bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of Equalizer Production System and Smart-Well Applications in Full-Field Studies
Authors: Su Ho-Jeen , Dogru Ali H.
Published: April 2009

Equalizer production systems and inflow control devices are used to mitigate water or gas-coning problems for mature fields. We have developed new modeling methods to simulate equalizer and interval control valve (ICV) performance in full-field multimillion-cell reservoir models under a parallel computational environment.

The authors present single-well performance predictions with and without an equalizer, and the results are significantly different in some cases. Full-field modeling with equalizers and ICV controls for several examples has been conducted. In such cases, many individual wells would have significantly improved performance. At full-field level, however, using equalizers or smart well applications without total field optimization would not improve performance much, for reasons discussed in this paper.

The frictional pressure loss across an equalizer can be considered as a skin, and we have developed an analytical well equation to include it. With this theoretical development, it is now possible to confirm or monitor equalizer performance in terms of pressure drop from pressure transient analysis.
A New Diagnostic Analysis Method for Waterflood Performance
Authors: Yang Zhengming
Published: April 2009

Despite the widespread application of reservoir simulation to study waterflood reservoirs, petroleum engineers still need simple predictive tools to forecast production decline, estimate ultimate oil recovery, and diagnose the production performance from the historical field data.

On the basis of the Buckley-Leverett (BL) equation and the assumption of a semilog relationship between the oil/water relative permeability ratio and water saturation, a consistent analytical solution can be derived as fo(1−fo)=(EVB)1tD

where fo is the oil fractional flow, tD is the fraction of cumulative liquid production to related formation volume, B is the relative permeability ratio parameter, and EV is the volumetric sweep efficiency. Two equivalent linear plots can be developed: a loglog plot and a reciprocal-of-time plot. The log-log plot has a slope of −1 and intercept of EV/B. The reciprocal time plot has a slope of EV/B and an intercept value of 0. Both plots can be applied for the diagnostic analysis of waterflood reservoirs.

Model and field case studies show the benefits of this technique as a production-decline-analysis tool in forecasting the waterflood production decline and the ultimate oil recovery. This method also can be applied as a diagnostic tool to evaluate various aspects of waterflood performance. Examples include assessing waterflood maturity, calculating volumetric sweep efficiency, distinguishing the normal waterflood breakthrough from the premature water breakthrough through hydraulic fractures, and examining the consequences of operational changes. The appropriate use of this analytical method will help to optimize the field waterflood operation.
A Critical Review for Proper Use of Water/Oil/Gas Transfer Functions in Dual-Porosity Naturally Fractured Reservoirs: Part II
Authors: Al-kobaisi M. , Kazemi H. , Ramirez B. , Ozkan E. , Atan S.
Published: April 2009

This paper continues the work presented in Ramirez et al. (2009). In Part I, we discussed the viability of the use of simple transfer functions to accurately account for fluid exchange as the result of capillary, gravity, and diffusion mass transfer for immiscible flow between fracture and matrix in dual-porosity numerical models. Here, we show additional information on several relevant topics, which include (1) flow of a low-concentration water-soluble surfactant in the fracture and the extent to which the surfactant is transported into the matrix; (2) an adjustment to the transfer function to account for the early slow mass transfer into the matrix before the invading fluid establishes full connectivity with the matrix; and (3) an analytical approximation to the differential equation of mass transfer from the fracture to the matrix and a method of solution to predict oil-drainage performance.

Numerical experiments were performed involving single-porosity, fine-grid simulation of immiscible oil recovery from a typical matrix block by water, gas, or surfactant-augmented water in an adjacent fracture. Results emphasize the viability of the transfer-function formulations and their accuracy in quantifying the interaction of capillary and gravity forces to produce oil depending on the wettability of the matrix. For miscible flow, the fracture/matrix mass transfer is less complicated because the in-terfacial tension (IFT) between solvent and oil is zero; nevertheless, the gravity contrast between solvent in the fracture and oil in the matrix creates convective mass transfer and drainage of the oil.
Indexing Tools for Indian Citrus Ringspot Virus (ICRSV)
Authors: Sharma Sanjeev , Singh Balwinder , Nagpal Avinash , S. Virk G. , A. Zaidi A.
Published: April 2009

Indian citrus ringspot virus (ICRSV) is known to cause serious disease problem in Kinnow (Citrus nobilis
Lour 􀀁 C. deliciosa Tenora). This paper reports the various methods viz. Bioassay, ELISA and RT-PCR for indexing of
ICRSV. Bioassay was performed on Chenopodium amaranticolor, Cucumis sativus, Nicotiana glutinosa, N. tabacum, Petunia
hybrida and Phaseolus vulgaris. However necrotic local lesions were observed only in case of Chenopodium amaranticolor
and Phaseolus vulgaris. Infected trees were also found positive by indirect ELISA. RT-PCR of the infected
plants showed an amplification of 539 bp fragment corresponding to coat protein gene and gene for nucleic acid binding
protein.
Socioeconomic Inequalities in the Prevalence and Management of Childhood Diarrhoea: Potential Health Gains to be Achieved
Authors: Forsberg Birger C. , Gwatkin Davidson , Tomson Göran , Allebeck Peter , Petzold Max G.
Published: April 2009

Background:

Diarrhoea represents a major burden of childhood disease in countries with low and middle incomes.
The need for targeting poorer socioeconomic groups has been forwarded as a priority in diarrhoea control. The aim
of this study was to determine the role of socioeconomic inequalities in the control of childhood diarrhoea.

