bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Agent Capecitabine: A Reference Treatment for Taxane-Pretreated Metastatic Breast Cancer?
Authors: Seidman Andrew D. , O'Shaughnessy Joyce , Misset Jean-Louis
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Identify evidence-based options for treatment of patients with taxane-refractory breast cancer. Explain reasons for and limitations of patient preference for oral chemotherapy. Manage treatment toxicities of capecitabine. Discuss the mechanism of action of capecitabine.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

The treatment of patients with metastatic breast cancer that has progressed despite previous anthracycline- and taxane-based therapy is a challenge for oncologists. Several agents, including vinorelbine, gemcitabine, pemetrexed, and particularly capecitabine, have been evaluated in this setting, either alone or in combination with other cytotoxic agents. The efficacy of many of these agents has not yet been clearly established in this setting, as the majority have been evaluated in a limited number of patients and predominantly in single-center trials. Furthermore, some agents with clinically meaningful activity are often associated with significant toxicity, particularly myelosuppression and neuropathy, while less toxic agents/regimens often exchange improved tolerability for reduced activity.

Capecitabine, an oral chemotherapeutic, is the agent that has been evaluated most extensively in this setting. A large, phase II trial (n = 163) conducted in North America demonstrated a disease control rate of 63%, including an objective response rate of 20%, median time to disease progression of 3.0 months, and median survival of approximately 1 year. Adverse events were typically mild to moderate in intensity and could be controlled with treatment interruption or, if necessary, dose adjustment to each individual's tolerable dose. Data recently reported from three other large trials in taxane-pretreated patients have revealed similar efficacy and tolerability. Together, these four trials show that single-agent capecitabine, in a population of 500 patients, consistently produced clinically meaningful efficacy, including median survival of approximately 1 year, with a favorable safety profile. Myelosuppression and alopecia were particularly rare. In addition, the oral administration of capecitabine, which enables convenient, patient-oriented therapy, makes it an attractive treatment for patients. Based primarily on the results of the pivotal trial, capecitabine received regulatory approval as treatment for anthracycline- and taxane-pretreated (paclitaxel-pretreated in the U.S.) metastatic breast cancer. In light of the confirmatory results of subsequent large trials, capecitabine is now considered a reference treatment in this setting, as no other agent has consistently demonstrated such high efficacy in as large a patient population.
Introduction: All Ireland Fatigue Coalition
Authors: Daly Peter A.
Published: August 2004

The first professional meeting and educational symposium of the All Ireland Fatigue Coalition (AIFC) convened in Dublin in September 2002, with an attendance of 350 health professionals who work in cancer research and cancer patient care. The AIFC is a multidisciplinary team of doctors, nurses, and other health care professionals from Ireland, Northern Ireland, and the U.S. whose mission is to champion the proactive management of cancer-related fatigue. The major goals of the symposium were to better understand the status and prevalence of cancer fatigue on the island of Ireland and to learn how to better assess and manage fatigue in cancer patients. An international faculty presented on topics ranging from defining the condition to developing an international protocol implementing a fatigue algorithm.
Anemia in Cancer: Some Pathophysiological Aspects
Authors: Dicato Mario
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Recognize the causes of anemia in cancer patients. Describe ways in which the action of erythropoietin is regulated. Explain the methods for treating anemia and indications for treatment.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

