bluuebunny/crossref_metadata_2025 huggingface dataset:
Compute Bound and I/O Bound Cellular Automata Simulations on FPGA Logic
Authors: Murtaza S. , Hoekstra A. G. , Sloot P. M. A.
Published: January 2009

FPGA-based computation engines have been used as Cellular Automata accelerators in the scientific community for some time now. With the recent availability of more advanced FPGA logic it becomes necessary to better understand the mapping of Cellular Automata to these systems. There are many trade-offs to consider when mapping a Cellular Automata algorithm from an abstract system to the physical implementation using FPGA logic. The trade-offs include both the available FPGA resources and the Cellular Automata algorithm's execution time. The most important aspect is to fully understand the behavior of the specified CA algorithm in terms of its execution times which are either compute bound or I/O bound. In this article, we present a methodology to categorize a specified CA algorithm as a compute bound or an I/O bound. We take the methodology further by presenting rigorous analysis for each of the two cases identifying the various parameters that control the mapping process and are defined both by the Cellular Automata algorithm and the given FPGA hardware specifications. This methodology helps to predict the performance of running Cellular Automata algorithms on specific FPGA hardware and to determine optimal values for the various parameters that control the mapping process. The model is validated for both compute and I/O bound two-dimensional Cellular Automata algorithms. We find that our model predictions are accurate within 7%.
What does control theory bring to systems research?
Authors: Zhu Xiaoyun , Uysal Mustafa , Wang Zhikui , Singhal Sharad , Merchant Arif , Padala Pradeep , Shin Kang
Published: January 2009

Feedback mechanisms can help today's increasingly complex computer systems adapt to changes in workloads or operating conditions. Control theory offers a principled way for designing feedback loops to deal with unpredictable changes, uncertainties, and disturbances in systems. We provide an overview of the joint research at HP Labs and University of Michigan in the past few years, where control theory was applied to automated resource and service level management in data centers. We highlight the key benefits of a control-theoretic approach for systems research, and present specific examples from our experience of designing adaptive resource control systems where this approach worked well. In addition, we outline the main limitations of this approach, and discuss the lessons learned from our experience.
Autograph
Authors: Povzner Anna , Keeton Kimberly , Merchant Arif , Morrey Charles B. , Uysal Mustafa , Aguilera Marcos K.
Published: January 2009

Storage management activities, such as reporting, file placement, migration and archiving, require the ability to discover files that belong to an application workflow by relying only on information from the file server. Some classes of application workflows, such as rendering an animated sequence from its graphics models or building an application from its source files, often exhibit a high degree of repeatability. We describe a system called Autograph that exploits this repeatability to discover files that belong to an application workflow. Our approach examines traces of file accesses, finds repeated and correlated accesses, and infers which files likely belong to the same workflow. Our solution targets server workflows and uses file server traces, which contain less process and file information than the local machine traces used in prior work. We show that Autograph successfully extracts workflow file signatures, even if the workflows are concurrent or share files.
Efficient detection of large-scale redundancy in enterprise file systems
Authors: Forman George , Eshghi Kave , Suermondt Jaap
Published: January 2009

In order to catch and reduce waste in the exponentially increasing demand for disk storage, we have developed very efficient technology to detect approximate duplication of large directory hierarchies. Such duplication can be caused, for example, by unnecessary mirroring of repositories by uncoordinated employees or departments. Identifying these duplicate or near-duplicate hierarchies allows appropriate action to be taken at a high level. For example, one could coordinate and consolidate multiple copies in one location.
Online file sharing
Authors: Grodzinsky Frances S. , Tavani Herman T.
Published: January 2009

This essay expands upon an earlier work (Grodzinsky and Tavani, 2005) in which we analyzed the implications of the
Verizon v RIAA
case for P2P Networks vis-à-vis concerns affecting personal privacy and intellectual property. In the present essay we revisit some of the concerns surrounding this case by analyzing the intellectual property and privacy issues that emerged in the
MGM Studios v. Grokster
case. These two cases illustrate some of the key tensions that exist between privacy and property interests in cyberspace. In our analysis, we contrast Digital Rights Management (DRM) and Interoperability and we examine some newer distribution models of sharing over P2P networks. We also analyze some privacy implications in the two cases in light of the theory of privacy as contextual integrity (Nissenbaum, 2004).
Social considerations for information technology offshoring
Authors: Vedder Richard , Guynes Carl S.
Published: January 2009

Recently, the outsourcing of Information Technology (IT) activities to offshore locations has been gaining significant momentum, with some associated backlash by the workforce in the United States. Based on their 2005 survey [6], Global Insight, a private consulting firm, estimated that U.S. companies will spend about $38.2 billion in offshore IT services by 2010, compared with about $15.2 billion in 2005, primarily because the expected cost savings will grow by $11.7 billion in the same time period. Binder writing in "Foreign Affairs" [2] states that offshoring expenditures will continue to increase dramatically, and the changes the offshoring phenomenon will bring will transform society. This paper focuses on the social impact of offshoring and the effects of the weighing of costs and benefits as a result of offshoring activities.
Dynamics of neutrophil extravasation and vascular permeability are uncoupled during aseptic cutaneous wounding
Authors: Kim Min-Ho , Curry Fitz-Roy E. , Simon Scott I.
Published: January 2009

