bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic characterization of a novel duck-origin picornavirus with six 2A proteins
Authors: Wang Xiaoyan , Liu Ning , Wang Fumin , Ning Kang , Li Yanbo , Zhang Dabing
Published: March 2014

A novel virus was detected from diseased ducks and completely determined. The virus was shown to have a picornavirus-like genome layout. Interestingly, the genome contained a total of up to six 2As, including four 2As (2A1–2A4) each having an NPGP motif, an AIG1-like 2A5, and a parechovirus-like 2A6. The 5′UTR was predicted to possess a hepacivirus/pestivirus-like internal ribosome entry site (IRES). However, the subdomain IIIe consisted of a 3 nt stem and five unpaired bases, distinct from those found in all other HP-like IRESs. The virus was most closely related to duck hepatitis A virus, with amino acid identities of 37.7 %, 39 % and 43.7 % in the P1, P2 and P3 regions, respectively. Based on these investigations, together with phylogenetic analyses, the virus could be considered as the founding member of a novel picornavirus genus that we tentatively named ‘Aalivirus’, with ‘Aalivirus A’ as the type species.
Breast cancer-associated protein – a novel binding partner of Mason-Pfizer monkey virus protease
Authors: Rumlová Michaela , Křížová Ivana , Hadravová Romana , Doležal Michal , Strohalmová Karolína , Keprová Alena , Pichová Iva , Ruml Tomáš
Published: March 2014

We identified breast cancer-associated protein (BCA3) as a novel binding partner of Mason-Pfizer monkey virus (MPMV) protease (PR). The interaction was confirmed by co-immunoprecipitation and immunocolocalization of MPMV PR and BCA3. Full-length but not C-terminally truncated BCA3 was incorporated into MPMV virions. We ruled out the potential role of the G-patch domain, a glycine-rich domain located at the C terminus of MPMV PR, in BCA3 interaction and virion incorporation. Expression of BCA3 did not affect MPMV particle release and proteolytic processing; however, it slightly increased MPMV infectivity.
Guinea pig cytomegalovirus GP129/131/133, homologues of human cytomegalovirus UL128/130/131A, are necessary for infection of monocytes and macrophages
Authors: Yamada Souichi , Fukuchi Saki , Hashimoto Kaede , Fukui Yoshiko , Tsuda Mihoko , Kataoka Michiyo , Katano Harutaka , Inoue Naoki
Published: March 2014

The GP129, GP131 and GP133 genes of guinea pig cytomegalovirus (GPCMV) are homologues of human cytomegalovirus UL128, UL130 and UL131A, respectively, which are essential for infection of endothelial and epithelial cells, and for viral transmission to leukocytes. Our previous study demonstrated that a GPCMV strain lacking the 1.6 kb locus that contains the GP129, GP131 and GP133 genes had a growth defect in animals. Here, we demonstrated that the WT strain, but not the 1.6 kb-deleted strain, formed capsids in macrophages prepared from the peritoneal fluid. To understand the mechanism, we prepared GPCMV strains defective in each of GP129, GP131 and GP133, and found that they were all essential for the infection of peritoneal, splenic and PBMC-derived macrophages/monocytes, and for expression of immediate-early antigens in the macrophages/monocytes, although they were dispensable for infection of fibroblasts. Monocyte/macrophage tropism could be one of the important determinants for viral dissemination in vivo.
Response to a population bottleneck can be used to infer recessive selection
Authors: Balick Daniel J. , Do Ron , Reich David , Sunyaev Shamil R.
Published: March 2014

Here we present the first genome wide statistical test for recessive selection. This test uses explicitly non-equilibrium demographic differences between populations to infer the mode of selection. By analyzing the transient response to a population bottleneck and subsequent re-expansion, we qualitatively distinguish between alleles under additive and recessive selection. We analyze the response of the average number of deleterious mutations per haploid individual and describe time dependence of this quantity. We introduce a statistic,BR, to compare the number of mutations in different populations and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. This test can be used to detect the predominant mode of selection on the genome wide or regional level, as well as among a sufficiently large set of medically or functionally relevant alleles.
Towards a new history and geography of human genes informed by ancient DNA
Authors: Pickrell Joseph K. , Reich David
Published: March 2014

Genetic information contains a record of the history of our species, and technological advances have transformed our ability to access this record. Many studies have used genome-wide data from populations today to learn about the peopling of the globe and subsequent adaptation to local conditions. Implicit in this research is the assumption that the geographic locations of people today are informative about the geographic locations of their ancestors in the distant past. However, it is now clear that long-range migration, admixture and population replacement have been the rule rather than the exception in human history. In light of this, we argue that it is time to critically re-evaluate current views of the peopling of the globe and the importance of natural selection in determining the geographic distribution of phenotypes. We specifically highlight the transformative potential of ancient DNA. By accessing the genetic make-up of populations living at archaeologically-known times and places, ancient DNA makes it possible to directly track migrations and responses to natural selection.
Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population
Authors: Dai Ningbin , Zheng Mingfeng , Wang Cheng , Ji Yong , Du Jiangbo , Zhu Chen , He Yisha , Zhu Meng , Zhu Xun , Sun Min , Dai Juncheng , Ma Hongxia , Chen Jingyu , Hu Zhibin , Gu Haiyong , Jin Guangfu , Shen Hongbing
Published: March 2014

Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome‐wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk‐related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case–control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81–0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double‐edged sword, as modulator between the carcinogenesis processes of stomach and esophagus.
Risk factors for hepatitis B virus reactivation after conformal radiotherapy in patients with hepatocellular carcinoma
Authors: Huang Wei , Zhang Wei , Fan Min , Lu Yanda , Zhang Jian , Li Hongsheng , Li Baosheng
Published: March 2014

This study investigated whether conformal radiotherapy affects hepatitis B virus (HBV) reactivation, and the risk factors for HBV reactivation in patients with HBV‐related hepatocellular carcinoma (HCC). Sixty‐nine patients with HCC were included in this retrospective study. Before radiotherapy (RT), all patients underwent imaging examinations and some baseline examinations, including CBC, liver function test, renal function test, α‐fetoprotein level, hepatitis B (HB) surface antigen, HB surface Ab, HB e antigen, HB e Ab, and serum HBV DNA quantification. During the period of RT and at least 16 weeks after the end of RT, CBCs were carried out weekly and the other tests were monitored monthly or more frequently if necessary. The clinical features and dosimetric parameters of RT were recorded. Univariate and multivariate logistic regression algorithms were used to analyze the risk factors of HBV reactivation. The incidence of complications in the study population was as follows: radiation‐induced liver disease, 17.4%; HBV reactivation, 24.6%; and HBV reactivation‐induced hepatitis, 21.7%. The HBV DNA level and dose volume parameters including normal liver volume, V20, and mean dose were associated with HBV reactivation. There was a relatively high incidence of HBV reactivation in HCC patients after the end of conformal RT. The serum HBV DNA level and some dosimetric parameters related to normal liver, including normal liver volume, V20, and mean dose, were the prognosis factors of HBV reactivation and should be carefully considered before conformal RT.
The child with difficult to control Congenital Adrenal Hyperplasia: is there a place for continuous subcutaneous hydrocortisone therapy
Authors: Hindmarsh Peter C.
Published: March 2014

The treatment of congenital adrenal hyperplasia requires administration of glucocorticoid and mineralocorticoid to replace the deficit resulting from the enzymatic block. During puberty, cortisol metabolism changes with an increase in clearance, which may lead to unstable control. This may require an increase in dosing frequency, and if this proves problematic, continuous subcutaneous hydrocortisone delivery using insulin pump technology can be valuable. The potential indications for such therapy along with some practical considerations are detailed in this Clinical Question report.
Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta‐analysis
Authors: Pommergaard H.‐C. , Gessler B. , Burcharth J. , Angenete E. , Haglind E. , Rosenberg J.
Published: March 2014

Aim

Colorectal anastomotic leakage is a serious complication. Despite extensive research, no consensus on the most important preoperative risk factors exists. The aim of this systematic review and meta‐analysis was to evaluate risk factors for anastomotic leakage in patients operated with colorectal resection.

Method

The databases MEDLINE, Embase and CINAHL were searched for prospective observational studies on preoperative risk factors for anastomotic leakage. Meta‐analyses were performed on outcomes based on odds ratios (OR) from multivariate regression analyses. The Newcastle–Ottawa scale was used for bias assessment within studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for quality assessment of evidence on outcome levels.

Results

This review included 23 studies evaluating 110 272 patients undergoing colorectal resection for cancer. The meta‐analyses found that a low rectal anastomosis [OR = 3.26 (95% CI: 2.31–4.62)], male gender [OR = 1.48 (95% CI: 1.37–1.60)] and preoperative radiotherapy [OR = 1.65 (95% CI: 1.06–2.56)] may be risk factors for anastomotic leakage. Primarily as a result of observational design, the quality of evidence was regarded as moderate or low for these risk factors according to the GRADE approach.

