bluuebunny/crossref_metadata_2025 huggingface dataset:
Structuring Strategic Design Management: Michael Porter's Value Chain
Authors: de Mozota Brigitte Borja
Published: September 2010

AS A RESOURCE, design management has an impact on a broad range of organizational activities. Brigitte Borja de Mozota conceptualizes this diversity in a framework, built on the ideas of Michael Porter, that forms bridges between design and business decision making—in operations, in support functions, and in the development of long‐term strategies. This clarifies the areas in which design is a corporate asset, helps order design management research and information, and offers pathways for creating effective design management curricula.
Developing a Framework for Design Management
Authors: Powell Earl N.
Published: September 2010

BASED ON YEARS of experience and countless interaction with executives, managers, designers, and consultants, Earl Powell distills the attitudes, knowledge, and skills essential to effective design management. These are examined under the headings of “purpose,” “people,” “presence,” “process,” “project,” and “practice.” The first three are intangible and qualitative. The second three are pragmatic and subject to more precise definition and measurement. To exploit design as a strategic asset, an organization must excel in all six.
Rapid Ideation in Action: Getting Good Ideas Quickly and Cheaply
Authors: Clark Brian , Reinertsen Donald G.
Published: September 2010

TRADITIONAL methodologies for developing new products are slow and often eliminate promising ideas. The intensive “rapid ideation” process presented by Brian Clark and Donald Reinertsen exploits interdisciplinary teams and model making to generate, evaluate, and refine a broad range of design alternatives in a short time frame. The technique offers improvements in speed, quality, and costs; it also strengthens cross‐functional communication, enhances understanding of technologies, and generates early customer feedback.
Experiential Marketing: A New Framework for Design and Communications
Authors: Schmitt Bernd
Published: September 2010

IN BERND SCHMITT'S conception of branding, consumers buy experiences rather than products or services. Thus, like many corporate executives, Schmitt asks: How can these experiences be managed? He articulates five distinct experience “modules,” followed by a review of strategies for analyzing the balance among those modules. It's a holistic view of marketing that integrates a broad spectrum of design elements to communicate with customers and influence their loyalty and purchase decisions.
Needfinding: The Why and How of Uncovering People's Needs
Authors: Patnaik Dev , Becker Robert
Published: September 2010

ALTHOUGH Robert Becker and Dev Patnaik acknowledge that needs don't generate specific product or service solutions, they know that the science of needfinding can be a dynamic platform for design. The authors define terms related to this process and outline the steps that help identify development opportunities. Critical need‐finding principles include letting consumers guide the flow of research, collecting data in a variety of different forms, and integrating research and design in a series of iterative stages as a way to fine‐tune results.
Brand is the Thing
Authors: Vossoughi Sohrab
Published: September 2010

DESIGN SHOULD BE an element of every organization's long‐term strategy. Sohrab Vossoughi sees this as especially important in conveying brand—the expression of a company's values, and the totality of the experiences imbedded in its products, services, communications, and environments. In this analysis, design is a business rather than an artistic exercise. It is richly three‐dimensional, extending far beyond graphics. And it emerges from sophisticated interdisciplinary research and planning.
The E‐Commerce Blueprint: Creating Online Brand Experiences
Authors: Norton David W. , Hansen Lise
Published: September 2010

ACONTINUING design challenge is to develop an Internet retail environment that transforms visitors into customers. Dave Norton and Lise Hansen believe success depends on a detailed understanding of the information potential customers want. This allows designers to devise relevant and compelling online experiences, a sequence of unique exchanges that build a relationship between a customer and a brand. A fascinating case study on the Royal Caribbean International Web site illustrates their design principles.
Suffusing the Organization with Design Consciousness
Authors: Marzano Stefano
Published: September 2010

IT'S CALLED “High Design,” but it's not about an elite sense of style. At Philips Design, Stefano Marzano explains, it refers to a philosophy that emphasizes the creation of solutions that fulfill genuine needs and that are of enduring value. It's an interdisciplinary approach that takes advantage of technology, but with an ethical, human touch. It's a way to open innovative frontiers in design, and it's a mode of thinking evident throughout Philips, from units developing consumer electronics to those making complex medical equipment.
Valuing design: Enhancing corporate performance through design effectiveness
Authors: Hertenstein Julie H. , Platt Marjorie B. , Brown David R.
Published: September 2010

It's an initial study, but the analysis indicates that good design is, indeed, good business. Julie H. Hertenstein, Marjorie B. Platt, and David R. Brown have devised a method for relating an organization's focus on design with bottom‐line outcomes. They use 12 measures of financial performance and investigate 51 companies in four industries over a five‐year time frame. Confirming a long‐held belief—design‐conscious firms generally do better.
Prototyping is the shorthand of innovation
Authors: Kelley Tom
Published: September 2010

