bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute toxicity and tissue distribution of CdSe/CdS‐MPA quantum dots after repeated intraperitoneal injection to mice
Authors: Haque Md. Mamunul , Im Hye‐Yeon , Seo Ji‐Eun , Hasan Mahbub , Woo Kyoungja , Kwon Oh‐Seung
Published: June 2012

Quantum dots (QDs) are novel tools with multiple biological and medical applications because of their superior photoemission and photostability characteristics. However, leaching of toxic metals from QDs is of great concern. Therefore, for the successful application of QDs in bioscience, it is essential to understand their biological fate and toxicity. We investigated toxicological effects and tissue distribution of mercaptopropionic acid‐conjugated cadmium selenide/cadmium sulfide (CdSe/CdS‐MPA) QDs after repeated intraperitoneal injection into BALB/c mice. The mice were injected every 3 days with various doses of QDs (0, 5, 10 and 25 mg kg−1). The subsequent effects of QDs on plasma levels of various biomarkers were evaluated at different time points (at 0, 1, 4, 7, 10, 13 and 15 days). Various tissue samples (spleen, liver, lung, kidneys, brain, heart and thymus) were collected for toxicity analysis, distribution testing, histopathological examination and inflammation assessment. No abnormal clinical signs or behaviors were recorded but the body weight of mice treated with 25 mg kg−1 QDs was significantly decreased from day 7 compared with control mice. QDs were observed in the liver, spleen, lung and kidneys, but not in brain or heart. Significantly higher levels of lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase were found in the plasma, liver and spleen. Histopathological examination did not show any tissue toxicity but the levels of interleukin‐6, a pro‐inflammatory marker, were increased in the plasma, liver and spleen. All of these findings provide insight into the observed toxicological effect levels and tissue‐specific distribution of CdSe/CdS‐MPA QDs. Copyright © 2012 John Wiley & Sons, Ltd.
DNA base stacking: The stacked uracil/uracil and thymine/thymine minima
Authors: Hunter Ruairidh S. , van Mourik Tanja
Published: June 2012

The potential energy surfaces of stacked uracil dimer (U/U) and stacked thymine dimer (T/T) have been explored at the counterpoise (CP)‐corrected M06‐2X/6‐31+G(d) level of theory, in the gas phase and in solution (with water and, for U/U, 1,4‐dioxane as the solvents) modeled by a continuum solvent using the polarizable continuum model. Potential energy scans were created by rotation of one monomer around its center‐of‐mass, whereas the other monomer remained still. Both face‐to‐back (one molecule exactly on top of the other) and face‐to‐face (one base molecule flipped by 180°) structures were considered. Five or six (dependent on whether CP correction is included or not) stacked uracil dimer minima and six stacked thymine dimer minima were located. A number of transition states on the U/U and T/T potential energy surfaces were likewise identified. The general effect of the continuum solvent is a flattening of the potential energy surface. Comparison of the gas‐phase M06‐2X/6‐31+G(d) U/U interaction energies with estimated CCSD(T)/complete basis set values (where available) show the excellent performance of this functional for stacking energies. © 2012 Wiley Periodicals, Inc.
Core competency review: Aortic stenosis and noncardiac surgery
Authors: Wright Douglas E. , Hunt Daniel P.
Published: June 2012

Aortic stenosis (AS) poses a risk of adverse cardiac events for patients undergoing surgical procedures. Perioperative mortality for patients with severe AS is as high as 14%. This review examines the accuracy of the history and physical examination in detecting AS and, subsequently, in assessing severity. The utility of echocardiography is addressed, and the relevant pathophysiology of AS is summarized. We also summarize what is known about perioperative risk for patients with AS. Journal of Hospital Medicine 2012;. © 2012 Society of Hospital Medicine
Strength in adversity: The influence of psychological capital on job search
Authors: Chen Don J. Q. , Lim Vivien K. G.
Published: June 2012

This study examined the influence of psychological capital on job search among displaced employees. On the basis of a sample of 179 retrenched professionals, managers, executives, and technicians, we found that psychological capital (self‐efficacy, hope, optimism, and resilience) was positively related with displaced employees' level of perceived employability, a coping resource. Perceived employability was positively related with problem‐focused and symptom‐focused coping strategies. Whereas problem‐focused coping was positively related with preparatory and active job search, symptom‐focused coping strategy was not. The relationship between psychological capital and preparatory and active job search was mediated by perceived employability and problem‐focused coping. Implications of our findings are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Treadmill running upregulates the expression of acetylcholine receptor in rat gastrocnemius following botulinum toxin A injection
Authors: Tsai Sen‐Wei , Tung Yu‐Tang , Chen Hsiao‐Ling , Shen Chih‐Jie , Chuang Chia‐Hui , Tang Ting‐Yu , Chen Chuan‐Mu
Published: June 2012

