bluuebunny/crossref_metadata_2025 huggingface dataset:
Navy Radar Trades at the Ship Interface
Authors: WHITE JAMES W. , BILLUPS AMY
Published: April 2009

The next generation radar suite will include a radar that has sensitivity far greater than shipboard radars in use today. Most likely the radar will be a multi‐faced, solid state, phased array system with each array consisting of thousands of individual radiating elements powered by transmit/receive (T/R) modules. It will likely need to be large, and the demands it makes on ship services will be unprecedented. Its electrical power demands could be larger than the total ship's load for present‐day ships. Array size could significantly impact topside design. This paper examines top‐level radar system design choices and illustrates the trends in the ship impact of those choices. Radar design options considered are aperture size and shape, coolant operating temperature, number of array faces, and power system architecture. These design options have an effect on the radar system's weight, footprint, power demand, and cooling load. The effects on ship design can be significant. The ship impact analyses consider a radar system that includes ship‐provided equipment such as electrical power distribution equipment and chill water plants. An analysis of radar systems, all with the same performance, shows that radar system power demand can change by as much as four megawatts for a notional surface combatant depending upon the radar designer's configuration choices. Radar system weight can vary by more than 100 metric tons. There is a cubic relationship between T/R module power and array face area for a constant sensitivity radar system. This relationship is examined to show that there is often a choice of T/R module power that minimizes radar ship impact. The exact choice of T/R module power depends upon the customer's preferences, the manufacturer's capabilities, and choice of vendors. This paper does not convey any official US government position or US Navy endorsement of any particular radar architecture or design approach.
Combat System Application of Change‐Tolerant Technology: Using Rules Engine for Decision Automation
Authors: PAYNE CATHERINE L. , SCHMID MARK E. , SHAPTER BARBARA A. , TAYLOR BRIAN T.
Published: April 2009

Advances in threats, geopolitical developments, and commercial technologies continually challenge combat system stability because they constantly create new demands and therefore requirements for the system. Because the life cycle of major Department of Defense (DoD) systems can last decades, long‐fielded systems in particular are vulnerable to requirements creep. One technique to mitigate the impact requirements volatility can have on a system is through the implementation of technologies that have been developed to allow the system to adapt while minimizing the effect of change on the system as a whole. This paper investigates the application of one such technology—Rules Engine—to the Decision Automation domain of two Navy combat systems. This paper also proposes modifications to the systems engineering process given that using change‐tolerant technologies affects the way a system can be developed and maintained.
Methods for Naval Ship Concept and Propulsion Technology Exploration in a CGX Case Study
Authors: STROCK JUSTIN , BROWN ALAN
Published: April 2009

In response to the Fiscal Year 2006 National Defense Authorization Act, the US Navy conducted an alternative propulsion study (APS) for surface combatants and amphibious warfare ships. The study looked at current and future propulsion technology and propulsion alternatives for three sizes of warships. In their analyses they developed 23 ship concepts, seven of which were considered medium surface combatants (MSCs). The report to Congress was based on cost analyses and operational effectiveness analyses of these variants. Their conclusions did not consider a true representative sample of feasible, non‐dominated designs in the design space. This paper revisits the APS for a fossil‐fueled MSC. It applies automated design methods with a variety of design tools, including the Advanced Ship and Submarine Evaluation Tool (ASSET), a simplified ship synthesis model (SSSM), and Model Center (MC) to improve the APS approach. It examines a range of power and propulsion alternatives using operational profiles and requirements similar to the APS in a notional MSC (CGXBMD). The automated process and tools presented in this paper provide a rational and thorough method to search a design space for non‐dominated concepts. These non‐dominated concepts represent the best basis for assessing technologies over a range of possibilities considering effectiveness, cost and risk. This automated approach and new tools are evaluated in the context of a CGXBMD case study. A number of conclusions relative to APS propulsion technologies are made. Most support the APS results.
A pilot study of the use and perceived utility of a scale to assess clinical dental teaching within a UK dental school restorative department
Authors: Woolley S. , Emanuel C. , Koshy B.
Published: April 2009

Introduction:  Feedback on individual teaching performance gives an important contribution and support to the reflective practices of educators. Unfortunately, feedback is an infrequent exercise provided to dental teachers about their teaching practices. The Effective Clinical Dental Teaching (ECDT) scale has been used previously to assess clinical teachers, but has not been used within the UK.

Methods:  This study looks at the use of the ECDT scale in the setting of a UK dental school, as a method of feedback collection and delivery in seven domains of clinical teaching. The ECDT was used to evaluate the teaching of 16 clinical teachers by dental undergraduates, and to investigate the opinions of these clinical teachers and clinical dental students about the utility of this scale.

