadership, were rated by their bosses, and then predicted how their bosses rated their leadership. While we found that women under‐predict their boss ratings compared with men, we did not find that boss gender or feedback played a role in this under‐prediction. In Study 2, 76 female leaders identified (via open‐ended questions) possible reasons and consequences of under‐prediction for women in organizations. Results from Study 2 reveal the following: (1) the reasons for women's under‐prediction include a lack of self‐confidence, differences in feedback needs, learned gender roles, and self‐sexism; and (2) the perceived consequences of under‐prediction are negative for both women and the organization. Copyright © 2013 John Wiley & Sons, Ltd.
Activation of hedgehog signaling during fracture repair enhances osteoblastic‐dependent matrix formation
Authors: Baht Gurpreet S , Silkstone David , Nadesan Puviindran , Whetstone Heather , Alman Benjamin A
Published: December 2013

Fracture repair is a well orchestrated process involving various cell types and signaling molecules. The hedgehog signaling pathway is activated in chondrocytes during fracture repair and is known to regulate chondrogenesis however, its role in osteoblasts during injury is yet unknown. In this study we observed tibial fracture repair in mice in which hedgehog signaling was modulated through genetic alterations of the pathway activator, smoothened. Levels of the hedgehog target genes Gli1 and Ptch1 in wildtype mice were upregulated in fracture calluses throughout the repair process. Forced activation of the hedgehog pathway in ubiquitous fashion resulted in increased matrix deposition in the fracture callus. Interestingly, inhibition in chondrocytes did not alter the fracture repair phenotype, while activation of hedgehog in osteoblasts was a requirement for normal fracture repair. In vitro, transcript levels of Gli1 and Ptch1 were elevated during osteoblastogenesis. Activation of hedgehog signaling positively affected osteoblastic differentiation and mineralization as detected using alkaline phosphatase and Von Kossa staining and Alp and Col1 expression. Here we show that the hedgehog signaling pathway plays a critical role in osteoblasts during fracture repair: inhibition of the pathway in osteoblasts leads to decreased matrix at the fracture site while activation increased matrix deposition.© 2013 The Authors. Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res J Orthop Res 32:581–586, 2014.
The role of vascular endothelial growth factor and vascular stability in diseases of the ear
Authors: London Nyall R. , Gurgel Richard K.
Published: December 2013

Objectives/Hypothesis

Vascular endothelial growth factor (VEGF) is a critical mediator of vascular permeability and angiogenesis and likely plays an important role in cochlear function and hearing. This review highlights the role of VEGF in hearing loss associated with vestibular schwannomas, otitis media with effusion, and sensorineural hearing loss.

Study Design

PubMed literature review.

Methods

A review of the literature was conducted to determine the role of VEGF in diseases affecting hearing.

Results

Therapeutic efficacy has been demonstrated for the anti‐VEGF agent bevacizumab in vestibular schwannomas, with tumor size reduction and hearing improvement in patients with neurofibromatosis type 2. The loss of functional Merlin, the protein product of the nf2 gene, results in a decrease in expression of the anti‐angiogenic protein SEMA3F through a Rac‐1–dependent mechanism, allowing VEGF to promote angiogenesis. Bevacizumab may therefore restore the angiogenic balance through inhibiting the relative increase in VEGF. Many of the clinical findings of otitis media with effusion can be reproduced by delivery of recombinant VEGF through transtympanic injection or submucosal osmotic pump. VEGF receptor inhibitors have been demonstrated to improve hearing in an animal model of otitis media with effusion. VEGF affects both the inner ear damage and repair processes in sensorineural hearing loss.

Conclusions

VEGF has an important role in vestibular schwannomas, otitis media with effusion, and sensorineural hearing loss. Laryngoscope, 124:E340–E346, 2014
A novel computerized surgeon–machine interface for robot‐assisted laser phonomicrosurgery
Authors: Mattos Leonardo S. , Deshpande Nikhil , Barresi Giacinto , Guastini Luca , Peretti Giorgio
Published: December 2013

Objectives/Hypothesis

To introduce a novel computerized surgical system for improved usability, intuitiveness, accuracy, and controllability in robot‐assisted laser phonomicrosurgery.

Study Design

Pilot technology assessment.

