bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer
Authors: Ginty Fiona , Adak Sudeshna , Can Ali , Gerdes Michael , Larsen Melinda , Cline Harvey , Filkins Robert , Pang Zhengyu , Li Qing , Montalto Michael C.
Published: June 2008

Purpose: The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC.

Experimental Design: Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3′-diaminobenzidine immunostained for Met.

Results: In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P ≤ 0.0005). Similar results were found with multivariate analysis. Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. In the 3,3′-diaminobenzidine–stained array, no associations were found with Met expression and survival.

Conclusions: These data indicate that the relative subcellular distribution of Met, as measured by novel automated image analysis, may be a valuable biomarker for estimating colon cancer prognosis.
Tumor Vascular Maturation and Improved Drug Delivery Induced by Methylselenocysteine Leads to Therapeutic Synergy with Anticancer Drugs
Authors: Bhattacharya Arup , Seshadri Mukund , Oven Steven D. , Tóth Károly , Vaughan Mary M. , Rustum Youcef M.
Published: June 2008

Purpose: Our previously reported therapeutic synergy between naturally occurring seleno-amino acid methylselenocysteine (MSC) and anticancer drugs could not be shown in vitro. Studies were carried out to investigate the potential role of MSC-induced tumor vascular maturation and increased drug delivery in the observed therapeutic synergy in vivo.

Experimental Design: Mice bearing s.c. FaDu human head and neck squamous cell carcinoma xenografts were treated with MSC (0.2 mg/d × 14 days orally). Changes in microvessel density (CD31), vascular maturation (CD31/α-smooth muscle actin), perfusion (Hoechst 33342/DiOC7), and permeability (dynamic contrast-enhanced magnetic resonance imaging) were determined at the end of the 14-day treatment period. Additionally, the effect of MSC on drug delivery was investigated by determining intratumoral concentration of doxorubicin using high-performance liquid chromatography and fluorescence microscopy.

Results: Double immunostaining of tumor sections revealed a marked reduction (∼40%) in microvessel density accompanying tumor growth inhibition following MSC treatment along with a concomitant increase in the vascular maturation index (∼30% > control) indicative of increased pericyte coverage of microvessels. Hoechst 33342/DiOC7 staining showed improved vessel functionality, and dynamic contrast-enhanced magnetic resonance imaging using the intravascular contrast agent, albumin-GdDTPA, revealed a significant reduction in vascular permeability following MSC treatment. Consistent with these observations, a 4-fold increase in intratumoral doxorubicin levels was observed with MSC pretreatment compared with administration of doxorubicin alone.

Conclusion: These results show, for the first time, the antiangiogenic effects of MSC results in tumor growth inhibition, vascular maturation in vivo, and enhanced anticancer drug delivery that are associated with the observed therapeutic synergy in vivo.
Advances in the Development of Cancer Therapeutics Directed against the RAS-Mitogen-Activated Protein Kinase Pathway
Authors: Sebolt-Leopold Judith S.
Published: June 2008

Among mammalian mitogen-activated protein kinase (MAPK) signaling cascades, the extracellular signal-related kinase (ERK) pathway has received the most attention in the oncology drug discovery arena. By virtue of its central role in promoting proliferation, survival, and metastasis, this pathway directly affects both the formation and progression of human tumors. The identification of non–ATP-competitive inhibitors of the MAPK kinase MAPK/ERK kinase (MEK) resulted in the first demonstration that the ERK pathway could be effectively shut down in a highly selective fashion. Subsequent discovery of the oncogenic nature of B-raf kinase led to the escalation of drug discovery efforts revolving around MEK and RAF. The emergence of multiple drug candidates targeting these downstream kinases provides us with the means for validating the importance of the RAS-RAF-MEK-ERK signaling cascade in human tumors. This article highlights the lessons learned in the clinical evaluation of MAPK pathway inhibitors as anticancer agents and the complexities surrounding optimization of their therapeutic potential in light of the challenges posed by genetic heterogeneity within patient populations.
Transforming Growth Factor-β Receptor Blockade Augments the Effectiveness of Adoptive T-Cell Therapy of Established Solid Cancers
Authors: Wallace Africa , Kapoor Veena , Sun Jing , Mrass Paul , Weninger Wolfgang , Heitjan Daniel F. , June Carl , Kaiser Larry R. , Ling Leona E. , Albelda Steven M.
Published: June 2008

Purpose: Adoptive cellular immunotherapy is a promising approach to eradicate established tumors. However, a significant hurdle in the success of cellular immunotherapy involves recently identified mechanisms of immune suppression on cytotoxic T cells at the effector phase. Transforming growth factor-β (TGF-β) is one of the most important of these immunosuppressive factors because it affects both T-cell and macrophage functions. We thus hypothesized that systemic blockade of TGF-β signaling combined with adoptive T-cell transfer would enhance the effectiveness of the therapy.

Experimental Design: Flank tumors were generated in mice using the chicken ovalbumin–expressing thymoma cell line, EG7. Splenocytes from transgenic OT-1 mice (whose CD8 T cells recognize an immunodominant peptide in chicken ovalbumin) were activated in vitro and adoptively transferred into mice bearing large tumors in the presence or absence of an orally available TGF-β receptor-I kinase blocker (SM16).