It was the pathway to discovering the structure of DNA. It was an early approach to understanding supersonic flight. It was the design source for Apple's first computer mouse. Taking on the role of storyteller, Tom Kelley narrates parables that joyfully share his insights on the value of prototyping. He offers many lessons that together make it abundantly clear that creative epiphanies and model building go hand in hand.
A Model on Liquid Penetration Into Soft Material With Application to Needle-Free Jet Injection
Authors: Chen Kai , Zhou Hua , Li Ji , Cheng Gary J.
Published: September 2010

A mathematical model has been presented for a high speed liquid jet penetration into soft solid by a needle-free injection system. The model consists of a cylindrical column formed by the initial jet penetration and an expansion sphere due to continuous deposition of the liquid. By solving the equations of energy conservation and volume conservation, the penetration depth and the radius of the expansion sphere can be predicted. As an example, the calculation results were presented for a typical needle-free injection system into which a silicon rubber was injected into. The calculation results were compared with the experimental results.
Identification of B-K near edge x-ray absorption fine structure peaks of boron nitride thin films prepared by sputtering deposition
Authors: Niibe Masahito , Miyamoto Kazuyoshi , Mitamura Tohru , Mochiji Kozo
Published: September 2010

Four π∗ resonance peaks were observed in the B-K near edge x-ray absorption fine structure spectra of boron nitride thin films prepared by magnetron sputtering. In the past, these peaks have been explained as the K-absorption of boron atoms, which are present in environment containing nitrogen vacancies, the number of which is 1–3 corresponding to the three peaks at higher photon energy. However, the authors found that there was a strong correlation between the intensities of these three peaks and that of O-K absorption after wide range scanning and simultaneous measurement of nitrogen and oxygen K-absorptions of the BN films. Therefore, the authors conclude that these three peaks at the higher energy side correspond to boron atoms bound to one-to-three oxygen atoms instead of three nitrogen atoms surrounding the boron atom in the h-BN structure. The result of the first-principles calculation with a simple cluster model supported the validity of this explanation.
The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K
Authors: Verdino Petra , Witherden Deborah A. , Havran Wendy L. , Wilson Ian A.
Published: September 2010

Skin Reaction

Lymphocytes in the skin known as γδ T cells provide an important barrier against infection and injury. Unlike classical αβ T cells, less is known about the molecular requirements of γδ T cell activation. Two studies demonstrate that the junctional adhesion molecule–like protein (JAML) is a costimulatory molecule for mouse γδ T.

Witherden
et al.

(p.
1205
; see the Perspective by

Shaw and Huang

) showed that JAML, binding to its ligand Coxsackie and adenovirus receptor (CAR), leads to proliferation, as well as cytokine and growth factor production by γδ T cells. In vivo, JAML-CAR interactions contributed to the wound healing response in mice.

Verdino
et al.

(p.
1210
; see the Perspective by

Shaw and Huang

) present a crystal structure of CAR/JAML, which revealed an intracellular signaling motif similar to that known for the αβ T cell costimulatory receptor that signals through phosphoinositide 3-kinase.
The Junctional Adhesion Molecule JAML Is a Costimulatory Receptor for Epithelial γδ T Cell Activation
Authors: Witherden Deborah A. , Verdino Petra , Rieder Stephanie E. , Garijo Olivia , Mills Robyn E. , Teyton Luc , Fischer Wolfgang H. , Wilson Ian A. , Havran Wendy L.
Published: September 2010

Skin Reaction

Lymphocytes in the skin known as γδ T cells provide an important barrier against infection and injury. Unlike classical αβ T cells, less is known about the molecular requirements of γδ T cell activation. Two studies demonstrate that the junctional adhesion molecule–like protein (JAML) is a costimulatory molecule for mouse γδ T.

Witherden
et al.

(p.
1205
; see the Perspective by

Shaw and Huang

) showed that JAML, binding to its ligand Coxsackie and adenovirus receptor (CAR), leads to proliferation, as well as cytokine and growth factor production by γδ T cells. In vivo, JAML-CAR interactions contributed to the wound healing response in mice.

Verdino
et al.

(p.
1210
; see the Perspective by

Shaw and Huang

) present a crystal structure of CAR/JAML, which revealed an intracellular signaling motif similar to that known for the αβ T cell costimulatory receptor that signals through phosphoinositide 3-kinase.
Fullerenes and Cosmic Carbon
Authors: Ehrenfreund Pascale , Foing Bernard H.
Published: September 2010

Hydrogen-poor conditions in a planetary nebula enable the detection of carbon-cage molecules C
60
and C
70
, confirming the existence of fullerenes in space.
China's Research Culture
Authors: Shi Yigong , Rao Yi
Published: September 2010

Government research funds in China have been growing at an annual rate of more than 20%, exceeding even the expectations of China's most enthusiastic scientists. In theory, this could allow China to make truly outstanding progress in science and research, complementing the nation's economic success. In reality, however, rampant problems in research funding—some attributable to the system and others cultural—are slowing down China's potential pace of innovation.
Novel Grant Promises Greener Buildings, Regional Growth
Authors: Mervis Jeffrey
Published: September 2010

