bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative approach for prioritizing cancer genes in sporadic colon cancer
Authors: Reid James F. , Gariboldi Manuela , Sokolova Viktorija , Capobianco Patrizia , Lampis Andrea , Perrone Federica , Signoroni Stefano , Costa Aurora , Leo Ermanno , Pilotti Silvana , Pierotti Marco A.
Published: August 2009

The current multistep carcinogenesis models of colon cancer do not fully capture the genetic heterogeneity of the disease, which is additionally complicated by the presence of passenger and driver genetic alterations. The aim of this study was to select in the context of this significant heterogeneity additional genes functionally related to colon cancer development. High‐throughput copy number and gene expression data of 36 microsatellite stable sporadic colon cancers resected from patients of a single institution characterized for mutations in APC, KRAS, TP53 and loss of 18q were analyzed. Genes whose expression correlated with the underlying copy number pattern were selected, and their association with the above listed mutations and overall survival was evaluated. Gain of 20q was strongly associated with TP53 mutation, and overall survival with alterations on 7p, 8p, 13q, 18q, and 20q. An association with 18q loss and gain of 8q24 was also observed. New candidate genes with a potential role in colon cancer are PLCG1 on 20q, DBC1 on 8q21, and NDGR1 on 8p24. In addition, an unexpected pattern of loss and mutability was found in the region upstream of the KRAS gene. By integrating copy number alterations with gene expression and mutations in colon cancer associated genes, we have developed a strategy that identifies previously known molecular features and additional players in the molecular landscape of colon cancer. © 2009 Wiley‐Liss, Inc.
IL‐1β enhances the antibacterial activity of astrocytes by activation of NF‐κB
Authors: Xia Yulei , Zhai Qiwei
Published: August 2009

Astrocytes have important immune functions in CNS, and astrocytes stimulated by interferon‐γ were showed to have direct antimicrobial function. However whether astrocytes without the stimulation of cytokines have antibacterial function, and how this function is regulated are still largely unknown. In this study, we found that primary cultured astrocytes inhibited the growth of both gram‐negative and gram‐positive bacteria. Further more, we showed that interleukin‐1β (IL‐1β) enhanced the antibacterial effect in a dose‐dependent manner, and the antibacterial effect of astrocytes from IL‐1β receptor‐deficient mice failed to be enhanced by IL‐1β. IL‐1β stimulated IκBα degradation, NF‐κB nuclear translocation, and transactivation in astrocytes. NF‐κB inhibitors blocked NF‐κB activation and the enhanced antibacterial effect induced by IL‐1β. In addition, overexpression of dominant negative IκBα in astrocytes inhibited IκBα degradation and NF‐κB transactivation, and also inhibited the enhanced antibacterial effect induced by IL‐1β. All these data demonstrated that IL‐1β enhanced the antibacterial activity of astrocytes by activation of NF‐κB. © 2009 Wiley‐Liss, Inc.
Epigenetic regulation of neuron‐dependent induction of astroglial synaptic protein GLT1
Authors: Yang Yongjie , Gozen Oguz , Vidensky Svetlana , Robinson Michael B. , Rothstein Jeffrey D.
Published: August 2009

Astroglial glutamate transporter EAAT2/GLT1 prevents glutamate‐induced excitotoxicity in the central nervous system. Expression of EAAT2/GLT1 is dynamically regulated by neurons. The pathogenesis of amyotrophic lateral sclerosis (ALS) involves astroglial dysfunction, including dramatic loss of EAAT2/GLT1. DNA methylation of gene promoters represents one of the most important epigenetic mechanisms in regulating gene expression. The involvement of DNA methylation in the regulation of astroglial EAAT2/GLT1 expression in different conditions, especially in ALS has not been explored. In this study, we established a procedure to selectively isolate a pure astrocyte population in vitro and in vivo from BAC GLT1 eGFP mice using an eGFP‐based fluorescence‐activated cell sorting approach. Astrocytes isolated from this procedure are GFAP+ and GLT1+ and respond to neuronal stimulation, enabling direct methylation analysis of GLT1 promoter in these astrocytes. To investigate the role of DNA methylation in physiological and pathological EAAT2/GLT1 expression, methylation status of the EAAT2/GLT1 promoter was analyzed in astrocytes from in vitro and in vivo paradigms or postmortem ALS motor cortex by bisulfite sequencing method. DNA demethylation on selective CpG sites of the GLT1 promoter was highly correlated to increased GLT1 mRNA levels in astrocytes in response to neuronal stimulation; however, low level of methylation was found on CpG sites of EAAT2 promoter from postmortem motor cortex of human amyotrophic lateral sclerosis patients. In summary, hypermethylation on selective CpG sites of the GLT1 promoter is involved in repression of GLT1 promoter activation, but this regulation does not play a role in astroglial dysfunction of EAAT2 expression in patients with ALS. © 2009 Wiley‐Liss, Inc.
Electrophysiologic facial nerve monitoring during parotidectomy
Authors: Eisele David W. , Wang Steven J. , Orloff Lisa A.
Published: August 2009

