bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights into the Complexation of Lead(II) by 1,4,7,10‐Tetrakis(carbamoylmethyl)‐1,4,7,10‐tetraazacyclododecane (DOTAM): Structural, Thermodynamic, and Kinetic Studies
Authors: Cuenot François , Meyer Michel , Espinosa Enrique , Bucaille Arnaud , Burgat Romain , Guilard Roger , Marichal‐Westrich Claire
Published: November 2007

The lead(II) coordination properties of the tetrapodal ligand DOTAM [1,4,7,10‐tetrakis(carbamoylmethyl)‐1,4,7,10‐tetraaza‐cyclododecane] have been investigated both in the solid state and in solution in order to ascertain the stereoactivity of the lone pair and to rationalize the structural effects of a cyclen‐based scaffold on the metal uptake kinetics. The crystal structure of the free base shows that the pendant acetamide groups are not equivalent: two are folded over the macrocycle and maintained by an intramolecular hydrogen bond involving an amide hydrogen atom and a neighboring tertiary amine of the cyclen ring, while the other two are extended and point away from the macrocyclic cavity. The spontaneous reaction between Pb2+ and DOTAM, even under mild acidic conditions, leads to a mononuclear complex. The crystal structure of [Pb(DOTAM)](NO3)2·3.5H2O reveals that the eight‐coordinate metal cation is trapped inside the core of the ligand, interacting with the four cyclen nitrogen and the four amide oxygen atoms. The helical layout of the folded arms leaves no significant gap in the coordination sphere of Pb2+, thus leading to a holodirected structure that is characteristic of a stereochemically inactive 6s2 electronic lone pair. While the coordination scheme is maintained in solution, variable temperature NMR studies enabled characterization of the dynamics related to the inversion of configuration of the amide substituents. Finally, the lead(II)‐binding mechanism in aqueous solution has been investigated over a wide p[H] range (1–7) by means of classical and stopped‐flow spectrophotometry. The complexation reaction proceeds in a single rate‐limiting step according to an Eigen–Winkler mechanism. (© WILEY‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Iron‐Only Hydrogenase Active Site Models Containing a Cysteinyl Group Coordinated through Its Sulfur Atom to One Iron Atom of the Diiron Subsite
Authors: Song Li‐Cheng , Ge Jian‐Hua , Yan Jing , Wang Hu‐Ting , Luo Xiang , Hu Qing‐Mei
Published: November 2007

We have developed a simple and convenient method for the synthesis of the first H‐cluster models in which a L‐cysteinyl group is coordinated to one of the two iron atoms of the diiron subsite through its sulfur atom. This synthetic method includes (i) treatment of the Boc‐protected L‐cysteine ester Boc‐NHCH(CH2SH)CO2Et (1, Boc = tert‐butoxycarbonyl) with EtONa to give the L‐cysteinyl mercaptide NaSCH2CH(NH‐Boc)CO2Et (2); (ii) further treatment of 2 with [Cp(CO)2FeI] to produce the metallothioether ligand Cp(CO)2FeSCH2CH(NH‐Boc)CO2Et (3); and (iii) treatment of the parent diiron complex [Fe2(μ‐SCH2)2CH2(CO)6] (4), [Fe2(μ‐SCH2)2N(tBu)(CO)6] (5), or [Fe2(μ‐SCH2)2N(C6H4OMe‐p)(CO)6] (6) with Me3NO·2H2O followed by ligand 3 to afford the target model compounds [Fe2(μ‐SCH2)2CH2(CO)5(ligand 3)] (7), [Fe2(μ‐SCH2)2N(tBu)(CO)5(ligand 3)] (8), or [Fe2(μ‐SCH2)2N(C6H4OMe‐p)(CO)5(ligand 3)] (9), respectively. All the new compounds 2, 3, and 7–9 have been characterized by elemental analysis and various spectroscopic techniques. The X‐ray diffraction analysis of 8 has confirmed that these models contain a cysteinyl sulfur atom not only coordinated to one Fe atom of the diiron subsite, but also to the Fe atom of the Cp(CO)2Fe moiety to form the linkage [FeCp‐(μ‐cysteinyl‐S)‐Fesubsite], which is similar to [Fecubane‐(μ‐cysteinyl‐S)‐Fesubsite] found in natural enzymes. In addition, spectroscopic and electrochemical measurements have further demonstrated that the linkage [FeCp‐(μ‐cysteinyl‐S)‐Fesubsite] can provide substantial electronic communication between the diiron subsite and the Cp(CO)2Fe moiety. Under electrochemical conditions, 8 has been shown to be a catalyst for HOAc proton reduction to dihydrogen, and a new type of E*2E2C mechanism for this catalytic reaction is suggested.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
The voluntary approach: An effective means of achieving sustainable development?
Authors: Brophy Michael , Netherwood Alan , Starkey Richard
Published: November 2007

This paper identifies two broad approaches to achieving sustainable development: (a) the voluntary approach and (b) legislative requirements. This paper concentrates on the limits of the voluntary approach. First, it examines the limits resulting from the way in which markets currently operate. It then goes on to look at four aspects of the voluntary approach: environmental policies; environmental management systems (standards); environmental charters and corporate environmental reporting –and notes the limitations of these methods in improving environmental performance. This paper argues that the voluntary approach will not deliver the increase in environmental performance necessary to bring about sustainable development and that this increase will result only from adopting a legislative approach. Copyright © 1995 John Wiley & Sons, Ltd and ERP Environment.
Geophysical and geochemical investigations at two early copper age settlements in the Körös River Valley, Southeastern Hungary
Authors: Yerkes Richard W. , Sarris Apostolos , Frolking Tod , Parkinson William A. , Gyucha Attila , Hardy Meredith , Catanoso Luigi
Published: November 2007

