bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and process design for rotavirus-like particle production in Saccharomyces cerevisiae
Authors: Rodríguez-Limas William A , Tyo Keith EJ , Nielsen Jens , Ramírez Octavio T , Palomares Laura A
Published: May 2011

Background

Virus-like particles (VLP) have an increasing range of applications including vaccination, drug delivery, diagnostics, gene therapy and nanotechnology. These developments require large quantities of particles that need to be obtained in efficient and economic processes. Production of VLP in yeast is attractive, as it is a low-cost protein producer able to assemble viral structural proteins into VLP. However, to date only single-layered VLP with simple architecture have been produced in this system. In this work, the first steps required for the production of rotavirus-like particles (RLP) in S. cerevisiae were implemented and improved, in order to obtain the recombinant protein concentrations required for VLP assembly.

Results

The genes of the rotavirus structural proteins VP2, VP6 and VP7 were cloned in four Saccharomyces cerevisiae strains using different plasmid and promoter combinations to express one or three proteins in the same cell. Performance of the best constructs was evaluated in batch and fed-batch cultures using a complete synthetic media supplemented with leucine, glutamate and succinate. The strain used had an important effect on recombinant protein concentration, while the type of plasmid, centromeric (YCp) or episomal (YEp), did not affect protein yields. Fed-batch culture of the PD.U-267 strain resulted in the highest concentration of rotavirus proteins. Volumetric and specific productivities increased 28.5- and 11-fold, respectively, in comparison with batch cultures. Expression of the three rotavirus proteins was confirmed by immunoblotting and RLP were detected using transmission electron microscopy.

Conclusions

We present for the first time the use of yeast as a platform to express multilayered rotavirus-like particles. The present study shows that the combined use of molecular and bioprocess tools allowed the production of triple-layered rotavirus RLP. Production of VLP with complex architecture in yeasts could lead to the development of new vaccine candidates with reduced restrictions by regulatory agencies, using the successful experience with other yeast-based VLP vaccines commercialized worldwide.
Association between metabolic abnormalities and HBV related hepatocelluar carcinoma in Chinese: A cross-sectional study
Authors: Zhao Jinyan , Zhao Yunpeng , Wang Hao , Gu Xing , Ji Jun , Gao Chunfang
Published: May 2011

Background

Previous studies suggested that the abnormality of metabolism is a newly identified risk factor in HBV-related hepatocellular carcinoma (HCC). The association between metabolic factors and hepatocellular carcinoma (HCC) has not been clarified up to now. This study was conducted to investigate the prevalence of metabolic abnormalities in HCC and to probe the association between metabolic parameters and liver function as well, so as to evaluate the interactions between metabolism and the development of HBV-related HCC.

Methods

Totally 179 cases of HBV-related HCC, who were surgically treated and pathologically confirmed were enrolled. HBV carriers (n = 100) and healthy controls (n = 150) were recruited from routine physical examination during the same period. Body mass index (BMI) was obtained from medical documentation. All the metabolic-related parameters and liver function tests were determined with routine biochemical or immunological analytic methods. Malondialdehyde (MDA) and total antioxidant capacity(TAOC)were detected by chemical analytic methods. A stratified analysis was conducted according to BMI, glycated albumin (GA), free fatty acids (FFA), and the relationships between the metabolic-related parameters and liver functions were analyzed in HCC and control subjects.

Results

HCC group showed significantly high levels of mean BMI, serum glucose, low serum lipids levels than controls (P < 0.05). Acquired by stratified analysis, the higher the BMI, the higher level of insulin and homeostasis model assessment for insulin resistance (HOMA-IR) (P < 0.01) were found in HCC patients. Elevated level of MDA and γ-glutamyltransferase (GGT) were revealed in those with high serum FFA level for the first time. Strong associations between metabolic factors and liver function were shown in HCC (P < 0.05). Higher GA level was strongly associated with increased risk of cancer compared to healthy controls (OR = 9.87, 95% confidence interval: 1.86~52.29). Serum triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were negative contributory factors for HCC (OR = 0.05, 95% confidence interval: 0.01~0.27 and OR = 0.32, 95% confidence interval, 0.11~0.95: respectively).

