bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel G‐quadruplex motif modulates promoter activity of human thymidine kinase 1
Authors: Basundra Richa , Kumar Akinchan , Amrane Samir , Verma Anjali , Phan Anh Tuân , Chowdhury Shantanu
Published: August 2010

G‐quadruplex motifs constitute unusual DNA secondary structures formed by stacking of planar hydrogen‐bonded G‐tetrads. Recent genome‐wide bioinformatics and experimental analyses have suggested the interesting possibility that G‐quadruplex motifs could be cis‐regulatory elements. Here, we identified a characteristic potential G‐quadruplex‐forming sequence element within the promoter of human thymidine kinase 1 (TK1). Our NMR, UV and CD spectroscopy and gel electrophoresis data suggested that this sequence forms a novel intramolecular G‐quadruplex with two G‐tetrads in K+ solution. The results presented here indicate the role of this G‐quadruplex motif in transcription of TK1 in cell‐based reporter assays. Specific nucleotide substitutions designed to destabilize the G‐quadruplex motif resulted in increased promoter activity, supporting direct involvement of the G‐quadruplex motif in transcription of TK1. These studies suggest that the G‐quadruplex motif may be an important target for controlling critical biological processes, such as DNA synthesis, mediated by TK1.
High‐resolution crystal structures of the flavoprotein NrdI in oxidized and reduced states – an unusual flavodoxin
Authors: Johansson Renzo , Torrents Eduard , Lundin Daniel , Sprenger Janina , Sahlin Margareta , Sjöberg Britt‐Marie , Logan Derek T.
Published: August 2010

The small flavoprotein NrdI is an essential component of the class Ib ribonucleotide reductase system in many bacteria. NrdI interacts with the class Ib radical generating protein NrdF. It is suggested to be involved in the rescue of inactivated diferric centres or generation of active dimanganese centres in NrdF. Although NrdI bears a superficial resemblance to flavodoxin, its redox properties have been demonstrated to be strikingly different. In particular, NrdI is capable of two‐electron reduction, whereas flavodoxins are exclusively one‐electron reductants. This has been suggested to depend on a lesser destabilization of the negatively‐charged hydroquinone state than in flavodoxins. We have determined the crystal structures of NrdI from Bacillus anthracis, the causative agent of anthrax, in the oxidized and semiquinone forms, at resolutions of 0.96 and 1.4 Å, respectively. These structures, coupled with analysis of all curated NrdI sequences, suggest that NrdI defines a new structural family within the flavodoxin superfamily. The conformational behaviour of NrdI in response to FMN reduction is very similar to that of flavodoxins, involving a peptide flip in a loop near the N5 atom of the flavin ring. However, NrdI is much less negatively charged than flavodoxins, which is expected to affect its redox properties significantly. Indeed, sequence analysis shows a remarkable spread in the predicted isoelectric points of NrdIs, from approximately pH 4–10. The implications of these observations for class Ib ribonucleotide reductase function are discussed.
DIP2 disco‐interacting protein 2 homolog A (Drosophila) is a candidate receptor for follistatin‐related protein/follistatin‐like 1 – analysis of their binding with TGF‐β superfamily proteins
Authors: Tanaka Masao , Murakami Kosaku , Ozaki Shoichi , Imura Yoshitaka , Tong Xiao‐Peng , Watanabe Takuo , Sawaki Toshioki , Kawanami Takafumi , Kawabata Daisuke , Fujii Takao , Usui Takashi , Masaki Yasufumi , Fukushima Toshihiro , Jin Zhe‐Xiong , Umehara Hisanori , Mimori Tsuneyo
Published: August 2010

Follistatin‐related protein (FRP)/follistatin‐like 1 (FSTL1) is a member of the follistatin protein family, all of which share a characteristic structure unit found in follistatin, called the FS domain. Developmental studies have suggested that FRP regulates organ tissue formation in embryos. Immunological studies showed that FRP modifies joint inflammation in arthritic disease, and modulates allograft tolerance. However, the principle physiological function of FRP is currently unknown. To address this issue, we cloned four FRP‐associated proteins using a two‐hybrid cloning method: disco‐interacting protein 2 homolog A from Drosophila (DIP2A), CD14, glypican 1 and titin. Only DIP2A was expected to be a membrane receptor protein with intracellular regions. Over‐expression of FLAG epitope‐tagged DIP2A augmented the suppressive effect of FRP on FBJ murine osteosarcoma viral oncogene homolog (FOS) expression, and the Fab fragment of IgG to FLAG blocked this effect. Knockdown of Dip2a leaded to Fos gene up‐regulation, and this was not affected by exogenous FRP. These in vitro experiments confirmed that DIP2A could be a cell‐surface receptor protein and mediate a FOS down‐regulation signal of FRP. Moreover, molecular interaction analyses using Biacore demonstrated that FRP bound to DIP2A and CD14, and also with proteins of the TGF‐β superfamily, i.e. activin, TGF‐β, bone morphogenetic protein 2/4 (BMP‐2/4), their receptors and follistatin. FRP binding to DIP2A was blocked by CD14, follistatin, activin and BMP‐2. FRP blocked the ligand–receptor binding of activin and BMP‐2, but integrated itself with that of BMP‐4. This multi‐specific binding may reflect the broad physiological activity of FRP.

