bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐related vulnerabilities along the hippocampal longitudinal axis
Authors: Ta Anh Tuan , Huang Shuo‐En , Chiu Ming‐Jang , Hua Mau‐Sun , Tseng Wen‐Yih Isaac , Chen Shen‐Hsing Annabel , Qiu Anqi
Published: September 2011

Evidence for an anterior‐posterior gradient of age‐related volume reduction along the hippocampal longitudinal axis has been reported in normal aging, but functional changes have yet to be systematically investigated. The current study applied an advanced brain mapping technique, large deformation diffeomorphic metric mapping (LDDMM), automatically delineating the hippocampus into the anterior and posterior segments based on anatomical landmarks. We studied this anterior‐posterior gradient in terms of structural and functional MRI in 66 participants aged from 19 to 79 years. The results showed age‐related structural volume reduction in both anterior and posterior hippocampi, with greater tendency for anterior decrease. FMRI task contrasts that robustly activated the anterior (associative/relational processing) and posterior (novelty) hippocampus independently, showed only significant reduction of activation in the anterior hippocampus as age increased. Our results revealed positive correlation between structural atrophy and functional decrease in the anterior hippocampi, regardless of task performance in normal aging. These findings suggest that anatomy and functions related to the anterior hippocampus may be more vulnerable to aging, than previously thought. Hum Brain Mapp 33:2415–2427, 2012. © 2011 Wiley Periodicals, Inc.
Buffalo (Bubalus bubalis) epiphyseal proteins give protection from arsenic and fluoride‐induced adverse changes in acetylcholinesterase activity in rats
Authors: Bharti Vijay K. , Srivastava R. S. , Anand Ajay K. , Kusum K.
Published: September 2011

The objective of this study was to determine the effect of fluoride (F) and arsenic (As) on the activity of acetylcholinesterase (AChE), a critically important nervous system enzyme, and to test the protective role of buffalo epiphyseal (pineal) proteins (BEP) in rats. Arsenic (20 mg/kg BW, intraperitoneally) and F (150 ppm, perorally) were exposed, and BEP was administered intraperitoneally (100 μ g/kg BW) along with F and As to rats for 7 days. As and F exposure significantly (p < 0.05) increased their levels in plasma and decreased the activity of AChE in plasma, RBCs, heart, and brain of rats. Interestingly, As‐ and F‐induced inhibition of AChE activities increased As and F levels in plasma, and organs were significantly (p < 0.05) counteracted by BEP administration. These findings indicate the protective role of buffalo (Bubalus bubalis) epiphyseal proteins on F‐ and As‐induced adverse changes in AChE activity as a candidate biomarker for neurotoxicity in female rats. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:10–15 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20407
Cyclin D3 promotes myogenic differentiation and Pax7 transcription
Authors: Gurung Ritika , Parnaik Veena K.
Published: September 2011

Differentiation of skeletal muscle myoblasts involves activation of muscle‐specific markers such as MyoD, Myf5, MRF4, and myogenin, followed by exit from the cell cycle, expression of structural proteins, and fusion into multinucleated myotubes. Cyclin D3 is upregulated during muscle differentiation, and expression of cyclin D3 in proliferating myoblasts causes early activation of myogenesis. In this study, we have identified the genes activated by cyclin D3 expression in C2C12 myoblasts and differentiated cells by real‐time PCR analysis. Cyclin D3 expression induced faster differentiation kinetics and increase in levels of myogenic genes such as MyoD, Myf5, and myogenin at an early stage during the differentiation process, although long‐term myogenic differentiation was not affected. Transcript levels of the transcription factor Pax7 that is expressed in muscle progenitors were enhanced by cyclin D3 expression in myoblasts. Components of a histone methyltransferase complex recruited by Pax7 to myogenic gene promoters were also regulated by cyclin D3. Further, the Pax7 promoter was upregulated in myoblasts expressing cyclin D3. Myoblasts that expressed cyclin D3 showed moderately higher levels of the cyclin‐dependent kinase inhibitor p21 and were stalled in G2/M phase of the cell cycle. Our findings suggest that cyclin D3 primes myoblasts for differentiation by enhancing muscle specific gene expression and cell cycle exit. J. Cell. Biochem. 113: 209–219, 2012. © 2011 Wiley Periodicals, Inc.
p38 MAPK activation, JNK inhibition, neoplastic growth inhibition, and increased gap junction communication in human lung carcinoma and Ras‐transformed cells by 4‐Phenyl‐3‐butenoic acid
Authors: Matesic Diane F. , Sidorova Tatyana S. , Burns Timothy J. , Bell Allison M. , Tran Paul L. , Ruch Randall J. , May Sheldon W.
Published: September 2011