Methods:

Household data on prevalence and case management of diarrhoea in children aged 0–4 years from 93 Demographic
Health Surveys (DHS) in 55 countries in 1990–2005 were analysed by wealth quintiles. Socioeconomic disparities
and trends in inequalities were assessed.

Findings:

Households in the poorest socioeconomic group consistently showed higher morbidity attributable to diarrhoea
and less frequent use of oral rehydration therapy (ORT) when compared with households in the richest socioeconomic
group. If the prevalence of diarrhoea in all households were the same as that in the best-performing wealth quintiles, the
prevalence of diarrhoea would be reduced by 22.8%. If all socioeconomic groups had adopted the ORT-use rates achieved
by the best-performing wealth quintiles, overall use of ORT would have increased by 21.5%. This corresponds to an increase
in treated episodes of diarrhoea of 481 million annually in the study population. Trend analysis did not show significant
changes in inequalities over time.

Interpretations:

To increase efficiency in the control of diarrhoeal diseases, preventive measures should be targeted to the
poor, rehydration products should be made more affordable and information on the importance of using ORT should be
disseminated more intensively to disadvantaged groups.
Redescription of Monticellius indicum Mehra, 1939 (Digenea: Spirorchiidae) from the Heart of Green Sea Turtles (Chelonia mydas) in Costa Rica
Authors: Santoro Mario , C. Greiner Ellis , Alberto Morales Juan , Rodríguez-Ortíz Beatriz
Published: April 2009

Monticellius indicum Mehra, 1939, is redescribed from the heart of green sea turtles (Chelonia mydas) at
Tortuguero National Park, Caribbean coast of Costa Rica. Of the 40 green turtles examined, only 5 (12.5%) were infected
with a mean intensity of 1.6. Our specimens are consistent with the original description based on a single fluke from the
heart of the same host species in the Arabian Sea, Pakistan, but our redescription provides an unreported range of variation
while adding new information about acetabulum structure and egg morphology.
The effectiveness of vocational education in promoting equity and occupational mobility amongst young people
Authors: Bartlett Will
Published: April 2009

This paper reviews current knowledge about the impact of vocational education and training on the labor market outcomes for young people in advanced market economies, and asks whether the results can be extrapolated to countries in the Western Balkans and the EU neighborhood. It draws four main policy conclusions. First, in transition countries, specialized vocational education should not be replaced by streaming or tracking within comprehensive school systems or integrated into general education programmes. Abandoning effective vocational schooling may worsen the labor market outcomes for the less able and disadvantaged young people. Inadequate vocational school systems should be strengthened, while ensuring effective pathways to higher levels of education. Second, while apprenticeship systems enable lower ability students and minorities to access the labor market, they may lock women into traditional female occupations. Well-organized and resourced school-based vocational education may be preferred by women who feel they could benefit from them, and may furthermore reduce school drop-out rates. Third, occupational mobility can be improved by effective school-based vocational education. If returns to such education are sufficiently high, they can incentives mobility. While for developed economies there is little difference in rates of return between general and vocational education, in transition economies, returns to vocational education are higher than returns to general education. Fourth, while occupational mobility is needed for countries undergoing structural change, it should be noted that too much mobility can also be harmful to the skill retention, especially for women. Special attention should therefore be given to providing complementary opportunities for retraining and for lifelong learning to all workers, but especially to women, to encourage and support the desired degree of mobility in the labor market.
Risk transfer solutions for the insurance industry
Authors: Njegomir Vladimir , Maksimovic Rado
Published: April 2009

The paper focuses on the traditional and alternative mechanisms for insurance risk transfer that are available to global as well as to domestic insurance companies. The findings suggest that traditional insurance risk transfer solutions available to insurance industry nowadays will be predominant in the foreseeable future but the increasing role of alternative solutions is to be expected as the complementary rather than supplementary solution to traditional transfer. Additionally, findings suggest that it is reasonable to expect that future development of risk transfer solutions in Serbia will follow the path that has been passed by global insurance industry.
Pricing of foreign currency options in the Serbian market
Authors: Jankovic Irena
Published: April 2009

The main idea of this paper is to find the most suitable approach to the valuation of foreign currency options in the Serbian financial market. Volatility analysis included the application of the GARCH model which resulted in the marginal volatility measure, which was used in the pricing of basic foreign currency options in the local market. The analysis is completed with an overview of the implementation of FX derivatives in the Serbian financial market.
European integration and social convergence: A qualitative appraisal
Authors: Attia Nicole , Bérenger Valérie
Published: April 2009

