bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging distress in the US real estate market? Dangers in the current market and tools to mitigate risk
Authors: Lattin A. Floyd , Ackah Amachie K.
Published: July 2006

Despite the recent downturn in the US economy, real estate has remained an extremely attractive investment class. Although the market has softened, property investors have, to date, been largely insulated from distress. Commercial real estate provides investors with cash flow; a hedge against price instability; low correlation to other asset classes; and low volatility of returns. While of these characteristics provide investors potential refuge, they need to be managed, particularly in difficult economic times. Credit risk, leverage risk, geographic market risk, and exit risk are all important elements. Although the US real estate industry, for once, has not been a cause of the recession, understanding and managing these risks is important for the commercial property market to escape the effects of the current downturn. These facts have placed stress on the property market and forced new roles on all participants in the capital structure of real estate investments. This paper will outline various dangers in the current real estate market as well as highlight tools that the industry can use that may mitigate these risks. The paper will also attempt to quantify today's property market dynamics in an effort to plot the current phase of the cycle. Copyright © 2002 Henry Stewart Publications.
The state of the North Asian real estate market: the rise in non‐performing loans, new investment vehicles and exit strategies and the need for government reforms
Authors: Feder Philip N. , Kim Lisa L.
Published: July 2006

The slowdown in global economies, exacerbated by the 11 September attacks, together with the hesitancy, inconsistency and intransigence of both governments and lenders in dealing with non‐performing loans (NPLs) has deepened the problems for Asia's already troubled economies. As the number of Asian NPLs has skyrocketed to an estimated US $2trn (an increase of 33 per cent in the last two years), the authors examine the reasons for the increase, discuss new exit strategies being tested in these markets and offer a prognosis for foreign investors in North Asian real estate. Copyright © 2002 Henry Stewart Publications.
Research review
Authors: Adair Alastair , Lim Lay Cheng
Published: July 2006

The aim of the Research Reviews is to focus on current academic research that contributes to and enhances professional practice. The objective is to provide the busy practitioner with a synopsis of leading edge research in the area and hopefully to stimulate a desire for greater understanding and application of knowledge and techniques that will enhance professional practice. Copyright © 2002 Henry Stewart Publications.
Monitoring of construction projects for third‐party funders and investors
Authors: Porter Stephen
Published: July 2006

This paper examines the practical role of professional advisers to funders and investors on real estate projects. It emphasises the advantages of an early appointment and will differentiate between the services and skills required during the due diligence and monitoring phases. It also explains the different types of service needed depending on the level of project and funding risk and concludes by highlighting and explaining the use of risk assessment and management during the project evaluation and implementation. Copyright © 2002 Henry Stewart Publications
Strategy for leasehold dispositions in high‐tech markets
Authors: Gilbert Kenneth J.
Published: July 2006

Effective leasehold disposition strategies must recognise how the structure of real estate markets has changed fundamentally since the major downturn in the mid‐1980s. Today, ownership is concentrated in the hands of fewer institutional investors. This ‘oligopoly’ structure enables landlords to hold a floor under lease rates in a declining market. While this floor would appear also to serve the interests of corporate tenants marketing excess lease space, this new market structure masks a serious problem: in most high‐tech sub‐markets, the majority of the vacant space is held by a few high‐tech tenants. These technology companies constitute an oligopoly structure similar to that of the owners, but with a major difference: their pricing ‘floor’ is exceedingly fragile since those leaseholds are a ‘wasting asset’. Ultimately, they must aggressively market space by cutting prices if they are to recover any value before their lease terms run out. As the pricing floor cracks, a downward pricing spiral will have negative consequences for companies that are late to recognise the situation. Corporations that align their leasehold disposition strategies with the new market structure and act decisively are most likely to maximise the value of their dispositions. Copyright © 2002 Henry Stewart Publications
The impact of news concerning development project launches and their take‐up rates on the stock prices of publicly listed property development companies
Authors: Ibrahim Muhammad Faishal , Ong Seow Eng , Loh Amanah Husain
Published: July 2006

A successful launch for a property development project has direct implications on the profitability of the development company. This paper examines the impact of news on the take‐up rates in property development launches on the stock prices of publicly listed property development companies. The implications of a study on stock price reaction to news on property development launches are clear. The property company could view good market response as an opportune time for raising financing in terms of equity as well as bonds or for refinancing. More fundamentally, a favourable market response can be viewed as a market endorsement of the financing structure for property development companies where project financing is widely used. When good take‐up rates are announced in the press, one expects the stock price of the development company to react positively. Empirical evidence from Singapore suggests that the cumulative average abnormal returns (CAARs) are flat on days subsequent to the announcement dates, but there exist significant movements some weeks after the condominium actual launch dates. When the launch date is used as the event date, the CAARs over the period following the launch date are positive for projects that sell well and negative for projects that do not. In addition, the cumulative returns correlate positively to the percentage of units sold over the launch period. Copyright © 2002 Henry Stewart Publications
The outlook for the UK economy
Authors: O'Carroll Lucy
Published: July 2006

