bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigating Systemic Spillovers from Currency Hedging
Authors: Chung Kyuil , Park Hail , Shin Hyun Song
Published: August 2012

Korea has been a forerunner in incorporating macroprudential policies to mitigate the vulnerabilities from currency crises that can turn into a more generalised liquidity crisis. This paper examines longer-term design issues for a more resilient and stable financial system that could be expected to complement the existing macroprudential measures in achieving a more stable financial system. In particular, the paper examines the rationale and mechanics of a new public financial institution, provisionally called the Exchange Stabilisation and Guarantee Corporation (ESGC) whose main role is to buy dollar forward positions from Korean exporting companies who wish to hedge the currency exposure from long-term export orders. The ESGC is intended to mitigate the risks arising from the reliance on the role of the banking sector in providing currency hedging services to exporters. Rapid growth of short-term foreign currency denominated debt has been the result of banks receiving forward dollar sales by exporters, and then hedging the long dollar position by borrowing short in dollars. A public institution that can buy dollars forward, but which is designed so that there is no need to hedge by taking short dollar debt, can mitigate the rapid increase in short-term dollar debt in booms.
The Limits to Planning
Authors: Millard-Ball Adam
Published: August 2012

If planning is to matter for urban development and policy, it is not sufficient for plans to be implemented. Plans and planning must also have a causal role—they must lead to outcomes that would not be realized otherwise. In case studies of municipal climate action planning in California, I find little evidence for any causal impacts. Instead, cities are using climate plans to codify policies that were likely to happen anyway. The results call for a more nuanced view of when it makes sense to plan, what types of plans are most useful, and how to evaluate a plan’s effects.
Assessing Learning Outcomes in U.S. Planning Studio Courses
Authors: Németh Jeremy , Long Judith Grant
Published: August 2012

This paper proposes a model for assessing learning outcomes specific to planning studio courses. We begin by reviewing literature on learning outcomes found in education theory, and summarize a generalized model for outcomes assessment. Next, we review the planning literature on learning outcomes, then present a snapshot of contemporary learning outcomes assessment in planning studio courses as informed by content analyses of syllabi and interviews with studio instructors. Finally, we propose a studio-specific assessment model, and conclude with some recommendations for accreditation guidelines for learning outcomes assessment.
Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats
Authors: Sokmen BB , Basaraner H , Yanardag R
Published: August 2012

The aim of this study was to investigate the effects of vitamin C, vitamin E and selenium (Se) on the skin tissue of streptozotocin-induced diabetic rats. Swiss albino rats were divided into four groups: control, control + antioxidants, diabetic, diabetic + antioxidants groups. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. Vitamin C (250 mg/kg), vitamin E (250 mg/kg) and Se (0.2 mg/kg) were given by gavage technique to rats of one diabetic and one control group for 30 days. In the diabetic group, the levels of serum urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation levels increased, but skin glutathione levels decreased. Treatment with vitamin C, vitamin E and Se reversed these effects. The present study showed that vitamin C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin-induced diabetes.
Use of quetiapine XR and quetiapine IR in clinical practice for hospitalized patients with schizophrenia: a retrospective study
Authors: Eriksson Lars , Hallerbäck Teresa , Jørgensen Leif , Carlborg Andreas
Published: August 2012

