bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated external cardioversion defibrillation monitoring in cardiac arrest: a randomized trial
Authors: Ali Bakhtiar , Bloom Heather , Veledar Emir , House Dorothy , Norvel Robert , Dudley Samuel C , Zafari A Maziar 
Published: June 2008

Abstract

Background
In-hospital cardiac arrest has a poor prognosis despite active electrocardiography monitoring. The initial rhythm of approximately 25% of in-hospital cardiopulmonary resuscitation (CPR) events is pulseless ventricular tachycardia/ventricular fibrillation (VT/VF). Early defibrillation is an independent predictor of survival in CPR events caused by VT/VF. The automated external cardioverter defibrillator (AECD) is a device attached by pads to the chest wall that monitors, detects, and within seconds, automatically delivers electric countershock to an appropriate tachyarrhythmia.

Study Objectives
• To evaluate safety of AECD monitoring in hospitalized patients.
• To evaluate whether AECDs provide earlier defibrillation than hospital code teams.

Methods
The study is a prospective trial randomizing patients admitted to the telemetry ward to standard CPR (code team) or standard CPR plus AECD monitoring (PowerHeart CRM). The AECD is programmed to deliver one 150 J biphasic shock to patients in sustained VT/VF. Data is collected using the Utstein criteria for cardiac arrest. The primary endpoint is time-to-defibrillation; secondary outcomes include neurological status and survival to discharge, with 3-year follow-up.

Results
To date, 192 patients have been recruited in the time period between 10/10/2006 to 7/20/2007. A total of 3,655 hours of telemetry data have been analyzed in the AECD arm. The AECD has monitored ambulatory telemetry patients in sinus rhythm, sinus tachycardia, supraventricular tachycardia, atrial flutter or fibrillation, with premature ventricular complexes and non-sustained VT without delivery of inappropriate shocks. One patient experienced sustained VT during AECD monitoring, who was successfully defibrillated (17 seconds after meeting programmed criteria). There are no events to report in the control arm. The patient survived the event without neurological complications. During the same time period, mean time to shock for VT/VF cardiac arrest occurring outside the telemetry ward was 230 ± 50 seconds.

Conclusion
AECD monitoring is safe and likely results in earlier defibrillation than standard telemetry monitoring.

Trial Registration
National Institutes of Health registration ID: NCT00382928
Systems analysis of quantitative shRNA-library screens identifies regulators of cell adhesion
Authors: Huang XiaoDong , Wang Jean YJ , Lu Xin 
Published: June 2008

AbstractBackgroundHigh throughput screens with RNA interference technology enable loss-of-function analyses of gene activities in mammalian cells. While the construction of genome-scale shRNA libraries has been successful, results of large-scale screening of those libraries can be difficult to analyze because of the relatively high noise levels and the fact that not all shRNAs in a library are equally effective in silencing gene expression.ResultsWe have screened a library consisting of 43,828 shRNAs directed against 8,500 human genes for functions that are necessary in cell detachment induced by a constitutively activated c-Abl tyrosine kinase. To deal with the issues of noise and uncertainty of knockdown efficiencies, we employed an analytical strategy that combines quantitative data analysis with biological knowledge, i.e. Gene Ontology and pathway information, to increase the power of the RNAi screening technique. Using this strategy we found 16 candidate genes to be involved in Abl-induced disruption of cell adhesion, and verified that the knockdown of IL6ST is associated with enhanced cell attachment.ConclusionOur results suggest that the power of genome-wide quantitative shRNA screens can be significantly increased when analyzed using a systems biology-based approach to identify functional gene networks.
Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response
Authors: Brucklacher Robert M , Patel Kruti M , VanGuilder Heather D , Bixler Georgina V , Barber Alistair J , Antonetti David A , Lin Cheng-Mao , LaNoue Kathryn F , Gardner Thomas W , Bronson Sarah K , Freeman Willard M 
Published: June 2008

AbstractBackgroundDespite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.ResultsUsing the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.ConclusionThese changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.
Identification of motifs that function in the splicing of non-canonical introns
Authors: Murray Jill I , Voelker Rodger B , Henscheid Kristy L , Warf M Bryan , Berglund J Andrew 
Published: June 2008

Abstract
Background
While the current model of pre-mRNA splicing is based on the recognition of four canonical intronic motifs (5' splice site, branchpoint sequence, polypyrimidine (PY) tract and 3' splice site), it is becoming increasingly clear that splicing is regulated by both canonical and non-canonical splicing signals located in the RNA sequence of introns and exons that act to recruit the spliceosome and associated splicing factors. The diversity of human intronic sequences suggests the existence of novel recognition pathways for non-canonical introns. This study addresses the recognition and splicing of human introns that lack a canonical PY tract. The PY tract is a uridine-rich region at the 3' end of introns that acts as a binding site for U2AF65, a key factor in splicing machinery recruitment.

