bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression Profiles Classify Human Osteosarcoma Xenografts According to Sensitivity to Doxorubicin, Cisplatin, and Ifosfamide
Authors: Bruheim Skjalg , Xi Yaguang , Ju Jingfang , Fodstad Oystein
Published: November 2009

Purpose: In osteosarcoma, aggressive preoperative and postoperative multidrug chemotherapy given to all patients has improved patient survival rate to the present level of ∼60%. However, no tumor marker is available that reliably can identify those patients who will or will not respond to chemotherapy.

Experimental Design: In an attempt to find leads to such markers, we have obtained microarray gene expression profiles from a panel of 10 different human osteosarcoma xenografts and related the results to their sensitivity to ifosfamide, doxorubicin, and cisplatin.

Results: The expression data identified genes with highly significant differential expression between poor and good responder xenografts to the three different drugs: 85 genes for doxorubicin, 74 genes for cisplatin, and 118 genes for ifosfamide. Technical validation with quantitative reverse transcription-PCR showed good correlation with the microarray expression data. Gene Ontology–guided analysis suggested that properties of the poorly responsive xenografts were resistance to undergo programmed cell death and, particularly for ifosfamide, a drive toward dedifferentiation and increased tumor aggressiveness. Leads toward metabolic alterations and involvement of mitochondrial pathways for apoptosis and stress response were more prominent for doxorubicin and cisplatin. Finally, small interfering RNA–mediated gene silencing of IER3 and S100A2 sensitized the human osteosarcoma cell line OHS to treatment with 4-hydroperoxyifosfamide.

Conclusions: The expression profiles contained several novel biomarker candidates that may help predict the responsiveness of osteosarcoma to doxorubicin, cisplatin, and ifosfamide. The potential of selected candidates will be further validated on clinical specimens from osteosarcoma patients. (Clin Cancer Res 2009;15(23):7161–9)
Protein Kinase A Activation Confers Resistance to Trastuzumab in Human Breast Cancer Cell Lines
Authors: Gu Long , Lau Sean K. , Loera Sofia , Somlo George , Kane Susan E.
Published: November 2009

Purpose: Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer. Among patients who initially respond to trastuzumab therapy, resistance typically arises within 1 year. BT/HerR cells are trastuzumab-resistant variants of Her2-positive BT474 breast cancer cells. The salient feature of BT/HerR cells is failure to downregulate phosphoinositide 3-kinase/Akt signaling on trastuzumab binding. The current work addresses the mechanism of sustained signaling in BT/HerR cells, focusing on the protein kinase A (PKA) pathway.

Experimental Design: We performed microarray analysis on BT/HerR and BT474 cell lines to identify genes that were upregulated or downregulated in trastuzumab-resistant cells. Specific genes in the PKA pathway were quantified using reverse transcription-PCR and Western hybridization. Small interfering RNA transfection was used to determine the effects of gene knockdown on cellular response to trastuzumab. Electrophoretic mobility shift assays were used to measure cyclic AMP–responsive element binding activity under defined conditions. Immunohistochemistry was used to analyze protein expression in clinical samples.

Results: BT/HerR cells had elevated PKA signaling activity and several genes in the PKA regulatory network had altered expression in these cells. Downregulation of one such gene, the PKA-RIIα regulatory subunit, conferred partial trastuzumab resistance in Her2-positive BT474 and SK-Br-3 cell lines. Forskolin activation of PKA also produced significant protection against trastuzumab-mediated Akt dephosphorylation. In patient samples, PKA signaling appeared to be enhanced in residual disease remaining after trastuzumab-containing neoadjuvant therapy.

Conclusions: Activation of PKA signaling may be one mechanism contributing to trastuzumab resistance in Her2-positive breast cancer. We propose a molecular model by which PKA confers its effects. (Clin Cancer Res 2009;15(23):7196–206)
Expression of Epidermal Growth Factor Receptor (EGFR) and Activated EGFR Predict Poor Response to (Chemo)radiation and Survival in Cervical Cancer
Authors: Noordhuis Maartje G. , Eijsink Jasper J.H. , ten Hoor Klaske A. , Roossink Frank , Hollema Harry , Arts Henriëtte J.G. , Pras Elisabeth , Maduro John H. , Reyners Anna K.L. , de Bock Geertruida H. , Wisman G. Bea A. , Schuuring Ed , van der Zee Ate G.J.
Published: November 2009

Purpose: Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of this study was to determine the relation between proteins involved in the EGFR pathway and response to (chemo)radiation and survival in a large, well-documented series of cervical cancer patients.

Experimental Design: Pretreatment tissue samples of 375 consecutive International Federation of Gynecologists and Obstetricians stage Ib to IVa cervical cancer patients treated with (chemo)radiation between January 1980 and December 2006 were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. Protein expression of EGFR, phosphorylated EGFR (pEGFR), PTEN, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase (pERK) was assessed by immunohistochemistry on tissue microarrays.

