bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus
Authors: Dolff Sebastian , Quandt Daniel , Wilde Benjamin , Feldkamp Thorsten , Hua Fan , Cai Xin , Specker Christof , Kribben Andreas , Kallenberg Cees GM , Witzke Oliver
Published: August 2010

Introduction

There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134.

Methods

Thirty-four patients (3 male, 31 female, mean age 41 ± 15 years) fulfilling at least four of the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE and 24 healthy controls were enrolled. T-cells from the peripheral blood were analysed by fluorescence activated cell sorting (FACS) for their expression levels of CD80, CD134 and CCR6. In vitro stimulated CD3+IL17+ cells were also investigated for the expression of these costimulatory markers. Finally, renal biopsies from SLE patients were evaluated for the presence of CD134 expressing T-cells.

Results

Percentages of IL-17 expressing T-cells were significantly increased in patients with active disease as compared to healthy controls (1.46 ± 0.58% versus 0.93 ± 0.30%, P = 0.007). The percentage of IL-17 producing T-cells was correlated with disease activity as assessed by systemic lupus erythematosus disease activity index (SLEDAI) (r = 0.53, P = 0.003). In patients, most of the IL-17 producing T-cells were confined to the CCR6
+
T-cell subset (80 ± 13%). Expression of CD80 and CD134 on the IL-17 producing T-cell subset was higher in SLE than in healthy controls (HC) (CD134: 71.78 ± 14.51% versus 51.45 ± 16.58%, P = 0.002; CD80: 25.5 ± 14.99% versus 14.99 ± 5.74%, P = 0.02). Also, patients with lupus nephritis expressed higher levels of CD134
+
on CD3+IL-17+ cells as compared to HC (72.69 ± 11.54% versus 51.45 ± 16.58%, P = 0.006). Furthermore, renal biopsies of lupus nephritis patients showed infiltration of CD134+ T cells.

Conclusions

Percentages of IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134+ T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion.
Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold capillaroscopy for assessment of digital microcirculation in systemic sclerosis
Authors: Correa Marcelo JU , Andrade Luis EC , Kayser Cristiane
Published: August 2010

Introduction

Laser Doppler imaging (LDI) is a relatively new method for assessing the functional aspect of superficial skin blood flow in systemic sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the dynamic behavior of digital skin microvascular blood flow before and after cold stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)), and biochemical (fingertip lacticemy (FTL)) microcirculation components.

Methods

Forty-four SSc patients and 40 healthy controls were included. After acclimatization, all subjects underwent NFC followed by LDI and FTL measurement. NFC was performed with a stereomicroscope under 10× to 20× magnification in the 10 digits of the hands. Skin blood flow of the dorsum of four fingertips (excluding the thumb) of the left hand was measured using LDI at baseline and for 30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was expressed as arbitrary perfusion units. FTL was determined on the fourth left finger before (pre-CS-FTL) and 10 minutes after CS.

Results

LDI showed significantly lower mean baseline FBF in SSc patients as compared with controls (296.9 ± 208.8 vs. 503.6 ± 146.4 perfusion units; P < 0.001) and also at all time points after CS (P < 0.001). There was a significant decrease in mean FBF after CS as compared with baseline in SSc patients and in controls, followed by recovery of the blood flow 27 minutes after CS in healthy controls, but not in SSc patients. FBF tended to be lower in patients with digital scars and previous ulceration/amputation (P = 0.06). There was no correlation between mean baseline FBF and NFC parameters. Interestingly, there was a negative correlation between FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc patients.

Conclusions

LDI showed lower digital blood flow in SSc patients when compared with healthy controls and correlated well with FTL both at baseline and after CS, allowing objective measurement of blood perfusion in SSc patients. The lack of correlation between functional and morphological microvascular abnormalities, measured by LDI and NFC, suggests they are complementary tools for evaluation of independent microangiopathy aspects in SSc patients.
Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations
Authors: Koay Debbie C , Zerillo Cynthia , Narayan Murli , Harris Lyndsay N , DiGiovanna Michael P
Published: August 2010

Introduction

HER2 and estrogen receptor (ER) are important in breast cancer and are therapeutic targets of trastuzumab (Herceptin) and tamoxifen, respectively. Retinoids inhibit breast cancer growth, and modulate signaling by HER2 and ER. We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects.