Results
Human introns were classified computationally into low- and high-scoring PY tracts by scoring the likely U2AF65 binding site strength. Biochemical studies confirmed that low-scoring PY tracts are weak U2AF65 binding sites while high-scoring PY tracts are strong U2AF65 binding sites. A large population of human introns contains weak PY tracts. Computational analysis revealed many families of motifs, including C-rich and G-rich motifs, that are enriched upstream of weak PY tracts. In vivo splicing studies show that C-rich and G-rich motifs function as intronic splicing enhancers in a combinatorial manner to compensate for weak PY tracts.

Conclusion
The enrichment of specific intronic splicing enhancers upstream of weak PY tracts suggests that a novel mechanism for intron recognition exists, which compensates for a weakened canonical pre-mRNA splicing motif.
Transmembrane TNF-α mediates “forward” and “reverse” signaling, inducing cell death or survival via the NF-κB pathway in Raji Burkitt lymphoma cells
Authors: Zhang Hailong , Yan Dan , Shi Xu , Liang Huifang , Pang Yan , Qin Nalin , Chen Hui , Wang Jing , Yin Bingjiao , Jiang Xiaodan , Feng Wei , Zhang Wenjie , Zhou Muxiang , Li Zhuoya 
Published: June 2008

AbstractInterestingly, some lymphoma cells, expressing high levels of transmembrane (tm)TNF-α, are resistant to secretory (s)TNF-α-induced necrosis but sensitive to tmTNF-α-mediated apoptosis. As tmTNF-α mediates “forward” as well as “reverse” signaling, we hypothesize that a balanced signaling between forward and reverse directions may play a critical role in determining the fate of cells bearing tmTNF-α. Using Raji cells as a model, we first added exogenous tmTNF-α on fixed, transfected NIH3T3 cells onto Raji cells to examine tmTNF-α forward signaling and its effects, showing that constitutive NF-κB activity and cellular inhibitor-of-apoptosis protein 1 transcription were down-regulated, paralleled with Raji cell death. As Raji cells express tmTNF-α, an inhibition of their tmTNF-α expression by antisense oligonucleotide caused down-regulation of NF-κB activity. Conversely, increasing tmTNF-α expression by suppressing expression of TNF-α-converting enzyme that cleaves tmTNF-α led to an enhanced activation of NF-κB, indicating that tmTNF-α, but not sTNF-α, contributes to constitutive NF-κB activation. We next transfected Raji cells with a mutant tmTNF-α lacking the intracellular domain to competitively suppress reverse signaling via tmTNF-α; as expected, constitutive NF-κB activity was decreased. In contrast, treating Raji cells with sTNFR2 to stimulate reverse signaling via tmTNF-α ehanced NF-κB activation. We conclude that tmTNF-α, when highly expressed on tumor cells and acting as a receptor, promotes NF-κB activation through reverse signaling, which is helpful to maintain tumor cell survival. On the contrary, tmTNF-α, when acting as a ligand, inhibits NF-κB activity through forward signaling, which is inclined to induce tumor cell death.
Osteoimmunology: Interactions of the Bone and Immune System
Authors: Lorenzo Joseph , Horowitz Mark , Choi Yongwon 
Published: June 2008

AbstractBone and the immune system are both complex tissues that respectively regulate the skeleton and the body’s response to invading pathogens. It has now become clear that these organ systems often interact in their function. This is particularly true for the development of immune cells in the bone marrow and for the function of bone cells in health and disease. Because these two disciplines developed independently, investigators in each don’t always fully appreciate the significance that the other system has on the function of the tissue they are studying. This review is meant to provide a broad overview of the many ways that bone and immune cells interact so that a better understanding of the role that each plays in the development and function of the other can develop. It is hoped that an appreciation of the interactions of these two organ systems will lead to better therapeutics for diseases that affect either or both.
Signal Transducer and Activator of Transcription 5b, c-Src, and Epidermal Growth Factor Receptor Signaling Play Integral Roles in Estrogen-Stimulated Proliferation of Estrogen Receptor-Positive Breast Cancer Cells
Authors: Fox Emily M. , Bernaciak Teresa M. , Wen Jie , Weaver Amanda M. , Shupnik Margaret A. , Silva Corinne M. 
Published: June 2008

