bluuebunny/crossref_metadata_2025 huggingface dataset:
Organizational learnability and innovability
Authors: Mi Dahlgaard‐Park Su , Dahlgaard Jens J.
Published: July 2010

Purpose

The purpose of this paper is to present and discuss the development of a system for assessing and improving technology development and innovations. The system components comprise: a framework or model for assessing, measuring, diagnosing and improving innovation enablers and results; a simple methodology for data collection, data analysis and prioritizing improvement areas; and an index for measuring the performance level of innovation, learning and lean (ILL) and the potentials to increase that level. To improve innovation, which is the most complex challenge for today's organizations, there is a need for such a system.

Design/methodology/approach

The first two system components have been developed and tested during a period of ten to 15 years in several industrial companies as well as service organizations. The last component has recently been developed to satisfy a need of all types of organizations.

Findings

With the last development, the ILL index, the three components comprise a system for assessing and improving innovations. As with any other system, the system components are interrelated.

Originality/value

This paper presents a system for assessing and improving innovations. As with any other system the system‐components are interrelated. To improve innovation, which is the most complex challenge for today's organizations, there is a need for such a system. It is hoped that the suggested system will be used within all types of organizations and all types of innovations – products, processes and services.
A simplified lean method to capture customer voice
Authors: Teehan Robert , Tucker Walter
Published: July 2010

Purpose

This paper tested a model to collect the voice of the customer to improve service delivery in call centers using the concept of failure demand. Customer responses are quantified for improvement in service delivery. There are many academic studies reporting effective and validated research methodologies to measure service quality. However, these methods are complex and unwieldy. The purpose of this paper is to adapt the lean service concept of working from the customer's viewpoint – to measure, then improve customer satisfaction, and thereby reduce costs.

Design/methodology/approach

A checklist of best practices for call centers was developed from the literature and multiple iterations used to develop a three part call evaluation system to include value demand, failure demand, not able to determine, and value demand as stated by the customer.

Findings

The findings indicated that the value/failure demand measurement system was useful and many failure demand occurrences occurred.

Research limitations/implications

This paper is limited to service providers in call centers and their managers. Call center operators logged customer perceptions so it has the potential to lack objectivity.

Practical implications

Service providers need simple tools to assess operations, improve quality, and efficiency. This paper will assist in the development of an easy‐to‐use and generic tool for the continuous improvement of services.

Originality/value

The paper is one of very few studies that use the actual customer voice to measure failure demand and call centers can apply this process.
Service quality in higher education – a review and research agenda
Authors: Sultan Parves , Yin Wong Ho
Published: July 2010

Purpose

The purpose of this paper is to explore the critical research issues in terms of service quality in higher education.

Design/methodology/approach

The paper critically examines a number of leading studies in satisfaction, service quality, and higher education.

Findings

The paper finds five critical research agenda in the field of service quality in higher education sector.

Research limitations/implications

The paper shows the research gaps of service quality in higher education through a review of literature. Future research should empirically address those gaps.

Practical implications

The growth of service quality literature started with commercial enterprises. Later, it is expanded in the management and marketing of higher education sector. Measuring and modeling service quality in higher education is new. The paper shows the nature and future directions of service quality research in higher education.

Originality/value

The research issues developed for this paper are relevant to antecedents, dimensions and consequences of service quality in the context of higher education.
Iranian generation Y female market segmentation
Authors: Heidarzadeh Hanzaee Kambiz , Aghasibeig Sara
Published: July 2010

Purpose

The purpose of the paper is to examine Iranian generation Y female decision making using Sproles and Kendall's consumer styles inventory as a basis for market segmentation.

Design/methodology/approach

Considering the high population of young Iranians, this research has focused on generation Y (those born after 1977) by administering a questionnaire to a non‐probability sample of female undergraduate students of Azad University, the Islamic Azad University Tehran branch.

Findings

The result showed six meaningful and distinct groups; the characteristics of each group were identified separately. These findings are useful for both domestic and international retailers and marketers seeking to effectively target young Iranian female consumers.

Originality/value

This is the first academic study focusing on generation Y female shopping behaviors that its findings are useful for both domestic and international retailers and marketers seeking to effectively target young Iranian female consumers.
Knowledge of ethics, perceived ethical problems and ethical judgments
Authors: Zakaria Maheran , Haron Hasnah , Ismail Ishak
Published: July 2010

Purpose

The paper aims to investigate: the influence of knowledge of ethics (KOE) on auditors' perceived ethical problems (PEB); the influence of PEB on ethical judgments (EJ); and the mediating impact of PEB that mediate the relationship between KOE and EJ.

Design/methodology/approach

A total of 940 questionnaires were distributed to auditors of audit firms in Malaysia and 250 auditors responded. However, only 224 questionnaires were usable. Data were analyzed using SPSS 16.0 and structural equation modeling (SEM) using AMOSS 16.0.

Findings

The results indicated that statistically significant relationships exist between KOE and PEB, PEB, and EJ. Additionally, PEB are found to mediate the relationship between KOE and EJ.

Practical implications

This paper provides important implication for audit firms to enhance sufficient knowledge of Malaysian Institute of Accountants (MIA)'s code of ethical principles among their members. Another implication is for professional bodies to design a complete and effective code of ethics, disseminate free information to members through web site and e‐notification and conduct professional development programs with the latest development on a regular basis.