Quetiapine fumarate, a first-line treatment for schizophrenia, exists in two formulations: extended release (XR) and immediate release (IR). This naturalistic, noninterventional study evaluated use of quetiapine XR/IR among in-patients with schizophrenia [ClinicalTrials.gov identifier: NCT01214135]. Data were collected from medical records. Categorical and numerical outcomes were compared using χ2 and t tests. Of 178 enrolled patients, 66% and 34% used quetiapine XR and IR respectively. Based on mean daily dose, XR was used as antipsychotic medication in 64% of patients compared with 40% of patients on IR (dose ≥ 400 mg/day; p = 0.002) and in higher doses than IR (494 versus 345 mg/day; p = 0.001; calculated averages). Schizophrenia was more commonly reported as reason for use of XR than IR (20% versus 0%; p = 0.0003). Patients with comorbid substance abuse or somatic disease were more likely to receive XR ( p = 0.003; p = 0.03). Treatment cessation due to nonadherence was less common in patients on XR (3.4% versus 12%; p = 0.03). Polypharmacy was seen in 98% of patients. Quetiapine XR/IR usage varies in hospitalized patients with schizophrenia. XR is more often used in antipsychotic dosage; IR is more commonly used at lower doses as add-on therapy. Both quetiapine XR and IR have their place in clinical practice and provide treatment choice in schizophrenia.
Development of wrought precipitation strengthened IN939 superalloy
Authors: Jahangiri M R , Arabi H , Boutorabi S M A
Published: August 2012

The potential of cast IN939 superalloy to be converted to wrought alloy has been explored in the present work. For this objective, bars of cast alloy were rolled under different conditions and then subjected to various heat treatment cycles. The results indicated that the yield strength, ultimate tensile strength and ductility of the wrought IN939 alloy are superior to the cast version. The stress rupture properties of wrought IN939 superalloy are better than those of the widely used superalloys, such as Nimonic 90 and Waspaloy, and approach the alloy Nimonic 105 properties. This is very notable because Nimonic 105 contains ∼45 vol.- γ′ that is much greater than the volume fraction of those strengthening precipitates in the alloy IN939 (∼35). On the whole, the wrought form of this alloy has a high potential for manufacturing hot components to be used safely under aggressive turbine environment.
Study on hot deformation behaviour of 316LN austenitic stainless steel based on hot processing map
Authors: Liu X G , Ji H P , Guo H , Jin M , Guo B F , Gao L
Published: August 2012

316LN is a type of austenitic stainless steel whose grain refinement only depends on hot deformation. The true stress–strain curves of 316LN were obtained by means of hot compression experiments conducted at a temperature range of 900–1200°C and at a strain rate range of 0·001–10 s−1. The influence of deformation parameters on the microstructure of 316LN was analysed. Both the constitutive equation for 316LN and the model of grain size after dynamic recrystallisation were established, and the effect of different deformation conditions on the microstructure was analysed. The results show that the suitable working region is the one with a relatively higher deformation temperature and a lower strain rate, in which the dynamic recrystallisation is finely conducted. Moreover, the working region that should be avoided during hot deformation was indicated.
Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole
Authors: Gerber Bernhard , Guggenberger Roman , Fasler David , Nair Gayathri , Manz Markus G. , Stussi Georg , Schanz Urs
Published: August 2012

We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment.
Cell-type specificity of ChIP-predicted transcription factor binding sites
Authors: Håndstad Tony , Rye Morten , Močnik Rok , Drabløs Finn , Sætrom Pål
Published: August 2012

Background

Context-dependent transcription factor (TF) binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding?

Results

We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity.

Conclusions

Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.
High throughput sequencing reveals novel and abiotic stress-regulated microRNAs in the inflorescences of rice
Authors: Barrera-Figueroa Blanca E , Gao Lei , Wu Zhigang , Zhou Xuefeng , Zhu Jianhua , Jin Hailing , Liu Renyi , Zhu Jian-Kang
Published: August 2012

Background

MicroRNAs (miRNAs) are small RNA molecules that play important regulatory roles in plant development and stress responses. Identification of stress-regulated miRNAs is crucial for understanding how plants respond to environmental stimuli. Abiotic stresses are one of the major factors that limit crop growth and yield. Whereas abiotic stress-regulated miRNAs have been identified in vegetative tissues in several plants, they are not well studied in reproductive tissues such as inflorescences.