Conclusion

Based on the best available evidence, important preoperative risk factors for colorectal anastomotic leakage have been identified. Knowledge on risk factors may influence treatment and procedure‐related decisions, and possibly reduce the leakage rate.
Modified technique for aortic cross‐clamping during liver donor procurement
Authors: Desai Chirag S. , Girlanda Raffaele , Hawksworth Jason , Fishbein Thomas M.
Published: March 2014

Undue tension on the donor vessels during organ procurement is associated with intimal dissection, which can form the nidus for the thrombosis of the hepatic artery (HA) and graft loss. According to the US OPTN database, 143 grafts were discarded in the last 15 yr due to vascular damage during procurement. The most common technique to expose the supraceliac aorta is dissection between the left lateral segment of the liver and the esophagus–stomach. In obese donors, due to restricted space and in pediatric donors where the vessels are very delicate and this space is very small, the replaced or accessory left HA(R/A LHA) is prone to damage if approached conventionally. We describe a technique for the exposure of the supraceliac aorta in which the aorta is approached from the left side behind the gastroesophageal junction that does not require division of the gastrohepatic ligament. From May 2007 to May 2013, 104 liver procurements were performed. Eighty‐nine (85.6%) were adults, and 15 (14.4%) were pediatric donors. Twenty‐three (22.1%) had R/A LHA. No donor organ suffered any damage. One adult recipient with R/A LHA suffered HA thrombosis not related to it. In summary, this technical modification offers improved safety during cadaveric procurement and increases the ease.
Beyond survival: how well do transplanted livers work? A preliminary comparison of standard‐risk, high‐risk, and living donor recipients
Authors: Miller‐Matero Lisa R. , Eshelman Anne , Paulson Daniel , Armstrong Rachel , Brown Kimberly A. , Moonka Dilip , Abouljoud Marwan
Published: March 2014

To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high‐risk donors (HRD) in addition to standard‐risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post‐transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self‐reported and objective measures of recovery. Eighty‐four patients provided baseline and six‐month post‐transplant data. There were generally no statistically significant differences at baseline or the six‐month follow‐up, suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.
Current Opinions on the Control and Role of Vascular Smooth Muscle Cell Adhesion, Calcium Sensitization, and the Cytoskeleton in Vascular Structure and Function
Authors: Martinez‐Lemus Luis A.
Published: March 2014

Vascular smooth muscle contraction and relaxation play a preponderant role on the active (acute) and structural (long‐term) control of vascular diameter. This editorial overview summarizes and highlights the opinions expressed in seven reviews contained in this special topic issue of Microcirculation. The reviews address diverse aspects of the mechanisms that influence cell adhesion, calcium homeostasis, and cytoskeletal remodeling, and how these mechanisms affect vascular structure and function at different levels of the circulation.
Angiogenesis: Growth Points
Authors: Egginton Stuart , Birot Olivier
Published: March 2014

This collection of papers is based on talks presented at the IUPS meeting in Birmingham, UK last summer, in a symposium as part of the ESM & EVBO program, sponsored by the British Microcirculation Society and Microcirculation. In this issue we discuss new insights into the control of angiogenesis, including regulation of different aspects of endothelial cell biology by the tissue stroma, during inflammatory disease, and active remodelling of the microcirculation. We address a variety of signalling modes that determine the endothelial responses to pro‐angiogenic stimuli, including necessary synergy among different pathways and processes. We present an update of recent developments, and identify some areas where significant progress will likely occur.
Homocysteine Disrupts Outgrowth of Microvascular Endothelium by an iNOS‐Dependent Mechanism
Authors: Mayo Jamie N. , Chen Cheng‐Hung , Liao Francesca‐Fang , Bearden Shawn E.
Published: March 2014

Objective

To test the hypothesis that Hcy impairs angiogenic outgrowth through an iNOS‐dependent mechanism.

Methods

Adult C57Bl/6 mouse choroid explants were used in angiogenic outgrowth assays. Mouse microvascular endothelial cells were studied in culture during scrape‐induced migration and dispersed cell locomotion experiments. Activity of iNOS was manipulated with pharmacology (1400W), siRNA, and by use of choroid explants from iNOS knockout mice (iNOS−/−).

Results

Hcy (20 μM) significantly decreased the area of endothelial outgrowth without altering the number of cells in the choroid explant angiogenic assay, resulting in more densely packed outgrowth. Hcy prevented the outward orientation of actin filaments and decreased the number of actin projections along the leading edge of outgrowth. Hcy also slowed outgrowth from the edge of a scraped endothelial monolayer and in cultures of dispersed cells, Hcy impaired cell locomotion without affecting proliferation. Inhibition of iNOS activity rescued the effect of Hcy on area of explant outgrowth, cell density, number of projections, cell locomotion, and rate of outgrowth following scraping.

Conclusions

Hcy impairs microvascular endothelial outgrowth, but not proliferation, by disrupting cell locomotion through an iNOS‐dependent mechanism.
Differential dendritic cell‐mediated activation and functions of invariant NKT‐cell subsets in oral cancer
Authors: Singh AK , Gaur P , Shukla NK , Das SN
Published: March 2014

Objectives

Invariant natural killer T (iNKT) cells are unique subset of glycolipid‐reactive T lymphocytes with potent antitumour characteristics. This study was planned to understand Th‐like cytokine profiles of iNKT‐cell subsets and modulation of their functions in response to glycolipid ligand and tumour cell lysate (TL).