Human lung neoplasms frequently express mutations that down‐regulate expression of various tumor suppressor molecules, including mitogen‐activated protein kinases such as p38 MAPK. Conversely, activation of p38 MAPK in tumor cells results in cancer cell cycle inhibition or apoptosis initiated by chemotherapeutic agents such as retinoids or cisplatin, and is therefore an attractive approach for experimental anti‐tumor therapies. We now report that 4‐phenyl‐3‐butenoic acid (PBA), an experimental compound that reverses the transformed phenotype at non‐cytotoxic concentrations, activates p38 MAPK in tumorigenic cells at concentrations and treatment times that correlate with decreased cell growth and increased cell‐cell communication. H2009 human lung carcinoma cells and ras‐transformed rat liver epithelial cells treated with PBA showed increased activation of p38 MAPK and its downstream effectors which occurred after 4 h and lasted beyond 48 h. Untransformed plasmid control cells showed low activation of p38 MAPK compared to ras‐transformed and H2009 carcinoma cells, which correlates with the reduced effect of PBA on untransformed cell growth. The p38 MAPK inhibitor, SB203580, negated PBA's activation of p38 MAPK downstream effectors. PBA also increased cell–cell communication and connexin 43 phosphorylation in ras‐transformed cells, which were prevented by SB203580. In addition, PBA decreased activation of JNK, which is upregulated in many cancers. Taken together, these results suggest that PBA exerts its growth regulatory effect in tumorigenic cells by concomitant up‐regulation of p38 MAPK activity, altered connexin 43 expression, and down‐regulation of JNK activity. PBA may therefore be an effective therapeutic agent in human cancers that exhibit down‐regulated p38 MAPK activity and/or activated JNK and altered cell–cell communication. J. Cell. Biochem. 113: 269–281, 2012. © 2011 Wiley Periodicals, Inc.
The transcription factor osterix (SP7) regulates BMP6‐induced human osteoblast differentiation
Authors: Zhu Fengchang , Friedman Michael S. , Luo Weijun , Woolf Peter , Hankenson Kurt D.
Published: September 2011

The transcription factor Osterix (Sp7) is essential for osteoblastogenesis and bone formation in mice. Genome wide association studies have demonstrated that Osterix is associated with bone mineral density in humans; however, the molecular significance of Osterix in human osteoblast differentiation is poorly described. In this study we have characterized the role of Osterix in human mesenchymal progenitor cell (hMSC) differentiation. We first analyzed temporal microarray data of primary hMSC treated with bone morphogenetic protein‐6 (BMP6) using clustering to identify genes that are associated with Osterix expression. Osterix clusters with a set of osteoblast‐associated extracellular matrix (ECM) genes, including bone sialoprotein (BSP) and a novel set of proteoglycans, osteomodulin (OMD), osteoglycin, and asporin. Maximum expression of these genes is dependent upon both the concentration and duration of BMP6 exposure. Next we overexpressed and repressed Osterix in primary hMSC using retrovirus. The enforced expression of Osterix had relatively minor effects on osteoblastic gene expression independent of exogenous BMP6. However, in the presence of BMP6, Osterix overexpression enhanced expression of the aforementioned ECM genes. Additionally, Osterix overexpression enhanced BMP6 induced osteoblast mineralization, while inhibiting hMSC proliferation. Conversely, Osterix knockdown maintained hMSC in an immature state by decreasing expression of these ECM genes and decreasing mineralization and hMSC proliferation. Overexpression of the Osterix regulated gene OMD with retrovirus promoted mineralization of hMSC. These results suggest that Osterix is necessary, but not sufficient for hMSC osteoblast differentiation. Osterix regulates the expression of a set of ECM proteins which are involved in terminal osteoblast differentiation. J. Cell. Physiol. 227: 2677–2685, 2012. © 2011 Wiley Periodicals, Inc.
Heparin‐integrin interaction in endothelial cells: Downstream signaling and heparan sulfate expression
Authors: Medeiros Valquíria P. , Paredes‐Gamero Edgar J. , Monteiro Hugo P. , Rocha Hugo A.O. , Trindade Edvaldo S. , Nader Helena B.
Published: September 2011

Endothelial cells (ECs) are a source of physiologically important molecules that are synthesized and released to the blood and/or to the subendothelial extracellular matrix such as a heparan sulfate proteoglycan (HSPG) with antithrombotic properties. Previously, we have shown that heparin stimulates the synthesis and modifies the sulfation pattern of this HSPG. Here the molecular mechanisms involved in the up‐regulation of HSPG synthesis by heparin in endothelial cells were decoded. The cells were stimulated with heparin and the expression of HSPG and intracellular pathways were evaluated by a combination of methods involving confocal microscopy, flow cytometry, Western blotting analyses, and [35S]‐sulfate metabolically labeling of the cells. We observed that the up‐regulation of HSPG synthesis evoked by heparin is dependent on the interaction of heparin with integrin since RGD peptide abolishes the effect. The activation of integrin leads to tyrosine‐phosphorylation of focal adhesion‐associated proteins such as FAK, Src, and paxillin. In addition, heparin induces ERK1/2 phosphorylation and inhibitors of Ras and MEK decreased heparin‐dependent HSPG synthesis. Moreover, heparin also induced intracellular Ca2+ release, PLCγ1 (phospholipase Cγ1) and CaMKII (calcium calmodulin kinase II) activation, as well as an increase in nitric oxide (NO) production. Finally, an intracellular Ca2+ chelator, Ca2+ signaling inhibitors, and an endothelial NO synthase inhibitor were all able to abolish the effect in heparan sulfate synthesis. In conclusion, the heparin‐induced up‐regulation of HSPG expression is associated with the phosphorylation of focal adhesion proteins and Ras/Raf/MEK/ERK MAP and Ca2+/NO pathways. J. Cell. Physiol. 227: 2740–2749, 2012. © 2011 Wiley Periodicals, Inc.
The Place of Development in Mathematical Evolutionary Theory
Authors: Rice Sean H.
Published: September 2011