Results

We used Illumina deep sequencing technology to sequence four small RNA libraries that were constructed from the inflorescences of rice plants that were grown under control condition and drought, cold, or salt stress. We identified 227 miRNAs that belong to 127 families, including 70 miRNAs that are not present in the miRBase. We validated 62 miRNAs (including 10 novel miRNAs) using published small RNA expression data in DCL1, DCL3, and RDR2 RNAi lines and confirmed 210 targets from 86 miRNAs using published degradome data. By comparing the expression levels of miRNAs, we identified 18, 15, and 10 miRNAs that were regulated by drought, cold and salt stress conditions, respectively. In addition, we identified 80 candidate miRNAs that originated from transposable elements or repeats, especially miniature inverted-repeat elements (MITEs).

Conclusion

We discovered novel miRNAs and stress-regulated miRNAs that may play critical roles in stress response in rice inflorescences. Transposable elements or repeats, especially MITEs, are rich sources for miRNA origination.
Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data
Authors: Strutton David R , Farkouh Raymond A , Rubin Jaime L , McGarry Lisa J , Loiacono Paul M , Klugman Keith P , Pelton Steven I , Gilmore Kristen E , Weinstein Milton C
Published: August 2012

Background

Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%.

Methods

This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant.

Results

Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program.

Conclusions

Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort.
Detection of P. aeruginosa harboring bla
CTX-M-2, bla
GES-1 and bla
GES-5,
bla
IMP-1 and bla
SPM-1causing infections in Brazilian tertiary-care hospital
Authors: Polotto Milena , Casella Tiago , de Lucca Oliveira Maria Gabriela , Rúbio Fernando G , Nogueira Mauricio L , de Almeida Margarete TG , Nogueira Mara CL
Published: August 2012

Background

Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs) and extended-spectrum beta-lactamases (ESBLs) have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital.

Methods

Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation.

Results

Despite the carbapenem resistance, genes for MBLs (bla
SPM-1 or bla
IMP-1) were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The bla
CTX-M-2 was the most prevalent ESBL gene (19.6%), followed by bla
GES-1 and bla
GES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST), the bla
SPM-1 or bla
IMP-1 genes were detected. In addition, bla
IMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the bla
CTX-M-2 gene. The co-existence of bla
CTX-M-2 with bla
IMP-1 is presently reported for the first time, as like as co-existence of bla
GES-1 with bla
IMP-1.

Conclusions

In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of bla
CTX-M-2,
bla
GES-1 and bla
GES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and the extraordinary ability presented by this pathogen to acquire multiple resistance mechanisms. These findings raise the concern about the future of antimicrobial therapy and the capability of clinical laboratories to detect resistant strains, since simultaneous production of MBLs and ESBLs is known to promote further complexity in phenotypic detection. Occurrence of intra-hospital clonal dissemination enhances the necessity of better observance of infection control practices.
The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan
Authors: Liu Jiung-Hsiun , Lin Shih-Yi , Hsu Chung-Yi , Lin Hsin-Hung , Liang Chih-Chia , Sung Fung-Chang , Huang Chiu-Ching
Published: August 2012

Background

The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases.

Methods

From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000–2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD.

Results

The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI) = 2.05 – 2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged < 40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR = 2.26, 95% CI = 1.94 - 2.63) and diabetes mellitus (HR = 2.44, 95% CI = 2.13 - 2.80), but not with hyperlipidemia (HR =1.13, 95% CI = 0.99-1.30).

Conclusions

This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently.
Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic
Authors: Robinson Caroline , Hiemstra Thomas F , Spencer Deborah , Waller Sarah , Daboo Laura , Karet Frankl Fiona E , Sandford Richard N
Published: August 2012

Background

ADPKD affects approximately 1:1000 of the worldwide population. It is caused by mutations in two genes,PKD1andPKD2. Although allelic variation has some influence on disease severity, genic effects are strong, withPKD2mutations predicting later onset of ESRF by up to 20 years. We therefore screened a cohort of ADPKD patients attending a nephrology out-patient clinic forPKD2mutations, to identify factors that can be used to offer targeted gene testing and to provide patients with improved prognostic information.

