bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing the MBSE Cultural Change: Organization, Coaching and Lessons Learned
Authors: Bonnet Stéphane , Voirin Jean‐Luc , Normand Véronique , Exertier Daniel
Published: October 2015

The extent of the cultural change needed to deploy MBSE should not be underestimated. Reshaping years of habits and practices is a gigantic challenge. For the last ten years, Thales has been strongly committed to make MBSE a reality and has successfully generalized the approach in all its business domains worldwide. This paper aims at sharing the Thales experience by explaining who the actors of this engineering transformation are and how systems engineers are accompanied in this change. Four years of intense on‐the‐field MBSE coaching in different engineering contexts result in a first collection of MBSE pitfalls and best practices from which emerges a parallel with Agile methods.
A Systems Engineering Approach to Architecture Development
Authors: Di Pietro David A.
Published: October 2015

Architecture development is often conducted prior to system concept design when there is a need to determine the best‐value mix of systems that works collectively in specific scenarios and time frames to accomplish a set of mission area objectives. While multiple architecture frameworks exist, they often require use of unique taxonomies and data structures. In contrast, this paper characterizes architecture development using terminology widely understood within the systems engineering community. Using a notional civil space architecture example, it employs a multi‐tier framework to describe the enterprise level architecture and illustrates how results of lower tier, mission area architectures integrate into the enterprise architecture. It also presents practices for conducting effective mission area architecture studies, including establishing the trade space, developing functions and metrics, evaluating the ability of potential design solutions to meet the required functions, and expediting study execution through the use of iterative design cycles.
System Interface Engineering
Authors: Scheithauer Dieter
Published: October 2015

The definition of the systems engineering value stream is based on modelling the information flow. Information flow models are beneficial for performing systems engineering management efficiently. The benefits of unidirectional information flow models may give the impression that systems engineering as its best is a deductive process with the stakeholder requirements leading to unique and unambiguous solutions. However, human communication and natural laws feature mutual dependencies that become evident in systems engineering especially when system interfaces and process interfaces are considered. This paper amends two previous papers on the systems engineering value stream by system interface engineering considerations. Starting with clarifying the scope of system interface engineering, the paper proposes a precise terminology and defines the additional system interface engineering activities integrated into the systems engineering value stream.
Utilizing MBSE Patterns to Accelerate System Verification
Authors: Cook David , Schindel William D.
Published: October 2015

In aerospace, automotive, health care, and other domains, the capability to effectively plan and perform system verification tests is increasingly a strategic differentiator. This paper reports on methods used to improve effectiveness of complex aircraft system tests, the gains achieved, and their connection to underlying methods and trends. These include use of Model‐Based Systems Engineering (MBSE), leveraged by Pattern‐Based Systems Engineering (PBSE) to generate configurable, re‐usable system models‐‐the focus of the INCOSE MBSE Patterns Challenge Team. (Patterns Challenge Team, 2013‐2015)

Distinctive aspects include (1) use of configurable, model‐based patterns of system descriptions, including configurable system verification tests, (2) improved ability of model‐based descriptions to integrate modeling tools and automated systems for test management, (3) use of models to describe both system under development and the development process, and (4) ability of these models to be integrated with other system life cycle management processes and information systems, for increased leverage.
Multi‐Stakeholder Trade Space Exploration Using Group Decision Making Methodologies
Authors: Garber Melissa , Sarkani Shahram , Mazzuchi Thomas A.
Published: October 2015

The focus of this paper is the intersection of Group Decision Making (GDM) methodologies with engineering trade studies, with the goal of improving the efficacy of trade study process models by directly accounting for multiple heterogeneous stakeholders and their preference structures. GDM methodologies are identified and mapped to classes of stakeholders, and to decision making approaches. The discussion includes topics of preference structures, utility theory, ordinality versus cardinality, cooperation, negotiation, and voting procedures. The work will be expanded in the future through development of a framework to standardize both the process of conducting trade studies with multiple stakeholders and the artifacts generated thereby. This will include framework application and validation.
Systems Engineering Practices Exhibited in the Creation of a Film Original Score
Authors: Salado Alejandro , Salado Carlos
Published: October 2015

Systems engineering has been successfully applied to a wide variety of industries, which include defense, space, energy, or transportation. All those systems have in common that they are engineered systems and/or socio‐technical ones. Yet, systems engineering is considered both an art and a science. Therefore, could systems engineering be or have been applied in the domain of art, even if not done explicitly? Being one of the authors of this paper a systems engineer and the other one a music composer, this paper reports on the reflections of mutual discussions about how each of us of carried out our activities in our respective domain. Interestingly, it turns out that engineering a space system and creating a film original score abstractly follow the same set of principles and practices.
Architectural Modelling Patterns for Systems of Systems
Authors: Ingram Claire , Payne Richard , Fitzgerald John
Published: October 2015

Patterns can support good decision‐making in architectural design by encouraging the re‐use of architectural concepts and allowing engineers to learn from experience gained in previous systems that have employed similar approaches. This paper presents modelling patterns for the architectural design of systems of systems (SoSs). Fundamental architectural principles for SoSs are introduced. We describe several architectural patterns suitable for SoS design, illustrating each pattern with an SoS example and identifying how it meets those fundamental SoS architectural principles. The patterns are presented as solutions to abstract architectural problems, which we hope will foster sharing of experiences and lessons across domains and disciplines.
Model‐based Product Line Engineering ‐‐ Enabling Product Families with Variants
Authors: Hause Matthew , Hummell James
Published: October 2015

