bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant VAC in a Patient With Extensive Necrotizing Fasciitis
Authors: Steinstraesser Lars , Sand Michael , Steinau Hans-Ulrich
Published: January 2009

The authors present a case of an extensive fulminant necrotizing fasciitis of the left flank, thigh, and lower parts of the leg treated with debridement, split-thickness skin grafting, and a giant negative pressure wound dressing covering 0.53 m 2 or 18% of the body surface. To the authors' knowledge, this is the largest split-thickness grafted body surface successfully treated with negative pressure wound dressing documented in the literature.
Conflicting Findings in Mixed Methods Research
Authors: Slonim-Nevo Vered , Nevo Isaac
Published: January 2009

Combining diverse methods in a single study raises a problem: What should be done when the findings of one method of investigation conflict with those of another? The authors illustrate this problem using an example in which three study phases—quantitative, qualitative, and intervention—are applied. The findings from the quantitative phase did not fit those from the qualitative phase; there were discrepancies within the qualitative phase itself, and the findings from the single-case evaluations of the intervention using standardized scales did not fit the findings derived from self-made scales. The authors explain these inconsistencies by way of the complementary approach: Conflicting findings should be integrated, and consistency is restored by admitting complexity in the phenomenon under investigation.
Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia
Authors: Wu Qing-Li , Zierold Claudia , Ranheim Erik A.
Published: January 2009

Wnt/Fzd signaling is known to play a key role in development, tissue-specific stem-cell maintenance, and tumorigenesis, particularly through the canonical pathway involving stabilization of β-catenin. We have previously shown that Fzd9−/− mice have a deficiency in pre-B cells at a stage when self-renewing division is occurring in preference to further differentiation, before light chain immunoglobulin recombination. To determine whether pathologic usurpation of this pathway plays a role in B-cell leukemogenesis, we examined the expression of Wnt/Fzd pathway genes in the Eμ-TCL1 mouse model of chronic lymphocytic leukemia. We find that, in the course of leukemogenesis, the expression of Wnt16, Wnt10α, Fzd1, and most dramatically, Fzd6, is progressively up-regulated in the transformed CD5+ B cells of these mice, as are β-catenin protein levels. Elimination of Fzd6 expression by crossing into Fzd6−/− mice significantly delays development of chronic lymphocytic leukemia in this model. Our findings suggest that the self-renewal signals mediated by Wnt/Fzd that are enlisted during B-cell development may be pathologically reactivated in the neoplastic transformation of mature B cells.
Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell–depleted allogeneic hematopoietic cell transplantation
Authors: Yu Junli , Venstrom Jeffrey M. , Liu Xiao-Rong , Pring James , Hasan Reenat S. , O'Reilly Richard J. , Hsu Katharine C.
Published: January 2009

Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient (“missing self”). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR (“missing ligand”), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell–depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-γ and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell–derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.
Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine
Authors: Höglund Andreas , Nilsson Lisa M. , Forshell Linus Plym , Maclean Kirsteen H. , Nilsson Jonas A.
Published: January 2009

Decitabine (also referred to as 5-aza-2′-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53−/− mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.
Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation
Authors: Bachanova Veronika , Verneris Michael R. , DeFor Todd , Brunstein Claudio G. , Weisdorf Daniel J.
Published: January 2009

Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced-intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m2 × 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P < .04) and improved overall survival (81%, P < .01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.
Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance
Authors: Vachon Celine M. , Kyle Robert A. , Therneau Terry M. , Foreman Barbara J. , Larson Dirk R. , Colby Colin L. , Phelps Tara K. , Dispenzieri Angela , Kumar Shaji K. , Katzmann Jerry A. , Rajkumar S. Vincent
Published: January 2009

We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.
Impact of genotyping errors on the type I error rate and the power of haplotype-based association methods
Authors: Marquard Vivien , Beckmann Lars , Heid Iris M , Lamina Claudia , Chang-Claude Jenny
Published: January 2009

Background

We investigated the influence of genotyping errors on the type I error rate and empirical power of two haplotype based association methods applied to candidate regions. We compared the performance of the Mantel Statistic Using Haplotype Sharing and the haplotype frequency based score test with that of the Armitage trend test.

Our study is based on 1000 replication of simulated case-control data settings with 500 cases and 500 controls, respectively. One of the examined markers was set to be the disease locus with a simulated odds ratio of 3. Differential and non-differential genotyping errors were introduced following a misclassification model with varying mean error rates per locus in the range of 0.2% to 15.6%.

