bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning from the Golden Age of Czechoslovak Animation: The Past as the Key to Unlocking Contemporary Issues
Authors: Joschko Lucie , Morgan Michael
Published: March 2008

Can Czech animators resurrect the Golden Age of Czech animation or will they succumb to the changes of an open market economy? The post-1989 privatization of animation studios and subsequent withdrawal of government funding are commonly considered as one of the most significant factors contributing to the current decline of Czech animated films. This article argues that a number of additional factors associated with the post-1989 change of political regime have impacted on Czech animation production. These factors include: (1) the change of themes due to the removal of the communist regime as the common antagonist; (2) the fragmentation of the Czech audience due to the importation of animated films from the west and new methods of distributing content; and (3) economic censorship pressuring artists and producers to ensure financial success. In examining the history of the Czech animation industry during and after the communist regime, the authors present an outline of the conditions of the Prague Spring in 1968, during which the Czech animated films further elevated their international reputation and experienced exponential growth. In contrast to these conditions, this article highlights the contemporary issues that are affecting Czech animation studios today.
Character Animation and the Embodied Mind—Brain
Authors: Power Patrick
Published: March 2008

This interdisciplinary investigation of aspects of 3D character animation synthesizes relevant research findings from diverse perspectives, including neuroscience, narratology, robotics, anthropology, cognitive psychology and philosophy of mind, and considers how they might be integrated as theory for animators and animation studies. The article focuses on the creative nature of character conception and creation in a 3D animated environment and on aspects of character — narrative and style, in particular. It examines how findings from interdisciplinary research on the embodied mind—brain, including neuroscientific research with regard to mentalizing and simulation theory, can inform the creative animation process and might be gainfully synthesized in an animation studies context to inform both pedagogy and creative practice.
Patriotism meets plurality: reporting the 2003 Iraq War in the British press
Authors: Goddard Peter , Robinson Piers , Parry Katy
Published: March 2008

In this article, the authors draw upon the results from a substantial content and framing analysis of the British media's treatment of the 2003 Iraq War to show how Britain's national press managed their coverage of the initial combat phase of the war against the background of substantial public and elite opposition. They show that reporting was dominated by coverage of the ongoing battle, that newspapers offered a similar subject agenda to one another and that coalition actors were prominent and likely to be reported neutrally. But the article uncovers a substantial diversity of opinion and tone across the British press and identifies five different editorial approaches to the conflict which are sustained across the news and editorial pages of different newspapers. Through a closer examination, the authors attempt to account for the existence of these approaches in relation to the effects of public opposition to the war, patriotism and newspapers' longstanding political allegiances. Finally, they suggest that, in the British press at least, this plurality of opinions and forms of coverage offers a challenge to longstanding assumptions about the extent to which the media have tended to offer support to official positions in relation to war.
Television journalism during terror attacks
Authors: Mogensen Kirsten
Published: March 2008

This article views television news coverage of ongoing terrorist attacks and their immediate aftermath as a special genre within journalism, and describes norms connected with the genre. The description is based on qualitative analyses of the coverage on the major American networks in the first 24 hours after the events on September 11, 2001, and on semi-structured personal interviews with 37 journalists who covered the events for ABC, CBS, NBC, CNN, MSNBC and FOX News. In accordance with legal and moral philosopher Alf Ross, each of the norms was expressed as a directive in the interviews and also reflected in the journalistic practices. The described norms form a coherent pattern if safeguarding the existing democracy and the general public is considered to be the main purpose. A coverage based on this pattern of norms can be compared to other forms of crisis management following attacks because it counteracts well known symptoms of national crisis.
The military and the media: shotgun wedding, rocky marriage, committed relationship
Authors: Cucolo Major General Tony
Published: March 2008

Major General Tony Cucolo, the US Army's Chief of Public Affairs, discusses the war raging on the information domain that places nations at risk as much as any weapon of mass effect or mass destruction, and the critical importance of a sustained, committed relationship between the military and the media. America in particular needs a credible, accountable, and self-policing free press; the US military must continue to move away from a culture of non-engagement and establish strong professional bonds with the media. Both parties should take stock of how each has grown and changed in recent years and re-commit to protect the ideals they defend, each in their own unique way.
Taking the state out of state—media relations theory: how transnational advocacy networks are changing the press—state dynamic
Authors: Aday Sean , Livingston Steven
Published: March 2008

Much of the political communication scholarship concerning state—media relations concludes that the media are highly dependent on and even subservient to the state. This is particular true during wartime. Partial and conditionally based exceptions to this general conclusion include event-driven news and the cascade model. We argue that another important exception to standard conclusions regarding state—media relations involves transnational advocacy organizations and epistemic communities.
Can the information war on terror be won? A polemical essay
Authors: Taylor Philip M.
Published: March 2008