Conclusions

Metabolic abnormalities are closely associated with the occurrence and development of HBV-related HCC. Oxidative stress and/or lipid peroxidation might be involved in the pathogenesis and acceleration of liver function impairments in HCC.
An application of the edge effect in measuring accessibility to multiple food retailer types in Southwestern Ontario, Canada
Authors: Sadler Richard C , Gilliland Jason A , Arku Godwin
Published: May 2011

Background

Trends in food retailing associated with the consolidation of smaller-format retailers into fewer, larger-format supercentres have left some rural areas with fewer sources of nutritious, affordable food. Access to nutritious, affordable food is essential for good dietary habits and combating health issues such as type-2 diabetes, obesity, and cardiovascular disease. Many studies on food environments use inaccurate or incomplete methods for locating food retailers, which may be responsible for mischaracterising food deserts. This study uses databases of every residence in and every food retailer in and around Middlesex County, Ontario, Canada. Residences were geocoded to their precise address, and network analysis techniques were performed in a geographic information system (GIS) to determine distances between every residence and different types of food retailers (grocery stores, fast food, fruit and vegetable sources, grocery stores plus fruit and vegetable sources, variety stores), both when considering and neglecting facilities outside the area of study, to account for a deficiency in analysis termed the 'edge effect'.

Results

Analysis of household accessibility to food outlets by neighbourhood socioeconomic distress level indicated that residents in the most distressed neighbourhoods tended to have better accessibility to all types of food retailers. In the most distressed neighbourhoods, 79 percent of residences were within walking distance of a grocery store, compared to only 10 percent in the least distressed neighbourhoods. When the edge effect was neglected, 37 percent of distance estimates proved inaccurate. Average accessibility to all food retailer types improved dramatically when food outlets adjacent to the study area were considered, thereby controlling for the edge effect.

Conclusion

By neglecting to consider food retailers just outside study area boundaries, previous studies may significantly over-report the actual distance necessary to travel for food. Research on food access spanning large rural regions requires methods that accurately geocode residents and their food sources. By implementing methods akin to those in this paper, future research will be better able to identify areas with poor food accessibility. Improving identification of food desert communities is a first step in facilitating more effective deployment of food policies and programs in those communities.
PreImplantation Factor (PIF) correlates with early mammalian embryo development-bovine and murine models
Authors: Stamatkin Christopher W , Roussev Roumen G , Stout Mike , Absalon-Medina Victor , Ramu Sivakumar , Goodman Chelsi , Coulam Carolyn B , Gilbert Robert O , Godke Robert A , Barnea Eytan R
Published: May 2011

Background

PreImplantation Factor (PIF), a novel peptide secreted by viable embryos is essential for pregnancy: PIF modulates local immunity, promotes decidual pro-adhesion molecules and enhances trophoblast invasion. To determine the role of PIF in post-fertilization embryo development, we measured the peptide's concentration in the culture medium and tested endogenous PIF's potential trophic effects and direct interaction with the embryo.

Methods

Determine PIF levels in culture medium of multiple mouse and single bovine embryos cultured up to the blastocyst stage using PIF-ELISA. Examine the inhibitory effects of anti-PIF-monoclonal antibody (mAb) added to medium on cultured mouse embryos development. Test FITC-PIF uptake by cultured bovine blastocysts using fluorescent microscopy.

Results

PIF levels in mouse embryo culture medium significantly increased from the morula to the blastocyst stage (ANOVA, P = 0.01). In contrast, atretic embryos medium was similar to the medium only control. Detectable - though low - PIF levels were secreted already by 2-cell stage mouse embryos. In single bovine IVF-derived embryos, PIF levels in medium at day 3 of culture were higher than non-cleaving embryos (control) (P = 0.01) and at day 7 were higher than day 3 (P = 0.03). In non-cleaving embryos culture medium was similar to medium alone (control). Anti-PIF-mAb added to mouse embryo cultures lowered blastocyst formation rate 3-fold in a dose-dependent manner (2-way contingency table, multiple groups, X2; P = 0.01) as compared with non-specific mouse mAb, and medium alone, control. FITC-PIF was taken-up by cultured bovine blastocysts, but not by scrambled FITC-PIF (control).