Results

We found that the type I error rate of all three test statistics hold the nominal significance level in the presence of nondifferential genotyping errors and low error rates. For high and differential error rates, the type I error rate of all three test statistics was inflated, even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The empirical power of all three association test statistics remained high at around 89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for high and nondifferential genotyping error rates.

Conclusion

Currently realistic genotyping error rates for candidate gene analysis (mean error rate per locus of 0.2%) pose no significant problem for the type I error rate as well as the power of all three investigated test statistics.
The UDP-glucosyltransferase multigene family in Bombyx mori
Authors: Huang Fei-Fei , Chai Chun-Li , Zhang Ze , Liu Zeng-Hu , Dai Fang-Yin , Lu Cheng , Xiang Zhong-Huai
Published: January 2009

Background

Glucosidation plays a major role in the inactivation and excretion of a great variety of both endogenous and exogenous compounds. A class of UDP-glycosyltransferases (UGTs) is involved in this process. Insect UGTs play important roles in several processes, including detoxication of substrates such as plant allelochemicals, cuticle formation, pigmentation, and olfaction. Identification and characterization of Bombyx mori UGT genes could provide valuable basic information for this important family and explain the detoxication mechanism and other processes in insects.

Results

Taking advantage of the newly assembled genome sequence, we performed a genome-wide analysis of the candidate UGT family in the silkworm, B. mori. Based on UGT signature and their similarity to UGT homologs from other organisms, we identified 42 putative silkworm UGT genes. Most of them are clustered on the silkworm chromosomes, with two major clusters on chromosomes 7 and 28, respectively. The phylogenetic analysis of these identified 42 UGT protein sequences revealed five major groups. A comparison of the silkworm UGTs with homologs from other sequenced insect genomes indicated that some UGTs are silkworm-specific genes. The expression patterns of these candidate genes were investigated with known expressed sequence tags (ESTs), microarray data, and RT-PCR method. In total, 36 genes were expressed in tissues examined and showed different patterns of expression profile, indicating that these UGT genes might have different functions.

Conclusion

B. mori possesses a largest insect UGT gene family characterized to date, including 42 genes. Phylogenetic analysis, genomic organization and expression profiles provide an overview for the silkworm UGTs and facilitate their functional studies in future.
Comparative transcriptomic analysis of Porphyromonas gingivalisbiofilm and planktonic cells
Authors: Lo Alvin W , Seers Christine A , Boyce John D , Dashper Stuart G , Slakeski Nada , Lissel J Patricia , Reynolds Eric C
Published: January 2009

Background

Porphyromonas gingivalis in subgingival dental plaque, as part of a mature biofilm, has been strongly implicated in the onset and progression of chronic periodontitis. In this study using DNA microarray we compared the global gene expression of a P. gingivalis biofilm with that of its planktonic counterpart grown in the same continuous culture.

Results

Approximately 18% (377 genes, at 1.5 fold or more, P-value < 0.01) of the P. gingivalis genome was differentially expressed when the bacterium was grown as a biofilm. Genes that were down-regulated in biofilm cells, relative to planktonic cells, included those involved in cell envelope biogenesis, DNA replication, energy production and biosynthesis of cofactors, prosthetic groups and carriers. A number of genes encoding transport and binding proteins were up-regulated in P. gingivalis biofilm cells. Several genes predicted to encode proteins involved in signal transduction and transcriptional regulation were differentially regulated and may be important in the regulation of biofilm growth.

Conclusion

This study analyzing global gene expression provides insight into the adaptive response of P. gingivalis to biofilm growth, in particular showing a down regulation of genes involved in growth and metabolic activity.
A compact phage display human scFv library for selection of antibodies to a wide variety of antigens
Authors: Pansri Potjamas , Jaruseranee Nanthnit , Rangnoi Kuntalee , Kristensen Peter , Yamabhai Montarop
Published: January 2009

Background

Phage display technology is a powerful new tool for making antibodies outside the immune system, thus avoiding the use of experimental animals. In the early days, it was postulated that this technique would eventually replace hybridoma technology and animal immunisations. However, since this technology emerged more than 20 years ago, there have only been a handful reports on the construction and application of phage display antibody libraries world-wide.

Results

Here we report the simplest and highly efficient method for the construction of a highly useful human single chain variable fragment (scFv) library. The least number of oligonucleotide primers, electroporations and ligation reactions were used to generate a library of 1.5 × 108individual clones, without generation of sub-libraries. All possible combinations of heavy and light chains, among all immunoglobulin isotypes, were included by using a mixture of primers and overlapping extension PCR. The key difference from other similar libraries was the highest diversity of variable gene repertoires, which was derived from 140 non-immunized human donors. A wide variety of antigens were successfully used to affinity select specific binders. These included pure recombinant proteins, a hapten and complex antigens such as viral coat proteins, crude snake venom and cancer cell surface antigens. In particular, we were able to use standard bio-panning method to isolate antibody that can bind to soluble Aflatoxin B1, when using BSA-conjugated toxin as a target, as demonstrated by inhibition ELISA.

