bluuebunny/crossref_metadata_2025 huggingface dataset:
High Levels of Serum Prolactin Protect Against Diabetic Retinopathy by Increasing Ocular Vasoinhibins
Authors: Arnold Edith , Rivera José C. , Thebault Stéphanie , Moreno-Páramo Daniel , Quiroz-Mercado Hugo , Quintanar-Stéphano Andrés , Binart Nadine , Martínez de la Escalera Gonzalo , Clapp Carmen
Published: September 2010

OBJECTIVE

Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sight-threatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men and test whether increased circulating PRL, by serving as a source of ocular vasoinhibins, can reduce the pathological RVP in diabetes.

RESEARCH DESIGN AND METHODS

Serum PRL was evaluated in 40 nondiabetic and 181 diabetic men at various stages of DR. Retinal vasoinhibins were measured in rats rendered hyperprolactinemic by placing two anterior pituitary grafts under the kidney capsule and in PRL receptor–null mice. RVP was determined in hyperprolactinemic rats subjected to the intraocular injection of vascular endothelial growth factor (VEGF) or made diabetic with streptozotocin.

RESULTS

The circulating levels of PRL increased in diabetes and were higher in diabetic patients without retinopathy than in those with proliferative DR. In rodents, hyperprolactinemia led to vasoinhibin accumulation within the retina; genetic deletion of the PRL receptor prevented this effect, indicating receptor-mediated incorporation of systemic PRL into the eye. Hyperprolactinemia reduced both VEGF-induced and diabetes-induced increase of RVP. This reduction was blocked by bromocriptine, an inhibitor of pituitary PRL secretion, which lowers the levels of circulating PRL and retinal vasoinhibins.

CONCLUSIONS

Circulating PRL influences the progression of DR after its intraocular conversion to vasoinhibins. Inducing hyperprolactinemia may represent a novel therapy against DR.
Antidepressant Medication Use, Weight Gain, and Risk of Type 2 Diabetes
Authors: Kivimäki Mika , Hamer Mark , Batty G. David , Geddes John R. , Tabak Adam G. , Pentti Jaana , Virtanen Marianna , Vahtera Jussi
Published: September 2010

OBJECTIVE

To examine antidepressant medication use as a risk factor for type 2 diabetes and weight gain.

RESEARCH DESIGN AND METHODS

A series of nested studies within a prospective cohort of 151,347 working-aged men and women including 9,197 participants with continuing antidepressant medication, 224 with severe depression, and 851 with incident type 2 diabetes during a mean follow-up of 4.8 years, as indicated by national health and prescription registers (the Public Sector study, Finland 1995–2005).

RESULTS

In the first analysis, the case subjects were individuals with incident type 2 diabetes compared with matched diabetes-free control subjects. Antidepressant use of ≥200 defined daily doses was associated with a doubling of diabetes risk in both participants with no indication of severe depression (odds ratio 1.93 [95% CI 1.48–2.51]) and participants with severe depression (2.65 [1.31–5.39]). In further analyses, the exposed group was antidepressant users and the reference group was nonusers matched for depression-related characteristics. The 5-year absolute risk of diabetes was 1.1% for nonusers, 1.7% for individuals treated with 200–399 defined daily doses a year, and 2.3% for those with ≥400 defined daily doses (Ptrend < 0.0001). An average self-reported weight gain, based on repeated surveys, was 1.4 kg (2.5%) among nonusers and 2.5 kg (4.3%) among users of ≥200 defined daily doses (Ptrend < 0.0001). Separate analyses for tricyclic antidepressants and selective serotonin reuptake inhibitors replicated these findings.

CONCLUSIONS

In these data, continuing use of antidepressant medication was associated with an increased relative risk of type 2 diabetes, although the elevation in absolute risk was modest.
Peripartum serum leptin and soluble leptin receptor levels in women with gestational diabetes
Authors: Chen Danqing , Xia Guiyu , Xu Ping , Dong Minyue
Published: September 2010

The purpose of the study was to clarify the alterations in serum leptin and soluble leptin receptor levels at term and early postpartum in gestational diabetes mellitus (GDM). Twenty women with normal pregnancy and 20 with GDM were recruited and blood samples were taken on the day of delivery and Days 1, 3 and 5 after delivery. Serum leptin levels were significantly higher in women with GDM than in the controls before delivery and decreased significantly after delivery (p < 0.001). After delivery there were no significant differences in serum leptin concentrations between women with GDM and the controls. Serum soluble leptin receptor concentrations did not differ neither between the two groups, nor before or after delivery. Leptin may play a role in GDM through a positive correlation with insulin resistance.
Gemachte Märkte: institutionelles Unternehmertum im Forstsektor | Made markets – institutional entrepreneurship in the forestry sector
Authors: Schlüter Achim , Nichiforel Liviu
Published: September 2010

Forestry markets are in a constant process of change of their rules of the game. This is due to the fact that preferences, scarcities and technological means are in a steady process of development. However, this process of change in the rules of the game does not only take place, as often assumed, on the political level, but it is a co-evolutionary process of political, administrative and market governance and emergence. The so-called institutional entrepreneurs play a major role in this process of change. The present paper takes a closer look at the activities of those entrepreneurs and their positive and negative effects, and develops an analytical framework, based on the Institutional Analysis and Development Framework. Current examples of institutional change in the forestry sector are used to illustrate our arguments.
Rechtliche Aspekte bei der Vermarktung von Nichtholz-Waldleistungen | Legal aspects of the marketing of non-wood forest services
Authors: Zimmermann Willi
Published: September 2010

