bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticoagulation and Microembolus Detection in a Case of Internal Carotid Artery Dissection
Authors: Koch Sebastian , Romano Jose G. , Bustillo Iszet Campo , Concha Mauricio , Forteza Alejandro M.
Published: November 2009

Background. Microembolic signals (MES) have been demonstrated by transcranial Doppler (TCD) in cases of internal carotid artery dissection. The influence of treatment on MES in arterial dissection is uncertain. The authors here present a case of internal carotid artery dissection in which we detected a reduction of MES after the initiation of intravenous heparin. Methods. A 37‐year‐old woman developed a right temporal headache 10 days prior to admission. This was followed by episodes of left arm numbness and weakness. Magnetic resonance imaging (MRI) showed a right frontal and deep subcortical ischemic infarct. Catheter angiography confirmed a right internal carotid artery dissection with intracranial extension. She was then monitored with TCD for MES before and after intravenous heparin was started. Results. The first TCD, performed 12 days after symptom onset, showed 39 MES during 60 minutes of insonation of the right middle cerebral artery. Treatment with intravenous heparin resulted in a decline in MES by 50% after 96 hours. This decline continued and no further MES were detected after 11 days of anticoagulation. Conclusion. The authors were able to demonstrate a decline of MES with heparin anticoagulation in a case of internal carotid artery dissection.
A Pilot Study of Microembolic Signals in Patients With Middle Cerebral Artery Stenosis
Authors: Wong K. S. , Gao S. , Lam W.W.M. , Chan Y. L. , Kay R.
Published: November 2009

Objective. There has been limited data on the frequency of microembolic signals in patients with middle cerebral artery (MCA) stenosis, especially during the acute phase of stroke. Using transcranial Doppler, the authors prospectively monitored the MCA segments distal to stenosis in 4 groups of patients for 30 minutes: (1) symptomatic patients with acute ischemic stroke and MCA stenosis, (2) asymptomatic group patients with asymptomatic MCA stenosis, (3) control patients with acute ischemic stroke of undetermined etiology, and (4) normal people. A total of 60 patients completed the study. There were no microembolic signals in the asymptomatic, control, and normal groups. Among 20 patients in the symptomatic group, microembolic signals were detected in 3 patients (15%). The number of emboli ranged from 1 to 6 per 30 minutes. This is the first report of the presence of microembolic signals in acute stroke patients with MCA stenosis.
Between reform and inertia: Bolivia's employment and social protection policies over the past 20 years
Authors: WANDERLEY Fernanda
Published: November 2009

With the coming to power in 2006 of Evo Morales' Movement Toward Socialism, Bolivia entered a new stage in its history: a period of ambitious political and economic reform aiming to transcend the neo‐liberal development model in place since 1985 and to renew the State on the basis of its new Constitution, drawn up in 2008. Against this background, this article examines changes in labour law and social protection during the 1980s and 1990s and takes stock of the challenges of implementing a development strategy focusing on full employment and equity.
Physiological responses of young cross‐bred calves immediately after long‐haul road transportation and after one week of habituation
Authors: UETAKE Katsuji , ISHIWATA Toshie , TANAKA Toshio , SATO Shusuke
Published: November 2009

ABATRACT

We investigated 10 suckling cross‐bred calves (Japanese Black (Wagyu) × Holstein) and collected data on the physiological stress responses of the young calves to long‐haul road transportation. All calves were male and 21–47 days of age. The calves were obtained at a livestock market and were transported from the market to the university in a commercial livestock vehicle. The total haul distance and time were 306.9 km and 7 h, respectively. The calves were deprived of food and water during transportation. Blood samples, electrocardiograms, and rectal temperatures were collected immediately after transportation and after one week of habituation at the university. Serum pH was significantly lower (P < 0.01), while serum triiodothyronine, aspartate aminotransferase, non‐esterified fatty acids (allP < 0.05), and heart rate (P < 0.01) were significantly higher immediately after transportation. The concentrations of blood lactic acid (P = 0.08) and serum alanine aminotransferase (P = 0.06) tended to be higher after transportation. These physiological responses suggest that the stress caused by long‐haul transportation causes significant effects on liver function in young calves.
Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer
Authors: Mitsudomi Tetsuya , Yatabe Yasushi
Published: November 2009

Epidermal growth factor receptor (EGFR) and its three related proteins (the ERBB family) are receptor tyrosine kinases that play essential roles in both normal physiological conditions and cancerous conditions. Upon binding its ligands, dynamic conformational changes occur in both extracellular and intracellular domains of the receptor tyrosine kinases, resulting in the transphosphorylation of tyrosine residues in the C‐terminal regulatory domain. These provide docking sites for downstream molecules and lead to the evasion of apoptosis, to proliferation, to invasion and to metastases, all of which are important for the cancer phenotype. Mutation in the tyrosine kinase domain of the EGFR gene was found in a subset of lung cancers in 2002. Lung cancers with an EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. Here, we review the discovery of EGFR, the EGFR signal transduction pathway and mutations of the EGFR gene in lung cancers and glioblastomas. The biological significance of such mutations and their relationship with other activated genes in lung cancers are also discussed.
Chitosan Oligosaccharides Inhibit the Expression of Interleukin‐6 in Lipopolysaccharide‐induced Human Umbilical Vein Endothelial Cells Through p38 and ERK1/2 Protein Kinases
Authors: Liu Hong‐Tao , Li Wen‐Ming , Li Xiu‐Ying , Xu Qing‐Song , Liu Qi‐Shun , Bai Xue‐Fang , Yu Chao , Du Yu‐Guang
Published: November 2009

