bluuebunny/crossref_metadata_2025 huggingface dataset:
Daptomycin as supportive treatment option in patients developing mediastinitis after open cardiac surgery
Authors: Weis Florian , Heyn Jens , Hinske Christian L , Vogt Ferdinand , Weis Marion , Kur Felix , Hagl Christian , Beiras-Fernandez Andres
Published: September 2012

Background

Mediastinitis is a severe complication after cardiac surgery. While improvement of prophylaxis and of medical and surgical therapy has reduced its incidence, the treatment of mediastinitis continues to be a challenging problem. Within this study, we report the successful use of daptomycin as supportive therapy in patients developing mediastinitis after open cardiac surgery.

Methods

The records of 21 consecutive patients who developed mediastinitis after cardiac surgery were retrospectively reviewed. After diagnosis, all patients received surgical debridement and antibiotic therapy with daptomycin. All patients were followed up to death or discharge.

Results

Clinical improvement after combined surgical and antibiotic therapy with daptomycin was found in 90.5% of the patients. The median time until clinical improvement occurred was 5 [4/6] days. Daptomycin was well-tolerated and no major adverse events during therapy were observed observed.

Conclusions

This study provides new and helpful information regarding the beneficial use of daptomycin as supportive treatment option in patients developing mediastinitis after cardiac surgery.
Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks
Authors: Martin Florian , Thomson Ty M , Sewer Alain , Drubin David A , Mathis Carole , Weisensee Dirk , Pratt Dexter , Hoeng Julia , Peitsch Manuel C
Published: September 2012

Background

High-throughput measurement technologies produce data sets that have the potential to elucidate the biological impact of disease, drug treatment, and environmental agents on humans. The scientific community faces an ongoing challenge in the analysis of these rich data sources to more accurately characterize biological processes that have been perturbed at the mechanistic level. Here, a new approach is built on previous methodologies in which high-throughput data was interpreted using prior biological knowledge of cause and effect relationships. These relationships are structured into network models that describe specific biological processes, such as inflammatory signaling or cell cycle progression. This enables quantitative assessment of network perturbation in response to a given stimulus.

Results

Four complementary methods were devised to quantify treatment-induced activity changes in processes described by network models. In addition, companion statistics were developed to qualify significance and specificity of the results. This approach is called Network Perturbation Amplitude (NPA) scoring because the amplitudes of treatment-induced perturbations are computed for biological network models. The NPA methods were tested on two transcriptomic data sets: normal human bronchial epithelial (NHBE) cells treated with the pro-inflammatory signaling mediator TNFα, and HCT116 colon cancer cells treated with the CDK cell cycle inhibitor R547. Each data set was scored against network models representing different aspects of inflammatory signaling and cell cycle progression, and these scores were compared with independent measures of pathway activity in NHBE cells to verify the approach. The NPA scoring method successfully quantified the amplitude of TNFα-induced perturbation for each network model when compared against NF-κB nuclear localization and cell number. In addition, the degree and specificity to which CDK-inhibition affected cell cycle and inflammatory signaling were meaningfully determined.

Conclusions

The NPA scoring method leverages high-throughput measurements and a priori literature-derived knowledge in the form of network models to characterize the activity change for a broad collection of biological processes at high-resolution. Applications of this framework include comparative assessment of the biological impact caused by environmental factors, toxic substances, or drug treatments.
Analysis of T-DNA alleles of flavonoid biosynthesis genes in Arabidopsis ecotype Columbia
Authors: Bowerman Peter A , Ramirez Melissa V , Price Michelle B , Helm Richard F , Winkel Brenda SJ
Published: September 2012

Background

The flavonoid pathway is a long-standing and important tool for plant genetics, biochemistry, and molecular biology. Numerous flavonoid mutants have been identified in Arabidopsis over the past several decades in a variety of ecotypes. Here we present an analysis of Arabidopsis lines of ecotype Columbia carrying T-DNA insertions in genes encoding enzymes of the central flavonoid pathway. We also provide a comprehensive summary of various mutant alleles for these structural genes that have been described in the literature to date in a wide variety of ecotypes.

Findings

The confirmed knockout lines present easily-scorable phenotypes due to altered pigmentation of the seed coat (or testa). Knockouts for seven alleles for six flavonoid biosynthetic genes were confirmed by PCR and characterized by UPLC for altered flavonol content.

Conclusion

Seven mutant lines for six genes of the central flavonoid pathway were characterized in ecotype, Columbia. These lines represent a useful resource for integrating biochemical and physiological studies with genomic, transcriptomic, and proteomic data, much of which has been, and continues to be, generated in the Columbia background.
BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation
Authors: Schläfli Anna M , Torbett Bruce E , Fey Martin F , Tschan Mario P
Published: September 2012

Background

Inhibitors of apoptosis (IAPs) were intensively investigated in the context of cancer where they promote tumor growth and chemoresistence. Overexpression of the IAP BIRC6 is associated with unfavorable clinical features and negatively impacts relapse-free survival in childhood acute myeloid leukemia (AML). Currently, BIRC6 levels in adult primary AML have not been compared to the expression in normal myeloid cells. Thus, we compared for the first time BIRC6 levels in adult primary AML patient samples to normal myeloid cells and studied its regulation and function during neutrophil differentiation.