Treadmill running is a commonly used training method for patients with spasticity to improve functional performance. Botulinum toxin has been widely used therapeutically to reduce contraction force of spastic muscle. However, the effects of treadmill running in neuromuscular junction expression and motor unit physiology on muscle following botulinum toxin injection are not well established. To assess the effects of treadmill running on neuromuscular recovery of gastrocnemius following botulinum toxin A (BoNT‐A) injection, we observed changes in gene expression. We hypothesized that the expression of acetylcholine receptor (AChR), myogenesis, and nerve plasticity could be enhanced. Twenty‐four Sprague–Dawley rats received botulinum toxin injection in right gastrocnemius and were then randomly assigned into untrained control and treadmill running groups. The rats assigned to the treadmill running group were trained on a treadmill 3 times/week with a running speed of 15 m/min for 8 weeks. The duration of training was 20 min per session. Muscle strength and gene expression of AChR subunit (α, β, δ, γ, and ε), MyoD, Myf‐5, MRF4, myogenin, p21, IGF‐1, GAP43, were analyzed. Treadmill running had no influence on gastrocnemius mass, but improved the maximal contraction force of the gastrocnemius in the treadmill running group (p < 0.05). Upregulation of GAP‐43, IGF‐1, Myo‐D, Myf‐5, myogenin, and AChR subunits α and β were found following treadmill running. The expression of genes associated with neurite and AChR regeneration following treadmill exercise was upregulated, which may have contributed to enhanced recovery of gastrocnemius strength. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:125–131, 2012
Job Embeddedness as a Moderator of the Impact of Organisational Justice on Turnover Intentions: a Study in Iran
Authors: Karatepe Osman M. , Shahriari Safoora
Published: June 2012

The purpose of this study was to examine job embeddedness as a moderator of the effects of distributive, procedural and interactional justice on turnover intentions. This study also investigated the relationship between the aforementioned justice dimensions and turnover intentions. Data were gathered from a sample of full‐time frontline hotel employees with a time lag of 2 weeks in Iran. The results demonstrated that the negative effects of distributive, procedural and interactional justice on turnover intentions were stronger among frontline employees with high levels of job embeddedness. The results further revealed that these justice dimensions had negative relationships with turnover intentions. Copyright © 2012 John Wiley & Sons, Ltd.
Modified Hyaluronan Hydrogels Support the Maintenance of Mouse Embryonic Stem Cells and Human Induced Pluripotent Stem Cells
Authors: Liu Yongxing , Charles Lyndon F. , Zarembinski Thomas I. , Johnson Kalle I. , Atzet Sarah K. , Wesselschmidt Robin L. , Wight Mark E. , Kuhn Liisa T.
Published: June 2012

These studies provide evidence for the ability of a commercially available, defined, hyaluronan‐gelatin hydrogel, HyStem‐C™, to maintain both mouse embryonic stem cells (mESCs) and human induced pluripotent stem cells (hiPSCs) in culture while retaining their growth and pluripotent characteristics. Growth curve and doubling time analysis show that mESCs and hiPSCs grow at similar rates on HyStem‐C™ hydrogels and mouse embryonic fibroblasts and Matrigel™, respectively. Immunocytochemistry, flow cytometry, gene expression and karyotyping reveal that both human and murine pluripotent cells retain a high level of pluripotency on the hydrogels after multiple passages. The addition of fibronectin to HyStem‐C™ enabled the attachment of hiPSCs in a xeno‐free, fully defined medium.

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Rapid eye movement sleep behavior disorder and subtypes of Parkinson's disease
Authors: Romenets Silvia Rios , Gagnon Jean‐Francois , Latreille Véronique , Panniset Michel , Chouinard Sylvain , Montplaisir Jacques , Postuma Ronald B.
Published: June 2012

Numerous studies have explored the potential relationship between rapid eye movement sleep behavior disorder (RBD) and manifestations of PD. Our aim was to perform an expanded extensive assessment of motor and nonmotor manifestations in PD to identify whether RBD was associated with differences in the nature and severity of these manifestations. PD patients underwent polysomnography (PSG) to diagnose the presence of RBD. Participants then underwent an extensive evaluation by a movement disorders specialist blinded to PSG results. Measures of disease severity, quantitative motor indices, motor subtypes, therapy complications, and autonomic, psychiatric, visual, and olfactory dysfunction were assessed and compared using regression analysis, adjusting for disease duration, age, and sex. Of 98 included patients, 54 had RBD and 44 did not. PD patients with RBD were older (P = 0.034) and were more likely to be male (P < 0.001). On regression analysis, the most consistent links between RBD and PD were a higher systolic blood pressure (BP) change while standing (−23.9 ± 13.9 versus −3.5 ± 10.9; P < 0.001), a higher orthostatic symptom score (0.89 ± 0.82 versus 0.44 ± 0.66; P = 0.003), and a higher frequency of freezing (43% versus14%; P = 0.011). A systolic BP drop >10 could identify PD patients with RBD with 81% sensitivity and 86% specificity. In addition, there was a probable relationship between RBD and nontremor predominant subtype of PD (P = 0.04), increased frequency of falls (P = 0.009), and depression (P = 0.009). Our results support previous findings that RBD is a multifaceted phenomenon in PD. Patients with PD who have RBD tend to have specific motor and nonmotor manifestations, especially orthostatic hypotension. © 2012 Movement Disorder Society
Re‐evaluating the paradigm of early free flap coverage in lower extremity trauma
Authors: Hill J. Bradford , Vogel Jeffrey E. , Sexton Kevin W. , Guillamondegui Oscar D. , Corral Gabriel A. Del , Shack R. Bruce
Published: June 2012

