bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Properties of Heterogeneous Magnetoelectroelastic Materials with Multi-Coated Inclusions
Authors: Bakkali Abdel , Azrar L. , Aljinadi A.A.
Published: April 2013

In this paper, the effective properties of magnetoelectroelastic heterogeneous materials with ellipsoidal multi-inclusions are modeled and numerically investigated. The modeling is based on the integral equation that takes into account the multi-coated effect as well as the magnetoelectroelastic interfacial operators and global and local concentration tensors. Various types and kinds of coatings can be considered. The effective properties are predicted based on various micromechanical models such as Mori-Tanaka, Self-Consistent and Incremental Self-Consistent. These properties are presented in terms of the volume fractions of the multi-coated inclusions, thicknesses of the coatings, type and kind of inclusions.
Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator
Authors: Zhang Ping-Xia , Murray Thomas S. , Villella Valeria R. , Ferrari Eleonora , Esposito Speranza , D'Souza Anthony , Raia Valeria , Maiuri Luigi , Krause Diane S. , Egan Marie E. , Bruscia Emanuela M.
Published: April 2013

We have previously reported that TLR4 signaling is increased in LPS-stimulated cystic fibrosis (CF) macrophages (MΦs), contributing to the robust production of proinflammatory cytokines. The heme oxygenase-1 (HO-1)/CO pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. In this study, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules enhances CAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations re-established HO-1 and CAV-1 cell surface localization in CF MΦs. Consistent with restoration of HO-1/CAV-1–negative regulation of TLR4 signaling, genetic or pharmacological (CO-releasing molecule 2) induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counterregulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1–dependent mechanism, exacerbating the CF MΦ response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease.
The Novel Role of IL-7 Ligation to IL-7 Receptor in Myeloid Cells of Rheumatoid Arthritis and Collagen-Induced Arthritis
Authors: Chen Zhenlong , Kim Seung-jae , Chamberlain Nathan D. , Pickens Sarah R. , Volin Michael V. , Volkov Suncica , Arami Shiva , Christman John W. , Prabhakar Bellur S. , Swedler William , Mehta Anjali , Sweiss Nadera , Shahrara Shiva
Published: April 2013

Although the role of IL-7 and IL-7R has been implicated in the pathogenesis of rheumatoid arthritis (RA), the majority of the studies have focused on the effect of IL-7/IL-7R in T cell development and function. Our novel data, however, document that patients with RA and greater disease activity have higher levels of IL-7, IL-7R, and TNF-α in RA monocytes, suggesting a feedback regulation between IL-7/IL-7R and TNF-α cascades in myeloid cells that is linked to chronic disease progression. Investigations into the involved mechanism showed that IL-7 is a novel and potent chemoattractant that attracts IL-7R+ monocytes through activation of the PI3K/AKT1 and ERK pathways at similar concentrations of IL-7 detected in RA synovial fluid. To determine whether ligation of IL-7 to IL-7R is a potential target for RA treatment and to identify their mechanism of action, collagen-induced arthritis (CIA) was therapeutically treated with anti–IL-7 Ab or IgG control. Anti–IL-7 Ab treatment significantly reduces CIA monocyte recruitment and osteoclast differentiation as well as potent joint monocyte chemoattractants and bone erosion markers, suggesting that both direct and indirect pathways might contribute to the observed effect. We also demonstrate that reduction in joint MIP-2 levels is responsible for suppressed vascularization detected in mice treated with anti–IL-7 Ab compared with the control group. To our knowledge, we show for the first time that expression of IL-7/IL-7R in myeloid cells is strongly correlated with RA disease activity and that ligation of IL-7 to IL-7R contributes to monocyte homing, differentiation of osteoclasts, and vascularization in the CIA effector phase.
Antigen-Stimulated CD4 T Cell Expansion Can Be Limited by Their Grazing of Peptide–MHC Complexes
Authors: De Boer Rob J. , Perelson Alan S.
Published: April 2013

It was recently shown that the expansion of CD4+ T cells during a primary immune reaction to a peptide from cytochrome c decreases ∼0.5 log for every log increase in the number of cognate precursor cells, and that this remains valid over more than four orders of magnitude (Quiel et al. 2011. Proc. Natl. Acad. Sci. USA. 108: 3312–3317). This observed “power law” was explained by a mechanism where nondividing mature T cells inhibit the proliferation of less-differentiated cells of the same specificity. In this article, we interpret the same data by a mechanism where CD4+ T cells acquire cognate peptide-MHC (pMHC) complexes from the surface of APCs, thereby increasing the loss rate of pMHC. We show that a mathematical model implementing this “T cell grazing” mechanism, and having a T cell proliferation rate that is determined by the concentration of pMHC, explains the data equally well. As a consequence, the data no longer unequivocally support the previous explanation, and the increased loss of pMHC complexes on APCs at high T cell densities is an equally valid interpretation of this striking data.
An empirical study of the reward preferences of South African employees
Authors: Snelgar Robin J. , Renard Michelle , Venter Danie
Published: April 2013