This polemical essay argues that, despite many presentational mistakes in the West's information war on terror since 9/11, the `propaganda' war is not yet lost. Indeed, it tentatively suggests that although those mistakes have made the task of `winning hearts and minds' in the Islamic world harder and longer, the root cause of failure to date lies with a failure to `know yourself' — i.e. to address those elements, such as foreign policy decisions, which fuel support for Al Qaida. Although the terrorist `organization' has proved exceptionally adept in its own propaganda, it is not just inept western propaganda that lies at the heart of the problem. It is the inability to see yourself as others see you, even if — or perhaps — you disagree with `them'.
Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism
Authors: Chen Jing , Petrus Mike , Bryant Bonita R. , Phuc Nguyen Vinh , Stamer Mindy , Goldman Carolyn K. , Bamford Richard , Morris John C. , Janik John E. , Waldmann Thomas A.
Published: March 2008

The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-κB motif in its proximal promoter, whereas IL-9 receptor-α (IL-9Rα) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Rα in ATL, a neutralizing monoclonal antibody directed toward IL-9Rα inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9Rα on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9Rα/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism.
BCR-ABL1 alters SDF-1α–mediated adhesive responses through the β2 integrin LFA-1 in leukemia cells
Authors: Chen Ying-Yu , Malik Mobeen , Tomkowicz Brian E. , Collman Ronald G. , Ptasznik Andrzej
Published: March 2008

Stromal-derived factor-1 (SDF-1) and its receptor, CXCR4, are essential for normal hematopoietic progenitor cell movement and adherence within the bone marrow microenvironment. In leukemia, the BCR-ABL1 oncoprotein inhibits SDF-1–dependent cell trafficking within the bone marrow through a mechanism that is not fully understood. Here, we report that BCR-ABL1 in malignant cells constitutively increases expression of activation-dependent epitopes of the β2 integrin LFA-1. This is associated with the complete loss of responsiveness of LFA-1 to SDF-1–induced “inside-out” signaling involving CXCR4 and Lyn, leading to aberrant adhesive responses. These data provide a novel, LFA-1–mediated mechanism whereby BCR-ABL1 inhibits SDF-1 action in malignant progenitors.
Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats
Authors: Graham Tracey , McIntosh Jenny , Work Lorraine M , Nathwani Amit , Baker Andrew H
Published: March 2008

Background

Vectors based on adeno-associated virus-8 (AAV8) have shown efficiency and efficacy for liver-directed gene therapy protocols following intravascular injection, particularly in relation to haemophilia gene therapy. AAV8 has also been proposed for gene therapy targeted at skeletal and cardiac muscle, again via intravascular injection. It is important to assess vector targeting at the level of virion accumulation and transgene expression in multiple species to ascertain potential issues relating to species variation in infectivity profiles.

Methods

We used AAV8 vectors expressing human factor IX (FIX) from the liver-specific LP-1 promoter and administered this virus via the intravascular route of injection into 12 week old Wistar Kyoto rats. We assessed FIX levels in serum by ELISA and transgene expression at sacrifice by immunohistochemistry using anti-FIX antibodies. Vector DNA levels in organs we determined by real time PCR.

Results

Administration of 1 × 1011 or 5 × 1011 scAAV8-LP1-hFIX vector particles/rat resulted in efficient production of physiological hFIX levels, respectively in blood assessed 4 weeks post-injection. This was maintained for the 4 month duration of the study. At 4 months we observed liver persistence of vector with minimal non-hepatic distribution.

Conclusion

Our results demonstrate that AAV8 is a robust vector for delivering therapeutic genes into rat liver following intravascular injection.
Hepatic abscess in a pre-existed simple hepatic cyst as a late complication of sigmoid colon ruptured diverticula: a case report
Authors: Chatzipetrou Maria , Avgerinos Efthimios , Christianakis Efstratios , Barmparas Galinos , Pashalidis Nikolaos , Stathoulopoulos Athanasios , Tsatsoulis Panayiotis , Smailis Dimitrios , Filippou Dimitrios
Published: March 2008

Introduction

Hepatic abscesses have been reported as a rare complication of diverticulitis of the bowel. This complication is recognized more commonly at the time of the diagnosis of diverticulitis, or ruptured diverticula, but also can be diagnosed prior to surgery, or postoperatively.

Case presentation

This report describes a man who developed an hepatic abscess within a simple hepatic cyst, two months after operation for ruptured diverticula of the sigmoid colon. The abscess was drained surgically and the patient made a complete recovery.