Early free flap coverage in lower extremity trauma is a practice largely supported by research that may be outdated and is frequently impractical due to logistics, resuscitation efforts, and associated injuries. Our objective was to re‐evaluate this paradigm to determine whether reconstructive timing impacts outcome in modern clinical practice. We reviewed 60 free flaps for traumatic lower extremity coverage from December 2005 to December 2010 by the plastic surgery service at an academic medical center. All reconstructions were >72‐hours from injury, spanning from 3 days to 2.2 years. The overall failure rate was 13.3% (8/60). Statistical analysis yielded no significant associations between reconstructive timing and flap failure or morbidity, although there was a trend toward fewer failures among latest reconstructions (>91 days) compared to within 30 days (P = 0.053). These findings support that delays may be safely utilized to allow patient and wound optimization without negatively impacting outcomes in free tissue transfer. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.
T2*‐relaxivity contrast imaging: First results
Authors: Sourbron Steven , Heilmann Melanie , Walczak Christine , Vautier Julien , Schad Lothar R. , Volk Andreas
Published: June 2012

In this study, T2*‐ relaxivity contrast imaging (RCI) is proposed for new contrast generation in MRI. The method produces images of relaxivities r*2,vasc and r*2,EES caused by susceptibility gradients across the vessel walls and cell membranes, respectively. The sensitivity to noise was assessed with a simulation study, and initial results are presented for five colorectal tumor xenografts in nude mice. Simulations show that the new relaxivity parameters are at least as accurate and precise as standard parameters such as plasma volume and interstitial volume. Mean values of both relaxivities were significantly different (r*2,vasc = 10.9 ± 2.9 mM−1 s−1 and r*2,EES = 15.6 ± 2.6 mM−1 s−1). r*2,vasc (r = 0.67) and r*2,EES (r = 0.52) were weakly correlated with plasma volume and interstitial volume, respectively. Images of r*2,vasc and r*2,EES reveal a different tumor structure than plasma volume and interstitial volume maps. These results suggest that relaxivity contrast imaging is practically feasible and might offer supplementary information compared to dynamic contrast‐enhanced‐MRI. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
A Retrospective study of complications of therapeutic plasma exchange in myasthenia
Authors: Guptill Jeffrey T. , Oakley Darlene , Kuchibhatla Maragatha , Guidon Amanda C. , Hobson‐Webb Lisa D. , Massey Janice M. , Sanders Donald B. , Juel Vern C.
Published: June 2012

Introduction:

Venous access for therapeutic plasma exchange (TPE) in myasthenia gravis (MG) can be achieved by central venous catheters (CVC) or peripheral veins (PV), and the preferred method varies among providers. We evaluated our institutional experience with TPE venous access method and complications.

Methods:

We reviewed all TPE‐treated MG patients (2005–2010) through blinded chart review. TPE complications were categorized as serious or minor. Serious complications ended the procedure and/or were potentially life‐threatening.

Results:

A total of 134 MG patients received 230 TPE courses; 56% were outpatient procedures. Whenever feasible, TPE was performed by PV access, which was successful in 75% of courses. Over 90% in both groups improved after TPE. Compared with PV access, CVCs were associated with more total (68% vs. 35%) and serious complications (41% vs. 4%), including 2 deaths.

Conclusions:

PV access for TPE can be used successfully in most MG patients and may reduce morbidity of the procedure. Muscle Nerve, 2013
Evaluating dermal myelinated nerve fibers in skin biopsy
Authors: Myers M. Iliza , Peltier Amanda C. , Li Jun
Published: June 2012

Although there has been extensive research on small, unmyelinated fibers in the skin, little research has investigated dermal myelinated fibers in comparison. Glabrous, nonhairy skin contains mechanoreceptors that afford a vantage point for observation of myelinated fibers that have previously been seen only with invasively obtained nerve biopsies. This review discusses current morphometric and molecular expression data of normative and pathogenic glabrous skin obtained by various processing and analysis methods for cutaneous myelinated fibers. Recent publications have shed light on the role of glabrous skin biopsy in identifying signs of peripheral neuropathy and as a potential biomarker of distal myelin and mechanoreceptor integrity. The clinical relevance of a better understanding of the role of dermal myelinated nerve terminations in peripheral neuropathy will be addressed in light of recent publications in the growing field of skin biopsy. Muscle Nerve, 2013
A dynamic two‐phase flow model for air sparging
Authors: Gao Shengyan , Meegoda Jay N. , Hu Liming
Published: June 2012

