bluuebunny/crossref_metadata_2025 huggingface dataset:
Biopsy or debulking surgery as initial surgery for locally advanced rhabdomyosarcomas in children?
Authors: Cecchetto Giovanni , Bisogno Gianni , De Corti Federica , Dall'Igna Patrizia , Inserra Alessandro , Ferrari Andrea , Garaventa Alberto , Scagnellato Angela , Carli Modesto
Published: October 2007

BACKGROUND.

The purpose of the current study was to analyze the influence of the initial surgical approach (biopsy vs resection with macroscopic residual tumors) on the outcome of patients with localized Intergroup Rhabdomyosarcoma Study (IRS) Group III rhabdomyosarcoma (RMS) enrolled in the Italian studies between 1979 and 2003.

METHODS.

Among the 394 patients evaluated, 323 underwent biopsy, as recommended by the protocols, and 71 patients underwent surgical resection with macroscopic residual tumors (debulking operation [DO]), although this procedure was discouraged. All these patients were classified at the same risk group and received the same treatment. The different characteristics (patient age, tumor site, T classification and size, histology) and outcome in the 2 groups were considered.

RESULTS.

The estimated 5‐year overall survival (OS) rates were 68.4% and 72.6%, respectively, after biopsy and DO(P = .38), and the rates of progression‐free survival (PFS) were 56.5% and 61.7%, respectively, after biopsy and DO (P = .41). The outcome did not differ significantly when considering other variables such as tumor site, size, and histology. Age > 10 years appeared to have little benefit in patients with DO; the OS was 62% after biopsy and 83.1% after DO (P = .06); the PFS was 49.7% and 72.8%, respectively after biopsy and DO (P = .04). No surgical complications due to the 2 procedures were reported, but in 2 cases the initial DO resulted in a mutilation.

CONCLUSIONS.

No significant advantages of DO versus biopsy were detected with regard to patient outcome. Biopsy, which is less aggressive, appears to be thebest option for patients with IRS Group III RMS. Cancer 2007. © 2007 American Cancer Society.
Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma
Authors: Hodgson David C. , Koh Eng‐Siew , Tran Tu Huan , Heydarian Mostafa , Tsang Richard , Pintilie Melania , Xu Tony , Huang Lei , Sachs Rainer K. , Brenner David J.
Published: October 2007

BACKGROUND.

Estimates of radiation‐related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved‐field RT and low‐dose (20 Gy) RT for mediastinal Hodgkin lymphoma.

METHODS.

Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved‐field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual‐level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation‐induced second cancer.

RESULTS.

ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20‐year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low‐dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient‐specific differences in normal tissue dose with IFRT led to 11‐fold and 3.6‐fold variations among individual's estimates of breast and lung cancer ERR, respectively.

CONCLUSIONS.

Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient‐specific counseling and the development of more effective RT techniques. Cancer 2007. © 2007 American Cancer Society.
Preoperative chemotherapy treatment of breast cancer—A review
Authors: Buzdar Aman U.
Published: October 2007

Despite proven benefits of neoadjuvant chemotherapy in patients with locally advanced, invasive breast cancer, no regimen is recommended as the treatment of choice. Neoadjuvant chemotherapy regimens encompass single‐agent and combination therapy and sequential treatment. For this report, the author reviewed the literature to determine which regimen, if any, was most beneficial. The results indicated that studies have yielded a wide range of response rates, but no single regimen has emerged as a clear leader. The literature is compounded further by lack of standardized criteria to determine pathologic complete response (which is predictive of survival benefits) and between‐study variation in the stringency by which this endpoint is defined. Given the lack of a preferred treatment regimen in the neoadjuvant setting, identifying patients who are likely to respond to specific agents could inform treatment decisions, improve treatment outcomes, and aid in avoiding unnecessary exposure to potential toxicities. The development of novel agents for use alone or in combination with existing agents may improve response rates further in the neoadjuvant setting, especially because a significant proportion of breast tumors can be resistant to many current antineoplastic agents. Particularly noteworthy are the epothilones and their analogs because of their low susceptibility to common tumor‐resistance mechanisms. Initial data have indicated that ixabepilone, which is an epothilone analog, has activity in the neoadjuvant setting, and predictive factors for response have been identified. The future of neoadjuvant therapy lies in tailoring treatment to individual patients by identifying response predictors and developing novel agents. This ultimately may lead to improved outcomes for women with breast cancer. Cancer 2007. © 2007 American Cancer Society.
Retracted: Response to dual blockade of epidermal growth factor receptor (EGFR) and cycloxygenase‐2 in nonsmall cell lung cancer may be dependent on the EGFR mutational status of the tumor
Authors: Gadgeel Shirish M. , Ali Shadan , Philip Philip A. , Ahmed Fakhara , Wozniak Antoinette , Sarkar Fazlul H.
Published: October 2007

BACKGROUND.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have demonstrated clinical benefit in patients with nonsmall cell lung cancer (NSCLC), particularly those with tumors that have EGFR‐TK domain mutations. Moreover, the EGFR and cyclooxygenase (COX)‐2 pathways are known to enhance the procarcinogenic effects of each other in different tumor types. Therefore, it was hypothesized that tumor EGFR mutation status may influence the effectiveness of simultaneous EGFR and COX‐2 inhibition in patients with NSCLC.