Product Lines are a group of related products manufactured or produced within or between collaborating organizations. To effectively manage a product line, one needs to understand both the similarities and differences between the different products and optimize the development lifecycle to leverage the similarities, and concentrate development on the differences. ISO 26550:2013 Software & Systems Engineering – Reference Model for Product Line Management & Engineering provides a standard for defining these similarities and differences as well as the choices between them. Model‐Based Systems and Software Engineering (MBSE) using the Systems Modeling Language (SysML) and the Unified Modeling Language (UML) provide a means of modeling systems and software. Bringing the two together allows users to model product lines in industry standard formats. These standards provide Model‐Based Product Line Engineering (MB‐PLE). Combining these with an execution engine means that product models can be created for specific products, whilst maintaining the original product line model. This provides significant ROI for aerospace companies.
Evaluation and comparison of the in vitro characteristics and chondrogenic capacity of four adult stem/progenitor cells for cartilage cell‐based repair
Authors: Shafiee Abbas , Kabiri Mahboubeh , Langroudi Lida , Soleimani Masoud , Ai Jafar
Published: October 2015

Cell‐based therapy is being considered as a promising approach to regenerate damaged cartilage. Though, autologous chondrocyte implantation is the most effective strategy currently in use, but is hampered by some drawbacks seeking comprehensive research to surmount existing limitations or introducing alternative cell sources. In this study, we aimed to evaluate and compare the in vitro characteristics and chondrogenic capacity of some easily available adult cell sources for use in cartilage repair which includes: bone marrow‐derived mesenchymal stem cells (MSC), adipose tissue‐derived MSC, articular chondrocyte progenitors, and nasal septum‐derived progenitors. Human stem/progenitor cells were isolated and expanded. Cell's immunophenotype, biosafety, and cell cycle status were evaluated. Also, cells were seeded onto aligned electrospun poly (l‐lactic acid)/poly (ε‐caprolactone) nanofibrous scaffolds and their proliferation rate as well as chondrogenic potential were assessed. Cells were almost phenotypically alike as they showed similar cell surface marker expression pattern. The aligned nanofibrous hybrid scaffolds could support the proliferation and chondrogenic differentiation of all cell types. However, nasal cartilage progenitors showed a higher proliferation potential and a higher chondrogenic capacity. Though, mostly similar in the majority of the studied features, nasal septum progenitors demonstrated a higher chondrogenic potential that in combination with their higher proliferation rate and easier access to the source tissue, introduces it as a promising cell source for cartilage tissue engineering and regenerative medicine. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 600–610, 2016.
Fabrication of interconnected porous calcite by bridging calcite granules with dicalcium phosphate dihydrate and their histological evaluation
Authors: Ishikawa Kunio , Koga Noriko , Tsuru Kanji , Takahashi Ichiro
Published: October 2015

Interconnected porous calcite has attracted attention as an artificial bone replacement material and as a precursor for the fabrication of carbonate apatite, which is also an artificial bone replacement material. In this study, calcite granules were exposed to acidic calcium phosphate solution, and the feasibility of fabricating interconnected porous calcite using this process was evaluated. No setting reaction was observed under the nonloading condition. In contrast, under loading conditions, calcite granules were bridged with dicalcium phosphate dihydrate crystals, and the calcite granules set into interconnected porous calcite foam. When applied 0.4 MPa of loading pressure during sample preparation, compressive strength of the obtained interconnected porous calcite was ∼1.5 MPa. The exposure of the calcite granules to acidic calcium phosphate solution under loading conditions was the key for the setting reaction to occur. This is because calcite granules cannot contact one another under the nonloading condition because of bubble formation on the surfaces of the calcite granules. The interconnected porous calcite revealed excellent tissue response, and new bone was able to penetrate into the porous calcite 2 weeks after implantation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A 104A: 652–658, 2016.
Spatio‐Temporal Parameters of Endosomal Signaling in Cancer: Implications for New Treatment Options
Authors: Stasyk Taras , Huber Lukas A.
Published: October 2015

The endo/lysosomal system in cells provides membranous platforms to assemble specific signaling complexes and to terminate signal transduction, thus, is essential for physiological signaling. Endocytic organelles can significantly extend signaling of activated cell surface receptors, and may additionally provide distinct locations for the generation of specific signaling outputs. Failures of regulation at different levels of endocytosis, recycling, degradation as well as aberrations in specific endo/lysosomal signaling pathways, such as mTORC1, might lead to different diseases including cancer. Therefore, a better understanding of spatio‐temporal compartmentalization of sub‐cellular signaling might provide an opportunity to interfere with aberrant signal transduction in pathological processes by novel combinatorial therapeutic approaches. J. Cell. Biochem. 117: 836–843, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals Inc.
Inline radiofrequency pre‐coagulation simplifies single‐incision laparoscopic minor liver resection
Authors: Weiss Michael , Mittermair Christof , Brunner Eberhard , Schirnhofer Jan , Obrist Christian , Pimpl Katharina , Hell Tobias , Weiss Helmut
Published: October 2015

Background

Single‐incision laparoscopy (SIL) has been developed to reduce surgical trauma, whereas technical difficulties in bleeding control limit the broad acceptance for hepatectomy. A novel minimized invasive strategy combining inline radiofrequency pre‐coagulation and transumbilical SIL is presented herein.