Conclusions

PIF is an early embryo viability marker that has a direct supportive role on embryo development in culture. PIF-ELISA use to assess IVF embryo quality prior to transfer is warranted. Overall, our data supports PIF's endogenous self sustaining role in embryo development and the utility of PIF- ELISA to detect viable embryos in a non-invasive manner.
Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR) from transfected cells and placenta explants
Authors: Chambers Anne E , Stanley Paul F , Randeva Harpal , Banerjee Subhasis
Published: May 2011

Placental hCG and pitutary LH transduce signals in target tissues through a common receptor (LHCGR). We demonstrate that recombinant LHCGR proteins which include the hormone-binding domain are secreted from transfected cells and that natural LHCGR is also secreted from human placental explants. LHCGR recombinant proteins representing varying lengths of the N-terminal extracellular domain were expressed in Chinese Hamster Ovary cells in suspension culture. Secretion was minimal up to 72h but by 96h 24-37% of the LHCGR had been released into the culture medium. The secreted proteins were folded and sensitive to glycosidases suggesting N-linked glycosylation. Secretion was independent of recombinant size and was mediated via structurally defined membrane vesicles (50-150nm). Similarly cultured human early pregnancy placental explants also released LHCGR via microvesicles. These studies provide the first experimental evidence of the possible mechanistic basis of the secretion of LHCGR.
Postural adaptations to long-term training in Prader-Willi patients
Authors: Capodaglio Paolo , Cimolin Veronica , Vismara Luca , Grugni Graziano , Parisio Cinzia , Sibilia Olivia , Galli Manuela
Published: May 2011

Background

Improving balance and reducing risk of falls is a relevant issue in Prader-Willi Syndrome (PWS). The present study aims to quantify the effect of a mixed training program on balance in patients with PWS.

Methods

Eleven adult PWS patients (mean age: 33.8 ± 4.3 years; mean BMI: 43.3 ± 5.9 Kg/m2) attended a 2-week training program including balance exercises during their hospital stay. At discharge, Group 1 (6 patients) continued the same exercises at home for 6 months, while Group 2 (5 patients) quitted the program. In both groups, a low-calorie, well-balanced diet of 1.200 kcal/day was advised. They were assessed at admission (PRE), after 2 weeks (POST1) and at 6-month (POST2). The assessment consisted of a clinical examination, video recording and 60-second postural evaluation on a force platform. Range of center of pressure (CoP) displacement in the antero-posterior direction (RANGEAPindex) and the medio-lateral direction (RANGEMLindex) and its total trajectory length were computed.

Results

At POST1, no significant changes in all of the postural parameters were observed. At completion of the home program (POST2), the postural assessment did not reveal significant modifications. No changes in BMI were observed in PWS at POST2.

Conclusions

Our results showed that a long-term mixed, but predominantly home-based training on PWS individuals was not effective in improving balance capacity. Possible causes of the lack of effectiveness of our intervention include lack of training specificity, an inadequate dose of exercise, an underestimation of the neural and sensory component in planning rehabilitation exercise and failed body weight reduction during the training. Also, the physiology of balance instability in these patients may possibly compose a complex puzzle not affected by our exercise training, mainly targeting muscle weakness.
Development of a new duplex real-time polymerase chain reaction assay for hepatitis B viral DNA detection
Authors: Sun Shipeng , Meng Shuang , Zhang Rui , Zhang Kuo , Wang Lunan , Li Jinming
Published: May 2011

Background

Quantification of hepatitis B virus (HBV) DNA can be used for diagnosing HBV infection and monitoring the effect of antiviral therapy. However, probably because of mismatches between the template and primer/probe, HBV DNA in some HBV infections could not be detected using currently available commercial assays with single primer/probe. By aligning the HBV sequences, we developed a duplex real-time polymerase chain reaction (PCR) assay using two sets of primers/probes and a specific armored DNA as internal control (IC).

Results

The limit of the duplex real-time PCR assay was 29.5 IU/ml, whereas the specificity was 100%. The within-run precision coefficient of variation (CV) ranged from 1.02% to 2.73%, while the between-run CV ranged from 0.83% to 1.25%. The optimal concentration of armored DNA IC in the HBV DNA duplex real-time PCR assay was 1 000 copies/ml. Data from 69 serum samples with HBV infection showed that the performance of the duplex real-time PCR assay was comparable to that of the COBAS Ampliprep/Cobas Taqman (CAP/CTM) HBV assay and was superior to those of the domestic commercial HBV assays.

Conclusions

The duplex real-time PCR assay is sufficiently sensitive, specific, accurate, reproducible and cost-effective for the detection of HBV DNA. It is suitable for high throughput screening and frequent HBV DNA level monitoring.
Inhibitory activity of 9-phenylcyclohepta[d]pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors
Authors: Huang Yang , Wang Xiaowei , Yu Xiaoling , Yuan Lin , Guo Ying , Xu Weisi , Liu Tiejun , Liu Junyi , Shao Yiming , Ma Liying
Published: May 2011

Background

The non-nucleoside reverse transcriptase inhibitor (NNRTI), as a major component of the highly active antiretroviral therapy (HAART) to HIV-1 (human immunodeficiency virus type 1) infected patients, required the development of new NNRTIs with improved resistance profile and decreased toxicity. Therefore, a series of novel compounds, 9-phenylcyclohepta[d]pyrimidinedione derivatives (PCPs), were designed based on the chemical structure of TNK-651, to detect anti-HIV-1 activity.