Abstract:  Chitosan oligosaccharides (COS) have been reported to exert anti‐fungal activities, antitumour activities and immuno‐enhancing effects. However, the potential roles of COS in the treatment of vascular inflammations remain unknown. In the present study, we examined the effects of COS on interleukin‐6 (IL‐6) production in human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). Induction of HUVECs with LPS (100 ng/ml) increased the mRNA expression and protein secretion of IL‐6 (versus the vehicle‐treated group, p < 0.01), which were significantly reverted by the pre‐treatment with COS (50–200 μg/ml) for 24 hr before LPS exposure (versus the LPS‐treated group, p < 0.05 or 0.01). Signal transduction studies showed that the pre‐treatment of HUVECs with COS (50–200 μg/ml) for 24 hr markedly inhibited the LPS‐induced over‐expression of phosphorylated p38 mitogen‐activated protein kinase (MAPK), phosphorylated ERK1/2 and nuclear factor κB (NF‐κB). Moreover, the LPS‐induced NF‐κB activation was suppressed by the specific ERK1/2 inhibitor PD98059 (30 μM) (versus the LPS‐treated group, p < 0.01), but not by the specific p38 MAPK inhibitor SB203580 (25 μM). Additionally, both MAPK inhibitors markedly suppressed LPS‐induced IL‐6 mRNA expression in HUVECs (versus the LPS‐treated group, p < 0.01). In conclusion, our results suggest that COS inhibit LPS‐induced up‐regulation of IL‐6 in HUVECs, and this can be regulated by at least two parallel signalling pathways: one via p38 MAPK pathway independent of NF‐κB activation and one via ERK1/2 pathway dependent on NF‐κB activation.
Raman scattering of carbon disulfide: The temperature effect
Authors: Wang Dake , Mittauer Kathryn , Reynolds Nicholas
Published: November 2009

A low-cost Raman system was constructed and used to perform Raman scattering measurements on liquid carbon disulfide at different sample temperatures. The ν1 and ν3 bands are identified based on the frequencies calculated by the normal mode analysis. The ratio of the intensities of the anti-Stokes and Stokes bands can be used to illustrate the Boltzmann distribution of the molecules among the vibrational energy levels.
Spreadsheet physics: Examples in meteorology and planetary science
Authors: Herman Rhett
Published: November 2009

By utilizing the iterative capabilities of spreadsheets, students who do not have a programming background may obtain numerical solutions to complex equations. This paper discusses two examples of spreadsheet programming. One models the structure of a planet using a set of ordinary differential equations depending on the radius of the planet. The other involves coupled partial differential equations in a model of a planetary atmosphere. The results of the planetary models are compared to the values for Earth and Neptune. The results of the atmospheric model are compared to values for Earth’s atmosphere.
Growth and Production of Eogammarus confervicolus (Amphipoda: Anisogammaridae) at a Log Storage Site and in Areas of Undisturbed Habitat within the Squamish Estuary, British Columbia
Authors: Stanhope M. J. , Levsngs C. D.
Published: November 2009

Growth and production of Eogammarus confervicolus was investigated in three contrasting habitats within the Squamish estuary: a log debris area, an embankment along the perimeter of a Carex lyngbyei marsh, and a Fucus distichus community. Eogammarus confervicolus annual production was highest in the "bank" habitat (21.38–21.65 g∙m−2∙yr−1) followed by Fucus (11.31–12.99 g∙m−2∙yr−1) and then wood debris (6.12–6.75 g∙m−2∙yr−1). P: B ratios were similar for the bivoltine wood debris and bank animals (4.67–5.15 and 5.94–6.01, respectively) but lower for the univoltine Fucus population (3.28–3.76). Growth rates were judged to be higher in bank and Fucus than in wood debris. Mortality rates were highest in wood debris. The food available for estuarine amphipods in wood debris habitats is thought to be inferior to that produced in marsh and algal communities. Despite the fact that E. confervicolus production in wood debris was much lower than in undisturbed locations, the possibility remains that such areas are still adequate food gathering areas for juvenile salmonids, if water quality conditions permit fish access to the log storage site.
Suitability of Vertical Slot and Denil Fishways for Passing North-Temperate, Nonsalmonid Fish
Authors: Schwalme Karl , Mackay William C. , Lindner Dieter
Published: November 2009

