bluuebunny/crossref_metadata_2025 huggingface dataset:
One Man Two Hats: What's All the Commotion!
Authors: Dahya Jay , Garcia Laura Galguera , Van Bommel Jos
Published: April 2009

We examine performance in publicly listed U.K. companies over a period that encompasses the issuance of the Cadbury Committee's Code of Best Practice, which calls for the abolition of the combined CEO/COB position. We find that companies splitting the combined CEO/COB position to conform to the Code's requirement did not exhibit any absolute or relative improvement in performance when compared to various peer‐group benchmarks. We do not necessarily scoff at mandated board structures, but the evidence suggests that this particular legislature coerced the abandonment of the combined CEO/COB position and appears to be wide of the mark.
Corporate Sustainability Performance and Idiosyncratic Risk: A Global Perspective
Authors: Lee Darren D. , Faff Robert W.
Published: April 2009

Does investing in sustainability leaders affect portfolio performance? Analyzing two mutually exclusive leading and lagging global corporate sustainability portfolios (Dow Jones) finds that (1) leading sustainability firms do not underperform the market portfolio, and (2) their lagging counterparts outperform the market portfolio and the leading portfolio. Notably, we find leading (lagging) corporate social performance (CSP) firms exhibit significantly lower (higher) idiosyncratic risk and that idiosyncratic risk might be priced by the broader global equity market. We develop an idiosyncratic risk factor and find that its inclusion significantly reduces the apparent difference in performance between leading and lagging CSP portfolios.
The “Best Corporate Citizens”: Are They Good for Their Shareholders?
Authors: Filbeck Greg , Gorman Raymond , Zhao Xin
Published: April 2009

Since 2000, Business Ethics magazine has published a list of the 100 Best Corporate Citizens. Our event study finds significant positive abnormal returns for new companies added to the annual listing on the press release date of the survey, both initially and in subsequent survey releases. Over longer holding periods, the top 100 companies consistently outperform the S&P 500, yet are not significantly different from a matched set of companies, with the exception of the initial survey year (2000). However, a rebalancing strategy based on new additions outperforms both the S&P 500 and a matched portfolio.
The Pricing of IPOs Post‐Sarbanes‐Oxley
Authors: Johnston Jarrod , Madura Jeff
Published: April 2009

The Sarbanes‐Oxley Act (SOX) imposes new requirements for firms going public. Many provisions of SOX should improve the transparency of U.S. firms going public and therefore reduce the uncertainty surrounding their valuation. We find that initial returns of initial public offerings (IPOs) in the United States have declined since SOX. Furthermore, the aftermarket performance of IPOs since SOX is significantly higher. While the expense of public reporting has increased in the United States because of SOX, the valuations of newly public firms at the time of the IPO are subject to less uncertainty and smaller aftermarket corrections.
Emergency Medicine Residency Applicant Perceptions of Unethical Recruiting Practices and Illegal Questioning in the Match
Authors: Jason Thurman R. , Katz Eric , Carter Wallace , Han Jin , Kayala Eve , McCoin Nicole , Storrow Alan B.
Published: April 2009

Objectives:  The authors hypothesized that unethical recruiting practices and illegal questioning occur during emergency medicine (EM) resident recruitment. The objectives were to estimate the prevalence of specific unethical recruiting practices and illegal questioning by EM programs based on the perceptions of residency applicants and to measure the effect of these perceptions on applicant appraisal of programs.

Methods:  This was a cross‐sectional survey of all applicants who matched to U.S. EM programs in 2005 and 2006. The survey questionnaire was developed by the study authors and was validated by pretesting on a small group representative of the study population. The survey addressed specific questions regarding program recruiting behaviors and interview questioning. The hyperlink to the secure anonymous online survey questionnaire was distributed to all EM program directors, asking them in turn to forward the hyperlink to their newly matched incoming residency class. All data were calculated with Score method with continuity correction and reported in proportions with 95% confidence intervals (CIs).

Results:  The authors received 671 survey responses. Among respondents, 56 (8.3%, 95% CI = 6.4% to 10.7%) stated that they were specifically asked to disclose at least one program’s position on their rank list by a program representative, and 44 (6.6%, 95% CI = 4.9% to 8.9%) reported that they matched at a program residing lower on their rank list than at least one other program that had informed the applicant they were ranked to match. Furthermore, 201 respondents (30.0%, 95% CI = 26.5% to 33.7%) believed that they were asked at least one illegal question during their interviews, the most common of which was inquiry into their marital status (189 respondents: 28.2%, 95% CI = 24.8% to 31.9%). Respondents were 11 times more likely to move a program to a lower position of preference on their rank order list (12.2%, 95% CI = 9.8% to 15.0%) rather than a higher position (1.1%, 95% CI = 0.5% to 2.3%) as a result of perceiving unethical recruiting behaviors or illegal questioning.