The production and marketing of forest goods and services are strongly influenced by legal conditions. Civil law lays down who is proprietor of something, who may determine over it and to what extent. The commercialization of the three ecosystem services “water filtration”, “carbon storage” and “protection from natural hazards” is confined to certain limits by the law of property. With the exception of carbon storage, the possibilities are further limited by the forest and water legislation of Confederation and the cantons. The subsidy regulations in forest law do however offer the possibility of setting mechanisms into motion for cooperative services which resemble commercialization. If these initial approaches are to be further developed or to become the rule, changes in legislation will become necessary in civil as well as in public law.
Vermarktung von Schutzleistungen des Waldes – das Beispiel des Kantons Bern | Marketing of protection services – the example of Canton Berne
Authors: Schmidt Roger
Published: September 2010

In Switzerland, payments to forest owners and enterprises compensating the costs of forestry measures for protecting houses and infrastructure from natural hazards – and thus providing benefits to the public – are now better than for other non-wood products and services. With the new system of Redistribution of Income and Responsibilities between the Confederation and the cantons (NFA), not only the financial contributions and the procedures between Confederation and cantons have been adapted. In Canton Berne, the entity responsible for the safety of the object to be protected (“Safety Agency”) is now included in the decision making process and the financing. Where housing is concerned, the communal authorities usually act as Safety Agency, where infrastructure is concerned the owner or operating authority. The Forestry Service of Canton Berne defines the procedures, advises the forest owners and Safety Agency, and provides public funding when the requirements are met. Forest owners and Safety Agency agree on the services to be provided and the remaining funding. The financial contributions of Confederation, cantons and Safety Agency do not compensate the forest owner for the protective effect of his forest, but for the actual dispositive and operative services provided. These need to be furnished in an efficient and transparent way.

Forest enterprises must also be able to make profits with the management of protection forests. Covering costs alone is not a sufficient incentive to ensure that the necessary measures are carried out in the long term.
Prolonged shedding of amantadine- and oseltamivir-resistant influenza A(H3N2) virus with dual mutations in an immunocompromised infant
Authors: Ruiz-Carrascoso Guillermo , Casas Inmaculada , Pozo Francisco , González-Vincent Marta , Pérez-Breña Pilar
Published: September 2010

In this study, we report a case of multidrug-resistant influenza A(H3N2) virus isolated from an immunosuppressed patient with prolonged viral shedding. We also describe the genetic characterization of the haemagglutinin, neuraminidase and M2 influenza genes. The virus contained the substitutions E119V in neuraminidase and V27A in M2, which produce resistance to oseltamivir and adamantanes, respectively. This is the first report of this dual mutation pattern in multidrug-resistant influenza A(H3N2) virus.
Mobile Multimedia
Authors: O’Grady Michael , O’Hare Gregory , Collier Rem
Published: September 2010

Delivering multimedia services to roaming subscribers raises significant challenges for content providers. There are a number of reasons for this; however, the principal difficulties arise from the inherent differences between the nature of mobile computing usage, and that of its static counterpart. The harnessing of appropriate contextual elements pertaining to a mobile subscriber at any given time offers significant opportunities for enhancing and customising service delivery. Dynamic content provision is a case in point. The versatile nature of the mobile subscriber offers opportunities for the delivery of content that is most appropriate to the subscriber’s prevailing context, and hence is most likely to be welcomed. To succeed in this endeavour requires an innate understanding of the technologies, the mobile usage paradigm and the application domain in question, such that conflicting demands may be reconciled to the subscriber’s benefit. In this paper, multimedia-augmented service provision for mobile subscribers is considered in light of the availability of contextual information. In particular, context-aware pre-caching is advocated as a means of maximising the possibilities for delivering context-aware services to mobile subscribers in scenarios of dynamic contexts.
Simplicity, Consistency, Universality, Flexibility and Familiarity
Authors: Picking Rich , Grout Vic , McGinn John , Crisp Jodi , Grout Helen
Published: September 2010

This paper describes the user interface design, and subsequent usability evaluation of the EU FP6 funded Easyline+ project, which involved the development of ambient assistive technology to support elderly and disabled people in their interaction with kitchen appliances. During this process, established usability design guidelines and principles were considered. The authors’ analysis of the applicability of these has led to the development of a new set of principles, specifically for the design of ambient computer systems. This set of principles is referred to as SCUFF, an acronym for simplicity, consistency, universality, flexibility and familiarity. These evaluations suggest that adoption of the SCUFF principles was successful for the Easyline+ project, and that they can be used for other ambient technology projects, either as complementary to, or as an alternative to more generic and partially relevant principles.
Agent-Directed Tracing of Multi-Scale Drug Disposition Events within Normal and Diseased In Silico Livers
Authors: Kim Sean H. J. , Park Sunwoo , Ropella Glen E. P. , Hunt C. Anthony
Published: September 2010