Methods

142 consecutive individuals presenting to a hospital nephrology out-patient service with a diagnosis of ADPKD and CKD stage 4 or less were screened for mutations inPKD2, following clinical evaluation and provision of a detailed family history (FH).

Results

PKD2mutations were identified in one fifth of cases. 12% of non-PKD2patients progressed to ESRF during this study whilst none with aPKD2mutation did (median 38.5 months of follow-up, range 16–88 months,p < 0.03). A significant difference was found in age at ESRF of affected family members (non-PKD2vs.PKD2, 54 yrs vs. 65 yrs;p < 0.0001). NoPKD2mutations were identified in patients with a FH of ESRF occurring before age 50 yrs, whereas aPKD2mutation was predicted by a positive FH without ESRF.

Conclusions

PKD2testing has a clinically significant detection rate in the pre-ESRF population. It did not accurately distinguish those individuals with milder renal disease defined by stage of CKD but did identify a group less likely to progress to ESRF. When used with detailed FH, it offers useful prognostic information for individuals and their families. It can therefore be offered to all but those whose relatives have developed ESRF before age 50.
Intraocular pressure vs intracranial pressure in disease conditions: A prospective cohort study (Beijing iCOP study)
Authors: Li Zhen , Yang Yingxin , Lu Yan , Liu Dachuan , Xu Erhe , Jia Jianping , Yang Diya , Zhang Xiaojun , Yang Huiqing , Ma Daqing , Wang Ningli
Published: August 2012

Background

The correlation between intracranial pressure (ICP) and intraocular pressure (IOP) is still controversial in literature and hence whether IOP can be used as a non-invasive surrogate of ICP remains unknown. The aim of the current study was to further clarify the potential correlation between ICP and IOP.

Methods

The IOP measured with Goldmann applanation tonometer was carried out on 130 patients whose ICP was determined via lumber puncture. The Pearson correlation coefficient between ICP and IOP was calculated, the fisher line discriminated analysis to evaluate the effectivity of using IOP to predict the ICP level.

Results

A significant correlation between ICP and IOP was found. ICP was correlated significantly with IOP of the right eyes (p < 0.001) and IOP of the left eyes (p = 0.001) and mean IOP of both eyes (p < 0.001), respectively. However, using IOP as a measurement to predict ICP, the accuracy rate was found to be 65.4%.

Conclusion

Our data suggested that although a significant correlation exists between ICP and IOP, caution needs to be taken when using IOP readings by Goldmann applanation tonometer as a surrogate for direct cerebrospinal fluid pressure measurement of ICP.
The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma
Authors: Qu Xu-Dong , Chen Cheng-Shi , Wang Jian-Hua , Yan Zhi-ping , Chen Jie-min , Gong Gao-quan , Liu Qin-xin , Luo Jian-jun , Liu Lin-xiao , Liu Rong , Qian Sheng
Published: August 2012

Background

The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.

Methods

Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.

Results

The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.

Conclusion

TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.
Characterization of purified and Xerogel immobilized Novel Lignin Peroxidase produced from Trametes versicolor IBL-04 using solid state medium of Corncobs
Authors: Asgher Muhammad , Iqbal Hafiz Muhammad Nasir , Irshad Muhammad
Published: August 2012

Background

Cost-effective production of industrially important enzymes is a key for their successful exploitation on industrial scale. Keeping in view the extensive industrial applications of lignin peroxidase (LiP), this study was performed to purify and characterize the LiP from an indigenous strain ofTrametes versicolorIBL-04. Xerogel matrix enzyme immobilization technique was applied to improve the kinetic and thermo-stability characteristics of LiP to fulfil the requirements of the modern enzyme consumer sector of biotechnology.