The UK economy is likely to put in a solid performance during the next two years. Economic activity is expected to grow at a below‐trend rate of around 1.7 per cent this year, with the impact of sharp equity market falls, a weak global economy and manufacturing sector fragility largely offset by a lower interest rate profile. Conditions remain in place for recovery to around‐trend growth in 2003–04, as the world economy picks up speed. That said, the probability on the central forecast has been reduced, reflecting increased downside risks. If the downside were to materialise, margin pressures would tend to intensify in thin trading markets. Business propositions should therefore be examined for vulnerability to potentially weak pricing leverage, as well as to the risk of more subdued demand growth for an extended period. Copyright © 2002 Henry Stewart Publications
Research review
Authors: Adair Alastair
Published: July 2006

The aim of the Research reviews is to focus on current academic research which contributes to and enhances professional practice. The objective is to provide the busy practitioner with a synopsis of leading edge research in the area and hopefully to stimulate a desire for greater understanding and application of knowledge and techniques that will enhance professional practice. The reader is encouraged to examine in depth each of the reviewed papers. This issue of the Research Review comprises of one UK research report and three US academic articles encompassing the following topics:

UK commercial property lending

Real estate risk

Synthetic debt

The UK research report focuses on the current state of commercial property lending whereas the three American papers present diverging perspectives on the measurement of real estate risk together with the emerging area of synthetic leases and synthetic debt. Copyright © 2002 Henry Stewart Publications
Investment fund vehicles for pan‐European real estate: a technical and commercial review
Authors: Brown David
Published: July 2006

The aim of this paper is to provide a technical and commercial review of pan‐European real estate investment fund vehicles, including a summary of their evolution to date, who their promoters and managers are, where the capital comes from and what type of real estate are they investing in. It goes on to provide detailed guidance on commercial aspects relevant in deciding on which type of investment vehicle to choose, the key attributes of the various vehicles and the specific regulatory and tax issues for major investor groups. The paper concludes by offering a view on progress towards future vehicles such as the ‘EuroREIT’. Copyright © 2003 Henry Stewart Publications
Co‐investing in mortgage loans: a portfolio strategy
Authors: Williams Jeffrey J.
Published: July 2006

The latter half of the 1990s witnessed a significant increase in co‐lending among US life insurance companies and other portfolio lenders. This paper will examine why co‐lending is attractive to portfolio lenders, detail the factors that have contributed to the growth in co‐lending, and will provide advice on selecting an appropriate co‐lender with which to invest and best practice guidelines on how to structure the deal. Copyright © 2003 Henry Stewart Publications
Financing corporate real estate: the impact of corporate real estate in the shareholder value equation
Authors: Hill Matthew
Published: July 2006

This paper aims to bring together the principles of shareholder value added (SVA) and the impact of operational real estate on the corporate occupier's financial management. As an introductory piece, it sets out to bridge the gap in understanding that often exists, either in the corporate finance department about the mechanics of real estate finance, or in the corporate real estate profession about the impact on corporate finance of real estate ownership and funding decisions. From this paper the reader should gain a better understanding of the mechanistic links between delivering shareholder value and the options and potential decisions in respect of a corporate occupier's real estate ownership and funding strategy. This paper demonstrates the theory by considering a number of relevant transactions carried out by corporate occupiers with their operational real estate in the ultimate pursuit of increasing shareholder value. Copyright © 2003 Henry Stewart Publications
Best practices in commercial real estate financing a guide to commercial mortgage transactions in the USA
Authors: Chadakoff Richard L. , Fischer Michael R. , Stein Joshua
Published: July 2006

For any commercial real estate loan in the USA, the closing and documentation process combines traditional principles and practices of US real estate law — some dating back centuries to English common law — with the global capital markets, a fast‐moving marketplace, and painful lessons learned in the USA's real estate depression of the early 1990s. Against that backdrop, lenders and borrowers must bring together dozens of processes, participants and other pieces to document and close any commercial mortgage loan. This paper focuses on all those elements, for comparison against commercial mortgage lending procedures in other countries and as a reminder of basic principles for commercial mortgage lenders and their advisors in the USA. Copyright © 2003 Henry Stewart Publications
US property market outlook for 2003
Authors: Louargand Marc , Gately Michael
Published: July 2006

US real estate professionals are adrift in a quandary on a sea of uncertainty. At the beginning of 2003 there are weak fundamental conditions in the space markets for all property types, while capital continues to pour into the asset class. Transactions in 2002 would seem to indicate that real estate has become more valuable as the result of the recession of 2001 and the ensuing weakness in the US economy that has shown itself as an utter lack of demand for office space and weak conditions in the other property sectors.

