bluuebunny/crossref_metadata_2025 huggingface dataset:
FOOT VOTING, POLITICAL IGNORANCE, AND CONSTITUTIONAL DESIGN
Authors: Somin Ilya
Published: November 2010

The strengths and weaknesses of federalism have been debated for centuries. But one major possible advantage of building decentralization and limited government into a constitution has been largely ignored in the debate so far: its potential for reducing the costs of widespread political ignorance. The argument of this paper is simple, but has potentially important implications: Constitutional federalism enables citizens to “vote with their feet,” and foot voters have much stronger incentives to make well-informed decisions than more conventional ballot box voters. The informational advantage of foot voting over ballot box voting suggests that decentralized federalism can increase citizen welfare and democratic accountability relative to policymaking in a centralized unitary state.

Ballot box voters have strong incentives to be “rationally ignorant” about the candidates and policies they vote on because the chance that any one vote will have a decisive impact on an electoral outcome is vanishingly small. For the same reason, they also have little or no incentive to make good use of the information they do possess. By contrast, “foot voters” choosing a jurisdiction in which to reside have much stronger incentives to acquire information and use it rationally; the decisions they make are individually decisive.
PLURALIST CONSTITUTIONALISM
Authors: Galston William A.
Published: November 2010

This essay explores the ways in which a broadly pluralist outlook can help illuminate longstanding issues of constitutional theory and practice. It begins with a common-sense understanding of pluralism as the diversity of observed practices within a general category (section 2). It turns out that many assumptions Americans and others often make about constitutional essentials are valid only locally but not generically. The essay then turns to pluralism in a more technical and philosophical sense—specifically, the account of value pluralism adumbrated by Isaiah Berlin and developed by his followers. Section 3 sketches this version of pluralism, and section 4 brings it to bear on a range of familiar constitutional issues. In the process, a distinction emerges between, on the one hand, areas of variation among constitutions and, on the other, some general truths about political life that define core constitutional functions. The essay concludes (section 5) with some brief reflections on the normative thrust of pluralist constitutional theory—in particular, a presumption in favor of the maximum accommodation of individual and group differences consistent with the maintenance of constitutional unity and civic order.
Storage allocation under processor sharing II: Further asymptotic results
Authors: SOHN EUNJU , KNESSL CHARLES
Published: November 2010

We consider a processor-sharing storage allocation model, which has m primary holding spaces and infinitely many secondary ones, and a single processor servicing the stored items. All of the spaces are numbered and ordered. An arriving customer takes the lowest available space. Dynamic storage allocation and the fragmentation of computer memory are well-known applications of this model. We define the traffic intensity ρ to be λ/μ, where λ is the customers' arrival rate and μ is the service rate of the processor. We study the joint probability distribution of the numbers of occupied primary and secondary spaces. We study the problem in two asymptotic limits: (1) m → ∞ with a fixed ρ < 1, and (2) ρ ↑ 1, m → ∞ with m(1-ρ) = O(1). The asymptotics yield insight into how many secondary spaces tend to be needed, and into the sample paths leading to the occupation of the two types of spaces. We show that the asymptotics lead to accurate numerical approximations.
Is there enough habitat for reintroduced populations of the Lesser Kestrel? A case study in eastern Spain
Authors: PÉREZ IRENE , NOGUERA JOSÉ CARLOS , MÍNGUEZ EDUARDO
Published: November 2010

The Lesser Kestrel Falco naumanni is one of the most endangered birds in Europe. Spanish populations have suffered large declines and disappeared from large areas of former distribution, thus leading to many reintroduction programmes. One of the main factors that could affect the population growth of reintroduced populations is the availability of suitable habitat for breeding and foraging. We investigated whether nest site availability is a limiting factor for a newly established population of Lesser Kestrels in eastern Spain. We developed univariate models to understand the relationship between building characteristics (area, height, roof condition, etc.) and occupancy and abundance of Lesser Kestrels, and multivariate models to predict the availability of nest-sites. Our results showed that the species selected medium-sized buildings with extensive land use in the surrounding area and an absence of trees. In addition, Lesser Kestrel abundance was explained by roof condition and distance to the nearest building. Multivariate models predicted that most of the buildings were not suitable for nesting by Lesser Kestrels and thus population growth may be limited due to lack of nest sites. Lack of suitable nest sites, conspecific attraction and Allee effects are all processes that may be limiting, resulting in the low population and colony sizes that were found and predicted. Based on this, we recommend the provision of nest boxes, the use of special tiles and the construction of breeding towers to improve building quality and therefore increase colony size. We also critically question the use of reintroduction projects to restore locally extinct populations for two reasons. First in this case the reintroduced population is near some larger colonies and there is a strong tendency for Lesser Kestrels to move from small to large colonies. Secondly, in a general strategy for the conservation of Lesser Kestrels, conservation of the main colonies is the priority rather than dedicating human and economic resources on manipulative actions for the establishment of new colonies.
The Effects of Prior Cognitive Control Task Exposure on Responses to Emotional Tasks in Healthy Participants
Authors: Calkins Amanda W. , Deveney Christen M. , Weitzman Meara L. , Hearon Bridget A. , Siegle Greg J. , Otto Michael W.
Published: November 2010