Conclusion

These results suggested that by using an optimized protocol and very high repertoire diversity, a compact and efficient phage antibody library can be generated. This advanced method could be adopted by any molecular biology laboratory to generate both naïve or immunized libraries for particular targets as well as for high-throughput applications.
Analysing the origin of long-range interactions in proteins using lattice models
Authors: Noivirt-Brik Orly , Unger Ron , Horovitz Amnon
Published: January 2009

Background

Long-range communication is very common in proteins but the physical basis of this phenomenon remains unclear. In order to gain insight into this problem, we decided to explore whether long-range interactions exist in lattice models of proteins. Lattice models of proteins have proven to capture some of the basic properties of real proteins and, thus, can be used for elucidating general principles of protein stability and folding.

Results

Using a computational version of double-mutant cycle analysis, we show that long-range interactions emerge in lattice models even though they are not an input feature of them. The coupling energy of both short- and long-range pairwise interactions is found to become more positive (destabilizing) in a linear fashion with increasing 'contact-frequency', an entropic term that corresponds to the fraction of states in the conformational ensemble of the sequence in which the pair of residues is in contact. A mathematical derivation of the linear dependence of the coupling energy on 'contact-frequency' is provided.

Conclusion

Our work shows how 'contact-frequency' should be taken into account in attempts to stabilize proteins by introducing (or stabilizing) contacts in the native state and/or through 'negative design' of non-native contacts.
Thrombin related peptide TP508 promoted fracture repair in a mouse high energy fracture model
Authors: Hanratty Brain M , Ryaby James T , Pan Xiao-Hua , Li Gang
Published: January 2009

Background

Thrombin related peptide (TP508) is a 23 amino-acid synthetic peptide that represents a portion of the receptor-binding domain of thrombin molecule. Previous studies have shown that TP508 can accelerate musculoskeletal tissue repair including fracture healing.

Objectives

The aim of this study was to investigate the effect of TP508 on fracture healing in a murine fracture model representing high energy fracture situation.

Methods

Eighty CD 1 mice underwent controlled quadriceps muscle crush and open transverse mid diaphyseal femoral fracture that was then fixed with an external fixator. Animals were randomised into four groups to receive an intra-operative dose of either 100 μg TP508 into the fracture gap; 100 μg TP508 into the surrounding damaged muscle tissues; 10 μg TP508 into the fracture gap, or control equal amount of saline into the fracture gap. Radiographic assessment was performed weekly for 5 weeks; histological analysis was at 3 and 5 weeks post fracture and biomechanical testing of the fractured bone was performed at 5 weeks post fracture.

Results

Mechanical testing data showed that the fracture stiffness was significantly higher in the group receiving 100 μg TP508 into the fracture gap than other groups. Histological and radiographic analysis revealed a trend of increase in bone formation in the 100 μg TP508 injected into the fracture gap group compared to the saline control group. It was noted that the scar tissues was significantly less in Group II comparing with the saline control group and there was increased blood vessel formation in the crushed muscles and fracture gap areas in the groups receiving TP508 comparing to the saline control group.

Conclusion

The results from this study demonstrated the use of thrombin related peptide TP508 in the situation of a high energy fracture can promote fracture healing and reduce the potential complications such as muscle fibrosis and fracture delayed or non-union.
Novel polymorphism of interleukin-18 associated with greater inflammation after cardiac surgery
Authors: Shaw David M , Sutherland Ainsley M , Russell James A , Lichtenstein Samuel V , Walley Keith R
Published: January 2009

Introduction

Interleukin (IL)-18 is a key modulator of the cytokine response that leads to organ dysfunction and prolonged intensive care unit (ICU) stay after cardiopulmonary bypass surgery. We hypothesised that variation in the pro-inflammatory gene IL-18 is associated with adverse clinical outcome because of a more intense inflammatory response.

Methods

Haplotypes of the IL-18 gene were inferred from genotypes of 23 Coriell Registry subjects. Four haplotype tag single nucleotide polymorphisms (-607 C/A, -137 G/C, 8148 C/T and 9545 T/G) identified four major haplotype clades. These polymorphisms were genotyped in 658 Caucasian patients undergoing cardiopulmonary bypass surgery. Clinical phenotypes were collected by retrospective chart review.