Orientation: Adapting traditional reward systems to focus on employee preferences has become a necessity as companies strive to attract, motivate and retain a skilled and high performing workforce.Research purpose: The aim of the study was to identify certain categories of rewards that employees consider to be most important, including base pay, contingency pay, benefits, performance and career management, quality work environment, and work–home integration. The impact of these reward categories on an organisation’s ability to attract, motivate and retain employees was explored, together with the influence of demographic variables on reward preferences.Motivation for the study: There is much debate over whether reward packages should be tailor-made to suit individual employees. It has been argued that a ‘one-size-fits-all’ approach with regard to rewards is no longer effective.Research design, approach and method: A structured questionnaire, based on the total rewards model, was used to achieve the objectives of the study. A sample of 250 employees from 11 medium-sized to large-sized organisations participated in the study.Main findings: The results showed that base pay is deemed to be the most preferred reward component amongst respondents; however, they are most dissatisfied with the level at which this reward is provided by their current employers. Base pay is also the most important reward when attracting and retaining employees. Differences between reward preferences and demographic variables, including age, gender and job level, were found.Practical/managerial implications: Organisations should design their reward systems according to the preferences of their employees by focusing on base pay and contingency or variable pay. These rewards will also serve to retain them; although, to motivate employees, non-cash awards and recognition should be emphasised.Contribution/value-add: This study contributes to literature on reward preferences, which is lacking in a South African context. It also provides support for segmentation of rewards based on certain demographic variables.
Topology of hypersurface singularities with 3-dimensional critical set
Authors: de Bobadilla Javier Fernández , Marco-Buzunáriz Miguel
Published: April 2013

In this paper, we prove that the Milnor fibre of a singularity over an isolated complete intersection singularity (i.c.i.s.) of dimension 3 has the homotopy type of a bouquet of spheres, provided that the function that defines the singularity has finite extended codimension with respect to the ideal that defines the i.c.i.s.
Degenerate singularities of one dimensional foliations
Authors: Ferrer Viviana , Vainsencher Israel
Published: April 2013

We give formulas for the degrees of the spaces of holomorphic foliations in the complex projective plane with a dicritical singularity of prescribed order. Blowing up such singularity induces, generically, a foliation with only finitely many leaves tangent to the exceptional line; we find the degree of the locus defined by imposing a leaf of total contact with the exceptional line.
Detecting linear dependence on an abelian variety via reduction maps
Authors: Jossen Peter
Published: April 2013

Let

A

be a geometrically simple abelian variety over a number field

k

, let

X

be a subgroup of

A(k)

and let

P\in A(k)

be a rational point. We prove that if

P

belongs to

X

modulo almost all primes of

k

then

P

already belongs to

X

.
Personal Consumption and Single Persons: A Reply to Kurt Krueger
Authors: Ireland Thomas R.
Published: April 2013

In the last issue of the Journal of Forensic Economics, Kurt Krueger responded to my earlier comment on his paper on “Personal Consumption and Single Persons.” In his response, he provided an incorrect characterization of my views. My response clarifies my own position with respect to testimony about personal consumption of single persons.
Personal Consumption and Single Persons: A Reply to Thomas R. Ireland
Authors: Krueger Kurt V.
Published: April 2013

After an exchange of comments, Ireland now agrees that could-based lost support analysis is appropriate as long as “could” is not represented as “would.” So, regarding the forensic economic convention of “could” or “contingent” based analysis in wrongful death, our exchange nets to zero.
NAFE and the Ethics Question
Authors: Thornton Robert J. , Brookshire Michael L.
Published: April 2013

Since its organization in 1986, the National Association of Forensic Economics (NAFE), its members, and its leaders have maintained a focus upon ethical issues facing forensic economists and such related issues as the certification of testifying economists and appropriate standards of qualifications and of ethical conduct. In recent years, NAFE sessions and membership surveys demonstrate that this focus upon ethical issues has not diminished.
Employee Tenure and Economic Losses in Wrongful Termination Cases
Authors: Baum Charles L.
Published: April 2013

