bluuebunny/crossref_metadata_2025_split huggingface dataset:
hsp70-Dependent Antiviral Immunity against Cytopathic Neuronal Infection by Vesicular Stomatitis Virus
Authors: Kim Mi Young , Ma Yuanmei , Zhang Yu , Li Jianrong , Shu Yaoling , Oglesbee Michael 
Published: July 2013

ABSTRACT

The major inducible 70-kDa heat shock protein (hsp70) protects against measles virus (MeV) neurovirulence in the mouse that is caused by a cell-associated noncytolytic neuronal infection. Protection is type I interferon (IFN) dependent, and we have established a novel axis of antiviral immunity in which hsp70 is released from virus-infected neurons to induce IFN-β in macrophages. The present work used vesicular stomatitis virus (VSV) to establish the relevance of hsp70-dependent antiviral immunity to fulminant cytopathic neuronal infections.
In vitro
, hsp70 that was constitutively expressed in mouse neuronal cells caused a modest increase in VSV replication. Infection induced an early extracellular release of hsp70 from viable cells, and the release was progressive, increasing with virus-induced apoptosis and cell lysis. The impact of this VSV-hsp70 interaction on neurovirulence was established in weanling male hsp70 transgenic and nontransgenic mice. Constitutive expression of hsp70 in neurons of transgenic mice enhanced viral clearance from brain and reduced mortality, and it was correlated with enhanced expression of type I IFN mRNA. Nontransgenic mice were also protected against neurovirulence and expressed increased type I IFN mRNA in brain when hsp70 was expressed by a recombinant VSV (rVSV-hsp70), indicating that hsp70 in the virus-infected cell is sufficient for host protection.
In vitro
data confirmed extracellular release of hsp70 from cells infected with rVSV-hsp70 and also showed that viral replication is not enhanced when hsp70 is expressed in this manner, suggesting that hsp70-mediated protection
in vivo
is not dependent on stimulatory effects of hsp70 on virus gene expression.
Antiviral RNA Silencing Initiated in the Absence of RDE-4, a Double-Stranded RNA Binding Protein, in Caenorhabditis elegans
Authors: Guo Xunyang , Zhang Rui , Wang Jeffrey , Lu Rui 
Published: July 2013

ABSTRACT

Small interfering RNAs (siRNAs) processed from double-stranded RNA (dsRNA) of virus origins mediate potent antiviral defense through a process referred to as RNA interference (RNAi) or RNA silencing in diverse organisms. In the simple invertebrate
Caenorhabditis elegans
, the RNAi process is initiated by a single Dicer, which partners with the dsRNA binding protein RDE-4 to process dsRNA into viral siRNAs (viRNAs). Notably, in
C. elegans
this RNA-directed viral immunity (RDVI) also requires a number of worm-specific genes for its full antiviral potential. One such gene is
rsd-2
(RNAi spreading defective 2), which was implicated in RDVI in our previous studies. In the current study, we first established an antiviral role by showing that
rsd-2
null mutants permitted higher levels of viral RNA accumulation, and that this enhanced viral susceptibility was reversed by ectopic expression of RSD-2. We then examined the relationship of
rsd-2
with other known components of RNAi pathways and established that
rsd-2
functions in a novel pathway that is independent of
rde-4
but likely requires the RNA-dependent RNA polymerase RRF-1, suggesting a critical role for RSD-2 in secondary viRNA biogenesis, likely through coordinated action with RRF-1. Together, these results suggest that RDVI in the single-Dicer organism
C. elegans
depends on the collective actions of both RDE-4-dependent and RDE-4-independent mechanisms to produce RNAi-inducing viRNAs. Our study reveals, for the first time, a novel siRNA-producing mechanism in
C. elegans
that bypasses the need for a dsRNA-binding protein.
The small eye phenotype in the EPIC-Norfolk eye study: prevalence and visual impairment in microphthalmos and nanophthalmos
Authors: Day Alexander C , Khawaja Anthony P , Peto Tunde , Hayat Shabina , Luben Robert , Broadway David C , Khaw Kay-Tee , Foster Paul J 
Published: July 2013