Background:Recent advances have been made in the application of cognitive training strategies as interventions for mental disorders. One novel approach, cognitive control training (CCT), uses computer-based exercises to chronically increase prefrontal cortex recruitment. Activation of prefrontal control mechanisms have specifically been identified with attenuation of emotional responses. However, it is unclear whether recruitment of prefrontal resources alone is operative in this regard, or whether prefrontal control is important only in the role of explicit emotion regulation. This study examined whether exposure to cognitive tasks before an emotional challenge attenuated the effects of the emotional challenge.Aims:We investigated whether a single training session could alter participants' reactivity to subsequent emotional stimuli on two computer-based tasks as well as affect ratings made during the study. We hypothesized that individuals performing the Cognitive Control (CC) task as compared to those performing the Peripheral Vision (PV) comparison task would (1) report reduced negative affect following the mood induction and the emotion task, and (2) exhibit reduced reactivity (defined by lower affective ratings) to negative stimuli during both the reactivity and recovery phases of the emotion task and (3) show a reduced bias towards threatening information.Method:Fifty-nine healthy participants were randomized to complete CC tasks or PV, underwent a negative mood induction, and then made valence and arousal ratings for IAPS images, and completed an assessment of attentional bias.Results:Results indicated that a single-session of CC did not consistently alter participants' responses to either task. However, performance on the CC tasks was correlated on subsequent ratings of emotional images.Conclusions:While overall these results do not support the idea that affective responding is altered by making healthy volunteers use their prefrontal cortex before the affective task, they are discussed in the context of study design issues and future research directions.
Subliminal Emotional Priming and Decision Making in a Simulated Hiring Situation
Authors: Skandrani-Marzouki Inès , Marzouki Yousri
Published: November 2010

The present study examines the unconscious influence of emotional information on decision making in a simulated hiring situation. We used a subliminal masked priming paradigm with varying faces as primes, which were presented for a duration of 50 ms and had two levels of emotion: positive emotion (happiness) and negative emotion (anger). These primes were followed by emotionally neutral target faces. Primes were congruent (same faces) or incongruent (different faces). Prime Emotion (positive vs. negative) was crossed with Prime Repetition (repeat vs. unrelated) in a 2 × 2 factorial design. Each participant was tested in all four of the experimental conditions, each of which had 5 different trials. The participants were asked to indicate as rapidly as possible whether they were “favorable” or “unfavorable” toward the selection of the candidate (target face). Two dependent measures were analyzed: number of target faces chosen (i.e., number of “favorable” responses to target faces) and reaction time (RT). Results revealed a strong effect of emotional priming. Participants tended to choose more target faces preceded by positive prime faces than by negative prime faces. Moreover, they reacted faster when presented with target faces preceded by negative primes. Despite its exploratory nature, this study provides further evidence for the role of emotional processing in modulating decision processes and extends the experimental manipulation of subliminal emotion to the case of the masked repetition priming technique.
The Four- vs. Alternative Six-Factor Structure of the French WISC-IV
Authors: Lecerf Thierry , Rossier Jérôme , Favez Nicolas , Reverte Isabelle , Coleaux Laurence
Published: November 2010

Exploratory and confirmatory factor analyses reported in the French technical manual of the WISC-IV provides evidence supporting a structure with four indices: Verbal Comprehension (VCI), Perceptual Reasoning (PRI), Working Memory (WMI), and Processing Speed (PSI). Although the WISC-IV is more attuned to contemporary theory, it is still not in total accordance with the dominant theory: the Cattell-Horn-Carroll (CHC) theory of cognitive ability. This study was designed to determine whether the French WISC-IV is better described with the four-factor solution or whether an alternative model based on the CHC theory is more appropriate. The intercorrelations matrix reported in the French technical manual was submitted to confirmatory factor analysis. A comparison of competing models suggests that a model based on the CHC theory fits the data better than the current WISC-IV structure. It appears that the French WISC-IV in fact measures six factors: crystallized intelligence (Gc), fluid intelligence (Gf), short-term memory (Gsm), processing speed (Gs), quantitative knowledge (Gq), and visual processing (Gv). We recommend that clinicians interpret the subtests of the French WISC-IV in relation to this CHC model in addition to the four indices.
Origins of large‐volume, compositionally zoned volcanic eruptions: New constraints from U‐series isotopes and numerical thermal modeling for the 1912 Katmai‐Novarupta eruption
Authors: Turner Simon , Sandiford Mike , Reagan Mark , Hawkesworth Chris , Hildreth Wes
Published: November 2010