Subjects and Methods

Cytokine profile of iNKT‐cell subsets was evaluated from the peripheral blood of eight oral squamous cell carcinoma (OSCC) patients by flow cytometry and enzyme‐linked immunosorbent assay (ELISA), while antitumour activity of iNKT cells was measured by methyl tetrazolium salt assay.

Results

CD4+ (CD4+CD8−) iNKT subset from OSCC patients showed significant (P < 0.01) expansion and higher IL‐4 production following activation with α‐GalCer‐pulsed DCs, while CD4−CD8− double negative (DN) and CD8+ (CD4−CD8+) iNKT subsets produced IFN‐γ predominantly. iNKT cells showed significantly (P = 0.02) increased secretion of IFN‐γ and enhanced cytotoxicity to KB and SCC‐4 tumour cells in response to α‐GalCer and TL‐pulsed DCs.

Conclusion

It appears that mutual balance/ratio of iNKT subsets may be important for their effector functions. Selectively expanded DN and CD8+ iNKT cells with α‐GalCer and TL may be a better candidate vaccine for iNKT‐cell‐based adoptive cancer immunotherapy.
Neural control of blood flow during exercise in human metabolic syndrome
Authors: Limberg Jacqueline K. , Morgan Barbara J. , Sebranek Joshua J. , Proctor Lester T. , Eldridge Marlowe W. , Schrage William G.
Published: March 2014

New Findings

What is the central question of this study?

α‐Adrenergic‐mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome when compared with control animals. Whether such findings can be translated to humans was previously unexamined.

What is the main finding and its importance?

We observed greater muscle sympathetic nerve activity and clonidine‐mediated vasoconstriction in adults with metabolic syndrome, yet preserved exercise blood flow when compared with age‐matched healthy control subjects. These results suggest that adults with metabolic syndrome exhibit compensatory vascular control mechanisms capable of counteracting altered adrenergic responsiveness, thus preserving blood flow responses to low‐intensity, dynamic hand‐grip exercise.

α‐Adrenergic‐mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α‐adrenergic responsiveness during exercise when compared with age‐matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α‐Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra‐arterially to assess α‐adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P < 0.05), but did not change in either group with dynamic exercise. Clonidine‐mediated vasoconstriction was greater in adults with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (P > 0.05). Interestingly, exercise‐mediated vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit greater resting MSNA and clonidine‐mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low‐intensity hand‐grip exercise when compared with age‐matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity.
Aero-Elastic-Control-Floater-Mooring Coupled Dynamic Analysis of Floating Offshore Wind Turbine in Maximum Operation and Survival Conditions
Authors: Bae Y. H. , Kim M. H.
Published: March 2014

Increasing numbers of floating offshore wind turbines (FOWTs) are planned in the coming years due to their high potential in the massive generation of clean energy from ocean wind. In the present study, a numerical prediction tool has been developed for the fully coupled dynamic analysis of an FOWT system in the time domain including aero-loading, tower/blade elasticity, blade-rotor dynamics and control, mooring dynamics, and platform motions so that the influence of aero-elastic-control dynamics on the hull-mooring performance and vice versa can be assessed. The Hywind spar design with a 5 MW National Renewable Energy Laboratory (NREL) turbine is selected as an example and two different collinear wind-wave-current environmental conditions, maximum operational and survival conditions, are applied for this study. The maximum operational condition means the maximum environmental condition with normal blade-turbine operation and the survival condition represents the extreme situation without any blade-turbine operation. Through this study, it is seen that the ultimate-loading environments for different structural components of the FOWT can be different. The developed technology and numerical tool are readily applicable to the design of any type of future FOWTs in any combinations of irregular waves, dynamic winds, and steady currents.
Methodology for Wind/Wave Basin Testing of Floating Offshore Wind Turbines
Authors: Martin Heather R. , Kimball Richard W. , Viselli Anthony M. , Goupee Andrew J.
Published: March 2014

Scale-model wave basin testing is often employed in the development and validation of large-scale offshore vessels and structures by the oil and gas, military, and marine industries. A basin-model test requires less time, resources, and risk than a full-scale test, while providing real and accurate data for numerical simulator validation. As the development of floating wind turbine technology progresses in order to capture the vast deep-water wind energy resource, it is clear that model testing will be essential for the economical and efficient advancement of this technology. However, the scale model testing of floating wind turbines requires accurate simulation of the wind and wave environments, structural flexibility, and wind turbine aerodynamics and thus requires a comprehensive scaling methodology. This paper presents a unified methodology for Froude scale model testing of floating wind turbines under combined wind and wave loading. First, an overview of the scaling relationships employed for the environment, floater, and wind turbine are presented. Afterward, a discussion is presented concerning suggested methods for manufacturing a high-quality, low-turbulence Froude scale wind environment in a wave basin to facilitate simultaneous application of wind and waves to the model. Subsequently, the difficulties of scaling the highly Reynolds number–dependent wind turbine aerodynamics is presented in addition to methods for tailoring the turbine and wind characteristics to best emulate the full-scale condition. Lastly, the scaling methodology is demonstrated using results from 1/50th-scale floating wind turbine testing performed at the Maritime Research Institute Netherlands (MARIN) Offshore Basin. The model test campaign investigated the response of the 126 -m rotor diameter National Renewable Energy Lab (NREL) horizontal axis wind turbine atop three floating platforms: a tension-leg platform, a spar-buoy, and a semisubmersible. The results highlight the methodology's strengths and weaknesses for simulating full-scale global response of floating wind turbine systems.
Estimation and Applications of Clear Sky Global Horizontal Irradiance at the Equator
Authors: Yang Dazhi , Walsh Wilfred M. , Jirutitijaroen Panida
Published: March 2014