METHODS.

Three NSCLC cell lines with varying EGFR mutation status and sensitivities to EGFR‐TKIs were selected: H3255 (L858R), H1650 (del E746‐A750), and H1781 (wild‐type EGFR). Cells were treated with erlotinib, gefitinib, or celecoxib alone, and the combination of both EGFR‐TKI inhibitors with celecoxib. Cell survival and apoptosis was assessed and correlated with the expression of COX‐2, EGFR, pEGFR, Akt, pAkt, expression, and derived prostaglandin E2 (PGE2).

RESULTS.

Celecoxib by itself was found to have no effects on cell growth or apoptosis in any of the cell lines. Erlotinib and gefitinib inhibited cell growth and induced apoptosis in both mutant cell lines and did so in H1781 cells at 10‐fold higher concentrations. Celecoxib when added to erlotinib or gefitinib significantly enhanced the antiproliferative and proapoptotic effects in both mutant cell lines but had no additional effects in H1781 cells. Greater down‐regulation of COX‐2, EGFR, pEGFR, Akt, pAkt, and PGE2 was found when H3255 cells were treated with the combination compared with any of the single agents alone.

CONCLUSIONS.

The results of the current study demonstrate that the effectiveness of the addition of celecoxib to an EGFR‐TKI is significantly greater in NSCLC cells with EGFR mutations, which is likely due to more complete inhibition of both pathways. Cancer 2007. © 2007 American Cancer Society.
Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas
Authors: Shoji Fumihiro , Yoshino Ichiro , Yano Tokujiro , Kometani Takuro , Ohba Taro , Kouso Hidenori , Takenaka Tomoyoshi , Miura Naoko , Okazaki Hiroshi , Maehara Yoshihiko
Published: October 2007

BACKGROUND.

The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas.

METHODS.

A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor.

RESULTS.

Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs ≥5 <20 vs ≥20 = 35% vs 55% vs 87.5%, respectively, P = .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P = .036) with an odds ratio of 4.70 (95% confidence interval, 1.1–21.1).

CONCLUSIONS.

The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas. Cancer 2007. © 2007 American Cancer Society.
Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies
Authors: Caillot Denis , Thiébaut Anne , Herbrecht Raoul , de Botton Stéphane , Pigneux Arnaud , Bernard Frédéric , Larché Jérôme , Monchecourt Françoise , Alfandari Serge , Mahi Lamine
Published: October 2007

BACKGROUND.

Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds.

METHODS.

Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high‐dose AmB regimen (10 mg/kg daily).

RESULTS.

Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high‐dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high‐dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion‐related reactions occurred in 3 patients in the high‐dose monotherapy group. A 2‐fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high‐dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively.

CONCLUSIONS.

The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study. Cancer 2007. © 2007 American Cancer Society.
R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice
Authors: Reiner Anton , Del Mar Nobel , Deng Yun‐Ping , Meade Christopher A. , Sun Zhiqiang , Goldowitz Daniel
Published: October 2007

The R6/2 mouse possesses mutant exon 1 of human Hdh, and R6/2 mice with 150 CAG repeats show neurological abnormalities by 10 weeks and die by 15 weeks. Few brain abnormalities, however, are evident at death, other than widespread ubiquitinated neuronal intranuclear inclusions (NIIs). We constructed R6/2t+/t− ↔ wildtype (WT) chimeric mice to prolong survival of R6/2 cells and determine if neuronal death and/or neuronal injury become evident with longer survival. ROSA26 mice (which bear a lacZ transgene) were used as WT to distinguish between R6/2 and WT neurons. Chimeric mice consisting partly of R6/2 cells lived longer than pure R6/2 mice (up to 10 months), with the survival proportional to the R6/2 contribution. Genotypically R6/2 cells formed NIIs in the chimeras, and these NIIs grew only slightly larger than in 12‐week pure R6/2 mice, even after 10 months. Additionally, neuropil aggregates formed near R6/2 neurons in chimeric mice older than 15 weeks. Thus, R6/2 neurons could survive well beyond 15 weeks in chimeras. Moreover, little neuronal degeneration was evident in either cortex or striatum by routine histological stains. Nonetheless, striatal shrinkage and ventricular enlargement occurred, and striatal projection neuron markers characteristically reduced in Huntington's disease were diminished. Consistent with such abnormalities, cortex and striatum in chimeras showed increased astrocytic glial fibrillary acidic protein. These results suggest that while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein. J. Comp. Neurol. 505:603–629, 2007. © 2007 Wiley‐Liss, Inc.
Patterns of laminins and integrins in the embryonic ventricular zone of the CNS
Authors: Lathia Justin D. , Patton Bruce , Eckley D. Mark , Magnus Tim , Mughal Mohamed R. , Sasaki Takako , Caldwell Maeve A. , Rao Mahendra S. , Mattson Mark P. , ffrench‐Constant Charles
Published: October 2007

