bluuebunny/crossref_metadata_2025 huggingface dataset:
Kullback–Leibler divergence for evaluating bioequivalence
Authors: Dragalin Vladimir , Fedorov Valerii , Patterson Scott , Jones Byron
Published: March 2003

In this paper we propose a methodology for evaluating the bioequivalence of two formulations of a drug that encompasses not only average bioequivalence (ABE), but also the more recently introduced measures of population bioequivalence (PBE) and individual bioequivalence (IBE). The latter two measures are concerned with prescribability (PBE) and switchability (IBE). The main idea is to use the Kullback–Leibler divergence (KLD) as a measure of discrepancy between the distributions of the two formulations. Two formulations are declared bioequivalent if the upper bound of a level‐αconfidence interval for the KLD is less than a given goalpost to be set by a regulator. This new methodology overcomes many of the disadvantages of the corresponding measures recommended by the FDA. In particular the KLD: (i) possesses the natural hierarchical property that IBE⟹PBE⟹ABE; (ii) satisfies the properties of a true distance metric; (iii) is invariant to monotonic transformations of the data; (iv) generalizes easily to the multivariate case where equivalence on more than one parameter (for example, AUC, Cmax and Tmax) is required; and (v) is applicable over a wide range of distributions of the response variable (for example, those in the exponential family). The performance of the KLD relative to the metric proposed in guidance by the FDA for the evaluation of individual bioequivalence is evaluated using a simulation study. Previously published retrospective analyses using the FDA‐proposed metric are contrasted with those based on the KLD. It is concluded that the KLD is a viable alternative to the FDA‐proposed metric and that its mathematical and statistical properties make it a readily interpretable measure of the differences between formulations. Copyright © 2003 John Wiley & Sons, Ltd.
Assessing individual bioequivalence using the structural equation model
Authors: Carrasco Josep‐Lluís , Jover Lluís
Published: March 2003

The structural equation model (SEM) is introduced as a useful approach for assessing individual bio‐equivalence. SEM parameters are estimated using a partial likelihood analysis and the hypotheses of individual bioequivalence is evaluated in a disaggregate way, testing separately the hypothesis concerning SEM parameters, and assessing the overall hypothesis of individual bioequivalence using the intersection‐union principle. Limits of bioequivalence for SEM parameters are proposed and a power analysis is carried out. Copyright © 2003 John Wiley & Sons, Ltd.
Paradigmatic metamorphosis and organizational development
Authors: Yolles Maurice , Guo Kaijun
Published: March 2003

Paradigms metamorphose when they develop a new frame of reference. Two examples of paradigmatic metamorphosis are examined that together can be argued to formulate an evolutionary approach to managerial cybernetics. Organization Development (OD) is a well‐established soft methodology used extensively to engineer cultural change in organizations. OD can be set within Viable Systems Theory (VST), itself a conceptual development of the managerial cybernetic theory that underlies the Viable Systems Model (VSM). To illustrate this, a frame of reference is created that looks at systemic transformational processes. VST can operate as a general framework for this within which OD, VSM, and indeed the principles of Habermas's theory of communicative action can be embedded. A result of this exploration is to show how a managerial cybernetic form of OD can be developed to improve the way organizations can be diagnosed in complex change situations that must be managed. Copyright © 2003 John Wiley & Sons, Ltd.
Systems thinking and the disclosure of a technological society: some philosophical reflections
Authors: Strijbos Sytse
Published: March 2003

This paper resulted from an interdisciplinary research project named ‘Disclosive Systems Thinking’ that aimed at stimulating cooperation and exchange between research in systems methodology on the one hand and philosophy, particularly philosophy of technology, on the other. Against the background of the history of the philosophy of technology, a proposal is made for an ‘integrative’ approach to technology. Two ideas are introduced that are fundamental to an integrative philosophy of technology. First, emphasis is laid on the systems dimensions of modern technology. Sociotechnical systems are identified as the environment of our lives in a modern ‘technological’ society. Second, the idea of the ‘disclosure’ of a technological society is advanced as implying a process of structuring and restructuring the variety of systems in our technological society in a way that contributes to the opening up of human life. Finally, ‘disclosive systems thinking’ is proposed as a practice‐oriented systems methodology that differs fundamentally both from ‘hard’ and ‘soft’ systems thinking in its view on normativity and human values. Copyright © 2003 John Wiley & Sons, Ltd.
Mexico
Authors: Hise Richard T. , Solano‐Méndez Roberto , Gresham Larry G.
Published: March 2003

Not understanding the cultural aspects of doing business overseas can jeopardize the success of international
negotiations, entry strategies, joint ventures, technology transfer, marketing, and human resources. This
article reports a study of the perceptions of U.S. and Mexican executives concerning the importance of 15
cultural dimensions of doing business in Mexico (our second largest trading partner). It found that,
whereas Mexican executives believed more strongly than U.S. executives that the cultural dimensions of doing
business in Mexico were more important than the product or service offered and the accompanying terms of sale,
the U.S. executives, surprisingly, assigned higher levels of importance to the 15 cultural variables. Both
Mexican and U.S. executives strongly agreed on which of the 15 variables were most important. All eight
subgroups of U.S. executives assigned higher levels of importance to the 15 cultural aspects of doing business
in Mexico than did their Mexican counterparts. When four comparisons of the executives of the eight subsets of
U.S. companies‐large vs. small, border location vs. nonborder location, doing business in Mexico vs. not
doing business there, and doing business there more than 5 years (pre‐NAFTA) vs. doing business
there 5 years or less (post‐NAFTA)—were made of the level of importance they attached to
the cultural variables, no significant differences were found. Based on the study's findings, implications
for doing business in Mexico are indicated. © 2003 Wiley Periodicals, Inc.
FDI in CEECs: How do Western investors survive?
Authors: Fabry Nathalie H. , Zeghni Sylvain H.
Published: March 2003