Results:  The study identified that there was a disparity between self and student perception of teaching. The total ECDT scores ranged from a minimum of 55% 66.6/125 to a maximum of 90% 113.8/125, with a mean group score of 73% 91.6/125. Most clinicians evaluated by students scored above 3/5 for all teaching domains, although there appeared to be significant differences between the four teacher groups. The majority of staff and students were in favour of the use of such a scale to support the progression and development of teaching styles.

Conclusion:  The ECDT scale is a useful tool for highlighting the areas of strength and deficiency within clinical dental teaching. Its use may complement peer review for individual teachers and identify future topics for staff development sessions. Further research is recommended to identify the individual strengths and weaknesses that different types of teacher may bring to curriculum teaching.
Career choice and attitudes towards dental education amongst dental students in Japan and Sweden
Authors: Karibe H. , Kawakami T. , Suzuki A. , Warita S. , Ogata K. , Aoyagi K. , Agholme M. B. , Dahllöf G.
Published: April 2009

The purpose of this study was to identify and compare the perspectives of dental students towards their career choice and dental education in Japan and Sweden. One hundred and fourteen dental students from the Nippon Dental University, Japan and 43 dental students from the Karolinska Institutet, Sweden participated in this study. Information was derived from a self‐answered questionnaire consisting of five items for career choice and six items for dental education. Chi‐square test and Wilcoxon signed‐rank test were used for comparison. Significant differences were detected for 10 questionnaire items between the two countries. Regarding motivation towards the career choice, 44% of Swedish students indicated interpersonal motives related to helping other people, whereas 32% of Japanese students indicated expectations of their family in the dental profession. As future career options, 64% of Japanese and 47% of Swedish students planned to work as general dentists. More Swedish students (37%) preferred specialisation than Japanese students (17%). Nearly three‐quarters of the Swedish students were satisfied with the teaching faculty of their school, whilst only 32% of the Japanese students indicated content. The perspectives of dental students were different in Japan and Sweden. This study provides a description of the perspectives of Japanese and Swedish dental students and enables better understanding of career decision and dental curriculum issues.
Evaluation of a virtual anatomy course for clinical undergraduates
Authors: Durham J. A. , Brettell S. , Summerside C. , McHanwell S.
Published: April 2009

Aim:  To implement and evaluate a series of interactive clinically applied anatomy tutorials for final year dental undergraduate students.

Methods:  A 6‐week voluntary virtual program of tutorials for final year dental undergraduates, with pre‐ and post‐tutorial testing, was evaluated using a priority sequence model (QualQuan). A purposive sample (n = 15) was taken of the year group (n = 69) and the initial qualitative phase in depth interviews were carried out until data saturation (n = 13). The emergent recurrent themes from the qualitative data were then phrased into a variety of non‐leading questions. These questions were issued in the form of an anonymous electronic questionnaire to the whole student body.

Results:  There was a good uptake of the tutorials with 84% of the students accessing at least one tutorial before sitting their final examinations. A response rate of 70% was achieved for the quantitative evaluative questionnaire phase of the study. Overall perceptions of the course were favourable although a number of modifications were suggested. These included a more concise presentation of the mainstream tutorial text with hyper links to more detailed content. Students also indicated a desire for more line diagrams. These changes, it was suggested, would help with the on‐line readability of the tutorials. The primary focus for the students’ learning appeared to be provided by the pre‐ and post‐tutorial tests even though explicit learning outcomes were provided for each tutorial.

Conclusion:  This study demonstrates that a well‐designed virtual course can help to vertically integrate, and make clinically relevant, one of the basic sciences underpinning dental surgery. It has shown that formative assessment acts as a powerful tool to focus student attention and direct student learning. This leads to the conclusion that formative assessments have to be designed with as much care and attention as summative assessments.
Are peripheral populations special? Congruent patterns in two butterfly species
Authors: Cassel‐Lundhagen Anna , Tammaru Toomas , Windig Jack J. , Ryrholm Nils , Nylin Sören
Published: April 2009

Populations at range margins may be genetically different from more central ones for a number of mutually non‐exclusive reasons. Specific selection pressures may operate in environments that are more marginal for the species. Genetic drift may also have a strong effect in these populations if they are small, isolated and/or have experienced significant bottlenecks during the colonisation phase. The question if peripheral populations are special, and if yes then how and why, is of obvious relevance for speciation theory, as well as for conservation biology. To evaluate the uniqueness of populations at range margins and the influence of gene flow and selection, we performed a morphometric study of two grassland butterfly species:Coenonympha arcaniaandC. hero(Lepidoptera: Nymphalidae). The samples were collected from Swedish populations that are peripheral and isolated from the main area of the species distributions and from populations in the Baltic states that are peripheral but connected to the main area of the species distributions. These samples were compared to those from central parts of the species distributions. The isolated populations in both species differed consistently from both peripheral and central populations in their wing size and shape. We interpret this as a result of selection caused by differences in population structure in these isolated locations, presumably favoring different dispersal propensity of these butterflies. Alternative explanations based on colonisation history, latitudinal effects, inbreeding or phenotypic plasticity appear less plausible. As a contrast, the much weaker and seemingly random among‐region differences in wing patterns are more likely to be ascribed to weaker selection pressures allowing genetic drift to be influential. In conclusion, both morphological data and results from neutral genetic markers in earlier studies of the same system provide congruent evidence of both adaptation and genetic drift in the isolated Swedish populations of both species.
Correlations between net primary productivity and foliar carbon isotope ratio across a Tibetan ecosystem transect
Authors: Luo Tianxiang , Zhang Lin , Zhu Huazhong , Daly Christopher , Li Mingcai , Luo Ji
Published: April 2009