ObjectiveTo describe the prevalence and phenotypic characteristics of small eyes in the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study.DesignCommunity cross-sectional study.SettingEast England population (Norwich, Norfolk and surrounding area).Participants8033 participants aged 48–92 years old from the EPIC-Norfolk Eye Study, Norfolk, UK with axial length measurements. Participants underwent a standardised ocular examination including visual acuity (LogMAR), ocular biometry, non-contact tonometry, autorefraction and fundal photography. A small eye phenotype was defined as a participant with one or both eyes with axial length of <21 mm.Outcome measuresPrevalence of small eyes, proportion with visual impairment, demographic and biometric factors.ResultsNinety-six participants (1.20%, 95% CI 0.98% to 1.46%) had an eye with axial length less than 21 mm, of which 74 (77%) were women. Prevalence values for shorter axial lengths were <20 mm: 0.27% (0.18% to 0.41%); <19 mm: 0.17% (0.11% to 0.29%); <18 mm: 0.14% (0.08% to 0.25%). Two participants (2.1%) had low vision (presenting visual acuity >0.48 LogMAR) and one participant was blind (>1.3 LogMAR). The prevalence of unilateral visual impairment was higher in participants with a small eye. Multiple logistic regression modelling showed presence of a small eye to be significantly associated with shorter height, lower body mass index, higher systolic blood pressure and lower intraocular pressure.ConclusionsThe prevalence of people with small eyes is higher than previously thought. While small eyes were more common in women, this appears to be related to shorter height and lower body mass index. Participants with small eyes were more likely to be blind or to have unilateral visual impairment.
Australia's temperate carbonate coast: sources, depositional environments and implications
Authors: Short Andrew D. 
Published: July 2013

Abstract
The 30 000 km-long Australian open coast is located between tropical and temperate latitudes (9°–42°S), with humid north and east coasts, and generally semi-arid–arid south and west coasts. The 9000 km-long temperate arid coast is dominated by carbonate shelf and inshore sediments that have supplied contemporary carbonate beach and dune systems, as well as very extensive Pleistocene calcarenite barrier systems that dominate much of the inner shelf, coast and near interior, and which, in places, have contributed to a blanketing of the downwind interior with calcareous loess deposits. Much of the contemporary coastal landscape and, to varying degrees, the adjacent interior is therefore dominated by a legacy of carbonate marine sediments. This paper reviews the reasons for the dominance of carbonate along this section of coast. It begins by examining the sources, followed by the transport and depositional mechanisms, the nature of the onshore carbonate deposits, including their diagenesis, and their longer-term impact on the coast.
Catalase Abrogates β-Lapachone–Induced PARP1 Hyperactivation–Directed Programmed Necrosis in NQO1-Positive Breast Cancers
Authors: Bey Erik A. , Reinicke Kathryn E. , Srougi Melissa C. , Varnes Marie , Anderson Vernon E. , Pink John J. , Li Long Shan , Patel Malina , Cao Lifen , Moore Zachary , Rommel Amy , Boatman Michael , Lewis Cheryl , Euhus David M. , Bornmann William G. , Buchsbaum Donald J. , Spitz Douglas R. , Gao Jinming , Boothman David A. 
Published: July 2013