Conclusion

The development of an hepatic abscess in a pre-existing hepatic cyst, secondary to diverticulitis, is a rare complication. A high degree of clinical suspicion is required for immediate diagnosis and treatment.
Simply denoise: Wavefield reconstruction via jittered undersampling
Authors: Hennenfent Gilles , Herrmann Felix J.
Published: March 2008

We present a new, discrete undersampling scheme designed to favor wavefield reconstruction by sparsity-promoting inversion with transform elements localized in the Fourier domain. The work is motivated by empirical observations in the seismic community, corroborated by results from compressive sampling, that indicate favorable (wavefield) reconstructions from random rather than regular undersampling. Indeed, random undersampling renders coherent aliases into harmless incoherent random noise, effectively turning the interpolation problem into a much simpler denoising problem. A practical requirement of wavefield reconstruction with localized sparsifying transforms is the control on the maximum gap size. Unfortunately, random undersampling does not provide such a control. Thus, we introduce a sampling scheme, termed jittered undersampling, that shares the benefits of random sampling and controls the maximum gap size. The contribution of jittered sub-Nyquist sampling is key in formu-lating a versatile wavefield sparsity-promoting recovery scheme that follows the principles of compressive sampling. After the behavior of the jittered-undersampling scheme in the Fourier domain is analyzed, its performance is studied for curvelet recovery by sparsity-promoting inversion (CRSI). The findings on synthetic and real seismic data indicate an improvement of several decibels over recovery from regularly undersampled data for the same amount of data collected.
Dual Effect of the Adapter Growth Factor Receptor-Bound Protein 14 (Grb14) on Insulin Action in Primary Hepatocytes
Authors: Carré Nadège , Caüzac Michèle , Girard Jean , Burnol Anne-Françoise
Published: March 2008

Tight control of insulin action in liver is a crucial determinant for the regulation of energy homeostasis. Growth factor receptor-bound protein 14 (Grb14) is a molecular adapter, highly expressed in liver, which binds to the activated insulin receptor and inhibits its tyrosine kinase activity. The physiological role of Grb14 in liver metabolism was unexplored. In this study we used RNA interference to investigate the consequences of Grb14 decrease on insulin-regulated intracellular signaling, and on glucose and lipid metabolism in mouse primary cultured hepatocytes. In Grb14-depleted hepatocytes, insulin-induced phosphorylation of Akt, and of its substrates glycogen synthase kinase 3 and fork-head box protein 1, was increased. These effects on insulin signaling are in agreement with the selective inhibitory effect of Grb14 on the receptor kinase. However, the metabolic and genic effects of insulin were differentially regulated after Grb14 down-regulation. Indeed, the insulin-mediated inhibition of hepatic glucose production and gluconeogenic gene expression was slightly increased. Surprisingly, despite the improved Akt pathway, the induction by insulin of sterol regulatory element binding protein-1c maturation was totally blunted. As a result, in the absence of Grb14, glycogen synthesis as well as glycolytic and lipogenic gene expression were not responsive to the stimulatory effect of insulin. This study provides evidence that Grb14 exerts a dual role on the regulation by insulin of hepatic metabolism. It inhibits insulin receptor catalytic activity, and acts also at a more distal step, i.e. sterol regulatory element binding protein-1c maturation, which effect is predominant under short-term inhibition of Grb14 expression.
An Estrogen Receptor-α Knock-In Mutation Provides Evidence of Ligand-Independent Signaling and Allows Modulation of Ligand-Induced Pathways in Vivo
Authors: Sinkevicius Kerstin W. , Burdette Joanna E. , Woloszyn Karolina , Hewitt Sylvia C. , Hamilton Katherine , Sugg Sonia L. , Temple Karla A. , Wondisford Fredric E. , Korach Kenneth S. , Woodruff Teresa K. , Greene Geoffrey L.
Published: March 2008

Estrogen-nonresponsive estrogen receptor-α (ERα) knock-in (ENERKI) mice were generated to distinguish between ligand-induced and ligand-independent ER-α actions in vivo. These mice have a mutation [glycine 525 to leucine (G525L)] in the ligand-binding domain of ERα, which significantly reduces ERα interaction with and response to endogenous estrogens, whereas not affecting growth factor activation of ligand-independent pathways. ENERKI mice had hypoplastic uterine tissues and rudimentary mammary gland ductal trees. Females were infertile due to anovulation, and their ovaries contained hemorrhagic cystic follicles because of chronically elevated levels of LH. The ENERKI phenotype confirmed that ligand-induced activation of ERα is crucial in the female reproductive tract and mammary gland development. Growth factor treatments induced uterine epithelial proliferation in ovariectomized ENERKI females, directly demonstrating that ERα ligand-independent pathways were active. In addition, the synthetic ERα selective agonist propyl pyrazole triol (PPT) and ER agonist diethylstilbestrol (DES) were still able to activate ligand-induced G525L ERα pathways in vitro. PPT treatments initiated at puberty stimulated ENERKI uterine development, whereas neonatal treatments were needed to restore mammary gland ductal elongation, indicating that neonatal ligand-induced ERα activation may prime mammary ducts to become more responsive to estrogens in adult tissues. This is a useful model for in vivo evaluation of ligand-induced ERα pathways and temporal patterns of response. DES did not stimulate an ENERKI uterotrophic response. Because ERβ may modulate ERα activation and have an antiproliferative function in the uterus, we hypothesize that ENERKI animals were particularly sensitive to DES-induced inhibition of ERα due to up-regulated uterine ERβ levels.
Discovery of a Cholecystokinin-Gastrin-Like Signaling System in Nematodes
Authors: Janssen Tom , Meelkop Ellen , Lindemans Marleen , Verstraelen Karen , Husson Steven J. , Temmerman Liesbet , Nachman Ronald J. , Schoofs Liliane
Published: March 2008