Geophysical and geochemical analyses conducted at the Early Copper Age
Stimulation inhibits the mobility of recycling peptidergic vesicles in astrocytes
Authors: Potokar Maja , Stenovec Matjaž , Kreft Marko , Kreft Mateja Erdani , Zorec Robert
Published: November 2007

Astrocytes are increasingly viewed as playing many roles in the integration of brain function. These cells store among other gliotransmitters also neuroactive peptides in membrane bound vesicles, the trafficking and release of which, may be changed in altered conditions, therefore affecting the physiological status of neurons. In general, peptidergic membrane‐bound secretory vesicles fuse with the plasma membrane in the process of exocytosis. Some of them are retrieved from the plasma membrane to be recycled back into the cytosol. The mobility of retrieving vesicles in astrocytes was not studied yet, however, understanding the mechanisms of such trafficking would highlight the communication paths between astrocytes and neurons. We labeled vesicles with antibodies against the vesicle atrial natriuretic peptide (ANP), which is stored inside secretory vesicles. ANP‐vesicles in astrocytes have been proposed to enter Ca2+‐dependent secretion and here we show that they are associated with synaptotagmin IV (SytIV), a regulator of exocytosis in astrocytes. Moreover, the results show that recycling ANP‐vesicles are to a significant extent acidic. Their velocity (0.06 ± 0.001 μm/s) is one order of magnitude lower than the velocity of vesicles trafficking to the plasma membrane (Potokar et al. (2005) Biochem Biophys Res Commun 329:678–683; Potokar et al. (2007) Traffic 8:12–20). Interestingly, ionomycin or ATP application further attenuated ANP‐vesicle mobility to 0.02 ± 0.002 and to 0.03 ± 0.001 μm/s, respectively. In summary, the mobility of recycling peptidergic vesicles appears to be slower than the vesicle traffic to the plasma membrane and it requires an intact cytoskeleton. Physiological implications of attenuated traffic of ANP‐vesicles are considered in the discussion. © 2007 Wiley‐Liss, Inc.
Functional neuroanatomical investigation of vision‐related acupuncture point specificity—A multisession fMRI study
Authors: Kong Jian , Kaptchuk Ted J. , Webb Julia Megan , Kong Jiang‐Ti , Sasaki Yuka , Polich Ginger R. , Vangel Mark G. , Kwong Kenneth , Rosen Bruce , Gollub Randy L
Published: November 2007

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple‐session experiment to test whether electroacupuncture stimulation at two TCM vision‐related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non‐acupoint (NAP). Six normal, acupuncture naïve subjects completed the study. Each subject participated in six identical scanning sessions. Voxelwise group analysis showed that electroacupuncture stimulation at both vision‐related acupoints and the NAP produced modest, comparable fMRI signal decreases in the occipital cortex, including the bilateral cuneus, calcarine fissure and surrounding areas, lingual gyrus, and lateral occipital gyrus. Further analysis of fMRI signal changes in occipital cortex showed no significant difference among the three points, UB 60, GB 37, and NAP. Our results thus do not support the view that acupuncture stimulation at vision‐related acupoints induces specific fMRI blood oxygen level dependent (BOLD) signal changes in the occipital cortex. We speculate that cross modal inhibition, produced by needling‐evoked somatosensory stimulation, may account for our finding of BOLD signal decreases in the occipital cortex. Given the complexity of acupuncture systems and brain activity, additional work is required to determine whether functional neuroanatomical correlates of acupoint specificity can be validated by means of brain imaging tools. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Modeling direct effects of neural current on MRI
Authors: Heller Leon , Barrowes Benjamin E. , George John S.
Published: November 2007

We investigate the effect of the magnetic field generated by neural activity on the magnitude and phase of the MRI signal in terms of a phenomenological parameter with the dimensions of length; it involves the product of the strength and duration of these currents. We obtain an analytic approximation to the MRI signal when the neuromagnetically induced phase is small inside the MRI voxel. The phase shift is the average of the MRI phase over the voxel, and therefore first order in that phase; and the reduction in the signal magnitude is one half the square of the standard deviation of the MRI phase, which is second order. The analytic approximation is compared with numerical simulations. For weak currents the agreement is excellent, and the magnitude change is generally much smaller than the phase shift. Using MEG data as a weak constraint on the current strength we find that for a net dipole moment of 10 nAm, a typical value for an evoked response, the reduction in the magnitude of the MRI signal is two parts in 105, and the maximum value of the overall phase shift is $ \approx 4 \cdot 10^{-3} $, obtained when the MRI voxel is displaced 2/3 the size of the neuronal activity. We also show signal changes over a large range of values of the net dipole moment. We compare these results with others in the literature. Our model overestimates the effect on the MRI signal. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Precise discrimination of object position in the human pulvinar
Authors: Fischer Jason , Whitney David
Published: November 2007

