bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Jurisprudential Considerations on Supreme Court Decisionmaking: A Study of Conflict Cases
Authors: Lindquist Stefanie A. , Klein David E.
Published: February 2006

In this study, we assess the impact of attitudinal and jurisprudential factors on the Supreme Court's resolution of intercircuit conflicts. In doing so, we depart from earlier efforts to assess the impact of legal factors that conceptualize law as an external constraint. Instead, we view jurisprudential considerations in terms of the justices' efforts to adopt the most legally persuasive position in light of accepted methods of legal reasoning. Our analyses reveal that the justices are (1) more likely to follow the reasoning process adopted by the majority of circuits involved in the conflict, (2) less likely to adopt the conflict position marred by contrary dissents and concurrences in the circuit court opinions, and (3) more likely to adopt the conflict position endorsed by prestigious circuit court judges. Our findings suggest that jurisprudential considerations, as well as attitudinal concerns, affect the justices' decisionmaking processes in a substantial minority of cases.
Honor and Dignity in the Film Unforgiven: Implications for Sociolegal Theory
Authors: Kamir Orit
Published: February 2006

This article calls attention to “honor” and “dignity” as two fundamental, antithetical bases of unique value systems, both highly significant to social orders and legal systems in the contemporary Western world. The article argues that in this comparative context, the relatively new dignity-based value system may be better defined and articulated; at the same time, the overlooked, traditional honor-based value system, which underlies much of contemporary reality, can be better identified and replaced or at least modified by a dignity-based one. Rather than look to specific sociolegal realities, the article presents this line of thought from a “law-and-film” perspective, i.e., through the close reading of a single feature film: Clint Eastwood's Unforgiven. This contemporary, widely familiar, and immensely popular Western exposes the ugly face of the honor-based value system at the heart of the Western film genre; further, it subversively undermines this value system, replacing it with a dignity-based one. In so doing, the film expresses deep faith in the human capacity to transform, calling on real-world social and legal systems to follow in its footsteps and apply the same critical analysis and reformative activism to Western law and society at large.
Colour Doppler examination of early and late orbital haemodynamic changes in eyes with eyelid oedema due to blunt trauma
Authors: Alp Mehmet Numan , Aksay Sevinç , Tola Muharrem , Ataseven Musa , Ölçer Tülay , Kural Gülcan
Published: February 2006

Purpose:  To evaluate the early and late alterations in orbital blood flow parameters in eyes with severe eyelid swelling due to blunt trauma by using colour Doppler ultrasonography (CDU).

Methods:  Blood flow parameters in the ophthalmic artery (OA), central retinal artery (CRA), short posterior ciliary arteries (SPCAs) and central retinal vein (CRV) were examined by CDU in 62 eyes of 31 patients with unilateral blunt trauma and in 32 eyes of 32 normal subjects. Patients were examined within the first 5 days and at least 1 month after trauma. The traumatized eyes of patients were designated ‘trauma eyes’, non‐traumatized fellow eyes were designated ‘fellow eyes’, and randomly chosen eyes of control subjects ‘control eyes’.

Results:  In the early phase, peak systolic velocity (PSV) and end diastolic velocity (EDV) in the OA in trauma eyes were statistically significantly higher than in both fellow eyes and control eyes: the p‐values for the differences in PSV and EDV between trauma eyes and fellow eyes were p < 0.001 and p = 0.001, respectively, while the p‐values for the differences in PSV and EDV between trauma eyes and control eyes were p = 0.002 and p = 0.019, respectively). No other blood flow parameters obtained at the first examination in all groups were statistically different. In the late phase, PSV in the OA in trauma eyes was found to be higher than that in both fellow eyes and control eyes, but the difference was significant only between trauma eyes and fellow eyes (p = 0.028). End diastolic velocity in the CRA was statistically significantly lower in fellow eyes than in control eyes (p = 0.046). No other blood flow parameters in any vessels examined in fellow eyes and control eyes were statistically significantly different during the study period.

Conclusion:  Blood flow velocities detected by CDU are increased in the OA in eyes with eyelid oedema due to blunt trauma and some of these changes may persist for up to 1 month. This effect seems to be a consequence of trauma‐induced hyperaemia in the orbital soft tissues rather than an expression of traumatic choroidal vasculopathy.
Correction of involutional lower eyelid medial ectropion with transconjunctival approach retractor plication and lateral tarsal strip
Authors: Fong Kenneth C. S. , Mavrikakis Ioannis , Sagili Suresh , Malhotra Raman
Published: February 2006

Aim:  We describe the technique and our results in managing lower eyelid involutional medial ectropion using a combination of lateral tarsal strip to address horizontal eyelid laxity, and transconjunctival inferior retractor plication to address inferior retractor dehiscence.

Methods:  Patients with symptoms of epiphora or signs of medial ectropion were offered this procedure. All had the following characteristics: medial lower eyelid eversion, punctal eversion >3 mm, medial canthal tendon laxity <4 mm, significant horizontal eyelid laxity and lacrimal systems that were patent to syringing.