Originality/value

The number of studies on the impact of PEB as a mediator that mediates the relationship between KOE and EJ is scarce. Therefore, this paper aims to fill this gap. The findings provide insights that it is imperative to emphasize the importance of KOE and PEB in enhancing auditors' EJ.
Microbial Community Changes in Response to Ethanol or Methanol Amendments for U(VI) Reduction
Authors: Vishnivetskaya Tatiana A. , Brandt Craig C. , Madden Andrew S. , Drake Meghan M. , Kostka Joel E. , Akob Denise M. , Küsel Kirsten , Palumbo Anthony V.
Published: July 2010

Microbial community responses to ethanol, methanol, and methanol plus humics amendments in relationship to U(VI) bioreduction were studied in laboratory microcosm experiments using sediments and ground water from a uranium-contaminated site in Oak Ridge, TN. The type of carbon source added, the duration of incubation, and the sampling site influenced the bacterial community structure upon incubation. Analysis of 16S rRNA gene clone libraries indicated that (i) bacterial communities found in ethanol- and methanol-amended samples with U(VI) reduction were similar due to the presence of
Deltaproteobacteria
and
Betaproteobacteria
(members of the families
Burkholderiaceae
,
Comamonadaceae
,
Oxalobacteraceae
, and
Rhodocyclaceae
); (ii) methanol-amended samples without U(VI) reduction exhibited the lowest diversity and the bacterial community contained 69.2 to 92.8% of the family
Methylophilaceae
; and (iii) the addition of humics resulted in an increase of phylogenetic diversity of
Betaproteobacteria
(
Rodoferax
,
Polaromonas
,
Janthinobacterium
,
Methylophilales
, and unclassified) and
Firmicutes
(
Desulfosporosinus
and
Clostridium
).
Effects of Ammonium and Nitrite on Growth and Competitive Fitness of Cultivated Methanotrophic Bacteria
Authors: Nyerges Györgyi , Han Suk-Kyun , Stein Lisa Y.
Published: July 2010

The effects of nitrite and ammonium on cultivated methanotrophic bacteria were investigated.
Methylomicrobium album
ATCC 33003 outcompeted
Methylocystis
sp. strain ATCC 49242 in cultures with high nitrite levels, whereas cultures with high ammonium levels allowed
Methylocystis
sp. to compete more easily.
M. album
pure cultures and cocultures consumed nitrite and produced nitrous oxide, suggesting a connection between denitrification and nitrite tolerance.
Oxalate-Degrading Activity inBifidobacterium animalissubsp.lactis: Impact of Acidic Conditions on the Transcriptional Levels of the Oxalyl Coenzyme A (CoA) Decarboxylase and Formyl-CoA Transferase Genes
Authors: Turroni Silvia , Bendazzoli Claudia , Dipalo Samuele C. F. , Candela Marco , Vitali Beatrice , Gotti Roberto , Brigidi Patrizia
Published: July 2010

Oxalic acid occurs extensively in nature and plays diverse roles, especially in pathological processes. Due to its highly oxidizing effects, hyperabsorption or abnormal synthesis of oxalate can cause serious acute disorders in mammals and can be lethal in extreme cases. Intestinal oxalate-degrading bacteria could therefore be pivotal in maintaining oxalate homeostasis and reducing the risk of kidney stone development. In this study, the oxalate-degrading activities of 14 bifidobacterial strains were measured by a capillary electrophoresis technique. Theoxcgene, encoding oxalyl-coenzyme A (CoA) decarboxylase, a key enzyme in oxalate catabolism, was isolated by probing a genomic library ofBifidobacterium animalissubsp.lactisBI07, which was one of the most active strains in the preliminary screening. The genetic and transcriptional organization ofoxcflanking regions was determined, unraveling the presence of two other independently transcribed open reading frames, potentially responsible for the ability ofB. animalissubsp.lactisto degrade oxalate. pH-controlled batch fermentations revealed that acidic conditions were a prerequisite for a significant oxalate degradation rate, which dramatically increased in cells first adapted to subinhibitory concentrations of oxalate and then exposed to pH 4.5. Oxalate-preadapted cells also showed a strong induction of the genes potentially involved in oxalate catabolism, as demonstrated by a transcriptional analysis using quantitative real-time reverse transcription-PCR. These findings provide new insights into the characterization of oxalate-degrading probiotic bacteria and may support the use ofB. animalissubsp.lactisas a promising adjunct for the prophylaxis and management of oxalate-related kidney disease.
Mechanism of ε-Poly-
l
-Lysine Production and Accumulation Revealed by Identification and Analysis of an ε-Poly-
l
-Lysine-Degrading Enzyme
Authors: Yamanaka Kazuya , Kito Naoko , Imokawa Yuuki , Maruyama Chitose , Utagawa Takashi , Hamano Yoshimitsu
Published: July 2010