Although with the Maastricht Treaty, European construction took a remarkable step forward, the robust pillar of the single currency started to shake the other one: the social welfare systems. The main goal of this contribution is to study the evolution of Social Protection in Europe by questioning the existence of a convergence between the different social welfare systems and the impact of the Treaty of Maastricht on this process. The evolution of the social protection concept in Europe, the reforms implemented in the most important domains of social protection: pensions, health and employment are analyzed. A common philosophy clearly appears. The welfare State is receding, calling more and more upon market mechanisms. Furthermore, the traditional binary typology is changing and countries are becoming more similar in their financing methods. We can thus say that a process of social convergence seems well and truly underway in the European Union.
Serbia’s EU integration process: The momentum of 2008
Authors: Ristic Irena
Published: April 2009

After four years of ambivalence, the relationship between the European Union and Serbia is again gaining a new opportunity to flourish. The new Serbian government is formed by parties which are strongly committed to Serbia?s EU integration and hence ready to carry out reforms and fully cooperate with the International Crime Tribunal for the former Yugoslavia. This paper presents the current relationship between Brussels and Belgrade and its main obstacles. It emphasizes both internal and external problems of this relationship and their interdependency. In this regard the author argues that only by a mutual commitment of both Serbia and the EU lasting peace will be achieved in the Western Balkans and the region stabilized.
A prospective study of comorbidity of alcohol and depression
Authors: Pradhan SN , Adhikary SR , Sharma SC
Published: April 2009

Objective: The aim of the work was to study the socio-demographic variables and their co-morbidity to alcohol consumption and presence of depressive symptomatology. Design: This was a prospective cross-sectional study. Materials and methods: The study was carried out in 53 patients, who were admitted in the wards of Kathmandu Medical College Teaching Hospital (KMCTH) with the diagnosis of mental and behavioural disorder due to the use of alcohol according to ICD-10. The patients were taken from 1st February 2006 to 30th December 2006. All patients were rated using Hamilton Depression Rating Scale (HDRS). Comparison of alcohol intake, depressive symptomatology and their associations with various socio-demographic variables were done using standard statistical procedures. Results: The present study has shown that more than 94.3% of the patients were suffering from depressive episode. Among all the patients, 11.3% were suffering from severe depressive episode. Alcohol intake was more significantly correlated (p = .002) with Brahmin and Chhetri caste. The other significant correlation of alcohol intake and sociodemographic variable was Nuclear family (p=.001). Among these patients the severity of depression was significantly (p= .001) associated with duration of alcohol intake. Marital status was another important factor affecting comorbidity of alcohol intake and presence of depressive symptoms (p =.002). Students of 10th to 12th grades of school were found to be using alcohol more often (45.3%). Middle socio-economic status (60.4%) was using alcohol more frequently than other socioeconomical classes. Conclusion: Severity of depression and alcohol intake was found to be significantly associated with various socio-demographic variables such as caste, family structure, marital status and educational status. Key words: Co-morbidity, ICD-10, Depression, alcohol-related disorders doi: 10.3126/kumj.v6i3.1709 Kathmandu University Medical Journal (2008), Vol. 6, No. 3, Issue 23, 340-345
Intraoperative consultation and smear cytology in the diagnosis of brain tumours
Authors: Kini JR , Jeyraj V , Jayaprakash CS , Indira S , Naik CNR
Published: April 2009

Background: Intraoperative smear cytology provides a rapid and reliable intraoperative diagnosis and guidance to the neurosurgeon during surgical resection and lesion targeting. It also helps the surgeon to monitor and modify the approach at surgery. Objectives: 1) To assess the utility of intraoperative smear cytology and correlate with the final histopathological diagnosis. 2) To describe the cytomorphological features of common brain tumours in smear preparation. Materials and methods: The material for this study was obtained from 100 consecutive biopsies of central nervous system neoplasms sent for intraoperative consultation. Smears were prepared from the biopsy samples sent in isotonic saline for immediate processing. The smears were stained by the rapid Haematoxylin and Eosin method. The cytomorphological features were noted and correlated with paraffin section findings. Results: Of the total 100 cases, 86 showed accuracy when compared with histopathological diagnosis. This was comparable with other studies. Of the remaining, two cases were frank errors, 12 cases showed partial correlation, with five cases showed incomplete typing of the cell type and seven, discrepancy in grading of tumours. The error percentage was 14%. Correlation with clinical details and radiological findings were helpful in improving the accuracy rate. Conclusions: Smear technique is a fairly accurate, relatively safe, rapid, simple, easily reproducible and cost effective tool to diagnose brain tumours. Smear cytology is of great value in intraoperative consultation of central nervous system pathology. Key words: Intraoperative consultation, smear cytology, central nervous system neoplasms   doi: 10.3126/kumj.v6i4.1734   Kathmandu University Medical Journal (2008), Vol. 6, No. 4, Issue 24, 453-457
Metallic vaginal ring pessary: A rare entity
Authors: Uprety UK , Regmi MC , Budhathoki B , Tiwari RR , Subedi S , Chhetri S
Published: April 2009