Last week, a consortium led by Pennsylvania State University won a federal competition for $129 million over 5 years to spur efforts to develop technologies for making buildings more energy efficient.
Mycoplasma agassiziiStrain Variation and Distinct Host Antibody Responses Explain Differences between Enzyme-Linked Immunosorbent Assays and Western Blot Assays
Authors: Wendland Lori D. , Klein Paul A. , Jacobson Elliott R. , Brown Mary B.
Published: September 2010

The precarious status of desert (Gopherus agassizii) and gopher (G. polyphemus) tortoises has resulted in conservation efforts that now include health assessment as an important component of management decision-making. Mycoplasmal upper respiratory tract disease (URTD) is one of very few diseases in chelonians for which comprehensive and rigorously validated diagnostic tests exist. In this study, serum samples obtained from eightGopherustortoises documented at necropsy to (i) be enzyme-linked immunosorbent assay (ELISA) seropositive using the PS6 antigen, (ii) be infected withMycoplasma agassiziias indicated by direct isolation of the pathogen from the respiratory surfaces, and (iii) have histological lesions of mycoplasmal URTD were used to evaluate four distinct clinical isolates ofM. agassiziias antigens for ELISA and Western blot analyses. Each animal sample reacted in the Western blot with its homologousM. agassiziistrain, but recognition of heterologousM. agassiziistrains was variable. Further, individual animals varied significantly with respect to the specific proteins recognized by the humoral immune response. An additional 114Gopherusserum samples were evaluated using ELISA antigens prepared from the four distinctM. agassiziistrains;A405values were significantly correlated (r2goodness of fit range, 0.708 to 0.771;P< 0.0001) for all antigens tested. The results confirm that strain variation is responsible for the observed differences between Western blot binding patterns. Thus, reliance on a singleM. agassiziistrain as an antigen in Western blot assays may provide false-negative results. This could have adverse consequences for the well-being of these environmentally sensitive hosts if false-negative animals were relocated to sites consisting of true-negative populations.
Impact of Long-Term Storage on Stability of Standard DNA for Nucleic Acid-Based Methods
Authors: Röder Barbara , Frühwirth Karin , Vogl Claus , Wagner Martin , Rossmanith Peter
Published: September 2010

Real-time PCR is dependent upon a calibration function for quantification. While long-term storage of standards saves cost and time, solutions of DNA are prone to degradation. We present here the benchmark treatment for preservation of DNA standards, involving storage in 50% glycerol-double-distilled water, whereby a deviation of 0.2 threshold cycle (

C
T

) values resulted after 100 days of storage.
Improved PCR Methods for Detection of African Rabies and Rabies-Related Lyssaviruses
Authors: Coertse Jessica , Weyer Jacqueline , Nel Louis H. , Markotter Wanda
Published: September 2010

Eleven different lyssavirus species, four of which occur on the African continent, are presently recognized. These viruses cause rabies, the burden of which is highest in the developing world, where routine laboratory diagnosis is often not available. From an epidemiological and control perspective, it is necessary that diagnostic methods detect the diversity of lyssaviruses present in different regions of the world. A published and widely used heminested reverse transcription-PCR (hnRT-PCR) was evaluated for its ability to detect a panel of diverse African lyssaviruses. Due to the limitations experienced for this assay, an alternative hnRT-PCR was developed. The new assay was found to be accurate and sensitive in the detection of African lyssavirus RNA in a variety of clinical specimens. The assay was further adapted to a real-time PCR platform to allow rapid, one-step, quantitative, and single-probe detection, and an internal control for the verification of sample preparation was included. The limit of detection of the real-time PCR assay was 10 RNA copies per reaction, with inter- and intra-assay variability below 4%. Subsequently, in demonstrating utility, both assays were successfully applied to antemortem rabies diagnosis in humans. We believe that the quantitative real-time PCR assay could find application as a routine confirmatory test for rabies diagnosis in the future and that it will serve as a valuable research tool in the biology of African lyssaviruses. Alternatively, the hnRT-PCR assay can be used in laboratories that do not have access to expensive real-time PCR equipment for sensitive diagnosis of lyssaviruses.
CD1d, a Sentinel Molecule Bridging Innate and Adaptive Immunity, Is Downregulated by the Human Papillomavirus (HPV) E5 Protein: a Possible Mechanism for Immune Evasion by HPV
Authors: Miura Shiho , Kawana Kei , Schust Danny J. , Fujii Tomoyuki , Yokoyama Terufumi , Iwasawa Yuki , Nagamatsu Takeshi , Adachi Katsuyuki , Tomio Ayako , Tomio Kensuke , Kojima Satoko , Yasugi Toshiharu , Kozuma Shiro , Taketani Yuji
Published: September 2010