Results: EGFR staining was present in 35.3%, pEGFR in 19.7%, PTEN in 34.1%, phosphorylated AKT in 4.1%, and pERK in 29.2% of tumors. pEGFR staining was related to PTEN (P = 0.001) and pERK staining (P = 0.004). EGFR staining was inversely related to PTEN (P = 0.011). In multivariate analysis, membranous staining of EGFR [hazard ratio (HR), 1.84; 95% confidence interval (95% CI), 1.20-2.82; P = 0.005] and cytoplasmic staining of pEGFR (HR, 1.71; 95% CI, 1.11-2.66; P = 0.016) were independent predictors of poor response to (chemo)radiation. Membranous EGFR staining also was an independent prognostic factor for poor disease-specific survival (HR, 1.54; 95% CI, 1.09-2.17; P = 0.014).

Conclusions: EGFR and pEGFR immunostainings are frequently observed and independently associated with poor response to therapy and disease-specific survival in cervical cancer patients primarily treated by (chemo)radiation. Our data present the EGFR pathway as a promising therapeutic target in already ongoing clinical trials. (Clin Cancer Res 2009;15(23):7389–97)
Phase I Clinical Trial of an Adenovirus/Prostate-Specific Antigen Vaccine for Prostate Cancer: Safety and Immunologic Results
Authors: Lubaroff David M. , Konety Badrinath R. , Link Brian , Gerstbrein Jack , Madsen Tammy , Shannon Mary , Howard Jeanne , Paisley Jennifer , Boeglin Diana , Ratliff Timothy L. , Williams Richard D.
Published: November 2009

Purpose: We performed a phase I clinical trial of adenovirus/prostate-specific antigen (PSA) vaccine in men with measurable metastatic hormone-refractory disease.

Experimental Design: Men with measurable metastatic disease received one vaccine injection. Toxicity, immune responses, changes in PSA doubling times, and patient survival were assessed. Thirty-two patients with hormone-refractory metastatic prostate cancer were treated with a single s.c. vaccine injection at one of three dose levels, either as an aqueous solution or suspended in a Gelfoam matrix. All patients returned for physical and clinical chemistry examinations at regular intervals up to 12 months after injections.

Results: The vaccine was deemed safe at all doses in both administration forms. There were no serious vaccine-related adverse events; the most prevalent were localized erythema/ecchymoses and cold/flu-like symptoms. Anti-PSA antibodies were produced by 34% of patients and anti-PSA T-cell responses were produced by 68%. PSA doubling time was increased in 48%, whereas 55% survived longer than predicted by the Halabi nomogram.

Conclusions: The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies. (Clin Cancer Res 2009;15(23):7375–80)
Can T-Cell Deficiency Affect Spatial Learning Ability following Toluene Exposure?
Authors: Win-Shwe Tin-Tin , Nakajima Daisuke , Fujimaki Hidekazu
Published: November 2009

Objective: The present studywas designed to investigate the possible role of T cells in spatial learning ability in mouse after toluene exposure. Method: Eight-week-old male wild-type (WT) and nude mice of BALB/c strain were exposed to toluene (0, 9 and 90 ppm) in a nose-only exposure chamber for 30 min per day for 3 consecutive days and then once per week for 4 weeks. Twenty-four hours after the completion of exposure, we examined the spatial learning ability in each mouse using the Morris water maze apparatus. Results: In the acquisition phase, a longer escape latency was observed in nude mice exposed to 90 ppm toluene on days 3 and 4 when compared with corresponding WT mice. However, the effect of toluene on the escape latency was not significant in nude mice. In the probe trial, WT mice exposed to 90 ppm toluene showed poor retention memory compared with the control group. In the reversal phase, we did not find any significant difference between groups. Conclusion: These results indicate that T-cell deficiency may affect spatial learning performance following toluene exposure.
The Modifier Protein of Glyceraldehyde-3-Phosphate Dehydrogenase Reduces Free Radical-Mediated Renal Damage in a Rat Model of Acute Kidney Injury
Authors: Li Zi-Long , Sun Ying-Hui , Fan Qiu-Ling , Wang Jun , Wang Juan , Ren Qing , Liang Zai-Fu , Ma Jian-Fei , Wang Li-Ning
Published: November 2009