Findings

We found significantly lower BIRC6 levels in particular AML subtypes as compared to granulocytes from healthy donors. The lowest BIRC6 expression was found in CD34+ progenitor cells. Moreover, BIRC6 expression significantly increased during neutrophil differentiation of AML cell lines and knocking down BIRC6 in NB4 acute promyelocytic leukemia (APL) cells significantly impaired neutrophil differentiation, but not cell viability.

Conclusion

Together, we found an association of low BIRC6 levels with an immature myeloid phenotype and describe a function for BIRC6 in neutrophil differentiation of APL cells.
Moving beyond GK–12
Authors: Ufnar J. A. , Kuner Susan , Shepherd V. L.
Published: September 2012

The National Science Foundation GK–12 program has made more than 300 awards to universities, supported thousands of graduate student trainees, and impacted thousands of K–12 students and teachers. The goals of the current study were to determine the number of sustained GK–12 programs that follow the original GK–12 structure of placing graduate students into classrooms and to propose models for universities with current funding or universities interested in starting a program. Results from surveys, literature reviews, and Internet searches of programs funded between 1999 and 2008 indicated that 19 of 188 funded sites had sustained in-classroom programs. Three distinct models emerged from an analysis of these programs: a full-stipend model, in which graduate fellows worked with partner teachers in a K–12 classroom for 2 d/wk; a supplemental stipend model in which fellows worked with teachers for 1 d/wk; and a service-learning model, in which in-classroom activity was integrated into university academic coursework. Based on these results, potential models for sustainability and replication are suggested, including establishment of formal collaborations between sustained GK–12 programs and universities interested in starting in-classroom programs; development of a new Teaching Experience for Fellows program; and integration of supplemental fellow stipends into grant broader-impact sections.
An Educational Intervention Designed to Increase Women's Leadership Self-Efficacy
Authors: Isaac Carol , Kaatz Anna , Lee Barbara , Carnes Molly
Published: September 2012

Women are sparsely represented in leadership in academic science, technology, engineering, mathematics, and medicine (STEMM). Cultural stereotypes about men, women, and leaders influence the attitudes, judgments, and decisions that others make about women and the choices women make for themselves. Multilevel interventions are needed to counteract the impact of these pervasive and easily activated stereotypes, which conspire in multiple ways to constrain women's entry, persistence, and advancement in academic STEMM. We describe an individual-level educational intervention. Using the transtheoretical model of behavioral change as a framework, we assessed the success of a semester course on increasing women's leadership self-efficacy for the first three cohorts of course participants (n = 30). Pre/post questionnaires showed gains in leadership self-efficacy, personal mastery, and self-esteem, and decreases in perceived constraints. Qualitative text analysis of weekly journals indicated increasing leadership self-efficacy as course participants applied course information and integrated strategies to mitigate the impact of societal stereotypes into their own leadership practices. Follow-up queries of the first two cohorts supported the enduring value of course participation. We conclude that providing strategies to recognize and mitigate the impact of gender stereotypes is effective in increasing leadership self-efficacy in women at early stages of academic STEMM careers.
Common Origins of Diverse Misconceptions: Cognitive Principles and the Development of Biology Thinking
Authors: Coley John D. , Tanner Kimberly D.
Published: September 2012

Many ideas in the biological sciences seem especially difficult to understand, learn, and teach successfully. Our goal in this feature is to explore how these difficulties may stem not from the complexity or opacity of the concepts themselves, but from the fact that they may clash with informal, intuitive, and deeply held ways of understanding the world that have been studied for decades by psychologists. We give a brief overview of the field of developmental cognitive psychology. Then, in each of the following sections, we present a number of common challenges faced by students in the biological sciences. These may be in the form of misconceptions, biases, or simply concepts that are difficult to learn and teach, and they occur at all levels of biological analysis (molecular, cellular, organismal, population, and ecosystem). We then introduce the notion of a cognitive construal and discuss specific examples of how these cognitive principles may explain what makes some misconceptions so alluring and some biological concepts so challenging for undergraduates. We will argue that seemingly unrelated misconceptions may have common origins in a single underlying cognitive construal. These ideas emerge from our own ongoing cross-disciplinary conversation, and we think that expanding this conversation to include other biological scientists and educators, as well as other cognitive scientists, could have significant utility in improving biology teaching and learning.
The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth
Authors: Kannan Madhuvanthi , Lee Shih-Ju , Schwedhelm-Domeyer Nicola , Stegmüller Judith
Published: September 2012

Axon growth is an essential event during brain development and is extremely limited due to extrinsic and intrinsic inhibition in the adult brain. The E3 ubiquitin ligase Cdh1-anaphase promoting complex (APC) has emerged as an important intrinsic suppressor of axon growth. In this study, we identify in rodents the E3 ligase Smurf1 as a novel substrate of Cdh1-APC and that Cdh1 targets Smurf1 for degradation in a destruction box-dependent manner. We find that Smurf1 acts downstream of Cdh1-APC in axon growth and that the turnover of RhoA by Smurf1 is important in this process. In addition, we demonstrate that acute knockdown of Smurf1 in vivo in the developing cerebellar cortex results in impaired axonal growth and migration. Finally, we show that a stabilized form of Smurf1 overrides the inhibition of axon growth by myelin. Taken together, we uncovered a Cdh1-APC/Smurf1/RhoA pathway that mediates axonal growth suppression in the developing mammalian brain.
Tup/Islet1 integrates time and position to specify muscle identity in Drosophila
Authors: Boukhatmi Hadi , Frendo Jean Louis , Enriquez Jonathan , Crozatier Michèle , Dubois Laurence , Vincent Alain
Published: September 2012

The LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component of cardiogenesis in Drosophila and vertebrates. We report here an additional major role for Drosophila Tup in specifying dorsal muscles. Tup is expressed in the four dorsal muscle progenitors (PCs) and tup-null embryos display a severely disorganized dorsal musculature, including a transformation of the dorsal DA2 into dorsolateral DA3 muscle. This transformation is reciprocal to the DA3 to DA2 transformation observed in collier (col) mutants. The DA2 PC, which gives rise to the DA2 muscle and to an adult muscle precursor, is selected from a cluster of myoblasts transiently expressing both Tinman (Tin) and Col. The activation of tup by Tin in the DA2 PC is required to repress col transcription and establish DA2 identity. The transient, partial overlap between Tin and Col expression provides a window of opportunity to distinguish between DA2 and DA3 muscle identities. The function of Tup in the DA2 PC illustrates how single cell precision can be reached in cell specification when temporal dynamics are combined with positional information. The contributions of Tin, Tup and Col to patterning Drosophila dorsal muscles bring novel parallels with chordate pharyngeal muscle development.
Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity
Authors: Struhl Gary , Casal José , Lawrence Peter A.
Published: September 2012

Many epithelia have a common planar cell polarity (PCP), as exemplified by the consistent orientation of hairs on mammalian skin and insect cuticle. One conserved system of PCP depends on Starry night (Stan, also called Flamingo), an atypical cadherin that forms homodimeric bridges between adjacent cells. Stan acts together with other transmembrane proteins, most notably Frizzled (Fz) and Van Gogh (Vang, also called Strabismus). Here, using an in vivo assay for function, we show that the quintessential core of the Stan system is an asymmetric intercellular bridge between Stan in one cell and Stan acting together with Fz in its neighbour: such bridges are necessary and sufficient to polarise hairs in both cells, even in the absence of Vang. By contrast, Vang cannot polarise cells in the absence of Fz; instead, it appears to help Stan in each cell form effective bridges with Stan plus Fz in its neighbours. Finally, we show that cells containing Stan but lacking both Fz and Vang can be polarised to make hairs that point away from abutting cells that express Fz. We deduce that each cell has a mechanism to estimate and compare the numbers of asymmetric bridges, made between Stan and Stan plus Fz, that link it with its neighbouring cells. We propose that cells normally use this mechanism to read the local slope of tissue-wide gradients of Fz activity, so that all cells come to point in the same direction.
NO/beta-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation
Authors: Ding Huawen , Keller Kevin C. , Martinez Ivann K. C. , Geransar Rose M. , zur Nieden Kai O. , Nishikawa Sandra G. , Rancourt Derrick E. , zur Nieden Nicole I.
Published: September 2012

Nitric oxide (NO) has been shown to play a crucial role in bone formation in vivo. We sought to determine the temporal effect of NO on murine embryonic stem cells (ESCs) under culture conditions that promote osteogenesis. Expression profiles of NO pathway members and osteoblast-specific markers were analyzed using appropriate assays. We found that NO was supportive of osteogenesis specifically during an early (day 3–5) phase of in vitro development. Furthermore, ESCs stably overexpressing the inducible NO synthase showed accelerated and enhanced osteogenesis in vitro and in bone explant cultures. To determine the role of NO in early lineage commitment, a time in ESC differentiation equivalent to primitive streak formation in vivo, ESCs were transfected with a T-brachyury-GFP reporter. Expression levels of T-brachyury and one of its upstream regulators beta-catenin, the major effector in the canonical Wnt pathway, were responsive to NO levels in differentiating primitive streak-like cells. Our results indicate that NO may be involved in early differentiation through regulation of beta-catenin and T-brachyury, controlling the specification of primitive streak-like cells, which may continue through differentiation to later become osteoblasts.
The SH2-domain-containing inositol 5-phosphatase (SHIP) limits neutrophil motility and wound recruitment in zebrafish
Authors: Lam Pui-ying , Yoo Sa Kan , Green Julie M. , Huttenlocher Anna
Published: September 2012