Members of the cholecystokinin (CCK)/gastrin family of peptides, including the arthropod sulfakinins, and their cognate receptors, play an important role in the regulation of feeding behavior and energy homeostasis. Despite many efforts after the discovery of CCK/gastrin immunoreactivity in nematodes 23 yr ago, the identity of these nematode CCK/gastrin-related peptides has remained a mystery ever since. The Caenorhabditis elegans genome contains two genes with high identity to the mammalian CCK receptors and their invertebrate counterparts, the sulfakinin receptors. By using the potential C. elegans CCK receptors as a fishing hook, we have isolated and identified two CCK-like neuropeptides encoded by neuropeptide-like protein-12 (nlp-12) as the endogenous ligands of these receptors. The neuropeptide-like protein-12 peptides have a very limited neuronal expression pattern, seem to occur in vivo in the unsulfated form, and react specifically with a human CCK-8 antibody. Both receptors and ligands share a high degree of structural similarity with their vertebrate and arthropod counterparts, and also display similar biological activities with respect to digestive enzyme secretion and fat storage. Our data indicate that the gastrin-CCK signaling system was already well established before the divergence of protostomes and deuterostomes.
3β-Hydroxysteroid-Δ24 Reductase Is a Hydrogen Peroxide Scavenger, Protecting Cells from Oxidative Stress-Induced Apoptosis
Authors: Lu Xiuli , Kambe Fukushi , Cao Xia , Kozaki Yasuko , Kaji Takahide , Ishii Takehisa , Seo Hisao
Published: March 2008

3β-Hydroxysteroid-Δ24 reductase (DHCR24) is an endoplasmic reticulum-resident, multifunctional enzyme that possesses antiapoptotic and cholesterol-synthesizing activities. To clarify the molecular basis of the former activity, we investigated the effects of hydrogen peroxide (H2O2) on embryonic fibroblasts prepared from DHCR24-knockout mice (DHCR24−/− mouse embryonic fibroblasts). H2O2 exposure rapidly induced apoptosis, which was associated with sustained activation of apoptosis signal-regulating kinase-1 and stress-activated protein kinases, such as p38 MAPK and c-Jun N-terminal kinase. Complementation of the mouse embryonic fibroblasts by adenovirus expressing DHCR24 attenuated the H2O2-induced kinase activation and apoptosis. Concomitantly, intracellular generation of reactive oxygen species (ROS) in response to H2O2 was also diminished by the adenovirus, suggesting a ROS-scavenging activity of DHCR24. Such antiapoptotic effects of DHCR24 were duplicated in pheochromocytoma PC12 cells infected with adenovirus. In addition, it was found that DHCR24 exerted cytoprotective effects in the tunicamycin-induced endoplasmic reticulum stress by eliminating ROS. Finally, using in vitro-synthesized and purified proteins, DHCR24 and its C-terminal deletion mutant were found to exhibit high H2O2-scavenging activity, whereas the N-terminal deletion mutant lost such activity. These results demonstrate that DHCR24 can directly scavenge H2O2, thereby protecting cells from oxidative stress-induced apoptosis.
Improved Lactational Nutrition and Postnatal Growth Ameliorates Impairment of Glucose Tolerance by Uteroplacental Insufficiency in Male Rat Offspring
Authors: Siebel Andrew L. , Mibus Amy , De Blasio Miles J. , Westcott Kerryn T. , Morris Margaret J. , Prior Larissa , Owens Julie A. , Wlodek Mary E.
Published: March 2008

Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth but also impairs mammary development and postnatal growth. We used cross fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age. Bilateral uterine vessel ligation (restricted) to induce uteroplacental insufficiency or sham surgery (control) was performed on d-18 gestation. Control, restricted, and reduced (reducing litter size of controls to match restricted) pups were cross fostered onto a control or restricted mother 1 d after birth. Restricted pups were born small compared with controls. Restricted males, but not females, remained lighter up to 6 months, regardless of postnatal environment. By 10 wk, restricted-on-restricted males ate more than controls. At 6 months restricted-on-restricted males had increased hypothalamic neuropeptide Y content compared with other groups, and together with reduced-on-restricted males had increased retroperitoneal fat weight (percent body weight) compared with control-on-controls. Restricted-on-restricted males had impaired glucose tolerance, reduced first-phase insulin secretion, but unaltered insulin sensitivity, compared with control-on-controls. In males, being born small and exposed to an impaired lactational environment adversely affects adult glucose tolerance and first-phase insulin secretion, but improving lactation partially ameliorates this condition. This study identifies early life as a target for intervention to prevent later diabetes after prenatal restraint.
Gene therapy for osteosarcoma: steps towards clinical studies
Authors: Dass Crispin R , Choong Peter F M
Published: March 2008