Background: The modifier protein (MP) of glyceraldehyde-3-phosphate dehydrogenase has been shown to promote growth of renal epithelial cells in vitro. The aim of this study was to show the in vivo effects of MP in a rat model of gentamicin-induced acute kidney injury (AKI). Method: MP was purified from monkey renal tubular epithelial cell line BSC-1 and confirmed by amino acid sequencing. Male Sprague-Dawley rats were divided into the following groups: normal control, gentamicin-treated, epidermal growth factor (EGF) plus gentamicin-treated, and MP plus gentamicin-treated, as well as control groups for EGF and MP alone. Levels of serum creatinine (SCr), serum and tissue lipid peroxide, nitric oxide and glutathione-S-hydrogenase for each group were measured on the 7th and 14th days of treatment. Tissue sections were studied with light microscopy. Results: The gentamicin-treated group showed a marked increase in SCr compared to the normal control group. Co-treatment of gentamicin with MP and/or EGF produced similar significant decreases preventing the increase in SCr. There were also significant reductions in serum and tissue homogenate levels of lipid peroxide and nitric oxide, accompanied by an increase in the level of glutathione-S-hydrogenase, in the MP co-treated groups compared to the gentamicin-treated group. AKI was confirmed histologically in the gentamicin-treated group, with damage to the tubular epithelium recorded. This was attenuated by MP co-treatment. There were also reductions in the expression of intercellular adhesion molecule-1 and proliferating cell nuclear antigen in the MP co-treated groups. Conclusion: Using a gentamicin model of AKI, MP was able to reduce free radical production in kidney tissue and in the circulation, thus preventing oxidant injury and minimizing damage in renal epithelial cells.
JNK/ATF2 Pathway Is Involved in Iodinated Contrast Media-Induced Apoptosis
Authors: Lee Hsiang-Chun , Sheu Sheng-Hsiung , Yen Hsueh-Wei , Lai Wen-Ter , Chang Jan-Gowth
Published: November 2009

Background/Aims: Notably, activating transcriptional factor 2 (ATF2), a histone-modification gene, is involved in oxidative stress-induced apoptosis. The aim of this study was to clarify the role of ATF2 in contrast media-induced nephropathy. Methods: Human embryonic kidney 293T cells were treated with four different contrast media:ionic high-osmolar diatrizoate; ionic low-osmolar iothalamate; non-ionic low-osmolar iohexol, and non-ionic iso-osmolar iodixanol. The mRNA expression of ATF2 was determined by real-time PCR. Short interfering RNA was used to knock down ATF2 mRNA expression. Phosphorylation of ATF2 was measured by Western blotting. Wistar rats were administered either diatrizoate or a normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive TUNEL stain. Results: Diatrizoate, iodixanol and iothalamate, but not iohexol, induced the expression of ATF2 mRNA and phosphorylation of ATF2 in 293T cells in a time-dependent manner. More apoptotic cells were in diatrizoate-treated kidney cells than in the saline injection group (p < 0.00001). Cell death was significantly increased by knockdown ATF2 expression in the presence of diatrizoate, indicating a protective role of ATF2 in contrast media-induced apoptosis. Conclusions: Differential activation of ATF2 by different contrast media provides a new insight into the mechanism and prevention of contrast-induced nephropathy.
Perception-Production Relations in the Voicing Contrast for Initial Stops in 3-Year-Olds
Authors: Bailey P.J. , Haggard M.P.
Published: November 2009

34 children (average age 3; 3) furnished perception and production data on five initial voiced-voiceless stop cognates. In addition to the usual systematic effects of place of articulation, significant individual differences were found in both mean produced values of voice onset time (VOT) and mean perceptual boundary in terms of VOT. There was a suggestion of within-sample cross-sectional age trends in both production and perception data. Some restricted correlations between the two types of data were observed and were interpreted as indicating an earlier development of perceptual cue usage than of articulatory control, possibly causative. The restriction appeared to be related to the very low variance in the perception measures. Consideration of average discrepancies between mean perception and mean production data suggested that interpretation of trends in production data may be assisted by taking a measure of the point of overlap between voiced and voiceless productions, rather than the simple average of their means.
Hypertension Improvement Project
Authors: Svetkey Laura P. , Pollak Kathryn I. , Yancy William S. , Dolor Rowena J. , Batch Bryan C. , Samsa Greg , Matchar David B. , Lin Pao-Hwa
Published: November 2009

Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients, blood pressure control rates remain low. In community-based primary care clinics, we performed a nested, 2×2 randomized, controlled trial of physician intervention versus control and/or patient intervention versus control. Physician intervention included internet-based training, self-monitoring, and quarterly feedback reports. Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss, Dietary Approaches to Stop Hypertension dietary pattern, exercise, and reduced sodium intake. The primary outcome was change in systolic blood pressure at 6 months. Eight primary care practices (32 physicians) were randomized to physician intervention or control groups. Within those practices, 574 patients were randomized to patient intervention or control groups. Patient mean age was 60 years, 61% were women, and 37% were black. Blood pressure data were available for 91% of patients at 6 months. The main effect of physician intervention on systolic blood pressure at 6 months, adjusted for baseline pressure, was 0.3 mm Hg (95% CI: −1.5 to 2.2;
P
=0.72). The main effect of the patient intervention was −2.6 mm Hg (95% CI: −4.4 to −0.7;
P
=0.01). The interaction of the 2 interventions was significant (
P
=0.03); the largest impact was observed with the combination of physician and patient intervention (−9.7±12.7 mm Hg). Differences between treatment groups did not persist at 18 months. Combined physician and patient interventions lowers blood pressure; future research should focus on enhancing effectiveness and sustainability of these interventions.
Divine Law and Local Custom in Northern Nigerian zinā Trials
Authors: Weimann Gunnar J.
Published: November 2009

