bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed Fiber Outgrowth from Transplanted Embryonic Cortex-Derived Neurospheres in the Adult Mouse Brain
Authors: Radojevic Vesna , Kapfhammer Josef P.
Published: February 2010

Neural transplantation has emerged as an attractive strategy for the replacement of neurons that have been lost in the central nervous system. Multipotent neural progenitor cells are potentially useful as donor cells to repopulate the degenerated regions. One important aspect of a transplantation strategy is whether transplanted cells are capable of fiber outgrowth with the aim of rebuilding axonal connections within the host brain. To address this issue, we expanded neuronal progenitor from the cortex of embryonic day 15 ubiquitously green fluorescent protein-expressing transgenic mice as neurospheres in vitro and grafted them into the entorhinal cortex of 8-week-old mice immediately after a perforant pathway lesion. After transplantation into a host brain with a lesion of the entorhino-hippocampal projection, the neurosphere-derived cells extended long fiber projections directed towards the dentate gyrus. Our results indicate that transplantation of neurosphere-derived cells might be a promising strategy to replace lost or damaged axonal projections.
Connectedness Degrees in L‐Fuzzy Topological Spaces
Authors: Shi Fu-Gui
Published: February 2010

The notion of separatedness degrees of L‐fuzzy subsets is introduced
in L‐fuzzy topological spaces by means of L‐fuzzy closure operators. Furthermore, the notion of
connectedness degrees of L‐fuzzy subsets is introduced. Many properties of connectedness in
general topology are generalized to L‐fuzzy topological spaces.
Evolutionary Aspects of Acaricide-Resistance Development in Spider Mites
Authors: Osakabe Masahiro (Mh.) , Uesugi Ryuji , Goka Koichi
Published: February 2010

Although the development of acaricide resistance in spider mites is a long-standing issue in agricultural fields, recent problems with acaricide resistance may be characterized by the development of complex- and/or multiresistance to acaricides in distinct classes. Such complexity of resistance is not likely to be a single mechanism. Pesticide resistance involves the microevolution of arthropod pests, and population genetics underlies the evolution. In this review, we address the genetic mechanisms of acaricide resistance evolution. We discuss genetic diversity and linkage of resistance genes, relationships between mite habitat and dispersal, and the effect of dispersal on population genetic structure and the dynamics of resistance genes. Finally, we attempt to present a comprehensive view of acaricide resistance evolution and suggest risks under globalization as well as possible approaches to managing acaricide resistance evolution or emergence.
Timing-Driven Nonuniform Depopulation-Based Clustering
Authors: Liu Hanyu , Akoglu Ali
Published: February 2010

Low-cost FPGAs have comparable number of Configurable Logic Blocks (CLBs) with respect to resource-rich FPGAs but have much less routing tracks. For CAD tools, this situation increases the difficulty of successfully mapping a circuit into the low-cost FPGAs. Instead of switching to resource-rich FPGAs, the designers could employ depopulation-based clustering techniques which underuse CLBs, hence improve routability by spreading the logic over the architecture. However, all depopulation-based clustering algorithms to this date increase critical path delay. In this paper, we present a timing-driven nonuniform depopulation-based clustering technique, T-NDPack, that targets critical path delay and channel width constraints simultaneously. T-NDPack adjusts the CLB capacity based on the criticality of the Basic Logic Element (BLE). Results show that T-NDPack reduces minimum channel width by 11.07% while increasing the number of CLBs by 13.28% compared to T-VPack. More importantly, T-NDPack decreases critical path delay by 2.89%.
Tight Junctions in Salivary Epithelium
Authors: Baker Olga J.
Published: February 2010

Epithelial cell tight junctions (TJs) consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins) define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.
New RTD‐Based General Threshold Gate Topologies and Application to Three‐Input XOR Logic Gates
Authors: Mirhoseini S. M. , Sharifi M. J. , Bahrepour D.
Published: February 2010

This paper presents two new general threshold gate (GTG) structures which are based on the monostable‐bistable element (MOBILE) as their main part. These new GTGs eliminate an RTD from the structure compared to old structures and lead to less elements count and better performance in terms of power consumption, maximum frequency, and power‐delay product (PDP). In the paper also two new single gate three‐input XOR logic gates based on the old GTGs and two ones based on the new GTGs are presented and simulated in HSPICE simulator.
Strong and Weak Convergence Theorems for Common Solutions of Generalized Equilibrium Problems and Zeros of Maximal Monotone Operators
Authors: Zeng L-C , Ansari QH , Shyu DavidS , Yao J-C
Published: February 2010

The purpose of this paper is to introduce and study two modified hybrid proximal-point algorithms for finding a common element of the solution set EP of a generalized equilibrium problem and the set "Equation missing" for two maximal monotone operators "Equation missing" and "Equation missing" defined on a Banach space "Equation missing". Strong and weak convergence theorems for these two modified hybrid proximal-point algorithms are established.
Ghrelin: Central Nervous System Sites of Action in Regulation of Energy Balance
Authors: Fry Mark , Ferguson Alastair V.
Published: February 2010

