bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional rundown of gamma‐aminobutyric acidAreceptors in human hypothalamic hamartomas
Authors: Li Guohui , Yang Kechun , Zheng Chao , Liu Qiang , Chang Yongchang , Kerrigan John F. , Wu Jie
Published: October 2010

Objective

Human hypothalamic hamartomas (HHs) are highly associated with treatment‐resistant gelastic seizures. HHs are intrinsically epileptogenic, although the basic cellular mechanisms responsible for seizure activity are unknown. Altered gamma‐aminobutyric acid (GABA) function can contribute to epileptogenesis in humans and animal models. Recently, functional GABAAreceptor (GABAAR) rundown has been described in surgically resected human temporal lobe epilepsy tissue. We asked whether functional GABAAR rundown also occurs in human HH neurons.

Methods

GABAAR‐mediated currents were measured using perforated patch‐clamp recordings in single neurons acutely dissociated from surgically resected HH tissue. In addition, functional GABAARs were expressed inXenopusoocytes after microinjection with membrane fractions from either HH or control hypothalamus, and were studied with 2‐electrode voltage‐clamp recordings.

Results

Perforated patch‐clamp recordings in dissociated HH neurons showed that repetitive exposure to GABA (5 consecutive exposures to 0.1 mM GABA with 1‐second duration and at 20‐second intervals) induced a time‐dependent rundown of whole‐cell currents in small HH neurons, whereas large HH neurons showed much less rundown using the same protocol. Functional rundown was not observed in HH neurons with repetitive exposure to glycine or glutamate. Two‐electrode voltage‐clamp recordings (6 consecutive exposures to 1 mM GABA with 10‐second duration and at 40‐second intervals) induced GABA current rundown inXenopusoocytes microinjected with HH membrane proteins, but not in the oocytes expressing hypothalamic membrane proteins derived from human autopsy controls. Functional rundown of GABA currents was significantly attenuated by intracellular application of adenosine triphosphate or the nonspecific phosphatase inhibitor, okadaic acid.

Interpretation

Neurons from surgically resected human HH demonstrate functional rundown of GABAAR‐mediated transmembrane currents in response to GABA agonist exposure. Rundown may be a marker for impaired GABAergic function and a contributing mechanism for seizure genesis within HH tissue. ANN NEUROL 2011
Reversible neural stem cell niche dysfunction in a model of multiple sclerosis
Authors: Rasmussen Stine , Imitola Jaime , Ayuso‐Sacido Angel , Wang Yue , Starossom Sarah C. , Kivisäkk Pia , Zhu Bing , Meyer Morten , Bronson Roderick T. , Garcia‐Verdugo Jose Manuel , Khoury Samia J.
Published: October 2010

Objective

The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing‐remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become activated and initiate regeneration during acute disease, but lose this ability during the chronic phases of disease. We hypothesized that chronic microglia activation contributes to the failure of the NSC repair potential in the SVZ.

Methods

Using bromodeoxyuridine injections at different time points during EAE, we quantified the number of proliferating and differentiating progenitors, and evaluated the structure of the SVZ by electron microscopy. In vivo minocycline treatment during EAE was used to address the effect of microglia inactivation on SVZ dysfunction.

Results

In vivo treatment with minocycline, an inhibitor of microglia activation, increases stem cell proliferation in both naive and EAE animals. Minocycline treatment decreases cortical and periventricular pathology in the chronic phase of EAE, improving the proliferation of Sox2 stem cells and NG2 oligodendrocyte precursors cells originating in the SVZ and their differentiation into mature oligodendrocytes.

Interpretation

These data suggest that failure of repair observed during chronic EAE correlates with microglia activation and that treatments targeting chronic microglial activation have the potential for enhancing repair in the CNS. ANN NEUROL 2011
Endogenous amyloid‐β is necessary for hippocampal synaptic plasticity and memory
Authors: Puzzo Daniela , Privitera Lucia , Fa' Mauro , Staniszewski Agnieszka , Hashimoto Gakuji , Aziz Fahad , Sakurai Mikako , Ribe Elena M. , Troy Carol M. , Mercken Marc , Jung Sonia S. , Palmeri Agostino , Arancio Ottavio
Published: October 2010

Objective:

The goal of this study was to investigate the role of endogenous amyloid‐β peptide (Aβ) in healthy brain.

Methods:

Long‐term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique.

Results:

We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ42, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7‐containing nicotinic acetylcholine receptors, and Aβ42 production.

Interpretation:

Endogenous Aβ42 is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease. Ann Neurol 2011;
Phase III dose‐comparison study of glatiramer acetate for multiple sclerosis
Authors: Comi Giancarlo , Cohen Jeffrey A. , Arnold Douglas L. , Wynn Daniel , Filippi Massimo ,   for the FORTE Study Group
Published: October 2010

Objective:

To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40mg compared to a 20mg dose.

Methods:

Patients with multiple sclerosis (MS) with ≥1 documented relapse in 12 months prior to screening, or ≥2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12‐month study. Analysis was by intent‐to‐treat.