Transport of macromolecules and transmigration of leukocytes across vascular endothelium are regulated by a tight molecular junction, but the mechanisms by which these two inflammatory events are differentially controlled in time and magnitude during aseptic cutaneous wounding remain elusive. A real-time fluorescence imaging technique was developed to simultaneously track influx of Alexa 680-labeled albumin and genetically tagged enhanced green fluorescent protein-neutrophils [polymorphonuclear neutrophils (PMN)] within the wound bed. Vascular permeability increased approximately threefold more rapidly than the rate of PMN influx, reaching a maximum at 12 h, on the order of ∼0.15% per minute versus ∼0.05% per minute for PMN influx, which peaked at 18 h. Systemic depletion of PMN with antibody blocked their extravasation to the wound but did not alter the increase in vascular permeability. In contrast, pretreatment with antiplatelet GPIb decreased permeability by 25% and PMN influx by 50%. Hyperpermeability stimulated by the endothelium-specific agonists VEGF or thrombin at 24 h postwounding was completely inhibited by blocking Rho-kinase-dependent signaling, whereas less inhibition was observed at 1 h and neutrophil influx was not perturbed. These data suggest that in aseptic wounds, the endothelium maintains a tight junctional barrier to protein leakage that is independent of neutrophil transmigration, partially dependent on circulating platelets, and associated with Rho-kinase-dependent signaling.
Antitumor Activity of 6‐(cyclohexylamino)‐1,3‐dimethyl‐5(2‐pyridyl)furo[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione and Its Ti(IV), Zn(II), Fe(III), and Pd(II) Complexes on K562 and Jurkat Cell Lines
Authors: Shabani Fahmideh , Ghammamy Shahriar , Mehrani Khayroallah , Teimouri Mohammad Bagher , Soleimani Masoud , Kaviani Saeid
Published: January 2009

(6‐(cyclohexylamino)‐1,3‐dimethyl‐5(2‐pyridyl)furo[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione) abbreviated as CDP was synthesized and characterized. Ti(IV), Zn(II), Fe(III), and Pd(II) metal complexes of this ligand are prepared by the reaction of salts of Ti(IV), Zn(II), Fe(III), and Pd(II) with CDP in acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT‐IR,  1H NMR,  13C NMR, and UV‐Visible spectroscopy. All complexes were characterized by several techniques using elemental analysis (C, H, N), FT‐IR, electronic spectra, and molar conductance measurements. The elemental analysis data suggest the stoichiometry to be 1:1 [M:L] ratio formation. The molar conductance measurements reveal the presence of 1:1 electrolytic nature complexes. These new complexes showed excellent antitumor activity against two kinds of cancer cells that are K562 (human chronic myeloid leukemia) cells and Jurkat (human T lymphocyte carcinoma) cells.
Evaluation of a Telemedicine System for the Transmission of Morpho/Immunological Data Aiming at the Inclusion of Patients in a Therapeutic Trial
Authors: Lesesve Jean-François , Garand Richard
Published: January 2009

Due to their high levels of achievement and efficiency, image digitalization and teletransmission tools are more and more frequently used. Applied to cellular haematology, these tools often contribute to diagnosis confrontation, sometimes within the framework of therapeutic trials. We present one of the first approaches of the use of telehaematology for the inclusion of patients in the GOELAMS chronic lymphocytic leukaemia 98 trial. The advantages were (1) the creation of a unique, protected, stable data bank that could be remotely consulted, (2) the use of digitized pictures which made expertise on identical documents possible, (3) the facility of computer exchanges between experts, in terms of reception as well as replying time delays. We were able to set out new standards of image sampling for CLL, solve the semantic divergences, and point out interobserver variability as regards morphology. The limiting factors were the important need for expert investment, but they more importantly concerned the first line morphologists who should benefit from adequate tools, in terms of computer equipment as well as members of staff, so as to apprehend this second reading system as a quality control procedure.
Improvements in Technology: A Path to Safer and More Effective Hemodialysis
Authors: Ward Richard A. , Ronco Claudio
Published: January 2009

Effective dialysis therapy is now understood to encompass both small and large solute removal, using approaches that minimize intradialytic symptoms and maximize patient safety. Achieving the goal of providing effective dialysis for an expanding population of patients with increasingly complex medical problems at a time of limited resources will require technological innovation. To address this need, the latest generation of ergonomically designed dialysis machines incorporates as standard features the technology required to perform on-line convective therapies to maximize large solute removal, on-line measurement of ionic clearance to monitor small solute removal and real-time data processing to guide the delivery of therapy. In addition, these machines feature feedback control systems that may help reduce the unpleasant side effects associated with fluid removal during hemodialysis. These technological innovations offer therapeutic versatility while, at the same time, reducing the burden on patient care personnel, and are likely to make an important contribution to delivering safer and more effective dialysis therapy.
Reassessing Marketing of Kidneys from the 2008 Perspective
Authors: Friedman Eli A. , Friedman Amy L.
Published: January 2009