The extracellular matrix (ECM) provides both a physical framework and a microenvironment that supplies instructive signals from the earliest stages of multicellular development. As a first step toward understanding the role of the ECM in regulating the behavior of neural stem cells (NSCs), here we show the localization of laminins, a heterotrimeric family of ECM molecules expressed in many different stem cell microenvironments, and their corresponding receptors in the embryonic murine ventricular zone (VZ) within which the NSCs undergo symmetrical and asymmetrical divisions required for cortical development. In addition to the presence of laminins containing both the α2 and α4 chains, we find distinct patterns of ECM receptor expression in the VZ and in the overlying cortex. Neural stem cells derived from the VZ express high levels of the integrin laminin receptor α6β1. At developmental stages at which NSCs undergo asymmetrical divisions, integrin β1 was unevenly distributed in some mitotic pairs at the ventricular wall. These results suggest a significant role in the regulation of NSC fate for laminin/integrin signaling within the microenvironment of the VZ and provide a framework for future molecular and cellular analyses of the role of the ECM in neural development. J. Comp. Neurol. 505:630–643, 2007. © 2007 Wiley‐Liss, Inc.
Auditory brainstem neural activation patterns are altered in EphA4‐ and ephrin‐B2‐deficient mice
Authors: Miko Ilona J. , Nakamura Paul A. , Henkemeyer Mark , Cramer Karina S.
Published: October 2007

Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin‐B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin‐B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c‐fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c‐fos‐positive neurons in EphA4−/− DCN after 8‐kHz pure tone stimulation was 42% lower than in wild‐type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c‐fos‐positive neurons was similar for mutant and wild‐type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin‐B2lacZ/+ mice than for wild‐type mice. We also examined these parameters in MNTB after exposure to 40‐kHz pure tones. Both EphA4−/− and ephrin‐B2lacZ/+ mice had significantly fewer c‐fos‐positive cells than wild‐type littermates. The labeled band of cells was narrower and laterally shifted in EphA4−/− mice compared with wild‐type mice. These differences in cell number and distribution suggest that EphA4 and ephrin‐B2 signaling influence auditory activation patterns. J. Comp. Neurol. 505:669–681, 2007. © 2007 Wiley‐Liss, Inc.
Depth‐profile analysis from X‐ray photoelectron spectroscopy on As‐implanted ZnO activated in ozone ambient
Authors: Jeong T. S. , Kim J. H. , Bae S. J. , Youn C. J.
Published: October 2007

Chemical bonds of As‐implanted ZnO annealed in ozone molecular (O3) ambient were analyzed through the x‐ray photoelectron spectroscopy as a function of the etching depth. With the etching depth increased to 25 nm from surface, the peaks of Zn2p and O1s core levels shifted toward the low‐binding energy, and the bonding formation of As 3d core level gradually varied from As2O5 to As2O3. The new peaks were observed, which were posited to high‐binding energy of 4.4 eV from Zn2p and O1s core levels. Finally, the chemical bonds of As‐based oxides were found to consist of Zn(AsO3)2, As2O5, and As2O3. (© 2007 WILEY ‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical inhomogeneities in Li2B4O7 single crystals
Authors: Kar S. , Verma S. , Bartwal K. S.
Published: October 2007

Lithium tetraborate, Li2B4O7 (LTB) crystals were grown by Czochralski technique. It belongs to tetragonal system with lattice parameter a = b = 9.479 Å, c = 10.286 Å. Transmission range of this crystal is 170 nm – 3300 nm. This material has attracted much attention because of its application in higher harmonic generation of Nd:YAG laser and radiation dosimetry. The grown crystals were characterized for their optical inhomogeneity using etch pit study, hardness, conoscopy, interferometry, and UV‐VIS transmittance techniques. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnetic field dependence of the relative critical current density in γ‐irradiated polycrystalline YBa2Cu3O7
Authors: Obaidat I. M. , Hamed F.
Published: October 2007

The effect of different doses of γ‐rays on the behavior of the critical current density, Jc in an YBa2Cu3O7 polycrystalline sample has been investigated at high temperatures. The samples were irradiated at room temperature by a 60Co γ‐ray source at a dose rate of 0.5 MR/h. Jc was found to increase significantly with after irradiation dose of 10 MR. Further irradiation dose of 50 MR produced a slight and field dependent enhancement of Jc above its values at 10 MR. The most interesting result is that the relative change in the critical current density was found to have a non‐monotonic behavior with the applied magnetic field. These results are discussed in terms of the roles of several mechanisms created by γ‐rays in the regions of the grain boundaries combined with the effect of the magnetic field on these mechanisms. (© 2007 WILEY ‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Nitric oxide in the crustacean brain: Regulation of neurogenesis and morphogenesis in the developing olfactory pathway
Authors: Benton J.L. , Sandeman D.C. , Beltz B.S.
Published: October 2007