The winds of uncertainty have not blown in this fashion since 1986 when office market fundamentals began to deteriorate while institutional funds poured into the transactions market. What should the investor believe? The poor conditions faced every day in the space market, or the ebullience found in the transactions market? Copyright © 2003 Henry Stewart Publications
The pitfalls of property valuation for commercial real estate lenders: using a comparative income approach to improve accuracy
Authors: Payne Thomas H. , Redman Arnold L.
Published: July 2006

This paper assesses valuation methods of income producing real estate used by real estate appraisers from the perspective of commercial property lenders. Imbedded in any valuation are assumptions made about income growth and property price appreciation. These assumptions are evaluated highlighting models most frequently used by appraisers. When using appraisals, commercial lenders should be particularly aware of growth‐related assumptions as they significantly impact the estimated value of any property. This paper provides a method of evaluating the sensitivity of a property's value to differing income growth scenarios using a perpetuity model. The comparative income growth (CIG) technique can improve lenders' risk analysis and loan decision making by building on information provided in property appraisal reports. Copyright © 2003 Henry Stewart Publications
Equity vs debt financing of REITs: a survey of determinants of the security issue decision
Authors: Howton Shawn D. , Howton Shelly W. , McWilliams Victoria
Published: July 2006

This study examines the determinants of the security issue decision for Real Estate Investment Trusts (REITs) for a sample of 664 REIT security issuances in the 1993–2001 period. REITs differ from industrial companies because they are sheltered from paying corporate income taxes if they pay out 95 per cent of income as dividends. This restriction forces REITs to use the external markets to raise capital more often than their industrial counterparts. For these reasons, REITs might have different incentives to issue debt versus equity than has been previously found for industrials. The results of the study find that the decision to issue equity is directly related to the expected cost of issuing debt and inversely related to the costs of issuing equity. Investment opportunities are not related to the security issue decision. These results are consistent with the pecking order hypothesis, which differs from previously examined industrial companies where the security issue decision was driven by agency costs. Copyright © 2003 Henry Stewart Publications
Property investment and development finance in Italy
Authors: Murray Neil
Published: July 2006

This paper looks at legal and practical issues which may arise for prospective lenders in relation to property investment and development loans concerning property in Italy. Whilst the issues discussed are necessarily subjective – and appropriate legal advice should be taken in all cases – it is hoped that the paper will provide a good overview from the perspective of the typical expectations of a UK lender, by reference to a UK deal, and the extent to which these can be met in Italy. Copyright © 2003 Henry Stewart Publications
Best practices in commercial real estate financing: the borrower's agenda in negotiating loan documents part 2
Authors: Stein Joshua
Published: July 2006

How should a borrower respond to a draft set of commercial mortgage loan documents? This paper, consisting of four quarterly instalments appearing in the 2003/2004 volume of this publication, seeks to answer that question. The author discusses business and legal issues that mortgage loan documents typically raise for a borrower; some structural variations and the special concerns they might create; the closing process; and some issues that a borrower may want to raise on its own initiative. Copyright © 2003 Henry Stewart Publications
The US economy and real estate outlook, June 2003
Authors: Gately Michael , Louargand Marc
Published: July 2006

The slumbering US job market has cooled hopes for significant improvement in the real estate markets and even the most optimistic are now pinning their hopes on next year. There is however a distinction among the major American markets as to which will lead the recovery, and which will be laggards. This distinction is based upon current market dynamics and regional economic growth engines and presents opportunities for those recognising such differences. The supply spigot for most commercial construction has thankfully been tightened and vacancy rates are generally at or near their peaks for this cycle. Underlying the ‘top‐line’ employment data, specific pockets of strength are evident. This article provides an overview of the American economy and real estate markets, and explores a strategy to capitalise on the improving market fundamentals. Copyright © 2003 Henry Stewart Publications
Corporate intentions to participate in emission trading
Authors: Pinkse Jonatan
Published: July 2006

The adoption of the Kyoto Protocol in 1997 has led to increasing business interest in the issue of climate change. It has also created much uncertainty for companies, particularly about the role of trading in realizing emission reductions. This paper investigates what drives multinational corporations to show interest in emission trading and carbon offset projects to deal with climate change. On the basis of an analysis of data of 136 companies derived from a questionnaire, it also examines the role that country of origin, industry affiliation and companies' environmental strategy play in this regard. Findings show that industry pressure and product and process innovations are the main determinants for multinational corporations to participate in the emission market. It appears that climate policy particularly induces energy‐related industries to reduce emissions, which puts them ahead of other industries with regard to their interest in emission trading. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
ISO 14001 – experiences, effects and future challenges: a national study in Austria
Authors: Schylander Elisabeth , Martinuzzi André
Published: July 2006