When calculating lost earnings in wrongful employment termination cases, economists should approximate the amount of time a terminated employee would have remained employed for the defendant employer accounting for the probabilities of surviving, participating in the labor force, being employed, and remaining employed for that particular employer. I develop a model for the annual probability of remaining with a particular employer using National Longitudinal Survey of Youth data, which tracks the employment experiences of a nationally-representative cohort of individuals over the 1979 through 2010 period. Many employment spells are relatively short, so short tenures are associated with a high probability of leaving an employer. After a point, somewhat longer tenures are associated with a higher probability of remaining with an employer an additional year.
Microwave Irradiation for Dry-Roasting of Hazelnuts and Evaluation of Microwave Treatment on Hazelnuts Peeling and Fatty Acid Oxidation
Authors: Ciarmiello Loredana F. , Piccirillo Pasquale , Gerardi Carmela , Piro Filippo , Luca Antonio De , D’Imperio Francesco , Rosito Valerio , Poltronieri Palmiro , Santino Angelo
Published: April 2013

European hazelnut is an important nut crop in Italy, where about 121,750 tons of in-shell nuts are produced every year. Roasting is the most important practice for hazelnut preservation and commonly is carried out in commercial electrical ovens at 120-160°C for 10-20 min. This needful practice is time and energy expensive, so the development of new processing methods is required to reduce processing costs and to obtain top quality roasted nuts. The aim of this study was to develop a simple microwave treatment for hazelnuts peeling and roasting.

With this aim, some physical (colour, temperature, moisture) and chemical (taste, lipoxygenase activity, fatty acids, vitamins, sensory attributes) features of inshell nuts and kernels of three Italian hazelnut varieties (Tonda di Giffoni, Tonda Romana and Nocchione) after conventional oven or microwave roasting were evaluated.

Results showed that microwave roasting of kernels for 450 s gave a higher peeling score than the conventional oven treatment. This paralleled with better colour and taste scores for microwaved roasted kernels. Furthermore, a 360-450 s microwave roasting was able to inactivate almost completely lipoxygenases, avoiding adverse effects on fatty acids hydroperoxides and PUFA content. A shorter microwave treatment (360 s) was enough to obtain good peeling and sensory scores of inshell hazelnuts.
 Taken together our results indicated that microwave technology can be successfully applied to both kernels and inshell hazelnuts to obtain suitable peeling and high quality roasted nuts.
Technology Transfer: Bridging academic research and society â€“ a communicative approach
Authors: Bennetzen Martin Vad , MÃ¸ller Lars Stig
Published: April 2013

To make basic research transcend the walls of a university for the benefit of the society, technology transfer processes such as patenting, market analysis, and economic assessment are essential. Therefore small dedicated units, called technology transfer offices, have emerged during the last four decades. The emergence is a manifestation of a general political intention to make basic research have direct impact on society â€“ to focus on application and publication, and not just the latter. The process is, however, not straightforward and different universities have different way of doing it. University of Southern Denmark has recently implemented a highly extrovert and progressive science-based communicative strategy providing an adequate framework for a â€œgrass-roots movingâ€ among researchers. By working on four frontlines we aim to ensure high degree of transparency in the technology transfer activities, to demythologize pseudo-idealistic and inadequate perceptions on the role of e.g. patents, to scout early-stage business opportunities, to map the competence landscape of the university and to ensure a three-faceted political alignment. We here present what we would call the SDU-model of doing technology transfer anno 2012. Despite the short timeline in which it has been implemented we already harvest the early fruits of the model, which encourage us hereby to present the model, its underlying strategy, its rationale and its perspectives. We believe that the model are unique with respect to the holistic four-frontline focus, addresses some of the major challenges of academic technology transfer and we are confident that universities worldwide could benefit from it or a context-dependent modified versions hereof.
Developing Cell Therapies: Enabling cost prediction by value systems modeling to manage developmental risk.
Authors: McCall Mark Joseph , Williams David John
Published: April 2013