Warming climate could affect leaf‐level carbon isotope composition (δ13C) through variations in photosynthetic gas exchange. However, it is still unclear to what extent variations in foliar δ13C can be used to detect changes in net primary productivity (NPP) because leaf physiology is only one of many determinants of stand productivity. We aim to examine how well site‐mean foliar δ13C and stand NPP co‐vary across large resource gradients using data obtained from the Tibetan Alpine Vegetation Transects (1900–4900 m, TAVT). The TAVT data indicated a robust negative correlation between foliar δ13C and NPP across ecosystems (NPP=−2.7224δ13C‐67.738, r2=0.60, p<0.001). The mean foliar δ13C decreased with increasing annual precipitation and its covariation with mean temperature and soil organic carbon and nitrogen contents. The results were further confirmed by global literature data. Pooled δ13C data from global literature and this study explained 60% of variations in annual NPP both from TAVT‐measures and MODIS‐estimates across 67 sites. Our results appear to support a conceptual model relating foliar δ13C and nitrogen concentration (Nmass) to NPP, suggesting that: 1) there is a general (negative) relationship between δ13C and NPP across different water availability conditions; 2) in water‐limited conditions, water availability has greater effects on NPP than Nmass; 3) when water is not limiting, NPP increases with increasing Nmass.
Red bacterial complex is associated with the severity of chronic periodontitis in a Thai population
Authors: Wara‐aswapati N , Pitiphat W , Chanchaimongkon L , Taweechaisupapong S , Boch JA , Ishikawa I
Published: April 2009

Background:  The distribution of periodontal pathogens differs in various geographic locations and racial/ethnic groups. This study investigated the microbiological features of chronic periodontitis (CP) patients in Thailand.

Methods:  Subgingival plaque samples from 20 non‐periodontitis subjects, 20 patients with mild CP, and 20 patients with moderate to severe CP were examined using polymerase chain reaction (PCR) to identify Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans.

Results:  In the moderate to severe CP patients, there was high prevalence of P. gingivalis (95%), T. forsythia (95%), T. denticola (80%), as well as the red complex (coexistence of all three species at the same lesion) (75%). A. actinomycetemcomitans was detected in only 35% of the patients in this study group. P. gingivalis was detected in as high as 45% of the non‐periodontitis controls. CP and disease severity were significantly related to the presence of T. forsythia together with T. denticola and the red complex. The red complex was not found in any non‐periodontitis site.

Conclusion:  Red complex bacteria were predominant periodontal pathogens of the moderate to severe form of CP in this Thai population. The presence of T. forsythia together with T. denticola, and the red complex species at the same site were significantly associated with the disease severity.
TATA Box‐Binding Protein gene is associated with risk for schizophrenia, age at onset and prefrontal function
Authors: Ohi K. , Hashimoto R. , Yasuda Y. , Kiribayashi M. , Iike N. , Yoshida T. , Azechi M. , Ikezawa K. , Takahashi H. , Morihara T. , Ishii R. , Tagami S. , Iwase M. , Okochi M. , Kamino K. , Kazui H. , Tanaka T. , Kudo T. , Takeda M.
Published: April 2009

Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box‐binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near‐infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.
Preparation of White Pigments from Nanosized Alkaline Earth Metal Titanates and Potassium Titanium Oxophosphate
Authors: Biswas Soumya Kanti , Ghorai Tanmay Kumar , Pramanik Panchanan
Published: April 2009

The aim of this work is to produce white pigments having less amount of Ti4+ than that of pure TiO2. It develops synthetic methods for the preparation of nanosized white pigments based on alkaline earth metal titanates and potassium titanium oxophosphate with a high surface area (30–80 m2/g) from ilmenite. The preparative methods involve the extraction of titanium as a water‐soluble titanium oxychloride from ilmenite and coprecipitation of constituent ions of pigments from their aqueous mixture solutions using a suitable precipitant. All the synthesized pigments have been characterized by X‐ray powder diffraction, transmission electron micrscope, and ultraviolet–visible spectroscopy study, energy‐dispersive X‐ray analysis, and Brunauer–Emmett–Teller surface area measurement.
Microwave Dielectric Properties and Chemical Resistance of Low‐Temperature‐Sintered CaZrB2O6 Ceramics
Authors: Kim Hyo Tae , Nam Myoung‐Hwa , Kim Jong‐Hee , Nahm Sahn
Published: April 2009