Results:  A total of 24 eyelids of 17 patients underwent this procedure over a 12‐month period. The mean age of the patients was 79.7 years; 11 were male and six were female. The mean follow‐up time was 18 months. Two eyes had undergone previous surgery. All patients had restoration of the eyelid margin to the globe and relief of symptoms. No complications were noted.

Discussion:  These results suggest that excision of posterior lamellar tissue is not necessary for correction of involutional medial ectropion. Transconjunctival plication or reattachment of retractors is easy to perform and allows for the repair of more than the medial portion of the retractors if required.
Gestational trophoblastic neoplasia
Authors: GHAEMMAGHAMI Fatemeh , ASHRAF‐GANJOOIE Tahereh
Published: February 2006

Gestational trophoblastic neoplasia (GTN) is one of the most curable malignancies because of the intrinsic sensitivity of the tumor to certain antineoplastic agents, effective sensitive assays for human chorionic gonadotropin (hCG), and identification of high‐risk factors that permit individualized treatment. Chemotherapy is the main modality of treatment in patients with GTN. The cure rate in patients with low‐risk GTN is 100%, and is estimated to exceed 80% in patients with high‐risk GTN. Management of GTN is based on staging (anatomical involvement staging) and scoring. Patients with persistent GTN and stage I or score ≤ 6 (low risk) should be managed with single agent chemotherapy (methotraxate or actinomycin), but patients with stage IV or score ≥ 7 (high risk) need combination chemotherapy. Gestational trophoblastic neoplasia is radiosensitive, because radiation has hemostatic and tumorocidal effect on GTN. Therefore, radiotherapy can be used in treatment of some patients with brain hepatic metastasis or in patients where chemotherapy is not possible due to medical problems. Surgery can be used in patients who are resistant to chemotherapy or in hemorrhagic cases. Surgical resection of the tumor is the main form of therapy for placental site trophoblastic tumor. This surgery consists of a hysterectomy for the majority of patients as the disease is confined to the uterus.
Carcinosarcoma of the uterus: A comparison of adjuvant therapy and outcome
Authors: WONG Lisa , SEE Hui Ti , KHOO‐TAN Hoon Seng , LOW John , FOOK‐CHONG Stephanie , LOW Jeffrey , TAY Sun Kuie
Published: February 2006

Background:  Uterine carcinosarcoma are rare and aggressive tumors. There is no consensus on the appropriate adjuvant therapy. Our aim is to compare the clinical outcome and role of adjuvant chemotherapy and radiotherapy in women with uterine carcinosarcoma.

Methods:  A retrospective review was carried out from 1995 to 2004 to obtain data on overall and disease‐free survival. The Kaplan‐Meier method and the log rank test was used to compare the survival by treatment given and the Cox proportional hazard regression model was used to adjust for age and stage.

Results:  Sixty‐six patients were identified. The median age was 60 years. 4 women did not undergo surgical staging and they were excluded. 32 (52%) patients received adjuvant chemotherapy with a combination of paclitaxel and carboplatin or cisplatin and ifosfamide. 36 (58%) patients received adjuvant radiotherapy. 23 patients (35%) had combined adjuvant chemotherapy and radiotherapy. Using the Cox regression model to adjust for age and stage of disease, patients who received multimodality treatment had improved survival compared to patients who had surgery only. (P = 0.001, HR = 9.0, 90% C.I. = 3.2, 25.4). Tumour recurrence occurred in 23 patients at a median duration of 10 months. The median survival was 53 months. The overall 5‐year survival was 53.2%.

Conclusion:  Surgery remains the mainstay of treatment for carcinosarcoma of the uterus. Our results suggest that patients who had multimodality adjuvant therapy with chemotherapy and radiotherapy had improved survival. Future treatment strategies should incorporate multimodality adjuvant chemotherapy and radiotherapy to provide local as well as distant control.
Are Emotions Natural Kinds?
Authors: Barrett Lisa Feldman
Published: February 2006

Laypeople and scientists alike believe that they know anger, or sadness, or fear, when they see it. These emotions and a few others are presumed to have specific causal mechanisms in the brain and properties that are observable (on the face, in the voice, in the body, or in experience)—that is, they are assumed to be natural kinds. If a given emotion is a natural kind and can be identified objectively, then it is possible to make discoveries about that emotion. Indeed, the scientific study of emotion is founded on this assumption. In this article, I review the accumulating empirical evidence that is inconsistent with the view that there are kinds of emotion with boundaries that are carved in nature. I then consider what moving beyond a natural-kind view might mean for the scientific understanding of emotion.
Mental Exercise and Mental Aging
Authors: Salthouse Timothy A.
Published: February 2006

It is widely believed that keeping mentally active will prevent age-related mental decline. The primary prediction of this mental-exercise hypothesis is that the rate of age-related decline in measures of cognitive functioning will be less pronounced for people who are more mentally active, or, equivalently, that the cognitive differences among people who vary in level of mental activity will be greater with increased age. Although many training studies, and comparisons involving experts, people in specific occupations, and people whose mental activity levels are determined by their self-reports, have found a positive relation between level of activity and level of cognitive functioning, very few studies have found an interactive effect of age and mental activity on measures of cognitive functioning. Despite the current lack of empirical evidence for the idea that the rate of mental aging is moderated by amount of mental activity, there may be personal benefits to assuming that the mental-exercise hypothesis is true.
Do Cognitive Changes Accompany Developments in the Adolescent Brain?
Authors: Kuhn Deanna
Published: February 2006