Methods

The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture, BT474 and SKBR3. Assays of proliferation, apoptosis, differentiation, cell cycle distribution, and receptor signaling were performed.

Results

In HER2-overexpressing/ER-positive BT474 cells, combining all-trans retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell growth, and altered cell differentiation and cell cycle. Only atRA/trastuzumab-containing combinations induced apoptosis. BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids (atRA, 9-cis-retinoic acid, 13-cis-retinoic acid, or N-(4-hydroxyphenyl) retinamide (fenretinide) (4-HPR)) combined with trastuzumab. In BT474 cells, none of the single agents except 4-HPR induced apoptosis, but again combinations of each retinoid with trastuzumab did induce apoptosis. In contrast, the single retinoid agents did cause apoptosis in SKBR3 cells; this was only modestly enhanced by addition of trastuzumab. The retinoid drug combinations altered signaling by HER2 and ER. Retinoids were inactive in trastuzumab-resistant BT474 cells.

Conclusions

Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells. Treatment with such combinations may have benefit for breast cancer patients.
Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial
Authors: Jhanji Shaman , Vivian-Smith Amanda , Lucena-Amaro Susana , Watson David , Hinds Charles J , Pearse Rupert M
Published: August 2010

Introduction

Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.

Methods

Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).

Results

135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).

Conclusions

Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.

Trial registration number

ISRCTN 94850719
Multiple distinct small RNAs originate from the same microRNA precursors
Authors: Zhang Weixiong , Gao Shang , Zhou Xuefeng , Xia Jing , Chellappan Padmanabhan , Zhou Xiang , Zhang Xiaoming , Jin Hailing
Published: August 2010

Background

MicroRNAs (miRNAs), which originate from precursor transcripts with stem-loop structures, are essential gene expression regulators in eukaryotes.

Results

We report 19 miRNA precursors in Arabidopsis that can yield multiple distinct miRNA-like RNAs in addition to miRNAs and miRNA*s. These miRNA precursor-derived miRNA-like RNAs are often arranged in phase and form duplexes with an approximately two-nucleotide 3'-end overhang. Their production depends on the same biogenesis pathway as their sibling miRNAs and does not require RNA-dependent RNA polymerases or RNA polymerase IV. These miRNA-like RNAs are methylated, and many of them are associated with Argonaute proteins. Some of the miRNA-like RNAs are differentially expressed in response to bacterial challenges, and some are more abundant than the cognate miRNAs. Computational and expression analyses demonstrate that some of these miRNA-like RNAs are potentially functional and they target protein-coding genes for silencing. The function of some of these miRNA-like RNAs was further supported by their target cleavage products from the published small RNA degradome data. Our systematic examination of public small-RNA deep sequencing data from four additional plant species (Oryza sativa, Physcomitrella patens, Medicago truncatula and Populus trichocarpa) and four animals (Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila) shows that such miRNA-like RNAs exist broadly in eukaryotes.

Conclusions

We demonstrate that multiple miRNAs could derive from miRNA precursors by sequential processing of Dicer or Dicer-like proteins. Our results suggest that the pool of miRNAs is larger than was previously recognized, and miRNA-mediated gene regulation may be broader and more complex than previously thought.
Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors
Authors: Jones Steven JM , Laskin Janessa , Li Yvonne Y , Griffith Obi L , An Jianghong , Bilenky Mikhail , Butterfield Yaron S , Cezard Timothee , Chuah Eric , Corbett Richard , Fejes Anthony P , Griffith Malachi , Yee John , Martin Montgomery , Mayo Michael , Melnyk Nataliya , Morin Ryan D , Pugh Trevor J , Severson Tesa , Shah Sohrab P , Sutcliffe Margaret , Tam Angela , Terry Jefferson , Thiessen Nina , Thomson Thomas , Varhol Richard , Zeng Thomas , Zhao Yongjun , Moore Richard A , Huntsman David G , Birol Inanc , Hirst Martin , Holt Robert A , Marra Marco A
Published: August 2010

Background

Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.