The introduction of Islamic criminal law in twelve northern states of the Nigerian federation after 1999 was widely perceived as an attempt to Islamise the Nigerian state. In this article it is argued that the “šarī'a project” started as a pre-election promise, but was immediately supported by Muslim reform groups whose aim was not the establishment of an Islamic state but rather the imposition of šarī'a compliant behaviour on Muslims. Particular emphasis was put on illicit sexual relations (zinā). However, Muslim societies of northern Nigeria have a notion of zinā which differs in important aspects from the classical doctrine, and certain forms of socially accepted extramarital sexuality still exist. Based on an analysis of a sample of šarī'a court trials for rape, sodomy, incest and zinā, it is shown that the judicial practice in šarī'a courts has helped to mitigate the effects of Islamic criminal law on the traditional societies in northern Nigeria. In particular, accusations based on suspicion and pregnancy out of wedlock as proof of zinā have been rejected by the courts, thereby confirming the privacy of the family compound and traditional conflict resolution through mediation. At the same time, male control over female sexuality has been strengthened.
Madness of Humankind: Moses Mendelssohn as a Critic of Sabbatianism
Authors: Kajon Irene
Published: November 2009

According to Kant, Mendelssohn could not accept the idea of the moral progress of humankind, maintained by Lessing in Erziehung des Menschengeschlechts (1780), because he erroneously inferred from some historical events a pessimistic view of the whole of history: as a dogmatic metaphysician Mendelssohn did not consider judgements about intelligible objects as “regulative,” i.e. pronounced by a faculty of judgement founded on practical reason, but as “constitutive,” i.e. endowed with scientifi c value. This article argues that the deepest reason of Mendelssohn’s criticism of Lessing’s philosophy of history was rather his rejection of Sabbatian messianism. Mendelssohn was accused of being the author of the Fragmente eines Ungenannten (composed by Hermann Samuel Reimarus) that—according to some Christian readers—described Jesus as a Sabbatai Zevi ante litteram and were inspired by Sabbatianism; Lessing, who in 1777 presented the first part of Erziehung as “objections” to the fourth Fragment he edited, nevertheless shared the Ungenannte’s critique of Jewish and Christian revelation and his eulogy of man’s autonomy. Mendelssohn’s denial of this authorship appears in his letter of September 24, 1781 to Herder, where he also mentions Moshe Hayym Luzzatto: while praising Luzzatto as author of the drama Layesharim Tehila and defending him against the persecution he suffered in Italy and Germany, Mendelssohn keeps him at a distance as writer of cabalistic texts and new Psalms which show a Sabbatian attitude. Mendelssohn was aware—as Karl Gotthelf Lessing wrote to his brother on October 26, 1769—of the Sabbatian Jacob Frank’s contemporary preaching in Poland and of the similarity between Sabbatianism and Bonnet’s and Lavater’s chiliastic Christianity. This article also argues that the criticism of Sabbatian messianism is the background of Mendelssohn’s unilateral interpretation of Judaism as centred on the synagogue.
Introduction
Authors: Merolla Daniela
Published: November 2009

Sculptures, paintings, drawings, performances, and films have often refashioned narratives of the origins of the cosmos and of human beings. The essays collected in Creation Myths and the Visual Arts investigate the interplay between image and narrative and offer critical approaches from literary studies, the history of art, archaeology, and anthropology on the interpretation and categorization of verbal and visual representations of “creation myths” from all over the world.
Filming African Creation Myths
Authors: Merolla Daniela
Published: November 2009

African film directors have made use of mythology and oral storytelling in countless circumstances. These filmmakers have explored the core role that orality plays in ideas of African identity and used mythological themes as allegorical forms in order to address present-day issues while working under dictatorial regimes. They have turned to mythology and oral storytelling because of their determination to convey an African philosophical approach to the world, often to counter the colonial and neo-colonial oversimplification of African cultures seen as bereft of grand narratives on the self and the world. Identity construction, critical allegorical messages, and philosophical approaches are discussed in this paper by looking at the interplay between verbal narrative and images in two “epic” films: Keïta, l'héritage du Griot (1995) directed by Dani Kouyaté, and Yeelen (1987) directed by Souleymane Cissé.
Empirics, Physicians, and Wonder Drugs in Early Modern Germany: The Case of the Panacea Amwaldina
Authors: Rankin Alisha
Published: November 2009

This essay examines the conflicting approaches towards marvelous cures in sixteenth-century Germany. As pharmaceutical substances flooded in from both east and west, they brought with them a market for "wonder drugs" that would cure any ailment. In this climate, university-trained physicians felt threatened by the rising popularity of cures hawked by empirical practitioners, while at the same time endorsing certain wonder drugs. Using the example of one particularly controversial empiric, Georg am Wald, and his wonder drug, the Panacea Amwaldina, this article parses the various factors that made the medical elite embrace certain cures while deriding others.
Bolatu's Pharmacy Theriac in Early Modern China
Authors: Nappi Carla
Published: November 2009