Neutrophil recruitment to sites of injury or infection is essential for host defense, but it needs to be tightly regulated to prevent tissue damage. Phosphoinositide 3-kinase (PI3K), that generates the phosphoinositide PI(3,4,5)P3, is necessary for neutrophil motility in vivo, however, the role of SH2-domain–containing 5-inositol phosphatase (SHIP) enzymes, that hydrolyzes PI(3,4,5)P3 to PI(3,4)P2, is not well understood. Here we show that SHIP phosphatases limit neutrophil motility in live zebrafish. Using real-time imaging of bioprobes specific for PI(3,4,5)P3 and PI(3,4)P2 in neutrophils, we found that PI(3,4,5)P3 and PI(3,4)P2 accumulate at the leading edge while PI(3,4)P2 also localizes to the trailing edge of migrating neutrophils in vivo. Depletion of SHIP phosphatases using morpholinos led to increased neutrophil 3D motility and neutrophil infiltration into wounds. The increase in neutrophil wound recruitment in SHIP morphants was rescued by treatment with low dose PI3Kγ inhibitor, suggesting that SHIP limits neutrophil motility by modulating PI3K signaling. Moreover, overexpression of the SHIP phosphatase domain in neutrophils impaired neutrophil 3D migration. Taken together, our findings suggest that SHIP phosphatases control neutrophil inflammation by limiting neutrophil motility in vivo.
Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET
Authors: Kleylein-Sohn Julia , Pöllinger Bernadette , Ohmer Michaela , Nigg Erich A. , Hemmings Brian A. , Wartmann Markus
Published: September 2012

Centrosomes represent the major microtubule organizing centres (MTOCs) of animal somatic cells and orchestrate bipolar spindle assembly during mitotic cell division. In meiotic cells, the kinesin HSET compensates for the lack of centrosomes by focusing acentrosomal MTOCs into two spindle poles. By clustering multiple centrosomes into two spindle poles, HSET also mediates bipolar mitosis in cancer cells with supernumerary centrosomes. However, although dispensable in non-transformed human cells, the role of HSET in cancer cells with two centrosomes has remained elusive. In this study, we demonstrate that HSET is required for proper spindle assembly, stable pole-focusing and survival of cancer cells irrespective of normal or supernumerary centrosome number. Strikingly, we detected pronounced acentrosomal MTOC structures in untreated mitotic cancer cells. While in most cancer cells these acentrosomal MTOCs were rapidly incorporated into the assembling bipolar spindle, some cells eventually established bipolar spindles with acentrosomal poles and free centrosomes. These observations demonstrate that acentrosomal MTOCs were functional and that both centrosomal and acentrosomal mechanisms were required for bipolar spindle organization. Our study shows that HSET is critical for clustering acentrosomal and centrosomal MTOCs during spindle formation in human cancer cells with two bona fide centrosomes. Furthermore, we show that in checkpoint-defective cancer cells, acentrosomal spindle formation and HSET-dependence are partially mediated by a constitutive activation of the DNA damage response. In summary, we propose that acentrosomal spindle assembly mechanisms are hyperactive in cancer cells and promote HSET, a key driver of acentrosomal spindle organization, as an attractive target for cancer therapy.
Division of the intermediate compartment at the onset of mitosis provides a mechanism for Golgi inheritance
Authors: Marie Michaël , Dale Hege A. , Kouprina Nina , Saraste Jaakko
Published: September 2012

As mammalian cells prepare for mitosis the Golgi ribbon is first unlinked into its constituent stacks and then transformed into spindle-associated, pleiomorphic membrane clusters in a process that remains enigmatic. Also, whether Golgi inheritance involves the incorporation of Golgi enzymes into a pool of coat protein I (COPI) vesicles, or their COPI-independent transfer to the endoplasmic reticulum (ER) remains unclear. Based on the observation that the intermediate compartment (IC) at the ER-Golgi boundary is connected to the centrosome, we examined its mitotic fate and possible role in Golgi breakdown. The use of multiple imaging techniques and markers revealed that the IC elements persist during the M phase, maintain their compositional and structural properties and remain associated with the mitotic spindle, forming circular arrays at the spindle poles. At G2/M transition, the movement of the pericentrosomal domain of the IC (pcIC) to the cell center and its expansion coincide with the unlinking of the Golgi ribbon. At prophase, coupled to centrosome separation, the pcIC divides together with recycling endosomes, providing novel landmarks for mitotic entry. We provide evidence that the permanent IC elements function as way stations during the COPI-dependent dispersal of Golgi components at prometa- and metaphase, indicating that they correspond to the previously described Golgi clusters. In addition, they continue to communicate with the vesicular “Golgi haze” and thus are likely to provide templates for Golgi reassembly. These results implicate the IC in mitotic Golgi inheritance, resulting in a model that integrates key features of the two previously proposed pathways.
Vimentin and the K-Ras-induced actin-binding protein control inositol-(1,4,5)-trisphosphate receptor redistribution during MDCK cell differentiation.
Authors: Dingli Florent , Parys Jan B. , Loew Damarys , Saule Simon , Mery Laurence
Published: September 2012