Air sparging (AS) is anin situsoil/groundwater remediation technology, which involves the injection of pressurized air/oxygen through an air sparging well below the zone of contamination. Characterizing the mechanisms governing movement of air through saturated porous media is critical for the design of an effective cleanup treatment system. In this research, micromechanical investigation was performed to understand the physics of air migration and subsequent spatial distribution of air at pore scale during air sparging. The void space in the porous medium was first characterized by pore network consisting of connected pore bodies and bonds. The biconical abscissa asymmetric concentric bond was used to describe the connection between two adjacent pore bodies. Then a rule‐based dynamic two‐phase flow model was developed and applied to the pore network model. A forward integration of time was performed using the Euler scheme. For each time step, the effective viscosity of the fluid was calculated based on fractions of two phases in each bond, and capillary pressures across the menisci was considered to compute the pressure field. The developed dynamic model was used to study the rate‐dependent drainage during air sparging. The effect of the capillary number and geometrical properties of the network on the dynamic flow properties of two‐phase flow including residual saturation, spatial distribution of air and water, dynamic phase transitions, and relative permeability‐capillary pressure curves were systematically investigated. Results showed that all the above information for describing the air water two‐phase flow are not intrinsic properties of the porous medium but are affected by the two‐phase flow dynamics and spatial distribution of each phase, providing new insight to air sparging. Copyright © 2012 John Wiley & Sons, Ltd.
Cellular ageing, increased mortality and FTLD‐TDP‐associated neuropathology in progranulin knockout mice
Authors: Wils Hans , Kleinberger Gernot , Pereson Sandra , Janssens Jonathan , Capell Anja , Van Dam Debby , Cuijt Ivy , Joris Geert , De Deyn Peter P , Haass Christian , Van Broeckhoven Christine , Kumar‐Singh Samir
Published: June 2012

Loss‐of‐function mutations in progranulin (GRN) are associated with frontotemporal lobar degeneration with intraneuronal ubiquitinated protein accumulations composed primarily of hyperphosphorylated TDP‐43 (FTLD‐TDP). The mechanism by which GRN deficiency causes TDP‐43 pathology or neurodegeneration remains elusive. To explore the role of GRN in vivo, we established Grn knockout mice using a targeted genomic recombination approach and Cre‐LoxP technology. Constitutive Grn homozygous knockout (Grn−/−) mice were born in an expected Mendelian pattern of inheritance and showed no phenotypic alterations compared to heterozygous (Grn+/−) or wild‐type (Wt) littermates until 10 months of age. From then, Grn−/− mice showed reduced survival accompanied by significantly increased gliosis and ubiquitin‐positive accumulations in the cortex, hippocampus, and subcortical regions. Although phosphorylated TDP‐43 could not be detected in the ubiquitinated inclusions, elevated levels of hyperphosphorylated full‐length TDP‐43 were recovered from detergent‐insoluble brain fractions of Grn−/− mice. Phosphorylated TDP‐43 increased with age and was primarily extracted from the nuclear fraction. Grn−/− mice also showed degenerative liver changes and cathepsin D‐positive foamy histiocytes within sinusoids, suggesting widespread defects in lysosomal turnover. An increase in insulin‐like growth factor (IGF)‐1 was observed in Grn−/− brains, and increased IGF‐1 signalling has been associated with decreased longevity. Our data suggest that progranulin deficiency in mice leads to reduced survival in adulthood and increased cellular ageing accompanied by hyperphosphorylation of TDP‐43, and recapitulates key aspects of FTLD‐TDP neuropathology. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Characterization of the timing and prevalence of receptor tyrosine kinase expression changes in oesophageal carcinogenesis
Authors: Paterson Anna L , O'Donovan Maria , Provenzano Elena , Murray Liam J , Coleman Helen G , Johnson Brian T , McManus Damian T , Novelli Marco , Lovat Laurence B , Fitzgerald Rebecca C
Published: June 2012

Despite being common in epithelial malignancies, the timing of receptor tyrosine kinase (RTK) up‐regulation is poorly understood and therefore hampers the identification of the receptor to target for effective treatment. We aimed to determine if RTK expression changes were early events in carcinogenesis. Oesophageal adenocarcinoma and its pre‐invasive lesion, Barrett's oesophagus, were used for immunohistochemical analysis of the RTK panel, EGFR, ErbB2, ErbB3, Met, and FGFR2, by utilizing a cohort of patients with invasive disease ($n = 367$) and two cohorts with pre‐invasive disease, one cross‐sectional ($n = 110$) and one longitudinal in time ($n = 91$). The results demonstrated that 51% of oesophageal adenocarcinomas overexpressed at least one of the RTK panel, with 21% of these overexpressing multiple receptors. Up‐regulation of RTK expression was an early event corresponding with low‐grade dysplasia development (25% in areas without dysplasia versus 63% in low‐grade dysplasia, $p < 0.001$). There was a trend for an increase in the prevalence of concomitant overexpression of multiple receptors as intestinal metaplasia progressed to low‐grade dysplasia, 7% versus 10%; and from low‐grade dysplasia to high‐grade dysplasia, 10% versus 19% ($p = 0.06$ and 0.24, respectively). The timing of receptor up‐regulation varied; FGFR, ErbB2, and Met overexpression occurred as dysplasia first developed, whilst EGFR overexpression was predominately seen in invasive disease and ErbB3 overexpression was uniformly rare. We provide evidence for a frequent and early role for multiple different RTKs in oesophageal carcinogenesis. Given the early timing of receptor deregulation, inhibiting RTKs in pre‐invasive disease may also represent a novel and effective chemopreventive strategy. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Endoplasmic reticulum stress disrupts placental morphogenesis: implications for human intrauterine growth restriction
Authors: Yung Hong wa , Hemberger Myriam , Watson Erica D , Senner Claire E , Jones Carolyn P , Kaufman Randal J , Charnock‐Jones D Stephen , Burton Graham J
Published: June 2012