Gene therapy, an applied form of biotechnology, relies on the delivery of foreign DNA into cells. More than 50% of all reported clinical trials for gene therapy are for cancer, though only a scant number for osteosarcoma. Osteosarcoma is a neoplasm afflicting young adults, who in their prime years of life suffer debilitation if not death. The disease is not entirely curable, even with surgery combined with aggressive chemotherapy. Thus, other forms of therapies are being evaluated, including gene therapy. There exist two major forms of gene transfer: viral and non-viral. This review only covers proof-of-principle work carried out in cancer beyond the cell culture stage, in animals. Drawing from the experiences of gene therapy against other cancers, studies for which have already reached the clinical phase, the review discusses potential pitfalls and solutions to enhance gene therapy for osteosarcoma.
Effect of ion-pairing and enhancers on scutellarin skin permeability
Authors: Wang Manli , Fang Liang , Ren Changshun , Li Ting
Published: March 2008

The aim of this work was to investigate the effect of enhancers and organic amines on the in-vitro percutaneous absorption of the major pharmacologically active compound, scutellarin, obtained from breviscapine extract. The donor vehicle consisted of isopropyl myristate-ethanol in a ratio of 4:1. Percutaneous absorption across full thickness rat skin was investigated in-vitro using 2-chamber diffusion cells, with reverse-phase HPLC for quantification of the permeating scutellarin. Organic amines increased scutellarin permeation by ion-pair formation. We also found that the cumulative amount of scutellarin over a period of 12 h of scutellarin was inversely related to the molecular weight of organic amines (r = 0.9134), as well as the logarithm of scutellarin permeability coefficient inversely related to the partition coefficient of organic amines (r = 0.8929). All the permeation enhancers tested increased the cumulative amount of scutellarin over a period of 12 h, and the order of this increase was n-methyl-2-pyrrolidone, oleic acid, menthol or Azone. Drug solubility in donor phase was markedly increased by Azone and n-methyl-2-pyrrolidone, and reduced by menthol and oleic acid. The combined effects of ethanolamine plus Azone, ethanolamine plus menthol, and Azone plus menthol were also investigated. Azone plus menthol had a synergistic effect on the cumulative amount of scutellarin over a period of 12 h.
Role of maltol in advanced glycation end products and free radicals: in-vitro and in-vivo studies
Authors: Kang Ki Sung , Yamabe Noriko , Kim Hyun Young , Yokozawa Takako
Published: March 2008

Inhibitors of advanced glycation end products (AGEs) have potential as preventive agents against diabetic complications. In-vitro AGE inhibitory activity, transition metal chelating, and free radical scavenging activity tests have been used to screen for and identify effective AGE inhibitors. In an ongoing project to elucidate AGE inhibiting active components of heat-processed ginseng, maltol was selected for more detailed investigation. Although there are several lines of evidence concerning the antioxidant activity of maltol, the in-vitro and in-vivo inhibitory effects of maltol on AGE generation have not been evaluated. In the present study, the in-vitro AGE inhibitory effects and free radical scavenging activity of maltol were investigated. In addition, the in-vivo therapeutic potential of maltol against diabetic renal damage was tested using streptozotocin (STZ)-diabetic rats. Maltol showed a stronger AGE inhibitory effect than aminoguanidine, a well known AGE inhibitor. In addition, the hydroxyl radical scavenging activity of maltol on electron spin resonance (ESR) spectrometry was slightly stronger than that of aminoguanidine. Therefore, maltol was found to have stronger in-vitro AGE inhibiting activity compared with aminoguanidine. The administration of 50 mgkg−1 per day of maltol suppressed the elevated serum levels of glycosylated protein, renal fluorescent AGEs, carboxymethyllysine, receptors for AGEs, and nuclear factor-kappaB p65 in diabetic control rats. These beneficial effects of maltol against STZ-diabetic renal damage were thought to result from its free radical scavenging and AGE inhibitory effects.
A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth
Authors: Lefèvre Gaelle , Michel Vincent , Weil Dominique , Lepelletier Léa , Bizard Emilie , Wolfrum Uwe , Hardelin Jean-Pierre , Petit Christine
Published: March 2008