Very little is known about the human pulvinar; suggestions for its function include relaying input from cortical areas, allocating visual attention, supporting feature binding, and other integrative processes. The diversity of hypotheses about pulvinar function highlights our lack of understanding of its basic role. A conspicuously missing piece of information is whether the human pulvinar encodes visual information topographically. The answer to this question is crucial, as it dramatically constrains the sorts of computational and cognitive processes that the pulvinar might carry out. Here we used fMRI to test for position‐sensitive encoding in the human pulvinar. Subjects passively viewed flickering Gabor stimuli, and as the spatial separation between Gabors increased, the correlation between patterns of activity across voxels within the right pulvinar decreased significantly. The results demonstrate the existence of precise topographic coding in the human pulvinar lateralized to the right hemisphere, and provide a means of functionally localizing this topographic region. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Preferences for ‘life‐saving’ programmes: Small for all or gambling for the prize?
Authors: Gyrd‐Hansen Dorte , Kristiansen Ivar Sønbø
Published: November 2007

Much of the literature on the value of life is based on the valuation of small reductions in mortality risk with many remaining life years if the fatal outcome is avoided. In contrast, this paper explores valuations of interventions which with varying probability levels offer smaller or moderate life year health gains. We interviewed 2900 respondents about hypothetical therapies that involved life year gains in the range of 1–180 months with a probability of 1 to 1/180, presented both in individual and societal perspectives. The results of the study indicate that the value of the hypothetical treatments is not a simple function of probability and gain. Rather, respondents seem to adopt thresholds when they value treatment offers. This results in kinked utility functions where the expected individual utility is significantly decreased when the gain in life expectancy is 6 months or less, and markedly increased if the probability of gains exceeds 1/12. There were only small differences in valuations across the individual and societal perspectives, suggesting that preferences for dispersion of health gains are not only a reflection of equity considerations. If the results of this study reflect widespread preferences, the standard methods in cost‐effectiveness/cost‐utility analysis may misinform decision makers. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of information in the utilization of preventive health‐care strategies: An application to breast cancer
Authors: Witt Julia
Published: November 2007

This paper investigates the net benefit of mammography. A theoretical expected utility (EU) model shows that increases in breast cancer risk, decreases in false‐negative and false‐positive rates, decreases in cost and increases/decreases in quality of life with early/late‐stage breast cancer increase the net benefit of mammography. The theoretical findings are tested in an empirical analysis using Canadian data. The empirical results are broadly consistent with the EU hypothesis. Results suggest that women at higher risk are more likely to obtain a mammogram. In particular, individuals are significantly more likely to have had a time‐appropriate mammogram if the mother's cause of death was breast cancer, and if the sister had breast cancer. The results also show that older age (related to higher risk and more accurate mammograms) increases mammography use, and that decreases in time and opportunity costs, and better health behaviours generally have the same effect. Copyright © 2007 John Wiley & Sons, Ltd.
Anthropometric factors and risk of melanoma in women: A pooled analysis
Authors: Olsen Catherine M. , Green Adèle C. , Zens Michael S. , Stukel Therese A. , Bataille Veronique , Berwick Marianne , Elwood J. Mark , Gallagher Richard , Holly Elizabeth A. , Kirkpatrick Connie , Mack Thomas , Østerlind Anne , Rosso Stefano , Swerdlow Anthony J. , Karagas Margaret R.
Published: November 2007

Anthropometric factors such as height, weight and body mass index are related to the occurrence of certain malignancies in women including cancers of the breast, ovary and endometrium. Several studies have investigated the relation between height and weight or body mass and the risk of cutaneous melanoma in women, but results have been inconsistent. We conducted a collaborative analysis of these factors using the original data from 8 case–control studies of melanoma in women (2,083 cases and 2,782 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure‐related factors. Women in the highest quartile of height had an increased risk of melanoma [pooled odds ratio (pOR) 1.3, 95% confidence interval (CI) 1.1–1.6]. We also found an elevated risk associated with weight gain in adult life of 2 kg or more (pOR 1.5, 95% CI 1.1–2.0). Stratifying by age at melanoma diagnosis (<50, ≥50 yr), we found this risk greater among women <50 yr of age. Associations were unaffected by adjustment for other known risk factors for melanoma. There was no evidence that the effects varied for different histologic subtypes of cutaneous melanoma. There was no association with body weight per se, body mass index, or body surface area, either recent or in young adulthood. In aggregate, data from these studies suggest that greater height and weight gain may be risk factors for cutaneous melanoma in women. © 2007 Wiley‐Liss, Inc.
Gene expression profiling related to the enhanced erythropoiesis in mouse bone marrow cells
Authors: Yang Hee‐Young , Jeong Dong Kee , Kim Seok‐Ho , Chung Kyoung‐Jin , Cho Eun‐Jin , Jin Cheng Hao , Yang Ung , Lee Sang Ryeul , Lee Dong‐Seok , Lee Tae‐Hoon
Published: November 2007