Facial nerve monitoring is an adjunctive method available to a surgeon during parotid surgery to assist with the functional preservation of the facial nerve. This review describes the goals, applications, technique, and benefits of electrophysiologic facial nerve monitoring during parotid surgery. A review and analysis of the relevant medical literature related to electrophysiologic facial nerve monitoring during parotid surgery are included. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Reoperative thyroidectomy for benign thyroid disease
Authors: Terris David J. , Khichi Sunny , Anderson Susan K. , Seybt Melanie W.
Published: August 2009

Background

Subtotal thyroidectomy for benign thyroid disease (BTD) may lead to delayed recurrence, thus necessitating reoperative surgery. We describe our experience with reoperative thyroidectomy for BTD and recommendations for definitive primary management.

Methods

Patients undergoing thyroid surgery between 2003 and 2007 by a single surgeon were prospectively assessed. Numerous clinical parameters were evaluated, including time interval between primary and reoperative surgery and complications.

Results

In all, 321 thyroidectomies were identified: 45 were reoperative and 22 were related to BTD after primary surgery done elsewhere. Median interval between the primary and reoperative procedure was 8.5 years. No recurrences followed total thyroidectomy or total thyroid lobectomy. There were no cases of permanent or transient recurrent laryngeal nerve (RLN) injury related to reoperative surgery. There was 1 case of transient hypocalcemia.

Conclusions

Although reoperative thyroidectomy can be performed safely in the hands of experienced surgeons, a thorough initial surgical procedure should obviate the need for exposure to this additional risk. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Esophageal stricture after radiotherapy in patients with head and neck cancer: Experience of a single institution over 2 treatment periods
Authors: Ahlberg Alexander , al‐Abany Massoud , Alevronta Eleftheria , Friesland Signe , Hellborg Henrik , Mavroidis Panayiotis , Lind Bengt K. , Laurell Göran
Published: August 2009

Background.

Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined.

Methods.

This was a retrospective case‐control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer.

Results.

The incidence of esophageal stricture after external beam radiation therapy (EBRT) was 3.3%. Seventy patients with stricture and 66 patients without stricture were identified. A multivariate analysis showed that there was increased risk of stricture in receiving enteral feeding during EBRT or in receiving a mean dose of >45 Gy to the upper esophagus.

Conclusions.

Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of >45 Gy to the upper esophagus. Treatment of the stricture with Savary–Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Percutaneous sclerotherapy of massive venous malformations of the face and neck using fibrin glue combined with OK‐432 and pingyangmycin
Authors: Chen Wei‐liang , Huang Zhi‐quan , Zhang Da‐ming , Chai Qiang
Published: August 2009

Background.

Surgical excision is useful only for localized and limited lesions. The purpose of this study was to evaluate the clinical curative effect of percutaneous sclerotherapy of massive venous malformations of the face and neck using fibrin glue combined with OK‐432 and pingyangmycin.

Methods.

Eighteen patients with massive venous malformations were treated with an injection of fibrin glue combined with OK‐432 and pingyangmycin.

Results.

All the patients had extreme swelling postoperatively with no major complications. The follow‐up period ranged from 6 to 12 months. Twelve lesions were completely involuted, 4 lesions were mostly involuted, and 2 lesions were partially involuted. All of the patients had normal liver and kidney functions. None of the patients presented with hematologic toxic effects or signs of pulmonary involvement.

Conclusion.

Percutaneous sclerotherapy using fibrin glue combined with OK‐432 and pingyangmycin provided a simple, safe, and reliable alternative treatment for massive venous malformations. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Hepatitis C Virus Infection and Its Clearance Alter Circulating Lipids
Authors: Corey Kathleen E. , Kane Erin , Munroe Craig , Barlow Lydia L. , Zheng Hui , Chung Raymond T.
Published: August 2009

Hepatitis C associated hypolipidemia has been demonstrated in studies from Europe and Africa. In two linked studies, we evaluated the relationship between hepatitis C infection and treatment with lipid levels in an American cohort and determined the frequency of clinically significant posttreatment hyperlipidemia. First, a case-control analysis of patients with and without hepatitis C was performed. The HCV Group consisted of 179 infected patients. The Uninfected Control Group consisted of 180 age-matched controls. Fasting cholesterol, low density lipoprotein (LDL), high density lipoprotein and triglycerides were compared. Next was a retrospective cohort study (Treated Hepatitis C Group) of 87 treated hepatitis C patients with lipid data before and after therapy was performed. In the case-control analysis, the HCV Group had significantly lower LDL and cholesterol than the Uninfected Control Group. In the retrospective cohort, patients in the Treated Hepatitis C Group who achieved viral clearance had increased LDL and cholesterol from baseline compared to patients without viral clearance. These results persisted when adjusted for age, sex, and genotype. 13% of patients with viral clearance had increased LDL and 33% experienced increases in cholesterol to levels warranting lipid lowering therapy.