In early modern China, natural history and medicine were shifting along with the boundaries of the empire. Naturalists struggled to cope with a pharmacy's worth of new and unfamiliar substances, texts, and terms, as plants, animals, and the drugs made from them travelled into China across land and sea. One crucial aspect of this phenomenon was the early modern exchange between Islamic and Chinese medicine. The history of theriac illustrates the importance of the recipe for the naturalization of foreign objects in early modern Chinese medicine. Theriac was a widely sought-after and hotly debated product in early modern European pharmacology, and arrived into the Chinese medical canon via Arabic and Persian texts. The dialogue between language and material objects was critical to the Silk Road drug trade, and transliteration was ultimately a crucial technology used to translate drugs and texts about them in the early modern world.
The Caribbean Court of Justice and Legal Integration within CARICOM: Some Lessons from the European Community
Authors: O'Brien Derek , Morano-Foadi Sonia
Published: November 2009

CARICOM, established under the Treaty of Chaguaramas, in 1973, has since its inception suffered from the repeated failure of member states to implement at the national level decisions taken by the Heads of Government at the regional level. The Caribbean Court of Justice (CCJ,) which has been vested with a compulsory and exclusive jurisdiction to interpret and apply the Revised Treaty of Chaguaramas, is intended to bridge this implementation gap. This has aroused expectations that the CCJ will play a role similar to that played by the ECJ in promoting legal integration. However, it is important to recognise that the ECJ has functioned within a particular jurisdictional framework and has benefited from the contribution of a diverse range of actors within the wider European legal community. It cannot, therefore, be assumed that the CCJ will be able to replicate the role played by the ECJ. The aim of this article is, accordingly, to review the jurisdictional framework within which the CCJ will function; to explore how this is likely to affect its relationship with the wider legal community within CARICOM; and, finally, to consider how this will impact upon legal integration within the region generally.
Accountability in Family Discourse
Authors: Sterponi Laura
Published: November 2009

This article explores morality as situated activity and approaches the discursive practice of accountability in Italian family dinner conversations as an avenue for understanding the construction of moral behaviour in everyday interpersonal interaction. The article focuses in particular on vicarious accounts, namely accounts, or explanations, provided by parents for a child’s misbehaviour. It examines the multiple socializing functions that vicarious accounts accomplish and the different dimensions of responsibility that they mobilize. While scaffolding children’s participation in episodes of accountability, vicarious accounts set up constraints on children’s autonomy of action, neutralizing more subversive and blameworthy interpretations of their problematic conduct. In this sense, vicarious accounts are qualified concessions and are face-saving acts both for the child whose action was signalled as improper and for the parent who initially requested the account.
Gaming and Territorial Negotiations in Family Life
Authors: Aarsand Pål André , Aronsson Karin
Published: November 2009

This article examines territorial negotiations concerning gaming, drawing on video recordings of gaming practices in middle-class families. It explores how private vs public gaming space was co-construed by children and parents in front of the screen as well as through conversations about games. Game equipment was generally located in public places in the homes, which can be understood in terms of parents’ surveillance of their children, on the one hand, and actual parental involvement, on the other. Gaming space emerged in the interplay between game location, technology and practices, which blurred any fixed boundaries between public and private, place and space, as well as traditional age hierarchies.
A summer temperature proxy from height increment of Scots pine since 1561 at the northern timberline in Fennoscandia
Authors: Lindholm Markus , Ogurtsov Maxim , Aalto Tarmo , Jalkanen Risto , Salminen Hannu
Published: November 2009

Height increments of 60 Scots pine trees were used to reconstruct mean June—August temperature variability at interannual to decadal scales from 1561 to 2004. Three standardization methods (67%, 33% flexible splines, and a fixed 22 years spline) were compared in building chronologies in order to optimize the frequency response in relation to major climatic forcing factors. The height-growth chronology built using the 33% spline standardization proved to have the most consistent and time-stable relationship with the summer temperatures. Among the monthly precipitation and temperature variables from previous June to current August, previous July shows the highest correlation with height growth. In addition, both previous June and previous August have significant positive correlations. Our final transfer model accounts for 32.5% of the dependent instrumental temperature variance between 1909 and 2004. The Fourier spectra of the height-growth chronology and mean summer temperature are very similar in appearance, both series having peaks at 2.7—3.2 years, 6.7 years and 15.7 years. Thus, the 444 years long summer temperature reconstruction is limited to high and medium frequencies. The coldest three summers in this record were experienced in years 1601, 1790 and 1903. Correspondingly, the summers of 1626, 1689 and 1598 were the warmest. The 1820s experienced the warmest 10-year mean, while the first decade of the twentieth century was the coldest. Among the 14 non-overlapping 30-year periods between 1561 and 1980, the period 1621—1650 was the warmest and the period 1591—1620 the coldest.
Perceptions of Preservice Teachers Regarding Feedback and Guided Reflection in an Instrumental Early Field Experience
Authors: Chaffin Charles , Manfredo Joseph
Published: November 2009