Inositol-(1,4,5)-triphosphate receptors (InsP3Rs) are ligand-gated Ca2+ channels that control Ca2+ release from intracellular stores and play a central role in a wide range of cellular responses. In most epithelial cells, InsP3Rs are not uniformly distributed within the endoplasmic reticulum (ER) membrane with the consequence that agonist stimulation results in compartmentalized Ca2+ signals. Despite these observations, little is known about the mechanisms that regulate the intracellular localization of InsP3Rs. Here, we report that exogenously expressed InsP3R1-GFP and endogenous InsP3R3 interact with the K-Ras-induced actin-binding protein (KRAP) in both differentiated and undifferentiated Madin-Darby canine kidney (MDCK) cells. KRAP mediates InsP3R clustering in confluent MDCK cells and functions as an adapter, linking InsP3Rs to vimentin intermediate filaments (IF). Upon epithelial differentiation, KRAP and vimentin are both required for InsP3R accumulation at the periphery of MDCK cells. Finally, KRAP associates with vimentin in chicken B lymphocytes and with keratins in a breast cancer cell line devoid of vimentin. Collectively, our data suggest that IF in conjunction with KRAP may govern the localization of InsP3Rs in a large number of cell types (including epithelial cells) and in various physiological or pathological contexts.
Karyopherin-independent spontaneous transport of amphiphilic proteins through the nuclear pore
Authors: Kumeta Masahiro , Yamaguchi Hideki , Yoshimura Shige H. , Takeyasu Kunio
Published: September 2012

Highly selective nucleocytoplasmic molecular transport is critical to eukaryotic cells, which is illustrated by the size-filtering diffusion and karyopherin-mediated passage mechanisms. However, a considerable number of large proteins without nuclear localization signals are localized to the nucleus. Here, we provide evidence for spontaneous migration of large proteins in a karyopherin-independent manner. Time-lapse observation of nuclear transport assay revealed that several large molecules spontaneously and independently pass through the NPC. The amphiphilic motifs were shown to be sufficient to overcome the selectivity barrier of the NPC. Furthermore, we report that the characteristic amphiphilic property of these proteins enables altered local conformation in hydrophobic solutions, so that elevated surface hydrophobicity facilitates passage through the nuclear pore. The molecular dynamics simulation revealed the conformational change of the amphiphilic structure that exposes the hydrophobic amino acid residues to the outer surface in hydrophobic solution. These results contribute to the understanding of both nucleocytoplasmic molecular sorting and the nature of the permeability barrier.
Proline Recognition through C–H···π Interaction within Crystal Structures of Dl-Proline–Calix[4]pyrogallolarene Molecular Complexes
Authors: Fujisawa Ikuhide , Harima Noriko , Takagi Kenji , Hiraoka Shuichi , Shionoya Mitsuhiko , Murayama Kazutaka , Itsuno Shinichi , Kato Ryo , Aoki Katsuyuki
Published: September 2012

X-ray analyses of two calix[4]pyrogallolarene complexes with Dl-proline have shown that they form host–guest-like 1:1 complexes in which the pyrrolidine ring of proline is incorporated into the bowl-shaped cavity of calix[4]pyrogallolarene through C–H···π interactions.
Phase-Transfer-Catalyzed Synthesis of Butyl 4-Methoxyphenylacetate and Its Simultaneous Hydrolysis by Potassium Hydroxide in Oil–Water Biphasic System
Authors: Wang Maw-Ling , Vivekanand Perumberkandigai Adikesavan , Yu Ming-Chan
Published: September 2012

Herein, we report for the first time simultaneous hydrolysis during the phase-transfer-catalyzed synthesis of butyl 4-methoxyphenylacetate using potassium hydroxide in biphasic medium. Effect of operating parameters on the reaction is presented. The yield of ester increases with the increase in the agitation speed up to 500 rpm and above that the conversion is not influenced by the agitation speed. At higher concentration of base, the hydrolysis product is more favored. Lower temperature and larger volume of water favors the esterfication. At high concentration of catalyst, sharp decrease in the yield of the ester is noticed. In the presence of highly polar solvents, the conversion of ester increases initially and then there was a sharp decrease. Rational explanations to account for the phenomena based on the results are made.
Fabrication of WO3-Based Composite Films and Improvement Its Photochromic Properties by Copper Doping
Authors: Miyazaki Hidetoshi , Inada Masaya , Suzuki Hisao , Ota Toshitaka
Published: September 2012

Tungsten-based photochromic composite films were fabricated using peroxopolytungstic acid methanol solution and transparent urethane resin. The composite films showed photochromic properties by UV–vis light irradiation. Photochromic properties of the films were improved with addition of the other elements of Cu. The reaction rate constants k of the films with the Cu/W ratio of 0, 0.1, 0.5, and 1 were 2.68 × 10−2, 3.33 × 10−2, 2.57 × 10−2, and 1.51 × 10−2 min−1, and the constant of the film with Cu/W of 0.1 was larger than that of the nondoped film.
γ-Methylidene-δ-valerolactones: New Reagents for Palladium-Catalyzed Intermolecular Cyclization Reactions
Authors: Shintani Ryo
Published: September 2012

New reagents, γ-methylidene-δ-valerolactones, have been developed for the synthesis of various cyclic organic compounds under palladium catalysis, and a full overview of the use of these reagents have been described. These reagents primarily act as precursors for 1,4-zwitterionic species through oxidative addition to palladium(0) followed by decarboxylation, thereby introducing a four-carbon unit in a newly formed cyclic framework. In some cases, they can also be used for the synthesis of ring-expanded lactones as well as spirocyclopropane derivatives, depending on the substituents and/or the reaction conditions. Some mechanistic aspects of the newly developed catalysis have also been discussed.
Carvedilol reduces the severity of atherosclerosis in apolipoprotein E-deficient mice via reducing superoxide production
Authors: Shimada Kana , Hirano Emi , Kimura Takeshi , Fujita Masatoshi , Kishimoto Chiharu
Published: September 2012