Results

A novel LiP was isolated from an indigenousT. versicolorIBL-04 strain.T. versicolorIBL-04 was cultured in solid state fermentation (SSF) medium of corn cobs and maximum LiP activity of 592 ± 6 U/mL was recorded after five days of incubation under optimum culture conditions. The crude LiP was 3.3-fold purified with specific activity of 553 U/mg after passing through the DEAE-cellulose and Sephadex-G-100 chromatography columns. The purified LiP exhibited a relatively low molecular weight (30 kDa) homogenous single band on native and SDS-PAGE. The LiP was immobilized by entrapping in xerogel matrix of trimethoxysilane (TMOS) and proplytetramethoxysilane (PTMS) and maximum immobilization efficiency of 88.6% was achieved. The free and immobilized LiPs were characterized and the results showed that the free and immobilized LiPs had optimum pH 6 and 5 while optimum temperatures were 60°C and 80°C, respectively. Immobilization was found to enhance the activity and thermo-stability potential of LiP significantly and immobilized LiP remained stable over broad pH and temperature range as compare to free enzyme. Kinetic constantsKmandVmaxwere 70 and 56 μM and 588 and 417 U/mg for the free and immobilized LiPs, respectively. Activity of this novel extra thermo-stable LiP was stimulated to variable extents by Cu2+, Mn2+and Fe2+whereas, Cystein, EDTA and Ag+showed inhibitory effects.

Conclusions

The indigenously isolated white rot fungal strainT. versicolorIBL-04 showed tremendous potential for LiP synthesis in SSF of corncobs in high titters (592 U/mL) than other reportedTrametes(Coriolus,Polyporus) species. The results obtained after dual phase characterization suggested xerogel matrix entrapment a promising tool for enzyme immobilization, hyper-activation and stabilization against high temperature and inactivating agents. The pH and temperature optima, extra thermo-stability features and kinetic characteristics of this novel LiP ofT. versicolorIBL-04 make it a versatile enzyme for various industrial and biotechnological applications.
Rational improvement of the engineered isobutanol-producing Bacillus subtilis by elementary mode analysis
Authors: Li Shanshan , Huang Di , Li Yong , Wen Jianping , Jia Xiaoqiang
Published: August 2012

Background

Isobutanol is considered as a leading candidate for the replacement of current fossil fuels, and expected to be produced biotechnologically. Owing to the valuable features, Bacillus subtilis has been engineered as an isobutanol producer, whereas it needs to be further optimized for more efficient production. Since elementary mode analysis (EMA) is a powerful tool for systematical analysis of metabolic network structures and cell metabolism, it might be of great importance in the rational strain improvement.

Results

Metabolic network of the isobutanol-producing B. subtilis BSUL03 was first constructed for EMA. Considering the actual cellular physiological state, 239 elementary modes (EMs) were screened from total 11,342 EMs for potential target prediction. On this basis, lactate dehydrogenase (LDH) and pyruvate dehydrogenase complex (PDHC) were predicted as the most promising inactivation candidates according to flux flexibility analysis and intracellular flux distribution simulation. Then, the in silico designed mutants were experimentally constructed. The maximal isobutanol yield of the LDH- and PDHC-deficient strain BSUL05 reached 61% of the theoretical value to 0.36 ± 0.02 C-mol isobutanol/C-mol glucose, which was 2.3-fold of BSUL03. Moreover, this mutant produced approximately 70 % more isobutanol to the maximal titer of 5.5 ± 0.3 g/L in fed-batch fermentations.

Conclusions

EMA was employed as a guiding tool to direct rational improvement of the engineered isobutanol-producing B. subtilis. The consistency between model prediction and experimental results demonstrates the rationality and accuracy of this EMA-based approach for target identification. This network-based rational strain improvement strategy could serve as a promising concept to engineer efficient B. subtilis hosts for isobutanol, as well as other valuable products.
Inaccurate identification of rotavirus genotype G9 as genotype G3 strains due to primer mismatch
Authors: Mitui Marcelo Takahiro , Chandrasena TGA Nilmini , Chan Paul KS , Rajindrajith Shaman , Nelson E Anthony S , Leung Ting Fan , Nishizono Akira , Ahmed Kamruddin
Published: August 2012