This work quantifies the highest risk activities and interdependencies in cell therapy new product development (NPD).Â  A simulation model based upon an activates based and information driven Â approach of the Design Structure Matrix (DSM), using Latin Hypercube sampling methods with discrete event simulation evaluated the interdependencies between critical development tasks.Â  Input data was collected from quarterly financial reports of cell therapy developers and developmental milestones as reported in company press releases and publications.Â  . Successfully planning and managing development processes is problematic in an emerging industry lacking precedents and standardised technology platforms.Â Â  Methods of understanding and reducing developmental uncertainty and risk are needed to aid resourcing decisions.Â  A particular requirement is to understand the impact of process and clinical development, in this highly regulated sector. Results from the model quantify the probability and impact of process iterations and failures that impact cost and duration of cell therapy NPD.Â  High impact areas quantified are the interdependence of Phase 1 clinical trials and investment, the scaling of the manufacturing process from Phase 1 to Phase 2 and Phase 2 to Phase 3.Â  The model also allows for the calculation of the probability of NPD success for given resource levels, time constraints and market conditions.Â  An application comparing alternative regulatory approaches indicates that the current favoured strategy of targeting an orphan indication gives little benefit for the tested clinic al indication because of reduced clinical trial recruitment rate.Â  While specifically developed for cell therapy NPD this modelling approach has potential application across the wider biotechnology industry.
Challenges and prospects for monoclonal antibodies in China
Authors: Shi Honghao , Chen Meiwan , Shi Yunzhen , Hu Hao , Wang Yitao
Published: April 2013

The technology of monoclonal antibodies has been developed since the 1990s and is attracting more and more attention in China during the 21st century. The first monoclonal antibody product was introduced by the Chinese local producer in 1999, and presently seven products are listed, of which three are humanized products. There are several technical constraints that are affecting the development of monoclonal antibodies in China: limitations to the number of drug targets, restricted biological diffusion, limitations to administration routes, and species-specific issues, as well as Chinaâ€™s own limitations in production and R&D capabilities. This article provides suggestions relevant for the Chinese development of monoclonal antibodies. In the long run China is expected to catch up with its own technology roadmap.
A Business Perspective on IP: Open Innovation vs. Open Source in Commercializing Biotechnology
Authors: Boni Arthur A.
Published: April 2013

Abstract â€“ In this article, we address the issues that are involved when developing a strategy for commercializing a discovery that is novel, useful, and non-obvious to someone skilled in the art.Â  Patent(s) may be used as one means of providing a competitive advantage, and in addition this method is quite common as a means to monetize the intellectual asset.Â  Alternatively, a more â€œopen-sourceâ€ method may be employed as is more typical in dealing with software products or services â€“ thereby opening up the field to collaboration and widespread use.Â  However, other means must then be developed to monetize the asset whether it involves a â€œhardwareâ€ component, software, or both. We argue that to answer these questions, one needs to be very strategic in framing the business model that would be most successful in commercializing the particular discovery keeping in mind that wide dissemination of the innovation is the objective. We focus on issues prevalent for innovation in biopharma, medtech, and medical IT, where high risk, long life cycle, capital-intensive investments are required for commercial introduction.
Should the HHS Decision to Overrule FDA on Plan B Be Reversed
Authors: Pitts Peter J.
Published: April 2013

On December 7, 2011, Secretary of Health and Human Services Kathleen Sebelius overruled a decision of the Food and Drug Administration (FDA) on the over-the-counter (OTC) status of emergency contraception. What will be the repercussions of Secretary Sebeliusâ€™s action? Why is the act itself of far greater long-term significance than the transitory regulatory action it impacts? By reversing an FDA decision, the Secretary has set a dangerous precedent for all-comers to lobby Congress, the Department of Health and Human Services (HHS) and the White House on any and all FDA decisionsâ€”directly inserting politics into what must be a scientifically driven process.
Getting Social with Biotechnology Business Development
Authors: McCready Tim
Published: April 2013

Social media is becoming increasingly important in business. While the lack of regulations makes marketing online to consumers a challenge in the life sciences, social media offers significant opportunities to the industry by complementing traditional business development and capital raising activities. Â  With relatively little effort and expense, companies can build networks, gain trust, and obtain introductions with previously inaccessible targets and distant markets. In embracing social media, individuals themselves become more approachable and open themselves up to business growth that might otherwise have been unattainable.
Hohokam to Akimel O’Odham: Obsidian Acquisition at the Historic Period Sacate Site (GR-909), Gila River Indian Community, Arizona
Authors: Loendorf Chris R. , Fertelmes Craig M. , Lewis Barnaby V.
Published: April 2013

Obsidian provenance studies within the Phoenix Basin of south-central Arizona have become increasingly comprehensive during the last four decades. As a result, broad regional and temporal trends have been defined regarding Preclassic (ca. A.D. 650–1150) and Classic period (ca.A.D. 1150–1450) socioeconomic interactions in the Hohokam core area. However, Historic period patterns are still poorly understood, and these data are essential for understanding the relationship between the prehistoric Hohokam and historical Akimel O’Odham. The association between the Akimel O’Odham and Hohokam has been debated since Euro-Americans first visited the area in the late 1600s, yet this issue is still not fully resolved. This article presents analyses of historical obsidian from the Sacate site that suggest that long-term trends in cultural patterns within the Phoenix Basin continued unbroken into the Historic period. These continuities provide another line of evidence that the Akimel O’Odham are the direct cultural descendants of the Hohokam.
Implications of New Radiocarbon Ages on Coiled Basketry from the Northern Great Basin
Authors: Connolly Thomas J.
Published: April 2013