Results: We observed markedly smaller tumors in the group receiving the combination of SM16 chow and adoptive transfer. Additional investigation revealed that TGF-β receptor blockade increased the persistence of adoptively transferred T cells in the spleen and lymph nodes, increased numbers of adoptively transferred T cells within tumors, increased activation of these infiltrating T cells, and altered the tumor microenvironment with a significant increase in tumor necrosis factor-α and decrease in arginase mRNA expression.

Conclusions: We found that systemic blockade of TGF-β receptor activity augmented the antitumor activity of adoptively transferred T cells and may thus be a useful adjunct in future clinical trials.
Phase II Study of Dasatinib in Philadelphia Chromosome–Negative Acute and Chronic Myeloid Diseases, Including Systemic Mastocytosis
Authors: Verstovsek Srdan , Tefferi Ayalew , Cortes Jorge , O'Brien Susan , Garcia-Manero Guillermo , Pardanani Animesh , Akin Cem , Faderl Stefan , Manshouri Taghi , Thomas Deborah , Kantarjian Hagop
Published: June 2008

Purpose: Molecular characterization of Philadelphia chromosome–negative (Ph−) chronic myeloproliferative disorders, such as systemic mastocytosis (SM), has provided a clear rationale for investigating novel targeted therapies. The tyrosine kinase (TK) inhibitor dasatinib is 325-fold more potent against Bcr-Abl TK than imatinib in vitro, significantly inhibiting wild-type KIT and platelet-derived growth factor receptor β TKs, and is active against cells carrying the mutant KIT-D816V gene.

Experimental Design: In this phase 2, open-label study, the efficacy of dasatinib (140 mg/d) was investigated in 67 patients with various Ph− myeloid disorders, including SM (n = 33; 28 KIT-D816V positive).

Results: The overall response rate to dasatinib in patients with SM was 33%. Only two patients, one with SM-myelofibrosis and one with SM-chronic eosinophilic leukemia, achieved complete response (elimination of mastocytosis) lasting for 5 and 16 months, respectively. Both patients were negative for KIT-D816V mutation, had low tryptase levels, abnormal WBC counts, and anemia, and had failed prior therapy with erythropoietin. Additional nine SM patients had symptomatic response, lasting 3 to 18+ months. Complete responses were achieved in two other patients (acute myeloid leukemia and hypereosinophilic syndrome). No responses were observed among patients with myelodysplastic syndromes and primary myelofibrosis. The majority of adverse events were grade 1/2.

Conclusion: These data show that dasatinib therapy may benefit a selected group of SM patients, primarily by improving their symptoms, but it does not eliminate the disease in the patients with KIT-D816V mutation.
Soluble ErbB3 Levels in Bone Marrow and Plasma of Men with Prostate Cancer
Authors: Lin Sue-Hwa , Lee Yu-Chen , Choueiri Michel B. , Wen Sijin , Mathew Paul , Ye Xiangcang , Do Kim-Anh , Navone Nora M. , Kim Jeri , Tu Shi-Ming , Yu-Lee Li-Yuan , Logothetis Christopher J.
Published: June 2008

Purpose: Prostate cancer tends to metastasize to bone and induce osteoblastic lesions. We identified a soluble form of ErbB3 (sErbB3), p45-sErbB3, in bone marrow supernatant from men with prostate cancer bone metastasis and showed that p45-sErbB3 enhances bone formation. We aimed to understand clinical implications of sErbB3 by establishing an ELISA to detect sErbB3 levels in bone marrow and plasma samples.

Experimental Design: We did ELISAs on marrow from 108 men [34 with androgen-dependent disease, 30 with androgen-independent disease (AI) but negative bone scan (AI/BS−), and 44 with AI and positive bone scan (AI/BS+)], sequential marrow from 5 men during treatment, plasma from 52 men before and after docetaxel treatment, and plasma from 95 men ages ≥70 years old without prostate cancer.

Results: Some men with clinically detectable bone metastasis had high sErbB3 levels. Within the AI/BS− group, higher sErbB3 levels seemed to yield lower rates of bone metastasis. In the AI/BS+ group, detectable bone metastases took longer to appear in men with higher sErbB3 levels than in men with lower sErbB3 levels (median, 82 versus 41 months). However, high sErbB3 levels did not confer survival benefit after metastasis development. Among men with metastatic progression in bone, docetaxel treatment reduced plasma sErbB3 (P < 0.0001) but did not affect bone-specific alkaline phosphatase (P = 0.206) or prostate-specific antigen (P = 0.906). sErbB3 was also detected in men without prostate cancer.

Conclusions: The apparent correlation between higher sErbB3 levels and longer time to bone metastasis suggests that sErbB3 participates in progression in bone of prostate cancer.
Prevalence of and Risk Factors for Hepatitis B Virus Infection among Street-Recruited Young Injection and Non-Injection Heroin Users in Barcelona, Madrid and Seville
Authors: Vallejo Fernando , Toro Carlos , De la Fuente Luis , Brugal M. Teresa , Soriano Vicente , Silva Teresa C. , Bravo María José , Ballesta Rosario , Barrio Gregorio
Published: June 2008