Results

Patients homozygous for the T allele of the 9545 T/G polymorphism had an increased occurrence of prolonged ICU stay (6.8% for TT genotype versus 2.7% for GG or GT genotype; p = 0.015). Patients homozygous for the T allele also had increased occurrence of low systemic vascular resistance index (62%) compared with the GG and GT genotypes (53%; p = 0.045). Patients homozygous for the T allele had increased serum IL-18 concentrations 24 hours post-surgery (p = 0.018), increased pro-inflammatory tumour necrosis factor alpha concentrations (p = 0.014) and decreased anti-inflammatory serum IL-10 concentrations (p = 0.018) 24 hours post-surgery.

Conclusions

The TT genotype of the IL-18 9545 T/G polymorphism is associated with an increased occurrence of prolonged ICU stay post-surgery and greater post-surgical inflammation. These results may be explained by greater serum IL-18, leading to greater pro-versus anti-inflammatory cytokine expression.
Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction
Authors: Steventon Ben , Araya Claudio , Linker Claudia , Kuriyama Sei , Mayor Roberto
Published: January 2009

The neural crest is induced by a combination of secreted signals. Although previous models of neural crest induction have proposed a step-wise activation of these signals, the actual spatial and temporal requirement has not been analysed. Through analysing the role of the mesoderm we show for the first time that specification of neural crest requires two temporally and chemically different steps: first, an induction at the gastrula stage dependent on signals arising from the dorsolateral mesoderm; and second, a maintenance step at the neurula stage dependent on signals from tissues adjacent to the neural crest. By performing tissue recombination experiments and using specific inhibitors of different inductive signals, we show that the first inductive step requires Wnt activation and BMP inhibition, whereas the later maintenance step requires activation of both pathways. This change in BMP necessity from BMP inhibition at gastrula to BMP activation at neurula stages is further supported by the dynamic expression of BMP4 and its antagonists, and is confirmed by direct measurements of BMP activity in the neural crest cells. The differential requirements of BMP activity allow us to propose an explanation for apparently discrepant results between chick and frog experiments. The demonstration that Wnt signals are required for neural crest induction by mesoderm solves an additional long-standing controversy. Finally,our results emphasise the importance of considering the order of exposure to signals during an inductive event.
Intermuscular tendons are essential for the development of vertebrate stomach
Authors: Le Guen Ludovic , Notarnicola Cécile , de Santa Barbara Pascal
Published: January 2009

Gastrointestinal motility is ensured by the correct coordination of the enteric nervous system and the visceral smooth muscle cells (SMCs), and defective development of SMCs results in gut malformations and intestinal obstructions. In order to identify the molecular mechanisms that control the differentiation of the visceral mesenchyme into SMCs in the vertebrate stomach, we developed microarrays to analyze the gene expression profiles of undifferentiated and differentiated avian stomachs. We identify Scleraxis, a basic-helix-loop-helix transcription factor, as a new marker of stomach mesenchyme and find that expression of Scleraxisdefines the presence of two tendons closely associated to the two visceral smooth muscles. Using targeted gene misexpression, we show that FGF signaling is sufficient to induce Scleraxis expression and to establish two tendon domains adjacent to the smooth muscle structures. We also demonstrate that the tendon organization is perturbed by altering Scleraxisexpression or function. Moreover, using primary cells derived from stomach mesenchyme, we find that undifferentiated stomach mesenchyme can give rise to both SMCs and tendon cells. These data show that upon FGF activation, selected stomach mesenchymal cells are primed to express Scleraxis and to differentiate into tendon cells. Our findings identify a new anatomical and functional domain in the vertebrate stomach that we characterize as being two intermuscular tendons closely associated with the visceral SMC structures. We also demonstrate that the coordinated development of both tendon and smooth muscle domains is essential for the correct morphogenesis of the stomach.
Impact of normalization on miRNA microarray expression profiling
Authors: Pradervand Sylvain , Weber Johann , Thomas Jérôme , Bueno Manuel , Wirapati Pratyaksha , Lefort Karine , Dotto G. Paolo , Harshman Keith
Published: January 2009