Methods

The novel system was developed involving a newly designed motorized laser micromanipulator, a touch‐screen display, and a graphics stylus. The system allows the control of a CO2 laser through interaction between the stylus and the live video of the surgical area. This empowers the stylus with the ability to have actual effect on the surgical site. Surgical enhancements afforded by this system were established through a pilot technology assessment using randomized trials comparing its performance with a state‐of‐the‐art laser microsurgery system. Resident surgeons and medical students were chosen as subjects in performing sets of trajectory‐following exercises. Image processing–based techniques were used for an objective performance assessment. A System Usability Scale–based questionnaire was used for the qualitative assessment.

Results

The computerized interface demonstrated superiority in usability, accuracy, and controllability over the state‐of‐the‐art system. Significant ease of use and learning experienced by the subjects were demonstrated by the usability score assigned to the two compared interfaces: computerized interface = 83.96% versus state‐of‐the‐art = 68.02%. The objective analysis showed a significant enhancement in accuracy and controllability: computerized interface = 90.02% versus state‐of‐the‐art = 75.59%.

Conclusions

The novel system significantly enhances the accuracy, usability, and controllability in laser phonomicrosurgery. The design provides an opportunity to improve the ergonomics and safety of current surgical setups.

Level of Evidence

N/A Laryngoscope, 124:1887–1894, 2014
Contribution of synchrotron radiation to photoactivation studies of biomolecular ions in the gas phase
Authors: Giuliani Alexandre , Milosavljević Aleksandar R. , Canon Francis , Nahon Laurent
Published: December 2013

Photon activation of ions in the visible and ultraviolet range attracts a growing interest, partly for its promising applications in tandem mass spectrometry. However, this task is not trivial, as it requires notably high brilliance photon sources. Hence, most of the work in that field has been performed using lasers. Synchrotron radiation is a source continuously tunable over a wide photon energy range and which possesses the necessary characteristics for ion activation. This review focuses on the array of applications of synchrotron radiation in photon activation of ions ranging from near UV to soft X‐rays. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 424–441, 2014.
Effects of 3‐hydroxyflavone on the cellular and molecular characteristics of bovine embryos produced by somatic‐cell nuclear transfer
Authors: Su Jianmin , Wang Yongsheng , Li Wenzhe , Gao Mingqing , Ma Yefei , Hua Song , Quan Fusheng , Zhang Yong
Published: December 2013

This study aimed to investigate the effects of 3‐hydroxyflavone, a natural antioxidant pigment enriched in vegetables, on the developmental cellular and molecular characteristics of bovine somatic‐cell nuclear transfer (SCNT) embryos. There were no significant differences in the cleavage rate at 48 hr of culture or in the inner cell mass (ICM)‐to‐trophectoderm (TE) ratio between 3‐hydroxyflavone addition and untreated (control) groups (P > 0.05). 3‐hydroxyflavone (20 µM) did, however, increase the cleavage rate at 24 hr of culture and the blastocyst‐formation rate on Days 6 and 7 (P < 0.05); decrease the levels of intracellular reactive oxygen species in two‐, four‐, and eight‐cell stage embryos (P < 0.05); increase H3K9ac levels in two‐ and four‐cell stages (P < 0.05); increase the total cell number; and decrease the apoptosis index in Day‐7 blastocysts. Furthermore, the addition of 3‐hydroxyflavone resulted in lower expression of the stress‐related gene HSP70.1 and pro‐apoptotic gene BAX, as well as higher expression of the anti‐apoptotic gene BCL‐xL and pluripotency‐related genes OCT4 and SOX2 in Day‐7 blastocysts produced by SCNT (P < 0.05). The addition of 3‐hydroxyflavone during in vitro culture thus exerted beneficial effects on preimplantation development of bovine SCNT embryos both at the cellular and molecular levels. Mol. Reprod. Dev. 2014. © 2014 Wiley Periodicals, Inc.
Convex gradient optimization for increased spatiotemporal resolution and improved accuracy in phase contrast MRI
Authors: Middione Matthew J. , Wu Holden H. , Ennis Daniel B.
Published: December 2013

Purpose

To evaluate convex gradient optimization (CVX) for increased spatiotemporal resolution and improved accuracy for phase‐contrast MRI (PC‐MRI).