This article emphasizes that knowledge transfer across a firm's boundaries, in a transition context,
implies a specific involvement of Western investors. They need to promote specific relationships within
affiliates. This article emphasizes two points. First, partners have few common practices and do not share the
same perception of the firm. This is the problem with building new capabilities. Second, Western firms have to
mobilize organizational resources to build efficient affiliates (new human resources management,
introduction of new functions, management by expatriates). Setting up new management rules to run an
affiliate in transition countries is costly and often underestimated by foreign investors. © 2003 Wiley
Periodicals, Inc.
Making international marketing decisions under WTO rules
Authors: Denis Jean‐Emile
Published: March 2003

With the conclusion of the Uruguay Round and the establishment of the World Trade Organization
(WTO) in April 1994, a comprehensive set of rules emerged that affect in a pervasive manner the
activities of firms on foreign markets. This body of rules is overwhelmingly presented in the literature from a
trade policy or legal viewpoint. The result is that, for many marketers, WTO rules are somewhat confusing, and
their impact on international business operation is difficult to assess. This paper is purely analytical and
does not aim to provide any contribution to international marketing theory. Its purpose is to identify which
rules, among the many the WTO system encompasses, are of direct concern to firms. It aims to expose in a
straightforward manner how they may be coped with or taken advantage of by international marketers. It focuses
on WTO measures, which deal with so‐called international marketing mix decisions, namely decisions
pertaining to (1) entry and international distribution, (2) product and service,
(3) pricing, and (4) international communication. Commitments made during the WTO Fourth
Ministerial Conference in Doha (November 9–14, 2001) that are relevant to issues raised in this
paper are accounted for. © 2003 Wiley Periodicals, Inc.
Doing business in China: Culture and practice
Authors: Stoltenberg Clyde D.
Published: March 2003

Ming‐Jer Chen. 2001. Inside Chinese Business: A Guide for Managers Worldwide. Boston:
Harvard Business School Press. 234 pages.

John B. Stuttard. 2000. The New Silk Road: Secrets of Business Success in China Today. New
York: John Wiley & Sons. 144 pages.

Yadong Luo. 2000. Strategy, Structure, and Performance of MNCs in China. Westport, CT:
Quorum Books. 302 pages.

Maria Lai‐Ling Lam. 2000. Working With Chinese Expatriates in Business Negotiations:
Portraits, Issues, and Applications. Westport, CT: Quorum Books. 188 pages.
Genotoxicity of water extracts from the River Yamuna at Mathura, India
Authors: Aleem Asma , Malik Abdul
Published: March 2003

Water samples were collected from the River Yamuna at Mathura, India, and concentrated by using XAD resins (Amberlite XAD‐4 and XAD‐8) and liquid–liquid extraction procedures. The genotoxicities of the extracted water samples were evaluated by the Ames Salmonella/mammalian microsome test, DNA repair of defective mutants, and bacteriophage λ systems. The results of the Salmonella test demonstrated that the XAD‐concentrated water samples had maximum mutagenicity with the TA98 strain, both with and without metabolic activation. The XAD‐concentrated water samples collected in the summer showed maximum mutagenic responses compared with those collected in other seasons, whereas the liquid–liquid extracted samples exhibited maximum mutagenic activity during the postmonsoon season. The damage brought about during DNA repair of defective mutants in the presence of XAD‐concentrated water samples was found to be remarkably high compared with the liquid–liquid extracted water samples at a dose level of 20 μL/mL of culture. All the mutants invariably exhibited significant decline in their colony‐forming units compared with their isogenic wild‐type counterparts. Survival was decreased by 86.7% and 65.1% in the polA− strain after 6 h of treatment with XAD‐concentrated and liquid–liquid extracted water samples, respectively. A significant decrease in the survival of bacteriophage λ was also observed when treated with test samples. The damage was more pronounced in lexA mutants when the phage was treated with XAD‐concentrated samples. The recA, lexA, and polA mutants of E. coli K‐12 were found to be sensitive to the test samples, suggesting damage to the DNA of exposed cells as well as to the role of recA+, lexA+, and polA+ genes in coping with the hazardous effect of the pollutants. The results demonstrated substantial genotoxicity and mutagenicity in the water samples tested. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 69–77, 2003.
Inhibition of CYP 1A2–dependent MROD activity in rat liver microsomes: An explanation of the hepatic sequestration of a limited subset of halogenated aromatic hydrocarbons
Authors: Chen Jin Jun , Chen Guo Sheng , Bunce Nigel J.
Published: March 2003

