bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Surface Forcing on Southern Hemisphere Atmospheric Blocking in the Australia–New Zealand Sector
Authors: Ummenhofer Caroline C. , McIntosh Peter C. , Pook Michael J. , Risbey James S.
Published: June 2013

Characteristics of atmospheric blocking in the Southern Hemisphere (SH) are explored in atmospheric general circulation model (AGCM) simulations with the Community Atmosphere Model, version 3, with a particular focus on the Australia–New Zealand sector. Preferred locations of blocking in SH observations and the associated seasonal cycle are well represented in the AGCM simulations, but the observed magnitude of blocking is underestimated throughout the year, particularly in late winter and spring. This is related to overly zonal flow due to an enhanced meridional pressure gradient in the model, which results in a decreased amplitude of the longwave trough/ridge pattern. A range of AGCM sensitivity experiments explores the effect on SH blocking of tropical heating, midlatitude sea surface temperatures, and land–sea temperature gradients created over the Australian continent during austral winter. The combined effects of tropical heating and extratropical temperature gradients are further explored in a configuration that is favorable for blocking in the Australia–New Zealand sector with warm SST anomalies to the north of Australia, cold to the southwest of Australia, warm to the southeast, and cool Australian land temperatures. The blocking-favorable configuration indicates a significant strengthening of the subtropical jet and a reduction in midlatitude flow, which results from changes in the thermal wind. While these overall changes in mean climate, predominantly forced by the tropical heating, enhance blocking activity, the magnitude of atmospheric blocking compared to observations is still underestimated. The blocking-unfavorable configuration with surface forcing anomalies of opposite sign results in a weakening subtropical jet, enhanced midlatitude flow, and significantly reduced blocking.
Application of a Bayesian Classifier of Anomalous Propagation to Single-Polarization Radar Reflectivity Data
Authors: Peter Justin R. , Seed Alan , Steinle Peter J.
Published: June 2013

A naïve Bayes classifier (NBC) was developed to distinguish precipitation echoes from anomalous propagation (anaprop). The NBC is an application of Bayes's theorem, which makes its classification decision based on the class with the maximum a posteriori probability. Several feature fields were input to the Bayes classifier: texture of reflectivity (TDBZ), a measure of the reflectivity fluctuations (SPIN), and vertical profile of reflectivity (VPDBZ). Prior conditional probability distribution functions (PDFs) of the feature fields were constructed from training sets for several meteorological scenarios and for anaprop. A Box–Cox transform was applied to transform these PDFs to approximate Gaussian distributions, which enabled efficient numerical computation as they could be specified completely by their mean and standard deviation. Combinations of the feature fields were tested on the training datasets to evaluate the best combination for discriminating anaprop and precipitation, which was found to be TDBZ and VPDBZ. The NBC was applied to a case of convective rain embedded in anaprop and found to be effective at distinguishing the echoes. Furthermore, despite having been trained with data from a single radar, the NBC was successful at distinguishing precipitation and anaprop from two nearby radars with differing wavelength and beamwidth characteristics. The NBC was extended to implement a strength of classification index that provides a metric to quantify the confidence with which data have been classified as precipitation and, consequently, a method to censor data for assimilation or quantitative precipitation estimation.
Automated Discrimination of Certain Brightness Fronts in RADARSAT-2 Images of the Ocean Surface
Authors: Jones Chris T. , Sikora Todd D. , Vachon Paris W. , Wolfe John , DeTracey Brendan
Published: June 2013

Automated classification of the signatures of atmospheric and oceanic processes in synthetic aperture radar (SAR) images of the ocean surface has been a difficult problem, partly because different processes can produce signatures that are very similar in appearance. For example, brightness fronts that are the signatures of horizontal wind shear caused by atmospheric processes that occur independently of properties of the ocean (WIN herein) often appear very similar to brightness fronts that are signatures of sea surface temperature (SST) fronts (SST herein). Using Moderate Resolution Imaging Spectroradiometer (MODIS)-derived SST for validation, 302 SAR SST and 193 SAR WIN signatures were collected from over 250 RADARSAT-2 images of the Gulf Stream region using a Canny edge detector. A vector consisting of textural and contextual features was extracted from each signature and used to train and test logistic regression, maximum likelihood, and binary tree classifiers. Following methods proven effective in the analysis of SAR images of sea ice, textural features included those computed from the gray-level co-occurrence matrix for regions along and astride each signature. Contextual features consisted of summaries of the wind vector field near each signature. Results indicate that signatures labeled SST can be automatically discriminated from signatures labeled WIN using the mean wind direction with respect to a brightness front with an accuracy of between 80% and 90%.
Evaluation of SSMIS Upper Atmosphere Sounding Channels for High-Altitude Data Assimilation
Authors: Hoppel Karl W. , Eckermann Stephen D. , Coy Lawrence , Nedoluha Gerald E. , Allen Douglas R. , Swadley Steven D. , Baker Nancy L.
Published: June 2013