We recently reported the first evidence of placental endoplasmic reticulum (ER) stress in the pathophysiology of human intrauterine growth restriction. Here, we used a mouse model to investigate potential underlying mechanisms. Eif2s1tm1RjK mice, in which Ser51 of eukaryotic initiation factor 2 subunit alpha (eIF2α) is mutated, display a 30% increase in basal translation. In Eif2s1tm1RjK placentas, we observed increased ER stress and anomalous accumulation of glycoproteins in the endocrine junctional zone (Jz), but not in the labyrinthine zone where physiological exchange occurs. Placental and fetal weights were reduced by 15% (97 mg to 82 mg, p < 0.001) and 20% (1009 mg to 798 mg, p < 0.001), respectively. To investigate whether ER stress affects bioactivity of secreted proteins, mouse embryonic fibroblasts (MEFs) were derived from Eif2s1tm1RjK mutants. These MEFs exhibited ER stress, grew 50% slower, and showed reduced Akt–mTOR signalling compared to wild‐type cells. Conditioned medium (CM) derived from Eif2s1tm1RjK MEFs failed to maintain trophoblast stem cells in a progenitor state, but the effect could be rescued by exogenous application of FGF4 and heparin. In addition, ER stress promoted accumulation of pro‐Igf2 with altered glycosylation in the CM without affecting cellular levels, indicating that the protein failed to be processed after release. Igf2 is the major growth factor for placental development; indeed, activity in the Pdk1–Akt–mTOR pathways was decreased in Eif2s1tm1RjK placentas, indicating loss of Igf2 signalling. Furthermore, we observed premature differentiation of trophoblast progenitors at E9.5 in mutant placentas, consistent with the in vitro results and with the disproportionate development of the labyrinth and Jz seen in placentas at E18.5. Similar disproportion has been reported in the Igf2‐null mouse. These results demonstrate that ER stress adversely affects placental development, and that modulation of post‐translational processing, and hence bioactivity, of secreted growth factors contributes to this effect. Placental dysmorphogenesis potentially affects fetal growth through reduced exchange capacity. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sex, Power, and Money: Prediction from the Dark Triad and Honesty–Humility
Authors: Lee Kibeom , Ashton Michael C. , Wiltshire Jocelyn , Bourdage Joshua S. , Visser Beth A. , Gallucci Alissa
Published: June 2012

Data were collected from two undergraduate student samples to examine (i) the relations of the ‘Dark Triad’ variables (Machiavellianism, Psychopathy, and Narcissism) with the HEXACO personality dimensions, as well as (ii) the ability of the aforementioned characteristics and of the Big Five personality factors to predict outcome variables related to sex, power, and money. Results indicated that the common variance of the Dark Triad was very highly correlated with low Honesty–Humility and that the unique variance of each of the Dark Triad variables also showed theoretically meaningful relations with the other five HEXACO factors. Furthermore, the Dark Triad and Honesty–Humility were strong predictors of three domains of outcome variables—Sex (short–term mating tendencies and sexual quid pro quos), Power (Social Dominance Orientation and desire for power), and Money (conspicuous consumption and materialism)—that were not well predicted by the dimensions of the Big Five. Copyright © 2012 John Wiley & Sons, Ltd.
Supportive care needs in newly diagnosed oral cavity cancer patients receiving radiation therapy
Authors: Chen Shu‐Ching , Lai Yeur‐Hur , Liao Chun‐Ta , Chang Joseph Tung‐Chien , Lin Chien‐Yu , Fan Kang‐Hsing , Huang Bing‐Shen
Published: June 2012

Objective

This study aimed to examine changes in physical symptom severity, functional status, supportive care needs, and related factors in oral cavity cancer patients during 6 months after beginning radiation therapy (RT) or concurrent chemotherapy and radiation therapy (CCRT).

Methods

A prospective longitudinal study was conducted involving oral cavity cancer patients from an RT clinic at a medical center in northern Taiwan. Patients were assessed for supportive care needs and physical symptoms at five time points: before the beginning of RT or CCRT and at 1, 2, 3, and 6 months after beginning RT or CCRT. The generalized estimating equation was used to identify predictors of overall needs as well as six specific dimensions of needs.

Results

A total of 82 patients completed the 6 months of follow‐up. Patients had moderate to high levels of supportive care needs over the 6 months. Although the highest information need was at the pretreatment phase, in general, the peak for overall and individual care needs was at 2 months since first receiving RT or CCRT. Patients without religious beliefs as well as those with higher educational level, functional level, overall physical symptom severity, and baseline anxiety reported more supportive care needs. Anxiety level before treatment was the most common factor across most supportive care needs. Individual physical symptoms, including fatigue, swallowing difficulty, and oral mucositis, were significantly related to higher physical and daily living needs.