Cirrhosis, a chronic liver disease, alters hepatic drug disposition; however, little is known about micro-mechanisms underpinning disease progression and how they contribute to changes in liver disposition properties. In this article, the authors present multilevel, agent-based and agent-directed In Silico Livers (ISLs) to probe plausible micro-mechanistic details for a cationic drug, diltiazem, in two different types of cirrhotic rat livers. Starting with ISLs that validated against diltiazem disposition data from normal livers, the authors systematically transformed ISL characteristics to achieve validation against perfusion outflow profiles from the two types of diseased livers. In this regard, the authors developed and implemented multilevel methods to trace each object representing diltiazem during simulated perfusion experiments. This enabled gaining heretofore-unavailable insight into plausible micro-mechanistic details from diltiazem’s perspective in normal and diseased livers. The authors posit that the presented ISL micro-mechanistic details may have disease caused counterparts during disposition.
Simulating Cooperative Behaviors in Dynamic Networks
Authors: Zhang Yu , Leezer Jason , Wong Kenny
Published: September 2010

Agent-based social simulation uses agent systems to study social behaviors and phenomena. A difficulty in producing social simulations lies in the problem of modeling the emergence of social norms. Although empirical evidence has provided insight into how human relationships are organized, the way in which those relationships are used to produce cooperative behavior where each agent only seeks to maximize its own utility is not well defined. This paper proposes a new rule called the Highest Rewarding Neighborhood (HRN) for social interactions. The HRN rule allows agents to remain selfish and be able to break relationships in order to maximize their utility. Our experiment shows that when agents are able to break unrewarding relationships that a Pareto-optimum strategy arises as the social norm. In addition, the authors conclude the rate and amount of Pareto-optimum strategy that arises is dependent on the network structure when the networks are dynamic, and the rate is independent of the network structure when the networks are static.
Effect of Access to Formal Market Information on Prices Received by Smallholder Farmers in Uganda
Authors: Kiiza Barnabas , Mugisha Johnny , Lwasa Stephen
Published: September 2010

Much work has been done to improve smallholder farmers’ adoption of new agricultural technology packages in Uganda; however, little commensurate effort has been made to improve their access to formal market information channels like mobile telephony, FM radio stations, Internet, and other information centers. This study is based on data obtained in 2006 from farmers affiliated to Uganda Cooperative Alliance and those who are not; however, both cohorts are located in the districts of Mukono and Masaka. Findings show that households in more remote locations are less likely to use formal channels, and conversely, perception of reliability of the information, membership in a farmers’ group and commercial orientation of the farmer, all increase the likelihood of their use. The authors’ findings indicate that farmers who have access to information from formal channels consistently obtain higher farm-gate prices than those who obtain information from informal channels.
Mobile Agriculture in South Africa
Authors: Maumbe Blessing Mukabeta
Published: September 2010

The rapid diffusion of mobile and wireless technologies is transforming agricultural development globally. In South Africa, rural e-government service delivery has been hampered by low Internet penetration. Mobile government offers a promising alternative to deliver public services to remote rural communities. In this regard, the author examines the potential of mobile and wireless technologies to deliver value-added services to rural communities in South Africa. An implementation framework comprising a multi-functional agro-portal and mobile agriculture services is proposed. The benefits and barriers of using mobile and wireless technologies in rural areas are examined, while key considerations and policy implications for mobile agriculture are discussed. The author advocates the development of “value-based” and “demand-driven” mobile agriculture services for the future growth and survival of mobile agriculture, which requires greater competition among service providers, use of multi-lingual e-content, integration of indigenous knowledge, mobile agriculture curriculum, mobile cyber-security, and customized value-added services for rural communities.
Analysis and Validation of Learning Technology Models, Standards and Specifications
Authors: Pawlowski Jan M. , Kozlov Denis
Published: September 2010

The paper presents a model for the analysis, comparison and validation of standards, specifications and in particular reference models in the field of Technology Enhanced Learning (TEL). The Reference Model Analysis Grid (RMAG) establishes categories of reference models and standards. Based on those categories, a set of criteria for the analysis and validation of standards was elaborated as a part of the ICOPER project that aims at interoperable open content for competency-based TEL. The analysis of standards in this context is targeted at developing a set of validated approaches that lead to a new reference model. Four standards were investigated, taking into account a broad range of aspects like practical and semantic interoperability and integration issues. In the case study, the authors analyzed both, the standards and specifications and the usefulness of the RMAG. The results of this case study can be used for further analyses of TEL standards as well as for reference models targeted at interoperability.
Application Profiles and Tailor-Made Conformance Test Systems
Authors: Dahn Ingo , Zimmermann Sascha
Published: September 2010

This article examines the potential of application profiles and domain profiles as means to adapt technical specifications of data structures to particular needs. The authors argue that application profiling is better suited to increase the use of formal specifications than the creation of new specifications. The authors also describe a method to generate specific conformance test systems for machine-readable application profiles. The authors describe the respective tool set of the SchemaProf Application Profiling Tool and the Generic Test System and report on the experience of their usage in developing and introducing the IMS Common Cartridge domain profile.
Community-Driven Specifications
Authors: Wilson Scott
Published: September 2010

This paper explores the issues and opportunities for specifications that develop outside of the traditional governance processes of industry consortia or formal standards organisations through a discussion and comparison of three specifications developed in the education sector: XCRI (eXchanging Course-Related Information), SWORD (Simple Web service Offering Repository Deposit), and LEAP2.0 (Learner Portfolios 2.0). In each case study, there are challenges, opportunities, and accomplishments, and the experiences of each project are compared to identify commonalities and differences. Based on these case studies, the paper applies the framework developed by Wilson and Velayutham (2009) to position the specifications against similar specifications from established consortia and formal standards. Finally, the topic of incubating specifications is discussed, with implications for funding agencies with an interest in supporting interoperability.
Integrated Strategy of Water Quality Monitoring and Simulation for Amazon Reservoirs
Authors: da Bessa Marcio R. M. , Brasil Antonio C. P.
Published: September 2010