Many classes of halogenated aromatic compounds (HACs) are highly lipophilic environmental contaminants that exert toxic effects via the Ah receptor signal transduction pathway and whose metabolism generally involves monooxygenase enzymes of the CYP 1A family. Despite their lipophilicity, a high proportion of the body burden of certain polychlorinated dibenzo‐p‐dioxins and coplanar polychlorinated biphenyls is sequestered in liver, a process believed to involve CYP 1A2. In this work we examined HAC‐induced inhibition of the demethylation of 7‐methoxyresorufin, a process that is selectively catalyzed by CYP 1A2. 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin, 3,3′,4,4′‐tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126) were found to be strong competitive inhibitors of methoxyresorufin‐O‐demethylase activity, consistent with the high ability of hepatic tissue to sequester these compounds selectively. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 115–119, 2003
An investigation of the role of vitamin E in the protection of mice against microcystin toxicity
Authors: Gehringer Michelle M. , Govender Sharlene , Shah Mrinal , Downing Timothy G.
Published: March 2003

The presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin‐LR (MC‐LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue‐green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane‐active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC‐LR extract (70% LD50) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S‐transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC‐LR extract and limited both the toxin‐induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC‐LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC‐LR. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 142–148, 2003.
Estimation of microcystins in the freshwater fish Oreochromis niloticus in an Egyptian fish farm containing a Microcystis bloom
Authors: Mohamed Zakaria A. , Carmichael Wayne W. , Hussein Ahmed A.
Published: March 2003

Microcystins (MCYSTs) that accumulated in different organs of the freshwater fish Oreochromis niloticus, collected from a fish farm in Egypt containing heavy blooms of Microcystis aeruginosa, were investigated using an enzyme‐linked immunosorbent assay (ELISA). The distribution of MCYSTs in the organs varied significantly. The highest MCYST level was recorded in the guts (821 ng/g fresh weight), followed by the livers (531.8 ng/g) and kidneys (400 ng/g). Smaller amounts of MCYST were detected in muscles (102 ng/g). The present study suggests that fish farms should be monitored for the presence of toxic cyanobacterial blooms to minimize the exposure of fish to potent hepatotoxins. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 137–141, 2003
The addition of activin A and inhibin A measurement to uterine artery Doppler velocimetry to improve the early prediction of pre‐eclampsia
Authors: Florio P. , Reis F. M. , Pezzani I. , Luisi S. , Severi F. M. , Petraglia F.
Published: March 2003

Objective

To evaluate whether the measurement of maternal serum activin A and inhibin A adds any clinically relevant information for the prediction of pre‐eclampsia in women with altered uterine artery Doppler velocimetry at 24 weeks of gestation.

Methods

This was a prospective, controlled, hospital‐based study involving 58 asymptomatic pregnant women at 24 weeks' gestation in whom a diastolic notch of the uterine artery waveform was noted at routine Doppler examination. Doppler assessment of the uterine artery waveform and measurement of maternal activin A and inhibin A serum levels by specific two‐site enzyme immunoassays were performed. The cut‐off points for defining ‘high’ serum activin A and inhibin A levels for prediction of pre‐eclampsia were chosen by receiver–operating characteristics (ROC) curve analysis. The probability of developing pre‐eclampsia was calculated for several combinations of results of hormone testing.

Results

Activin A and inhibin A levels were higher in patients who developed pre‐eclampsia (n = 18; mean ± standarderror: 2.69 ± 0.35 ng/mL and 131.2 ± 22.7 pg/mL, respectively) than in those who did not present with pre‐eclampsia at follow‐up (n = 40; activin A: 1.79 ± 0.18 ng/mL and inhibin A: 91.9 ± 6.2 pg/mL; P < 0.05). Activin A at the cut‐off value of 1.7 multiples of the median (MoM) achieved a sensitivity of 61% and a specificity of 89%, whereas inhibin A at the cut‐off value of 1.8 MoM combined a sensitivity of 39% with a specificity of 92% for prediction of pre‐eclampsia. The probability of pre‐eclampsia was 31% in the whole study population, 86% if both activin A and inhibin A were elevated and 17% if both hormone markers were unaltered.

Conclusion

The measurement of serum activin A and inhibin A levels may add significant prognostic information for predicting pre‐eclampsia in pregnant women showing specific Doppler alterations in the late second trimester. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Comparison of color Doppler uterine artery indices in a population at high risk for adverse outcome at 24 weeks' gestation
Authors: Albaiges G. , Missfelder‐Lobos H. , Parra M. , Lees C. , Cooper D. , Nicolaides K. H.
Published: March 2003

Objective

To compare uterine artery Doppler velocity and impedance indices in the presence and absence of uterine artery waveform notches, in the prediction of adverse pregnancy outcome in high‐risk women.

Methods

One hundred and fifty‐seven women identified at Doppler screening as being at ‘high risk’ underwent a further uterine artery Doppler assessment at 24 weeks' gestation. Pulsatility and resistance indices and minimum, time averaged and time averaged maximum velocities were measured, and the presence of bilateral notches noted. Adverse outcomes were pre‐eclampsia, birth weight less than the tenth centile, placental abruption and intrauterine death. The best cut‐off for each parameter was assessed by univariate logistic regression, and the comparative performance of the screening parameters was assessed using kappa values.

Results

The best performing index in the presence of bilateral notches was mean resistance index, for a cut‐off of 0.67, giving a kappa value of 0.65. Mean pulsatility index and lowest pulsatility index performed similarly well, both with kappa values of 0.58. All velocity indices apart from lowest minimum velocity had kappa values of < 0.4. When indices were analyzed, irrespective of notch status, mean resistance and mean pulsatility indices performed similarly, with kappa values of 0.49 and 0.46, respectively; mean minimum velocity had a kappa value of 0.4.