Structured digital abstract

A list of the large number of protein‐protein interactions described in this article is available via the MINT article ID MINT‐7990613
Prevention of Wellbore Clogging by Intermittent Abstraction
Authors: Van Beek Kees , Breedveld Rob , Tas Martijn , Kollen René
Published: August 2010

Wellfield “Tull en ’t Waal” (water utility Vitens Midden Nederland) suffers extensively from wellbore (or mechanical) clogging. To prevent this type of clogging, wells have been operated intermittently since August 2005 using a carrousel well operation schedule. Since the introduction of this schedule, wellbore clogging has become minimal.
Relative Vulnerability of Public Supply Wells to VOC Contamination in Hydrologically Distinct Regional Aquifers
Authors: Kauffman Leon J. , Chapelle Francis H.
Published: August 2010

A process‐based methodology was used to compare the vulnerability of public supply wells tapping seven study areas in four hydrologically distinct regional aquifers to volatile organic compound (VOC) contamination. This method considers (1) contributing areas and travel times of groundwater flowpaths converging at individual supply wells, (2) the oxic and/or anoxic conditions encountered along each flowpath, and (3) the combined effects of hydrodynamic dispersion and contaminant‐ and oxic/anoxic‐specific biodegradation. Contributing areas and travel times were assessed using particle tracks generated from calibrated regional groundwater flow models. These results were then used to estimate VOC concentrations relative to an unspecified initial concentration (C/C0) at individual public supply wells. The results show that the vulnerability of public supply wells to VOC contamination varies widely between different regional aquifers. Low‐recharge rates, long travel times, and the predominantly oxic conditions characteristic of Basin and Range aquifers in the western United States leads to lower vulnerability to VOCs, particularly to petroleum hydrocarbons such as benzene and toluene. On the other hand, high recharge rates and short residence times characteristic of the glacial aquifers of the eastern United States leads to greater vulnerability to VOCs. These differences lead to distinct patterns of C/C0 values estimated for public supply wells characteristic of each aquifer, information that can be used by resource managers to develop monitoring plans based on relative vulnerability, to locate new public supply wells, or to make land‐use management decisions.
Research Article: Synthesis, Biological Evaluation and Molecular Modeling Studies ofN‐aryl‐2‐arylthioacetamides as Non‐nucleoside HIV‐1 Reverse Transcriptase Inhibitors
Authors: Xiaohe Zhu , Yu Qin , Hong Yan , Xiuqing Song , Rugang Zhong
Published: August 2010

A series ofN‐aryl‐2‐arylthioacetamide derivatives (2–4) designed as non‐nucleoside reverse transcriptase inhibitors was synthesized and evaluated for their inhibitory activity against HIV‐1 (IIIB) replication in MT‐4 cell cultures. The compounds2–4were performed by the reaction of thiols and 2‐chloro‐N‐substituted‐acetamides and active in the lower micromolar concentration (1.25–20.83 μm). The studies of structure–activity relationship suggested that 1H‐benzo[d]imidazole ring at arylthio moiety strongly improved the anti‐HIV activity and consistent with the experimental data. The results of molecular modeling and docking within the RT non‐nucleoside binding site using AutoDockconfirmed that the3series, similar to other non‐nucleoside reverse transcriptase inhibitors such asN‐(5‐chloro‐2‐pyridinyl)‐N’‐[2‐(4‐ethoxy‐3‐fluoro‐2‐pyridinyl)ethyl]‐thiourea (PETT), was assumed in a butterfly‐like conformation and helped to rationalize some SARs and the biological activity data.
Research Article: Computer‐Assisted Design of Pro‐drugs for Antimalarial Atovaquone
Authors: Karaman Rafik , Hallak Hussein
Published: August 2010

Density Functional Theory (DFT) and ab initio calculation results for the proton transfer reaction in Kirby’s enzyme models 1‐6 reveal that the reaction rate is largely dependent on the existence of a hydrogen bonding net in the reactants and the corresponding transition states. Further, the distance between the two reacting centers and the angle of the hydrogen bonding formed along the reaction path has profound effects on the rate. Hence, the study on the systems reported herein could provide a good basis for designing antimalarial (atovaquone) pro‐drug systems that can be used to release the parent drug in a controlled manner. For example, based on the calculated log EM, the cleavage process for pro‐drug 1Pro may be predicted to be about 1011 times faster than that for a pro‐drug 4Pro and about 104 times faster than pro‐drug 2Pro: rate 1Pro > rate 2Pro > rate 4Pro. Thus, the rate by which the pro‐drug releases the antimalarial drug can be determined according to the nature of the linker (Kirby’s enzyme model 1‐6).
Appearance of Tissue Transglutaminase in Astrocytes in Multiple Sclerosis Lesions: A Role in Cell Adhesion and Migration?
Authors: Van Strien Miriam E. , Drukarch Benjamin , Bol John G. , Van Der Valk Paul , Van Horssen Jack , Gerritsen Wouter H. , Breve John J. , Van Dam Anne‐Marie
Published: August 2010