The planar polarity and staircase-like pattern of the hair bundle are essential to the mechanoelectrical transduction function of inner ear sensory cells. Mutations in genes encoding myosin VIIa, harmonin, cadherin 23,protocadherin 15 or sans cause Usher syndrome type I (USH1, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa leading to blindness) in humans and hair bundle disorganization in mice. Whether the USH1 proteins are involved in common hair bundle morphogenetic processes is unknown. Here, we show that mouse models for the five USH1 genetic forms share hair bundle morphological defects. Hair bundle fragmentation and misorientation (25-52° mean kinociliary deviation, depending on the mutant) were detected as early as embryonic day 17. Abnormal differential elongation of stereocilia rows occurred in the first postnatal days. In the emerging hair bundles, myosin VIIa, the actin-binding submembrane protein harmonin-b, and the interstereocilia-kinocilium lateral link components cadherin 23 and protocadherin 15, all concentrated at stereocilia tips, in accordance with their known in vitro interactions. Soon after birth,harmonin-b switched from the tip of the stereocilia to the upper end of the tip link, which also comprises cadherin 23 and protocadherin 15. This positional change did not occur in mice deficient for cadherin 23 or protocadherin 15. We suggest that tension forces applied to the early lateral links and to the tip link, both of which can be anchored to actin filaments via harmonin-b, play a key role in hair bundle cohesion and proper orientation for the former, and in stereociliary elongation for the latter.
Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity
Authors: Endoh Mitsuhiro , Endo Takaho A. , Endoh Tamie , Fujimura Yu-ichi , Ohara Osamu , Toyoda Tetsuro , Otte Arie P. , Okano Masaki , Brockdorff Neil , Vidal Miguel , Koseki Haruhiko
Published: March 2008

The Polycomb group (PcG) proteins mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes 1 (PRC1) and 2(PRC2). Although PRC2 has been shown to share target genes with the core transcription network, including Oct3/4, to maintain embryonic stem (ES)cells, it is still unclear whether PcG proteins and the core transcription network are functionally linked. Here, we identify an essential role for the core PRC1 components Ring1A/B in repressing developmental regulators in mouse ES cells and, thereby, in maintaining ES cell identity. A significant proportion of the PRC1 target genes are also repressed by Oct3/4. We demonstrate that engagement of PRC1 at target genes is Oct3/4-dependent,whereas engagement of Oct3/4 is PRC1-independent. Moreover, upon differentiation induced by Gata6 expression, most of the Ring1A/B target genes are derepressed and the binding of Ring1A/B to their target loci is also decreased. Collectively, these results indicate that Ring1A/B-mediated Polycomb silencing functions downstream of the core transcriptional regulatory circuitry to maintain ES cell identity.
The mandible opening response: quantifying aggression elicited by chemical cues in ants
Authors: Guerrieri Fernando J. , d'Ettorre Patrizia
Published: March 2008

Social insects have evolved efficient recognition systems guaranteeing social cohesion and protection from enemies. To defend their territories and threaten non-nestmate intruders, ants open their mandibles as a first aggressive display. Albeit chemical cues play a major role in discrimination between nestmates and non-nestmates, classical bioassays based on aggressive behaviour were not particularly effective in disentangling chemical perception and behavioural components of nestmate recognition by means of categorical variables. We therefore developed a novel bioassay that accurately isolates chemical perception from other cues. We studied four ant species: Camponotus herculeanus, C. vagus, Formica rufibarbis and F. cunicularia. Chemical analyses of cuticular extracts of workers of these four species showed that they varied in the number and identity of compounds and that species of the same genus have more similar profiles. The antennae of harnessed ants were touched with a glass rod coated with the cuticular extract of (a) nestmates, (b) non-nestmates of the same species, (c) another species of the same genus and (d) a species of a different genus. The mandible opening response (MOR) was recorded as the aggressive response. In all assayed species, MOR significantly differed among stimuli, being weakest towards nestmate odour and strongest towards odours originating from ants of a different genus. We thus introduce here a new procedure suitable for studying the chemical basis of aggression in ants.
The effect of increasing inertia upon vertical ground reaction forces and temporal kinematics during locomotion
Authors: De Witt John K. , Hagan R. Donald , Cromwell Ronita L.
Published: March 2008

The addition of inertia to exercising astronauts could increase ground reaction forces and potentially provide a greater health benefit. However,conflicting results have been reported regarding the adaptations to additional mass (inertia) without additional net weight (gravitational force) during locomotion. We examined the effect of increasing inertia while maintaining net gravitational force on vertical ground reaction forces and temporal kinematics during walking and running. Vertical ground reaction force was measured for 10 healthy adults (five male/five female) during walking (1.34 m s–1) and running (3.13 m s–1) using a force-measuring treadmill. Subjects completed locomotion at normal weight and mass and at 10, 20, 30 and 40% of added inertial force. The added gravitational force was relieved with overhead suspension, so that the net force between the subject and treadmill at rest remained equal to 100% body weight. Ground reaction forces were affected by the added inertial force, but not to the magnitude predicted by the increase in mass, suggesting that adaptations in motion occurred. Vertical ground reaction force production and adaptations in gait temporal kinematics were different between walking and running. Peak vertical impact forces and loading rates increased with increased inertia during walking, and decreased during running. As inertia increased, peak vertical propulsive forces decreased during walking and did not change during running. Stride time increased during walking and running,and contact time increased during running. The increased inertial forces were utilized independently from gravitational forces by the motor control system when determining coordination strategies.
Biochemical and functional characterization of the actin-binding activity of the B subunit of yeast vacuolar H+-ATPase
Authors: Zuo Jian , Vergara Sandra , Kohno Shinya , Holliday L. Shannon
Published: March 2008