Conclusions:  These results demonstrate that among survey respondents, some perceived unethical recruiting behaviors and illegal questioning in the 2005 and 2006 Match. Perceptions of such behaviors appeared to have a negative impact on applicant appraisal of EM residency programs.
Time‐dependent Variations in Ischemia‐modified Albumin Levels in Mesenteric Ischemia
Authors: Gunduz Abdulkadir , Turkmen Suha , Turedi Suleyman , Mentese Ahmet , Yulug Esin , Ulusoy Hülya , Karahan Suleyman Caner , Topbas Murat
Published: April 2009

Objectives:  The objective was to determine the value of ischemia‐modified albumin (IMA) in the diagnosis of mesenteric embolism. The authors investigated whether or not plasma IMA levels rose in the acute period in a rat model of mesenteric ischemia and the related time‐dependent changes.

Methods:  In this randomized, controlled, nonblinded trial, 36 mature female Wistar rats were divided into six groups: three control (Groups I, III, and V) and three ischemia (Groups II, IV, and VI). In the control groups, blood was sampled at 30 minutes (Group I), 2 hours (Group III), and 6 hours (Group V) following a simple laparotomy. In the ischemia groups, following laparotomy, the superior mesenteric artery (SMA) was clamped using a bulldog clamp, and blood samples were taken at 30 minutes (Group II), 2 hours (Group IV), and 6 hours (Group VI).

Results:  Plasma IMA levels in the ischemia groups were significantly higher compared to those of the control groups (p < 0.004). In addition, levels were higher in the 6‐hour blood samples of the ischemia group than in the 2‐hour and 30‐minute samples (p < 0.001). Serum IMA was also higher in the 2‐hour blood samples of the ischemia group than in the 30‐minute samples (p < 0.001).

Conclusions:  These preliminary findings suggest that serum IMA levels may represent a significant parameter in the early diagnosis of acute mesenteric ischemia and that further studies are necessary.
The Incremental Benefit of a Shortness‐of‐breath Biomarker Panel in Emergency Department Patients with Dyspnea
Authors: Singer Adam J. , Thode, Jr Henry C. , Green Gary B. , Birkhahn Robert , Shapiro Nathan I. , Cairns Charles , Baumann Brigitte M. , Aghababian Richard , Char Douglas , Hollander Judd E.
Published: April 2009

Objectives:  The objective was to determine the incremental benefit of a shortness‐of‐breath (SOB) point‐of‐care biomarker panel on the diagnostic accuracy of emergency department (ED) patients presenting with dyspnea.

Methods:  Adult ED patients at 10 U.S. EDs with SOB were included. The physician’s estimates of the pretest clinical probability of heart failure (HF), acute myocardial infarction (MI), and pulmonary embolism (PE) were recorded using deciles (0%–100%). Blood samples were analyzed using a SOB point‐of‐care biomarker panel (troponin I, myoglobin, creatinine kinase‐myocardial band isoenzyme [CK‐MB], D‐dimer, and B‐type natriuretic peptide [BNP]). Thirty‐day follow‐up for MI, HF, and PE was performed. Data were analyzed using logistic regression and receiver operating characteristics (ROC) curve analysis.

Results:  Of 301 patients, the mean (±standard deviation [SD]) age was 61 (±18) years; 56% were female, 58% were white, and 38% were African American. Diagnoses included MI (n = 54), HF (n = 91), and PE (n = 16) in a total of 129 (43%) of the patients. High pretest clinical certainty (≥80%) identified 60 of these 129 (46.5%) cases. The SOB point‐of‐care biomarker panel identified 66 additional cases of MI (n = 24), HF (n = 31), and PE (n = 11). The overall adjusted sensitivity for any diagnosis was increased from 65% to 70% with the addition of the SOB point‐of‐care biomarker panel (difference = 5%, 95% CI = −1.1% to 11%) while specificity was increased from 82% to 83% (difference = 1%, 95% CI = −4% to 7%). The model containing pretest probability and the results of the SOB panel had an area under the curve (AUC) of 83.4% (95% CI = 78.4% to 88.5%), which was not significantly better than the AUC of 80.4% (95% CI = 75.1% to 85.7%) for clinical probability alone.

Conclusions:  The addition of the SOB panel of markers did not improve the AUC for diagnosing the combined set of clinical conditions. Using the disease‐specific SOB biomarkers increased the sensitivity on a disease‐by‐disease basis; however, specificity was reduced.
Long‐term pheromone‐mediated mating disruption of the Mediterranean flour moth, Ephestia kuehniella, in a flourmill
Authors: Sieminska Edyta , Ryne Camilla , Löfstedt Christer , Anderbrant Olle
Published: April 2009

Several studies have indicated that mating disruption (MD) successfully reduces population densities of stored product moths, for example, the Mediterranean flour moth, Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae). However, practical issues, such as finding control plots, replication, and lack of similarity between replicates, often incur problems in full‐scale investigations and often draw focus from the added results. We here present results from long‐term monitoring of E. kuehniella populations in two similar flourmills in Poland, one treated with pheromone for MD and one left untreated and used as control. Pheromone‐mediated MD was applied during 2 years. Thirty pheromone dispensers (one per 100 m3 factory volume), each releasing about 2 mg (Z,E)‐9,12‐tetradecadienyl acetate per day, were used. Pheromone‐baited traps were used to monitor the moth populations in the MD mill and in a nearby untreated mill. The reduction in trap catch during the MD treatment was about 90% or more, compared with the untreated mill or pre‐treatment periods of the MD mill. The reduction was larger during the 2nd year of MD than during the 1st year. These results contribute to the picture that MD is an effective method to control moth species infesting stored products.
Tumour virology – history, status and future challenges
Authors: KALLAND KARL‐HENNING , KE XI‐SONG , ØYAN ANNE MARGRETE
Published: April 2009