It has been shown that oxidative stress may play an important role in the development of atherosclerosis, and carvedilol has the capacity of reducing oxidative stress. Accordingly, we assessed the hypothesis that carvedilol may reduce the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice in addition to its hemodynamic effects. Atherosclerosis was induced in apoE-deficient mice fed a high-fat diet containing 0.3% cholesterol. Mice were orally treated with propranolol (30 mg/kg/day), metoprolol (75 mg/kg/day) and carvedilol (10 mg/kg/day) over eight weeks (each group n = 7−9). Fatty streak plaque developed in apoE-deficient mice, and was suppressed in mice treated with all three drugs. The accumulation of macrophages and expression of CD4+ and CD8+ cells in the lesions were decreased by the treatment of the drugs, of which carvedilol was the most effective. In addition, carvedilol reduced superoxide production in aortic walls detected by ethidium staining. There were no significant changes in blood pressure among the study groups. The heart rates in the treated groups were decreased by 4%–12% compared with the control group, with carvedilol yielding the highest suppression of heart rate. The β-blocker treatment did not significantly modify the serum lipid profiles. Carvedilol may suppress atherosclerosis via reducing superoxide production, in addition to the hemodynamic modifications in this animal model.
Chronically inadequate sleep results in abnormal bone formation and abnormal bone marrow in rats
Authors: Everson Carol A , Folley Anne E , Toth Jeffrey M
Published: September 2012

Insufficient sleep over long durations of the lifespan is believed to adversely affect proper development and healthful aging, although how this might become manifested is unknown. In the present study, rats were repeatedly sleep-restricted during 72 days to permit maladaptations to evolve, thereby permitting study. Densitometric and histomorphometric analyses were performed on harvested bone. In sleep-restricted rats, bone lined by osteoid was reduced 45-fold and osteoid thickness was decreased, compared with controls. This corresponded to a decrease in osteoblast number and activity. The percentage of bone lined by osteoclasts did not differ from that of controls. Plasma concentrations of an osteoclast marker (TRACP 5b) were increased in sleep-restricted rats, indicating increased bone resorption. The low amount of new bone formation without a reduction in bone resorption is diagnostic of osteopenia. Bone mineral density was decreased in femurs from sleep-restricted rats compared with controls, indicating osteoporosis. Red marrow in sleep-restricted rats contained only 37% of the fat and more than twice the number of megakaryocytes compared with that of the control rats. These findings in marrow suggest changed plasticity and increased hematopoiesis. Plasma concentrations of insulin-like growth factor-1, a known, major mediator of osteoblast differentiation and the proliferation of progenitor cells, was decreased by 30% in sleep-restricted rats. Taken together, these findings suggest that chronically inadequate sleep affects bone metabolism and bone marrow composition in ways that have implications for development, aging, bone healing and repair, and blood cell differentiation.
New perspectives on strengthening science journalism in developing countries: Approach and first results of the ‘SjCOOP’ mentoring project
Authors: Mbarga Gervais , Lublinski Jan , Fleury Jean-Marc
Published: September 2012

Many different educational and training sessions focusing on science journalism have been offered to journalists in Africa in the past decades. However, there is still insufficient quality reporting on health, environment, technology and science. We propose a new, flexible and needs-oriented
concept for the professionalization of journalists. Its main elements are peer-to-peer mentoring and building of professional associations using online tools for training, networking and journalistic research, a combination of approaches and an in situ delivery. It has been put into practice
through the Science Journalism Cooperation (SjCOOP) project in Africa and in the Middle East.
Patterns of news media consumption among young people in Libya
Authors: Elareshi Mokhtar , Gunter Barrie
Published: September 2012

The purpose of the study was to investigate patterns of major local and non-local news suppliers operating across a range of media – broadcast and print – and relationships between Libyan undergraduate students’ consumption of different news media platforms. A survey
was administered to a sample of 400 students at Al-Fateh University using a stratified random sampling approach with sampling strata set by demographic groups. The new TV news services played an important role in attracting young Libyans with information they desire. The spread of new news
media sources (TV, radio and print) in Libya has created a new type of news product that transcends national boundaries. The findings indicated that there were distinct news consumption-related population sub-groups defined in part by news platform (TV versus radio versus print) and in part
by type of news supplier (local versus international TV news operations). These findings indicated the emergence of new niche markets in news in Libya.
Community radio regulation and its challenges in Ghana
Authors: Ufuoma Akpojivi
Published: September 2012

The emergence of community radio in Ghana’s media sphere has changed the political economy of communications in Ghana. The participatory platform of the medium has led to citizens’ empowerment and facilitated the political, economic and social development of this new democracy.
Marginalized communities are now able to question policies. The views expressed during these participatory programmes like live phone-in have helped to promote accountability and transparency within government circles and the corporate world. However, concerns have been raised over the serious
allegations and mischievous remarks made on community radio stations and how they can be regulated. This article shall argue that the complex and intricate nature of the regulatory mechanism and the conceptualization of community radio have made it difficult for the regulatory body, National
Media Commission (NMC) to regulate the community radio. Seeing that Ghana is a multi-ethnic state, her democracy may be endangered if the content from community radio stations which could heat up the polity is not regulated.
The printed press’s representations of the 2005–2007chikungunya epidemic in Réunion:Political polemics and (post)colonial disease
Authors: Jansen Karine Aasgaard
Published: September 2012

From 2005 to 2007 the French overseas department and Indian Ocean island of Réunion experienced for the first time ever an epidemic of chikungunya. Chikungunya is a vector-spread disease by mosquitoes that leads to painful rheumatic symptoms, and infected approximately one-third
of the island’s population of approximately 802,000 inhabitants.