Methods

A conventional flow‐compensated and flow‐encoded (FCFE) PC‐MRI sequence was compared with a CVX PC‐MRI sequence using numerical simulations, flow phantom experiments, and in vivo experiments. Flow measurements within the ascending aorta, main pulmonary artery, and right/left pulmonary arteries of normal volunteers (N = 10) were acquired at 3T and analyzed using a conventional FCFE sequence and a CVX sequence with either higher spatial resolution or higher temporal resolution. All sequences mitigated chemical shift–induced phase errors and used equivalent breath‐hold durations.

Results

Chemical shift–optimized PC‐MRI has increased sequence efficiency when using CVX, which can provide either higher spatial or higher temporal resolution compared with conventional FCFE PC‐MRI. Numerical simulations, flow phantom experiments, and in vivo experiments indicate that CVX measurements of total flow and peak velocity are increased and more accurate when compared with FCFE.

Conclusion

CVX PC‐MRI increases sequence efficiency while reducing chemical shift–induced phase errors. This can be used to provide either higher spatial or higher temporal resolution than conventional chemical shift–mitigated PC‐MRI methods to provide more accurate measurements of blood flow and peak velocity. Magn Reson Med 72:1552–1564, 2014. © 2013 Wiley Periodicals, Inc.
3D Multi‐slab diffusion‐weighted readout‐segmented EPI with real‐time cardiac‐reordered k‐space acquisition
Authors: Frost Robert , Miller Karla L. , Tijssen Rob H.N. , Porter David A. , Jezzard Peter
Published: December 2013

Purpose

The aim of this study was to develop, implement, and demonstrate a three‐dimensional (3D) extension of the readout‐segmented echo‐planar imaging (rs‐EPI) sequence for diffusion imaging.

Theory and Methods

Potential k‐space acquisition schemes were assessed by simulating their associated spatial point spread functions. Motion‐induced phase artifacts were also simulated to test navigator corrections and a real‐time reordering of the k‐space acquisition relative to the cardiac cycle. The cardiac reordering strategy preferentially chooses readout segments closer to the center of 3D k‐space during diastole. Motion‐induced phase artifacts were quantified by calculating the voxel‐wise temporal variation in a set of repeated diffusion‐weighted acquisitions. Based on the results of these simulations, a 2D navigated multi‐slab rs‐EPI sequence with real‐time cardiac reordering was implemented. The multi‐slab implementation enables signal‐to‐noise ratio‐optimal repetition times of 1–2 s.

Results

Cardiac reordering was validated in simulations and in vivo using the multi‐slab rs‐EPI sequence. In comparisons with standard k‐space acquisitions, cardiac reordering was shown to reduce the variability due to motion‐induced phase artifacts by 30–50%. High‐resolution diffusion tensor imaging data acquired with the cardiac‐reordered multi‐slab rs‐EPI sequence are presented.

Conclusion

A 3D multi‐slab rs‐EPI sequence with cardiac reordering has been demonstrated in vivo and is shown to provide high‐quality 3D diffusion‐weighted data sets. Magn Reson Med 72:1565–1579, 2014. © 2013 Wiley Periodicals, Inc.
Leadership in Temporary Organizations: A Review of Leadership Theories and a Research Agenda
Authors: Tyssen Ana K. , Wald Andreas , Spieth Patrick
Published: December 2013

Projects and other temporary forms of organizing are different from standard organizational processes. As most leadership theories are based on the assumption of stable organizational environments, the increase in temporary forms of organizing poses specific challenges to leadership theories. We evaluate existing leadership theories in terms of their applicability on temporary environments and identify theories, which are adaptable to temporary settings and therefore may be the basis for empirical investigations in this field. On this basis we derive a research agenda by proposing individual leadership theories and combinations of different leadership approaches to be further assessed in research.
Inhaled corticosteroids and bone mineral density at school age: A follow‐up study after early childhood wheezing
Authors: Sidoroff Virpi H. , Ylinen Mari K. , Kröger Liisa M. , Kröger Heikki P.J. , Korppi Matti O.
Published: December 2013

Objective

The aim of the study was to evaluate the association between previous use of ICS and bone mineral density (BMD) at school age in a cohort followed after early childhood wheezing.