A vertical slot fishway and two Denil fishways (of 10 and 20% slope) built into a weir on the Lesser Slave River (55°18′N, 115°45′W) were studied from May 12 to June 25, 1984, to determine how effectively these designs pass north-temperate, nonsalmonid fishes. Thousands of spottail shiner (Notropis hudsonius), substantial numbers (> 100) of northern pike (Esox lucius), longnose sucker (Catostomus catostomus), white sucker (Catostomus commersoni), immature yellow perch (Perca flavescens), and lesser numbers of burbot (Lota lota), adult yellow perch, lake whitefish (Coregonus clupeaformis), and trout-perch (Percopsis omiscomaycus) ascended the fishways. Walleye (Stizostedion vitreum) and goldeye (Hiodon alosoides), although probably moving extensively through the river, did not use the fishways. Although high water levels allowed most fish to surmount the weir, of those that chose the fishway, pike strongly preferred to ascend the Denil fishways and the two sucker species preferred to ascend the vertical slot. Therefore, a combination of several different fishways may be required for the most efficient passage of a wide variety of species. Plasma glucose and lactate measurements on pike revealed that ascending the Denil fishways was only moderately stressful for these fish.
Molecular mechanism by which pioglitazone preserves pancreatic β-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARγ agonist
Authors: Kanda Yukiko , Shimoda Masashi , Hamamoto Sumiko , Tawaramoto Kazuhito , Kawasaki Fumiko , Hashiramoto Mitsuru , Nakashima Koji , Matsuki Michihiro , Kaku Kohei
Published: November 2009

Pioglitazone preserves pancreatic β-cell morphology and function in diabetic animal models. In this study, we investigated the molecular mechanisms by which pioglitazone protects β-cells in diabetic db/db mice. In addition to the morphological analysis of the islets, gene expression profiles of the pancreatic islet were analyzed using laser capture microdissection and were compared with real-time RT-PCR of db/db and nondiabetic m/m mice treated with or without pioglitazone for 2 wk or 2 days. Pioglitazone treatment (2 wk) ameliorated dysmetabolism, increased islet insulin content, restored glucose-stimulated insulin secretion, and preserved β-cell mass in db/db mice but had no significant effects in m/m mice. Pioglitazone upregulated genes that promote cell differentiation/proliferation in diabetic and nondiabetic mice. In db/db mice, pioglitazone downregulated the apoptosis-promoting caspase-activated DNase gene and upregulated anti-apoptosis-related genes. The above-mentioned effects of pioglitazone treatment were also observed after 2 days of treatment. By contrast, the oxidative stress-promoting NADPH oxidase gene was downregulated, and antioxidative stress-related genes were upregulated, in db/db mice treated with pioglitazone for 2 wk, rather than 2 days. Morphometric results for proliferative cell number antigen and 4-hydroxy-2-noneal modified protein were consistent with the results of gene expression analysis. The present results strongly suggest that pioglitazone preserves β-cell mass in diabetic mice mostly by two ways; directly, by acceleration of cell differentiation/proliferation and suppression of apoptosis (acute effect); and indirectly, by deceleration of oxidative stress because of amelioration of the underlying metabolic disorder (chronic effect).
Intermittent exercise abolishes the diurnal variation in endothelial-dependent flow-mediated dilation in humans
Authors: Jones Helen , Green Daniel J. , George Keith , Atkinson Greg
Published: November 2009

It is currently unclear to what extent diurnal variation and exercise effect endothelium-dependent nitric oxide (NO)-mediated vasodilation. Therefore, we measured brachial artery flow-mediated dilation (FMD) in 10 males (mean age = 28 yr, SD = 7), before and after a bout of intermittent cycling at 70% peak oxygen uptake on separate days beginning either at 0800 or 1600. Edge-detection and wall-tracking software was used to measure changes in arterial diameter, while shear rate (SR) was assessed using simultaneously derived blood flow velocity and B-mode diameter data. The FMD data were analyzed before and after normalization for SR with repeated-measures models. Before exercise, mean ± SD FMD was 7 ± 3% in the morning compared with 11 ± 6% in the afternoon ( P = 0.01). This diurnal variation persisted after data were normalized for SR, which was found to be unaffected by time of day ( P = 0.33). Postexercise SR was higher than at baseline (pre-exercise) ( P = 0.01) to a similar extent at both times of day. FMD was unaffected by exercise in the morning ( P = 0.96) but decreased by 4 ± 3% following exercise in the afternoon ( P = 0.01) so that postexercise measurements did not differ between times of day. These data indicate that endothelium-dependent FMD is lower in the morning, and this finding was not altered by normalization of FMD for diurnal variation in SR. This infers a reduced function of the intrinsic endothelial NO-vasodilator system in the morning. We also report, for the first time, that a bout of intermittent exercise abolishes this diurnal variation in endothelium-dependent FMD.
Th17: A New Participant in Gut Dysfunction in Mice Infected withTrichinella spiralis
Authors: Fu Yu , Wang Wenfeng , Tong Jingjing , Pan Qi , Long Yanqing , Qian Wei , Hou Xiaohua
Published: November 2009

Trichinella spiralisinfection in rodents is a well-known model of intestinal inflammation associated with hypermotility. Our aim was to elucidate if Th17 cells were involved in the development of gastrointestinal hypermotility in this experimental model. Intestinal inflammation was observed by hematoxylin-eosin (HE) staining. Jejunal smooth muscle contractility was investigated in response to acetylcholine (Ach). The effects of IL-17 on jejunum smooth muscle contractility were explored. Flow cytometry was used to analyze the proportion of Th17 cells in jejunum. The levels of IL-17, IL-23, and TGF-β1 in jejunum were measured by Western blot. Our results showed that the inflammation in jejunum was severe at 2 weeks postinfection (PI), which was not discernible at 8 weeks PI. Jejunal smooth muscle contractility was increased at 2 weeks PI and kept higher at 12 weeks PI. The proportion of Th17 cells and the expression of IL-17 were upregulated in jejunum at 2 weeks PI and normalized at 8 weeks PI. When jejunual smooth muscle strips were cultured with IL-17, contractions elicited by Ach were enhanced in a concentration-dependent manner. Our data suggest that Th17 cells are increased during acute infection withTrichinella spiralisand IL-17 may contribute to jejunal muscle contractility in mice.
Existence Results for Second‐Order Impulsive Neutral Functional Differential Equations with Nonlocal Conditions
Authors: Li Meili , Kou Chunhai
Published: November 2009