Peroxiredoxin II knockout (Prdx II−/−) mice had a spontaneous phenotype of hemolytic anemia. In this study, we found that Ter‐119+CD71+ cells increased in Prdx II−/− mice bone marrow (BM) at 8 weeks of age. We examined the differential expression profiles to bone marrow cells (BMCs) between Prdx II+/+ and Prdx II−/− mice using a cDNA microarray. We identified the 136 candidates were differentially expressed a greater twofold increase or decrease than EPO receptor. In this study, we focused on the up‐regulated NBPs during erythropoietic differentiation. According to cDNA microarray results, six NBPs except zfp‐127 were up‐regulated during erythropoiesis in Prdx II−/− mice. Among the six candidates, eIF3‐p44, hnRNPH1, G3bp, and Zfpm‐1 were dramatically increased at day 7 of the in vitro erythropoietic differentiation of human CD34+ cells. However, DJ‐1 and Rbm3 were slightly increased only at day 12. Our results suggest that up‐regulated NBPs might be involved during erythropoietic differentiation. J. Cell. Biochem. 104: 295–303, 2008. © 2007 Wiley‐Liss, Inc.
PTH/cAMP/PKA signaling facilitates canonical Wnt signaling via inactivation of glycogen synthase kinase‐3β in osteoblastic Saos‐2 cells
Authors: Suzuki Akira , Ozono Keiichi , Kubota Takuo , Kondou Hiroki , Tachikawa Kanako , Michigami Toshimi
Published: November 2007

Although the intermittent administration of PTH is known to stimulate the bone formation, the underlying mechanisms are not fully understood. Here we investigated the crosstalk between PTH/cAMP signaling and canonical Wnt signaling using the human osteoblastic cell line Saos‐2. Treatment with PTH or forskolin, an activator of adenylate cyclase, facilitated T‐cell factor (TCF)‐dependent transactivation in a dose‐dependent manner, which was abolished by pre‐treatment with a PKA inhibitor, H89. Wnt3a and forskolin synergistically increased the TCF‐dependent transactivation. Interestingly, intermittent treatment with PTH enhanced the TCF‐dependent transactivation more profoundly than continuous treatment. In addition to the effects on TCF‐dependent reporter activity, treatment with PTH or forskolin resulted in the increased expression of endogenous targets of Wnts, Wnt‐induced secreted protein 2 (WISP2) and naked cuticle 2 (NKD2). We then investigated the convergence point of PTH/cAMP signaling and the canonical Wnt pathway. Western blotting demonstrated that GSK‐3β was rapidly phosphorylated at Ser9 on treatment with PTH or forskolin, leading to its inactivation. Moreover, overexpression of a constitutively active mutant of GSK‐3β abolished the TCF‐dependent transactivation induced by forskolin. On the other hand, overexpression of the Wnt antagonist Dickkopf‐1 (DKK1) failed to cancel the effects of forskolin on the canonical Wnt pathway. Interestingly, treatment with Wnt3a markedly reduced the forskolin‐induced expression of receptor activator of NF‐κB ligand (RANKL), a target gene of PTH/cAMP/PKA. These results suggest that cAMP/PKA signaling activates the canonical Wnt pathway through the inactivation of GSK‐3β, whereas Wnt signaling might inhibit bone resorption through a negative impact on RANKL expression in osteoblasts. J. Cell. Biochem. 104: 304–317, 2008. © 2007 Wiley‐Liss, Inc.
Partitioning or bundling? Perceived fairness of the surcharge makes a difference
Authors: Sheng Shibin , Bao Yeqing , Pan Yue
Published: November 2007

Partitioned pricing charges a base price and a surcharge instead of an equivalent all‐inclusive price. In contrast, a bundling strategy offers a bundled price instead of separate prices for products in one package. Which pricing practice is more profitable? Previous research has shown conflicting results. This research identifies the boundary conditions which circumscribe the profitability of partitioned and bundled pricing. Results of three experiments indicate that the relative significance of the surcharge to the base price influences consumers' perception of the fairness of the surcharge, which in turn influences consumer purchase intentions. Furthermore, given the same level of surcharge, consumers' perceptions of the fairness of the surcharge moderates the effect of the pricing strategies. Thus, perceived fairness of the surcharge appears to be the key in determining whether or not the partitioning strategy is more profitable than the bundling strategy. © 2007 Wiley Periodicals, Inc.
An empirical analysis of the effect of volunteer labor on public library employment
Authors: Stine William F.
Published: November 2007

This study is an empirical investigation of the effect of library volunteers on public library demand for paid workers. Unlike previous studies, it estimates the impacts on different types of paid labor. The main purpose is to test whether volunteer labor replaced or complemented paid employees. A translog cost function is used to derive cost shares and elasticities of substitution for Pennsylvania public libraries. Cross‐elasticity estimates of substitution and input demand suggest a strong complementary relation between volunteers and professional workers. Most of the other Allen cross elasticities were not statistically significant. None of the estimates indicate that paid labor was being replaced by volunteers. Copyright © 2007 John Wiley & Sons, Ltd.
Carbon isotopic ratio analysis by gas chromatography/combustion/isotope ratio mass spectrometry for the detection of gamma‐hydroxybutyric acid (GHB) administration to humans
Authors: Saudan Christophe , Augsburger Marc , Mangin Patrice , Saugy Martial
Published: November 2007