Abstract
17β-Estradiol (E2) acts through the estrogen receptor α (ERα) to stimulate breast cancer proliferation. Here, we investigated the functional relationship between ERα and signal transducer and activator of transcription (STAT)5b activity in ER+ MCF-7 and T47D human breast cancer cells after specific knockdown of STAT5b. STAT5b small interfering RNA (siRNA) inhibited E2-induced bromodeoxyuridine (BrdU) incorporation in both cell lines, as well as the E2-induced increase in MCF-7 cell number, cyclin D1 and c-myc mRNA, and cyclin D1 protein expression, indicating that STAT5b is required for E2-stimulated breast cancer proliferation. E2 treatment stimulated STAT5b tyrosine phosphorylation at the activating tyrosine Y699, resulting in increased STAT5-mediated transcriptional activity, which was inhibited by a Y669F STAT5b mutant. E2-induced STAT5-mediated transcriptional activity was inhibited by overexpressing a kinase-defective epidermal growth factor receptor (EGFR), or the EGFR tyrosine kinase inhibitor tyrphostin AG1478, indicating a requirement for EGFR kinase activity. Both E2-induced STAT5b tyrosine phosphorylation and STAT5-mediated transcription were also inhibited by the ER antagonist ICI 182,780 and the c-Src inhibitor PP2, indicating additional requirements for the ER and c-Src kinase activity. EGFR and c-Src kinase activities were also required for E2-induced cyclin D1 and c-myc mRNA. Together, these studies demonstrate positive cross talk between ER, c-Src, EGFR, and STAT5b in ER+ breast cancer cells. Increased EGFR and c-Src signaling is associated with tamoxifen resistance in ER+ breast cancer cells. Here we show that constitutively active STAT5b not only increased basal DNA synthesis, but also conferred tamoxifen resistance. Because STAT5b plays an integral role in E2-stimulated proliferation and tamoxifen resistance, it may be an effective therapeutic target in ER+ breast tumors.
Experimental investigation of nasal airflow
Authors: Doorly D , Taylor D J , Franke P , Schroter R C 
Published: June 2008

The airway geometry of the nasal cavity is manifestly complex, and the manner in which it controls the airflow to accomplish its various physiological functions is not fully understood. Since the complex morphology and inaccessibility of the nasal passageways precludes detailed in-vivo measurements, either computational simulation or in-vitro experiments are needed to determine how anatomical form and function are related. The fabrication of a replica model of the nasal cavity, of a high optical clarity and derived from in-vivo scan data is described here, together with characteristics of the flow field investigated using particle image velocimetry (PIV) and flow visualization. Flow visualization is shown to be a capable and convenient technique for identifying key phenomena. Specifically the emergence of the jet from the internal nasal valve into the main cavity, how it impacts on the middle turbinate, and the large enhancement of dispersion that accompanies the initial appearance of flow instability are revealed as particularly significant features. The findings from the visualization experiments are complemented by PIV imaging, which provides quantitative detail on the variations in velocity in different regions of the nasal cavity. These results demonstrate the effectiveness of the cavity geometry in partitioning the flow into high shear zones, which facilitate rapid heat transfer and humidification from the nasal mucosa, and slower zones affording greater residence times to facilitate olfactory sensing. The experimental results not only provide a basis for comparison with other computational modelling but also demonstrate an alternative and flexible means to investigate complex flows, relevant to studies in different parts of the respiratory or cardiovascular systems.
Microhaemodynamics within the blade tip clearance of a centrifugal turbodynamic blood pump
Authors: Antaki J F , Diao C-G , Shu F-J , Wu J-C , Zhao R , Kameneva M V 
Published: June 2008

A persistent challenge facing the quantitative design of turbodynamic blood pumps is the great disparity of spatial scales between the primary and auxiliary flow paths. Fluid passages within journals and adjacent to the blade tips are often on the scale of several blood cells, confounding the application of macroscopic continuum models. Yet, precisely in these regions there exists the highest shear stress, which is most likely to cause cellular trauma. This disparity has motivated these microscopic studies to visualize the kinematics of the blood cells within the small clearances of a miniature turbodynamic blood pump. A transparent model of a miniature centrifugal pump having an adjustable tip clearance (50–200μm) was prepared for direct optical visualization of the region between the impeller blade tip and the stationary housing. Synchronized images of the blood cells were obtained by a microscopic visualization system, consisting of an inverted microscope fitted with long-working-distance objective lens (40×), mercury lamp, and high-resolution charge-coupled device camera electronically triggered by the rotation of the impeller. Experiments with 7μm fluorescent particles revealed the influence of the gap dimension on the trajectory across the blade thickness. The lateral component of velocity (perpendicular to the blade) was dramatically enhanced in the 50μm gap compared with the 200μm gap, thereby reducing the exposure time. Studies with diluted bovine blood (Ht=0.5 per cent) showed that the concentration of cells traversing the gap is also reduced dramatically (30 per cent) as the blade tip clearance is reduced from 200μm to 50μm. These results motivate further investigation into the microfluidic phenomena responsible for cellular trauma within turbodynamic blood pumps.
Quasi-static axial cutting of AA6061 T4 and T6 round extrusions
Authors: Majumder A. , Altenhof W. , Vijayan V. , Jin S Y. 
Published: June 2008