Results:

A total of 1,155 patients randomized to GA 20mg (n = 586) or 40mg (n = 569). The groups were well‐matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88–1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20mg group, 0.35 for the 40mg group, and 0.27 for patients from both groups who completed the entire 1‐year treatment. A total of 77% of patients remained relapse‐free in both groups. Both groups showed a reduction in mean number of gadolinium‐enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40mg dose compared with 20mg dose. Both doses were well‐tolerated with a safety profile similar to that observed in previous studies of 20mg GA.

Interpretation:

In relapsing‐remitting MS patients, both the currently‐approved GA 20mg and 40mg doses were safe and well‐tolerated, with no gain in efficacy for the higher dose. Ann Neurol 2011;69:75–82.
Mediterranean diet and magnetic resonance imaging–assessed cerebrovascular disease
Authors: Scarmeas Nikolaos , Luchsinger José A. , Stern Yaakov , Gu Yian , He Jing , DeCarli Charlie , Brown Truman , Brickman Adam M.
Published: October 2010

Objective:

Cerebrovascular disease is 1 of the possible mechanisms of the previously reported relationship between Mediterranean‐type diet (MeDi) and Alzheimer's disease (AD). We sought to investigate the association between MeDi and MRI infarcts.

Methods:

High‐resolution structural MRI was collected on 707 elderly 65 years or older community residents of New York with available dietary assessments administered an average of 5.8 years (3.22 standard deviations [SDs]) before the MRI. Participants were divided into 3 groups of adherence to MeDi (low, middle, and high tertiles). We examined the association of increasing adherence to MeDi with presence of infarcts on MRI. Models were run without adjustment, adjusted for basic demographic and clinical factors, and adjusted for vascular risk factors.

Results:

A total of 222 participants had at least 1 infarct. In the unadjusted model, compared to the low adherence group, those in the moderate MeDi adherence group had a 22% reduced odds of having an infarct (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.55–1.14), while participants in the highest MeDi adherence group had a 36% reduced odds (OR, 0.64; 95% CI, 0.42–0.97; p for trend = 0.04). In adjusted models, the association between MeDi adherence and MRI infarcts remained essentially unchanged. The association of high MeDi adherence with infarcts was comparable to that of hypertension (40% reduced probability), did not vary by infarct size or after excluding patients with dementia (n = 46) or clinical strokes (n = 86). There was no association between MeDi and white matter hyperintensities.

Interpretation:

Higher adherence to the MeDi is associated with reduced cerebrovascular disease burden. Ann Neurol 2011
Apomorphine treatment in Alzheimer mice promoting amyloid‐β degradation
Authors: Himeno Eri , Ohyagi Yasumasa , Ma Linqing , Nakamura Norimichi , Miyoshi Katsue , Sakae Nobutaka , Motomura Kyoko , Soejima Naoko , Yamasaki Ryo , Hashimoto Tetsuya , Tabira Takeshi , M. LaFerla Frank , Kira Jun‐ichi
Published: October 2010

Objective:

Intracellular amyloid β‐protein (Aβ) contributes to neurodegeneration in Alzheimer disease (AD). Apomorphine (APO) is a dopamine receptor agonist for Parkinson disease and also protects against oxidative stress. Efficacy of APO for an AD mouse model and effects of APO on cell cultures are studied.

Methods:

The triple transgenic AD mouse model (3xTg‐AD) has 2 familial AD‐related gene mutations (APPKM670/671NL/PS1M146V) and a tau gene mutation (TauP301L). Six‐month‐old 3xTg‐AD mice were treated with subcutaneous injections of APO once a week for 1 month. Memory function was evaluated by Morris water maze before and after the treatment. Brain tissues were examined by immunohistochemical staining and Western blotting. Effects of APO on intracellular Aβ degradation, activity of Aβ‐degrading enzymes, and protection against oxidative stress were studied in cultured SH‐SY5Y cells.

Results:

After APO treatment, short‐term memory function was dramatically improved. Significant decreases in the levels of intraneuronal Aβ, hyper‐phosphorylated tau (p‐tau), p53, and heme oxygenase‐1 proteins were observed. Moreover, APO promoted degradation of intracellular Aβ, increased activity of proteasome and insulin‐degrading enzyme, protected against H2O2 toxicity, and decreased p53 protein levels in the cultured cells.

Interpretation:

3xTg‐AD mice show intraneuronal Aβ accumulation and memory disturbances before extracellular Aβ deposition. Our data demonstrating improvement of memory function of 3xTg‐AD mice with decreases in intraneuronal Aβ and p‐tau levels by APO treatment strongly suggest that intraneuronal Aβ is an important therapeutic target and APO will be a novel drug for AD. Ann Neurol 2011
Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl‐11C]‐2‐(4′‐methylaminophenyl)‐ 6‐hydroxybenzothiazole
Authors: Stankoff Bruno , Freeman Leorah , Aigrot Marie‐Stéphane , Chardain Audrey , Dollé Frédéric , Williams Anna , Galanaud Damien , Armand Lucie , Lehericy Stéphane , Lubetzki Catherine , Zalc Bernard , Bottlaender Michel
Published: October 2010

Objective:

Imaging of myelin tracts in vivo would greatly improve the monitoring of demyelinating diseases such as multiple sclerosis (MS). To date, no imaging technique specifically targets demyelination and remyelination. Recently, amyloid markers related to Congo red have been shown to bind to central nervous system (CNS) myelin. Here we questioned whether the thioflavine‐T derivative 2‐(4′‐methylaminophenyl)‐6‐hydroxybenzothiazole (PIB), which also binds to amyloid plaques, could serve as a myelin marker.