Progressive improvements in all aspects of the kidney transplant regimen establish this form of renal replacement therapy as superior to peritoneal or hemodialysis in terms of extent of rehabilitation and long-term recipient survival. Continuous growth in the number of patients with kidney failure sustained by dialytic therapy has not been associated with substantially increased deceased donor kidney contributions, causing intensified stressful waiting periods for potential recipients lacking a live kidney donor. Neither public relation campaigns nor local government efforts have substantially increased kidney donation. Buying a donor kidney is illegal and condemned as fostering exploitation of poor people by the wealthy. Widely publicized examples of coercion of unwilling donors create a negative image of harmful, inhumane conduct deployed to obtain kidneys sold and transplanted under unsavory circumstances. Yet efforts to establish and test governmental programs to supervise and sustain acceptable standards for the sale and implantation of kidneys from fully informed, medically evaluated and protected, fairly compensated donors have been resisted and frustrated by those who consider such compensation loathsome. Accordingly, while selling kidneys is prohibited by law, pressure from those wanting to quench the number of deaths of wait-listed dialysis patients continues forcing reexamination of an issue that, like prohibition of the possession and sale of alcohol in the United States in 1920, places the will of a people in opposition to unreasonably restrictive laws. The debate continues.
Enhancing Hemodialysis Efficacy through Neuromuscular Stimulation
Authors: Madhavan Guruprasad , Nemcek Mary A. , Martinez David G. , McLeod Kenneth J.
Published: January 2009

Beat-to-beat blood pressure monitoring was used to assess the efficacy of reflex-mediated, calf muscle pump stimulation to enhance cardiovascular refilling in subjects in the supine and seated positions, with extension of this stimulation technology to dialysis evaluated in 2 dialysis patients. Micromechanical stimulation (50 μm at 45 Hz) of the plantar surface was found to significantly increase both the rate and volume of cardiovascular refilling relative to that observed for subjects in the supine position. During hemodialysis, calf muscle pump stimulation permitted significantly increased ultrafiltrate removal, specifically from 78 to 96% of clinical goal, while serving to maintain both blood pressure and blood volume.
Extracellular Volume and Aldosterone Interaction in Chronic Kidney Disease
Authors: Klemmer Philip J. , Bomback Andrew S.
Published: January 2009

Since the advent of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, little attention has been given to the potential proinflammatory effects of aldosterone in high-volume states on the kidney and cardiovascular system. In order to be correctly interpreted, aldosterone levels require a volume cofactor which can now be determined by measurement of extracellular fluid volume by means of bioimpedance. Chronic kidney disease patients frequently have expanded extracellular volume (ECV) in the presence of elevated aldosterone levels. This combination may lead to cardiovascular and renal inflammation and fibrosis that can be mitigated by more precise control of ECV and/or blockade of the mineralocorticoid receptor.
Cardiac Disease in the Dialysis Patient: Good, Better, Best Clinical Practice
Authors: Hampl Hannelore , Riedel Eberhard
Published: January 2009

Proven strategies to reduce cardiovascular events and cardiac mortality in hemodialysis patients are given on the basis of pathophysiology. This is an overview of our clinical know-how acquired during the last 30 years. We try to answer the following questions: (1) how to reduce cardiovascular events and cardiac mortality in hemodialysis patients; (2) how to achieve regression of left ventricular hypertrophy, the most important predictor of sudden cardiac death; (3) how to manage iron status during full correction of renal anemia to prevent iron deficiency-induced reactive thrombocytosis, which is recognized to cause fatal stroke and cardiovascular thrombosis; (4) how to maintain responsiveness to erythropoiesis-stimulating agents during correction of renal anemia, thereby avoiding unnecessarily high doses and so reaching ultimate cost-effectiveness. Conclusion: Normalization of renal anemia is not responsible for increased risk of cardiovascular events/cardiac mortality. The inability to adequately address iron status in hemoglobin normalization studies and the underprescription of effective cardiac/antihypertensive medication might explain the adverse outcome. Effective cardiac/antihypertensive medication, intensive iron therapy during normalization of hemoglobin, optimized correction of metabolic acidosis and supplementation of vitamins which are involved in the energy metabolism should be considered to significantly improve the outcome of hemodialysis patients.
Study of 5-Aza-CdR on Transcription Regulation of RASSF1A Gene in the BIU87 Cell Line
Authors: Liu Xuefeng , Dai Xianwei , Wu Bin
Published: January 2009

Objectives: To investigate the effect of 5-Aza-CdR on methylation and expression of RASSF1A gene in the human bladder cancer BIU87 cell line. Methods: Cultured BIU87 cells were treated with increasing concentrations (0.1, 0.5, 1.0, 5.0 μmol/l) of 5-Aza-CdR. MTT was used to detect the proliferation of BIU87 cells. The methylation status and expression level of RASSF1A gene in BIU87 cells were analyzed by methylation-specific polymerase chain reaction and RT-PCR before and after treatment with 5-Aza-CdR. Meanwhile, Western blot was used to detect the changes of RASSF1A protein. Results: In this study we found that the growth velocity of the BIU87 cell line was suppressed to various degrees after having been treated with different concentrations of 5-Aza-CdR, and the survival rate decreased with increasing 5- Aza-CdR concentrations. Besides, the methylation status of RASSF1A was obviously reversed and mRNA was re-expressed after treatment with 5-Aza-CdR. Expression of RASSF1A protein increased with increasing 5-Aza-CdR concentrations. Conclusions: Our results suggest that the tumor-suppressive effect of 5-Aza-CdR may result from reactivation of silenced RASSF1A through a demethylation function.
Recent Therapeutic Strategies Improve Renal Outcome in Patients with IgA Nephropathy
Authors: Komatsu Hiroyuki , Fujimoto Shouichi , Hara Seiichiro , Fukuda Akihiro , Fukudome Keiichi , Yamada Kazuhiro , Sato Yuji , Kitamura Kazuo
Published: January 2009