Development plays a critical role in structuring the joint offspring–parent phenotype distribution. It thus must be part of any truly general evolutionary theory. Historically, the offspring–parent distribution has often been treated in such a way as to bury the contribution of development, by distilling from it a single term, either heritability or additive genetic variance, and then working only with this term. I discuss two reasons why this approach is no longer satisfactory. First, the regression of expected offspring phenotype on parent phenotype can easily be nonlinear, and this nonlinearity can have a pronounced impact on the response to selection. Second, even when the offspring–parent regression is linear, it is nearly always a function of the environment, and the precise way that heritability covaries with the environment can have a substantial effect on adaptive evolution. Understanding these complexities of the offspring–parent distribution will require understanding of the developmental processes underlying the traits of interest. I briefly discuss how we can incorporate such complexity into formal evolutionary theory, and why it is likely to be important even for traits that are not traditionally the focus of evo–devo research. Finally, I briefly discuss a topic that is widely seen as being squarely in the domain of evo–devo: novelty. I argue that the same conceptual and mathematical framework that allows us to incorporate developmental complexity into simple models of trait evolution also yields insight into the evolution of novel traits. J. Exp. Zool. (Mol. Dev. Evol.) 318B:480–488, 2012. © 2011 Wiley Periodicals, Inc.
The source of chilopod sensory information: External structure and distribution of antennal sensilla in Scutigera coleoptrata (chilopoda, Scutigeromorpha)
Authors: Sombke Andy , Rosenberg Jörg , Hilken Gero , Westermann, Martin , Ernst Alfred
Published: September 2011

The investigation of the antennae of Scutigera coleoptrata (Linnaeus, 1758) by scanning electron microscopy (SEM) revealed the presence of five types of sensilla: sensilla trichodea, beak‐like sensilla, cone‐shaped sensilla brachyconica on the terminal article, sensory cones at the antennal nodes, and the shaft organ. Alongside the presence and absence of antennal sensillar types, three unique characters were found in the Scutigeromorpha: the presence of long antennae with nodes bearing sensory cones, the presence of a bipartite shaft including the shaft organ, and the presence of beak‐like sensilla. Neuroanatomical data showed that the animals' brains are equipped with well‐developed primary olfactory and mechanosensory centers, suggesting that the antennae must be equipped with specialized sensilla to perceive chemosensory and mechanosensory cues. With the evidence provided in this article for the Scutigeromorpha, SEM data are available at last on the antennal sensilla for all five chilopod taxa, allowing a comparative discussion of antennal morphology in Chilopoda. J. Morphol., 2011. © 2011Wiley‐Liss, Inc.
Survival analysis of gastric cancer patients with tumor thrombus in the portal vein
Authors: Eom Bang Wool , Lee Jun Ho , Lee Jong Seok , Kim Min Ju , Ryu Keun Won , Choi Il Ju , Cho Soo‐Jeong , Lee Jong Yeul , Rhee Jiyoung , Nam Byung‐Ho , Kim Young‐Woo
Published: September 2011

Background

A tumor thrombus in the portal vein originating from gastric cancer is a rare condition. Little is known about the development of portal vein tumor thrombus (PVTT) and its effect on the survival of gastric cancer patients.

Methods

PVTT originating from gastric cancer was identified retrospectively with computed tomography in 51 patients, from January 2002 to June 2007. PVTT was classified by metastatic routes as follows: lymph node (LN), hepatic mass, and hematogenous type. The median survival from PVTT, and the factors affecting the survival of gastric cancer patients with PVTT were analyzed.

Results

The median survival of gastric cancer patients with PVTT (N = 51) was 5.4 months. The median survival was compared according to clinical characteristics, and multivariate analysis proved that female and hepatic mass type were independent risk factors for poor prognosis. The characteristics of the hepatic mass type were old age, higher proportion of tumors located in the upper‐third of the stomach, and liver metastasis, compared to the LN or the hematogeneous type.

Conclusions

PVTT originating from gastric cancer was a poor prognostic factor and the median survival from PVTT was different according to several clinical factors. J. Surg. Oncol. 2012; 105:310–315. © 2011 Wiley Periodicals, Inc.
Quantitative determination of bovine caseinoglycomacropeptide in infant formulas by ultra‐high‐performance liquid chromatography‐electrospray‐ionization mass spectrometry
Authors: Zhang Jingshun , Ren Yiping , Ma Zhenyi , Huang Baifen , Cai Zengxuan , Li Duo
Published: September 2011

An ultra‐high‐performance liquid chromatography‐electrospray ionization coupled to mass spectrometry method has been developed for determining caseinoglycomacropeptide (CGMP) in infant formulas by selected ion reaction and area monitoring modes. The present study focused on the optimization of sample pretreatment, chromatographic resolution and mass spectrometry parameters. After a simple sample pretreatment, the two genetic variants of caseinoglycomacropeptide, CGMPA and CGMPB, were separated using a BEH300 C18 column by gradient elution. The established method was extensively validated by determining the linearity (R2 >0.999), average recovery (95.8–118.4%), inter‐day precision (relative standard deviation ≤7.81%) and intra‐day precision (relative standard deviation ≤6.99%) based on two scan modes. To further verify the applicability of the method, 21 brands of commercial available infant formulas were analyzed. The results showed that the present method is selective, sensitive and reliable for separating and quantifying two genetic variants (CGMPA and CGMPB) of caseinoglycomacropeptide in infant formulas with complex matrix.
T‐cadherin in the mammalian cochlea
Authors: Listyo Alwin , Brand Yves , Setz Cristian , Radojevic Vesna , Resink Therese , Levano Soledad , Bodmer Daniel
Published: September 2011

Objectives/Hypothesis:

Cadherins are a superfamily of transmembrane glycoproteins, which mediate calcium‐dependent intercellular adhesions. T‐cadherin is an atypical member of the cadherin family in regard to its structure; it acts as a signalling receptor rather than an adhesion molecule. In this study we examine the role of T‐cadherin in the mammalian cochlea.