Dolomite‐type borate ceramics consisting of CaZrB2O6 were synthesized via a conventional solid‐state reaction route; low‐temperature sintering was explored using Bi2O3–CuO additives of 1–7 wt% for low‐temperature co‐fired ceramics applications. For several sintering temperatures, the microwave dielectric properties and chemical resistance of the ceramics were investigated. The CaZrB2O6 ceramics with 3 wt% Bi2O3–CuO addition could be sintered below 925°C, and the microwave dielectric properties of the low‐temperature samples were ɛr=10.55, Q×f=87,350 GHz, and τf=+2 ppm/°C. The chemical resistance test result showed that both CaZrB2O6‐ and Bi2O3–CuO‐added CaZrB2O6 ceramics were durable in basic solution but were degraded in acid solution.
A comparative study of four rotary NiTi instruments in preserving canal curvature, preparation time and change of working length
Authors: Vahid Alavieh , Roohi Neda , Zayeri Farid
Published: April 2009

The purpose of this ex vivo study was to compare working time, working length changes and shaping effects using ProTaper, ProFile, FlexMaster and Mtwo rotary instruments. A total of 96 mesiobuccal roots of the first maxillary molars were prepared using these instruments. Using pre and post‐radiographs, canal curvature and working length were measured. In addition, the time required for canal preparation was recorded. Data was statistically analysed using one‐way anova and Duncan's post‐hoc tests. ProTaper significantly lessened the canal curvature (P < 0.001), and Mtwo rotary instruments took significantly less instrumentation time (P < 0.001). No significant difference was observed between the four groups in changing working lengths (P = 0.081). According to the results of the study, the Mtwo rotary instruments required significantly less instrumentation time, and the ProTaper significantly changed the canal curvature.
New foundations of cost–benefit analysis
Authors: Adler Matthew , Posner Eric A.
Published: April 2009

This article responds to the criticisms of New Foundations of Cost–Benefit Analysis that appeared in a review by Amy Sinden, Douglas A. Kysar, and David M. Driesen. We argue that their criticisms are either based on misunderstandings of our approach or are too demanding, in the sense that no reasonable decision procedure would satisfy them. We illustrate this second argument by demonstrating that their preferred approach – feasibility analysis – has little to recommend it.
Responsive regulation at the Dutch Food and Consumer Product Safety Authority: An empirical assessment of assumptions underlying the theory
Authors: Mascini Peter , Wijk Eelco Van
Published: April 2009

Responsive regulation usually boils down to the assumption that enforcers should not shift to coercing before it has become clear that persuading does not work. This presupposes that it is possible to determine what the correct enforcement style is, that enforcers can apply the most suitable style, and that enforcers control the negative unintended consequences of their conduct. We have studied the applicability of these presuppositions at the Dutch Food and Consumer Product Safety Authority by way of observations, interviews, and a survey. The applicability of all three presuppositions has proven problematic; enforcement agents apply different styles in comparable cases; they are impeded in applying the most appropriate style; and they do not control the perverse consequences of their conduct because regulatees tend to perceive it as more coercive than intended by inspectors. Our findings are not unique to this inspectorate and hence raise questions about the applicability of the theory of responsive regulation.
Exchangeability, Correlation, and Bayes' Effect
Authors: O'Neill Ben
Published: April 2009

We examine the difference between Bayesian and frequentist statistics in making statements about the relationship between observable values. We show how standard models under both paradigms can be based on an assumption of exchangeability and we derive useful covariance and correlation results for values from an exchangeable sequence. We find that such values are never negatively correlated, and are generally positively correlated under the models used in Bayesian statistics. We discuss the significance of this result as well as a phenomenon which often follows from the differing methodologies and practical applications of these paradigms – a phenomenon we call Bayes' effect.
Homer Sarasohn and American Involvement in the Evolution of Quality Management in Japan, 1945–1950
Authors: Fisher Nicholas I.
Published: April 2009

The history of Quality Management, and of the role of Statistics in Quality Management, is inextricably bound to the reconstruction of Japan immediately following the Second World War, and then to developments in the United States over three decades later. Even though these periods are, in societal history, just moments ago, yet there is profound lack of agreement about what was actually done, and who should be recognized for their contributions. This paper draws on historical materials recently made publicly available in order to clarify what actually took place between 1946 and 1950, and in particular the contribution of a remarkable engineer, Homer Sarasohn.
Oral Health Self‐Care Behaviors of Rural Older Adults
Authors: Arcury Thomas A. , Bell Ronny A. , Anderson Andrea M. , Chen Haiying , Savoca Margaret R. , Kohrman Teresa , Quandt Sara A.
Published: April 2009