Background: To evaluate the prevalence of hepatitis B virus (HBV) and associated factors in 949 heroin users (HU): injectors (IHUs) and non-injectors (NIHUs). Methods: Cross-sectional study; structured questionnaire administered by computer-assisted personal interviewing and audio computer-assisted self-interviewing; dry blood samples analysed for the hepatitis B core antigen and hepatitis B surface antigen; bivariate analysis and logistic regression. Results: The prevalence of infection was significantly higher in IHUs (22.5%) than in NIHUs (7.4%) in the three cities. In the logistic analysis of male IHUs, infection was found to be associated with living in Seville, age over 25, foreign nationality, having had a sexual partner who traded sex, hepatitis C virus infection, and having injected for more than 5 years. In female IHUs, HBV infection was associated with age over 25, having injected as the first main route of administration, and having begun to inject before 18 years of age. In NIHUs, the associated factors were female gender, foreign nationality and having been tattooed. In young IHUs, the prevalence of HBV infection remains four times higher than in the general population of the same age group. Conclusion: The vaccination strategy urgently needs to be reinforced and redesigned to achieve acceptable control of the HBV infection in the most vulnerable groups, with special attention to immigrants.
Alcohol Drinking in Young Adults: The Predictive Value of Personality when Peers Come Around
Authors: van Schoor Guido , Bot Sander M. , Engels Rutger C.M.E.
Published: June 2008

This study examined whether personality traits and peer drinking affect alcohol consumption in young adults. Data were analyzed from a study that was conducted in a ‘bar laboratory’ in which ad-lib drinking of peer groups was observed. The findings indicate that extroversion is moderately associated with self-reported daily drinking, while low emotional stability is modestly associated with alcohol-related problems. With regard to drinking in the observational drinking setting, personality is not associated with young adults’ actual alcohol consumption. Further, peer drinking levels were strongly related to young adults’ drinking. Besides, agreeableness interacted with the effects of peer drinking on young adults’ drinking in such a way that agreeable individuals adapted their actual alcohol consumption more easily than others when socializing in a high- or a low-drinking peer group. We concluded that drinking in a peer context, irrespective of personality, played a major role in forming young adults’ drinking. However, personality (i.e. agreeableness) definitely played a role to the extent of the individuals’ adaptation to peer drinking norms.
Long-Term Outcomes of Treatment-Resistant Heroin Addicts with and without DSM-IV Axis 1 Psychiatric Comorbidity (Dual Diagnosis)
Authors: Maremmani Icro , Pacini Matteo , Lubrano Sonia , Perugi Giulio , Tagliamonte Alessandro , Pani Pier Paolo , Gerra Gilberto , Shinderman Marc
Published: June 2008

Objective: The aim of this study was to compare the long-term outcomes of treatment-resistant heroin addicts with and without DSM-IV axis I psychiatric comorbidity (dual diagnosis). Method: 129 heroin addicts who also met criteria for treatment resistance, 66 with one or more DSM-IV axis I psychiatric diagnosis (DD patients), and 63 without DSM-IV axis I psychiatric comorbidity (NDD patients) were monitored prospectively (6 years on average, min. 1, max. 9) along a methadone maintenance treatment program (MMTP). Results: The rates for survival-in-treatment were about 50% for NDD patients and about 70% for DD patients. After 4 years of treatment onwards, such rates tended to become stable. DD patients showed better outcome measures than NDD patients. A significantly higher methadone dose was needed to have DD patients stabilized. Conclusions: Contrary to expectations, treatment-resistant patients with psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.
Effect of Methadone Treatment on Incarceration Rates among Injection Drug Users
Authors: Werb Daniel , Kerr Thomas , Marsh David , Li Kathy , Montaner Julio , Wood Evan
Published: June 2008

Background: Methadone maintenance treatment (MMT) has been shown to dramatically reduce illicit opioid use and criminal activity among injection drug users (IDU). However, questions remain concerning the effect of MMT in reducing rates of incarceration among IDU. We therefore sought to investigate the long-term effect of MMT on rates of incarceration. Methods: We performed a generalized estimating equation longitudinal analysis of factors associated with incarceration among participants in the Vancouver Injection Drug Users Study (VIDUS). We also recorded whether participants reported having difficulty accessing drug treatment during the study period. Results: Among 1,247 active IDU, 624 (50.0%) reported being incarcerated at least once during the 6-year study period. In multivariate analysis, there was a strong negative association between methadone treatment and incarceration (adjusted odds ratio = 0.64, 95% CI: 0.54–0.76, p < 0.001) despite intensive covariate adjustment. Conclusions: Given our findings concerning the strong negative association between MMT and incarceration, and the reported high-risk injection practices of incarcerated IDU, limiting the availability of MMT has the potential to further exacerbate the high levels of HIV transmission found among IDU who are in need of treatment both in their communities and in correctional facilities.
Relationship between Negative Experiences and Drinking Experience among 15- to 16-Year-Old Adolescents in Finland
Authors: Lavikainen Hanna , Ahlström Salme , Metso Leena , Nevalainen Jaakko , Lintonen Tomi
Published: June 2008