Methods

A cohort of 21 selected patients underwent transumbilical SIL hepatectomies (segmentectomies II–VI) utilizing inline radiofrequency pre‐coagulation for hepatic transection (Habib 4X). Bleeding control, postoperative complications and positive resection margins in malignant diseases served as primary and secondary outcome parameters, respectively.

Results

Single‐incision laparoscopy was successfully completed in all patients. A total of 33 segments were retrieved: mean resection time was 66 ± 35 min, including 11 anatomical (52.38%) and 10 non‐anatomical (47.62%) resections. Sixteen patients (76.19%) underwent concomitant abdominal surgery. No substantial blood loss occurred. Neither additional staplers nor clips were necessary to control any bleeding or bile leakage. One pleural effusion counted for the only postoperative complication. Free margins could be achieved in all but one resection (12/13 patients with malignancies; 92.31%). Ninety‐day mortality was zero.

Conclusions

The combination of SIL and inline radiofrequency pre‐coagulation proved to be a simple, efficacious and safe technique in minor hepatectomy.
Single‐stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis: a multicenter, non‐randomized, open‐label and exploratory clinical trial
Authors: Eto Kazunori , Kawakami Hiroshi , Haba Shin , Yamato Hiroaki , Okuda Toshinori , Yane Kei , Hayashi Tsuyoshi , Ehira Nobuyuki , Onodera Manabu , Matsumoto Ryusuke , Matsubara Yu , Takagi Tomofumi , Sakamoto Naoya ,   on behalf of the Hokkaido Interventional EUS/ERCP study (HONEST) group
Published: October 2015

Background

Two‐stage treatment involving stone removal after drainage is recommended for mild to moderate acute cholangitis associated with choledocholithiasis. However, single‐stage treatment has some advantages. We aimed to assess the efficacy and safety of single‐stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis.

Methods

A multicenter, non‐randomized, open‐label, exploratory clinical trial was performed in 12 institutions. A total of 50 patients with a naïve papilla and a body temperature ≥37 °C who were diagnosed with mild to moderate cholangitis associated with choledocholithiasis were enrolled between August 2012 and February 2014.

Results

Of the 50 patients, 15 had mild cholangitis and 35 had moderate cholangitis. The median number of common bile duct stones was 2 (range, 1–8), and the median diameter of the common bile duct stones was 7.5 mm (range, 1–18). The cure rate of acute cholangitis within 4 days after single‐stage treatment was 90% (45/50) based on a body temperature <37 °C for ≥24 h. The incidence of complications was 10% (5/50).

Conclusion

Single‐stage endoscopic treatment may be effective and safe for mild to moderate acute cholangitis associated with choledocholithiasis (clinical trial registration number: UMIN000008494).
Clinical analysis of patients suffering from chronic hepatitis B superinfected with other hepadnaviruses
Authors: Fu Jia , Guo Dan , Gao Dandan , Huang Wenxiang , Li Ziqiong , Jia Bei
Published: October 2015

To compare the clinical manifestations, laboratory examinations, and prognoses of patients with chronic hepatitis B (CHB) who were superinfected with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV). Two hundred and eleven patients with confirmed CHB in our hospital, a tertiary teaching hospital in China, between 2005 and 2014 were analyzed retrospectively. Among 211 patients with CHB, 35 were superinfected with HAV, 31 were superinfected with HCV, 22 were superinfected with HDV, and 53 were superinfected with HEV. We analyzed and compared the clinical features of the five groups. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), serum albumin (Alb), and the serum levels of HBV DNA. The peak values of ALT, AST, and TBil were significantly higher in all of the superinfected groups. Lower peak Alb concentration and PTA were also observed in the superinfected patients, with the exception of patients in the CHB + HAV group. The CHB + HCV, and CHB + HEV groups had higher death rates than the CHB monoinfected group, and the difference was statistically significant. Further analysis of the liver failure groups showed that the level of HBV DNA was not correlated with prognosis. The comparison of clinical outcomes revealed that CHB patients superinfected with HCV, HDV, and HEV compared with CHB monoinfection had statistically greater incidences of exacerbation of the condition and poor prognosis, whereas the patients superinfected with HAV generally had better outcomes. J. Med. Virol. 88:1003–1009, 2016. © 2015 Wiley Periodicals, Inc.
Contribution of atmospheric internal processes to the interannual variability of the South Asian summer monsoon
Authors: Hsu Pang‐Chi , Yang Yue
Published: October 2015