Methods

As part of a prospective follow‐up study after hospitalization for wheezing at <24 months of age, BMD was measured in 89 children at 12.3 (median) years of age. Data on ICS use were collected by interviewing the parents, and this was supplemented with data from patient records. Cumulative doses and the duration of ICS use were calculated. Areal BMD (BMDareal, g/cm2) was measured by dual energy X‐ray absorptiometry (DXA), and apparent volumetric BMD (aBMDvol, g/cm3) was calculated, for the lumbar spine and femoral neck. Weight, height and pubertal stage were recorded.

Findings

Age, sex, and pubertal stage were significantly associated with BMDareal and aBMDvol of the lumbar spine and BMDareal of the femoral neck. The regular use of ICS for >6 months at age <6 years was associated with a lower BMD of the lumbar spine. A lower BMDareal and aBMDvol of the femoral neck were associated with higher cumulative doses of ICS at age 0–12.3 (median) years. The results were robust to adjustment for age, sex, pubertal stage, height, weight, and use of systemic steroids.

Conclusion

ICS use during childhood may be related to a decrease in BMD at late school age. It is important to use the lowest possible ICS dose that maintains adequate asthma control. Pediatr Pulmonol. 2015; 50:1–7. © 2013 Wiley Periodicals, Inc.
Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design
Authors: Mabanglo Mark F. , Hast Michael A. , Lubock Nathan B. , Hellinga Homme W. , Beese Lorena S.
Published: December 2013

Species of the fungal genus Aspergillus are significant human and agricultural pathogens that are often refractory to existing antifungal treatments. Protein farnesyltransferase (FTase), a critical enzyme in eukaryotes, is an attractive potential target for antifungal drug discovery. We report high‐resolution structures of A. fumigatus FTase (AfFTase) in complex with substrates and inhibitors. Comparison of structures with farnesyldiphosphate (FPP) bound in the absence or presence of peptide substrate, corresponding to successive steps in ordered substrate binding, revealed that the second substrate‐binding step is accompanied by motions of a loop in the catalytic site. Re‐examination of other FTase structures showed that this motion is conserved. The substrate‐ and product‐binding clefts in the AfFTase active site are wider than in human FTase (hFTase). Widening is a consequence of small shifts in the α‐helices that comprise the majority of the FTase structure, which in turn arise from sequence variation in the hydrophobic core of the protein. These structural effects are key features that distinguish fungal FTases from hFTase. Their variation results in differences in steady‐state enzyme kinetics and inhibitor interactions and presents opportunities for developing selective anti‐fungal drugs by exploiting size differences in the active sites. We illustrate the latter by comparing the interaction of ED5 and Tipifarnib with hFTase and AfFTase. In AfFTase, the wider groove enables ED5 to bind in the presence of FPP, whereas in hFTase it binds only in the absence of substrate. Tipifarnib binds similarly to both enzymes but makes less extensive contacts in AfFTase with consequently weaker binding.
Upregulation of androgen‐responsive genes and transforming growth factor‐β1 cascade genes in a rat model of non‐bacterial prostatic inflammation
Authors: Funahashi Yasuhito , O'Malley Katherine J. , Kawamorita Naoki , Tyagi Pradeep , DeFranco Donald B. , Takahashi Ryosuke , Gotoh Momokazu , Wang Zhou , Yoshimura Naoki
Published: December 2013

BACKGROUND

Prostatic inflammation is associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen‐responsive genes and growth factors in the prostate.

METHODS

Prostatic inflammation was induced by formalin injection into bilateral ventral lobes of the prostate of male SD rats. After 28 days, the prostate was harvested for analyses of proinflammatory cytokines, androgen‐responsive genes in the epithelium, and TGF‐β1 cascade genes in the stroma. Some rats were given a COX‐2 inhibitor (celecoxib; 10 mg/kg/day) by oral gavage for 28 days.