The news that the brain continues to develop through much of adolescence risks becoming an explanation for anything and everything about teenagers and suggests the need for closer analysis. Central to such analysis is clarifying what develops at a psychological level during these years. An examination of contemporary research data on adolescent cognitive development identifies increased executive control as a major dimension of cognitive development during the second decade of life. Such development is consistent with changes occurring in the brain during this period.
Experimental studies on air entrainment and oxygen content downstream of sharp‐crested weirs
Authors: Baylar Ahmet , Bagatur Tamer
Published: February 2006

The concentration of dissolved oxygen (DO) is an important indicator of water quality because aquatic life survives on the DO in water. A free overfall jet from a weir plunging into downstream water causes entrainment of air bubbles if the free overfall jet velocity exceeds a certain critical value and hence aeration occurs. This paper investigates the free overfall jets from sharp‐crested weirs and their effect on air entrainment and aeration efficiency. The results indicate that the air entrainment and aeration efficiency of triangular sharp‐crested weirs are significantly better than those for the other sharp‐crested weir types. Therefore, the triangular sharp‐crested weirs can be used as highly effective aerators in streams, rivers, constructed channels, fish hatcheries, water treatment plants, etc. Regression equations were obtained for the triangular sharp‐crested weirs relating air entrainment rate and aeration efficiency to drop height, discharge and angle in the triangular sharp‐crested weir. There was good agreement between the measured values and the values computed from the predictive equations.
GRW: A Case Study in Quantum Ontology
Authors: Lewis Peter J.
Published: February 2006

This article provides an overview of the philosophical literature on the GRW theory of quantum mechanics, and argues for a particular position regarding that literature. Much of the literature is ontological; it attempts to defend a conception of what the world is like according to the GRW theory against perceived competitors. I argue that there is no real debate here, since these supposedly conflicting positions are better regarded as alternative and compatible ways of describing the world of the GRW theory.
Grazing lawns contribute to the subsistence of mesoherbivores on dystrophic savannas
Authors: J. T. Verweij Richard , Verrelst Jochem , Loth Paul E. , M. A. Heitkönig Ignas , M. H. Brunsting Arend
Published: February 2006

Resource manipulation, such as the creation and maintenance of grazing lawns, may shape the structure of herbivore communities. We tested the hypothesis that grazing lawns contribute towards the subsistence of the Kobus kob kob in a dystrophic West African savanna, where kob and Hippopotamus amphibius both occur. Comparison of the foliage of grazing lawns and ungrazed swards shows that hippo lawns are more nutritious with regard to both structure and nutrients; kob lawns are higher in nutrients only. Up to the early dry season, hippo lawns meet kob energy and protein demand, thereafter, the shortness of the sward limits intake. Kob lawns always provide sub‐maintenance values. Grazing on ungrazed swards is least profitable. We suggest that grazing lawns are essential for the daily subsistence of mesoherbivores, particularly on nutrient‐poor soil, and that megaherbivores facilitate their food supply, for at least part of the year.
Sex biases in dispersal and philopatry: insights from a meta‐analysis based on capture–mark–recapture studies of damselflies
Authors: Beirinckx Kirsten , Van Gossum Hans , J. Lajeunesse Marc , R. Forbes Mark
Published: February 2006

Sex‐biased dispersal is well known for birds and mammals, typically by females and males, respectively. Little is known about general patterns of sex‐biased dispersal in other animal taxa. We reviewed return rates for a model group of invertebrates (damselflies) and explored putative costs and benefits of dispersal by males and females. We used published capture–mark–recapture data and examined whether a sex bias existed in likelihood of recapture at least once, at both emergence and/or breeding sites. We assessed whether this metric of likelihood of recapture was indicative of dispersal or philopatry, and whether any emerging pattern(s) were consistent across damselfly families. Using a meta‐analysis, we found a higher likelihood of recapture at least once for males than for females at both natal sites and breeding sites, which seemed attributable to higher female‐biased dispersal, although female‐biased mortality cannot be discounted particularly for some species. Sex biases in dispersal among damselflies may be understood based on sex differences in maturation rate and foraging behaviour, both of which should affect the costs and benefits of dispersing. This hypothesis may be useful for explaining patterns of dispersal in other animal taxa.
Community modification by a grass invader has differing impacts for marine habitats
Authors: D. Hacker Sally , N. Dethier Megan
Published: February 2006