The purpose of this study was to examine the perceptions of 4 preservice music teachers regarding elements of verbal and written feedback as well as guided reflection during an early field experience program at a large midwestern university. Participants were observed and interviewed regarding their perceptions of various forms of feedback and guided reflection activities embedded within an early field experience program. Participants identified individual written feedback, modeling, and class seminars as most beneficial, enabling them to reflect on past teaching episodes as well as plan for subsequent lessons. The results of this study suggest that individualized feedback, whether written or verbal, may be an effective measure for facilitating preservice teacher reflection during early field experience.
Punishing Terrorists
Authors: Bradley-Engen Mindy S. , Damphousse Kelly R. , Smith Brent L.
Published: November 2009

The empirical literature on the theory and practice of sentencing politically motivated offenders such as terrorists in U.S. federal courts is limited. Thus, we know relatively little about the dealings between terrorist offenders and the criminal justice system or how these interactions may be influenced by changes in American legal or political context. This study summarizes previous findings relative to sentencing disparity among terrorists and nonterrorists in U.S. federal courts prior to the imposition of the U.S. Sentencing Guidelines. We then identify events occurring after the advent of the guidelines, including the early acts of terrorism on American soil. We evaluate the sentencing of terrorists versus nonterrorists following the confluence imposition of the guidelines and these events. We determine whether and how the sentencing disparity between terrorist and nonterrorist has changed since the implementation of the U.S. Sentencing Guidelines and the terrorist events of the early 1990s. Based on our findings, we put forth suggestions as to the possible ways these conditions may have affected sentencing outcomes.
Randomized Controlled Trial of the Prevent— Teach—Reinforce (PTR) Tertiary Intervention for Students With Problem Behaviors
Authors: Iovannone Rose , Greenbaum Paul E. , Wang Wei , Kincaid Don , Dunlap Glen , Strain Phil
Published: November 2009

Although there is literature supporting the effectiveness of tertiary behavioral supports, the majority of the studies have been conducted with single-subject designs. The Prevent—Teach—Reinforce (PTR) model is a standardized model of a school-based tertiary intervention. This study reports initial results from a randomized controlled trial to compare whether the PTR model, as implemented by typical school personnel, is more effective than interventions typically used (i.e., services as usual). To date, 245 students in Grades K-8 have been enrolled in the study, and preliminary results show that students who received the PTR intervention had significantly higher social skills and academic engaged time and significantly lower problem behavior when compared with students who received services as usual. Teachers gave high social validity ratings to the intervention. Implications for widescale school adoption are discussed.
Proving the power of social marketing: The UK’s growing evidence base
Authors: Reynolds Dr Lucy
Published: November 2009

Dr Lucy Reynolds manages ShowCase, the National Social Marketing Centre’s new online collection of social marketing case studies. Having developed this programme since July 2008, Lucy shares her experience of the UK’s growing proficiency in social marketing delivery
The integration of health promotion and social marketing
Authors: Griffiths Jenny , Blair-Stevens Clive , Parish Richard
Published: November 2009

The urgency and scale of contemporary health challenges are enormous. The review It’s Our Health!1 published in 2006 found that social marketing had considerable potential to increase the effectiveness of health improvement work, with the intention that it should build on core health promotion principles and not replace them. Health promotion has, however, lost its focus and identity in recent years in some parts of the country, partly due to repeated organizational change, and it has suffered from a lack of proactive workforce development. Over the last year, the National Social Marketing Centre (NSMC) and the Shaping the Future of Health Promotion Collaboration (StFofHP), hosted by the Royal Society for Public Health (RSPH), have explored the relationship between social marketing and health promotion and led a debate with stakeholders. A Delphi consultation with an expert panel drawn from specialists and strategic leaders in several settings, and the academic community, is currently under way and will report in the autumn. Findings so far emphasize the wide variation in understanding and interpretation of the two skill sets, much confusion about definitions and what added value both health promotion and social marketing bring to health improvement. Some of the distinctive contributions of both are described in this paper.
Synthesis and processing of nanosized sodium potassium niobate powders
Authors: O'Callaghan S. A. , Knowles K. M.
Published: November 2009

Sodium potassium niobate powders have been produced successfully using a Pechini sol–gel method modified with a novel niobium precursor. The decomposition of the gels produced by this method was observed with thermogravimetric analysis and evolved gas mass spectrometry. This showed three main weight loss stages up to 1000°C arising from the loss of water, methane and carbon dioxide. The effect of different heat treatments of the equimolar gel was studied and correlated to particle properties and phase development. The resultant calcined powders were nanosized and single phase with some residual organic material and water. The effect of varying the composition between sodium niobate and potassium niobate was also studied and correlated to particle size and phase development.
I–V relations and enhanced mobility of metal vacancies in acceptor doped polycrystalline BaTiO3 under oxygen activity gradient
Authors: Ya'akobovich A. , Baltianski S. , Tsur Y.
Published: November 2009

Acceptor doped barium titanate ceramic samples were prepared and exposed to oxygen activity gradients at elevated temperatures. When an oxygen activity gradient is imposed on such a pellet, a pin junction is formed. In situ measurements of the I–V relations were performed under various oxygen activity gradients. These measurements show very strong memory effects. An explanation of this behaviour is suggested based on the assumption of enhanced mobility of metal vacancies due to the oxygen activity gradient.
Luminescent impurity ion probe and low temperature phase of SrTiO3 nanoparticles
Authors: Potůček Z. , Trepakov V. A. , Makarova M. V. , Sazama P. , Badalyan A. G. , Dejneka A. , Jastrabik L.
Published: November 2009