Objectives: This analysis describes the dental self‐care behaviors used by a multiethnic sample of older adults and delineates the associations of self‐care behaviors with personal characteristics and oral health problems. Methods: A cross‐sectional comprehensive oral health survey conducted with a random, multiethnic (African‐American, American Indian, white) sample of 635 community‐dwelling rural adults aged 60 years and older was completed in two rural southern counties. Results: Rural older adults engage in a variety of self‐care behaviors, including the use of over‐the‐counter (OTC) medicine (12.1 percent), OTC dental products (84.0 percent), salt (50.9 percent), prayer (6.1 percent), and complementary therapies (18.2 percent). Some gender and ethnic class differences are apparent, with greater use by women of OTC medicine and salt and greater use by African‐Americans and American Indians of OTC medicine and OTC dental products. The use of dental self‐care behaviors appears to be driven by need. Those reporting oral pain, bleeding gums, and dry mouth have greater odds of engaging in most of the dental self‐care behaviors, including the use of complementary therapies. Conclusions: The major factor leading to the use of self‐care behaviors is need. Although oral pain does increase the use of self‐care behaviors, so do bleeding gums and dry mouth. Research and practice should address self‐care behaviors used for oral health problems in addition to pain. Investigators should expand analysis of dental self‐care behavior and the relationship of self‐care behavior to the use of professional services. Further research also should explore the use of complementary therapies in dental self‐care.
Performing Gender in Augustan Criticism and Pope's To a Lady
Authors: JONES TOM
Published: April 2009

This piece explores the performance of gender in literary criticism of the period 1660‐1740 and in Pope's To A Lady. Arguing that the use of gendered terms in literary criticism is part of the performance of gender, the essay draws on Judith Butler's work. The essay traces the use of explicitly and implicitly gendered terms in literary criticism in order to suggest the gender value assigned to particular technical aspects of verse. The essay closes with a reading of To a Lady which argues that the poem explores the relationship between the ideas of female inconstancy and male artistic virtue.
‘Mi Li’ Revisited: Horace Walpole and the Idea of China
Authors: NASH PAUL
Published: April 2009

Some time in the early 1780s Horace Walpole wrote a Chinese fairy tale to amuse himself and to entertain a young girl of his acquaintance. Named ‘Mi Li’ after its protagonist, it was printed in 1785, together with five others, under the title Hieroglyphic Tales. The tale is a satire, directed at the East India Company's pursuit of profit and Britain's transforming mercantile–colonial enterprise after the American revolutionary war. This paper represents an effort to understand ‘Mi Li’ within the context of contemporary ideas about China and English attitudes towards a wider world.
Performing the Woman of Sensibility: Suzanne Curchod Necker and the Hospice de Charité
Authors: BOON SONJA
Published: April 2009

This paper explores the problematic relationship between feminine propriety and public female ambition by examining the ways in which the well‐known salonnière and philanthropist, Suzanne Curchod Necker, deployed the principles of normative femininity – womanly propriety founded upon the values of modesty, sensibility, charity and above all, domesticity – as a masquerade, not only to propel herself into the public sphere of ideas, but also and perhaps more significantly, through her leadership of the experimental Hospice de Charité, to acquire significant political influence.
Administration at the Supreme Court of Canada: Challenges and change in the Charter era
Authors: Macfarlane Emmett
Published: April 2009

Abstract:This article presents a descriptive account of administration at the Supreme Court of Canada. Since 1975, the Court has gained considerable control over its docket, attained administrative independence from the federal Department of Justice and seen its role transformed following the enactment of the Charter of Rights. This new context has brought a host of challenges, requiring procedural reforms and adaptation to technological developments to ensure institutional efficiency. The institution's role under the Charter has also enhanced its public prominence, placing normative pressure on the Court to enact measures to increase transparency, particularly with regards to its relationship with the media. Drawing on interviews with former justices and Court staff members, as well as secondary material, this article examines these changes and their implications.

Sommaire :Cet article décrit l'administration de la Cour Suprême du Canada. Depuis 1975, la Cour a considérablement augmenté le contrôle de son registre, a acquis une indépendance administrative par rapport au ministère fédéral de la Justice et a vu son rôle se transformer suite à l'adoption de la Charte des droits et libertés. Ce nouveau contexte a apporté pléthore de défis, exigeant à la fois des réformes procédurales et une adaptation aux changements technologiques afin d'assurer son efficacité institutionnelle. L'adoption de la Charte a aussi augmenté le profil de la Cour auprès de la population, en exerçant une pression normative et en l'obligeant à adopter des mesures supplémentaires pour accroître sa transparence, en particulier en ce qui concerne son rapport avec les médias. En s'appuyant sur des entrevues avec d'anciens juges et membres du personnel de la Cour et d'autres documents, cet article examine ces changements et leurs implications.
Wittgenstein's Rule‐Following Considerations and Moral Particularism
Authors: LOTFI SHIDAN
Published: April 2009