There is increasing recognition of invasive species impacts but less is known about how modifications may differ under variable environmental contexts. In particular, it is generally unknown whether impacts of single invasive species can vary among habitats and what the consequences of this variability may be. We used a multi‐site comparative approach to examine the impacts of a single invader, the marine grass Spartina anglica, on estuarine habitats with different native species assemblages and physical conditions. We found that range (extent), abundance, and effects on sediment and native plant species vary depending on the habitat invaded. S. anglica has by far the greatest range and abundance in mudflats and low salinity marshes compared to high salinity marshes and cobble beaches. Changes in sediment characteristics also substantially differed among habitats, with invaded areas in some habitats experiencing greater sediment accretion, water content, and salinity than other habitats. In addition, in opposition to the theory that strong invaders decrease species diversity, we found that native plant diversity in our plots increased within invaded areas in some habitats while it declined in others. These variable modifications suggest that single invaders, even species that are considered strong interactors, do not produce the same effect in all habitats. We suggest that understanding impact variability can help predict how invasive species will respond to environmental changes, new habitats, and management strategies.
Influence of marine‐derived nutrients from spawning salmon on aquatic insect communities in southeast Alaskan streams
Authors: Lessard JoAnna L. , Merritt Richard W.
Published: February 2006

The objective of this study was to evaluate the influence of the nutrient transfer system between anadromous salmon and aquatic insect communities across multiple, natural stream systems. Between 2000 and 2002, we sampled seven streams in southeast Alaska, seasonally. Of the seven study streams, four received large annual salmon runs (high‐run streams), and three were no‐run streams. All the streams selected had a natural waterfall barrier to salmon, providing an upstream control reach for each study stream. Insect density, biomass, richness, diversity and functional feeding groups were analyzed before, during and after the fall salmon run in each stream section (i.e. above and below the barrier) of the seven study streams between 2001 and 2002. Results showed that diversity and richness were similar across stream sections and run size within each period, except for during the run when both were significantly lower in downstream sections of high‐run streams. Functional feeding group patterns showed higher abundance and biomass of collector–gatherers and shredders during the post spawning, carcass decomposition period. High‐run streams had upstream sections with greater abundance and biomass of mayflies (dominated by Baetidae, Heptageniidae and Ephemerellidae) during the run, and downstream sections with greater abundance and biomass of dipterans (dominated by Chironomidae). This study suggests that the often published positive relationship between MDN and stream insect abundance and biomass may only exist for certain taxa, primarily chironomid midges.
Food web complexity affects stoichiometric and trophic interactions
Authors: Liess Antonia , Olsson Jens , Quevedo Mario , Eklöv Peter , Vrede Tobias , Hillebrand Helmut
Published: February 2006

The stoichiometry of trophic interactions has mainly been studied in simple consumer–prey systems, whereas natural systems often harbour complex food webs with abundant indirect effects. We manipulated the complexity of trophic interactions by using simple laboratory food webs and complex field food webs in enclosures in Lake Erken. In the simple food web, one producer assemblage (periphyton) and its consumers (benthic snails) were amended by perch, which was externally fed by fish food. In the complex food web, two producer assemblages (periphyton and phytoplankton), their consumers (benthic invertebrates and zooplankton) and perch feeding on zooplankton were included. In the simple food web perch affected the stoichiometry of periphyton and increased periphyton biomass and the concentration of dissolved inorganic nitrogen. Grazers reduced periphyton biomass but increased its nutrient content. In the complex food web, in contrast to the simple food web, perch affected periphyton biomass negatively but increased phytoplankton abundance. Perch had no influence on benthic invertebrate density, zooplankton biomass or periphyton stoichiometry. Benthic grazers reduced periphyton biomass and nutrient content. The difference between the simple and the complex food web was presumably due to the increase of pelagic cyanobacteria (Gloeotrichia sp.) with fish presence in the complex food web, thus fish had indirect negative effects on periphyton biomass through nutrient competition and shading by cyanobacteria. We conclude that the higher food web complexity through the presence of pelagic primary producers (in this case Gloeotrichia sp.) influences the direction and strength of trophic and stoichiometric interactions.
Empirical evaluation of observation scale effects in community time series
Authors: Hampton Stephanie E. , Schindler Daniel E.
Published: February 2006

Natural communities are highly complex and dynamic over time, with populations structured by numerous abiotic and biotic forces acting through direct and indirect pathways. Multispecies Autoregressive (MAR) modeling can be used to partition effects of variables that are interrelated and temporally autocorrelated in time series from natural systems. Here we address two main questions in applying MAR models to community time series. First, what is the effect of observation scale on interpretation of community dynamics? We used a 10‐year weekly planktonic time series from Lake Washington to construct multiple “biweekly” and “monthly” data sets, and compared resulting community interaction models. Direct abiotic effects and intraspecific autocorrelation were apparent using all data sets. Biotic interactions were more apparent using biweekly and monthly data, indicating that time lags longer than one week were necessary to detect numerical response to interspecific interactions. Second, we examined effects of dropping the winter months from our analyses to simulate the common practice of sampling only during the “growing season” in long‐term ecological studies. We found that biotic interactions remained similarly characterized in models using only non‐winter months, but that the importance of seasonal physical factors nearly disappeared in non‐winter models. Exclusion of winter data in sampling designs may therefore allow us to characterize biotic interactions, although it may not help us understand populations’ relationships to seasonal abiotic variables. The models supported many previous findings from experimental and qualitative investigations of Lake Washington community interactions, implying that MARs provided plausible characterizations of community dynamics, but some previously unconsidered relationships did emerge, such as the importance of cryptomonads and picoplankton for zooplankton growth. We conclude that explicit consideration of time lags in biotic response is necessary to understand relative importance of abiotic and biotic factors, and that sampling regime can therefore strongly influence our interpretations of community dynamics.
Morphological variation does not influence locomotor performance within a cohort of hatchling lizards (Amphibolurus muricatus, Agamidae)
Authors: A. Warner Daniel. , Shine Richard
Published: February 2006