Optical absorption and photoluminescence of Cr3+ impurity ion probe were studied on nanocrystalline SrTiO3/Cr(0·1%) powders with an average particle size between 13 and 100 nm prepared by the Pechini type polymeric sol–gel method. Only Oh1 cubic perovskite phase was revealed in the powders at room temperature. The optical absorption edge and the position of the zero-phonon emission R-line of the octahedral Cr3+ centres shifted to higher energies with decreasing particle size. The temperature shift of the R-line position appeared for all powders nearly the same as the ‘dielectric related’ one in the bulk crystals, evidencing that SrTiO3 retains quantum paraelectric behaviour down to a particle size of about 10 nm. However, behaviour of the R-line position was unstable at low temperatures in powders with a particle size of about 13 and 20 nm. This instability was speculated as a manifestation of a possible low temperature ferroelectric phase transition in small enough SrTiO3 nanoparticles.
Evaluation of oxide ion diffusivity in YAG ceramics
Authors: Haneda H. , Sakaguchi I. , Ohashi N. , Saito N. , Matsumoto K. , Nakagawa T. , Yanagitani T. , Yagi H.
Published: November 2009

Transparent yttrium aluminium garnet (YAG) polycrystal can be used as a host material for a solid state laser. In the present study, the authors prepared completely transparent YAG ceramics from active powder. The optical and mechanical properties of YAG ceramics are very sensitive to point defects. In order to examine the relationship between these properties and point defects, it is first necessary to characterise the defects. The authors report the effect of doping on oxygen diffusivity in several YAG ceramics, doped with various elements. Although Nd doping slightly increases the oxygen diffusion coefficient and the number of oxygen vacancies increases with increasing Nd concentration in as sintered materials, the variation of the oxygen diffusion coefficient in well annealed samples is small. These results suggest that the oxygen vacancies exist in non-equilibrium. However, grain boundary diffusivity was not influenced by preannealing before the oxygen diffusion experiments. The oxygen defect structure in transparent YAG ceramics is also discussed.
Pure and Gd doped LAMOX powders and thin films obtained by chemical route
Authors: Weber I. T. , Baracho P. R. , Rangel F. , Paris E. C. , Muccillo E. N. S.
Published: November 2009

The present work deals with the preparation of pure and Gd doped LAMOX powders and thin films by a Pechini's based solution method. Gd doping proved to be efficient not only in stabilising the β form at room temperature but also in reducing the particle size and improving the film quality. Best results for both particles and films were achieved using 10 mol.-% dopant, which corresponds to the solubility limit. Concerning substrates, it was verified that they play a key role in film microstructure. Homogeneous and crack free films were obtained on glass, silicon and alumina substrates. Film density is quite dependent on the type of substrate, and glass substrates provided the densest films. The average thickness is ∼150 nm for one layer film.
PTEN is a tumor suppressor in CML stem cells and BCR-ABL–induced leukemias in mice
Authors: Peng Cong , Chen Yaoyu , Yang Zhongfa , Zhang Haojian , Osterby Lori , Rosmarin Alan G. , Li Shaoguang
Published: November 2009

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is inactivated in many human cancers. However, it is unknown whether PTEN functions as a tumor suppressor in human Philadelphia chromosome–positive leukemia that includes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) and is induced by the BCR-ABL oncogene. By using our mouse model of BCR-ABL–induced leukemias, we show that Pten is down-regulated by BCR-ABL in leukemia stem cells in CML and that PTEN deletion causes acceleration of CML development. In addition, overexpression of PTEN delays the development of CML and B-ALL and prolongs survival of leukemia mice. PTEN suppresses leukemia stem cells and induces cell-cycle arrest of leukemia cells. Moreover, PTEN suppresses B-ALL development through regulating its downstream gene Akt1. These results demonstrate a critical role of PTEN in BCR-ABL–induced leukemias and suggest a potential strategy for the treatment of Philadelphia chromosome–positive leukemia.
Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia
Authors: Friedberg Jonathan W. , Sharman Jeff , Sweetenham John , Johnston Patrick B. , Vose Julie M. , LaCasce Ann , Schaefer-Cutillo Julia , De Vos Sven , Sinha Rajni , Leonard John P. , Cripe Larry D. , Gregory Stephanie A. , Sterba Michael P. , Lowe Ann M. , Levy Ronald , Shipp Margaret A.
Published: November 2009

Certain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.
Clinical trial to assess the effect of physical exercise on endothelial function and insulin resistance in pregnant women
Authors: Ramírez-Vélez Robinson , Aguilar Ana C , Mosquera Mildrey , Garcia Ronald G , Reyes Laura M , López-Jaramillo Patricio
Published: November 2009

Background

Preeclampsia (PE) is a common maternal disease that complicates 5 to 10% of pregnancies and remains as the major cause of maternal and neonatal mortality. Cost-effective interventions aimed at preventing the development of preeclampsia are urgently needed. However, the pathogenesis of PE is not well known. Multiple mechanisms such as oxidative stress, endothelial dysfunction and insulin resistance may contribute to its development. Regular aerobic exercise recovers endothelial function; improves insulin resistance and decreases oxidative stress. Therefore the purpose of this clinical trial is to determine the effect of regular aerobic exercise on endothelial function, on insulin resistance and on pregnancy outcome.