Vaginal pessaries still have role in the management of uterovaginal prolapse especially in elderly women, unfit for surgery and as a temporary relief for women waiting for surgery. Forgotten vaginal pessaries may cause serious complications. We here by present a case with metallic vaginal ring pessary for 16 years without significant symptoms. Key words: Prolapse, Ring pessary, Metallic pessary     doi: 10.3126/kumj.v6i4.1745     Kathmandu University Medical Journal (2008), Vol. 6, No. 4, Issue 24, 508-510
Medical negligence: An insight
Authors: Shrestha R
Published: April 2009

doi: 10.3126/kumj.v6i4.1751     Kathmandu University Medical Journal (2008), Vol. 6, No. 4, Issue 24, 533-534
Acute cytomegalovirus hepatitis in immunocompetent host
Authors: Al-Mahtab Mamun , Rahman S , Khan M
Published: April 2009

Background: In inmunocompetent hosts, cytomegalovirus (CMV) infection is generally asymptomatic. It may however present as infectious mononucleosis. Serious complications have rarely been reported. We report three cases of acute CMV hepatitis in immunocompetent men for the first time from Bangladesh. All three presented to us with features of acute hepatitis of variable duration preceded by prodrome. Other probable causes of acute hepatitis were ruled out and none had any clinical stigmata of cirrhosis. All the three patients underwent uneventful recovery. Although more common in the immunocompromised, CMV can occasionally produce symptomatic hepatitis in the immunocompetent host. Disease is self limiting, but supportive measures are needed. Key words: Cytomegalo virus, Acute hepatitis, Immunocompetent host doi: 10.3126/kumj.v7i1.1772 Kathmandu University Medical Journal (2009), Vol. 7, No. 1, Issue 25, 79-81
In response to the article entitled “Surgery for recurrent lower lip carcinoma” by Maharjan S et al, published in KUMJ, 2008 Vol. 6, No. 3, Issue 23, 375-378.
Authors: Bhandary S
Published: April 2009

doi: 10.3126/kumj.v7i1.1774 Kathmandu University Medical Journal (2009), Vol. 7, No. 1, Issue 25, 86-88
Correction: Goldbeck, R.A., et al. Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c. Int. J. Mol. Sci. 2009, 10, 1476-1499.
Authors: Goldbeck Robert  A. , Chen Eefei , Kliger David  S.
Published: April 2009

By mistake, we omitted the support from the National Institutes of Health (U.S.A.) in the Acknowledgements section in our paper recently published in Int. J. Mol. Sci. [1]. Therefore, the Acknowledgements section is revised as follows: [...]
Synthesis of N-(N’-benzoylhydrazinomethyl)benzamide
Authors: Popovski Emil
Published: April 2009

Our previous research has shown that (benzamidomethyl)triethylammonium chloride (1) is an excellent benzamidomethylating agent for different types of compounds in aqueous media because of the mild reaction conditions, high yields and simple isolation of products [1,2,3].[...]
Irrigated Area Maps and Statistics of India Using Remote Sensing and National Statistics
Authors: Thenkabail Prasad S. , Dheeravath Venkateswarlu , Biradar Chandrashekhar  M. , Gangalakunta Obi Reddy  P. , Noojipady Praveen , Gurappa Chandrakantha , Velpuri Manohar , Gumma Muralikrishna , Li Yuanjie
Published: April 2009

The goal of this research was to compare the remote-sensing derived irrigated areas with census-derived statistics reported in the national system. India, which has nearly 30% of global annualized irrigated areas (AIAs), and is the leading irrigated area country in the World, along with China, was chosen for the study. Irrigated areas were derived for nominal year 2000 using time-series remote sensing at two spatial resolutions: (a) 10-km Advanced Very High Resolution Radiometer (AVHRR) and (b) 500-m Moderate Resolution Imaging Spectroradiometer (MODIS). These areas were compared with the Indian National Statistical Data on irrigated areas reported by the: (a) Directorate of Economics and Statistics (DES) of the Ministry of Agriculture (MOA), and (b) Ministry of Water Resources (MoWR). A state-by-state comparison of remote sensing derived irrigated areas when compared with MoWR derived irrigation potential utilized (IPU), an equivalent of AIA, provided a high degree of correlation with R2 values of: (a) 0.79 with 10-km, and (b) 0.85 with MODIS 500-m. However, the remote sensing derived irrigated area estimates for India were consistently higher than the irrigated areas reported by the national statistics. The remote sensing derived total area available for irrigation (TAAI), which does not consider intensity of irrigation, was 101 million hectares (Mha) using 10-km and 113 Mha using 500-m. The AIAs, which considers intensity of irrigation, was 132 Mha using 10-km and 146 Mha using 500-m. In contrast the IPU, an equivalent of AIAs, as reported by MoWR was 83 Mha. There are “large variations” in irrigated area statistics reported, even between two ministries (e.g., Directorate of Statistics of Ministry of Agriculture and Ministry of Water Resources) of the same national system. The causes include: (a) reluctance on part of the states to furnish irrigated area data in view of their vested interests in sharing of water, and (b) reporting of large volumes of data with inadequate statistical analysis. Overall, the factors that influenced uncertainty in irrigated areas in remote sensing and national statistics were: (a) inadequate accounting of irrigated areas, especially minor irrigation from groundwater, in the national statistics, (b) definition issues involved in mapping using remote sensing as well as national statistics, (c) difficulties in arriving at precise estimates of irrigated area fractions (IAFs) using remote sensing, and (d) imagery resolution in remote sensing. The study clearly established the existing uncertainties in irrigated area estimates and indicates that both remote sensing and national statistical approaches require further refinement. The need for accurate estimates of irrigated areas are crucial for water use assessments and food security studies and requires high emphasis.
What makes a Good Festival? Understanding the Event Experience
Authors: Morgan Michael
Published: April 2009