Viruses enter host cells in order to complete their life cycles and have evolved to exploit host cell structures, regulatory factors and mechanisms. The virus and host cell interactions have consequences at multiple levels, spanning from evolution through disease to models and tools for scientific discovery and treatment. Virus‐induced human cancers arise after a long duration of time and are monoclonal or oligoclonal in origin. Cancer is therefore a side effect rather than an essential part of viral infections in humans. Still, 15–20% of all human cancers are caused by viruses. A review of tumour virology shows its close integration in cancer research. Viral tools and experimental models have been indispensible for the progress of molecular biology. In particular, retroviruses and DNA tumour viruses have played major roles in our present understanding of the molecular biology of both viruses and the host. Recently, additional complex relationships due to virus and host co‐evolution have appeared and may lead to a further understanding of the overall regulation of gene expression programmes in cancer.
Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence
Authors: BLADER IRA J. , SAEIJ JEROEN P.
Published: April 2009

Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect most warm‐blooded animals and cause severe and life‐threatening disease in developing fetuses and in immune‐compromised patients. Although Toxoplasma was discovered over 100 years ago, we are only now beginning to appreciate the importance of the role that parasite modulation of its host has on parasite growth, bradyzoite development, immune evasion, and virulence. The goal of this review is to highlight these findings, to develop an integrated model for communication between Toxoplasma and its host, and to discuss new questions that arise out of these studies.
Innate recognition of intracellular pathogens: detection and activation of the first line of defense
Authors: RASMUSSEN SIMON B. , REINERT LINE S. , PALUDAN SØREN R.
Published: April 2009

The innate immune system constitutes the first line of defense against infections and is also important for initiating the development of an adaptive immune response. The innate immune system recognizes microbial infection through germline‐encoded pattern recognition receptors, which are responsible for decoding the microbial fingerprint and activating an appropriate response against the invading pathogen. In this review, we present and discuss current knowledge on how the innate immune system recognizes intracellular pathogens, activates intracellular signaling, induces gene expression, and orchestrates the microbicidal response against pathogens with a habitat within host cells.
Co‐evolutionary arms race between brood parasites and their hosts at the nestling stage
Authors: Soler Manuel
Published: April 2009

Traditionally it was thought that the arms race between brood parasites and their hosts was confined to the egg stage of the breeding cycle because many host species are able to reject mimetic parasitic eggs but they are unable to reject strongly different parasitic chicks. However, recently, new cases of chick rejection, discrimination, or mimicry, have been published confirming the possibility that an equivalent arms race to that found at the egg stage could ever be played out at the chick stage. Here, I review the evidence for the existence of a co‐evolutionary arms race at the nestling stage. Recent findings include new deceiving strategies used by brood parasitic chicks, defensive strategies used by foster parents and adaptive strategies of host nestlings. This review shows that both chick discrimination and relationships between brood parasites and their hosts at the nestling stage are much more complicated than previously believed. At least in some brood parasite‐host systems, an arms race at the nestling stage is working.
Evidence for a maternal effect benefiting extra‐pair offspring in a songbird, the house wren Troglodytes aedon
Authors: Scott Johnson L. , Brubaker Jessica L. , Johnson Bonnie G.P. , Masters Brian S.
Published: April 2009

Female birds are hypothesized to mate outside the pairbond to secure alleles that enhance the fitness potential of their offspring. To test this, researchers typically compare fitness‐related attributes of extra‐pair (EP) and within‐pair (WP) half‐siblings. Often neglected, however, is the possibility that females may provide EP offspring with certain non‐genetic advantages. For example, in species in which eggs hatch asynchronously, females may place EP offspring amongst earlier‐laid eggs in the clutch. Because they tend to hatch first, chicks from earlier‐laid eggs are often larger and more developed than their nestmates and thus have a competitive advantage. We tested for an association between offspring paternity and position in the laying/hatching sequence in a Wyoming population of the house wren Troglodytes aedon. Eggs in this population always hatch asynchronously, usually in the order laid, over 24–48 h, setting up a stair‐step‐like size hierarchy within broods early in the nestling stage. This suggested that we could thus use a chick's mass relative to that of its nestmates as an index of the chick's position in the laying sequence. We first confirmed this, showing that position in the laying sequence explains 70% of the variance in chick size relative to nestmates. We then compared masses of EP and WP offspring shortly after hatching in 27 broods with mixed paternity. On average, EP offspring weighed 14% more than their WP counterparts, a highly significant difference. Our results therefore suggest that EP offspring are more likely than WP offspring to occur in earlier‐laid eggs, thus gaining a size‐based competitive advantage. We recommend that, when comparing EP and WP half‐siblings in species in which eggs hatch asynchronously, researchers test for this potential maternally derived effect on offspring performance.
A guide to hair follicle analysis by transmission electron microscopy: technique and practice
Authors: Morioka Kiyokazu
Published: April 2009