Conclusion:

Hepatitis C is associated with decreased cholesterol and LDL levels. This hypolipidemia resolves with successful hepatitis C treatment but persists in nonresponders. A significant portion of successfully treated patients experience LDL and cholesterol rebound to levels associated with increased coronary disease risk. Lipids should be carefully monitored in persons receiving antiviral therapy. (Hepatology 2009;50:1030–1037.)
Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma #
Authors: Yang Muh-Hwa , Chen Chih-Li , Chau Gar-Yang , Chiou Shih-Hwa , Su Chien-Wei , Chou Teh-Ying , Peng Wei-Li , Wu Jaw-Ching
Published: August 2009

The epithelial-mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC). Reduced E-cadherin and nonmembranous β-catenin expression, the hallmarks of EMT, were shown in 60.2% and 51.5% of primary HCC samples, respectively. Overexpression of Snail, Twist, or Slug, the major regulators of EMT, was identified in 56.9%, 43.1%, and 51.4% of primary HCCs, respectively. Statistical analysis determined that Snail and Twist, but not Slug, are major EMT inducers in HCC: overexpression of Snail and/or Twist correlated with down-regulation of E-cadherin, nonmembranous expression of β-catenin, and a worse prognosis. In contrast, there were no such significant differences in samples that overexpressed Slug. Coexpression of Snail and Twist correlated with the worst prognosis of HCC. Hepatitis C-associated HCC was significantly correlated with Twist overexpression. HCC cell lines with increased Snail and Twist expression (e.g., Mahlavu) exhibited a greater capacity for invasiveness/metastasis than cells with low endogenous Twist/Snail expression (e.g., Huh-7). Overexpression of Snail or/and Twist in Huh-7 induced EMT and invasiveness/metastasis, whereas knockdown of Twist or Snail in Mahlavu reversed EMT and inhibited invasiveness/metastasis. Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E-cadherin transcription. Conclusion: Our study provides a comprehensive profile of EMT markers in HCC, and the independent and collaborative effects of Snail and Twist on HCC metastasis were confirmed through different assays. (Hepatology 2009.)
Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach
Authors: Bellan Cristiana , Stefano Lazzi , Giulia De Falco , Rogena Emily A. , Lorenzo Leoncini
Published: August 2009

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an “aggressive B‐cell non‐Hodgkin's lymphoma”, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of “B‐cell lymphoma, unclassificable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma”, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.
El Niño and prediction of anomalous monthly rainfalls in Ecuador
Authors: Rossel Frédéric , Cadier Eric
Published: August 2009

The coastal regions of Northern Peru and Southern Ecuador are well known for their sensitivity to the El Niño/Southern Oscillation (ENSO) phenomenon. Abundant rainfall is generally related to hot weather in the eastern tropical Pacific and to the weakened South Pacific trade winds, which allow the inter‐tropical convergence zone (ITCZ) to migrate far to the south and to convey warm moist air to the coastal area. A new monthly rainfall index series has been established using data from a network of 75 rainfall stations in Ecuador's coastal region. Throughout the analysis, a distinction is made between a ‘dependent’ data set (1964–1982) used as a training period and an ‘independent’ portion of the record (1983–1993) reserved for validation. Multiple regression models are developed to predict monthly rainfall in the Guayaquil area, using as predictors precipitation, sea surface temperature (SST), meridional and zonal wind in the eastern equatorial Pacific, with all predictions being based on a one‐month lead time. The resulting equations were used to predict rainfall anomalies in the independent data set. There is considerable predictive power for the rainy months of the year, the best predictability being for the period from March to May. The multiple linear correlations explain 60–82% of the monthly precipitation variance. The north region's pre‐season rainfall is the most powerful predictor for the rainy season peak in Guayaquil, whereas the eastern equatorial Pacific SST is the most powerful predictor for the end of the rainy season. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis and evaluation of two fluorine‐18 labelled phenylbenzothiazoles as potential in vivo tracers for amyloid plaque imaging
Authors: Serdons K. , Vanderghinste D. , Van Eeckhoudt M. , Borghgraef P. , Kung H. , Van Leuven F. , de Groot T. , Bormans G. , Verbruggen A.
Published: August 2009