Results

1-[(benzyloxy)methyl]-9-phenyl-cyclohepta[d] pyrimidinedione (BmPCP) among four PCPs has antiviral activity on laboratory-adapted HIV strains (HIV-1 SF33). The results showed 50% inhibition concentrations (IC50s) of BmPCP were 0.34 μM, 1.72 μM and 1.96 μM on TZM-bl, peripheral blood mononuclear cells (PBMCs) and MT4, respectively. It was also effective against infection by the predominant HIV-1 isolates in China, with IC50s at low μM levels. Its selectivity index (SI) ranged from 67 to 266 in different cells. The results of time-of-addition assay demonstrated that BmPCP inhibited HIV-1 infection by targeting the post entry of the HIV-1 replication cycle. For inhibition of HIV-1 reverse transcriptase activity, the IC50 values of BmPCP and NVP were 1.51 and 3.67 μM, respectively.

Conclusions

BmPCP with a novel structure acts as a NNRTI to inhibit HIV-1 replication and can serve as a lead compound for further development of new anti-HIV-1 drugs.
Activation of ATP-Sensitive Potassium Channels Antagonize Nociceptive Behavior and Hyperexcitability of DRG Neurons from Rats
Authors: Du Xiaona , Wang Chao , Zhang Hailin
Published: May 2011

Background:

Nociceptive responses to noxious stimuli are initiated at peripheral nociceptor terminals. Ion channels play a vital role in pain signal initiation and conduction. Activation of KATP channels has been implicated in mediating the analgesic effects of agents such as morphine. However, systematic studies regarding the effects of KATP activators on nociception and neuronal excitability are scarce.

Results:

In this study, we describe the antagonistic effects of KATP activators pinacidil and diazoxide on nocifensive behavior induced by bradykinin (BK), thermo and mechanical stimuli, and the bradykinin-induced hyperexcitability of DRG neurons. We also found that KATP activators can moderately activate KATP in DRG neurons. Because the effects of KATP activators can be reversed by the KATP blocker glyburide, direct activation of KATP is most likely the underlying mechanism.

Conclusion:

This systematic study clearly demonstrates that activation of KATP could have significant modulatory effects on the excitability of sensory neurons and thus on sensory behaviors, such as nociception. KATP activators can be evaluated clinically for the treatment of pain symptoms.
A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort
Authors: Yu Jindan , He Xue , Yao Dan , Li Zhongyue , Li Hui , Zhao Zhengyan
Published: May 2011

Background

Synaptic genes,NLGN3andNLGN4X, two homologous members of the neuroligin family, have been supposed as predisposition loci for autism spectrum disorders (ASDs), and defects of these two genes have been identified in a small fraction of individuals with ASDs. But no such rare variant in these two genes has as yet been adequately replicated in Chinese population and no common variant has been further investigated to be associated with ASDs.

Methods

7 known ASDs-related rare variants inNLGN3andNLGN4Xgenes were screened for replication of the initial findings and 12 intronic tagging single nucleotide polymorphisms (SNPs) were genotyped for case-control association analysis in a total of 229 ASDs cases and 184 control individuals in a Chinese Han cohort, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.

Results

We found that a common intronic variant, SNP rs4844285 inNLGN3gene, and a specific 3-marker haplotype XA-XG-XT(rs11795613-rs4844285-rs4844286) containing this individual SNP were associated with ASDs and showed a male bias, even after correction for multiple testing (SNP allele: P = 0.048, haplotype:P = 0.032). Simultaneously, none of these 7 known rare mutation ofNLGN3andNLGN4Xgenes was identified, neither in our patients with ASDs nor controls, giving further evidence that these known rare variants might be not enriched in Chinese Han cohort.

Conclusion

The present study provides initial evidence that a common variant inNLGN3gene may play a role in the etiology of ASDs among affected males in Chinese Han population, and further supports the hypothesis that defect of synapse might involvement in the pathophysiology of ASDs.
Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study
Authors: Zheng Fanfan , Wang Lifang , Jia Meixiang , Yue Weihua , Ruan Yan , Lu Tianlan , Liu Jing , Li Jun , Zhang Dai
Published: May 2011

Background

Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

Methods

We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.