Conclusions

In a high‐risk population, uterine artery Doppler mean resistance indices perform better than do velocity indices in the prediction of adverse pregnancy outcome, irrespective of notch status. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal ultrasound diagnosis of Nager syndrome
Authors: Paladini D. , Tartaglione A. , Lamberti A. , Lapadula C. , Martinelli P.
Published: March 2003

Nager syndrome, or acrofacial dysostosis, is a rare malformation complex characterized by facial anomalies (external ear abnormalities and micrognathia) and limb defects (radial hypoplasia and absence of the thumb and/or other digits). Since its first description in 1948, more than 80 cases have been reported in the pediatric literature. However, there is only one previous report on the prenatal recognition of the syndrome, which was at 30 weeks of gestation. We report here a further case of Nager syndrome, prospectively diagnosed at 23 weeks of gestation. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Three‐dimensional multiplanar time‐motion ultrasound or anatomical M‐mode of the fetal heart: a new technique in fetal echocardiography
Authors: Jürgens J. , Chaoui R.
Published: March 2003

Objective

To assess the application of a three‐dimensional multiplanar rendering technique for examination of the fetal heart.

Material and Methods

Free‐hand acquisition of a three‐dimensional volume was performed without moving or tilting the transducer. While the anatomical plane shows the four cardiac chambers, the two other orthogonal planes show vertical and horizontal time‐axis planes as M‐mode traces. Because off‐line plane positioning is possible on three‐dimensional multiplanar reconstruction, M‐mode traces can be obtained from different stored cardiac structures independently of the fetal position. Fifty‐two women with normal singleton pregnancies at 22–40 weeks underwent transabdominal ultrasound examination and five women with singleton fetuses between 13 and 15 weeks were assessed transvaginally. Clinical application of the echocardiographic technique was tested in a further two fetuses with arrhythmia.

Results

Off‐line M‐mode traces from atrioventricular valve excursions and myocardial contractions were possible in 45/52 (86.5%) cases examined at 22–40 weeks. Among the 32 fetuses in which visualization of the outflow tracts was attempted, M‐mode traces of the aortic and pulmonary valves were possible in 22 (68.7%) and 20 (62.5%) cases, respectively. In three of five cases examined transvaginally, M‐mode traces could be registered. Both cases with supraventricular extrasystoles (26 and 31 weeks) were easily diagnosed using this technique.

Conclusion

The new technique presented here enables the easy acquisition of optimal M‐mode traces from different fetal heart structures. Based on our promising findings we would recommend that, in the future, three‐dimensional multiplanar imaging should not be limited to automatic volume acquisition but should include the free‐hand technique. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Adaptive space decomposition for fast visualization of soft objects
Authors: Min KyungHa , Lee In‐Kwon , Park Chan‐Mo
Published: March 2003

We present a fast visualization scheme of soft objects by introducing an efficient evaluation method for a field function. The evaluation of a field function includes distance computation between a point in space and the defining primitives of the soft object. If the unnecessary distance computations between a point in space and the components that do not influence the point can be avoided, the evaluation can be accelerated. For this purpose, we decompose the space into adaptive‐sized cells according to the bounding volume of the components and build a data structure called an interval tree through which the influencing components for a point are sought. The bounding volume of a component is generated by considering the radius of a component and k‐DOPs. The proposed scheme can be used in many applications for soft objects such as modeling and rendering, especially in the interactive modeling process. Copyright © 2003 John Wiley & Sons, Ltd.
Reliability‐based Design Methods to Determine the Extreme Response Distribution of Offshore Wind Turbines
Authors: Cheng P. W. , van Bussel G. J. W. , van Kuik G. A. M. , Vugts J. H.
Published: March 2003

In this article a reliability‐based approach to determine the extreme response distribution of offshore wind turbines is presented. Based on hindcast data, the statistical description of the offshore environment is formulated. The contour lines of different return periods can be determined. Simulations are carried out for a prototype design of a 3 MW offshore wind turbine. Statistical methods are applied to determine the distribution of the extreme responses. Three approaches are used here. In the MAX approach, only the maximum of each simulation is taken into account. The POT (peak over threshold) approach takes also local maxima into consideration. The process model uses the statistical properties of the process to predict the extremes. All three methods show similar results, but POT and the process model require fewer simulations. Comparison is made for the 100 year response between these reliability‐based models and a deterministic model. For this specific turbine the deterministic model underestimates the maximum flap moment but overestimates the maximum overturning moment of the support structure compared with the estimates of the reliability‐based methods. The application of the reliability‐based model can be extended to include other extreme load situations and achieve a more efficient structural design. Copyright © 2003 John Wiley & Sons, Ltd.
Estimating Wind Energy Potential Offshore in Mediterranean Areas
Authors: Lavagnini Alfredo , Sempreviva Anna M. , Barthelmie Rebecca J.
Published: March 2003