Moral particularists have seen Wittgenstein as a close ally. One of the main reasons for this is that particularists such as Jonathan Dancy and John McDowell have argued that Wittgenstein's so‐called “rule‐following considerations” (RFCs) provide support for their skepticism about the existence and/or role of rules and principles in ethics. In this paper, I show that while Wittgenstein's RFCs challenge the notion that competence with language, i.e., the ability to apply concepts properly, is like mechanically following a rule, he does not reject the idea that there are rules that govern proper use of language. I then argue that while the RFCs may, at best, support a weak form of particularism that denies that moral competence is dependent on an explicit grasp of rules, they do not support a stronger version of particularism that denies that there are any true rules or principles in ethics.
Epistemic Supervenience and Internalism: A Trilemma
Authors: RULOFF COLIN
Published: April 2009

Epistemic Internalism (EI) is the claim that an agent S is justified in believing that p at a time t iff S has either an actual or potential direct awareness of the grounds or properties that confer justification on p at t. In this paper I argue that EI does not provide the proponent of EI with an intuitively clear analysis of epistemic justification. More exactly, after identifying two different versions of EI – a weak version and a strong version – I offer some general considerations for thinking that neither the weak version nor the strong version provides the proponent of EI with a plausible analysis of epistemic justification and conclude, therefore, that EI itself cannot be considered a plausible analysis of epistemic justification.
Enhanced cardiac sympathetic afferent reflex involved in sympathetic overactivity in renovascular hypertensive rats
Authors: Zhu Guo‐Qing , Xu Yao , Zhou Li‐Min , Li Yue‐Hua , Fan Le‐Ming , Wang Wei , Gao Xing‐Ya , Chen Qi
Published: April 2009

Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two‐kidney one‐clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT1) receptors in mediating the CSAR was determined. Under urethane and α‐chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with sham‐operated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1‐containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT1 receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT1 receptors are involved in the enhanced CSAR in 2K1C rats.
Dihydropyridine‐ and voltage‐sensitive Ca2+entry in human parathyroid cells
Authors: Yokoyama Keitaro , Matsuba Douchi , Adachi‐Akahane Satomi , Takeyama Hiroshi , Tabei Isao , Suzuki Akifumi , Shibasaki Toshiaki , Iida Rinako , Ohkido Ichiro , Hosoya Tatsuo , Suda Norio
Published: April 2009

Patch‐clamp and fluorescence measurements of cytoplasmic Ca2+concentration ([Ca2+]i) were performed to directly detect extracellular Ca2+entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo‐3 AM or fluo‐4 AM showed a transient increase in fluorescence (Ca2+transient) following 10 s exposure to 150 mmK+solution in the presence of millimolar concentrations of external Ca2+. The Ca2+transient was completely inactivated after 30–40 s exposure to the high‐K+solution, was reduced by dihydropyridine antagonists and was enhanced by FPL‐64176, an L‐type Ca2+channel agonist. The electrophysiological and pharmacological properties of the whole‐cell Ca2+and Ba2+currents were similar to those of L‐type Ca2+channels. The Ca2+transients induced by 10 s exposure to 3.0 mmextracellular Ca2+concentration ([Ca2+]o) were inhibited by dihydropyridine antagonists and were partly inactivated following 30–40 s exposure to the high‐K+solution. These results demonstrate, for the first time, that human parathyroid cells express L‐type‐like Ca2+channels that are possibly involved in the [Ca2+]o‐induced change in [Ca2+]i. This Ca2+entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca2+‐sensing receptor is poorly expressed.
Nonhuman Primates Are Protected from Smallpox Virus or Monkeypox Virus Challenges by the Antiviral Drug ST-246
Authors: Huggins John , Goff Arthur , Hensley Lisa , Mucker Eric , Shamblin Josh , Wlazlowski Carly , Johnson Wendy , Chapman Jennifer , Larsen Tom , Twenhafel Nancy , Karem Kevin , Damon Inger K. , Byrd Chelsea M. , Bolken Tove' C. , Jordan Robert , Hruby Dennis
Published: April 2009

ST-246, a potent orthopoxvirus egress inhibitor, is safe and effective at preventing disease and death in studies of small-animal models involving challenge by several different pathogenic poxviruses. In this report, the antiviral efficacy of ST-246 in treatment of nonhuman primates infected with variola virus or monkeypox virus was assessed. The data indicate that oral dosing once per day with ST-246 protects animals from poxvirus disease, as measured by reductions in viral load and numbers of lesions and enhancement of survival.
Assessment of Malaria In Vitro Drug Combination Screening and Mixed-Strain Infections Using the Malaria Sybr Green I-Based Fluorescence Assay
Authors: Co Edgie-Mark A. , Dennull Richard A. , Reinbold Drew D. , Waters Norman C. , Johnson Jacob D.
Published: April 2009