RESULTS

The formalin‐injected prostate exhibited widespread low‐grade inflammation (<50 leukocytes/10,000 μm2) along with focal high‐grade inflammation (>100 leukocytes/10,000 μm2) in limited areas. Compared to control, formalin‐injected prostate exhibited a 2.5‐fold to sixfold increased protein expression of IL‐1α, IL‐1β, and IL‐6. In the low‐grade inflammatory regions, threefold to ninefold and twofold to threefold upregulations of mRNA levels of androgen receptors/androgen‐responsive genes and TGF‐β1 cascade genes were respectively, observed in the epithelium and stroma obtained by laser‐capture microdissection. Positive staining for androgen receptors in the epithelial nuclei, and TGF‐β1, IL‐6, and COX‐2 in the stroma was increased in the low‐grade inflammation area. COX‐2 inhibitor treatment suppressed these upregulations of cytokines, androgen‐responsive, and TGF‐β1 cascade genes.

CONCLUSIONS

Prostatic inflammation induced increased expression of androgen‐responsive genes in the epithelium and TGF‐β1 cascade genes in the stroma, which were suppressed by COX‐2 inhibitors, suggesting that activation of these genes in the low‐grade inflammatory region might be involved in the development of symptomatic BPH. Prostate 74:337–345, 2014. © 2013 Wiley Periodicals, Inc.
Skp2 regulates androgen receptor through ubiquitin‐mediated degradation independent of Akt/mTOR pathways in prostate cancer
Authors: Li Bo , Lu Wenfu , Yang Qing , Yu Xiuping , Matusik Robert J. , Chen Zhenbang
Published: December 2013

BACKGROUND

The intervention of advanced prostate cancer (PCa) in patients has been commonly depending on androgen deprivation therapy. Despite of tremendous research efforts, however, molecular mechanisms on AR regulation remain poorly understood, particularly for castration resistant prostate cancer (CRPC). Targeting AR and associated factors is considered an effective strategy in PCa treatment.

METHODS

Human prostate cancer cells were used in this study. Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or overexpression of plasmids. Dual luciferase reporter assay was applied for AR activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and immunofluorescence were applied to detect the proteins.

RESULTS

Our results demonstrated that Skp2 directly involves the regulation of AR expression through ubiquitination‐mediated degradation. Skp2 interacted with AR protein in PCa cells, and enforced expression of Skp2 resulted in a decreased level and activity of AR. By contrast, Skp2 knockdown increased the protein accumulation and activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent alterations of PSA level in PCa cells. AR ubiquitination was significantly increased upon Skp2 overexpression but greatly reduced upon Skp2 knockdown. AR mutant at K847R abrogated Skp2‐mediated ubiquitination of AR. NVP‐BEZ235, a dual PI3K/mTOR inhibitor, remarkably inhibited Skp2 level with a striking elevation of AR.

CONCLUSIONS

The results indicate that Skp2 is an E3 ligase for proteasome‐dependent AR degradation, and K847 on AR is the recognition site for Skp2‐mediated ubiquitination. Our findings reveal an essential role of Skp2 in AR signaling. Prostate 74:421–432, 2014. © 2013 Wiley Periodicals, Inc.
Green Technology with Silicides and Related Materials
Authors: Maeda Yoshihito , Suzuki Motofumi
Published: December 2013

We, the organizing committee, are very pleased to publish the proceedings of the Asia‐Pacific Conference on Green Technology with Silicides and Related Materials (APAC‐SILICIDE 2013) for scientists, researchers and students with interest in the science and technology of semiconducting silicides and related materials. In the last five years, studies of silicides have shown rapid progress, mainly because of success in high‐quality crystal growth, thin‐film synthesis, development of light‐emitting diodes, and photonic applications.

Researchers in the Asia‐Pacific and other areas have constantly contributed to the progress in investigating the fundamental properties and applications. This movement was the motivation to organize APAC‐SILICIDE 2013 that follows upon APAC‐SILICIDE 2010 in Tsukuba and APAC‐SILICIDE 2006 in Kyoto. These proceedings were published as special issues of Thin Solid Films 515 (2007) and Thin Solid Films 519 (2011), and involved advanced silicide science and technology towards sustainability of optoelectronics, photonics, and spintronics.

We believe that these professional conferences are timely to discuss the most recent and advanced results in order to stimulate an international connection between semiconducting silicides research and the development of sustainable semiconductor technology. These conferences surely covered crucial technical areas of semiconducting silicides and related materials. The APAC‐SILICIDE 2013 covered the following technical areas: Silicide Green Technology (newly launched area), Electronics, Spintronics and Photonics, Crystal growth, Structural analyses, Surface sciences and technology, Optical, electrical, electronic and magnetic properties, Theory and Simulations. Attractive studies and fruitful discussions at this conference have been harvested into 55 manuscripts of invited and contributed presentations in this volume.