Study Design:

This study investigated the expression of T‐cadherin in the inner ear under physiologic and pathologic conditions.

Methods:

Expression of T‐cadherin in the rat cochlea was analyzed by reverse‐transcriptase polymerase chain reaction (RT‐PCR), real‐time RT‐PCR, Western blot, and immunohistochemistry.

Results:

We detected T‐cadherin mRNA expression in three different components in the cochlea of postnatal mouse, namely the organ of Corti (OC), the spiral ganglion (SG), and the stria vascularis (SV). The SG and SV showed a higher T‐cadherin mRNA level than the OC. T‐cadherin protein was detected by Western blotting in the OC, SG, and SV. Immunofluorescence microscopy of adult mouse cochlea revealed the presence of T‐cadherin in the apical parts of the inner and outer hair cells as well as in the SV and SG. OCs treated with gentamicin for 3, 6, or 12 hours did not show any change in T‐cadherin gene expression compared to control explants maintained in culture medium alone.

Conclusions:

T‐cadherin is expressed within the cochlea. T‐cadherin seems to have a wide variety of functions in the inner ear, ranging from mechanical functions to functions in response to hair cell damage and loss.
Clinical experience in diagnosis and management of superior semicircular canal dehiscence in children
Authors: Lee Gi Soo , Zhou Guangwei , Poe Dennis , Kenna Margaret , Amin Manali , Ohlms Laurie , Gopen Quinton
Published: September 2011

Objectives/Hypothesis:

To identify clinical characteristics of pediatric superior semicircular canal dehiscence (SSCD) and explore suitable options of management.

Study Design:

Retrospective review.

Methods:

The study comprised 10 patients with auditory and/or vestibular symptoms suspicious for SSCD. One patient pursued care at another institution, and two did not return for follow‐up. Subsequently, seven patients (11 ears, 6 females and 1 male, aged 5–11 years) were included. Patients were evaluated using high‐resolution temporal bone computed tomography. Those suspected of having SSCD underwent vestibular evoked myogenic potential testing for confirmation in addition to routine audiologic tests.

Results:

All seven patients had auditory and/or vestibular impairment. Auditory symptoms included autophony, tinnitus, and conductive or mixed hearing loss. Bone conduction responses were occasionally better than 0 dB HL. Vestibular dysfunction included vertigo, often in response to loud noises, and chronic disequilibrium. One patient underwent surgical repair for disabling vestibular symptoms with dramatic improvement in both auditory and vestibular symptoms postoperatively. The remaining six were closely monitored with routine exams.

Conclusions:

In contrast to adults, children with SSCD usually present with auditory symptoms first, although they share some similarities with adults in clinical manifestations of SSCD. Our study shows that SSCD syndrome, a well‐accepted clinical entity, exists in the pediatric population. Conservative management is preferred for children with SSCD; nevertheless, surgical intervention is necessary for those with disabling vestibular symptoms. To date, this is the first clinical case series of symptomatic pediatric patients with SSCD.
Evolution in the management of facial nerve schwannoma
Authors: Wilkinson Eric P. , Hoa Michael , Slattery William H. , Fayad Jose N. , Friedman Rick A. , Schwartz Marc S. , Brackmann Derald E.
Published: September 2011

Objective:

To design a treatment algorithm based on experience with facial nerve schwannomas (FNS) over a 30‐year period.

Study Design:

Retrospective chart review.

Method:

Seventy‐nine patients with facial nerve schwannomas seen from 1979 through 2009 at a tertiary referral private otologic practice were categorized by treatment modality. Interventions included surgical resection with grafting, bony decompression, observation, or stereotactic radiation. Outcome measures included House‐Brackmann facial nerve grade before and after intervention as well as change in facial nerve grade, tumor size, involved segments of nerve, time to intervention.

Results:

Thirty‐seven patients (46.8%) ultimately underwent surgical excision with grafting or primary anastomosis, 21 (26.6%) underwent bony decompression alone, 15 (19.0%) were managed with observation only, and 6 (7.6%) had stereotactic radiation. Through 1995, 85% of cases had surgical resection and none had observation only. Of the 52 patients seen after 1995, 27% had surgical resection and grafting, 33% had bony decompression, 29% were managed with observation alone, and 11% had radiotherapy. Facial nerve grade was maintained or improved over the follow‐up period (mean time = 3.9 years) in 78.9% of the decompression group and 100% of the observation and radiation groups compared to 54.8% of the resection group (P ≤ .012).

Conclusions:

Surgical resection and grafting, once widely accepted and practiced, has in many cases given way to observation, bony decompression, or stereotactic radiation. A wide armamentarium of options is available to the neurotologist treating facial nerve schwannomas with the ability to preserve facial function for a longer period of time.
Injection of human mesenchymal stem cells improves healing of vocal folds after scar excision—A xenograft analysis
Authors: Svensson Bengt , Nagubothu Srinivasa R. , Cedervall Jessica , Chan Roger W. , Le Blanc Katrina , Kimura Miwako , Ährlund‐Richter Lars , Tolf Anna , Hertegård Stellan
Published: September 2011

Objectives:

Using a xenograft model the aim was to analyze if injection of human mesenchymal stem cells (hMSC) into the rabbit vocal fold (VF), after excision of an established scar, can improve the functional healing of the VF.