Nitric oxide (NO) plays major roles during development and in adult organisms. We examined the temporal and spatial patterns of nitric oxide synthase (NOS) appearance in the embryonic lobster brain to localize sources of NO activity; potential NO targets were identified by defining the distribution of NO‐induced cGMP. Staining patterns are compared with NOS and cyclic 3,5 guanosine monophosphate (cGMP) distribution in adult lobster brains. Manipulation of NO levels influences olfactory glomerular formation and stabilization, as well as levels of neurogenesis among the olfactory projection neurons. In the first 2 days following ablation of the lateral antennular flagella in juvenile lobsters, a wave of increased NOS immunoreactivity and a reduction in neurogenesis occur. These studies implicate nitric oxide as a developmental architect and also support a role for this molecule in the neural response to injury in the olfactory pathway. Developmental Dynamics 236:3047–3060, 2007. © 2007 Wiley‐Liss, Inc.
Survey of the morphogenetic dynamics of the ventricular surface of the developing mouse neocortex
Authors: Nishizawa Yuji , Imafuku Hiroshi , Saito Kanako , Kanda Rieko , Kimura Miyako , Minobe Sayaka , Miyazaki Fumiko , Kawakatsu Shoji , Masaoka Makoto , Ogawa Masaharu , Miyata Takaki
Published: October 2007

To understand the morphogenetic dynamics of the inner surface of the embryonic pallial (neocortical) wall, we immunohistochemically surveyed the cellular endfeet facing the lateral ventricle and found that the average endfoot area was minimal at embryonic day (E)12 in mice. This endfoot narrowing at E12 may represent a change in the mode of cell production at the surface from a purely proliferative mode that retains all daughter cells to a more differentiation‐directed mode that allows some daughter cells to leave the surface. The apices of cells undergoing mitosis were 1.5–3.9 times larger than the overall cell apices and 6.7–8.7 times smaller than the cross‐sectional area of mitotic somata. En face time‐lapse monitoring of each endfoot permitted observation of its cell cycle‐dependent size changes, division, and relationships with neighboring endfeet. Planar divisions oriented along the lateral–medial axis were less abundant than those oriented along the rostral–caudal axis at E10 and E11, but basal body distribution in each endfoot was random. Developmental Dynamics 236:3061–3070, 2007. © 2007 Wiley‐Liss, Inc.
The A17 enhancer directs expression of Myf5 to muscle satellite cells but Mrf4 to myonuclei
Authors: Chang Ted Hung‐Tse , Vincent Stéphane D. , Buckingham Margaret E. , Zammit Peter S.
Published: October 2007

The myogenic regulatory factors, Myf5 and Mrf4, play key roles in the specification and differentiation of skeletal muscle, respectively. Many cis‐acting regulatory elements at the Mrf4/Myf5 locus have been identified, including the A17 enhancer. During development, A17 in conjunction with the Mrf4 or Myf5 promoter, directs transgene expression either to embryonic or fetal muscles. We now show that this enhancer also regulates Mrf4/Myf5 transcription in the adult. A17 linked to the Myf5 promoter drives expression in muscle satellite cells, whereas with the Mrf4 promoter, A17 directs transgene expression to myonuclei. Interestingly, expression of A17‐Mrf4‐nlacZ transgenes in myonuclei varies between muscles, revealing muscle autonomous transcriptional regulation. During muscle repair, satellite cells are induced to proliferate and differentiate to provide new myonuclei. A17 directs Myf5 expression in satellite cell progeny while it only drives the Mrf4 promoter after differentiation. Importantly, therefore, this promoter‐specific activity directed by A17 reflects aspects of the expression profiles of the endogenous Myf5 and Mrf4 genes. Developmental Dynamics 236:3419–3426, 2007. © 2007 Wiley‐Liss, Inc.
Second chromosome genes required for heart development in Drosophila melanogaster
Authors: Tao Ye , Christiansen Audrey E. , Schulz Robert A.
Published: October 2007