Uncharged derivatives of thioflavin‐T have known in vitro and in vivo affinity for amyloid β. We synthesized and evaluated two derivatives with a fluorine‐18 labelled fluoropropoxy substituent either at the 6‐position or at the 2′‐position of the 2‐(4′‐aminophenyl)‐1,3‐benzothiazole core with the aim to get suitable radiotracers to perform amyloid plaque imaging. The fluorine‐18 labelled compounds were obtained by nucleophilic substitution of the corresponding tosyl precursors with [18F]fluoride with a radiochemical yield of 50%, yielding 6‐(3′′‐[18F]fluoropropoxy)‐2‐(4′‐aminophenyl)‐1,3‐benzothiazole ([18F]2) and 2‐[2′‐(3′′‐[18F]fluoropropoxy)‐4′‐aminophenyl]‐1,3‐benzothiazole ([18F]3) with a specific activity between 33 and 51 GBq/µmol. The identity of the radiolabelled compounds was confirmed using radio‐LC‐MS and by comparing retention times on RP‐HPLC. Biodistribution studies in healthy mice showed for both compounds a relatively high initial brain uptake, which was significantly higher for [18F]2 than for [18F]3 (4.5% ID/g versus 3.0% ID/g, p<0.05). Wash‐out from control brain was faster for [18F]3. In vitro binding affinity tests using human AD brain homogenates revealed that only compound 2 has affinity for fibrillar amyloid β (Ki=14.5 nM). This was confirmed by the incubation of transgenic APP mouse brain sections with the cold compounds, where 3 did not stain any structure whereas 2 stained amyloid plaques present in APP mouse brain. These data suggest that [18F]2 may be a useful tracer for in vivo visualization of fibrillar amyloid β. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of deuterium labelled diclofenac with improved isotopic enrichment
Authors: Wu Keying , Tian Lei , Li Hongye , Li Jian , Chen Liqin
Published: August 2009

A five‐step synthesis of deuterium‐labelled diclofenac starting from 2‐phenyl[2H5] acetic acid is described. The synthesis prevents deuterium from scrambling during the reaction. It offers the labelled compound with over 99% isotopic enrichment. It also provides a possible alternative route for the synthesis of deuterium‐labelled 4′‐hydroxydiclofenac, which is the principal human metabolite of diclofenac. Copyright © 2009 John Wiley & Sons, Ltd.
Developing a sustainability ethic in leaders
Authors: Middlebrooks Anthony , Miltenberger Lauren , Tweedy James , Newman Grant , Follman Joanna
Published: August 2009

The triple bottom line of fiscal, social, and environmental success considerably alters how organizations (and stakeholders) measure sustainable success. More important, however, is the conceptual shift required to understand and successfully lead organizations within this increasingly accepted paradigm. This article uses a mixed‐methods approach to explore the conceptual development of a sustainability ethic in aspiring leaders. More specifically, the authors report research examining the curriculum and pedagogy of a leadership education effort, in this case a college‐level course, aimed at effecting change in both individual aspiring leaders and their immediate community. The article describes the philosophical and research base for the curriculum and specific activities with their pedagogical approach. Results show evidence of increased awareness, importance, and commitment to sustainability as well as changes in how students conceptualize sustainability leadership. Findings offer insights for further developing leadership education for sustainability.
LDR 2 LDR: University faculty communicating practice through theory
Authors: Waite Duncan
Published: August 2009

An act of leadership is always an act of practical theory. We lead because we hold visions of the world as it ought to be, because of the not yet, because of the potential that we see in ideas and people. Yet, there still exists a perceived binary between leadership theory (in the strong sense) and leadership practice, a binary that divides organizations, classrooms, and the differing bodies of leadership literature. In this Symposium, Duncan Waite and his colleagues discuss the barriers they have faced in bringing theory to the educational leadership classroom, as well as the promise they feel theory holds for more productive, equitable, and humane schooling organizations.
Collective leadership: Practice, theory, and praxis
Authors: Guajardo Miguel A.
Published: August 2009

An act of leadership is always an act of practical theory. We lead because we hold visions of the world as it ought to be, because of the not yet, because of the potential that we see in ideas and people. Yet, there still exists a perceived binary between leadership theory (in the strong sense) and leadership practice, a binary that divides organizations, classrooms, and the differing bodies of leadership literature. In this Symposium, Duncan Waite and his colleagues discuss the barriers they have faced in bringing theory to the educational leadership classroom, as well as the promise they feel theory holds for more productive, equitable, and humane schooling organizations.
Performing tip‐enhanced Raman spectroscopy in liquids
Authors: Schmid Thomas , Yeo Boon‐Siang , Leong Grace , Stadler Johannes , Zenobi Renato
Published: August 2009