ε-Poly-
l
-lysine (ε-PL) is produced by
Streptomyces albulus
NBRC14147 as a secondary metabolite and can be detected only when the fermentation broth has an acidic pH during the stationary growth phase. Since strain NBRC14147 produces ε-PL-degrading enzymes, the original chain length of the ε-PL polymer product synthesized by ε-PL synthetase (Pls) is unclear. Here, we report on the identification of the gene encoding the ε-PL-degrading enzyme (PldII), which plays a central role in ε-PL degradation in this strain. A knockout mutant of the
pldII
gene was found to produce an ε-PL of unchanged polymer chain length, demonstrating that the length is not determined by ε-PL-degrading enzymes but rather by Pls itself and that the 25 to 35
l
-lysine residues of ε-PL represent the original chain length of the polymer product synthesized by Pls
in vivo
. Transcriptional analysis of
pls
and a kinetic study of Pls further suggested that the Pls catalytic function is regulated by intracellular ATP, high levels of which are required for full enzymatic activity. Furthermore, it was found that acidic pH conditions during ε-PL fermentation, rather than the inhibition of the ε-PL-degrading enzyme, are necessary for the accumulation of intracellular ATP.
Impact of Multiple β-Ketothiolase Deletion Mutations in
Ralstonia eutropha
H16 on the Composition of 3-Mercaptopropionic Acid-Containing Copolymers
Authors: Lindenkamp Nicole , Peplinski Katja , Volodina Elena , Ehrenreich Armin , Steinbüchel Alexander
Published: July 2010

β-Ketothiolases catalyze the first step of poly(3-hydroxybutyrate) [poly(3HB)] synthesis in bacteria by condensing two molecules of acetyl coenzyme A (acetyl-CoA) to acetoacetyl-CoA. Analyses of the genome sequence of
Ralstonia eutropha
H16 revealed 15 isoenzymes of PhaA in this bacterium. In this study, we generated knockout mutants of various
phaA
homologues to investigate their role in and contributions to poly(3HB) metabolism and to suppress biosynthesis of 3HB-CoA for obtaining enhanced molar 3-mercaptopriopionate (3MP) contents in poly(3HB-
co
-3MP) copolymers when cells were grown on gluconate plus 3-mercaptopropionate or 3,3′-dithiodipropionate.
In silico
sequence analysis of PhaA homologues, transcriptome data, and other aspects recommended the homologues
phaA
,
bktB
, H16_A1713/H16_B1771, H16_A1528, H16_B1369, H16_B0381, and H16_A0170 for further analysis. Single- and multiple-deletion mutants were generated to investigate the influence of these β-ketothiolases on growth and polymer accumulation. The deletion of single genes resulted in no significant differences from the wild type regarding growth and polymer accumulation during cultivation on gluconate or gluconate plus 3MP. Deletion of
phaA
plus
bktB
(H16Δ2 mutant) resulted in approximately 30% less polymer accumulation than in the wild type. Deletion of H16_A1713/H16_B1771, H16_A1528, H16_B0381, and H16_B1369 in addition to
phaA
and
bktB
gave no differences in comparison to the H16Δ2 mutant. In contrast, deletion of H16_A0170 additionally to
phaA
and
bktB
yielded a mutant which accumulated about 30% poly(3HB) (wt/wt of the cell dry weight [CDW]). Although we were not able to suppress poly(3HB) biosynthesis completely, the copolymer compositions could be altered significantly with a lowered percentage ratio of 3HB constituents (from 85 to 52 mol%) and an increased percentage ratio of 3MP constituents (from 15 to 48 mol%), respectively. In this study, we demonstrated that PhaA, BktB, and H16_A0170 are majorly involved in poly(3HB) synthesis in
R. eutropha
H16. A fourth β-ketothiolase or a combination of several of the other β-ketothiolases contributed to a maximum of only 30% (wt/wt of CDW) of the remaining (co)polymer.
Peroxisomes Are Required for Efficient Penicillin Biosynthesis in
Penicillium chrysogenum
Authors: Meijer Wiebe H. , Gidijala Loknath , Fekken Susan , Kiel Jan A. K. W. , van den Berg Marco A. , Lascaris Romeo , Bovenberg Roel A. L. , van der Klei Ida J.
Published: July 2010

In the fungus
Penicillium chrysogenum
, penicillin (PEN) production is compartmentalized in the cytosol and in peroxisomes. Here we show that intact peroxisomes that contain the two final enzymes of PEN biosynthesis, acyl coenzyme A (CoA):6-amino penicillanic acid acyltransferase (AT) as well as the side-chain precursor activation enzyme phenylacetyl CoA ligase (PCL), are crucial for efficient PEN synthesis. Moreover, increasing PEN titers are associated with increasing peroxisome numbers. However, not all conditions that result in enhanced peroxisome numbers simultaneously stimulate PEN production. We find that conditions that lead to peroxisome proliferation but simultaneously interfere with the normal physiology of the cell may be detrimental to antibiotic production. We furthermore show that peroxisomes develop in germinating conidiospores from reticule-like structures. During subsequent hyphal growth, peroxisome proliferation occurs at the tip of the growing hyphae, after which the organelles are distributed over newly formed subapical cells. We observed that the organelle proliferation machinery requires the dynamin-like protein Dnm1.
Extraintestinal
Escherichia coli
Carrying Virulence Genes in Coastal Marine Sediments
Authors: Luna G. M. , Vignaroli C. , Rinaldi C. , Pusceddu A. , Nicoletti L. , Gabellini M. , Danovaro R. , Biavasco F.
Published: July 2010