More than 30% of cancer patients experience anemia and its side effect, fatigue. Its causes can be numerous, but anemia is usually secondary to an imbalance of cytokines. Among these, tumor necrosis factor-alpha seems to be the major culprit, creating anemia by blunting the physiological effect of erythropoietin. Pharmacologically increasing the erythropoietin level corrects the anemia in about half the treated patients. Several studies have shown that quality of life is substantially improved through such therapy.
Liposomal Anthracyclines and New Treatment Approaches for Breast Cancer
Authors: Wolff Antonio C.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the rationale for combining growth factor pathway modulators and cytotoxic agents in the treatment of breast cancer. Discuss clinical trials examining the efficacy and safety of trastuzumab in combination with other agents, including liposomal anthracyclines, in the treatment of breast cancer. Discuss new directions in breast cancer research.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Breast cancer research is entering a new and promising phase, with greater focus on patient quality of life and therapy selection based on specific targets of interest. Growth factor pathway modulators represent an area of increasing interest for clinicians treating various cancer types, including breast cancer. Therapeutic strategies combining cytotoxic drugs with specific targets using small molecules and targeted antibody therapy may help circumvent potential growth factor survival mechanisms in solid tumors. One of the challenges when combining these agents, however, is the potential for pharmacodynamic and pharmacokinetic interactions, making safety an important consideration. An example of a growth factor pathway modulator with clinical application in breast cancer is trastuzumab. Based on its efficacy in metastatic disease, ongoing clinical trials are examining trastuzumab in combination with chemotherapy in the adjuvant setting. Concerns about the cardiac safety of trastuzumab given concomitantly with conventional anthracyclines support ongoing investigations of regimens combining it with liposomal anthracyclines, based on available data indicating a more favorable cardiac safety profile with liposomal formulations.
Liposomal Anthracyclines in Metastatic Breast Cancer: Clinical Update
Authors: Rivera Edgardo
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Differentiate liposomal anthracycline formulations. Describe the efficacies and tolerabilities of liposomal anthracyclines as single agents and in combination therapy in the treatment of metastatic breast cancer. Compare the efficacies and tolerabilities of liposomal anthracyclines with those of conventional anthracyclines.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Anthracyclines are a mainstay of therapy for patients with metastatic breast cancer. However, their use has been limited by associated toxicities, including myelosuppression, alopecia, nausea and vomiting, stomatitis, and most importantly, cardiotoxicity. Liposomal anthracyclines were developed to increase the therapeutic index of conventional anthracyclines by maintaining antitumor efficacy while improving the safety profile. There are currently three liposomal formulations: liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin. Only one phase I study has been conducted with liposomal daunorubicin for metastatic breast cancer. Liposomal doxorubicin has shown comparable efficacy with conventional doxorubicin and less toxicity. Pegylated liposomal doxorubicin is the most widely studied of the liposomal anthracyclines and has demonstrated similar efficacy to conventional doxorubicin and a better safety profile, including significantly less cardiotoxicity, in patients with metastatic breast cancer. Pegylated liposomal doxorubicin has shown efficacy as a single agent and in combination with many agents, including cyclophosphamide, paclitaxel, docetaxel, and gemcitabine, with response rates ranging from 33%-75%. Growing evidence supports the use of pegylated liposomal doxorubicin as first-line treatment for patients with metastatic breast cancer, owing to its antitumor activity in both anthracycline-naïve patients and in patients with previous anthracycline exposure.
Blocked Pathways: FTIs Shut Down Oncogene Signals
Authors: Sebti Saïd M.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe how mutations in ras oncogenes affect cell signal transduction pathways and disrupt cell growth, differentiation, proliferation, and survival. Identify the mechanisms of action of two classes of prenylation inhibitors, the farnesyl transferase inhibitors (FTIs) and the geranylgeranyl transferase-I inhibitors (GGTIs). Explain the in vitro and in vivo antitumor activity of FTIs and GGTIs in multiple myeloma and myelodysplastic syndrome.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Ras proteins play fundamental roles in cell signal transduction pathways that regulate cell growth, differentiation, proliferation, and survival. ras mutations are among the most frequently encountered genetic abnormalities in human cancers and play a key role in tumorigenesis. The enzymatic attachment of a 15- or 20-carbon moiety to the Ras protein through farnesylation or geranylgeranylation, respectively, is a required step in the proper localization and activation of Ras. Inhibition of the catalytic enzymes, farnesyl transferase and geranylgeranyl transferase, is a novel, mechanism-based, targeted approach to cancer therapy development. Geranylgeranyl transferase inhibitors suppress tumor growth by accumulating cells in the G1/S cell cycle phase. One mechanism by which farnesyl transferase inhibitors suppress tumor growth is by inhibiting bipolar spindle formation, thereby blocking progression from prophase to metaphase. Although the exact molecular target responsible for the antitumor activity of farnesyl transferase inhibitors is unclear, at least in some tumor cells, inhibition of phosphoinositide-3-OH kinase/Akt-mediated cell survival pathways may play a critical role. Identifying the farnesylated proteins that are targeted by farnesyl transferase inhibitors and the tumor molecular signatures that dictate which set of patients will respond to farnesyl transferase inhibitors are critical end points for future mechanistic studies.
Formation of Arrayed Droplets by Soft Lithography and Two‐Phase Fluid Flow, and Application in Protein Crystallization
Authors: Zheng B. , Tice J. D. , Ismagilov R. F.
Published: August 2004

This paper presents an overview of our recent work on the use of soft lithography and two‐phase fluid flow to form arrays of droplets. The crucial issues in the formation of stable arrays of droplets and alternating droplets of two sets of aqueous solutions include the geometry of the microchannels, the capillary number, and the water fraction of the system. Glass capillaries could be coupled to the PDMS microchannels and droplets could be transferred into glass capillaries for long‐term storage. The arrays of droplets have been applied to screen the conditions for protein crystallization with microbatch and vapor diffusion techniques.
Three‐Dimensional Nanofabrication with Rubber Stamps and Conformable Photomasks
Authors: Jeon S. , Menard E. , Park J.‐U. , Maria J. , Meitl M. , Zaumseil J. , Rogers J. A.
Published: August 2004

This article briefly describes two recently developed soft‐lithographic techniques that can be used to fabricate complex, well‐defined three‐dimensional (3D) nanostructures. The first relies on the single or multilayer transfer of thin solid ‘ink' coatings from high‐resolution rubber stamps. The second uses these stamps as conformable phase masks for proximity field nanopatterning of thin layers of transparent photopolymers. Although both techniques use the same pattern‐transfer elements, they rely on completely different physical principles and they provide complementary patterning capabilities. The operational simplicity of the techniques, their ability to pattern large areas quickly, and the flexibility in the geometry of structures that can be formed with them suggest general utility for 3D nanomanufacturing.
Micropatterned Environments in Cell Biology
Authors: Raghavan S. , Chen C. S.
Published: August 2004