To take better advantage of the water quality monitoring systems and modeling processes practices in Amazon reservoirs, this study carried out a strategic methodology to couple these two tools. As a result, Information Monitoring and a Modeling Cycle are presented in this paper. The authors integrate the well-known Processes of Simulation and Systems of Monitoring & Assessment practices and incorporated improvements realized by efforts over the past 15 years, that is, UN/ECE Task Force on Monitoring & Assessment, and National Water Quality Monitoring Council and Brazilian Reservoir (NWQMC/USA) monitoring programs.
Building an Eco-Innovation Cluster
Authors: De Gouvea Raul , Kassicieh Sul
Published: September 2010

This paper discusses the creation of an innovation water cluster in the Brazilian Amazon region, capitalizing in the region’s unique global competitive advantage in the development of a water innovation economy. The existence of academic institutions, research agencies, a manufacturing park, and unique natural resources offer the right environment for the creation of this water eco-innovation cluster in the city of Manaus. The development of an innovation economy in the city of Manaus in the Amazon will promote a new cycle of economic development in the region, and induce a new cycle of attraction of environmental technology companies to the Amazon region of Brazil. In addition, it will also address social objectives of the Amazon region, increasing social-economic welfare and promoting eco-competitiveness as a cornerstone of the nation’s economy. This paper outlines a link between cluster theory and a water diamond model with sustainability as its major goal.
Towards Tool-Support for Usable Secure Requirements Engineering with CAIRIS
Authors: Faily Shamal , Fléchais Ivan
Published: September 2010

Understanding how to better elicit, specify, and manage requirements for secure and usable software systems is a key challenge in security software engineering, however, there lacks tool-support for specifying and managing the voluminous amounts of data the associated analysis yields. Without these tools, the subjectivity of analysis may increase as design activities progress. This paper describes CAIRIS (Computer Aided Integration of Requirements and Information Security), a step toward tool-support for usable secure requirements engineering. CAIRIS not only manages the elements associated with task, requirements, and risk analysis, it also supports subsequent analysis using novel approaches for analysing and visualising security and usability. The authors illustrate an application of CAIRIS by describing how it was used to support requirements analysis in a critical infrastructure case study.
Poetic song of Hester. Secondary infertility: Losing infants, inheriting a child
Authors: Gravett Ilse , Müller Julian C.
Published: September 2010

The aim of the article was to explore the narrative of Hester, a black South African woman, who is living with secondary infertility. The perspective is that of postfoundational practical theology, feminist theology and social constructionist narrative methodology. Fertility, as one of the most intimate areas of human existence, lies at the heart of life itself. Within the African tradition, motherhood is seen as almost sacred. Despite Hester’s multiple identities, one which is that of adoptive mother, the absence of biological children causes her to be regarded as a ‘childless’ woman. That identity not only disproportionately defines her, but also stigmatises her as shameful and an outsider. Within the traditional African worldview being healthy (including being fertile) is seen as being in harmony with the societal order and systemic, spiritual and religious environment.Hester’s social construction of her ‘self’ is that of helplessness, reflected in her near illiteracy, low economic status, socio-cultural position and lack of skills. Her childlessness reinforced her helplessness. Her ‘woundedness’ was perpetuated by the fact that she could not share her painful story openly. In the article Hester’s story is presented as a poem, titled: ‘the thing that doesn’t want to come out’. The article concludes with Hester’s reconstruction of ‘self’ as a woman, although poor, also blessed.
Synthesis of Peptide‐Oligonucleotide Conjugates Using a Heterobifunctional Crosslinker
Authors: Williams Berea A.R. , Chaput John C.
Published: September 2010

Peptide‐oligonucleotide conjugates (POCs) are molecular chimeras composed of a nucleic acid moiety covalently attached to a polypeptide moiety. POCs have been used in numerous applications from therapeutics to nanotechnology, and most recently as combinatorial agents in the assembly of bivalent protein affinity reagents. This unit describes the synthesis and purification of POC molecules using the heterobifunctional crosslinking reagent succinimidyl‐4‐(N‐maleimidomethyl)cyclohexane‐1‐carboxylate (SMCC), which enables amine‐modified oligonucleotides to become covalently linked to cysteine‐modified polypeptides. This solution‐based protocol consists of a two‐step synthesis followed by a single purification step. Curr. Protoc. Nucleic Acid Chem. 42:4.41.1‐4.41.20. © 2010 by John Wiley & Sons, Inc.
Impact of systemic sclerosis on occupational and professional activity with attention to patients with digital ulcers
Authors: Bérezné A. , Seror R. , Morell‐Dubois S. , de Menthon M. , Fois E. , Dzeing‐Ella A. , Nguyen C. , Hachulla E. , Guillevin L. , Poiraudeau S. , Mouthon L.
Published: September 2010

Objective

To evaluate the impact of systemic sclerosis (SSc; scleroderma) and digital ulcers (DUs) on daily living and professional activities.

Methods

We prospectively evaluated 189 SSc patients for employment status and disability during meetings of the French SSc patient association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%).