A causal link between morphology and performance is a central tenet of ecomorphological analyses, but there are few detailed analyses of exactly how morphological variation within a hatchling cohort maps onto locomotor performance, and especially whether or not different tasks favour different morphologies (or vice versa). We measured morphological traits (including body length, mass, head size, limb proportions and fluctuating asymmetry [FA]) on a large sample of laboratory‐incubated hatchling lizards (Amphibolurus muricatus, Agamidae), and used principal component analysis to reduce this data set to four major axes of variation (size, shape and two FA axes). Running speeds of each lizard were measured on raceways at four inclines, from level (0°) through to steep (45°). Unsurprisingly, steeper inclines reduced locomotor speeds. Absolute body size was the only morphological trait that was consistently related to sprinting performance, and the relationships were similar at each incline. Within‐cohort variation in body shape and FA among this large sample was unrelated to locomotor speeds, thus challenging the common assumption of a causal link between these variables. The only exception was a weak trend for greater hind limb length to enhance locomotor performance more at steep inclines than at shallower angles. In general, our data suggest that different morphological traits do not differentially maximize locomotor performance up variable inclines. Overall, our data provide a cautionary note about the generality of causal connections between within‐cohort morphological variation and locomotor performance under different environmental contexts.
Green’s Function for a Closed, Infinite, Circular Cylindrical Elastic Shell
Authors: Simmonds J. G.
Published: February 2006

An acceptable variant of the Koiter–Morley equations for an elastically isotropic circular cylindrical shell is replaced by a constant coefficient fourth-order partial differential equation for a complex-valued displacement-stress function. An approximate formal solution for the associated “free-space” Green’s function (i.e., the Green’s function for a closed, infinite shell) is derived using an inner and outer expansion. The point wise error in this solution is shown rigorously to be of relative order (h∕a)(1+h∕a∣x∣), where h is the constant thickness of the shell, a is the radius of the mid surface, and ax is distance along a generator of the mid surface.
Surface Stress and Reversing Size Effect in the Initial Yielding of Ultrathin Films
Authors: Gioia G. , Dai X.
Published: February 2006

Very recent experiments indicate that in free-standing metallic films of constant grain size the initial yield stress increases as the film becomes thinner, it peaks for a thickness on the order of 100nm, and then starts to decrease. This reversing size effect poses two challenges: (1) It cannot be explained using currently available models and (2) it appears to contradict the classical experimental results due to J. W. Beams [1959, “Mechanical Properties of Thin Films of Gold and Silver,” in Structure and Properties of Thin Films, Wiley, New York, pp. 183–198]. Here we show that the reversing size effect can be explained and the contradiction dispelled by taking into account how the initial yielding is affected by the surface stress. We also predict that the mode of failure of a film changes from ductile to brittle for a thickness on the order of 100nm, in accord with experiments.
An Energy Balance Criterion for Nanoindentation-Induced Single and Multiple Dislocation Events
Authors: Gerberich William W. , Mook W. M. , Chambers M. D. , Cordill M. J. , Perrey C. R. , Carter C. B. , Miller R. E. , Curtin W. A. , Mukherjee R. , Girshick S. L.
Published: February 2006

Small volume deformation can produce two types of plastic instability events. The first involves dislocation nucleation as a dislocation by dislocation event and occurs in nanoparticles or bulk single crystals deformed by atomic force microscopy or small nanoindenter forces. For the second instability event, this involves larger scale nanocontacts into single crystals or their films wherein multiple dislocations cooperate to form a large displacement excursion or load drop. With dislocation work, surface work, and stored elastic energy, one can account for the energy expended in both single and multiple dislocation events. This leads to an energy balance criterion which can model both the displacement excursion and load drop in either constant load or fixed displacement experiments. Nanoindentation of Fe-3% Si (100) crystals with various oxide film thicknesses supports the proposed approach.
Transitions to Asexuality Result in Excess Amino Acid Substitutions
Authors: Paland Susanne , Lynch Michael
Published: February 2006

Theory predicts that linkage between genetic loci reduces the efficiency of purifying selection. Because of the permanent linkage of all heritable genetic material, asexual lineages may be exceptionally prone to deleterious-mutation accumulation in both nuclear and organelle genes. Here, we show that the ratio of the rate of amino acid to silent substitution (
K
a
/
K
s
) in mitochondrial protein-coding genes is higher in obligately asexual lineages than in sexual lineages of the microcrustacean
Daphnia pulex
. Using a phylogeny-based approach to quantify the frequency of mutational-effect classes, we estimate that mitochondrial protein-coding genes in asexual lineages accumulate deleterious amino acid substitutions at four times the rate in sexual lineages. These results support the hypothesis that sexual reproduction plays a prominent role in reducing the mutational burden in populations.
X-ray Structure of a Self-Compartmentalizing Sulfur Cycle Metalloenzyme
Authors: Urich Tim , Gomes Cláudio M. , Kletzin Arnulf , Frazão Carlos
Published: February 2006