CD1d and CD1d-restricted natural killer T (NKT) cells serve as a natural bridge between innate and adaptive immune responses to microbes. CD1d downregulation is utilized by a variety of microbes to evade immune detection. We demonstrate here that CD1d is downregulated in human papillomavirus (HPV)-positive cellsin vivoandin vitro. CD1d immunoreactivity was strong in HPV-negative normal cervical epithelium but absent in HPV16-positive CIN1 and HPV6-positive condyloma lesions. We used two cell lines forin vitroassay; one was stably CD1d-transfected cells established from an HPV-negative cervical cancer cell line, C33A (C33A/CD1d), and the other was normal human vaginal keratinocyte bearing endogenous CD1d (Vag). Flow cytometry revealed that cell surface CD1d was downregulated in both C33A/CD1d and Vag cells stably transfected with HPV6 E5 and HPV16 E5. Although the steady-state levels of CD1d protein decreased in both E5-expressing cell lines compared to empty retrovirus-infected cells, CD1d mRNA levels were not affected. Confocal microscopy demonstrated that residual CD1d was not trafficked to the E5-expressing cell surface but colocalized with E5 near the endoplasmic reticulum (ER). In the ER, E5 interacted with calnexin, an ER chaperone known to mediate folding of CD1d. CD1d protein levels were rescued by the proteasome inhibitor, MG132, indicating a role for proteasome-mediated degradation in HPV-associated CD1d downregulation. Taken together, our data suggest that E5 targets CD1d to the cytosolic proteolytic pathway by inhibiting calnexin-related CD1d trafficking. Finally, CD1d-mediated production of interleukin-12 from the C33A/CD1d cells was abrogated in both E5-expressing cell lines. Decreased CD1d expression in the presence of HPV E5 may help HPV-infected cells evade protective immunological surveillance.
Conserved and Variable Features of Gag Structure and Arrangement in Immature Retrovirus Particles
Authors: de Marco Alex , Davey Norman E. , Ulbrich Pavel , Phillips Judith M. , Lux Vanda , Riches James D. , Fuzik Tibor , Ruml Tomas , Kräusslich Hans-Georg , Vogt Volker M. , Briggs John A. G.
Published: September 2010

The assembly of retroviruses is driven by oligomerization of the Gag polyprotein. We have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of
in vitro
-assembled Gag particles from human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus. These represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. Comparison of the three structures reveals the features of the supramolecular organization of Gag that are conserved between genera and therefore reflect general principles of Gag-Gag interactions and the features that are specific to certain genera. All three Gag proteins assemble to form approximately spherical hexameric lattices with irregular defects. In all three genera, the N-terminal domain of CA is arranged in hexameric rings around large holes. Where the rings meet, 2-fold densities, assigned to the C-terminal domain of CA, extend between adjacent rings, and link together at the 6-fold symmetry axis with a density, which extends toward the center of the particle into the nucleic acid layer. Although this general arrangement is conserved, differences can be seen throughout the CA and spacer peptide regions. These differences can be related to sequence differences among the genera. We conclude that the arrangement of the structural domains of CA is well conserved across genera, whereas the relationship between CA, the spacer peptide region, and the nucleic acid is more specific to each genus.
SOME RESULTS ON A NEW CLASS OF SHOCK MODELS
Authors: RANGAN ALAGAR , TANSU AYŞE
Published: September 2010

Traditional shock models view system failure time as a first passage problem. Yeh Lam proposed a new class of models called δ-shock models in which failure was dependent on the frequency of shocks. The present work generalizes Yeh Lam's results for renewal shock arrivals and random threshold. Several special cases and an optimal replacement problem are also discussed.
Does the Order Between Dividend Payment and New Stock Issuance Matter to Stock Price? — Evidence from Taiwan
Authors: Twu Mia
Published: September 2010

I argue that paying dividends before issuing new stock can increase the stock price in the case when firms announce dividend payments and new stock issuance contemporaneously. It enables issuing firms to disentangle the agency problem of paying dividends by newly-raised funds from dividend information for new stock issuances. I employ the seasoned offerings of Taiwan listed firms as the sample, because of their practice of paying dividends once a year. The conditional event study strongly supports this argument and explains why previous studies fail to detect the information conveyed by dividends for new stock issuances.
CEO Turnover in Reverse Splits
Authors: Wang Li-Hsun , Lin Chu-Hsiung , Chen Hsien-Ming
Published: September 2010

This study examines the application of CEO turnover on reverse stock splits firms. Using Taiwanese samples, we find that non-CEO turnover firms receive negative long-term abnormal returns, and their financial performances continue to decline following reverse splits. These findings are consistent with prior studies. Contrarily, neither significantly negative long-term abnormal returns nor changes on financial performance were found for CEO turnover firms. This study concludes that applying CEO turnover is suggestive in reverse splits. Additionally, we find that reverse split firms raise debt and concern with their short-term solvency following splits.
On distributing symmetric streaming computations
Authors: Feldman Jon , Muthukrishnan S. , Sidiropoulos Anastasios , Stein Cliff , Svitkina Zoya
Published: September 2010

A common approach for dealing with large datasets is to stream over the input in one pass, and perform computations using sublinear resources. For truly massive datasets, however, even making a single pass over the data is prohibitive. Therefore, streaming computations must be distributed over many machines. In practice, obtaining significant speedups using distributed computation has numerous challenges including synchronization, load balancing, overcoming processor failures, and data distribution. Successful systems in practice such as Google's MapReduce and Apache's Hadoop address these problems by only allowing acertain classof highly distributable tasks defined by local computations that can be applied in any order to the input.