Results

We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.

Conclusions

Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.
Retained drains causing a bronchoperitoneal fistula: a case report
Authors: Pesce Catherine , Galvagno Samuel M , Efron David T , Kieninger Alicia A , Stevens Kent
Published: May 2011

Introduction

Bronchoperitoneal fistulas are extremely rare. We present a case where retained surgical drains from a previous surgery resulted in erosion and fistula formation. This condition required an extensive surgical procedure and advanced ventilator techniques.

Case presentation

A 24-year-old African-American man presented to our Emergency Department with a one-week history of fever, dyspnea, cough, and abdominal pain. A computed tomography scan of his chest and abdomen revealed bilateral lower lobe pneumonia and two retained Jackson-Pratt drains in the right upper quadrant. He was taken to the operating room for drain removal, a right hemicolectomy, debridement of a duodenal injury, a Roux-en-y duodenojejunostomy, and an end ileostomy. He subsequently became increasing hypoxemic in the intensive care unit and a bronchoperitoneal fistula was diagnosed. He required high-frequency oscillatory ventilation followed by lung isolation, and was successfully resuscitated using these techniques.

Conclusion

To the best of our knowledge, this is the first known case report of a bronchoperitoneal fistula caused by retained surgical drains. This is also the first known report that details successful management of this condition with advanced ventilatory techniques. This case highlights the importance of follow-up for trauma patients since retained surgical drains have the potential to cause life-threatening complications. When faced with this condition, clinicians should be aware of advanced ventilatory methods that can be employed in the intensive care unit. In this case, these techniques proved to be life-saving.
Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome
Authors: Bixler Georgina V , VanGuilder Heather D , Brucklacher Robert M , Kimball Scot R , Bronson Sarah K , Freeman Willard M
Published: May 2011

Background

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia.

Methods

The retina transcriptome (22,523 genes and transcript variants) was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point.

Results

Transcriptomic alterations in response to diabetes (1376 probes) were clustered according to insulin responsiveness. More than half (57%) of diabetes-induced mRNA changes (789 probes) observed at three months were fully normalized to control levels with insulin therapy, while 37% of probes (514) were only partially normalized. A small set of genes (5%, 65 probes) was significantly dysregulated in the insulin-treated diabetic rats. qPCR confirmation of findings and examination of a one month time point allowed genes to be further categorized as prevented or rescued with insulin therapy. A subset of genes (Ccr5, Jak3, Litaf) was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA expression.

Conclusions

These results provide the first genome-wide examination of the effects of insulin therapy on retinal gene expression changes with diabetes. While insulin clearly normalizes the majority of genes dysregulated in response to diabetes, a number of genes related to inflammatory processes, microvascular integrity, and neuronal function are still altered in expression in euglycemic diabetic rats. Gene expression changes not rescued or prevented by insulin treatment may be critical to the pathogenesis of diabetic retinopathy, as it occurs in diabetic patients receiving insulin replacement, and are prototypical of metabolic memory.
Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines
Authors: Lam Siew Hong , Lee Serene GP , Lin Chin Y , Thomsen Jane S , Fu Pan Y , Murthy Karuturi RK , Li Haixia , Govindarajan Kunde R , Nick Lin CH , Bourque Guillaume , Gong Zhiyuan , Lufkin Thomas , Liu Edison T , Mathavan Sinnakaruppan
Published: May 2011

Background

The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines.

Methods

Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen) and an anti-estrogen (ICI 182,780). Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa).

Results

Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE), is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry points for estrogen regulation.

Conclusion

The findings demonstrate the use of zebrafish for characterizing estrogen-like environmental carcinogens and anti-estrogen drug screening. From an evolutionary perspective, our findings suggest that estrogen regulation of cell cycle is perhaps one of the earliest forms of steroidal-receptor controlled cellular processes. Our study provides first evidence of molecular conservation of estrogen-responsiveness between zebrafish and human cancer cell lines, hence demonstrating the potential of zebrafish for estrogen-related cancer research.
Rheumatoid arthritis mimicking metastatic squamous cell carcinoma
Authors: Gomez-Rivera Fernando , El-Naggar Adel K , Guha-Thakurta Nandita , Kupferman Michael E
Published: May 2011