Upper atmosphere sounding (UAS) channels of the Special Sensor Microwave Imager/Sounder (SSMIS) were assimilated using a high-altitude version of the Navy Global Environmental Model (NAVGEM) in order to investigate their potential for operational forecasting from the surface to the mesospause. UAS radiances were assimilated into NAVGEM using the new Community Radiative Transfer Model (CRTM) that accounts for Zeeman line splitting by geomagnetic fields. UAS radiance data from April 2010 to March 2011 are shown to be in good agreement with coincident temperature measurements from the Sounding of the Atmosphere Using Broadband Emission Radiometry (SABER) instrument that were used to simulate UAS brightness temperatures. Four NAVGEM experiments were performed during July 2010 that assimilated (i) no mesospheric observations, (ii) UAS data only, (iii) SABER and Microwave Limb Sounder (MLS) mesospheric temperatures only, and (iv) SABER, MLS, and UAS data. Zonal mean temperatures and observation − forecast differences for the UAS-only and SABER+MLS experiments are similar throughout most of the mesosphere, and show large improvements over the experiment assimilating no mesospheric observations, proving that assimilation of UAS radiances can provide a reliable large-scale constraint throughout the mesosphere for operational, high-altitude analysis. This is confirmed by comparison of solar migrating tides and the quasi-two-day wave in the mesospheric analyses. The UAS-only experiment produces realistic tidal and two-day wave amplitudes in the summer mesosphere in agreement with the experiments assimilating MLS and SABER observations, whereas the experiment with no mesospheric observations produces excessively strong mesospheric winds and two-day wave amplitudes.
Computational cloning of drug target genes of a parasitic nematode, Oesophagostomum dentatum
Authors: Romine Nathan M , Martin Richard J , Beetham Jeffrey K
Published: June 2013

Background

Gene identification and sequence determination are critical requirements for many biological, genomic, and bioinformatic studies. With the advent of next generation sequencing (NGS) technologies, such determinations are predominantly accomplished in silico for organisms for which the genome is known or for which there exists substantial gene sequence information. Without detailed genomic/gene information, in silico sequence determination is not straightforward, and full coding sequence determination typically involves time- and labor-intensive PCR-based amplification and cloning methods.

Results

An improved method was developed with which to determine full length gene coding sequences in silico using de novo assembly of RNA-Seq data. The scheme improves upon initial contigs through contig-to-gene identification by BLAST nearest–neighbor comparison, and through single-contig refinement by iterative-binning and -assembly of reads. Application of the iterative method produced the gene identification and full coding sequence for 9 of 12 genes and improved the sequence of 3 of the 12 genes targeted by benzimidazole, macrocyclic lactone, and nicotinic agonist classes of anthelminthic drugs in the swine nodular parasite Oesophagostomum dentatum. The approach improved upon the initial optimized assembly with Velvet that only identified full coding sequences for 2 genes.

Conclusions

Our reiterative methodology represents a simplified pipeline with which to determine longer gene sequences in silico from next generation sequence data for any nematode for which detailed genetic/gene information is lacking. The method significantly improved upon an initial Velvet assembly of RNA-Seq data that yielded only 2 full length sequences. The identified coding sequences for the 11 target genes enables further future examinations including: (i) the use of recombinant target protein in functional assays seeking a better understanding of the mechanism of drug resistance, and (ii) seeking comparative genomic and transcriptomic assessments between parasite isolates that exhibit varied drug sensitivities.
High-throughput sequencing of methylated cytosine enriched by modification-dependent restriction endonuclease MspJI
Authors: Huang Xiaojun , Lu Hanlin , Wang Jun-Wen , Xu Liqin , Liu Siyang , Sun Jihua , Gao Fei
Published: June 2013

Background

As a well-known epigenomic modification, DNA methylation is found to be common in plants and plays an important role in many biological processes. Relying on the unique feature of methylation-dependent digestion, the family of methylation-requiring restriction-like endonuclease, such as MspJI and its homologs, was suggested for a potential usage in methylation detection.

Results

In this study, we combine MspJI digestion and electrophoretic band selection with next generation high-throughput sequencing technology to detect 5-methylcytosines in Arabidopsis genome. By developing a bioinformatics workflow to attribute the CNNR sites recognized by MspJI to the reference genome, we fulfilled the systematic assessment of this method.