Vacuolar H+-ATPase (V-ATPase) is a fundamentally important enzyme in eukaryotic cells that is responsible for acidification of endocytic compartments. The B subunits of V-ATPases from mammals and tobacco hornworm have been shown to bind actin filaments. Actin-binding activity by the B subunit is required for targeting V-ATPases to the plasma membrane of osteoclasts. Bacterially expressed B subunit from the yeast Saccharomyces cerevisiae bound actin filaments with a Kd of 195 nmol l–1. The actin-binding domain of the B subunit was altered by mutations that reduced or eliminated the actin-binding activity. Mutants assembled properly with endogenous yeast subunits when expressed in B subunit-null yeast and bafilomycin-sensitive ATPase activity was not significantly different from yeast transformed with wild-type B subunit. Yeast containing the mutant subunits grew as well at pH 7.5 as wild-type. Screening null yeast or null yeast transformed with wild-type or mutant B subunits with sub-lethal doses of various drugs revealed that yeast containing the mutant B subunits were more sensitive to cycloheximide and wortmannin than those transformed with wild-type B subunits. These results suggest that actin-binding activity confers on the B subunit of yeast a function that is distinct from its role in the enzymatic activity of the proton pump.
Identification of novel genes includingDermo-1, a marker of dermal differentiation, expressed in trout somitic external cells
Authors: Dumont Emmanuelle , Rallière Cecile , Rescan Pierre-Yves
Published: March 2008

The external cell layer that surrounds the fish primary myotome provides the myogenic precursors necessary for muscle growth, suggesting that this epithelium is equivalent to the amniote dermomyotome. In this study we report the identification of a trout orthologue of the dermal marker Dermo-1, and show that trout somitic external cells, which are all potentially myogenic as indicated by the transcription of Pax7 gene,express Dermo-1. This finding and our previous observation that external cells express collagen I show that these cells have dermis-related characteristics in addition to exhibiting myogenic features. In an effort to identify novel genes expressed in the external cell epithelium we performed an in situ hybridisation screen and found both collectin sub-family member 12,a transmembrane C-type lectin, and Seraf, an EGF-like repeat autocrine factor. In situ hybridisation of staged trout embryos revealed that the expression of Dermo-1, collectin sub-family member 12 and Seraf within the external cell layer epithelium was preceded by a complex temporal and spatial expression pattern in the early somite.
An orthogonal-array-based design-of-experiments method for designing a vehicle hood and bumper structure
Authors: Lee J-W , Shin M-K , Yoon K-H , Park G-J
Published: March 2008

Although the numbers of pedestrian fatalities and injuries are steadily declining worldwide, pedestrian protection is still an important issue. Extensive research has been carried out for pedestrian protection in order to establish appropriate regulations for pedestrian safety. The automobile hoods and bumpers are fairly important for pedestrian protection because pedestrians frequently collide with them during accidents, and they should be designed for the safety of the pedestrians. A new design method for hoods and bumpers is proposed to enhance pedestrian protection by using an orthogonal-array-based design-of-experiments method. Two analysis methods, namely a real experiment and a computer simulation, are utilized to design safe structures of the hood and the bumper. A real experiment is very expensive while computer simulation has modelling imperfections. A design method which uses an experiment and simulation simultaneously is developed. Orthogonal arrays are employed to link the two analyses. The minimum number of experiments is allocated to some rows of an orthogonal array and the simulations are allocated to the rest of the rows to save the cost. Real experiments and computer simulations are conducted for the rows of orthogonal arrays. Design problems are formulated and the orthogonal arrays are directly used to find the design variables by performing the analysis-of-means process in a discrete space. Mathematical error analysis is conducted. Based on the proposed method, a hood and a bumper are designed to protect pedestrians. The results show that the errors are distributed uniformly and a precise design is obtained.
Principal component analysis of vehicle acceleration gain and translation of voice of the customer
Authors: Lee Sangdon
Published: March 2008

Principal component analysis (PCA) is applied to characterize the underlying structures of the acceleration gain surface (AGS) of 15 midsize sedans and to link them with customer preference. The AGS can be characterized by two principal components (PCs), the first PC representing the overall slope of AGS and the second PC representing the linearity of AGS. Findings indicate that customer preference is associated with the AGS linearity. PCA thus proves itself a valuable method for translating the voice of the customer as well as for setting effective and efficient vehicle acceleration gain targets.
Investigation of a multi-objective optimization tool for engine calibration
Authors: Wu M H , Lin W , Duan S Y
Published: March 2008