Results

In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.

Conclusions

We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.
Murine amniotic fluid stem cells contribute mesenchymal but not epithelial components to reconstituted mammary ducts
Authors: Klemmt Petra AB , Vafaizadeh Vida , Groner Bernd
Published: August 2010

Introduction

Amniotic fluid harbors cells indicative of all three germ layers, and pluripotent fetal amniotic fluid stem cells (AFSs) are considered potentially valuable for applications in cellular therapy and tissue engineering. We investigated whether it is possible to direct the cell fate of AFSs in vivo by transplantation experiments into a particular microenvironment, the mammary fat pad. This microenvironment provides the prerequisites to study stem cell function and the communication between mesenchymal and epithelial cells. On clearance of the endogenous epithelium, the ductal tree can be reconstituted by the transfer of exogenously provided mammary stem cells. Analogously, exogenously provided stem cells from other tissues can be investigated for their potential to contribute to mammary gland regeneration.

Methods

We derived pluripotent murine AFSs, measured the expression of stem cell markers, and confirmed their in vitro differentiation potential. AFSs were transplanted into cleared and non cleared fat pads of immunocompromised mice to evaluate their ability to assume particular cell fates under the instructive conditions of the fat-pad microenvironment and the hormonal stimulation during pregnancy.

Results

Transplantation of AFSs into cleared fat pads alone or in the presence of exogenous mammary epithelial cells caused their differentiation into stroma and adipocytes and replaced endogenous mesenchymal components surrounding the ducts in co-transplantation experiments. Similarly, transplantation of AFSs into fat pads that had not been previously cleared led to AFS-derived stromal cells surrounding the elongating endogenous ducts. AFSs expressed the marker protein α-SMA, but did not integrate into the myoepithelial cell layer of the ducts in virgin mice. With pregnancy, a small number of AFS-derived cells were present in acinar structures.

Conclusions

Our data demonstrate that the microenvironmental cues of the mammary fat pad cause AFSs to participate in mammary gland regeneration by providing mesenchymal components to emerging glandular structures, but do not incorporate or differentiate into ductal epithelial cells.
Gas chimney identification through seismic attribute analysis in the Gippsland Basin, Australia
Authors: Nourollah Hadi , Keetley Jeff , O'Brien Geoffrey
Published: August 2010

Chimneys are vertical chaotic disturbances in seismic sections related to the propagation of fluids (especially gas) through fissures and fractures in rocks. They can be indicative of mud diapirism, active gas seepage, migration pathways or hydrocarbon reservoirs themselves (Aminzadeh et al., 2002).
Intellectual Property
Authors: Walker David A.
Published: August 2010

The Intellectual Property department in each issue of Geophysics provides U.S. patent abstracts, published patent abstracts of U.S. patent applications, and published abstracts filed under the Patent Cooperation Treaty (PCT).
Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories
Authors: Baehner Frederick L. , Achacoso Ninah , Maddala Tara , Shak Steve , Quesenberry Charles P. , Goldstein Lynn C. , Gown Allen M. , Habel Laurel A.
Published: August 2010

Purpose

The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate ≥ 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node–negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study.

Patients and Methods

Breast cancer specimens from the Kaiser–Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units ≥ 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines.

Results

HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients.

Conclusion

There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.
Delays in Adjuvant Chemotherapy Treatment Among Patients With Breast Cancer Are More Likely in African American and Hispanic Populations: A National Cohort Study 2004-2006
Authors: Fedewa Stacey A. , Ward Elizabeth M. , Stewart Andrew K. , Edge Stephen B.
Published: August 2010

Purpose

Previous studies have indicated poorer survival among women receiving adjuvant chemotherapy > 90 days after surgery compared with women receiving adjuvant chemotherapy within 90 days of surgery.

Patients and Methods

Women diagnosed between 2004 and 2006 with invasive breast cancer (stages I to III) and treated with surgery and adjuvant chemotherapy were selected from the National Cancer Database (n = 107,587). We evaluated factors associated with prolonged time to start adjuvant chemotherapy (≥ 60 and ≥ 90 days after surgical resection) using multivariable log binomial models to estimate risk ratios (RRs) and 95% CIs.