Aims: To assess the relationship between negative experiences and frequency of alcohol drinking and drunkenness among 15- to 16-year-old adolescents in Finland. Methods: A school-based survey as part of the European School Project on Alcohol and Other Drugs (ESPAD) conducted in Finland in 2003. Nationally representative sample of Finnish adolescents, aged 15–16 (n = 3,321). Response rate 92%. Negative experiences, alcohol use and drunkenness were assessed using a self-administered questionnaire. Logistic regression analysis was used to examine the relationship between negative experiences and drinking experience. Results: Prevalence of negative experiences increased with increased frequency of drinking and drunkenness. Certain harms (troubles with the police, engaging in regretted and unprotected sexual intercourse) were experienced primarily with frequent drinking and drunkenness (>20 occasions). Logistic regression analysis indicated that only the drunkenness-related drinking style was significantly related to troubles with the police and engaging in sexual intercourse regretted the next day. Conclusions: While under-aged youths experience many problems in relationship to their alcohol use, certain problems are highly associated with frequent and heavy drinking, especially with drunkenness-related drinking style. These findings should be acknowledged when implementing effective alcohol education and alcohol-related policies to reduce under-aged alcohol use and related harms.
Permeation and Metabolism of a Novel Ascorbic Acid Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate, in Human Living Skin Equivalent Models
Authors: Shibayama H. , Hisama M. , Matsuda S. , Ohtsuki M.
Published: June 2008

A novel amphiphilic vitamin C (VC) derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which possesses a C18 alkyl chain attached to a stable ascorbate derivative, sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated as a topical prodrug of VC with transdermal activity in human living skin equivalent (LSE) models. The permeation assay used was EPI-606X in the Franz-type diffusion cell system. VCP-IS-2Na exhibited much better permeability than VC and VCP-Na. The accumulation assays applied were EPI-200X and LSE-high by the dynamic system. The increased skin accumulation of VCP-IS-2Na was superior to that of VCP-Na and VC. VCP-IS-2Na that is susceptible to enzymatic hydrolysis by esterase and/or phosphatase released VC in the skin. Measurement of the metabolites that permeated and accumulated from the skin model suggested that VCP-IS-2Na was mainly metabolized via VCP-Na to VC in EPI-606X and EPI-200X, while it was mainly metabolized directly to VC in TESTSKIN LSE-high. Thus, these characteristics indicate that the novel VC derivative, VCP-IS-2Na, may be advantageous as a readily available source of VC for skin care applications.
HBx Inhibits the Growth of CCL13-HBX-Stable Cells via the GSK-3β/β-Catenin Cascade
Authors: Kuo Chan-Yen , Wu Cheng-Chung , Hsu Shih-Lan , Hwang Guang-Yuh
Published: June 2008

Objective: The hepatitis B virus X protein (HBx) plays critical roles in cell survival via modulation of signaling pathways. In our previous studies, we reported that HBx inhibited the growth of CCL13-HBx-stable cells (Chang-HBx cells) in vitro and tumor formation in vivo in CCL13-HBx-cell-injected nude mice; however, this inhibition mechanism is unclear. Methods: To investigate the role of HBx in Wnt-3/β-catenin signaling pathways, we focused on the key molecules GSK-3β and β-catenin, and analyzed by Western blotting and immunofluorescence staining. Results: Results indicated that following HBx induction, GSK-3β activity was up-regulated, the expression and accumulation of β-catenin in the nucleus were decreased, and cell proliferation was suppressed. Inhibition of GSK-3β activity by pharmacological inhibitors rescued the expression and accumulation of β-catenin in the nucleus and facilitated cell proliferation and growth following HBx induction. The localization of β-catenin, which is involved in cell proliferation, and mediated by GSK-3β activation was also demonstrated. Conclusion: Our findings suggest that HBx negatively regulated proliferation of CCL13-HBx-stable cells via the GSK-3β/β-catenin cascade.
RNAi Targeting Embryonic Myosin Heavy Chain Isoform Inhibited Bound Thrombin-Induced Migration of Vascular Smooth Muscle Cells
Authors: Sunagawa Masanori , Shimada Seiji , Nakamura Mariko , Kosugi Tadayoshi
Published: June 2008

To investigate the effect of bound thrombin, a complex of α-thrombin with fibrin fragments derived from clots, on proliferation and migration of cultured rabbit vascular smooth muscle cells, cell proliferation was measured by WST-1 reagent and migration was evaluated by counting migrated cells through pores of cell culture insert (8 μm size) after 48-hour treatment with bound thrombin (10 U/ml). To examine the role of an embryonic myosin heavy chain isoform (SMemb) in these effects by bound thrombin, the cells were subsequently treated for 48 h with an siRNA expression vector (ORF-2/pSilencer) directed against the open reading frame of SMemb mRNA. SMemb and plasminogen activator inhibitor-1 mRNA expressions were measured by Northern blot analysis. Bound thrombin significantly increased SMemb mRNA expression by 1.4 ± 0.01-fold and significantly increased plasminogen activator inhibitor-1 mRNA expression by 2.65 ± 0.69-fold (p < 0.01 vs. PBS treatment for each), which were abolished by treatment with ORF-2/pSilencer. Although bound thrombin had no effect on cell proliferation, bound thrombin significantly increased migration by 1.93 ± 0.20-fold (p < 0.05). ORF-2/pSilencer treatment significantly reduced the bound thrombin-stimulated migration activity by 1.28 ± 0.15-fold (p < 0.05). Thus, SMemb plays an important role in bound thrombin-induced cell migration activity of cultured vascular smooth muscle cells.
The Mechanism of Hyperoside Protection of ECV-304 Cells against tert-Butyl Hydroperoxide-Induced Injury
Authors: Li Hai Bo , Yi Xin , Gao Jian Mei , Ying Xi Xiang , Guan Hong Quan , Li Jian Chun
Published: June 2008