Ghrelin, a peptide hormone secreted by the stomach, has been shown to regulate energy homeostasis by modulating electrical activity of neurons in the central nervous system (CNS). Like many circulating satiety signals, ghrelin is a peptide hormone and is unable to cross the blood-brain barrier without a transport mechanism. In this review, we address the notion that the arcuate nucleus of the hypothalamus is the only site in the CNS that detects circulating ghrelin to trigger orexigenic responses. We consider the roles of a specialized group of CNS structures called the sensory circumventricular organs (CVOs), which are not protected by the blood-brain barrier. These areas include the subfornical organ and the area postrema and are already well known to be key areas for detection of other circulating hormones such as angiotensin II, cholecystokinin, and amylin. A growing body of evidence indicates a key role for the sensory CVOs in the regulation of energy homeostasis.
An Occlusion Approach with Consistency Constraint for Multiscopic Depth Extraction
Authors: Niquin Cédric , Prévost Stéphanie , Remion Yannick
Published: February 2010

This is a new approach to handle occlusions in stereovision algorithms in the multiview context using images destined for autostereoscopic displays. It takes advantage of information from all views and ensures the consistency of their disparity maps. We demonstrate its application in a correlation-based method and a graphcuts-based method. The latter uses a new energy, which merges both dissimilarities and occlusions evaluations. We discuss the results on real and virtual images.
Assessment of Landslide Susceptibility by Decision Trees in the Metropolitan Area of Istanbul, Turkey
Authors: Nefeslioglu H. A. , Sezer E. , Gokceoglu C. , Bozkir A. S. , Duman T. Y.
Published: February 2010

The main purpose of the present study is to investigate the possible application of decision tree in landslide susceptibility assessment. The study area having a surface area of 174.8 km2 locates at the northern coast of the Sea of Marmara and western part of Istanbul metropolitan area. When applying data mining and extracting decision tree, geological formations, altitude, slope, plan curvature, profile curvature, heat load and stream power index parameters are taken into consideration as landslide conditioning factors. Using the predicted values, the landslide susceptibility map of the study area is produced. The AUC value of the produced landslide susceptibility map has been obtained as 89.6%. According to the results of the AUC evaluation, the produced map has exhibited a good enough performance.
Detection of BCR-ABL Positive Cells in an Asymptomatic Patient: A Case Report and Literature Review
Authors: Bayraktar Soley , Goodman Mark
Published: February 2010

We report a case of an asymptomatic 39-year-old male who was incidentally found to have a white blood cell count of 15 000/ associated with a positive BCR-ABL/t(9;22)(q34;q11) chromosomal translocation detected in 51/300 of cells by FISH and RT-PCR from peripheral blood. Within the next 3 months, leukocytosis spontaneously subsided; however, BCR-ABL by RT-PCR and FISH was persistent both in peripheral blood and bone marrow. The patient was not started on any therapy and is being followed regularly with laboratory checkup and physical examination for monitoring signs and symptoms of chronic myeloid leukemia (CML) and biological behavior of his BCR-ABL transcripts. At 1 year of surveillance, he is disease free; however he has persistent detection of BCR-ABL fusion gene. Our case is challenging because actual risk of developing CML in BCR-ABL positive healthy, asymptomatic patients is not known.
A Transmit Beamforming and Nulling Approach with Distributed Scheduling to Improve Cell Edge Throughput
Authors: Wong Wendy C. , Li Qinghua , Talwar Shilpa
Published: February 2010

We propose a transmit scheme for WiMAX systems, where multiple base stations (BSs) employ downlink transmit beamforming and nulling for interference mitigation, with minimal coordination amongst BSs. This scheme improves system throughput and robustness, by increasing cell edge and overall cell throughputs by 68% and 19%, respectively, and by delivering improvement for mobile speed up to 60 km/h. First, cell edge users suffering from severe interferences are identified. Next, the RRM unit allocates resource to serving cell edge users only. BSs will schedule to serve their cell edge users independently using the allocated resources by the RRM. A special uplink sounding region is designed for BSs to learn the interference environment and form proper beams and nulls. The nulls formed towards users served by other BSs reduced interference from a BS towards these users and is the basic building block of our algorithm.
Interaction of Botulinum Toxin with the Epithelial Barrier
Authors: Fujinaga Yukako
Published: February 2010

Botulinum neurotoxin (BoNT) is a protein toxin (~150 kDa), which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex) and the interaction of these toxins with the epithelial barrier.
hsa-miR-29c* Is Linked to the Prognosis of Malignant Pleural Mesothelioma
Authors: Pass Harvey I. , Goparaju Chandra , Ivanov Sergey , Donington Jessica , Carbone Michele , Hoshen Moshe , Cohen Dalia , Chajut Ayelet , Rosenwald Shai , Dan Harel , Benjamin Sima , Aharonov Ranit
Published: February 2010