Apart from the external forcings, the interannual variability of the South Asian summer monsoon can arise from atmospheric internal dynamics, although its mechanism has not been fully understood. Based on a three‐dimensional mean kinetic energy (MKE) budget equation, the contributions of internally generated processes associated with mean flow–transient eddy interaction and circulation–heating feedback to the interannual variability of the South Asian summer monsoon were diagnosed using two reanalysis data sets. In years with enhanced convections over South Asia, a strengthened low (high)‐level MKE related to southwesterly (easterly) jet is observed over the Arabian Sea. The enhancement of MKE at the low level is maintained by both the anomalous barotropic energy conversion between eddy kinetic energy (EKE) and MKE and the baroclinic energy conversion from mean available potential energy (MAPE) to MKE. Among the three‐dimensional barotropic energy conversion processes, the vertical eddy momentum flux interacting with the monsoon vertical wind shear anomaly plays a leading role in supporting the MKE anomaly. Moreover, the contribution of eddy activities related to the intraseasonal oscillation (ISO) of 20–90 days is larger than that of high‐frequency (<20 days) disturbances. This mean flow–ISO interaction dominates the atmospheric energy conversion processes and external boundary factors that may exert the interannual variations of monsoonal MKE in the lower troposphere. Different from the low‐level dynamics, scale interaction between eddies and the mean flow shows an insignificant contribution to the strengthening of the easterly jet in the higher troposphere. The Niño3.4 sea surface temperature anomaly appears to be a key factor modulating the interannual variations of the high‐level monsoon easterly.
Product comparison model in otolaryngology: Equivalency analysis of absorbable hemostatic agents after endoscopic sinus surgery
Authors: Antisdel Jastin L. , Meyer Annika , Comer Brett , Jang David , Gurrola Jose , Khabbaz Eyad , Christopher Kara , Kountakis Stilianos
Published: October 2015

Objectives/Hypothesis

Evidence‐based medicine in otolaryngology literature continues to be lacking, especially with regard to new products brought to market. The marketing of products often includes statements of benefit that have limited objective support in research or literature. To address this, and to adequately determine product equivalency/superiority, careful evaluation must be made. In order to establish standards for this process in rhinology products, we directly compare three different absorbable hemostatic agents in patients with chronic rhinosinusitis (CRS) after undergoing endoscopic sinus surgery (ESS), using both objective and subjective outcomes.

Study Design

Double‐blinded prospective (level 1) comparison and equivalency analysis of three plant‐based absorbable hemostatic agents (carboxymethylcellulose [CMC] gel, mucopolysaccharide hemospheres (MPH), and potato starch wafer) in patients undergoing bilateral ESS.

Methods

Patients with medically refractory CRS who underwent bilateral ESS were recruited and prospectively followed. At the conclusion of ESS, one of three different hemostatic agents was applied to each nasal passage. Subjective patient data was obtained using rated symptoms compared between the two sides (nasal obstruction, bleeding, pain, and nasal discharge) at baseline and on postoperative days 1, 7, and 14. Objective data was obtained by blinded endoscopic scoring to rate mucosal edema, inflammation, granulation, crusting, infection, and synechiae formation on postoperative weeks 1, 3, and 6.

Results

Forty‐eight patients who underwent ESS for CRS were included. There is no statistical difference in subjective scores for any of the variables measured, although (MPH) nearly reached statistical significance at postoperative day 7 for increased pain (P = 0.06) and obstruction (P = 0.22). Objective measures showed equivalency between all products, except the CMC gel approached significance at week 3 for increased crusting (P = 0.10), granulation (P = 0.24), and debridement (P = 0.07). At 6 weeks, increased debridement (P = 0.14) also approached significance.

Conclusion

Careful and deliberate consideration should be taken when choosing products to assist our surgical endeavors. Subjectively, patients treated with MPH showed near‐significant increases in pain and obstruction. In objective measures, CMC gel nearly reaches significance for more postoperative debridement, with increased crusting and inflammation. Product choice could consider these factors, although it remains at the discretion of the surgeon. This model of comparison allows careful product comparison and should be applied to other hemostatics, as well as other materials in use in otolaryngology.

Level of Evidence

1b. Laryngoscope, 126:S5–S13, 2016
The chemistry, mechanism and function of tricresyl phosphate (TCP) as an anti‐wear lubricant additive
Authors: Guan Bihan , Pochopien Bernadeta A. , Wright Dominic S.
Published: October 2015

The detailed understanding of the physical and reaction chemistry of engineering lubricants is key to new developments in the future. Here, we draw together the main chemical/engineering literature in the first systematic review of the standard anti‐wear additive used as an aviation lubricant, tricresyl phosphate (TCP), focusing on understanding the links between the surface chemistry, tribology and decomposition of TCP. While there is still debate concerning the mechanism of TCP, it is clear that it is activated by moisture, oxygen or oxidised metal surfaces. Its anti‐wear properties arise from the resulting formation of iron phosphate or polyphosphate on the contact surfaces. Evidence stresses the importance of chemistry at the boundary layer and a mechanism involving pre‐coordination of TCP at the surface, resulting in activation at the P‐centre and subsequent attack by residual H2O or surface O2−. This perspective provides a potential baseline for the development of future phosphorus‐based high‐performance additives. Copyright © 2015 John Wiley & Sons, Ltd.
Versatile Protein Nanogels Prepared by In Situ Polymerization
Authors: Ye Yanqi , Yu Jicheng , Gu Zhen
Published: October 2015

Proteins with unique structure and function have tremendous applications for cancer treatment, vaccination, diagnosis, regenerative medicine, and therapies for loss‐of‐function genetic diseases. A general method of loading and delivering active forms of proteins toward cells and tissues is highly desirable for remaining activity, enhancing stability, and avoiding potential immunogenicity of proteins. Nanogels with cross‐linked structure provide a versatile platform for storage and release of proteins. Herein, the recent advances in protein nanogels made by the in situ polymerization method, from preparation to application are summarized. A range of stimuli‐responsive formulations for on‐demand release, in a spatial, temporal, and dosage‐controlled manner, is highlighted. Future opportunities as well as challenges of protein nanogels are also discussed.