Numerous microorganisms oxidize sulfur for energy conservation and contribute to the global biogeochemical sulfur cycle. We have determined the 1.7 angstrom–resolution structure of the sulfur oxygenase reductase from the thermoacidophilic archaeon
Acidianus ambivalens
, which catalyzes an oxygen-dependent disproportionation of elemental sulfur. Twenty-four monomers form a large hollow sphere enclosing a positively charged nanocompartment. Apolar channels provide access for linear sulfur species. A cysteine persulfide and a low-potential mononuclear non-heme iron site ligated by a 2-His-1-carboxylate facial triad in a pocket of each subunit constitute the active sites, accessible from the inside of the sphere. The iron is likely the site of both sulfur oxidation and sulfur reduction.
RETRACTED:
Cdx2
Gene Expression and Trophectoderm Lineage Specification in Mouse Embryos
Authors: Deb Kaushik , Sivaguru Mayandi , Yong Hwan Yul , Roberts R. Michael
Published: February 2006

Controversy exists as to whether individual blastomeres from two-cell-stage mouse embryos have identical developmental properties and fate. We show that the transcription factor Cdx2 is expressed in the nuclei of cells derived from the late-dividing but not the first-dividing blastomere of two-cell embryos and, by lineage tracing and RNA interference knock-down experiments, that this lagging cell is the precursor of trophectoderm.
Cdx2
mRNA is localized toward the vegetal pole of oocytes, reorients after fertilization, and becomes concentrated in the late-dividing, two-cell-stage blastomere. The asymmetrical distribution of
Cdx2
gene products in the oocyte and embryo defines the lineage to trophectoderm.
Changes in the Velocity Structure of the Greenland Ice Sheet
Authors: Rignot Eric , Kanagaratnam Pannir
Published: February 2006

Using satellite radar interferometry observations of Greenland, we detected widespread glacier acceleration below 66° north between 1996 and 2000, which rapidly expanded to 70° north in 2005. Accelerated ice discharge in the west and particularly in the east doubled the ice sheet mass deficit in the last decade from 90 to 220 cubic kilometers per year. As more glaciers accelerate farther north, the contribution of Greenland to sea-level rise will continue to increase.
On Making the Right Choice: The Deliberation-Without-Attention Effect
Authors: Dijksterhuis Ap , Bos Maarten W. , Nordgren Loran F. , van Baaren Rick B.
Published: February 2006

Contrary to conventional wisdom, it is not always advantageous to engage in thorough conscious deliberation before choosing. On the basis of recent insights into the characteristics of conscious and unconscious thought, we tested the hypothesis that simple choices (such as between different towels or different sets of oven mitts) indeed produce better results after conscious thought, but that choices in complex matters (such as between different houses or different cars) should be left to unconscious thought. Named the “deliberation-without-attention” hypothesis, it was confirmed in four studies on consumer choice, both in the laboratory as well as among actual shoppers, that purchases of complex products were viewed more favorably when decisions had been made in the absence of attentive deliberation.
Plasma Acceleration Above Martian Magnetic Anomalies
Authors: Lundin R. , Winningham D. , Barabash S. , Frahm R. , Holmström M. , Sauvaud J.-A. , Fedorov A. , Asamura K. , Coates A. J. , Soobiah Y. , Hsieh K. C. , Grande M. , Koskinen H. , Kallio E. , Kozyra J. , Woch J. , Fraenz M. , Brain D. , Luhmann J. , McKenna-Lawler S. , Orsini R. S. , Brandt P. , Wurz P.
Published: February 2006

Auroras are caused by accelerated charged particles precipitating along magnetic field lines into a planetary atmosphere, the auroral brightness being roughly proportional to the precipitating particle energy flux. The Analyzer of Space Plasma and Energetic Atoms experiment on the Mars Express spacecraft has made a detailed study of acceleration processes on the nightside of Mars. We observed accelerated electrons and ions in the deep nightside high-altitude region of Mars that map geographically to interface/cleft regions associated with martian crustal magnetization regions. By integrating electron and ion acceleration energy down to the upper atmosphere, we saw energy fluxes in the range of 1 to 50 milliwatts per square meter per second. These conditions are similar to those producing bright discrete auroras above Earth. Discrete auroras at Mars are therefore expected to be associated with plasma acceleration in diverging magnetic flux tubes above crustal magnetization regions, the auroras being distributed geographically in a complex pattern by the many multipole magnetic field lines extending into space.
Electrodes with High Power and High Capacity for Rechargeable Lithium Batteries
Authors: Kang Kisuk , Meng Ying Shirley , Bréger Julien , Grey Clare P. , Ceder Gerbrand
Published: February 2006