Conclusions

According to the assessment, here we provide the method for generating a detailed map of plant methylome that could be feasible, reliable and economical in methylation investigation.
Risk factors for subclinical atherosclerosis in HIV-infected patients under and over 40 years: a case–control study
Authors: Albuquerque Valéria Maria Gonçalves , Zírpoli Josefina Claudia , de Barros Miranda-Filho Demócrito , Albuquerque Maria de Fátima Pessoa Militão , Montarroyos Ulisses Ramos , de Alencar Ximenes Ricardo Arraes , Lacerda Heloísa Ramos
Published: June 2013

Background

Cardiovascular diseases (CVD) are a major cause of death in people with AIDS. Factors contributing to atherosclerosis include traditional risk factors, antiretrovirals and inflammatory factors related to HIV infection. This study set out to compare risk factors associated with subclinical atherosclerosis in individuals under and over 40 years of age.

Methods

Case–control study with 697 HIV/AIDS individuals without HAART or who remain on their first antiretroviral regimen. Of the total, 351 individuals under 40 years and 346 over 40 years were analyzed separately. Subclinical atherosclerosis was assessed by carotid intima-media thickness, using B-mode ultrasound. Multivariate logistic regression was performed to find predictors of subclinical atherosclerosis in the entire group. Subsequent analysis excluded patients with major risk factors for CVD. Magnitudes of associations were expressed by odds ratio (OR) statistical significance, using a 95% confidence interval and p-value <0.05.

Results

In the <40 years group subclinical atherosclerosis was associated with male gender (OR: 2.77, 95% CI: 1.43–5.34), nonwhite race (OR: 3.01, 95% CI: 1.23-6.53), obesity (OR: 5.13, 95% CI: 1.79–14.7) and metabolic syndrome (OR: 3.30, 95% CI: 1.44–7.58). In the group ≥40 years predictors of subclinical atherosclerosis were overweight and obesity (OR = 2.53, 95% CI, 0.85–7.54), current CD4 ≥350 cells/mL (OR: 2.81, 95% CI: 1.22–6.47) and NNRTI use ≥ 5 years (OR: 2.65, 95% CI: 1.10-6.37) or PI use >5 years (OR: 1.81, 95% CI: 0.38-8.59). In the multivariate model excluding patients with major risk factors for CVD, age, male sex and nonwhite race were associated with subclinical atherosclerosis in the <40 y group, while in the ≥40 y group, age, HIV viral load >10,000 copies and the use of NNRTI (OR: 7.60, 95% CI: 1.61-35.8) or PI ≥5 years (OR: 3.62, 95% CI: 0.48-26.8) were associated with subclinical atherosclerosis.

Conclusions

In young people the fight against obesity and metabolic syndrome is the main aim in the prevention of CVD. In individuals aged ≥40 y, the prevention of obesity is also of great importance. Moreover, the effects of uncontrolled viremia and the prolonged use of HAART appear to be more harmful in the older group.
Association between genomic recurrence risk and well-being among breast cancer patients
Authors: Retèl Valesca P , Groothuis-Oudshoorn Catharina GM , Aaronson Neil K , Brewer Noel T , Rutgers Emiel JT , van Harten Wim H
Published: June 2013

Background

Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients’ well-being.

Methods

Participants were Dutch women from 10 hospitals being treated for early stage breast cancer who were enrolled in the MINDACT trial (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). As part of the trial, they received a disease recurrence risk estimate based on a 70-gene signature and on standard clinical criteria as scored via a modified version of Adjuvant! Online. \Women completed a questionnaire 6–8 weeks after surgery and after their decision regarding adjuvant chemotherapy. The questionnaire assessed perceived understanding, knowledge, risk perception, satisfaction, distress, cancer worry and health-related quality of life (HRQoL), 6–8 weeks after surgery and decision regarding adjuvant chemotherapy.

Results

Women (n = 347, response rate 62%) reported high satisfaction with and a good understanding of the GEP information they received. Women with low risk estimates from both the standard and genomic tests reported the lowest distress levels. Distress was higher predominately among patients who had received high genomic risk estimates, who did not receive genomic risk estimates, or who received conflicting estimates based on genomic and clinical criteria. Cancer worry was highest for patients with higher risk perceptions and lower satisfaction. Patients with concordant high-risk profiles and those for whom such profiles were not available reported lower quality of life.

Conclusion

Patients were generally satisfied with the information they received about recurrence risk based on genomic testing. Some types of genomic test results were associated with greater distress levels, but not with cancer worry or HRQoL.