Microfabrication and materials‐science‐based approaches provide a powerful new set of tools to control the spatial organization and temporal presentation of cellular cues. In this progress report, we highlight recent advances in the technological development and application of these tools to study how cells sense and respond to their microenvironment.
Crystallization in Patterns: A Bio‐Inspired Approach
Authors: Aizenberg J.
Published: August 2004

Nature produces a wide variety of exquisite, highly functional mineralized tissues using simple inorganic salts. Biomineralization occurs within specific microenvironments, and is finely tuned by cells and specialized biomacromolecules. This article surveys bio‐inspired approaches to artificial crystallization based on the above concept: that is, the use of organized organic surfaces patterned with specific initiation domains on a sub‐micrometer scale to control patterned crystal growth. Specially tailored self‐assembled monolayers (SAMs) of ω‐terminated alkanethiols were micropatterned on metal films using soft lithography and applied as organic templates for the nucleation of calcium carbonate. Crystallization results in the formation of large‐area, high‐resolution inorganic replicas of the underlying organic patterns. SAMs provide sites for ordered nucleation, and make it possible to control various aspects of the crystallization process, including the precise localization of particles, nucleation density, crystal sizes, crystallographic orientation, morphology, polymorph, stability, and architecture. The ability to construct periodic arrays of uniform oriented single crystals, large single crystals with controlled microporosity, or films presenting patterns of crystals offers a potent methodology to materials engineering.
Form and Function in Multilayer Assembly: New Applications at the Nanoscale
Authors: Hammond P. T.
Published: August 2004

New frontiers in materials and polymer science include the development of assembly processes that are flexible, allow the access and implementation of nanoscale structure and order, can provide access to a broad range of materials systems, and yet can be implemented at relatively low cost. The ability to fine tune the composition of nanostructured thin films on the nanometer length scale, when combined with inexpensive patterning and templating routes, provides a powerful tool for nano‐ and microscale assembly of devices and novel new material systems. The layer‐by‐layer electrostatic assembly technique is a rich, versatile, and significantly inexpensive approach to the formation of thin films via alternating adsorption of positively and negatively charged species from aqueous solutions; this method has also been extended to include the alternation of polymers with hydrogen‐bond donor and acceptor groups. Polymer organic and organic/inorganic thin films formed using this technique may contain a number of different functional groups, including electro‐optic, electroluminescent, conducting, and dielectric layers, and functional organic and inorganic nanoparticles. Newly developed materials systems based on alternating layer methods will be addressed, as well as a number of frontier areas and future areas for the use of these systems, ranging from nanomechanical composites to electrochemical devices and templated deposition of functional microspheres. Both new functionalities incorporated within these materials and new means of patterning and templating these structures in two and three dimensions will be addressed in this review.
Whitesides' Group: Writing a Paper
Authors: Whitesides G. M.
Published: August 2004

Insights into conducting research and the writing of scientific papers are given by Prof. Whitesides in this short essay. The manuscript and its guidelines has been circulated within the Whitesides' research group since 1989.
Soft Lithography and the Art of Patterning — A Tribute to Professor George M. Whitesides
Authors: Xia Y.
Published: August 2004

This special issue of Advanced Materials has been put together in honor of the 65th birthday of Professor George Whitesides. A very brief outline of his work, along with a summary of the contributions to the issue are provided in this Guest Editorial.
Patterning: Principles and Some New Developments
Authors: Geissler M. , Xia Y.
Published: August 2004

This article provides an overview of various patterning methodologies, and it is organized into three major sections: generation of patterns, replication of patterns, and three‐dimensional patterning. Generation of patterns from scratch is usually accomplished by serial techniques that are able to provide arbitrary features. The writing process can be carried out in many different ways. It can be achieved using a rigid stylus; or a focused beam of photons, electrons, and other energetic particles. It can also be accomplished using an electrical or magnetic field; or through localized add‐on of materials such as a liquid‐like ink from an external source. In addition, some ordered but relatively simple patterns can be formed by means of self‐assembly. In replication of patterns, structural information from a mask, master, or stamp is transferred to multiple copies with the use of an appropriate material. The patterned features on a mask are mainly used to direct a flux of radiation or physical matter from a source onto a substrate, whereas a master/stamp serves as the original for replication based on embossing, molding, or printing. The last section of this article deals with three‐dimensional patterning, where both vertical and lateral dimensions of a structure need to be precisely controlled to generate well‐defined shapes and profiles. The article is illustrated with various examples derived from recent developments in this field.
Theoretische Chemie des Golds
Authors: Pyykkö Pekka
Published: August 2004

Die besonderen Eigenschaften des Golds sind entscheidend durch relativistische Effekte bestimmt. Mittlerweile existiert eine Vielzahl zuverlässiger Rechnungen zu Goldverbindungen, deren Kernaussagen hier dargestellt werden. Besonderes Augenmerk liegt auf den aurophilen Wechselwirkungen in mehrkernigen Goldverbindungen.
Titelbild: Ab Initio NMR Spectra for Molecular Systems with a Thousand and More Atoms: A Linear‐Scaling Method (Angew. Chem. 34/2004)
Authors: Ochsenfeld Christian , Kussmann Jörg , Koziol Felix
Published: August 2004