Background/Aims: Various treatment options for IgA nephropathy (IgAN) have been developed, particularly over the past decade. Nevertheless, whether such therapeutic interventions improve actual renal outcome as compared with previous therapies remains obscure. Methods: We examined data from 304 patients with IgAN whose serum creatinine value at renal biopsy was <2.0 mg/dl and who had been followed up for >12 months. We assigned the patients to groups according to the period of diagnosis (group E, between 1981 and 1995, n = 130; group L, between 1996 and 2006, n = 174). Results: Significantly more patients had received steroid therapy and renin-angiotensin system inhibitors (RAS-I) in group L than in group E (steroid 51.7 vs. 15.4%, p < 0.001; RAS-I 42.0 vs. 1.5%, p < 0.001). Forty patients overall reached end-stage renal disease (ESRD) within 81.9 ± 55.1 months of observation. Kaplan-Meier analysis showed that the 10-year renal survival rate of group L persisted and significantly differed from that of group E (95.7 vs. 75.2%, p = 0.005). The Cox proportional hazards model adjusted for known prognostic markers demonstrated that initial therapeutic interventions in group L prevented ESRD, with a hazard ratio of 0.29 (95% CI 0.11–0.76, p = 0.011). Conclusion: Although this study is not a prospective trial, our results indicate that aggressive therapeutic intervention for IgAN over the past decade has improved actual renal outcome.
Pater Desiderius Lenz at Beuron: History, Egyptology, and Modernism in Nineteenth-Century German Monastic Art
Authors: Davenport Nancy
Published: January 2009

The text is an introduction to the art made by a Benedictine community of artist/monks in the village of Beuron in the state of Hohenzollern-Sigmaringen in southwestern Germany in the late nineteenth and early twentieth centuries. The founder of the school, Pater Desiderius Lenz, studied art in Munich, received a scholarship to work in Rome, but discovered the source for his work in the flat two-dimensional colored drawings and prints of Egyptian art in albums published by the German archaeologist, Richard Lepsius. The iconic and non-empathetic style of Beuron art inspired by Lenz's ideas and writings is discussed with respect to its source in the Benedictine experience, bonded as it is to the church walls and to the Gregorian chanting of the monastic choirs. But at the same time, because of its rejection of the form and expression of the three-dimensional world of man and nature, it is characterized as being Modernist as well, an early by-product of that twentieth century stylistic phenomenon. Through Lenz's first architectural project, the St. Maurus Chapel above the Danube near Beuron, and his evolving exploration of the subject of the Pieta, his Egypto-Modernist religious imagery is described.
The End of the Democratic Transition? Analyzing the Quality of Democracy Model in Post-Communism
Authors: Ciobanu Monica
Published: January 2009

The problem addressed in this article is the adequacy of the recently developed quality of democracy model in analyzing post-communist democracies in the context of their recent accession into the European Union. In order to provide some clarification of this question, the conceptual framework is utilized in light of past and recent political developments in Bulgaria, Hungary, Poland and Romania. Several procedural and substantive dimensions of the model are examined, particularly participation and competition, accountability, governance, rule of law, corruption and aspects of popular legitimacy. The main conclusion is that while the model proves its ability to understand some of the specific dynamics and peculiarities of these cases, it is less successful in showing how democratic legitimacy becomes institutionalized.
Acceding to the Norm: The Accession of LDCs to the WTO
Authors: Hawthorne Helen
Published: January 2009

Least-developed countries (LDCs) have been included in the multilateral trade regime since the days of the General Agreement on Tariffs and Trade (GATT), with the majority joining during the 1960s and 1970s following their independence. The Doha Round of negotiations of the World Trade Organization (WTO) has focused significant attention on the role and impact of LDCs that are currently WTO members as well as the process of accession for those remaining outside the organization. This article examines the accession experiences of LDCs joining both the GATT and the WTO with regard to international development norms, and demonstrates that the manner in which the majority of LDCs acceded to the multilateral trade regime has enabled them to have a greater impact on the multilateral trade organization than would otherwise have been possible.
Bilateralism and Multilateralism: Taiwan's Trade Liberalization Trajectory
Authors: Huang Chen-wei
Published: January 2009

