bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells
Authors: Nakayama Satoshi , Torikoshi Yasuhiro , Takahashi Takeshi , Yoshida Tomokazu , Sudo Tamotsu , Matsushima Tomoko , Kawasaki Yuko , Katayama Aya , Gohda Keigo , Hortobagyi Gabriel N , Noguchi Shinzaburo , Sakai Toshiyuki , Ishihara Hideki , Ueno Naoto T
Published: February 2009

Introduction

Paclitaxel is used widely in the treatment of breast cancer. Not all tumors respond to this drug, however, and the characteristics that distinguish resistant tumors from sensitive tumors are not well defined. Activation of the spindle assembly checkpoint is required for paclitaxel-induced cell death. We hypothesized that cyclin-dependent kinase (CDK) 1 activity and CDK2 activity in cancer cells, which reflect the activation state of the spindle assembly checkpoint and the growth state, respectively, predict sensitivity to paclitaxel.

Methods

Cell viability assays and DNA and chromatin morphology analyses were performed in human breast cancer cell lines to evaluate sensitivity to paclitaxel and the cell cycle response to paclitaxel. We then examined the specific activities of CDK1 and CDK2 in these cell lines and in xenograft models of human breast cancer before and after paclitaxel treatment. Protein expression and kinase activity of CDKs and cyclins were analyzed using a newly developed assay system.

Results

In the cell lines, biological response to paclitaxel in vitro did not accurately predict sensitivity to paclitaxel in vivo. Among the breast cancer xenograft tumors, however, tumors with significantly increased CDK1 specific activity after paclitaxel treatment were sensitive to paclitaxel in vivo, whereas tumors without such an increase were resistant to paclitaxel in vivo. Baseline CDK2 specific activity was higher in tumors that were sensitive to paclitaxel than in tumors that were resistant to paclitaxel.

Conclusions

The change in CDK1 specific activity of xenograft tumors after paclitaxel treatment and the CDK2 specific activity before paclitaxel treatment are both associated with the drug sensitivity in vivo. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting paclitaxel sensitivity.
Prediction of extubation outcome: a randomised, controlled trial with automatic tube compensation vs. pressure support ventilation
Authors: Cohen Jonathan , Shapiro Maury , Grozovski Elad , Fox Ben , Lev Shaul , Singer Pierre
Published: February 2009

Introduction

Tolerance of a spontaneous breathing trial is an evidence-based strategy to predict successful weaning from mechanical ventilation. Some patients may not tolerate the trial because of the respiratory load imposed by the endotracheal tube, so varying levels of respiratory support are widely used during the trial. Automatic tube compensation (ATC), specifically developed to overcome the imposed work of breathing because of artificial airways, appears ideally suited for the weaning process. We further evaluated the use of ATC in this setting.

Methods

In a prospective study, patients who had received mechanical ventilation for more than 24 hours and met defined criteria for a weaning trial, underwent a one-hour spontaneous breathing trial with either ATC (n = 87) or pressure support ventilation (PSV; n = 93). Those tolerating the trial were immediately extubated. The primary outcome measure was the ability to maintain spontaneous, unassisted breathing for more than 48 hours after extubation. In addition, we measured the frequency/tidal volume ratio (f/VT) both with (ATC-assisted) and without ATC (unassisted-f/VT) at the start of the breathing trial as a pretrial predictor of extubation outcome.

Results

There were no significant differences in any of the baseline characteristics between the two groups apart from a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score in the ATC group (p = 0.009). In the PSV group, 13 of 93 (14%) patients failed the breathing trial compared with only 6 of 87 (6%) in the ATC group; this observed 8% difference, however, did not reach statistical significance (p = 0.12). The rate of reintubation was not different between the groups (total group = 17.3%; ATC = 18.4% vs. PSV = 12.9%, p = 0.43). The percentage of patients who remained extubated for more than 48 hours was similar in both groups (ATC = 74.7% vs. PSV = 73.1%; p = 0.81). This represented a positive predictive value for PSV of 0.85 and ATC of 0.80 (p = 0.87). Finally, the ATC-assisted f/VT was found to have a significant contribution in predicting successful liberation and extubation compared with the non-significant contribution of the unassisted f/VT (unassisted f/VT, p = 0.19; ATC-assisted f/VT, p = 0.005).

Conclusions

This study confirms the usefulness of ATC during the weaning process, being at least as effective as PSV in predicting successful extubation outcome and significantly improving the predictive value of the f/VT.

Trial registration

Current Controlled Trials ISRCTN16080446
Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome
Authors: Huh Jin Won , Jung Hoon , Choi Hye Sook , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck
Published: February 2009

Introduction

In acute respiratory distress syndrome (ARDS), adequate positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by minimising overinflation and cyclic recruitment-derecruitment of the lung. We evaluated whether setting the PEEP using decremental PEEP titration after an alveolar recruitment manoeuvre (ARM) affects the clinical outcome in patients with ARDS.