This article explores the nature of extraordinary experiences through a netnographic analysis of the views of committed attendees at the 2005 Sidmouth Folk Festival. After uncertainty over finance and the withdrawal of the previous event management company, the festival eventually went
ahead under a different, collaborative organization and on a reduced scale. The new format was vigorously debated by posters to an Internet message board, Mudcat Cafe, providing a wide-ranging and unprompted set of opinions on the criteria for a successful festival. To provide a framework
for analyzing these responses, a holistic prism model was developed from the literature to bring together the main external and internal elements of the festival experience: "Design and Programming," "Physical Organization," "Social Interaction," "Personal Benefits," "Symbolic Meanings," and
"Cultural Communication." This was used to analyze the messages and explore the way in which festival-goers evaluate their experience. The findings support the view that festivals provide a space and time away from everyday life in which intense extraordinary experiences can be created and
shared. These are evaluated through a subjective response to the whole event, interpreted within the broader narrative context of the consumer's life and their values.
Event Management Body Of Knowledge (EMBOK): The Future of Event Industry Research
Authors: Robson Linda M.
Published: April 2009

Quantitative methods have dominated tourism research for many years, so it should come as no surprise that they are prominent in event industry research. Surveys, in particular, are used frequently in both academic and industry research. They garner a great deal of information, but
is this the only option? The International Event Management Body Of Knowledge (EMBOK) Committee believes they have developed a model that is aimed specifically at researching issues within the event industry. It includes paradigms, definitions, and domains that can be mixed and matched to
create thousands of potential research topics. This article looks at the status of the EMBOK Model and how well it accomplishes what it says it can do.
Commercializing the Carnivalesque: The V Festival and Image/Risk Management
Authors: Anderton Chris
Published: April 2009

The V Festival has been held since 1996, and was the first large-scale outdoor rock and pop music festival in Britain to be held at two sites simultaneously over one weekend. Developed as a mainstream alternative to the Glastonbury and Reading Festivals, it struggled to create a distinctive
identity or gain critical acceptance, especially among the more radical or countercultural of festival-goers and press. Managed by a consortium of highly successful concert promoters, it actively embraces commercialism, sponsorship deals, and a forward-thinking ethos of quality and customer
service. However, rather than escaping the countercultural and carnivalseque imagery and meanings historically associated with outdoor rock and pop music festivals it has, to varying degrees, commodified, modernized, or subverted them. In the process, it has gained considerable popularity
among festival-goers and secured the plaudits of music industry professionals. The event is at the forefront of initiatives regarding festival policing and safety, and offers a role model for the many new commercial events that are established each year. This article considers how the concept
of the countercultural carnivalesque has been used in relation to large-scale outdoor music festivals, before examining the V Festival through a cultural economic focus. It demonstrates how the beliefs and backgrounds of its organizers have influenced the management and image of the event,
and how it has helped to transform the large-scale outdoor music festival market more generally.
Computational Methods for Protein Sequence Comparison and Search
Authors: Xu Dong
Published: April 2009

Protein sequence comparison and search has become commonplace not only for bioinformatics researchers but also for experimentalists in many cases. Because of the exponential growth in sequence data, sequence comparison in particular has become an increasingly important tool. Relating a new gene sequence to other known sequences often reveals its function, structure, and evolution. Many sequence comparison and search tools are available through public Web servers, and biologists can use them easily with little knowledge of computers or bioinformatics. This unit provides some theoretical background and describes popular tools for dot plot, sequence search against a database, multiple sequence alignments, protein tree construction, and protein family and motif search. Step‐by‐step examples are provided to illustrate how to use some of the most well‐known tools. Finally, some general advice is given on combining different sequence analysis tools for biological inference.Curr. Protoc. Protein Sci. 56:2.1.1‐2.1.27. © 2009 by John Wiley & Sons, Inc.
Imaging Protein‐Protein Interactions by Förster Resonance Energy Transfer (FRET) Microscopy in Live Cells
Authors: Brzostowski Joseph A. , Meckel Tobias , Hong Jiang , Chen Alice , Jin Tian
Published: April 2009