We report a case of a cervical rheumatoid nodule in close relation to the hyoid bone mimicking a metastatic carcinoma. A 74-year-old female with a 15-year history of rheumatoid arthritis (RA) on treatment with methotrexate presented with tenderness of the right base of tongue. Imaging demonstrated a 1.4 cm cystic lesion at the hyoid bone. Biopsies were unsuccessful and the patient required surgical resection of the mass. A trans-cervical approach was used. Pathology revealed a necrotizing granuloma compatible with rheumatoid etiology. The clinician should be aware that, in a patient with a neck mass, in the presence of active RA, rheumatoid nodules should be part of the differential diagnosis.
Impact of Awareness of Terminal Illness and Use of Palliative Care or Intensive Care Unit on the Survival of Terminally Ill Patients With Cancer: Prospective Cohort Study
Authors: Yun Young Ho , Lee Myung Kyung , Kim Seon Young , Lee Woo Jin , Jung Kyung Hae , Do Young Rok , Kim Samyong , Heo Dae Seog , Choi Jong Soo , Park Sang Yoon , Jeong Hyun Sik , Kang Jung Hun , Kim Si-Young , Ro Jungsil , Lee Jung Lim , Park Sook Ryun , Park Sohee
Published: May 2011

Purpose

We conducted this study to evaluate the validity of the perception that awareness of their terminal prognosis and use of palliative care or nonuse of an intensive care unit (ICU) causes patients to die sooner than they would otherwise.

Patients and Methods

In this prospective cohort study at 11 university hospitals and the National Cancer Center in Korea, we administered questionnaires to 619 consecutive patients immediately after they were determined by physicians to be terminally ill. We followed patients during 6 months after enrollment and assessed how their survival was affected by the disclosure of terminal illness and administration of palliative care or nonuse of the ICU.

Results

In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased patients. Nineteen percent of the patients died within 1 month, while 41.3% lived for 3 months, and 17.7% lived for 6 months. Once the cancer was judged terminal, the median survival time was 69 days. On multivariate analysis, neither patient awareness of terminal status at baseline (adjusted hazard ratio [aHR], 1.20; 95% CI, 0.96 to 1.51), use of a palliative care facility (aHR, 0.96; 95% CI, 0.76 to 1.21), nor general prostration (aHR, 1.23; 95% CI, 0.96 to 1.57) was associated with reduced survival. Use of the ICU (aHR, 1.47; 95% CI, 1.06 to 2.05) and poor Eastern Cooperative Oncology Group performance status (aHR, 1.37; 95% CI, 1.10 to 1.71) were significantly associated with poor survival.

Conclusion

Patients' being aware that they are dying and entering a palliative care facility or ICU does not seem to influence patients' survival.
Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure
Authors: Peck Amy R. , Witkiewicz Agnieszka K. , Liu Chengbao , Stringer Ginger A. , Klimowicz Alexander C. , Pequignot Edward , Freydin Boris , Tran Thai H. , Yang Ning , Rosenberg Anne L. , Hooke Jeffrey A. , Kovatich Albert J. , Nevalainen Marja T. , Shriver Craig D. , Hyslop Terry , Sauter Guido , Rimm David L. , Magliocco Anthony M. , Rui Hallgeir
Published: May 2011

Purpose

To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy.

Patients and Methods

Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays.

Results

Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001).

Conclusion

Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.
Clinical End Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer
Authors: Olsen Elise A. , Whittaker Sean , Kim Youn H. , Duvic Madeleine , Prince H. Miles , Lessin Stuart R. , Wood Gary S. , Willemze Rein , Demierre Marie-France , Pimpinelli Nicola , Bernengo Maria Grazia , Ortiz-Romero Pablo L. , Bagot Martine , Estrach Teresa , Guitart Joan , Knobler Robert , Sanches José Antonio , Iwatsuki Keiji , Sugaya Makoto , Dummer Reinhard , Pittelkow Mark , Hoppe Richard , Parker Sareeta , Geskin Larisa , Pinter-Brown Lauren , Girardi Michael , Burg Günter , Ranki Annamari , Vermeer Maartan , Horwitz Steven , Heald Peter , Rosen Steve , Cerroni Lorenzo , Dreno Brigette , Vonderheid Eric C.
Published: May 2011

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.
Characteristics and Outcomes of Breast Cancer in Women With and Without a History of Radiation for Hodgkin's Lymphoma: A Multi-Institutional, Matched Cohort Study
Authors: Elkin Elena B. , Klem Michelle L. , Gonzales Anne Marie , Ishill Nicole M. , Hodgson David , Ng Andrea K. , Marks Lawrence B. , Weidhaas Joanne , Freedman Gary M. , Miller Robert C. , Constine Louis S. , Myrehaug Sten , Yahalom Joachim
Published: May 2011

Purpose

To compare characteristics and outcomes of breast cancer in women with and without a history of radiation therapy (RT) for Hodgkin's lymphoma (HL).