Abstract:  Hair follicles contain several tissues and cell types that differentiate down distinct pathways to provide for growth, keratinization and the maintenance of the hair shaft. Electron microscopy is useful for examining the morphological characteristics of developing hair follicles, including special types of keratinization, the timing of keratinization, programmed cell death, cell adhesion and separation, cell movement and changes in organelles. Hair follicles are one of the more challenging targets for electron microscopic analysis, and the use of neonatal animals combined with careful treatment of the samples can yield informative photomicrographs. Detailed protocols and examples of a number of techniques are presented here.
Migration and penetration of a fluorescent textile dye into the skin –in vivo versus in vitro methods
Authors: Meinke Martina , Abdollahnia Mandana , Gähr Frank , Platzek Thomas , Sterry Wolfram , Lademann Jürgen
Published: April 2009

Abstract:  The amount of textile dye migration from the textile and penetration into the skin is relevant when assessing the risk of textile dyes. In this paper, in vivo methods were developed using a harmless textile dye with a strong fluorescence and were then compared with in vitro methods. For the in vivo method, the textile was applied to the lower back of six volunteers wearing the textile 12 h and to the lower back of 12 volunteers during 30 min active sport. The maximum skin absorption of 55 ± 17 ng/cm2 was obtained in the group engaged in sports. The in vitro methods, which involved the application of the textile to the pig ear skin, was shown to yield similar results to the 12 h in vivo group (31.2 ± 9.6 ng/cm2 vs 27 ± 14 ng/cm2). The migration of the textiles into artificial sweat resulted in approximately 20 μg/cm2. The disadvantage of such textile extract applications on pig ear skin is discussed. It could be demonstrated that the absorption of the dye is strongly correlated to the amount of sweat, whereas the contact time was less important.
Fine tuning the immune response through B7‐H3 and B7‐H4
Authors: Yi Kyung H. , Chen Lieping
Published: April 2009

Summary:  B7‐H3 and B7‐H4 belong to a new class of immune regulatory molecules, which primarily execute their functions in peripheral tissues to fine tune immune responses in target organs. In normal circumstances, while the mRNA for both molecules is broadly distributed, tight control at the post‐transcriptional level is imposed. Under a pathogenic environment, such as inflammation and cancer, the control is often aberrant. Upon engaging their receptors, these molecules regulate the immune response in positive or negative ways depending on the expression and type of cells bearing the receptors. Thus, manipulation of the expression of these molecules and/or their receptors may represent a realistic opportunity to fine tune immune responses and to design new immunotherapeutic approaches.
Yin–Yang of costimulation: crucial controls of immune tolerance and function
Authors: Nurieva Roza I. , Liu Xikui , Dong Chen
Published: April 2009

Summary:  In addition to signals from the T‐cell receptor complex, it has been recognized for many years that a ‘second’ signal, most notably from CD28, is also important in T‐cell activation. In the recent years, many new members of CD28 family as well as the molecules that share structural homology to CD28 ligands CD80 and CD86 have been discovered. Interestingly, some of these proteins function to dampen T‐cell activation and regulate the induction of T‐cell tolerance. Therefore, positive and negative costimulation are the two sides of the coin to fine tune T‐cell receptor signaling to determine the outcome of T‐cell receptor engagement‐tolerance versus function.
CD28 and CTLA‐4 coreceptor expression and signal transduction
Authors: Rudd Christopher E. , Taylor Alison , Schneider Helga
Published: April 2009

Summary: T‐cell activation is mediated by antigen‐specific signals from the TCRζ/CD3 and CD4–CD8–p56lck complexes in combination with additional co‐signals provided by coreceptors such as CD28, inducible costimulator (ICOS), cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), programmed death (PD‐1), and others. CD28 and ICOS provide positive signals that promote and sustain T‐cell responses, while CTLA‐4 and PD‐1 limit responses. The balance between stimulatory and inhibitory co‐signals determines the ultimate nature of T‐cell responses where response to foreign pathogen is achieved without excess inflammation and autoimmunity. In this review, we outline the current knowledge of the CD28 and CTLA‐4 signaling mechanisms [involving phosphatidylinositol 3 kinase (PI3K), growth factor receptor‐bound protein 2 (Grb2), Filamin A, protein kinase C θ (PKCθ), and phosphatases] that control T‐cell immunity. We also present recent findings on T‐cell receptor‐interacting molecule (TRIM) regulation of CTLA‐4 surface expression, and a signaling pathway involving CTLA‐4 activation of PI3K and protein kinase B (PKB)/AKT by which cell survival is ensured under conditions of anergy induction.
Molecular mechanisms of T‐cell receptor and costimulatory molecule ligation/blockade in autoimmune disease therapy
Authors: Podojil Joseph R. , Miller Stephen D.
Published: April 2009