We analyze Singapore global horizontal irradiance (GHI) measurements and propose a clear sky GHI model for equatorial regions. The empirical formulation simplifies the atmosphere radiative transfer to a single exponential term. The results are benchmarked using locally collected data. Two applications of the clear sky model are briefly discussed.
Quantitative Evaluation of the Thermal Heterogeneity on the Surface of Cryotherapy Cooling Pads
Authors: Khoshnevis Sepideh , Nordhauser Jennifer E. , Craik Natalie K. , Diller Kenneth R.
Published: March 2014

We have investigated thermal operating characteristics of 13 commercially available cryotherapy units (CTUs) and their associated cooling pads using IR imaging. Quantitative examination of the temperature profiles from pad IR images shows diverse, nonuniform temperature distribution patterns. The extent of heterogeneity of the temperature fields was quantified via standard image analysis methods, including thresholding, spatial gradient diagrams, and frequency histogram distributions. A primary conclusion of this study is that it is a misnomer to characterize the thermal performance of a CTU and cooling pad combination in terms of a single therapeutic temperature.
A Simulation Protocol for Exercise Physiology in Fontan Patients Using a Closed Loop Lumped-Parameter Model
Authors: Kung Ethan , Pennati Giancarlo , Migliavacca Francesco , Hsia Tain-Yen , Figliola Richard , Marsden Alison , Giardini Alessandro ,   MOCHA Investigators
Published: March 2014

Background: Reduced exercise capacity is nearly universal among Fontan patients, though its etiology is not yet fully understood. While previous computational studies have attempted to model Fontan exercise, they did not fully account for global physiologic mechanisms nor directly compare results against clinical and physiologic data. Methods: In this study, we developed a protocol to simulate Fontan lower-body exercise using a closed-loop lumped-parameter model describing the entire circulation. We analyzed clinical exercise data from a cohort of Fontan patients, incorporated previous clinical findings from literature, quantified a comprehensive list of physiological changes during exercise, translated them into a computational model of the Fontan circulation, and designed a general protocol to model Fontan exercise behavior. Using inputs of patient weight, height, and if available, patient-specific reference heart rate (HR) and oxygen consumption, this protocol enables the derivation of a full set of parameters necessary to model a typical Fontan patient of a given body-size over a range of physiologic exercise levels. Results: In light of previous literature data and clinical knowledge, the model successfully produced realistic trends in physiological parameters with exercise level. Applying this method retrospectively to a set of clinical Fontan exercise data, direct comparison between simulation results and clinical data demonstrated that the model successfully reproduced the average exercise response of a cohort of typical Fontan patients. Conclusion: This work is intended to offer a foundation for future advances in modeling Fontan exercise, highlight the needs in clinical data collection, and provide clinicians with quantitative reference exercise physiologies for Fontan patients.
Thermally Induced Apoptosis, Necrosis, and Heat Shock Protein Expression in Three-Dimensional Culture
Authors: Song Alfred S. , Najjar Amer M. , Diller Kenneth R.
Published: March 2014

This study was conducted to compare the heat shock responses of cells grown in 2D and 3D culture environments as indicated by the level of heat shock protein 70 expression and the incidence of apoptosis and necrosis of prostate cancer cell lines in response to graded hyperthermia. PC3 cells were stably transduced with a dual reporter system composed of two tandem expression cassettes—a conditional heat shock protein promoter driving the expression of green fluorescent protein (HSPp-GFP) and a cytomegalovirus (CMV) promoter controlling the constitutive expression of a “beacon” red fluorescent protein (CMVp-RFP). Two-dimensional and three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well plates for evaluation of their time-dependent response to supraphysiological temperature. To induce controlled hyperthermia, culture plates were placed on a flat copper surface of a circulating water manifold that maintained the specimens within ±0.1 °C of a target temperature. Hyperthermia protocols included various combinations of temperature, ranging from 37 °C to 57 °C, and exposure times of up to 2 h. The majority of protocols were focused on temperature and time permutations, where the response gradient was greatest. Post-treatment analysis by flow cytometry analysis was used to measure the incidences of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain), and HSP70 transcription (GFP expression). Cells grown in 3D compared with 2D culture showed reduced incidence of apoptosis and necrosis and a higher level of HSP70 expression in response to heat shock at the temperatures tested. Cells responded differently to hyperthermia when grown in 2D and 3D cultures. Three-dimensional culture appears to enhance survival plausibly by activating protective processes related to enhanced-HSP70 expression. These differences highlight the importance of selecting physiologically relevant 3D models in assessing cellular responses to hyperthermia in experimental settings.
Performance and Emissions Characteristics of Diesel-Ignited Gasoline Dual Fuel Combustion in a Single-Cylinder Research Engine
Authors: Dwivedi U. , Carpenter C. D. , Guerry E. S. , Polk A. C. , Krishnan S. R. , Srinivasan K. K.
Published: March 2014