Methods

Fifty-seven patients with early ARDS were randomly assigned to a group given decremental PEEP titration following ARM or a table-based PEEP (control) group. PEEP and inspired fraction of oxygen (FiO2) in the control group were set according to the table-based combinations of FiO2 and PEEP of the ARDS network, by which we aimed to achieve a PEEP level compatible with an oxygenation target. In the decremental PEEP titration group, the oxygen saturation and static compliance were monitored as the patients performed the ARM along with the extended sigh method, which is designed to gradually apply and withdraw a high distending pressure over a prolonged period, and the decremental titration of PEEP.

Results

The baseline characteristics did not differ significantly between the control and decremental PEEP titration groups. Initial oxygenation improved more in the decremental PEEP titration group than in the control group. However, dynamic compliance, tidal volume and PEEP were similar in the two groups during the first week. The duration of use of paralysing or sedative agents, mechanical ventilation, stay in the intensive care unit and mortality at 28 days did not differ significantly between the decremental PEEP titration and control groups.

Conclusions

The daily decremental PEEP titration after ARM showed only initial oxygenation improvement compared with the table-based PEEP method. Respiratory mechanics and patient outcomes did not differ between the decremental PEEP titration and control groups.

Trial registration

ClinicalTrials.gov identifier: ISRCTN79027921.
PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data
Authors: Korbel Jan O , Abyzov Alexej , Mu Xinmeng Jasmine , Carriero Nicholas , Cayting Philip , Zhang Zhengdong , Snyder Michael , Gerstein Mark B
Published: February 2009

Personal-genomics endeavors, such as the 1000 Genomes project, are generating maps of genomic structural variants by analyzing ends of massively sequenced genome fragments. To process these we developed Paired-End Mapper (PEMer; http://sv.gersteinlab.org/pemer). This comprises an analysis pipeline, compatible with several next-generation sequencing platforms; simulation-based error models, yielding confidence-values for each structural variant; and a back-end database. The simulations demonstrated high structural variant reconstruction efficiency for PEMer's coverage-adjusted multi-cutoff scoring-strategy and showed its relative insensitivity to base-calling errors.
Oxidative modifications of S100 proteins: functional regulation by redox
Authors: Lim Su Yin , Raftery Mark J , Goyette Jesse , Hsu Kenneth , Geczy Carolyn L
Published: February 2009

Alterations in the capability of CF lung macrophage to respond and clear airway pathogens might contribute to the development of lung disease in cystic fibrosis.

Several S100 Ca2+–binding proteins undergo various post–translational modifications that may alter their intracellular and extracellular functions. S100A8 and S100A9, two members of this family, are particularly susceptible to oxidative modification. These proteins, abundantly expressed in neutrophils and activated macrophages, are associated with acute and chronic inflammatory conditions, including microbial infections, cystic fibrosis, rheumatoid arthritis, and atherosclerosis. They have diverse intracellular roles including NADPH oxidase activation and arachidonic acid transport and can be secreted via a Golgi–independent pathway to exert extracellular functions. Many pro–inflammatory functions have been described for S100A8 and S100A9, but they are also implicated in anti–inflammatory roles in wound–healing and protection against excessive oxidative tissue damage, the latter as a result of their exquisite capacity to scavenge oxidants. Similarly, their genes are induced by proinflammatory (LPS and TNF–α) stimuli, but induction is IL–10–dependent, and anti–inflammatory glucocorticoids induce or amplify expression. S100A8 and S100A9 were described recently as damage–associated molecular pattern molecules, which provide a novel, conceptual framework for understanding their functions. However, because of this designation, recent reviews focus solely on their pro–inflammatory functions. Here, we summarize the mounting evidence from functional and gene regulation studies that these proteins may also play protective roles. This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post–translational, oxidative modifications may act as a regulatory switch.
Defective IL-10 production in severe phenotypes of Crohn’s disease
Authors: Correa Ismael , Veny Marisol , Esteller Miriam , Piqué Josep M , Yagüe Jordi , Panés Julián , Salas Azucena
Published: February 2009

Loss of tolerance toward commensal bacteria has been invoked as a mechanism for Crohn’s disease. IL-10 is a key anti-inflammatory cytokine that plays a role in induction and maintenance of tolerance. The aim of this study is to determine IL-10 production in response to bacterial components in Crohn’s disease patients, who were classified according to their phenotypes as stricturing, penetrating, or inflammatory. Peripheral blood was obtained from Crohn’s disease patients and healthy controls. Cytokine production was measured in whole blood cultures, isolated CD4+ cells, and monocyte-derived dendritic cells (MDDCs). Under unstimulated conditions, IL-10, but not IL-12, was down-regulated significantly in blood cultures of patients with severe phenotypes, compared with inflammatory, nonpenetrating, nonstricturing Crohn’s disease patients. In response to LPS, IL-10 was up-regulated more significantly in patients with no fistulae or fibrosis. Study of IL-10 production by isolated cell subsets showed that DCs, but not CD4+ T cells, from penetrating Crohn’s disease produced significantly less IL-10 in response to LPS. Differences were not associated with the 1082A/G polymorphism in the IL-10 gene promoter. We show a defect in IL-10 production in whole blood cell cultures and MDDCs in patients with severe forms of Crohn’s disease. This defect in IL-10 production by a group of Crohn’s disease patients may represent a mechanism mediating more severe manifestations of the disease. We propose that treatment with IL-10 or IL-10-inducing therapies could be of particular benefit to these group of patients.
Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous Bisphosphonates
Authors: Fizazi Karim , Lipton Allan , Mariette Xavier , Body Jean-Jacques , Rahim Yasmin , Gralow Julie R. , Gao Guozhi , Wu Ling , Sohn Winnie , Jun Susie
Published: February 2009