The fundamental question that arises is: How does the class of computational tasks supported by these systems differ from the class for which streaming solutions exist?

We introduce a simple algorithmic model for massive, unordered, distributed (mud) computation, as implemented by these systems. We show that in principle, mud algorithms are equivalent in power to symmetric streaming algorithms. More precisely, we show that any symmetric (order-invariant) function that can be computed by a streaming algorithm can also be computed by a mud algorithm, with comparable space and communication complexity. Our simulation uses Savitch's theorem and therefore has superpolynomial time complexity. We extend our simulation result to some natural classes of approximate and randomized streaming algorithms. We also give negative results, using communication complexity arguments to prove that extensions to private randomness, promise problems, and indeterminate functions are impossible. We also introduce an extension of the mud model to multiple keys and multiple rounds.
Geodesic delaunay triangulations in bounded planar domains
Authors: Oudot Steve Y. , Guibas Leonidas J. , Gao Jie , Wang Yue
Published: September 2010

We introduce a new feature size for bounded domains in the plane endowed with an intrinsic metric. Given a point
x
in a domain
X
, the
systolic feature size
of
X
at
x
measures half the length of the shortest loop through
x
that is not null-homotopic in
X
. The resort to an intrinsic metric makes the systolic feature size rather insensitive to the local geometry of the domain, in contrast with its predecessors (local feature size, weak feature size, homology feature size). This reduces the number of samples required to capture the topology of
X
, provided that a reliable approximation to the intrinsic metric of
X
is available. Under sufficient sampling conditions involving the systolic feature size, we show that the geodesic Delaunay triangulation
D

x

(
L
) of a finite sampling
L
is homotopy equivalent to
X
. Under similar conditions,
D

x

(
L
) is sandwiched between the geodesic witness complex
C

W

X

(
L
) and a relaxed version
C

W

X,ν

(
L
). In the conference version of the article, we took advantage of this fact and proved that the homology of
D

x

(
L
) (and hence the one of
X
) can be retrieved by computing the persistent homology between
C

W

X

(
L
) and
C

W

X,ν

(
L
). Here, we investigate further and show that the homology of
X
can also be recovered from the persistent homology associated with inclusions of type
C

W

X,ν

(
L
)↪
C

W

X,ν′

(
L
), under some conditions on the parameters ν≤ν′. Similar results are obtained for Vietoris-Rips complexes in the intrinsic metric. The proofs draw some connections with recent advances on the front of homology inference from point cloud data, but also with several well-known concepts of Riemannian (and even metric) geometry. On the algorithmic front, we propose algorithms for estimating the systolic feature size of a bounded planar domain
X
, selecting a landmark set of sufficient density, and computing the homology of
X
using geodesic witness complexes or Rips complexes.
Fast asynchronous Byzantine agreement and leader election with full information
Authors: Kapron Bruce M. , Kempe David , King Valerie , Saia Jared , Sanwalani Vishal
Published: September 2010

We resolve two long-standing open problems in distributed computation by describing polylogarithmic protocols for Byzantine agreement and leader election in the asynchronous full information model with a nonadaptive malicious adversary. All past protocols for asynchronous Byzantine agreement had been exponential, andnoprotocol for asynchronous leader election had been known. Our protocols tolerate up to (1/3 − ϵ) ⋅nfaulty processors, for any positive constant ϵ. They are Monte Carlo, succeeding with probability 1 −o(1) for Byzantine agreement, and constant probability for leader election. A key technical contribution of our article is a new approach for emulating Feige's lightest bin protocol, even with adversarial message scheduling.
Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis
Authors: Hyodo Toshitake , Oda Takashi , Kikuchi Yuichi , Higashi Keishi , Kushiyama Taketoshi , Yamamoto Kojiro , Yamada Muneharu , Suzuki Shigenobu , Hokari Ryota , Kinoshita Manabu , Seki Shuhji , Fujinaka Hidehiko , Yamamoto Tadashi , Miura Soichiro , Kumagai Hiroo
Published: September 2010

The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (TEM) without affecting the function of naïve T cells (TN) and central memory T cells (TCM). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4+T cells and some of the CD8+T cells had the TEMphenotype (CD45RC−CD62L−). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that TEMand some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.
Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in vitro cyst growth of human ADPKD cyst epithelial cells
Authors: Yamaguchi Tamio , Reif Gail A. , Calvet James P. , Wallace Darren P.
Published: September 2010