The existence of mild solutions for second‐order impulsive semilinear neutral functional differential equations with nonlocal conditions in Banach spaces is investigated. The results are obtained by using fractional power of operators and Sadovskii′s fixed point theorem.
Cytokine Expression in CD3+ Cells in an Infant with Food Protein-Induced Enterocolitis Syndrome (FPIES): Case Report
Authors: Mori F. , Barni S. , Cianferoni A. , Pucci N. , de Martino M. , Novembre E.
Published: November 2009

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by severe vomiting, diarrhea, and often failure to thrive in infants. Symptoms typically resolve after the triggering food-derived protein is removed from the diet and recur within few hours after the re-exposure to the causal protein. The diagnosis is based on clinical symptoms and a positive food challenge. In this study, we report a case of FPIES to rice in an 8-month-old boy. We performed a double-blind placebo-controlled food challenge (DBPCFC) to rice and we measured the intracellular T cell expression of interleukin-4 (IL-4); IL-10, and interferon (IFN-) pre-and post-challenge during an acute FPIES reaction and when tolerance to rice had been achieved. For the first time we describe an increase in T cell IL-4 and decrease in IFN- expression after a positive challenge with rice (i.e. rice triggered a FPIES attack) and an increase in T cell IL-10 expression after rice challenge 6 months later after a negative challenge (i.e., the child had acquired tolerance to rice) in an 8 month old with documented FPIES to rice. A Th2 activation associated with high IL-4 levels may contribute to the pathophysiology of the disease. On the other hand, T cell-derived IL-10 may play a role in the acquisition of immunotolerance by regulating the Th1 and Th2 responses.
Effect of MWNTs and SiC-Coated MWNTs on Properties of PEEK/LCP Blend
Authors: Nayak Ganesh Chandra , Rajasekar R. , Bose Saswata , Das Chapal Kumar
Published: November 2009

Multiwall carbon nanotubes (MWNTs) were modified with polycarbosilane-derived silicon carbide (SiC) to improve its dispersion in the polymer matrix. PEEK/LCP/MWNTs nanocomposites were prepared by melt blending. TEM images show the improved dispersion of SiC-coated MWNTs against agglomerated structure of pure MWNTs in the blend. FESEM images shows better fibrillation of LCP in presence of SiC-coated MWNTs. TGA reveals that nanocomposites with SiC-coated MWNTs shows higher thermal stability than MWNTs filled blend system. Based on enhanced dispersion, storage modulus, tensile modulus and tensile strength were increased drastically with the incorporation of SiC-coated MWNTs. Glass transition temperature of the nanocomposites shows significant improvement with the incorporation of MWNTs.
Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia
Authors: Guglielmelli Tommasina , Merlini Roberta , Giugliano Emilia , Saglio Giuseppe
Published: November 2009

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least2×109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.
EWS/FLI and Its Downstream Target NR0B1 Interact Directly to Modulate Transcription and Oncogenesis in Ewing's Sarcoma
Authors: Kinsey Michelle , Smith Richard , Iyer Anita K. , McCabe Edward R.B. , Lessnick Stephen L.
Published: November 2009

Most Ewing's sarcomas harbor chromosomal translocations that encode fusions between EWS and ETS family members. The most common fusion, EWS/FLI, consists of an EWSR1-derived strong transcriptional activation domain fused, in-frame, to the DNA-binding domain–containing portion of FLI1. EWS/FLI functions as an aberrant transcription factor to regulate genes that mediate the oncogenic phenotype of Ewing's sarcoma. One of these regulated genes, NR0B1, encodes a corepressor protein, and likely plays a transcriptional role in tumorigenesis. However, the genes that NR0B1 regulates and the transcription factors it interacts with in Ewing's sarcoma are largely unknown. We used transcriptional profiling and chromatin immunoprecipitation to identify genes that are regulated by NR0B1, and compared these data to similar data for EWS/FLI. Although the transcriptional profile overlapped as expected, we also found that the genome-wide localization of NR0B1 and EWS/FLI overlapped as well, suggesting that they regulate some genes coordinately. Further analysis revealed that NR0B1 and EWS/FLI physically interact. This protein-protein interaction is likely to be relevant for the development of Ewing's sarcoma because mutations in NR0B1 that disrupt the interaction have transcriptional consequences and also abrogate oncogenic transformation. Taken together, these data suggest that EWS/FLI and NR0B1 physically interact, coordinately modulate gene expression, and mediate the transformed phenotype of Ewing's sarcoma. [Cancer Res 2009;69(23):9047–55]
DNA Replication Licensing Factors and Aneuploidy Are Linked to Tumor Cell Cycle State and Clinical Outcome in Penile Carcinoma
Authors: Kayes Oliver J. , Loddo Marco , Patel Nimish , Patel Pranav , Minhas Suks , Ambler Gareth , Freeman Alex , Wollenschlaeger Alex , Ralph David J. , Stoeber Kai , Williams Gareth H.
Published: November 2009

Purpose: The DNA replication licensing machinery is integral to the control of proliferation, differentiation, and maintenance of genomic stability in human cells. We have analyzed replication licensing factors (RLF), together with DNA ploidy status, to investigate their role in progression of penile squamous cell carcinoma and to assess their utility as novel prognostic tools.