Purpose

Patients with bone metastases and elevated urinary N-telopeptide (uNTx), representing excessive bone resorption, are at increased risk for skeletal-related events (SREs), cancer progression, and death. Osteoclast-mediated bone resorption is regulated by RANKL. We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients with bone metastases and elevated uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy.

Patients and Methods

Eligible patients had histologically confirmed malignancy, ≥ 1 bone metastases, and uNTx levels higher than 50 nmol/L bone collagen equivalents (BCE)/mM creatinine despite IV BPs. They were stratified by tumor type and screening uNTx levels (50 to 100 or > 100 nmol/L BCE/mM creatinine), and randomly assigned to continue IV BPs every 4 weeks or receive subcutaneous denosumab 180 mg every 4 weeks or every 12 weeks.

Results

Among 111 patients accrued, the primary end point of uNTx levels lower than 50 nmol/L BCE/mM creatinine (uNTx < 50) at week 13 was achieved by 49 (71%) of 69 patients in the denosumab arms, compared with 10 (29%) of 35 patients in the IV BP arm (P < .001). The proportion of patients with uNTx lower than 50 was maintained at week 25 (64% denosumab arms; 37% IV BP arm; P = .01). The incidence of SREs was six (8%) of 73 and six (17%) of 35 in the denosumab group and IV BP group, respectively. Rates of adverse events were similar between treatment groups.

Conclusion

Among patients with elevated uNTx despite ongoing IV BP therapy, denosumab normalized uNTx levels more frequently than the continuation of IV BP. Fewer patients receiving denosumab experienced on-study SREs than those receiving IV BPs.
Phase I Trial of AEG35156 Administered as a 7-Day and 3-Day Continuous Intravenous Infusion in Patients With Advanced Refractory Cancer
Authors: Dean Emma , Jodrell Duncan , Connolly Kate , Danson Sarah , Jolivet Jacques , Durkin Jon , Morris Stephen , Jowle Debra , Ward Tim , Cummings Jeff , Dickinson Gemma , Aarons Leon , LaCasse Eric , Robson Lesley , Dive Caroline , Ranson Malcolm
Published: February 2009

Purpose

To establish the maximum-tolerated dose and evaluate tolerability, pharmacokinetics, pharmacodynamic effects, and antitumor activity of AEG35156, a second-generation antisense to X-linked inhibitor of apoptosis (XIAP) protein, in patients with advanced refractory malignant tumors.

Patients and Methods

This was a first-in-man, open-label, phase I dose-escalation study. AEG35156 was administered by continuous intravenous infusion over 7 days (7DI) or 3 days (3DI) of a 21-day treatment cycle. Dose escalation started at 48 mg/m2/d and continued until consistent dose-limiting toxicity (DLT) was observed.

Results

Thirty-eight patients were entered in seven cohorts. Grade 3 to 4 adverse events were uncommon and were predominantly abnormal laboratory values: elevated ALT, thrombocytopenia, and lymphopenia. DLTs comprised elevated hepatic enzymes, hypophosphatemia, and thrombocytopenia. The maximum-tolerated doses were defined as 125 mg/m2/d for the 7DI regimen and ≤ 213 mg/m2/d for the 3DI schedule. AEG35156 area under the plasma concentration curve and peak plasma concentration increased proportionally with dose. Suppression of XIAP mRNA levels was maximal at 72 hours (mean suppression, 21%), and this coincided with a dramatic decrease in circulating tumor cells in a patient with non-Hodgkin's lymphoma. Two further patients had unconfirmed partial responses. Circulating biomarkers of cell death and apoptosis altered in association with drug infusion and toxicity.

Conclusion

In this first-in-man study, AEG35156 was well tolerated, with predictable toxicities, pharmacokinetic properties, and clinical evidence of antitumor activity in patients with refractory lymphoma, melanoma, and breast cancer. Phase I/II trials of AEG35156 chemotherapy combinations are ongoing in patients with pancreatic, breast, non–small-cell lung cancer, acute myeloid leukemia, lymphoma, and solid tumors for which docetaxel is indicated.
The Sacred Clade and the Rhizomatic Dis-ease of History
Authors: Kubiak Anthony
Published: February 2009

The recent past has seen a shift away from more philosophically complex, theoretically dense approaches to literary criticism (psychoanalysis, deconstruction, phenomenology) in favor of more material or “empirical” (historiographical, historical materialist) approaches to interpretation—a shift away from the aesthetic and toward an ascetic model of reading. But this shift is in fact no shift at all, but merely the logical outcome of a historicist and materialist approach to meaning that has always been in thrall to scientific methodologies. Even structuralist and poststructural readings of texts show signs of this scientific longing for material meanings in the world, a longing that art itself, especially theater, has refused to sanction. We are living, it seems, in a postmaterial world, whose very impossibility suggests infinite possibilities of meaning.
Sheet Music Iconography and Music in the History of Transatlantic Minstrelsy
Authors: Foster Daniel H.
Published: February 2009