Whether or not bilateralism and regionalism have threatened multilateralism has been debated in the literature. In recent years, the United States has argued that the increasing numbers of regional and bilateral trading arrangements made under the Bush administration are 'complementary' to the World Trade Organization (WTO). Accordingly, the case of Taiwan's bilateral trade negotiations with the United States and its accession to the WTO provide a useful case study for examining the relations between bilateralism and multilateralism. This article not only aims to study the role of bilateralism and multilateralism in Taiwan's liberalization process, it also seeks to compare the two types of trade diplomacy in terms of power relations, decision-making and negotiation, and the influence of negotiation on economic liberalization. The article is divided into three sections: the first section focuses on US–Taiwan bilateral trade negotiations during the 1970s and 1980s; the second section mainly discusses the process of Taiwan's WTO accession; and the final section examines Taiwan's bilateral and multilateral trade diplomacy after its accession.
Developing Objective Operational Definitions for Monitoring Drought
Authors: Quiring Steven M.
Published: January 2009

Drought is a complex phenomenon that is difficult to accurately describe because its definition is both spatially variant and context dependent. Decision makers in local, state, and federal agencies commonly use operational drought definitions that are based on specific drought index thresholds to trigger water conservation measures and determine levels of drought assistance. Unfortunately, many state drought plans utilize operational drought definitions that are derived subjectively and therefore may not be appropriate for triggering drought responses. This paper presents an objective methodology for establishing operational drought definitions. The advantages of this methodology are demonstrated by calculating meteorological drought thresholds for the Palmer drought severity index, the standardized precipitation index, and percent of normal precipitation using both station and climate division data from Texas. Results indicate that using subjectively derived operational drought definitions may lead to over- or underestimating true drought severity. Therefore, it is more appropriate to use an objective location-specific method for defining operational drought thresholds.
An Adjoint Sensitivity Study of Buoyancy- and Wind-Driven Circulation on the New Jersey Inner Shelf
Authors: Zhang Weifeng G. , Wilkin John L. , Levin Julia C. , Arango Hernan G.
Published: January 2009

Adjoint sensitivity analysis is used to study the New York Bight circulation for three idealized situations: an unforced buoyant river plume, and upwelling and downwelling wind forcing. A derivation of adjoint sensitivity is presented that clarifies how the method simultaneously addresses initial, boundary, and forcing sensitivities. Considerations of interpretation and appropriate definitions of sensitivity scalar indices are discussed. The adjoint method identifies the oceanic conditions and forcing that are “dynamically upstream” to a region or feature of interest, as well as the relative roles of the prior ocean state, forcing, and dynamical influences. To illustrate the method, which is quite general, the authors consider coastal sea surface temperature (SST) variability and define the adjoint scalar index as the temporal–spatial mean squared SST anomaly on a segment of the New Jersey coast at the conclusion of a 3-day period. In the absence of wind, surface temperature advection dominates the SST anomaly with two sources of surface water identified. Downwelling winds amplify upstream advective influence. Sensitivity to temperature is separated into direct advection and the dynamic effect on density stratification and mixing. For upwelling conditions, this decomposition shows that coastal SST is controlled by both advection from the south and subsurface, but above the 5-m depth, and temperature-related density stratification between 5 and 15 m to 10 km offshore. By identifying the timing and location of ocean conditions crucial to subsequent prediction of specific circulation features, the adjoint sensitivity method has application to quantitative evaluation of observational sampling strategies.
Inferring Convective Weather Characteristics with Geostationary High Spectral Resolution IR Window Measurements: A Look into the Future
Authors: Sieglaff Justin M. , Schmit Timothy J. , Menzel W. Paul , Ackerman Steven A.
Published: January 2009

A high spectral resolution geostationary sounder can make spectrally detailed measurements of the infrared spectrum at high temporal resolution, which provides unique information about the lower-tropospheric temperature and moisture structure. Within the infrared window region, many spectrally narrow, relatively weak water vapor absorption lines and one carbon dioxide absorption line exist. Frequent measurement of these absorption lines can provide critical information for monitoring the evolution of the lower-tropospheric thermodynamic state. This can improve short-term convective forecasts by monitoring regions of changing atmospheric stability. While providing valuable observations, the current geostationary sounders are spectrally broad and do not resolve the important spectrally narrow absorption lines needed to observe the planetary boundary layer. The usefulness of high spectral resolution measurements from polar-orbiting instruments has been shown in the literature, as has the usefulness of high temporal resolution measurements from geostationary instruments. Little attention has been given to the combination of high temporal along with high spectral resolution measurements. This paper demonstrates the potential utility of high temporal and high spectral resolution infrared radiances.
From implicit to explicit language knowledge in intervention: Introduction to the Special Issue on intervention and metalanguage
Authors: Ravid Dorit , Hora Anat
Published: January 2009

The Special Issue is themed on intervention programs which set educational and clinical goals and use explicit language instruction to achieve them. This introduction to the Special Issue explores the non-obvious relationship between intervention, metalinguistics and the study of developmental psycholinguistics. Intervention is typically designed to remedy and accelerate processes that are assumed to be naturally occurring under optimal circumstances. Beyond employing intervention to test hypotheses in developmental cognitive science, most intervention studies are explicitly constructed to improve impaired or non-optimal language skills. The introduction reviews the two major themes of this issue: the problematic yet uniquely efficacious role of intervention studies in gauging the variables that can be modified to improve language and literacy skills; and the origins and nature of metalinguistic awareness in development. The five papers appearing in this Special Issue each highlight a different facet of the relationship between intervention and metalanguage.
A Fluorescence Lifetime-Based Assay for Protease Inhibitor Profiling on Human Kallikrein 7
Authors: Doering Klaus , Meder Gabriele , Hinnenberger Manuela , Woelcke Julian , Mayr Lorenz M. , Hassiepen Ulrich
Published: January 2009