Ein echtes Puzzle ist die Zuordnung der NMR‐Signale von Molekülen mit mehr als tausend Atomen. Abhilfe lässt sich durch die Ab‐initio‐Berechnung der Spektren schaffen: C. Ochsenfeld et al. stellen in ihrer Zuschrift auf S. 4585 ff. eine Methode vor, mit deren Hilfe bei einem geringeren Rechenaufwand (durch Verringerung der Dimension der Berechnung von kubisch auf linear) eine näherungsweise Lösung der Schrödinger‐Gleichung gelingt.
Theoretical Chemistry of Gold
Authors: Pyykkö Pekka
Published: August 2004

Gold is an element whose unique properties are strongly influenced by relativistic effects. A large body of appropriate calculations now exist and their main conclusions are summarized. The theoretical interpretation of the aurophilic attraction is discussed in detail.
Cover Picture: Ab Initio NMR Spectra for Molecular Systems with a Thousand and More Atoms: A Linear‐Scaling Method (Angew. Chem. Int. Ed. 34/2004)
Authors: Ochsenfeld Christian , Kussmann Jörg , Koziol Felix
Published: August 2004

A missing link between theory and experiment for the difficult puzzle of assigning NMR spectra for molecules with more than a thousand atoms is provided by the calculation of ab initio NMR spectra, as symbolized in the cover picture. In their Communication on page 4485 ff., C. Ochsenfeld et al. describe how an approximate solution of the Schrödinger equation becomes possible by reducing the computational effort from cubic to linear.
Structure transition in myosin association with the change of concentration: Solubility equilibrium under specified KCl and pH condition
Authors: Tsunashima Yoshisuke , Akutagawa Tohru
Published: August 2004

We observed, for the first time, the elementary process for the ordered self‐assembly formation of myosin in solution. It was realized exclusively under the specific condition of 200 mM KCl, 5 mM phosphate buffer, pH 7.08, at 15–20°C, which is called the transition‐generating condition (TGC). Described more in detail: pure myosin extracted from rabbit skeletal muscle exhibited the structural transition in its association form only when the myosin concentration c was changed under TGC. The myosin solubility was saturated in both edges of the total myosin concentration c > 10.0 mg/mL (solubility region II) and c ≦ 0.25 mg/mL (solubility region I). In the intermediate region, the association structure of myosin changed stepwise with decreasing c. The steps were classified into four regions: region I (c ≦ 0.25 mg/mL), II (0.25 ≦ c ≦ 0.50 mg/mL), III (0.50 ≦ c ≦ 5.0 mg/mL), and IV (c > 5.0 mg/mL). In each region except II, the plot of the relative soluble myosin concentration caq/c against c−1 gave a straight line of different slopes, certifying that myosin constructs self‐assemblies by the closed association mechanism and that the self‐assembly takes dual structures in each region. In region II, a drastic transition occurred in the self‐assembled dual structures. Here, a highly associated (insoluble) giant assembly would break into soluble assemblies composed of several myosin molecules. The solubility region I originates a driving force for this structural transition. The basic binding unit of the self‐assembly would be a parallel myosin‐dimer constructed by the intermolecular axial staggers of 14.3 and 43 nm, as is observed by X‐ray diffraction for the thick filament assembly or light meromyosin paracrystals. Myosin could take a single rod‐like chain form only in an extremely low concentration region of c ≦ caq,0 (= 0.053 mg/mL). The association behavior revealed in the present study suggests strongly that the complementary charge cluster and its electrostatic interaction between parallel myosin rods play a crucial role for the ordered self‐assembly formation and that the specific electrostatic atmosphere of the solution under TGC is essential to the association mechanism in skeletal muscle myosin, or the thick filament formation of the mammals. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Development of an automated water toxicity biosensor using Thiobacillus ferrooxidans for monitoring cyanides in natural water for a water filtering plant
Authors: Okochi Mina , Mima Koji , Miyata Maki , Shinozaki Youhei , Haraguchi Satoshi , Fujisawa Minoru , Kaneko Masao , Masukata Tadashi , Matsunaga Tadashi
Published: August 2004

An on‐line biosensor consisting of immobilized Thiobacillus ferrooxidans and an oxygen electrode was developed for automated monitoring of acute toxicity in water samples. T. ferrooxidans is an obligatory acidophilic, autotrophic bacterium and derives its energy by the oxidation of ferrous ion, elemental sulfur, and reduced sulfur compounds including metal sulfides. The assay is based on the monitoring of a current increase by addition of toxicoids, which is caused by the inhibition of bacterial respiration and decrease in oxygen consumption. Optimum cell number on the membrane was 5.0 × 108 cells. The steady‐state current was obtained when concentration of FeSO4 was above 3.6 mM at pH 3. The sensor response of T. ferrooxidans immobilized membrane for 5.0 μM KCN was within an error of 10% for 30 membranes. A linear relationship was obtained at KCN concentration in the range of 0.5–3.0 μM in a flow‐type monitoring system. Minimum detectable concentrations of KCN, Na2S, and NaN3 were 0.5, 1.2, and 0.07 μM, respectively. The monitoring system contained two biosensors and these sensors were cleaned with sulfuric acid (pH 1.5) twice a day. This treatment could remove fouling on microbial immobilized membrane by natural water and ferrous precipitation in the flow cell. This flow‐type monitoring sensor was operated continuously for 5 months. Also, T. ferrooxidans immobilized membrane can be stored for one month at 4°C when preserved with wet absorbent cotton under argon gas. © 2004 Wiley Periodicals, Inc.
Real time quantitative PCR as a method to evaluate xenotropic murine leukemia virus removal during pharmaceutical protein purification
Authors: Shi Liming , Chen Qi , Norling Lenore A. , Lau Allen S.L. , Krejci Sherrie , Xu Yuan
Published: August 2004