This essay focuses on how aural and visual media intersected with class when, in 1843, blackface performers began to call themselves minstrels. Not merely a rebaptism, this new name marked a rebirth. Whereas blackface was originally a working-class theatrical experience passed on orally from performer to performer and from performer to audience, blackface minstrels sought to reassure the middle classes that they were emulating more sophisticated European musical traditions. What both the covers and the contents of post-1843 blackface sheet music reveal is that these minstrels tried to establish themselves as part of the growing concert tradition in the United States by showcasing their performances as more presentational and less representational. Because blackface relied increasingly on the publishing industry and the visual medium of sheet music, it also began to rely more on the eye, and because sheet music assumes a certain level of literacy and luxury, this reliance on the eye encouraged blackface's growth as a middle-class phenomenon.
Report
Authors: Klett Renate
Published: February 2009

Originally published in the Frankfurter Allgemeine Zeitung

Translated by Douglas Langworthy
The Communist Dracula Pageant
Authors: Washburn Anne
Published: February 2009

By Americans, for Americans a play about the Romanian Revolution of 1989 with hallucinations, phosphorescence, and bears
The Lost Envelope (Excerpt)
Authors: Mujomba Pierre
Published: February 2009

Translated by Jill Mac Dougall
Genetic dissection of the mechanisms underlying telomere-associated diseases: impact of the TRF2 telomeric protein on mouse epidermal stem cells
Authors: Stout Gerdine J. , Blasco Maria A.
Published: February 2009

TRF2 is a telomere-binding protein involved in the protection of chromosome ends. Interestingly, TRF2 is overexpressed in a number of human cancers. Mice with increased TRF2 expression (K5TRF2 mice) display a severe skin phenotype including an increase in skin cancer and premature skin degeneration, which includes increased skin hyperpigmentation and skin dryness; these pathologies are concomitant with dramatic telomere shortening and increased chromosomal instability. Here, we show that K5TRF2 mice have a severe epidermal stem cell (ESC) dysfunction, which is reversed by abrogation of p53 in the absence of rescue of telomere length. Importantly, p53 deletion also rescues severe skin hyperpigmentation in these mice through regulation of alpha-melanocyte-stimulating hormone (α-MSH). In addition, skin carcinogenesis is accelerated in K5TRF2/p53−/−mice owing to attenuated p21 induction, which enables cell proliferation to resume. Altogether, these results reveal the existence of a DNA damage-dependent checkpoint that acts on ESCs with critically short telomeres and restricts skin proliferation, thereby increasing protection against skin cancer; however, the checkpoint also leads to premature skin aging phenotypes. Finally, the results described here are relevant to our understanding of the pathobiology of those human diseases that are characterized by the presence of critically short telomeres (hereafter referred to as ‘telopathies’), such as dyskeratosis congenita which causes severe skin phenotypes including skin hyperpigmentation and skin cancer.
Parallel systems with different types of defence resource expenditure under two sequential attacks
Authors: Hausken K , Levitin G
Published: February 2009

The paper compares the efficiency of single and double attack against a system consisting of identical parallel elements (one-out-of- N system). An attacker tries to maximize the system vulnerability (probability of total destruction) whereas the defender tries to minimize it. The attacker and the defender distribute their constrained resources optimally across two attacks. The attacker chooses the number of elements to attack in the first attack. The defender protects all elements before the first attack and protects all surviving elements before the second attack. Both agents decide how to distribute their resources between the two attacks before the first attack. Two cases are considered. In the first, all the elements that survive the first attack keep their protection in the second attack. In the second, only the elements that are not attacked in the first attack keep their protection in the second attack, while elements that are attacked but survive do not keep their protection. The attacker's resource is expendable and lasts only one attack. Both agents observe which elements are destroyed and not destroyed in the first attack, and apply their remaining resources into attacking and protecting the remaining elements in the second attack. The optimal attack and defence strategy against a system with a fixed number of elements is analysed as a solution of a minmax game.
Synthesis and Photoinduced Cross-linking Reactions of 4,5′,8-Trimethylpsoralen-incorporated Oligodeoxyribonucleotide
Authors: Kobori Akio , Takaya Kazutaka , Higuchi Maiko , Yamayoshi Asako , Murakami Akira
Published: February 2009

Photo-induced cross-linking reaction at a certain position in nucleic acids, occurring in a sequence specific manner, would be the key to inhibitor the growth of carcinoma cells, which has a point mutation in the ras gene. We newly synthesized 4,5′,8-trimethylpsoralen nucleoside and examined its photoinduced cross-linking activities in DNA duplexes after UVA irradiation.
Ordered Pillar Array Structures of TiO2 by Nanoimprinting Using Anodic Porous Alumina as Molds
Authors: Yanagishita Takashi , Endo Takehide , Yamaguchi Yukiyasu , Nishio Kazuyuki , Masuda Hideki
Published: February 2009