Results

The average time to adjuvant chemotherapy was 41.46 days (± 24.46 days). Overall, 85.2% and 95.8% of women received adjuvant chemotherapy within 60 and 90 days of surgery, respectively. African American and Hispanic patients had higher risk of 60-day delay (RR, 1.36; 95% CI, 1.30 to 1.41 and RR, 1.31; 95% CI, 1.23 to 1.39, respectively) and 90-day delay (RR, 1.56; 95% CI, 1.44 to 1.69 and RR, 1.41; 95% CI, 1.26 to 1.59, respectively) compared with white patients. Insurance type, stage, comorbidity, and facility type were also associated with adjuvant chemotherapy delay.

Conclusion

The majority of women in our study received adjuvant chemotherapy within the time frame (90 days) for which there is no evidence of poorer outcome. However, the rate of delay varied by patient and by clinical and facility factors. Future studies on the role of structural, physician, clinical, and patient factors in adjuvant chemotherapy delay in populations of women with higher rates of delay and potential interventions are needed.
Technology Evolution: Is It Survival of the Fittest?
Authors: Zietman Anthony , Goitein Michael , Tepper Joel E.
Published: August 2010

New technologies are constantly being developed and introduced into medical practice. Their potential or actual use raises questions of efficacy and cost. All too often financial considerations of profit primarily determine whether a technology will be adopted. In an era in which the need to control costs has become clear, this situation is undesirable. The assessment of efficacy can, however, be very difficult, and the control of financial aspects is likewise problematic. In this article, we address these problems and suggest potential solutions, using proton radiotherapy as an example that may be relevant to the development of other medical devices.
The occipital lateral plate mesoderm is a novel source for vertebrate neck musculature
Authors: Theis Susanne , Patel Ketan , Valasek Petr , Otto Anthony , Pu Qin , Harel Itamar , Tzahor Eldad , Tajbakhsh Shahragim , Christ Bodo , Huang Ruijin
Published: August 2010

In vertebrates, body musculature originates from somites, whereas head muscles originate from the cranial mesoderm. Neck muscles are located in the transition between these regions. We show that the chick occipital lateral plate mesoderm has myogenic capacity and gives rise to large muscles located in the neck and thorax. We present molecular and genetic evidence to show that these muscles not only have a unique origin, but additionally display a distinct temporal development, forming later than any other muscle group described to date. We further report that these muscles, found in the body of the animal, develop like head musculature rather than deploying the programme used by the trunk muscles. Using mouse genetics we reveal that these muscles are formed in trunk muscle mutants but are absent in head muscle mutants. In concordance with this conclusion, their connective tissue is neural crest in origin. Finally, we provide evidence that the mechanism by which these neck muscles develop is conserved in vertebrates.
The Bicoid gradient is shaped independently of nuclei
Authors: Grimm Oliver , Wieschaus Eric
Published: August 2010

Morphogen gradients provide embryos with positional information, yet how they form is not understood. Binding of the morphogen to receptors could affect the formation of the morphogen gradient, in particular if the number of morphogen binding sites changes with time. For morphogens that function as transcription factors, the final distribution can be heavily influenced by the number of nuclear binding sites. Here, we have addressed the role of the increasing number of nuclei during the formation of the Bicoid gradient in embryos of Drosophila melanogaster. Deletion of a short stretch of sequence in Bicoid impairs its nuclear accumulation. This effect is due to a ∼4-fold decrease in nuclear import rate and a ∼2-fold reduction in nuclear residence time compared with the wild-type protein. Surprisingly, the shape of the resulting anterior-posterior gradient as well as the centre-surface distribution are indistinguishable from those of the normal gradient. This suggests that nuclei do not shape the Bicoid gradient but instead function solely during its interpretation.
Making and unmaking myths of the American frontier
Authors: Slatta Richard W.
Published: August 2010