Since GHB (gamma‐hydroxybutyric acid) is naturally produced in the human body, clinical and forensic toxicologists must be able to discriminate between endogenous levels and a concentration resulting from exposure. To suggest an alternative to the use of interpretative concentration cut‐offs, the detection of exogenous GHB in urine specimens was investigated by means of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). GHB was isolated from urinary matrix by successive purification on Oasis MCX and Bond Elute SAX solid‐phase extraction (SPE) cartridges prior to high‐performance liquid chromatography (HPLC) fractioning using an Atlantis dC18 column eluted with a mixture of formic acid and methanol. Subsequent intramolecular esterification of GHB leading to the formation of γ‐butyrolactone (GBL) was carried out to avoid introduction of additional carbon atoms for carbon isotopic ratio analysis. A precision of 0.3‰ was determined using this IRMS method for samples at GHB concentrations of 10 mg/L. The 13C/12C ratios of GHB in samples of subjects exposed to the drug ranged from −32.1 to −42.1‰, whereas the results obtained for samples containing GHB of endogenous origin at concentration levels less than 10 mg/L were in the range −23.5 to −27.0‰. Therefore, these preliminary results show that a possible discrimination between endogenous and exogenous GHB can be made using carbon isotopic ratio analyses. Copyright © 2007 John Wiley & Sons, Ltd.
Mokken Scale Analysis for Dichotomous Items Using Marginal Models
Authors: van der Ark L. Andries , Croon Marcel A. , Sijtsma Klaas
Published: November 2007

Scalability coefficients play an important role in Mokken scale analysis. For a set of items, scalability coefficients have been defined for each pair of items, for each individual item, and for the entire scale. Hypothesis testing with respect to these scalability coefficients has not been fully developed. This study introduces marginal modelling as a framework to derive the standard errors for the scaling coefficients and test hypotheses about these coefficients. Several examples demonstrate the possibilities of marginal modelling in Mokken scale analysis. These possibilities include testing whether Mokken’s criteria for a scale are satisfied, testing whether scalability coefficients of different items are equal, and testing whether scalability coefficients are equal across different groups.
Evaluating macrolichens and environmental variables as predictors of the diversity of epiphytic microlichens
Authors: BERGAMINI Ariel , STOFER Silvia , BOLLIGER Janine , SCHEIDEGGER Christoph
Published: November 2007

In contrast to the frequently assessed macrolichens, microlichens are rarely considered in biodiversity assessments despite their high species richness. Microlichens require generally a higher species identification effort than macrolichens. Thus, microlichens are more expensive to assess. Here we evaluate if macrolichen richness can be used as an indicator of total and threatened microlichen richness. Furthermore, we tested if different sets of environmental variables (modelled climatic variables, forest structure, altitude, etc.) improve the regression models based on macrolichens only or even replace the macrolichens as predictors. Multiple linear regressions were used to model species richness of microlichens, and Poisson regressions for threatened microlichens.

On 237 forest plots (200 m2) distributed randomly across Switzerland, 77 macrolichens and 219 microlichens occurred. Macrolichen richness was positively related to the richness of microlichens (=0·27) and, in combination with threatened macrolichens as an additional predictor, also to the number of threatened microlichens (=0·14). Environmental variables alone and in different combinations explained between 0·20 and 0·41 () of the total variation of microlichen richness, and between 0·09 and 0·29 () of the total variation of threatened microlichen richness. All models based on environmental variables were considerably improved when macrolichens were included. Furthermore, macrolichen richness turned out to be the most important variable in explaining species richness of all, as well as threatened microlichens. The best models for total microlichen richness reached a of 0·56. Threatened microlichens were more difficult to model with the best model reaching a of 0·29.

We conclude that in biodiversity assessments with scarce resources, lichen sampling could be focused on the better known macrolichens, at least in many temperate lowland and mountain forests. In combination with environmental variables, reliable predictions of microlichen richness can be expected. If the focus is on threatened microlichens, however, models were not reliable and specialized taxonomists are necessary to assess these species in the field.
Law, liberty, and Christian morality
Authors: SWAN KYLE
Published: November 2007

There is a long liberal political tradition of marshalling arguments aimed at convincing Christians that distinctively Christian reasons for issuing coercive laws are not sufficient to justify those laws. In the first part of this paper I argue that the two most popular of these arguments, attributable to Locke, will not reliably convince committed biblical Christians, nor, probably, should they. In the second part I argue that even if the Lockean arguments fail, committed biblical Christians should think that God has authorized the state only to fill the same general role that political liberals have identified for it.
A reply to Schlesinger's theodicy
Authors: GWIAZDA JEREMY
Published: November 2007

In Religion and Scientific Method, George Schlesinger presented a strikingly original theodicy. In this paper, I explain the strategy underlying Schlesinger's argument. I then present a parallel argument to indicate the weakness of Schlesinger's theodicy. Finally, I show that Schlesinger's theodicy assumes a false principle, and therefore fails.
Modified Newton's method applied to potential field based navigation for nonholonomic robots in dynamic environments
Authors: Ren Jing , McIsaac Kenneth A. , Patel Rajni V.
Published: November 2007

This paper is to investigate inherent oscillations problems of Potential Field Methods (PFMs) for nonholonomic robots in dynamic environments. In prior work, we proposed a modification of Newton's method to eliminate oscillations for omnidirectional robots in static environment. In this paper, we develop control laws for nonholonomic robots in dynamic environment using modifications of Newton's method. We have validated this technique in a multirobot search-and-forage task. We found that the use of the modifications of Newton's method, which applies anywhereC2continuous navigation functions are defined, can greatly reduce oscillations and speed up robot's movement, when compared to the standard gradient approaches.
Chronische Müdigkeit
Authors: Mettler  , Battegay  , Zimmerli
Published: November 2007