Despite the recognized potential of long-term survival or even growth of fecal indicators bacteria (FIB) in marine sediments, this compartment is largely ignored by health protection authorities. We conducted a large-scale study over approximately 50 km of the Marche coasts (Adriatic Sea) at depths ranging from 2 to 5 m. Total and fecal coliforms (FC) were counted by culture-based methods.
Escherichia coli
was also quantified using fluorescence
in situ
hybridization targeting specific 16S rRNA sequences, which yielded significantly higher abundances than culture-based methods, suggesting the potential importance of viable but nonculturable
E. coli
cells. Fecal coliforms displayed high abundances at most sites and showed a prevalence of
E. coli.
FC isolates (
n
= 113) were identified by API 20E, additional biochemical tests, and internal transcribed spacer-PCR.
E. coli
strains, representing 96% of isolates, were then characterized for genomic relatedness and phylogenetic group (A, B1, B2, and D) of origin by randomly amplified polymorphic DNA and multiplex-PCR. The results indicated that
E. coli
displayed a wide genotypic diversity, also among isolates from the same station, and that 44 of the 109
E. coli
isolates belonged to groups B2 and D. Further characterization of B2 and D isolates for the presence of 11 virulence factor genes (
pap
,
sfa/foc
,
afa
,
eaeA
,
ibeA
,
traT
,
hlyA
,
stx
1
,
stx
2
,
aer
, and
fyuA
) showed that 90% of B2 and 65% of D isolates were positive for at least one of these. Most of the variance of both
E. coli
abundance and assemblage composition (>62%) was explained by a combination of physical-chemical and trophic variables. These findings indicate that coastal sediments could represent a potential reservoir for commensal and pathogenic
E. coli
and that
E. coli
distribution in marine coastal sediments largely depends upon the physical and trophic status of the sediment. We conclude that future sampling designs aimed at monitoring the microbiological quality of marine coastal areas should not further neglect the analysis of the sediment and that monitoring of these environments can be improved by including molecular methods as a complement of culture-based techniques.
Central Role of Manganese in Regulation of Stress Responses, Physiology, and Metabolism in
Streptococcus pneumoniae
Authors: Ogunniyi Abiodun D. , Mahdi Layla K. , Jennings Michael P. , McEwan Alastair G. , McDevitt Christopher A. , Van der Hoek Mark B. , Bagley Christopher J. , Hoffmann Peter , Gould Katherine A. , Paton James C.
Published: July 2010

The importance of Mn
2+
for pneumococcal physiology and virulence has been studied extensively. However, the specific cellular role(s) for which Mn
2+
is required are yet to be fully elucidated. Here, we analyzed the effect of Mn
2+
limitation on the transcriptome and proteome of
Streptococcus pneumoniae
D39. This was carried out by comparing a deletion mutant lacking the solute binding protein of the high-affinity Mn
2+
transporter, pneumococcal surface antigen A (PsaA), with its isogenic wild-type counterpart. We provide clear evidence for the Mn
2+
-dependent regulation of the expression of oxidative-stress-response enzymes SpxB and Mn
2+
-SodA and virulence-associated genes
pcpA
and
prtA
. We also demonstrate the upregulation of at least one oxidative- and nitrosative-stress-response gene cluster, comprising
adhC
,
nmlR
, and
czcD
, in response to Mn
2+
stress. A significant increase in 6-phosphogluconate dehydrogenase activity in the
psaA
mutant grown under Mn
2+
-replete conditions and upregulation of an oligopeptide ABC permease (AppDCBA) were also observed. Together, the results of transcriptomic and proteomic analyses provided evidence for Mn
2+
having a central role in activating or stimulating enzymes involved in central carbon and general metabolism. Our results also highlight the importance of high-affinity Mn
2+
transport by PsaA in pneumococcal competence, physiology, and metabolism and elucidate mechanisms underlying the response to Mn
2+
stress.
Analysis of the Role of the Type III Effector Inventory ofPseudomonas syringaepv. phaseolicola 1448a in Interaction with the Plant
Authors: Zumaquero Adela , Macho Alberto P. , Rufián José S. , Beuzón Carmen R.
Published: July 2010

InPseudomonas syringae, the type III secretion system (T3SS) is essential for disease in compatible hosts and for eliciting the hypersensitive response in incompatible hosts.P. syringaepathovars secrete a variable number of type III effectors that form their secretomes. The secretome ofPseudomonas syringaepv. phaseolicola 1448a (Pph1448a) currently includes 22 experimentally validated effectors, one HrpL-regulated candidate for which translocation results have been inconsistent, two translocated candidates for whichin plantaexpression has not been established, one bioinformatically identified candidate, and six candidates that have been experimentally discarded. We analyzed the translocation and/or expression of these and other candidates to complete thePph1448a effector inventory, bringing this inventory to 27 bona fide effectors, including a new one that does not belong to any of the previously described effector families. We developed a simple process for rapidly making single and double knockout mutants and apply it to the generation of an effector mutant collection that includes single knockouts for the majority of thePph1448a effector inventory. We also generated two double mutant strains containing effectors with potentially redundant functions and analyzed the virulence of the single and double mutant strains as well as strains expressing each of the effectors from a plasmid. We demonstrate that AvrB4-1 and AvrB4-2, as well as HopW1-1 and HopW1-2, are fully redundant and contribute to virulence in bean plants, thus validating this approach for dissecting the contribution of thePph1448a type III effector inventory to virulence. We also analyzed the effect that the expression of these four effectors fromPseudomonas syringaepv. tomato DC3000 (PtoDC3000) has during its interaction withArabidopsis thaliana, establishing that AvrB4-1, but not the others, determines a restriction of bacterial growth that takes place mostly independently of the salicylic acid (SA)-signaling pathway.
CrfA, a Small Noncoding RNA Regulator of Adaptation to Carbon Starvation in
Caulobacter crescentus
Authors: Landt Stephen G. , Lesley Joseph A. , Britos Leticia , Shapiro Lucy
Published: July 2010