Multiple Sclerosis (MS) is a neuroinflammatory disease mainly affecting young adults. A major pathological hallmark of MS is the presence of demyelinated lesions in the central nervous system. In the active phase of the disease, astrocytes become activated, migrate and contribute to local tissue remodeling that ultimately can result in an astroglial scar. This process is facilitated by extracellular matrix proteins, including fibronectin. Tissue Transglutaminase (TG2) is a multifunctional enzyme with a ubiquitous tissue distribution and it has been shown that inflammatory cytokines can induce TG2 activity. In addition, TG2 is known to mediate cell adhesion and migration. We therefore hypothesized that TG2 is present in MS lesions and plays a role in cell adhesion and/or migration. Our studies showed that TG2 immunoreactivity appeared in astrocytes in active and chronic active MS lesions. These TG2 positive astrocytes partly co‐localized with fibronectin. Additional in vitro studies showed that TG2 mediated astrocytoma adhesion to and migration on the extracellular matrix protein fibronectin. We therefore speculate that TG2 mediates the enhanced interaction of astrocytes with fibronectin in the extracellular matrix of MS lesions, thereby contributing to astrocyte adhesion and migration, and thus in tissue remodeling and possibly glial scarring.
Presence of Tissue Transglutaminase in Granular Endoplasmic Reticulum is Characteristic of Melanized Neurons in Parkinson's Disease Brain
Authors: Wilhelmus Micha M. M. , Verhaar Robin , Andringa Gerda , Bol John G. J. M. , Cras Patrick , Shan Ling , Hoozemans Jeroen J. M. , Drukarch Benjamin
Published: August 2010

Parkinson's disease (PD) is characterized by the accumulation of α‐synuclein aggregates and degeneration of melanized neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross‐linking. In PD brain, tTG‐induced cross‐links have been identified in α‐synuclein monomers, oligomers and α‐synuclein aggregates. However, whether tTG and α‐synuclein occur together in PD affected neurons remains to be established. Interestingly, using immunohistochemistry, we observed a granular distribution pattern of tTG, characteristic of melanized neurons in PD brain. Apart from tTG, these granules were also positive for typical endoplasmic reticulum (ER)‐resident chaperones, that is, protein disulphide isomerase, ERp57 and calreticulin, suggesting a direct link to the ER. Additionally, we observed the presence of phosphorylated pancreatic ER kinase (pPERK), a classical ER stress marker, in tTG granule positive neurons in PD brain, although no subcellular colocalization of tTG and pPERK was found. Our data therefore suggest that tTG localization to granular ER compartments is specific for stressed melanized neurons in PD brain. Moreover, as also α‐synuclein aggregates were observed in tTG granule positive neurons, these results provide a clue to the cellular site of interaction between α‐synuclein and tTG.
Prevalence of High‐Risk Cardiovascular Conditions and the Status of Hypertension Management Among Hypertensive Adults 65 Years and Older in the United States: Analysis of a Primary Care Electronic Medical Records Database
Authors: Biskupiak Joseph E. , Kim Jaewhan , Phatak Hemant , Wu David
Published: August 2010

J Clin Hypertens (Greenwich).

This study compared the prevalence of high‐risk cardiovascular (CV) conditions, antihypertensive medication treatment patterns, and demographic and clinical characteristics associated with blood pressure (BP) goal attainment between elderly (65 years and older) and nonelderly (younger than 65 years) adults with hypertension. Retrospective cohort study was conducted using an electronic medical record database among patients receiving at least 1 antihypertensive medication. CV risk profiles were assessed by International Classification of Diseases, 9th Revision diagnosis codes. Treatment patterns were assessed by the number of antihypertensive medications prescribed. BP goal attainment was determined by the mean of the last 2 BP readings during 1 year of follow‐up. Logistic regression estimated the odds of achieving BP goal. There were 61,355 nonelderly (mean age, 51.8 years) and 47,796 elderly (mean age, 73.2 years) patients in the study. Elderly patients had statistically significant higher levels of isolated systolic hypertension and complicated hypertension. Elderly patients had statistically significant higher levels of prescribing patterns characterized by multiple antihypertensive medications but statistically significant lower levels of BP goal attainment. Age 65 years and older, African American race, body mass index ≥30, and the presence of complicated hypertension were found to be statistically significant factors contributing to a lower likelihood of BP goal attainment. Despite aggressive antihypertensive treatment, elderly patients are less likely to achieve BP goals. J Clin Hypertens (Greenwich). 2010;12:935–944. © 2010 Wiley Periodicals, Inc.
ORIGINAL ARTICLE: Comparison of a Commonwealth‐initiated regional radiation oncology facility in Toowoomba with a Queensland Health facility
Authors: Poulsen M , Middleton M , McQuitty S , Ramsay J , Gogna K , Martin J , Khoo E , Wong W , Fairweather R , Walpole E
Published: August 2010