The editors would like to take this opportunity to thank all reviewers and members of the publishing committee for their timely and rapid action.

Finally, we, the organizing committee, mourn for the loss of Professor Li‐Jen Chou, Department of Materials Science and Engineering, National Tsing Hua University, before this conference. He was a distinguished researcher in silicide nanoelectronics and contributed to organizing this conference as a member of the international advisory committee. We would like to express our sorrow for the loss of Professor Chou.

December 2013
Abnormal thermal conductivity of [720]‐oriented BaTiO3 single crystal
Authors: Zhao K. Y. , Zeng H. R. , Zhang X. W. , Xu K. Q. , Yu H. Z. , Li G. R. , Luo H. S.
Published: December 2013

The 3ω ‐scanning thermal microscopy and piezoresponse force microscopy techniques were combined to characterize the local thermal conductivity (λ) of ferroelastic domains in [720]‐oriented and [001]‐oriented BaTiO3 single crystal. The [720]‐oriented BaTiO3 showed a local λ value of 3.39 W/m·K, while it was 5.95 W/m·K for [001]‐oriented BaTiO3. The underlying mechanism for such drastic thermal conductivity reduction in [720]‐oriented BaTiO3 is ascribed to a stronger phonon‐scattering effect due to the high strains appearing in [720]‐oriented BaTiO3 single crystals. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An extension of the placebo‐based pattern‐mixture model
Authors: Lu Kaifeng
Published: December 2013

Pattern‐mixture models provide a general and flexible framework for sensitivity analyses of nonignorable missing data in longitudinal studies. The placebo‐based pattern‐mixture model handles missing data in a transparent and clinically interpretable manner. We extend this model to include a sensitivity parameter that characterizes the gradual departure of the missing data mechanism from being missing at random toward being missing not at random under the standard placebo‐based pattern‐mixture model. We derive the treatment effect implied by the extended model. We propose to utilize the primary analysis based on a mixed‐effects model for repeated measures to draw inference about the treatment effect under the extended placebo‐based pattern‐mixture model. We use simulation studies to confirm the validity of the proposed method. We apply the proposed method to a clinical study of major depressive disorders. Copyright © 2013 John Wiley & Sons, Ltd.
Diagnostics of T1279 ECMWF analysis winds in the Mediterranean basin by comparison with ASCAT 12.5 km winds
Authors: Zecchetto S. , Accadia C.
Published: December 2013

This article aims to understand to what extent the winds fields from an advanced numerical weather prediction system and from a satellite scatterometer describe the same spatial and temporal features of the wind in the Mediterranean Sea. We investigated wind fields for the period February 2010 to February 2012 using the ASCAT scatterometer data with 12.5 km wind vector cells and the analysis wind fields from the ECMWF T1279 global model. The ASCAT–ECMWF mean relative bias and centred root mean square deviation of wind speed, normalized by scatterometer wind speed wsc, Δws/wsc and , have been found to be 7 and 23%. An interesting result is the identification of dependence of both Δws/wsc and on the distance from the coast, indicating the coastal areas as the main source of discrepancy between the two datasets. From 50 to 200 km away from coast, decreases from 40 to 25% and Δws/wsc from 8 to 4%. These results gain more importance considering that the Mediterranean Sea is essentially a coastal sea (50% of its surface lies within 50 km from the coast). Both Δws and have been found to depend nonlinearly on the wind speed. The seasonal variation of Δws/wsc and shows that they are in phase opposition, with higher values of during the warm season (April to October). It is hypothesized that local coastal circulations like land/sea breezes could explain the observed mismatch between model and observations. The reported findings emphasize a common feature of the present atmospheric models forecasting winds over regional basins like the Mediterranean. Copyright © 2010 Royal Meteorological Society
Bayesian sequential meta‐analysis design in evaluating cardiovascular risk in a new antidiabetic drug development program
Authors: Chen Ming‐Hui , Ibrahim Joseph G. , Amy Xia H. , Liu Thomas , Hennessey Violeta
Published: December 2013