Small noncoding regulatory RNAs (sRNAs) play a key role in the posttranscriptional regulation of many bacterial genes. The genome of
Caulobacter crescentus
encodes at least 31 sRNAs, and 27 of these sRNAs are of unknown function. An overexpression screen for sRNA-induced growth inhibition along with sequence conservation in a related
Caulobacter
species led to the identification of a novel sRNA, CrfA, that is specifically induced upon carbon starvation. Twenty-seven genes were found to be strongly activated by CrfA accumulation. One-third of these target genes encode putative TonB-dependent receptors, suggesting CrfA plays a role in the surface modification of
C. crescentus
, facilitating the uptake of nutrients during periods of carbon starvation. The mechanism of CrfA-mediated gene activation was investigated for one of the genes predicted to encode a TonB-dependent receptor, CC3461. CrfA functions to stabilize the CC3461 transcript. Complementarity between a region of CrfA and the terminal region of the CC3461 5′-untranslated region (5′-UTR) and also the behavior of a deletion of this region and a site-specific base substitution and a 3-base deletion in the CrfA complementary sequence suggest that CrfA binds to a stem-loop structure upstream of the CC3461 Shine-Dalgarno sequence and stabilizes the transcript.
Whole Genome Sequences of Two
Xylella fastidiosa
Strains (M12 and M23) Causing Almond Leaf Scorch Disease in California
Authors: Chen J. , Xie G. , Han S. , Chertkov O. , Sims D. , Civerolo E. L.
Published: July 2010

Xylella fastidiosa
is a Gram-negative plant-pathogenic bacterium causing many economically important diseases, including almond leaf scorch disease (ALSD) in California. Genome information greatly facilitates research on this nutritionally fastidious organism. Here we report the complete genome sequences of two ALSD strains of this bacterium, M12 and M23.
Complete Genome Sequence of
Beijerinckia indica
subsp.
indica
Authors: Tamas Ivica , Dedysh Svetlana N. , Liesack Werner , Stott Matthew B. , Alam Maqsudul , Murrell J. Colin , Dunfield Peter F.
Published: July 2010

Beijerinckia indica
subsp.
indica
is an aerobic, acidophilic, exopolysaccharide-producing, N
2
-fixing soil bacterium. It is a generalist chemoorganotroph that is phylogenetically closely related to facultative and obligate methanotrophs of the genera
Methylocella
and
Methylocapsa
. Here we report the full genome sequence of this bacterium.
Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease
Authors: Hamamdzic Damir , Fenning Robert S. , Patel Dhavalkumar , Mohler Emile R. , Orlova Ksenia A. , Wright Alexander C. , Llano Raul , Keane Martin G. , Shannon Richard P. , Birnbaum Morris J. , Wilensky Robert L.
Published: July 2010

Atherosclerosis is an inflammatory process leading to enhanced cellular proliferation, apoptosis, and vasa vasorum (VV) neovascularization. While both diabetes mellitus (DM) and hypercholesterolemia (HC) predispose to atherosclerosis, the precise interaction of these risk factors is unclear. Akt is a central node in signaling pathways important for inflammation, and we hypothesized that DM/HC would lead to aberrant Akt signaling and advanced, complex atherosclerosis. DM was induced in pigs by streptozotocin and HC by a high-fat diet. Animals were randomized to control (non-DM, non-HC), DM only, HC only, and DM/HC groups. Coronary artery homogenates were analyzed by immunoblotting for proteins involved in the Akt pathway, including phosphorylated (p)-Akt (Ser473), p-GSK-3β (Ser9), activated NF-κB p65, and VEGF. Immunohistochemical staining for Ki67 (cell proliferation), terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) (apoptosis), and von Willebrand factor (vWF) (neovascularization) was performed. Neovascularization was visualized with micro-computerized tomography (CT). Only DM/HC animals developed advanced atherosclerosis and showed decreased p-Akt (Ser473) and p-GSK-3β (Ser9) levels ( P < 0.01 and P < 0.05, respectively). DM/HC arteries demonstrated increased cellular proliferation ( P < 0.001), apoptosis ( P < 0.01), and activation of NF-κB p65 ( P < 0.05). Induction of DM/HC also resulted in significant VV neovascularization by enhanced VEGF expression ( P < 0.05), increased vWF staining ( P < 0.01), and increased density by micro-CT. In conclusion, DM and HC synergistically resulted in complex atherosclerosis associated with attenuated p-Akt (Ser473) levels. Aberrant Akt signaling correlated with increased inflammation, cellular proliferation, apoptosis, and VV neovascularization. Our results revealed a synergistic effect of DM and HC in triggering abnormal Akt signaling, resulting in advanced atherosclerosis.
MiRNA-196 Is Upregulated in Glioblastoma But Not in Anaplastic Astrocytoma and Has Prognostic Significance
Authors: Guan Yanlei , Mizoguchi Masahiro , Yoshimoto Koji , Hata Nobuhiro , Shono Tadahisa , Suzuki Satoshi O. , Araki Yukie , Kuga Daisuke , Nakamizo Akira , Amano Toshiyuki , Ma Xinlong , Hayashi Kenshi , Sasaki Tomio
Published: July 2010

Purpose: MicroRNAs (miRNA) are short noncoding RNAs that can play critical roles in diverse biological processes. They are implicated in tumorigenesis and function both as tumor suppressors and as oncogenes. The clinical significance of miRNA expression profiles in malignant gliomas remains unclear.

