bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer risk assessment of ethyl carbamate in alcoholic beverages from Brazil with special consideration to the spirits cachaça and tiquira
Authors: Lachenmeier Dirk W , Lima Maria CP , Nóbrega Ian CC , Pereira José AP , Kerr-Corrêa Florence , Kanteres Fotis , Rehm Jürgen
Published: June 2010

Background

Ethyl carbamate (EC) is a multi-site carcinogen in experimental animals and probably carcinogenic to humans (IARC group 2A). Traces of EC below health-relevant ranges naturally occur in several fermented foods and beverages, while higher concentrations above 1 mg/l are regularly detected in only certain spirits derived from cyanogenic plants. In Brazil this concerns the sugarcane spirit cachaça and the manioc (cassava) spirit tiquira, which both regularly exceed the national EC limit of 0.15 mg/l. This study aims to estimate human exposure in Brazil and provide a quantitative risk assessment.

Methods

The human dietary intake of EC via alcoholic beverages was estimated based on WHO alcohol consumption data in combination with own surveys and literature data. This data comprises the EC contents of the different beverage groups cachaça, tiquira, other spirits, beer, wine, and unrecorded alcohol (as defined by the WHO; including alcohol which is not captured in routine government statistics nor taxed). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses obtained from dose-response modelling of animal experiments. Lifetime cancer risk was calculated using the T25 dose descriptor.

Results

Considering differences between pot-still and column-still cachaça, its average EC content would be 0.38 mg/l. Tiquira contained a considerably higher average EC content of 2.34 mg/l. The whole population exposure from all alcoholic beverages was calculated to be around 100 to 200 ng/kg bw/day, with cachaça and unrecorded alcohol as the major contributing factors. The MOE was calculated to range between 400 and 2,466, with the lifetime cancer risk at approximately 3 cases in 10,000. An even higher risk may exist for binge-drinkers of cachaça and tiquira with MOEs of up to 80 and 15, respectively.

Conclusions

According to our risk assessment, EC poses a significant cancer risk for the alcohol-drinking population in Brazil, in addition to that of alcohol alone. Model calculations show that the implementation of the 0.15 mg/l limit for cachaça would be beneficial, including an increase of the MOE by a factor between 3 to 6. The implementation of policy measures for tiquira and unrecorded alcohol also appears to be advisable.
Mucus extravasation and retention phenomena: a 24-year study
Authors: Hayashida Alethea M , Zerbinatti Daniel CZ , Balducci Ivan , Cabral Luiz Antonio G , Almeida Janete D
Published: June 2010

Background

Mucoceles are benign lesions related to the minor salivary glands and their respective ducts frequently affecting oral structures which are generally asymptomatic. Mucoceles are generally characterized by swollen nodular lesions preferentially located on the lower lip and differ from the so-called ranulas, which are lesions located on the floor of the mouth and related to the sublingual or submandibular glands.

Methods

The objective of the present study was to analyze data such as age, gender, race and site of the lesion of 173 mucocele cases diagnosed at the Discipline of Stomatology, São José dos Campos Dental School, UNESP, over a period of 24 years (April 1980 to February 2003).

Results

Of the 173 cases analyzed, 104 (60.12%) were females and 69 (39.88%) were males. Age ranged from 4 to 70 years (mean ± SD: 17 ± 9.53) and most patients were in the second decade of life (n = 86, 49.42%); white (n = 124, 71.68%). The lower lip was the site most frequently affected by the lesions (n = 135, 78.03%), whereas the lowest prevalence was observed for the soft palate, buccal mucosa, and lingual frenum.

Conclusion

In this study, mucoceles predominated in white female subjects in the second decade of life, with the lower lip being the most frequently affected site.
Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial
Authors: Norell Håkan , Poschke Isabel , Charo Jehad , Wei Wei Z , Erskine Courtney , Piechocki Marie P , Knutson Keith L , Bergh Jonas , Lidbrink Elisabet , Kiessling Rolf
Published: June 2010

Background

Adjuvant trastuzumab (Herceptin) treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2/neu (Her2)-specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA (pDNA) vaccine in humans.

Patients and Methods

The vaccine, encoding a full-length signaling-deficient version of the oncogene Her2, was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients treatment was discontinued after one vaccine cycle due to rapid tumor progression or disease-related complications. The primary objective was the evaluation of safety and tolerability of the vaccine regimen. As a secondary objective, treatment-induced Her2-specific immunity was monitored by measuring antibody production as well as T-cell proliferation and cytokine production in response to Her2-derived antigens.