The inability to forecast outcomes for malignant mesothelioma prevents clinicians from providing aggressive multimodality therapy to the most appropriate individuals who may benefit from such an approach. We investigated whether specific microRNAs (miR) could segregate a largely surgically treated group of mesotheliomas into good or bad prognosis categories. A training set of 44 and a test set of 98 mesothelioma tumors were analyzed by a custom miR platform, along with 9 mesothelioma cell lines and 3 normal mesothelial lines. Functional implications as well as downstream targets of potential prognostic miRs were investigated. In both the training and test sets, hsa-miR-29c* was an independent prognostic factor for time to progression as well as survival after surgical cytoreduction. The miR was expressed at higher levels in epithelial mesothelioma, and the level of this miR could segregate patients with this histology into groups with differing prognosis. Increased expression of hsa-miR-29c* predicted a more favorable prognosis, and overexpression of the miR in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion, and colony formation. Moreover, major epigenetic regulation of mesothelioma is mediated by hsa-miR-29c* and was shown through downregulation of DNA methyltransferases as well as upregulation of demethylating genes. A single miR has the potential to be a prognostic biomarker in mesothelioma, and validation of these findings as well as investigation of its downstream targets may give insight for potential therapies in the future. Cancer Res; 70(5); 1916–24
Evaluation of Treatment-Associated Inflammatory Response on Diffusion-Weighted Magnetic Resonance Imaging and 2-[18F]-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography Imaging Biomarkers
Authors: Galbán Craig J. , Bhojani Mahaveer S. , Lee Kuei C. , Meyer Charles R. , Van Dort Marcian E. , Kuszpit Kyle K. , Koeppe Robert A. , Ranga Rajesh , Moffat Bradford A. , Johnson Timothy D. , Chenevert Thomas L. , Rehemtulla Alnawaz , Ross Brian D.
Published: February 2010

Purpose: Functional imaging biomarkers of cancer treatment response offer the potential for early determination of outcome through the assessment of biochemical, physiologic, and microenvironmental readouts. Cell death may result in an immunologic response, thus complicating the interpretation of biomarker readouts. This study evaluated the temporal effect of treatment-associated inflammatory activity on diffusion magnetic resonance imaging and 2-[18F]-fluoro-2-deoxy-d-glucose-positron emission tomography imaging (FDG-PET) biomarkers to delineate the effects of the inflammatory response on imaging readouts.

Experimental Design: Rats with intracerebral 9L gliosarcomas were separated into four groups consisting of control, an immunosuppressive agent dexamethasone (Dex), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and BCNU+Dex. Animals were imaged using diffusion-weighted magnetic resonance imaging and FDG-PET at 0, 3, and 7 days posttreatment.

Results: In the BCNU- and BCNU+Dex-treated animal groups, diffusion values increased progressively over the 7-day study period to ∼23% over baseline. The FDG percentage change of standard uptake value decreased at day 3 (−30.9%) but increased over baseline levels at day 7 (+20.1%). FDG-PET of BCNU+Dex-treated animals were found to have percentage of standard uptake value reductions of −31.4% and −24.7% at days 3 and 7, respectively, following treatment. Activated macrophages were observed on day 7 in the BCNU treatment group with much fewer found in the BCNU+Dex group.

Conclusions: Results revealed that treatment-associated inflammatory response following tumor therapy resulted in the accentuation of tumor diffusion response along with a corresponding increase in tumor FDG uptake due to the presence of glucose-consuming activated macrophages. The dynamics and magnitude of potential inflammatory response should be considered when interpreting imaging biomarker results. Clin Cancer Res; 16(5); 1542–52
The FLT3 Internal Tandem Duplication Mutation Is a Secondary Target of the Aurora B Kinase Inhibitor AZD1152-HQPA in Acute Myelogenous Leukemia Cells
Authors: Grundy Martin , Seedhouse Claire , Shang Shilli , Richardson Jaineeta , Russell Nigel , Pallis Monica
Published: February 2010

Aurora kinases play an essential role in orchestrating chromosome alignment, segregation, and cytokinesis during mitotic progression and both aurora-A and B are frequently overexpressed in a variety of human malignancies. In this study, we report the effects of AZD1152-HQPA, a highly selective inhibitor of aurora-B kinase, in acute myeloid leukemia (AML) cell lines and primary samples. We show that AZD1152-HQPA inhibits the phosphorylation of Histone H3 (pHH3) on serine 10 resulting in polyploid cells, apoptosis, and loss of viability in a panel of AML cell lines. We also show that AZD1152-HQPA sensitivity in our cell lines is irrespective of p53 status and the FLT3-ITD–expressing MOLM-13 and MV4-11 cell lines are particularly sensitive to AZD1152-HQPA. Internal tandem duplications (ITD) within the FLT3 tyrosine kinase receptor are found in ∼25% of AML patients and are associated with a poor prognosis. Here, we report that AZD1152-HQPA directly targets phosphorylated FLT3 along with inhibiting its downstream target phospho–signal transducer and activator of transcription 5 (STAT5) in the FLT3-ITD cell lines. We show pHH3 expression in primary AML blasts and its inhibition by AZD1152-HQPA at low doses in all of our primary samples tested. AZD1152-HQPA inhibits the clonogenic potential of primary AML samples, with FLT3-ITD samples being the most sensitive (P = 0.029). FLT3-ITD primary samples are also more sensitive to pHH3 inhibition (P = 0.022) and are particularly sensitive to pSTAT5 downregulation after treatment with AZD1152-HQPA compared with FLT3 wild-type samples (P = 0.007). We conclude that mutant FLT3 is a secondary target of AZD1152-HQPA and that FLT3-ITD primary samples are particularly sensitive to the drug. Mol Cancer Ther; 9(3); 661–72
Accuracy of the Extent of Bladder Cancer Nodal Metastases Found at Pelvic Lymphadenectomy at the Time of Cystectomy: Relation to Primary Tumor Stage
Authors: Rabbani Farhang , Lee Cheryl , Chang Sam S. , Lerner Seth P. , Wood David P. , Herr Harry W.
Published: February 2010

