bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downloadable Software Algorithm Reduces Inappropriate Shocks Caused by Implantable Cardioverter-Defibrillator Lead Fractures
Authors: Swerdlow Charles D. , Gunderson Bruce D. , Ousdigian Kevin T. , Abeyratne Athula , Sachanandani Haresh , Ellenbogen Kenneth A. 
Published: September 2010

Background—
Downloadable software upgrades are common in consumer electronics but not in implantable medical devices. Fractures of implantable cardioverter-defibrillator (ICD) leads present commonly as inappropriate shocks. A lead-integrity alert (LIA) designed to reduce inappropriate shocks is the first software download approved to enhance nominally functioning, previously implanted ICDs.

Methods and Results—

We performed a prospective study to determine whether an LIA could reduce inappropriate shocks. Patients were included if they had ICD lead fractures confirmed by analysis of explanted leads. The LIA group included the first 213 patients who met the inclusion criteria after the LIA was approved who had the LIA downloaded. The LIA is triggered either by high impedance or rapid oversensing. It responds by delaying detection of ventricular fibrillation and initiating a patient alert every 4 hours. The control group included the first 213 patients who did not have the LIA downloaded. They were monitored by conventional daily impedance measurements that respond with a daily alert. The LIA group had a 46% relative reduction (95% confidence interval 34% to 55%) in the percentage of patients with ≥1 inappropriate shock (LIA 38% versus control 70%,
P
<0.001) and a 50% relative reduction (95% confidence interval 33% to 61%) in the percentage with ≥5 shocks (25% versus 50%,
P
<0.001). The LIA group also had a higher percentage of patients who either did not receive a shock or had ≥3 days of warning before the shock (72% versus 50%,
P
<0.001).

Conclusions—
A software download that upgrades previously implanted ICDs without surgical revision reduces inappropriate shocks caused by lead fractures.
The Influence of El Niño–Southern Oscillation and the Atlantic Multidecadal Oscillation on Caribbean Tropical Cyclone Activity
Authors: Klotzbach Philip J. 
Published: September 2010

Abstract
Caribbean basin tropical cyclone activity shows significant variability on interannual as well as multidecadal time scales. Comprehensive statistics for Caribbean hurricane activity are tabulated, and then large-scale climate features are examined for their impacts on this activity. The primary interannual driver of variability is found to be El Niño–Southern Oscillation, which alters levels of activity due to changes in levels of vertical wind shear as well as through column stability. Much more activity occurs in the Caribbean with La Niña conditions than with El Niño conditions. On the multidecadal time scale, the Atlantic multidecadal oscillation is shown to play a significant role in Caribbean hurricane activity, likely linked to its close relationship with multidecadal alterations in the size of the Atlantic warm pool and the phase of the Atlantic meridional mode. When El Niño–Southern Oscillation and the Atlantic multidecadal oscillation are examined in combination, even stronger relationships are found due to a combination of either favorable or unfavorable dynamic and thermodynamic factors. For example, 29 hurricanes tracked into the Caribbean in the 10 strongest La Niña years in a positive Atlantic multidecadal oscillation period compared with only two hurricanes tracking through the Caribbean in the 10 strongest El Niño years in a negative Atlantic multidecadal oscillation period.
Real-Time Bias Reduction for Satellite-Based Precipitation Estimates
Authors: Tian Yudong , Peters-Lidard Christa D. , Eylander John B. 
Published: September 2010