Results

No clinical manifestations of acute toxicity, autoimmunity or cardiotoxicity were observed after administration of Her2-pDNA in combination with GM-CSF, IL-2 and trastuzumab. No specific T-cell proliferation followingin vitrostimulation of freshly isolated PBMC with recombinant human Her2 protein was induced by the vaccination. Immediately after all three cycles of vaccination no or even decreased CD4+T-cell responses towards Her2-derived peptide epitopes were observed, but a significant increase of MHC class II restricted T-cell responses to Her2 was detected at long term follow-up. Since concurrent trastuzumab therapy was permitted, λ-subclass specific ELISAs were performed to specifically measure endogenous antibody production without interference by trastuzumab. Her2-pDNA vaccination induced and boosted Her2-specific antibodies that could be detected for several years after the last vaccine administration in a subgroup of patients.

Conclusion

This pilot clinical trial demonstrates that Her2-pDNA vaccination in conjunction with GM-CSF and IL-2 administration is safe, well tolerated and can induce long-lasting cellular and humoral immune responses against Her2 in patients with advanced breast cancer.

Trial registration

The trial registration number at the Swedish Medical Products Agency for this trial is Dnr151:785/2001.
The effect of pharmacological treatment on gait biomechanics in peripheral arterial disease patients
Authors: Huisinga Jessie M , Pipinos Iraklis I , Johanning Jason M , Stergiou Nicholas
Published: June 2010

Background

Pharmacological treatment has been advocated as a first line therapy for Peripheral Arterial Disease (PAD) patients suffering from intermittent claudication. Previous studies document the ability of pharmacological treatment to increase walking distances. However, the effect of pharmacological treatment on gait biomechanics in PAD patients has not been objectively evaluated as is common with other gait abnormalities.

Methods

Sixteen patients were prescribed an FDA approved drug (Pentoxifylline or Cilostazol) for the treatment of symptomatic PAD. Patients underwent baseline gait testing prior to medication use which consisted of acquisition of ground reaction forces and kinematics while walking in a pain free state. After three months of treatment, patients underwent repeat gait testing.

Results

Patients with symptomatic PAD had significant gait abnormalities at baseline during pain free walking as compared to healthy controls. However, pharmacological treatment did not produce any identifiable alterations on the biomechanics of gait of the PAD patients as revealed by the statistical comparisons performed between pre and post-treatment and between post-treatment and the healthy controls.

Conclusions

Pharmacological treatment did not result in statistically significant improvements in the gait biomechanics of patients with symptomatic PAD. Future studies will need to further explore different cohorts of patients that have shown to improve significantly their claudication distances and/or their muscle fiber morphology with the use of pharmacological treatment and determine if this is associated with an improvement in gait biomechanics. Using these methods we may distinguish the patients who benefit from pharmacotherapy and those who do not.
Intracytoplasmic stable expression of IgG1 antibody targeting NS3 helicase inhibits replication of highly efficient hepatitis C Virus 2a clone
Authors: Chandra Partha K , Hazari Sidhartha , Poat Bret , Gunduz Feyza , Prabhu Ramesh , Liu Gerald , Burioni Roberto , Clementi Massimo , Garry Robert F , Dash Srikanta
Published: June 2010

Background

Hepatitis C virus (HCV) infection is a major public health problem with more than 170 million cases of chronic infections worldwide. There is no protective vaccine currently available for HCV, therefore the development of novel strategy to prevent chronic infection is important. We reported earlier that a recombinant human antibody clone blocks viral NS3 helicase activity and inhibits replication of HCV 1b virus. This study was performed further to explore the mechanism of action of this recombinant antibody and to determine whether or not this antibody inhibits replication and infectivity of a highly efficient JFH1 HCV 2a virus clone.

Results

The antiviral effect of intracellular expressed antibody against the HCV 2a virus strain was examined using a full-length green fluorescence protein (GFP) labeled infectious cell culture system. For this purpose, a Huh-7.5 cell line stably expressing the NS3 helicase gene specific IgG1 antibody was prepared. Replication of full-length HCV-GFP chimera RNA and negative-strand RNA was strongly inhibited in Huh-7.5 cells stably expressing NS3 antibody but not in the cells expressing an unrelated control antibody. Huh-7.5 cells stably expressing NS3 helicase antibody effectively suppressed infectious virus production after natural infection and the level of HCV in the cell free supernatant remained undetectable after first passage. In contrast, Huh-7.5 cells stably expressing an control antibody against influenza virus had no effect on virus production and high-levels of infectious HCV were detected in culture supernatants over four rounds of infectivity assay. A recombinant adenovirus based expression system was used to demonstrate that Huh-7.5 replicon cell line expressing the intracellular antibody strongly inhibited the replication of HCV-GFP RNA.