More than 60000 organizations worldwide have implemented environmental management systems (EMSs). About 800 of them are located in Austria. As Austria was one of the leading countries in promoting the EU scheme EMAS, and as there has been no specific study on Austrian experiences with ISO 14001, the purpose of this study is to describe the experiences with and effects of ISO 14001 in Austria. The results show that ISO 14001 often leads to reduced environmental impact, especially in the area of waste. A strong driving force behind implementation is the expected improvement of an organization's image. The average repayment time on an investment in an EMS is less than two years. Legal compliance tends to be difficult to implement, but on the other hand it works well in daily practice. To develop an EMS into a sustainability management system, the two most important challenges are to improve coordination between the EMS and the organization's strategies and to synchronize the EMS with central value chains. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Why SMEs invest in environmental measures: sustainability evidence from small and medium‐sized printing firms
Authors: Masurel Enno
Published: July 2006

Why do SMEs invest in environmental measures? From the literature we know that most SMEs are rather slow in adopting these sustainable measures, but then the following question arises: why are other SMEs fast in this respect? From our research, it becomes clear that improving the working conditions is the most important reason why these fast‐going SMEs invest in environmental measures, as this probably improves their employees' motivation and performance. This explanation connects ‘planet’ and ‘people’ with each other, and does not exclude ‘profit’, which completes the traditional sustainability circle. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Time horizons of environmental versus non‐environmental costs: evidence from US tort lawsuits
Authors: Regnier Eva , Tovey Craig
Published: July 2006

One explanation for a positive correlation between environmental and financial performance at the firm level is a bias in firms' investment evaluation processes caused by systematic differences between environmental and other investment opportunities. One of these systematic differences, often hypothesized but still unverified, is that environmental costs occur farther in the future than other costs. We empirically test this hypothesis, and find statistically significant support for it. In our data set the mean time lag for environmental costs was more than ten years, compared with five years for the control set costs. Such a difference could induce managers to accept too much environmental liability if they evaluate investments using discounted cash flow methods with a discount rate based on the firm‐wide cost of capital. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Corporate discourse and environmental performance in Argentina
Authors: Vazquez Diego A. , Liston‐Heyes Catherine
Published: July 2006

There is substantial research and policy interest in the relationship between firms and the natural environment, including how this relationship is influenced by regulators, international pressures, rival firms and stakeholder demands. With some exceptions, the ‘softer’ dimensions of environmental aspect management – how attitudes, beliefs and perceptions and the human factors drive corporate behaviour – have been understudied. The work that exists tends to be informal, and allows little scope for the statistical validation that is required for robust inference. This paper examines whether corporate values towards the environment affect a firm's environmental performance. It uses survey methods as well as content and discourse analyses of interview text and corporate reports and web sites to explore the links between managerial ‘mindsets’ and the environmental performance of the firms of which they are a part. Though the application is Argentina, the lessons learned can be generalized to other developing and industrialized countries. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Modeling of Droplet Separation Kinetics in Granular Bed Filters Based on MRI Measurements
Authors: van Buren V. , von Garnier A. , Reimert R.
Published: July 2006

In droplet separation by granular bed filters, the transient loading regime plays an important role because, for gases with low droplet concentrations, steady state will be reached only after a long time. A mathematical model describing this transient loading regime as well as steady state was developed. It is based on differential balances for the dispersed droplets and for the separated liquid. The time‐dependent and spatially resolved liquid loading is calculated and compared with data obtained by magnetic resonance imaging (MRI), a noninvasive measuring technique. The good agreement between simulated and measured loading curves proves the general applicability of the model.
Combination of Time‐Dependent Self‐Diffusion Measurements (Dynamic Imaging) with Magnetic Resonance Imaging
Authors: Tillich J. E. , Guthausen G. , Holz M.
Published: July 2006

The new NMR method, demonstrated in the present work, allows within local small volumes the determination of integral structural parameters like the surface‐to‐pore volume ratio or the tortuosity of a fluid‐filled porous medium. A combination of conventional imaging (MRI) with measurements of observation‐time dependent self‐diffusion (dynamic imaging) was used.
Microwave Heating: A New Approach of Simulation and Validation
Authors: Knoerzer K. , Regier M. , Schubert H.
Published: July 2006