Methods:

PIB fixation to myelin was studied by fluorescence in the normal and dysmyelinating mouse brain, as well as in the postmortem brain of MS patients. Positron emission tomography (PET) experiments were conducted using [11C]PIB in baboons and in a proof of concept clinical study in 2 MS patients.

Results:

Applied directly on tissue sections or after intraperitoneal injection, PIB stained CNS myelin, and the decrease in the level of fixation paralleled the amount of myelin loss in a dysmyelinating mutant. In normally myelinated areas of postmortem MS brain, demyelinated and remyelinated lesions were clearly distinguishable by the differential intensity of labeling observed with PIB. PET using intravenously injected radiolabeled [11C]PIB imaged CNS myelin in baboons and humans. In MS patients, the dynamic analysis of PET acquisitions allowed quantitative assessment of demyelination.

Interpretation:

PIB could be used as an imaging marker to quantify myelin loss and repair in demyelinating diseases. Ann Neurol 2011;
Oxetane als vielseitige Bausteine in der Wirkstoff‐Forschung und Synthese
Authors: Burkhard Johannes A. , Wuitschik Georg , Rogers‐Evans Mark , Müller Klaus , Carreira Erick M.
Published: October 2010

Erhebliche Geld‐ und Personalressourcen werden jährlich für die Entwicklung neuer Medikamente aufgewendet. Doch trotz verbesserter Techniken, die den Zugang zu unerforschtem chemischem Raum ermöglichen, überwinden nur wenige der neuen Verbindungen die zahlreichen physikochemischen und pharmakologischen Hürden in der Wirkstoff‐Forschung und ‐Entwicklung. Es hat sich gezeigt, dass der Einbau einer Oxetaneinheit in das molekulare Gerüst einer Verbindung deren Eigenschaften wesentlich verbessern kann. Von besonderem Interesse sind dabei Oxetane, die nur in der 3‐Position substituiert sind, da ihr Einbau in ein Molekülgerüst kein neues Stereozentrum erzeugt. Dieser Kurzaufsatz gibt einen Überblick über die jüngsten Fortschritte bei der Herstellung und Verwendung 3‐substituierter Oxetane. Ebenso werden Veränderungen physiko‐ und biochemischer Eigenschaften bei der Einführung einer Oxetaneinheit in Abhängigkeit von der Einbauposition diskutiert.
Kolloidale Organisation: der Weg vom Partikel zu kolloidalen Molekülen und Kristallen
Authors: Li Fan , Josephson David P. , Stein Andreas
Published: October 2010

Kolloidale Partikel können genau wie Atome (die Bausteine der Moleküle, Makromoleküle und Kristalle) als Baueinheiten für Materialien betrachtet werden. Periodische Anordnungen von Kolloiden – kolloidale Kristalle – haben in den letzten 20 Jahren viel Aufmerksamkeit erregt, im Wesentlichen wegen ihrer einzigartigen photonischen Eigenschaften. Die archetypischen Opalstrukturen beruhen auf dicht gepackten Anordnungen von Kügelchen mit Durchmessern im Submikrometerbereich. Das Interesse an der Strukturierung von Materialien in diesem Größenbereich, aber mit komplexeren Eigenschaften und idealerweise durch Selbstorganisationsprozesse, hat zu großen Fortschritten bei der Kontrolle der Eigenschaften sowohl der Baueinheiten als auch ihrer Anordnungen geführt. Erforderlich dafür sind Kolloide, kolloidale Cluster und kolloidale “Moleküle” mit speziellen Formen und der Fähigkeit zur Bildung einer gerichteten Bindung, eine Kontrolle über kurz‐ und langreichweitige Wechselwirkungen sowie Möglichkeiten zur Positionierung und Orientierung dieser Bausteine. Dieser Aufsatz beleuchtet jüngste experimentelle und theoretische Fortschritte bei der Organisation von Kolloiden mit einer Größe von mehr als 50 nm.
Die Wasserstoffbrücke – eine aktualisierte Definition
Authors: Desiraju Gautam R.
Published: October 2010

Die Wasserstoffbrücke ist eine Wechselwirkung, bei der ein Wasserstoffatom von zwei Atomen statt nur einem angezogen wird und als Brücke zwischen den beiden wirkt. Die Anziehung wird mit zunehmender Elektronegativität jedes der beiden Atome stärker. In klassischer Betrachtungsweise sind Wasserstoffbrücken weitgehend elektrostatisch, in manchen Fällen sogar teilkovalent. Das Konzept der Wasserstoffbrücke wurde im Laufe der Zeit immer wieder erweitert, um auch schwächere und dispersivere Wechselwirkungen einzubeziehen, sofern eine gewisse elektrostatische Beschaffenheit der Wechselwirkung gegeben ist. In der Praxis wird eine enorme Vielfalt an sehr starken, starken, mäßig starken, schwachen und sehr schwachen Wasserstoffbrücken beobachtet. Aktuell werden schwache Wasserstoffbrücken mit vielen Fragen der Strukturchemie und der Biologie in Verbindung gebracht. Während starke Wasserstoffbrücken von allen bestehenden Definitionen der Erscheinung erfasst werden, können schwächere zu Problemen bei der Benennung und zu Konflikten mit bestehenden Definitionen führen. Kürzlich wurde der International Union of Pure and Applied Chemistry (IUPAC) eine Empfehlung für eine aktualisierte Definition des Begriffs “Wasserstoffbrücke” vorgelegt. In diesem Essay soll die vorgeschlagene Definition ausführlich erläutert werden.
Colloidal Assembly: The Road from Particles to Colloidal Molecules and Crystals
Authors: Li Fan , Josephson David P. , Stein Andreas
Published: October 2010