Abstract
A new approach to reduce biases in satellite-based estimates in real time is proposed and tested in this study. Currently satellite-based precipitation estimates exhibit considerable biases, and there have been many efforts to reduce these biases by merging surface gauge measurements with satellite-based estimates. Most of these efforts require timely availability of surface gauge measurements. The new proposed approach does not require gauge measurements in real time. Instead, the Bayesian logic is used to establish a statistical relationship between satellite estimates and gauge measurements from recent historical data. Then this relationship is applied to real-time satellite estimates when gauge data are not yet available. This new scheme is tested over the United States with six years of precipitation estimates from two real-time satellite products [i.e., the Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) research product 3B42RT and the NOAA Climate Prediction Center (CPC) Morphing technique (CMORPH)] and a gauge analysis dataset [i.e., the CPC unified analysis]. The first 4-yr period was used as the training period to establish a satellite–gauge relationship, which was then applied to the last 2 yr as the correction period, during which gauge data were withheld for training but only used for evaluation. This approach showed that satellite biases were reduced by 70%–100% for the summers in the correction period. In addition, even when sparse networks with only 600 or 300 gauges were used during the training period, the biases were still reduced by 60%–80% and 47%–63%, respectively. The results also show a limitation in this approach as it tends to overadjust both light and strong events toward more intermediate rain rates.
Technology, Design, and Operation of an Autonomous Buoy System in the Western English Channel
Authors: Smyth T. J. , Fishwick J. R. , Gallienne C. P. , Stephens J. A. , Bale A. J. 
Published: September 2010

Abstract
A buoy system has been developed to continually monitor the operationally demanding coastal and open-shelf environment of the western English Channel. The buoys measure a range of physical and biogeochemical parameters on an hourly basis at two established long-term monitoring sites and the data are relayed to shore in near–real time using radio communications. This paper describes the technological challenges faced in such long-term marine deployments including the mooring design, warning systems, command and control, and radio communications, and how each were overcome. The fine temporal frequency data are used within an operational oceanography context, will underpin the long-term sustained observations in the western English Channel, and will form the basis of improvements to finescale ecosystem modeling to better predict any changes in the U.K. shelf seas.
A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors
Authors: Goldstein Matthew J. , Varghese Bindu , Brody Joshua D. , Rajapaksa Ranjani , Kohrt Holbrook , Czerwinski Debra K. , Levy Shoshana , Levy Ronald 
Published: September 2010

AbstractWe designed a whole tumor cell vaccine by “loading” lymphoma tumor cells with CG-enriched oligodeoxynucleotide (CpG), a ligand for the Toll-like receptor 9 (TLR9). CpG-loaded tumor cells were phagocytosed, delivering both tumor antigen(s) and the immunostimulatory CpG molecule to antigen-presenting cells (APCs). These APCs then expressed increased levels of costimulatory molecules and induced T-cell immunity. TLR9 was required in the APCs but not in the CpG-loaded tumor cell. We demonstrate that T cells induced by this vaccine are effective in adoptive cellular therapy for lymphoma. T cells from vaccinated mice transferred into irradiated, syngeneic recipients protected against subsequent lymphoma challenge and, remarkably, led to regression of large and established tumors. This therapeutic effect could be transferred by CD4+ but not by CD8+ T cells. A CpG-loaded whole-cell vaccination is practical and has strong potential for translation to the clinical setting. It is currently being tested in a clinical trial of adoptive immunotherapy for mantle-cell lymphoma.
Zebrafish fin immune responses during high mortality infections with viral haemorrhagic septicemia rhabdovirus. A proteomic and transcriptomic approach
Authors: Encinas Paloma , Rodriguez-Milla Miguel A , Novoa Beatriz , Estepa Amparo , Figueras Antonio , Coll Julio 
Published: September 2010

Abstract

Background
Despite rhabdoviral infections being one of the best known fish diseases, the gene expression changes induced at the surface tissues after the natural route of infection (infection-by-immersion) have not been described yet. This work describes the differential infected versus non-infected expression of proteins and immune-related transcripts in fins and organs of zebrafish Danio rerio shortly after infection-by-immersion with viral haemorrhagic septicemia virus (VHSV).

Results
Two-dimensional differential gel electrophoresis detected variations on the protein levels of the enzymes of the glycolytic pathway and cytoskeleton components but it detected very few immune-related proteins. Differential expression of immune-related gene transcripts estimated by quantitative polymerase chain reaction arrays and hybridization to oligo microarrays showed that while more transcripts increased in fins than in organs (spleen, head kidney and liver), more transcripts decreased in organs than in fins. Increased differential transcript levels in fins detected by both arrays corresponded to previously described infection-related genes such as complement components (c3b, c8 and c9) or class I histocompatibility antigens (mhc1) and to newly described genes such as secreted immunoglobulin domain (sid4), macrophage stimulating factor (mst1) and a cluster differentiation antigen (cd36).

