bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the hydrocarbon and carbon monoxide emissions in moderately and highly dilute Low Temperature Combustion
Authors: Sogbesan Oluwasujibomi , Davy Martin H , Garner Colin P
Published: May 2014

Low-temperature combustion in diesel engines offers attractive benefits through simultaneous reduction in the nitrogen oxide emissions and the soot emissions. However, it is known that the in-cylinder conditions typical of low-temperature combustion operation tend to produce high emissions of unburned hydrocarbons and carbon monoxide, reducing the combustion efficiency. The present study develops from the hypothesis that this characteristic poor combustion efficiency is due to the in-cylinder mixture preparation strategies which are non-optimally matched to the requirements of the low-temperature combustion mode. In this work, the effects of three key fuel path parameters, namely the injection fuel quantity ratio, the dwell and the injection timing, on the carbon monoxide and hydrocarbon emissions were examined using a central-composite-design design-of-experiments method. The experiments were performed on a single-cylinder diesel research engine operating in a mixing-controlled low-temperature combustion mode at high and moderate exhaust gas recirculation rates with a split fuel injection for all conditions. The experiments identified the potential of fuel metering control for optimising the hydrocarbon emissions in low-temperature combustion by showing the effects of the fuel control parameters on the fuel mixing quality and the emission formation mechanisms. The response surfaces created from the detailed statistical analysis give a potent visualisation of the constraints on low-temperature combustion operation. This in turn allowed improved prescription of combustion modifications with the potential to moderate the negative effects observed.
An investigation of semiphysical artificial neural networks for multi-fuel combustion phasing control of spark ignition engines
Authors: Xiao Baitao , Wang Shu , Prucka Robert G
Published: May 2014

The number of engine control actuators and potential fuel sources are constantly increasing to meet fuel economy targets and global energy demand. The increased engine control complexity resulting from new actuators and fuels motivates the use of model-based control methodologies over map-based empirical approaches. Purely physics-based control techniques have the potential to decrease calibration burdens but must be complex to represent nonlinear engine behavior with low computational requirements. Artificial neural networks are recognized as powerful tools for modeling systems which exhibit nonlinear relationships, but they lack physical significance. Combining these two techniques to produce semiphysical artificial neural network models which provide acceptable accuracy while minimizing the artificial neural network size, the calibration effort and the computational intensity is the focus of this research. To minimize the size of the neural network, sensitivity analyses are carried out on the critical inputs and the minimum number of required neurons. The most critical physical parameters are selected as follows: the laminar flame speed; the turbulence intensity; the total in-cylinder mass. The control algorithm derivation is described, and the process validated in real time using an engine dynamometer. The real-time experimental results demonstrate that the semiphysical artificial neural network approach can produce accurate ignition timing control for both gasoline and E85. Robustness of the semiphysical neural network approach is also discussed on the basis of the real-time experimental results.
An emergence solution to the reasoning dual processes interaction problem
Authors: Wastell Colin A.
Published: May 2014

In a desire to account for experimental evidence that is said to indicate that human reasoning is subject to errors and biases, some scholars have championed dual process theories of reasoning. These scholars have attempted to resolve the dual processes interaction problem by proposing either additional processes or one system dominating the other. Utilising modularity theory, this article asserts that human reasoning consists of a multitude of modules that interact via dynamical emergent processes based on information input and output requirements. The proposed solution combines research from modularity and emergence theories.
A general framework for the use of logistic regression models in meta-analysis
Authors: Simmonds Mark C , Higgins Julian PT
Published: May 2014

Where individual participant data are available for every randomised trial in a meta-analysis of dichotomous event outcomes, “one-stage” random-effects logistic regression models have been proposed as a way to analyse these data. Such models can also be used even when individual participant data are not available and we have only summary contingency table data. One benefit of this one-stage regression model over conventional meta-analysis methods is that it maximises the correct binomial likelihood for the data and so does not require the common assumption that effect estimates are normally distributed. A second benefit of using this model is that it may be applied, with only minor modification, in a range of meta-analytic scenarios, including meta-regression, network meta-analyses and meta-analyses of diagnostic test accuracy. This single model can potentially replace the variety of often complex methods used in these areas. This paper considers, with a range of meta-analysis examples, how random-effects logistic regression models may be used in a number of different types of meta-analyses. This one-stage approach is compared with widely used meta-analysis methods including Bayesian network meta-analysis and the bivariate and hierarchical summary receiver operating characteristic (ROC) models for meta-analyses of diagnostic test accuracy.
Another Person in the Room
Authors: Kosny Agnieszka , MacEachen Ellen , Lifshen Marni , Smith Peter
Published: May 2014