Colloidal particles may be considered as building blocks for materials, just like atoms are the bricks of molecules, macromolecules, and crystals. Periodic arrays of colloids (colloidal crystals) have attracted much interest over the last two decades, largely because of their unique photonic properties. The archetype opal structures are based on close‐packed arrays of spheres of submicrometer diameter. Interest in structuring materials at this length scale, but with more complex features and ideally by self‐assembly processes, has led to much progress in controlling features of both building blocks and assemblies. The necessary ingredients include colloids, colloidal clusters, and colloidal “molecules” which have special shapes and the ability to bind directionally, the control over short‐range and long‐range interactions, and the capability to place and orientate these bricks. This Review highlights recent experimental and theoretical progress in the assembly of colloids larger than 50 nm.
Identification of pollution sources in the Romanian Somes River using graphical analysis of concentration profiles
Authors: Ani Elisabeta‐Cristina , Avramenko Yuri , Kraslawski Andrzej , Agachi Paul Serban
Published: October 2010

The paper describes a method for the identification of pollution sources along a river, based on the analysis of graphical information obtained from long‐term monitoring data. Concentration profiles collected during 2004 at monthly resolution in the Romanian Somes River are employed. The graphical analysis method is based on the comparison of experimental concentration profiles against reference profiles showing concentration evolution along the river after pollutant release. Known nitrate and lead pollution sources along the river were used as reference in order to verify the applicability of the proposed method. Results show that the graphical analysis method enables detection of the majority of sources, and it could be used to investigate the seasonal existence of pollution sources. Moreover, the technique can help guide the definition of the structure of mathematical models for the transport of pollutants in rivers. Copyright © 2010 Curtin University of Technology and John Wiley & Sons, Ltd.
Seasonally tracking vertical and horizontal distribution of unionid mussels (Pronodularia japanensis): implications for agricultural drainage management
Authors: Negishi Junjiro N. , Doi Hideyuki , Katano Izumi , Kayaba Yuichi
Published: October 2010

The vertical and horizontal distribution of unionoid mussels (Pronodularia japanensis) were examined in spring, late summer and winter for different size classes, including juveniles (<20 mm) and large adults (>50 mm), in an agricultural drainage channel in Central Japan.

A large number of small‐sized juveniles were found at the surface (0–3 cm depth) in spring, whereas approximately half of the adults remained in the deep layer (3–8 cm depth). Most individuals were found in the surface layer irrespective of size classes in summer, and approximately 70% of all individuals descended to the deep layer in winter.

Horizontal distribution did not substantially change across seasons and high density patches were consistently found in the areas where substrate appeared to be stable or hydraulically sheltered. Spatial distribution of small juveniles was relatively well predicted by the abundance of adults.

The size–frequency distribution was multi‐modal in three seasons and estimated numbers of newly recruited juveniles were highly variable in recent years, suggesting that juveniles were rarely found owing to irregular reproduction and/or recruitment not the overlooked habitat preferred by small‐sized juveniles.

As P. japanensis is characterized by the behaviour of burrowing down to a depth of ∼10 cm, maintaining the processes of sediment deposition appears to be one of the critical criteria for the conservation of mussel habitats in agricultural drainage channel systems, which are commonly lined with smooth concrete materials. Copyright © 2010 John Wiley & Sons, Ltd.
The value of traditional troughs as freshwater shelters for amphibian diversity
Authors: Garcia‐Gonzalez Claudia , Garcia‐Vazquez Eva
Published: October 2010

Changes in agricultural activities in the Trubia valley (North Iberia, south Europe), mainly substituting husbandry by rural tourism, are modifying trough function: from cattle watering to abandonment or transformation into decorative elements. In the valley, natural ponds are disappearing by desiccation and are scarce or absent.

In the present troughs, constructed by artificial deviation of small streams or fountains, eight amphibian species have been found, representing 57% of the amphibian species recorded in the region. Seven of them were in larval development stages.

Moderate management, presence of sediments in the bottom and abundant floating vegetation were identified as the main factors contributing to amphibian species richness. Trough management significantly correlated with species richness and also with the presence and the genetic population variation of the model species Lissotriton helveticus (palmate newt). Most amphibian species cannot develop in excessively cleaned troughs devoid of vegetation and invertebrates.