This article is based upon a discourse analysis of text and images of 111 articles on chikungunya in Réunion’s two main newspapers. During the epidemic the Réunionese printed press functioned as a
provider of information, and an instigator of political polemics. The newspapers’ criticism responded to ‘orientalist’ representations of chikungunya within national press – and officialdom, but also reflected local perceptions of neglect and abandonment by the French
nation state. While taking issue with other studies of press coverage of the outbreak, however, I argue that the polemics illustrate historical Réunionese geopolitical identifications with France, instead of postcolonial opposition.
Film Review
Authors: Carelli Fabiana
Published: September 2012

A ILHA DOS ESPÍRITOS/THE ISLAND OF THE SPIRITS, LICÍNIO AZEVEDO (2010) Mozambique: Ébano Multimedia

This article is a critical review of the documentary film A ilha dos espíritos/The Island of the Spirits (2010), by the Brazilian-Mozambican film-maker
Licínio Azevedo.
SCREEN WRITING CONFERENCE,BRUSSELS, SEPTEMBER2011,CONFERENCE REPORT
Authors: Pallant Chris
Published: September 2012

‘Beyond Boundaries: Screenwriting Across Media’, The Fourth Research Network Conference, Université Libre de Bruxelles, Brussels, 8–10 September 2011
‘European soft money’: Eurimages and the Nordic experience
Authors: Aas Nils Klevjer
Published: September 2012

The Council of Europe’s fund for the co-production of cinematographic works, Eurimages, has since its inception in 1989 provided nearly half a billion euros towards the funding of European films. Several films originating in the Nordic countries have been the recipients of this
supra-national funding. Drawing on his experience as a national representative to the Board of Management of Eurimages over the last dozen years, the author attempts – with a particular emphasis on the last five years – to identify the motives of Nordic film producers and film-makers
that have successfully applied for support from the fund, and to correlate their strategies with the aims and operating procedures of Eurimages.
‘Listen to that gramophone’ – Part-talkie production at AB Svensk Filmindustri
Authors: Natzén Christopher
Published: September 2012

The film ‘Konstgjorda Svensson’/‘Artificial Svensson’ (Edgren, 1929) has recently been restored with its original soundtrack by the Swedish Film Institute. The restoration shows how film production companies in Sweden tried to connect the new medium of sound
film to other sound technologies like radio and gramophone. Using the case study of early sound film production at the company Svensk Filmindustri,this article examines how gramophonic recordings of music facilitated the assimilation of sound and dialogue within the diegesis, making for a
smooth conversion to sound. A distinguishing feature during the first sound years was that dialogue and sound created a heightened media-sensitivity. Music that adheres more to the demands of the narrative than to the image per se facilitated this process, masking the technical construction
of the film medium.
Talking heads, imagined communities: Steam of Life and the affective politics of intimate documentary
Authors: Koivunen Anu
Published: September 2012

In a cycle of new Finnish documentaries, male confessional talk abounds. Beyond the successful Miesten vuoro/Steam of Life (Joonas Berghäll and Mika Hotakainen, 2010), several recent documentaries propose to give voice to ordinary Finnish men who reveal their true feelings to other
men. In this article, Steam of Life is discussed as a case of intimate documentary, drawing on both the political aesthetics of feminist documentary and the transnational, late modern rhetoric of confession.Employing the complex affective legacies of the talking head, the film engages in performative
politics of gender and nation. It mobilizes a discourse on the nation as a male network, and importantly evokes nation as a sentimental community, a community based on feeling. In so doing, however, it de-individualizes the speaking subjects. While purporting to give voice to the male protagonists,
the film makes them anonymous soldiers of the nation, thereby denying them their own voices.
First wave on film: Ray Gange, Rude Boy and The Great Rock ‘n’ Roll Swindle
Authors: Kiszely Philip
Published: September 2012

This article will explore The Great Rock ‘n’ Roll Swindle (Julien Temple) and Rude Boy (Jack Hazan and David Mingay) (both 1980), the two highest-profile films to emerge from and treat cinematically Britain’s first wave of punk rock. Featuring the Sex Pistols and the
Clash, respectively, each film attempts to tell its tale in an oppositional manner. Both do so, however, from within dominant industrial and discursive modes of practice. Taking as its keynote Stacy Thompson’s dialectical approach to punk cinema, the article considers these seemingly
irreconcilable positions by tracing implied cinematic traditions and questioning the role of the protagonist. It goes on to centre its attention on Rude Boy specifically, analysing the position of the fan as a key figure within the narrative. An in-depth interview with Ray Gange, the novice
actor/fan at the heart of the film, concludes the piece.
Optimal dividend-payout in random discrete time
Authors: Albrecher Hansjörg , Bäuerle Nicole , Thonhauser Stefan
Published: September 2012