Conclusion

Recombinant human anti-HCV NS3 antibody clone inhibits replication of HCV 2a virus and infectious virus production. Intracellular expression of this recombinant antibody offers a potential antiviral strategy to inhibit intracellular HCV replication and production.
Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles
Authors: Venkatachari Narasimhan J , Walker Leah A , Tastan Oznur , Le Thien , Dempsey Timothy M , Li Yaming , Yanamala Naveena , Srinivasan Alagarsamy , Klein-Seetharaman Judith , Montelaro Ronald C , Ayyavoo Velpandi
Published: June 2010

HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC) method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection.
Detection of squirrel poxvirus by nested and real-time PCR from red (Sciurus vulgaris) and grey (Sciurus carolinensis) squirrels
Authors: Atkin Janus W , Radford Alan D , Coyne Karen P , Stavisky Jenny , Chantrey Julian
Published: June 2010

Background

Squirrel poxvirus (SQPV) is highly pathogenic to red squirrels (Sciurus vulgaris), and is a significant contributing factor to the local extinction of the species in most parts of England and Wales, where infection is endemic in Eastern grey squirrel (Sciurus carolinensis) populations. Although a nested PCR assay has been used successfully to study the epidemiology of SQPV, samples have a long processing time and the assay is not quantifiable.

Results

This project describes the design and optimization of a real-time PCR for SQPV. Comparison with the nested PCR showed the real-time assay to be more sensitive by one log and able to detect approximately 144 genome copies per mg of tissue.

Conclusions

The real-time PCR has been used to quantify viral genome load in tissues from diseased and apparently healthy red and grey squirrels, and suggests that the titre of virus in tissues from diseased red squirrels is considerably higher than that found even in a grey squirrel with cutaneous lesions.
The biological context of HIV-1 host interactions reveals subtle insights into a system hijack
Authors: Dickerson Jonathan E , Pinney John W , Robertson David L
Published: June 2010

Background

In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.

Results

After correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.

Conclusions

Our results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.
A circuit model of the temporal pattern generator of Caenorhabditis egg-laying behavior
Authors: Zhang Mi , Schafer William R , Breitling Rainer
Published: June 2010

Background

Egg-laying behavior in the nematode C. elegans displays a distinct clustered temporal pattern: egg-laying events occur primarily in bursts or active phases, separated by inactive phases during which eggs are retained. The onset of the active phase can be modeled as a Poisson process with a time constant of approximately 20 minutes, while egg-laying events within an active phase occur with a faster time constant of approximately 20 seconds. Here we propose a cellular model for how the temporal pattern of egg-laying might be generated, based on genetic and cell-biological experiments and statistical analyses.

Results

We suggest that the HSN neuron is the executive neuron driving egg-laying events. We propose that the VC neurons act as "single egg counters" that inhibit HSN activity for short periods in response to individual egg-laying events. We further propose that the uv1 neuroendocrine cells are "cluster counters", which inhibit HSN activity for longer periods and are responsible for the time constant of the inactive phase. Together they form an integrated circuit that drives the clustered egg-laying pattern.

Conclusions

The detailed predictions derived from this model can now be tested by straightforward validation experiments.
Evaluation of neonatally-induced mild diabetes in rats: Maternal and fetal repercussions
Authors: Iessi Isabela L , Bueno Aline , Sinzato Yuri K , Taylor Kristin N , Rudge Marilza VC , Damasceno Débora C
Published: June 2010

Many experimental studies have been performed to evaluate mild diabetes effects. However, results are divergent regarding glycemia and insulin measurement, fetal macrossomia, and placental weights. The aim was to investigate repercussions of neonatally-induced mild diabetes on the maternal organism and presence of congenital defects in their offspring in other mild diabetes model. On the day of birth, female offspring were distributed into two groups: Group streptozotocin (STZ): received 100 mg STZ/kg body weight, and Control Group: received vehicle in a similar time period. Maternal weights and glycemias were determined at days 0, 7, 14 and 21 of pregnancy. At day 21 of pregnancy, the rats were anesthetized and a laparotomy was performed to weigh and analyze living fetuses and placentas. The fetuses were classified as small (SPA), appropriate (APA) and large (LPA) for pregnancy age. Fetuses were also analyzed for the presence of external anomalies and processed for skeletal anomaly and ossification sites analysis. Statistical significance was considered as p < 0.05. In STZ group, there was increased glycemia at 0 and 14 days of pregnancy, lower weights throughout pregnancy, higher placental weight and index, an increased proportion of fetuses classified as SPA and LPA, and their fetuses presented with an increased frequency of abnormal sternebra, and absent cervical nuclei, which were not enough to cause the emergence of skeletal anomalies. Thus, this study shows that mild diabetes altered fetal development, characterized by intrauterine growth restriction. Further, the reached glycemia does not lead to any major congenital defects in the fetuses of streptozotocin-induced mild diabetic rats.
UHRF1 is a genome caretaker that facilitates the DNA damage response to γ-irradiation
Authors: Mistry Helena , Tamblyn Laura , Butt Hussein , Sisgoreo Daniel , Gracias Aileen , Larin Meghan , Gopalakrishnan Kalpana , Hande Manoor Prakash , McPherson John Peter
Published: June 2010

Background

DNA double-strand breaks (DSBs) caused by ionizing radiation or by the stalling of DNA replication forks are among the most deleterious forms of DNA damage. The ability of cells to recognize and repair DSBs requires post-translational modifications to histones and other proteins that facilitate access to lesions in compacted chromatin, however our understanding of these processes remains incomplete. UHRF1 is an E3 ubiquitin ligase that has previously been linked to events that regulate chromatin remodeling and epigenetic maintenance. Previous studies have demonstrated that loss of UHRF1 increases the sensitivity of cells to DNA damage however the role of UHRF1 in this response is unclear.