Experimental Design: In this study, we examined the expression levels of 365 mature human miRNAs in 12 malignant gliomas, including 8 glioblastomas and 4 anaplastic astrocytomas, using TaqMan real-time quantitative PCR arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-196a, -196b, -21, and -15b, by analyzing 92 malignant gliomas by conventional real-time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 39 glioblastoma patients by Kaplan-Meier method and multivariate analysis.

Results: Expression profiles in glioblastomas and anaplastic astrocytomas suggested that 16 miRNAs were candidate markers associated with the malignant progression of gliomas. Among them, miR-196a showed the most significant difference (P = 0.0038), with miR-196b also having a high significance (P = 0.0371). Both miRNAs showed increased expression levels in glioblastomas relative to both anaplastic astrocytomas and normal brains in the validation study. Furthermore, patients with high miR-196 expression levels showed significantly poorer survival by the Kaplan-Meier method (P = 0.0073). Multivariate analysis showed that miR-196 expression levels were an independent predictor of overall survival in all 39 glioblastoma patients (P = 0.021; hazard ratio, 2.81).

Conclusions: Our results suggest that miR-196 may play a role in the malignant progression of gliomas and may be a prognostic predictor in glioblastomas. Clin Cancer Res; 16(16); 4289–97. ©2010 AACR.
Diminished Sensitivity of Chronic Lymphocytic Leukemia Cells to ABT-737 and ABT-263 Due to Albumin Binding in Blood
Authors: Vogler Meike , Furdas Silviya D. , Jung Manfred , Kuwana Tomomi , Dyer Martin J.S. , Cohen Gerald M.
Published: July 2010

Purpose: Inhibition of the antiapoptotic BCL2 family is one of the most promising areas of anticancer drug development. However, ABT-737, a specific BCL2 inhibitor, is neither orally bioavailable nor metabolically stable. To overcome these problems, the structurally related molecule ABT-263 was synthesized and recently entered clinical trials in hematologic malignancies, including chronic lymphocytic leukemia (CLL). Almost all laboratory studies have been carried out with ABT-737 rather than ABT-263, the drug being used in clinical trials. Currently there are no published data on the comparative effects of these inhibitors. To gain insight into the potential value or limitations of ABT-263 in the clinic, we assessed its ability to induce apoptosis in clinically relevant cellular models of CLL.

Experimental Design: The susceptibility of freshly isolated primary CLL cells to these inhibitors was compared in standard culture conditions and in conditions that more closely mimic in vivo conditions in a whole blood assay system.

Results: ABT-737 was more potent than ABT-263 at inducing apoptosis in CLL cells. In whole blood, ∼100-fold higher concentrations of both drugs were required to induce apoptosis. We found that ABT-263 was highly bound by albumin and that an increased albumin binding of ABT-263 as compared with ABT-737 accounted for the differential sensitivity of CLL cells.

Conclusions: Our data indicate that the exquisite in vitro sensitivity of CLL cells to BCL2 inhibitors may be lost in vivo due to high cell densities and the albumin binding of ABT-263. Modification of ABT-263 may yield a BCL2 inhibitor with greater bioavailability and more favorable pharmacokinetics. Clin Cancer Res; 16(16); 4217–25. ©2010 AACR.
The Law and Role of Contracts in The Muscovite Tsardom
Authors: Weickhardt George
Published: July 2010

Muscovite law, which was advanced and well-articulated in many areas, developed no coherent theory of contracts. Even the Law Code of 1649 contains few provisions on contracts and virtually none on the sale of goods or free (non-serf, non-slave) labor. The Muscovite tsardom did, however, adopt some simple provisions that served to reduce the possibility of disputes about whether there was a contract and what its terms were, such as requiring all important contracts to be in writing. Muscovite law also made it clear that consent to a contract had to be freely given, without duress or fraud. The article attempts to explain the lack of any law regulating the sale of goods and free labor.
How Muscovy Governed: Seventeenth-Century Russian Central Administration
Authors: Brown Peter
Published: July 2010

The modern Russian state's first governmental administration, the chancellery system (prikaznaia sistema), guided Muscovy from the 1470s to the 1710s. A handful of state secretaries (d'iaki), subordinate clerks (pod'iachie), and several nascent bureaus matured into over ten permanent, well-codified bodies with decision-making boards, archives, professional hierarchies, and merit-based hiring and promotion by the 1550s. By the 1670s there were 60 chancelleries, and their Moscow staffs by the 1690s had increased to about 3,000, from the highest civil ranks (boyars and okol'niche) through the professional administrative ranks: duma state secretaries (dumnye d'iaki), the state secretaries, and clerks. The chancelleries (prikazy) discharged an array of state, royal court, and church functions, but military concerns were foremost. An arresting internal complexity typified the larger, more important chancelleries, like the Military and Foreign Affairs Chancelleries, divided into sub-units. The chancellery system was entirely homegrown, owning nothing to Roman Imperial and Medieval Latin traditions. The Russians borrowed some paperwork (scrolls) and zealous attention to that from the Mongols, as they did Byzantine and Lithuanian legal elements. Documentary language was a vernacular, Middle Russian register, with burgeoning specialized vocabulary and phraseology. Strict oaths guided conduct, though judicial bureau personnel were notorious for bribe-taking. Foreign travel accounts commented on the obsequiousness of documentary format wherein petitioners referred to themselves as “slaves” (kholopy) and used first-name diminutives. Seventeenth-century Muscovite centralized administration acquired Weber's hallmark features of a bureaucracy; the prikazy guided Muscovy and acculturated its subjects, from tsar to peasant, into its rationale, mechanisms, and operations. Weathering major social traumas and challenges, such as Ivan the Terrible's Oprichnina, the Time of Troubles, the Thirteen Years' War, and the 1682 Musketeers' Uprising, the chancelleries provided the bureaucratic continuity for the Imperial Russian and Soviet states.
"Revolutionary Church" or "Church Revolution"? Some Recent Studies on the History of the Russian Orthodox Church in 1917
Authors: Leont'eva Tatiana
Published: July 2010