Recently, the Center for Drug Evaluation and Research at the Food and Drug Administration released a guidance that makes recommendations about how to demonstrate that a new antidiabetic therapy to treat type 2 diabetes is not associated with an unacceptable increase in cardiovascular risk. One of the recommendations from the guidance is that phases II and III trials should be appropriately designed and conducted so that a meta‐analysis can be performed. In addition, the guidance implies that a sequential meta‐analysis strategy could be adopted. That is, the initial meta‐analysis could aim at demonstrating the upper bound of a 95% confidence interval (CI) for the estimated hazard ratio to be < 1.8 for the purpose of enabling a new drug application or a biologics license application. Subsequently after the marketing authorization, a final meta‐analysis would need to show the upper bound to be < 1.3. In this context, we develop a new Bayesian sequential meta‐analysis approach using survival regression models to assess whether the size of a clinical development program is adequate to evaluate a particular safety endpoint. We propose a Bayesian sample size determination methodology for sequential meta‐analysis clinical trial design with a focus on controlling the familywise type I error rate and power. We use the partial borrowing power prior to incorporate the historical survival meta‐data into the Bayesian design. We examine various properties of the proposed methodology, and simulation‐based computational algorithms are developed to generate predictive data at various interim analyses, sample from the posterior distributions, and compute various quantities such as the power and the type I error in the Bayesian sequential meta‐analysis trial design. We apply the proposed methodology to the design of a hypothetical antidiabetic drug development program for evaluating cardiovascular risk. Copyright © 2013 John Wiley & Sons, Ltd.
Mechanisms of Antibacterial Activity of MgO: Non‐ROS Mediated Toxicity of MgO Nanoparticles Towards Escherichia coli
Authors: Leung Yu Hang , Ng Alan M. C. , Xu Xiaoying , Shen Zhiyong , Gethings Lee A. , Wong Mabel Ting , Chan Charis M. N. , Guo Mu Yao , Ng Yip Hang , Djurišić Aleksandra B. , Lee Patrick K. H. , Chan Wai Kin , Yu Li Hong , Phillips David Lee , Ma Angel P. Y. , Leung Frederick C. C.
Published: December 2013

The toxicity of metal oxide nanomaterials and their antimicrobial activity is attracting increasing attention. Among these materials, MgO is particularly interesting as a low cost, environmentally‐friendly material. The toxicity of MgO, similar to other metal oxide nanomaterials, is commonly attributed to the production of reactive oxygen species (ROS). We investigated the toxicity of three different MgO nanoparticle samples, and clearly demonstrated robust toxicity towards Escherichia coli bacterial cells in the absence of ROS production for two MgO nanoparticle samples. Proteomics data also clearly demonstrate the absence of oxidative stress and indicate that the primary mechanism of cell death is related to the cell membrane damage, which does not appear to be due to lipid peroxidation.
Comparison of trapping and camera survey methods for determining presence of allegheny woodrats
Authors: Castleberry Steven B. , Mengak Michael T. , Menken Theron E.
Published: December 2013

Declines in Allegheny woodrat (Neotoma magister) distribution and numbers have been documented in the northern and western portions of the range for >30 years. Population trends in other parts of the range are uncertain, largely due to a lack of, or inconsistent, survey effort. We examined the efficacy of the trapping protocol currently used by many state and federal agencies for determining presence or absence of Allegheny woodrats at 17 study sites in western Virginia, USA. We compared trapping results with a remote camera methodology to determine whether remote cameras provide an effective alternative to trapping. We found that detection probabilities were high after 2 survey nights for both the trapping (0.86 ± 0.06) and camera (0.97 ± 0.03) methodologies. Percent of sites with documented woodrat presence after 2 nights was 88% and 94% for traps and cameras, respectively. We conclude that both methods are adequate for determining presence or absence of Allegheny woodrats and that each method has distinct advantages depending on the objectives. © 2013 The Wildlife Society.
IonNeurONet – Deutsches Netzwerk für neurologische und ophthalmologische Ionenkanalerkrankungen
Authors: Zurek B. , Graessner H. , Lerche H.
Published: December 2013