Study Design:

Prospective design with an experimental xenograft model.

Methods:

The VFs of 12 New Zealand rabbits were injured by a bilateral localized resection. After 9 weeks the scar after the resection was excised and hMSC were injected into the VFs. After another 10 weeks 10 VFs were dissected and stained for histology. Lamina propria thickness and relative content of collagen type I were measured. Viscoelasticity of 14 VFs at phonatory frequencies was quantified by a simple‐shear rheometer. The hMSC survival was determined using a human DNA specific reference probe, that is, FISH analysis.

Results:

The viscoelastic measurements, that is, dynamic viscosity and elastic shear modulus for the hMSC‐treated VFs, were found to be similar to those of normal controls and were significantly lower than those of untreated controls (P < .05). A significant reduction in lamina propria thickness was also shown for the hMSC treated VFs compared with the untreated VFs (P < .05). This histologic finding corresponded with the viscoelastic results. No hMSC survived 10 weeks after the injection.

Conclusions:

Human mesenchymal stem cells injected into the rabbit VF following the excision of a chronic scar, were found to enhance the functional healing of the VF with reduced lamina propria thickness and restored viscoelastic shear properties.
ORL emergencies boot camp: Using simulation to onboard residents
Authors: Malekzadeh Sonya , Malloy Kelly M. , Chu Eugenia E. , Tompkins Jared , Battista Alexis , Deutsch Ellen S.
Published: September 2011

Objectives/Hypothesis:

Incoming otolaryngology residents are expected to triage and manage airway, bleeding, and other emergencies with little prior experience. Simulation‐based education has become increasingly important as it provides tools to develop psychomotor skills and judgment early in residency, using realistic experiences while eliminating patient risk. We hypothesize that a Boot Camp course emphasizing basic otolaryngology management will increase participants' confidence and be perceived as useful in developing their knowledge, technical skills, self‐confidence, and improving clinical performance, both immediately and 6 months following the course.

Study Design:

Survey.

Methods:

A 1‐day Boot Camp was developed consisting of six technical skills stations (mask ventilation, intubation, flexible laryngoscopy, microlaryngoscopy/bronchoscopy, epistaxis control, and cricothyroidotomy); a session involving telephone inquiry triage, and two complex airway scenarios addressing medical management and emphasizing team leadership. Residents completed questionnaires before, immediately, and 6 months following course completion.

Results:

Thirty residents enrolled, 27 participated in the course, and 24 completed all three surveys. Previous experiences and confidence levels were variable; 26 of 30 (87%) identified emergency airway management as a concern before attending the course. A Fisher's exact test demonstrated improved confidence (P < .05) for every skill. An overwhelming majority of participants agreed or strongly agreed the intervention was useful in developing their knowledge, technical skills, self‐confidence, and improving clinical performance.

Conclusions:

An intensive, simulation‐based Boot Camp addressing airway, bleeding, and other otolaryngology emergencies was successful in improving junior otolaryngology residents' confidence and was perceived as useful in developing knowledge, technical skills, self‐confidence, and improving clinical performance.
Augmented image guidance improves skull base navigation and reduces task workload in trainees: A preclinical trial
Authors: Dixon Benjamin J. , Daly Michael J. , Chan Harley , Vescan Allan , Witterick Ian J. , Irish Jonathan C.
Published: September 2011

Objectives/Hypothesis:

Our group has developed an augmented image guidance system that incorporates intraoperative cone‐beam computed tomography (CBCT), virtual or augmented displays, and image registration. We assessed the potential benefits of augmented endoscopy derived from this system for use during skull base navigation. Specifically, we wished to evaluate target localization accuracy and the effect on task workload and confidence.

Study Design:

Prospective, sequential, paired preclinical trial.

Methods:

A single cadaver head underwent computed tomography, and critical structures were contoured. The specimen was reimaged after endoscopic dissection and deformable registration allowed contours to be displayed on postablation CBCT imaging. A real‐time virtual view including anatomical contours was provided parallel to the real endoscopic image. Twelve subjects were asked to endoscopically localize seven skull base landmarks in a conventional manner. The same exercise was then performed with augmented endoscopy. Precise three‐dimensional (3D) localization was recorded with a tracked probe. The NASA task load index was completed after each exercise. A short questionnaire was also administered.

Results:

The real‐time augmented image guidance system aided localization in 85% of responses and increased confidence in 97%. There was a significant reduction in mental demand, effort, and frustration when the technology was employed, with an increase in perceived performance (P < .05). Three dimensional navigational precision was improved for all landmarks.