Several drug development strategies, including optimization of new antimalarial drug combinations, have been used to counter malaria drug resistance. We evaluated the malaria Sybr green I-based fluorescence (MSF) assay for its use in in vitro drug combination sensitivity assays. Drug combinations of previously published synergistic (atovaquone and proguanil), indifferent (chloroquine and azithromycin), and antagonistic (chloroquine and atovaquone) antimalarial drug interactions were tested against
Plasmodium falciparum
strains D6 and W2 using the MSF assay. Fifty percent inhibitory concentrations (IC
50
s) were calculated for individual drugs and in fixed ratio combinations relative to their individual IC
50
s. Subsequent isobologram analysis and fractional inhibitory concentration determinations demonstrated the expected drug interaction pattern for each combination tested. Furthermore, we explored the ability of the MSF assay to examine mixed parasite population dynamics, which are commonly seen in malaria patient isolates. Specifically, the capacity of the MSF assay to discern between single and mixed parasite populations was determined. To simulate mixed infections in vitro, fixed ratios of D6 and W2 strains were cocultured with antimalarial drugs and IC
50
s were determined using the MSF assay. Dichotomous concentration curves indicated that the sensitive and resistant parasites composing the genetically heterogeneous population were detectable. Biphasic analysis was performed to obtain subpopulation IC
50
s for comparison to those obtained for the individual malaria strains alone. In conclusion, the MSF assay allows for reliable antimalarial drug combination screening and provides an important method to discern between homogenous and heterogeneous parasite populations.
High-Throughput Screening Identifies Novel Inhibitors of the Acetyltransferase Activity of
Escherichia coli
GlmU
Authors: Pereira Mark P. , Blanchard Jan E. , Murphy Cecilia , Roderick Steven L. , Brown Eric D.
Published: April 2009

The bifunctional GlmU protein catalyzes the formation of UDP-
N
-acetylglucosamine in a two-step reaction using the substrates glucosamine-1-phosphate, acetyl coenzyme A, and UTP. This metabolite is a common precursor to the synthesis of bacterial cell surface carbohydrate polymers, such as peptidoglycan, lipopolysaccharide, and wall teichoic acid that are involved in the maintenance of cell shape, permeability, and virulence. The C-terminal acetyltransferase domain of GlmU exhibits structural and mechanistic features unique to bacterial UDP-
N
-acetylglucosamine synthases, making it an excellent target for antibacterial design. In the work described here, we have developed an absorbance-based assay to screen diverse chemical libraries in high throughput for inhibitors to the acetyltransferase reaction of
Escherichia coli
GlmU. The primary screen of 50,000 drug-like small molecules identified 63 hits, 37 of which were specific to acetyltransferase activity of GlmU. Secondary screening and mode-of-inhibition studies identified potent inhibitors where compound binding within the acetyltransferase active site was requisite on the presence of glucosamine-1-phosphate and were competitive with the substrate acetyl coenzyme A. These molecules may represent novel chemical scaffolds for future antimicrobial drug discovery. In addition, this work outlines the utility of catalytic variants in targeting specific activities of bifunctional enzymes in high-throughput screens.
Pharmacokinetics of Nikkomycin Z after Single Rising Oral Doses
Authors: Nix David E. , Swezey Robert R. , Hector Richard , Galgiani John N.
Published: April 2009

Nikkomycin Z is an antifungal drug that inhibits chitin synthase. This agent is under development as an orphan product for treatment of coccidioidomycosis. Safety and pharmacokinetics of nikkomycin Z were evaluated in healthy male subjects following single, rising oral doses ranging from 250 mg to 2,000 mg. A total of 12 subjects were recruited and divided into two groups. Group 1 (
n
= 6) received two out of three doses of 250 mg, 1,000 mg, or 1,750 mg and a placebo randomly in place of one of the doses. Group 2 (
n
= 6) received two out of three doses of 500 mg, 1,500 mg, or 2,000 mg and a placebo in place of one of the doses. Subjects were confined to the study unit overnight prior to dosing, and 12 blood samples were collected over 24 h postdosing while subjects were confined. Subjects returned for additional blood samples and safety evaluations at 48 h and 72 h after each dose. There was a 2-week washout period between doses. Plasma drug concentrations were determined using a validated high-performance liquid chromatography method. Nikkomycin Z was absorbed after oral administration, reaching a maximum concentration in serum of 2.21 μg/ml at 2 h postdose and an area under the concentration-time curve from 0 h to infinity of 11.3 μg·h/ml for the 250-mg dose. Pharmacokinetics appeared linear over the range of 250 to 500 mg; however, relative bioavailability was about 62 to 70% for the 1,000-mg dose and 42 to 47% for doses between 1,500 and 2,000 mg. The mean terminal half-life ranged from 2.1 to 2.5 h and was independent of dose. No serious or dose-related adverse events were observed. This study provides a basis for pharmacokinetic simulations and continued studies of nikkomycin Z administered in multiple doses.
Susceptibility of Highly Pathogenic H5N1 Influenza Viruses to the Neuraminidase Inhibitor Oseltamivir Differs In Vitro and in a Mouse Model
Authors: Govorkova Elena A. , Ilyushina Natalia A. , McClaren Jennifer L. , Naipospos Tri S. P. , Douangngeun Bounlom , Webster Robert G.
Published: April 2009