Despite an extensive and expanding body of scholarly studies, myths and myth-making remain a central element of the American West. After placing myth-making about the American West in a wider context, this article explores recent literature about the centrality of myths in envisioning the region. For example, scholars have debunked three of the West's central myths, rugged individualism, American exceptionalism and frontier violence, but all remain alive and well in popular culture and political rhetoric. Among the specific topics analysed are mythologized people (George Armstrong Custer, Buffalo Bill Cody), places (Monument Valley) and cultural production (political, commercial, visual and print). The article also probes the motives and varieties of myth-makers, past and present, and the ways in which women and Native American writers today challenge mythical depictures in traditional western popular culture.
Uptake and metabolism of arsenate, methylarsonate and arsenobetaine by axenic cultures of the phytoplankton Dunaliella tertiolecta
Authors: Duncan Elliott , Foster Simon , Maher William
Published: August 2010

Axenic cultures of the phytoplankton Dunaliella tertiolecta were dosed with either arsenate [As(V)], methylarsonate (MA) or arsenobetaine (AB) at environmentally realistic concentrations (2 μg l-1) to investigate incorporation and transformation of arsenic species. Total arsenic concentrations in cultures dosed with As(V) were significantly higher than those dosed with MA and AB (6–10 μg g-1 compared to 1–3 μg g-1). Arsenic concentrations in As(V)-dosed cultures increased over time, whereas arsenic concentrations in MA- and AB-dosed cultures remained constant, indicating that As(V) is rapidly and continuously incorporated into the cell in comparison to MA and AB. Arsenic was found predominantly in the residue fractions (29–55%) of all cultures, irrespective of culture age. This was attributed to the ability of inorganic arsenic as arsenite [As(III)] to bind to proteins and/or phytochelatins. 2-Dimethylarsinoylethanol (DMAE) was the main arsenic species found in lipid cell fractions. Within the water-soluble and residue cell fractions, arsenic was isolated primarily as As(V), although it is likely the extraction procedure may have converted some As(III) to As(V). Small amounts of As(III), MA, dimethylarsinate (DMA) and arsenoribosides were also found in the lipid and water soluble As fractions. All cultures showed an increase in DMA and arsenoriboside species over time. The significance of these results is that while AB, the major arsenical in marine animals, is not produced or accumulated by this phytoplankton species, the possible precursors to AB formation are produced.
Meiotic Chromosome Segregation in Triploid Strains ofSaccharomyces cerevisiae
Authors: Charles Jordan St , Hamilton Monica L , Petes Thomas D
Published: August 2010

Meiosis in triploids results in four highly aneuploid gametes because six copies of each homolog must be segregated into four meiotic products. Using DNA microarrays and other physical approaches, we examined meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae. In most tetrads with four viable spores, two of the spores had two copies of a given homolog and two spores had only one copy. Chromosomes segregated randomly into viable spores without preferences for generating near haploid or near diploid spores. Using single-nucleotide polymorphisms, we showed that, in most tetrads, all three pairs of homologs recombined. Strains derived from some of the aneuploid spore colonies had very high frequencies of mitotic chromosome loss, resulting in genetically diverse populations of cells.
Prevalence of Streptococcal Pharyngitis and Streptococcal Carriage in Children: A Meta-analysis
Authors: Shaikh Nader , Leonard Erica , Martin Judith M.
Published: August 2010

OBJECTIVES:

Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing of children who present with symptoms of pharyngitis. We conducted a meta-analysis to determine the (1) prevalence of streptococcal infection among children who presented with sore throat and (2) prevalence of streptococcal carriage among asymptomatic children.

METHODS:

We searched Medline for articles on pediatric streptococcal pharyngitis. We included articles in our review when they contained data on the prevalence of group A Streptococcus (GAS) from pharyngeal specimens in children who were younger than 18 years. Two evaluators independently reviewed, rated, and abstracted data from each article. Prevalence estimates were pooled in a meta-analysis and stratified according to age group.