The aim was to compare a private Commonwealth‐initiated regional radiation oncology facility in Toowoomba with a Queensland Health facility (QHF) in Brisbane. The comparison concentrated on staffing, case mix and operational budgets, but was not able to look at changes in access to services. Data were collected from the two facilities from January 2008 to June 2008 inclusive. A number of factors were compared, including case mix, staffing levels, delay times for treatment, research, training and treatment costs. The case mix between the two areas was similar with curative treatments making up just over half the work load in both centres and two‐thirds the work being made up of cancers of breast and prostate. Staffing levels were leaner in Toowoomba, especially in the areas of nursing, administration and trial coordinators. Research activity was slightly higher in Toowoomba. The average medicare cost per treatment course was similar in both centres ($5000 per course). Total costs of an average treatment including patient, State and Commonwealth costs, showed a 30% difference in costing favouring Toowoomba. This regional radiation oncology centre has provided state‐of‐the‐art cancer care that is close to home for patients living in the Darling Downs region. Both public and private patients have been treated with modest costs to the patient and significant savings to QH. The case mix is similar to the QHF, and there has been significant activity in clinical research. A paperless working environment is one factor that has allowed staffing levels to be reduced. Ongoing support from Governments are required if private facilities are to participate in important ongoing staff training.
ORIGINAL ARTICLE: Radiological review of intercostal artery: Anatomical considerations when performing procedures via intercostal space
Authors: Choi S , Trieu J , Ridley L
Published: August 2010

Introduction: The aim of this study was to closely examine the course of the intercostal arteries within the intercostal spaces particularly with regard to where the arteries were located in relation to their adjacent ribs. The degree of tortuosity of the arteries was also examined, along with anatomical differences in different age groups.

Methods: A total of 81 patients between the age of 30 and 90 years who had underwent a CT examination of the chest for any indication were included in the study. All studies were performed on a dual source 64 slice CT (Siemens Definition Erlangen Germany). Analysis of the intercostal arteries was performed on a CT workstation using volume rendered 3D reconstructions F, or each patient the 10'n intercostals pacesb ilaterally were examined for the course and tortuosity of the intercostal arteries.

Results: The ICA is located relatively inferiorly in the intercostal space at costovertebral junction and it gradually becomes more superiorly positioned within the intercostal space it as courses laterally. This finding was consistent in all age groups. In addition, analysis of the data demonstrated increasing intercostal artery tortuosity with advancing age.

Conclusion: In this study we have examined the course of the posterior intercostal arteries using MDCT. This study confirms the classical description of the course of ICA. We have shown that in the medial chest, posteriorly, the artery is located in the inferior half of the intercostal space. As it moves away from the costovertebral junction it travels closer to the inferior border of the rib above and reaches the intercostal groove. We have also shown that the artery tends to be more tortuous in elderly patients, decreasing the area of “safe” space for interventions. Both of these findings are relevant to radiologists and non‐radiologists performing interventional procedures via the intercostal space.
ORIGINAL ARTICLE: Long‐term outcomes of vertebroplasty for osteoporotic compression fractures
Authors: Thillainadesan J , Schlaphoff G , Gibson KA , Hassett GM , McNeil HP
Published: August 2010

Introduction: This study aimed to determine outcomes of percutaneous vertebroplasty for osteoporotic vertebral compression fractures (VCFs).

Methods: Prospective assessment of short‐term (≤6 weeks), medium‐term (6 months) and long‐term (29 months) outcomes of vertebroplasty, followed by a retrospective long‐term follow‐up of patients treated with vertebroplasty compared with conservative therapy. Outcomes measured were visual analogue scale pain scores, analgesic use, disability scores using the Roland Morris Disability questionnaire and a number of new VCFs.

Results: In 27 patients with acute VCFs followed prospectively, vertebroplasty resulted in significant reductions in pain levels (56‐mm reduction on a 100‐mm scale) and disability scores (11.8‐point reduction on a 24‐point scale) at all follow‐up points up to a mean of 29 months compared with pre‐vertebroplasty levels (P < 0.001). Analgesic use was significantly less intense in the short and medium term after vertebroplasty (P < 0.005). In 25 patients who had vertebroplasty for VCF, a sustained reduction in all outcomes was demonstrated at a mean follow‐up of 30 months, with less pain, significantly lower disability scores (P < 0.05) and less analgesic use (P < 0.05) compared with nine conservatively treated subjects. During the follow‐up period, six new VCFs occurred in 4/25 vertebroplasty patients compared with four new VCFs in 2/9 control subjects.