Trial registration

ISRCTN: ISRCTN18543567
Effectiveness of a prevention of mother-to-child HIV transmission program in Guangdong province from 2007 to 2010
Authors: Li Bing , Zhao Qingguo , Zhang Xiaozhuang , Wu Li , Chen Tingting , Liang Zhijiang , Xu Longchang , Yu Shouyi
Published: June 2013

Background

To achieve the goal of United Nations of elimination of new HIV infections, a program of prevention of mother-to-child transmission (PMTCT) was launched in Guangdong province. The objective of this study is to evaluate the effectiveness of the PMTCT program.

Methods

The retrospective cross-section analysis was conducted using the data of case reported cards of HIV positive mothers and their infants from 2007 to 2010 in Guangdong province, and 108 pairs of eligible subjects were obtained. We described the data and compared the rates of MTCT by various PMTCT interventions respectively.

Results

The overall rate of HIV MTCT was 13.89% (15) among 108 pairs of HIV positive mothers and their infants; 60.19% (65) of the mothers ever received ARVs, 80.56% (87) of infants born to HIV positive mothers ever received ARVs, but 16.67% (18) of the mothers and infants neither received ARVs. Among all the mothers and infants, who both received ARVs, received triple ARVs, mother received ARVs during pregnancy, and both received ARVs and formula feeding showed the lower rates of HIV MTCT, and the rates were 8.06%, 2.50%, 5.77%, and 6.67% respectively. In infants born to HIV positive mother, who received mixed feeding had a higher HIV MTCT up to 60.00%. Delivery mode might not relative to HIV MTCT.

Conclusions

The interventions of PMTCT program in Guangdong could effectively reduce the rate of HIV MTCT, but the effectiveness of the PMTCT program were heavily cut down by the lower availability of the PMTCT interventions.
Vascular complications and changes in body mass index in Japanese type 2 diabetic patients with abdominal obesity
Authors: Nagao Hirofumi , Kashine Susumu , Nishizawa Hitoshi , Okada Takuya , Kimura Takekazu , Hirata Ayumu , Fukuda Shiro , Kozawa Junji , Maeda Norikazu , Kitamura Tetsuhiro , Yasuda Tetsuyuki , Okita Kohei , Hibuse Toshiyuki , Tsugawa Mamiko , Imagawa Akihisa , Funahashi Tohru , Shimomura Iichiro
Published: June 2013

Background

Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) < 25 kg/m2) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI.

Methods

We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ≥85 cm for males and ≥90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity.

Results

Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI < 25 kg/m2) with abdominal obesity were similar in obese patients (BMI ≥25 kg/m2). The mean BMI of the patients with abdominal obesity was < 25 kg/m2 at 20 years of age, but reached maximum to more than 30 kg/m2 in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI < 25 kg/m2), but developed abdominal obesity by the time of admission.

Conclusion

These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease.
Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats
Authors: Li Hong , Bian Yunfei , Zhang Nana , Guo Jia , Wang Cheng , Lau Wayne Bond , Xiao Chuanshi
Published: June 2013

Background

Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown.

Methods

Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation.

Results

IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p < 0.05) and myocardial tissue (9.8 ± 0.60 pmol/L, p < 0.01) compared to pre-MI control values (43.62 ± 3.47 pmol/L and 4.4 ± 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p < 0.05 or p < 0.01).

Conclusions

By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury.
Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study
Authors: Zhang Qiangye , Yang Hongchao , Wang Jian , Li Aiwu , Zhang Wentong , Cui Xinhai , Wang Kelai
Published: June 2013

Background

Both clinical and preclinical studies revealed that regular intake of green tea reduced the prevalence of depressive symptoms, as well as produced antidepressant-like effects in rodents. Evidence proposed that disturbed reward learning has been associated with the development of anhedonia, a core symptom of depression. However, the relationship between green tea and reward learning is poorly investigated. Our goal was to test whether chronic treatment with green tea in healthy subjects affects the process of reward learning and subsequently regulates the depressive symptoms.

Methods

Seventy-four healthy subjects participated in a double-blind, randomized placebo-controlled study with oral administration of green tea or placebo for 5weeks. We used the monetary incentive delay task to evaluate the reward learning by measurement of the response to reward trial or no-reward trial. We compared the reaction time of reward responsiveness between green tea and placebo treatment. Furthermore, we selected Montgomery-Asberg depression rating scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HRSD-17) to estimate the depressive symptoms in these two groups.

Results

The results showed chronic treatment of green tea increased reward learning compared with placebo by decreasing the reaction time in monetary incentive delay task. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with participants treated with placebo.