Summary:  Pro‐inflammatory CD4+ T‐cell‐mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes, are hypothesized to be initiated and maintained by activated antigen‐presenting cells presenting self antigen to self‐reactive interferon‐γ and interleukin‐17‐producing CD4+ T‐helper (Th) type 1/Th17 cells. To date, the majority of Food and Drug Administration‐approved therapies for autoimmune disease primarily focus on the global inhibition of immune inflammatory activity. The goal of ongoing research in this field is to develop both therapies that inhibit/eliminate activated autoreactive cells as well as antigen‐specific treatments, which allow for the directed blockade of the deleterious effects of self‐reactive immune cell function. According to the two‐signal hypothesis, activation of a naive antigen‐specific CD4+ T cell requires both stimulation of the T‐cell receptor (TCR) (signal 1) and stimulation of costimulatory molecules (signal 2). There also exists a balance between pro‐inflammatory and anti‐inflammatory immune cell activity, which is regulated by the type and strength of the activating signal as well as the local cytokine milieu in which the naive CD4+ T cell is activated. To this end, the majority of ongoing research is focused on the delivery of suboptimal TCR stimulation in the absence of costimulatory molecule stimulation, or potential blockade of stimulatory accessory molecules. Therefore, the signaling pathways involved in the induction of CD4+ T‐cell anergy, as apposed to activation, are topics of intense interest.
Timing and tuning of CD27–CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology
Authors: Nolte Martijn A. , Van Olffen Ronald W. , Van Gisbergen Klaas P. J. M. , Van Lier René A. W.
Published: April 2009

Summary:  After binding its natural ligand cluster of differentiation 70 (CD70), CD27, a tumor necrosis factor receptor (TNFR)‐associated factor‐binding member of the TNFR family, regulates cellular activity in subsets of T, B, and natural killer cells as well as hematopoietic progenitor cells. In normal immune responses, CD27 signaling appears to be limited predominantly by the restricted expression of CD70, which is only transiently expressed by cells of the immune system upon activation. Studies performed in CD27‐deficient and CD70‐transgenic mice have defined a non‐redundant role of this receptor–ligand pair in shaping adaptive T‐cell responses. Moreover, adjuvant properties of CD70 have been exploited for the design of anti‐cancer vaccines. However, continuous CD27–CD70 interactions may cause immune dysregulation and immunopathology in conditions of chronic immune activation such as during persistent virus infection and autoimmune disease. We conclude that optimal tuning of CD27–CD70 interaction is crucial for the regulation of the cellular immune response. We provide a detailed comparison of costimulation through CD27 with its closely related family members 4‐1BB (CD137), CD30, herpes virus entry mediator, OX40 (CD134), and glucocorticoid‐induced TNFR family‐related gene, and we argue that these receptors do not have a unique function per se but that rather the timing, context, and intensity of these costimulatory signals determine the functional consequence of their activity.
Translating costimulation blockade to the clinic: lessons learned from three pathways
Authors: Ford Mandy L. , Larsen Christian P.
Published: April 2009

Summary:  As the recognition that costimulatory signals are critical for optimal T‐cell activation, proliferation, and differentiation, there has been an explosion in the study of costimulatory molecules and their roles in enhancing anti‐donor T‐cell responses following transplantation. Here, we focus on the bench‐to‐beside translation of blocking agents designed to target three critical costimulatory pathways: the CD28/CD80/CD86 pathway, the CD154/CD40 pathway, and the lymphocyte function associated antigen‐1/intercellular adhesion molecule pathway. While blockade of each of these pathways proved promising in inhibiting donor‐reactive T‐cell responses and promoting long‐term graft survival in murine models of transplantation, the progression of development of therapeutic agents to block these pathways has each taken a slightly different course. Both logistical and biological pitfalls have accompanied the translation of blockers of all three pathways into clinically applicable therapies, and the development of costimulatory blockade as a substitute for current standard‐of‐care calcineurin inhibitors has by no means reached completion. Collaboration between both the basic and clinical arenas will further propel the development of costimulation blockers currently in the pipeline, as well as of novel methods to target these critical pathways during transplantation.
Dynamic regulation of T‐cell costimulation through TCR–CD28 microclusters
Authors: Yokosuka Tadashi , Saito Takashi
Published: April 2009

Summary:  T‐cell activation requires contact between T cells and antigen‐presenting cells (APCs) to bring T‐cell receptors (TCRs) and major histocompatibility complex peptide (MHCp) together to the same complex. These complexes rearrange to form a concentric circular structure, the immunological synapse (IS). After the discovery of the IS, dynamic imaging technologies have revealed the details of the IS and provided important insights for T‐cell activation. We have redefined a minimal unit of T‐cell activation, the ‘TCR microcluster’, which recognizes MHCp, triggers an assembly of assorted molecules downstream of the TCR, and induces effective signaling from TCRs. The relationship between TCR signaling and costimulatory signaling was analyzed in terms of the TCR microcluster. CD28, the most valuable costimulatory receptor, forms TCR–CD28 microclusters in cooperation with TCRs, associates with protein kinase C θ, and effectively induces initial T‐cell activation. After mature IS formation, CD28 microclusters accumulate at a particular subregion of the IS, where they continuously assemble with the kinases and not TCRs, and generate sustained T‐cell signaling. We propose here a ‘TCR–CD28 microcluster’ model in which TCR and costimulatory microclusters are spatiotemporally formed at the IS and exhibit fine‐tuning of T‐cell responses by assembling with specific players downstream of the TCR and CD28.
Molecular mechanism and function of CD40/CD40L engagement in the immune system
Authors: Elgueta Raul , Benson Micah J. , De Vries Victor C. , Wasiuk Anna , Guo Yanxia , Noelle Randolph J.
Published: April 2009