Reverse transcription (RT)-PCR is now the standard method for typing group A rotaviruses (RVA) to monitor the circulating genotypes in a population. Selection of primers that can accurately type the circulating genotypes is crucial in the context of vaccine introduction and correctly interpreting the impact of vaccination on strain distribution. To our knowledge this study is the first report from Asia of misidentification of genotype G9 as G3 due to a primer-template mismatch. We tested two published G-genotype specific primers sets, designed by Gouvea and colleagues (Set A) and Iturriza‐Gomara and colleagues (Set B) on RVA from Hong Kong and Sri Lanka. Among 52 rotaviruses typed as G3 by set A primers, 36 (69.2%) were identified as G9 by nucleotide sequencing and set B primers. Moreover, of 300 rotaviruses tested, 28.3% were untypable by set A primers whereas only 12.3% were untypable by set B primers. Our findings reinforce the need to periodically monitor the primers used for RVA genotyping.
Clinically significant bleeding in incurable cancer patients: effectiveness of hemostatic radiotherapy
Authors: Cihoric Nikola , Crowe Susanne , Eychmüller Steffen , Aebersold Daniel M , Ghadjar Pirus
Published: August 2012

Background

This study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients.

Methods

Patients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (OS) and acute toxicity. The bleeding score before and after RT were compared using the Wilcoxon signed rank test. Time to event endpoints were estimated using the Kaplan Meier method.

Results

Overall 62 patients were analyzed including 1 patient whose benign cause of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37–93) years. Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients, respectively. A median dose of 20 (range, 5–45) Gy of hemostatic RT was applied to the bleeding site. At the end of RT, there was a statistically significant difference in bleeding (p < 0.001); it was graded as 0 (n = 39), 1 (n = 12), 2 (n = 6), 3 (n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3-19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to bleeding. No grade 3 or above acute toxicity was observed.

Conclusions

Hemostatic RT seems to be a safe and effective treatment for clinically and statistically significantly reducing bleeding in incurable cancer patients.
Promoting community knowledge and action for malaria control in rural Cambodia: potential contributions of Village Malaria Workers
Authors: Lim Sachiko , Yasuoka Junko , Poudel Krishna C , Ly Po , Nguon Chea , Jimba Masamine
Published: August 2012

Background

Cambodia has been investing in Village Malaria Workers (VMWs) to improve malaria case management in rural areas. This study assessed the quality of the VMWs’ services compared to those by a government-run health center from the perspective of community members. We focused on VMWs’ contribution to promote their action to control malaria. A community-based cross-sectional study was conducted in Kampot province in 2009. Interviews were conducted at every accessible household in a village with VMWs (n = 153) and a village with a health center (n = 159), using interviewer administered questionnaire. Preference of the interview was given to female household head. Multiple regression analyses were run to compare knowledge about malaria, preventive measures taken, and time before first malaria treatment between the two villages.

Findings

The villagers perceived the VMWs’ services equally as good as those provided by the health center. After controlling for confounding factors, the following indicators did not show any statistical significance between two villages: community members’ knowledge about malaria transmission (AOR = 0.60, 95% CI = 0.30-1.22) and government-recommended antimalarial (AOR = 0.55, 95% CI = 0.25-1.23), preventive measures taken (Beta = −0.191, p = 0.315), and time before the first treatment (Beta = 0.053, p = 0.721). However, knowledge about malaria symptoms was significantly lower in the village with VMWs than the village with a health center (AOR = 0.40, 95% CI = 0.19-0.83).

Conclusions

VMWs played an equivalent role as the health center in promoting malaria knowledge, action, and effective case management. Although VMWs need to enhance community knowledge about malaria symptoms, the current government policy on VMWs is reasonable and should be expanded to other malaria endemic villages.
Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy
Authors: Brunner Stefan , Todica Andrei , Böning Guido , Nekolla Stefan G , Wildgruber Moritz , Lehner Sebastian , Sauter Martina , Übleis Christopher , Klingel Karin , Cumming Paul , Franz Wolfgang Michael , Hacker Marcus
Published: August 2012

Background

We performed an initial evaluation of non-invasive ECG-gated [18 F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study.