Currently the distribution of microwave processes in industrial applications is sparsely spread. Reasons for this are, in particular, the inhomogeneous heating patterns and the lack of optimization potential, due to the lack of possibilities for simulation of coupled electromagnetic and thermal processes. In this work two commercial software packages have therefore been coupled to simulate local and time specified temperature distributions of microwave treated samples. The results are validated by the sophisticated magnetic resonance imaging (MRI) technique, in order to avoid the problems of measuring temperature distributions in microwave fields. This method of measurement is non‐invasive, shows high 3D spatial and time resolutions, and does not influence the electromagnetic field.
Structure Characterization of Filled Polymers by Means of MRI
Authors: Eisenreich N. , Geißler A. , Geißler E. , Götz J.
Published: July 2006

The structure of foams and filled polymers can be analyzed by means of Magnetic Resonance Imaging (MRI). It is also possible to observe the deformation behavior of the structure of foams and filled polymers in situ. A displacement experiment was performed in a magnet and observed by MRI. The NMR images are analyzed by image processing. Average distances between particles are estimated by the use of the autocorrelation function and the spectrum of the autocorrelation function. The spectrum shows the spatial frequency of the distances. The displacement field was calculated by the cross‐correlation function. Thus, information concerning the particle distances and micromechanical deformation can be obtained by NMR imaging methods by combining autocorrelation and cross‐correlation. Such data are important for the evaluation of the mechanical strength of filled polymers.
Magnetic Resonance Imaging in Chemical Engineering: Basics and Practical Aspects
Authors: Hardy E. H.
Published: July 2006

The huge potential of nuclear magnetic resonance imaging is increasingly exploited in chemical engineering. However, optimal use of this rather complex method requires some background knowledge. In this paper, first the basic principles are presented in a form dedicated to readers with an engineering formation. Subsequently, practical aspects such as resolution in space and time are discussed. Emphasis is put on established methods implemented on standard magnetic resonance imaging (MRI) hardware, as mainly used in the research presented in this issue.
Filtration of Colloidal Suspensions – MRI Investigation and Numerical Simulation
Authors: Erk A. , Hardy E. H. , Althaus T. , Stahl W.
Published: July 2006

The principle mechanisms of solid‐liquid separation processes are sedimentation and filtration, both including the formation and compression of a liquid‐saturated bulk. The compressive properties of the bulk determine the operating parameters of solid‐liquid separation devices and the achievable separation results. Information about the solids volume fraction of the bulk is essential for a better understanding of the physical mechanisms and precise modeling. A numerical model for the calculation of the local solids volume fraction during formation and compression of filter cakes and sediments was developed. The calculated results are compared with experimental NMR data.
Application of Magnetic Resonance Imaging (MRI) to Determine the Influence of Fluid Dynamics on Desulfurization in Bench Scale Reactors
Authors: Nguyen N. L. , Reimert R. , Hardy E. H.
Published: July 2006

The influence of fluid dynamics on the hydrodesulfurization (HDS) reactions of a diesel oil in bench‐scale reactors was evaluated. The porosities and liquid saturations of catalyst beds were quantified by using the MRI technique. The gas‐liquid systems used in the experiments were nitrogen diesel and hydrogen diesel. An apparatus was especially constructed, allowing in situ measurements of gas and liquid distributions in packed beds at elevated pressure and temperature up to 20 bar and 200 °C, respectively. The reactor itself had a length of 500 mm and an internal diameter of 19 mm. The packed beds used in this MRI study consisted of: (1) 2 mm diameter nonporous spherical glass beads and (2) 1.3 mm diameter porous Al2O3 trilobes having the same size as the original trilobe catalyst used in HDS bench‐scale experiments. The superficial gas and liquid velocities were set within the range of trickle flow, e.g., u0G = 20–500 mm/s and u0L = 0.1–6 mm/s. In parallel with the MRI experiments, the hydrodesulfurization of a gas oil was investigated in a bench‐scale plant. Its reactor had the same dimensions of the trickle‐bed column used in the MRI experiments and was filled with original trilobe catalyst. These catalytic experiments were carried out at a wide range of operating conditions (p = 30–80 bar, T = 300–380 °C, LHSV = 1–4 h–1). The results of both fluid dynamic and catalytic reaction experiments were then combined for developing a simulation model to predict the HDS performance by accounting for fluid dynamic nonidealities.
Powder Structure Transition under the Recrystallization Conditions in the RESS Process
Authors: Ksibi H. , Ben Moussa A. , Baccar M.
Published: July 2006