Diesel-ignited gasoline dual fuel combustion experiments were performed in a single-cylinder research engine (SCRE), outfitted with a common-rail diesel injection system and a stand-alone engine controller. Gasoline was injected in the intake port using a port-fuel injector. The engine was operated at a constant speed of 1500 rev/min, a constant load of 5.2 bar indicated mean effective pressure (IMEP), and a constant gasoline energy substitution of 80%. Parameters such as diesel injection timing (SOI), diesel injection pressure, and boost pressure were varied to quantify their impact on engine performance and engine-out indicated specific nitrogen oxide emissions (ISNOx), indicated specific hydrocarbon emissions (ISHC), indicated specific carbon monoxide emissions (ISCO), and smoke emissions. Advancing SOI from 30 degrees before top dead center (DBTDC) to 60 DBTDC reduced ISNOx from 14 g/kW h to less than 0.1 g/kW h; further advancement of SOI did not yield significant ISNOx reduction. A fundamental change was observed from heterogeneous combustion at 30 DBTDC to “premixed enough” combustion at 50–80 DBTDC and finally to well-mixed diesel-assisted gasoline homogeneous charge compression ignition (HCCI)-like combustion at 170 DBTDC. Smoke emissions were less than 0.1 filter smoke number (FSN) at all SOIs, while ISHC and ISCO were in the range of 8–20 g/kW h, with the earliest SOIs yielding very high values. Indicated fuel conversion efficiencies were ∼ 40–42.5%. An injection pressure sweep from 200 to 1300 bar at 50 DBTDC SOI and 1.5 bar intake boost showed that very low injection pressures lead to more heterogeneous combustion and higher ISNOx and ISCO emissions, while smoke and ISHC emissions remained unaffected. A boost pressure sweep from 1.1 to 1.8 bar at 50 DBTDC SOI and 500 bar rail pressure showed very rapid combustion for the lowest boost conditions, leading to high pressure rise rates, higher ISNOx emissions, and lower ISCO emissions, while smoke and ISHC emissions remained unaffected by boost pressure variations.
Particulate Matter Emission Comparison of Spark Ignition Direct Injection (SIDI) and Port Fuel Injection (PFI) Operation of a Boosted Gasoline Engine
Authors: Su Jianye , Lin Weiyang , Sterniak Jeff , Xu Min , Bohac Stanislav V.
Published: March 2014

Spark ignition direct injection (SIDI) gasoline engines, especially in downsized boosted engine platforms, are increasing their market share relative to port fuel injection (PFI) engines in U.S., European and Chinese vehicles due to better fuel economy by enabling higher compression ratios and higher specific power output. However, particulate matter (PM) emissions from engines are becoming a concern due to adverse human health and environment effects, and more stringent emission standards. To conduct a PM number and size comparison between SIDI and PFI systems, a 2.0 L boosted gasoline engine has been equipped and tested with both systems at different loads, air fuel ratios, spark timings, fuel pressures and injection timings for SIDI operation and loads, air fuel ratios and spark timings for PFI operation. Regardless of load, air fuel ratio, spark timing, fuel pressure, and injection timing, particle size distribution from SIDI and PFI is shown to be bimodal, exhibiting nucleation and accumulation mode particles. SIDI produces particle numbers that are an order of magnitude greater than PFI. Particle number can be reduced by retarding spark timing and operating the engine lean, both for SIDI and PFI operation. Increasing fuel injection pressure and optimizing injection timing with SIDI also reduces PM emissions. This study provides insight into the differences in PM emissions from boosted SIDI and PFI engines and an evaluation of PM reduction potential by varying engine operating parameters in boosted SIDI and PFI gasoline engines.
A Linear Least-Squares Algorithm for Double-Wiebe Functions Applied to Spark-Assisted Compression Ignition
Authors: Hellström Erik , Stefanopoulou Anna , Jiang Li
Published: March 2014