Fluorescence lifetime is an intrinsic parameter describing the fluorescence process. Changes in the fluorophore's physicochemical environment can lead to changes in the fluorescence lifetime. When used as the readout in biological assays, it is thought to deliver superior results to conventional optical readouts. Hence it has the potential to replace readout technologies currently established in drug discovery such as absorption, luminescence or fluorescence intensity. Here we report the development of an activity assay for human kallikrein 7, a serine protease involved in skin diseases. As a probe, we have selected a blue-fluorescent acridone dye, featuring a remarkably long lifetime that can be quenched by either of the 2 natural amino acids, tyrosine and tryptophan. Incorporating this probe and 1 of the quenching amino acids on either side of the scissile bond of the substrate peptide enables us to monitor the enzymatic activity by quantifying the increase in the fluorescence lifetime signal. A systematic investigation of substrate structures has led to a homogenous, microplate-based, compound profiling assay that yields inhibitory constants down into the single-digit nanomolar range. This type of assay has now been added to our standard portfolio of screening techniques, and is routinely used for compound profiling. ( Journal of Biomolecular Screening 2009:1-9)
Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant
Authors: Rank Gerhard , Sutton Rosemary , Marshall Vikki , Lundie Rachel J. , Caddy Jacinta , Romeo Tony , Fernandez Kate , McCormack Matthew P. , Cooke Brian M. , Foote Simon J. , Crabb Brendan S. , Curtis David J. , Hilton Douglas J. , Kile Benjamin T. , Jane Stephen M.
Published: January 2009

Insights into the role of ankyrin-1 (ANK-1) in the formation and stabilization of the red cell cytoskeleton have come from studies on the nb/nb mice, which carry hypomorphic alleles of Ank-1. Here, we revise several paradigms established in the nb/nb mice through analysis of an N-ethyl-N-nitrosourea (ENU)–induced Ank-1–null mouse. Mice homozygous for the Ank-1 mutation are profoundly anemic in utero and most die perinatally, indicating that Ank-1 plays a nonredundant role in erythroid development. The surviving pups exhibit features of severe hereditary spherocytosis (HS), with marked hemolysis, jaundice, compensatory extramedullary erythropoiesis, and tissue iron overload. Red cell membrane analysis reveals a complete loss of ANK-1 protein and a marked reduction in β-spectrin. As a consequence, the red cells exhibit total disruption of cytoskeletal architecture and severely altered hemorheologic properties. Heterozygous mutant mice, which have wild-type levels of ANK-1 and spectrin in their RBC membranes and normal red cell survival and ultrastructure, exhibit profound resistance to malaria, which is not due to impaired parasite entry into RBC. These findings provide novel insights into the role of Ank-1, and define an ideal model for the study of HS and malarial resistance.
DFP: a Bioconductor package for fuzzy profile identification and gene reduction of microarray data
Authors: Glez-Peña Daniel , Álvarez Rodrigo , Díaz Fernando , Fdez-Riverola Florentino
Published: January 2009

Background

Expression profiling assays done by using DNA microarray technology generate enormous data sets that are not amenable to simple analysis. The greatest challenge in maximizing the use of this huge amount of data is to develop algorithms to interpret and interconnect results from different genes under different conditions. In this context, fuzzy logic can provide a systematic and unbiased way to both (i) find biologically significant insights relating to meaningful genes, thereby removing the need for expert knowledge in preliminary steps of microarray data analyses and (ii) reduce the cost and complexity of later applied machine learning techniques being able to achieve interpretable models.

Results

DFP is a new Bioconductor R package that implements a method for discretizing and selecting differentially expressed genes based on the application of fuzzy logic. DFP takes advantage of fuzzy membership functions to assign linguistic labels to gene expression levels. The technique builds a reduced set of relevant genes (FP, Fuzzy Pattern) able to summarize and represent each underlying class (pathology). A last step constructs a biased set of genes (DFP, Discriminant Fuzzy Pattern) by intersecting existing fuzzy patterns in order to detect discriminative elements. In addition, the software provides new functions and visualisation tools that summarize achieved results and aid in the interpretation of differentially expressed genes from multiple microarray experiments.