Experimental Design: In a cohort of 141 patients, we linked protein expression profiles of the standard proliferation marker Ki67 and the RLFs Mcm2 and geminin to clinicopathologic variables, ploidy status, and clinical outcome.

Results: Increased Ki67, Mcm2, and geminin levels were each significantly associated with arrested tumor differentiation (P < 0.0001) and aneuploidy (P ≤ 0.01). Accelerated cell cycle progression was linked to increasing tumor size, stage, and depth of invasion. Aneuploid tumors significantly correlated with tumor grade (P < 0.0001). Biomarker expression and DNA ploidy status were significant predictors of locoregional disease progression [Mcm2 (P = 0.02), geminin (P = 0.02), Ki67 (P = 0.03), and aneuploidy (P = 0.03)] in univariate analysis. Importantly, aneuploidy was a strong independent prognosticator for overall survival (hazard ratio, 4.19; 95% confidence interval, 1.17-14.95; P = 0.03). Used in conjunction with conventional pathologic information, multiparameter analysis of these variables can stratify patients into low- or high-risk groups for disease progression (Harrell's c-index = 0.88).

Conclusions: Our findings suggest that RLFs and tumor aneuploidy may be used as an adjunct to conventional prognostic indicators, identifying men at high risk of disease progression. Our results also identify the DNA replication initiation pathway as a potentially attractive therapeutic target in penile squamous cell carcinoma. (Clin Cancer Res 2009;15(23):7335–44)
A Four-Gene Signature from NCI-60 Cell Line for Survival Prediction in Non–Small Cell Lung Cancer
Authors: Hsu Yi-Chiung , Yuan Shinsheng , Chen Hsuan-Yu , Yu Sung-Liang , Liu Chia-Hsin , Hsu Pin-Yen , Wu Guani , Lin Chia-Hung , Chang Gee-Chen , Li Ker-Chau , Yang Pan-Chyr
Published: November 2009

Purpose: Metastasis is the main cause of mortality in non–small cell lung cancer (NSCLC) patients. Genes that can discriminate the invasion ability of cancer cells may become useful candidates for clinical outcome prediction. We identify invasion-associated genes through computational and laboratorial approach that supported this idea in NSCLC.

Experimental Design: We first conducted invasion assay to characterize the invasion abilities of NCI-60 lung cancer cell lines. We then systematically exploited NCI-60 microarray databases to identify invasion-associated genes that showed differential expression between the high and the low invasion cell line groups. Furthermore, using the microarray data of Duke lung cancer cohort (GSE 3141), invasion-associated genes with good survival prediction potentials were obtained. Finally, we validated the findings by conducting quantitative PCR assay on an in-house collected patient group (n = 69) and by using microarray data from two public western cohorts (n = 257 and 186).

Results: The invasion-associated four-gene signature (ANKRD49, LPHN1, RABAC1, and EGLN2) had significant prediction in three validation cohorts (P = 0.0184, 0.002, and 0.017, log-rank test). Moreover, we showed that four-gene signature was an independent prognostic factor (hazard ratio, 2.354, 1.480, and 1.670; P = 0.028, 0.014, and 0.033), independent of other clinical covariates, such as age, gender, and stage.

Conclusion: The invasion-associated four-gene signature derived from NCI-60 lung cancer cell lines had good survival prediction power for NSCLC patients. (Clin Cancer Res 2009;15(23):7309–15)
Phase I and Pharmacokinetic Study of Angiotensin-(1-7), an Endogenous Antiangiogenic Hormone
Authors: Petty W. Jeffrey , Miller Antonius A. , McCoy Thomas P. , Gallagher Patricia E. , Tallant E. Ann , Torti Frank M.
Published: November 2009

Purpose: Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system with antiproliferative and antiangiogenic properties. The primary objective of this study was to establish the recommended phase II dose of Ang-(1-7) for treating patients with advanced cancer. Secondary objectives were to assess toxicities, pharmacokinetics, clinical activity, and plasma biomarkers.

Experimental Design: Patients with advanced solid tumors refractory to standard therapy were treated with escalating doses of Ang-(1-7) in cohorts of three patients. Ang-(1-7) was administered by s.c. injection once daily for 5 days on a 3-week cycle. Tumor measurements were done every two cycles and treatment was continued until disease progression or unacceptable toxicity.

Results: Eighteen patients were enrolled. Dose-limiting toxicities encountered at the 700 μg/kg dose included stroke (grade 4) and reversible cranial neuropathy (grade 3). Other toxicities were generally mild. One patient developed a 19% reduction in tumor measurements. Three additional patients showed clinical benefit with stabilization of disease lasting more than 3 months. On day 1, Ang-(1-7) administration led to a decrease in plasma placental growth factor (PlGF) levels in patients with clinical benefit (P = 0.04) but not in patients without clinical benefit (P = 0.25). On day 5, PlGF levels remained lower in patients with clinical benefit compared with patients without clinical benefit (P = 0.04).