Chinese hamster ovary cells used for pharmaceutical protein production express noninfectious retrovirus‐like particles. To assure the safety of pharmaceutical proteins, validation of the ability of manufacturing processes to clear retrovirus‐like particles is required for product registration. Xenotropic murine leukemia virus (X‐MuLV) is often used as a model virus for clearance studies. Traditionally, cell‐based infectivity assay has been the standard virus quantification method. In this article, a real time quantitative PCR (Q‐PCR) method has been developed for X‐MuLV detection/quantification. This method provides accurate and reproducible quantification of X‐MuLV particle RNA (pRNA) over a linear dynamic range of at least 100,000‐fold with a quantification limit of approximately 1.5 pRNA copies μL−1. It is about 100‐fold more sensitive than the cell‐based infectivity assay. High concentrations of protein and cellular DNA present in test samples have been demonstrated to have no impact on X‐MuLV quantification. The X‐MuLV clearance during chromatography and filtration procedures determined by this method is highly comparable with that determined by the cell‐based infectivity assay. X‐MuLV clearance measured by both methods showed that anion exchange chramotography (QSFF) and DV50 viral filtration are robust retrovirual removal steps. In addition, combination of the two methods was able to distinguish the viral removal from inactivation by the Protein A chromatography, and fully recognize the viral clearance capacity of this step. This new method offers significant advantages over cell‐based infectivity assays. It could be used to substitute cell‐based infectivity assays for process validation of viral removal procedures, but not inactivation steps. Its availability should greatly facilitate and reduce the cost of viral clearance evaluations for new biologic product development. © 2004 Wiley Periodicals, Inc.
Subminute and sensitive determination of the neurotransmitter serotonin in urine by capillary electrophoresis with laser‐induced ﬂuorescence detection
Authors: Román David Arráez , Carretero Antonio Segura , Blanco Carmen Cruces , Gutiérrez Alberto Fernández
Published: August 2004

In this work, a sub‐minute and sensitive capillary electrophoresis with laser‐induced ﬂuorescence (CE‐LIF) method was developed for the analysis and quantitation of the neurotransmitter 5‐hydroxytryptamine (5‐HT) or serotonin in urine. The method involves precolumn derivatization with ﬂuorescein isothiocyanate isomer I (FITC) using an excitation light from an argon ion laser of 488 nm and a 520 nm band pass emission ﬁlter. Different variables that affect derivatization (pH, FITC concentration, reaction time and temperature) and separation (buffer concentration, pH, applied voltage and injection time) were studied. The linear dynamic range obtained was between 0 and 188 nm with a detection limit of 16 nm with a RSD between 2 and 9%. The applicability of the proposed method was demonstrated by analysis of 5‐HT in human urine, establishing a concentration of 57 nm in control urine. The method was validated by standard‐addition methodology. Copyright © 2004 John Wiley & Sons, Ltd.
Efﬁciency of antidepressant drugs as monoamine reuptake inhibitors: analysis of the hydrophobicity inﬂuence using biopartitioning micellar chromatographic data
Authors: Quiñones‐Torrelo C. , Sagrado S. , Villanueva‐Camañas R. M. , Medina‐Hernández M. J.
Published: August 2004

The reuptake blockade of biogenic amines by antidepressants is related not only to their therapeutics effects, but also to their side effects and potential drug–drug interactions. As an alternative to classical quantitative structure–activity relationships studies, in this work we propose different quantitative retention–activity relationships (QRAR) models that are able to describe the monoamine reuptake inhibition by antidepressants. The retention of compounds is measured using a biopartitioning micellar chromatography (BMC) system that can simulate the same hydrophobic, electronic and steric molecular interactions as those that condition drug activity. Since all the compounds considered in this work are structurally related because all of them share the same molecular features as the corresponding basic pharmacophore, the results obtained show that there is a retention range in which antidepressants present the highest monoamine reuptake inhibitor potency. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitation of normal and formaldehyde‐modiﬁed deoxynucleosides by high‐performance liquid chromatography/UV detection
Authors: Zhong Weiguang , Hee Shane Que
Published: August 2004