Conclusions: Vertebroplasty provides significant and clinically meaningful reductions in pain, analgesic use, and disability in the short, medium and long term. Compared with conservative therapy, vertebroplasty provides significantly greater functional improvement and reduction in analgesic use. The procedure is relatively safe with no clearly increased risk of new vertebral fractures.
ORIGINAL ARTICLE: Enlarged hilar and mediastinal lymph nodes in chronic obstructive pulmonary disease
Authors: Kirchner J , Kirchner EM , Goltz JP , Obermann A , Kickuth R
Published: August 2010

Introduction:  To evaluate the frequency of enlarged hilar or mediastinal lymph nodes in patients suffering from chronic obstructive pulmonary disease (COPD).

Methods:  In a retrospective study, 89 patients with proven COPD were analysed. Exclusion criteria were history of malignant disease or clinical evidence of pneumonia. Prevalence, size, and localisation of enlarged lymph nodes were assessed by multi‐slice computed tomography (MSCT) and correlated with the clinical stages following the GOLD classification as well as the MSCT findings of bronchitis and emphysema.

Results:  44/89 (49%) of our patients showed enlarged lymph nodes. Lymph node enlargement was more often seen in the mediastinum (48%) than the hilar region (20%). The most common localisation of enlarged mediastinal lymph nodes was the regional station 7 following the ATS mapping (infracarinal). Patients with a stage I following the GOLD classification showed enlarged lymph nodes in 49% (18/37), stage II in 46% (12/26), stage III in 58% (7/12) and stage IV in 50% (7/14). These findings did not differ significantly (P > 0.05). Severe airway wall thickening (42/89) was significantly more often associated with an increase of nodal enlargement (64%) (P < 0.05).

Conclusion:  The present study demonstrates that enlarged hilar and mediastinal lymph nodes may occur in a rather high percentage of patients suffering from COPD, especially in those with the MSCT finding of severe bronchitis.
ORIGINAL ARTICLE: Retrospective audit of the investigation of patients with suspected acute subarachnoid haemorrhage
Authors: Muhammed O , Teubner D , Jones DN , Slavotinek JP
Published: August 2010

Introduction:  Recommended investigational care (RIC) of emergency department (ED) patients with suspected subarachnoid haemorrhage comprises lumbar puncture (LP) to detect xanthochromia if the preceding CT scan is negative.

Methods:  Retrospective audit of the investigational care of 100 consecutive ED patients presenting with possible subarachnoid haemorrhage.

Results:  Of the 100 patients, 91 had negative CT, and 36 (39.6%) of these patients had an LP performed to detect xanthochromia (i.e. RIC). Fifty‐five of 91 (60.4%) patients did not receive RIC.

Of the 55 patients who did not receive RIC, 25 (45.5%) had a documented senior clinical decision not to perform an LP; 15 (27.3%) had no documented reason; five (9.1%) refused consent; two (3.6%) had an LP but no xanthochromia requested, one patient did not have an LP because of technical issues, six patients underwent CT angiography (CTA), and one patient underwent magnetic resonance angiography (MRA), in the absence of a LP, following a negative CT. Two patients underwent CTA following a negative xanthochromia result. Patients admitted to the emergency extended care unit had 6.85 times the odds of receiving RIC (95% CI 2.20–21.4).

Conclusions:  Fifty‐five (55) of 91 (60%) ED patients did not receive RIC. Fifteen of the 55 did not have any documented justification for not performing an LP with xanthochromia testing. Admission to an emergency extended care unit was a predictor of receiving RIC. Inappropriate use of CTA and MRA was identified. These findings have important implications for patient safety. Multifaceted strategies are required to close this evidence–practice gap.
PICTORIAL ESSAY: Role of FDG PET/CT in imaging of renal lesions
Authors: Kochhar R , Brown RK , Wong CO , Dunnick NR , Frey KA , Manoharan P
Published: August 2010

Focal incidental renal lesions are commonly encountered on positron emission tomography (PET)/computed tomography (CT) imaging. The vast majority of these lesions are benign. However, the interpretation of renal lesions can be problematic if the imaging criteria of simple cysts are not met. Limited literature exists on the characterisation of renal masses with metabolic imaging. The purpose of this article is to focus on the imaging features of benign and malignant renal masses with PET/CT. The lesions discussed include renal cyst, angiomyolipoma, oncocytoma, renal cell carcinoma, renal metastases and other infiltrating neoplastic processes affecting the kidney. Both the anatomical and metabolic features which characterise these benign and malignant entities are described. We emphasise the importance of viewing the CT component to identify the typical morphological features and discuss how to best use hybrid imaging for management of renal lesions. Metabolic imaging has a promising role in the imaging of renal lesions and can help prevent unnecessary biopsies and ensure optimal management of suspicious lesions.
ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy
Authors: Marsh JC , Gielda BT , Herskovic AM , Wendt JA , Turian JV
Published: August 2010

Introduction:  The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI).

Methods and Materials:  We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0‐cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V100 ≥ 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V100.

Results:  In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V100 for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27–17.5).