Conclusions: Ang-(1-7) is a first-in-class antiangiogenic drug with activity for treating cancer that is linked to reduction of plasma PlGF levels. The recommended phase II dose is 400 μg/kg for this administration schedule. (Clin Cancer Res 2009;15(23):7398–404)
Effects of Acute Cold Stress on Phagocytosis of Apoptotic Cells: The Role of Corticosterone
Authors: Sesti-Costa Renata , Baccan Gyselle Chrystina , Chedraoui-Silva Silvana , Mantovani Bernardo
Published: November 2009

Background and Aims: Stress can alter many aspects of the immune response, and many studies have been conducted on the effects of stress on inflammatory processes, but little is known about its influence on the resolution of inflammation in tissue homeostasis, which includes the clearance of apoptotic cells by macrophages in a non-phlogistic way. In the present study, we investigated the effect of acute cold stress on the phagocytosis of apoptotic cells by macrophages. Methods: Mice were submitted to acute cold stress (4°C for 4 h) and the capacity of peritoneal macrophages to phagocyte apoptotic thymocytes and to secrete anti-inflammatory cytokines was evaluated. Plasma corticosterone and catecholamine levels were investigated to assess their effect on the phagocytic capacity of macrophages in vitro. Results: We showed that acute cold stress decreases phagocytosis of apoptotic cells at the inflammatory site by lipopolysaccharide-activated macrophages but did not affect resting macrophages. The inhibitory effect on phagocytosis is accompanied by a reduced level of TGF-β and higher IL-10 secretion. After stress, plasma concentrations of corticosterone increased 6-fold, epinephrine 2-fold and norepinephrine 1.7-fold compared to control mice. In vitro experiments showed that the decrease in phagocytosis after stress could be attributed, at least in part, to the effects of corticosterone; epinephrine and norepinephrine had no effect. Conclusions: The current study shows that acute cold stress decreases phagocytosis of apoptotic cells from an inflammatory environment by macrophages, and this inhibition is mediated by the intracellular glucocorticoid receptor.
Upregulation of Transient Receptor Potential Vanilloid Type-1 Receptor Expression in Oral Lichen Planus
Authors: Bán Ágnes , Marincsák Rita , Bíró Tamás , Perkecz Anikó , Gömöri Éva , Sándor Katalin , Tóth István Balázs , Bánvölgyi Ágnes , Szolcsányi János , Pintér Erika
Published: November 2009

Objectives: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. Its etiology is still unclear. Neurogenic components might contribute to the inflammatory process. The oral mucosa is richly innervated by sensory fibers. Mediators secreted by inflammatory cells activate sensory nerves via transient receptor potential vanilloid receptor 1 (TRPV1) and lead to the release of neuropeptides. So far, TRPV1 receptor expression was detected on neurons. Only recently, TRPV1 receptors were identified in nonneuronal tissues. The aim of the present study was to detect the presence of TRPV1 receptors and peripheral expression of receptor mRNA in normal oral mucosa and mucous membranes from OLP patients. Methods: Presence of TRPV1 receptor proteins in the mucosal tissue was assessed by immunohistochemistry. Expression of TRPV1 receptor mRNA was determined by quantitative RT-PCR. Results: We provided qualitative and quantitative immunohistochemical evidence that TRPV1 receptors are present in normal human oral mucosa and that their expression is increased in OLP. The number of immunopositive cells was elevated in the epithelium, and vascular endothelial cells, lymphocytes and fibroblasts of the subepithelium were also labeled in samples obtained from OLP patients. The local expression of nonneuronal TRPV1 receptors was proven at mRNA level using quantitative real-time RT-PCR. Conclusions: Since the number of TRPV1 receptor-positive nonneural cells is increased in inflammatory conditions, we hypothesize that TRPV1-receptor-mediated processes might play role in the pathogenesis of OLP.
A Multicenter Pilot Study of a Bronchial Valve for the Treatment of Severe Emphysema
Authors: Sterman D.H. , Mehta A.C. , Wood D.E. , Mathur P.N. , McKenna, Jr. R.J. , Ost D.E. , Truwit J.D. , Diaz P. , Wahidi M.M. , Cerfolio R. , Maxfield R. , Musani A.I. , Gildea T. , Sheski F. , Machuzak M. , Haas A.R. , Gonzalez H.X. , Springmeyer S.C.
Published: November 2009

Background: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. Objective: To study the safety and effectiveness of the IBV® Valve for the treatment of severe emphysema. Methods: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. Results: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (–8.2 ± 16.2, mean ± SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean –294 ± 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV1, exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. Conclusion: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.
Some Phonetic Aspects of Breaking in West Frisian
Authors: de Graaf Tjeerd , Tiersma Peter
Published: November 2009

Breaking in West Frisian is a process where falling diphthongs [iÉ™], [iÉ™], [uÉ™] and [oÉ™] are converted to the corresponding rising (broken) diphthongs [jr], [jε], [wo] and [wa] under the influence of a following syllable or consonant cluster. The length of various diphthongs in several pairs of morphologically related words was measured for ten speakers, and the duration of the broken or unbroken diphthong in the derived word was compared with that of the base word. We found that there was reduction in the length of the diphthong in all cases where another syllable was added. The degree of shortening depended on factors such as the phonetic environment, the nature of the diphthong and the type of suffix which was affixed. Several tentative conclusions were reached regarding the relationship of shortening and breaking and the historical development of the process.
Laryngeal Adjustments in the Production of the Fricative Consonants and Devoiced Vowels in Japanese
Authors: Yoshioka Hirohide
Published: November 2009