Cross-language research poses many challenges. When researchers and participants do not speak the same language, meanings expressed by participants might not be understood in the same way by researchers, and the richness of participants’ experiences might be lost. This can lead to the misrepresentation and silencing of issues faced by these participants, especially newcomers. In this article, we critically examine our experience conducting qualitative interviews with injured immigrant workers with the help of professional interpreters. Using examples from our field notes and transcripts, we outline some of the key difficulties we faced: varying styles of interpretation, breeches of interview conventions, and miscommunications with interpreters. We discuss how these issues affected our study design, rapport with participants and, ultimately, data quality. We end with a discussion of how to improve cross-language and cross-cultural research.
More Than Just Fun and Games
Authors: Karriker Joy H. , Aaron Joshua R.
Published: May 2014

Simulations like the BSG and Glo-Bus allow students the opportunity to practice their integrated, strategic management skills in a relatively risk-free environment or “live case.” We review these games and address their strengths, along with the challenges associated with their classroom application. Because of their sound designs and intimacy with the principles of strategic management, the BSG and Glo-Bus provide unique and particularly rich contexts for student application of capstone constructs through complex, yet enjoyable, competitive frameworks.
Prediction and analysis of ductile fracture in sheet metal forming—Part II: Application of the modified Ayada criterion
Authors: Liu HS , Fu MW
Published: May 2014

Ductile fracture occurs due to micro-void nucleation, growth, and final coalescence into micro-crack. In this paper, a modified Ayada ductile criterion is implemented for prediction and analysis of the ductile fracture in sheet metal forming. To enhance calculation efficiency, an algorithm for efficient calculation of damage value is proposed. The finite element formulations for obtaining the generalized strain distribution and the damage value distribution by using the modified Ayada ductile criterion are presented. Case studies show that the simulation-based predictions with the built-in modified Ayada ductile fracture criterion have a good agreement with the experimental results. Furthermore, the comparison of the predictions by using the Ayada and the modified criteria shows that the latter is more conservative and hence safer for the design of deformed parts, forming processes, and tooling.
Nephrotoxicity Risk Factors and Intravenous Vancomycin Dosing in the Immediate Postoperative Period Following Antibiotic-Impregnated Cement Spacer Placement
Authors: Reed Erica E. , Johnston Jessica , Severing Jennifer , Stevenson Kurt B. , Deutscher Meredith
Published: May 2014

Background: Several case reports have documented acute kidney injury (AKI) attributable to antibiotic-impregnated cement (AIC) spacers. Objectives: To identify AKI risk factors among patients who underwent AIC placement and determine whether vancomycin-AIC placement affects systemic vancomycin dosing. Methods: Phase 1 was a case-control study to identify AKI risk factors among patients who underwent AIC placement. Cases experienced AKI; controls had unchanged renal function. Phase 2 was a retrospective cohort study. Patients who received ≥72 hours of intravenous (IV) vancomycin were divided into 2 groups according to whether they underwent vancomycin-AIC placement. Primary outcome was number of vancomycin dosing changes. Results: Phase 1: Among 26 cases and 74 controls AKI risk factors on univariate and multivariable analysis included exposure to angiotensin-converting-enzyme (ACE) inhibitor exposure within 7 days of AIC placement (42% vs 20%, P = 0.03) and piperacillin-tazobactam within 7 days following AIC placement (31% vs 12%, P = 0.03). Phase 2: Among 53 patients who underwent vancomycin-AIC placement and 104 who underwent another surgery type, vancomycin was adjusted more frequently in patients who underwent vancomycin-AIC placement (28% vs 15%, P = 0.06). Conclusions: Among patients who undergo AIC placement with vancomycin and/or tobramycin, exposure to ACE inhibitors and piperacillin-tazobactam are associated with increased risk of AKI in the immediate postoperative period. No empirical adjustments to IV vancomycin dosing are necessary in patients undergoing vancomycin-AIC placement.
A general approach to tune the vibration properties of the mounting system in the high-speed and heavy-duty engine
Authors: Zhang Baocheng , Zhan Haifei , Gu Yuantong
Published: May 2014