Conclusions

Our findings reveal that chronic green tea increased the reward learning and prevented the depressive symptoms. These results also raised the possibility that supplementary administration of green tea might reverse the development of depression through normalization of the reward function.
On the solutions of two special types of Riccati difference equation via Fibonacci numbers
Authors: Tollu Durhasan T , Yazlik Yasin , Taskara Necati
Published: June 2013

In this study, we investigate the solutions of two special types of the Riccati difference equation

x

n
+
1

=

1

1
+

x
n

and

y

n
+
1

=

1

−
1
+

y
n

such that their solutions are associated with Fibonacci numbers.

MSC: 11B39, 39A10, 39A13.
Post-treatment of secondary wastewater treatment plant effluent using a two-stage fluidized bed bioreactor system
Authors: Safari Golam Hossein , Yetilmezsoy Kaan , Mahvi Amir Hossein , Zarrabi Mansur
Published: June 2013

The aim of this study was to investigate the performance of a two-stage fluidized bed reactor (FBR) system for the post-treatment of secondary wastewater treatment plant effluents (Shahrak Gharb, Tehran, Iran). The proposed treatment scheme was evaluated using pilot-scale reactors (106-L of capacity) filled with PVC as the fluidized bed (first stage) and gravel for the filtration purpose (second stage). Aluminum sulfate (30 mg/L) and chlorine (1 mg/L) were used for the coagulation and disinfection of the effluent, respectively. To monitor the performance of the FBR system, variation of several parameters (biochemical oxygen demand (BOD5), chemical oxygen demand (COD), turbidity, total phosphorous, total coliform and fecal coliform) were monitored in the effluent wastewater samples. The results showed that the proposed system could effectively reduce BOD5 and COD below 1.95 and 4.06 mg/L, respectively. Turbidity of the effluent could be achieved below 0.75 NTU, which was lower than those reported for the disinfection purpose. The total phosphorus was reduced to 0.52 mg/L, which was near the present phosphorous standard for the prevention of eutrophication process. Depending on both microorganism concentration and applied surface loading rates (5–10 m/h), about 35 to 75% and 67 to 97% of coliform were removed without and with the chlorine addition, respectively. Findings of this study clearly confirmed the efficiency of the FBR system for the post-treatment of the secondary wastewater treatment plant effluents without any solid problem during the chlorination.
African American Men With Very Low–Risk Prostate Cancer Exhibit Adverse Oncologic Outcomes After Radical Prostatectomy: Should Active Surveillance Still Be an Option for Them?
Authors: Sundi Debasish , Ross Ashley E. , Humphreys Elizabeth B. , Han Misop , Partin Alan W. , Carter H. Ballentine , Schaeffer Edward M.
Published: June 2013

Purpose

Active surveillance (AS) is a treatment option for men with very low–risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low–risk PCa, we evaluated oncologic outcomes of AA men with very low–risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP).

Patients and Methods

We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low–risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features.

Results

AA men with very low–risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03).

Conclusion

AA men with very low–risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low–risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.
Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin
Authors: Hodi F. Stephen , Corless Christopher L. , Giobbie-Hurder Anita , Fletcher Jonathan A. , Zhu Meijun , Marino-Enriquez Adrian , Friedlander Philip , Gonzalez Rene , Weber Jeffrey S. , Gajewski Thomas F. , O'Day Steven J. , Kim Kevin B. , Lawrence Donald , Flaherty Keith T. , Luke Jason J. , Collichio Frances A. , Ernstoff Marc S. , Heinrich Michael C. , Beadling Carol , Zukotynski Katherine A. , Yap Jeffrey T. , Van den Abbeele Annick D. , Demetri George D. , Fisher David E.
Published: June 2013

Purpose

Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities.

Patients and Methods

We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy.

Results

Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment.

Conclusion

Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.
Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B
Authors: Huang Yi-Hsiang , Hsiao Liang-Tsai , Hong Ying-Chung , Chiou Tzeon-Jye , Yu Yuan-Bin , Gau Jyh-Pyng , Liu Chun-Yu , Yang Muh-Hwa , Tzeng Cheng-Hwai , Lee Pui-Ching , Lin Han-Chieh , Lee Shou-Dong
Published: June 2013

Purpose

The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.

Patients and Methods

Eighty patients with CD20+lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39).

Results

Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion.