image
Coacervation of Elastin‐Like Recombinamer Microgels
Authors: Singh Smriti , Demco Dan Eugen , Rahimi Khosrow , Fechete Radu , Rodriguez‐Cabello José Carlos , Möller Martin
Published: October 2015

The investigation of the coacervation (self‐aggregation) behavior of biomicrogels which can potentially be used as drug carriers is an important topic, because self‐aggregation can not only cause loss of activity, but also toxicity and immunogenicity. To study this effect microgels from elastin‐like recombinamer are synthesized using miniemulsion technique. The existence of coacervation for such microgels, at different concentrations and temperatures, is studied and proved by cryo‐field emission scanning clectron microscopy (cryo‐FESEM), cryo‐transmission electron microscopy (cryo‐TEM), and by a novel 1H high‐resolution magic angle sample spinning (HRMAS), nuclear magnetic resonance (NMR) spectroscopy, and relaxometry methods. The findings by 1H HRMAS NMR spectroscopy and relaxometry show simultaneous processes of volume phase temperature transition and coacervation with different sensitivity for hydrophobic and hydrophilic amino acid side‐chains in the microgel. The coacervation process is more evidential by the behavior of glycine α‐CH2, 1H NMR peak as compared to the proline β‐CH2.

image
Alternating Intramolecular and Intermolecular Catalyst‐Transfer Suzuki–Miyaura Condensation Polymerization: Synthesis of Boronate‐Terminated π‐Conjugated Polymers Using Excess Dibromo Monomers
Authors: Nojima Masataka , Kosaka Kentaro , Kato Masaru , Ohta Yoshihiro , Yokozawa Tsutomu
Published: October 2015

The Suzuki–Miyaura coupling polymerization of dibromoarene 1 and arylenediboronic acid (ester) 2 with a Pd catalyst having a high propensity for intramolecular catalyst transfer is reported. The polymerization of excess 1 with 2 affords high‐molecular‐weight π‐conjugated polymer having boronic acid (ester) moieties at both ends, contrary to Flory's principle. This unstoichiometric polycondensation behavior is accounted for by intramolecular transfer of the Pd catalyst on 1. In the polymerization of 1 and 2 having different aryl residues, high‐molecular‐weight polymer is obtained when the stronger donor aromatic is used as the dibromo monomer and the weaker donor or acceptor aromatic is used as diboronic acid (ester) monomer. The pinacol boronate moieties at both ends of the obtained poly(p‐phenylene) (PPP) can be converted to benzoic acid ester, hydroxyl group, and bromine. Furthermore, the reaction of the pinacol boronate‐terminated PPP with poly(3‐hexylthiophene) (P3HT) having bromine at one end yields a triblock copolymer of P3HT‐b‐PPP‐b‐P3HT.

image
Oncogenic activin C interacts with decorin in colorectal cancer in vivo and in vitro
Authors: Bi Xiuli , Xia Xichun , Fan Dongdong , Mu Teng , Zhang Qiuhua , Iozzo Renato V. , Yang Wancai
Published: October 2015

Activin C is a member of the transforming growth factor‐β (TGF‐β) superfamily with various biological activities. Decorin is a member of the small leucine‐rich proteoglycan family, which can bind to TGF‐β and modulate TGF‐β‐mediated signaling. In the decorin‐deficient mouse model, we found that the expression of activin C was remarkably increased in the intestine of Dcn−/− mice compared to the expression of activin C in the intestine of Dcn+/+ mice. Addition of activin C protein to colorectal cancer cells or over‐expression of activin C in these cells stimulated cell growth, migration, and invasion in vitro. Enhanced AP‐1 expression in colorectal cancer cells was found to be associated with the oncoprotein‐like effects of activin C through the JNK/AP‐1 pathway, and not the Smad signaling pathway. However, these effects were abolished when decorin expression was restored by transfecting the cells with a decorin‐expressing plasmid or by reducing the expression of activin C via interfering RNA. Further analysis demonstrated that decorin could directly bind to and accelerate the degradation of activin C. In conclusion, our data provided the first evidence demonstrating the oncogenic role of activin C in intestinal tumorigenesis of decorin‐deficient mice and colorectal cancer cells. © 2015 Wiley Periodicals, Inc.
Selective spectroscopic imaging of hyperpolarized pyruvate and its metabolites using a single‐echo variable phase advance method in balanced SSFP
Authors: Varma Gopal , Wang Xiaoen , Vinogradov Elena , Bhatt Rupal S. , Sukhatme Vikas P. , Seth Pankaj , Lenkinski Robert E. , Alsop David C. , Grant Aaron K.
Published: October 2015

Purpose

In balanced steady state free precession (bSSFP), the signal intensity has a well‐known dependence on the off‐resonance frequency, or, equivalently, the phase advance between successive radiofrequency (RF) pulses. The signal profile can be used to resolve the contributions from the spectrally separated metabolites. This work describes a method based on use of a variable RF phase advance to acquire spatial and spectral data in a time‐efficient manner for hyperpolarized 13C MRI.