Many outstanding questions in biology and medicine require analytical tools that provide imaging and chemical information with high spatial resolution. Tip‐enhanced Raman spectroscopy (TERS) has been shown to allow both topographic and label‐free chemical information to be obtained with a lateral resolution of approximately 20–50 nm, but has been performed only in air or ultrahigh vacuum until now. Since most biological samples such as cells and tissues can only be studied in their active state if they are kept in aqueous buffers, TERS in liquids would be a crucial step towards nanoscale chemical analysis of living biological entities. For the first time, we introduce TERS experiments that have been performed with both the tip and sample completely immersed in water. We demonstrate that SiOx/Ag‐coated AFM tips provide enhancement factors of >104 with visible light irradiation and are robust enough to be used in water. Furthermore, the tips have been protected from contaminants by adsorbing a self‐assembled monolayer (SAM) of ethanethiolate on their Ag surfaces. The protection layer caused the enhancement to drop by a factor of approximately 5, but successfully prevented the adsorption of analyte molecules, carbon, and other contamination to the tip. Furthermore, our experiments have shown that the formation of carbonaceous contamination by laser irradiation on the tip is dramatically slowed down when TERS experiments are performed in water. Finally, a proof‐of‐principle study on SAMs of thiophenolate on Au surfaces demonstrates the feasibility of performing TERS in liquids. Copyright © 2009 John Wiley & Sons, Ltd.
Kinetic study of hydroperoxide epoxidation of 1‐octene in the presence of molybdenum disilicide as a catalyst in a low concentration range of olefin
Authors: Trach Yuriy B. , Makota Oksana I.
Published: August 2009

The kinetic regularities of the influence of low 1‐octene concentrations on its epoxidation by tert‐butyl hydroperoxide in the presence of molybdenum disilicide (MoSi2) as a catalyst were investigated. The minimum in the dependence of the initial rate of hydroperoxide consumption on 1‐octene concentration was observed. The kinetic scheme of epoxidation, which includes the competition between hydroperoxide and olefin for the catalytic active centers, was proposed. The equation for the reaction rate was derived according to the kinetic scheme. The kinetic parameters of epoxidation were calculated. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 623–628, 2009
Selective Fluorescence Quenching by Group 8 Metal Ions of a Water‐Soluble Poly(p‐phenylene vinylene) Derivative Bearing Oligo(oxyethylene) Pendants
Authors: Kim Kyu‐Nam , Kwon Young‐Wan , Choi Dong Hoon , Jin Jung‐Il
Published: August 2009

A new fluorescing, water‐soluble derivative of poly(p‐phenylene vinylene), poly[2,5‐bis(oligooxyethylene)‐1,4‐phenylene vinylene], P(OE‐PV), is synthesized via a multistep route. The UV‐vis absorption and photoluminescence properties of the polymer are studied in aqueous solutions in the presence of 25 different metal ions. Among the ions studied, Fe(III), Os(III) and Ru(III) are found to effectively quench the fluorescence of P(OE‐PV). The Ru(III) is the most efficient in the fluorescence quenching. This observation implies that the polymer is a sensitive and selective chemosensor for these ions. It is suggested that the photoinduced electron transfer from the excited state of P(OE‐PV) to the metal ions may be the quenching mechanism application to the present systems.

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Novel Thermosets from the Cationic Copolymerization of Modified Linseed Oils and Dicyclopentadiene
Authors: Xia Ying , Henna Phillip H. , Larock Richard C.
Published: August 2009

A series of soft to tough copolymers have been prepared by the cationic copolymerization of the modified linseed oils Dilulin or ML189 with DCPD. Soxhlet extraction and solid‐state 13C NMR spectra indicate that the bulk copolymers consist of a cross‐linked oil/DCPD network interpenetrated with certain amounts of soluble components. The Tgs of the resulting Dil/DCPD and ML189/DCPD copolymers are in the range 15–83 and 8–77 °C, respectively, and increase linearly with the increase of the DCPD amount. The room‐temperature storage moduli range from 4.43 × 106 to 1.52 × 109 Pa for the Dil/DCPD copolymers and from 3.72 × 106 to 1.44 × 109 Pa for the ML189/DCPD copolymers.

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LRRK2 R1628P variant is a risk factor of Parkinson's disease among Han‐Chinese from mainland China
Authors: Zhang Zijuan , Burgunder Jean‐Marc , An Xingkai , Wu Yan , Chen Wenjun , Zhang Jinhong , Wang Yingcheng , Xu Yanming , Gou Yingru , Yuan Guanggu , Mao Xueye , Peng Rong
Published: August 2009

Mutations in LRRK2, the gene that encodes leucine‐rich repeat kinase 2 (LRRK2), are associated with autosomal dominant and sporadic forms of Parkinson's disease (PD) and are the most common genetic causes of PD. Recently, a R1628P variant has been reported as a risk factor for PD in Taiwan and Singapore. To determine the association of this variant and PD in the Han‐Chinese population from mainland China, we analyzed its frequency in a cohort of 600 patients and 459 unrelated healthy controls. Forty (6.7%) patients were heterozygous and 3 (0.5%) homozygous for the R1628P variant, which was significantly more frequent than in the controls [2.4% heterozygous and 0.0% homozygous, Odds ratio = 3.14, 95%CI: 1.60–6.17, P < 0.01]. Considering the age at onset, this difference was found only in late‐onset PD (older than 50) [Odds ratio = 3.76, 95% CI: 1.90–7.45, P < 0.01]. Our data confirms that the LRRK2 R1628P variant is associated with an increased risk to develop late onset PD in the ethnic Han‐Chinese population. © 2009 Movement Disorder Society
Physical assessment as a predictor of mortality in people with Parkinson's disease: A study over 7 years
Authors: Gray William K. , Hildreth Anthony , Bilclough Julie A. , Wood Brian H. , Baker Katherine , Walker Richard W.
Published: August 2009