Abstract
Improving patient outcome by personalized therapy involves a thorough understanding of an agent's mechanism of action. β-Lapachone (clinical forms, Arq501/Arq761) has been developed to exploit dramatic cancer-specific elevations in the phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase (NQO1). NQO1 is dramatically elevated in solid cancers, including primary and metastatic [e.g., triple-negative (ER−, PR−, Her2/Neu−)] breast cancers. To define cellular factors that influence the efficacy of β-lapachone using knowledge of its mechanism of action, we confirmed that NQO1 was required for lethality and mediated a futile redox cycle where ∼120 moles of superoxide were formed per mole of β-lapachone in 2 minutes. β-Lapachone induced reactive oxygen species (ROS), stimulated DNA single-strand break-dependent poly(ADP-ribose) polymerase-1 (PARP1) hyperactivation, caused dramatic loss of essential nucleotides (NAD+/ATP), and elicited programmed necrosis in breast cancer cells. Although PARP1 hyperactivation and NQO1 expression were major determinants of β-lapachone–induced lethality, alterations in catalase expression, including treatment with exogenous enzyme, caused marked cytoprotection. Thus, catalase is an important resistance factor and highlights H2O2 as an obligate ROS for cell death from this agent. Exogenous superoxide dismutase enhanced catalase-induced cytoprotection. β-Lapachone–induced cell death included apoptosis-inducing factor (AIF) translocation from mitochondria to nuclei, TUNEL+ staining, atypical PARP1 cleavage, and glyceraldehyde 3-phosphate dehydrogenase S-nitrosylation, which were abrogated by catalase. We predict that the ratio of NQO1:catalase activities in breast cancer versus associated normal tissue are likely to be the major determinants affecting the therapeutic window of β-lapachone and other NQO1 bioactivatable drugs. Mol Cancer Ther; 12(10); 2110–20. ©2013 AACR.
Ectopic fat: the true culprit linking obesity and cardiovascular disease?
Authors: Morelli Mariangela , Gaggini Melania , Daniele Giuseppe , Marraccini Paolo , Sicari Rosa , Gastaldelli Amalia 
Published: July 2013

SummaryObesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardiometabolic diseases.
The Relationships among Wind, Horizontal Pressure Gradient, and Turbulent Momentum Transport during CASES-99
Authors: Sun Jielun , Lenschow Donald H. , Mahrt Larry , Nappo Carmen 
Published: July 2013

Abstract
Relationships among the horizontal pressure gradient, the Coriolis force, and the vertical momentum transport by turbulent fluxes are investigated using data collected from the 1999 Cooperative Atmosphere–Surface Exchange Study (CASES-99). Wind toward higher pressure (WTHP) adjacent to the ground occurred about 50% of the time. For wind speed at 5 m above the ground stronger than 5 m s−1, WTHP occurred about 20% of the time. Focusing on these moderate to strong wind cases only, relationships among horizontal pressure gradients, Coriolis force, and vertical turbulent transport in the momentum balance are investigated. The magnitude of the downward turbulent momentum flux consistently increases with height under moderate to strong winds, which results in the vertical convergence of the momentum flux and thus provides a momentum source and allows WTHP.
In the along-wind direction, the horizontal pressure gradient is observed to be well correlated with the quadratic wind speed, which is demonstrated to be an approximate balance between the horizontal pressure gradient and the vertical convergence of the turbulent momentum flux. That is, antitriptic balance occurs in the along-wind direction when the wind is toward higher pressure. In the crosswind direction, the pressure gradient varies approximately linearly with wind speed and opposes the Coriolis force, suggesting the importance of the Coriolis force and approximate geotriptic balance of the airflow. A simple one-dimensional planetary boundary layer eddy diffusivity model demonstrates the possibility of wind directed toward higher pressure for a baroclinic boundary layer and the contribution of the vertical turbulent momentum flux to this phenomenon.
Flap Selection and Functional Outcomes in Total Glossectomy with Laryngeal Preservation
Authors: Rihani Jordan , Lee Michael R. , Lee Thomas , Ducic Yadranko 
Published: July 2013

ObjectiveReconstruction of total glossectomy defects has been revolutionized by the popularity of free flap use in the head and neck. Challenging defects can be addressed with a variety of different free and pedicled flaps. The purpose of this study is to review our method of flap selection in cases of total glossectomy defects with laryngeal preservation, with an emphasis on the variations of these defects and patient body habitus.Study DesignCase series with chart review.SettingTertiary care referral center.Subjects and MethodsAll patients undergoing total glossectomy with laryngeal preservation (TGLP) by the senior author (YD) from September 1997 to May 2012. Objective data regarding patient demographics, existing defect, method of reconstruction, adjuvant treatment, operative details, outcomes, and complications were recorded. Both means and frequency of prolonged tracheostomy or gastrostomy tube were used to assess outcomes.ResultsOne hundred and three patients were identified. Ninety‐four met inclusion criteria. All patients were T3 or T4 stage tumors. Mean follow‐up was 3.4 years. Fifty‐nine patients (62%) underwent free flap reconstruction while the remaining 35 (37%) were treated with a pedicled pectoralis myocutaneous flap. Tracheostomy decannulation and gastrostomy tube removal rates were 84% and 29%, respectively. No patients were converted to total laryngectomy.ConclusionOptimal reconstruction of TGLP defects may be accomplished with either pedicled or free‐tissue flap reconstruction. Selecting an ideal flap for reconstruction of total glossectomy defects should be patient specific and based on matching donor flap bulk. This treatment approach demonstrates high tracheostomy and gastric tube independence.
Superior neurologic recovery after 15 minutes of normothermic cardiac arrest using an extracorporeal life support system for optimized blood pressure and flow
Authors: Trummer G , Foerster K , Buckberg GD , Benk C , Mader I , Heilmann C , Liakopoulos O , Beyersdorf F 
Published: July 2013