A sensitive and selective method was developed for the ﬁrst time to quantify simultaneously the normal and formaldehyde (FA)‐modiﬁed bases in human placental DNA treated with 100 ppm FA for 20 h at 37°C. Digestion of DNA to deoxynucleosides with DNase I, phosphodiesterase and alkaline phosphatase occurred in that order with centrifugation steps. The normal and FA‐modiﬁed deoxynucleosides were then resolved from one another and reagent blank interferences to produce selective separation through high performance liquid chromatography–ultraviolet detection at 254 nm. A C18 reversed‐phase column facilitated the resolution using 5 mm ammonium acetate and a gradient of 0–6% methanol at ﬂow rates of 0.3–1.4 mL/min before column cleaning. The lower quantiﬁable limits for deoxyadenosine, deoxyguanosine, deoxycytidine, thymidine, N6‐hydroxymethyldeoxyadenosine (N6‐dA), N2‐hydroxymethyldeoxyguanosine (N2‐dG) and N4‐hydroxymethyldeoxycytidine (N4‐dC) were 11, 7.6, 12, 15, 10, 10 and 22 pmol, respectively. The abundance order of the modiﬁed deoxynucleosides was N6‐dA > N2‐dG > N4‐dC. dT did not form hydroxymethyl derivatives. The respective concentrations were about 6.0, 10.0 and 23 pmol of modiﬁed deoxynucleosides in 80 µg of human placental DNA after treatment with 100 µg/mL of formalin for 20 h at 37°C. The stabilities of N6‐dA and N2‐dG were much better at −20°C than at 25°C, where the respective halftimes were about 50.1 and 21.0 h. Copyright © 2004 John Wiley & Sons, Ltd.
An HPLC assay of hydroxyl radicals by the hydroxylation reaction of terephthalic acid
Authors: Linxiang Li , Abe Yoshihiro , Nagasawa Yukiko , Kudo Risa , Usui Noriko , Imai Kazuhiro , Mashino Tadahiko , Mochizuki Masataka , Miyata Naoki
Published: August 2004

An HPLC assay for hydroxyl radicals is described. The hydroxyl radical was trapped by terephthalic acid (non‐ﬂuorescent), and 2‐hydroxyl terephthalic acid (fluorescent) was quantitated by HPLC‐ﬂuorescence detection. At a terephthalic acid concentration of 4.25 mmol/L, the hydroxyl radical formed in the Fenton reaction was successfully assayed in the concentration range of hydrogen peroxide of 2.5–50 µmol/L, where the concentration of Fe(II) was 50 µmol/L. The ﬂuorescence of 2‐hydroxy terephthalate was stable at 24 h, and its detection limit by this method was 5 nmol/L (100 fmol). Copyright © 2004 John Wiley & Sons, Ltd.
A rapid and simple method for determination of halothane, isoﬂurane and sevoﬂurane in blood using gas chromatography
Authors: Atherley Richard J. , Antognini Joseph F.
Published: August 2004

We have developed a technique to determine the concentration of volatile anesthetics (halothane, isoﬂurane and sevoﬂurane) in blood that is a modiﬁcation of a method used for volatile anesthetics in Krebs solution. Methylene chloride was the internal standard and chloroform was used to extract the volatile anesthetic from blood. The congealed blood proteins were separated from the chloroform solvent (containing anesthetic) using a two‐compartment vial that ﬁltered out the proteinaceous material during centrifuging. Recovery averaged 102%. Linearity was excellent (r = 0.992–0.999) in the 50–600, 50–300 and 50–300 µg/mL range for halothane, isoﬂurane and sevoﬂurane, respectively. Intra‐day and inter‐day precisions were likewise excellent, with relative standard deviations <5.3 and <7.1%, respectively. Accuracy ranged from 0.8 to 9.5% of the estimated theoretical value. Extracted anesthetic in chloroform solvent was stable over 4–5 days, with <3% variability. The time from obtaining the blood sample to determination of the concentration from the chromatographic peak was 15 min or less. Copyright © 2004 John Wiley & Sons, Ltd.
A mathematical theory of strong emergence using multiscale variety
Authors: Bar‐Yam Yaneer
Published: August 2004

We argue conceptually and then demonstrate mathematically that it is possible to define a scientifically meaningful notion of strong emergence. A strong emergent property is a property of the system that cannot be found in the properties of the system's parts or in the interactions between the parts. The possibility of strong emergence follows from an ensemble perspective, which states that physical systems are only meaningful as ensembles rather than individual states. Emergent properties reside in the properties of the ensemble rather than of any individual state. A simple example is the case of a string of bits including a parity bit, i.e. the bits are constrained to have, e.g., an odd number of ON bits. This constraint is a property of the entire system that cannot be identified through any set of observations of the state of any or all subsystems of the system. It is a property that can only be found in observations of the state of the system as a whole. A collective constraint is a property of the system, however, the constraint is caused when the environment interacts with the system to select the allowable states. Although selection in this context does not necessarily correspond to biological evolution, it does suggest that evolutionary processes may lead to such emergent properties. A mathematical characterization of multiscale variety captures the implications of strong emergent properties on all subsystems of the system. Strong emergent properties result in oscillations of multiscale variety with negative values, a distinctive property. Examples of relevant applications in the case of social systems include various allocation, optimization, and functional requirements on the behavior of a system. Strongly emergent properties imply a global to local causality that is conceptually disturbing (but allowed!) in the context of conventional science, and is important to how we think about biological and social systems. © 2004 Wiley Periodicals, Inc. Complexity 9: 15–24, 2004
Sex promotes gamete selection: A quantitative comparative study of features favoring the evolution of sex
Authors: Jaffe Klaus
Published: August 2004