The primary aim of this study was to ascertain whether a battery of physical function measures in a Parkinson's disease (PD) patient cohort predicted mortality status at 7‐year follow‐up. Secondary aims were establishing which specific tests were the most useful, and whether PD phenotype was a predictor. A retrospective correlation design was used in this study. A cohort of 109 PD patients underwent baseline physiotherapy assessment of gait, balance, posture, muscle strength, and ability to change postural set. We compared mortality status at 7‐year follow‐up and baseline physical assessment tests. Tinetti gait and balance scores, UPDRS score, 10‐m walk test (time, velocity, and number of strides), posture in standing, lying to sitting, sitting to standing, getting up from floor assessments, and time to ascend and descend four steps were found to be statistically significant physical predictors of mortality at 7‐year follow‐up. In addition, age, sex, and mini‐mental state examination were significant nonphysical predictors of mortality. Using Cox regression, a survival model was constructed with age, sex, and Tinetti gait score as independent predictors of mortality. The results of this study suggest that there is a link between reduced physical function and an increased mortality risk in PD populations. © 2009 Movement Disorders Society
Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations
Authors: Limousin Nadège , Konofal Eric , Karroum Elias , Lohmann Ebba , Theodorou Ioannis , Dürr Alexandra , Arnulf Isabelle
Published: August 2009

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep‐wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video‐polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35–60 years, from seven families) and 11 sex‐matched patients with iPD (aged 51–65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent. © 2007 Movement Disorder Society
Launching invasive, first‐in‐human trials against Parkinson's disease: Ethical considerations
Authors: Kimmelman Jonathan , London Alex John , Ravina Bernard , Ramsay Tim , Bernstein Mark , Fine Alan , Stahnisch Frank W. , Emborg Marina Elena
Published: August 2009

The decision to initiate invasive, first‐in‐human trials involving Parkinson's disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable risk‐benefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies. © 2009 Movement Disorder Society
On a generalized Appell system and monogenic power series
Authors: Bock S. , Gürlebeck K.
Published: August 2009

Recently Appell systems of monogenic polynomials in ℝ3were constructed by several authors. Main purpose of this paper is the description of another Appell system that is complete in the space of square integrable quaternion‐valued functions. A new Taylor‐type series expansion based on the Appell polynomials is presented, which can be related to the corresponding Fourier series analogously as in the complex one‐dimensional case. These results find applications in the description of the hypercomplex derivative, the monogenic primitive of a monogenic function and the characterization of functions from the monogenic Dirichlet space. Copyright © 2009 John Wiley & Sons, Ltd.
Interface crack problems for metallic–piezoelectric composite structures
Authors: Natroshvili D. , Stratis I. G. , Zazashvili S.
Published: August 2009

We investigate three‐dimensional interface crack problems (ICP) for metallic–piezoelectric composite bodies. We give a mathematical formulation of the physical problem when the metallic and piezoelectric bodies are bonded along some proper part of their boundaries where an interface crack occurs. By potential methods the ICP is reduced to an equivalent strongly elliptic system of pseudodifferential equations on manifolds with boundary. We study the solvability of this system in different function spaces and prove uniqueness and existence theorems for the original ICP. We analyse the regularity properties of the corresponding electric and mechanical fields near the crack edges and near the curves where the boundary conditions change. In particular, we characterize the stress singularity exponents and show that they can be explicitly calculated with the help of the principal homogeneous symbol matrices of the corresponding pseudodifferential operators. We present some numerical calculations that demonstrate that the stress singularity exponents essentially depend on the material parameters. Copyright © 2009 John Wiley & Sons, Ltd.
Myocardial perfusion MRI with sliding‐window conjugate‐gradient HYPR
Authors: Ge Lan , Kino Aya , Griswold Mark , Mistretta Charles , Carr James C. , Li Debiao
Published: August 2009

First‐pass perfusion MRI is a promising technique for detecting ischemic heart disease. However, the diagnostic value of the method is limited by the low spatial coverage, resolution, signal‐to‐noise ratio (SNR), and cardiac motion‐related image artifacts. In this study we investigated the feasibility of using a method that combines sliding window and CG‐HYPR methods (SW‐CG‐HYPR) to reduce the acquisition window for each slice while maintaining the temporal resolution of one frame per heartbeat in myocardial perfusion MRI. This method allows an increased number of slices, reduced motion artifacts, and preserves the relatively high SNR and spatial resolution of the “composite images.” Results from eight volunteers demonstrate the feasibility of SW‐CG‐HYPR for accelerated myocardial perfusion imaging with accurate signal intensity changes of left ventricle blood pool and myocardium. Using this method the acquisition time per cardiac cycle was reduced by a factor of 4 and the number of slices was increased from 3 to 8 as compared to the conventional technique. The SNR of the myocardium at peak enhancement with SW‐CG‐HYPR (13.83 ± 2.60) was significantly higher (P < 0.05) than the conventional turbo‐FLASH protocol (8.40 ± 1.62). Also, the spatial resolution of the myocardial perfection images was significantly improved. SW‐CG‐HYPR is a promising technique for myocardial perfusion MRI. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Theory of Q‐ball imaging redux: Implications for fiber tracking
Authors: Barnett Alan
Published: August 2009