Results

Seventy‐eight (41.2%) patients had diffuse SSc. The mean ± SD age was 54 ± 13 years, and the mean ± SD disease duration was 9.3 ± 8.4 years at the time of evaluation. Sixty (31.7%) patients had at least one DU. Assessed using the Health Assessment Questionnaire (mean ± SD 1.12 ± 0.79 versus 1.39 ± 0.84; P = 0.001), the Cochin Hand Function Scale (mean ± SD 20.2 ± 18.3 versus 27.8 ± 19.1; P < 0.0001), and the Hospital Anxiety Scale (mean ± SD 9.9 ± 5 versus 8.5 ± 4.2; P = 0.04), global disability, hand disability, and anxiety, respectively, were significantly higher in patients with DUs than in others. Most patients reported a limitation in daily activities related to SSc, as assessed by a daily activity limitation scale (mean ± SD 4.4 ± 2.9) and an increased need for help in the home. Patients reported needing mean ± SD 4 ± 13.5 hours per month of paid household help related to SSc and mean ± SD 1.5 ± 10 hours per month related to DUs, with significant differences between patients with or without DUs (P = 0.004). Among the 113 patients in the workforce, 67 (59.3%) were employed, 42 (37.2%) were employed full time, 36 (31.8%) received full disability pension, and 27 (23.9%) were on sick leave, with no difference between patients with or without DUs.

Conclusion

SSc has a significant impact on activities of daily living and work disability. The need for external home help and disability are increased for those patients with DUs.
Effects of community‐deliverable exercise on pain and physical function in adults with arthritis and other rheumatic diseases: A meta‐analysis
Authors: Kelley George A. , Kelley Kristi S. , Hootman Jennifer M. , Jones Dina L.
Published: September 2010

Objective

To use the meta‐analytic approach to determine the effects of community‐deliverable exercise on pain and physical function in adults with arthritis and other rheumatic diseases (AORD).

Methods

Data sources consisted of 6 electronic databases, cross‐referencing from retrieved studies and expert review. Study selection included 1) randomized controlled trials; 2) ≥1 exercise intervention group; 3) community‐deliverable exercise interventions ≥4 weeks in duration; 4) control group; 5) adults ages ≥18 years with rheumatoid arthritis, osteoarthritis, fibromyalgia, lupus, gout, or ankylosing spondylitis; 6) published and unpublished studies; 7) studies published in any language between January 1, 1980, and January 1, 2008; and 8) data available for pain and/or physical function. Data abstraction included dual coding by 2 of the authors. Standardized effect sizes (g) and random‐effects models were used to pool pain and physical function outcomes. Data were analyzed according to per‐protocol and intent‐to‐treat (ITT) results. The minimally clinically important difference (MCID) and number needed to treat (NNT) were also calculated.

Results

Thirty‐three studies representing 3,180 men and women (1,857 exercise, 1,323 control) with rheumatoid arthritis, osteoarthritis, and fibromyalgia were included. Statistically significant and clinically important improvements were observed for pain (per‐protocol g = −0.37 [95% confidence interval (95% CI) −0.53, −0.21], MCID −18%; ITT g = −0.20 [95% CI −0.33, −0.07], MCID −9%, NNT 9) and physical function (per‐protocol g = 0.37 [95% CI 0.21, 0.52], MCID 15%; ITT g = 0.34 [95% CI 0.25, 0.43], MCID 10%, NNT 5).

Conclusion

Community‐deliverable exercise improves pain and physical function in adults with the types of AORD included in the analysis. Dose‐response as well as studies in those with other types of AORD is needed.
In Vivo Evaluation of a pH‐Sensitive Pullulan–Doxorubicin Conjugate
Authors: Lu Dianxiang , Liang Jie , Fan Yujiang , Gu Zhongwei , Zhang Xingdong
Published: September 2010

A pH‐sensitive pullulan–doxorubicin conjugate is evaluated in vivo by comparison with doxorubicin with respect to hemolytic activity, biodistribution, biosafety, cardiotoxicity and antitumor effects. Hemolytic studies show that doxorubicin caused 8.38% hemolysis at 250 mg L−1, while no hemolysis is observed with pullulan–doxorubicin conjugate at the same drug concentration. The circulation time of pullulan–doxorubicin conjugate is relatively longer than that of doxorubicin, and the concentration in tumors for pullulan–doxorubicin conjugate increases to about double that of doxorubicin within 240 min after injection of drugs via the lateral vein. In vivo safety research shows that pullulan–doxorubicin conjugate shows better biosafety than free doxorubicin, confirmed by acute toxicity, systemic toxicity and histopathological observations. The cardiotoxicity of pullulan–doxorubicin conjugate is much lower than that of free doxorubicin, as confirmed by TEM and ECG. In vivo antitumor activity assays show that the pullulan–doxorubicin conjugate has an antitumor efficacy comparable to that of doxorubicin.
Processing Technologies for 3D Nanostructured Tissue Engineering Scaffolds
Authors: Meng Decheng , Erol Melek , Boccaccini Aldo R.
Published: September 2010

Engineered scaffolds made from synthetic or natural biomaterials are crucial elements in tissue engineering strategies. Numerous biomaterials are being used to fabricate scaffolds, including glasses, ceramics, metals, polymers, and their composites. Although materials chemistry and scaffold architecture (pore size, pore volume) are important factors affecting cell–surface interactions, the roughness and topography of the scaffold surface plays an essential part too, especially nanoscale features are relevant. Extensive research has been carried out on introducing nanoscale features on 2D, flat surfaces, but much limited efforts have been focused on nanostructuring the surface of 3D scaffolds. This paper specifically reviews the current techniques that are available to introduce or engineer nanoscale topography on the surfaces of 3D scaffolds or on 2D surfaces that can be successfully assembled into 3D scaffolds via post‐processing. The literature reviewed provides evidence about the influence of nanoscale topography on cell attachment, migration, and proliferation. While the paper is focused on bone tissue scaffolds, several technologies reviewed are equally applicable to scaffolds suitable for engineering and regeneration of other tissues.
Amphiphilic Poly(Amino Acid) Nanoparticles Induce Size‐Dependent Dendritic Cell Maturation
Authors: Kim Hyungjin , Uto Tomofumi , Akagi Takami , Baba Masanori , Akashi Mitsuru
Published: September 2010