An algorithm for determining the four tuning parameters in a double-Wiebe description of the combustion process in spark-assisted compression ignition engines is presented where the novelty is that the tuning problem is posed as a weighted linear least-squares problem. The approach is applied and shown to describe well an extensive data set from a light-duty gasoline engine for various engine speeds and loads. Correlations are suggested for the four parameters based on the results, which illustrates how the double-Wiebe approach can also be utilized in a predictive simulation. The effectiveness of the methodology is quantified by the accuracy for describing and predicting the heat release rate and predicting the cylinder pressure. The root-mean square errors between the measured and predicted cylinder pressures are 1bar or less, which corresponds to 2% or less of the peak cylinder pressure.
Robust Adaptive Tracking Control of Autonomous Underwater Vehicle-Manipulator Systems
Authors: Santhakumar Mohan , Kim Jinwhan
Published: March 2014

This paper proposes a new tracking controller for autonomous underwater vehicle-manipulator systems (UVMSs) using the concept of model reference adaptive control. It also addresses the detailed modeling and simulation of the dynamic coupling between an autonomous underwater vehicle and manipulator system based on Newton–Euler formulation scheme. The proposed adaptation control algorithm is used to estimate the unknown parameters online and compensate for the rest of the system dynamics. Specifically, the influence of the unknown manipulator mass on the control performance is indirectly captured by means of the adaptive control scheme. The effectiveness and robustness of the proposed control scheme are demonstrated using numerical simulations.
Design and Simulation of Pressure Coordinated Control System for Hybrid Vehicle Regenerative Braking System
Authors: Yang Yang , Zou Jiahang , Yang Y. , Qin Datong
Published: March 2014

In order to solve the limitations and complexity of a pressure coordinated control system for hybrid regenerative braking, a new pressure coordinated control system applicable for a regenerative braking system of hybrid electric vehicles is proposed in this paper based on an appropriate transformation on a traditional hydraulic braking system equipped with an antilock braking system (ABS). The system can realize regenerative braking and traditional ABS braking simultaneously. It also has greatly improved driver's brake pedal feel. The system model has been simulated and analyzed based on AMESim-simulink cosimulation. The simulation results show the effectiveness and feasibility of the system, which lay the foundation for design and optimization of the regenerative braking system.
A Constant-Force Compliant Gripper for Handling Objects of Various Sizes
Authors: Wang Jung-Yuan , Lan Chao-Chieh
Published: March 2014

This paper presents the design, simulation, and testing of a compliant gripper that can provide a constant gripping force to handle objects of various sizes. Maintaining a proper gripping force is challenging when manipulating delicate objects with uncertain sizes and stiffnesses. To avoid damage and provide a stable grip of an object, force feedback is often required so that the gripping force can be directly or indirectly regulated. Without using additional sensors and control, the proposed gripper passively maintains a constant prespecified contact force between fingertip and object. The gripper is designed to have a constant input force generated by a constant-force mechanism (CFM). Transmitted through a statically balanced (SB) mechanism, a constant gripping force is obtained at the fingertip. After a formulation to find the optimal gripper configuration, the design is verified through comparison with simulation results. Finally, a prototype of the constant-force gripper is demonstrated. The novel gripper is expected to serve as a reliable alternative for object manipulation.
Microbial Community Dynamics and Stability during an Ammonia-Induced Shift to Syntrophic Acetate Oxidation
Authors: Werner Jeffrey J. , Garcia Marcelo L. , Perkins Sarah D. , Yarasheski Kevin E. , Smith Samuel R. , Muegge Brian D. , Stadermann Frank J. , DeRito Christopher M. , Floss Christine , Madsen Eugene L. , Gordon Jeffrey I. , Angenent Largus T.
Published: March 2014

Anaerobic digesters rely on the diversity and distribution of parallel metabolic pathways mediated by complex syntrophic microbial communities to maintain robust and optimal performance. Using mesophilic swine waste digesters, we experimented with increased ammonia loading to induce a shift from aceticlastic methanogenesis to an alternative acetate-consuming pathway of syntrophic acetate oxidation. In comparison with control digesters, we observed shifts in bacterial 16S rRNA gene content and in functional gene repertoires over the course of the digesters' 3-year operating period. During the first year, under identical startup conditions, all bioreactors mirrored each other closely in terms of bacterial phylotype content, phylogenetic structure, and evenness. When we perturbed the digesters by increasing the ammonia concentration or temperature, the distribution of bacterial phylotypes became more uneven, followed by a return to more even communities once syntrophic acetate oxidation had allowed the experimental bioreactors to regain stable operation. The emergence of syntrophic acetate oxidation coincided with a partial shift from aceticlastic to hydrogenotrophic methanogens. Our 16S rRNA gene analysis also revealed that acetate-fed enrichment experiments resulted in communities that did not represent the bioreactor community. Analysis of shotgun sequencing of community DNA suggests that syntrophic acetate oxidation was carried out by a heterogeneous community rather than by a specific keystone population with representatives of enriched cultures with this metabolic capacity.
Phylogenetic Profiles of In-House Microflora in Drains at a Food Production Facility: Comparison and Biocontrol Implications of Listeria-Positive and -Negative Bacterial Populations
Authors: Fox Edward M. , Solomon Katie , Moore John E. , Wall Patrick G. , Fanning Séamus
Published: March 2014