Conclusions:  It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.
REVIEW ARTICLE: Paediatric nasopharyngeal rhabdomyosarcoma: A case series and literature review
Authors: Healy JN , Borg MF
Published: August 2010

Rhabdomyosarcoma (RMS) is the most common soft tissue tumour in children, with the head and neck region accounting for 35–40% of cases. Nasopharyngeal RMSs tend to grow rapidly and invade adjacent structures. Both the Intergroup Rhabdomyosarcoma Studies and the European Studies have established that the ideal management of this disease is multimodal, using a combination of surgery, chemotherapy and radiotherapy. This case series examines the role of radiotherapy in the management of paediatric nasopharyngeal RMSs, with particular reference to long‐term morbidity and disease‐free survival. The cases of five children with nasopharyngeal RMS were reviewed and a systematic review of the literature contained in the PubMed databases was conducted to establish 24 individually detailed cases. Management in all patients was multimodal, using a combination of chemotherapy, radiotherapy as well as surgery. External beam radiotherapy is an integral component of treatment for nasopharyngeal RMSs. With more patients surviving for longer periods, more long‐term sequelae of radiotherapy have been reported. Complications include sensorineural deafness, endocrine manifestations following radiation of the pituitary gland, cranial nerve palsies, second malignancies within the radiation field, cataract formation, retinopathy and growth disturbance. Morbidity from radiotherapy may be considerable and depends on the field and dose of radiation. Current advances in radiotherapy are aimed at improving the rate of tumour control and reducing such complications. Recent improvements in imaging and conformal techniques have the potential to reduce the morbidity associated with radiotherapy in this cohort.
Human hair melanins: what we have learned and have not learned from mouse coat color pigmentation
Authors: Ito Shosuke , Wakamatsu Kazumasa
Published: August 2010

Hair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur‐containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase‐related proteins are involved in eumelanogenesis, while only the additional presence of cysteine is necessary for pheomelanogenesis. Other important proteins involved in melanogenesis include P protein, MATP protein, α‐MSH, agouti signaling protein (ASIP), MC1R (the receptor for MSH and ASIP), and SLC7A11, a cystine transporter. Many studies have examined the effects of loss‐of‐function mutations of those proteins on mouse coat color pigmentation. In contrast, much less is known regarding the effects of mutations of the corresponding proteins on human hair pigmentation except for MC1R polymorphisms that lead to pheomelanogenesis. This perspective will discuss what we have/have not learned from mouse coat color pigmentation, with special emphasis on the significant roles of pH and the level of cysteine in melanosomes in controlling melanogenesis. Based on these data, a hypothesis is proposed to explain the diversity of human hair pigmentation.
Sunscreen prevention of melanoma in man and mouse
Authors: Klug Heather L. P. , Tooze Janet A. , Graff‐Cherry Cari , Anver Miriam R. , Noonan Frances P. , Fears Thomas R. , Tucker Margaret A. , De Fabo Edward C. , Merlino Glenn
Published: August 2010

View the pubcast on this paper at http://www.scivee.tv/node/25768
Cancer stem cells versus phenotype‐switching in melanoma
Authors: Hoek Keith S. , Goding Colin R.
Published: August 2010

Tumours comprise multiple phenotypically distinct subpopulations of cells, some of which are proposed to possess stem cell‐like properties, being able to self‐renew, seed and maintain tumours, and provide a reservoir of therapeutically resistant cells. Here, we use melanoma as a model to explore the validity of the cancer stem cell hypothesis in the light of accumulating evidence that melanoma progression may instead be driven by phenotype‐switching triggered by genetic lesions that impose an increased sensitivity to changes in the tumour microenvironment. Although at any given moment cells within a tumour may exhibit differentiated, proliferative or invasive phenotypes, an ability to switch phenotypes implies that most cells will have the potential to adopt a stem cell‐like identity. Insights into the molecular events underpinning phenotype‐switching in melanoma highlight the close relationship between signalling pathways that generate, maintain and activate melanocyte stem cells as well as the inverse correlation between proliferation and invasive potentials. An understanding of phenotype‐switching in melanoma, and in particular the signalling events that regulate the expression of the microphthalmia‐associated transcription factor Mitf, points to new therapeutic opportunities aimed at eradicating therapeutically resistant stem cell‐like melanoma cells.
Latanoprost versus timolol as first choice therapy in patients with ocular hypertension. A cost‐effectiveness analysis
Authors: Peeters Andrea , Schouten Jan S.A.G. , Severens Johan L. , Hendrikse Fred , Prins Martin H. , Webers Carroll A.B.
Published: August 2010

Purpose: To determine the cost‐effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol.

Methods: Two strategies for OH therapy are modelled, (1) ‘starting with timolol’ and (2) ‘starting with latanoprost’. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side‐effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow‐up with IOP‐dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP‐lowering effect of drugs is based on meta‐analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients.

Results: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (±0.017) mm Hg (strategy 1) and to 16.5 (±0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were € 367 and € 469, respectively. Lifetime blindness and costs were 0.0334 years and € 3 514 (strategy 1) and 0.0318 years and € 4 397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately € 537 000.