Conclusion

Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.
Triacetyl-3-hydroxyphenyladenosine, a derivative of cordycepin, attenuates atherosclerosis in apolipoprotein E-knockout mice
Authors: Zhao Zhenmei , Song Guohua , Tian Hua , Yu Yang , Tian Xiangyu , Liu Jia , Yao Shutong , Luo Tian , Qin Shucun
Published: June 2013

The cholesterol-modulating, immune-regulating and anti-inflammatory properties of cordycepin are well documented. Here we examined the effects of triacetyl-3-hydroxyphenyladenosine (THPA), a derivative of cordycepin, on the development of atherosclerosis (AS) in apolipoprotein E-knockout (apoE-/-) mice. The atherosclerotic lesion formation displayed by the oil red O staining-positive area was reduced significantly in either the aortic root section or the whole aorta en face in THPA-administrated apoE-/- mice. Plasma analysis by enzymatic method or enzyme-linked immunosorbent assay (ELISA) showed that high-density lipoprotein-cholesterol (HDL-C) was decreased, whereas apolipoprotein A-I (apoA-I) levels were markedly increased by THPA. In addition, ELISA and spectrophotometric measurement showed that plasma levels of tumor necrosis factor-α, interleukin-1 and malondialdehyde were decreased in mice treated with THPA. Realtime polymerase chain reaction detection disclosed that the expression of several transporters involved in reverse cholesterol transport was induced by THPA, and the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, was also elevated in the THPA-treated groups. Moreover, THPA enhanced the expression of endothelial nitric oxide synthase (NOS), and reduced the expression of inducible NOS and lectin-like oxidized LDL receptor-1 in the aorta, suggesting that THPA can exert endothelial protection effects. In addition, the expression or activation of several proinflammatory factors in the aorta was suppressed by THPA. In conclusion, our results reveal the inhibitory effects of THPA on AS in apoE-/- mice.
Laser-treatedNucleus pulposusas an innovative model of intervertebral disc degeneration
Authors: Lucas Olivier , Hamel Olivier , Blanchais Anne , Lesoeur Julie , Abadie Jérôme , Fellah Borhane Hakim , Fusellier Marion , Gauthier Olivier , Bord Eric , Grimandi Gaël , Vinatier Claire , Guicheux Jérôme , Clouet Johann
Published: June 2013

This study describes an innovative experimentally induced model of intervertebral disc degeneration. This innovative approach is based on the induction of extracellular matrix disorders in the intervertebral disc (IVD) using a diode laser. For this study, 15 one-year-old and five 30-month-old New Zealand White rabbits were used. Two procedures were tested to trigger IVD degeneration: needle aspiration (reference technique) and a laser approach. The IVD degeneration process was assessed 20, 40, 60, 90 and 120 days after surgery by X-ray radiography (IVD height), magnetic resonance imaging (MRI) (T2 intensity of IVD signal) and histological analysis using modified Boos’ scoring. Our data indicate that a marked IVD degeneration was found compared with sham-operated animals regardless of the procedure tested. A significant decrease in disc height on X-ray radiographs was first demonstrated. In addition, MRI disc signals were significantly reduced in both groups. Finally, a statistically significant increase in Boos’ scoring was found in both laser and aspiration-induced IVD degeneration. Interestingly, IVD degeneration induced by laser treatment was more progressive compared with aspiration. Moreover, the histological results indicated that laser-induced disc degeneration was quite similar to that obtained during the natural aging process as observed in 30-month-old rabbits. Our study describes the consistency of this innovative experimentally-induced animal model of IVD degeneration. The radiological, MRI and histological data confirm its relevance. The histological examination indicates that IVD degeneration induced by laser treatment is comparable to the degenerative process observed during the onset of spontaneous IVD degeneration. This model could be a useful tool to help us validate biomaterial-assisted, cell-based, regenerative medicine strategies for the prevention and treatment of IVD degeneration.
Prenatal testosterone exposure as a model for the study of endocrine-disrupting chemicals on the gerbil prostate
Authors: Biancardi Manoel F , Perez Ana PS , Góes Rejane M , Santos Fernanda CA , Vilamaior Patrícia SL , Taboga Sebastião R
Published: June 2013

The development of the prostate depends on a precise androgenic control, so sensible interferences may predispose this gland to develop prostatic diseases during life. These aspects are of interest and preoccupation, since human beings are exposed to a growing number of endocrine-disrupting chemicals with androgenic potential. Therefore, our aim was to evaluate the prostates of adult gerbils exposed to testosterone during intrauterine life. Serological, morphological, morphometric-stereologic, immunohistochemical and three-dimensional reconstruction analyses were used. We found that the testosterone effects were dose-dependent and more harmful to females, leading to the development of masculine characteristics, evidenced by an increased anogenital distance, and absence of vaginal opening and the ectopic development of prostatic tissue. Moreover, premalignant lesions, such as prostatic intraepithelial neoplasia, were observed in addition to inflammatory foci in the prostate. The results showed that the prenatal exposure to testosterone may affect the reproductive system, disrupting developmental processes and increasing susceptibility to the development of prostatic diseases in the Mongolian gerbil.
Stretch magnitude- and frequency-dependent cyclooxygenase 2 and prostaglandin E2 up-regulation in human endometrial stromal cells: Possible implications in endometriosis
Authors: Li Xiaochuan , Gong Xianghui , Zhu Lan , Leng Jinhua , Fan Qingbo , Sun Dawei , Lang Jinghe , Fan Yubo
Published: June 2013