Objective: Sudden cardiac arrest is one of the leading causes of death. Conventional CPR techniques after cardiac arrest provide circulation with reduced and varying blood flow and pressure. We hypothesize that using pressure- and flow-controlled reperfusion of the whole body improves neurological recovery and survival after 15 min of normothermic cardiac arrest. Methods: Pigs were randomized in two experimental groups and exposed to 15 min of ventricular fibrillation (VF). After this period, the animals in the control group received conventional CPR with open chest compression (n=6), while circulation in the treatment group (n=6) was established with an extracorporeal life support system (ECLS) to control blood pressure and flow. Follow-up included the assessment of neurological recovery and magnetic resonance imaging (MRI) for up to 7 days. Results: Five of the six animals in the control group died, one animal was resuscitated successfully. In the treatment group, 1/6 could not be separated from ECLS. Five out of the six pigs survived and were transferred to the animal facility. One animal was unable to walk and had to be sacrificed 30 hours after ECLS. The remaining 4 animals of the treatment group and the surviving pig from the control group showed complete neurological recovery. Brain MRI revealed no pathological changes. Conclusion: We were able to demonstrate a significant improvement in survival after 15 minutes of normothermic cardiac arrest. These results support our hypothesis that using an ECLS for pressure- and flow-controlled circulation after circulatory arrest is superior to conventional CPR.
Radiation exposure of the radiologist’s eye lens during CT-guided interventions
Authors: Heusch Philipp , Kröpil Patric , Buchbender Christian , Aissa Joel , Lanzman Rotem S , Heusner Till A , Ewen Klaus , Antoch Gerald , Fürst Günther 
Published: July 2013

Background In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist’s eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. Purpose To determine the interventionalist’s equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. Material and Methods During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens’ radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. Results For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03–218.9 µSv) for a median exposure time of 26.2 s (range, 1.1–94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1–335.5 µSv/min). Conclusion Estimating 50–200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.
A case study of electro-hydraulic loading and testing technology for composite insulators based on iterative learning control
Authors: Wang Shou-Kun , Wang Jun-Zheng , Zhao Jiang-bo 
Published: July 2013

In order to simulate the vibrating condition of composite insulators in breeze, and carry out its fatigue test under loading and vibrating conditions, the electro-hydraulic loading and testing technology for the composite insulators is researched in this study. A compound electro-hydraulic loading system is first designed, including two subsystems, the static proportional loading system and the dynamic servo loading system. Then, the working principle based on this system is analyzed, and the mathematic model of electro-hydraulic servo system is also built, proved to be an inertial element with high gain. The control method based on proportional–derivative-type iterative learning control has been applied to such a dynamic servo loading system, to achieve the high-precision control for dynamic load force with repetitive regularity. Both mathematic simulation and actual experiments have been designed and carried out, and their results proved that the load principle and the control method are feasible and applicable and have the ability of achieving high-precision control effects. Based on this discussed electro-hydraulic technology, an actual electro-hydraulic loading and testing system for different kinds of composite insulators has been researched and developed, with the advanced technology indices of six loading channels, 20 kN maximum dynamic force, 0.3 kN force control precision and 100 Hz maximum vibrating frequency.
SLE disease per se contributes to deterioration in bone mineral density, microstructure and bone strength
Authors: Tang XL , Griffith JF , Qin L , Hung VW , Kwok AW , Zhu TY , Kun EW , Leung PC , Li EK , Tam L-S 
Published: July 2013