Heart development is an evolutionarily conserved process. The cardiac organ of Drosophila melanogaster is the dorsal vessel, a linear contractile tissue with cellular and morphogenetic similarities to the primitive heart tube formed at an early stage of vertebrate heart formation. Abundant evidence shows comparable intercellular signaling pathways and transcription factor networks are utilized in Drosophila and vertebrates, to specify cardiac progenitor cells and instruct their differentiation and function in forming the mature heart. With this proven conservation in mind, we screened the second chromosome of Drosophila for genetic intervals that harbor additional loci required for normal dorsal vessel morphogenesis. Our studies identified numerous regions, that when deleted, culminated in dorsal vessels with abnormal cell numbers and/or structural properties. Certain of the deficiency intervals were further characterized to identify individual genes essential for proper cardiac organ formation. Our analyses identified eight genes of diverse functions that are needed for dorsal vessel development. Several of these sequences have known vertebrate homologues, further supporting a conserved genetic basis for heart formation in Drosophila and higher eukaryotes. genesis 45:607–617, 2007. © 2007 Wiley‐Liss, Inc.
A unique mouse strain expressing Cre recombinase for tissue‐specific analysis of gene function in palate and kidney development
Authors: Lan Yu , Wang Qingru , Ovitt Catherine E. , Jiang Rulang
Published: October 2007

Mammalian palate development is a multistep process, involving initial bilateral downward outgrowth of the palatal shelves from the oral side of the maxillary processes, followed by stage‐specific palatal shelf elevation to the horizontal position above the developing tongue and subsequent fusion of the bilateral palatal shelves at the midline to form the intact roof of the oral cavity. While mutations in many genes have been associated with cleft palate pathogenesis, the molecular mechanisms regulating palatal shelf growth, patterning, and elevation are not well understood. Genetic studies of the molecular mechanisms controlling palate development in mutant mouse models are often complicated by early embryonic lethality or gross craniofacial malformation. We report here the development of a mouse strain for tissue‐specific analysis of gene function in palate development. We inserted an IresCre bicistronic expression cassette into the 3′ untranslated region of the mouse Osr2 gene through gene targeting. We show, upon crossing to the R26R reporter mice, that Cre expression from the Osr2IresCre knockin allele activated β‐galactosidase expression specifically throughout the developing palatal mesenchyme from the onset of palatal shelf outgrowth. In addition, the Osr2IresCre mice display exclusive Cre‐mediated recombination in the glomeruli tissues derived from the metanephric mesenchyme and complete absence of Cre activity in other epithelial and mesenchymal tissues in the developing metanephric kidney. These data indicate that the Osr2IresCre knockin mice provide a unique tool for tissue‐specific studies of the molecular mechanisms regulating palate and kidney development. genesis 45:618–624, 2007. © 2007 Wiley‐Liss, Inc.
Developmental regulation ofBhSGAMP‐1, a gene encoding an antimicrobial peptide in the salivary glands ofBradysia hygida(Diptera, Sciaridae)
Authors: Candido‐Silva Juliana A. , Zanarotti Gabriela M. , Gallina Ana P. , de Almeida Jorge C.
Published: October 2007

It has recently become clear that the innate immune systems of insects and mammals are highly conserved; in general, these systems are stimulated upon infection by microorganisms. We found in the flyBradysia hygida, a reiterated gene, which codes for a secretory peptide similar to plant‐seed antimicrobial peptides. This geneBhSGAMP‐1is activated and expressed exclusively in the salivary glands of the larvae, while they are preparing to molt. In functional tests, synthetic BhSGAMP‐1 peptide had broad spectrum antibiotic activity. Secretion of BhSGAMP‐1 in the saliva could help prevent microbial infection during molting, by killing harmful microorganisms in the immediate vicinity of the animal. This is the first description of developmentally regulated defense peptide secretion in animals. genesis 45:630‐638, 2007. © 2007 Wiley‐Liss, Inc.
BAC transgenic expression efficiency: bicistronic versus ATG‐fusion strategies
Authors: Lin Tao , Yasumoto Hiroaki , Tsai Robert Y.L.
Published: October 2007

Bacterial artificial chromosome (BAC)‐based transgene can be expressed bicistronically with the target gene or fused to its translation start codon. To compare the transgene expression efficiencies of these two methods, mice were created that expressed green fluorescent protein (GFP) from the genomic locus of nucleostemin using the bicistronic (NSiGFP) or the ATG‐fusion approach (NSmGFP). Three lines with 1, 2, and 4 copies of the NSiGFP transgene, and two lines with 1 copy of the NSmGFP transgene were generated. Of the three NSiGFP lines, only the 4‐copy line can match the NSmGFP lines in their GFP protein expression levels. Analyses of the GFP and nucleostemin RNA transcript levels exclude IRES inefficiency and suggest premature termination of the bicistronic message as the cause for low GFP expression in the NSiGFP mice. This work provides important information for designing BAC transgenics when the transgene expression level is crucial. 45:647–652, 2007. © 2007 Wiley‐Liss, Inc.
What kind of evidence do we need for evaluating therapeutic interventions?
Authors: Haslum Mary N.
Published: October 2007