Der 40 jährige Explorand wurde uns wegen chronischer Müdigkeit zur IV-Begutachtung überwiesen. Im Rahmen einer langjährigen Polytoxikomanie hatte sich der Explorand mit Hepatitis C infiziert, weswegen er mit Interferon therapiert wurde. Aus den uns vorliegenden Unterlagen ging hervor, dass ebenfalls eine Anämie, eine Depression und eine Methadonsubstitution bestanden. Unsere Abklärungen ergaben, dass der Explorand zudem eine Hashimoto-Thyreoiditis hat.
Stochastic optimization of multireservoir systems via reinforcement learning
Authors: Lee Jin‐Hee , Labadie John W.
Published: November 2007

Although several variants of stochastic dynamic programming have been applied to optimal operation of multireservoir systems, they have been plagued by a high‐dimensional state space and the inability to accurately incorporate the stochastic environment as characterized by temporally and spatially correlated hydrologic inflows. Reinforcement learning has emerged as an effective approach to solving sequential decision problems by combining concepts from artificial intelligence, cognitive science, and operations research. A reinforcement learning system has a mathematical foundation similar to dynamic programming and Markov decision processes, with the goal of maximizing the long‐term reward or returns as conditioned on the state of the system environment and the immediate reward obtained from operational decisions. Reinforcement learning can include Monte Carlo simulation where transition probabilities and rewards are not explicitly known a priori. The Q‐Learning method in reinforcement learning is demonstrated on the two‐reservoir Geum River system, South Korea, and is shown to outperform implicit stochastic dynamic programming and sampling stochastic dynamic programming methods.
Large‐scale forcing impact on biomass variability in the South Atlantic Bight
Authors: Signorini Sergio R. , McClain Charles R.
Published: November 2007

The Gulf Stream western front (GSF) follows the shelf slope topography for a great extent of the South Atlantic Bight (SAB). Sub‐surface intrusions of the Gulf Stream are known to provide nutrient‐rich waters to the outer shelf regions of the SAB and, consequently, promote phytoplankton growth. These intrusions are much more frequent during summer and are responsible for a significant portion of the annual SAB shelf carbon production. Based on the analysis of satellite ocean color data, sea surface temperature (SST), sea surface height (SSH), and climatologic data sets, we present evidence for a connection between these Gulf Stream intrusions and the seasonal variability of the size and strength of the North Atlantic Subtropical Gyre (NASG). The intensity and frequency of intrusions depend on the proximity of the GSF to the shelf, which is modulated by the seasonal expansion and contraction of the NASG.
Incident field excitation of random cables
Authors: Pincenti John C. , Uslenghi Piergiorgio L. E.
Published: November 2007

This work considers the problem of characterizing the response of a cable bundle in the presence of an external electromagnetic field when the orientation of the cable is not well defined or is unknown. To do this, cable bundles are modeled as multiconductor transmission lines. Because of the random nature of the cable, an exact solution is not in general possible. Therefore a solution is approximated by segmenting the cable into a number of small uniform sections that can be solved and combined to form an overall solution. The orientation of these sections is allowed to vary randomly, thereby modeling the various twists and bends that may be found in a practical application. The line is excited by an external electromagnetic field. The voltages and currents generated at the terminations of the cable are calculated using a numerical approach to solve the multiconductor transmission line equations in the frequency domain. Because the exact positioning of the cable is not known, statistical data for the response are needed. To obtain statistical data, a large number of randomly generated cables are generated and solved.
A search for hydroacoustic signals associated with the 2 June 1988 temperature anomaly at axial seamount
Authors: Walker Daniel A.
Published: November 2007

Data from the Wake Island hydrophone array is examined for signals possibly associated with sudden decreases in bottom temperature at Axial Seamount which is located on the Juan de Fuca Ridge. In spite of the extreme sensitivity of the Wake hydrophones to small explosive charges and unreported shallow focus earthquakes along the Juan de Fuca Ridge, and to unreported episodes of submarine volcanism, no sustained signals were found which appear to be related to the observed temperature anomalies. Because of intermittent recording problems, some hydroacoustic signals of extremely short duration, possibly associated with the temperature anomalies, could have escaped detection in the eight hours subsequent to the occurrence of these anomalies. However, no such signals could have escaped detection during an eight hour period prior to the onset of the observed anomalies since the recording system was working properly. The absence of signals indicates that sustained teleacoustically detectable submarine volcanism was not associated with the 2 June 1988 temperature anomaly.
Autophagy after Experimental Intracerebral Hemorrhage
Authors: He Yangdong , Wan Shu , Hua Ya , Keep Richard F , Xi Guohua
Published: November 2007