We present the results of a combined U‐series isotope and numerical modeling study of the 1912 Katmai‐Novarupta eruption in Alaska. A stratigraphically constrained set of samples have compositions that range from basalt through basaltic andesite, andesite, dacite, and rhyolite. The major and trace element range can be modeled by 80–90% closed‐system crystal fractionation over a temperature interval from 1279°C to 719°C at 100 MPa, with an implied volume of parental basalt of ∼65 km3. Numerical models suggest, for wall rock temperatures appropriate to this depth, that 90% of this volume of magma would cool and crystallize over this temperature interval within a few tens of kiloyears. However, the range in 87Sr/86Sr, (230Th/238U), and (226Ra/230Th) requires open‐system processes. Assimilation of the host sediments can replicate the range of Sr isotopes. The variation of (226Ra/230Th) ratios in the basalt to andesite compositional range requires that these were generated less than several thousand years before eruption. Residence times for dacites are close to 8000 years, whereas the rhyolites appear to be 50–200 kyr old. Thus, the magmas that erupted within only 60 h had a wide range of crustal residence times. Nevertheless, they were emplaced in the same thermal regime and evolved along similar liquid lines of descent from parental magmas with similar compositions. The system was built progressively with multiple inputs providing both mass and heat, some of which led to thawing of older silicic material that provided much of the rhyolite.
A parallel 3‐D staggered grid pseudospectral time domain method for ground‐penetrating radar wave simulation
Authors: Huang Qinghua , Li Zhanhui , Wang Yanbin
Published: November 2010

We presented a parallel 3‐D staggered grid pseudospectral time domain (PSTD) method for simulating ground‐penetrating radar (GPR) wave propagation. We took the staggered grid method to weaken the global effect in PSTD and developed a modified fast Fourier transform (FFT) spatial derivative operator to eliminate the wraparound effect due to the implicit periodical boundary condition in FFT operator. After the above improvements, we achieved the parallel PSTD computation based on an overlap domain decomposition method without any absorbing condition for each subdomain, which can significantly reduce the required grids in each overlap subdomain comparing with other proposed algorithms. We test our parallel technique for some numerical models and obtained consistent results with the analytical ones and/or those of the nonparallel PSTD method. The above numerical tests showed that our parallel PSTD algorithm is effective in simulating 3‐D GPR wave propagation, with merits of saving computation time, as well as more flexibility in dealing with complicated models without losing the accuracy. The application of our parallel PSTD method in applied geophysics and paleoseismology based on GPR data confirmed the efficiency of our algorithm and its potential applications in various subdisciplines of solid earth geophysics. This study would also provide a useful parallel PSTD approach to the simulation of other geophysical problems on distributed memory PC cluster.
Using the Wiimote as a sensor in water research
Authors: Hut R. W. , Weijs S. V. , Luxemburg W. M. J.
Published: November 2010

The $40 “Wiimote” (an input device belonging with the Nintendo® Wii™ game system) can be used by hydrologists as a sensor. The device contains three accelerometers and an infrared camera with built‐in source tracking. It communicates by Bluetooth®. Because of the efforts of the hacking community it is now easy to let the Wiimote communicate with a standard personal computer. Using a floating evaporation pan as an example, we show that the Wiimote, although it may have potential drawbacks when used in field campaigns, is a good addition to the hydrologist's bag of tools, especially for proof of concept testing.
Mechanical stress induces production of angiogenic regulators in cultured human gingival and periodontal ligament fibroblasts
Authors: Yoshino Hiroyuki , Morita Ikuo , Murota Sei‐itsu , Ishikawa Isao
Published: November 2010

Background:  As periodontal tissues are constantly exposed to mechanical stress during mastication, the relationship between mechanical stimulation and biochemical phenomena has been extensively investigated.

Objectives:  The aim of the present study was to assess the change in the production of angiogenic regulators produced by human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (HPLF), cultured on a flexible substrate, before and after application of cyclic tensile stretching.

Materials and methods:  Both cell types were stretched in a Flexercell Strain Unit to 7, 14 and 21% elongation, at a frequency of 12 cycles/min. Medium cultured with HGF or HPLF was examined by enzyme‐linked immunosorbent assay (ELISA) for vascular endothelial growth factor (VEGF), Western blotting of pigment epithelium‐derived factor (PEDF) and in vitro angiogenesis assay. The residual cells were analyzed by reverse transcription‐polymerase chain reaction (RT‐PCR) for both VEGF and PEDF mRNA expression.

Results:  Stretching increased the VEGF mRNA level and VEGF secretion in both HGF and HPLF. The concentration of VEGF in the conditioned medium of the stretched HPLF was almost the same as that of stretched HGF. In the in vitro angiogenesis assay, the conditioned medium of HPLF after stretching showed a dramatic increase in tube formation. In contrast, stretched HGF did not show enhanced tube formation, despite the increase in VEGF secretion by stretched HGF. The mRNA levels of PEDF, an inhibitor of angiogenesis, were higher in HGF than HPLF. The protein level of PEDF in HGF was also higher than that in HPLF.