Conclusions

A systematic clinical assessment to detect patients' care needs is necessary to improve the provision of timely cancer care and meet patients' healthcare needs. Copyright © 2012 John Wiley & Sons, Ltd.
Designing redox potential‐controlled protein switches based on mutually exclusive proteins
Authors: Peng Qing , Kong Na , Wang Hui‐Chuan Eileen , Li Hongbin
Published: June 2012

Synthetic/artificial protein switches provide an efficient means of controlling protein functions using chemical signals and stimuli. Mutually exclusive proteins, in which only the host or guest domain can remain folded at a given time owing to conformational strain, have been used to engineer novel protein switches that can switch enzymatic functions on and off in response to ligand binding. To further explore the potential of mutually exclusive proteins as protein switches and sensors, we report here a new redox‐based approach to engineer a mutually exclusive folding‐based protein switch. By introducing a disulfide bond into the host domain of a mutually exclusive protein, we demonstrate that it is feasible to use redox potential to switch the host domain between its folded and unfolded conformations via the mutually exclusive folding mechanism, and thus switching the functionality of the host domain on and off. Our study opens a new and potentially general avenue that uses mutually exclusive proteins to design novel switches able to control the function of a variety of proteins.
Use of the novel technique of analytical ultracentrifugation with fluorescence detection system identifies a 77S monosomal translation complex
Authors: Wang Xin , Zhang Chongxu , Chiang Yueh‐Chin , Toomey Shaun , Power Matthew P. , Granoff Mitchell E. , Richardson Roy , Xi Wen , Lee Darren J. , Chase Susan , Laue Thomas M. , Denis Clyde L.
Published: June 2012

A fundamental problem in proteomics is the identification of protein complexes and their components. We have used analytical ultracentrifugation with a fluorescence detection system (AU‐FDS) to precisely and rapidly identify translation complexes in the yeast Saccharomyces cerevisiae. Following a one‐step affinity purification of either poly(A)‐binding protein (PAB1) or the large ribosomal subunit protein RPL25A in conjunction with GFP‐tagged yeast proteins/RNAs, we have detected a 77S translation complex that contains the 80S ribosome, mRNA, and components of the closed‐loop structure, eIF4E, eIF4G, and PAB1. This 77S structure, not readily observed previously, is consistent with the monosomal translation complex. The 77S complex abundance decreased with translational defects and following the stress of glucose deprivation that causes translational stoppage. By quantitating the abundance of the 77S complex in response to different stress conditions that block translation initiation, we observed that the stress of glucose deprivation affected translation initiation primarily by operating through a pathway involving the mRNA cap binding protein eIF4E whereas amino acid deprivation, as previously known, acted through the 43S complex. High salt conditions (1M KCl) and robust heat shock acted at other steps. The presumed sites of translational blockage caused by these stresses coincided with the types of stress granules, if any, which are subsequently formed.
Protein flexibility is key to cisplatin crosslinking in calmodulin
Authors: Li Huilin , Wells Stephen A. , Jimenez‐Roldan J. Emilio , Römer Rudolf A. , Zhao Yao , Sadler Peter J. , O'Connor Peter B.
Published: June 2012

Chemical crosslinking in combination with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) has significant potential for studying protein structures and protein–protein interactions. Previously, cisplatin has been shown to be a crosslinker and crosslinks multiple methionine (Met) residues in apo‐calmodulin (apo‐CaM). However, the inter‐residue distances obtained from nuclear magnetic resonance structures are inconsistent with the measured distance constraints by crosslinking. Met residues lie too far apart to be crosslinked by cisplatin. Here, by combining FTICR MS with a novel computational flexibility analysis, the flexible nature of the CaM structure is found to be key to cisplatin crosslinking in CaM. It is found that the side chains of Met residues can be brought together by flexible motions in both apo‐CaM and calcium‐bound CaM (Ca4‐CaM). The possibility of cisplatin crosslinking Ca4‐CaM is then confirmed by MS data. Therefore, flexibility analysis as a fast and low‐cost computational method can be a useful tool for predicting crosslinking pairs in protein crosslinking analysis and facilitating MS data analysis. Finally, flexibility analysis also indicates that the crosslinking of platinum to pairs of Met residues will effectively close the nonpolar groove and thus will likely interfere with the binding of CaM to its protein targets, as was proved by comparing assays for cisplatin‐modified/unmodified CaM binding to melittin. Collectively, these results suggest that cisplatin crosslinking of apo‐CaM or Ca4‐CaM can inhibit the ability of CaM to recognize its target proteins, which may have important implications for understanding the mechanism of tumor resistance to platinum anticancer drugs.
Simplified proteomics approach to discover protein–ligand interactions
Authors: Chang Youngil , Schlebach Jonathan P. , VerHeul Ross A. , Park Chiwook
Published: June 2012

Identifying targets of biologically active small molecules is an essential but still challenging task in drug research and chemical genetics. Energetics‐based target identification is an approach that utilizes the change in the conformational stabilities of proteins upon ligand binding in order to identify target proteins. Different from traditional affinity‐based capture approaches, energetics‐based methods do not require any labeling or immobilization of the test molecule. Here, we report a surprisingly simple version of energetics‐based target identification, which only requires ion exchange chromatography, SDS PAGE, and minimal use of mass spectrometry. The complexity of a proteome is reduced through fractionation by ion exchange chromatography. Urea‐induced unfolding of proteins in each fraction is then monitored by the significant increase in proteolytic susceptibility upon unfolding in the presence and the absence of a ligand. Proteins showing a different degree of unfolding with the ligand are identified by SDS PAGE followed by mass spectrometry. Using this approach, we identified ATP‐binding proteins in the Escherichia coli proteome. In addition to known ATP‐binding proteins, we also identified a number of proteins that were not previously known to interact with ATP. To validate one such finding, we cloned and purified phosphoglyceromutase, which was not previously known to bind ATP, and confirmed that ATP indeed stabilizes this protein. The combination of fractionation and pulse proteolysis offers an opportunity to investigate protein–drug or protein–metabolite interactions on a proteomic scale with minimal instrumentation and without modification of a molecule of interest.
The meteorology of Black Saturday
Authors: Engel Chermelle B. , Lane Todd P. , Reeder Michael J. , Rezny Michael
Published: June 2012