In autosomal dominant polycystic kidney disease (ADPKD), aberrant proliferation of the renal epithelial cells is responsible for the formation of numerable fluid-filled cysts, massively enlarged kidneys, and progressive loss of renal function. cAMP agonists, including arginine vasopressin, accelerate cyst epithelial cell proliferation through protein kinase A activation of the B-Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway. The mitogenic effect of cAMP is equally potent and additive to growth factor stimulation. Here, we determined whether Sorafenib (BAY 43–9006), a small molecule Raf inhibitor, inhibits proliferation of cells derived from the cysts of human ADPKD kidneys. We found that nanomolar concentrations of Sorafenib reduced the basal activity of ERK, inhibited cAMP-dependent activation of B-Raf and MEK/ERK signaling, and caused a concentration-dependent inhibition of cell proliferation induced by cAMP, epidermal growth factor, or the combination of the two agonists. Sorafenib completely blocked in vitro cyst growth of human ADPKD cystic cells cultured within a three-dimensional collagen gel. These data demonstrate that cAMP-dependent proliferation of human ADPKD cyst epithelial cells is blocked by Sorafenib and suggest that small molecule B-Raf inhibitors may be a therapeutic option to reduce the mitogenic effects of cAMP on cyst expansion.
Characterization of mesonephric development and regeneration using transgenic zebrafish
Authors: Zhou Weibin , Boucher Rudrick C. , Bollig Frank , Englert Christoph , Hildebrandt Friedhelm
Published: September 2010

The zebrafish is a valuable vertebrate model for kidney research. The majority of previous studies focused on the zebrafish pronephros, which comprises only two nephrons and is structurally simpler than the mesonephros of adult fish and the metanephros of mammals. To evaluate the zebrafish system for more complex studies of kidney development and regeneration, we investigated the development and postinjury regeneration of the mesonephros in adult zebrafish. Utilizing two transgenic zebrafish lines ( wt1b::GFP and pod::NTR-mCherry), we characterized the developmental stages of individual mesonephric nephrons and the temporal-spatial pattern of mesonephrogenesis. We found that mesonephrogenesis continues throughout the life of zebrafish, with a rapid growth phase during the juvenile period and a slower phase in adulthood such that the total nephron number of juvenile and adult fish linearly correlates with body mass. Following gentamicin-induced renal injury, the zebrafish mesonephros can undergo de novo regeneration of mesonephric nephrons, a process known as neonephrogenesis. We found that wt1b expression was induced in individually dispersed cells in the mesonephric interstitium as early as 48 h following injury. These wt1b-expressing cells formed aggregates by 72–96 h following injury which proceeded to form nephrons. This suggests that wt1b may serve as an early marker of fated renal progenitor cells. The synchronous nature of regenerative neonephrogenesis suggests that this process may be useful for studies of nephron development.
Decision-Making, Errors, and Confidence in the Brain
Authors: Rolls Edmund T. , Grabenhorst Fabian , Deco Gustavo
Published: September 2010

To provide a fundamental basis for understanding decision-making and decision confidence, we analyze a neuronal spiking attractor-based model of decision-making. The model predicts probabilistic decision-making with larger neuronal responses and larger functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) responses on correct than on error trials because the spiking noise-influenced decision attractor state of the network is consistent with the external evidence. Moreover, the model predicts that the neuronal activity and the BOLD response will become larger on correct trials as the discriminability Δ I increases and confidence increases and will become smaller as confidence decreases on error trials as Δ I increases. Confidence is thus an emergent property of the model. In an fMRI study of an olfactory decision-making task, we confirm these predictions for cortical areas including medial prefrontal cortex and the cingulate cortex implicated in choice decision-making, showing a linear increase in the BOLD signal with Δ I on correct trials, and a linear decrease on error trials. These effects were not found in a control area, the orbitofrontal cortex, where reward value useful for the choice is represented on a continuous scale but that is not implicated in the choice itself. This provides a unifying approach to decision-making and decision confidence and to how spiking-related noise affects choice, confidence, synaptic and neuronal activity, and fMRI signals.
Roles of Adiponectin and Oxidative Stress in the Regulation of Membrane Microviscosity of Red Blood Cells in Hypertensive Men—An Electron Spin Resonance Study
Authors: Tsuda Kazushi
Published: September 2010