Assume that the surplus process of an insurance company is described by a general Lévy process and that possible dividend pay-outs to shareholders are restricted to random discrete times which are determined by an independent renewal process. Under this setting we show that the optimal dividend pay-out policy is a band-policy. If the renewal process is a Poisson process, it is further shown that for Cramér–Lundberg risk processes with exponential claim sizes and its diffusion limit the optimal policy collapses to a barrier-policy. Finally, a numerical example is given for which the optimal bands can be calculated explicitly. The random observation procedure studied in this paper also allows for an interpretation in terms of a random walk model with a certain type of random discounting.
A Bayesian sequential testing problem of three hypotheses for Brownian motion
Authors: Zhitlukhin Mikhail V. , Shiryaev Albert
Published: September 2012

We consider a sequential testing problem of three hypotheses that the unknown drift of a Brownian motion takes one of three values. We show that this problem can be solved by a reduction to an optimal stopping problem for local times of the observable process. For the case of “large” periods of observation, we derive integral equations for the optimal stopping boundaries and study their limit behaviour. Other cases will be considered in subsequent papers.

The work can be regarded as a further step in the sequential testing problem of two hypotheses for Brownian motion, solved more than 30 years ago (see [4]).
On the exact distribution of the estimated expected utility portfolio weights: Theory and applications
Authors: Bodnar Taras , Schmid Wolfgang
Published: September 2012

In this paper we consider the portfolio weights obtained by maximizing the expected quadratic utility function. The unknown parameters of the return process, the mean vector and the covariance matrix, are estimated by their sample counterparts. Assuming independent and multivariate normally distributed returns we derive the conditional density of the estimated weights given the mean vector of the asset returns and the unconditional density of the estimated weights. Moreover, the characteristic function of the estimated weights is calculated and it is used to determine the moments of higher order. Furthermore a test for the mean-variance efficiency is presented.
Central limit theorem for the integrated squared error of the empirical second-order product density and goodness-of-fit tests for stationary point processes
Authors: Heinrich Lothar , Klein Stella
Published: September 2012

Spatial point processes are mathematical models for irregular or random point patterns in the d-dimensional space, where usually d = 2 or d = 3 in applications. The second-order product density and its isotropic analogue, the pair correlation function, are important tools for analyzing stationary point processes. In the present work we derive central limit theorems for the integrated squared error (ISE) of the empirical second-order product density and for the ISE of the empirical pair correlation function when the observation window expands unboundedly. The proof techniques are based on higher-order cumulant measures and the Brillinger-mixing property of the underlying point processes. The obtained Gaussian limits are used to construct asymptotic goodness-of-fit tests for checking point process hypotheses even in the non-Poissonian case.
Risk margin for a non-life insurance run-off
Authors: Wüthrich Mario V. , Embrechts Paul , Tsanakas Andreas
Published: September 2012

For solvency purposes insurance companies need to calculate so-called best-estimate reserves for outstanding loss liability cash flows and a corresponding risk margin for non-hedgeable insurance-technical risks in these cash flows. In actuarial practice, the calculation of the risk margin is often not based on a sound model but various simplified methods are used. In the present paper we properly define these notions and we introduce insurance-technical probability distortions. We describe how the latter can be used to calculate a risk margin for non-life insurance run-off liabilities in a mathematically consistent way.
A note on optimal consumption and investment in a geometric Ornstein–Uhlenbeck market
Authors: Ziehaus Christina
Published: September 2012

We consider the problem of maximizing the utility of consumption and terminal wealth in a geometric Ornstein–Uhlenbeck market. We calculate the optimal consumption and wealth processes for power, logarithmic and exponential utility as well as their behavior depending e.g. on subjective discounting or the time horizon. We also use a specific example to show the identity of the solutions calculated by the primal and the dual method.
Adaptive estimation for an inverse regression model with unknown operator
Authors: Marteau Clement , Loubes Jean-Michel
Published: September 2012

We are interested in the problem of estimating a regression function φ observed with a correlated noise Y = φ(X)+U. Contrary to the usual regression model, U is not centered conditionaly on X but rather on an observed variable W. Hence this model turns to be a difficult inverse problem where the corresponding operator is unknown since it is related to the joint distribution of (X,W). We focus on the case where the eigenvalues of the corresponding operator are observed with small perturbations and, using a well adapted spectral cut-off estimation procedure, we build a data driven estimates and derive an oracle inequality.
Some multivariate risk indicators: Minimization by using a Kiefer–Wolfowitz approach to the mirror stochastic algorithm
Authors: Cénac P. , Maume-Deschamps V. , Prieur C.
Published: September 2012

We consider some risk indicators of vectorial risk processes. These indicators take into account the dependencies between business lines as well as some temporal dependencies. By using stochastic algorithms, we may estimate the minimum of these risk indicators, under a fixed total capital constraint. This minimization may apply to capital reserve allocation.