Q‐ball imaging is widely used to determine fiber directions for fiber tracking. In q‐ball imaging the directional dependence of water diffusion in tissue is described by Tuch's orientation distribution function (ODF); a different function, the q‐ball orientation distribution function, is measured using high angular resolution magnetic resonance diffusion imaging (HARDI). Tuch's ODF is assumed to be well approximated by the q‐ball ODF. In this study it is shown that: 1) the q‐ball ODF is not a good approximation to Tuch's ODF; 2) the properties of the q‐ball ODF depend strongly on q, the area of the diffusion sensitization gradients; and 3) the q‐ball ODF for a composite system is the weighted average of the q‐ball ODFs for each subsystem, but the weighting factor is the product of the percent composition and a renormalization factor. In addition, a derivation is presented of the q‐ball ODF for a system described by a Gaussian distribution and expressions are derived for both the dependence of the angular resolution on q and for the relation between the angular resolution and the signal loss. These findings might be useful in the design and interpretation of fiber‐tracking experiments. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Partial volume effect (PVE) on the arterial input function (AIF) in T1‐weighted perfusion imaging and limitations of the multiplicative rescaling approach
Authors: Hansen Adam E. , Pedersen Henrik , Rostrup Egill , Larsson Henrik B.W.
Published: August 2009

The partial volume effect (PVE) on the arterial input function (AIF) remains a major obstacle to absolute quantification of cerebral blood flow (CBF) using MRI. This study evaluates the validity and performance of a commonly used multiplicative rescaling of the AIF to correct for the PVE. In a group of six patients, perfusion imaging was performed using a T1‐weighted approach that minimizes confounding susceptibility artifacts. Various degrees of PVE were induced on the AIF and subsequently corrected using four different schemes of multiplicative AIF rescaling. Our results show that a multiplicative rescaling is not always applicable and can introduce a CBF bias. An easily measurable quantity denoted the tissue signal fraction (TSF) is proposed as a measure of the applicability of a multiplicative rescaling. For the present CBF quantification method, a TSF of <0.4 results in a CBF bias <15% after AIF rescaling. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Bounding the expected number of rectilinear full Steiner trees
Authors: Wulff‐Nilsen Christian
Published: August 2009

Given a finite set Z of n points, called terminals, in ℝd, the Rectilinear Steiner Tree Problem asks for a tree of minimal L1‐length spanning Z. An optimal solution has a unique decomposition into full Steiner trees (FSTs). By using geometric properties and combinatorial arguments, we bound the expected number of FSTs satisfying simple necessary conditions for being part of an optimal solution. More specifically, we show that the expected number of FSTs spanning exactly K terminals and satisfying the empty lune property, a weak version of the bottleneck property, and the so‐called empty hyperbox property is O(n(log log n)2(d−1)) for K = 3 and O(n(log log n)d−1 log K−2n) for K > 3, assuming terminals are randomly distributed in a hypercube with a uniform distribution. In the plane, we improve an earlier bound by showing that the expected number of FSTs with the Hwang form spanning exactly K terminals and satisfying the empty lune property and the so‐called disjoint lunes property is O(nπK). © 2009 Wiley Periodicals, Inc. NETWORKS, 2010
Constraint preconditioning for nonsymmetric indefinite linear systems
Authors: Sun Li‐Ying , Liu Jun
Published: August 2009

This paper introduces and presents theoretical analyses of constraint preconditioning via a Schilders'‐like factorization for nonsymmetric saddle‐point problems. We extend the Schilders' factorization of a constraint preconditioner to a nonsymmetric matrix by using a different factorization. The eigenvalue and eigenvector distributions of the preconditioned matrix are determined. The choices of the parameter matrices in the extended Schilders' factorization and the implementation of the preconditioning step are discussed. An upper bound on the degree of the minimum polynomial for the preconditioned matrix and the dimension of the corresponding Krylov subspace are determined, as well as the convergence behavior of a Krylov subspace method such as GMRES. Numerical experiments are presented. Copyright © 2009 John Wiley & Sons, Ltd.
An enhanced‐physics‐based scheme for the NS‐α turbulence model
Authors: Miles William W. , Rebholz Leo G.
Published: August 2009