The aim of the present study was to investigate the mechanism of hyperoside protecting ECV-304 cells against tertbutyl hydroperoxide (TBHP)-induced injury. ECV-304 cell viability was measured by MTT assay. Cellular morphologic changes were observed using phase contrast microscopy. The genotoxic effects of TBHP and the protective ability of hyperoside were assessed by the Comet test. Lipid peroxidation was measured by HPLC method. The cellular redox status was determined from GSH/GSSG ratios. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Western blot analysis was used to evaluate the levels of cytochrome c, p53, SIRT1, Bax and Bcl-2 expression. The results showed that 128 µmol/l hyperoside could effectively protect TBHP-treated ECV-304 cells from death, increase superoxide dismutase activity and significantly decrease malondialdehyde production. Hyperoside was effective in protecting against the induction of oxidized DNA bases and redox state alterations induced by TBHP. Furthermore, the release of proapoptotic cytochrome c from mitochondria was reduced by hyperoside, which increased the expression of antiapoptotic SIRT1 and inhibited the translocation of Bax from cytoplasm to mitochondria. Taken together, these results indicate that hyperoside is effective in protecting against the oxidative damage induced by TBHP. The mechanism of hyperoside protecting against ECV-304 cell apoptosis by TBHP is related with resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members.
Immunological Features of Human Corneal Endothelial Cells
Authors: Wang F.
Published: June 2008

Purpose: To investigate the function of human corneal endothelial cells (HCEC) as immunological cells. Methods: Expression of HLA-DP, -DQ, -DR, CD40, CD80 and CD86 was determined by immunohistochemical methods. Purified peripheral blood mononuclear cells were cocultured with HCEC, part of which had been pretreated with γ-interferon (IFN), and activation of lymphocytes was determined by fluorescence-activated cell sorting analysis. Results: In the coculture system, T lymphocytes were activated by corneal endothelial cells; HLA-DP, -DQ, -DR and CD40 expressions were increased by γ-IFN pretreatment. Costimulatory CD80 was shown on the endothelial cells. Conclusions: HCEC can be assumed to be involved in the rejection process of corneal transplants as potential antigen-presenting cells.
Auditory Sensitivity of an Acoustic Parasitoid (Emblemasoma sp., Sarcophagidae, Diptera) and the Calling Behavior of Potential Hosts
Authors: Farris H.E. , Oshinsky M.L. , Forrest T.G. , Hoy R.R.
Published: June 2008

Using field broadcasts of model male calling songs, we tested whether Tibicen pruinosa and T. chloromera (Hemiptera: Cicadidae) are candidate hosts for acoustic parasitoid flies. The model calling song of T. pruinosa attracted 90% of the flies (Sarcophagidae: Emblemasoma sp.; all larvapositing females) when broadcast simultaneously with the model T. chloromera song, a phonotactic bias reconfirmed in single song playbacks. In paired broadcasts of model T. pruinosa songs with different relative amplitudes (3 dB or 6 dB), significantly more flies were attracted to the more powerful song, a result consistent with the responses predicted by a model proposed by Forrest and Raspet [1994]. Using intracellular recordings and dye injections, we characterized the sensitivity of auditory units in sound-trapped flies. Intracellular recordings from six auditory units (5 interneurons, 1 afferent) revealed best sensitivity for frequencies near 3–4 kHz, matching the predominant spectral components of the calling songs of both species of cicada. Interestingly, although flies could be attracted to T. pruinosa broadcasts throughout the day, hourly censuses of singing males revealed that calling occurred exclusively at dusk. Furthermore, the duration of the dusk chorus in T. pruinosa was significantly shorter than the midday chorus of the less attractive song of T. chloromera. We propose that the tight temporal aggregation of the dusk chorus time could function to reduce risk from attracted parasitoids.
Partial Peroxisome Proliferator-Activated Receptor Agonist Angiotensin Receptor Blockers
Authors: Towfighi Amytis , Ovbiagele Bruce
Published: June 2008

Background and Purpose: Although their primary mechanism of action is blood pressure lowering, emerging data suggest that select angiotensin receptor blockers (ARBs), which partially activate the peroxisome proliferator-activated receptor γ (PPAR-γ), may effectively treat insulin resistance and dyslipidemia without the toxicity sometimes associated with full PPAR-γ agonists. Since up to 50% of the patients with ischemic stroke and transient ischemic attack harbor insulin resistance, drugs that simultaneously control hypertension and insulin resistance could be particularly useful for stroke prevention. Summary of Review: This review presents the experimental and preliminary clinical evidence supporting a promising role for partial PPAR-γ agonist ARBs in treating insulin resistance and the metabolic syndrome in patients with ischemic cerebrovascular disease. Conclusion: Partial PPAR-γ agonist ARBs by virtue of their multiple beneficial mechanisms of action could provide a single multipronged strategy for reducing future vascular events in persons with, or at risk for, stroke.
Importance of Leukoaraiosis on CT for Tissue Plasminogen Activator Decision Making: Evaluation of the NINDS rt-PA Stroke Study
Authors: Demchuk Andrew M. , Khan Firosh , Hill Michael D. , Barber Philip A. , Silver Brian , Patel Suresh , Levine Steven R.
Published: June 2008