Coiled basketry dates to more than 8,000 years ago in the Eastern Great Basin and is found in the Western Basin by 4,500 years ago. In the Northern Great Basin, archaeological basketry is dominated by twineware; fewer than 20 fragments of coiled basketry have been reported. Coiling has long been thought to have appeared very late in the Northern Basin, and the perceived late presence of coiling in the north has been considered by some to be an indicator of a late Numic incursion from the south. Recent direct radiocarbon dating of fiber samples from the coiled specimens from the Northern Great Basin undermines the previous assumptions of a uniformly late age. Though rare, coiling has a consistent presence in the region for more than 2,500 years. Further, its distribution suggests that this technological influence may have derived primarily from eastern, rather than southern, sources.
Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method
Authors: Cheng Hongyan , Qin Qin , Sun Xinchen , Li Fan , Sun Ning , Cheng Lu , Lu Zuhong , Chen Baoan
Published: April 2013

Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n = 115). The three-dimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G+G/G) were associated with significantly longer progression-free survival (PFS) (6.0 m vs. 10.6 m, log-rank P = 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P = 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 ( P = 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P > 0.05). In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.
Inverse Planning Optimization Method for Intensity Modulated Radiation Therapy
Authors: Lan Yihua , Ren Haozheng , Li Cunhua , Min Zhifang , Wan Jinxin , Ma Jianxin , Hung Chih-Cheng
Published: April 2013

In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between the dose conformity and the total number of monitor units. This idea can be extended to other fluence map optimization model, and we believe it can also achieve good performance.
IMRT or 3D-CRT in Glioblastoma? A Dosimetric Criterion for Patient Selection
Authors: Lorentini S. , Amelio D. , Giri M. G. , Fellin F. , Meliadò G. , Rizzotti A. , Amichetti M. , Schwarz M.
Published: April 2013

Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% ( p = 0.4) for scenario 0 to 7.8% ( p = 0.02) for scenario 3, passing through 2.54% ( p = 0.18) and 5.93% ( p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.
Exploring the amyloid proteome in immunoglobulin‐derived lymph node amyloidosis using laser microdissection/tandem mass spectrometry
Authors: D'Souza Anita , Theis Jason , Quint Patrick , Kyle Robert , Gertz Morie , Zeldenrust Steven , Vrana Julie , Dogan Ahmet , Dispenzieri Angela
Published: April 2013

Amyloidosis affecting lymph nodes (LN) may occur in the setting of systemic amyloidosis or as an entity localized to the site of production (peritumoral). Why some LN amyloid remains peritumoral is unknown. We speculated that the composition of amyloid in these two presentations differs. We analyzed the amyloid proteome in LN amyloid samples to identify differences between the systemic and peritumoral subtypes. In immunoglobulin‐derived LN amyloidosis (N = 26), 70% had heavy chain amyloid (AH or mixed AH/AL). True localized LN amyloidosis was rare, with only 2 patients without a monoclonal protein component. Nineteen patients (73%) had typical amyloid syndromes (100% of AL vs 67% of AH/AL, P = 0.02). A trend to improved survival for the AH/AL group in comparison to AL (median 5‐year survival 48 vs. 19 months, P = 0.06) was seen. Mass spectrometric amyloid analysis is a powerful tool for characterizing amyloid and may provide additional prognostic information. Am. J. Hematol. 88:577–580, 2013. © 2013 Wiley Periodicals, Inc.
Decreased external skeletal robustness due to reduced physical activity?
Authors: Rietsch Katrin , Eccard Jana A. , Scheffler Christiane
Published: April 2013

Objectives

Childhood obesity is a global problem, e.g., due to physical inactivity. External skeletal robustness (Frame‐Index) has decreased in German schoolchildren. An association between Frame‐Index and physical activity was assumed. Further often body mass index (BMI) is analyzed without reference to bone structure. Therefore, we analyze relationships between Frame‐Index, BMI, % body fat, and physical activity.

Methods

In a cross‐sectional study, 691 German children aged 6–10 years were investigated. BMI, % body fat, Frame‐Index, total steps p.w., sports club rate p.w., training time p.d., and TV‐time p.d. were determined.