Conclusion:  These findings suggest that under mechanical stress HPLF promotes angiogenesis via expression of VEGF, whereas under the same conditions angiogenesis is not promoted in HGF, due to the expression of PEDF.
Polymorphisms in the +252(A/G) lymphotoxin‐alpha and the −308(A/G) tumor necrosis factor‐alpha genes and susceptibility to chronic periodontitis in a Czech population
Authors: Fassmann Antonin , Holla Lydie Izakovicova , Buckova Dana , Vasku Anna , Znojil Vladimir , Vanek Jiri
Published: November 2010

Background:  Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease.

Methods:  In this study, we investigated an association between chronic periodontitis and two previously described bi‐allelic polymorphisms in the TNF locus: a G to A transition at position −308 in the 5′promoter region of the TNF‐α gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin α (LT‐α) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age‐ and gender‐matched unrelated control subjects.

Results:  The TNF‐α (−308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT‐α (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT‐α 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF‐α and LT‐α) between the control and the patient groups were found using a simulation by applying the Monte‐Carlo method (P < 0.01).

Conclusion:  Our data suggest that combined genotypes composed of the TNF‐α and LT‐α gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT‐α gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population.
In vivo administration of recombinant TNF‐α promotes bone resorption in mice
Authors: Gašperšič Rok , Štiblar‐Martinčič Draga , Osredkar Joško , Skalerič Uroš
Published: November 2010

Background:  In vitro studies demonstrated that proinflammatory cytokine tumor necrosis factor alpha (TNF‐α) modulates bone metabolism.

Objective:  The aim of our study was to confirm the ability of TNF‐α to induce osteoclastogenesis and bone resorption in an in vivo experiment, with the use of calvarial model in mice.

Materials and methods:  Twenty C57‐Black mice were divided into four groups with five animals in each. The first group was infused subcutaneously on their back with recombinant mouse (rm) TNF‐α via osmotic minipumps for 3 d, the second group was similarly infused with phosphate‐buffered saline (PBS), the third group was infused with rmTNF‐α to the region above the parietal bone and the fourth group with PBS in the same manner. Number of osteoclasts on parietal bone was determined morphometrically. Serum calcium and phosphates were monitored colorimetrically.

Results:  Serum calcium level and number of osteoclasts on parietal bone were significantly greater after infusion of rmTNF‐α above the parietal bone, whereas after subcutaneous delivery these parameters were similar to the control group.

Conclusion:  We are concluding that TNF‐α has the ability to change the bone metabolism in a paracrine manner only.
Changes in gingival crevicular fluid matrix metalloproteinase‐8 levels during periodontal treatment and maintenance
Authors: Kinane D. F. , Darby I. B. , Said S. , Luoto H. , Sorsa T. , Tikanoja S. , Mäntylä P.
Published: November 2010

Objectives:  The aim of this study was to investigate the effect of scaling and root planing (SRP) and the maintenance phase of treatment on the gingival crevicular fluid (GCF) matrix metalloproteinase‐8 (MMP‐8) levels.

Materials and methods:  Clinical measurements and GCF samples were taken from four sites in 20 adult periodontitis patients before and after SRP and during a 3‐month maintenance phase of treatment. MMP‐8 levels were measured from GCF samples by time‐resolved immunofluorometric assay (IFMA) with monoclonal antibodies.

Results:  SRP improved the clinical indices as would be predicted, 6.1 mm (SD = 1.4) at baseline compared with 4.3 mm (SD = 1.6) post‐treatment (P < 0.001). Attachment level (AL) reduced but not significantly between these two visits 13.4 mm (SD = 2.4) compared with 12.8 mm (SD = 2.4) (P < 0.08) post therapy. GCF MMP‐8 levels reduced after initial treatment from 33.8 μg/30 s sample to 23.5 μg/30 s, which just failed to reach statistical significance (P = 0.07). However, when MMP‐8 levels were expressed as a concentration, the differences following initial therapy were significant (54.1 ng/μL at baseline compared with 34.2 ng/μL post treatment; P < 0.005). The difference, however, between the baseline MMP‐8 levels (33.8 ng/30 s) and the final visit (16 ng/30 s) following maintenance was markedly significant (P < 0.001) for both absolute amounts and on a concentration basis.

Conclusion:  In conclusion, clinical improvement following SRP was associated with significant reductions in MMP‐8 levels. The GCF concentration of MMP‐8 decreased after initial therapy but reduced even more dramatically (approximately 50%) following a 3‐month period of maintenance (P < 0.001).
Lethal photosensitization of periodontal pathogens by a red‐filtered Xenon lamp in vitro
Authors: Matevski Donco , Weersink Robert , Tenenbaum Howard C. , Wilson Brian , Ellen Richard P. , Lépine Guylaine
Published: November 2010

Background:  The ability of Helium–Neon (He–Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT).

Objectives:  We investigated the potential of a conventional light source (red‐filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials.

Materials and methods:  Porphyromonas gingivalis 381 was used as the primary test bacterium.

Results:  Treatment with a 2.2 J/cm2 light dose and 50 µg/ml TBO concentration resulted in a bacterial kill of 2.43 ± 0.39 logs with the He–Ne laser control and 3.34 ± 0.24 logs with the lamp, a near 10‐fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 ± 0.68 logs kill).