Contemporary Russian scholars usually try to abstain from any criticism to Russian Orthodox Church' actions in past and present. Meanwhile a situation in 1917 was very confused: the Holy Synod supported the abdication of its formal head – the Tsar. So historians discussed: what it was – "revolutionary Church" or "revolution inside Church"? One of them insists that bishops become "liberals", another argue that they operated accordingly old religious canons. In reality the full scale revolution inside Church took place: believers tried to overthrow the "reactionary" and "counterrevolutionary" bishops and priests as "serfs of old regime", rank and file clergy supported them.
Memory of the Revolution as a trauma inflicted on contemporary social conscience in Russia
Authors:   Prokhorov
Published: July 2010

Many painful ideological problems existing in contemporary Russia are determined by the inadequacy of perception of the country's revolutionary past. This misperception stems from both the consequences of the decades-long mythologization of the October Revolution and its leaders and from the more recent attempts to get rid of the dependence on Bolshevik propaganda. Contemporary historic memory in Russia is beset with one major contradiction: the desire to part with the myth, and the inability to do so. Although, traditionally, images of the past are usually adapted in order to suit the needs of modernity, this task has become much easier in contemporary society with its powerful mass media fitted with visual networks. Historic memory, previously shaped by legends, folklore, rites and rituals, now comes under relentless fire from the dilettantes pretending to have discovered some "true" vision of the past, and illustrating this vision by incongruous video footage. As a result, images of the past inevitably lose their former edifying role and become a means of inculcation by propagating political and moral stereotypes advantageous to the authorities. The wave of discussions on the Russian Revolution, which rose in connection with its current anniversary, was yet another indication that today's ideologists, with their inept denunciations, are only aggravating the trauma inflicted on social conscience.
The oldest fossil strepsipteran larva (Insecta: Strepsiptera) from the Geisel Valley, Germany (Eocene)
Authors: Pohl Hans
Published: July 2010

The only known fossil strepsipteran first-instar larva from Eocene brown coal is re-examined and redescribed, and photographs together with a detailed interpretative illustration are presented. The original preparation of the minute larva in a 1-mm-thick piece of brown coal of the Geisel valley precludes a detailed examination. After remounting, additional details of the larva are recognisable. A cladistic analysis of 60 morphological characters of 24 recent first-instar strepsipteran larva and the fossil larva confirm the placement in Strepsiptera and in Stylopidia with good support. A placement in Myrmecolacidae or even in the recent genus Stichotrema is rejected. Thus, Pseudococcites Haupt, 1950 comb.rev. is re-established and †Pseudococcites eocaenicus is moved to Stylopidia as incertae sedis.
A taxonomic review of Pelidnoptera Rondani (Diptera: Sciomyzoidea), with discovery of a related new genus and species from Asia
Authors: Ghorpadé Kumar , Knutson Lloyd , Sueyoshi Masahiro
Published: July 2010

The genus Pelidnoptera Rondani is taxonomically reviewed based on examination of the type series. Pelidnoptera triangularis, sp.n. from Japan, the Russian Far East and Nepal, and Akebono vernalis, gen. & sp.n. from Japan are described and illustrated. The lectotype of P. leptiformis (Schiner) is designated here based on the examination of syntypes in the Naturhistorisches Museum, Wien.
Public Consultation and GMO Policy—A Very British Experiment
Authors: Macrory Richard
Published: July 2010

This article describes the UK experience with public consultation procedures in the field of environmental policy and law. It analyses the different challenges for such procedures, particularly on issues where there seems to be a conflict between scientific information on environmental or health risks and deeply held public values. As a conscious departure from established practices GM Nation tried to engage the public in a new form of debate about the risks and benefits associated with GM agriculture. The article describes how this exercise was conducted, how it actually worked out in practice and also discusses some of the criticisms raised and problems encountered.
Moving Towards Phase III—Key Elements of the Review of the EU Emissions Trading Scheme
Authors: Marr Simon , Enzmann Johannes
Published: July 2010

With the Climate and Energy Package the European Commission has also published its draft for a revised EU Emissions Trading Scheme from 2013 onwards. The draft revision of the EU ETS serves as the EU's main pillar to fight climate change in that it requires a reduction of mainly CO2 of 21% below 2005 figures for the EU's major emissions sources in the energy and industry sectors. In addition, most notably the EU is proposing an EU wide cap and harmonised allocation rules, in order to exploit the full potential of emissions trading making national allocation plans ghosts of the past. The revised EU ETS gives investors into CDM projects the necessary long time planning security for investments into projects. At the same time it sends out a strong signal to the international negotiations for a post-2012 climate agreement in that it allows the use of more project based generated credits within the EU ETS once an ambitious post 2012 agreement is concluded.
The European Carbon Market in Action: Lessons from the First Trading Period
Authors: Ellerman Denny , Convery Frank , de Perthuis Christian
Published: July 2010