Conclusions:

Real‐time augmented image‐guided surgery increases accuracy and confidence in trainee surgeons and decreases task workload during skull base navigation. This technology shows great promise in assisting in skull base surgery even for experienced surgeons.
Conscious change leadership: Achieving breakthrough results
Authors: Anderson Dean , Anderson Linda Ackerman
Published: September 2011

To drive organizational change that is “wildly successful,” leaders should look beyond change management and project management, the authors say. They explain why “conscious change leadership” is the answer. They guide readers to understanding change within three focus areas: content, people, and process. Furthermore, there are three types of change facing today's leaders: developmental, transitional, and transformational. Strategies are presented for how to consciously navigate transformational change. This is important, because “your success will be in direct correlation to your level of awareness and worldview.”
Toxicology and risk assessment of acrolein in food
Authors: Abraham Klaus , Andres Susanne , Palavinskas Richard , Berg Katharina , Appel Klaus E. , Lampen Alfonso
Published: September 2011

Acrolein is an α,β‐unsaturated aldehyde formed by thermal treatment of animal and vegetable fats, carbohydrates and amino acids. In addition it is generated endogenously. As an electrophile, acrolein forms adducts with gluthathione and other cellular components and is therefore cytotoxic. Mutagenicity was shown in some in vitro tests. Acrolein forms different DNA adducts in vivo, but mutagenic and cancerogenous effects have not been demonstrated for oral exposure. In subchronic oral studies, local lesions were detected in the stomach of rats. Systemic effects have not been reported from basic studies. A WHO working group established a tolerable oral acrolein intake of 7.5 μg/kg body weight/day. Acrolein exposure via food cannot be assessed due to analytical difficulties and the lack of reliable content measurements. Human biomonitoring of an acrolein urinary metabolite allows rough estimates of acrolein exposure in the range of a few μg/kg body weight/day. High exposure could be ten times higher after the consumption of certain foods. Although the estimation of the dietary acrolein exposure is associated with uncertainties, it is concluded that a health risk seems to be unlikely.
Interaction of hydrated protons with octyl‐phenyl‐N,N‐diisobutylcarbamoylmethyl phosphine oxide (CMPO): NMR and theoretical study
Authors: Kříž Jaroslav , Dybal Jiří , Makrlík Emanuel , Vaňura Petr
Published: September 2011

Interaction of octyl‐phenyl‐N,N‐diisobutylcarbamoylmethylphosphine oxide (CMPO, the ‘classical’ rare metal extraction agent) with fully ionized hydrated protons (HP) was studied in acetonitrile‐d3 using 1H, 13C, 31P NMR, PFG NMR and magnetic relaxation. The experimental results were confronted with high‐precision ab initio DFT calculations. Relative chemical shifts of NMR signals of CMPO (0.01 mol/L) under the presence of HP in the molar ratio β = 0–2.0 mol/mol show binding between CMPO and HP. Self‐diffusion measurements using 1H PFG NMR demonstrate that larger complexes with higher content of CMPO are generally formed at β < 0.75. Analyzing the collective dependence of 13C and 31P NMR chemical shifts on β by the use of program LETAGROP, we obtained very good fitting for the assumed coexistence of two complexes (CMPO)2·HP (C2) and CMPO.HP (C1). The logarithms of the respective stabilization constants log Ki were found to be 7.518 (C2) and 4.581 (C1). The system dynamics was studied by measuring the transverse 1H NMR relaxation using CPMG sequence with varying delays tp between the π pulses in the mixtures with β = 0.4–0.8. The following exchange correlation times were obtained: τ10 = 2.35 × 10−5, τ20 = 0.82 × 10−4, τ21 = 0.45 × 10−3s. The DFT calculations support the conclusion that the complexes C1 and C2 are the main species in the mixtures of CMPO with HP. They also agree with the NMR and FTIR observation that the main site to which H3O+ is bound is the PO group, whereas the amide group does not form a strong bond with the ion when excess water molecules are present. Copyright © 2011 John Wiley & Sons, Ltd.
Formyl migration product of chanoclavine‐I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation
Authors: Xie Xiulan , Wallwey Christiane , Matuschek Marco , Steinbach Klaus , Li Shu‐Ming
Published: September 2011

A previous study showed that together with the festuclavine synthase FgaFS, the old yellow enzyme FgaOx3 from Aspergillus fumigatus catalyzed the conversion of chanoclavine‐I aldehyde to festuclavine in the biosynthesis of ergot alkaloids. In the absence of FgaFS, a mixture containing two compounds with a ratio of 7:3 was detected in the enzyme assay of FgaOx3. NMR experiments including (DQF)‐COSY, HSQC, HMBC and NOESY identified their structures as E/Z isomers of N‐methyl‐N‐[(5R,10R)‐10‐(2‐oxo‐propyl)‐2,4,5,10‐tetrahydrobenzo[cd]indol‐5‐yl]formamide and proved the migration of the formyl group at C‐8 in chanoclavine I‐aldehyde to N‐6 in the identified products. Copyright © 2011 John Wiley & Sons, Ltd.
Family involvement in small, local nongovernmental organizations
Authors: Jakimow Tanya
Published: September 2011

The involvement of family members in nongovernmental organizations (NGOs) has been largely overlooked in the literature on the nonprofit and voluntary sector. This study draws on the family business literature to explore the main features of family involvement and the implications for organizational survival and effectiveness. It shows that the family is an important research variable. Exploring the NGO sector in India, the article demonstrates that family involvement can significantly influence the management of human and material resources, governance, and decision making. Although there are several advantages to family involvement, a large overlap of family and organization can threaten credibility and legitimacy. Family‐based NGOs must stress their value orientation to counter negative perceptions.
Patients' experiences of seeking health care for lower urinary tract symptoms
Authors: Welch Lisa C. , Taubenberger Simone , Tennstedt Sharon L.
Published: September 2011