The role of laryngeal adjustments for phonetic variations of voicing in Japanese-vowel devoicing and intervocalic /h/ voicing – was investigated using laryngeal electromyography (EMG) and fiberoptic endoscopy. The results indicated that the vowel devoicing was accompanied by EMG activity patterns of the posterior cricoarytenoid and interarytenoid different from those for fully voiced vowels, causing the glottis to be wide open. In this respect, it may be concluded that vowel devoicing mainly reflects a kind of free variation at a higher level than the EMG signals. In contrast, the voicing of /h/ occurred while the glottis remained as wide as it did for voiceless /h/ or /s/ with comparable EMG patterns of those muscles, despite the presence of vocal fold vibrations. Therefore, it may be that this latter phenomenon is chiefly dependent on some other condition at the level of the glottis.
Der Einfluß von Qualität und Quantität auf die Perzeption betonter Vokale des Deutschen (The Influence of Quality and Quantity on the Perception of Stressed Vowels in German)
Authors: Sendlmeier W.F.
Published: November 2009

It was the aim of this analysis to obtain information on the importance of such features as quantity and quality of vowels in an emphasized position in German words. In order to do this, the durations of emphasized vowels of spoken words were modified by a digital signal processing technique. The modified words were presented to native speakers for auditory judgments. The results of this research show that there is no uniform answer to the question of the perceptive, and thus phonological relevance of duration of German vowels.
Melanocortins Mimic the Effects of Leptin to Restore Reproductive Function in Lean Hypogonadotropic Ewes
Authors: Backholer Kathryn , Bowden Marissa , Gamber Kevin , Bjørbæk Christian , Iqbal Javed , Clarke Iain J.
Published: November 2009

Background/Aims: Leptin restores gonadotropic function in lean hypogonadotropic animals by an unknown mechanism. We aimed to test the hypothesis that restoration of gonadotropic function is a result of an upregulation of central acetylated melanocortin production. Methods and Results: Lean ovariectomised (OVX) ewes received intracerebroventricular (i.c.v.) infusions of leptin (or vehicle) for 3 days, which upregulated proopiomelanocortin (POMC) mRNA and restored pulsatile luteinizing hormone (LH) secretion. A melanocortin agonist (MTII), but not naloxone treatment, reinstated pulsatile LH secretion in lean OVX ewes. We treated (i.c.v.) lean OVX ewes with leptin (or vehicle) and measured peptide levels and post-translational modification in the arcuate nucleus (ARC). Levels of β-endorphin (β-END) were lower in lean animals, with no effect of leptin treatment. Desacetyl-α-MSH was the predominant form of α-melanocyte-stimulating hormone (α-MSH) in the ARC and levels were similar in all groups. In another group of lean and normal-weight OVX ewes, we measured the different forms of α-MSH in ARC, hypothalamus (ARC-removed) and the preoptic area (POA). Acetylated α-MSH levels were lower in lean animals in the terminal beds of the hypothalamus and POA but not the ARC. Conclusions: Leptin corrects the hypogonadotropic state in the lean condition by upregulation of POMC gene expression, and may increase transport and acetylation of melanocortins to target cells in the brain. Melanocortin treatment restores LH secretion in lean animals.
Morphological Analysis of 13
LMNA
Variants Identified in a Cohort of 324 Unrelated Patients With Idiopathic or Familial Dilated Cardiomyopathy
Authors: Cowan Jason , Li Duanxiang , Gonzalez-Quintana Jorge , Morales Ana , Hershberger Ray E.
Published: November 2009

Background—

Mutations in the
LMNA
gene, encoding lamins A/C, represent a significant cause of dilated cardiomyopathy. We recently identified 18 protein-altering
LMNA
variants in a cohort of 324 unrelated patients with dilated cardiomyopathy. However, at least one family member with dilated cardiomyopathy in each of 6 pedigrees lacked the
LMNA
mutation (nonsegregation), whereas small sizes of 5 additional families precluded definitive determinations of segregation, raising questions regarding contributions by those variants to disease.

Methods and Results—

We have consequently expressed, in COS7 cells, GFP-prelamin A (GFPLaA) fusion constructs incorporating the 6 variants in pedigrees with nonsegregation (R101P, A318T, R388H, R399C, S437Hfsx1, and R654X), the 4 variants in pedigrees with unknown segregation (R89L, R166P [in 2 families], I210S, R471H), and 3 additional missense variants (R190Q, E203K, and L215P) that segregated with disease. Confocal immunofluorescence microscopy was used to characterize GFP-lamin A localization and nuclear morphology. Abnormal phenotypes were observed for 10 of 13 (77%) variants (R89L, R101P, R166P, R190Q, E203K, I210S, L215P, R388H, S437Hfsx1, and R654X), including 4 of 6 showing nonsegregation and 3 of 4 with uncertain segregation. All 7 variants affecting coil 1B and the lamin A-only mutation, R654X, exhibited membrane-bound GFP-lamin A aggregates and nuclear shape abnormalities. Unexpectedly, R388H largely restricted GFP-lamin A to the cytoplasm. Equally unexpected were unique streaked aggregates with S437Hfsx1 and giant aggregates with both S437Hfsx1 and R654X.