Objectives: To determine the minimum number of nodes (nmin) that need to be removed to ascertain N₀ status with 90/95% certainty, and to determine the maximum number of nodes theoretically involved for a given number ‘m’ of involved nodes reported out of a total of ‘n’ nodes examined. Methods: 2,025 patients underwent cystectomy and pelvic lymphadenectomy, with pathologic stage ≤pT2 in 1,132 (55.9%) and ≧pT3 in 893 (44.1%). A mathematical model was utilized, using incidences derived from those having ≧10 nodes retrieved. Results: For stage ≤pT2 and 0, 1, or 2 positive nodes reported, nmin are 2, 27, and 28, respectively, for 90% accuracy and 12, 29, and 29, respectively, for 95% accuracy. For stage ≧pT3 and 0, 1, or 2 positive nodes reported, nmin are 19, 28, and 29, respectively, for 90% accuracy and 24, 29, and 30, respectively, for 95% accuracy. Conclusions: Accuracy of the extent of nodal involvement depends on the number of positive nodes reported, total number of nodes retrieved, and pathologic stage. This model allows clinicians to assess potential underestimation of the ‘true’ number of involved nodes for a given number of positive nodes out of a total number reported.
Bacillus Calmette-Guérin versus Gemcitabine for Intravesical Therapy in High-Risk Superficial Bladder Cancer: A Randomised Prospective Study
Authors: Porena Massimo , Del Zingaro Michele , Lazzeri Massimo , Mearini Luigi , Giannantoni Antonella , Bini Vittorio , Costantini Elisabetta
Published: February 2010

Objective: To evaluate the safety, tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin (BCG) in the treatment of high-risk superficial bladder cancer. Method: 64 patients with high-risk superficial bladder cancer (pT1 and/or G3 and/or CIS) were assigned to interventions (gemcitabine or BCG) in a randomised controlled trial. All the patients were evaluated for recurrence and progression rates (primary endpoint) and safety and tolerability (secondary endpoint). Results: The two groups were comparable in terms of baseline characteristics. Tolerability was better for gemcitabine, whereas the BCG group experienced the need for delayed treatment or withdrawal in 12.5% of cases. At a mean follow-up of 44 months, the recurrence rate in patients treated with BCG was 28.1%; the recurrence rate in patients who received gemcitabine was 53.1% (p = 0.037). Time to recurrence was shorter in patients treated with BCG (25.6 vs. 39.4 months, p = 0.042). No patients developed disease progression. Conclusions: Gemcitabine is significantly inferior to BCG, but given its favourable toxicity profile, it may be useful for patients intolerant to or otherwise unable to receive BCG.
Outcome of Surgical Treatment of Patients with Upper versus Lower Urinary Tract Urothelial Carcinoma: Stage-by-Stage Comparison
Authors: Moussa S. , Yafi F.A. , El-Hakim A. , Fahmy N. , Aprikian A. , Tanguay S. , Anidjar M. , Kassouf W.
Published: February 2010

Objectives: It remains controversial whether we can apply similar principles in the management of upper urinary tract urothelial carcinoma (UUT-UC) based on the behavior of bladder urothelial carcinoma (B-UC). We sought to assess whether UUT-UC and B-UC have similar biology and performed a stage-by-stage comparative analysis of outcome between the 2 groups. Methods: A retrospective review was performed on patients who underwent nephroureterectomy for UUT-UC and radical cystectomy for B-UC from 1991 to 2006. Standard variables were collected and recurrence-free and overall survival (OS) rates were calculated. Results: 280 patients with a median age of 69 years were included (99 UUT-UC treated via nephroureterectomy and 181 B-UC treated via radical cystectomy). Median follow-up was 29 months. None received neoadjuvant chemotherapy. Patients with UUT-UC presented less commonly with invasive disease compared to those with B-UC (44 vs. 77% were >pT2). Overall, 5-year OS for the B-UC group was significantly lower than for the UUT-UC group (60.8 vs. 74.5%, p = 0.02). However, when patients were stratified by stage (>pT2), patients with B-UC had similar OS compared to those with UUT-UC (54.6 vs. 60.8%, p = 0.74). Conclusion: Invasive UUT-UC appears to have similar tumor biology compared to B-UC. Whether we can safely extrapolate on the benefit of neoadjuvant and adjuvant strategies to patients with UUT-UC requires further investigation.
Bone Marrow Mesenchymal Stem Cells Induce Angiogenesis and Promote Bladder Cancer Growth in a Rabbit Model
Authors: Zhang Keqin , Shi Benkang , Chen Jun , Zhang Dongqing , Zhu Yaofeng , Zhou Changkuo , Zhao Haifeng , Jiang Xianzhou , Xu Zhishun
Published: February 2010