RESULTS:

Of the 266 articles retrieved, 29 met all inclusion criteria. Among children of all ages who present with sore throat, the pooled prevalence of GAS was 37% (95% confidence interval [CI]: 32%–43%). Children who were younger than 5 years had a lower prevalence of GAS (24% [95% CI: 21%–26%]). The prevalence of GAS carriage among well children with no signs or symptoms of pharyngitis was 12% (95% CI: 9%–14%).

CONCLUSIONS:

Prevalence rates of GAS disease and carriage varied by age; children who were younger than 5 years had lower rates of throat cultures that were positive for GAS.
Influence of Deposition Parameters on Surface Texturing of ZnO:Al Films Prepared by In-line RF Magnetron Sputtering
Authors: Cho Jun-Sik , Kim Young-Jin , Lee Jeong Chul , Park Sang-Hyun , Yoon Kyung Hoon
Published: August 2010

A systematic study on the effect of sputtering deposition parameters on material properties of Al doped ZnO (ZnO:Al) films prepared by an in-line rf magnetron sputtering and on surface morphology of the films after wet etching process was carried out. For application to silicon thin film solar cells as a front electrode, the as-deposited films were surface-textured by a dilute HCl solution to improve the light scattering properties such as haze and angle resolved distribution of scattered light on the film surfaces. The microstructure of as-deposited films is affected significantly by the working pressure and film compactness decreases with increasing working pressure from 1.5 mTorr to 10 mTorr. High quality ZnO:Al films with electrical resistivity of 4.25 × 10-4 Ω cm and optical transmittance of 80% in a visible range are obtained at low working pressure of 1.5 mTorr and substrate temperature of 100℃. Crater-like surface morphologies are observed on the textured ZnO:Al films after wet etching. The size and shape of craters are closely dependent on the microstructure and film compactness of as-deposited films. Haze values of the textured ZnO:Al films are improved in a whole wavelength of 300 – 1100 nm compared to commercial SnO2:F films (Asahi U type) and incident light on the textured films is scattered effectively with 30° angle.
Increasing the Potential of Bioactive Glass as a Scaffold for Bone Tissue Engineering
Authors: Ammar Mohamed , Kaplan Max , Quinn Therese , Jedlicka Sabrina
Published: August 2010

Bioactive glass is known for its potential as a bone scaffold due to its ability to stimulate osteogenesis and differentiation of stem cells into bone cells. In an attempt to investigate if we can increase these potentials, we decorated the structure of the bioactive glass made by the sol-gel technique with 3 peptides sequences from different proteins known for their potentials to stimulate the osteogensis process (fibronectin, BMP-2 and protein kinase CKI). This material was tested with Human Mesenchymal Stem Cells (hMSCs) and MC-3T3 preosteoblasts to see the difference in the effect on uncommitted and committed cells. The bioactive glass sol with and without the peptides was dip coated onto glass cover slips, leading to a film of the material, surface decorated with the peptides of choice. The two cell types were seeded onto the materials in standard proliferation medium without additives for differentiation induction. Cells were also grown on tissue culture treated cover slips with and without differentiation induction media as positive and negative controls, respectively. The cells were grown on the materials for a total of five weeks, and were tested at four time points (weekly from week two) by immunocytochemical assays to investigate the levels of different osteogenic markers (osteopontin, osteocalcin and osteonectin) and by qRT-PCR to investigate the mRNA potential of the same proteins. On the native bioactive glass samples, the hMSCs and the MC-3T3s adhered poorly. On peptide-decorated samples, the hMSC adhered poorly, however, the MC-3T3 cells appear to differentiate at a rate that is equal to or faster than the positive control, indicating that the peptide effect is similar to that achieved by traditional BMP-2 soluble protein techniques. This supports our hypothesis that adding specific peptide sequences known for their effects in cells adhesion, proliferation and differentiation can increase the potential of the bioactive glass as a scaffold for bone tissue engineering. The data, however, leads to some questions regarding the MC-3T3 cell model for use in further studies.
Optically Active Defects in an InAsP/InP Quantum Well Monolithically Integrated on SrTiO3 (001)
Authors: Cheng Jun , El Akra Ahiram , Bru-Chevallier Catherine , Patriarche Gilles , LARGEAU Ludovic , Regreny Philippe , Hollinger Guy , Saint-Girons Guillaume
Published: August 2010