Conclusions—

This work expands the recognized spectrum of lamin A localization abnormalities in dilated cardiomyopathy. It also provides evidence supporting pathogenicity of 10 of 13 tested
LMNA
variants, including some with uncertain or nonsegregation.
Features of Carcinoid Heart Disease Identified by 2- and 3-Dimensional Echocardiography and Cardiac MRI
Authors: Bhattacharyya Sanjeev , Toumpanakis Christos , Burke Margaret , Taylor Andrew M. , Caplin Martyn E. , Davar Joseph
Published: November 2009

Background—

Carcinoid heart disease is a rare form of valvular heart disease. We sought describe the spectrum of carcinoid heart disease identified by echocardiography and cardiac MRI.

Method and Results—

Two hundred fifty-two patients with carcinoid syndrome underwent a range of investigations including 2D transthoracic echocardiography, 3D transthoracic echocardiography and transesophageal echocardiography, and cardiac MRI. Fifty-two patients had evidence of carcinoid heart disease. Involvement of the tricuspid, pulmonary, mitral, and aortic valves were found in 47 (90%), 36 (69%), 15 (29%), and 14 (27%), respectively. Myocardial metastases were found in 2 (3.8%) patients. Several patterns of disease were identified depending on the extent and severity to which each leaflet and its associated subvavlular apparatus was affected. Thirteen of 15 (87%) patients with left-sided carcinoid involvement had a patent foramen ovale. Three patients with severe degree of shunting had severe valvular regurgitation. Patients with mild/moderate degree of shunting had mild or moderate valvular regurgitation. Three-dimensional transthoracic echocardiography/transesophageal echocardiography provided detailed anatomic information particularly for the tricuspid and pulmonary valves. Cardiac MRI allowed complementary assessment of valvular heart disease and delineation of myocardial metastases. Gallium-68 octreotide positron emission tomography identified neuroendocrine metastases.

Conclusions—

Carcinoid heart disease is a heterogeneous disease with a wide spectrum of echocardiographic findings. A multimodality approach is needed in patients with this complex pathology.
Popularizing Islamic Knowledge through Oral Epic: A Malian Bard in a Media Age
Authors: Zappa Francesco
Published: November 2009

This article explores a rather understudied feature of West African oral epics, namely its role as a channel for the transmission and popularization of Islamic religious knowledge. The documentary basis of analysis is provided by a set of oral texts performed in the Bambara language by a Malian griot (i.e. a member of an endogamous bards' lineage) and marketed in audiotape recorded form through the channels of local informal economy. Special attention is devoted to the multiple roles played by the bard in his complex relationship to Islamic knowledge. In spite of his abundant references to learned, sometimes even esoteric doctrines in texts appealing to a broad, undifferentiated audience, at a closer look the main goal of his popularizing attitude appears to be the reassertion of the legitimacy of traditionally trained local scholars and religious leaders, acting as his patrons, through a compelling magnification of their superior knowledge. What is at stake is precisely the defence of a locally rooted epistemological model against the challenges coming from Islamic reformers who promote alternative (and more rationalising) understandings of religious knowledge and authority. Seizing the new opportunities offered by the mediatization of his verbal art, the griot engages effectively in the religious debates that animate an increasingly globalised national public sphere.
Maritime Delimitation in the Black Sea Case (Romania v. Ukraine)
Authors: Anderson David
Published: November 2009

In a unanimous decision, the ICJ determined, in accordance with the UN Convention on the Law of the Sea, the single maritime boundary between the respective EEZs and continental shelves of Romania and Ukraine. The Court clarified its methodology for delimiting the EEZ/continental shelf, following a three-stage process. First, it drew a provisional equidistance line between what it decided were the most appropriate basepoints on the two coasts; secondly, it considered whether this line required adjustment; and finally, it verified that the line did not lead to an inequitable result. The Judgment contains important interpretations of several articles in the Convention, notably Articles 74 and 83.
Witnesses before the International Criminal Court
Authors: Ngane Sylvia Ntube
Published: November 2009

It is an established rule of international law that all witnesses shall testify at the seat of the court. The witness scheme of the International Criminal Court (ICC) is a complex one which provides for direct and indirect judicial authority over witnesses. This article grabbles with the complexities of the ICC procedural rules with regard to witnesses, concentrating on three components in the ICC witness scheme: testimony, cooperation and protection. Part I of this article examines the general rule of witness testimony before the Court and different alternatives for the giving of testimonial evidence when a witness cannot be present before the Court. The ICC's powers to compel witnesses are extremely limited and it is forced to rely on traditional legal assistance such as depositions. Part II discusses the exercise of indirect judicial authority by the Court through the assistance of States in relation to witnesses. It analyses provisions on State cooperation with witnesses, national implementing legislation with regard to witnesses and assesses the effectiveness of this legislation. The subsequent practice of State Parties as reflected by their implementing legislation on witnesses proves that a consistent practice does not exist. This section also examines the cooperation between the ICC and international organisations as regards witnesses. Part III examines the ICC Witness Protection Scheme; it looks at the ways in which witnesses are protected and it cites the practice of other tribunals. It then looks at the ICC's Victims and Witness Unit vis-à-vis the policies and mechanisms in place.