Objectives: To investigate the effect of mesenchymal stem cells (MSCs) in the process of tumor development and the possibility of MSCs differentiating into vascular endothelial cells in the tumor microenvironment. Material and Methods: Twenty male New Zealand rabbits were randomly divided into 2 groups: a test group and a control group. MSCs were isolated and cultured by bone marrow cell adherence. The bladder tumor models were built by embedding a VX2 mass in swelled bladder mucosa in all of the rabbits (n = 20). One week later, 4′,6-diamidino-2-phenylindole-labeling MSCs were transplanted into tumor tissue in the test group (n = 10). Culture medium was injected into the tumor tissue of the control group (n = 10). The maximum diameter of the tumor mass was measured by ultrasound at 2 and 4 weeks after the VX2 tumor mass was embedded. All animals were sacrificed at 4 weeks. The double labeling immunofluorescence for CD146 was performed to reveal whether engrafted cells can differentiate into vascular endothelial cells. Vascular density was compared between the 2 groups. Results: There was no significant difference in the maximum diameters of the tumor masses between the 2 groups at 2 weeks (test group 0.77 ± 0.15 cm vs. control group 0.71 ± 0.15 cm, p > 0.05). The maximum diameters appeared larger in the test group at 4 weeks (test group 3.82 ± 0.94 cm vs. control group 2.28 ± 0.54 cm, p < 0.05). Immunofluorescence studies revealed some engrafted MSCs expressing a vascular endothelial cell phenotype (CD146). Furthermore, vascular density was augmented in the test group in comparison to the control group (10.1 ± 0.70/0.2 mm2 vs. 8.24 ± 0.81/0.2 mm2, p < 0.05). Conclusions: Engrafted MSCs can differentiate into vascular endothelial cells and contribute to angiogenesis in the tumor microenvironment, which may be the major pathway of promoting tumor growth.
Successful Treatment with Paclitaxel/Carboplatin Chemotherapy in Advanced Adenocarcinoma of the Urinary Tract Producing Carcinoembryonic Antigen, Carbohydrate Antigen 19-9 and Carbohydrate Antigen 125
Authors: Kato Manabu , Onishi Takehisa , Hoshina Akira , Yabana Tadasihi
Published: February 2010

Primary adenocarcinoma of the urinary tract producing tumor markers is extremely rare. We report 2 cases of advanced adenocarcinoma of the urinary tract producing carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125), which were completely resected after induction chemotherapy with paclitaxel and carboplatin. Patient 1 was a 72-year-old woman with adenocarcinoma of the right renal pelvis and ureter. Patient 2 was a 73-year-old woman with adenocarcinoma of the bladder. Serum levels of CEA, CA19-9 and CA125 were extremely elevated in both cases. They were successfully treated with paclitaxel puls carboplatin followed by surgery. Both patients were proved to have achieved pathological complete regression by surgical specimens and have been alive without recurrence for more than 18 and 6 months, respectively.
Plasma N-Terminal Pro-Brain Natriuretic Peptide as Prognostic Marker in Fatal Cardial Decompensation with Sunitinib Malate Therapy
Authors: Staehler Michael , Haseke Nicolas , Zilinberg Katja , Stadler Thomas , Stief Christian G.
Published: February 2010

A 74-year-old man with metastatic renal cell carcinoma and a history of cardiac failure was treated with sunitinib malate. MUGA echocardiography could not detect a relevant change in the ejection fraction although the clinical situation of the patient worsened dramatically. The only parameter to hint at the deteriorated cardiac function was plasma N-terminal pro-brain natriuretic peptide (BNP). Finally, the patient died after only one cycle of sunitinib treatment. We propose to prospectively include BNP for the early detection of cardiovascular decompensation in high-risk patients. Future studies concerning the relevance of BNP in drug-related cardiotoxicity are urgently needed.
Clinical Characteristics of Central European and North American Samples of Pregnant Women Screened for Opioid Agonist Treatment
Authors: Unger A.S. , Martin P.R. , Kaltenbach K. , Stine S.M. , Heil S.H. , Jones H.E. , Arria A.M. , Coyle M.G. , Selby P. , Fischer G.
Published: February 2010

Background: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. Methods: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. Results: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). Conclusion: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women.
LRRK2 and the Stress Response: Interaction with MKKs and JNK-Interacting Proteins
Authors: Hsu C.H. , Chan D. , Wolozin B.
Published: February 2010