Summary:  During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen‐presenting cells, as well as non‐immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non‐immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti‐tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.
The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T‐cell activation
Authors: Cai Guifang , Freeman Gordon J.
Published: April 2009

Summary:  CD160 is a newly identified ligand for HVEM (herpes virus entry mediator). Previously identified HVEM ligands include BTLA (B‐ and T‐lymphocyte attenuator), LIGHT (lymphotoxin‐like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes) and LTα (lymphotoxin‐α). The binding of LIGHT or LTα to HVEM delivers a costimulatory signal, whereas the binding of BTLA or CD160 to HVEM delivers a coinhibitory signal. Thus, HVEM is a bidirectional switch regulating T‐cell activation in a costimulatory or coinhibitory fashion whose outcome depends on the ligand engaged. The cysteine‐rich domain 1 (CRD1) of HVEM is essential for the binding of coinhibitory ligands CD160 and BTLA but not costimulatory ligand LIGHT. Deletion or blockade of HVEM CRD1 abolishes the binding of CD160 and BTLA, but not LIGHT, and converts HVEM to a dominant costimulatory molecule, possibly through the loss of negative signaling by CD160/BTLA. Therapies targeting the CRD1 of HVEM to block BTLA and CD160 binding are being developed to enhance immune responses and vaccination.
Endocytic Regulation of Notch Signalling During Development
Authors: Fürthauer Maximilian , González‐Gaitán Marcos
Published: April 2009

Delta/Notch signalling is of major importance for embryonic development and adult life. While endocytosis is often viewed as a way to down‐regulate biological signals, ligand and receptor internalization are essential for Notch activation. The development of Drosophila mecanosensory bristles is a powerful model to study Delta/Notch signalling. Following the asymmetric division of bristle precursor cells, Delta ligands and Notch receptors traffic differently in the two daughter cells, leading to directional signal activation. Recent evidence suggests that in addition to differential ligand endocytosis after division, a subpopulation of multivesicular endosomes ensures the directional transport of Delta/Notch already during asymmetric cell division. Biochemical analysis suggests that different phases of endocytic Delta trafficking exert complementary but distinct actions required for ligand recycling, ligand/receptor interaction and ligand‐mediated receptor activation, respectively. Finally, novel data suggest that different endosomal compartments may act as Delta/Notch signalling platforms. In this review, we discuss the implications of these novel findings for our cell biological understanding of Delta/Notch signalling.
Instrument fracture: mechanisms, removal of fragments, and clinical outcomes
Authors: CHEUNG GARY S.P.
Published: April 2009

Instrument fracture can be an unpleasant mishap during non‐surgical root canal treatment. While most stainless‐steel instruments appear to fail by excessive amounts of torque, the combined action of torsional stress and cyclic loading (i.e. fatigue, as a result of rotational bending, or repeated torsion) is responsible for the breakage of NiTi rotary files in use. Factors affecting the incidence and mode of failures include the instrumentation technique, use of torque‐controlled motor, the dimension and surface condition of the instrument, rotation rate, radius (and, to a certain extent, angle) of canal curvature, and the presence of a straight‐line access and a ‘glide path’ to the apical portion of the canal. If breakage should occur clinically, the patient should be informed of the incident and consideration should be given as to whether or not to remove the fragment. Managed properly, the presence of a broken fragment per se may not adversely affect the outcome of root canal treatment. This review examines the various aspects (including mechanisms, contributing factors, prognosis and management) of instrument fracture. Emphasis is placed on the separation of nickel–titanium rotary files and ways to prevent this in the clinical situation.
Longitudinal tooth fractures: findings that contribute to complex endodontic diagnoses
Authors: RIVERA ERIC M. , WALTON RICHARD E.
Published: April 2009

The purpose of this review is to describe and discuss the diagnostic and treatment challenges related to tooth fractures primarily in the vertical plane, that is, the long axis of the crown and/or root. This includes when and how to identify and determine the extent of the fracture, when a coronal restoration should be placed, when root canal treatment is needed, and when a tooth or root should be extracted based on the location and extent of the fracture. The term ‘longitudinal fractures’ is used because they usually represent vertical extensions of fractures over distance and time. These fractures often present problems with diagnosis and treatment, but should be considered as findings only. They are not to be considered as pulpal or periapical diagnoses, but as pathways for bacteria that may induce pulpal and/or periapical inflammation or disease. Longitudinal fractures are divided into five definitive classifications, generally from least to most severe: (1) craze lines; (2) fractured cusp; (3) cracked tooth; (4) split tooth; and (5) vertical root fracture. These differ but have frequently been confused or combined in clinical articles, creating misunderstanding and resulting in incorrect diagnosis and inappropriate treatment. These classifications have been devised to provide global definitions that researchers and clinicians can use to eliminate this confusion. This review is subdivided into these five classifications as to incidence, pathogenesis, clinical features, etiologies, diagnosis, treatment, prognosis, and prevention.
Prejudice against obesity among 10‐year‐olds: a nationwide population‐based study
Authors: Hansson Lena M , Karnehed Nina , Tynelius Per , Rasmussen Finn
Published: April 2009

Aims:  Population‐based research on children's possible prejudice against thin, obese and average body sizes is scarce. This study examined children's prejudice against various body sizes of both sexes. The effects of sex, body size, place of residence and socio‐economic status (SES) on children's prejudice were also investigated.