Size‐regulated amphiphilic poly(amino acid) nanoparticles (NPs) composed of poly(γ‐glutamic acid) (γ‐PGA) and the hydrophobic amino acid derivative, L‐phenylalanine ethyl ester (Phe) are prepared to evaluate the effects of particle size on dendritic cell (DC) uptake of NPs and their immune stimulatory activities as delivery carriers and adjuvants. The size of the Phe‐conjugated γ‐PGA NPs (γ‐PGA–Phe NPs) is easily controlled by regulating the aggregated γ‐PGA–Phe numbers. Each of the differently sized γ‐PGA–Phe NPs could efficiently encapsulate ovalbumin (OVA), and the amount of encapsulated OVA per milligram of NPs is almost the same despite the differences in size. The DC uptake of small NPs is lower than for the larger NPs, but the effect of DC activation by NPs is high in the small sizes. The DC activation is significantly affected by the size of the NPs, which suggests that not only the uptake process of the NPs, but also the surface interactions between the NPs and DCs, is important for the induction of DC maturation. The precisely size‐controllable γ‐PGA–Phe NPs have significant potential as an antigen carrier and vaccine adjuvant. These results should provide guidelines for adjuvant design in the development of an effective vaccine.
Galactose Encapsulated Multifunctional Nanoparticle for HepG2 Cell Internalization
Authors: Lai Chian‐Hui , Lin Chia‐Yi , Wu Huan‐Ting , Chan Hau‐Shien , Chuang Yung‐Jen , Chen Chien‐Tien , Lin Chun‐Cheng
Published: September 2010

The fluorescent dye Cy3 and galactose derivatives are covalently assembled with different ratios on the surfaces of magnetic nanoparticles (MNPs) to produce multifunctional HepG2 cancer cell–targeting agents and the effect of ligand spatial orientation on the MNP surface is investigated on targeting specificity. By using a mixture of bis‐N‐hydroxysuccinimide ester (a bifunctional linker) and OSu‐activated Cy3 (w/w = 30:1), stable and quantifiable fluorescent MNPs (Cy3@MNPs) are synthesized that could be subsequently loaded with galactosyl ligands. A mono‐antennary and two different tri‐antennary galactosyl ligands are individually immobilized on Cy3@MNPs, and the uptake efficiencies of the resulting galactosyl Cy3@MNPs by HepG2 and HeLa cells are investigated using confocal microscopy. The confocal images show that galactosyl Cy3@MNPs are sprayed over cytoplasm of the HepG2 cells, indicating that the MNP uptake occurs via receptor‐mediated endocytosis that is followed by release from endosomes. The results also reveal that the ligand spatial orientation affects the efficiency of the receptor‐mediated endocytosis and one of the tri‐antennary galactosyl ligands shows the best uptake efficiency owing to the optimal spatial presentation of the galactosyl moieties. Overall, it is shown that the MNP is a good ligand carrier and that, when pre‐assembled, the multivalent ligand structure enhances the interactions between the surface ligands of the MNPs and receptors of HepG2 cells. Additionally, the galactosyl Cy3@MNPs are not cytotoxic, indicating that they may potentially be used for in vivo applications.
Sustained Release of a Monoclonal Antibody from Electrochemically Prepared Mesoporous Silicon Oxide
Authors: Andrew Jennifer S. , Anglin Emily J. , Wu Elizabeth C. , Chen Michelle Y. , Cheng Lingyun , Freeman William R. , Sailor Michael J.
Published: September 2010

Nanostructured mesoporous silica (SiO2) films are used to load and release the monoclonal antibody bevacizumab (Avastin) in vitro. A biocompatible and biodegradable form of mesoporous SiO2 is prepared by electrochemical etching of single crystalline Si, followed by thermal oxidation in air at 800°C. Porous SiO2 exhibits a negative surface charge at physiological pH (7.4), allowing it to spontaneously adsorb the positively charged antibody from an aqueous phosphate buffered saline solution. This electrostatic adsorption allows bevacizumab to be concentrated by >100× (300 mg bevacziumab per gram of porous SiO2 when loaded from a 1 mg mL−1 solution of bevacziumab). Drug loading is monitored by optical interferometric measurements of the thin porous film. A two‐component Bruggeman effective medium model is employed to calculate percent porosity and film thickness, and is further used to determine the extent of drug loading into the porous SiO2 film. In vitro drug release profiles are characterized by an enzyme‐linked immunosorbent assay (ELISA), which confirms that the antibody is released in its active, VEGF‐binding form. The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 98% of drug is released over a period of one month.
Self‐Assembling TiO2 Nanorods on Large Graphene Oxide Sheets at a Two‐Phase Interface and Their Anti‐Recombination in Photocatalytic Applications
Authors: Liu Jincheng , Bai Hongwei , Wang Yinjie , Liu Zhaoyang , Zhang Xiwang , Sun Darren Delai
Published: September 2010