The belief that randomized controlled trials provide a ‘gold standard’ for evaluating therapeutic interventions is challenged. The need for research designs that produce valid and reliable information about interventions, which is clinically/educationally relevant and personally important, is discussed together with possibilities for broadening the methods of enquiry and evaluation of interventions. It is also suggested that there is an opportunity to further support the development of rigour in reporting intervention studies irrespective of the epistemology employed. Copyright © 2007 John Wiley & Sons, Ltd.
Test–retest effects in treatment studies of reading disability: the devil is in the detail
Authors: McArthur Genevieve
Published: October 2007

Reynolds and Nicolson (Dyslexia, 2007; 13: 78–96) claim to show that the ‘dyslexia dyspraxia attention‐deficit treatment’ (DDAT) benefits children with reading difficulties. However, Rack, Snowling, Hulme, and Gibbs (Dyslexia, 2007; 13: 97–104) argue that because this study did not include an untrained control group then ‘all that needs to be postulated to explain the results reported is that children improve their scores on the DST screening tests simply as a result of repeated testing on the same activities’ (p. 102). How likely is it that the linguistic gains reported by Reynolds and Nicolson (Dyslexia, 2007; 13: 78–96) are due to test–retest effects? The results of previous exercise‐ and auditory‐based treatment studies that included an untrained control group suggest that test–retest effects explain gains on around 50% of real‐word reading tests, 33% of phonological recoding tests, 33% of phonological awareness tests, 17–25% of spoken language tests, and 15% of spelling tests. In addition, longer periods of time between test and retest sessions are associated with test–retest effects on measures of reading but not spoken language. These findings suggest that two of the four linguistic gains reported by Reynolds and Nicolson (Dyslexia, 2007; 13: 78–96) are due to test–retest effects (phonemic segmentation and working memory). The remaining two tests are measures of spoken language and not reading. Hence, the data reported by Reynolds and Nicolson (Dyslexia, 2007; 13: 78–96) are not sufficient to support DDAT as an effective treatment for children with reading difficulties. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis and X‐ray Characterization of Mono‐ and Polynuclear Thiolatocopper(I) Complexes: The Effect of Steric Bulk on Coordination Number and Nuclearity
Authors: Zeevi Shiri , Tshuva Edit Y.
Published: October 2007

We have synthesized a number of CuI complexes of thiophenolato ligands with different alkyl substituents in the ortho positions in a single‐step procedure starting from a readily available copper(I) precursor to evaluate the coordination preferences of the metal atom. In most cases similar reaction conditions led to the formation of two complexes: a mononuclear complex and a polynuclear cluster, as evident from X‐ray crystallography. One dinuclear complex formed has the unique geometry of an L2Cu2(μ‐L)2 core that has not previously been observed for related systems. The steric bulk around the metal atom has a clear effect on the coordination sphere of the complex obtained. Ligands with no ortho substituents and those with one substituent with a size varying from methyl to tert‐butyl all lead to the formation of three‐coordinate complexes for the mononuclear species, and clusters of different sizes where larger substituents lead to larger cages and all copper centers are three‐coordinate as well. The introduction of two methyl substituents (one in each ortho position) leads to either a mononuclear two‐coordinate copper complex or a polynuclear cluster where two copper centers are three‐coordinate and three are two‐coordinate.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Benzoazocines from Substituted Tetrahydroisoquinolines and Activated Alkynes in a Tetrahydropyridine Ring Expansion
Authors: Voskressensky Leonid G. , Listratova Anna V. , Borisova Tatiana N. , Alexandrov Grigoriy G. , Varlamov Alexey V.
Published: October 2007

Tetrahydroisoquinolines underwent tandem piperidine ring enlargement in the presence of activated alkynes in acetonitrile or methanol, producing tetrahydrobenzo[d]azocines in high yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Tetrathiafulvalene–Imine–Pyridine Assemblies for Pb2+ Recognition
Authors: Balandier Jean‐Yves , Belyasmine Ahmed , Sallé Marc
Published: October 2007

A series of donor–π–acceptor systems incorporating a tetrathiafulvalene moiety as the donating unit have been designed and synthesized. The efficiency of the imine (–C=N–) bond as a conjugated π‐linker in promoting intramolecular charge transfer is demonstrated and supported by calculations at the B3LYP/6‐31G(d,p) level of theory. This property has been explored in the case of pyridyl‐substituted systems which exhibit in particular a high binding affinity and selectivity for Pb2+ (log K = 3.5 in CH2Cl2/CH3CN), as shown by UV/Vis and 1H NMR titrations as well as by remarkable colorimetric and electrochemical signaling.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Unusual Magnesium Chloride Catalyzed Non‐Evans anti‐Aldol Reactions of an Enolizable L‐Threose Derivative
Authors: McNulty James , Nair Jerald J. , Sliwinski Marcin , Harrington Laura E. , Pandey Siyaram
Published: October 2007