Conclusion

DFP integrates with other packages of the Bioconductor project, uses common data structures and is accompanied by ample documentation. It has the advantage that its parameters are highly configurable, facilitating the discovery of biologically relevant connections between sets of genes belonging to different pathologies. This information makes it possible to automatically filter irrelevant genes thereby reducing the large volume of data supplied by microarray experiments. Based on these contributions GENE CBR, a successful tool for cancer diagnosis using microarray datasets, has recently been released.
Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay
Authors: Knight Louise A , Kurbacher Christian M , Glaysher Sharon , Fernando Augusta , Reichelt Ralf , Dexel Susanne , Reinhold Uwe , Cree Ian A
Published: January 2009

Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effectsin vitroand in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation.
Low Spigelian hernia in a 6-year-old boy presenting as an incarcerated inguinal hernia: a case report
Authors: Christianakis Efstratios , Paschalidis Nikolaos , Filippou Georgios , Rizos Spiros , Smailis Dimitrios , Filippou Dimitrios
Published: January 2009

Introduction

Lower Spigelian hernia is a very rare entity. The clinical findings are similar to those of inguinal hernias and in many cases may be misdiagnosed. In the literature, only a few references to this entity have been reported in children. To the best of our knowledge, this is the first case report of a lower Spigelian hernia in a child who presented with an acute painful scrotum.

Case presentation

We discuss the case of a 6-year-old Greek boy who presented to our emergency department complaining of severe pain in the left inguinal area and scrotum. The acute painful swelling started suddenly, without any obvious cause. The initial diagnosis was incarcerated inguinal hernia which was reduced with difficulty. Five days later, the patient still experienced mild pain during palpation and he was operated on. During the operation, a large lower Spigelian hernia was revealed and reconstructed.

Conclusion

Although Spigelian hernias are rare in children and difficult to diagnose, physicians should be aware of them and include them in the differential diagnosis.
Determination of a Binding Site of Cu and Ni Metal Ions with Oxytocin Peptide by Electrospray Tandem Mass Spectrometry and Multiple Mass Spectrometry
Authors: Jeong Hye-Jin , Kim Ho-Tae
Published: January 2009

The structures of a [NiII, CuII—oxytocin] complex were investigated by electrospray ionization-mass spectrometry in positive mode. The fragmentation patterns of the [NiII, CuII + OT]2+ complex were analyzed by tandem mass spectrometry and multiple mass spectrometry in the gas-phase. Conformations of metalII ion binding to oxytocin (OT) have been studied to explain the biological activity difference in the physiological solution. The [NiII + OT]2+ and [CuII + OT]2+ complexes were observed as the main ions in MS spectra. The Cys1–Tyr2–Ile3–Gln4 sequence of oxytocin is suggested to be a binding site for the [NiII + OT]2+ gas-phase complex and Ile3–Gln4–Asn5–Cys6 sequence for the [CuII + OT]2+ gas-phase complex. The specific binding site of CuII ion in the [CuII + OT]2+ complex is explained as a reason of the negligible effect on the [CuII—oxytocin] biological activity in aqueous solution.
Pulmonary Myxoma in a Sheep
Authors: Ilhan F. , Yener Z.
Published: January 2009

Pulmonary myxoma is an uncommon neoplasm. A pale tan, lobulated, and well-circumscribed mass was discovered at slaughter in the left lung of a 5-year-old sheep. Histologically, the tumor was composed of spindloid to stellate cells in a myxoid matrix. Neoplastic cells were immunohistochemically positive for vimentin but did not express cytokeratins, S-100 protein, smooth muscle actin, desmin, or p53. On the basis of the histologic and immunohistochemical findings, this tumor was diagnosed as a myxoma.
Neue Regelungen für die Gesellschafterliste und die Geschäftsanteile sowie der gutgläubige Erwerb von Geschäftsanteilen nach dem MoMiG – Folgen für die GmbH-Beratung
Authors: Gottschalk Eckart
Published: January 2009

Am 1.11.2008 trat das Gesetz zur Modernisierung des GmbH-Rechts und zur Bekämpfung von Missbräuchen (MoMiG) in Kraft. Nach § 16 Abs. 3 GmbHG können nunmehr Geschäftsanteile einer GmbH von dem in der Gesellschafterliste eingetragenen Veräußerer gutgläubig erworben werden. Legitimationsgrundlage für den gutgläubigen Erwerb ist die Gesellschafterliste (§ 40 GmbHG), die damit zum »Rechtscheinsträger« aufgewertet wird. Mit der Einführung eines gutgläubigen Erwerbs von Geschäftsanteilen betritt der Gesetzgeber nach intensiver Diskussion Neuland. Die neuen Regelungen gelten sowohl für die klassische GmbH als auch für die neu eingeführte Unternehmergesellschaft (haftungsbeschränkt) (§ 5 a GmbHG).

Im Folgenden wird zunächst die Neuregelung der Gesellschafterliste dargestellt (I.) und einige eher technische Änderungen bei den Regelungen zu den Geschäftsanteilen erörtert (II.). Im Anschluss daran wird der neue Gutglaubenstatbestand in § 16 Abs. 3 GmbHG näher untersucht (III.). Bei der Darstellung der neuen Vorschriften sollen jeweils insbesondere die Folgen für die GmbH-Beratung näher dargestellt werden.
Design and Results of a Study to Measure Environmental Factors in Airliner Cabins and to Assess the Health and Comfort of Passengers and Crew Using Surveys
Authors: Myers Jeffrey D. , Spicer Chester W. , Goodwin Bradley P.
Published: January 2009