In the absence or decline of natural ponds and other water points, traditional troughs can be considered refuges for amphibians. Traditional management actions such as moderate cleaning and protecting vegetation and bottom sediments from these freshwater points are recommended. Promoting the traditional management of troughs is easy and, together with the protection of natural ponds, can help to prevent the decline of amphibian species. Copyright © 2010 John Wiley & Sons, Ltd.
A Novel Terminal Web‐Like Structure in Cortical Lens Fibers: Architecture and Functional Assessment
Authors: Al‐Ghoul Kristin J. , Lindquist Timothy P. , Kirk Spencer S. , Donohue Sean T.
Published: October 2010

This study describes a novel cytoskeletal array in fiber cells of the ocular lens of the rat and shows its relationship to the classical terminal web of other epithelial tissues. Naive adult Sprague‐Dawley rats (n = 28) were utilized. F‐actin, fodrin, myosin IIA, and CP49 distribution was assessed in anterior and posterior polar sections. For functional analysis, lenses were cultured with or without cytochalasin‐D for 3 hr, then processed for confocal microscopy or assessed by laser scan analysis along sutures. Phalloidin labeling demonstrated a dense mesh of F‐actin adjacent to posterior sutural domains to a subcapsular depth of 400 μm. Anterior polar sections revealed a comparable actin structure adjacent to anterior suture branches however, it was not developed in superficial fibers. Fodrin and myosin were localized within the web‐like actin apparatus. The data was used to construct a model showing that the cytoskeletal array is located within the blunt, variable‐width fiber ends that abut at sutures such that the “terminal web” flanks the suture on either side. Treatment with cytochalasin‐D resulted in partial disassembly of the “terminal web” and perturbed cellular organization. Laser scan analysis revealed that cytochalasin‐D treated lenses had significantly greater focal variability than control lenses (P = 0.020). We conclude that cortical fibers of rat lenses contain a bipolar structure that is structurally and compositionally analogous to classical terminal webs. The results indicate that the lens “terminal web” functions to stabilize lens fiber ends at sutures thus minimizing structural disorder, which in turn, promotes the establishment and maintenance of lens transparency. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Intratumoral Lymphatics and Lymphatic Vessel Invasion Detected by D2‐40 Are Essential for Lymph Node Metastasis in Bladder Transitional Cell Carcinoma
Authors: Ma Yong , Hou Youcui , Liu Binghua , Li Xuemei , Yang Shucai , Ma Jing
Published: October 2010

Bladder cancer is frequently associated with regional lymph node metastasis at the time of diagnosis or after initial treatment, and lymph node metastasis is crucial for clinical therapeutic strategies. Lymphangiogenesis, detected by antibodies specific for lymphatic endothelial cells, is correlated with cancer spread, but the mechanisms that underlie lymphatic spread and the role of lymphangiogenesis in cancer metastasis has been less clear. The aim of this study was to investigate the association of vascular endothelial growth factor (VEGF)‐D expression, intratumoral lymphatics, and lymphatic invasion associated with lymph node metastasis as well as the prognostic analysis in patients with bladder transitional cell carcinoma (TCC). The VEGF‐D expression was evaluated by immunohistochemistry in 72 specimens, and tumoral lymphatic vessels were measured by D2‐40. Counts of lymph vessels were taken in intratumoral and peritumoral areas. Survival analyses and their independent roles were investigated using univariate and multivariate analysis models. The high expression of VEGF‐D was closely associated with the intratumoral lymphatic vessels, tumoral lymphatic invasion, and lymph node metastasis as well as a shorter overall survival. Higher lymphatic vessel density, intratumoral lymphatics, and lymphatic invasion showed a significant association with lymph node metastasis. Univariate analysis indicated that VEGF‐D, intratumoral lymphatics, and lymphatic invasion were associated with overall survival, but they were not independent prognostic factors for bladder TCC in multivariate analysis. We conclude that VEGF‐D plays an essential role in tumoral lymphangiogenesis. Intratumoral lymphatics and lymphatic invasion are important predictive factors of pelvic lymph node metastasis in patients with bladder cancer. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Expressions of Neutrophil Gelatinase‐Associated Lipocalin in Gastric Cancer: A Potential Biomarker for Prognosis and an Ancillary Diagnostic Test
Authors: Wang Hui‐Ju , He Xu‐Jun , Ma Ying‐Yu , Jiang Xiao‐Ting , Xia Ying‐Jie , Ye Zai‐Yuan , Zhao Zhong‐Sheng , Tao Hou‐Quan
Published: October 2010

The aim of this study was to explore the clinical significance of neutrophil gelatinase‐associated lipocalin (NGAL) in the development and prognosis of gastric cancer. NGAL tumor levels were determined in 333 GC patients by immunohistochemistry. NGAL in blood samples from 63 healthy donors and 60 gastric cancer patients were also determined by enzyme‐linked immunosorbent assay. Rate of NGAL expression was correlated with the size of tumor (69.3% in >4 cm tumors vs. 46.1% in ≤4 cm tumors), Lauren's classification (84.3% in diffuse type vs. 28.2% in intestinal type), lymph node metastasis (75.6% vs. 16.4% with no metastasis), vascular invasion (74.9% vs. 26.8% with no invasion), distant metastasis (94.3% vs. 50.3% with no distant metastasis), and TNM stage (81.8% in TNM III+IV vs. 20.5% in TNM I+II). NGAL expression can be used as an independent prognostic factor in gastric cancer as indicated by multivariate analysis. Positivity for serum NGAL was higher than that for carbohydrate antigen determinant, CA19‐9 (38.1% vs. 12.5%) in TNM I, and higher than that for carcinoembryonic antigen, CEA (58.3% vs. 8.3%) and CA19‐9 (58.3% vs. 8.3%) in TNM II. In conclusion, serum NGAL has great potential to be used as an ancillary test for diagnosis of gastric cancer. Increased expression of NGAL in tumors suggests gastric cancer is likely to be at an advanced stage with invasion and metastasis, and also poor prognosis. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Total Synthesis and Biological Evaluation of a Series of Macrocyclic Hybrids and Analogues of the Antimitotic Natural Products Dictyostatin, Discodermolide, and Taxol
Authors: Paterson Ian , Naylor Guy J. , Gardner Nicola M. , Guzmán Esther , Wright Amy E.
Published: October 2010