This study was undertaken to investigate possible relationships among plasma adiponectin, 8-iso-prostaglandin F2α(8-iso-PG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of microviscosity) in hypertensive and normotensive men using an electron spin resonance-method. The order parameter (S) for the spin-label agent (5-nitroxide stearate) in red blood cell (RBC) membranes was higher in hypertensive men than in normotensive men, indicating that membrane fluidity was decreased in hypertension. Plasma adiponectin and NO metabolites levels were lower in hypertensive men than in normotensive men. In contrast, plasma 8-iso-PG F2αlevels were increased in hypertensive men compared with normotensive men. Plasma adiponectin concentration was correlated with plasma NO-metabolites, and inversely correlated with plasma 8-iso-PG F2α. The order parameter (S) of RBCs was inversely correlated with plasma adiponectin and plasma NO metabolite levels, and positively correlated with plasma 8-iso-PG F2α, suggesting that the reduced membrane fluidity of RBCs might be associated with hypoadiponectinemia, endothelial dysfunction, and increased oxidative stress. In a multivariate regression analysis, adiponectin and 8-iso-PG F2αwere significant determinants of membrane fluidity of RBCs after adjustment for general risk factors. These results suggest that adiponectin and oxidative stress might have a close correlation with rheologic behavior and microcirculation in hypertension.
Metformin Prevents Tobacco Carcinogen–Induced Lung Tumorigenesis
Authors: Memmott Regan M. , Mercado Jose R. , Maier Colleen R. , Kawabata Shigeru , Fox Stephen D. , Dennis Phillip A.
Published: September 2010

Activation of the mammalian target of rapamycin (mTOR) pathway is an important and early event in tobacco carcinogen–induced lung tumorigenesis, and therapies that target mTOR could be effective in the prevention or treatment of lung cancer. The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMP-activated protein kinase (AMPK), which can inhibit the mTOR pathway. To test this, A/J mice were treated with oral metformin after exposure to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that are achievable in humans. mTOR was inhibited in lung tumors but only modestly. To test whether intraperitoneal administration of metformin might improve mTOR inhibition, we injected mice and assessed biomarkers in liver and lung tissues. Plasma levels of metformin were significantly higher after injection than oral administration. In liver tissue, metformin activated AMPK and inhibited mTOR. In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal–regulated kinase (ERK), and mTOR. This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR. Based on these data, we repeated the NNK–induced lung tumorigenesis study using intraperitoneal administration of metformin. Metformin decreased tumor burden by 72%, which correlated with decreased cellular proliferation and marked inhibition of mTOR in tumors. These studies show that metformin prevents tobacco carcinogen–induced lung tumorigenesis and support clinical testing of metformin as a chemopreventive agent. Cancer Prev Res; 3(9); 1066–76. ©2010 AACR.
Quantitative Assessment of Mitral Regurgitation
Authors: Shanks Miriam , Siebelink Hans-Marc J. , Delgado Victoria , van de Veire Nico R.L. , Ng Arnold C.T. , Sieders Allard , Schuijf Joanne D. , Lamb Hildo J. , Ajmone Marsan Nina , Westenberg Jos J.M. , Kroft Lucia J. , de Roos Albert , Bax Jeroen J.
Published: September 2010

Background—

Quantification of mitral regurgitation severity with 2-dimensional (2D) imaging techniques remains challenging. The present study compared the accuracy of 2D transesophageal echocardiography (TEE) and 3-dimensional (3D) TEE for quantification of mitral regurgitation, using MRI as the reference method.

Methods and Results—

Two-dimensional and 3D TEE and cardiac MRI were performed in 30 patients with mitral regurgitation. Mitral effective regurgitant orifice area (EROA) and regurgitant volume (Rvol) were estimated with 2D and 3D TEE. With 3D TEE, EROA was calculated using planimetry of the color Doppler flow from en face views and Rvol was derived by multiplying the EROA by the velocity time integral of the regurgitant jet. Finally, using MRI, mitral Rvol was quantified by subtracting the aortic flow volume from left ventricular stroke volume. Compared with 3D TEE, 2D TEE underestimated the EROA by a mean of 0.13 cm
2
. In addition, 2D TEE underestimated the Rvol by 21.6% when compared with 3D TEE and by 21.3% when compared with MRI. In contrast, 3D TEE underestimated the Rvol by only 1.2% when compared with MRI. Finally, one third of the patients in grade 1 and ≥50% of the patients in grade 2 and 3, as assessed with 2D TEE, would have been upgraded to a more severe grade, based on the 3D TEE and MRI measurements.

Conclusions—

Quantification of mitral EROA and Rvol with 3D TEE is feasible and accurate as compared with MRI and results in less underestimation of the Rvol as compared with 2D TEE.
Cortical Networks Representing Object Categories and High-level Attributes of Familiar Real-world Action Sounds
Authors: Lewis James W. , Talkington William J. , Puce Aina , Engel Lauren R. , Frum Chris
Published: September 2010