The design and results of a study to relate human comfort and health to the airliner cabin environment are described. Rationale for studying the airliner cabin environment, the scope of the study, the experimental design, and flight selection are presented. This study was unique in including both in-flight passenger and crew surveys and a variety of measurements of the physical and chemical environment in the cabins of airliners in revenue service. It was found that, even with a very small sample, various physical parameters were statistically related to reported human comfort as measured by the survey instrument. For example, higher levels of carbon dioxide in the cabin during cruising were associated with lower ratings of the overall air quality in the cabin, less satisfaction with the odor in the cabin, and less satisfaction with the freshness of the air in the cabin. This paper focuses on the process for developing the study design and results from the survey. Companion papers discuss the results of the cabin chemical and physical environmental measurements.
Recovery of Birth WeightzScore Within 2 Years of Diagnosis Is Positively Associated With Pulmonary Status at 6 Years of Age in Children With Cystic Fibrosis
Authors: Lai HuiChuan J. , Shoff Suzanne M. , Farrell Philip M. ,   with the Wisconsin Cystic Fibrosis Neonatal Screening Group
Published: January 2009

OBJECTIVE. We recently reported that 60% of children newly diagnosed with cystic fibrosis who had pancreatic insufficiency responded to treatment initiation and achieved catch-up weight gain to a level comparable with their birth weight z score within 2 years of diagnosis (“responders”), whereas the remaining 40% failed to do so (“nonresponders”). The present study examined the impact of this early weight recovery on subsequent growth pattern and pulmonary status at 6 years of age.

PATIENTS AND METHODS. Sixty-three children with cystic fibrosis who had pancreatic insufficiency but no meconium ileus, and were enrolled in the Wisconsin Cystic Fibrosis Neonatal Screening Project, were studied. Responders were defined by a recovery of weight z score comparable with that at birth within 2 years of diagnosis. From ages 2 to 6, growth was measured by both height and BMI. Pulmonary status was evaluated by symptoms, spirometry, quantitative chest radiography, and respiratory microbiology.

RESULTS. The majority (71%) of the responders maintained their early weight recovery through 6 years of age, whereas only 32% of the nonresponders achieved substantial growth improvement from 2 to 6 years of age. Proportionately fewer responders reported cough symptoms (10% daytime cough; 22% nighttime cough) compared with nonresponders (41% daytime cough; 45% nighttime cough) at age 6. The percentage of predicted forced expiratory volume in 1 second at age 6 was 11% higher in responders (99.5% ± 13.9%) compared with nonresponders (88.3% ± 18.5%). Responders had significantly better Brasfield (20.1 ± 1.4) and Wisconsin chest radiograph (8.3 ± 3.3) scores compared with nonresponders (Brasfield: 18.9 ± 1.8; Wisconsin: 12.3 ± 8.3). Respiratory microbiology results were not significantly different. Multiple regression analyses indicated that the positive association between responder and percent predicted forced expiratory volume in 1 second at 6 years of age remained statistically significant after controlling for infections with Pseudomonas aeruginosa and Staphylococcus aureus and chest radiograph scores. Growth patterns from 2 to 6 years of age were not associated with pulmonary measures at age 6.

CONCLUSIONS. Patients with cystic fibrosis with pancreatic insufficiency who achieved early growth recovery within 2 years of diagnosis had fewer cough symptoms, higher lung function, and better chest radiograph scores at 6 years of age.
Evaluation of an Intimate Partner Violence Curriculum in a Pediatric Hospital
Authors: Johnson Norah L. , Klingbeil Carol , Melzer-Lange Marlene , Humphreys Candi , Scanlon Matthew C. , Simpson Pippa
Published: January 2009

OBJECTIVE. Intimate partner violence harms victims as well as families and communities. Many barriers account for limited intimate partner violence screening by nurses. The purpose of this study was to measure how participation in a curriculum about screening parents for intimate partner violence, at a pediatric hospital, affects a nurse's knowledge, attitudes, behaviors, and self-efficacy for intimate partner violence screening.

METHODS. In this interventional, longitudinal study, data were collected before participation in an intimate partner violence screening curriculum, after participation, and 3 months later. The measurement tool was adapted from Maiuro's (2000) Self-efficacy for Screening for Intimate Partner Violence Questionnaire.

RESULTS. Sixty-eight pediatric nurses completed all aspects of the study. At baseline, 18 (27%) nurses self-reported seeing a parent with an injury, and of those only 7 (39%) followed up with intimate partner violence screening. Factor analysis was performed on the baseline Self-efficacy for Screening for Intimate Partner Violence Questionnaire by using varimax rotation. Five factors were identified: conflict, fear of offending parent, self-confidence, appropriateness, and attitude. Only fear of offending parent was significantly different from times 1 to 3, indicating that nurses were less fearful after the training. Cronbach's α value for the total questionnaire at baseline was .85. Nurses reported significant improvement (baseline to 3-month follow-up) in several self-efficacy items.

CONCLUSIONS. Participation in a 30-minute curriculum on intimate partner violence screening was associated with improvements in self-efficacy and significantly lower fear of offending parents 3 months after training. Nurses also showed improvement in the perception of resources available for nurses to manage intimate partner violence. Thirty-minute hospital-based curriculums that include victim testimonial video and practice role-playing to simulate parent interactions are recommended.