The meteorological conditions are investigated over the state of Victoria, Australia on 7 February 2009, the day of the ‘Black Saturday’ fires. Daytime temperatures exceeding 45°C, strong surface winds and extremely dry conditions combined to produce the worst fire weather conditions on record. A high‐resolution nested simulation with the UK Met Office Unified Model and available observations are used to identify the important mesoscale features of the day. The highest resolution domain has horizontal grid spacing of 444 m and reproduces most aspects of the observed meteorological conditions. These include organized horizontal convective rolls, a strong late‐afternoon cool change with many of the characteristics of an unsteady gravity current, a weaker late‐evening cold front and propagating nocturnal bores. These mesoscale phenomena introduce variability in the winds, temperature and humidity at short temporal and spatial scales, which in turn lead to large spatial and temporal variability in fire danger. Copyright © 2012 Royal Meteorological Society
Tight upper tail bounds for cliques
Authors: DeMarco Robert , Kahn Jeff
Published: June 2012

With ξk =ξ the number of copies of Kk in the usual (Erdős‐Rényi) random graph G(n,p), p ≥ n‐2/(k‐1) and η > 0, we show when k > 1

This is tight up to the value of the constant in the exponent. © 2012 Wiley Periodicals, Inc. Random Struct. Alg., 2012
Efficient pairing‐free provably secure identity‐based proxy blind signature scheme
Authors: Tan Zuowen
Published: June 2012

In a proxy signature scheme, an original signer delegates her signing capability to a proxy signer who generates a signature on message on behalf of the original signer. By the combination of a blind signature with a proxy signature, the proxy signer can produce a proxy blind signature on message. Identity‐based public key cryptosystem has an efficient key management as compared with certificate‐based public key settings. In this paper, we propose an efficient identity‐based pairing‐free proxy blind signature scheme. The proxy blind signature scheme is provably secure upon the discrete logarithm assumptions in the random oracle model. Compared with other proxy blind signature schemes in the literature, the proposed proxy blind signature scheme is more efficient. Copyright © 2012 John Wiley & Sons, Ltd.
High dynamic range isotope ratio measurements using an analog electron multiplier
Authors: Williams P. , Lorincik J. , Franzreb K. , Hervig R. L.
Published: June 2012

We have explored measurement and accuracy issues in the use of an electron multiplier detector as a fast analog amplifier rather than in pulse‐counting mode. The electron multiplier on a Cameca IMS 3f instrument was modified to allow both analog and digital signals to be recorded simultaneously. The digital signal was picked up on the last dynode and the analog signal was recorded at the anode (operated near ground potential). The digital signal was differentiated to convert the positive pulse at the last dynode to a negative‐going signal that could be processed by the digital electronics of the IMS 3f and fed into the pulse counting system. The analog signal was amplified by an operational amplifier with a 106 ohm feedback resistor and the resulting signal was fed into the voltage/frequency convertor that normally processes the electrometer output from the Faraday cup collector. Isotope ratio measurements were explored for negative ion signals of the silicon and sulfur isotopes under Cs+ primary ion bombardment. For 32S and 34S signals of ~ 3 × 107 and ~ 1.3 × 106 counts/s respectively and 1 s counting times for each isotope, the standard deviations of the means of 140 ratio measurements averaged 0.3 per mil. Measurements on two sulfide samples with isotope ratios previously determined to differ by 13.6 per mil were within 1.2 ± 0.5 per mil of the previous difference value. Sources of residual error are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Time‐of‐flight SIMS depth profiling of Na in SiO2 glass using C60 sputter ion beam
Authors: Kobayashi Daisuke , Yamamoto Yuichi , Isemura Tsuguhide
Published: June 2012

A depth profile analysis of SiO2 glass ion implanted with 23Na+ was carried out on a time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) with OX, Cs and buckminsterfullerene (C60) ion sputtering. The Na migration in SiO2 glass during both analysis process and sputter process was investigated under the various operating conditions. During the analysis process, 23Na+ intensity stayed constant on the dose density of the Bi primary ion regardless of the conditions and went up using higher primary ion current. The Na profile in SiO2 glass similar to that of the Lindard–Scharff–Schiott theory was successfully acquired by the use of C60 ion sputtering regardless of the operating conditions. It is considered that Na does not migrate during the sputter process with C60 sputter ion beam. In addition, the detection limit of Na depth profile with C60 ion sputtering was almost the same with existing dynamic SIMS analysis with Cs primary ion. Thus, the ToF‐SIMS with C60 ion sputtering is shown to be more versatile than the existing method by avoiding the necessity to optimize the operating conditions. Copyright © 2012 John Wiley & Sons, Ltd.
Accounting for heaping in retrospectively reported event data – a mixture‐model approach
Authors: Bar Haim Y. , Lillard Dean R.
Published: June 2012