Results

We demonstrate that UHRF1 plays a critical role for facilitating the response to DSB damage caused by γ-irradiation. UHRF1-depleted cells exhibit increased sensitivity to γ-irradiation, suggesting a compromised cellular response to DSBs. UHRF1-depleted cells show impaired cell cycle arrest and an impaired accumulation of histone H2AX phosphorylation (γH2AX) in response to γ-irradiation compared to control cells. We also demonstrate that UHRF1 is required for genome integrity, in that UHRF1-depleted cells displayed an increased frequency of chromosomal aberrations compared to control cells.

Conclusions

Our findings indicate a critical role for UHRF1 in maintenance of chromosome integrity and an optimal response to DSB damage.
Radiation-induced DNA damage and repair in human γδ and αβ T-lymphocytes analysed by the alkaline comet assay
Authors: Lisowska Halina , Deperas-Kaminska Marta , Haghdoost Siamak , Parmryd Ingela , Wojcik Andrzej
Published: June 2010

It has been shown by a number of authors that the radiosensitivity of peripheral blood mononuclear cells (PBMC) is higher in cancer patients compared to healthy donors, which is interpreted as a sign of genomic instability. PBMC are composed of different cell subpopulations which are differently radiosensitive and the difference between cancer patients and healthy donors could also be due to different composition of their PBMC pools. Gamma-delta T-lymphocytes play an important role in immunosurveillance and are promising cells for immunotherapy. Their abundance is frequently reduced in cancer patients so should their sensitivity to radiation be lower than that of other T-lymphocytes, this could, at least partly explain the low radiosensitivity of PBMC from healthy individuals compared to cancer patients. The present investigation was carried out to test this. Using the alkaline comet assay we analysed the level of DNA damage and repair in isolated γδ T-lymphocytes, pan T-lymphocytes and in total PBMC exposed in vitro to gamma radiation. We found no difference in the level of DNA damage and the capacity of DNA repair between the T cell populations. This is the first study that addresses the question of sensitivity to radiation of gamma-delta T-cells.
Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases
Authors: Takahashi Yuko , Haga Shiori , Ishizaka Yukihito , Mimori Akio
Published: June 2010

Introduction

Angiotensin-converting enzyme (ACE) 2, a homolog of ACE, converts angiotensin (Ang) II into Ang(1-7), and the vasoprotective effects of Ang(1-7) have been documented. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with connective tissue diseases to constrictive vasculopathy, pulmonary arterial hypertension (PAH), or persistent digital ischemia.

Methods

Serum was examined from 42 patients with systemic lupus erythematosus (SLE), scleroderma, or mixed connective tissue disease. Eighteen vasculopathy patients with PAH (five cases) and/or persistent digital ischemia (16 cases) were compared with 24 patients without these vasculopathies (control patients) for serum reactivity to purified recombinant human ACE2, using an ELISA.

Results

The sera from 17 of the 18 (94%) vasculopathy patients had ELISA scores above the baseline level determined using control sera from 28 healthy subjects, and the mean ELISA score in the vasculopathy patients was significantly higher than that in the control patients (P < 0.0005). The relative activity of serum ACE2, which was defined using a reference serum, correlated inversely with the ELISA scores for serum anti-ACE2 antibodies in the 18 vasculopathy patients (R2 = 0.6872). The IgG fraction from vasculopathy patients, but not from healthy subjects, inhibited ACE2 activities in vitro. Consistent with this, immunosuppressive therapy given to one SLE patient with digital necrosis markedly decreased the anti-ACE2 antibody titer and restored serum ACE2 activity.

Conclusions

Autoantibodies to ACE2 may be associated with constrictive vasculopathies.
Extravascular lung water index measurement in critically ill children does not correlate with a chest x-ray score of pulmonary edema
Authors: Lemson Joris , van Die Lya E , Hemelaar Anique EA , van der Hoeven Johannes G
Published: June 2010

Introduction

Extravascular lung water index (EVLWI) can be measured at the bedside using the transpulmonary thermodilution technique (TPTD). The goal of this study was to compare EVLWI values with a chest x-ray score of pulmonary edema and markers of oxygenation in critically ill children.

Methods

This was a prospective observational study in a pediatric intensive care unit of a university hospital. We included 27 critically ill children with an indication for advanced invasive hemodynamic monitoring. No specific interventions for the purpose of the study were carried out. Measurements included EVLWI and other relevant hemodynamic variables. Blood gas analysis, ventilator parameters, chest x-ray and TPTD measurements were obtained within a three-hour time frame. Two radiologists assessed the chest x-ray and determined a score for pulmonary edema.