Endometriosis, with a prevalence rate ranging from 6% to 10%, is the major contributor to pelvic pain and subfertility, and considerably reduces the quality of life in affected women. However, the pathogenesis of this disease remains largely unknown. The present study aimed to uncover the role of hyperperistalsis in the pathogenesis of endometriosis, by exploring the response of human endometrial stromal cells (ESCs) to the cyclic stretch in vitro. ESCs isolated from 18 different endometrium biopsies undergoing hysterectomy for myoma were subjected to uniaxial cyclic stretches with different magnitude and frequency using the Uniaxial Tension System. Expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in stretched and unstretched ESCs were assessed by realtime quantitative polymerase chain reaction and Western blot. Production of prostaglandin E2 (PGE2) in the culture medium was measured by enzyme-linked immunosorbent assay. The cyclic stretch mimicking hyperperistalsis in endometriosis (5% elongation at 4 cycles/min) stimulated quick up-regulations of COX-2 and mPGES-1 simultaneously on both transcriptional and translational levels, and delayed PGE2 overproduction was also noted in ESCs. As the stretch magnitude or frequency increased, so did overexpression of COX-2 and PGE2 ( P < 0.05). By contrast, the cyclic stretch mimicking physiological peristalsis (3% elongation at 2 cycles/min) did not induce significant COX-2, mPGES-1 or PGE2production within 12 h. Both COX-2 and mPEGS-1 are PGE2 synthases, and the aberrant COX-2 and PGE2 production play important roles in the pathogenesis of endometriosis. Therefore, the present findings revealed that increased stretch stimuli from the hyperperistalsis of endometriosis were capable of causing the aberrant COX-2 and PGE2 expression in the endometrium by mechanotransduction, in a magnitude and frequency-dependent manner. It implied possible roles of hyperperistalsis in the pathogenesis of endometriosis, particularly in the view of COX-2 and PGE2.
Establishment and assessment of the perinatal mouse facial nerve axotomy model via a subauricular incision approach
Authors: Wang Hui , Fang Fan , Yi Jing , Xiang Zhenghua , Sun Meiqing , Jiang Hua
Published: June 2013

A reliable animal model of facial nerve (FN) injury forms the basis for effective scientific studies of injury and repair of the FN. Currently, rodents are the most widely used animal model for such studies, most of which adopt a postauricular incision approach. However, it is difficult to carry out the procedure on perinatal rodents owing to characteristics of anatomy and the direction of incision. Based on anatomical studies on the extracranial segment of the FN in mice, we established a FN axotomy model by using a subauricular incision (SI) approach. The effect and the outcome of the FN transection were evaluated by electrophysiology, behavioral assessment and histological observation in 20 healthy four-week-old BALB/c mice. Favorable results were obtained in all of the mice and none died during the operation or subsequent observation period. Compared with the classic postauricular incision approach, the SI approach possesses multiple advantages including easier access, more satisfactory exposure of the FN trunk, minimal invasion and providing a larger operation field, which would be critical for those studies on the rodent in early development or delicate surgical manipulations.
Age-related decline of mast cell regeneration in senescence-accelerated mice (SAMP1) after chemical myeloablation due to senescent stromal cell impairment
Authors: Tsuboi Isao , Harada Tomonori , Hirabayashi Yoko , Kanno Jun , Inoue Tohru , Aizawa Shin
Published: June 2013

An age-related decline in immune functions is referred to as immunosenescence. Mast cells play an important role in the immune system. However, it has not yet been determined if aging may affect mast-cell development. In the present study, we examined the age-related change in mast-cell development after myeloablation with 5-fluorouracil (5-FU) in senescence accelerated mice (SAMP1), which exhibit senescence-mimicking stromal cell impairment after 30 weeks of age. We found that aged mice with stromal cell impairment (30-36 weeks old) showed a lower recovery of the number of femoral mast-cell progenitors (colony-forming unit [CFU]-mast) (64% of steady state), whereas young mice (8-12 weeks old) showed a higher recovery (122% of steady state). Stromal cells influence mast-cell development by producing positive regulators such as stem cell factor (SCF) and negative regulators such as transforming growth factor-beta (TGF-β). The ratio of the gene expression of SCF to that of TGF-β (SCF/TGF-β βratio) indicates the balance of positive and negative regulation of mast-cell development. SCF/TGF-β βratio increased in both the young and aged mice after 5-FU treatment. However, the SCF/TGF-β βratio rapidly decreased in aged mice, whereas it remained high in young mice. The number of femoral CFU-mast in the S-phase after 5-FU treatment reflects the activation of positive-dominant regulation for mast-cell development by stromal cells. Aged mice showed lower recovery of the number of femoral CFU-mast in the S-phase (47% of steady state), whereas young mice showed a higher recovery (205% of steady state). These results suggest that mast-cell development declines with aging due to stromal-cell functional impairment, which contributes to immunosenescence.
Mechanisms of action for light therapy: A review of molecular interactions
Authors: Prindeze Nicholas J , Moffatt Lauren T , Shupp Jeffrey W
Published: June 2013