When event data are retrospectively reported, more temporally distal events tend to get ‘heaped’ on even multiples of reporting units. Heaping may introduce a type of attenuation bias because it causes researchers to mismatch time‐varying right‐hand side variables. We develop a model‐based approach to estimate the extent of heaping in the data and how it affects regression parameter estimates. We use smoking cessation data as a motivating example, but our method is general. It facilitates the use of retrospective data from the multitude of cross‐sectional and longitudinal studies worldwide that collect and potentially could collect event data. Copyright © 2012 John Wiley & Sons, Ltd.
Multiple comparisons of drug efficacy between subgroups defined by genetic polymorphisms
Authors: Tu Yi‐Hsuan , Hsu Jason C.
Published: June 2012

In contrast to using genome‐wide association studies to discover associations between genes or single‐nucleotide polymorphisms in the genome with disease status or outcome, some recent pharmacogenomic studies have focused on whether polymorphisms in genes involved in metabolizing drugs significantly impact their efficacy. Whether a drug starts as an active compound and gets metabolized and eliminated from the body or starts as an inactive compound and gets metabolized to an active form, patients in subgroups separated by polymorphism of a gene needed to metabolize the drug might derive differential benefit from that drug. With the use of the Clopidogrel in Unstable Angina to Prevent Recurrent Events trial for Plavix as an example, this article proposes Multiple Comparisons with Control Subgroup and Multiple Comparisons with the Best Subgroup as methods to infer whether some subgroups of patients derive more or less benefit than wild‐type patients and which subgroup or subgroups of patients derive maximum benefit or practically maximum benefit from the drug. Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic Nanobeads Decorated with Silver Nanoparticles as Cytotoxic Agents and Photothermal Probes
Authors: Di Corato Riccardo , Palumberi Domenico , Marotta Roberto , Scotto Marco , Carregal‐Romero Susana , Rivera_Gil Pilar , Parak Wolfgang J. , Pellegrino Teresa
Published: June 2012

A versatile method for decorating magnetic nanobeads (being composite materials from polymers and superparamagnetic nanoparticles) with silver nanoparticles of 3–6 nm size is presented. Control over the silver nanoparticle coverage at the nanobead surface is achieved by changing the reaction parameters. Moreover, the silver‐decorated magnetic nanobeads (Ag‐MNBs) are studied with respect to their in vitro cytotoxicity on two distinct tumour cell lineages under different parameters, i.e., dose, incubation time, magnetic field applied during the culturing, silver ion leakage, and colloidal stability. It is found that enhanced magnetically mediated cellular uptake and silver ion leakage from the Ag‐MNBs surface are the main factors which affect the toxicity of the Ag‐MNBs and allow the half‐maximal inhibitory dose of silver to be reduced to only 32 μg mL−1. Furthermore, a synergic cytotoxicity induced by photo‐activation of silver nanoparticles was also found.
Novel Heneicosadienoic and Tricosadienoic Acid Isomers in Ovaries of Marine Archaeogastropods
Authors: Kawashima Hideki , Ohnishi Masao
Published: June 2012

To investigate unusual odd‐chain fatty acids (FA) from gonads of archaeogastropods, limpets Cellana grata and Cellana toreuma, a subfraction enriched in FA with two double bonds extracted from the gonads was obtained by using argentation thin‐layer chromatography. The resulting fraction was analyzed by using capillary gas chromatography–mass spectrometry of its methyl esters, 3‐pyridylcarbinol esters and pyrrolidide derivatives. Six novel all‐cis diene isomers were identified as 7,18‐heneicosadienoic (21:2Δ7,18), 8,14‐tricosadienoic (23:2Δ8,14), 9,15‐tricosadienoic (23:2Δ9,15), 7,18‐tricosadienoic (23:2Δ7,18), 9,18‐tricosadienoic (23:2Δ9,18), and 9,20‐tricosadienoic (23:2Δ9,20) acids. In the present study, the differences in the proportion of tricosadienoic acid isomers between the ovary lipids of C. grata and C. toreuma were recognized.
B-Cell Ligand Processing Pathways Detected by Large-Scale Comparative Analysis
Authors: Towfic Fadi , Gupta Shakti , Honavar Vasant , Subramaniam Shankar
Published: June 2012

The initiation of B-cell ligand recognition is a critical step for the generation of an immune response against foreign bodies. We sought to identify the biochemical pathways involved in the B-cell ligand recognition cascade and sets of ligands that trigger similar immunological responses. We utilized several comparative approaches to analyze the gene coexpression networks generated from a set of microarray experiments spanning 33 different ligands. First, we compared the degree distributions of the generated networks. Second, we utilized a pairwise network alignment algorithm, BiNA, to align the networks based on the hubs in the networks. Third, we aligned the networks based on a set of KEGG pathways. We summarized our results by constructing a consensus hierarchy of pathways that are involved in B cell ligand recognition. The resulting pathways were further validated through literature for their common physiological responses. Collectively, the results based on our comparative analyses of degree distributions, alignment of hubs, and alignment based on KEGG pathways provide a basis for molecular characterization of the immune response states of B-cells and demonstrate the power of comparative approaches (e.g., gene coexpression network alignment algorithms) in elucidating biochemical pathways involved in complex signaling events in cells.