Through its Emissions Trading Scheme (EU ETS), the European Union is leading the world's first effort to mobilize market forces to tackle global climate change. This article, examines how the EU ETS has performed thus far, at the conclusion of the scheme's first trading phase (2005–2007). Insights drawn from this analysis may inform not only the scheme's future operation, but also the establishment of greenhouse gas trading programs outside Europe. This interim analysis finds that Phase I of the EU ETS (2005–2007) has successfully established a carbon price for significant segments of economic activity in Europe, as well as the necessary trading infrastructure and experience; that the price on carbon has so far had limited impact on the industrial competitiveness of European industry; that it has provided an important stimulus to greenhouse gas emission reductions outside of Europe, primarily through the Clean Development Mechanism; and that the EU ETS provides useful lessons for other countries seeking to limit GHG emissions and for future global climate negotiations.
The Main Results of the Ninth Conference of the Parties to the UN Convention on Biological Diversity
Authors: Buck Matthias
Published: July 2010

The Ninth Conference of the Parties to the UN Convention on Biological Diversity (COP9) in May 2008 in Bonn was one of the major international environmental meetings in 2008. Its decisions significantly advance global biodiversity politics on a range of critical issues and thereby help achieving the global target of substantially reducing current rates of biodiversity loss by 2010. This article describes the main decision adopted by COP9 on biofuels, marine biodiversity, biodiversity and climate change, access and benefit-sharing and the science-policy interface of international biodiversity politics.
Happy end of a long saga—Agreement on the Directive for the Protection of the Environment through Criminal Law
Authors: Zeitler Helge Elisabeth
Published: July 2010

Only one year ago, the proposal for a Directive on the Protection of the Environment through criminal law was presented in this Journal, when discussions in the Council had just started—in May 2008, political agreement between Council and the European Parliament was already reached. Despite of the Directive being less far-reaching than one could have hoped for—this a success story, if alone for the fact that it will bring finally a binding European instrument on environmental crime. The following article will focus on the content of the agreed text and the most significant differences compared to the original proposal of the Commission of March 2007.
Risk assessment in technical legislation: what are the limits to the Commission's discretion under comitology?
Authors: Rusche Tim Maxian , Maxianova Karola
Published: July 2010

By its judgment of 1 April 2008, the European Court of Justice annuls Commission Decision 2005/717/EC exempting deca BDE from the use restriction under the ROHS Directive 2002/95/EC. The Court states that by not complying with the formal conditions of Article 5 (1) (b) of the Directive, the Commission exceeded its implementing powers. As the Court finds that the Commission failed to respect these formal conditions, it does not need to address the pleas of the applicants relating to more fundamental questions regarding risk assessment and risk management under comitology. The authors put this judgment in the broader context of risk regulation on both sides of the Atlantic, and close with an outlook on risk regulation under the new comitology rules introducing regulatory procedure with scrutiny.
The implementation of the IPPC Directive from a comparative perspective and lessons for its recast (Part II)
Authors: Bohne Eberhard
Published: July 2010

This contribution presents a comparative empirical and legal evaluation of the implementation of the IPPC directive in eight EU member states focusing on the integrated approach of the directive. The national transpositions left existing national administrative structures and procedures basically unchanged. Holistic integrated permitting does not occur in any of the countries under study. Explaining the findings with incremental political theory, they serve as the basis for some reflections on the planned recast of the IPPC directive and the prospects for better regulation. While the first part of the article (JEEPL 5.1, 2008, 1–33) displayed the basic shortcomings of the IPPC review process (1.), the concepts of integration under the Directive (2.) and the empricial analysis of the national approaches to integrated permitting (3.1–3.3) this second part explains and evaluates the findings with regard to the pending revision of the directive.
New Developments in European Environmental Legislation
Authors: Falke Josef
Published: July 2010

This section reports on significant political initiatives as well as legal acts and political strategies adopted in the environmental field between February and July 2008.
The polluter pays principle and State aid for environmental protection
Authors: Stoczkiewicz Marcin
Published: July 2010

The polluter pays principle is one of the Treaty-based principles of the Community environmental law. It provides that the polluter is financially liable for compliance with the requirements set by the existing legislation concerning environmental protection and has, therefore, i.a. been referred to as non-subsidisation principle. Nonetheless, the polluter pays principle is also a key principle within the European Commission's practice of controlling State aid for environmental objectives. This contribution explores the apparent paradox of basing the policy on controlling State aid for environmental protection on the polluter pays principle and delineates approaches to reconcile that principle with State aid practice.
EU policies for Sustainable Consumption and Production—the Action Plan on Sustainable Consumption and Production and Sustainable Industrial Policy
Authors: Lorz Bettina
Published: July 2010

The need to move towards sustainable consumption and production has been recognised since the First Earth Summit in Rio de Janeiro. Yet progress in translating policy commitment into tangible measures has been slow. For the EU, the Action Plan on Sustainable Consumption and Production and Sustainable Industrial Policy presented by the Commission in July 2008 is an important step in that direction. It builds upon and further develops a life-cycle oriented product policy, and also addresses the consumption dimension. This article looks at implementation and application of the Action Plan. This is presenting a number of challenges: setting up and implementing a coherent legal framework, providing the requisite tools and steering voluntary processes. It concludes by looking to the future and the challenges for EU policies.