TiO2 nanorods are self‐assembled on the graphene oxide (GO) sheets at the water/toluene interface. The self‐assembled GO–TiO2 nanorod composites (GO–TiO2 NRCs) can be dispersed in water. The effective anchoring of TiO2 nanorods on the whole GO sheets is confirmed by transmission electron microscopy (TEM), X‐ray diffraction (XRD), Fourier transform IR spectroscopy (FTIR), and thermogravimetric analysis (TGA). The significant increase of photocatalytic activity is confirmed by the degradation of methylene blue (MB) under UV light irridiation. The large enhancement of photocatalytic activity is caused by the effective charge anti‐recombination and the effective absorption of MB on GO. The effective charge transfer from TiO2 to GO sheets is confirmed by the significant photoluminescence quenching of TiO2 nanorods, which can effectively prevent the charge recombination during photocatalytic process. The effective absorption of MB on GO is confirmed by the UV‐vis spectra. The degradation rate of MB in the second cycle is faster than that in the first cycle because of the reduction of GO under UV light irradiation.
An Organocatalytic Domino Thia‐Michael/Aldol Condensation Reaction: Highly Enantioselective Synthesis of Functionalized Dihydrothiophenes
Authors: Tang Jie , Xu Dan Qian , Xia Ai Bao , Wang Yi Feng , Jiang Jun Rong , Luo Shu Ping , Xu Zhen Yuan
Published: September 2010

An organocatalytic domino thia‐Michael/aldol condensation reaction of α, β‐unsaturated aldehydes with 1, 4‐dithiane‐2,5‐diol catalyzed by chiral diphenylprolinol TMS ether has been developed, which provides a new practical and direct route to chiral dihydrothiophenes with high yields (up to 90%) and excellent enantioselectivities (up to>99%ee). The catalytic mechanism of the domino reaction was further confirmed through the APCI‐MS detection of proposed reaction intermediates.
Efficient and Highly Chemoselective Direct Reductive Amination of Aldehydes using the System Silane/Oxorhenium Complexes
Authors: Sousa Sara C. A. , Fernandes Ana C.
Published: September 2010

This work reports a novel method for direct reductive amination of aldehydes with silanes catalyzed by several high‐valent oxorhenium(V) and oxorhenium(VII) complexes. The catalytic system PhSiH3/ReIO2(PPh3)2 (2.5 mol%) was very efficient for the synthesis of secondary amines and highly chemoselective, tolerating a wide range of functional groups such as NO2, CF3, SO2R, CO2R, F, Cl, Br, I, CN, OH, OCH3, SCH3, NCOR, and double bonds. This novel method was also employed in the synthesis of tertiary amines with moderate yields.
A Tripodal Peptidic Titanium Phosphonate as a Homochiral Porous Solid Medium for the Heterogeneous Enantioselective Hydration of Epoxides
Authors: Milo Anat , Neumann Ronny
Published: September 2010

A porous, homochiral titanium‐phosphonate material based on a tripodal peptide scaffold was used as a heterogeneous reaction medium for the enantioselective hydration (>99%) of styrene oxide. This titanium‐phosphonate material, which was shown to contain confined chiral spaces, was prepared by polymerization of L‐leucine onto a tris(2‐aminoethyl)amine initiator, followed by capping with phosphonate groups and completed by non‐aqueous condensation with titanium isopropoxide. Circular dichroism confirmed that the peptide tethers yielded a secondary structure. X‐ray powder diffraction and transmission electron microscopy supported by a semi‐empirical model showed the likely formation of a porous, lamellar material that was quantified by nitrogen adsorption.
Macrocyclic Palladium(II) Complexes in CC Coupling Reactions: Efficient Catalysis by Controlled Temporary Release of Active Species
Authors: Röhlich Christoph , Köhler Klaus
Published: September 2010

Stabilization of palladium species against agglomeration is essential for reasonable catalytic activity in CC coupling reactions. In contrast to common methods of palladium(0) complex or particle stabilization, a new concept is introduced here: it is demonstrated that a controlled release of palladium from an inactive precatalyst provides stability, too, and leads to high catalytic activity. This paper presents surprising catalytic results for Heck and Suzuki reactions with aryl chlorides and bromides, using three highly stable macrocyclic palladium complexes as catalyst precursors. Three different behaviour patterns for the macrocyclic complexes can be deduced from the evaluation of catalytic activities, UV‐Vis spectroscopy, recycling studies of immobilized complexes, and ligand addition experiments. (i) Palladium tetraphenylporphyrin reversibly releases only extremely low amounts of palladium during the reactions, and low coupling activities are observed. (ii) Release of palladium from its phthalocyanine complex is irreversible; cumulative release of palladium into the reaction mixtures leads to high catalytic activity. (iii) Extraordinary results were obtained with a Robson‐type complex of palladium, which reversibly releases effectual amounts of palladium into solution under reaction conditions. This controlled release prevents the formation of inactive palladium agglomerates under harsh conditions and leads to high catalytic performances. Even strongly deactivated electron‐rich aryl chlorides (4‐chloroanisole) can be completely and selectively converted by the in situ formed anionic palladium halide complexes; the addition of typical stabilizing additives (TBAB) was found to be unnecessary. The bimetallic palladium complex is regenerated at the end of the reaction. These results contribute to the current understanding of the active species in CC coupling reactions of Heck and Suzuki types.
A Remarkable Titanium‐Catalyzed Asymmetric Strecker Reaction using Hydrogen Cyanide at Room Temperature
Authors: Ramalingam Balamurugan , Seayad Abdul Majeed , Chuanzhao Li , Garland Marc , Yoshinaga Kazuhiko , Wadamoto Manabu , Nagata Takushi , Chai Christina L. L.
Published: September 2010