Methods

Mice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline.

Results

LV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis.

Conclusions

LVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.
IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1β-mediated degradation of nucleus pulposus in vitro
Authors: Gorth Deborah J , Mauck Robert L , Chiaro Joseph A , Mohanraj Bhavana , Hebela Nader M , Dodge George R , Elliott Dawn M , Smith Lachlan J
Published: August 2012

Introduction

Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1β) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model.

Methods

IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1β and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests.

Results

IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1β as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days.

Conclusions

In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1β on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation.
Magnetic compass orientation in two strictly subterranean rodents: learned or species-specific innate directional preference?
Authors: Oliveriusová Ludmila , Němec Pavel , Králová Zuzana , Sedláček František
Published: August 2012

Evidence for magnetoreception in mammals remains limited. Magnetic compass orientation or magnetic alignment has been conclusively demonstrated in only a handful of mammalian species. The functional properties and underlying mechanisms have been most thoroughly characterized in Ansell's mole-rat, Fukomys anselli, which is the species of choice due to its spontaneous drive to construct nests in the south-eastern sector of a circular arena using the magnetic field azimuth as the primary orientation cue. Due to the remarkable consistency between experiments, it is generally believed that this directional preference is innate. To test the hypothesis that spontaneous south-eastern directional preference is a shared, ancestral feature of all African mole rats (Bathyergidae, Rodentia), we employed the same arena assay to study magnetic orientation in two other mole-rat species, the social giant mole-rat Fukomys mechowii and the solitary silvery mole-rat Heliophobius argenteocinereus. Both species exhibited spontaneous western directional preference and deflected their directional preference according to shifts in the direction of magnetic north, clearly indicating that they were deriving directional information from the magnetic field. Because all of the experiments were performed in total darkness, our results strongly suggest that all African mole rats use a light-independent magnetic compass for near-space orientation. However, the spontaneous directional preference is not common and may be either innate but species-specific, or learned. We propose an experiment that should be performed to distinguish between these two alternatives.
The sender-receiver matching hypothesis: support from the peripheral coding of acoustic features in songbirds
Authors: Gall Megan D. , Brierley Lauren E. , Lucas Jeffrey R.
Published: August 2012

The sender-receiver matching hypothesis predicts that species-specific features of vocalizations will be reflected in species-specific auditory processing. This hypothesis has most often been invoked to explain correlations between vocal frequency ranges and the frequency range of auditory sensitivity; however it could apply to other structure features, such as the rise time of stimuli. We explored this hypothesis in five songbird species that vary in the rise times and frequency range of their vocalizations. We recorded auditory evoked potentials (AEPs) to onset and sustained portions of stimuli that varied in both frequency and rise time. AEPs are gross potentials generated in the auditory nerve and brainstem and measured from the scalp. We found that species with shorter rise times in their vocalizations had greater amplitude and shorter latency onset AEPs than species with longer rise times. We also found that species with lower frequency and/or more tonal vocalizations had stronger sustained AEPs that follow the sound pressure changes in the stimulus (i.e. frequency following responses) than species with higher frequency and/or less tonal vocalizations. This is the first study in songbirds to show that acoustic features such as rise time and tonality are reflected in peripheral auditory processing.
Surviving the Global Financial Crisis: Foreign Ownership and Establishment Performance
Authors: Alfaro Laura , Chen Maggie Xiaoyang
Published: August 2012

We examine the differential response of establishments to the recent global financial crisis with particular emphasis on the role of foreign ownership. Using a worldwide establishment panel dataset, we investigate how multinational subsidiaries around the world responded to the crisis relative to local establishments. We find that, first, multinational subsidiaries fared on average better than local counterfactuals with similar economic characteristics. Second, among multinational subsidiaries, establishments sharing stronger vertical production and financial linkages with parents exhibited greater resilience. Finally, in contrast to the crisis period, the effect of foreign ownership and linkages on establishment performance was insignificant in noncrisis years. (JEL F23, G01, L22, M16)
Book Reviews
Authors: Rand Graham K.
Published: August 2012

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an email from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor.