Conclusion: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high.
Australian CEO Remuneration*
Authors: Heaney Richard , Tawani Vineet , Goodwin John
Published: August 2010

Cross‐sectional analysis of the remuneration paid by a sample of 1,144 listed Australian companies in 2006 to their CEOs highlights the variation in the level and composition of remuneration both within and across industries. Average annual CEO remuneration for 2006 is $730,000 with 79% short‐term, 14% long‐term and 7% post‐employment remuneration. These components of remuneration structure, company size and corporate governance measures provide insight into the variation in CEO remuneration. There is no evidence of a positive relation between current year CEO remuneration and following year performance.
Effects on the PNG Economy of a Major LNG Project*
Authors: Dixon Peter B. , Kauzi Gae , Rimmer Maureen T.
Published: August 2010

ExxonMobil is undertaking an LNG project in Papua New Guinea (PNG) with setup expenditures in 2010–2012 of $A12 billion and annual export revenue averaging $A4 billion (2010 prices) over 2013–2042. These are huge numbers relative to PNG’s GDP and exports ($A10 billion and $A6 billion in 2010). This paper uses a dynamic computable general equilibrium (CGE) model to estimate impacts in PNG on consumption, sectoral outputs, wages, trade and the real exchange rate under three macroeconomic management scenarios. The Project offers significant benefits but figures on Project size give an exaggerated impression. The focus should be on the use of PNG factors of production and revenues flowing to the government.
Special Taxation of Alcoholic Beverages to Correct Market Failures*
Authors: Freebairn John
Published: August 2010

In most countries, including Australia, special excise and other taxes are imposed on beer, wine and spirits. This study reviews the market failure arguments for special taxation of alcoholic beverages, evaluates the pros and cons of different externality correction taxes in terms of the tax base and tax rate, and uses the results to suggest reforms. A common specific tax per litre of alcohol by volume across the different beverages levied on a consumption base at the wholesale level, and indexed by a wage index, is proposed.
Excise and Import Taxes on Wine Versus Beer and Spirits: An International Comparison*
Authors: Anderson Kym
Published: August 2010

Nearly all countries tax the domestic consumption of alcoholic beverages. However, the rates of taxation, and the tax instruments used, vary enormously between countries. This study provides estimates, for a wide range of high‐income and developing countries, of the consumer tax equivalents (CTEs) of wine, beer and spirits taxes as of 2008. It encompasses wholesale sales taxes, excise taxes and import tariffs expressed both in dollars per litre of alcohol and as a percentage of what the wholesale price would be without those taxes (as many taxes are volumetric and so their percentage CTE rates vary with the price of the product). The wine CTE tends to be lower in countries with a large wine industry, by which standard Australia is shown to have relatively high wine CTEs at least for premium wine. However, because Australia uses a percentage tax rather than the far more commonly used volumetric tax measure, it has a relatively low rate for non‐premium wine.
How Should Macroeconomic Policy Respond to Foreign Financial Crises?*
Authors: Makin Anthony J.
Published: August 2010

This paper examines the impact of global financial crises on the Australian economy and how monetary and fiscal policy may be used to manage economic downturns that result. To do so, it presents a straightforward analytical framework incorporating financial wealth, exchange rate expectations, foreign demand and interest rate risk to analyse the key role played by the nominal exchange rate in insulating national income from the worst effects of foreign financial crises. In the event the economy is not fully insulated by exchange rate depreciation, it shows that, in principle, monetary policy is a superior instrument to fiscal stimulus for restoring aggregate demand to the full employment level. Since monetary policy is not handicapped by numerous problems that render fiscal stimulus less effective, it should normally be considered a sufficient instrument on its own.
What Do the Bingers Drink? Micro‐Unit Evidence on Negative Externalities and Drinker Characteristics of Alcohol Consumption by Beverage Types*
Authors: Srivastava Preety , Zhao Xueyan
Published: August 2010

The recent debate on alcohol tax reform, recommendations from the national preventative health task force and from the Henry Tax Review in Australia have highlighted the need for quantifying externalities of excessive alcohol consumption by beverage types. This paper presents microlevel information from the Australian National Drug Strategy Household Surveys to examine the association between risky drinking behaviour, drinker characteristics, health and labour market status, and types of alcohol beverages consumed. Drinkers of regular‐strength beer (RSB) and ready‐to‐drink spirits in a can (RTDC) have the highest incidences of heavy bingeing, whereas low‐alcohol beer, fortified wine or bottled wine drinkers are least likely. Bottled spirits, RSB and RTDC are most likely to be linked to risky behaviour such as property damage, stealing, and verbal and physical abuse under alcohol influence. All three spirit products are overwhelmingly the favourable drinks for the underage and young drinkers. Risky drinking behaviour is not found to be associated with the alcohol strength of the products.
Carbon Leakages, Consumption‐based Carbon Taxes and International Climate Change Agreements
Authors: Clarke Harry
Published: August 2010