Conclusions
The genes described would contribute to the knowledge of the earliest molecular events occurring in the fish surfaces at the beginning of natural rhabdoviral infections and/or might be new candidates to be tested as adjuvants for fish vaccines.
Burst expansion, distribution and diversification of MITEs in the silkworm genome
Authors: Han Min-Jin , Shen Yi-Hong , Gao Ying-Hui , Chen Li-Yong , Xiang Zhong-Huai , Zhang Ze 
Published: September 2010

Abstract

Background
Miniature inverted-repeat transposable elements (MITEs) are widespread in plants and animals. Although silkworm (Bombyx mori) has a large amount of and a variety of transposable elements, the genome-wide information of the silkworm MITEs is unknown.

Results
We used structure-based and homology approaches to search for MITEs in the silkworm genome. We identified 17 MITE families with a total of 5785 members, accounting for ~0.4% of the genome. 7 of 17 MITE families are completely novel based on the nucleotide composition of target site duplication (TSD) and/or terminal inverted repeats (TIR). Silkworm MITEs were widely and nonrandom distributed in the genome. One family named BmMITE-2 might experience a recent burst expansion. Network and diversity analyses for each family revealed different diversification patterns of the silkworm MITEs, reflecting the signatures of genome-shocks that silkworm experienced. Most silkworm MITEs preferentially inserted into or near genes and BmMITE-11 that encodes a germline-restricted small RNA might silence its the closest genes in silkworm ovary through a small RNA pathway.

Conclusions
Silkworm harbors 17 MITE families. The silkworm MITEs preferred to reside in or near genes and one MITE might be involved in gene silence. Our results emphasize the exceptional role of MITEs in transcriptional regulation of genes and have general implications to understand interaction between MITEs and their host genome.
Overproduced Brucella abortus PdhS-mCherry forms soluble aggregates in Escherichia coli, partially associating with mobile foci of IbpA-YFP
Authors: Van der Henst Charles , Charlier Caroline , Deghelt Michaël , Wouters Johan , Matroule Jean-Yves , Letesson Jean-Jacques , De Bolle Xavier 
Published: September 2010

Abstract

Background
When heterologous recombinant proteins are produced in Escherichia coli, they often precipitate to form insoluble aggregates of unfolded polypeptides called inclusion bodies. These structures are associated with chaperones like IbpA. However, there are reported cases of "non-classical" inclusion bodies in which proteins are soluble, folded and active.

Results
We report that the Brucella abortus PdhS histidine kinase fused to the mCherry fluorescent protein forms intermediate aggregates resembling "non-classical" inclusion bodies when overproduced in E. coli, before forming "classical" inclusion bodies. The intermediate aggregates of PdhS-mCherry are characterized by the solubility of PdhS-mCherry, its ability to specifically recruit known partners fused to YFP, suggesting that PdhS is folded in these conditions, and the quick elimination (in less than 10 min) of these structures when bacterial cells are placed on fresh rich medium. Moreover, soluble PdhS-mCherry foci do not systematically colocalize with IpbA-YFP, a marker of inclusion bodies. Instead, time-lapse experiments show that IbpA-YFP exhibits rapid pole-to-pole shuttling, until it partially colocalizes with PdhS-mCherry aggregates.

Conclusion
The data reported here suggest that, in E. coli, recombinant proteins like PdhS-mCherry may transit through a soluble and folded state, resembling previously reported "non-classical" inclusion bodies, before forming "classical" inclusion bodies. The dynamic localization of IbpA-YFP foci suggests that the IbpA chaperone could scan the E. coli cell to find its substrates.
Detection of sexually transmitted infection and human papillomavirus in negative cytology by multiplex-PCR
Authors: Shim Hyo-Sub , Noh Songmi , Park Ae-Ran , Lee Young-Nam , Kim Jong-Kee , Chung Hyun-Jae , Kang Keum-Soon , Cho Nam Hoon 
Published: September 2010

Abstract

Background
The aim of this study was to determine the prevalence of human papillomavirus (HPV) and 15 species that cause sexually transmitted infections (STIs) in negative cytology. In addition, we compared the diagnostic performance of multiplex polymerase chain reaction (PCR) with widely available techniques used to detect HPV.