New applications such as hybrid electric vehicles and power backup require rechargeable batteries that combine high energy density with high charge and discharge rate capability. Using ab initio computational modeling, we identified useful strategies to design higher rate battery electrodes and tested them on lithium nickel manganese oxide [Li(Ni
0.5
Mn
0.5
)O
2
], a safe, inexpensive material that has been thought to have poor intrinsic rate capability. By modifying its crystal structure, we obtained unexpectedly high rate-capability, considerably better than lithium cobalt oxide (LiCoO
2
), the current battery electrode material of choice.
SCH 503034, a Mechanism-Based Inhibitor of Hepatitis C Virus NS3 Protease, Suppresses Polyprotein Maturation and Enhances the Antiviral Activity of Alpha Interferon in Replicon Cells
Authors: Malcolm B. A. , Liu R. , Lahser F. , Agrawal S. , Belanger B. , Butkiewicz N. , Chase R. , Gheyas F. , Hart A. , Hesk D. , Ingravallo P. , Jiang C. , Kong R. , Lu J. , Pichardo J. , Prongay A. , Skelton A. , Tong X. , Venkatraman S. , Xia E. , Girijavallabhan V. , Njoroge F. G.
Published: February 2006

Cleavage of the hepatitis C virus (HCV) polyprotein by the viral NS3 protease releases functional viral proteins essential for viral replication. Recent studies by Foy and coworkers strongly suggest that NS3-mediated cleavage of host factors may abrogate cellular response to alpha interferon (IFN-α) (E. Foy, K. Li, R. Sumpter, Jr., Y.-M. Loo, C. L. Johnson, C. Wang, P. M. Fish, M. Yoneyama, T. Fujita, S. M. Lemon, and M. Gale, Jr., Proc. Natl. Acad. Sci. USA102:2986-2991, 2005, and E. Foy, K. Li, C. Wang, R. Sumpter, Jr., M. Ikeda, S. M. Lemon, and M. Gale, Jr., Science300:1145-1148, 2003). Blockage of NS3 protease activity therefore is expected to inhibit HCV replication by both direct suppression of viral protein production as well as by restoring host responsiveness to IFN. Using structure-assisted design, a ketoamide inhibitor, SCH 503034, was generated which demonstrated potent (overall inhibition constant, 14 nM) time-dependent inhibition of the NS3 protease in cell-free enzyme assays as well as robust in vitro activity in the HCV replicon system, as monitored by immunofluorescence and real-time PCR analysis. Continuous exposure of replicon-bearing cell lines to six times the 90% effective concentration of SCH 503034 for 15 days resulted in a greater than 4-log reduction in replicon RNA. The combination of SCH 503034 with IFN was more effective in suppressing replicon synthesis than either compound alone, supporting the suggestion of Foy and coworkers that combinations of IFN with protease inhibitors would lead to enhanced therapeutic efficacy.
Susceptibility of
Cryptococcus neoformans
Biofilms to Antifungal Agents In Vitro
Authors: Martinez Luis R. , Casadevall Arturo
Published: February 2006

Microbial biofilms contribute to virulence and resistance to antibiotics by shielding microbial cells from host defenses and antimicrobial drugs, respectively.
Cryptococcus neoformans
was demonstrated to form biofilms in polystyrene microtiter plates. The numbers of CFU of disaggregated biofilms, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2
H
-tetrazolium hydroxide reduction, and light and confocal microscopy were used to measure the fungal mass, the metabolic activity, and the appearance of
C. neoformans
biofilms, respectively. Biofilm development by
C. neoformans
followed a standard sequence of events: fungal surface attachment, microcolony formation, and matrix production. The susceptibilities of
C. neoformans
cells of the biofilm and planktonic phenotypes to four antifungal agents were examined. The exposure of
C. neoformans
cells or preformed cryptococcal biofilms to fluconazole or voriconazole did not result in yeast growth inhibition and did not affect the metabolic activities of the biofilms, respectively. In contrast, both
C. neoformans
cells and preformed biofilms were susceptible to amphotericin B and caspofungin. However,
C. neoformans
biofilms were significantly more resistant to amphotericin B and caspofungin than planktonic cells, and their susceptibilities to these drugs were further reduced if cryptococcal cells contained melanin. A spot enzyme-linked immunosorbent assay and light and confocal microscopy were used to investigate how antifungal drugs affected
C. neoformans
biofilm formation. The mechanism by which amphotericin B and caspofungin interfered with
C. neoformans
biofilm formation involved capsular polysaccharide release and adherence. Our results suggest that biofilm formation may diminish the efficacies of some antifungal drugs during cryptococcal infection.
Potent Antiscrapie Activities of Degenerate Phosphorothioate Oligonucleotides
Authors: Kocisko David A. , Vaillant Andrew , Lee Kil Sun , Arnold Kevin M. , Bertholet Nadine , Race Richard E. , Olsen Emily A. , Juteau Jean-Marc , Caughey Byron
Published: February 2006