Ordered pillar array structures of TiO2 were prepared by nanoimprinting process using ordered anodic porous alumina as a mold. The shape of the obtained pillars of TiO2 corresponded to that of the holes of anodic porous alumina used as a mold. The geometric structure of the TiO2 pillar array could be controlled by the condition of the formation of the anodic porous alumina molds.
Synthesis and Characterization of 2,3,7,8,12,13-Hexabromotruxene and Its Hexaaryl Derivatives
Authors: Lai Wen-Yong , He Qi-Yuan , Ma Zhun , Huang Wei
Published: February 2009

The first synthesis of 2,3,7,8,12,13-hexabromotruxene is reported. Its potential for further functionalization toward highly substituted conjugated materials is examined.
Controllable Fabrication of Multibranched TiO2 Nanotubes via a Two-step Anodization Method
Authors: Jin Zhen , Fei Guang Tao , Hu Xiao Ye , Xu Shao Hui , Zhang Li De
Published: February 2009

Multibranched TiO2 nanotubes have been controllably fabricated through a two-step anodization method. By tailoring the diameter ratio of the stem and branch accurate by multibranched, such as two-, three-, and four-branched, TiO2 nanotubes were obtained. The relationship of the diameter ratio and the branch number also has been discussed. This method provides a powerful approach to produce multibranched TiO2 nanotubes, which should have great potential application in future nanoscale systems.
Characterizing multiple exogenous and endogenous small RNA populations in parallel with subfemtomolar sensitivity using a streptavidin gel-shift assay
Authors: Ebhardt H. Alexander , Unrau Peter J.
Published: February 2009

Here we present a simple and inexpensive gel-shift assay for the detection and quantification of small RNAs. The assay is at least 5–10 times more sensitive than a conventional Northern, and is highly scalable. Total RNA is first size purified to enrich the desired size range, phosphatase treated, and then radiolabeled to high specific activity using polynucleotide kinase. The resulting RNA stock is then hybridized to an excess of biotinylated DNA probe oligonucleotide, prior to mixing with streptavidin and loading on a native gel. The amount of supershifted material was proportional to the amount of labeled target RNA in the sample. We applied this method to verify sequencing data originally obtained from a four-point comparison study on the effect of endogenous expression of HC-Pro on Y-satellite/cucumber mosaic virus infection in tobacco plants. The results of the streptavidin gel-shift assay were consistent with the concentrations of small RNA infected plants inferred by our original cloning data, and rapidly provided information about the relative concentration of a number of viral and endogenous small RNAs. Further straightforward improvements to this simple methodology might be expected to improve the methods sensitivity by as much as another 10-fold.
Ribozyme-mediated reduction of wild-type and mutant cartilage oligomeric matrix protein (COMP) mRNA and protein
Authors: Alcorn Joseph L. , Merritt Thomas M. , Farach-Carson Mary C. , Wang Huiqui H. , Hecht Jacqueline T.
Published: February 2009

Dominant-negative mutations in the homopentameric extracellular matrix glycoprotein cartilage oligomeric matrix protein (COMP) result in inappropriate intracellular retention of misfolded COMP in the rough endoplasmic reticulum of chondrocytes, causing chondrocyte cell death, which leads to two skeletal dysplasias: pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1). COMP null mice show no adverse effects on normal bone development and growth, suggesting a possible therapy involving removal of COMP mRNA. The goal of this study was to assess the ability of a hammerhead ribozyme (Ribo56, designed against the D469del mutation) to reduce COMP mRNA expression. In COS7 cells transfected with plasmids that overexpress wild-type or mutant COMP mRNA and Ribo56, the ribozyme reduced overexpressed normal COMP mRNA by 46% and mutant COMP mRNA by 56% in a dose-dependent manner. Surprisingly, the use of recombinant adenoviruses to deliver wild-type or mutant COMP mRNA and Ribo56 simultaneously into COS7 cells proved problematic for the activity of the ribozyme to reduce COMP expression. However, in normal human costochondral cells (hCCCs) infected only with adenoviruses expressing Ribo56, expression of endogenous wild-type COMP mRNA was reduced in a dose-dependent manner by 50%. In chondrocytes that contain heterozygous COMP mutations (D469del, G427E and D511Y) that cause PSACH, Ribo56 was more effective at reducing COMP mRNA (up to 70%). These results indicate that Ribo56 is effective at reducing mutant and wild-type COMP levels in cells and suggests a possible mode of therapy to reduce the mutant protein load.
Centralization of Tax Administration in Nigeria: The Legal and Efficiency Considerations
Authors: Bolodeoku Ige Omotayo
Published: February 2009