A gap between experiencing symptoms and receiving effective treatment persists for people with lower urinary tract symptoms (LUTS), even for those who seek health care. In order to better understand how patients experience treatment seeking for LUTS, we interviewed a racially diverse sample of 90 men and women with a range of LUTS about their experiences seeking care. Thematic analysis revealed that patients often disclosed urinary symptoms first to primary care providers during a general examination or a visit for another health problem. Patients seek provider assistance typically when symptoms have intensified or are causing worry, and a desire for treatment trumps potential embarrassment; among women patients, feeling comfortable with a provider also is important for disclosing LUTS. © 2011 Wiley Periodicals, Inc. Res Nurs Health 34:496–507, 2011
Determination of the amino acid sequence requirements for catalysis by the highly proficient orotidine monophosphate decarboxylase
Authors: Yuan Ji , Cardenas Ana Maria , Gilbert Hiram F. , Palzkill Timothy
Published: September 2011

Orotidine 5′‐monophosphate decarboxylase (ODCase) catalyzes the decarboxylation of orotidine 5′‐monophosphate to uridine 5′‐monophosphate during pyrimidine nucleotide biosynthesis. This enzyme is one of the most proficient known, exhibiting a rate enhancement of over 17 orders of magnitude over the uncatalyzed rate. An interesting question is whether the high proficiency of ODCase is associated with a highly optimized sequence of active site residues. This question was addressed by randomizing 24 residue positions in and around the active site of the E. coli ODCase (pyrF) by site‐directed mutagenesis. The libraries of mutants were selected for function from a multicopy plasmid or by single‐copy replacement at the pyrF locus on the E. coli chromosome. Stringent sequence requirements for function were found for the mutants expressed from the chromosomal pyrF locus. Six positions were not tolerant of substitutions and several others accepted very limited substitutions. In contrast, all positions could be substituted to some extent when the library mutants were expressed from a multicopy plasmid. For the conserved quartet of charged residues Lys44‐Asp71‐Lys73‐Asp76, a cysteine substitution was found to provide function at positions 71 and 76. A lower pKa for both cysteine mutants supports a mechanism whereby the thiolate group of cysteine substitutes for the negatively charged aspartate side chain. The partial function mutants such as D71C and D76C exhibit reduced catalytic efficiency relative to wild type but nevertheless provide a rate enhancement of 15 orders of magnitude over the uncatalyzed rate indicating the catalytic proficiency of the enzyme is robust and tolerant of mutation.
A structural study of Hypocrea jecorina Cel5A
Authors: Lee Toni M. , Farrow Mary F. , Arnold Frances H. , Mayo Stephen L.
Published: September 2011

Interest in generating lignocellulosic biofuels through enzymatic hydrolysis continues to rise as nonrenewable fossil fuels are depleted. The high cost of producing cellulases, hydrolytic enzymes that cleave cellulose into fermentable sugars, currently hinders economically viable biofuel production. Here, we report the crystal structure of a prevalent endoglucanase in the biofuels industry, Cel5A from the filamentous fungus Hypocrea jecorina. The structure reveals a general fold resembling that of the closest homolog with a high‐resolution structure, Cel5A from Thermoascus aurantiacus. Consistent with previously described endoglucanase structures, the H. jecorina Cel5A active site contains a primarily hydrophobic substrate binding groove and a series of hydrogen bond networks surrounding two catalytic glutamates. The reported structure, however, demonstrates stark differences between side‐chain identity, loop regions, and the number of disulfides. Such structural information may aid efforts to improve the stability of this protein for industrial use while maintaining enzymatic activity through revealing nonessential and immutable regions.
HLA‐DP2 binding prediction by molecular dynamics simulations
Authors: Doytchinova Irini , Petkov Peicho , Dimitrov Ivan , Atanasova Mariyana , Flower Darren R.
Published: September 2011

Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA‐DP, HLA‐DQ, and HLA‐DR. They are involved in many autoimmune diseases. In contrast to HLA‐DR and HLA‐DQ proteins, the X‐ray structure of the HLA‐DP2 protein has been solved quite recently. In this study, we have used structure‐based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA‐DP2‐peptide binding. A combinatorial library of 247 peptides was built using the “single amino acid substitution” approach and docked into the HLA‐DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard–Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard–Jones energies normalized over all positions for anchor residues only plus cross terms between anchor‐residues.
Temperature dependence of inner tube growth from ferrocene‐filled single‐walled carbon nanotubes
Authors: Liu Xianjie , Kuzmany Hans , Saito Takeshi , Pichler Thomas
Published: September 2011

The growth of inner tubes from ferrocene‐filled single‐walled carbon nanotubes was studied with Raman spectroscopy. Special attention was paid to inner tubes formation based on the annealing temperature and the outer tube diameter. Besides the presence of inner tubes radial breathing mode, a new Raman feature appears around 1250 cm−1, which is always related to the appearance of the inner tube. The thermal stability of the inner tube strongly depends on the outer tube diameter. The inner tube formed inside outer tube with 1 nm diameter is destructed at 1000 °C, but it can survive more than 1300 °C with outer tube diameter of about 1.6 nm. Furthermore, the splitting of G line and the shift of 2D line were discussed regarding to the appearance of inner tubes.
Contamination of silicon by iron at temperatures below 800 °C
Authors: Murphy J. D. , Falster R. J.
Published: September 2011