A variety of organic substances used in pharmaceutical and agro‐alimentary industries are often required as fine powders with a controlled size. The RESS process (rapid expansion of supercritical solution) allows the micronization of thermally labile materials and the formation of small particles with a similar morphology and a narrow size distribution. The goal of this study is to improve the description of the jet/particle system in the RESS process. An experimental investigation shows that the particle structure of processed caffeine could be enormously altered when recrystallization chamber conditions were varied. Indeed, long needles, yarns, or fibers of the material could be obtained by changing the operating pressure and temperature. Numerical simulations were performed to describe the effects of hydrodynamic parameters upon the developed jet and the recrystallized particles. These calculations showed isovalues and profiles of velocity, density, and temperature of the carbon dioxide jet by which recrystallized particles were transported and deposited on the flat plate.
NMR Methods Investigating the Mobility of Partly Fluorinated Hydrocarbons in Polymers
Authors: Neutzler S. , Oellrich L. R.
Published: July 2006

By applying different NMR methods, the penetration of polymers (FPM, EPDM, HNBR) by partly fluorinated hydrocarbons (HFC) has been investigated and characterized. NMR proved to be capable in delivering qualitative as well as quantitative information about the fluid in the polymer sample. The concentration, as well as the diffusion coefficient of the HFC in the polymer, has been determined. Localized methods furthermore allow a characterization of the swelling of the polymer on the macroscopic scale. The penetration and swelling kinetics can be determined. Probe molecules help to obtain information on the microscopic scale.
Catecholase Activity of a Copper(II) Complex with a Macrocyclic Ligand: Unraveling Catalytic Mechanisms
Authors: Koval Iryna A. , Selmeczi Katalin , Belle Catherine , Philouze Christian , Saint‐Aman Eric , Gautier‐Luneau Isabelle , Schuitema Anna Maria , van Vliet Marcel , Gamez Patrick , Roubeau Olivier , Lüken Matthias , Krebs Bernt , Lutz Martin , Spek Anthony L. , Pierre Jean‐Louis , Reedijk Jan
Published: July 2006

We report the structure, properties and a mechanism for the catecholase activity of a tetranuclear carbonato‐bridged copper(II) cluster with the macrocyclic ligand [22]pr4pz (9,22‐dipropyl‐1,4,9,14,17,22,27,28,29, 30‐decaazapentacyclo[22.2.1.14,7.111,14. 117,20]triacontane‐5,7(28),11(29),12,18, 20(30),24(27),25‐octaene). In this complex, two copper ions within a macrocyclic unit are bridged by a carbonate anion, which further connects two macrocyclic units together. Magnetic susceptibility studies have shown the existence of a ferromagnetic interaction between the two copper ions within one macrocyclic ring, and a weak antiferromagnetic interaction between the two neighboring copper ions of two different macrocyclic units. The tetranuclear complex was found to be the major compound present in solution at high concentration levels, but its dissociation into two dinuclear units occurs upon dilution. The dinuclear complex catalyzes the oxidation of 3,5‐di‐tert‐butylcatechol to the respective quinone in methanol by two different pathways, one proceeding via the formation of semiquinone species with the subsequent production of dihydrogen peroxide as a byproduct, and another proceeding via the two‐electron reduction of the dicopper(II) center by the substrate, with two molecules of quinone and one molecule of water generated per one catalytic cycle. The occurrence of the first pathway was, however, found to cease shortly after the beginning of the catalytic reaction. The influence of hydrogen peroxide and di‐tert‐butyl‐o‐benzoquinone on the catalytic mechanism has been investigated. The crystal structures of the free ligand and the reduced dicopper(I) complex, as well as the electrochemical properties of both the CuII and the CuI complexes are also reported.
Total Synthesis of the Cyclodepsipeptide Apratoxin A and Its Analogues and Assessment of Their Biological Activities
Authors: Ma Dawei , Zou Bin , Cai Guorong , Hu Xiaoyi , Liu Jun O.
Published: July 2006

A novel total synthesis of apratoxin A is described, with key steps including the assembly of its ketide segment through a D‐proline‐catalyzed direct aldol reaction and Oppolzer's anti aldol reaction and the preparation of its thiazoline unit in a biomimetic synthesis. An oxazoline analogue of apratoxin A has also been elaborated by a similar approach. This compound has a potency against HeLa cell proliferation only slightly lower than that of apratoxin A, whilst a C(40)‐demethylated oxazoline analogue of apratoxin A displays a much lower cytotoxicity and the C(37)‐epimer and C(37) demethylation product of this new analogue are inactive. These results suggest that the two methyl groups at C(37) and C(40) and the stereochemistry at C(37) are essential for the potent cellular activity of the oxazoline analogue of apratoxin A. Further biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase.
Automated Protein–Ligand Crystallography for Structure‐Based Drug Design
Authors: Mooij Wijnand T. M. , Hartshorn Michael J. , Tickle Ian J. , Sharff Andrew J. , Verdonk Marcel L. , Jhoti Harren
Published: July 2006