Methods:  In 2005, a nationally representative sample of 10‐year‐old children (N = 1409) responded to a questionnaire measuring stereotypes and prejudice against thin, average‐weight and obese silhouettes.

Results:  As estimated by odds ratios (ORs), children were more likely to report prejudice against obesity (OR = 53, 95% confidence interval [CI]: 42–67) and thinness (OR = 20, 95% CI: 16–26) than against average body weight. The risk of being prejudiced varied with child's sex and with sex and body size of the silhouette figure. No association was found between own body weight and prejudice against various body sizes. Children with high SES were more likely to be prejudiced against obesity compared with children with low SES (OR = 1.2, 95% CI: 1.1–1.4).

Conclusion:  This large, population‐based study showed that Swedish 10‐year‐old children hold stereotypical attitudes and are prejudiced against not only peers with obesity but also those with thin body sizes. Interestingly, no association was found between own body weight and prejudice against various body sizes.
Effect of dietary dried milky sludge on productive performance and egg quality in laying Japanese quails
Authors: SUPPADIT Tawadchai , JATURASITHA Sanchai , SELASAT Wirote , NORKEAW Rakkeart , POUNGSUK Pukkapong , PRIPWAI Nakarin
Published: April 2009

The experiment was conducted to study the effectiveness of dried milky sludge (DMS) as a feed source for laying Japanese quails. The DMS was incorporated into the experimental diets at levels of 0, 5.0, 10.0, 15.0 and 20.0%. Four hundred quails were used in a completely randomized design. The results revealed that the daily egg‐laying rate, feed cost/100 egg weight, egg width, egg length, egg weight, shell quality characteristics in terms of breaking time, Young's modulus, work, max force, fracturability, breaking stress, stiffness and power, as well as color intensity and yolk height improved significantly with increasing levels of DMS in the diet (P < 0.05), while feed intake/bird/day, mortality and eggshell thickness showed no significant differences (P > 0.05). From this experiment, it was found that DMS incorporated into the experimental diet at the 20.0% level yielded the most productive performance and best egg quality.
Plasma concentration of anti‐diuretic hormone and urine volume in response to intraruminal administration of acetate, propinata and butyrate in suckling calves
Authors: IRIKI Tsunenori , NAKAMURA Tomomi , OBIGATA Rui , ONDA Ken
Published: April 2009

Acetate, propionate, and butyrate were intraruminally administered to dry feed‐fed suckling calves to evaluate their effects on plasma ketone bodies, anti‐diuretic hormone (ADH) concentrations, and urine volume. Four male Holstein calves (5–7 weeks old) were given 1.0 L of warm water or 0.5 mole of one of the acids in 1.0 L of warm water. A 4 × 4 Latin square design was adopted for the experiment. The acetate group showed significantly higher plasma acetate concentrations than the other three groups between 0.25 h and 2.0 h after administration (P < 0.01). Plasma glucose concentrations did not differ markedly among the groups. The butyrate group showed significantly higher plasma ketone body concentrations than the other three groups until the end of the experiment (P < 0.01). Plasma ADH concentrations quickly rose in the butyrate group and remained significantly higher than in the other three groups from 0.25 h to 2.5 h after administration (P < 0.05). In accordance with the elevation of plasma ADH levels, the butyrate group showed decreases in urine volume and increases in urine osmolarity (P < 0.05). Plasma osmolarity and hematocrit values (Ht) were not different among the groups. These results suggest that the administration of acetate and propionate had little effect on ADH secretion.
THE RELATIVE SENSITIVITY OF COMPUTED TOMOGRAPHY AND MYELOGRAPHY FOR IDENTIFICATION OF THORACOLUMBAR INTERVERTEBRAL DISK HERNIATIONS IN DOGS
Authors: ISRAEL SARAH K. , LEVINE JONATHAN M. , KERWIN SHARON C. , LEVINE GWENDOLYN J. , FOSGATE GEOFFREY T.
Published: April 2009

We compared the relative sensitivity of computed tomography (CT) and myelography for identification of disk herniation in dogs. Criteria for patient selection included presurgical CT, myelography, or both and surgical or necropsy confirmation of disk herniation between the T3 and L6 vertebral articulations. Imaging findings were described as positive or inconclusive. Adverse events such as hypotension, cardiac arrhythmias, seizures, death, and lower urinary tract infection were compared between imaging groups. One hundred and eighty‐two dogs met the inclusion criteria, with 116 dogs having myelography performed as the initial diagnostic imaging modality and 66 dogs having CT performed as the initial modality. The relative sensitivity for locating the site of disk herniation was 83.6% when myelography was the first test performed and 81.8% when CT was the first test performed. CT was more sensitive than myelography at detecting lesions in chronically affected dogs (P=0.025). Myelography was more sensitive than CT at detecting lesions in smaller dogs (<5 kg;P=0.004). Dogs that received both imaging modalities were significantly more likely to die or be euthanized compared with myelography alone (P<0.001). Both myelography and CT are reasonable diagnostic imaging modalities for locating the site of disk herniation. CT should be considered especially in heavier, more chronically affected dogs. The major limitations of this study include lack of randomization to imaging modality and the use of surgical exploration or necropsy as the gold standard.
PULMONARY HYPERTENSION IN DOGS WITH MITRAL REGURGITATION ATTRIBUTABLE TO MYXOMATOUS VALVE DISEASE
Authors: CHIAVEGATO DAVID , BORGARELLI MICHELE , D'AGNOLO GINO , SANTILLI ROBERTO A.
Published: April 2009