Since multi-objective optimizations are becoming more important in engine calibration, the paper investigates multi-objective genetic algorithms in the application of engine optimization. Although several multi-objective genetic algorithms have been developed and some have been applied successfully in the automotive industry, it is difficult to determine which multi-objective genetic algorithm outperforms others in finding the set of optimal solutions or Pareto-optimal front in a practical multi-objective optimization problem. Based on some widely used multi-objective genetic algorithms, the paper proposes a combined scheme to deal with the difficulties in finding the optimal solution set during the engine calibration process. In the proposed approach the real-coded representation is employed in the genetic algorithm and the elitist strategy is applied for each multi-objective genetic algorithm used. To assess the proposed approach, two computational examples are given to minimize the brake specific fuel consumption and to maximize the output power torque simultaneously. The results show that the proposed approach is well suited to multi-objective optimization in engine calibration.
A novel wheel/tyre dynamics model and derivation of a generalized friction law
Authors: Gong ShaoWei , Ting Kwun-Lon
Published: March 2008

Based on the fundamentals of differential calculus, and the basic concept of finite element analysis, as well as the principles of linear decomposition and superposition, this research presents a novel wheel/tyre dynamics model. It provides a closed-form solution over an infinitesimal time interval to resolve the wheel—tyre transient process by making the non-linear wheel/tyre dynamics linear and holding the wheel slip constant. Important issues, such as the force transmission, motion generation, and energy dissipation, can therefore be predicted step by step throughout the entire wheel transient process. With the analysis of the wheel/tyre dynamics model in a longitudinal braking process, it allows derivation of a generalized friction law, which has given a more comprehensive description of the physical phenomenon of friction in general.
Development and validation of a new hybrid break-up model for the modelling of hollow-cone fuel spray
Authors: Shim Y S , Choi G M , Kim D J
Published: March 2008

In the present study, a numerical study and an experimental study on the break-up process of a hollow-cone fuel spray were performed. This was done to develop a new hybrid break-up model and to validate this model under various ambient pressure conditions. The new hybrid break-up model was composed of the linearized instability sheet atomization (LISA) model for the primary break-up and the aerodynamically progressed Taylor analogy break-up (APTAB) model, with consideration for the deformed droplet shape, for the secondary break-up. The APTAB model was used instead of the Taylor analogy break-up (TAB) model used in the previous hybrid break-up model (the LISA—TAB model). The hybrid break-up models were implemented in modified KIVA code. The calculated results of the spray characteristics, such as the spray tip penetration, spray width, Sauter mean diameter, and droplet velocity, by means of the LISA—APTAB model were compared with the calculated results via the LISA—TAB model and the experimental results found with the laser-induced exciplex fluorescence technique and the phase Doppler anemometry (PDA) system. The calculations and the experiment were performed under ambient pressures of 0.1 MPa and 0.5 MPa and an ambient temperature of 293 K. It was found that the calculated results from the LISA—APTAB model showed good agreement with the experimental results. The discrepancies between the calculated results and the experimental results in spray characteristics were reduced by a considerable margin by adopting the APTAB model instead of the TAB model for the secondary break-up process.
Investigation of methyl tertiary butyl ether—diesel combustion and odorous emissions in a direct-injection diesel engine
Authors: Roy M M
Published: March 2008

This study investigated methyl tertiary butyl ether (MTBE)-blended diesel fuel combustion and odorous emissions in a direct-injection diesel engine during and after engine warm-up at idling. A few per cent of MTBE (5 vol %) blended in diesel fuel gives lower formaldehyde (HCHO) and an improved exhaust odour than with neat diesel fuel owing to good mixture formation and combustion for lower boiling point and oxygen (O2) of the blend. With the 10 and 15 vol % MTBE blends, the very-low-boiling-point MTBE forms an overlean mixture and diminishes the positive effect of the O2 content of MTBE causing the exhaust odour and odorous emissions to deteriorate. Ignition delay of all MTBE blends is about 1—3° crank angle longer than that of neat diesel fuel depending on the engine running conditions. However, the combustion pressures and temperatures of the 5 vol % MTBE blend are similar to or a very little lower than that of neat diesel fuel. However, the 10 and 15 vol % MTBE blends show considerable decreases in the combustion pressures and temperatures.
Combustion characteristics of a compression ignition engine fuelled with diesel—ethanol blends
Authors: Li W , Ren Y , Wang X-B , Miao H , Jiang D-M , Huang Z-H
Published: March 2008

Combustion characteristics were analysed in a compression ignition engine fuelled with diesel—ethanol blends with and without a cetane number improver. The results show that, for the same brake mean effective pressure and engine speed, the maximum cylinder pressure Pmax, the ignition delay, the premixed combustion duration, and the fraction of heat release in premixed combustion phase will increase, while the diffusive combustion duration, the fraction of diffusive combustion phase, and the total combustion duration decrease with increase in the ethanol fraction in the blends. Meanwhile, the centre of the heat release curve moves close to the top dead centre, and the maximum rate (d Qb/d φ)max of heat release and the maximum rate (d p/d φ)max of pressure rise increase with increase in the ethanol fraction in the blends. The addition of a cetane number improver is beneficial to the decrease in the ignition delay, the cylinder peak pressure, the maximum rate of pressure rise, and the combustion noise when operating on diesel—ethanol blends.