Increasing evidence supports a putative link between LRRK2 function and the MAP kinase cascades. We recently demonstrated that LRRK2 binds to MKK6, -3, and -7. Previous studies demonstrated that scaffold proteins are essential in the regulation of subcellular localization of stress kinase complexes. The c-jun NH2-terminal kinase (JNK)-interacting proteins (JIPs) are a group of scaffold proteins that play an important role in the regulation of MAP kinase signaling cascades. JIP1–3 are known to regulate the specificity and localization of the JNK pathway, while JIP4 is a specific scaffolding protein for the p38 pathway. We demonstrate that LRRK2 binds to JIP1–4, and is associated with increased levels of total JIP1, -3, -4, oligomeric JIP and ubiquitinated JIP. These results are consistent with a putative role of LRRK2 in regulating the stress kinase cascade.
Transgenic Zebrafish as a Novel Animal Model to Study Tauopathies and Other Neurodegenerative Disorders in vivo
Authors: Paquet Dominik , Schmid Bettina , Haass Christian
Published: February 2010

Our ageing society is confronted with a dramatic increase in patients suffering from tauopathies such as Alzheimer’s disease, frontotemporal dementia and others. Typical neuropathological lesions including tangles composed of hyperphosphorylated tau protein as well as severe neuronal cell death characterize these disorders. No mechanism-based cures are available at present. Genetically modified animals are invaluable models to understand the molecular disease mechanisms and to screen for modifying compounds. We recently introduced tau-transgenic zebrafish as a novel model for tauopathies. Our model allows recapitulating key pathological features of tauopathies within an extremely short time. Moreover, life imaging of tau-dependent neuronal cell death was performed for the very first time. This demonstrated tau-dependent neuronal cell loss independent of tangle formation. Finally, we exemplified that the zebrafish frontotemporal dementia model can be used to screen for drugs that prevent abnormal tau phosphorylation and neuronal cell death.
Current-Day Prevalence of Ménière’s Syndrome
Authors: Harris Jeffrey P. , Alexander Thomas H.
Published: February 2010

Previously reported prevalence rates of Ménière’s syndrome (MS) have ranged from 3.5 per 100000 to 513 per 100000. Recent data regarding the prevalence in the United States are lacking. To further assess the current-day prevalence of MS in the US, data from a medical and pharmaceutical claims database containing information for over 60 million unique patients were analyzed. Patients in the database are representative of the national, commercially insured population on a variety of demographic measures including age, gender, health plan type, and geographic location. A 3-year period from 2005 to 2007 was analyzed. The prevalence of MS was 190 per 100000 with a female:male ratio of 1.89:1. The prevalence increased with increasing age, ranging from 9 per 100000 for patients under age 18 to 440 per 100000 for patients 65 years and older.
Nano-Indentation Characterisation of Natural Carious White Spot Lesions
Authors: Huang T.T.Y. , He L.H. , Darendeliler M.A. , Swain M.V.
Published: February 2010

The aim of this paper was to characterise the mechanical properties (MPs) and microstructural features of natural enamel white spot lesions (WSLs) using nano-indentation. Five natural WSLs from 4 extracted sound premolar teeth were cross-sectioned. Elastic modulus and hardness were measured systematically across the WSLs at intervals of 25 and 50 µm. The WSLs showed a large reduction in MPs compared to sound counterpart: elastic modulus was up to 83% lower (77.0 ± 2.2 to 13.4 ± 2.1 GPa) and hardness up to 91% lower (3.39 ± 0.41 to 0.29 ± 0.07 GPa). The intact surface layer above WSLs had less than 34% reduction in MPs. Detailed MP measurements were mapped as two-dimensional contour plots. Typically, WSLs displayed steep MP gradients at the lesion boundary and more uniform MPs with isolated variations in the lesion body. Despite the large reduction in MPs, the microstructure of WSLs remained intact. We postulate that loss of mineral and change of the hierarchical microstructure at the crystallite level contributed to the overall MPs of WSLs.
Transcranial Doppler for Brain Death in Infants: The Role of the Fontanelles
Authors: Vicenzini E. , Pulitano P. , Cicchetti R. , Randi F. , Papov P. , Spadetta G. , Sirimarco G. , Ricciardi M.C. , Di Piero V. , Lenzi G.L. , Mecarelli O.
Published: February 2010

Objective: Transcranial Doppler (TCD) is a sensitive technique for circulatory arrest diagnosis in brain death when patterns such as reverberant flow and short systolic spikes are observed. In infants, the nonossified fontanelles compensate for intracranial hypertension. We describe TCD patterns in infants with brain death, different from adults, with the hemodynamic modifications induced by anterior fontanelle compression. Method: TCD was performed in 2 infants with diagnosed brain death admitted to the neonatal intensive care unit. Results: TCD showed a large peak ‘reverberant’ flow, with a high peak systolic velocity and a consistent retrograde component, away from the brain. Compression of the anterior fontanelle induced, at first, a reduction in systolic flow with the subsequent appearance of the characteristic short systolic spikes. Upon compression removal, a brief increase in the systolic flow was observed before the prompt reappearance of the reverberant flow. Conclusion: TCD for brain death diagnosis should be done cautiously in infants. In these cases, reverberating flow may be indicative of circulatory arrest even if with a large peak and with a high peak systolic velocity. Heavy fontanelle compression may reproduce the classical adult TCD patterns of brain death, thus supporting the diagnosis of cerebral circulatory arrest.
Assessment and Optimization of Cell Engraftment After Transplantation Into the Heart
Authors: Terrovitis John V. , Smith Rachel Ruckdeschel , Marbán Eduardo
Published: February 2010