This unit describes an acceptor‐sensitized emission FRET method using a confocal microscope for image acquisition. In contrast to acceptor photobleaching, which is an end‐point assay that destroys the acceptor fluorophore, the sensitized emission method is amenable for FRET measurements in live cells and can be used to measure changes in FRET efficiency over time. The purpose of this unit is to provide a basic starting point for understanding and performing the sensitized emission method with a simple teaching tool for live‐cell imaging. References that discuss the vagaries of acquiring and analyzing FRET between individually tagged molecules are provided. Curr. Protoc. Protein Sci. 56:19.5.1‐19.5.12. © 2009 by John Wiley & Sons, Inc.
The CLIP‐CHIP Oligonucleotide Microarray: Dedicated Array for Analysis of All Protease, Nonproteolytic Homolog, and Inhibitor Gene Transcripts in Human and Mouse
Authors: Kappelhoff Reinhild , Overall Chris
Published: April 2009

The CLIP‐CHIP oligonucleotide microarray allows the analysis of mRNA transcript levels in a tissue sample for all proteases, nonproteolytic homologs, and protease inhibitors of the human and mouse genome. In the protocol presented in this unit, total RNA is extracted from a tissue, and the resulting mRNA is reverse transcribed into cDNA and dsDNA and then amplified in an in vitro transcription reaction. The amplified antisense RNA is labeled with a fluorescent dye and hybridized to the CLIP‐CHIP, which contains unique oligonucleotides that are specifically designed for the protease, nonproteolytic homologs, protease inhibitors, and control samples. After hybridization, the fluorescence intensity of each spot is measured, thus identifying mRNA transcripts that are expressed and allowing basic quantification of expressed transcripts. Curr. Protoc. Protein Sci. 56:21.19.1‐21.19.16. © 2009 by John Wiley & Sons, Inc.
Novel exon 1 mutations in MECP2 implicate isoform MeCP2_e1 in classical Rett syndrome
Authors: Saunders Carol J. , Minassian Berge E. , Chow Eva W.C. , Zhao Weiwei , Vincent John B.
Published: April 2009

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X‐linked MECP2 gene. Recently, a new MeCP2 isoform was described, MeCP2_e1, which skips exon 2 and has an alternative N‐terminus, translated from exon 1, whereas MeCP2_e2 is translated from a start codon in exon 2. Since the incorporation of exon 1 into standard sequencing protocols for RTT, few exon 1 mutations have been described and are thus assumed to be only rare causes of RTT. Also, studies have suggested that the frameshift mutations identified in exon 1 affect both isoforms. Our aim in this study was to assess the frequency of mutations in exon 1, their relationship to phenotype, and the implications on the etiological role for the isoform MeCP2_e1 in RTT, versus the previously described isoform, MeCP2_e2. We sequenced MECP2 in 51 females with various clinical presentations, including developmental delay, autism, atypical and classical RTT, referred to our laboratories for testing. In patients with identified mutations, X‐chromosome inactivation was analyzed. We identified four patients with exon 1 mutations; three were novel (c.1A > T; c.1A > G; c.5C > T), two of which affected the start codon, one a missense change, and one patient had a previously reported splice site mutation, c.62 + 1delGT. The four patients fit criteria for classical RTT, and thus these findings add support to previous reports that exon 1 mutations may be associated with a severe phenotype. Also, these findings add significant weight to the mounting evidence suggesting that the MeCP2_e1 isoform is the etiologically relevant form of the protein. © 2009 Wiley‐Liss, Inc.
FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome
Authors: Felder Bärbel , Radlwimmer Bernhard , Benner Axel , Mincheva Antoaneta , Tödt Grischa , Beyer Kim S. , Schuster Claudia , Bölte Sven , Schmötzer Gabriele , Klauck Sabine M. , Poustka Fritz , Lichter Peter , Poustka Annemarie
Published: April 2009

We describe a patient with autism and brachymetaphalangy, meeting criteria for 2q37 deletion syndrome (also called Albright Hereditary Osteodystrophy‐like syndrome or Brachydactyly‐Mental Retardation syndrome, OMIM 600430). Our molecular cytogenetic studies, including array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH), define the extent of the de novo deletion to a 3.5 Mb region on 2q37.3. Although a number of reports of patients with 2q37 deletion syndrome have been published, it remains unclear if gene expression and/or translation are altered by the deletion, thus contributing to the observed phenotypes. To address this question, we selected several candidate genes for the neuropsychiatric and skeletal anomalies found in this patient (autism and brachymetaphalangy). The deleted region in 2q37.3 includes the FERM, RhoGEF and pleckstrin domain protein 2 (FARP2), glypican 1 (GPC1), vigilin (HDLBP), kinesin family member 1A (KIF1A) and proline–alanine‐rich STE20‐related kinase (PASK), all of which are involved in skeletal or neural differentiation processes. Expression analyses of these genes were performed using RNA from lymphoblastoid cell lines of the patient and his family members. Here we demonstrate that three of these genes, FARP2, HDLBP, and PASK, are considerably downregulated in the patient's cell line. We hypothesize that haploinsufficiency of these genes may have contributed to the patient's clinical phenotype. © 2009 Wiley‐Liss, Inc.
Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis
Authors: Vogt Johannes , Paul Friedemann , Aktas Orhan , Müller‐Wielsch Kathrin , Dörr Jan , Dörr Susanne , Bharathi B. Suman , Glumm Robert , Schmitz Christoph , Steinbusch Harry , Raine Cedric S. , Tsokos Michael , Nitsch Robert , Zipp Frauke
Published: April 2009

Objective

Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE).