Profiling miRNA levels in cells with miRNA microarrays is becoming a widely used technique. Although normalization methods for mRNA gene expression arrays are well established, miRNA array normalization has so far not been investigated in detail. In this study we investigate the impact of normalization on data generated with the Agilent miRNA array platform. We have developed a method to select nonchanging miRNAs (invariants) and use them to compute linear regression normalization coefficients or variance stabilizing normalization (VSN) parameters. We compared the invariants normalization to normalization by scaling, quantile, and VSN with default parameters as well as to no normalization using samples with strong differential expression of miRNAs (heart–brain comparison) and samples where only a few miRNAs are affected (by p53 overexpression in squamous carcinoma cells versus control). All normalization methods performed better than no normalization. Normalization procedures based on the set of invariants and quantile were the most robust over all experimental conditions tested. Our method of invariant selection and normalization is not limited to Agilent miRNA arrays and can be applied to other data sets including those from one color miRNA microarray platforms, focused gene expression arrays, and gene expression analysis using quantitative PCR.
What Fraction of Stock Option Grants to Top Executives Have Been Backdated or Manipulated?
Authors: Heron Randall A. , Lie Erik
Published: January 2009

We estimate that 13.6% of all option grants to top executives during the period 1996–2005 were backdated or otherwise manipulated. Our study primarily focuses on grants that were unscheduled and at-the-money, of which we estimate that 18.9% were manipulated. The fraction is 23.0% before the new two-day filing requirement took effect on August 29, 2002, and 10.0% afterward. For the minority of grants that are not filed within the required two-day window, the fraction of manipulated grants remains as high as 19.9%. We further find a higher frequency of manipulation among tech firms, small firms, and firms with high stock price volatility. In addition, firms that use smaller (non-big-five) auditing firms are more likely to file their grants late. Finally, at the firm level, we estimate that 29.2% of firms manipulated grants to top executives at some point between 1996 and 2005.
R&D in the Pharmaceutical Industry: A World of Small Innovations
Authors: Ganuza Juan-José , Llobet Gerard , Domínguez Beatriz
Published: January 2009

It is commonly argued that in recent years pharmaceutical companies have targeted their research and development (R&D) at small improvements of existing compounds instead of riskier drastic innovations. In this paper, we show that the bias in the pharmaceutical industry toward small innovations might be driven by the low sensitivity of the demand. In particular, small innovations get a proportionally larger reward because pharmaceutical firms target them at the inelastic segments of the demand. As a consequence, firms find it relatively more profitable to invest in small innovations. We also study the effect on R&D incentives of marketing strategies and regulatory instruments aimed at controlling pharmaceutical expenditure.
Trading as Entertainment?
Authors: Dorn Daniel , Sengmueller Paul
Published: January 2009

Among 1,000 German brokerage clients for whom both survey responses and actual trading records are available, investors who report enjoying investing or gambling turn over their portfolio at twice the rate of their peers. Including entertainment attributes as additional explanatory variables in cross-sectional regressions of portfolio turnover on objective investor attributes more than doubles the fraction of the total variation of portfolio turnover that can be explained. The results are robust to controlling for gender and proxies for overconfidence constructed from survey responses. Nonpecuniary benefits of trading thus appear to offer a straightforward explanation of the “excessive trading puzzle.”
Alliance Structure and the Scope of Knowledge Transfer: Evidence from U.S.-Japan Agreements
Authors: Oxley Joanne , Wada Tetsuo
Published: January 2009

Prior research suggests that equity joint ventures (JVs) are particularly effective vehicles for accessing complex technology. Different schools of thought have emphasized different reasons why joint ventures might support greater knowledge transfer than “bare” license agreements: incentive alignment, organizational embeddedness, and enhanced administrative controls. We probe and refine these theoretical perspectives, drawing out implications of the different theories for the extent and speed of alliance-related knowledge transfer, as well as for knowledge “leakage” in areas not directly related to alliance activities. Using a proprietary data set derived from regulatory filings with the Japanese government we test these implications in our empirical analysis of U.S.-Japan agreements. The picture that emerges from the analysis is one of particularly intense but contained knowledge transfer in equity joint ventures, relative to bare license agreements: knowledge transfers directly related to the alliance activity are enhanced in the JV, and the speed of integration into the Japanese firm's subsequent innovations also increases. In marked contrast, leakage of unrelated technology is significantly reduced. These findings suggest that administrative structures that reduce technology leakage are a key feature of the equity joint venture, a result that is inconsistent with a “pure” knowledge-based perspective on alliances.
Information Exchange in Group Decision Making: The Hidden Profile Problem Reconsidered
Authors: Lightle John P. , Kagel John H. , Arkes Hal R.
Published: January 2009

Group decision making provides a mechanism for channeling individual members' knowledge into productive organizational outcomes. However, in hidden profile experiments in which group members have common information favoring an inferior choice, with private information favoring a superior choice, groups typically choose an inferior alternative. We report a hidden profile experiment where we induce homogenous preferences over choice characteristics and provide financial incentives so that the common purpose assumptions of the model hold more completely than in past experiments.