Abstract
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Myocardial regeneration using stem and progenitor cell transplantation in the injured heart has recently become a major goal in the treatment of cardiac disease. Experimental studies and clinical applications have generally been encouraging, although the functional benefits that have been attained clinically are modest and inconsistent. Low cell retention and engraftment after myocardial delivery is a key factor limiting the successful application of cell therapy, irrespective of the type of cell or the delivery method. To improve engraftment, accurate methods for tracking cell fate and quantifying cell survival need to be applied. Several laboratory techniques (histological methods, real-time quantitative polymerase chain reaction, radiolabeling) have provided invaluable information about cell engraftment. In vivo imaging (nuclear medicine modalities, bioluminescence, and MRI) has the potential to provide quantitative information noninvasively, enabling longitudinal assessment of cell fate. In the present review, we present several available methods for assessing cell engraftment, and we critically discuss their strengths and limitations. In addition to providing insights about the mechanisms mediating cell loss after transplantation, these methods can evaluate techniques for augmenting engraftment, such as tissue engineering approaches, preconditioning, and genetic modification, allowing optimization of cell therapies.
Solar Cycles in 150 Years of Global Sea Surface Temperature Data
Authors: Zhou Jiansong , Tung Ka-Kit
Published: February 2010

The purpose of the present work is to demonstrate that a solar cycle response exists in surface temperature using the longest global dataset available, which is in the form of 1854–2007 sea surface temperature (SST), with an emphasis on methods and procedures, data quality, and statistical tests and the removal of deterministic signals, such as volcano aerosol forcing and greenhouse gas warming. Using the method of composite-mean difference (CMD) projection, signals of warming during solar maximum and cooling during solar minimum years are found in the global SST over the 14 cycles, dispelling previous claims that the solar cycle response before 1920 is opposite to that of the modern era. The magnitude of the solar cycle response averaged over the oceans between 60°S and 60°N is about 0.1°C of warming for each W m−2 variation of the solar constant (but is slightly lower, at ~0.085°C, when periods of suspected bad data are averaged in, which is consistent with previous work). The signal is robust provided that the years near the Second World War are excluded, during which transitions from British ships to U.S. ships introduced warm bias in the SST, as recently pointed out by D. Thompson and his colleagues. Monte Carlo tests show that the extracted signal has less than 0.02% chance of being a random occurrence. This establishes the existence of a solar cycle response at the earth’s surface at high statistical confidence. Contamination of the signal by volcano aerosols is estimated using the multiple CMD inversion method and found to be small over this long record, although ENSO contamination varies depending on the period chosen but is also small.

The multidecadal trend of response to solar forcing is found to account for no more than a quarter of the observed warming in SST during the past 150 yr, under a reasonable but unproven assumption that the climate response to secular solar forcing and to solar cycle forcing has the same spatial pattern.
An Evaluation Metric for Intraseasonal Variability and its Application to CMIP3 Twentieth-Century Simulations
Authors: Xavier Prince K. , Duvel Jean-Philippe , Braconnot Pascale , Doblas-Reyes Francisco J.
Published: February 2010

The intraseasonal variability (ISV) is an intermittent phenomenon with variable perturbation patterns. To assess the robustness of the simulated ISV in climate models, it is thus interesting to consider the distribution of perturbation patterns rather than only one average pattern. To inspect this distribution, the authors first introduce a distance that measures the similarity between two patterns. The reproducibility (realism) of the simulated intraseasonal patterns is then defined as the distribution of distances between each pattern and the average simulated (observed) pattern. A good reproducibility is required to analyze the physical source of the simulated disturbances. The realism distribution is required to estimate the proportion of simulated events that have a perturbation pattern similar to observed patterns. The median value of this realism distribution is introduced as an ISV metric. The reproducibility and realism distributions are used to evaluate boreal summer ISV of precipitations over the Indian Ocean for 19 phase 3 of the Coupled Model Intercomparison Project (CMIP3) models. The 19 models are classified in increasing ISV metric order. In agreement with previous studies, the four best ISV metrics are obtained for models having a convective closure totally or partly based on the moisture convergence. Models with high metric values (poorly realistic) tend to give (i) poorly reproducible intraseasonal patterns, (ii) rainfall perturbations poorly organized at large scales, (iii) small day-to-day variability with overly red temporal spectra, and (iv) less accurate summer monsoon rainfall distribution. This confirms that the ISV is an important link in the seamless system that connects weather and climate.
Atmospheric Response to the Gulf Stream: Seasonal Variations*
Authors: Minobe Shoshiro , Miyashita Masato , Kuwano-Yoshida Akira , Tokinaga Hiroki , Xie Shang-Ping
Published: February 2010

The atmospheric response to the Gulf Stream front in sea surface temperature is investigated using high-resolution data from satellite observations and operational analysis and forecast. Two types of atmospheric response are observed with different seasonality and spatial distribution.