Relatively few studies have been performed on the evaluation of offshore wind resources, and these have been conducted mostly in Northern Europe. In Mediterranean areas the lack of such studies is mainly linked to (1) the difficulty of meteorological monitoring in deeper waters, (2) the complex orography, frequently extending down to the coasts, (3) the sea breeze wind regimes and (4) local winds such as the Bora, Mistral and Sciroc. In the North Adriatic Sea, a shallow basin of the Mediterranean, the first reason is not applicable, but the others are sufficient to make the evaluation of wind speed methods challenging. In this article we estimate the wind climatology at a platform located 15 km offshore of Venice based on 7 years of data and compare it with the wind climatology obtained by five different methods using the long‐term data from four coastal meteorological stations, Venezia Tessera, Venezia San Nicolò, Ronchi and Rimini. We discuss the applicability of these methods and find that the WAsP® model of Risø National Laboratory is still the best tool for wind climate estimates. The results of two new methods are promising, but the methods still require some development. Copyright © 2003 John Wiley & Sons, Ltd.
On the Modelling of a Floating Offshore Wind Turbine
Authors: Henderson Andrew R. , Patel Minoo H.
Published: March 2003

The location of wind turbines on floating structures offshore would allow an immense resource to be tapped without the drawbacks large developments can have on public opinion. There are, however, potentially significant technical and cost drawbacks. This article describes the theory and results of research work aimed at developing analytical tools for evaluating the performance of floating offshore wind farms. The principal problem addressed here is the development of analytical tools for modelling the turbine loads and fatigue damage due to the vessel motion. The effect that the motion would have on the wind turbine is found by calculating the aerodynamic and inertial loads on the blades in a two‐dimensional state domain representing the blade and the vessel motion respectively. Using a double Fourier transform, discrete deterministic frequency spectra of the loads are found and the fatigue damage is evaluated. Undertaking the calculations for vessel motion in each degree of freedom allows appropriate weightings to be developed, which can be used for the optimization of candidate supporting vessels by evaluating the motion response directly. Copyright © 2003 John Wiley & Sons, Ltd.
Die Kristallstruktur von wasserfreiem Melaminiumchlorid
Authors: Jing Haipeng , Ströbele Markus , Weisser Martina , Meyer H.‐Jürgen
Published: March 2003

Crystal Structure of non‐aqueous Melaminium Chloride

Melaminium chloride was obtained as colorless, needle‐shaped, single crystalline material from solid state reactions between melamin and ammonium chloride. The structure of [C3N6H7]Cl was refined by single crystal X‐ray diffraction: I2/m, Z = 8, a = 852.87(4), b = 1704.4(1) c = 918.44(4) pm and β = 92.165(6)°. The crystal structure contains melaminium ions stacked to columns along [100] and linked via N‐H···N bridges to form bands along [001]. Both of the two distinct chloride ions are stabilized by six hydrogen bonds through distorted trigonal prismatic arrangements of hydrogen atoms to yield a supramolecular structure.
The Crystal Structure of ζ2‐Al3Cu4‐δ
Authors: Gulay L. D. , Harbrecht Bernd
Published: March 2003

The crystal structure of the ζ2‐phase Al3Cu4‐δ was determined by means of X‐ray powder diffraction: a = 409.72(1) pm, b = 703.13(2) pm, c = 997.93(3) pm, space group Imm2, Pearson symbol oI24‐3.5, RI = 0.0696. ζ2‐Al3Cu4‐δ forms a distinctive a × √3a × 2c superstructure of a metal deficient Ni2In‐type‐related structure. The phase is meta‐stable at ambient temperature. Between 400 °C and 450 °C it decomposes into ζ1‐Al3Cu4 and η2‐AlCu. Entropic contributions to the stability of ζ2‐Al3Cu4‐δ are reflected in three statistically or partially occupied sites.
Miscibility Gap in the System Cesium Amide/Ammonia, CsNH2/NH3 — Thermodynamic Investigations
Authors: Peters Dieter , Jacobs Herbert
Published: March 2003

The system CsNH2/NH3 is investigated between —50 °C and 120 °C: Partial pressures of ammonia, DTA and density measurements are given as a function of concentration and temperature.

Thermodynamic interpretations of the data show that the solutions deviate strongly from the behaviour of ideal mixtures. A monoammoniate of CsNH2 is stable up to 17 °C. Dilute solutions (≤ 30 mole % CsNH2) have a miscibility gap above 79 ± 5 °C with an almost colourless solution of lower density clearly separated from a yellow one.

Phase separation is discussed on the basis of hydrogen bonds between NH ions as acceptors and NH3 molecules both solvating cesium ions.
Sr3(BS3)2 und Sr3(B3S6)2: Zwei neue nicht‐oxidische Chalkogenoborate mit trigonal‐planar koordiniertem Bor
Authors: Hammerschmidt A. , Döch M. , Püttmann C. , Krebs B.
Published: March 2003