The following books are reviewed in this issue of Interfaces, 42(4), July–August 2012: Optimal Strategies in Sports Economics and Management, Sergiy Butenko, Jaime Gil-Lafuente, and Panos M. Pardalos, eds.; Foundations of Location Analysis, H. A. Eiselt and Vladimir Marianov, eds; Metaheuristics: From Design to Implementation, El-Ghazali Talbi; Data Mining: Concepts, Methods and Applications in Management and Engineering Design, Yong Yin, Ikou Kaku, Jiafu Tang, and Jian-Ming Zhu.
Robust Assortment Optimization in Revenue Management Under the Multinomial Logit Choice Model
Authors: Rusmevichientong Paat , Topaloglu Huseyin
Published: August 2012

We study robust formulations of assortment optimization problems under the multinomial logit choice model. The novel aspect of our formulations is that the true parameters of the logit model are assumed to be unknown, and we represent the set of likely parameter values by a compact uncertainty set. The objective is to find an assortment that maximizes the worst-case expected revenue over all parameter values in the uncertainty set. We consider both static and dynamic settings. The static setting ignores inventory consideration, whereas in the dynamic setting, there is a limited initial inventory that must be allocated over time. We give a complete characterization of the optimal policy in both settings, show that it can be computed efficiently, and derive operational insights. We also propose a family of uncertainty sets that enables the decision maker to control the trade-off between increasing the average revenue and protecting against the worst-case scenario. Numerical experiments show that our robust approach, combined with our proposed family of uncertainty sets, is especially beneficial when there is significant uncertainty in the parameter values. When compared to other methods, our robust approach yields over 10% improvement in the worst-case performance, but it can also maintain comparable average revenue if average revenue is the performance measure of interest.
Learning Consumer Tastes Through Dynamic Assortments
Authors: Ulu Canan , Honhon Dorothée , Alptekinoğlu Aydın
Published: August 2012

How should a firm modify its product assortment over time when learning about consumer tastes? In this paper, we study dynamic assortment decisions in a horizontally differentiated product category for which consumers' diverse tastes can be represented as locations on a Hotelling line. We presume that the firm knows all possible consumer locations, comprising a finite set, but does not know their probability distribution. We model this problem as a discrete-time dynamic program; each period, the firm chooses an assortment and sets prices to maximize the total expected profit over a finite horizon, given its subjective beliefs over consumer tastes. The consumers then choose a product from the assortment that maximizes their own utility. The firm observes sales, which provide censored information on consumer tastes, and it updates beliefs in a Bayesian fashion. There is a recurring trade-off between the immediate profits from sales in the current period (exploitation) and the informational gains to be exploited in all future periods (exploration). We show that one can (partially) order assortments based on their information content and that in any given period the optimal assortment cannot be less informative than the myopically optimal assortment. This result is akin to the well-known “stock more” result in censored newsvendor problems with the newsvendor learning about demand through sales when lost sales are not observable. We demonstrate that it can be optimal for the firm to alternate between exploration and exploitation, and even offer assortments that lead to losses in the current period in order to gain information on consumer tastes. We also develop a Bayesian conjugate model that reduces the state space of the dynamic program and study value of learning using this conjugate model.
Democratizing Strategy: How Crowdsourcing Can Be Used for Strategy Dialogues
Authors: Stieger Daniel , Matzler Kurt , Chatterjee Sayan , Ladstaetter-Fussenegger Florian
Published: August 2012

Crowdsourcing is typically associated with the incorporation of company-external stakeholders such as customers in the value creating process. This article proposes a framework for a company-internal application of crowdsourcing methods. It presents a set of five goals companies can pursue employing internal crowdsourcing. The practical approach of an Austrian medium-sized technology company is described in detail, including insights on software design and appropriate procedures.