Background: Leukoaraiosis is associated with microhemorrhages on T2*-weighted magnetic resonance imaging of the brain. Such hemorrhages have been postulated to be responsible for symptomatic intracerebral hemorrhage (ICH) after thrombolytic treatment. We examined the relationship between small-vessel ischemic disease and symptomatic ICH within the NINDS rt-PA Stroke Study. Methods: Baseline CT scans from the NINDS rt-PA Stroke Study were re-evaluated retrospectively by blinded expert CT readers using the van Swieten Score (vSS) for leukoaraiosis. The scale examined the severity of white-matter changes on 3 serial CT slices and graded separately for the 2 distinct regionsanterior and posterior to the central sulcus: 0 = no lesion, 1 = partlyinvolving the white matter, and 2 = extending up to the cortex. Results: 603 CT scans were interpreted. The risk of symptomatic ICH increased with higher vSS in both the placebo and treatment groups. The absolute risk of symptomatic hemorrhage was 7.9% in the rt-PA-treated cohort among patients with severe white-matter disease (vSS = 3–4) versus 2.9% receiving placebo. Among severe leukoaraiosis patients (vSS = 3–4), no differential treatment effect was seen with rt-PA patients achieving better outcomes than placebo, modified Rankin score 0–1 in 31.6% of rt-PA-treated versus 14.7% of placebo-treated patients. Conclusion: The results from the present study do not support the concept that leukoaraiosis present on baseline noncontrast CT scanning is critical to thrombolysis decision making in the first 3 h from symptom onset. No clear leukoaraiosis threshold was identified below which no benefit or harm could be seen from intravenous rt-PA therapy.
Influence of Antiplatelet Pre-Treatment on the Risk of Symptomatic Intracranial Haemorrhage after Intravenous Thrombolysis
Authors: Bravo Yolanda , Martí-Fàbregas Joan , Cocho Dolores , Rodríguez-Yáñez M. , Castellanos M. , Pérez de la Ossa N. , Roquer J. , Obach V. , Maestre J. , Martí-Vilalta Josep Lluis
Published: June 2008

Background: The influence of antiplatelet agents (AP) in the development of a symptomatic intracranial haemorrhage (SICH) after intravenous rt-PA is not well known. We assessed the hypothesis that pre-treatment with AP may increase that risk. Methods: We studied data from consecutive patients with ischaemic stroke treated with intravenous rt-PA within the first 3 h after symptom onset. We recorded the antecedent of any AP therapy previous to thrombolysis. A follow-up CT was performed routinely 24–36 h after the infusion of rt-PA. Intracranial bleeding was categorized according to the criteria of the European Cooperative Acute Stroke Study II (ECASS II) into haemorrhagic infarction type 1 and 2 and parenchymal haemorrhage type 1 and 2. SICH was diagnosed if it was of the parenchymal haemorrhage type, occurred within the first 36 h and was associated with neurological deterioration. Results: Of a total of 605 patients, 137 (22.6%) were pre-treated with AP, most of them (n = 106) with aspirin. Any type of intracranial haemorrhage was observed in 119 patients (19.7%), without differences between the AP (18.4%) and the non-AP (20.2%) groups. Parenchymal haemorrhage was observed in 41 patients (8.5%) and SICH in 26 (4.3%). There was a non-significant rise in the frequency of SICH in the AP group compared with the non-AP group (6.6 vs. 3.6% p = 0.10). Conclusions: Pre-treatment with AP non-significantly increases the risk of SICH and therefore this antecedent should not be a contraindication for intravenous thrombolysis.
Visual Grading System for Vasospasm Based on Perfusion CT Imaging: Comparisons with Conventional Angiography and Quantitative Perfusion CT
Authors: Wintermark Max , Dillon William P. , Smith Wade S. , Lau Benison C. , Chaudhary Saadia , Liu Songling , Yu Melissa , Fitch Melissa , Chien Jeffrey D. , Higashida Randall T. , Ko Nerissa U.
Published: June 2008

Background: The purpose of this study was to compare simple visual grading of perfusion CT (PCT) maps to a more quantitative, threshold-based interpretation of PCT parameters in the characterization of presence and severity of vasospasm. Methods: Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 paired PCT and digital subtraction angiography (DSA) examinations. A neuroradiologist and a neurologist reviewed the PCT mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume maps independently; they evaluated five anatomical regions (frontal, temporal, parietal, occipital/thalami, and basal ganglia/insula) and graded them for abnormality (0 if normal, 1 if abnormal in <50% of the region, and 2 if abnormal in ≧50% of the region). A third neuroradiologist blinded to the PCT results reviewed the DSA examinations and assessed 19 segments for the presence or absence of vasospasm. Correlation between PCT and DSA scores was assessed, as well as the sensitivity and specificity of PCT compared to DSA used as a gold standard. Results: MTT (R2 = 0.939) and CBF (R2 = 0.907) scores correlated best with DSA scores (p < 0.001). MTT scoring had a sensitivity of 92% and a specificity of 86% compared to DSA; CBF scoring had a sensitivity of 75% and a specificity of 95%. The interobserver agreement between neuroradiologist and neurologist was found to have kappa = 0.789 for MTT and 0.658 for CBF. Conclusion: We propose a user-friendly visual grading system for PCT maps in patients with suspected vasospasm. This visual approach compares favorably to the results of DSA. Sensitive MTT maps should be used for screening, and specific CBF maps for confirmation of vasospasm.
Springtime Intensification of the Great Plains Low-Level Jet and Midwest Precipitation in GCM Simulations of the Twenty-First Century
Authors: Cook Kerry H. , Vizy Edward K. , Launer Zachary S. , Patricola Christina M.
Published: June 2008

Simulations from 18 coupled atmosphere–ocean GCMs are analyzed to predict changes in the climatological Great Plains low-level jet (GPLLJ) and Midwest U.S. hydrology resulting from greenhouse gas increases during the twenty-first century. To build confidence in the prediction, models are selected for analysis based on their twentieth-century simulations, and their simulations of the future are diagnosed to ensure that the response is reasonable. Confidence in the model projections is also bolstered by agreement among models, in a so-called multimodel ensemble, and by analogy with present-day interannual variability.