Systematische Studien zur Synthese neuer Erdalkalimetallthioborate und zum Kationeneinfluß auf die Strukturen ternärer Verbindungen dieses Typs führten zu den Strontiumthioboraten Sr3(BS3)2 und Sr3(B3S6)2. Die neuen Verbindungen wurden aus Strontiumsulfid, amorphem Bor und Schwefel in Festkörperreaktionen bei einer Temperatur von 1123 K dargestellt. Die Kristallstrukturen wurden durch Röntgenstrukturanalysen an Einkristallen bestimmt. Sr3(BS3)2 kristallisiert in der monoklinen Raumgruppe C2/c (Nr. 15) mit a = 10, 187(4) Å, b = 6, 610(2) Å, c = 15, 411(7) Å, β = 102, 24(3)° und Z = 4. Die Kristallstruktur von Sr3(B3S6)2 ist trigonal, Raumgruppe R3¯ (Nr. 148), mit a = 8, 605(1) Å, c = 21, 542(4) Å und Z = 3. Sr3(BS3)2 enthält isolierte [BS3]3—‐Anionen mit Bor in trigonal‐planarer Koordination. Die Strontiumkationen befinden sich zwischen Schichten von Orthothioborat‐Anionen. Im Sr3(B3S6)2 liegen neben Strontiumkationen [B3S6]3—‐Anionen vor.
CoSm(SeO3)2Cl, CuGd(SeO3)2Cl, MnSm(SeO3)2Cl, CuGd2(SeO3)4 und CuSm2(SeO3)4: Übergangsmetallhaltige Selenite von Samarium und Gadolinum
Authors: Wickleder Mathias S. , Hamida Makram Ben
Published: March 2003

Bei der Umsetzung von CoCl2, Sm2O3 und SeO2 in evakuierten Quarzglasampullen bilden sich blaue Einkristalle von CoSm(SeO3)2Cl (triklin, ${\rm P} \bar 1$, Z = 4, a = 712, 3(1), b = 889, 5(2), c = 1216, 2(2) pm, α = 72, 25(1)°, β = 71, 27(1)°, γ = 72, 08(1)°, Rall = 0, 0586). Beim Umsatz mit MnCl2 werden blaßrosa Einkristalle von MnSm(SeO3)2Cl erhalten (triklin, ${\rm P} \bar 1$, Z = 2, a = 700, 8(2), b = 724, 1(2), c = 803, 4(2) pm, α = 86, 90(3)°, β = 71, 57(3)°, γ = 64, 33(3)°, Rall = 0, 0875). Lindgrüne Einkristalle von CuGd(SeO3)2Cl (triklin, ${\rm P} \bar 1$, Z = 4, a = 704, 3(4), b = 909, 6(4), c = 1201, 0(7) pm, α = 70, 84(4)°, β = 73, 01(4)°, γ = 70, 69(4)°, Rall = 0, 0450) bilden sich bei der Reaktion von CuCl2 und Gd2O3 mit SeO2. In CoSm(SeO3)2Cl liegen [CoO4Cl2]‐Oktaeder vor, die über eine Kante und eine Ecke zu Ketten verknüpft sind. Auch die Mn2+‐Ionen in MnSm(SeO3)2Cl sind oktaedrisch von vier Sauerstoff‐ und zwei Chloridliganden umgeben. Die Verknüpfung der Polyeder erfolgt zu Ketten erfolgt hier jedoch ausschließlich über Kanten. Sowohl in der Cobalt‐ als auch in der Mangan‐Verbindung sind die Sm3+‐Ionen acht‐ bzw. neunfach von Sauerstoffatomen und Chloridionen umgeben. In CuGd(SeO3)2Cl sind die Cu2+‐Ionen verzerrt quadratisch‐planar von drei Sauerstoffatomen und einem Chloridion umgeben. Ein weiterer Cl—‐ bzw. Sauerstoffligand ergänzen die [CuO3Cl]‐Einheiten zu stark elongierten Oktaedern. Letztere sind wiederum über zwei Kanten zu Ketten verknüpft. Den Gd3+‐Ionen kommen die Koordinationzahlen „8 + 1”︁ bzw. neun zu. Werden die Oxide Sm2O3 bzw. Gd2O3 mit CuO und SeO2 umgesetzt, bilden sich die tiefblauen Selenite CuM2(SeO3)4 (M = Sm/Gd, monoklin, P21/c, Z = 2, a = 1050, 4(3)/1051, 0(2), b = 696, 6(2)/693, 5(1), c = 822, 5(2)/818, 5(2) pm, β = 110, 48(2)°/110, 53(2)°, Rall = 0, 0341/0, 0531). Beide enthalten isolierte quadratisch‐planare [CuO4]‐Gruppen und unregelmäßige [MO9]‐Polyeder.
(CuBr)3P4Se4: A Low Symmetric Variant of the (CuI)3P4Se4 Structure Type
Authors: Reiser Sara , Nilges Tom , Pfitzner Arno
Published: March 2003

Bright orange (CuBr)3P4Se4 is obtained from the reaction of CuBr, P, and Se in stoichiometric amounts (CuBr : P : Se = 3 : 4 : 4). The composition and the crystal structure of the compound were determined from single crystal X‐ray diffraction data. Lattice constants are a = 33.627(2) Å, b = 6.402(1) Å, c = 19.059(1) Å, β = 90.19(3) °, V = 4103.2(3) Å3, and Z = 12. The compound crystallizes in a structure that is related to (CuI)3P4Se4. Cages of β‐P4Se4 are stacked along the b‐axis and are separated by columns of copper(I) bromide. However, the coordination of the β‐P4Se4 cage molecules to the copper atoms in the CuBr columns in (CuBr)3P4Se4 is quite different from (CuI)3P4Se4. The monoclinic compound (space group: P21, no. 4) has an almost orthorhombic metric in combination with a threefold superstructure in [100]. Structural aspects of (CuBr)3P4Se4 are discussed with respect to the heavier homologue (CuI)3P4Se4.
Palynological Features as a Systematic Marker in Artemisia L. and Related Genera (Asteraceae, Anthemideae) ‐ II: Implications for Subtribe Artemisiinae Delimitation
Authors: Martín J. , Torrell M. , Korobkov A. A. , Vallès J.
Published: March 2003