Methods
We recruited 235 women of reproductive age who had negative cytology findings in a liquid-based cervical smear. STIs were identified by multiplex PCR, and HPV genotypes by multiplex PCR, hybrid capture 2, and DNA microaray; discordant results were analyzed by direct sequencing.

Results
Approximately 96.6% of patients with negative cytology results were positive for pathogens that cause STIs. The pathogens most frequently detected were Gardnerella vaginalis, Ureaplasma urealyticum. The incidence of HPV in negative cytology was 23.3%. Low-risk HPV infection was significantly correlated with Chalmaydia trachomatis, and high-risk HPV infection was significantly correlated with Group β streptococcus. The analytical sensitivities of the multiplex PCR and DNA microarray were higher than 80%, and the analytical specificity was nearly 100% for all tests.

Conclusions
Multiplex PCR yielded results that most of patients with negative cytology were positive for pathogens that cause STIs, and were more similar to that of DNA microarray, than that of hybrid capture 2 in terms of analytical sensitivity and prediction value of HPV infection.
Transcriptional profiling of ErbB signalling in mammary luminal epithelial cells - interplay of ErbB and IGF1 signalling through IGFBP3 regulation
Authors: Worthington Jenny , Bertani Mariana , Chan Hong-Lin , Gerrits Bertran , Timms John F 
Published: September 2010

Abstract

Background
Members of the ErbB family of growth factor receptors are intricately linked with epithelial cell biology, development and tumourigenesis; however, the mechanisms involved in their downstream signalling are poorly understood. Indeed, it is unclear how signal specificity is achieved and the relative contribution each receptor has to specific gene expression.

Methods
Gene expression profiling of a human mammary luminal epithelial cell model of ErbB2-overexpression was carried out using cDNA microarrays with a common RNA reference approach to examine long-term overlapping and differential responses to EGF and heregulin beta1 treatment in the context of ErbB2 overexpression. Altered gene expression was validated using quantitative real time PCR and/or immunoblotting. One gene of interest was targeted for further characterisation, where the effects of siRNA-mediated silencing on IGF1-dependent signalling and cellular phenotype were examined and compared to the effects of loss of ErbB2 expression.

Results
775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e.g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were enhanced in ErbB2-overexpressing cells, whilst loss of ErbB2 expression by siRNA silencing reduced IGF1 signalling. Furthermore, IGFBP3 knockdown resulted in basal ERK and Akt activation in luminal epithelial cells and increased invasiveness and anchorage-independent colony formation in SKBR3 cells.

Conclusions
These data show IGFBP3 as a negative regulator of transformation and that its down-regulation enhances IGF1-dependent signalling. They also show that ErbB2 can up-regulate IGF1-dependent signalling, possibly via the regulated expression of IGFBP3.
Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma
Authors: Nykopp Timo K , Rilla Kirsi , Tammi Markku I , Tammi Raija H , Sironen Reijo , Hämäläinen Kirsi , Kosma Veli-Matti , Heinonen Seppo , Anttila Maarit 
Published: September 2010

Abstract

Background
Hyaluronan accumulation correlates with the degree of malignancy in many solid tumor types, including malignant endometrial carcinomas. To elucidate the mechanism of hyaluronan accumulation, we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), and correlated them with hyaluronan content and HAS1-3 immunoreactivity.

Methods
A total of 35 endometrial tissue biopsies from 35 patients, including proliferative and secretory endometrium (n = 10), post-menopausal proliferative endometrium (n = 5), complex atypical hyperplasia (n = 4), grade 1 (n = 8) and grade 2 + 3 (n = 8) endometrioid adenocarcinomas were divided for gene expression by real-time RT-PCR, and paraffin embedded blocks for hyaluronan and HAS1-3 cytochemistry.