In Nigeria, the recently enacted Federal Inland Revenue Service (Establishment) Act 2007 is generating controversy as to whether, among other considerations, the Act centralizes the administration of all federally enacted tax laws, especially those covered by item D7 of the second schedule to Nigeria's 1999 Constitution. In its contribution to the debate, this article assesses the Act from two perspectives, namely law and efficiency. On the legal consideration, the article takes the position that, indeed, the Act centralizes administration of the federal tax laws contemplated by item D7, consistently with the relevant constitutional provisions. On the efficiency consideration, however, the article argues that the centralization effected by the Act is inefficient. It argues that a proper impact assessment of the Act, in light of the constitution which recognizes states as the only beneficiaries of the revenue collected by the affected laws, would have revealed the inevitability of agency problems and costs, which would be difficult to address due to a lack of motivation or incentives in a federal collecting agency and a lack of disciplinary power in the states-beneficiaries. It further argues that the horizontal transition implicit in the Act's reform would create avoidable waste that is bound to arise from an abandonment of years of resources which the pre-Act tax administration framework has created.
Stop and Search, Terrorism and the Human Rights Deficit
Authors: Edwards Richard A.
Published: February 2009

This paper discusses the judgment of the House of Lords in Gillan [2006] UKHL 12, where the law lords examined the compatibility of the power in ss. 44 and 45 of the Terrorism Act 2000 to stop and search individuals with the Human Rights Act 1998. It is argued that the decision of the House of Lords that ss. 44 and 45 are compatible with Convention rights was wrong for a number of reasons. Not only did the House of Lords fail to interpret and apply the applicable Convention rights correctly, it also missed an important opportunity to develop the principle of legality in the context of the Human Rights Act. Moreover, the House failed to deal adequately with the troubling question of whether the exercise and use of the stop and search power under the Terrorism Act was racially discriminatory. These issues take on a particular importance not only because of the greater use of the power since the so-called ‘7/7 attacks’, but also because of the disparate impact that the use of the power has on racial minorities.
Planning: A Roadblock to Renewable Energy in the UK
Authors: Crowhurst Georgina , Davidson Simone
Published: February 2009

This article considers the planning system as one of the major roadblocks to renewable energy projects and looks at illustrative examples of renewable energy projects that have been held up in this system. It also analyses some of the recent measures put forward to promote renewable energy projects and addresses the shortcomings in the planning system.
Authenticating ‘Things’ in English Law: Principles for Adducing Tangible Evidence in Common Law Jury Trials
Authors: Pattenden Rosemary
Published: February 2009

This article explores the true nature of authentication of tangible evidence in English law and kindred jurisdictions. It first identifies general principles governing the respective roles of judge and jury in the authentication of tangible evidence embedded within the case law of England and Wales. Those principles are then compared and contrasted to the rules governing authentication of evidence under the US Federal Rules of Evidence. Finally, general principles of authentication in English law are examined in relation to the authentication of forensic science evidence; film, video, photographs and sound recordings; private documents; computer output; and recorded confessions.
The Use and Abuse of Psychiatric Evidence in Rape Trials
Authors: Ellison Louise
Published: February 2009

This article examines how psychiatric evidence can be misused in rape trials and argues in favour of more stringent limits on cross-examination to protect rape complainants from improper attacks on their credibility.
Exit the Polibation Officer? Decoupling Police and Probation
Authors: Nash Mike
Published: February 2009

Since 1999 the pages of this journal have periodically carried articles based on the idea of a ‘polibation’ officer, or variants on that theme. The idea arose from the possible outcomes of increasingly closer collaboration between police and probation services under the public protection umbrella. Eight years on it is evident that, in a variety of settings, roles have been established which take individual practitioners some way from their roots in terms of professional practice and culture. This article briefly revisits this process and explores the pros and cons of fused roles. It concludes with the announcement of a split in the functions of the Home Office which results, at least on paper, in a decoupling of police and probation services. The future of the polibation officer is considered in this light.
Policing the Pearl: Historical Transformations of Law Enforcement in Hong Kong
Authors: Deflem Mathieu , Featherstone Richard , Li Yunqing , Sutphin Suzanne
Published: February 2009

In this article we discuss historical patterns and dynamics of policing in Hong Kong since the formation of the first police force in the then British colony in 1844 until the handover to China in 1997 when a policy of ‘one country, two systems' was implemented. We specifically focus on the changes that took place in the organisation of the police function and how these changes responded to shifting socio-structural conditions in political, economic and legal respects and, comparatively, to what extent institutional dynamics of Hong Kong police organisation and culture were responsible for dominant policing styles. We argue that the case of Hong Kong policing shows that internal developments of police culture and police management are, independently from broader societal developments, essential components to bring about changes towards the adoption of civilian police practices that enjoy both effectiveness and accountability.
An Evaluation of a Police Debriefing Programme: Outcomes for Police Officers Five Years after a Police Shooting
Authors: Addis Nicola , Stephens Christine
Published: February 2009

To evaluate the effectiveness of a debriefing programme to reduce traumatic stress in a police organisation, officers involved in a shooting were surveyed by questionnaire, five years after the event. The results showed that 79 per cent of 57 officers had not received debriefing, despite its mandatory status. Those who had received debriefing had higher post-traumatic stress disorder (PTSD) scores; however, regression of PTSD and health scores, on stress perceptions, social support, other trauma, and debriefing, showed that debriefing had no significant effect. These results support those of other controlled studies suggesting that debriefing does not mitigate PTSD and may exacerbate symptoms. A number of limitations of the present study are discussed in terms of suggestions for urgent evaluation of such programs in organisational settings.
Counting Crimes — The Importance of Understanding Crime Concentration for the Design and Evaluation of Crime Reduction Strategies
Authors: Rogerson Michelle
Published: February 2009