Nevertheless, groups continue to choose an inferior alternative most of the time. These failures primarily result from mistakes in recalling information. Mistakes in recalling common information (which favors an inferior candidate) are typically corrected, whereas mistakes in recalling the private information needed to uncover the hidden profile cannot be corrected. Therefore, the dismal performance of groups in pooling the information needed to identify the superior option primarily result from the structure of the problem rather than deficiencies in how groups share and process information. The discussions necessary to resolve mistakes in recalling common information also help to explain the often noted fact that groups spend a disproportionate amount of time discussing common information.
Surgical training: what has changed?
Authors: Mickute Zita
Published: January 2009

This may or may not surprise you but the surgical training pathway has changed – and significantly so. Perhaps you have heard surgeons grumbling behind their theatre masks about the gloomy outlook for the surgical profession; they may have even gone as far as to warn you to steer clear of surgery altogether. The pessimistic whingeing about the state of the NHS seems almost a mandatory preoccupation for most doctors, and almost binds them in a common cause of sufferance.
Audio-Visual Archives at the College
Authors: Pappas Lydia
Published: January 2009

You may not know about the audio-visual material held in the archives at the College: it has not previously been sorted or listed in any way. As a specialist film archivist I looked through the collection, assessed its condition for future accessibility and advised on conservation and preservation issues. The small collections of films seem to have come mostly from the personal collections of fellows of the College, who donated films in their lifetime or after their deaths.
Colledge Fund Boosts ENT Surgery
Authors: Narula Tony
Published: January 2009

The Lionel Colledge Memorial Travelling Fellowship was established by Miss Cecilia Colledge in 1979 in memory of her father Lionel Colledge, the distinguished surgeon, to promote and advance the study and knowledge of surgery: in particular, head and neck surgery.
Winning Hearts and Minds
Authors: Towell Elaine
Published: January 2009

Around 3,000 people in the UK received an organ transplant in the past year; 1,000 others weren't so lucky and died while on the waiting list. More than 8,000 are still waiting. Many people who need a transplant do not even reach the waiting list. According to the government's organ donation taskforce report, need is at minimum 50% more than is currently available. There is little doubt that urgent solutions need to be found to help these thousands of patients, many of whom are desperately ill.
Isolation and evaluation of some physicochemical properties of Parkia biglobosa starch
Authors: Ihegwuagu Nnemeka Edith , Omojola Moses Olubayo , Emeje Martins Ochobiojo , Kunle Olobayo Olufunsho
Published: January 2009

This paper describes the isolation and physicochemical characterization of starch obtained from Parkia biglobosa (African locust bean). The results show that the properties of starch from this source compare favorably with those of corn starch BP, and suggest that it could be useful as a stabilizer in baking powders and as an emulsifier in the food industry.
Neem chemicals disturb the behavioral response of Liriomyza huidobrensis to conspecific-induced potato volatiles
Authors: Facknath Sunita , Stewart-Jones Alex , Wright Denis J.
Published: January 2009

Plants respond to insect attack by releasing complex blends of phytogenic volatile organic compounds. Selection of a host plant by the leafminer Liriomyza huidobrensis is influenced by such volatile chemicals (allelochemicals) released by the host plant. In the case of potato plants, the allelochemicals identified are mainly volatile monoterpenes and sesquiterpenes. A potato plant that is already infested by other individuals of the same species of insects shows a quantitative difference in emission of such allelochemicals, which in turn plays an important role in the host preference behavior exhibited by the insect. Olfactometer tests (using whole, potted potato plants as well as excised leaves) showed that L. huidobrensis adults were more attracted to already infested plants for feeding and egg-laying than they were to uninfested plants, demonstrating that volatile chemicals from infested plants function as kairomones in this insect-plant relationship. However, when the potato plants were grown in soil treated with aqueous neem extract, this relationship was disturbed and the insects did not exhibit any consistent feeding or egg-laying response to neem-treated infested or uninfested host plants. This indicates that neem compounds disturb secondary metabolite production in the potato plant, which in turn has an influence on insects that use volatile plant allelochemicals as cues for host identification and location. Results of this study can help in a better understanding of neem as an environment-friendly botanical pesticide for use in sustainable agriculture.
Chemical basis for resistance in sweetpotato Ipomoea batatas to the sweetpotato weevil Cylas puncticollis
Authors: Stevenson Philip C. , Muyinza Harriet , Hall David R. , Porter Elaine A. , Farman Dudley I. , Talwana Herbert , Mwanga Robert O. M.
Published: January 2009