Results

A total of 103 measurements from 24 patients were eligible for final analysis. Mean age was two years (range: two months to eight years). Median cardiac index was 4.00 (range: 1.65 to 10.85) l/min/m2. Median EVLWI was 16 (range: 6 to 31) ml/kg. The weighted kappa between the chest x-ray scores of the two radiologists was 0.53. There was no significant correlation between EVLWI or chest x-ray score and the number of ventilator days, severity of illness or markers of oxygenation. There was no correlation between EVLWI and the chest x-ray score. EVLWI was significantly correlated with age and length (r2 of 0.47 and 0.67 respectively).

Conclusions

The extravascular lung water index in critically ill children does not correlate with a chest x-ray score of pulmonary edema, nor with markers of oxygenation.
Role of Three-Dimensional Echocardiography in Breast Cancer: Comparison With Two-Dimensional Echocardiography, Multiple-Gated Acquisition Scans, and Cardiac Magnetic Resonance Imaging
Authors: Walker Jonathan , Bhullar Navdeep , Fallah-Rad Nazanin , Lytwyn Matthew , Golian Mehrdad , Fang Tielan , Summers Arthur R. , Singal Pawan K. , Barac Ivan , Kirkpatrick Iain D. , Jassal Davinder S.
Published: June 2010

Purpose

In patients with breast cancer, the administration of doxorubicin and trastuzumab is associated with an increased risk of cardiotoxicity. Although multiple-gated acquisition (MUGA) scans and two-dimensional transthoracic echocardiography (TTE) are conventional methods for baseline and serial assessment of left ventricular ejection fraction (LVEF) in these patients, little is known about the use of real-time three-dimensional TTE (RT3D TTE) in this clinical setting. The aim of this study was to assess the accuracy of MUGA, 2D TTE, and RT3D TTE for determining LVEF in comparison to cardiac magnetic resonance imaging (CMR).

Methods

Between 2007 and 2009 inclusive, 50 female patients with human epidermal growth factor receptor 2–positive breast cancer received adjuvant trastuzumab after doxorubicin. Serial MUGA, 2D TTE, RT3D TTE, and CMR were performed at baseline, 6, and 12 months after the initiation of trastuzumab.

Results

A comparison of left ventricular end diastolic volume (LVEDV) demonstrated a modest correlation between 2D TTE and CMR (r = 0.64 at baseline; r = 0.69 at 12 months, respectively). A comparison of LVEDV between RT3D TTE and CMR demonstrated a stronger correlation (r = 0.87 at baseline; r = 0.95 at 12 months, respectively). Although 2D TTE demonstrated a weak correlation with CMR for LVEF assessment (r = 0.31 at baseline, r = 0.42 at 12 months, respectively), both RT3D TTE and MUGA showed a strong correlation when compared with CMR (r = 0.91 at baseline; r = 0.90 at 12 months, respectively).

Conclusion

As compared with conventional MUGA, RT3D TTE is a feasible, accurate, and reproducible alternate imaging modality for the serial monitoring of LVEF in patients with breast cancer.
Quality of Care for Breast Cancer for Uninsured Women in California Under the Breast and Cervical Cancer Prevention Treatment Act
Authors: Malin Jennifer L. , Diamant Allison L. , Leake Barbara , Liu Yihang , Thind Amardeep , Kahn Katherine L. , Schneider Eric C. , Epstein Arnold M. , Maly Rose C.
Published: June 2010

Purpose

The objective of this study was to evaluate the quality of care provided to uninsured women with breast cancer who received treatment through the Breast and Cervical Cancer Prevention Treatment Program (BCCTP).

Methods

Participants included women with stage I to III breast cancer (n = 658) from a consecutive sample of women 18 years or older who received coverage through the California BCCTP between February 2003 and September 2005 who consented to a survey and medical record review (61% response rate). Quality of breast cancer care was evaluated using 29 evidence-based quality measures developed for the National Initiative for Cancer Care Quality (NICCQ). NICCQ, a largely insured cohort of women diagnosed with stage I to III breast cancer in 1998, was used to benchmark the results.

Results

Twenty-three percent of women presented with stage III disease compared with fewer than 10% nationally. Patients received 93% of recommended care (95% CI, 92% to 93%). Adherence to recommended care within domains ranged from 87% for post-treatment surveillance (95% CI, 84% to 90%) to 97% for diagnostic evaluation (95% CI, 96% to 97%). Compared to the NICCQ cohort, adherence to quality measures was as good or better for the BCCPT cohort in all domains except post-treatment surveillance.