Autophagy contributes to ischemic brain injury, but it is not clear if autophagy occurs after intracerebral hemorrhage (ICH). This study examined whether ICH-induced cell death is partly autophagic. It then examined the role of iron in inducing this form of cell death after ICH. Male, adult Sprague-Dawley rats received an infusion of autologous whole blood or ferrous iron into the right basal ganglia. Control rats (sham) had a needle insertion. The rats were killed at 1, 3, 7, or 28 days later. Some rats were treated with either deferoxamine or vehicle after ICH. Microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and cathepsin D, a lysosomal biomarker, were measured by Western blot analysis and immunohistochemistry. Immunofluorescent double-labeling was used to identify the cell types expressing cathepsin D. Electron microscopy was performed to examine the cellular ultrastructure changes after ICH. We found that conversion of LC3-I to LC3-II, cathepsin D expression, and vacuole formation are increased in the ipsilateral basal ganglia after ICH. Intracerebral infusion of iron also resulted in enhanced conversion of LC3-I to LC3-II and increased cathepsin D levels. Deferoxamine (an iron chelator) treatment significantly reduced the conversion of LC3-I to LC3-II and cathepsin D levels after ICH. Our results demonstrated that autophagy occurs after ICH, and iron has a key role in ICH-induced autophagy. This also suggests that iron-induced autophagy may play a role in brain injury in other diseases associated with iron overload.
Antitumour metal compounds: more than theme and variations
Authors: Jakupec Michael A. , Galanski Mathea S. , Arion Vladimir B. , Hartinger Christian G. , Keppler Bernhard K.
Published: November 2007

The coordination chemistry of ruthenium (and gallium) allows the pathophysiological conditions of solid tumours to be exploited, enabling the development of antineoplastic complexes profoundly different from platinum drugs in their mode of action.
Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux
Authors: MULCAHY Jane V. , RIDDELL Dave R. , OWEN James S.
Published: November 2007

Although studies in recombinant cells indicate that scavenger receptor class B, type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice overexpressing or deficient in SR-BI endorse its physiological function as selectively sequestering cholesteryl esters from high-density lipoproteins (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that differs only in the C-terminal cytoplasmic domain. Here, we identify several putative signalling motifs in the C-terminus of human SR-BII, which are absent from SR-BI, and hypothesize that these motifs interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. ‘Pull-down’ assays using a panel of tagged SH3 (Src homology 3) domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3 domain of phospholipase C-γ1; this interaction was not, however, detected under more physiological conditions. Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins. Consistent with its caveolar localization, expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO–SR-BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless, when CHO-SR-BII cells were pre-loaded with cholesteryl [3H]oleate and incubated with HDL, cholesteryl ester stores were not reduced compared with control cells. We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters.
Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity
Authors: Oliver McINTYRE J. , FINGLETON Barbara , WELLS K. Sam , PISTON David W. , LYNCH Conor C. , GAUTAM Shiva , MATRISIAN Lynn M.
Published: November 2007

The present study describes the in vivo detection and imaging of tumour-associated MMP-7 (matrix metalloproteinase-7 or matrilysin) activity using a novel polymer-based fluorogenic substrate PB-M7vis, which serves as a selective ‘proteolytic beacon’ (PB) for this metalloproteinase. PB-M7vis is built on a PAMAM (polyamido amino) dendrimer core of 14.2 kDa, covalently coupled with an Fl (fluorescein)-labelled peptide Fl(AHX)RPLALWRS(AHX)C (where AHX stands for aminohexanoic acid) and with TMR (tetramethylrhodamine). PB-M7vis is efficiently and selectively cleaved by MMP-7 with a kcat/Km value of 1.9×105 M−1·s−1 as measured by the rate of increase in Fl fluorescence (up to 17-fold for the cleavage of an optimized PB-M7vis) with minimal change in the TMR fluorescence. The Km value for PB-M7vis is approx. 0.5 µM, which is approx. two orders of magnitude lower when compared with that for an analogous soluble peptide, indicating efficient interaction of MMP-7 with the synthetic polymeric substrate. With MMP-2 or -3, the kcat/Km value for PB-M7vis is approx. 56- or 13-fold lower respectively, when compared with MMP-7. In PB-M7vis, Fl(AHX)RPLALWRS(AHX)C is a selective optical sensor of MMP-7 activity and TMR serves to detect both the uncleaved and cleaved reagents. Each of these can be visualized as subcutaneous fluorescent phantoms in a mouse and optically discriminated based on the ratio of green/red (Fl/TMR) fluorescence. The in vivo specificity of PB-M7vis was tested in a mouse xenograft model. Intravenous administration of PB-M7vis gave significantly enhanced Fl fluorescence from MMP-7-positive tumours, but not from control tumours (P<0.0001), both originally derived from SW480 human colon cancer cells. Prior systemic treatment of the tumour-bearing mice with an MMP inhibitor BB-94 {[4-(N-hydroxyamino)-2R-isobutyl-3S-(thienylthiomethyl)-succinyl]-l-phenylalanine-N-methylamide}, markedly decreased the Fl fluorescence over the MMP-7-positive tumour by approx. 60%. Thus PB-M7vis functions as a PB for in vivo detection of MMP-7 activity that serves to light this optical beacon and is, therefore, a selective in vivo optical molecular imaging contrast reagent.
Structure and regulation of the mDot1 gene, a mouse histone H3 methyltransferase
Authors: ZHANG Wenzheng , HAYASHIZAKI Yoshihide , KONE Bruce C.
Published: November 2007