Conclusions:  The data indicate that PDT utilizing a conventional light source is at least as effective as laser‐induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 µg/ml TBO.
Application of denaturing gradient gel electrophoresis (DGGE) to the analysis of microbial communities of subgingival plaque
Authors: Fujimoto C. , Maeda H. , Kokeguchi S. , Takashiba S. , Nishimura F. , Arai H. , Fukui K. , Murayama Y.
Published: November 2010

Objectives:  Denaturing gradient gel electrophoresis (DGGE) was applied to the microbiologic examination of subgingival plaque.

Materials and methods:  The PCR primers were designed from conserved nucleotide sequences on 16S ribosomal RNA gene (16SrDNA) with GC rich clamp at the 5′‐end. Polymerase chain reaction (PCR) was performed using the primers and genomic DNAs of typical periodontal bacteria. The generated 16SrDNA fragments were separated by denaturing gel.

Results:  Although the sizes of the amplified DNA fragments were almost the same among the species, 16SrDNAs of the periodontal bacteria were distinguished according to their specific sequences. The microflora of clinical plaque samples were profiled by the PCR‐DGGE method, and the dominant 16SrDNA bands were cloned and sequenced. Simultaneously, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia were detected by an ordinary PCR method. In the deep periodontal pockets, the bacterial community structures were complicated and P. gingivalis was the most dominant species, whereas the DGGE profiles were simple and Streptococcus or Neisseria species were dominant in the shallow pockets. The species‐specific PCR method revealed the presence of A. actinomycetemcomitans, P. gingivalis and P. intermedia in the clinical samples. However, corresponding bands were not always observed in the DGGE profiles, indicating a lower sensitivity of the DGGE method.

Conclusion:  Although the DGGE method may have a lower sensitivity than the ordinary PCR methods, it could visualize the bacterial qualitative compositions and reveal the major species of the plaque. The DGGE analysis and following sequencing may have the potential to be a promising bacterial examination procedure in periodontal diseases.
A systematic screen for protein–lipid interactions in Saccharomyces cerevisiae
Authors: Gallego Oriol , Betts Matthew J , Gvozdenovic‐Jeremic Jelena , Maeda Kenji , Matetzki Christian , Aguilar‐Gurrieri Carmen , Beltran‐Alvarez Pedro , Bonn Stefan , Fernández‐Tornero Carlos , Jensen Lars Juhl , Kuhn Michael , Trott Jamie , Rybin Vladimir , Müller Christoph W , Bork Peer , Kaksonen Marko , Russell Robert B , Gavin Anne‐Claude
Published: November 2010

Protein–metabolite networks are central to biological systems, but are incompletely understood. Here, we report a screen to catalog protein–lipid interactions in yeast. We used arrays of 56 metabolites to measure lipid‐binding fingerprints of 172 proteins, including 91 with predicted lipid‐binding domains. We identified 530 protein–lipid associations, the majority of which are novel. To show the data set's biological value, we studied further several novel interactions with sphingolipids, a class of conserved bioactive lipids with an elusive mode of action. Integration of live‐cell imaging suggests new cellular targets for these molecules, including several with pleckstrin homology (PH) domains. Validated interactions with Slm1, a regulator of actin polarization, show that PH domains can have unexpected lipid‐binding specificities and can act as coincidence sensors for both phosphatidylinositol phosphates and phosphorylated sphingolipids.
Three serendipitous pathways in E. coli can bypass a block in pyridoxal‐5′‐phosphate synthesis
Authors: Kim Juhan , Kershner Jamie P , Novikov Yehor , Shoemaker Richard K , Copley Shelley D
Published: November 2010

Bacterial genomes encode hundreds to thousands of enzymes, most of which are specialized for particular functions. However, most enzymes have inefficient promiscuous activities, as well, that generally serve no purpose. Promiscuous reactions can be patched together to form multistep metabolic pathways. Mutations that increase expression or activity of enzymes in such serendipitous pathways can elevate flux through the pathway to a physiologically significant level. In this study, we describe the discovery of three serendipitous pathways that allow synthesis of pyridoxal‐5′‐phosphate (PLP) in a strain of E. coli that lacks 4‐phosphoerythronate (4PE) dehydrogenase (PdxB) when one of seven different genes is overexpressed. We have characterized one of these pathways in detail. This pathway diverts material from serine biosynthesis and generates an intermediate in the normal PLP synthesis pathway downstream of the block caused by lack of PdxB. Steps in the pathway are catalyzed by a protein of unknown function, a broad‐specificity enzyme whose physiological role is unknown, and a promiscuous activity of an enzyme that normally serves another function. One step in the pathway may be non‐enzymatic.
Unraveling condition‐dependent networks of transcription factors that control metabolic pathway activity in yeast
Authors: Fendt Sarah‐Maria , Oliveira Ana Paula , Christen Stefan , Picotti Paola , Dechant Reinhard Christoph , Sauer Uwe
Published: November 2010