A cutting deformation mode of AA6061 T4 and T6 round extrusions with two different wall thicknesses of 1.587 and 3.175 mm was experimentally investigated under quasi-static loading conditions. A heat treated 4140 steel alloy cutter was developed and used to initiate cutting deformation in the extrusions to investigate the load—displacement and energy absorption characteristics under uniaxial compressive loading. This research extended the observations associated with cutting deformation of lightweight extrusions already completed by the authors on AA6061 T6 tubes with a wall thickness of 3.175 mm. Clean cutting behaviour was observed for the extrusions with a T6 temper and wall thickness of 1.587 mm and for extrusions with a T4 temper and wall thickness of 3.175 mm. Extrusions with a T4 temper and wall thickness of 1.587 mm exhibited characteristics of braided cutting. An almost constant cutting force was observed for the cutting deformation mode, however, variations in the cutting force were observed for the AA6061 T4 extrusions with a wall thickness of 1.587 mm after approximately 50 mm crosshead displacement. The average total energy absorption (TEA), as a result of the cutting deformation, was observed to be 2.0 and 2.7 kJ for the AA6061 T4 and T6 extrusions with a wall thickness of 1.587 mm, respectively. Average TEA for the AA6061 T4 extrusions with a wall thickness of 3.175 mm was observed to be 4.2 kJ under the cutting deformation.
Polyethylene-carbon material for polymer electrolyte membrane fuel cell bipolar plates
Authors: Greenwood P. , Chen R. , Thring R. H. 
Published: June 2008

Bipolar plates are the interconnects between cells within a fuel cell stack. They must be highly electrically conductive in order to maximize the voltage across the stack and must be highly thermally conductive to aid cooling of the stack. Traditionally, bipolar plates are made from graphite or stainless steel; both have drawbacks such as low mechanical strength and corrosion problems, respectively. In order to overcome the problems associated with these common materials and to improve on the electrical and thermal conductivity aspects as well as decrease costs and improve manufacturability, a mixture of polyethylene and carbon was investigated. Composites of polyethylene and carbon were mixed using a two-roll mill and injection moulded. Micrographs of the polyethylene-carbon (PE-C) blends show how the microstructure of the polyethylene network and carbon particles provide increased mechanical properties but further addition of carbon leads to the degradation of these properties. Increasing carbon content led to an ever-increasing electrical conductivity. The material was tested for tensile and flexural properties, resulting in a maximum tensile and flexural strength of ∼24 MPa (at 26 wt% carbon in polyethylene) and ∼35 MPa (at 40 wt% carbon in polyethylene), respectively. The samples displayed electrical conductivity, with a maximum of 1.19 S/cm in-plane and 1.05 S/cm through-plane being achieved at a carbon loading of 65 wt%. The PE-C composite displayed low densities of 1.56 g/cm3 and desirable mechanical strength close to the US Department of Energy target level of 44.26 MPa for flexural strength. It was concluded that PE-C composites with different types of carbon and carbon fibres should be tested in order to reach the electrical conductivity target levels of 100 S/cm.
Adhesively bonded T-joints in polyvinyl chloride windows
Authors: Chaves F J P. , da Silva L F M. , de Castro P M S T. 
Published: June 2008

The main objective of this study was to assess the applicability of adhesives to connect a transom to a polyvinyl chloride window frame. A modified methacrylate adhesive was selected and tested for its mechanical properties, environmental ageing, and glass transition temperature. Adhesively bonded T-joints were manufactured and tested, and compared with the conventional screw-fastened T-joints in terms of joint strength. The initial geometry of the adhesively bonded T-joints was optimized with a finite element analysis (FEA). Finally, the various manufacturing processes (welding, screw fastening, and adhesive, bonding) were compared in economical terms, which is a critical parameter for the industry. The joint strength results show that adhesively bonded joints perform as well or better than the conventional screw-fastened joints. The FEA indicates that further improvements are possible with little changes in the geometry. The adhesive bonding process is also attractive in economical terms.