Crime statistics are most frequently concerned with the incidence of crime (usually quoted as a rate per population), occasionally statistics are concerned with prevalence (number or proportion of victims within the population) but the concentration of crime (number of crimes per victim) is rarely quoted. This paper aims to demonstrate the importance of all three indicators of crime, prevalence, concentration and incidence, for understanding crime levels through an analysis of self-reported victimisation data from 39 high-crime areas. The analysis illustrates that areas can have high crime either as a result of high levels of victimisation (prevalence), high numbers of crimes per victim (concentration) or a combination of both. These underlying dimensions of a crime problem must be understood in order to select the most suitable crime prevention interventions, and to target them appropriately.
Victims of Criminal Investigations: Experiences of Adults in Two Communities in Osun State, Nigeria
Authors: Agunbiade Ojo Melvin , Opatola Mustapha Olayiwola
Published: February 2009

Criminal investigation represents a crucial stage in the process of crime management and justice realisation in any modern society; but the criminal investigation process is prone to abuse. This study examines the experiences of adults who have been interrogated for a criminal offence or offences in two communities in Osun State (Southwestern Nigeria). Thirty-five adults within the age range of 18–64 years, who are residents in the two communities (Ile-Ife and Modakeke-Ife) were systematically selected from the police records of investigated criminals, while 15 crime-investigating, experienced police officers were purposively selected from a divisional police headquarters and two police stations within the two communities. A qualitative, in-depth interview technique was used in generating relevant data. The selection of cases was from lists of reported and investigated criminal cases at three police stations namely: a divisional police station and one police station from each of the two communities. Findings revealed that many of the participants are sceptical about the readiness of the Nigerian police to respect and protect the fundamental human rights of suspects. In conclusion, there is a high preponderance of delay in criminal investigations and a lack of adequate training for police officers saddled with the responsibilities of crime investigation in the locality. This finding may be extended to the increasing rate of delay in criminal investigations in Nigeria and the perversion of justice. Hence, urgent attention is needed in addressing the loss of confidence in the Nigerian police by the public especially in crime protection and investigation.
Urban and Small Town Comparison of Citizen Demand for Police Services
Authors: Johnson Richard R. , Rhodes Trisha N.
Published: February 2009

Little is known about the similarities and differences that exist between urban and small town police agencies with regard to citizen calls for service. The research about citizen demand for policing services in the USA has focused overwhelmingly on city police agencies and the research methodologies used made direct comparisons with smaller agencies impossible. The present research involved a comparison of calls for service from three urban municipal police departments and three small town departments for the same two-week period of time using identical coding schemes. The findings suggest that urban agencies receive proportionately more order maintenance calls, small town agencies receive proportionately more service calls, and both types of agencies receive similar proportions of law enforcement-related calls. The urban agencies, however, dealt with larger proportions of more serious crimes.
Illegal Drug Use by Police Officers: Using Research and Investigations to Inform Prevention Strategies1
Authors: Gorta Angela
Published: February 2009

Illegal drug use by police officers is a concern in many jurisdictions. The Police Integrity Commission, an independent oversight agency in New South Wales, Australia, conducted a large-scale project on the use of illegal drugs by some NSW police officers. This project, codenamed Operation Abelia, sought to provide a better understanding of the nature of the problem of officer illegal drug use and to identify what can be done to minimise such illegal drug use. This paper outlines how research and investigations were combined to identify areas where further intervention is most likely to assist in minimising illegal drug use by officers. It also provides an overview of the Police Integrity Commission's nine-part strategy for strengthening the NSW Police Force's approach to minimising illegal drug use by its officers. The paper ends with examples of some of the policy, procedural and legislative changes that have resulted from this project.
Locus of Control and Self-Efficacy as Means of Tackling Police Corruption in Nigeria
Authors: Aremu Amos Oyesoji , Pakes Francis , Johnston Les
Published: February 2009

The study investigated the effect of two existential-phenomenological counselling techniques (locus of control and self-efficacy) on the reduction of police corruption-facilitating attitudes in Nigeria. Three hundred police personnel from three State Police Commands participated in the study. These participants who ranged in age between 26 and 53 (Mean = 35.4) were allocated into one of two experimental conditions or a non-treatment control groups and as well matched into commissioned and noncommissioned groups. Participants treated with locus of control and self-efficacy (both involved six weekly sessions) showed significant reduction in a post-test corruption measure. Participants in the self-efficacy condition demonstrated a higher level of change than their counterparts in the locus of control condition. These findings and their implications for integrity-based policing are discussed.
Ignition Interlock Monthly Data Reports
Authors: Fulkerson Andrew
Published: February 2009