The magnesium chloride catalyzed anti‐aldol reaction of phenyl acetate derived oxazolidinones proceeds readily with enolizable L‐threose derivative 8 to provide anti‐aldol adducts in high yields and with very high diastereoselectivities. The reaction is also efficient with aromatic aldehydes and provides slightly lower diastereoselectivities. This extension allows access to stereochemically defined fragments applicable to the synthesis of alkaloid and phenylpropanoid derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Finite‐volume multi‐stage schemes for shallow‐water flow simulations
Authors: Guo Wen‐Dar , Lai Jihn‐Sung , Lin Gwo‐Fong
Published: October 2007

A finite‐volume multi‐stage (FMUSTA) scheme is proposed for simulating the free‐surface shallow‐water flows with the hydraulic shocks. On the basis of the multi‐stage (MUSTA) method, the original Riemann problem is transformed to an independent MUSTA mesh. The local Lax–Friedrichs scheme is then adopted for solving the solution of the Riemann problem at the cell interface on the MUSTA mesh. The resulting first‐order monotonic FMUSTA scheme, which does not require the use of the eigenstructure and the special treatment of entropy fixes, has the generality as well as simplicity. In order to achieve the high‐resolution property, the monotonic upstream schemes for conservation laws (MUSCL) method are used. For modeling shallow‐water flows with source terms, the surface gradient method (SGM) is adopted. The proposed schemes are verified using the simulations of six shallow‐water problems, including the 1D idealized dam breaking, the steady transcritical flow over a hump, the 2D oblique hydraulic jump, the circular dam breaking and two dam‐break experiments. The simulated results by the proposed schemes are in satisfactory agreement with the exact solutions and experimental data. It is demonstrated that the proposed FMUSTA schemes have superior overall numerical accuracy among the schemes tested such as the commonly adopted Roe and HLL schemes. Copyright © 2007 John Wiley & Sons, Ltd.
Codex für Codex
Authors: Wagner Bettina
Published: October 2007

In den Handschriften aus dem Regensburger Benediktinerkloster St. Emmeram spiegeln sich die Kultur und der Alltag des Mittelalters. Was die Mönche einst schrieben und sammelten, wird nun in detektivischer Kleinarbeit rekonstruiert
Die neuen Alten kommen
Authors: Unterstell Rembert
Published: October 2007

Generation 55plus: Die Berliner Senior Research Group testet Haushalts‐ und Hightechgeräte und fördert damit die Entwicklung seniorengerechter Produkte
„Ganz natürlich”︁
Authors: Schaeffer Magdalena
Published: October 2007

Wie die Physikerin und zweifache Mutter Elisa Resconi Wissenschaft und Familie verbindet
Sicher zur Wahl
Authors: Finetti Marco
Published: October 2007

Die Fachkollegien der DFG werden neu besetzt: Jürgen Nehmer über einen besonderen Urnengang
Wo Wissenschaft Brücken baut
Authors: Streier Eva‐Maria
Published: October 2007

Mit russischen und deutschen Archäologen auf Grabungskampagne im Kaliningrader Gebiet
König Midas und seine Nachkommen
Authors: Meyer Axel
Published: October 2007

Die Buntbarsche sind die vielfältigste Familie unter den Fischen und Wirbeltieren. Viele der mehr als 3000 Arten sind in den Kraterseen Nicaraguas anzutreffen – und werfen ein bemerkenswertes Licht auf die Wege der Evolution
Neural correlates of strategic memory retrieval: Differentiating between spatial‐associative and temporal‐associative strategies
Authors: de Rover Mischa , Petersson Karl Magnus , van der Werf Sieberen P. , Cools Alexander R. , Berger Hans J. , Fernández Guillén
Published: October 2007

Remembering complex, multidimensional information typically requires strategic memory retrieval, during which information is structured, for instance by spatial‐ or temporal associations. Although brain regions involved in strategic memory retrieval in general have been identified, differences in retrieval operations related to distinct retrieval strategies are not well‐understood. Thus, our aim was to identify brain regions whose activity is differentially involved in spatial‐associative and temporal‐associative retrieval. First, we showed that our behavioral paradigm probing memory for a set of object‐location associations promoted the use of a spatial‐associative structure following an encoding condition that provided multiple associations to neighboring objects (spatial‐associative condition) and the use of a temporal‐associative structure following another study condition that provided predominantly temporal associations between sequentially presented items (temporal‐associative condition). Next, we used an adapted version of this paradigm for functional MRI, where we contrasted brain activity related to the recall of object‐location associations that were either encoded in the spatial‐ or the temporal‐associative condition. In addition to brain regions generally involved in recall, we found that activity in higher‐order visual regions, including the fusiform gyrus, the lingual gyrus, and the cuneus, was relatively enhanced when subjects used a spatial‐associative structure for retrieval. In contrast, activity in the globus pallidus and the thalamus was relatively enhanced when subjects used a temporal‐associative structure for retrieval. In conclusion, we provide evidence for differential involvement of these brain regions related to different types of strategic memory retrieval and the neural structures described play a role in either spatial‐associative or temporal‐associative memory retrieval. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Number and volume raindrop size distributions in Taiwan
Authors: Lu Jau‐Yau , Su Chih‐Chiang , Lu Tai‐Fang , Maa Ming‐Ming
Published: October 2007