Objective The objective of this report is to assess the effect of systemic lupus erythematosus (SLE) disease itself on deterioration of bone mineral density (BMD), microstructure and bone strength. Method Thirty age-matched SLE patients on long-term glucocorticoids (GC) (SLE/GC), 30 SLE patients without GC (SLE/non-GC) and 60 healthy controls were examined. Areal BMD (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), and architectural parameters at the nondominant distal radius were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone strength was estimated by HR-pQCT-based micro-finite element analysis. Results Adjusted for menopausal status and adjusted calcium level, when compared with controls, SLE/non-GC patients had significantly lower aBMD at femoral neck and total hip, and diminished radial total vBMD, cortical area, vBMD and thickness, respectively, by 8.3%, 8%, 2.7% and 9.2%, as well as significant compromised bone strength (stiffness, failure load and apparent modulus) by 8.3%, 9.1% and 9.5%, respectively. Similar alterations were also found in SLE/GC patients when compared to controls. In the premenopausal subgroup analysis, when compared with controls, total hip aBMD and radial cortical area were significantly lower in SLE/non-GC patients, and cortical area and thickness were significantly deficit in SLE/GC patients. However, no significant difference in any bone variables was present between SLE/GC and SLE/non-GC patients in the entire cohort or in the premenopausal subgroup. Conclusion SLE disease per se contributes to the deterioration in bone density, cortical microstructure and bone strength. This might help to explain the considerably higher fracture risk seen in SLE patients.
Physicochemical and immunological studies on mitochondrial DNA modified by peroxynitrite: implications of neo-epitopes of mitochondrial DNA in the etiopathogenesis of systemic lupus erythematosus
Authors: Al-Shobaili HA , Rasheed Z 
Published: July 2013

Background and objective Recent evidence has demonstrated that mitochondria possess their own nitric oxide synthase (mtNOS) and can produce endogenous reactive-nitrogen-species (RNS) including peroxynitrite (ONOO–). This study was undertaken to investigate the role of mitochondrial DNA (mtDNA) damage by ONOO– in systemic lupus erythematosus (SLE) autoimmunity. Methods MtDNA was isolated from fresh goat liver and modified by ONOO–, generated by synergistic action of nitric oxide (NO) and superoxide (O–2) donors. Modifications occurring in mtDNA were characterized by physicochemical techniques. SLE patients ( n = 50) with varying disease activity according to the SLE Disease Activity Index (SLEDAI) and healthy controls ( n = 34) were evaluated for antibodies to native and ONOO–-modified mtDNA by immunoassays. Gel retardation assays were performed to cross-examine the immunoassay results using affinity-purified SLE immunoglobulin G (IgG). Nitrosative stress in SLE patients was studied by measuring nitrotyrosine and inducible NO synthase (iNOS). Results The ONOO– caused extensive damage to mtDNA as evident by ultraviolet (UV) hyperchromicity and loss of florescence intensity. Thermal melting studies, agarose gel electrophoresis and nuclease S1 digestibility clearly indicate structural perturbation in mtDNA by ONOO–. Quenching studies with specific NO or O–2 quenchers confirmed that the damaging agent was ONOO–. SLE autoantibodies exhibited enhanced binding with ONOO–-mtDNA as compared to their native analog. Interestingly, not only was there an increased number of subjects positive for ONOO–-mtDNA, but also the levels of anti-ONOO–-mtDNA antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ≥ 20 as compared with SLE patients with lower SLEDAI scores (SLEDAI < 20). Normal healthy controls showed negligible binding with either antigen. Furthermore, SLE patients had higher levels of nitrotyrosine and iNOS compared with their respective healthy controls. Conclusions Our novel results provide an important insight into the immunological basis of anti-DNA autoantibody generation in SLE. Our data conclude that modification of mtDNA by ONOO– causes structural perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen in SLE. The mtDNA modified by ONOO– may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.