Conclusion

The BCCTP has made important inroads in providing poor, uninsured women with access to high quality care when faced with the diagnosis of breast cancer; however, many present at an advanced stage, which is associated with worse outcomes.
CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells
Authors: O'Brien Karen B. , Alberich-Jordà Meritxell , Yadav Neelu , Kocher Olivier , DiRuscio Annalisa , Ebralidze Alexander , Levantini Elena , Sng Natasha J. L. , Bhasin Manoj , Caron Tyler , Kim Daehoon , Steidl Ulrich , Huang Gang , Halmos Balázs , Rodig Scott J. , Bedford Mark T. , Tenen Daniel G. , Kobayashi Susumu
Published: June 2010

Coactivator-associated arginine methyltransferase I (CARM1; PRMT4) regulates gene expression by multiple mechanisms including methylation of histones and coactivation of steroid receptor transcription. Mice lacking CARM1 are small, fail to breathe and die shortly after birth, demonstrating the crucial role of CARM1 in development. In adults, CARM1 is overexpressed in human grade-III breast tumors and prostate adenocarcinomas, and knockdown of CARM1 inhibits proliferation of breast and prostate cancer cell lines. Based on these observations, we hypothesized that loss of CARM1 in mouse embryos would inhibit pulmonary cell proliferation, resulting in respiratory distress. By contrast, we report here that loss of CARM1 results in hyperproliferation of pulmonary epithelial cells during embryonic development. The lungs of newborn mice lacking CARM1 have substantially reduced airspace compared with their wild-type littermates. In the absence of CARM1, alveolar type II cells show increased proliferation. Electron microscopic analyses demonstrate that lungs from mice lacking CARM1 have immature alveolar type II cells and an absence of alveolar type I cells. Gene expression analysis reveals a dysregulation of cell cycle genes and markers of differentiation in the Carm1 knockout lung. Furthermore, there is an overlap in gene expression in the Carm1 knockout and the glucocorticoid receptor knockout lung, suggesting that hyperproliferation and lack of maturation of the alveolar cells are at least in part caused by attenuation of glucocorticoid-mediated signaling. These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells.
Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis
Authors: Buschmann Ivo , Pries Axel , Styp-Rekowska Beata , Hillmeister Philipp , Loufrani Laurent , Henrion Daniel , Shi Yu , Duelsner Andre , Hoefer Imo , Gatzke Nora , Wang Haitao , Lehmann Kerstin , Ulm Lena , Ritter Zully , Hauff Peter , Hlushchuk Ruslan , Djonov Valentin , van Veen Toon , le Noble Ferdinand
Published: June 2010

In the developing chicken embryo yolk sac vasculature, the expression of arterial identity genes requires arterial hemodynamic conditions. We hypothesize that arterial flow must provide a unique signal that is relevant for supporting arterial identity gene expression and is absent in veins. We analyzed factors related to flow, pressure and oxygenation in the chicken embryo vitelline vasculature in vivo. The best discrimination between arteries and veins was obtained by calculating the maximal pulsatile increase in shear rate relative to the time-averaged shear rate in the same vessel: the relative pulse slope index (RPSI). RPSI was significantly higher in arteries than veins. Arterial endothelial cells exposed to pulsatile shear in vitro augmented arterial marker expression as compared with exposure to constant shear. The expression of Gja5 correlated with arterial flow patterns: the redistribution of arterial flow provoked by vitelline artery ligation resulted in flow-driven collateral arterial network formation and was associated with increased expression of Gja5. In situ hybridization in normal and ligation embryos confirmed that Gja5 expression is confined to arteries and regulated by flow. In mice, Gja5 (connexin 40) was also expressed in arteries. In the adult, increased flow drives arteriogenesis and the formation of collateral arterial networks in peripheral occlusive diseases. Genetic ablation of Gja5 function in mice resulted in reduced arteriogenesis in two occlusion models. We conclude that pulsatile shear patterns may be central for supporting arterial identity, and that arterial Gja5 expression plays a functional role in flow-driven arteriogenesis.
Parallel auto-parking of a model vehicle using a self-organizing fuzzy controller
Authors: Huang S-J , Lin G-Y
Published: June 2010

The vehicle backward auto-parking process can be divided into three steps. First, the relative position between the Ego car and an available parking space should be detected using additional sensors, and the two-dimensional (2D) environmental map can be constructed. Then, the optimal parking trajectory is planned online based on this 2D environmental map. Finally, the auto-parking controller executes the real-time vehicle motion path estimation and the planned parking trajectory-tracking control. Here, multiple ultrasonic sensors were installed on a model vehicle to construct the 2D map of the area surrounding the vehicle. A sinusoidal function parking trajectory is planned and the corresponding state variable trajectories of the X and Y components and front-wheel steering angle are derived. A model-free intelligent self-organizing fuzzy controller is proposed to track the parking path by regulating the deviation of a selected state variable. The output command is the real-time front-wheel steering angle. This intelligent controller has a system-learning mechanism without expertise knowledge or a trial-and-error process. It is implemented on a one-sixth model vehicle for experimental study. The experimental results are compared with those of a non-linear feedback linearization controller.
The Emerging Role of Ion/Ion Reactions in Biological Mass Spectrometry: Considerations for Reagent Ion Selection
Authors: McLuckey Scott A.
Published: June 2010