Iron‐related defects are deleterious in silicon‐based integrated circuits and photovoltaics, ruining devices and acting as strong recombination centres. Unless great care is taken, iron contamination will result from high temperature processing and so it is essential to understand the degree to which this can occur. Iron solubility data above ∼800 °C have been summarised by Istratov et al. (Appl. Phys. A 69, 13 (1999)), but many processes are performed at lower temperatures for which solubility data are scarce. We have studied iron contamination below ∼800 °C. Iron concentrations in intention‐ ally contaminated air‐annealed Czochralski silicon samples were determined from the change in minority carrier lifetime due to photodissociation of FeB pairs measured by quasi‐steady‐state photoconductance. In the ∼600 to 800 °C temperature range the iron concentration was found to vary according to $ 1.3 \times 10^{21} \; {\rm exp} \;\left (‐ { {1.8\;{\rm eV} } \over {kT} } \right)\;{\rm cm}^{‐3}. It is therefore the case that significantly more iron can dissolve in silicon at these temperatures than extrapolation of higher temperature data suggests, with the enhancement being by a factor of >20 at 600 °C. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A decoupled exponential random graph model for prediction of structure and attributes in temporal social networks
Authors: Ouzienko Vladimir , Guo Yuhong , Obradovic Zoran
Published: September 2011

The analysis of social networks often assumes time invariant scenario, while in practice actor attributes and links in such networks often evolve over time and are inextricably dependent on each other. In this article, we propose a new method to predict actor attributes and links in temporal networks. Our approach takes into account the attributes corresponding to the participating actors together with topological and structural changes of the network over time. This is achieved by building two conditional predictors to jointly infer links and actor attributes. The proposed prediction method was significantly more accurate than alternatives when evaluated on synthetic data sets and two well‐studied real‐life temporal social networks. In addition, the new algorithm is computationally more efficient than a related alternative scaling up linearly with the number of temporal observations and quadratically with the number of actors considered. © 2011 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 4: 470–486, 2011
A statistical model of signal–noise in scanning electron microscopy
Authors: Timischl F. , Date M. , Nemoto S.
Published: September 2011

A statistical model describing signal‐noise generation and development along the signal formation process in a standard scanning electron microscope (SEM) using an Everhart–Thornley secondary electron detector is derived. Noise in the detector signal is modeled to originate from a cascade of five signal conversion stages. Based on the derived model, general conclusions are drawn concerning the total signal‐to‐noise ratio (SNR) at each stage, and the influence of each stage on the total SNR of the detector signal. The model is furthermore applied to a real‐world SEM, and verified by experimental data. SCANNING 34: 137–144, 2012. © 2011 Wiley Periodicals, Inc.
Comparison of approaches for microscopic imaging of skin lymphatic vessels
Authors: Wu Xiufeng , Yu Zheyuan , Liu Ningfei
Published: September 2011

Assessment of skin lymphatic vessels is of great significance in understanding their roles in many pathological conditions. Our aim was to identify the optimal approach for investigation of cutaneous lymphatic system. We performed comparative studies on skin lymphatic vessels using immunohistochemistry of tissue sections, computer graphic reconstruction method together with immunohistochemically stained serial sections and whole mount fluorescence in human lower limb. Lymphatic vessels were identified with podoplanin antibody. The relative merits and drawbacks of each method in evaluation of structure, spatial organization, and distribution of cutaneous lymphatic vessels were described. Immunohistology of tissue sections enabled the investigation of the structure and distribution of the whole cutaneous lymphatic system in two‐dimensional slices, whereas three‐dimensional morphology of only the most superficial lymph capillary network immediately under the epidermis could be evaluated with the whole mount technique. Meanwhile, only little segmentation of skin lymphatic vessel from five immunohistochemically stained serial sections was reconstructed and evaluated due to expense and special skills required using computer graphic three‐dimensional reconstruction. Furthermore, a great number of artifacts and special skills required in its processes leaded to less accurate structure of skin lymphatic vessels. Our findings demonstrated that the use of either of the proposed techniques alone could not allow a comprehensive analysis of the skin lymphatic system due to their relative drawbacks. Combination of immunohistology of tissue sections and three‐dimensional whole‐mount preparations appears to be the best candidate for comprehensive evaluation of skin lymphatic system. SCANNING 34: 174–180, 2012. © 2011 Wiley Periodicals, Inc.
Real‐time noninvasive optical diagnosis for colorectal cancer using multiphoton microscopy
Authors: Ying Mingang , Zhuo Shuangmu , Chen Gang , Zhuo Changhua , Lu Jianping , Zhu Weifeng , Xie Shusen , Chen Jianxin , Yan Jun
Published: September 2011

In contrast to colonoscopy biopsy, which contains several disadvantages such as bleeding, sampling error, crush artifact, and time‐consuming pathological procedure, multiphoton microscopy (MPM) enables direct noninvasive visualization of tissue architecture and cell morphology in live tissues without the administration of exogenous contrast agents. We performed a proof‐of‐principle study to evaluate the feasibility of using MPM to make real‐time noninvasive optical diagnosis of colorectal cancer by investigating 30 fresh, unfixed, and unstained full‐thickness colorectal specimens. We found that MPM images demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphism in the cancerous tissues. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear‐cytoplasmic ratio, were clearly observed in MPM images, which were comparable to golden standard hematoxylin‐eosin staining images. Our findings showed that MPM had the potential to make real‐time noninvasive optical diagnosis of colorectal cancer. With miniaturization and integration of colonoscopy, MPM has a promising future in real‐time noninvasive “optical biopsy” for colorectal cancer. SCANNING 34: 181–185, 2012. © 2011 Wiley Periodicals, Inc.