The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule‐stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22‐membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide‐derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late‐stage diversification strategy and the construction of a small library of methyl‐ether derivatives, along with the first triple hybrids bearing the side‐chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti‐proliferative activity of these compounds in a series of human cancer cell lines, including the taxol‐resistant NCI/ADR‐Res cell line, allowed the proposal of various structure–activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin.
Seasonal variations in the diurnal patterns of convection in Cameroon–Nigeria and their neighboring areas
Authors: Vondou Derbetini A. , Nzeukou Armand , Lenouo André , Mkankam Kamga F.
Published: October 2010

High‐resolution (5‐km, 30‐min) Meteosat 7 infrared images are used to document seasonal variations of the diurnal cycle of convective activity over Cameroon and Nigeria during the period 1998‐2002. Cloud fraction, considered to diagnose the properties of cold clouds, is derived by using a threshold of brightness temperatures less than 235 K, thus providing a detailed view of regional differences in the diurnal patterns. The features of the diurnal cycle of convection were investigated for six sampled regions. Over land, the diurnal cycle of convection is mainly controlled by the radiative heating and associated low‐level destabilization. Strong spatial variations exist in the seasonal amplitude of diurnal cycle, highlighting that complex orography, land‐sea contrast and coastline curvature play an important role in modulating the spatial and diurnal patterns of convection. There is consistent noon diurnal peak without obvious seasonal variations of the phase over the ocean. Copyright © 2010 Royal Meteorological Society
Discriminating between natural and anthropogenic aerosol contributions to optical depth over Afro‐Asian region
Authors: Deepshikha S. , Srinivasan J.
Published: October 2010

To accurately assess the impact of anthropogenic aerosols on climate, spatial and temporal distribution of its radiative properties is essential. The first step towards separating the radiative impact of natural aerosol from its anthropogenic counterparts is to gather information on natural aerosols. In this paper, we have used data from multiple satellites to derive the anthropogenic aerosol fraction (AAF) over the Afro‐Asian region. The AAF was largest during the pre‐monsoon season (May–June) and lowest during winter. We have shown that over desert locations the AAF was unexpectedly large (>0.4) and the regionally (and annually) averaged anthropogenic fraction over the Afro‐Asian region was 0.54 ± 0.12. Copyright © 2010 Royal Meteorological Society
Increase in the pre‐monsoon rainfall over the Indian summer monsoon region
Authors: Sathiyamoorthy V. , Shukla Bipasha Paul , Pal P.K.
Published: October 2010

Examination of the Global Precipitation Climatology Project (GPCP) and Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) rainfall datasets, both available for the past 31 years (1979–2009), suggests that rainfall has increased considerably over the pre‐monsoon rainfall belts of the Bay of Bengal (BoB) and Southeast Arabian Sea (SEA) during May. The rainfall rate has increased by 83.9% (94.5%) over SEA and 54.6% (19.6%) over BoB in the GPCP (CMAP) dataset during the study period. During the study period, the atmospheric temperature has increased over north/northwestern parts of the Indian summer monsoon region in May, which has possibly caused more rain by enhancing the meridional pressure gradient. Copyright © 2010 Royal Meteorological Society
The dependency of geoengineered sulfate aerosol on the emission strategy
Authors: Niemeier U. , Schmidt H. , Timmreck C.
Published: October 2010

The climatic effect of geoengineered stratospheric sulfate aerosol depends on the strategy for sulfur emission that determines the microphysical evolution of the resulting sulfate layer, in particular the radius and radiative impact of the aerosols. Simulations with a three‐dimensional general circulation model (GCM), including an aerosol microphysical model, show e.g. decreasing sulfate lifetime with increasing emission rate. Furthermore, scenarios that differ with respect to location, local and temporal distribution and chemical composition of the emissions are studied. The study shows detailed information on particle radius, sulfate burden and radiative impact for these scenarios. Copyright © 2010 Royal Meteorological Society
The methodology of multiple criteria decision making/aiding in public transportation
Authors: Zak Jacek
Published: October 2010

The paper presents methodological overview of the application of Multiple Criteria Decision Making/Aiding (MCDM/A) in public transportation. It explains why MCDM/A methodology is so important while dealing with different categories of decision problems that arise in mass transit systems. Major features and basic notions of MCDM/A methodology are presented. Different categories of MCDM/A methods are characterized and classified. Two case studies demonstrate possible applications of MCDM/A methodology in public transportation. In the first case study multiple objective evaluation of the mass transit system developments' scenarios is carried out. Four variants of the mass transit system are evaluated by a consistent family of criteria with an application of ELECTRE III method. The second case study refers to optimization of the crew size in the mass transit system operated by a public transportation company (PTC). Multiple objective mathematical programing problem is formulated and solved by a combination of an original, customized heuristic procedure implemented in a computer software PEOPLE and the Light Beam Search (LBS) method. Copyright © 2010 John Wiley & Sons, Ltd.
Development of an integrated system based vehicle tracking algorithm with shadow removal and occlusion handling methods
Authors: Oh Jutaek , Min Joonyoung , Heo Byungdo
Published: October 2010

Video image processing system (VIPS) is more efficient than other detecting systems. However, VIPS involves outdoor images and is very sensitive to the external environment, which could greatly decrease its accuracy according to rapid environmental changes. To obtain accurate traffic data accordingly, VIPS must address the problems such as growing shadows in transition; distortion of images due to the headlights at night; noises caused by the rain, snow or fog; and occlusions.

This study intends to accurately calculate traffic data while addressing the shadow and occlusion problems, which are the most difficult tasks for the image‐detector‐based traffic data system. In this study, an algorithm for the individual vehicle tracking collection was developed to address the occlusion problem and to eliminate the noises or shadows caused by external environmental factors. A traffic data collection system was also proposed in order to accurately track individual vehicles that pass through the detection region. In addition, establishing an integrated system with shadow removal and occlusion handling using an image processing was also proposed. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of combined radiofrequency radiation exposure on the cell cycle and its regulatory proteins
Authors: Lee Kwan‐Yong , Kim Bong Cho , Han Na‐Kyung , Lee Yun‐Sil , Kim Taehong , Yun Jae‐Hoon , Kim Nam , Pack Jeong‐Ki , Lee Jae‐Seon
Published: October 2010

The aim of this study was to investigate whether single or combined radio frequency (RF) radiation exposure has effects on the cell cycle and its regulatory proteins. Exposure of MCF7 cells to either single (837 MHz) or combined (837 and 1950 MHz) RF radiation was conducted at specific absorption rate values of 4 W/kg for 1 h. During the exposure period, the chamber was made isothermal by circulating water through the cavity. After RF radiation exposure, DNA synthesis rate and cell cycle distribution were assessed. The levels of cell cycle regulatory proteins, p53, p21, cyclins, and cyclin‐dependent kinases were also examined. The positive control group was exposed to 0.5 and 4 Gy doses of ionizing radiation (IR) and showed changes in DNA synthesis and cell cycle distribution. The levels of p53, p21, cyclin A, cyclin B1, and cyclin D1 were also affected by IR exposure. In contrast to the IR‐exposed group, neither the single RF radiation‐ nor the combined RF radiation‐exposed group elicited alterations in DNA synthesis, cell cycle distribution, and levels of cell cycle regulatory proteins. These results indicate that neither single nor combined RF radiation affect cell cycle progression. Bioelectromagnetics 32:169–178, 2011. © 2010 Wiley‐Liss, Inc.
Effects of exposure to electromagnetic fields emitted by GSM 900 and WCDMA mobile phones on cognitive function in young male subjects
Authors: Sauter Cornelia , Dorn Hans , Bahr Achim , Hansen Marie‐Luise , Peter Anita , Bajbouj Malek , Danker‐Hopfe Heidi
Published: October 2010

Results of studies on the possible effects of electromagnetic fields emitted by mobile phones on cognitive functions are contradictory, therefore, possible effects of long‐term (7 h 15 min) electromagnetic field (EMF) exposure to handset‐like signals of Global System for Mobile Communications (GSM) 900 and Wideband Code‐Division Multiple Access (WCDMA) on attention and working memory were studied. The sample comprised 30 healthy male subjects (mean ± SD: 25.3 ± 2.6 years), who were tested on nine study days in which they were exposed to three exposure conditions (sham, GSM 900 and WCDMA) in a randomly assigned and balanced order. All tests were presented twice (morning and afternoon) on each study day within a fixed timeframe. Univariate comparisons revealed significant changes when subjects were exposed to GSM 900 compared to sham, only in the vigilance test. In the WCDMA exposure condition, one parameter in the vigilance and one in the test on divided attention were altered compared to sham. Performance in the selective attention test and the n‐back task was not affected by GSM 900 or WCDMA exposure. Time‐of‐day effects were evident for the tests on divided and selective attention, as well as for working memory. After correction for multiple testing, only time‐of‐day effects remained significant in two tests, resulting in faster reactions in the afternoon trials. The results of the present study do not provide any evidence of an EMF effect on human cognition, but they underline the necessity to control for time of day. Bioelectromagnetics 32:179–190, 2011. © 2010 Wiley‐Liss, Inc.
Psychopharmaka im Sozialismus. Arzneimittelregulierung in der Deutschen Demokratischen Republik in den 1960er Jahren
Authors: Klöppel Ulrike , Balz Viola
Published: October 2010

Psychotropic Drugs in Socialism? Drug Regulation in the German Democratic Republic in the 1960s. The peculiarities of drug regulation in the GDR are best described by a historical reconstruction of a concrete field of practice. The article analyses the regulation of psychotropic drugs by focussing on the centralised planning and control of pharmaceutical research and development in the 1960s. Its starting point is the observation that an introduction of certain psychotropic drugs like tranquilizers was initially controversial in the GDR. As a consequence, the key question is how an agreement over their medical and economic benefit was reached eventually. The article shows how in the course of the 1960s a discursive arrangement between the medical profession, pharmaceutical industry and the state apparatus emerged, which was supported by an increased political involvement of leading scientists and the directing staff of enterprises.
Fluorescence spectrometric study on the interaction of tamibarotene with bovine serum albumin
Authors: Ye Huazhen , Qiu Bin , Lin Zhenyu , Chen Guonan
Published: October 2010

The interaction between tamibarotene and bovine serum albumin (BSA) was studied using fluorescence quenching technique and ultraviolet–visible spectrophotometry. The results of experiments showed that tamibarotene could strongly quench the intrinsic fluorescence of BSA by a dynamic quenching mechanism. The apparent binding constant, number of binding site and corresponding thermodynamic parameters at different temperatures were calculated respectively, and the main interaction force between tamibarotene and BSA was proved to be hydrophobic force. Synchronous fluorescence spectra showed that tamibarotene changed the molecular conformation of BSA. When BSA concentration was 1.00 × 10−6 mol L−1, the quenched fluorescence ΔF had a good linear relationship with the concentration of tamibarotene in the range 1.00 × 10−6 to 12.00 × 10−6 mol L−1 with the detection limit of 6.52 × 10−7 mol L−1. Copyright © 2010 John Wiley & Sons, Ltd.
Fabrication of highly porous scaffolds for tissue engineering based on star‐shaped functional poly(ε‐caprolactone)
Authors: Theiler Stefan , Mela Petra , Diamantouros Stefanos E. , Jockenhoevel Stefan , Keul Helmut , Möller Martin
Published: October 2010

The potential of novel functional star‐shaped poly(ε‐caprolactone)s of controlled molecular weight and low molecular weight distribution bearing acrylate end groups as material for biomedical applications was demonstrated in this study. The polymers were functionalized via Michael‐type addition of amino acid esters containing amino or thiol groups showing the potential for immobilization of biomolecules. Furthermore, scaffolds of different geometries were prepared by uniaxial freezing of polymer solutions followed by freeze drying. Different solvents and polymer concentrations were investigated, resulting in scaffolds with porosities between 76 and 96%. Mechanical properties of the scaffolds were investigated and the morphology was determined via scanning electron microscopy. Scaffolds with interconnected channels were prepared using benzene, 1,2‐dichloroethane or dioxane as solvent. The tubular longitudinal pores in honeycomb arrangement extend throughout the full extent of the scaffolds (typical pore sizes: 20–100 µm). Biotechnol. Bioeng. 2011; 108:694–703. © 2010 Wiley Periodicals, Inc.
Label‐free identification of bacterial microcolonies via elastic scattering
Authors: Bae Euiwon , Bai Nan , Aroonnual Amornrat , Bhunia Arun K. , Hirleman E. Daniel
Published: October 2010

Label‐free microcolony identification via elastic light scattering was investigated for three different genera: Salmonella enterica serovar Montevideo, Listeria monocytogenes F4244, and Escherichia coli DH5α. Microcolonies were defined as bacterial colonies in their late‐lag phase to early‐exponential phase with the diameter range of 100–200 µm. To link biophysical characteristics with corresponding scattering patterns, a phase contrast microscope and a confocal displacement meter were used to measure the colony diameter and its 3D height profile. The results indicated that the growth characteristics of microcolonies were encoded in their morphologies which correlated to the characteristic diffraction patterns. Proposed methodology was able to classify three genera based on comprehensive phenotypic map which incorporated growth speed, ring count, and colony diameter. While the proposed method illustrated the possibility of discriminating microcolonies in their early growth stage, more thorough biophysical understanding is needed to expand the technology to other species. Biotechnol. Bioeng. 2011; 108:637–644. © 2010 Wiley Periodicals, Inc.
Fragmentation of a highly purified monoclonal antibody attributed to residual CHO cell protease activity
Authors: Gao Sharon X. , Zhang Ying , Stansberry‐Perkins Kensey , Buko Alex , Bai Shujun , Nguyen Vanessa , Brader Mark L.
Published: October 2010

Monoclonal antibody (mAb) fragmentation can be a widespread problem across the biotechnology industry and there is a current need to better understand the underlying principles. Here, we report an example of a high‐purity human IgG1 mAb prepared from CHO cells exhibiting fragmentation that can be attributed to residual proteolytic enzyme activity. The concomitant occurrence of proteolytic and non‐proteolytic peptide bond cleavage is shown and the respective fragmentation patterns characterized using high‐resolution LC–MS. Fragmentation rates are monitored by SE‐HPLC and SDS–PAGE over the pH range 4–6 and characterized in the presence and absence of pepstatin A, an inhibitor of acidic proteases. After 20 days at 40°C, pH 4, ∼60% decrease in BIIB‐mAb monomer peak occurred attributed to residual proteolytic activity. At pH 5, this value was ∼13%. These results have implications for formulation design studies and the interpretation of accelerated stability data. A simple method to screen for acidic protease activity using the proteolytic enzyme inhibitor pepstatin A is described. Biotechnol. Bioeng. 2011; 108:977–982. © 2010 Wiley Periodicals, Inc.