The aim of this work was to determine the basis of resistance in a sub-Saharan sweetpotato variety, New Kawogo, to the African sweetpotato weevil Cylas puncticollis. This insect feeds on the roots, reducing quality and yield, and is the most important production constraint of sweetpotato in Africa. Laboratory bioassays were designed to determine how the performance of weevils differed on susceptible and resistant roots. Subsequently, liquid chromatography-mass spectrometry (LC-MS) analysis of the root surface and root latex identified quantitative and qualitative differences in the chemical profiles with higher levels of octadecyl and hexadecyl esters of hydroxycinnamic acids reported in the resistant variety. The compounds were synthesized to confirm their identity and incorporated into artificial diets for bioassays on C. puncticollis. High levels of mortality and developmental inhibition were recorded for larvae feeding on treated diets, and the effect was dose-dependent. Thus, in contrast to previous work on resistant African sweetpotato cultivars, resistance in New Kawogo is not only active, but is quantifiable and manageable for breeding. Work is underway to determine what effect these compounds have on the weevils at a molecular level. The inheritance of the root latex esters will be studied in new crosses and mapped in new populations using quantitative trait loci (QTLs) that are currently being developed.
Nanometer-scale dynamics of charges generated by radiations in condensed matter
Authors: Saeki Akinori , Tagawa Seiichi
Published: January 2009

The dynamics of short-lived charges generated by pulsed radiations such as electron beam (EB) and photon was investigated to elucidate their reactivity, electronic properties, and spatial behavior on a nanometer scale. Chemical reactions of radical cations (hole) and anions (electron) in condensed matter (organic liquids, polymers, and conjugated materials) occupy an important place in postoptical nanolithography and organic electric devices. The spatiotemporal evolution of charges during geminate ion recombination was measured by a highly improved picosecond (ps) pulse radiolysis and incorporated into a Monte Carlo simulation to clarify the key role of the charges in the formation of latent image roughness of chemically amplified resists (CARs). The dynamics and alternating-current (AC) mobility of transient charge carriers in conjugated materials such as polymer and organic crystals were studied by the combination of microwave conductivity and optical spectroscopies, revealing the potential plausibility for high-performance electric devices. Anisotropy measurement and methodology to resolve the sum of mobility into hole and electron components without electrodes have also been demonstrated.
Massive Visceral Pentastomiasis Caused by Porocephalus crotali in a Dog
Authors: Brookins M. D. , Wellehan J. F. X. , Roberts J. F. , Allison K. , Curran S. S. , Childress A. L. , Greiner E. C.
Published: January 2009

The testes of a 5-year-old, male, crossbred Schnauzer dog were the indicator organs for detection of massive pentastomiasis. Necropsy revealed numerous additional encysted parasites within the mesenteric lymph nodes, omentum, liver, sub-serosa of the small and large intestines, mesentery, and lungs. The nymphs had a pseudosegmented body, containing large eosinophilic glands and a chitinous cuticle with characteristic pores. Their hook configuration was consistent with that of Porocephalus. A pentastomid-specific 18S rRNA polymerase chain reaction (PCR) was designed and used to amplify template for sequencing. The sequence of the PCR product was 99.7% homologous with the reference sequence for P. crotali. This pentastomid parasite has been reported in North American snakes of genera Crotalus and Agkistrodon. Mammals are intermediate hosts, and snakes are the definitive hosts. Porocephalus crotali has been reported in dogs only once, and molecular methods have not been used previously to identify the species in clinical pentastomiasis.
Gas Bubbles in Seals, Dolphins, and Porpoises Entangled and Drowned at Depth in Gillnets
Authors: Moore M. J. , Bogomolni A. L. , Dennison S. E. , Early G. , Garner M. M. , Hayward B. A. , Lentell B. J. , Rotstein D. S.
Published: January 2009

Gas bubbles were found in 15 of 23 gillnet-drowned bycaught harp ( Pagophilus groenlandicus), harbor ( Phoca vitulina) and gray ( Halichoerus grypus) seals, common ( Delphinus delphis) and white-sided ( Lagenorhyncus acutus) dolphins, and harbor porpoises ( Phocaena phocaena) but in only 1 of 41 stranded marine mammals. Cases with minimal scavenging and bloating were chilled as practical and necropsied within 24 to 72 hours of collection. Bubbles were commonly visible grossly and histologically in bycaught cases. Affected tissues included lung, liver, heart, brain, skeletal muscle, gonad, lymph nodes, blood, intestine, pancreas, spleen, and eye. Computed tomography performed on 4 animals also identified gas bubbles in various tissues. Mean ± SD net lead line depths (m) were 92 ± 44 and ascent rates (ms-1) 0.3 ± 0.2 for affected animals and 76 ± 33 and 0.2 ± 0.1, respectively, for unaffected animals. The relatively good carcass condition of these cases, comparable to 2 stranded cases that showed no gas formation on computed tomography (even after 3 days of refrigeration in one case), along with the histologic absence of bacteria and autolytic changes, indicate that peri- or postmortem phase change of supersaturated blood and tissues is most likely. Studies have suggested that under some circumstances, diving mammals are routinely supersaturated and that these mammals presumably manage gas exchange and decompression anatomically and behaviorally. This study provides a unique illustration of such supersaturated tissues. We suggest that greater attention be paid to the radiology and pathology of bycatch mortality as a possible model to better understand gas bubble disease in marine mammals.
Immunohistochemical Expression of p63 and ΔNp63 in Mixed Tumors of Canine Mammary Glands and Its Relation with p53 Expression
Authors: Bertagnolli A. C. , Cassali G. D. , Genelhu M. C. L. S. , Costa F. A. , Oliveira J. F. C. , Gonçalves P. B. D.
Published: January 2009