Pulmonary hypertension has been associated with mitral insufficiency caused by chronic degenerative valve disease in dogs. Our aim was to search for associations between left atrial to aortic root ratio, end‐systolic and end‐diastolic volume indices, and changes in the right ventricular to right atrial pressure gradient as estimated by the peak velocity of tricuspid regurgitation in dogs with chronic degenerative valve disease and different classes of heart failure. Dogs, for which follow‐up was available were evaluated for changes in the right ventricular to right atrial systolic pressure gradient over time. Three hundred and forty‐four dogs were studied; 51 in the International Small Animal Cardiac Health Council class 1a, 75 in class 1b, 113 in class 2, 97 in class 3a, and 8 in class 3b. The mean values for right ventricular to right atrial systolic pressure gradient, end‐systolic volume index, end‐diastolic volume index, and left atrial to aortic ratio were 49.2 ± 17.1 mmHg, 149.12 ± 60.8 and 37.7 ± 21.6 ml/m2, and 1.9 ± 0.5, respectively. A weak positive correlation was found between the right ventricular to right atrial systolic pressure gradient and the left atrial to aorta ratio (r=0.242, P<0.0001), end‐diastolic volume index (r=0.242, P<0.0001), and end‐systolic volume index (r=0.129, P<0.001). Follow up was available for 49 dogs. Of these, 18 had an increased, 12 a decreased, and 19 a stable right ventricular to right atrial systolic pressure gradient despite therapy. The equivalence point between the sensitivity and specificity curves of about 80% in the coincident point corresponded to a right ventricular to right atrial systolic pressure gradient of 48 mmHg. Our results suggest an association between the progressive nature of chronic degenerative mitral valve disease and pulmonary hypertension. It is of clinical interest that, with a right ventricular to right atrial systolic pressure gradient pressure gradient at or above 48 mmHg, pulmonary hypertension does not appear to improve despite therapy targeted at lowering the left atrial load.
MAGNETIC RESONANCE IMAGING CONTRAST ENHANCEMENT OF THE TRIGEMINAL NERVE IN DOGS WITHOUT EVIDENCE OF TRIGEMINAL NEUROPATHY
Authors: PETTIGREW ROGER , RYLANDER HELENA , SCHWARZ TOBIAS
Published: April 2009

Brain magnetic resonance images from 42 dogs imaged between 2002 and 2007 were reviewed retrospectively to establish the incidence of trigeminal nerve contrast enhancement. These dogs had otherwise normal MR images and no clinical evidence of trigeminal nerve disease. Contrast enhancement of the entire trigeminal nerve was seen in 39 dogs and in the region of the trigeminal ganglion in all 42 dogs. When contrast enhancement of the trigeminal nerve was observed, the intensity was subjectively less than or equal to that of the pituitary gland. Contrast enhancement of the trigeminal nerve was seen in 42 dogs with no clinical evidence of trigeminal nerve pathology.
MAGNETIC RESONANCE IMAGING FEATURES OF PARASPINAL INFECTION IN THE DOG AND CAT
Authors: HOLLOWAY ANDREW , DENNIS RUTH , McCONNELL FRASER , HERRTAGE MIKE
Published: April 2009

The magnetic resonance (MR) imaging findings in 22 dogs and two cats with confirmed paraspinal infection of the thoracolumbar spine were characterized. These findings included extensive T2‐hyperintense areas (24/24), abscessation (20/24), mild inherent T1‐hyperintensity of muscle and abscesses (18/24), and postcontrast enhancement (24/24). Changes involved the vertebral canal in four patients. The longus coli muscles were affected in one cat. Thoracolumbar changes in the remaining 23 patients involved the iliopsoas and epaxial muscles in 23/23 and 19/23 patients, respectively. Iliopsoas muscle abscessation was unilateral in 12/23, and bilateral in 6/24 patients. Abscessation involved both epaxial and iliopsoas muscles in 2/23 patients and the epaxial muscles alone in one patient. A contrast‐enhancing sinus tract within the deep thoracolumbar fascia was present in 10/23 patients. Lumbar vertebrae periosteal reactions were identified in 19/23 patients on MR images compared with 15/17 patients with radiography. A focal area of signal void suspected to represent foreign material was seen in 5/23 patients but foreign material was actually found in only two of these five. There was no recurrence of clinical signs following MR imaging and revision surgery. MR imaging permits the severity and extent of changes associated with paraspinal infection to be characterized and allows the location, number and any communication of sinus tracts to be documented.