Results

Total steps (P < 0.001), BMI (P < 0.001), and % body fat (P = 0.024) are positively linked to Frame‐Index. Total steps (P < 0.001), sports club rate (P = 0.001), and training time (P < 0.001) are negatively associated with % body fat. Total steps (P = 0.017) are negatively linked to BMI. TV‐time is positively related to BMI (P < 0.001) and % body fat (P < 0.001). % Body fat is affected by age (P < 0.001), sex (P = 0.028), and total steps (P = 0.002). BMI is influenced by age (P < 0.001), and Frame‐Index by sex (P < 0.001) and total steps (P = 0.029). Principal component analysis indicates an association between BMI and TV‐time and Frame‐Index and total steps.

Conclusions

We demonstrate an association between external skeletal robustness and physical activity, which is not captured by in BMI measurements. Children should be physically active in order to maintain skeletal robustness. Am. J. Hum. Biol. 25:404–410, 2013. © 2013 Wiley Periodicals, Inc.
The cortisol response in policemen: Intraindividual variation, not concentration level, predicts truncal obesity
Authors: Sharp Dan S. , Andrew Michael E. , Fekedulegn Desta B. , Burchfiel Cecil M. , Violanti John M. , Wactawski‐Wende Jean , Miller Diane B.
Published: April 2013

Objectives

Chronic stress, characteristic of police work, affects the hypothalamic‐pituitary‐adrenal axis' control of cortisol production. Capacity to vary cortisol may be the appropriate measurement to interpret associations with chronic diseases, including obesity, best measured by variability within a person, not central tendency.

Methods

On each of 217 policemen, 18 saliva specimens were obtained for cortisol. Statistical models examined the associations of within‐subjects (W‐S) cortisol standard deviation (SD) and W‐S cortisol mean with waist circumference and four body composition indexes: BMI, and three derived from DEXA: fat‐mass, and trunk and extremities lean‐mass. Explained variance and the functional nature of associations are reported.

Results

Associations of anthropometrics with W‐S cortisol mean were not statistically significant at P < 0.05; all associations with W‐S cortisol SD were significant. The association of trunk lean mass index (LMIt) with W‐S cortisol SD dominated all models. Associations of W‐S cortisol SD with other indexes vanished when models contained LMIt ; when any other index was included in models predicting LMIt, associations with W‐S cortisol SD remained significant. The functional association between LMIt and W‐S cortisol SD is progressively “hockey stick,” monotonic increasing, and flattens at joint high values.

Conclusions

Results support inferences that LMIt measures visceral adiposity and W‐S cortisol variability appears to be an appropriate construct to measure in association with visceral adiposity. The “hockey stick” character of the association is consistent with other investigations suggesting obesity is associated with less W‐S cortisol variation; however, the monotonic increase and flattening of association at increasing W‐ScortisolSD values suggests a more complex association, potentially interpretable by allostasis models of causation. Am. J. Hum. Biol. 25:499–507, 2013. © 2013 Wiley Periodicals, Inc.
VENOM COMPONENTS OF Asobara japonica IMPAIR CELLULAR IMMUNE RESPONSES OF HOST Drosophila melanogaster
Authors: Furihata Shunsuke X. , Matsumoto Hitoshi , Kimura Masahito T. , Hayakawa Yoichi
Published: April 2013

The endoparasitoid wasp Asobara japonica has highly poisonous venom: the host Drosophila larvae are killed by envenomation at a dose that is naturally injected by the female wasp at parasitism. This insecticidal venom is neutralized, however, because A. japonica introduces lateral oviduct components soon after venom injection at oviposition. Although the venom and lateral oviduct components of this parasitoid have been partially characterized, how the venom components favor successful development of wasp eggs and larvae in the host remains ambiguous. Here, we demonstrated that A. japonica venom did not affect host humoral immune responses, determined as expression of antimicrobial peptide (AMP) genes, but significantly diminished two cellular responses, spreading and phagocytosis, by host hemocytes. Moreover, venom components drastically elevated a serine protease‐like activity 4 h after its injection. The lateral oviduct components did not negate the detrimental effects of the venom on host cellular immunities, but significantly reduced the venom‐induced elevation of protease activity. Both active factors in venom and lateral oviduct components were roughly characterized as heat‐labile substances with a molecular mass of at least 10 kDa. Finally, venom of A. japonica, with a wide host range, was found to be much more toxic than that of Asobara rossica, which has a limited host range. These results reveal that A. japonica venom toxicity allows exploitation of a broader range of host insects because it is essential to overcome cellular immune responses of the host for successful parasitism.
FOUR SERINE PROTEASE cDNAS FROM THE MIDGUT OF Plutella xylostella AND THEIR PROTEINASE ACTIVITY ARE INFLUENCED BY THE ENDOPARASITOID, Cotesia vestalis
Authors: Shi Min , Zhu Ni , Yi Yin , Chen Xue‐xin
Published: April 2013