Methods

We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high‐precision stereology.

Results

Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL‐deficient T lymphocytes.

Interpretation

Our study indicates that damage to lower motor neurons and TRAIL‐mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310–332
Intracortical electroencephalography in acute brain injury
Authors: Waziri Allen , Claassen Jan , Stuart R. Morgan , Arif Hiba , Schmidt J. Michael , Mayer Stephan A. , Badjatia Neeraj , Kull Lewis L. , Connolly E. Sander , Emerson Ronald G. , Hirsch Lawrence J.
Published: April 2009

Objective

Continuous electroencephalography (EEG) is used in patients with neurological injury to detect electrographic seizures and clinically important changes in brain function. Scalp EEG has poor spatial resolution, is often contaminated by artifact, and frequently demonstrates activity that is suspicious for but not diagnostic of ictal activity. We hypothesized that bedside placement of an intracortical multicontact electrode would allow for improved monitoring of cortical potentials in critically ill neurological patients.

Methods

Sixteen individuals with brain injury, requiring invasive neuromonitoring, underwent implantation of an eight‐contact minidepth electrode.

Results

Intracortical EEG (ICE) was successfully performed and compared with scalp EEG in 14 of these 16 individuals. ICE provided considerable improvement in signal‐to‐noise ratio compared with surface EEG, demonstrating clinically important findings in 12 of 14 patients (86%) including electrographic seizures (n = 10) and acute changes related to secondary neurological injury (n = 2, 1 ischemia, 1 hemorrhage). In patients with electrographic seizures detected by ICE, scalp EEG demonstrated no concurrent ictal activity in six, nonictal‐appearing rhythmic delta in two, and intermittently correlated ictal activity in two. In two patients with secondary neurological complications, ICE demonstrated prominent attenuation 2 to 6 hours before changes in other neuromonitoring modalities and more than 8 hours before the onset of clinical deterioration.

Interpretation

ICE can provide high‐fidelity intracranial EEG in an intensive care unit setting, can detect ictal discharges not readily apparent on scalp EEG, and can identify early changes in brain activity caused by secondary neurological complications. We predict that ICE will facilitate the development of EEG‐based alarm systems and lead to prevention of secondary neuronal injury. Ann Neurol 2009;66:366–377
Differential effects of high‐frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke
Authors: Ameli Mitra , Grefkes Christian , Kemper Friederike , Riegg Florian P. , Rehme Anne K. , Karbe Hans , Fink Gereon R. , Nowak Dennis A.
Published: April 2009

Objective

Facilitation of cortical excitability of the ipsilesional primary motor cortex (M1) may improve dexterity of the affected hand after stroke. The effects of 10Hz repetitive transcranial magnetic stimulation (rTMS) over ipsilesional M1 on movement kinematics and neural activity were examined in patients with subcortical or cortical stroke.

Methods

Twenty‐nine patients with impaired dexterity after stroke (16 subcortical middle cerebral artery [MCA] strokes, 13 MCA strokes involving subcortical tissue and primary or secondary cortical sensorimotor areas) received 1 session of 10Hz rTMS (5‐second stimulation, 25‐second break, 1,000 pulses, 80% of the resting motor threshold) applied over: 1) ipsilesional M1 and 2) vertex (control stimulation). For behavioral testing, 29 patients performed index finger and hand tapping movements with the affected and unaffected hand prior to and following each rTMS application. For functional magnetic resonance imaging, 18 patients performed index finger tapping movements with the affected and unaffected hand before and after each rTMS application.

Results

Ten‐Hz rTMS over ipsilesional M1, but not over vertex, improved movement kinematics in 14 of 16 patients with subcortical stroke, but not in patients with additional cortical stroke. Ten‐Hz rTMS slightly deteriorated dexterity of the affected hand in 7 of 13 cortical stroke patients. At a neural level, rTMS over ipsilesional M1 reduced neural activity of the contralesional M1 in 11 patients with subcortical stroke, but caused a widespread bilateral recruitment of primary and secondary motor areas in 7 patients with cortical stroke. Activity in ipsilesional M1 at baseline correlated with improvement of index finger tapping frequency induced by rTMS.

Interpretation

The beneficial effects of 10Hz rTMS over ipsilesional M1 on motor function of the affected hand depend on the extension of MCA stroke. Neural activity in ipsilesional M1 may serve as a surrogate marker for the effectiveness of facilitatory rTMS. Ann Neurol 2009;66:298–309
Fast food and neighborhood stroke risk
Authors: Morgenstern Lewis B. , Escobar James D. , Sánchez Brisa N. , Hughes Rebecca , Zuniga Belinda G. , Garcia Nelda , Lisabeth Lynda D.
Published: April 2009

Objective

To investigate the association between the number of fast food restaurants and ischemic stroke in neighborhoods.