Abstract: Using optical and scanning electron microscopy, we completed a palynological study of the subtribe Artemisiinae (Asteraceae, Anthemideae), which we started in a previous paper. This subtribe contains different genera with a systematic position that, in many cases, has been controversial. There is a group of genera closely related to Artemisia, and another one more related to Chrysanthemum sensu lato. We confirm the existence of two pollen morphological patterns ‐ concerning exine ornamentation ‐ in the tribe Anthemideae and in the subtribe Artemisiinae as currently considered: one with long spines (Anthemis type) and the other with short spinules (Artemisia type). This feature is a good taxonomic marker, well correlated with other morphological and with molecular characters. This enables a new delimitation of the subtribe Artemisiinae, which is characterized by pollen grain ornamentation constituted by short spinules (microechinate pollen), and should be restricted to Artemisia and the closely related genera that share this trait.
Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse
Authors: Wiltshire Tim , Pletcher Mathew T. , Batalov Serge , Barnes S. Whitney , Tarantino Lisa M. , Cooke Michael P. , Wu Hua , Smylie Kevin , Santrosyan Andrey , Copeland Neal G. , Jenkins Nancy A. , Kalush Francis , Mural Richard J. , Glynne Richard J. , Kay Steve A. , Adams Mark D. , Fletcher Colin F.
Published: March 2003

The nature and organization of polymorphisms, or differences, between genomes of individuals are of great interest, because these variations can be associated with or even underlie phenotypic traits, including disease susceptibility. To gain insight into the genetic and evolutionary factors influencing such biological variation, we have examined the arrangement (haplotype) of single-nucleotide polymorphisms across the genomes of eight inbred strains of mice. These analyses define blocks of high or low diversity, often extending across tens of megabases that are delineated by abrupt transitions. These observations provide a striking contrast to the haplotype structure of the human genome.
Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors
Authors: Maretto Silvia , Cordenonsi Michelangelo , Dupont Sirio , Braghetta Paola , Broccoli Vania , Hassan A. Bassim , Volpin Dino , Bressan Giorgio M. , Piccolo Stefano
Published: March 2003

Wnt/β-catenin signaling plays key roles in several developmental and pathological processes. Domains of Wnt expression have been extensively investigated in the mouse, but the tissues receiving the signal remain largely unidentified. To define which cells respond to activated β-catenin during mammalian development, we generated the β-catenin-activated transgene driving expression of nuclear β-galactosidase reporter (BAT-gal) transgenic mice, expressing the
lacZ
gene under the control of β-catenin/T cell factor responsive elements. Reporter gene activity is found in known organizing centers, such as the midhindbrain border and the limb apical ectodermal ridge. Moreover, BAT-gal expression identifies novel sites of Wnt signaling, like notochord, endothelia, and areas of the adult brain, revealing an unsuspected dynamic pattern of β-catenin transcriptional activity. Expression of the transgene was analyzed in mutant backgrounds. In lipoprotein receptor-related protein 6-null homozygous mice, which lack a Wnt coreceptor, BAT-gal staining is absent in mutant tissues, indicating that BAT-gal mice are bona fide
in vivo
indicators of Wnt/β-catenin signaling. Analyses of BAT-gal expression in the adenomatous polyposis coli (multiple intestinal neoplasia/+) background revealed βcatenin transcriptional activity in intestinal adenomas but surprisingly not in normal crypt cells. In summary, BAT-gal mice unveil the entire complexity of Wnt/β-catenin signaling in mammals and have broad application potentials for the identification of Wnt-responsive cell populations in development and disease.
Structural basis for recognition by an
in vitro
evolved affibody
Authors: Högbom Martin , Eklund Malin , Nygren Per-Åke , Nordlund Pär
Published: March 2003

The broad binding repertoire of antibodies has permitted their use in a wide range of applications. However, some uses of antibodies are precluded due to limitations in the efficiency of antibody generation.
In vitro
evolved binding proteins, selected from combinatorial libraries generated around various alternative structural scaffolds, are promising alternatives to antibodies. We have solved the crystal structure of a complex of an all α-helical
in vitro
selected binding protein (affibody) bound to protein Z, an IgG Fc-binding domain derived from staphylococcal protein A. The structure of the complex reveals an extended and complementary binding surface with similar properties to protein–antibody interactions. The surface region of protein Z recognized by the affibody is strikingly similar to the one used for IgG
1
Fc binding, suggesting that this surface contains potential hot-spots for binding. The implications of the selected affibody binding-mode for its application as a universal binding protein are discussed.
The spatial targeting and nuclear matrix binding domains of SRm160
Authors: Wagner Stefan , Chiosea Simion , Nickerson Jeffrey A.
Published: March 2003