Serine proteinases, which include trypsins and chymotrypsins, play numerous roles in lepidopteran larvae, such as digestion, zymogen activation, and immune defense. Studies of lepidopteran serine proteinases could increase understanding of their feeding preference (polyphagous and monophagous) and facilitate identification of protease inhibitors, which can be engineered for pest management. In this paper, four full‐length cDNAs encoding one chymotrypsin and three trypsins were cloned from larval midguts of the diamondback moth, Plutella xylostella. Real‐time quantitative polymerase chain reaction (PCR) analysis showed all four serine protease genes were downregulated after P. xylostella was parasitized by the parasitoid wasp Cotesia vestalis. Trypsin and chymotrypsin enzymatic activities within the midgut of nonparasitized and C. vestalis‐parasitized P. xylostella larvae were examined using N‐a‐benzoyl‐arg p‐nitroanilide and N‐succinyl‐ala‐ala‐pro‐phe p‐nitroanilide as substrates. Trypsin and chymotrypsin activities were decreased in parasitized larvae as compared to untreated larvae, with the effect being more pronounced over time. Chymotrypsin activity in particular exhibited a significant decrease in activity. The correlation of decreased enzymatic activity and transcript abundance suggests parasitization induced downregulation of serine proteinase gene transcripts.
A joint model for longitudinal continuous and time‐to‐event outcomes with direct marginal interpretation
Authors: Efendi Achmad , Molenberghs Geert , Njagi Edmund Njeru , Dendale Paul
Published: April 2013

Joint modeling of various longitudinal sequences has received quite a bit of attention in recent times. This paper proposes a so‐called marginalized joint model for longitudinal continuous and repeated time‐to‐event outcomes on the one hand and a marginalized joint model for bivariate repeated time‐to‐event outcomes on the other. The model has several appealing features. It flexibly allows for association among measurements of the same outcome at different occasions as well as among measurements on different outcomes recorded at the same time. The model also accommodates overdispersion. The time‐to‐event outcomes are allowed to be censored. While the model builds upon the generalized linear mixed model framework, it is such that model parameters enjoy a direct marginal interpretation. All of these features have been considered before, but here we bring them together in a unified, flexible framework. The model framework's properties are scrutinized using a simulation study. The models are applied to data from a chronic heart failure study and to a so‐called comet assay, encountered in preclinical research. Almost surprisingly, the models can be fitted relatively easily using standard statistical software.
N‐Sulfotestosteronan, A Novel Substrate for Heparan Sulfate 6‐O‐Sulfotransferases and its Analysis by Oxidative Degradation
Authors: Li Guoyun , Masuko Sayaka , Green Dixy E. , Xu Yongmei , Li Lingyun , Zhang Fuming , Xue Changhu , Liu Jian , DeAngelis Paul L. , Linhardt Robert J.
Published: April 2013

Testosteronan, an unusual glycosaminoglycan (GAG) first isolated from the microbe Comamonas testosteroni, was enzymatically synthesized in vitro by transferring uridine diphosphate sugars on β‐p‐nitrophenyl glucuronide acceptor. After chemically converting testosteronan to N‐sulfotestosteronan it was tested as a substrate for sulfotransferases involved in the biosynthesis of the GAG, heparan sulfate. Studies using 35S‐labeled 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS) showed that only 6‐O‐sulfotransferases acted on N‐sulfotestosteronan. An oxidative depolymerization reaction was explored to generate oligosaccharides from 34S‐labeled 6‐O‐sulfo‐N‐sulfotestosteroran using 34S‐labeled PAPS because testosteronan was resistant to all of the tested GAG‐degrading enzymes. Liquid chromotography‐mass spectrometric analysis of the oxidatively depolymerized polysaccharides confirmed the incorporation of 34S into ∼14% of the glucosamine residues. Nuclear magnetic resonance spectroscopy also showed that the sulfo groups were transferred to ∼20% of the 6‐hydroxyl groups in the glucosamine residue of N‐sulfotestosteronan. The bioactivity of 6‐O‐sulfo‐N‐sulfotestosteronan was examined by performing protein‐binding studies with fibroblast growth factors and antithrombin (AT) III using a surface plasmon resonance competition assay. The introduction of 6‐O‐sulfo groups enhanced N‐sulfotestosteronan binding to the fibroblast growth factors, but not to AT III. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 675–685, 2013.
Toward engineering efficient peptidomimetics. Screening conformational landscape of two modified dehydroaminoacids
Authors: Buczek Aneta , Makowski Maciej , Jewgiński Michał , Latajka Rafał , Kupka Teobald , Broda Małgorzata A.
Published: April 2013