The optical properties of an InAsP/InP quantum well grown on a SrTiO3(001) substrate are analyzed. At 13K, the photoluminescence (PL) yield of the well is comparable to that of a reference well grown on an InP substrate. Increasing the temperature leads to the activation of non-radiative mechanisms for the sample grown on SrTiO3. The main non-radiative channel is related to the thermal excitation of the holes to the first heavy hole excited state, followed by the non-radiative recombination of the carriers on twins and/or domain boundaries, in the immediate vicinity of the well.
Island Structured Dielectric Thin Films by Scalable Self-Assembly
Authors: Sriram Sharath , Bhaskaran Madhu , Mitchell Arnan
Published: August 2010

A self-assembly driven process to synthesize island-structured dielectric films is presented. An intermetallic reaction in platinized silicon substrates provides preferential growth sites for the complex oxide dielectric (strontium-doped lead zirconate titanate) layer. Microscopy and spectroscopy analyses have been used to propose a mechanism for this structuring process. This provides a simple and scalable process to synthesize films with increased surface area for sensors, especially those materials with a complex chemistry.
GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin
Authors: Schiariti Michele , Saladini Angela , Papalia Francesco , Grillo Placido , Nesta Cristina , Cuturello Domenico , Missiroli Bindo , Puddu Paolo Emilio
Published: August 2010

Background:

There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world.

Methods:

We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox’s regression.

Results:

There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17).

Conclusions:

In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did.
Review of Matrix Metalloproteinases’ Effect on the Hybrid Dentin Bond Layer Stability and Chlorhexidine Clinical Use to Prevent Bond Failure
Authors: Moon Peter C , Weaver Jared , Brooks Carol N
Published: August 2010

This review describes the relationship between dentin collagen hybrid bond layer degradation and the Matrix Metalloproteinases (MMPs) after their release by acid etch and rinse adhesives and self etching bonding adhesives that can reduce the bond stability over time. MMP-2, MMP-8 and MMP-9 are indicated as the active proteases that breakdown the collagen fibrils in the hybrid bond layer. Phosphoric acid in the acid etch and rinse bonding process and acid primers in the self etch process are implicated in the release of these proteases and their activation by several non-collagen proteins also released from dentin by the etching. MMPs are released in saliva by salivary glands, by cells in the gingival crevices to crevicular fluid and by pulpal odontoblasts cells to the dentinal fluids. These sources may affect the hybrid layer also. Evidence of the bond strength deterioration over time and the ability of Chlorhexidine to prevent bond deterioration by inhibiting MMP action are discussed. Dentin Bonding procedure utilizing Chlorhexidine for different application times and concentrations are being developed. The application of 2% Chlorhexidine to the phosphoric acid etch surface after rinsing off the acid is the only procedure that has been clinically tested for a longer period of time and shown to prevent bond strength degradation so far. The adoption of this procedure is recommended as means of improving bond stability at this time.
Benchmarking the Effectiveness of Universal Designs
Authors: Scott Danford Gary , Grimble Michael , L. Maisel Jordana
Published: August 2010

Evaluating the effectiveness of universally designed environment is typically done through
case studies conducted by experts in field settings. The logistics and costs associated with field case
studies, however, inevitably constrain not only the individuals who can participate, but also the
environments that can be studied - further compromising case studies’ already limited generalizability
and frustrating evidence-based universal design practice. This chapter discusses an alternative standard
for evaluating the effectiveness of universally designed environments that removes these constraints
and enhances case studies’ generalizability by moving them from the field to the internet.
Using Human Factors Research as an Evidence Base
Authors: Steinfeld Edward
Published: August 2010