An approach to automate protein–ligand crystallography is presented, with the aim of increasing the number of structures available to structure‐based drug design. The methods we propose deal with the automatic interpretation of diffraction data for targets with known protein structures, and provide easy access to the results. Central to the system is a novel procedure that fully automates the placement of ligands into electron density maps. Automation provides an objective way to structure solution, whereas manual placement can be rather subjective, especially for data of low to medium resolution. Ligands are placed by docking into electron density, whilst taking care of protein–ligand interactions. The ligand fitting procedure has been validated on both public domain and in‐house examples. Some of the latter deal with cocktails of low‐molecular weight compounds, as used in fragment‐based drug discovery by crystallography. For such library‐screening experiments we show that the method can automatically identify which of the compounds from a cocktail is bound.
Rational Design of Aziridine‐Containing Cysteine Protease Inhibitors with Improved Potency: Studies on Inhibition Mechanism
Authors: Vicik Radim , Helten Holger , Schirmeister Tanja , Engels Bernd
Published: July 2006

To enable a rational design of improved cysteine protease inhibitors, the present work investigates trends in the inhibition potency of aziridine derivatives with a substituted nitrogen center. To predict the influence of electron‐withdrawing substituents, quantum chemical computations of the ring opening of N‐formylated, N‐methylated, and N‐unsubstituted aziridines with thiolate were performed. They revealed that the N‐formyl group leads to a strong decrease of the reaction barrier and a considerable increase in exothermicity due to stabilization of the transition state. In contrast, a nucleophilic attack at the carbonyl carbon atom is characterized by very low reaction barriers, suggesting a reversible reaction, thus providing the theoretical background for the reversible inhibition of cysteine proteases by peptidyl aldehydes. Reactions of aziridine building blocks (diethyl aziridine‐2,3‐dicarboxylate 1, diethyl 1‐formyl aziridine‐2,3‐dicarboxylate 2) with a model thiolate in aqueous solution which were followed by NMR spectroscopy and mass spectrometry, showed the N‐formylated compound 2 to readily undergo a ring‐opening reaction. In contrast, the reaction of 1 with the thiolate is much slower. Enzyme assays with the cysteine protease cathepsin L showed 2 to be a 5000‐fold better enzyme inhibitor than 1. Dialysis assays clearly proved irreversible inhibition. These experiments, together with the results obtained with the model thiolate, indicate that the main inhibition mechanism of the N‐formylated aziridine 2 is the ring‐opening reaction rather than the reversible attack of the active site cysteine residue at the carbonyl carbon atom.
Influence of tumor type, disease status, and patient age on self‐reported interest regarding participation in cancer clinical trials
Authors: Markman Maurie , Petersen Judith , Montgomery Robert
Published: July 2006

There is limited information available regarding the reasons cancer patients decide to enter clinical trials. To explore this issue, aggregate responses to the question, “Are you interested in learning about clinical trials for your condition?” obtained from >115,000 cancer patients (or their families) who entered data into 1 of several proprietary decision‐support programs embedded within approximately 100 well‐established cancer‐related Internet sites were analyzed. The percentage of patients (or their families) who expressed interest in learning about clinical trials ranged from as low as 21% (endometrial and cervix cancer patients >80 years of age; n = 178) to as high as 85% (recurrent ovarian cancer patients, age 51–60; n = 842). Patients >80 years of age, regardless of sex, tumor type, or status of disease, were considerably less likely to be interested in clinical trial information than younger individuals. Whereas there were no differences between males and females in their desire to obtain information, patients with self‐declared more “serious conditions” (e.g., metastatic breast cancer, recurrent prostate cancer), and those with specific cancers having a widely recognized poor prognosis (e.g., nonsmall cell lung cancer), were more likely to request study information. In the current evaluation of a large database of individuals who elected to participate in 1 of several cancer‐related decision‐support programs, major differences in self‐expressed interest in obtaining information regarding clinical trials was observed. Particularly notable was the reduced desire to gather such information among the very elderly, and the increased interest by patients with the most serious cancer‐related conditions. Cancer 2006. © 2006 American Cancer Society.
A randomized trial to improve early detection and prevention practices among siblings of melanoma patients
Authors: Geller Alan C. , Emmons Karen M. , Brooks Daniel R. , Powers Catherine , Zhang Zi , Koh Howard K. , Heeren Timothy , Sober Arthur J. , Li Frederick , Gilchrest Barbara A.
Published: July 2006

BACKGROUND.

Identifying high‐risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first‐degree relatives of melanoma patients represent a risk group who may experience a ‘teachable moment’ for enhanced education and risk reduction.

METHODS.

We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently‐diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: 1) an initial motivational and goal‐setting telephone intervention session delivered by the health educator; 2) three sets of computer‐generated materials specifically tailored to individual responses from the baseline survey; 3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and 4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened.