Theory and Methods

The technique relies on the frequency response from a bSSFP acquisition to acquire relatively rapid, high‐resolution images that may be reconstructed to separate contributions from different metabolites. The ability to produce images from spectrally separated metabolites was demonstrated in vitro, as well as in vivo following administration of hyperpolarized 1‐13C pyruvate in mice with xenograft tumors.

Results

In vivo images of pyruvate, alanine, pyruvate hydrate, and lactate were reconstructed from four images acquired in 2 s with an in‐plane resolution of 1.25 × 1.25 mm2 and 5 mm slice thickness.

Conclusion

The phase advance method allowed acquisition of spectroscopically selective images with high spatial and temporal resolution. This method provides an alternative approach to hyperpolarized 13C spectroscopic MRI that can be combined with other techniques such as multiecho or fluctuating equilibrium bSSFP. Magn Reson Med 76:1102–1115, 2016. © 2015 Wiley Periodicals, Inc.
Continuous urethral pressure measurements; measurement techniques; pressure variations; clinical interpretations; and clinical relevance. A Systematic Literature Analysis
Authors: Kummeling Maxime T.M. , Rosier Peter F.W.M. , Elzevier Henk W. , Groenendijk Pieter M.
Published: October 2015

Aims

The clinical relevance of urethral pressure variations (UPV) in the pathophysiology of over active bladder syndrome (OAB) has remained controversial to date. Some studies report an association with OAB and/or detrusor over activity (DO). Recently the International Consultation on Incontinence—Research Society recommended new clinical research to be performed on this subject. We provide a systematic review of the literature to specify this recommendation.

Methods

Literature search was performed in PubMed, Embase, Web of Science, Cochrane, Central, Cinahl, Academic Science Premier, Science Direct, and Wiley Online using a sensitive search string combination. All authors independently reviewed and scored full text papers and consensus about methodological quality was obtained according to Oxford Level of Evidence (LoE).

Results

Four hundred eighty seven abstracts were screened, 25 papers met all predefined inclusion selection criteria. Incidence figures of UPV varied between 2% and 95%. Studies are of poor methodological quality with Oxford LoE scores of 3B and 4. Measurement methods and techniques show a large variety. The above mentioned association of DO/OAB with UPV is however frequently reported.

Conclusion

There exists a phenomenon of UPV, apart from DO, which may be a separate entity within OAB syndrome. Large variation in measurement techniques and patient populations hinders fundamental research as well as clinical progress. Clinical relevance of UPV and consequences for treatment therefore are yet to be established. Future prospective research with well‐defined patient population and standardised urodynamic measurement techniques is needed. Results of standardized and objective evaluations should be compared to clinical signs and symptoms by validated questionnaires. Neurourol. Urodynam. 36:51–56, 2017. © 2015 Wiley Periodicals, Inc.
Comparative and quantitative proteomics reveal the adaptive strategies of oyster larvae to ocean acidification
Authors: Dineshram R. , Q. Quan , Sharma Rakesh , Chandramouli Kondethimmanahalli , Yalamanchili Hari Krishna , Chu Ivan , Thiyagarajan Vengatesen
Published: October 2015

Decreasing pH due to anthropogenic CO2 inputs, called ocean acidification (OA), can make coastal environments unfavorable for oysters. This is a serious socioeconomical issue for China which supplies >70% of the world's edible oysters. Here, we present an iTRAQ‐based protein profiling approach for the detection and quantification of proteome changes under OA in the early life stage of a commercially important oyster, Crassostrea hongkongensis. Availability of complete genome sequence for the pacific oyster (Crassostrea gigas) enabled us to confidently quantify over 1500 proteins in larval oysters. Over 7% of the proteome was altered in response to OA at pHNBS 7.6. Analysis of differentially expressed proteins and their associated functional pathways showed an upregulation of proteins involved in calcification, metabolic processes, and oxidative stress, each of which may be important in physiological adaptation of this species to OA. The downregulation of cytoskeletal and signal transduction proteins, on the other hand, might have impaired cellular dynamics and organelle development under OA. However, there were no significant detrimental effects in developmental processes such as metamorphic success. Implications of the differentially expressed proteins and metabolic pathways in the development of OA resistance in oyster larvae are discussed. The MS proteomics data have been deposited to the ProteomeXchange with identifiers PXD002138 (http://proteomecentral.proteomexchange.org/dataset/PXD002138).
The “busy life” of unliganded estrogen receptors
Authors: Stellato Claudia , Porreca Immacolata , Cuomo Danila , Tarallo Roberta , Nassa Giovanni , Ambrosino Concetta
Published: October 2015

Understanding of the role of estrogen receptors (ERα and ERβ) in the pathophysiology of breast cancer (BC) has considerably increased in last decades. Despite sharing a similar structure, these two transcription factors often exert opposite roles in BC. In addition, it has been shown that their transcriptional activity is not strictly associated to ligand activation and that unliganded ERs are able to “have a life on their own.” This appears to be mainly due to ligand‐independent mechanisms leading to ERs PTMs or to their recruitment to specific protein complexes, dependent on cellular context. Furthermore, a significant unliganded ER activity, probably independent by the activation of other pathways, has been recently reported to affect gene transcription, microRNA expression, and downstream proteome. In this review, we describe recent findings on nuclear and cytoplasmic unliganded ERα and ERβ activity. We focus on functional genomics, epigenomics, and interaction proteomics data, including PTM induced by ERs‐modulated miRNAs in the BC context. A better comprehension of the molecular events controlled by unliganded ERs activity in BC pathogenesis is crucial since it may impact the therapeutic approach to the initial or acquired resistance to endocrine therapies, frequently experienced in the treatment of BC.
Dynamic changes of histone H3 marks during Caenorhabditis elegans lifecycle revealed by middle‐down proteomics
Authors: Sidoli Simone , Vandamme Julien , Salcini Anna Elisabetta , Jensen Ole N.
Published: October 2015