Methods and design

64 pregnant women will be included in a blind, randomized clinical trial, and parallel assignment. The exercise group will do regular aerobic physical exercise: walking (10 minutes), aerobic exercise (30 minutes), stretching (10 minutes) and relaxation exercise (10 minutes) in three sessions per week. Control group will do the activities of daily living (bathing, dressing, eating, and walking) without counselling from a physical therapist.

Trial registration

NCT00741312.
Regulation of macrophage motility by Irgm1
Authors: Henry Stanley C , Traver Maria , Daniell Xiaojou , Indaram Maanasa , Oliver Tim , Taylor Gregory A
Published: November 2009

Irgm1 controls macrophage motility by regulating the positioning of specific GKS IRG proteins to the plasma membrane, leading to altered Rac activity and actin remodelling.

IRG are a family of IFN-regulated proteins that are critical for resistance to infection. Mouse IRG proteins are divided into GMS and GKS subfamilies, based on a sequence within the G1 GTP-binding motif. The GMS proteins have a particularly profound impact on immunity, as typified by Irgm1, of which absence leads to a complete loss of resistance to a variety of intracellular bacteria and protozoa. The underlying molecular and cellular mechanisms are not clear. Here, we use time-lapse microscopy and cell-tracking analysis to demonstrate that Irgm1 is required for motility of IFN-γ-activated macrophages. The absence of Irgm1 led to decreased actin remodeling at the leading edge of migrating macrophages, as well as decreased Rac activation. Although Irgm1 did not localize to the leading edge of migrating macrophages, it was found to regulate the localization of a GKS IRG protein, Irgb6, which in turn, concentrated on the plasma membrane in the advancing lamellipodia, in close apposition to molecular components that regulate membrane remodeling, including Rac, paxillin, and actin. Thus, Irgm1 likely controls macrophage motility by regulating the positioning of specific GKS IRG proteins to the plasma membrane, which in turn, modulate cytoskeletal remodeling and membrane dynamics.
Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis
Authors: Echave Pedro , Machado-da-Silva Gisela , Arkell Rebecca S. , Duchen Michael R. , Jacobson Jake , Mitter Richard , Lloyd Alison C.
Published: November 2009

Cells generate new organelles when stimulated by extracellular factors to grow and divide; however, little is known about how growth and mitogenic signalling pathways regulate organelle biogenesis. Using mitochondria as a model organelle, we have investigated this problem in primary Schwann cells, for which distinct factors act solely as mitogens (neuregulin) or as promoters of cell growth (insulin-like growth factor 1; IGF1). We find that neuregulin and IGF1 act synergistically to increase mitochondrial biogenesis and mitochondrial DNA replication, resulting in increased mitochondrial density in these cells. Moreover, constitutive oncogenic Ras signalling results in a further increase in mitochondrial density. This synergistic effect is seen at the global transcriptional level, requires both the ERK and phosphoinositide 3-kinase (PI3K) signalling pathways and is mediated by the transcription factor ERRα. Interestingly, the effect is independent of Akt-TOR signalling, a major regulator of cell growth in these cells. This separation of the pathways that drive mitochondrial biogenesis and cell growth provides a mechanism for the modulation of mitochondrial density according to the metabolic requirements of the cell.
The growth-promoting effect of KGF on limbal epithelial cells is mediated by upregulation of ΔNp63α through the p38 pathway
Authors: Cheng Chien-Chia , Wang Der-Yuan , Kao Ming-Hui , Chen Jan-Kan
Published: November 2009

Corneal epithelial stem cells are thought to reside in the limbus, the transition zoon between cornea and conjunctiva. Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are two paracrine factors that regulate the proliferation, migration and differentiation of the limbal epithelial cells; however, the underlying mechanisms are still poorly understood. In an ex vivo limbal explant culture, we found that KGF is a more potent growth stimulator for the epithelial outgrowth than HGF. Immunofluorescence studies of the epithelial outgrowth from cells treated with HGF or KGF showed similar expression patterns of keratin-3 and keratin-14. Interestingly, p63 was highly expressed in KGF-treated limbal epithelial sheets but not in those treated with HGF. Kinase inhibitor studies showed that induction of ΔNp63α expression by KGF is mediated via the p38 pathway. The effect of KGF on limbal epithelial outgrowth was significantly reduced when endogenous ΔNp63α was suppressed, suggesting that KGF-induced limbal epithelial outgrowth is dependent on the expression of ΔNp63α. Our findings strongly suggest that limbal keratocytes regulate limbal epithelial cell growth and differentiation through a KGF paracrine loop, with ΔNp63α expression as one of the downstream targets.