We study a new enhanced‐physics‐based numerical scheme for the NS‐alpha turbulence model that conserves both energy and helicity. Although most turbulence models (in the continuous case) conserve only energy, NS‐alpha is one of only a very few that also conserve helicity. This is one reason why it is becoming accepted as the most physically accurate turbulence model. However, no numerical scheme for NS‐alpha, until now, conserved both energy and helicity, and thus the advantage gained in physical accuracy by modeling with NS‐alpha could be lost in a computation. This report presents a finite element numerical scheme, and gives a rigorous analysis of its conservation properties, stability, solution existence, and convergence. A key feature of the analysis is the identification of the discrete energy and energy dissipation norms, and proofs that these norms are equivalent (provided a careful choice of filtering radius) in the discrete space to the usual energy and energy dissipation norms. Numerical experiments are given to demonstrate the effectiveness of the scheme over usual (helicity‐ignoring) schemes. A generalization of this scheme to a family of high‐order NS‐alpha‐deconvolution models, which combine the attractive physical properties of NS‐alpha with the high accuracy gained by combining α‐filtering with van Cittert approximate deconvolution. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2010
Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma
Authors: Kats‐Ugurlu Gursah , Roodink Ilse , de Weijert Mirjam , Tiemessen Dorien , Maass Cathy , Verrijp Kiek , van der Laak Jeroen , de Waal Rob , Mulders Peter , Oosterwijk Egbert , Leenders William
Published: August 2009

Tumour metastasis is the result of a complex sequence of events, including migration of tumour cells through stroma, proteolytic degradation of stromal and vessel wall elements, intravasation, transport through the circulation, extravasation and outgrowth at compatible sites in the body (the ‘seed and soil’ hypothesis). However, the high incidence of metastasis from various tumour types in liver and lung may be explained by a stochastic process as well, based on the anatomical relationship of the primary tumour with the circulation and mechanical entrapment of metastatic tumour cells in capillary beds. We previously reported that constitutive VEGF‐A expression in tumour xenografts facilitates this type of metastatic seeding by promoting shedding of multicellular tumour tissue fragments, surrounded by vessel wall elements, into the circulation. After transport through the vena cava, such fragments may be trapped in pulmonary arteries, allowing them to expand to symptomatic lesions. Here we tested whether this process has clinical relevance for clear cell renal cell carcinoma (ccRCC), a prototype tumour in the sense of high constitutive VEGF‐A expression. To this end we collected and analysed outflow samples from the renal vein, directly after tumour nephrectomy, in 42 patients diagnosed with ccRCC. Tumour fragments in venous outflow were observed in 33% of ccRCC patients and correlated with the synchronous presence or metachronous development of pulmonary metastases (p < 0.001, Fisher's exact test). In patients with tumours that, in retrospect, were not of the VEGF‐A‐expressing clear cell type, tumour fragments were never observed in the renal outflow. These data suggest that, in ccRCC, a VEGF‐A‐induced phenotype promotes a release of tumour cell clusters into the circulation that may contribute to pulmonary metastasis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
New evidence for tumour embolism as a mode of metastasis
Authors: Hart Ian R
Published: August 2009

The demonstration that a significant proportion of patients with renal carcinomas of the clear cell type have tumour cell clumps or aggregates in venous outflow from the kidney has interest from two viewpoints. Firstly, the association of this occurrence with high VEGF‐A production by the cancer seems to suggest a novel mode of ‘budding’ invasion where nests of tumour cells enter the dilated and mechanically fragile new vessels supplying the cancerous growth. Secondly, with the association of fragment occurrence and metastatic development, the entrance of clumps into the circulation indicates that epithelial–mesenchymal transition (EMT) is not an obligatory step for the disseminatory behaviour of all cancers. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dynamic mechanical analysis of pineapple leaf/glass hybrid fiber reinforced polyester composites
Authors: Devi L. Uma , Bhagawan S.S. , Thomas S.
Published: August 2009

The dynamic mechanical properties of randomly oriented intimately mixed hybrid composites based on pineapple leaf fibers (PALF) and glass fibers (GF) in unsaturated polyester (PER) matrix were investigated. The PALFs have high‐specific strength and improve the mechanical properties of the PER matrix. In this study, the volume ratio of the two fibers was varied by incorporating small amounts of GF such as PALF/GF, 90/10, 80/20, 70/30, and 50/50, keeping the total fiber loading constant at 40 wt%. The dynamic modulus of the compositeswas found to increase on GF addition. The intimately mixed (IM) hybrid composites with PALF/GF, 80/20 (0.2 Vf GF) showed highest E′ values and least damping. Interestingly, the impact strength of the composites was minimum at this volume ratio. The composites with 0.46 Vf GF or PALF/GF (50/50) showed maximum damping behavior and highest impact strength. The results were compared with hybrid composites of different layering patterns such as GPG (GF skin and PALF core) and PGP (PALF skin and GF core). IM and GPG hybrid composites are found more effective than PGP. The activation energy values for the relaxation processes in different composites were calculated. The overall results showed that hybridization with GF enhanced the performance properties. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers