bluuebunny/crossref_metadata_2025 huggingface dataset:
Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer1
Authors: Lara Primo N. , Chansky Kari , Shibata Taro , Fukuda Haruhiko , Tamura Tomohide , Crowley John , Redman Mary W. , Natale Ronald , Saijo Nagahiro , Gandara David R
Published: August 2010

BACKGROUND:

Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient‐level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results.

METHODS:

Patients with documented extensive stage SCLC and adequate end‐organ function were randomized to intravenously receive either cisplatin 60 mg/m2 Day 1 + irinotecan 60 mg/m2 Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m2 Day 1 + etoposide 100 mg/m2 Days 1‐3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS).

RESULTS:

Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared.

CONCLUSIONS:

Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected. Cancer 2010. © 2010 American Cancer Society.
Influence of abdominal adiposity, waist circumference, and body mass index on clinical and pathologic findings in patients treated with radiotherapy for localized prostate cancer
Authors: Zilli Thomas , Chagnon Miguel , Van Nguyen Thu , Bahary Jean‐Paul , Guay Jean‐Pierre , Dufresne Alix , Taussky Daniel
Published: August 2010

BACKGROUND:

Increased body mass index (BMI) has been associated with more aggressive prostate cancer (PC). The relation among abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), waist circumference (WC), and BMI was compared with clinical and pathologic findings in patients treated with radiotherapy for localized PC.

METHODS:

VAT, SAT, WC (all measured by planning abdominopelvic computed tomography scan) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity measures significantly predicted risk for secondary malignancies.

RESULTS:

Of 276 analyzed patients, 80 (29%) were obese (BMI ≥ 30 kg/m2). Median BMI at baseline was 27.6 kg/m2 (interquartile range [IQR], 25.1‐30.5 kg/m2). Increased SAT and VAT were associated with a higher National Comprehensive Cancer Network (NCCN) PC risk group (P = .0001 and .008, respectively). Greater SAT was associated with a higher Gleason score (GS) (P = .030). Younger age at diagnosis was significantly correlated with higher SAT and BMI, whereas increased prostate size was found in patients with higher BMI, WC, SAT, and VAT. At a median follow‐up of 42.3 months (IQR, 32.3‐59.9 months), 15 secondary malignancies were observed. On multivariate analysis, VAT was a significant predictor for secondary cancers (adjusted hazards ratio, 1.014; P = .0001).

CONCLUSIONS:

Measurements of greater abdominal adiposity were strongly associated with adverse pathologic features in patients with localized PC, including higher GS and NCCN PC risk groups. Moreover, VAT was found to be a strong risk factor for secondary malignancies. Cancer 2010. © 2010 American Cancer Society.
Incidence of atypical teratoid/rhabdoid tumors in children
Authors: Woehrer Adelheid , Slavc Irene , Waldhoer Thomas , Heinzl Harald , Zielonke Nadine , Czech Thomas , Benesch Martin , Hainfellner Johannes A. , Haberler Christine
Published: August 2010

BACKGROUND:

Atypical teratoid/rhabdoid tumors are highly malignant embryonal central nervous system (CNS) tumors that were defined as an entity in 1996. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Atypical teratoid/rhabdoid tumors display a complex histomorphology, which renders them prone to misdiagnosis. They occur predominantly in young children, with an estimated prevalence of 1% to 2% among all pediatric CNS tumors. However, population‐based data on the incidence of these tumors are not yet available.

METHODS:

A nation‐wide survey of malignant high‐grade CNS tumors (World Health Organization grade III/IV), diagnosed in children (aged birth to 14 years) from 1996 to 2006 was conducted by the Austrian Brain Tumor Registry. A central histopathology review was performed including the assessment of SMARCB1 (INI1) protein status.

RESULTS:

A total of 311 newly diagnosed, malignant CNS tumors were included. Atypical teratoid/rhabdoid tumors constituted the sixth most common entity (6.1%), referring to an age‐standardized incidence rate of 1.38 per 1,000,000 person‐years in children. Peak incidence was found in the birth to 2 years age group, where they were as common as CNS primitive neuroectodermal tumors and medulloblastomas. A total of 47.4% of atypical teratoid/rhabdoid tumors were initially diagnosed, whereas 52.6% were retrospectively detected by the central review. The 5‐year survival of atypical teratoid/rhabdoid tumor patients was 39.5%, with 66.7% in the correctly diagnosed group versus 15.0% in the not recognized group (P = .0469).

CONCLUSIONS:

Clinicians and pathologists should be aware of the high incidence of atypical teratoid/rhabdoid tumors in young children to optimize diagnostic and therapeutic management of patients with these tumors. Cancer 2010. © 2010 American Cancer Society.
Evaluation of the Seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification
Authors: Ahn Hye Seong , Lee Hyuk‐Joon , Hahn Seokyung , Kim Woo‐Ho , Lee Kuhn Uk , Sano Takeshi , Edge Stephen B , Yang Han‐Kwang
Published: August 2010

BACKGROUND:

The seventh TNM staging system for gastric cancer of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) had a more detailed classification than the sixth TNM staging system for both the tumor (T) and lymph nodes (N). The authors compared survival rates assessed by the seventh staging system with those by the sixth system.

METHODS:

The authors analyzed the prospectively collected database on patients with gastric cancer who underwent surgery at Seoul National University Hospital between 1986 and 2006, and calculated the survival rates of 9998 cases with primary cancer, R0 resection, and >14 retrieved lymph nodes.

RESULTS:

The 5‐year cumulative survival rates (5YSR) according to the seventh edition T or N classifications were significantly different. The 5YSR according to seventh edition of the TNM staging system were 95.1% (stage IA), 88.4% (stage IB), 84.0% (stage IIA), 71.7% (stage IIB), 58.4% (stage IIIA), 41.3% (stage IIIB), and 26.1% (stage IIIC), which were significantly different from each other. The 5YSR of the seventh edition T2 and T3 classifications had significant differences in patients with every N classification, and the 5YSR of seventh edition N1 and N2 classifications had significant differences in T2 patients, T3 patients, and T4 patients. Each stage in the sixth edition was divided into the seventh edition stage with different survival rates. In addition, the number of homogenous groupings in seventh edition TNM stages was increased from 1 to 2.

CONCLUSIONS:

The seventh system provided a more detailed classification of prognosis than the sixth system, especially between T2 and T3 tumors and N1 and N2 tumors, although further studies were found to be needed for the N3a and N3b classification. Cancer 2010. © 2010 American Cancer Society.
Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer
Authors: Donnem Tom , Andersen Sigve , Al‐Shibli Khalid , Al‐Saad Samer , Busund Lill‐Tove , Bremnes Roy M.
Published: August 2010

BACKGROUND:

Notch signaling plays a key role in embryonic vascular development and angiogenesis. The authors aimed to study the prognostic role of the angiogenesis‐related Notch ligands and receptors and investigate the prognostic impact of the coexpression of vascular endothelial growth factor‐A (VEGF‐A) and Notch signaling.

METHODS:

Tumor tissue samples from 335 resected patients with stage I to IIIA nonsmall cell lung cancer (NSCLC) were obtained, and tissue microarrays were constructed from duplicate cores of tumor cells and tumor‐related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers Notch‐1, Notch‐4, Delta‐like ligand 4 (DLL4), and Jagged‐1.

RESULTS:

There were 191 squamous cell carcinomas (SCCs), 113 adenocarcinomas (ACs), and 31 large cell carcinomas. In AC, low tumor cell Delta‐like ligand 4 expression was an independent negative prognostic factor (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.4‐6.3 [P = .006]), whereas high tumor cell Notch‐1 expression was an independent negative prognostic factor (HR, 2.2; 95% CI, 1.2‐4.1 [P<.001]). In SCC, low stromal Delta‐like ligand 4 expression was an independent indicator of poor prognosis (HR, 3.3; 95% CI, 1.8‐6.1 [P<.001]). The coexpression of Notch‐1 and VEGF‐A had a significant prognostic impact (P<.001). For Notch‐1 and VEGF‐A, low/low (n = 142) versus high/high (n = 35) expression resulted in 5‐year survival rates of 69% and 32%, respectively.

CONCLUSIONS:

Delta‐like ligand 4 and Notch‐1 are independent prognostic factors in NSCLC, but have diverse impacts in SCC and AC. The coexpression of tumor cell Notch‐1/VEGF‐A has a major impact on survival. Cancer 2010. © 2010 American Cancer Society.
Analysis of pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy and subsequent use of adjuvant radiation in a national cohort
Authors: Schreiber David , Rineer Justin , Yu James B. , Olsheski Michelle , Nwokedi Emmanuel , Schwartz David , Choi Kwang , Rotman Marvin
Published: August 2010

BACKGROUND:

The Surveillance, Epidemiology, and End Results database was analyzed to explore the pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy as well as the use of adjuvant radiation in this population.

METHODS:

Identified were patients from 2004 to 2006 with clinically staged T1c‐2cNx‐0M0 prostate adenocarcinoma who underwent radical prostatectomy. All patients had complete clinical and pathologic data. The use of postoperative radiation was recorded. Logistic regression analysis was performed to identify unadjusted and adjusted predictors for extraprostatic disease or positive surgical margins and for adjuvant radiation use.

RESULTS:

A total of 35,642 patients were identified. For those patients with Gleason 7 (4 + 3) and a prostate‐specific antigen (PSA) level of ≥10.1 ng/mL or Gleason 8 to 10 with any PSA level, the rate of organ‐confined disease with negative surgical margins was found to be <50%. Of those with indications for adjuvant radiation, 11.1% received the treatment.

CONCLUSIONS:

This large population‐based study detailed the risk of extraprostatic extension and positive surgical margins in a broad setting across multiple regions and communities, as well as the use of adjuvant radiation for these patients. As of 2006, 11.1% of patients who had indications for adjuvant radiation received this treatment, providing a useful baseline for future patterns of care studies. Cancer 2010. © 2010 American Cancer Society.
Management of acral myxoinflammatory fibroblastic sarcoma
Authors: Tejwani Ajay , Kobayashi Wendy , Chen Yen‐Lin Evelyn , Rosenberg Andrew E. , Yoon Sam , Raskin Kevin A. , Rosenthal Daniel I. , Nielsen Gunnlaugur P. , Hornicek Francis J. , DeLaney Thomas F.
Published: August 2010

BACKGROUND:

Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low‐grade sarcoma that commonly affects the distal extremities. From the published cases, therapy for AMFS to date has been comprised of excision or amputation, with limited use of radiotherapy (RT) or chemotherapy. In this report, the outcome of 17 patients with AMFS treated at the study institution was reported.

METHODS:

A retrospective review of all cases of AMFS identified in the Sarcoma Database in the Department of Radiation Oncology at the study institution was conducted. Treatment records and data from follow‐up visits of patients were reviewed.

RESULTS:

Seventeen patients were identified. All the patients underwent surgical resection (15 excisions and 2 amputations). Positive surgical margins after excisions were noted in 5 patients and were widely positive in 1 patient. Of the 17 patients, 14 patients received some form of RT. The average total dose was 56.4 Gray (Gy). Eight patients received preoperative RT alone, 5 patients received preoperative RT and postoperative RT, and 1 patient received preoperative RT and intraoperative RT. Median follow‐up was 24.5 months. One patient presented with recurrent disease and was treated with resection, and both pre‐ and postoperative RT. He was free of disease 23 months after his last treatment. No local recurrence was noted in the remaining patients. Of the 14 patients undergoing preoperative RT, complete pathologic necrosis or no tumor was noted in 1 of the patients. No metastatic disease was observed in any of the patients. There was no significant radiation toxicity observed in any of the patients.

CONCLUSIONS:

Data were consistent with local control of distal extremity sarcomas with resection and RT, suggesting that limb‐sparing surgery with this treatment combination is an appropriate option in the limb‐sparing control of patients with AMFS, even those with positive surgical margins. Cancer 2010. © 2010 American Cancer Society.
Cytology of endobronchial ultrasound‐guided transbronchial needle aspiration versus conventional transbronchial needle aspiration
Authors: Stoll Lisa Marie , Yung Rex Chin Wei , Clark Douglas P. , Li Qing Kay
Published: August 2010

BACKGROUND:

Conventional endoscopic transbronchial needle aspiration (TBNA) is a common procedure used to obtain samples for diagnosing and staging lung lesions. Recently, endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has been developed and increasingly used by clinicians. Clinical data suggest that EBUS‐TBNA has higher sensitivity and specificity than conventional TBNA in staging lung cancers. In this study, the authors have investigated the cytological features and compared the diagnostic yield of these procedures in lung cancer patients.

METHODS:

A computer search of the cytopathology archives at The Johns Hopkins Hospital revealed 188 EBUS‐TBNA cases (308 lymph nodes; 47 lung lesions) and 74 TBNA cases (106 lymph nodes; 44 lung lesions) over a 28‐month period. All cytological material was correlated with available corresponding surgical material.

RESULTS:

The most frequently sampled lymph nodes were stations 4R and 7 in both TBNA and EBUS‐TBNA; in addition, the EBUS‐TBNA showed a wide range of lymph node sampling. EBUS‐TBNA had a significantly lower nondiagnostic rate (8.7%) compared with TBNA (28.3%, P < .05) in staging lung cancers. In lymph node sampling, the sensitivity and specificity were 54.5% and 100% in the TBNA group and 85.2% and 100% in the EBUS‐TBNA group. In lung specimens, the nondiagnostic rates of TBNA and EBUS‐TBNA were 6.8% and 4.3%, respectively (P > .05), and the sensitivity and specificity were 78.9% and 100% in the TBNA group; and 89.5% and 100% in the EBUS‐TBNA group.

CONCLUSIONS:

Findings indicated that EBUS‐FNA cytology is an optimal modality for diagnosing and staging in lung cancer patients, in comparison to conventional TBNA. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
The diagnosis of non‐Hodgkin lymphoma using fine‐needle aspiration cytopathology
Authors: Wakely Paul E.
Published: August 2010

The utility of fine‐needle aspiration biopsy in patients with non‐Hodgkin lymphoma remains unsettled. Competing philosophies continue to debate its proper role in this cancer.
Quantitative analysis of the bilateral brainstem projections from the whisker and forepaw regions in rat primary motor cortex
Authors: Alloway Kevin D. , Smith Jared B. , Beauchemin Kyle J.
Published: August 2010

The whisker region in rat primary motor (MI) cortex projects to several brainstem regions, but the relative strength of these projections has not been characterized. We recently quantified the MI projections to bilateral targets in the forebrain (Alloway et al. [2009] J Comp Neurol 515:548–564), and the present study extends those findings by quantifying the MI projections to bilateral targets in the brainstem. We found that both the whisker and forepaw regions in MI project most strongly to the basal pons and superior colliculus. While the MI forepaw region projects mainly to the ipsilateral basilar pons, the MI whisker region has significantly more connections with the contralateral side. This bilateral difference suggests that corticopontine projections from the MI whisker region may have a role in coordinating bilateral whisker movements. Anterograde tracer injections in MI did not reveal any direct projections to the facial nucleus, but retrograde tracer injections in the facial nucleus revealed some labeled neurons in MI cortex. The number of retrogradely labeled neurons in MI, however, was dwarfed by a much larger number of labeled neurons in the superior colliculus and other brainstem regions. Together, our anterograde and retrograde tracing results indicate that the superior colliculus provides the most effective route for transmitting information from MI to the facial nucleus. J. Comp. Neurol. 518:4546–4566, 2010. © 2010 Wiley‐Liss, Inc.
Expression patterns of corticotropin‐releasing factor, arginine vasopressin, histidine decarboxylase, melanin‐concentrating hormone, and orexin genes in the human hypothalamus
Authors: Krolewski David M. , Medina Adriana , Kerman Ilan A. , Bernard Rene , Burke Sharon , Thompson Robert C. , Bunney William E. , Schatzberg Alan F. , Myers Richard M. , Akil Huda , Jones Edward G. , Watson Stanley J.
Published: August 2010

The hypothalamus regulates numerous autonomic responses and behaviors. The neuroactive substances corticotropin‐releasing factor (CRF), arginine‐vasopressin (AVP), histidine decarboxylase (HDC), melanin‐concentrating hormone (MCH), and orexin/hypocretins (ORX) produced in the hypothalamus mediate a subset of these processes. Although the expression patterns of these genes have been well studied in rodents, less is known about them in humans. We combined classical histological techniques with in situ hybridization histochemistry to produce both 2D and 3D images and to visually align and quantify expression of the genes for these substances in nuclei of the human hypothalamus. The hypothalamus was arbitrarily divided into rostral, intermediate, and caudal regions. The rostral region, containing the paraventricular nucleus (PVN), was defined by discrete localization of CRF‐ and AVP‐expressing neurons, whereas distinct relationships between HDC, MCH, and ORX mRNA‐expressing neurons delineated specific levels within the intermediate and caudal regions. Quantitative mRNA signal intensity measurements revealed no significant differences in overall CRF or AVP expression at any rostrocaudal level of the PVN. HDC mRNA expression was highest at the level of the premammillary area, which included the dorsomedial and tuberomammillary nuclei as well as the dorsolateral hypothalamic area. In addition, the overall intensity of hybridization signal exhibited by both MCH and ORX mRNA‐expressing neurons peaked in distinct intermediate and caudal hypothalamic regions. These results suggest that human hypothalamic neurons involved in the regulation of the HPA axis display distinct neurochemical patterns that may encompass multiple local nuclei. J. Comp. Neurol. 518:4591–4611, 2010. © 2010 Wiley‐Liss, Inc.
Astroglial structures in the zebrafish brain
Authors: Grupp Larissa , Wolburg Hartwig , Mack Andreas F.
Published: August 2010

To understand components shaping the neuronal environment we studied the astroglial cells in the zebrafish brain using immunocytochemistry for structural and junctional markers, electron microscopy including freeze fracturing, and probed for the water channel protein aquaporin‐4. Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) showed largely overlapping immunoreactivity: GFAP in the main glial processes and GS in main processes and smaller branches. Claudin‐3 immunoreactivity was spread in astroglial cells along their major processes. The ventricular lining was immunoreactive for the tight‐junction associated protein ZO‐1, in the telencephalon located on the dorsal, lateral, and medial surface due to the everting morphogenesis. In the tectum, subpial glial endfeet were also positive for ZO‐1. Correspondingly, electron microscopy revealed junctional complexes between subpial glial endfeet. However, in freeze‐fracture analysis tight junctional strands were not found between astroglial membranes, either in the optic tectum or in the telencephalon. Occurrence of aquaporin‐4, the major astrocytic water channel in mammals, was demonstrated by polymerase chain reaction (PCR) analysis and immunocytochemistry in tectum and telencephalon. Localization of aquaporin‐4 was not polarized but distributed along the entire radial extent of the cell. Interestingly, their membranes were devoid of the orthogonal arrays of particles formed by aquaporin‐4 in mammals. Finally, we investigated astroglial cells in proliferative areas. Brain lipid basic protein, a marker of early glial differentiation but not GS, were present in some proliferation zones, whereas cells lining the ventricle were positive for both markers. Thus, astroglial cells in the zebrafish differ in many aspects from mammalian astrocytes. J. Comp. Neurol. 518:4277–4287, 2010. © 2010 Wiley‐Liss, Inc.
Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina
Authors: Pérez de Sevilla Müller Luis , Do Michael Tri H. , Yau King‐Wai , He Shigang , Baldridge William H.
Published: August 2010

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subtype of ganglion cell in the mammalian retina that expresses the photopigment melanopsin and drives non‐image‐forming visual functions. Three morphological subtypes of ipRGCs (M1, M2, and M3) have been described based on their dendritic stratifications in the inner plexiform layer (IPL), but the question of their potential interactions via electrical coupling remains unsettled. In this study, we have addressed this question in the mouse retina by, injecting the tracer Neurobiotin into ipRGCs that had been genetically labelled with the fluorescent protein, tdTomato. We confirmed the presence of the M1–M3 subtypes of ipRGCs based on their distinct dendritic stratifications. All three subtypes were tracer coupled to putative amacrine cells situated within the ganglion cell layer (GCL) but not the inner nuclear layer (INL). The cells tracer coupled to the M1 and M2 cells were shown to be widefield GABA‐immunoreactive amacrine cells. We found no evidence of homologous tracer coupling of ipRGCs or heterologous coupling to other types of ganglion cells. J. Comp. Neurol. 518:4813–4824, 2010. © 2010 Wiley‐Liss, Inc.
Expression pattern of membrane‐associated guanylate kinases in interneurons of the visual cortex
Authors: Akgul Gulcan , Wollmuth Lonnie P.
Published: August 2010

GABAergic interneurons are key elements regulating the activity of local circuits, and abnormal inhibitory circuits are implicated in certain psychiatric and neurodevelopmental diseases. The glutamatergic input that interneurons receive is a key determinant of their activity, yet its molecular structure and development, which are often distinct from those of glutamatergic input to pyramidal cells, are poorly defined. The membrane‐associated guanylate kinase (MAGUK) homologs PSD‐95/SAP90, PSD‐93/chapsyn110, SAP97, and SAP102 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons. We therefore studied the cell‐type‐specific and developmental expression of MAGUKs in the nonoverlapping parvalbumin (PV)‐ and somatostatin (SOM)‐positive interneurons in the visual cortex. These interneuron subtypes account for the vast majority of interneurons in the cortex and have different functional properties and postsynaptic structures, being either axodendritic (PV+) or axospinous (SOM+). To study cell‐type‐specific MAGUK expression, we used DIG‐labeled riboprobes against each MAGUK along with antibodies against either PV or SOM and examined tissue from juvenile (P15) and adult mice. Both PV+ and SOM+ interneurons express mRNA for PSD‐95, PSD‐93, and SAP102 in P15 and adult tissue. In contrast, these interneuron subtypes express SAP97 at P15, but for adult visual cortex we found that most PV+ and SOM+ interneurons show low or no expression of SAP97. Given the importance of SAP97 in regulating AMPA receptor GluA1 subunit and NMDA receptor subunits at glutamatergic synapses, these results suggest a developmental shift in glutamate receptor subunit composition and regulation of glutamatergic synapses on PV+ and SOM+ interneurons. J. Comp. Neurol. 518:4842–4854, 2010. © 2010 Wiley‐Liss, Inc.
Cxcr4 and Cxcl12 expression in radial glial cells of the brain of adult zebrafish
Authors: Diotel Nicolas , Vaillant Colette , Gueguen Marie‐Madeleine , Mironov Svetlana , Anglade Isabelle , Servili Arianna , Pellegrini Elisabeth , Kah Olivier
Published: August 2010

Unlike that of mammals, the brain of adult teleost fish exhibits an intense and widespread neurogenic activity as a result of the persistence of radial glial cells acting as neural progenitors throughout life. Because chemokines, notably CXCL12, and their receptors, such as CXCR4, play key roles in mammalian embryonic neurogenesis, we investigated Cxcr4 and Cxcl12 expressions in the brain of adult zebrafish and their potential relationships with cell proliferation. Cxcr4 expression was found to be restricted to radial glial cells in the adult zebrafish, where it is co‐expressed with established radial glial cell markers, such as brain lipid‐binding protein (Blbp) or the estrogen‐synthesizing enzyme aromatase B (Cyp19a1b). Double stainings combining proliferating cell nuclear antigen (PCNA) and Cxcr4 immunolabelling indicated that there is no obvious association between Cxcr4 expression and radial glial cell proliferation. Interestingly, cxcl12a messengers were detected in ventricular regions, in cells corresponding to aromatase B‐immunoreactive radial glial cells. Altogether, our data demonstrate Cxcl12 and Cxcr4 expression in radial glial cells of the brain of adult zebrafish, supporting important roles for the Cxcl12/Cxcr4 pair in brain development and functioning. J. Comp. Neurol. 518:4855–4876, 2010. © 2010 Wiley‐Liss, Inc.
Subdivisions of the turtle Pseudemys scripta subpallium based on the expression of regulatory genes and neuronal markers
Authors: Moreno Nerea , Morona Ruth , López Jesús M. , González Agustín
Published: August 2010

The patterns of distribution of a set of conserved brain developmental regulatory transcription factors and neuronal markers were analyzed in the subpallium of the juvenile turtle, Pseudemys scripta. Immunohistochemical techniques were used with a combination of primary antibodies for the identification of the main boundaries and subdivisions in the basal telencephalon. In the basal ganglia, the combinatorial expression on Pax6, Nkx2.1, and GABA was a powerful tool for the identification of the nucleus accumbens, the dorsal portion of the striatum, and the pallidal regions. It was also possible to suggest migratory streams of neurons from the pallidum into the striatal regions. On the basis of GABA, Pax6, Tbr1, tyrosine hydroxylase, Darpp32, and Nkx2.1 combinatorial expression patterns, the boundaries of the septal subdivisions and their embryological origin were assessed. In particular, the bed nucleus of the stria terminalis was identified. Within the amygdaloid complex, the striatal central amygdala was characterized by Pax6 expression, whereas Orthopedia gene expression highlighted, at least, a subdivision of the medial amygdala. A newly identified preoptic commissural area and the boundaries of the preoptic area were assessed, mainly by the localization of Nkx2.1 expression. Finally, additional data were obtained by combining immunohistochemistry and tracing techniques on the interneuronal nature of the cholinerginergic, nitrergic, and Nkx2.1‐positive striatal cells. Taken together, all the results of the present study allowed recognizing main features in the organization of the subpallium in reptiles that, in most cases, are shared with other amniotes and amphibians. J. Comp. Neurol. 518:4877–4902, 2010. © 2010 Wiley‐Liss, Inc.
A data dependency based strategy for intermediate data storage in scientific cloud workflow systems
Authors: Yuan Dong , Yang Yun , Liu Xiao , Zhang Gaofeng , Chen Jinjun
Published: August 2010

Many scientific workflows are data intensive where large volumes of intermediate data are generated during their execution. Some valuable intermediate data need to be stored for sharing or reuse. Traditionally, they are selectively stored according to the system storage capacity, determined manually. As doing science in the cloud has become popular nowadays, more intermediate data can be stored in scientific cloud workflows based on a pay‐for‐use model. In this paper, we build an intermediate data dependency graph (IDG) from the data provenance in scientific workflows. With the IDG, deleted intermediate data can be regenerated, and as such we develop a novel intermediate data storage strategy that can reduce the cost of scientific cloud workflow systems by automatically storing appropriate intermediate data sets with one cloud service provider. The strategy has significant research merits, i.e. it achieves a cost‐effective trade‐off of computation cost and storage cost and is not strongly impacted by the forecasting inaccuracy of data sets' usages. Meanwhile, the strategy also takes the users' tolerance of data accessing delay into consideration. We utilize Amazon's cost model and apply the strategy to general random as well as specific astrophysics pulsar searching scientific workflows for evaluation. The results show that our strategy can reduce the overall cost of scientific cloud workflow execution significantly. Copyright © 2010 John Wiley & Sons, Ltd.
Electrochemical Probes for Detection and Analysis of Exocytosis and Vesicles
Authors: Mellander Lisa , Cans Ann‐Sofie , Ewing Andrew G.
Published: August 2010

Unraveling the mechanistic details of neurotransmitter exocytosis is arguably among the most important molecular problems in neuroscience today. Investigations at single cells, particularly with electrochemical methods, have given unique chemical and biological insight into this process at the fundamental level. The rapid response time (submillisecond) of microelectrodes makes them well suited for monitoring the dynamic process of exocytosis. We review here recent developments in electrochemical techniques to spatially and simultaneously detect exocytosis across a single cell and to measure the transmitter content of single vesicles removed from cells. The former method is used to demonstrate dynamic heterogeneity in release across a cell, and in the latter work comparison is made between vesicle content and release to conclude that only a fraction of the transmitter is released during full exocytosis.
Electrochemically Assisted Fabrication of Metal Atomic Wires and Molecular Junctions by MCBJ and STM‐BJ Methods
Authors: Tian Jing‐Hua , Yang Yang , Zhou Xiao‐Shun , Schöllhorn Bernd , Maisonhaute Emmanuel , Chen Zhao‐Bin , Yang Fang‐Zu , Chen Yong , Amatore Christian , Mao Bing‐Wei , Tian Zhong‐Qun
Published: August 2010

Atomic wires (point contacts) and molecular junctions are two fundamental units in the fields of nanoelectronics and devices. This Minireview introduces our recent approaches aiming to develop versatile methods to fabricate and characterize these unique metallic and molecular structures reliably. Electrochemical methods are coupled with mechanically controllable break junction (EC‐MCBJ) or scanning tunneling microscopy (STM) break junction (EC‐STMBJ) methods to fabricate metallic point contacts and metal/molecule/metal junctions. With the designed electrodeposition method, the metal of interest (e.g. Au, Cu, Fe or Pd) is deposited in a controlled way on the original electrode pair, on a chip for MCBJ or on the STM tip, to make the metallic contact. Then, various metal atomic wires and molecular junctions can be fabricated and characterized systematically. Herein, we measured the quantized conductance through the construction of histograms of these metal atomic point contacts and of single molecules including benzene‐1,4‐dithiol (BDT), ferrocene‐bisvinylphenylmethyl dithiol (Fc‐VPM), 4,4′‐bipyridine (BPY), 1,2‐di(pyridin‐4‐yl)ethene (BPY‐EE), and 1,2‐di(pyridin‐4‐yl)ethane (BPY‐EA). Finally, we briefly discussed the future of EC‐MCBJ and EC‐STM for nanoelectronics and devices, for example, for the formation of heterogeneous metal‐based atomic point contacts and molecular junctions.
Probing the Hydrogen Bonding Structure in the Rieske Protein
Authors: El Khoury Youssef , Trivella Aurélien , Gross Julien , Hellwig Petra
Published: August 2010

The use of the far‐infrared spectral range presents a novel approach for analysis of the hydrogen bonding in proteins. Here it is presented for the analysis of FeS vibrations (500–200 cm−1) and of the intra‐ and intermolecular hydrogen bonding signature (300–50 cm−1) in the Rieske protein from Thermus thermophilus as a function of temperature and pH. Three pH values were adequately chosen in order to study all the possible protonation states of the coordinating histidines. The FeS vibrations showed pH‐dependent shifts in the FIR spectra in line with the change of protonation state of the histidines coordinating the [2Fe2S] cluster. Measurements of the low‐frequency signals between 300 and 30 K demonstrated the presence of a distinct overall hydrogen bonding network and a more rigid structure for a pH higher than 10. To further support the analysis, the redox‐dependent shifts of the secondary structure were investigated by means of an electrochemically induced FTIR difference spectroscopic approach in the mid infrared. The results confirmed a clear pH dependency and an influence of the immediate environment of the cluster on the secondary structure. The results support the hypothesis that structure‐mediated changes in the environment of ironsulfur centers play a critical role in regulating enzymatic catalysis. The data point towards the role of the overall internal hydrogen bonding organization for the geometry and the electronic properties of the cluster.
Aspects of the Atmospheric Chemistry of Amides
Authors: Barnes Ian , Solignac Geraldine , Mellouki Abdelwahid , Becker Karl H.
Published: August 2010

The gas‐phase reactions of six amides, formamide, N‐methyl formamide, N,N‐dimethyl formamide, acetamide, N‐methyl acetamide and N,N‐dimethyl acetamide with the atmospheric oxidants OH radicals and Cl atoms, but in a number of cases also with NO3 radicals and ozone, are presented and discussed. Kinetic and mechanistic information available from previous experimental work is combined with new kinetic and product information from this study, obtained in a photoreactor using in situ FTIR spectrometry, to elucidate the gas‐phase photooxidation mechanisms of the amides and assess potential environmental implications.
Efficient Platinum‐Free Counter Electrodes for Dye‐Sensitized Solar Cell Applications
Authors: Ahmad Shahzada , Yum Jun‐Ho , Butt Hans‐Jürgen , Nazeeruddin Mohammad K. , Grätzel Michael
Published: August 2010

Nanoporous layers of poly(3,4‐propylenedioxythiophene) (PProDOT) were fabricated by electrical‐field‐assisted growth using hydrophobic ionic liquids as the growing medium. A series of PProDoT layers was prepared with three different ionic liquids to control the microstructure and electrochemical properties of the resulting dye‐sensitized solar cells, which were highly efficient and showed a power conversion efficiency of >9 % under different sunlight intensities. The current–voltage characteristics of the counter electrodes varied depending on the ionic liquids used in the synthesis of PProDOT. The most hydrophobic ionic liquids exhibited high catalytic properties, thus resulting in high power conversion efficiency and allowing the fabrication of platinum‐free, stable, flexible, and cost‐effective dye‐sensitized solar cells.
Effect of rapid thermal annealing on Zn1‐xCdxO layers grown by radio‐frequency magnetron co‐sputtering
Authors: Yu J. H. , Kim J. H. , Park D. S. , Jeong T. S. , Youn C. J. , Hong K. J.
Published: August 2010

Zn1‐xCdxO layers were deposited on the sapphire substrate using the radio‐frequency magnetron co‐sputtering system. The grown Zn1‐xCdxO layers were carried out in the post‐annealing treatment for 1 min at the 800 °C oxygen‐ambient by the rapid thermal annealing (RTA) method. X‐ray diffraction (XRD) experiment shows that the Zn1‐xCdxO layers are changed from the single phase of the hexagonal structure at 0≤x ≤0.08 to the double phase of hexagonal‐and‐cubic structure at x =0.13. Thus, the maximum Cd‐composition ratio with the hexagonal structure was found out to be x =0.08. Also, the crystallinity of Zn1‐xCdxO layers at x =0.13 was remarkably improved by the RTA annealing treatment. This crystal quality improvement was thought to be associated with the relaxation of the compressive strain remaining in the Zn1‐xCdxO layers. Therefore, the results of XRD and transmittance lead that the crystal quality of the Zn1‐xCdxO layers forming the hexagonal ZnO phase is better than that forming the cubic CdO phase. Consequently, the reliable formation and the crystallinity of the Zn1‐xCdxO layers were achieved by using the RTA method of short‐time thermal‐annealing at the high temperature. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An Alternative Solvent‐Free Synthesis of Nopinone under Ball‐Milling Conditions: Investigation of Reaction Parameters
Authors: Szuppa Tony , Stolle Achim , Ondruschka Bernd , Hopfe Wieland
Published: August 2010

A new method for the oxidative cleavage of β‐pinene (1) yielding nopinone (2) with potassium permanganate as oxidant under solvent‐free conditions was established. The reaction was performed in a conventional ball mill with use of a grinding auxiliary. The auxiliary has the ability to sorb liquid reactants such as 1 on its surface to make liquid(s) accessible for mechanical impact. Different reaction parameters and technical variables were assessed concerning their influence on yield and selectivity of 2. Different chemical parameters such as oxidants, grinding auxiliaries, and quantities were investigated. Also tuning parameters including milling time, rotation frequency, and number of milling balls were explored.
Fast‐squarer circuits using 3‐bit‐scan without overlapping bits
Authors: Perri Stefania , Corsonello Pasquale
Published: August 2010

This paper presents a novel technique to design fast‐squaring circuits. The proposed approach speeds up squaring operations combining the 3‐bit scan without overlapping bits and the folding technique.

Several hardware implementations of squarer circuits designed as described here are characterized for several operand wordlengths. Obtained results demonstrate that, using the ST 90 nm 1V CMOS technology, a 32‐bit squarer exploiting the novel way of generating partial products reaches a 769 MHz running frequency, dissipates less than 19.3 mW on average and occupies ∼91 000µm2of silicon area. Copyright © 2010 John Wiley & Sons, Ltd.
Encapsulated apocrine papillary carcinoma of the breast: Case report with clinicopathologic and immunohistochemical study
Authors: Laforga J. B. , Gasent J. M. , Sánchez I.
Published: August 2010

We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50‐year‐old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine‐needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP‐15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.
Anti‐anxiety and sedative profile evaluation of imidazo[1,2‐a]pyridine derivatives
Authors: López‐Martínez Margarita , Salgado‐Zamora Héctor , San‐Juan Eduardo Ramírez , Zamudio Sergio , Picazo Ofir , Campos Maria Elena , Naranjo‐Rodriguez Elia B.
Published: August 2010

Three imidazo[1,2‐a]pyridine‐3‐nitrosated (L‐1, L‐2, L‐3) and a 3‐formyl imidazo[1,2‐a]pyridine thiosemicarbazone (L‐4) were synthesized and evaluated for their effects in the elevated plus maze, burying behavior test, rotarod performance, the horizontal wire test, and locomotor activity. L‐2 and L‐3 increased the percent time spent in the open arms of the plus maze at doses of 1 and 2 mg/kg without modifying the number of total entries. In addition, L‐2 and L‐3 (1 mg/kg) increased the number of open arm entries indicating anxiolytic‐like activity at this dose. In the burying behavioral test, L‐1 (2–8 mg/kg), L‐2 (8 mg/kg), and L‐3 (4 and 8 mg/kg), induced a clear reduction in cumulative burying behavior, without modifying burying behavior latency, thus reducing experimental anxiety. In the rotarod test, L‐1 and L‐2 impaired rotarod performance only at the highest evaluated dose (64 mg/kg) at which reduction of motor activity was observed and thereby no conclusions about myorelaxant effects can be proposed. All compounds showed a clear sedative effect and corresponding ED50values were obtained. Results indicate that compounds L‐1, L‐2, and L‐3 show a sedative and an anxiolytic profile. Drug Dev Res 71:371–381, 2010. © 2010 Wiley‐Liss, Inc.
Cognitive dysfunction in patients with type 2 diabetes
Authors: Reijmer Yael D. , van den Berg Esther , Ruis Carla , Jaap Kappelle L. , Biessels Geert Jan
Published: August 2010

People with diabetes mellitus are at increased risk of cognitive dysfunction and dementia. This review explores the nature and severity of cognitive changes in patients with type 2 diabetes. Possible risk factors such as hypo‐ and hyperglycemia, vascular risk factors, micro‐ and macrovascular complications, depression and genetic factors will be examined, as well as findings from brain imaging and autopsy studies. We will show that type 2 diabetes is associated with modest cognitive decrements in non‐demented patients that evolve only slowly over time, but also with an increased risk of more severe cognitive deficits and dementia. There is a dissociation between these two ‘types’ of cognitive dysfunction with regard to affected age groups and course of development. Therefore, we hypothesize that the mild and severe cognitive deficits observed in patients with type 2 diabetes reflect separate processes, possibly with different risk factors and aetiologies. Copyright © 2010 John Wiley & Sons, Ltd.
Endothelial cell migration during murine yolk sac vascular remodeling occurs by means of a rac1 and FAK activation pathway in vivo
Authors: Enciso Josephine M. , Konecny Christine M. , Karpen Heidi E. , Hirschi Karen K.
Published: August 2010

The molecular mechanism(s) controlling cell migration during vascular morphogenesis in vivo remain largely undefined. To address this within a physiological context, we used retinaldehyde dehydrogenase‐2 (Raldh2) null mouse embryos and demonstrate that retinoic acid (RA) deficiency results in abnormal yolk sac vascular remodeling due to decreased Rac1 activation, increased RhoA activation, and increased focal adhesions. Vinculin was increased in Raldh2−/− yolk sacs, and molecular events important for focal adhesion turnover, FAK phosphorylation (Tyr397) and FAK‐paxillin association, were decreased. RA‐rescue of vascular remodeling down‐regulated vinculin and restored FAK phosphorylation (Tyr397) and FAK‐paxillin association. Furthermore, vascular rescue with vascular endothelial growth factor‐A, Indian hedgehog, and basic fibroblast growth factor restored FAK phosphorylation (Tyr397) in the endothelium of Raldh2−/− yolk sacs. Our results provide new insights into the regulation of endothelial cell migration during vascular remodeling in vivo by adding the Rac1 and FAK activation pathway as a critical mediator of focal adhesion formation and turnover during vascular remodeling. Developmental Dynamics 239:2570–2583, 2010. © 2010 Wiley‐Liss, Inc.
Organogenesis and tumorigenesis: Insight from the JAK/STAT pathway in the Drosophila eye
Authors: Wang Ying‐Hsuan , Huang Min‐Lang
Published: August 2010

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is one of the main signaling pathways in eukaryotic cells. This pathway is used during diverse growth and developmental processes in multiple tissues to control cell proliferation, differentiation, survival, and apoptosis. In addition to its role during development, the JAK/STAT pathway has also been implicated in tumorigenesis. Drosophila melanogaster is a powerful genetic tool, and its eyes have been used extensively as a platform to study signaling pathways. Many reports have demonstrated that the JAK/STAT pathway plays pleiotropic roles in Drosophila eye development. Its functions and activation are decided by its interplay with other signal pathways and the epigenetic status. In this review, we focus on the functions and regulation of the JAK/STAT pathway during eye development and provide some insights into the study of this pathway in tumorigenesis. Developmental Dynamics 239:2522–2533, 2010. © 2010 Wiley‐Liss, Inc.