The GCMs agree that the GPLLJ will be more intense in April, May, and June in the future. The selected models even agree on the reason for this intensification, namely, a westward extension and strengthening of the North Atlantic subtropical high (the Bermuda high) that occurs when greenhouse gas–induced warming over the continental United States exceeds that of the subtropical Atlantic in the spring. Accompanying the changes in the GPLLJ are springtime precipitation increases of 20%–40% in the upper Mississippi Valley, which are closely associated with intensified meridional moisture convergence by the jet, with decreases to the south, which results in reduced moist static stability in the region. The simulated differences in the Midwest circulation and hydrology in the spring for the twenty-first century are similar to the observed moisture balance and circulation anomalies for May and, especially, June of 1993, a year of devastating floods throughout the Mississippi Valley.
Synoptic Wave Perturbations and Convective Systems over Equatorial Africa
Authors: Nguyen Hanh , Duvel Jean-Philippe
Published: June 2008

Spectral analysis of the outgoing longwave radiation (OLR) time series over equatorial Africa reveals large oscillations of the convection with periods of between 3 and 6 days. In March and April, when the intertropical convergence zone (ITCZ) migrates northward and crosses equatorial Africa, this periodic behavior is most pronounced with a marked peak at 5–6 days. Robust horizontal and vertical patterns, consistent with a convectively coupled Kelvin wave, can be extracted by a simple composite technique based only on the phase of the convective oscillations over equatorial Africa. The composite reveals differences between continental and adjacent oceanic regions. Over the continent, the stronger oscillation of the convection is associated with larger temperature and moisture anomalies near the surface, suggesting an influence of diabatic processes on the amplitude of the perturbations. Some convective events over equatorial Africa are triggered by waves propagating eastward over the equatorial Atlantic. However, this cannot explain the robust periodic behavior observed over equatorial Africa because the convective variability over the Amazon basin and the equatorial Atlantic have different spectral characteristics with no marked peak at 5–6 days in March and April.

The mesoscale convective systems embedded in these synoptic disturbances are studied using satellite brightness temperature at higher spatial (0.5°) and temporal (3 h) resolution than the OLR (respectively, 2.5° and daily average). The diurnal and the wave modulations of occurrence, size, and life cycle of the mesoscale convective systems are inspected. These systems are generated preferentially over the western slopes of the Rift Valley highlands. They propagate west-southwestward over the Congo basin where they reach their maximum size. The 5–6-day perturbations do not modify the diurnal triggering of convective systems notably, but the perturbations do modify their development into larger organized convection, especially over the Congo basin. The implication of these results for understanding the physical source of these 5–6-day perturbations is discussed.
Residual Diagnosis of Diabatic Heating from ERA-40 and NCEP Reanalyses: Intercomparisons with TRMM
Authors: Chan Steven C. , Nigam Sumant
Published: June 2008

Diabatic heating is diagnosed from the 40-yr ECMWF Re-Analysis (ERA-40) circulation as a residue in the thermodynamic equation. The heating distribution is compared with the heating structure diagnosed from NCEP and 15-yr ECMWF Re-Analysis (ERA-15) circulation and latent heating generated from Tropical Rainfall Measuring Mission (TRMM) observations using the convective–stratiform heating (CSH) algorithm.

The ERA-40 residual heating in the tropics is found to be stronger than NCEP’s (and ERA-15), especially in July when its zonal–vertical average is twice as large. The bias is strongest over the Maritime Continent in January and over the eastern basins and Africa in July. Comparisons with precipitation indicate ERA-40 heating to be much more realistic over the eastern Pacific but excessive over the Maritime Continent, by at least 20% in January.

Intercomparison of precipitation estimates from heating-profile integrals and station and satellite analyses reveals the TRMM CSH latent heating to be chronically weak by as much as a factor of 2! It is the low-side outlier among nine precipitation estimates in three of the four analyzed regions. No less worrisome is the inconsistency between the integral of the CSH latent heating profile in the tropics and the TRMM precipitation retrievals constraining the CSH algorithm (e.g., the 3A25 analysis).