The issue of devising an efficient and equitable global climate change mitigation agreement is examined. While the possibility of catastrophic damages contingent on unmitigated climate change provides cogent reasons for self‐interested, large countries to unilaterally mitigate there are practical reasons for them not to do so. A key concern for developed countries is possible carbon leakages. For developing countries, the need to pursue growth objectives can restrict the proclivity to mitigate. Carbon leakage issues can be addressed using border tax adjustments although these raise computational complexity, GATT‐rules consistency and equity issues for developing countries. If the efficiency gains from utilising border tax adjustments are to be realised, compensation schemes must address these equity issues. An analysis is provided explicitly addressing the role of China and the United States.
Flow and Pressure Distribution in Fuel Cell Manifolds
Authors: Lebæk Jesper , Bang Mads , Kær Søren Knudsen
Published: August 2010

The manifold is an essential part of the fuel cell stack. Evidently, evenly distributed reactants are a prerequisite for an efficient fuel cell stack. In this study, the cathode manifold ability to distribute air to the cells of a 70 cell stack is investigated experimentally. By means of 20 differential pressure gauges, the flow distribution is mapped for several geometrical and operating conditions. Special attention is given to the inlet conditions of the manifold. Here, a diffuser design was constructed in order to replace the conventional circular inlet design. The diffuser design showed significant improvements to the flow distribution in comparison to the circular design. Moreover, the best flow distribution was found using a U-shaped configuration.
The Use of a High Temperature Wind Tunnel for MT-SOFC Testing—Part I: Detailed Experimental Temperature Measurement of an MT-SOFC Using an Avant-Garde High Temperature Wind Tunnel and Various Measurement Techniques
Authors: Lawlor V. , Zauner G. , Hochenauer C. , Mariani A. , Griesser S. , Carton J. G. , Klein K. , Kuehn S. , Olabi A. G. , Cordiner S. , Meissner D. , Buchinger G.
Published: August 2010

The purpose of the first part of this study was to compare four different temperature measuring methods. The application of these tools for possible temperature monitoring or calibration of monitors of microtubular solid oxide fuel cells (MT-SOFCs) is explored. It was found that a thermographic camera is very useful to visualize the temperature gradient on the outside of a cell, while an electrochemical impedance spectroscopy method was useful for estimating the core temperature of a test cell. A standard thermocouple was also used in combination with the previous two methods. Furthermore, an inexpensive laser guided thermometer was also tested for MT-SOFC temperature measurement. This initial study has opened up a range of questions not only about the effect of the experimental apparatus on the measurement results but also about the radial temperature distribution through a MT-SOFC in a working mode. Both these topics will be further investigated in part II of this study through a computational fluid dynamics study. This should provide additional interesting information about any differences between testing single cells and those within a bundle of cells. The discussed results are expected to be mainly temperature related, which should have direct consequences on power output and optimized gas inlet temperatures.
Numerical Analysis of a Steam Reformer Coupled With a Combustion Burner
Authors: Park Joonguen , Bae Joongmyeon , Lee Shinku , Kim Myungjun
Published: August 2010

This study focuses on a numerical simulation of a steam reforming system. The steam reforming system consisted of a cylindrical steam reformer and a combustion burner. The heat was supplied to an endothermic steam reformer from combustion gases. The correlation between the performance and the shape of the system was studied using two different configurations. The first configuration utilized a flame guide between the combustion burner and the steam reformer, whereas the other did not. The flame guide changed the flow of the combustion gas, which affected the heat transfer rate from the burner to the reformer. Reactor temperature profiles, heat transfer rates, fuel conversions, and hydrogen yields were calculated. In addition, the fuel feed ratio between the burner and the steam reformer was manipulated as an operating parameter.
Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein Networks
Authors: Liu Hongrong , Jin Lei , Koh Sok Boon S. , Atanasov Ivo , Schein Stan , Wu Lily , Zhou Z. Hong
Published: August 2010

Human Adenovirus Structures

Human adenoviruses may be a common cause of acute infections in humans, but they can also be used as vectors for vaccine and therapeutic gene transfer. Rational engineering of safe adenovirus vectors has been hampered by a lack of high-resolution structural information. Two papers now describe the structure of human adenovirus using complementary techniques.

Reddy
et al.

(p.
1071
; see the Perspective by

Harrison

) have determined the crystal structure at 3.5 angstrom resolution, while

Liu
et al.

(p.
1038
; see the Perspective by

Harrison

) solved the structure to 3.6 angstrom resolution by electron microscopy. Together the structures provide insights into viral assembly, stabilization, and cell entry mechanisms.
Comment on “A Southern Tyrant Reptile”
Authors: Herne Matthew C. , Nair Jay P. , Salisbury Steven W.
Published: August 2010

Benson
et al
. (Brevia, 26 March 2010, p. 1613) reported on an Australian tyrannosauroid, represented by a pubis from the late Early Cretaceous of Victoria. However, our examination of this specimen reveals that the critical character used for this referral is not present. We contend that the bone likely belongs to a currently recognized group of Australian theropod or another group not currently known.