The advent of ionization methods that can produce multiply charged gaseous ions has enabled the development of gas-phase ion/ion reactions in analytical mass spectrometry. Ion/ion chemistry has proved to be a particularly effective means for converting ions from one type to another and allows for a decoupling of the ionization method from the nature of the ion subjected to tandem mass spectrometry. A growing array of applications has been developed based on a variety of reaction types, including electron transfer, proton transfer, charge inversion, metal transfer etc. Most ion/ion reactions take place following the formation of a stable bound orbit between the reactants. As reactants approach closely enough for chemistry to occur, they can react by small charged particle transfer (i.e. electron transfer and proton transfer) at crossing points in the interaction potential. Alternatively, the reactants can collide to form a relatively long-lived complex. A wide range of chemical reactions can result from the long-lived complex, which include multiple charged particle transfers and covalent bond formation. For a given analyte ion, the major reaction pathway is determined by the characteristics of the reagent ion. An appreciation of the factors that underlie the partitioning of ion/ion reaction products is important in the design and selection of reagent ions to effect transformations of interest. Important considerations for reagent ion selection are discussed here within the context of a generalized scheme for ion/ion reaction dynamics.
Mass Spectrometry-Based Characterization of New Drugs and Methods of Performance Manipulation in Doping Control Analysis
Authors: Thevis Mario , Thomas Andreas , Kohler Maxie , Beuck Simon , Möller Ines , Schäfer Mathias , Rodchenkov Grigory , Yin Sheng , Loo Joseph A. , Geyer Hans , Schänzer Wilhelm
Published: June 2010

Efficient and comprehensive sports drug testing necessitates frequent updating and proactive, preventive anti-doping research and the early implementation of new, emerging drugs into routine doping controls is an essential aspect. Several new drugs and drug candidates with potential for abuse, including so-called Rycals (ryanodine receptor calstabin complex stabilizers, for example, S-107), hypoxia-inducible factor (HIF) stabilizers and peroxisome-proliferator-activated receptor (PPAR) δ agonists (for example, GW1516), were studied using different mass spectrometry- and ion mobility-based approaches and their gas-phase dissociation behaviors were elucidated. The detailed knowledge of fragmentation routes allows a more rapid identification of metabolites and structurally related, presumably “tailor-made”, analogs potentially designed for doping purposes. The utility of product ion characterization is demonstrated, in particular, with GW1516, for which oxidation products were readily identified in urine samples by means of diagnostic fragment ions, as measured using high-resolution/high-accuracy mass spectrometry and higher energy collision-induced dissociation (HCD).
Mixing Laser Spectroscopy and Mass Spectrometry-Infrared Spectra of Metal Cation–Hydrogen Complexes
Authors: Dryza Viktoras , Poad Berwyck L.J. , Bieske Evan J.
Published: June 2010

We describe recent experiments in which mass spectrometry and laser spectroscopy are combined to characterize Li+–H2, Na+–H2, B+–H2 and Al+–H2 complexes in the gas-phase. The infrared spectra, which feature full resolution of rotational sub-structures, are recorded by monitoring M+ photofragments as the infrared wavelength is scanned. The spectra deliver detailed information on the way, in which a hydrogen molecule is attached to a metal cation including the intermolecular separation, the force constant for the intermolecular bond and the H–H stretching frequency. The complexes all possess T-shaped equilibrium geometries and display a clear correlation between the length and force constant of the intermolecular bond and the dissociation energy. In contrast, the data do not support any straight forward correlation between the frequency shift for the H–H stretch mode and the dissociation energy.
Multi-Step Evolution of Protein Conformation on Electrospray into the Gas Phase
Authors: McLafferty Fred W. , Castro Sergio , Breuker Kathrin
Published: June 2010

In the gas phase, some properties of native versus denatured protein conformations correspond to those in solution, such as affinity for protons and physical cross section. However, the capacity for hydrogen/deuterium exchange is the opposite, with ubiquitin 7+ and 13+ ions exchanging > 60 D and ~15 D atoms, respectively. A variety of experimental methods now delineate a series of conformational perturbations that can occur in the 10−12 s to 10+2 s following electrospray, including side-chain collapse, hydrophobic and electrostatic non-covalent bond unfolding and refolding into a variety of non-native structures.
Inductively-Coupled Plasma Mass Spectrometry in Proteomics, Metabolomics and Metallomics Studies
Authors: Mounicou Sandra , Szpunar Joanna , Lobinski Ryszard
Published: June 2010