The Ser-Arg (SR)-related protein SRm160 is a coactivator of pre-mRNA splicing. It bridges splicing factors located at the 5′ splice site, branch site, and 3′ splice site. Recently, SRm160 has also been shown to be involved in mRNA export as part of an exon-junction complex. SRm160 is highly concentrated in splicing speckles but is also present in long branched intranuclear tracks connecting splicing speckles with sites at the nuclear lamina. In this study we identified domains of SRm160 important for spatial targeting within the nucleus and for binding to the nuclear matrix. Using a series of FLAG- and enhanced GFP-conjugated deletion mutants we found two contiguous sequences that independently target SRm160 to nuclear matrix sites at splicing speckled domains: amino acids 300–350 and 351–688. Constructs containing amino acids 300–350 were also targeted to sites peripheral to speckled domains where most mRNA originate subsequent to splicing. Sequences from the N-terminal domain localized proteins to the nuclear lamina near sites where mRNA leaves the nucleus.
Generalized singular value decomposition for comparative analysis of genome-scale expression data sets of two different organisms
Authors: Alter Orly , Brown Patrick O. , Botstein David
Published: March 2003

We describe a comparative mathematical framework for two genome-scale expression data sets. This framework formulates expression as superposition of the effects of regulatory programs, biological processes, and experimental artifacts common to both data sets, as well as those that are exclusive to one data set or the other, by using generalized singular value decomposition. This framework enables comparative reconstruction and classification of the genes and arrays of both data sets. We illustrate this framework with a comparison of yeast and human cell-cycle expression data sets.
Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells
Authors: Qi Huilin , Aguiar Dean J. , Williams Shelly M. , La Pean Alison , Pan Wei , Verfaillie Catherine M.
Published: March 2003

Single human bone marrow-derived mesodermal progenitor cells (MPCs) differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and endothelial cells. To identify genes involved in the commitment of MPCs to osteoblasts we examined the expressed gene profile of undifferentiated MPCs and MPCs induced to the osteoblast lineage for 1–7 days by cDNA microarray analysis. As expected, growth factor, hormone, and signaling pathway genes known to be involved in osteogenesis were activated during differentiation. In addition, 41 transcription factors (TFs) were differentially expressed over time, including TFs with known roles in osteoblast differentiation and TFs not known to be involved in osteoblast differentiation. As the latter group of TFs coclustered with osteogenesis-specific TFs, they may play a role in osteoblast differentiation. When we compared the gene expression profile of MPCs induced to differentiate to chondroblasts and osteoblasts, significant differences in the nature and/or timing of gene activation were seen. These studies indicate that
in vitro
differentiation cultures in which MPCs are induced to one of multiple cell fates should be very useful for defining signals important for lineage-specific differentiation.
Human specific loss of olfactory receptor genes
Authors: Gilad Yoav , Man Orna , Pääbo Svante , Lancet Doron
Published: March 2003

Olfactory receptor (OR) genes constitute the basis for the sense of smell and are encoded by the largest mammalian gene superfamily of >1,000 genes. In humans, >60% of these are pseudogenes. In contrast, the mouse OR repertoire, although of roughly equal size, contains only ≈20% pseudogenes. We asked whether the high fraction of nonfunctional OR genes is specific to humans or is a common feature of all primates. To this end, we have compared the sequences of 50 human OR coding regions, regardless of their functional annotations, to those of their putative orthologs in chimpanzees, gorillas, orangutans, and rhesus macaques. We found that humans have accumulated mutations that disrupt OR coding regions roughly 4-fold faster than any other species sampled. As a consequence, the fraction of OR pseudogenes in humans is almost twice as high as in the non-human primates, suggesting a human-specific process of OR gene disruption, likely due to a reduced chemosensory dependence relative to apes.
Computational and experimental analysis of DNA shuffling
Authors: Maheshri Narendra , Schaffer David V.
Published: March 2003

We describe a computational model of DNA shuffling based on the thermodynamics and kinetics of this process. The model independently tracks a representative ensemble of DNA molecules and records their states at every stage of a shuffling reaction. These data can subsequently be analyzed to yield information on any relevant metric, including reassembly efficiency, crossover number, type and distribution, and DNA sequence length distributions. The predictive ability of the model was validated by comparison to three independent sets of experimental data, and analysis of the simulation results led to several unique insights into the DNA shuffling process. We examine a tradeoff between crossover frequency and reassembly efficiency and illustrate the effects of experimental parameters on this relationship. Furthermore, we discuss conditions that promote the formation of useless “junk” DNA sequences or multimeric sequences containing multiple copies of the reassembled product. This model will therefore aid in the design of optimal shuffling reaction conditions.
The evolution of altruistic punishment
Authors: Boyd Robert , Gintis Herbert , Bowles Samuel , Richerson Peter J.
Published: March 2003

Both laboratory and field data suggest that people punish noncooperators even in one-shot interactions. Although such “altruistic punishment” may explain the high levels of cooperation in human societies, it creates an evolutionary puzzle: existing models suggest that altruistic cooperation among nonrelatives is evolutionarily stable only in small groups. Thus, applying such models to the evolution of altruistic punishment leads to the prediction that people will not incur costs to punish others to provide benefits to large groups of nonrelatives. However, here we show that an important asymmetry between altruistic cooperation and altruistic punishment allows altruistic punishment to evolve in populations engaged in one-time, anonymous interactions. This process allows both altruistic punishment and altruistic cooperation to be maintained even when groups are large and other parameter values approximate conditions that characterize cultural evolution in the small-scale societies in which humans lived for most of our prehistory.
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Authors: Listenberger Laura L. , Han Xianlin , Lewis Sarah E. , Cases Sylvaine , Farese Robert V. , Ory Daniel S. , Schaffer Jean E.
Published: March 2003

Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.