Recently, a new class of histone methyltransferases that plays an indirect role in chromatin silencing by targeting a conserved lysine residue in the nucleosome core was described, namely the Dot1 (disruptor of telomeric silencing) family [Feng, Wang, Ng, Erdjument-Bromage, Tempst, Struhl and Zhang (2002) Curr. Biol. 12, 1052–1058; van Leeuwen, Gafken and Gottschling (2002) Cell (Cambridge, Mass.) 109, 745–756; Ng, Feng, Wang, Erdjument-Bromage, Tempst, Zhang and Struhl (2002) Genes Dev. 16, 1518–1527]. In the present study, we report the isolation, genomic organization and in vivo expression of a mouse Dot1 homologue (mDot1). Expressed sequence tag analysis identified five mDot1 mRNAs (mDot1a–mDot1e) derived from alternative splicing. mDot1a and mDot1b encode 1540 and 1114 amino acids respectively, whereas mDot1c–mDot1e are incomplete at the 5´-end. mDot1a is closest to its human counterpart (hDot1L), sharing 84% amino acid identity. mDot1b is truncated at its N- and C-termini and contains an internal deletion. The five mDot1 isoforms are encoded by 28 exons on chromosome 10qC1, with exons 24 and 28 further divided into two and four sections respectively. Alternative splicing occurs in exons 3, 4, 12, 24, 27 and 28. Northern-blot analysis with probes corresponding to the methyltransferase domain or the mDot1a-coding region detected 7.6 and 9.5 kb transcripts in multiple tissues, but only the 7.6 kb transcript was evident in mIMCD3-collecting duct cells. Transfection of mDot1a–EGFP constructs (where EGFP stands for enhanced green fluorescent protein) into human embryonic kidney (HEK)-293T or mIMCD3 cells increased the methylation of H3-K79 but not H3-K4, -K9 or -K36. Furthermore, DMSO induced mDot1 gene expression and methylation specifically at H3-K79 in mIMCD3 cells in a time- and dose-dependent manner. Collectively, these results add new members to the Dot1 family and show that mDot1 is involved in a DMSO-mediated signal-transduction pathway in collecting duct cells.
ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405-Gln406 to generate glial hyaluronate binding protein
Authors: WESTLING Jennifer , GOTTSCHALL Paul E. , THOMPSON Vivian P. , COCKBURN Amber , PERIDES George , ZIMMERMANN Dieter R. , SANDY John D.
Published: November 2007

Human brain tissue from cerebellum and hippocampus was obtained between 2 h and 24 h post mortem and, after extraction in the presence of proteinase inhibitors, proteoglycans were purified by anion-exchange chromatography. The versican component was characterized by Western analysis with antibodies to the N-terminal peptide (LF99), the N-terminal globular domain (12C5) and the two GAG (glycosaminoglycan) attachment regions (anti-GAG-α and anti-GAG-β). The results indicated that versican V2 is the major variant in all brain samples, and that it exists as the full-length form and also as at least six C-terminally truncated forms. The major immunoreactive species present is a 64 kDa product, which we identified by biochemical and immunological analysis as the brain protein previously termed GHAP (glial hyaluronate binding protein) [Perides, Lane, Andrews, Dahl and Bignami (1989) J. Biol. Chem. 264, 5981–5987]. Immunological analysis of purified human GHAP using a new anti-neoepitope antiserum (JSCNIV) showed that its C-terminal sequence is NIVSFE405, and digestion of human cerebellum proteoglycans with ADAMTS4 (aggrecanase-1, where ADAMTS, a disintegrin and metalloproteinase with thrombospondin-1-like motifs) indicated that GHAP is a product of cleavage of versican V0 or V2 at the Glu405–Gln406 bond. Since human cerebellum extracts contained multiple forms of ADAMTS4 protein on Western analysis, these data suggest that one or more members of the ‘aggrecanase’ group of the ADAMTS family (ADAMTS 1, 4, 5 and 9) are responsible for turnover of versican V2 in the adult human brain.
Cystinuria-specific rBAT(R365W) mutation reveals two translocation pathways in the amino acid transporter rBAT-b0,+AT
Authors: PINEDA Marta , WAGNER Carsten A. , BRÖER Angelika , STEHBERGER Paul A. , KALTENBACH Simone , GELPÍ Josep Ll. , MARTÍN del RÍO Rafael , ZORZANO Antonio , PALACÍN Manuel , LANG Florian , BRÖER Stefan
Published: November 2007

Apical reabsorption of dibasic amino acids and cystine in kidney is mediated by the heteromeric amino acid antiporter rBAT/b0,+AT (system b0,+). Mutations in rBAT cause cystinuria type A, whereas mutations in b0,+AT cause cystinuria type B. b0,+AT is the catalytic subunit, whereas it is believed that rBAT helps the routing of the rBAT/b0,+AT heterodimeric complex to the plasma membrane. In the present study, we have functionally characterized the cystinuria-specific R365W (Arg365→Trp) mutation of human rBAT, which in addition to a trafficking defect, alters functional properties of the b0,+ transporter. In oocytes, where human rBAT interacts with the endogenous b0,+AT subunit to form an active transporter, the rBAT(R365W) mutation caused a defect of arginine efflux without altering arginine influx or apparent affinities for intracellular or extracellular arginine. Transport of lysine or leucine remained unaffected. In HeLa cells, functional expression of rBAT(R365W)/b0,+AT was observed only at the permissive temperature of 33 °C. Under these conditions, the mutated transporter showed 50% reduction of arginine influx and a similar decreased accumulation of dibasic amino acids. Efflux of arginine through the rBAT(R365W)/b0,+AT holotransporter was completely abolished. This supports a two-translocation-pathway model for antiporter b0,+, in which the efflux pathway in the rBAT(R365W)/b0,+AT holotransporter is defective for arginine translocation or dissociation. This is the first direct evidence that mutations in rBAT may modify transport properties of system b0,+.