We applied a middle‐down proteomics strategy for large‐scale protein analysis during in vivo development of Caenorhabditis elegans. We characterized PTMs on histone H3 N‐terminal tails at eight time points during the C. elegans lifecycle, including embryo, larval stages (L1–L4), dauer, and L1/L4 postdauer. Histones were analyzed by our optimized middle‐down protein sequencing platform using high mass accuracy MS/MS. This allows quantification of intact histone tails and detailed characterization of distinct histone tails carrying cooccurring PTMs. We measured temporally distinct combinatorial PTM profiles during C. elegans development. We show that the doubly modified form H3K23me3K27me3, which is rare or nonexistent in mammals, is the most abundant PTM in all stages of C. elegans lifecycle. The abundance of H3K23me3 increased during development and it was mutually exclusive of the active marks H3K18ac, R26me1, and R40me1, suggesting a role for H3K23me3 in silent chromatin. We observed distinct PTM profiles for normal L1 larvae and for L1‐postdauer larvae, or L4 and L4 postdauer, suggesting that histone PTMs mediate an epigenetic memory that is transmitted during dauer formation. Collectively, our data describe the dynamics of histone H3 combinatorial code during C. elegans lifecycle and demonstrate the feasibility of using middle‐down proteomics to study in vivo development of multicellular organisms. All MS data have been deposited in the ProteomeXchange with identifier PXD002525 (http://proteomecentral.proteomexchange.org/dataset/PXD002525).
Hyperbranched polymer structures via flexible blade flow coating
Authors: Liu Yujie , Lee Dong Yun , Monteux Cécile , Crosby Alfred J.
Published: October 2015

Evaporative self‐assembly has been shown to be a scalable method for organizing nonvolatile solutes, for example, nanoparticles; however, the influence of substrate surface energy on this technique has not been studied extensively. In this work, we utilized an evaporative self‐assembly process based upon flexible blade flow coating to fabricate organized structures that have been modified to systematically vary surface energy. We focused on patterning of polystyrene. We observed a variety of polystyrene structures including dots, hyperbranched patterns, stripes, and lines that can be deposited on substrates with a range of wetting properties. We explained the mechanism for these structural formations based on the competition between Marangoni flow, friction, and viscosity. The development of this fundamental knowledge is important for controlling hierarchical manufacturing of nanoscale objects with different surface chemistries and compositions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 32–37
Photoswitching and Thermoresponsive Properties of Conjugated Multi‐chromophore Nanostructured Materials
Authors: Bhattacharyya Santanu , Jana Bikash , Sain Sumanta , Barman Monoj Kumar , Pradhan Swapan Kumar , Patra Amitava
Published: October 2015

Conjugated multi‐chromophore organic nanostructured materials have recently emerged as a new class of functional materials for developing efficient light‐harvesting, photosensitization, photocatalysis, and sensor devices because of their unique photophysical and photochemical properties. Here, we demonstrate the formation of various nanostructures (fibers and flakes) related to the molecular arrangement (H‐aggregation) of quaterthiophene (QTH) molecules and their influence on the photophysical properties. XRD studies confirm that the fiber structure consists of >95% crystalline material, whereas the flake structure is almost completely amorphous and the microstrain in flake‐shaped QTH is significantly higher than that of QTH in solution. The influence of the aggregation of the QTH molecules on their photoswitching and thermoresponsive photoluminescence properties is revealed. Time‐resolved anisotropic studies further unveil the relaxation dynamics and restricted chromophore properties of the self‐assembled nano/microstructured morphologies. Further investigations should pave the way for the future development of organic electronics, photovoltaics, and light‐harvesting systems based on π‐conjugated multi‐chromophore organic nanostructured materials.
Cation Exchange Synthesis and Unusual Resistive Switching Behaviors of Ag2Se Nanobelts
Authors: Guo Zheng , Li Min‐Qiang , Liu Jin‐Huai , Huang Xing‐Jiu
Published: October 2015

Ag2Se nanobelts are prepared through employing ZnSe nanobelts as templates via a facile cation exchange approach. The templates are derived from precursor ZnSe·0.5N2H4 nanobelts, which are synthesized by a simple hydrothermal method. As‐synthesized precursor nanobelts are with 200 nm in width and several hundreds of micrometers in length. Annealed in N2, they are transformed into ZnSe nanobelts with preserving their initial morphology. Following with a complete replacement of Zn2+ by Ag+, Ag2Se nanobelts with single crystalline are obtained via a cation‐exchange reaction. Combined with the Langmuir–Blodgett assembly technique, regular films of ZnSe nanobelts can be achieved on transparent glass substrates and Si wafers with interdigital Au electrode arrays. Further, the optical and electrical evolutions are investigated from ZnSe nanobelts to Ag2Se nanobelts. Finally, the resistive switching characteristic are carefully explored for Ag2Se nanobelts regularly arranged on interdigital Au microelectrodes. The results indicate that it is analogous to complementary resistive switching behaviors, which is different from that of traditional two terminal devices about previously reported Ag2Se. In order to clarify this phenomenon, a possible mechanism has been proposed and indirectly demonstrated through in situ SEM (scanning electron microscropy) observation.
MiR-375 is Essential for Human Spinal Motor Neuron Development and May Be Involved in Motor Neuron Degeneration
Authors: Bhinge Akshay , Namboori Seema C. , Bithell Angela , Soldati Chiara , Buckley Noel J. , Stanton Lawrence W.
Published: October 2015