Patients and Methods

Women with breast cancer diagnosed from 1980 to 2006 after RT for HL were identified from eight North American hospitals and were matched three-to-one with patients with sporadic breast cancer by age, race, and year of breast cancer diagnosis. Information on patient, tumor and treatment characteristics, and clinical outcomes was abstracted from medical records.

Results

A total of 253 patients with breast cancer with a history of RT for HL were matched with 741 patients with sporadic breast cancer. Median time from HL to breast cancer diagnosis was 18 years. Median age at breast cancer diagnosis was 42 years. Breast cancer after RT for HL was more likely to be detected by screening, was more likely to be diagnosed at an earlier stage, and was more likely to be bilateral at diagnosis. HL survivors had an increased risk of metachronous contralateral breast cancer (adjusted hazard ratio [HR], 4.3; 95% CI, 1.7 to 11.0) and death as a result of any cause (adjusted HR, 1.9; 95% CI, 1.1 to 3.3). Breast cancer–specific mortality was also elevated, but this difference was not statistically significant (adjusted HR, 1.6; 95% CI, 0.7 to 3.4).

Conclusion

In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions.
On Literary Worlds
Authors: Hayot Eric
Published: May 2011

Is it possible to come up with a better theory of the world than the ones governing contemporary debates on world literature and world-systems, to invent one more closely connected to the literary itself? This essay rethinks the relationship between “world” and literature, not to produce a mediating relay between world literature and world-systems but to see if a third analysis, focusing on the ontology of composed works, can bring “world” differently into the picture. The essay also investigates whether such a theory makes any difference to our understanding of world literature or to the history of worldedness as an aesthetic and cultural phenomenon: as a symptom and as a compass for the history, in other words, of totality as a function of the human imagination. Along the way, the essay develops five variables with which to analyze literary worlds, taken to refer to the represented totality of the work's diegetic space.
A comparative study of the typhidot (Dot-EIA) and Widal tests in blood culture positive cases of typhoid fever
Authors: Khoharo Haji Khan
Published: May 2011

Seventy-six blood culture positive typhoid cases and forty-eight controls were studied. The typhidot test was positive in 74 (97.36%) cases, with a sensitivity, specificity and positive predictive value of 96%, 89.5%, and 95%, respectively, compared to the Widal test which was positive in 56 (73.68%) cases with a sensitivity, specificity, and positive predictive value of 72%, 87%, and 87%, respectively ( P = 0.001). In the control group, seven (14.5%) cases tested positive for the Widal test and two (4.16%) for the typhidot ( P = 0.001), yielding the sensitivity and specificity for the Widal test and the typhidot test of 63% and 83%, and 85% and 97%, respectively. We conclude that the Dot-EIA (enzyme immunoassay; typhidot) is a more sensitive and specific test which is easy to perform and more reliable compared to the Widal test and that it is useful in early therapy.
Reduced HIV transmission at subsequent pregnancy in a resource-poor setting
Authors: Gumbo Felicity Zvanyadza , Kandawasvika Gwendoline Quintoline , Duri Kerina , Mapingure Munyaradzi Paul , Kurewa Nyaradzai Edith , Nathoo Kusum , Rusakaniko Simbarashe , Chirenje Mike Zvavahera , Stray-Pedersen Babill
Published: May 2011

Several studies indicate that HIV-infected women continue to have children. We set out to determine the trend in HIV transmission at subsequent pregnancies. From 2002–2003, pregnant women were enrolled in a single dose nevirapine-based Prevention of Mother-to-Child Transmission of HIV (PMTCT) programme. Six years later, women with subsequent children in this cohort were identified and their children's HIV status determined. From 330 identified HIV-infected mothers, 73 had second/subsequent children with HIV results. Of these, nine (12.3%, 95% confidence interval [CI]: 4.6–20.1%) children were HIV-infected. Of the 73 second children, 51 had older siblings who had been initially enrolled in the study with definitive HIV results with an infection rate of 17/51 (33.3%, 95% CI: 19.9–46.7). About 35% of the women had been on antiretroviral drugs. These results demonstrate lower subsequent HIV transmission rates in women on a national PMTCT programme in a resource-poor setting with the advent of antiretroviral therapy.
Centralized vs. Decentralized Ambulance Diversion: A Network Perspective
Authors: Deo Sarang , Gurvich Itai
Published: May 2011