While drunken driving arrest rates have plummeted since the 1980s, repeat drunken driving offenders remain a serious and often deadly problem. One intervention which has demonstrated promise in reducing repeat Driving While Intoxicated (DWI) offences is the ignition interlock. The ignition interlock is a breath-alcohol testing device attached to the ignition system of a motor vehicle which prevents the vehicle from starting if the driver produces a breath sample which exceeds a pre-determined alcohol level. The ignition interlock device also collects data as to the number of attempted starts, breath-alcohol levels from the starts, retests and violations resulting in the vehicle being ‘locked out’ and unavailable for use. This paper examines the data reports collected on a sample of interlock users who were court-ordered to install the device as a result of a DWI conviction in the state of Arkansas. Almost half of the subjects experienced one or more violations with a breath alcohol level that exceeded the 0.08 g/dl legal limit. More than 20 per cent had violations at the very high level of 0.15 g/dl. These data suggest that the ignition interlock may be very effective in preventing DWI recidivism among the problem ‘hard-core’ drunk driver.
The Concept of Consent under the Sexual Offences Act 2003
Authors: Elvin Jesse
Published: February 2009

This article examines the provisions relating to consent under the Sexual Offences Act 2003. It considers whether the law in this area now possesses a satisfactory level of clarity following a number of recent Court of Appeal decisions, and concludes that there may be a need for further legislative reform in this respect.
Minding the Gap in Unlawful and Dangerous Act Manslaughter: A Moral Defence of One-Punch Killers
Authors: Mitchell Barry
Published: February 2009

Whilst it is true that the one-punch killer has crossed a moral threshold and acted wrongfully by committing an assault, his victim's death may be both unforeseen and unforeseeable. The gap between what was foreseen/foreseeable and death may thus be considerable. This article suggests it is too great; convicting the killer of manslaughter places too much weight on the element of luck. The task then is to identify an appropriate principle for regulating the gap and in the course of tackling this task the article considers and rejects, inter alia, a recent recommendation by the Law Reform Commission of Ireland.
A Critical Analysis of the Law of Stalking in Scotland
Authors: Middlemiss Sam , Sharp Laura
Published: February 2009

This article analyses the current law of stalking in Scotland in the light of various legal changes which have taken place since the enactment of the Protection from Harassment Act 1997. The various types of crime that can apply to stalking in Scotland are given detailed consideration particularly in relation to monitoring and control of stalkers and enforcement of legal measures against them. Changes in the common law rules dealing with criminal law in Scotland have cast doubt on its continued ability to deal with this problem and the complex, ad hoc nature of statutory protection introduced in recent years against stalkers in Scotland has done little to provide certainty in this area. Although the legal rules in England dealing with this are by no means perfect the utilisation of the two criminal offences in the Protection from Harassment Act 1997 to combat stalking behaviour has had some success. The current legal rules in Scotland are compared with those in England where arguably there is a more developed system of legal protection.
On steady flows of incompressible fluids with implicit power-law-like rheology
Authors: Bulíček Miroslav , Gwiazda Piotr , Málek Josef , Świerczewska-Gwiazda Agnieszka
Published: February 2009

We consider steady flows of incompressible fluids with power-law-like rheology given by an implicit constitutive equation relating the Cauchy stress and the symmetric part of the velocity gradient in such a way that it leads to a maximal monotone (possibly multivalued) graph. Such a framework includes standard Navier–Stokes and power-law fluids, Bingham fluids, Herschel–Bulkley fluids, and shear-rate dependent fluids with discontinuous viscosities as special cases. We assume that the fluid adheres to the boundary.

Using tools such as the Young measures, properties of spatially dependent maximal monotone operators and Lipschitz approximations of Sobolev functions, we are able to extend the results concerning large data existence of weak solutions to those values of the power-law index that are of importance from the point of view of engineering and physical applications.
A Collection of Ds Insertional Mutants Associated With Defects in Male Gametophyte Development and Function in Arabidopsis thaliana
Authors: Boavida Leonor C , Shuai Bin , Yu Hee-Ju , Pagnussat Gabriela C , Sundaresan Venkatesan , McCormick Sheila
Published: February 2009

Functional analyses of the Arabidopsis genome require analysis of the gametophytic generation, since ∼10% of the genes are expressed in the male gametophyte and ∼9% in the female gametophyte. Here we describe the genetic and molecular characterization of 67 Ds insertion lines that show reduced transmission through the male gametophyte. About half of these mutations are male gametophytic-specific mutations, while the others also affect female transmission. Genomic sequences flanking both sides of the Ds element were recovered for 39 lines; for 16 the Ds elements were inserted in or close to coding regions, while 7 were located in intergenic/unannotated regions of the genome. For the remaining 16 lines, chromosomal rearrangements such as translocations or deletions, ranging between 30 and 500 kb, were associated with the transposition event. The mutants were classified into five groups according to the developmental processes affected; these ranged from defects in early stages of gametogenesis to later defects affecting pollen germination, pollen tube growth, polarity or guidance, or pollen tube–embryo sac interactions or fertilization. The isolated mutants carry Ds insertions in genes with diverse biological functions and potentially specify new functions for several unannotated or unknown proteins.