In winter, surface wind convergence is strong over the Gulf Stream proper between Cape Hatteras and the Great Banks, consistent with atmospheric pressure adjustments to sea surface temperature gradients. The surface convergence is accompanied by enhanced precipitation and the frequent occurrence of midlevel clouds. Local evaporation and precipitation are roughly in balance over the Florida Current and the western Gulf Stream proper. In summer, strong precipitation, enhanced high clouds, and increased lightning flash rate are observed over the Florida Current and the western Gulf Stream proper, without seasonal surface convergence enhancement. For the precipitation maximum over the Florida Current, local evaporation supplies about half of the water vapor, and additional moisture is transported from the south on the west flank of the North Atlantic subtropical high.

Atmospheric heating estimated by a Japanese reanalysis reveals distinct seasonal variations. In winter, a shallow-heating mode dominates the Gulf Stream proper, with strong sensible heating in the marine atmospheric boundary layer and latent heating in the lower troposphere. In summer, a deep-heating mode is pronounced over the Florida Current and the western Gulf Stream proper, characterized by latent heating in the middle and upper troposphere due to deep convection. Possible occurrences of these heating modes in other regions are discussed.
Antarctic Intermediate Water and Subantarctic Mode Water Formation in the Southeast Pacific: The Role of Turbulent Mixing
Authors: Sloyan Bernadette M. , Talley Lynne D. , Chereskin Teresa K. , Fine Rana , Holte James
Published: February 2010

During the 2005 austral winter (late August–early October) and 2006 austral summer (February–mid-March) two intensive hydrographic surveys of the southeast Pacific sector of the Southern Ocean were completed. In this study the turbulent kinetic energy dissipation rate ε, diapycnal diffusivity κ, and buoyancy flux Jb are estimated from the CTD/O2 and XCTD profiles for each survey. Enhanced κ of O(10−3 to 10−4 m2 s−1) is found near the Subantarctic Front (SAF) during both surveys. During the winter survey, enhanced κ was also observed north of the “subduction front,” the northern boundary of the winter deep mixed layer north of the SAF. In contrast, the summer survey found enhanced κ across the entire region north of the SAF below the shallow seasonal mixed layer. The enhanced κ below the mixed layer decays rapidly with depth. A number of ocean processes are considered that may provide the energy flux necessary to support the observed diffusivity. The observed buoyancy flux (4.0 × 10−8 m2 s−3) surrounding the SAF during the summer survey is comparable to the mean buoyancy flux (0.57 × 10−8 m2 s−3) associated with the change in the interior stratification between austral summer and autumn, determined from Argo profiles. The authors suggest that reduced ocean stratification during austral summer and autumn, by interior mixing, preconditions the water column for the rapid development of deep mixed layers and efficient Antarctic Intermediate Water and Subantarctic Mode Water formation during austral winter and early spring.
A Boy Unable to Move His Arm
Authors: Cantu Rebecca M. , Steele Russell W.
Published: February 2010

An 11-year-old boy presented with inability to move his right arm, back and neck pain, and fever. He has a history of recurrent vesicular rash on his face three times over the past two years. Magnetic resonance imaging (MRI) showed diffuse expansile cervical cord, leading to a diagnosis of transverse myelitis. After 3 days of intravenous solumedrol, the patient was discharged, but returned the following day with a vesicular rash to the right arm, as well as vomiting, malaise and diffuse pruritus.Wright-Giemsa stain of the vesicles revealed herpes group virus and culture was positive for herpes simplex type 1.
Role Expectations as Antecedents of Citizenship and the Moderating Effects of Work Context
Authors: Dierdorff Erich C. , Rubin Robert S. , Bachrach Daniel G.
Published: February 2010

In this field study of 198 incumbents, we examine how facets of work context affect the relationship between employees’ role expectations and supervisor ratings of their citizenship. Building on an emerging focus in the citizenship literature, we expand the scope of role perceptions to capture employees’ beliefs about the importance of various work activities and worker attributes needed for successful role performance (i.e., role expectations). Results support the role theory framework that we develop and suggest that aspects of both the social and task context moderate the relationship between employees’ role expectations for prosocial role requirements and citizenship. Implications of these results for both theory and practice in the citizenship area are discussed, as are directions for further research.
Smoking Cessation Program in Outpatient Clinics of Family Medicine Department in Taiwan: A Longitudinal Evaluation
Authors: Hsueh Kuang-Chieh , Chen Chih-Yin , Yang Yi-Hsin , Huang Chih-Ling
Published: February 2010

The Government of Taiwan has imposed a tobacco health tax of NT$5 (US$0.14) per pack of cigarettes since January 2002. The Department of Health has now begun to fund a smoking cessation program that provides nicotine-replacement therapy (NRT) and brief counseling by physicians in outpatient clinics. The purpose of the current study was to evaluate the smoking cessation program with a 3-year follow-up review implemented at outpatient clinics, which were run by the Family Medicine Department in a medical center, with a total of 772 adult participants. The abstinence rates were 99.7%, 49.2%, 37.7%, 30.2%, and 22.7%, at the 1-, 3-, 6-, 12-, and 36-month points, respectively. The frequency of clinic visits is a major factor predicting long-term cessation. The results indicate the need to pursue implementation and evaluation of multidisciplinary interventions in smoking cessation clinics with a longer follow-up, including the promotion of compliance to increase clinic visits and prevent relapse.