In contrast to visual object processing, relatively little is known about how the human brain processes everyday real-world sounds, transforming highly complex acoustic signals into representations of meaningful events or auditory objects. We recently reported a fourfold cortical dissociation for representing action (nonvocalization) sounds correctly categorized as having been produced by human, animal, mechanical, or environmental sources. However, it was unclear how consistent those network representations were across individuals, given potential differences between each participant's degree of familiarity with the studied sounds. Moreover, it was unclear what, if any, auditory perceptual attributes might further distinguish the four conceptual sound-source categories, potentially revealing what might drive the cortical network organization for representing acoustic knowledge. Here, we used functional magnetic resonance imaging to test participants before and after extensive listening experience with action sounds, and tested for cortices that might be sensitive to each of three different high-level perceptual attributes relating to how a listener associates or interacts with the sound source. These included the sound's perceived concreteness, effectuality (ability to be affected by the listener), and spatial scale. Despite some variation of networks for environmental sounds, our results verified the stability of a fourfold dissociation of category-specific networks for real-world action sounds both before and after familiarity training. Additionally, we identified cortical regions parametrically modulated by each of the three high-level perceptual sound attributes. We propose that these attributes contribute to the network-level encoding of category-specific acoustic knowledge representations.
Indigenous Medicine as Commodity
Authors: Islam Nazrul
Published: September 2010

This article explores how indigenous medicine, ayurveda in particular, has been transformed into health products for middle-class consumers in a modern Indian society. Consumerism has been developed and the patients and the general public become the ready consumers of ayurvedic health products. In this process of commodification, large pharmaceutical companies have appreciated ayurveda and redefine the nature of ayurvedic drugs and drug production for profit maximization. There is steady growth of local and international market for herbal-based drugs, health supplements and beauty products. As a result of this demand, ayurveda has been propagated as a natural healing system, and ayurvedic medicine/health products are featured as natural remedies, which equates ‘herbal’ with ayurveda, and people often misunderstand herbal products as ayurvedic products. The article concludes that the entire situation has ideologically contaminated ayurveda, and that ayurveda has lost ground as a complete way of healthy life to restore and maintain health.
Demographic and lifestyle variables associated with obesity
Authors: Worthy Sheri L , Lokken Kristine , Pilcher Kenneth , Boeka Abbe
Published: September 2010

Objective: Overweight and obesity rates are associated with chronic diseases and higher rates of disability and continue to rise in the United States and worldwide. The purpose of this study was to build on past research and further investigate demographic and lifestyle variables associated with increased body mass index (BMI: kg/m 2).

Methods: Personal Information Worksheets were completed by 125 bariatric surgery candidates and 213 community dwelling individuals providing a sample size of 338. Hierarchical regression analysis was performed on three sets of independent variables (demographic characteristics, lifestyle variables and consumer response) and one dependent variable (BMI).

Results: Lower levels of education and physical activity, higher levels of diet soda consumption and number of dieting attempts, and likelihood of starting a diet programme based on advertising testimonials were predictive of higher BMI.

Conclusion: This research highlights the need for more education emphasizing the importance of increased healthy behaviours versus use of diet products and fad diets to improve success of weight loss efforts.
Are incentive schemes effective in changing young people’s behaviour? A systematic review
Authors: Kavanagh Josephine , Oakley Ann , Harden Angela , Trouton Alex , Powell Chloe
Published: September 2010

Objective: To examine the impact of single or dual component incentive schemes on health and social behaviours, in young people.

Design: A systematic review.

Method: Systematic and comprehensive cross-disciplinary searches were conducted to identify research. Following screening for relevance, included studies were quality assessed and data extracted. Both outcome and process evaluation studies were included in either a statistical meta-analysis or narrative synthesis.

Results: Sixteen trials and seven process evaluations were included in the review. There is some evidence to show that incentives are effective in improving single health behaviours, but not complex health behaviours. Incentives had no impact on levels of reported effort, or attendance in education studies. Whilst viewed favourably by young people, incentives did not necessarily translate into improvements in targeted behaviours.

Conclusion: Evidence suggests that incentives schemes do not provide policy makers or practitioners with a simple route to improving young people’s health or other behaviours. However, there is evidence that incentives can be useful in encouraging positive health behaviour change where a simple or single action is required.
The impact of additional weekdays of active commuting to school on children achieving a criterion of 300+ minutes of moderate-to-vigorous physical activity
Authors: Daly-Smith Andy JW , McKenna Jim , Radley Duncan , Long Jonathan
Published: September 2010

Objective: To investigate the value of additional days of active commuting for meeting a criterion of 300+ minutes of moderate-to-vigorous physical activity (MVPA; 60+ mins/day x 5) during the school week.

Methods: Based on seven-day diaries supported by teachers, binary logistic regression analyses were used to predict achievement of MVPA criteria according to days of active commuting to and from school. MVPA was recorded across five time points: (a) before school, (b) walking/cycling to and from school, (c) during school, (d) in school-based clubs and (e) during leisure time. The study was conducted in Derby, UK, in June 2006.

Results: Active commuting was reported by 4218 (78 per cent of 5422) children for an average daily commuting time of 18.4 ± 16.4 minutes. Children who commuted on more days in the week were most likely to achieve the MVPA criterion. Every day of active commuting doubled the chances of meeting the MVPA criterion; in Year 10 girls this effect was stronger (odds ratio 6.45).

Conclusion: Results confirm the ubiquity of active commuting among young people. Even one additional day of active commuting helps to meet established criteria. In older girls active commuting is uniquely powerful in contributing to attainment of public health targets of MVPA.