One of the most important operational challenges faced by emergency departments (EDs) in the United States is patient overcrowding. In periods of overcrowding, an ED can request the emergency medical services (EMS) agency to divert incoming ambulances to neighboring hospitals, a phenomenon known as “ambulance diversion.” The EMS agency may accept this request provided that at least one of the neighboring EDs is not on diversion. From an operations perspective, properly executed ambulance diversion should result in resource pooling and reduce the overcrowding and delays in a network of EDs. Recent evidence indicates, however, that this potential benefit is not always realized. In this paper, we provide one potential explanation for this discrepancy and suggest potential remedies. Using a queueing game between two EDs that aim to minimize their own waiting time, we find that decentralized decisions regarding diversion explain the lack of pooling benefits. Specifically, we find the existence of a defensive equilibrium, wherein each ED does not accept diverted ambulances from the other ED. This defensiveness results in a depooling of the network and, subsequently, in delays that are significantly higher than when a social planner coordinates diversion. The social optimum is itself difficult to characterize analytically and has limited practical appeal because it depends on problem parameters such as arrival rates and length of stay. Instead, we identify an alternative solution that does not require the exact knowledge of the parameters and may be used by the EMS agencies to coordinate diversion decisions when defensive diversion is present. We show that this solution is approximately optimal for the social planner's problem. Moreover, it is Pareto improving over the defensive equilibrium whereas the social optimum, in general, might not be.

This paper was accepted by Yossi Aviv, operations management.
Modeling the Loss Distribution
Authors: Chava Sudheer , Stefanescu Catalina , Turnbull Stuart
Published: May 2011

In this paper, we focus on modeling and predicting the loss distribution for credit risky assets such as bonds and loans. We model the probability of default and the recovery rate given default based on shared covariates. We develop a new class of default models that explicitly accounts for sector specific and regime dependent unobservable heterogeneity in firm characteristics. Based on the analysis of a large default and recovery data set over the horizon 1980–2008, we document that the specification of the default model has a major impact on the predicted loss distribution, whereas the specification of the recovery model is less important. In particular, we find evidence that industry factors and regime dynamics affect the performance of default models, implying that the appropriate choice of default models for loss prediction will depend on the credit cycle and on portfolio characteristics. Finally, we show that default probabilities and recovery rates predicted out of sample are negatively correlated and that the magnitude of the correlation varies with seniority class, industry, and credit cycle.

This paper was accepted by Wei Xiong, finance.
Market Timing with Option-Implied Distributions: A Forward-Looking Approach
Authors: Kostakis Alexandros , Panigirtzoglou Nikolaos , Skiadopoulos George
Published: May 2011

We address the empirical implementation of the static asset allocation problem by developing a forward-looking approach that uses information from market option prices. To this end, we extract constant maturity S&P 500 implied distributions and transform them to the corresponding risk-adjusted ones. Then we form optimal portfolios consisting of a risky and a risk-free asset and evaluate their out-of-sample performance. We find that the use of risk-adjusted implied distributions times the market and makes the investor better off than if she uses historical returns' distributions to calculate her optimal strategy. The results hold under a number of evaluation metrics and utility functions and carry through even when transaction costs are taken into account. Not surprisingly, the reported market timing ability deteriorated during the recent subprime crisis. An extension of the approach to a dynamic asset allocation setting is also presented.

This paper was accepted by Wei Xiong, finance.
Solution of the Train Platforming Problem
Authors: Caprara Alberto , Galli Laura , Toth Paolo
Published: May 2011

In this paper we study a general formulation of the train platforming problem, which contains as special cases all the versions previously considered in the literature as well as a case study from Rete Ferroviaria Italiana, the Italian Infrastructure Manager. In particular, motivated by our case study, we consider a general quadratic objective function, and propose a new way to linearize it by using a small number of new variables along with a set of constraints that can be separated efficiently by solving an appropriate linear program. The resulting integer linear programming formulation has a continuous relaxation that leads to strong bounds on the optimal value. For the instances in our case study, the solution approach based on this relaxation produces solutions that are much better than those produced by a simple heuristic method currently in use, and that often turn out to be (nearly) optimal.