While the neuraminidase (NA) inhibitor oseltamivir is currently our first line of defense against a pandemic threat, there is little information about whether in vitro testing can predict the in vivo effectiveness of antiviral treatment. Using a panel of five H5N1 influenza viruses (H5 clades 1 and 2), we determined that four viruses were susceptible to the drug in vitro (mean 50% inhibitory concentration [IC50], 0.1 to 4.9 nM), and A/Turkey/65-1242/06 virus was slightly less susceptible (mean IC50, 10.8 nM). Two avian viruses showed significantly greater NA enzymatic activity (Vmax) than the human viruses, and the five viruses varied in their affinity for the NA substrate MUNANA (Km, 64 to 300 μM) and for oseltamivir carboxylate (Ki, 0.1 to 7.9 nM). The protection of mice provided by a standard oseltamivir regimen (20 mg/kg/day for 5 days) also varied among the viruses used. We observed (i) complete protection against the less virulent A/chicken/Jogjakarta/BBVET/IX/04 virus; (ii) moderate protection (60 to 80% survival) against three viruses, two of which are neurotropic; and (iii) no protection against A/Turkey/65-1242/06 virus, which induced high pulmonary expression of proinflammatory mediators (interleukin-1α [IL-1α], IL-6, alpha interferon, and monocyte chemotactic protein 1) and contained a minor subpopulation of drug-resistant clones (I117V and E119A NA mutations). We found no correlation between in vitro susceptibility and in vivo protection (Spearman rank correlation coefficient ρ = −0.1;P> 0.05). Therefore, the in vivo efficacy of oseltamivir against highly pathogenic H5N1 influenza viruses cannot be reliably predicted by susceptibility testing, and more prognostic ways to evaluate anti-influenza compounds must be developed. Multiple viral and host factors modulate the effectiveness of NA inhibitor regimens against such viruses and new, more consistently effective treatment options, including combination therapies, are needed.
Genome-Scale Model of
Streptococcus thermophilus
LMG18311 for Metabolic Comparison of Lactic Acid Bacteria
Authors: Pastink Margreet I. , Teusink Bas , Hols Pascal , Visser Sanne , de Vos Willem M. , Hugenholtz Jeroen
Published: April 2009

In this report, we describe the amino acid metabolism and amino acid dependency of the dairy bacterium
Streptococcus thermophilus
LMG18311 and compare them with those of two other characterized lactic acid bacteria,
Lactococcus lactis
and
Lactobacillus plantarum
. Through the construction of a genome-scale metabolic model of
S. thermophilus
, the metabolic differences between the three bacteria were visualized by direct projection on a metabolic map. The comparative analysis revealed the minimal amino acid auxotrophy (only histidine and methionine or cysteine) of
S. thermophilus
LMG18311 and the broad variety of volatiles produced from amino acids compared to the other two bacteria. It also revealed the limited number of pyruvate branches, forcing this strain to use the homofermentative metabolism for growth optimization. In addition, some industrially relevant features could be identified in
S. thermophilus
, such as the unique pathway for acetaldehyde (yogurt flavor) production and the absence of a complete pentose phosphate pathway.
Phenotypic Diversity of Infectious Red Sea Bream Iridovirus Isolates from Cultured Fish in Japan
Authors: Shinmoto Hajime , Taniguchi Ken , Ikawa Takuya , Kawai Kenji , Oshima Syun-ichirou
Published: April 2009

Megalocytivirus
is causing economically serious mass mortality by infecting fish in and around the Pacific region of Asia. The recent emergence of many new iridoviruses has drawn attention to the marked taxonomic variation within this virus family. Most studies of these viruses have not included extensive study of these emergent species. We explored the emergence of red sea bream iridovirus (RSIV) on a fish farm in Japan, and we specifically endeavored to quantify genetic and phenotypic differences between RSIV isolates using in vitro and in vivo methods. The three isolates had identical major capsid protein sequences, and they were closely related to Korean RSIV isolates. In vitro studies revealed that the isolates differed in replication rate, which was determined by real-time quantitative PCR of viral genomes in infected cells and cell culture supernatant, and in cell viability, estimated by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay for infected cells. In vivo studies showed that the isolates exhibit different virulence characteristics: infected red sea bream showed either acute death or subacute death according to infection with different isolates. Significant differences were seen in the antigenicity of isolates by a formalin-inactivated vaccine test. These results revealed that variant characteristics exist in the same phylogenetic location in emergent iridoviruses. We suggest that this strain variation would expand the host range in iridoviral epidemics.