Methods

This work was a prespecified part of the Brain Attack in Corpus Christi (BASIC) project. Ischemic stroke cases were prospectively ascertained in Nueces County, Texas. Home addresses were geocoded and used to establish the census tract for each stroke case. Census tracts were used as proxies for neighborhoods (n = 64). Using a standard definition, fast food restaurants were identified from a commercial list. Poisson regression was used to study the association between the number of fast food restaurants in the neighborhood, using a 1‐mile buffer around each census tract, and the risk of stroke in the neighborhood. Models were adjusted for demographics and neighborhood socioeconomic status (SES).

Results

There were 1,247 completed ischemic strokes from January 2000 through June 2003 and 262 fast food restaurants. The median number of fast food restaurants per census tract including buffer was 22 (interquartile range, 12–33). Adjusting for neighborhood demographics and SES, the association of fast food restaurants with stroke was significant (p = 0.02). The association suggested that the risk of stroke in a neighborhood increased by 1% for every fast food restaurant (relative risk, 1.01; 95% confidence interval [CI], 1.00–1.01). The relative risk of stroke comparing neighborhoods in the 75th to the 25th percentile of the distribution of fast food restaurants was 1.13 (95% CI, 1.02–1.25).

Interpretation

Controlling for demographic and SES factors, there was a significant association between fast food restaurants and stroke risk in neighborhoods in this community‐based study. Ann Neurol 2009;66:165–170
A novel recessive Nefl mutation causes a severe, early‐onset axonal neuropathy
Authors: Yum Sabrina W. , Zhang Junxian , Mo Katie , Li Jian , Scherer Steven S.
Published: April 2009

Objective

To report the first cases of a homozygous recessive mutation in NEFL, the gene that encodes the light subunit of neurofilaments.

Methods

Clinical and electrophysiologic data were evaluated, and a sural nerve biopsy from one affected child was examined by immunohistochemistry and electron microscopy. The ability of the mutant protein to form filaments was characterized in an established cell culture system.

Results

Four of five siblings developed of a severe, progressive neuropathy beginning in early childhood. Serial nerve conduction studies showed progressively reduced amplitudes with age and pronounced slowing at all ages. Visual‐evoked responses were slowed in three children, indicating that central nervous system axons were subclinically involved. All four affected children were homozygous for a nonsense mutation at glutamate 210 (E210X) in the NEFL gene; both parents were heterozygous carriers. A sural nerve biopsy from an affected patient showed markedly reduced numbers of myelinated axons; the remaining myelinated axons were small and lacked intermediate filaments. The E210X mutant protein did not form an intermediate filament network and did not interfere with the filament formation by wild‐type human light subunit of neurofilaments in SW‐13 vim− cells.

Interpretation

This is the first demonstration of a recessive NEFL mutation, which appears to cause a simple loss of function, resulting in a severe, early‐onset axonal neuropathy with unique features. These results confirm that neurofilaments are the main determinant of axonal caliber and conduction velocity, and demonstrate for the first time that neurofilaments are required for the maintenance of myelinated peripheral nervous system axons. Ann Neurol 2009;66:759–770
Comparing bibliometric statistics obtained from the Web of Science and Scopus
Authors: Archambault Éric , Campbell David , Gingras Yves , Larivière Vincent
Published: April 2009

For more than 40 years, the Institute for Scientific Information (ISI, now part of Thomson Reuters) produced the only available bibliographic databases from which bibliometricians could compile large‐scale bibliometric indicators. ISI's citation indexes, now regrouped under the Web of Science (WoS), were the major sources of bibliometric data until 2004, when Scopus was launched by the publisher Reed Elsevier. For those who perform bibliometric analyses and comparisons of countries or institutions, the existence of these two major databases raises the important question of the comparability and stability of statistics obtained from different data sources. This paper uses macrolevel bibliometric indicators to compare results obtained from the WoS and Scopus. It shows that the correlations between the measures obtained with both databases for the number of papers and the number of citations received by countries, as well as for their ranks, are extremely high (R2 ≈ .99). There is also a very high correlation when countries' papers are broken down by field. The paper thus provides evidence that indicators of scientific production and citations at the country level are stable and largely independent of the database.
How to normalize cooccurrence data? An analysis of some well‐known similarity measures
Authors: Eck Nees Jan van , Waltman Ludo
Published: April 2009

In scientometric research, the use of cooccurrence data is very common. In many cases, a similarity measure is employed to normalize the data. However, there is no consensus among researchers on which similarity measure is most appropriate for normalization purposes. In this article, we theoretically analyze the properties of similarity measures for cooccurrence data, focusing in particular on four well‐known measures: the association strength, the cosine, the inclusion index, and the Jaccard index. We also study the behavior of these measures empirically. Our analysis reveals that there exist two fundamentally different types of similarity measures, namely, set‐theoretic measures and probabilistic measures. The association strength is a probabilistic measure, while the cosine, the inclusion index, and the Jaccard index are set‐theoretic measures. Both our theoretical and our empirical results indicate that cooccurrence data can best be normalized using a probabilistic measure. This provides strong support for the use of the association strength in scientometric research.