The immunohistochemical expression of p63, ΔNp63, and p53 was studied in mixed tumors of canine mammary glands (13 benign mixed tumors and 19 carcinomas arising from benign mixed tumors) to determine the role of p63 and its isoform ΔNp63 in the development of mixed tumors, as well as to assess its relation with p53. P63 was expressed in myoepithelial cells of all benign mixed tumors and in 18 of 19 carcinomas in mixed tumors. The p63-negative carcinoma in mixed tumors was invasive, and a loss of p63 was detected in the other malignant tumors showing a discontinuous p63-stained myoepithelial layer. ΔNp63 was expressed in all benign mixed tumors but only in p63-positive carcinomas in mixed tumors. Despite its positive correlation with p63 expression in carcinomas in mixed tumors ( r = 0.8323, P < .00001), ΔNp63 expression showed a decrease in benign tumors. Positivity for p53 was detected in 2 of 13 and 1 of 19 benign mixed tumors and carcinomas in mixed tumors, respectively. There was no correlation between p63 or ΔNp63 and p53 expression. Our data support the notion that the decrease of p63 expression, in particular of its isoform ΔNp63, seems to be an important factor in the development of carcinomas in mixed tumors.
Case Reports: Disseminated Chlorellosis in a Dog
Authors: Quigley R. R. , Knowles K. E. , Johnson G. C.
Published: January 2009

An adult dog with ataxia and a lingual mass, previously diagnosed as protothecosis, was euthanized. At the postmortem examination, the lingual mass, regions of the lungs and hilar lymph nodes, liver, mesenteric and sublumbar lymph nodes, and spinal meninges had pronounced green discoloration. Histologically, pyogranulomatous inflammation and algal organisms were found in the tongue, spinal meninges, hilar and mesenteric lymph nodes, liver, and lung. The algae had cell walls positive for periodic acid-Schiff and cytoplasmic granules. Ultrastructurally, the algae had a well-defined cell wall, stacks of grana and thylakoid membrane, and dense bodies, typical of starch granules. The organisms were identified as Chlorella, a green alga, based on the results of histochemistical and electron microscopic examination. To the author's knowledge this is the first report of disseminated Chlorella infection and the first report in a companion animal.
Epithelioid Cells in Mediastinal Lymph Nodes of Cattle without Cancer
Authors: Komine M. , Kawasako K. , Okamoto M. , Matsuda K. , Hirayama K. , Takehana K. , Koiwa M. , Kurosawa T. , Taniyama H.
Published: January 2009

Epithelioid cells are found in lymph nodes in cases of metastatic carcinoma; however, epithelioid cells with benign features have also been discovered incidentally in lymph nodes. Epithelioid cells were observed in mediastinal lymph nodes of cattle without cancer during routine diagnostic necropsy. To explain this finding, the authors evaluated the prevalence and histopathologic, immunohistochemical, and ultrastructural features retrospectively using mediastinal lymph nodes from 110 cattle and found that 66 of the lymph nodes contained epithelioid cells. In all 66 nodes, most of the epithelioid cells were individual or aggregated in nodal sinuses; in 21 nodes, some epithelioid cells formed tubular structures. The individual and aggregated epithelioid cells were mostly considered to be mesothelial in origin by immunohistochemical and ultrastructural examination; presumably, they entered the lymph nodes via lymphatic vessels, because they were found in afferent lymphatic vessels and nodal sinuses. Although the presence of epithelioid cells in lymph nodes prompts suspicion of metastatic carcinoma, the epithelioid cells in these bovine lymph nodes did not disrupt nodal architecture, lacked atypia or mitotic figures, and did not invade nodal parenchyma.