The transcription factor REST is a key suppressor of neuronal genes in non-neuronal tissues. REST has been shown to suppress proneuronal microRNAs in neural progenitors indicating that REST-mediated neurogenic suppression may act in part via microRNAs. We used neural differentiation of Rest-null mouse ESC to identify dozens of microRNAs regulated by REST during neural development. One of the identified microRNAs, miR-375, was upregulated during human spinal motor neuron development. We found that miR-375 facilitates spinal motor neurogenesis by targeting the cyclin kinase CCND2 and the transcription factor PAX6. Additionally, miR-375 inhibits the tumor suppressor p53 and protects neurons from apoptosis in response to DNA damage. Interestingly, motor neurons derived from a spinal muscular atrophy patient displayed depressed miR-375 expression and elevated p53 protein levels. Importantly, SMA motor neurons were significantly more susceptible to DNA damage induced apoptosis suggesting that miR-375 may play a protective role in motor neurons.
Changes in habitat use and nesting density in a declining seabird colony
Authors: Rebstock Ginger A. , Boersma P. Dee , García‐Borboroglu Pablo
Published: October 2015

Seabirds in expanding colonies select the highest‐quality nesting habitat, but habitat selection has seldom been studied in declining colonies. We studied a colony of Magellanic penguins (Spheniscus magellanicus) that declined from 314,000 active nests in 1987 to 201,000 in 2014. As expected, nest quality and reproductive success were higher in burrow habitats than in other habitats, and nest density decreased with distance from shore. Contrary to predictions, the steepest declines did not occur in the poorest‐quality habitat (scrub) or near the inland colony edge and the colony area did not shrink. In agreement with predictions, penguins shifted from nests with less cover to nests with more cover. The highest nest densities and the steepest declines were in habitats of large bushes and bush clusters. As the population declined penguins abandoned nests on the edges of large bushes. Constraints on penguin habitat‐use changes include strong area and nest‐site fidelity, increased avian predation in high‐density areas, soil characteristics, and the costs of making and maintaining nests. Contrary to conventional wisdom we found low‐density, poor‐quality scrub habitat (which covers >70 % of the colony area) contained 45 % of active nests, produced 44 % of fledglings, and was as important as high‐quality habitat for reproductive output. Our research shows that all habitats in a declining colony of seabirds have value for conservation.
A lepidopterous cocoon from Thera and evidence for silk in the Aegean Bronze Age
Authors: Panagiotakopulu E. , Buckland P.C. , Day P.M. , Doumas C. , Sarpaki A. , Skidmore P.
Published: October 2015

What were the fine garments vividly painted in the Minoan frescoes made of? Fine cotton (cotton from Egypt is still prized today)? Or the yet finer fabric of silk? And if silk, where did the stuff, or knowledge of cultivating the silk-worms, come from? A cocoon from Santorini offers new evidence.
Early pregnancy vitamin D status and risk for adverse maternal and infant outcomes in a bi-ethnic cohort: the Behaviors Affecting Baby and You (B.A.B.Y.) Study
Authors: Nobles Carrie J. , Markenson Glenn , Chasan-Taber Lisa
Published: October 2015

Vitamin D deficiency is common during pregnancy and higher in Hispanic as compared with non-Hispanic white women. However, the association between vitamin D deficiency and adverse pregnancy outcomes remains unclear and may vary across ethnic groups, in part because of genetic variation in the metabolism of vitamin D. Few studies have included Hispanic women. Therefore, we investigated this association among 237 participants in the Behaviors Affecting Baby and You Study, a randomised trial of an exercise intervention among ethnically diverse prenatal care patients in Massachusetts. Baseline serum 25-hydroxyvitamin D (25(OH)D) was measured at 15·2 (sd 4·7) weeks’ gestation. Information on adverse pregnancy outcomes was abstracted from medical records. Mean 25(OH)D was 30·4 (sd 12·0) ng/ml; 53·2 % of participants had insufficient (<30 ng/ml) and 20·7 % had deficient (<20 ng/ml) 25(OH)D levels. After adjusting for month of blood draw, gestational age at blood draw, gestational age at delivery, age, BMI and Hispanic ethnicity, women with insufficient and deficient vitamin D had infants with birth weights 139·74 (se 69·16) g (P=0·045) and 175·52 (se 89·45) g (P=0·051) lower compared with women with sufficient vitamin D levels (≥30 ng/ml). Each 1 ng/ml increase in 25(OH)D was associated with an increased risk for gestational diabetes mellitus among Hispanic women only (relative risk 1·07; 95 % CI 1·03, 1·11) in multivariable analysis. We did not observe statistically significant associations between maternal vitamin D status and other pregnancy outcomes. Our findings provide further support for an adverse impact of vitamin D deficiency on birth weight in Hispanic women.