Knowledge of rainfall characteristics is very important for the accurate estimation of rainfall kinetic energy and prediction of soil erosion. In this study, a reliable and efficient data collection and analysis system was developed to analyse the natural raindrop data collected in subtropical Taiwan. Both raindrop size distributions by number and volume were carefully analysed. The seasonal variations of the rainfall erosivity factor R, which is an index of the erosive potential of rainfall and a function of rainfall kinetic energy, was also discussed. An isoerodent map of Taiwan was also developed based on the rainfall data recorded by 158 automated rainfall‐measuring stations within 26 years. Copyright © 2007 John Wiley & Sons, Ltd.
Improving the predictions of a MIKE SHE catchment‐scale application by using a multi‐criteria approach
Authors: Vázquez R. F. , Willems P. , Feyen J.
Published: October 2007

This paper suggests a multi‐criteria protocol for appropriately evaluating the predictions of hydrologic models during calibration and evaluation stages. The protocol includes different statistical, analytical and visual criteria such as analysis of peak and low flows, cumulative volumes, extreme value statistics, performance statistics, etc. Furthermore, the protocol assesses the physical consistency of model predictions by filtering the total observed hydrograph into different flow‐components (baseflow, interflow and overland flow) and using these filtered data in the calibration and evaluation processes. Based on the distributed modelling of a medium size catchment, it is shown that application of the suggested protocol, and in particular the use of the filtered flow‐components in model calibration, enhances the physical consistency of model predictions, adding considerable value to the calibration process. Copyright © 2007 John Wiley & Sons, Ltd.
Quantifying the altered hydrologic connectivity of forest roads resulting from decommissioning and relocation
Authors: Eastaugh C. S. , Rustomji P. K. , Hairsine P. B.
Published: October 2007

The decommissioning of roads is occurring in many forest environments with the aim of reducing the negative impacts of road runoff on water quality and aquatic habitat. Works associated with decommissioning are expensive so prior assessment of the outcomes of various options is merited. This paper presents a method of quantifying the degree to which a road is hydrologically connected to the stream network and thus the likely impacts of constructing a road of different configurations upon water quality. The method permits comparisons between different road network management options and is useful for assessing the likely result of decommissioning works. Emphasis is placed on quantifying the uncertainty of key performance measures. The procedures developed here are an extension of the probabilistic ‘volume to breakthrough’ model recently formulated by Australian water quality researchers and allow the quantification of road/stream connectivity without the need for extensive parameterization. To demonstrate its utility, the model was applied to an actual road decommissioning and replacement project in southeast Australia. Road areas and drainage outlets were surveyed in the field and flow paths to streams derived from a 1 metre resolution LiDAR based digital elevation model. The results demonstrate that the actual road decommissioning examined in this case was unlikely to reduce runoff to the stream network and that the overall impact of the works in conditions of design storms are likely to result in a net reduction in stream water quality. Copyright © 2007 John Wiley & Sons, Ltd.
Rainfall‐induced landslides and debris flows
Authors: Crosta Giovanni B. , Frattini Paolo
Published: October 2007

In this preface we introduce the special issue on rainfall‐induced landslides and debris flows. The topic is of high interest for many practical and scientific reasons. In fact, rainfall is the most relevant factor for the triggering of both shallow and deep‐seated landslides, and rainfall analysis is the most frequently adopted approach for forecasting the occurrence of such phenomena. The six papers of the special issue cover most of the key issues relative to rainfall‐induced landslides. Starting from the analysis of these contributions, we identify and discuss, in this paper, several main topics that deserve further research in the field of rainfall‐induced landslide, such as the uncertainty of the data, the quality of geotechnical analysis, the validation of the models, and the applicability of results in the framework of natural hazards. Copyright © 2007 John Wiley & Sons, Ltd.
Children's understanding of advertising: an investigation using verbal and pictorially cued methods
Authors: Owen Laura , Auty Susan , Lewis Charlie , Berridge Damon
Published: October 2007

Conflicting results on children's understanding of advertising may stem from differences in research methods. Most studies are conducted using interviewing techniques, employing only verbal questioning. In the present study, 136 children of two age groups (7 and 10 years) were first asked what advertising was for and, after responding, shown depictions of possible reasons. The results indicate that although older children are more likely than younger ones to understand that advertising seeks to promote selling, pictorial cues allow a much larger proportion of all children to indicate their understanding than verbal questioning does on its own, with younger children especially showing improvement. Thus, seven‐year‐olds seem to have an implicit understanding of the persuasive intent of advertising that they are unable to articulate in response to investigators' questions. Multiple methods appear to offer a means of evaluating the level of sophistication in children' understanding of advertising. Copyright © 2007 John Wiley & Sons, Ltd.