Results
The mRNA levels of HAS1-3 were not consistently changed, while the immunoreactivity of all HAS proteins was increased in the cancer epithelium. Interestingly, HAS3 mRNA, but not HAS3 immunoreactivity, was increased in post-menopausal endometrium compared to normal endometrium (p = 0.003). The median of HYAL1 mRNA was 10-fold and 15-fold lower in both grade 1 and grade 2+3 endometrioid endometrial cancers, as compared to normal endometrium (p = 0.004-0.006), and post-menopausal endometrium (p = 0.002), respectively. HYAL2 mRNA was also reduced in cancer (p = 0.02) and correlated with HYAL1 (r = 0.8, p = 0.0001). There was an inverse correlation between HYAL1 mRNA and the epithelial hyaluronan staining intensity (r = -0.6; P = 0.001).

Conclusion
The results indicated that HYAL1 and HYAL2 were coexpressed and significantly downregulated in endometrioid endometrial cancer and correlated with the accumulation of hyaluronan. While immunoreactivity for HASs increased in the cancer cells, tumor mRNA levels for HASs were not changed, suggesting that reduced turnover of HAS protein may also have contributed to the accumulation of hyaluronan.
Short-hairpin RNA-induced suppression of adenine nucleotide translocase-2 in breast cancer cells restores their susceptibility to TRAIL-induced apoptosis by activating JNK and modulating TRAIL receptor expression
Authors: Jang Ji-Young , Jeon Yoon-Kyung , Choi Yun , Kim Chul-Woo 
Published: September 2010

Abstract

Background
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL; apo2 ligand) induces apoptosis in cancer cells but has little effect on normal cells. However, many cancer cell types are resistant to TRAIL-induced apoptosis, limiting the clinical utility of TRAIL as an anti-cancer agent. We previously reported that the suppression of adenine nucleotide translocase-2 (ANT2) by short-hairpin RNA (shRNA) induces apoptosis of breast cancer cells, which frequently express high levels of ANT2. In the present study, we examined the effect of RNA shRNA-induced suppression of ANT2 on the resistance of breast cancer cells to TRAIL-induced apoptosis in vitro and in vivo.

Results
ANT2 shRNA treatment sensitized MCF7, T47 D, and BT474 cells to TRAIL-induced apoptosis by up-regulating the expression of TRAIL death receptors 4 and 5 (DR4 and DR5) and down-regulating the TRAIL decoy receptor 2 (DcR2). In MCF7 cells, ANT2 knockdown activated the stress kinase c-Jun N-terminal kinase (JNK), subsequently stabilizing and increasing the transcriptional activity of p53 by phosphorylating it at Thr81; it also enhanced the expression and activity of DNA methyltransferase 1 (DNMT1). ANT2 shRNA-induced overexpression of DR4/DR5 and TRAIL sensitization were blocked by a p53 inhibitor, suggesting that p53 activation plays an important role in the transcriptional up-regulation of DR4/DR5. However, ANT2 knockdown also up-regulated DR4/DR5 in the p53-mutant cell lines BT474 and T47 D. In MCF7 cells, ANT2 shRNA treatment led to DcR2 promoter methylation and concomitant down-regulation of DcR2 expression, consistent with the observed activation of DNMT1. Treatment of the cells with a demethylating agent or JNK inhibitor prevented the ANT2 shRNA-induced down-regulation of DcR2 and activation of both p53 and DNMT1. In in vivo experiments using nude mice, ANT2 shRNA caused TRAIL-resistant MCF7 xenografts to undergo TRAIL-induced cell death, up-regulated DR4/DR5, and down-regulated DcR2. Co-treatment with ANT2 shRNA and TRAIL efficiently suppressed tumor growth in these mice.

Conclusions
ANT2 suppression by shRNA might be exploited to overcome TRAIL-resistance in cancer.