Which transcription factors control the distribution of metabolic fluxes under a given condition? We address this question by systematically quantifying metabolic fluxes in 119 transcription factor deletion mutants of Saccharomyces cerevisiae under five growth conditions. While most knockouts did not affect fluxes, we identified 42 condition‐dependent interactions that were mediated by a total of 23 transcription factors that control almost exclusively the cellular decision between respiration and fermentation. This relatively sparse, condition‐specific network of active metabolic control contrasts with the much larger gene regulation network inferred from expression and DNA binding data. Based on protein and transcript analyses in key mutants, we identified three enzymes in the tricarboxylic acid cycle as the key targets of this transcriptional control. For the transcription factor Gcn4, we demonstrate that this control is mediated through the PKA and Snf1 signaling cascade. The discrepancy between flux response predictions, based on the known regulatory network architecture and our functional 13C‐data, demonstrates the importance of identifying and quantifying the extent to which regulatory effectors alter cellular functions.
Coupling governs entrainment range of circadian clocks
Authors: Abraham Ute , Granada Adrián E , Westermark Pål O , Heine Markus , Kramer Achim , Herzel Hanspeter
Published: November 2010

Circadian clocks are endogenous oscillators driving daily rhythms in physiology and behavior. Synchronization of these timers to environmental light–dark cycles (‘entrainment’) is crucial for an organism's fitness. Little is known about which oscillator qualities determine entrainment, i.e., entrainment range, phase and amplitude. In a systematic theoretical and experimental study, we uncovered these qualities for circadian oscillators in the suprachiasmatic nucleus (SCN—the master clock in mammals) and the lung (a peripheral clock): (i) the ratio between stimulus (zeitgeber) strength and oscillator amplitude and (ii) the rigidity of the oscillatory system (relaxation rate upon perturbation) determine entrainment properties. Coupling among oscillators affects both qualities resulting in increased amplitude and rigidity. These principles explain our experimental findings that lung clocks entrain to extreme zeitgeber cycles, whereas SCN clocks do not. We confirmed our theoretical predictions by showing that pharmacological inhibition of coupling in the SCN leads to larger ranges of entrainment. These differences between master and the peripheral clocks suggest that coupling‐induced rigidity in the SCN filters environmental noise to create a robust circadian system.
Seasonal reproduction in a fluctuating energy environment: Insolation-driven synchronized broadcast spawning in corals
Authors: Ananthasubramaniam Bharath , Nisbet Roger , Morse Daniel , Doyle Francis
Published: November 2010

Background/Question/Methods:

Colonies of spawning corals reproduce in mass-spawning events, in which polyps within each colony release sperm and eggs for fertilization in the water column, with fertilization occurring only between gametes from different colonies. Participating colonies synchronize their gamete release to a window of a few hours once a year (for the species Acropora digitifera we study experimentally). This remarkable synchrony is essential for successful coral reproduction and thus, maintenance of the coral reef ecosystem that is currently under threat from local and global environmental effects such as pollution, global warming and ocean acidification. The mechanisms determining this tight synchrony in reproduction are not well understood, although several influences have been hypothesized and studied including lunar phase, solar insolation, and influences of temperature and tides. Moreover, most corals are in a symbiotic relationship with photosynthetic algae (Symbiodinium spp.) that live within the host tissue. Experiments supported by detailed bioenergetic modeling of the coral-algae symbiosis have shown that corals receive >90% of their energy needs from these symbionts. We develop a bioenergetic integrate-and-fire model in order to investigate whether annual insolation rhythms can entrain the gametogenetic cycles that produce mature gametes to the appropriate spawning season, since photosynthate is their primary source of energy. We solve the integrate-and-fire bioenergetic model numerically using the Fokker-Planck equation and use analytical tools such as rotation number to study entrainment.

Results/Conclusions:

In the presence of short-term fluctuations in the energy input, our model shows that a feedback regulatory mechanism is required to achieve coherence of spawning times to within one lunar cycle, in order for subsequent cues such as lunar and diurnal light cycles to unambiguously determine the “correct” night of spawning. Entrainment to the annual insolation cycle is by itself not sufficient to produce the observed coherence in spawning. The feedback mechanism can also provide robustness against population heterogeneity due to genetic and environmental effects. We also discuss how such bioenergetic, stochastic, integrate-and-fire models are also more generally applicable: for example to aquatic insect emergence, synchrony in cell division and masting in trees.
Early Transition and Rare Earth Metal Complexes with N-Heterocyclic Carbenes
Authors: Schaper Lars-Arne , Tosh Evangeline , Herrmann Wolfgang A.
Published: November 2010

This chapter gives an overview of early transition and rare earth metal complexes bearing N-heterocyclic carbene ligands. The most common synthetic routes to mono- and bimetallic complexes and thorough description of the bonding in these compounds is presented. These descriptions provide a strong basis to evaluate the compounds reactivity and catalytic activity.
Applications for Activity-based Probes in Drug Discovery
Authors: Edgington L.E. , Bogyo M.
Published: November 2010