Explaining the maintenance of sexual reproduction remains one of the greatest challenges in biology. The theoretical oddity of sex is based on at least three advantages that asexual organisms have over sexual ones: (1) Asexuals, by not producing males, have a twofold advantage over sexuals, regarding the number of reproductive individuals; (2) sexuals have an evolutionary disadvantage over asexuals, in that a rare alleles that increases fitness of one parent, for example, is not necessarily transmitted to the offspring, due to segregation; and (3) asexuals do not have to find a mate in order to reproduce. Here I present the results of evolutionary tournaments performed using the agent‐based computer simulation Biodynamica. The tournaments explored the relative merits of various features that have been proposed to affect the putative advantages of sexual reproduction, including ploidy, mate selection, large reproductive variance of males, low mutation rates, gamete selection, reduced cost for the production of males, thelytoky vs. parthenogenesis, variable environments, and complex genomes. The model allowed for a quantitative comparison of the effect of these features on the adaptive value of sex. The results showed that the production of large number of gametes (for example “masting” in massive flowering of trees or spermatozoa of most animals) inducing gamete selection, together with nonrandom mate selection, increased variance in male reproductive success and/or low mutation rates, allowed sexual agents to out‐breed asexual ones, despite the three disadvantages for sex cited above. The wok suggests that gamete cycles and alloiogenesis, common to most sexual plants, fungi, and animals, should be viewed as a new level for natural selection to work. Mate and gamete selection are more efficient in the use of biomass, energy, and time than natural selection at the level of organisms, helping to make sexual reproduction an evolutionary success. © 2004 Wiley Periodicals, Inc. Complexity 9: 43–51, 2004
The emergence of dynamical complexity: An exploration using elementary cellular automata
Authors: Mizraji Eduardo
Published: August 2004

This work concerns the interaction between two classical problems: the forecasting of the dynamical behaviors of elementary cellular automata (ECA) from its intrinsic mathematical laws and the conditions that determine the emergence of complex dynamics. To approach these problems, and inspired by the theory of reversible logical gates, we decompose the ECA laws in a “spectrum” of dyadic Boolean gates. Emergent properties due to interactions are captured generating another spectrum of logical gates. The combined analysis of both spectra shows the existence of characteristic bias in the distribution of Boolean gates for ECA belonging to different dynamical classes. These results suggest the existence of signatures capable to indicate the propensity to develop complex dynamics. Logical gates “exclusive‐or” and “equivalence” are among these signatures of complexity. An important conclusion is that within ECA space, interactions are not capable to generate signatures of complexity in the case these signatures are absent in the intrinsic law of the automaton. © 2004 Wiley Periodicals, Inc. Complexity 9: 33–42, 2004
Contextual regularity and complexity of neuronal activity: From stand‐alone cultures to task‐performing animals
Authors: Ayali A. , Fuchs E. , Zilberstein Y. , Robinson A. , Shefi O. , Hulata E. , Baruchi I. , Ben‐Jacob E.
Published: August 2004

Precursors of the superior information processing capabilities of our cortex can most probably be traced back to simple invertebrate systems. Using a unique set of newly developed neuronal preparations and state‐of‐the‐art analysis tools, we show that insect neurons have the ability to self‐regulate the information capacity of their electrical activity. We characterize the activity of a distinct population of neurons under progressive levels of structural and functional constraints: self‐formed networks of neuron clusters in vitro; isolated ex vivo ganglions; in vivo task‐free, and in vivotask‐forced neuronal activity in the intact animal. We show common motifs and identify trends of increasing self‐regulated complexity. This important principle may have played a key role in the gradual transition from simple neuronal motor control to complex information processing. © 2004 Wiley Periodicals, Inc. Complexity 9: 25–32, 2004
Application of signal‐adapted wavelet to on‐line partial discharge measurement
Authors: Su Jianshe , Xu Shuzhen , Chen Chen
Published: August 2004

This paper develops an approach for optimal selection of signal‐adapted wavelet in de‐noising. The new method employs Wu's elimination algorithm to construct compacted orthogonal wavelets. The threshold cost function is used as the objective function during choosing of the wavelet. The approach is validated by its application to de‐noising for on‐line partial discharge (PD) measurement. The physical experiments and field tests show that the method improves the suppression of noise for on‐line PD measurement with stronger robustness. Copyright © 2004 John Wiley & Sons, Ltd.
Introduction: Evaluation and development
Authors: Picciotto Robert
Published: August 2004

Over the past two decades, development priorities have been fundamentally reshaped. Evaluation has contributed to this redesign and a remarkable consensus has emerged among development practitioners. In turn, the new directions of development policy have created fresh challenges for evaluation.
A framework for evaluating policy adjustment programs: Lessons from a cross‐country evaluation
Authors: Branson William H. , Jayarajah Carl
Published: August 2004