Listeria
species experience complex interactions with other microorganisms, which may promote growth and colonization of the organism in local environments or negatively affect them. This study investigated the microbial community at a food production facility, examining interactions between
Listeria
and the associated microbiome.
Listeria
species can be transferred between zones in the production environment by individuals or equipment, and drains may act as a reservoir for the organism, reflecting the microbial flora potentially in the production environment. Drains that were colonized by
Listeria
species and those determined to be free of
Listeria
were examined. In each case, 16S rRNA gene analysis was performed using the PhyloChip platform. Some general similarities in bacterial population structure were observed when
Listeria
-negative and -positive drain communities were compared, with some distinct differences also noted. These included increased populations of the genera
Prevotella
and
Janthinobacterium
associated with the absence of
Listeria
species, whereas
Enterococcus
and
Rhodococcus
were in higher abundance in drains colonized by
Listeria
species. Based on these results, a selection of bacterial species were grown in coculture biofilm with a
Listeria monocytogenes
strain identified as having colonized a drain at the facility. Mixed-species biofilm experiments showed that
Janthinobacterium
inhibited attachment and subsequent biofilm formation of
L. monocytogenes
; however,
Enterococcus gallinarum
significantly increased it. The results of this study suggest the microbial community in food processing facilities can impact the colonization of
Listeria
species and that influencing the microbiome in favor of antilisterial species may reduce the colonization of
Listeria
species and limit the likelihood of product/process contamination.
Massive Infection of Seabird Ticks with Bacterial Species Related to Coxiella burnetii
Authors: Wilkinson David A. , Dietrich Muriel , Lebarbenchon Camille , Jaeger Audrey , Le Rouzic Céline , Bastien Matthieu , Lagadec Erwan , McCoy Karen D. , Pascalis Hervé , Le Corre Matthieu , Dellagi Koussay , Tortosa Pablo
Published: March 2014

Seabird ticks are known reservoirs of bacterial pathogens of medical importance; however, ticks parasitizing tropical seabirds have received less attention than their counterparts from temperate and subpolar regions. Recently,
Rickettsia africae
was described to infect seabird ticks of the western Indian Ocean and New Caledonia, constituting the only available data on bacterial pathogens associated with tropical seabird tick species. Here, we combined a pyrosequencing-based approach with a classical molecular analysis targeting bacteria of potential medical importance in order to describe the bacterial community in two tropical seabird ticks,
Amblyomma loculosum
and
Carios
(
Ornithodoros
)
capensis
. We also investigated the patterns of prevalence and host specificity within the biogeographical context of the western Indian Ocean islands. The bacterial community of the two tick species was characterized by a strong dominance of
Coxiella
and
Rickettsia
. Our data support a strict
Coxiella
-host tick specificity, a pattern resembling the one found for
Rickettsia
spp. in the same two seabird tick species. Both the high prevalence and stringent host tick specificity suggest that these bacteria may be tick symbionts with probable vertical transmission. Detailed studies of the pathogenicity of these bacteria will now be required to determine whether horizontal transmission can occur and to clarify their status as potential human pathogens. More generally, our results show that the combination of next generation sequencing with targeted detection/genotyping approaches proves to be efficient in poorly investigated fields where research can be considered to be starting from scratch.
Australian Dust Storm Associated with Extensive Aspergillus sydowii Fungal “Bloom” in Coastal Waters
Authors: Hallegraeff Gustaaf , Coman Frank , Davies Claire , Hayashi Aiko , McLeod David , Slotwinski Anita , Whittock Lucy , Richardson Anthony J.
Published: March 2014

A massive central Australian dust storm in September 2009 was associated with abundant fungal spores (150,000/m
3
) and hyphae in coastal waters between Brisbane (27°S) and Sydney (34°S). These spores were successfully germinated from formalin-preserved samples, and using molecular sequencing of three different genes (the large subunit rRNA gene [LSU], internal transcribed spacer [ITS[, and beta-tubulin gene), they were conclusively identified as
Aspergillus sydowii
, an organism circumstantially associated with gorgonian coral fan disease in the Caribbean. Surprisingly, no human health or marine ecosystem impacts were associated with this Australian dust storm event. Australian fungal cultures were nontoxic to fish gills and caused a minor reduction in the motility of
Alexandrium
or
Chattonella
algal cultures but had their greatest impacts on
Symbiodinium
dinoflagellate coral symbiont motility, with hyphae being more detrimental than spores. While we have not yet seen any soft coral disease outbreaks on the Australian Great Barrier Reef similar to those observed in the Caribbean and while this particular fungal population was non- or weakly pathogenic, our observations raise the possibility of future marine ecosystem pathogen impacts from similar dust storms harboring more pathogenic strains.