Effective peptidomimetics should posses structural rigidity and appropriate interaction pattern leading to potential spatial and electronic matching to the target receptor site. Rational design of such small bioactive molecules could push chemical synthesis and molecular modeling toward faster progress in medicinal chemistry. Conformational properties of N‐t‐butoxycarbonyl‐glycine‐(E/Z)‐dehydrophenylalanine N′,N′‐dimethylamides (Boc‐Gly‐(E/Z)‐ΔPhe‐NMe2) in chloroform were studied by NMR and IR spectroscopy. The experimental findings were supported by extensive calculations at DFT(B3LYP, M06‐2X) and MP2 levels of theory and the β‐turn tendency for both isomers of the studied dipeptide were determined in vacuum and in solution. The theoretical data and experimental IR results were used as an additional information for the NMR‐based determination of the detailed solution conformations of the peptides. The obtained results reveal that N‐methylation of C‐terminal amide group changes dramatically the conformational properties of studied dehydropeptides. Theoretical conformational analysis reveals that the tendency to adopt β‐turn conformations is much weaker for the N‐methylated Z isomer (Boc‐Gly‐(Z)‐ΔPhe‐NMe2), both in vacuum and in polar environment. On the contrary, N‐methylated E isomer (Boc‐Gly‐(E)‐ΔPhe‐NMe2) can easily adopt β‐turn conformation, but the backbone torsion angles (φ1, ψ1, φ2, ψ2) are off the limits for common β‐turn types. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 28–40, 2014.
Spatiotemporal expression of zic genes during vertebrate inner ear development
Authors: Chervenak Andrew P. , Hakim Ibrahim S. , Barald Kate F.
Published: April 2013

BACKGROUND: Inner ear development involves signaling from surrounding tissues, including the adjacent hindbrain, periotic mesenchyme, and notochord. These signals include SHH, FGFs, BMPs, and WNTs from the hindbrain and SHH from the notochord. Zic genes, which are expressed in the dorsal neural tube and act during neural development, have been implicated as effectors of these pathways. This report examines whether Zic genes' involvement in inner ear development is a tenable hypothesis based on their expression patterns. RESULTS: In the developing inner ear of both the chick and mouse, all of the Zic genes were expressed in the dorsal neural tube and variably in the periotic mesenchyme, but expression of the Zic genes in the otic epithelium was not found. The onset of expression differed among the Zic genes; within any given region surrounding the otic epithelium, multiple Zic genes were expressed in the same place at the same time. CONCLUSIONS: Zic gene expression in the region of the developing inner ear is similar between mouse and chick. Zic expression domains overlap with sites of WNT and SHH signaling during otocyst patterning, suggesting a role for Zic genes in modulating signaling from these pathways. Developmental Dynamics 242:897–908, 2013. © 2013 Wiley Periodicals, Inc.
Drosophila semaphorin2b is required for the axon guidance of a subset of embryonic neurons
Authors: Emerson Mark M. , Long Jennifer B. , Van Vactor David
Published: April 2013

Background: The process of axon guidance is important in establishing functional neural circuits. The differential expression of cell‐autonomous axon guidance factors is crucial for allowing axons of different neurons to take unique trajectories in response to spatially and temporally restricted cell non‐autonomous axon guidance factors. A key motivation in the field is to provide adequate explanations for axon behavior with respect to the differential expression of these factors. Results: We report the characterization of a predicted secreted semaphorin family member, semaphorin2b (Sema‐2b) in Drosophila embryonic axon guidance. Misexpression of Sema‐2b in neurons causes highly penetrant axon guidance phenotypes in specific longitudinal and motoneuron pathways; however, expression of Sema‐2b in muscles traversed by these motoneurons has no effect on axon guidance. In Sema‐2b loss‐of‐function embryos, specific motoneuron and interneuron axon pathways display guidance defects. Specific visualization of the neurons that normally express Sema‐2b reveals that this neuronal cohort is strongly affected by Sema‐2b loss‐of‐function alleles. Conclusions: While secreted semaphorins have been implicated as cell non‐autonomous chemorepellants in a variety of contexts, here we report previously undescribed Sema‐2b loss‐of‐function and misexpression phenotypes that are consistent with a cell‐autonomous role for Sema‐2b. Developmental Dynamics 242:861–873, 2013. © 2013 Wiley Periodicals, Inc.