Human Factors and Ergonomics (HFE) research is a key source of evidence for universal
design. However, the level of knowledge translation from HFE to universal design practice is low, even
though the Principles of Universal Design actually are based on HFE knowledge. Several areas of HFE
research on functional performance have direct relevance to universal design: anthropometry,
biomechanics, perception, and cognition. Knowledge from a relatively new area, emotional design, has
the potential to be especially valuable. Many theories, tools, and research findings from HFE can be
applied in universal design practice. But there are several barriers to increasing knowledge translation
from this field, the most significant being the vast amount of knowledge to assimilate. Three strategies
are proposed to overcome this barrier and bring the two fields into closer alignment. They include
adoption of a system to conceptualize the range of functional performance problems encountered by
people in using the built environment, redefining universal design to make it more directly related to
HFE, and conducting systematic reviews to collect and evaluate knowledge that addresses key design
questions. Adopting these strategies can not only help in knowledge translation from science to practice
but also help HFE research develop an agenda that is more relevant to universal design.
Measuring Physiological and Biomechanical Responses to Cold and Icy Conditions: Preliminary Findings
Authors: A. Hsu Jennifer , Li Yue , Fernie Geoff
Published: August 2010

Studies conducted in countries all over the world have linked winter climate to increased
risks of morbidity and mortality. However, researchers have yet to understand the overall effect of the
winter climate including consequences of such factors as surface conditions on the human body. The
main objectives of this project were to develop a portable ambulatory system for data collection in cold
climates and use it to observe physiological and biomechanical effects of cold temperatures and icy
surfaces. Furthermore, a laboratory-based experiment was designed in order to obtain datasets on 11
young and healthy subjects. Participants were observed in a cold chamber walking at a comfortable
pace in three test conditions: (1) on ice with a safety harness, and on a rough surface while (2) wearing
a harness, and (3) without a harness. The ambulatory monitoring system was used to simultaneously
record blood pressure, heart rate, skin temperature, muscle activity, gait parameters and foot pressure,
and subjective responses were used to derive a comprehensive understanding of the body's responses.
Preliminary findings of this study include results which indicate that heart rate is significantly elevated
prior to traversal over ice and blood pressure rises significantly within ten minutes of exposure to cold
are also presented.
Walking in Winter
Authors: Li Yue , Row Brandi , Hsu Jennifer , Fernie Geoff
Published: August 2010

Winter in many parts of Canada and the US is an enormous problem for older people. We
know that every winter there are many older people who do not get out of their houses for up to three
months because they cannot move around safely in the snow, ice, or slushy conditions. This paper
describes our efforts at the Toronto Rehabilitation Institute to address the difficulties faced by
vulnerable people in winter. The first challenge comes from identifying their perceptions of problems
caused by winter. We have subsequently studied the physiologic response to cold and outdoor walking
behaviour in wintry conditions in order to understand the problems in greater depth and be able to
develop solutions. Emphasis has also been given to investigation of the reported difficulty donning and
doffing winter jackets and coats and the effectiveness and safety of winter footwear. Our continuing
effort will be focused on the universal design of streetscapes, street furniture, winter clothing, footwear,
and improved assistive mobility devices. We are also determining safe exposure levels to cold weather
in order to inform the public of the risks associated with mobility in winter and to provide objective
criteria for public agency responses to ensure safety and social interventions to reduce isolation in
winter.
Post Occupancy Evaluation: Aquarium
Authors: Bruce Carrie
Published: August 2010

Informal learning environments, such as aquaria, are attracting an increasingly diverse visitor
population as the number of people with disabilities living in the community has grown. These
environments are particularly important as they provide unique opportunities for visitors with
disabilities to participate with friends and family in shared educational or entertainment activities that
feature biological diversity and inspire conservation. While there are general guidelines to assist these
settings in designing accessible spaces for visitors with disabilities, they are not specific enough nor do
they guarantee that exhibits will be usable by all visitors. As a result of these issues with current
guidelines, there is a need to understand the barriers and facilitators to exhibit access that are
experienced by visitors with disabilities as a method of providing an evidence base for exhibit design
practice. This paper reports on the findings from a post-occupancy evaluation that was conducted at the
Georgia Aquarium that: 1) documented the current exhibit display and interpretation design practices;
2) provided visitor feedback on the usability of exhibit displays and interpretation; and 3) discussed the
needs of visitors with disabilities. The findings indicate that there are several characteristics of the
display, interpretation, and surrounding exhibit environment that act as barriers or facilitators to exhibit
access for people with disabilities.