IonNeurONet ist ein vom Bundesministerium für Bildung und Forschung (BMBF) gefördertes Verbundforschungsprojekt der Universitäten Tübingen und Ulm sowie der CeGaT GmbH, Tübingen, mit dem Ziel, die Erkrankungsmechanismen seltener neurologischer und ophthalmologischer Ionenkanalerkrankungen aufzuklären, die als Basis für die Entwicklung neuer Therapien dienen können. Der Aufbau eines klinischen Netzwerks soll die nationale Versorgung für diese seltenen und oftmals unerkannten Erkrankungen bereitstellen. Ein auf Next Generation Sequencing (NGS) basierends schnelles und effizientes genetisches Diagnostikwerkzeug wurde bereits entwickelt. Es wird fortlaufend durch neue Krankheitsgene, die mittels Exomsequenzierung identifiziert wurden, ergänzt. Weitere Teilprojekte beschäftigen sich mit detaillierten funktionellen physiologischen Studien in heterologen Expressionssystemen sowie in Muskel- und Nervenzellen. Das Projekt etabliert Plattformen für genetische und bioinformatische Analysen, automatisierte und detaillierte funktionelle Studien, intrazellulären Transport von Membranproteinen und induzierte pluripotente Stammzellen.
The evolution of a stratified turbulent cloud
Authors: Maffioli Andrea , Davidson P. A. , Dalziel S. B. , Swaminathan N.
Published: December 2013

Localized regions of turbulence, or turbulent clouds, in a stratified fluid are the subject of this study, which focuses on the edge dynamics occurring between the turbulence and the surrounding quiescent region. Through laboratory experiments and numerical simulations of stratified turbulent clouds, we confirm that the edge dynamics can be subdivided into materially driven intrusions and horizontally travelling internal wave-packets. Three-dimensional visualizations show that the internal gravity wave-packets are in fact large-scale pancake structures that grow out of the turbulent cloud into the adjacent quiescent region. The wave-packets were tracked in time, and it is found that their speed obeys the group speed relation for linear internal gravity waves. The energetics of the propagating waves, which include waveforms that are inclined with respect to the horizontal, are also considered and it is found that, after a period of two eddy turnover times, the internal gravity waves carry up to 16 % of the cloud kinetic energy into the initially quiescent region. Turbulent events in nature are often in the form of decaying turbulent clouds, and it is therefore suggested that internal gravity waves radiated from an initial cloud could play a significant role in the reorganization of energy and momentum in the atmosphere and oceans.
Theoretical study of the generation of soap films: role of interfacial visco-elasticity
Authors: Seiwert Jacopo , Dollet Benjamin , Cantat Isabelle
Published: December 2013

In this work, we study theoretically the thickness of a liquid film (typically made of a surfactant solution) pulled out of a bath at constant speed in the absence of gravity, when it features a viscous or an elastic interfacial rheology. We show that a purely viscous rheology does not lead to the extraction of a steady state film of constant thickness. In contrast, the thickness of the film is well defined in the elastic case, which allows us to compute it. This thickness depends on the capillary number of the experiment, and on the elasticity of the interface. It is always lower than or equal to that obtained for an incompressible interface predicted by Frankel (Mysels, Shinoda and Frankel, Soap Films: Studies of their Thinning and a Bibliography, 1959), which is recovered in the limit of an arbitrary large elasticity.
A PROBABILISTIC PROOF OF THE OPEN MAPPING THEOREM FOR ANALYTIC FUNCTIONS
Authors: MARKOWSKY GREG
Published: December 2013

The conformal invariance of Brownian motion is used to give a short proof of the Open Mapping theorem for analytic functions.
(STRONGLY) GORENSTEIN FLAT MODULES OVER GROUP RINGS
Authors: BAHLEKEH ABDOLNASER
Published: December 2013

Let $\Gamma $ be a group and ${\Gamma }^{\prime } $ be a subgroup of $\Gamma $ of finite index. Let $M$ be a $\Gamma $-module. It is shown that $M$ is (strongly) Gorenstein flat if and only if it is (strongly) Gorenstein flat as a ${\Gamma }^{\prime } $-module. We also provide some criteria in which the classes of Gorenstein projective and strongly Gorenstein flat $\Gamma $-modules are the same.