The potential of inductively-coupled plasma mass spectrometry (ICP-MS) and its complementarity to soft-ionization MS techniques are discussed in the context of the analysis for biomolecules. ICP-MS offers detection limits in the attomolar range, regardless of the molecular environment of the target element. The sensitivity is hardly affected by the sample matrix, chromatographic mobile phase, or co-eluted compounds. The abundance sensitivity over six decades and the linear dynamic range over nine decades make simultaneous multi-isotopic analysis routinely possible. The manuscript discusses the state-of-the-art of ICP-MS for the detection of proteins in gel electrophoresis and of peptides in 2D high-performance liquid chromatography. The possibilities of quantification to the degree of some post-translational modifications are highlighted. Attention is also paid to the role of ICP-MS in protein quantification via metal-coded labeling and to the use of differentially-labeled antibodies for the multiplexed biomarker analysis. The key role of ICP-MS in the emerging area of metallomics is briefly discussed.
Structures of Products from Positive Ion–Molecule Reactions by Means of Vibrational Spectroscopy
Authors: Oomens Jos , Morton Thomas Hellman
Published: June 2010

Examples of various approaches to determining gaseous ion structures are described. Two cases are presented in which infrared multiple photon dissociation (IRMPD) spectroscopy provides characteristic information. Comparison with DFT-calculated normal modes differentiates isomers. The IRMPD spectrum of the even-electron C8D8F+ product ion from the ion–molecule reaction of CF3+ with perdeuterated acetophenone exhibits a degree of resolution sufficient to identify C6D5CFCD3+ and rule out ring-fluorinated isomers. The dimerization of phenylacetylene with its molecular ion has been explored, with the conclusion that a mixture of product ions is formed. The best match to the experimental spectrum is achieved by superimposing the bands calculated for ionized 1-phenylazulene and ionized 1,2-diphenylcyclobutadiene.
Surface Studies of Heterogeneous Catalysts by Time-of-Flight Secondary Ion Mass Spectrometry
Authors: Grams Jacek
Published: June 2010

The aim of this paper was to present potentialities of time-of-flight secondary ion mass spectrometry (ToF-SIMS) in the studies of heterogeneous catalysts. The results of ToF-SIMS investigations of Co/Al2O3, Mo/Al2O3, Co–Mo/Al2O3, Au/Al2O3, Pt/TiO2 and Pd/TiO2 systems were described. It was demonstrated that, in this case, an application of ToF-SIMS makes possible the determination of surface composition of investigated catalysts (including an identification of surface contaminants), characterization of interactions between an active phase and support, estimation of active phase dispersion on the analyzed surface, comparison of the degree of metal oxidation after treatment of the catalyst in different conditions, investigation of catalyst deactivation processes (formation of new chemical compounds, adsorption of various impurities and poisons on the catalyst surface) and determination of organic precursors of catalysts.
Electrochemical Reactions and Ionization Processes
Authors: Girault Hubert , Liu BaoHong , Qiao Liang , Bi HongYan , Prudent Michel , Lion Niels , Abonnenc Mélanie
Published: June 2010

Electrochemical or photo-electrochemical reactions in both electrospray ionization and laser desorption ionization are discussed stressing the role of the electrode reaction in influencing the ionization process. In particular, upon application of a high voltage during electrospray ionization, the emitter includes a working electrode, where redox reactions are observed, such as electro-generation of benzoquinone and metal ions. In contrast, the target plate in laser-induced desorption ionization also acts as a photo-electrode, especially when modified with a mesoporous semiconductor. We illustrate here how these electrochemical reactions can be used for tagging purposes and for oxidative or reductive dissociation reactions.
From Homo Economicus to Homo Sapiens
Authors: Thaler Richard H
Published: June 2010

In responding to a request for predictions about the future of economics, I predict that Homo Economicus will evolve into Homo Sapiens, or, more simply put, economics will become more related to human behavior. My specific predictions are that Homo Economicus will start to lose IQ, will become a slower learner, will start interacting with other species, and that economists will start to study human cognition, human emotion, and will distinguish more clearly between normative and descriptive theories.
The Future of Microeconomic Theory
Authors: Allen Beth
Published: June 2010

The question of what constitutes good economic theory is analyzed. Current good and bad aspects of its methodologies are discussed. Interdisciplinary work that goes beyond the social sciences is advocated. The future predictions are presented concerning research in game theory and the economics of information. Finally, the importance of technology and the need for microeconomists to understand it better are argued.
How Far Will International Economic Integration Go?
Authors: Rodrik Dani
Published: June 2010

This article speculates about the future of the world economy 100 years from now. It argues that the spread of markets is restricted by the reach of jurisdictional boundaries, and that national sovereignty imposes serious constraints on international economic integration. The political trilemma of the world economy is that international economic integration, the nation-state, and mass politics cannot co-exist. We have to pick two out of three. The article predicts that it will be the nation-state system that disappears, with global federalism taking its place.
Environmental Problems and Policy: 2000–2050
Authors: Portney Paul R
Published: June 2010

The next 50 years will see more use of market-based tools for environmental protection. Regulatory authorities everywhere will require polluters to report emissions. Authority will leak away from national governments; some will be devolved to lower levels of government, but some will be lost to international bodies. Environmental conditions will continue to improve steadily in developed countries. The developing countries will be less fortunate; at least until rising incomes provide the impetus for stricter standards. Some losses will be irreversible, as with species that are extinguished.