Close to perfect enantioselectivity (up to 98% ee) is obtained for the formation of amino nitriles using hydrogen cyanide (HCN) as the cyanide source at room temperature for the first time. In an operationally simple process, the catalyst generated from a partially hydrolyzed titanium alkoxide (PHTA) and (S)‐N‐salicyl‐β‐amino alcohol ligand, catalyzes the cyanation of imines in a short reaction time.
Synthesis of diblock and triblock copolymers from butyl acrylate and styrene by reverse iodine transfer polymerization
Authors: Enríquez‐Medrano Francisco J. , Guerrero‐Santos Ramiro , Hernández‐Valdez Martín , Lacroix‐Desmazes Patrick
Published: September 2010

Well‐defined AB and BA diblock copolymers were obtained by a one‐pot two‐step sequential block copolymerization by reverse iodine transfer polymerization (RITP), A being a poly(styrene) block and B a poly(butyl acrylate) block. High monomer conversions during the formation of the first block avoided the purification steps before growing the second block. In a third sequential step, the diblock copolymers were further extended to synthesize ABA and BAB triblock copolymers. Furthermore, the synthesis of ABA and BAB copolymers in only two steps by RITP was investigated starting with the formation of the central block using 2,5‐di(2‐ethylhexanoylperoxy)‐2,5‐dimethylhexane as a difunctional initiator and then resuming the polymerization to grow the external blocks in a second step. The obtained copolymers were analyzed by size exclusion chromatography, transmission electron microscopy, and differential scanning calorimetry. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Influence of chitosan posttreatment parameters on the fixation of pigment‐based inks on ink‐jet‐printed cotton fabrics
Authors: Momin Nasar H. , Padhye Rajiv , Khatri Awais
Published: September 2010

Cotton fabrics were digitally printed with pigment‐based black ink with an HP Desk‐Jet 880C printer. These ink‐jet‐printed fabrics were posttreated with chitosan samples for the fixation of the pigment‐based ink on the cotton. The influence of various parameters, including the molecular weight (MW), application method (pad–dry–cure vs pad–batch), concentration, and pH, on the degree of fixation (DF) of the pigment‐based inks was examined. The chitosan‐posttreated cotton samples were evaluated for their color strength, DF, color difference, and whiteness index values and their colorfastness properties. Chitosan samples with MWs of 150,000 and greater than 375,000 showed 100% (complete) fixation of the pigment‐based inks on the cotton fabrics. DF drastically decreased in the chitosan with an MW of less than 5000. Both the pad–dry–cure and pad–batch methods were found to be suitable for chitosan application onto ink‐jet‐printed fabrics. Chitosan with an MW of 150,000 showed 100% fixation at concentrations ranging from 0.3 to 1%. A further decrease in the concentration significantly decreased the fixation. High fixation values were achieved at acidic pH, whereas a neutral to alkaline pH resulted in poor fixation. The colorfastness properties for each parameter studied are also discussed. The posttreatment of the digitally printed cotton with chitosan was found to be very effective in fixing the pigment‐based inks. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Constituents of cupuliferae, XIII: New and revised structures of acylated flavonoids from Quercus Suber L.
Authors: Romussi Giovanni , Bignardi Gaetano , Pizza Cosimo , De Tommasi Nunziatina
Published: September 2010

From leaves of Quercus suber L. in addition to ten known glycosides, two new acylated flavonoids have been isolated and identified as 3‐O‐kaempferol 2‐O‐(trans‐p‐coumaroyl)‐β‐D‐glucopyranoside (1) and 3‐O‐kaempferol 2,3‐di‐O‐acetyl‐4‐O‐(cis‐p‐coumaroyl)‐6‐O‐(trans‐p‐coumaroyl)‐β‐D‐glucopyranoside (3). The structures of the previously described 3‐O‐kaempferol 2,4‐di‐O‐(trans‐p‐coumaroyl)‐β‐D‐glucopyranoside2) and 3‐O‐kaempferol 3,6‐di‐O‐acetyl‐2,4‐di‐O‐(trans‐p‐coumaroyl)‐β‐D‐glucopyranoside3) were revised to 3‐O‐kaempferol 2,6‐di‐O‐(trans‐p‐coumaroyl)‐β‐D‐glucopyranoside (4) and 3‐O‐kaempferol 3,4‐di‐O‐acetyl‐2,6‐di‐O‐(trans‐p‐coumaroyl)‐β‐D‐glu‐copyranoside (5).
Prodrugs nichtsteroidaler antirheumatika, 3. mitt.: Synthese und hydrolyse von acyloxy‐2‐oxopropanen
Authors: Schwenker Gerhard , Stiefvater Karlheinz
Published: September 2010

Synthesis and Hydrolysis of Acyloxy‐2‐oxopropanes

2‐Oxopropylesters are examined as potential prodrugs of acidic non‐steroidal anti‐inflammatory drugs. The esters are characterized by a high degree of chemical lability at pH 7.4 (37°C) while exhibiting a higher stability at pH < 7. The rate of the non‐enzymatic hydrolysis at pH 7.4 is dependent on steric and electronic effects which can be contributed to the particular acyloxy‐rest.