The path to a new therapeutic drug is long and difficult and involves many stages including validation of a target, design and selection of a lead compound and finally development of the lead into a drug. This chapter will discuss a relatively new technology that makes use of small molecules termed activity based probes (ABPs). These probes bind in the active site of a target enzyme or class of enzymes in an activity dependent fashion. Thus probe labeling serves as an indirect readout of enzyme activity, allowing the dynamic regulation of the target enzyme to be monitored using a number of biochemical and cell biological methods. In addition, labeled targets can be directly isolated by affinity methods, thereby allowing identification of potentially valuable drug targets based solely on their ability to bind a small molecule. Finally, because of the high degree of selectivity of ABPs for a given target protein class, they can be used for studies of drug binding and efficacy in complex cellular mixtures, intact cells and even in whole animals. These attributes of ABPs make them extremely valuable reagents for use at multiple points in the drug discovery process.
Chemical Biology of Stem Cell Modulation
Authors: Davies Stephen G. , Russell Angela J.
Published: November 2010

Realising the enormous potential of stem cells for regenerative medicine and drug discovery is one of the next major challenges in science. Before stem cell technology can be fully realised, obstacles remain to be overcome, including the development of cost-effective, efficient and scalable culture methods. Stem cells are capable of dividing perpetually and differentiating to all tissue types in the adult body, such as bone, muscle, nerves and all organs. The transformation of a stem cell to a fully differentiated cell within adult tissue occurs via a number of steps controlled by a combination of cellular events. The use of small molecules to control the destiny of stem cells in vitro and in vivo is an emerging discipline which offers unprecedented advantages over other techniques in terms of speed, cost, reproducibility and the ability to influence stem cell fate reversibly. This chapter summarizes the current state of the art of small molecule manipulation of stem cells and outlines how these discoveries can revolutionise drug discovery.
Chemical Biology of Histone Modifications
Authors: Rose Nathan R. , Schofield Christopher J. , Heightman Tom D.
Published: November 2010

Here we review current knowledge on the enzymes and related binding proteins that are involved in covalent modifications to histones. We begin with a brief overview of the field aimed at the non-expert, then focus on the covalent modifications themselves as catalysed by specific enzymes. We also focus on the consequences of these modifications for binding interactions with other proteins that modulate gene expression. The field is one that is rapidly evolving and we hope to convey some of the excitement that we feel about recent discoveries in histone science, particularly from a molecular perspective. Two inhibitors of histone modifying enzymes are in clinical use, with more likely to be introduced in the near future. Thus, the development of modifiers of histone biochemistry is of medicinal as well as basic interest.
Antibody–Drug Conjugates in Oncology
Authors: Hamann Philip R. , Dushin Russell G.
Published: November 2010

Antibody conjugates have been the subject of active research for as long or longer than monoclonal antibodies have been available in practical quantities. The species conjugated have varied from fluorescent tags to radioisotopes, from phytotoxins such as ricin to enzymes capable of activating prodrugs, and from traditional chemotherapeutic agents to derivatives of potently cytotoxic natural products. All of these have shown some utility, whether as experimental tools or as clinically approved therapeutic or imaging agents. However, practical considerations for therapeutic applications have led to the pursuit of antibody-drug conjugates (ADCs) of potently cytotoxic natural products as the most active area of research. These ADCs will be the topic of this review, with an emphasis on the evolution of the most common ADCs currently in or approaching clinical trials.
Efficiency and efficacy of multi‐channel gastric electrical stimulation
Authors: Chen J. D. Z. , Xu X. , Zhang J. , Abo M. , Lin X. , Mccallum R. W. , Ross B.
Published: November 2010

Abstract  Gastric electrical stimulation (GES) using single channel has been under investigation for its therapeutic potential for gastroparesis. The aim of this study was to study the efficacy and efficiency of multi‐channel GES in accelerating gastric emptying in dogs. The study was performed in eight dogs, and gastric emptying of liquid was assessed in three randomized sessions of control, one‐channel GES and four‐channel GES. It was found that (i) GES of both one‐channel and four‐channel was able to completely entrain the slow waves in the entire stomach. However, the stimulation energy required by four‐channel GES was only 1% of that required by one‐channel GES. (ii) Four‐channel, but not one‐channel, GES significantly and substantially accelerated gastric emptying. An increase of 121.0 and 93.9% was noted with four‐channel GES at 30 and 60 min after the meal, respectively. It was concluded that four‐channel GES is substantially more efficient and effective than conventional single‐channel GES in improving gastric emptying. It is worthy to explore its therapeutic potential for gastroparesis in clinical settings.
108 years of change in spatial pattern following selective harvest of aPinus ponderosastand in northern Arizona, USA
Authors: Sánchez Meador A.J. , Moore M.M. , Bakker J.D. , Parysow P.F.
Published: November 2010

Questions:How did an initial tree harvest in 1894 influence the spatial and temporal patterns ofPinus ponderosarecruitment? How do these patterns compare to our understanding ofP. ponderosastand dynamics prior to Euro‐American settlement? How might spatial pattern information, particularly with respect to patch characteristics, inform current restoration and management practices?