Confronting TRMM’s diagnosis of latent heating from local rainfall retrievals and local cumulus-model heating profiles with heating based on the large-scale assimilated circulation is a defining attribute of this study.
Control of Lower-Limb Overturning Circulation in the Southern Ocean by Diapycnal Mixing and Mesoscale Eddy Transfer
Authors: Ito Taka , Marshall John
Published: June 2008

A simple model is developed of the lower limb of the meridional overturning circulation in the Southern Ocean based on residual-mean theory. It is hypothesized that the strength of the lower-limb overturning (Ψ) is strongly controlled by the magnitude of abyssal diapycnal mixing (κ) and that of mesoscale eddy transfer (K). In particular, it is argued that Ψ ∝ κK. The scaling and associated theory find support in a suite of sensitivity experiments with an idealized ocean general circulation model. This study shows that intense diapycnal mixing is required to close the buoyancy budget of the lower-limb overturning circulation, in contrast to the upper limb, where air–sea buoyancy fluxes can provide the required diabatic forcing.
Ten Years of TRMM/VIRS On-Orbit Calibrations and Multiyear Comparisons of VIRS and MODIS
Authors: Lyu Cheng-Hsuan , Barnes William L.
Published: June 2008

After 10 years of successful operation of the Tropical Rainfall Measuring Mission (TRMM)/Visible Infrared Scanner (VIRS), based on sensor performance, the authors have reexamined the calibration algorithms and identified several ways to improve the current VIRS level-1B radiometric calibration software. This study examines the trends in VIRS on-orbit calibration results by using lunar measurements to enable separation of the solar diffuser degradation from that of the VIRS Earth-viewing sensor and by comparing the radiometric data with two nearly identical Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on board the NASA Earth Observing System (EOS) Terra and Aqua satellites. For the VIRS, with spectral bands quite similar to several of the MODIS bands, the integrated lunar reflectance data were measured, from January 1998 to March 2007, at phase angles ranging from 0.94° to 121.8°. The authors present trending of the lunar data over periods of 4 yr (Aqua/MODIS), 6 yr (Terra/MODIS), and 10 yr (TRMM/VIRS) and use these observations to examine instrument radiometric stability. The VIRS-measured lunar irradiances are compared with the MODIS-measured lunar irradiances at phase angles around 54°–56°. With the upcoming modified VIRS level-1B version 7 calibration algorithm, the VIRS, along with MODIS, should provide better references for intercalibrating multiple Earth-observing sensors.
Sara Ruddick's Theory of Maternal Thinking Applied To Traditional Irish Mothering
Authors: Radosh Polly F.
Published: June 2008

This paper uses Sara Ruddick's theory of maternal thinking to explain patterns of Irish mothering that developed in Ireland following the Great Famine of 1845–1852. Ruddick's central thesis, that maternal thinking develops strategies for preserving the life of the child, fostering the child's growth, and shaping an acceptable child, is applied to the intersecting influences of famine memory, religion, education, and emigration in post-famine Ireland. The strict, moralistic, and highly inhibiting features of Irish culture that dominated the nineteenth and twentieth centuries are traceable to patterns of mothering that developed after the famine. While Irish mothers are often blamed for instilling values that stressed sexual repression and guilt, other cultural factors influenced maternal thinking. Mothers did foster highly repressive moral values that encouraged permanent celibacy and delayed marriage. This paper examines the larger cultural features that derived from political oppression and the famine as they imprinted these values.
Anachronisms or Failures? Family Strategies in the Sixteenth Century, as Drawn From Collective Biographies of Solicitors in Aix-En-Provence
Authors: Dolan Claire
Published: June 2008

This article highlights the patterns that can be observed in the matrimonial alliances of solicitors in sixteenth-century Aix-en-Provence and family strategies understood as a corpus of rational decisions bearing on the long term. Defined this way, family strategies applied to sixteenth-century solicitors are an anachronism. The new and unstable context in which the sixteenth-century solicitor found himself prevented families from having a clear view of the objectives to achieve and from devising a rational strategy. The article presents the model that most of the solicitors' alliances followed and suggests the obstacles that appeared before the main actor in family planning, the one who wielded paternal authority, in the creation of these alliances. The example of the Maria family shows women who decided, against the will of their family, whom they would marry. This article highlights the historian's reconstruction of typical family behavior and the limited possibilities that families had to plan over the long term.
The Market in Concubines in Jiangnan During Ming-Qing China
Authors: Hsieh Bao Hua
Published: June 2008

The traffic in concubines flourished in Ming-Qing Jiangnan as a result of large scale interactions of political and socioeconomic contexts. How women were situated within the system is central to this study, which revolves around two major arguments. First, the traffic in concubines as a means for disaster relief during difficult times was legitimized as a benevolent policy. Second, women were not necessarily the victims of the commercialized market in concubines. To study concubinage in general and individual concubines in the market system in Jiangnan, the following issues command attention: the political and socioeconomic conditions fostering concubinage, the market system of women, the roles of brokers, the value indicators and resultant prices, the transaction procedures for the sale of women with specific contents of contracts, the effects of the market system on the concubines'lives, and the regulations of law and the judicial practice in penal cases.
Cross-Cultural Analysis of Student Writing
Authors: Donahue Tiane
Published: June 2008

Text analysis traditions in France and the United States include discourse analysis, critical linguistics, French functional linguistics, Bakhtinian dialogics, and “generous reading.” These frames have not been used, however, in cross-cultural analysis of university student writing. The author presents a study of 250 student texts from French and U.S. introductory university courses, using a methodology for cross-cultural analysis that draws on other French and U.S. methodologies, particularly those using the dialogic utterance as a unit of analysis, but extended by the tools of reprise-modification and textual movement. The results provide a complex picture of university students' writing as a site of social-textual dynamics, resisting more traditional contrastive approaches while reintroducing a focus on the text. The interpretive analysis brought out more commonality than difference; the author hypothesizes that students entering the university share a discourse of learning and negotiation across cultural contexts. The methodology supports cross-cultural analysis beyond “discourses of difference.”