Five decades after the first documented use of a laser for wound healing, research in light therapy has yet to elucidate the underlying biochemical pathways causing its effects. The aim of this review is to summarize the current research into the biochemical mechanisms of light therapy in order to better direct future studies. The implication of cytochrome c oxidase as the photoacceptor modulating light therapy is reviewed, as are the predominant hypotheses of the biochemical pathways involved in the stimulation of wound healing, cellular proliferation, production of transcription factors and other reported stimulatory effects.
Optimal Control of a Brownian Production/Inventory System with Average Cost Criterion
Authors: Wu Jingchen , Chao Xiuli
Published: June 2013

In this paper we study a stochastic production/inventory system with finite production capacity and random demand. The cumulative production and demand are modeled by a two-dimensional Brownian motion process. There is a setup cost for switching on the production and a convex holding and shortage cost, and our objective is to find the optimal production/inventory control that minimizes the average cost. Both lost-sales and backlog cases are studied. For the lost-sales model we show that, within a large class of policies, the optimal production strategy is either to produce according to an (s, S) policy, or never turn on the machine at all (thus it is optimal for the firm to not enter the business); whereas for the backlog model, we prove that the optimal production policy is always of the (s, S) type. Our approach first develops a lower bound for the average cost among a large class of nonanticipating policies and then shows that the value function of the desired policy reaches the lower bound. The results offer insights on the structure of the optimal control policies as well as the interplays between system parameters.
External quality assessment of HbA1c and its effect on comparison between Swedish pediatric diabetes clinics. Experiences from the Swedish pediatric diabetes quality register (Swediabkids) and Equalis
Authors: Lindblad Bengt , Nordin Gunnar
Published: June 2013

Background: To explore to what extent measurement error can explain the variation of mean patient HbA1c between clinics.

Methods: For each year 2005–2010 data from 5380–6985 children, age <18 years, in 35–43 Swedish pediatric clinics was analyzed. Each year 13,000–19,000 HbA1c analyses were evaluated. Year mean HbA1c for each patient was calculated for HbA1c values when insulin dose was ≥0.5 U/kg. In Sweden HbA1c values were during the study period standardized to the Mono S level, HbA1c(Mono S)%, but are given also in the international unit HbA1c(IFCC), mmol/mol. Performance of locally measured HbA1c is monitored by Equalis through monthly external quality assessment (EQA) schemes.

Results: The yearly mean bias term for each clinic varied from −0.54 to 0.41 HbA1c(Mono S)%. The bias between clinic HbA1c and target value improved during the 6 years and the mean bias was for 79%–88% of clinics within the recommended level ±0.14 HbA1c% the last 2 years. Inter-clinic mean HbA1c had a wide interquartile range, 0.30–0.43 HbA1c(Mono S)% [3.2–4.5 HbA1c(IFCC)mmol/mol].

Conclusions: Regular participation in EQA schemes is necessary when comparing HbA1c values. The measurement error decreased during the 6-year period and explained from 28% to <10% of the inter-clinic variation in year mean clinic HbA1c.
On volumes determined by subsets of Euclidean space
Authors: Greenleaf Allan , Iosevich Alex , Mourgoglou Mihalis
Published: June 2013

Given E ⊂ ℝ
d
, define the volume set of E,
𝒱(E) = {det(x
1,x
2,...,xd
) : xj
∈ E}.
In ℝ3, we prove that 𝒱(E) has positive Lebesgue measure if either the Hausdorff dimension of E ⊂ ℝ3 is greater than 13/5, or E is a product set of the form E = B
1×B
2×B
3 with Bj
⊂ ℝ,
dimℋ(Bj
) > 2/3,
j = 1,2,3. We show that the same conclusion holds for 𝒱(E) of Salem subsets E ⊂ ℝ
d
with
dimℋ(E) > d - 1, and give applications to discrete combinatorial geometry.