This chapter presents a macroeconomic framework for evaluating the effects of policy‐based adjustment programs, with an illustration from a recent World Bank evaluation.
Assessing institutional development: The legal framework that shapes public institutions
Authors: Stanton Thomas H.
Published: August 2004

Assessing the quality of public institutions requires analysis of the legal framework that influences the performance, capacity, accountability, and life cycle of government agencies and private instrumentalities.
Evaluating environmental impacts: The process of unnatural selection
Authors: Winpenny James T.
Published: August 2004

Why do so many environmental projects develop unforeseen problems? The survival of flawed projects is due to biases in their selection and appraisal, compounded by weaknesses in evaluation methods and inadequate organizational learning processes.
Measuring the performance of agricultural and rural development programs
Authors: Kumar Krishna
Published: August 2004

This chapter critically examines the appropriateness of a comprehensive performance measurement system, based on standard performance indicators, to agricultural and rural development programs in poor countries.
Evaluating gender impacts
Authors: Moser Caroline O. N.
Published: August 2004

The recent shift in focus from “Women in Development” to “Gender and Development” has resulted in changes in the evaluation practices of development agencies. Although most of the indicators used to assess the gender impact of programs and projects still measure implementation progress rather than outcomes, a rich arsenal of techniques is available to enhance the impact of evaluation on the gender dimension of development.
Including culture in evaluation research
Authors: Klitgaard Robert
Published: August 2004

Sociocultural settings are missing variables in most evaluations of development projects and policies. An impending renaissance in applied sociocultural studies will enhance evaluation research and improve prospects for sustainable development impacts.
The listening dimension of evaluation
Authors: Salmen Lawrence F.
Published: August 2004

Listening is essential to understanding, and understanding is the basis of competent evaluation. Systematic client consultation is on the way to becoming a primary ingredient of project identification and design. Systematic listening provides feedback needed for accurate and relevant evaluation.
Evaluating public services: A case study on Bangalore, India
Authors: Paul Samuel
Published: August 2004

A survey of citizens of Bangalore asked what they thought of the public utilities and related agencies that delivered the city's essential services. The survey findings shed light on the state of the public services in Bangalore and show how “voice” mechanisms can be used to demand better service and greater accountability from public service suppliers.
Postscript: Development questions and evaluation answers
Authors: Rist Ray C.
Published: August 2004

Based on the prior chapters, this postscript pulls together a framework for improving the interface between evaluation and development.
An empirical examination of the pricing of exchange‐traded barrier options
Authors: Easton Steve , Gerlach Richard , Graham Melissa , Tuyl Frank
Published: August 2004

Actively traded barrier options were introduced on the Australian Stock Exchange in 1998. This market provides a unique laboratory in which to empirically examine their pricing. This is particularly so given that, for a number of these options, otherwise identical standard European options were simultaneously traded. As a result, the pricing of barrier options may be compared both with their theoretical valuations and with the pricing of otherwise identical European options. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:1049–1064, 2004
Weather derivatives valuation and market price of weather risk
Authors: Cao Melanie , Wei Jason
Published: August 2004

This paper has two objectives: (1) to propose and implement a valuation framework for temperature derivatives (a specific class of weather derivatives); and (2) to study the significance of the market price of weather risk. The objectives are accomplished by generalizing the Lucas model of 1978 to include the weather as another fundamental source of uncertainty in the economy. Daily temperature is modeled by incorporating such key properties as seasonal cycles and uneven variations throughout the year. The temperature variable is related to the aggregate dividend or output through both contemporaneous and lagged correlations, as corroborated by the data. Numerical analysis shows that the market price of weather risk is significant for temperature derivatives. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:1065–1089, 2004
Hedging long‐term commodity risk: A comment
Authors: Lien Donald , Wang Yan
Published: August 2004

Y. V. Veld‐Merkoulova and F. A. de Roon (2003) adopted an encompassing model to demonstrate their linear yield assumption on the term structure of futures prices gains more empirical support than the linear price assumption proposed by A. Neuberger (1999). This comment points out the test procedure adopted is inappropriate and proposes an alternative non‐nested hypothesis testing method. Using the crude oil data, we find that the linear price assumption outperforms the linear yield assumption but is inferior to a generalized version of the linear yield assumption. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:1093–1099, 2004
Comparing alternative assumptions on the term structure of futures prices: Reply
Authors: De Roon Frans A. , Veld‐Merkoulova Yulia V.
Published: August 2004

Donald Lien and Yan Wang (this issue) suggest an alternative test for different specifications of the term structure of futures prices, as used in our recently published paper in The Journal of Futures Markets. Our paper (Y. V. Veld‐Merkoulova and F. A. de Roon, 2003) focuses on developing optimal hedging strategies in case sufficiently long‐term futures contracts are not available (or not actively traded) on the exchange. One of the preliminary steps underlying this strategy was to compare linear and log‐linear term structures of futures prices in order to choose an appropriate specification. Although this is not the main issue of our paper, it is certainly important to use the correct econometric procedure in testing alternative model specifications. The results found by Lien and Wang do not contradict our conclusion that a linear term structure of futures yields is superior to a linear term structure of futures prices. However, as we point out here, the tests suggested by Lien and Wang are not without flaws. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:1101–1104, 2004