RESULTS.

494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06–2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two‐thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups.

CONCLUSIONS.

This study is the one of the first, to our knowledge, to address skin cancer risk‐reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease. Cancer 2006. © 2006 American Cancer Society.
What motivates men age ≥ 50 years to participate in a screening program for melanoma?
Authors: Janda Monika , Youl Philippa H. , Lowe John B. , Baade Peter D. , Elwood Mark , Ring Ian T. , Aitken Joanne F.
Published: July 2006

BACKGROUND.

The screening behavior and screening outcomes of men age ≥50 years was investigated within a randomized controlled trial of a community‐based intervention of screening for melanoma, consisting of a community education program, an education program for medical practitioners, and the provision of dedicated skin‐screening clinics.

METHODS.

Data from cross‐sectional telephone surveys before (559 completed interviews), at the end (591 completed interview), and at 2 years after the intervention (445 completed interviews) were analyzed. In addition, the authors analyzed data from skin‐screening clinics within the intervention program (3355 men age ≥50 years participated).

RESULTS.

During the intervention period men age ≥50 years increased both their screening behavior and intention to screen. Those men age ≥50 years who reported a past history of removal of a mole as well as other risk factors for skin cancer and positive attitudes toward screening were more likely to participate in skin screening across time. Men age ≥50 years accounted for 20.5% of all skin‐screening clinic attendees, 31.3% of those referred for a suspicious lesion, 48.5% of melanomas, and 45% of all keratinocyte carcinomas diagnosed within the screening program, respectively.

CONCLUSIONS.

The intervention program successfully motivated men age ≥50 years to attend screening for skin cancer, resulting in the highest yield of skin cancer within this subgroup of the population. Messages addressing skin cancer risk factors and attitudes toward skin cancer and screening could be used to target a screening program for melanoma toward men age ≥50 years. Cancer 2006. © 2006 American Cancer Society.
Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts
Authors: Takei Yoshifumi , Kadomatsu Kenji , Goto Tatsunori , Muramatsu Takashi
Published: July 2006

BACKGROUND.

Midkine (MK) is a heparin‐binding growth factor that promotes the growth, migration, and survival of various cells. Its overexpression has been observed in many human malignancies, making it an attractive therapeutic target.

METHODS.

We established a human midkine blockade system involving RNA interference.

RESULTS.

The synthetic small interfering RNA (siRNA) targeting human midkine almost completely inhibited the secretion of midkine by a human prostate cancer cell line, PC‐3, and consequently suppressed the proliferation and anchorage‐independent growth of the transfected cells. The midkine siRNA, together with atelocollagen, significantly suppressed the growth of PC‐3 tumors, which had been subcutaneously xenografted. These inhibitory effects of midkine siRNA were augmented by combinational treatment with a chemotherapeutic, paclitaxel (PTX), both in vitro and in vivo. The dose of PTX (12 mg/kg) used for the combinational treatment did not cause leukopenia or liver damage, which are often reported as serious adverse effects of PTX. The effect of the combination on tumor growth was comparable with that of PTX alone at higher doses that have exhibited severe adverse effects. Midkine siRNA suppressed mainly cell proliferation and slightly angiogenesis, whereas PTX enhanced apoptosis and slightly suppressed angiogenesis. The combination treatment was particularly effective for suppression of angiogenesis; consequently, it had striking effects on all aspects (proliferation, apoptosis, and angiogenesis).

CONCLUSIONS.

We established a novel and safe cancer therapy strategy involving midkine siRNA combined with PTX, with less adverse effects. Cancer 2006. © 2006 American Cancer Society.
Influence of Electric Field on the Phase Transitions of the Hexagonal Cylinder Phase of Diblock Copolymers
Authors: Li Xin , Jiang Ying , Li Yinchang , Liang Haojun
Published: July 2006

We have used the cell dynamic simulations (CDS) method to study the evolution of asymmetric and symmetric diblock copolymers under electric fields. For symmetric diblock copolymers, long‐range‐ordered lamellar phases form readily under electric fields. For asymmetric diblock copolymers, sphere‐to‐cylinder phase transitions occur rapidly when strong electric fields are applied, but it takes longer for the system to form hexagonal cylinder structures. The results of these simulations suggest that the sphere phase is stable under weak electric fields, but a threshold electric intensity exists for the sphere‐to‐cylinder phase transition. In addition, we also studied the kinetic pathways of the transition of the lamellar phase to the hexagonal cylinder phase of the asymmetric diblock copolymers under electric fields. Hexagonal cylinder structures form when the lamellar phase is subjected to a sudden temperature jump. The scattering functions suggest that the hexagonal cylinder structures are very regular and possess very few flaws.