Location:A 2.59‐ha permanent sample plot in the Fort Valley Experimental Forest, Flagstaff, Arizona. The plot was selectively harvested in 1894 and measured in 1909 and 2002.

Methods:We used historical stem‐map and ledger data, contemporary data, and dendrochronological techniques to reconstruct stand structure (tree size, age, location) in three scenarios: (1) unharvested (1909), (2) harvested (1909), and (3) contemporary (2002). We used Clark and Evans' R, Ripley'sK(t) univariate analysis, and correlogram analysis to assess the spatial pattern in each scenario. We also used Ripley'sK12(t) bivariate analysis and tree age data to examine spatial and temporal recruitment patterns as observed in the contemporary scenario.

Results and Conclusions:The unharvested stand was aggregated at scales up to 28 m. The selective harvest accentuated the spatial patchiness of the stand in 1909 and changed spatial patterns by homogenizing tree size within patches. By 2002, the stand was a single patch dominated by small trees. Post‐harvest recruitment patterns were not spatially random;Pinusseedlings initially established in natural grass openings and then proceeded to fill‐in stump patches created by harvesting. Knowledge of spatial pattern should be explicitly incorporated into restoration activities in these forests.
Mammals, agri‐environment schemes and set‐aside – what are the putative benefits?
Authors: MACDONALD D. W. , TATTERSALL F. H. , SERVICE K. M. , FIRBANK L. G. , FEBER R. E.
Published: November 2010

The impacts of agricultural intensification on farmland wildlife have been the subject of increasing concern, particularly over the last two decades. Population declines have occurred for a number of mammalian species, sometimes drastically so, and changes in farming practice are believed to be significant contributory factors.

The major policy instruments for delivering environmental benefits on farmland are agri‐environment schemes. These encourage farmers to adopt more environmentally sensitive farming practices to promote farmland biodiversity. Additionally, compulsory set‐aside, which reduces agricultural surplus, could also have positive impacts on wildlife. In this paper we consider some of the putative benefits of agri‐environment schemes and set‐aside for mammals.

We review how establishment and management options within agri‐environment schemes and set‐aside might affect habitat resources for mammals. For example, conservation headlands increase plant and invertebrate resources within the crop edge for mammals such as wood mice. Grassy field margins can support communities of smaller mammals, and hedgerows may act as important commuting and hunting routes. Their potential will depend on factors such as seed mixtures used, timing and severity of cutting, and length of time they have been in place.

At a farm level, habitat heterogeneity may be increased through organic agriculture, which is supported by some agri‐environment schemes. Studies suggest significant benefits to mammals, including wood mice and bats. However, it is increasingly recognized that effective conservation of farmland mammals must seek solutions at the landscape scale, addressing such issues as habitat connectivity between farms. One approach may be the better targeting of scheme agreements.

We suggest that agri‐environment schemes and set‐aside can contribute to the conservation of mammals on farmland. Recent policy changes are likely to have further positive impacts on farmland wildlife but appropriate mammal monitoring programmes must be developed rigorously to assess their effects.
Negative photoconductivity due to intraband transitions in GaN/AlN quantum dots
Authors: Vardi A. , Bahir G. , Schacham S. E. , Kandaswamy P. K. , Monroy E.
Published: November 2010

In-plane photoconductivity (PC) measurements in a GaN/AlN quantum dots (QDs) layer show a TM-polarized infrared (IR) peak, at 0.9 eV, and a visible-UV (vis-UV) peak, at 2.8 eV. Based on the energy and polarization dependence, the 0.9 eV is associated with the polarized S to Pz intraband transition within the QDs. The IR PC turns from positive PC (PPC) to negative PC (NPC) as temperature is raised, increasing exponentially from 50 to 300 K. Vis-UV radiation renders PPC at all temperatures. Combined with vis-UV radiation, the IR PC is negative even at low temperatures. Based on these observations, we suggest a model in which IR excited carriers in the QD layer are coupled to deep levels (DLs) in the AlN barrier and turn immobile, i.e., NPC is observed. Vis-UV radiation re-excites them into the QDs, resulting in PPC. At lower temperatures coupling into the DL becomes inefficient, thus, IR excitation results in PPC. This model was translated into rate equations. Simulations based on these rate equations reproduce well the experimental results.
High frequency asynchronous magnetic bead rotation for improved biosensors
Authors: Kinnunen Paivo , Sinn Irene , McNaughton Brandon H. , Kopelman Raoul
Published: November 2010

Biosensors with increasingly high sensitivity are crucial for probing small scale properties. The asynchronous magnetic bead rotation (AMBR) sensor is an emerging sensor platform, based on magnetically actuated rotation. Here the frequency dependence of the AMBR sensor’s sensitivity is investigated. An asynchronous rotation frequency of 145 Hz is achieved. This increased frequency will allow for a calculated detection limit of as little as a 59 nm change in bead diameter, which is a dramatic improvement over previous AMBR sensors and further enables physical and biomedical applications.