Although transmissible spongiform encephalopathies (TSEs) are incurable, a key therapeutic approach is prevention of conversion of the normal, protease-sensitive form of prion protein (PrP-sen) to the disease-specific protease-resistant form of prion protein (PrP-res). Here degenerate phosphorothioate oligonucleotides (PS-ONs) are introduced as low-nM PrP-res conversion inhibitors with strong antiscrapie activities in vivo. Comparisons of various PS-ON analogs indicated that hydrophobicity and size were important, while base composition was only minimally influential. PS-ONs bound avidly to PrP-sen but could be displaced by sulfated glycan PrP-res inhibitors, indicating the presence of overlapping binding sites. Labeled PS-ONs also bound to PrP-sen on live cells and were internalized. This binding likely accounts for the antiscrapie activity. Prophylactic PS-ON treatments more than tripled scrapie survival periods in mice. Survival times also increased when PS-ONs were mixed with scrapie brain inoculum. With these antiscrapie activities and their much lower anticoagulant activities than that of pentosan polysulfate, degenerate PS-ONs are attractive new compounds for the treatment of TSEs.
Mefloquine Induces Dose-Related Neurological Effects in a Rat Model
Authors: Dow G. , Bauman R. , Caridha D. , Cabezas M. , Du F. , Gomez-Lobo R. , Park M. , Smith K. , Cannard K.
Published: February 2006

Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis. Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine.
Inactivation of Herpes Simplex Virus Clinical Isolates by Using a Combination Microbicide
Authors: Isaacs Charles E. , Rohan Lisa , Xu Weimin , Jia Jun Hua , Mietzner Timothy , Hillier Sharon
Published: February 2006

A combination microbicide using the lipid-ether 1-0-octyl-sn-glycerol (OG) (3 mM) and peptide LSA5 (9 μM) synergistically inactivated six clinical isolates of herpes simplex virus type 2 (HSV-2) by 30- to 100-fold and five of six HSV-1 isolates by 10-fold more than the sum of OG and LSA5 used individually within 30 min. OG plus LSA5 inactivated all HSV clinical isolates by ≥1,000-fold in 10 to 40 min.
Medium Plays a Role in Determining Expression of
acrB
,
marA
, and
soxS
in
Escherichia coli
Authors: Bailey Andrew M. , Webber Mark A. , Piddock Laura J. V.
Published: February 2006

Analysis of expression of
acrB
,
marA
, and
soxS
in rich and minimal media, at early and late logarithmic growth phases, showed that
acrB
had increased expression in minimal medium compared to rich medium, but expression decreased dose dependently upon exposure to ciprofloxacin.
Correlation between Reduced Daptomycin Susceptibility and Vancomycin Resistance in Vancomycin-Intermediate
Staphylococcus aureus
Authors: Cui Longzhu , Tominaga Eiji , Neoh Hui-min , Hiramatsu Keiichi
Published: February 2006

We present here findings of a strong positive correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate
Staphylococcus aureus
(VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with vancomycin resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin resistance in
S. aureus
.
Potent In Vitro Synergism of Fluconazole and Berberine Chloride against Clinical Isolates of
Candida albicans
Resistant to Fluconazole
Authors: Quan Hua , Cao Ying-Ying , Xu Zheng , Zhao Jing-Xia , Gao Ping-Hui , Qin Xiao-Feng , Jiang Yuan-Ying
Published: February 2006

In vitro interaction of fluconazole and berberine chloride was investigated against 40 fluconazole-resistant clinical isolates of
Candida albicans
. Synergism in fungistatic activity was found with the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed the synergistic interaction, but no antagonistic action was observed.
Effects of Lipid Formulations of Amphotericin B on Activity of Human Monocytes against
Aspergillus fumigatus
Authors: Dotis J. , Simitsopoulou M. , Dalakiouridou M. , Konstantinou T. , Taparkou A. , Kanakoudi-Tsakalidou F. , Walsh T. J. , Roilides E.
Published: February 2006

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex, and amphotericin B colloidal dispersion (ABCD) on antifungal activity of human monocytes (MNCs), an important component of antifungal host defense, against
Aspergillus fumigatus
were compared to those of deoxycholate amphotericin B (DAMB). MNCs from healthy volunteers were incubated with 1 or 5 μg/ml DAMB and 5 or 25 μg/ml lipid formulations for 22 h. Drug-pretreated or untreated MNCs were then washed and assayed for the following: (i) activity against
A. fumigatus
hyphae by XTT assay at MNC:hypha ratios of 10:1 and 20:1; (ii) production of superoxide anion (O
2
−
) from MNCs in response to hyphae by cytochrome
c
reduction; (iii) production of hydrogen peroxide (H
2
O
2
) and H
2
O
2
-dependent intracellular intermediates (DIIs), such as OH
−
and HOCl, from MNCs in response to
A. fumigatus
culture supernatant by flow cytometric measurement of dihydrorhodamine-1,2,3 oxidation. With the exception of 1 μg/ml DAMB and 5 μg/ml LAMB or ABCD at 10:1, all amphotericin B formulations at both concentrations and MNC:hypha ratios enhanced MNC-induced damage of
A. fumigatus
hyphae compared to results with untreated cells (
P
< 0.01). While MNC O
2
−
production upon hyphal challenge, an early event in oxidative burst, was not affected by the drugs, production of H
2
O
2
and DIIs, late events, were significantly increased by all four drugs (
P
< 0.01). At clinically relevant concentrations, both conventional amphotericin B and its lipid formulations enhance antihyphal activity of MNCs against
A. fumigatus
in association with significant augmentation of H
2
O
2
and DIIs but not O
2
−
, further demonstrating the immunomodulatory antifungal activities of these agents.