The majority of the current research on the mounting system has emphasised on the low/medium power engine, rare work has been reported for the high-speed and heavy-duty engine, the vibration characteristics of which exhibits significantly increased complexity and uncertainty. In this work, a general dynamics model was firstly established to describe the dynamic properties of a mounting system with various numbers of mounts. Then, this model was employed for the optimization of the mounting system. A modified Powell conjugate direction method was developed to improve the optimization efficiency. Basing on the optimization results obtained from the theoretical model, a mounting system was constructed for a V6 diesel engine. The experimental measurement of the vibration intensity of the mounting systems shows excellent agreement with the theoretical calculations, indicating the validity of the model. This dynamics model opens a new avenue in assessing and designing the mounting system for a high-speed and heavy-duty engine. On the other hand, the delineated dynamics model, and the optimization algorithm should find wide applications for other mounting systems, such as the power transmission system which usually has various uncertain mounts.
Research on the characteristics of transverse dynamic stiffness of an inclined shallow cable
Authors: Dan Danhui , Xu Bin , Huang Hongwei , Yan Xing-fei
Published: May 2014

Based on the governing equation of inclined cable segment vibration, an equilibrium equation formulated in dynamic stiffness is built to describe the force balance status at arbitrary location along cable where transverse force is applied. A closed-form solution to transverse dynamic stiffness matrix corresponding to two degrees-of-freedom and dynamic stiffness corresponding to one degree-of-freedom is proposed herein, which considers the effects of sag, flexural rigidity, clamped boundary condition, and inclined angle of real inclined cable simultaneously. A real cable damper system vibration test is used to verify the rationality and credibility of the proposed closed-form solution. The effects of cable parameters above mentioned on the dynamic stiffness of cable are investigated by using this approach. It shows that, by the influence of these factors, the cable transverse dynamic stiffness takes on complicated behaviors. Due to the marked errors or even wrong results induced, it is unreasonable to evaluate the cable transverse dynamic stiffness both by the approach of taut string theory and by treating the inclined angle to horizontal attitude.
A novel health monitoring scheme for smart structures
Authors: Arsava Sarp K , Chong Jo Woon , Kim Yeesock
Published: May 2014

This paper proposes a multiclass nonlinear relevance vector machine (MNRVM) model for health monitoring of smart structures equipped with magnetorheological (MR) dampers. The proposed model will be used to classify the damage statuses of the integrated structure-control systems subjected to ambient excitations. A numerical model of a three-story building equipped with an MR damper is studied to demonstrate the effectiveness of the proposed health monitoring schemes. Dynamic responses of the smart structures subjected to random excitations are measured. Discrete wavelet transform is applied to the obtained data to compress and filter noises of the measured data. As a next step, the compressed and de-noised signals are used for developing autoregressive (AR) models. Then the MNRVM is applied to the AR-coefficient data to classify them with respect to the damage statuses. As a baseline, the support vector machine (SVM) algorithm is considered. It is demonstrated that the proposed MNRVM framework is effective in classifying various damage statuses of the nonlinear smart structures subjected to ambient excitations. Simulation results also show that the MNRVM performs similar to the SVM with faster computation time.
Modeling and design of an electrically actuated resonant microswitch
Authors: Jrad Mohamed , Younis Mohammad I , Najar Fehmi
Published: May 2014

Modeling and simulation of a new device concept of an electrically actuated resonant switch (EARS) is presented in this paper. This EARS can be tuned to be triggered at low levels of acceleration, as low as those of earthquakes. The device is made by mounting an electrostatically actuated cantilever microbeam, with a tip mass, on top of a compliant board or a printed circuit board (PCB), which is modeled as a hinged–hinged beam. A distributed-parameter model of the device is derived for the microbeam and the PCB using Hamilton’s principle based on Euler–Bernoulli beam theory. The equations are then discretized using the Galerkin procedure. A nonlinear numerical dynamic analysis is performed in order to characterize the behavior and performance of the device when subjected to acceleration pulses. A parametric study showing several curves of dynamic pull-in thresholds for various values of electric voltage loads and frequencies of excitation is conducted. It is shown that the device can be triggered at a wide range of accelerations ranging from 0.33  g to 200  g for various values of DC and AC voltages.
Effect of shear stress alteration on atherosclerotic plaque vulnerability in cholesterol-fed rabbits
Authors: den Dekker Wijnand K , Tempel Dennie , Speelman Lambert , Huizingh Jeroen , Ramos Allan , Gijsen Frank J , Wentzel Jolanda J , Cheng Caroline , Duckers Henricus J
Published: May 2014

Previously, we created an experimental murine model for the induction of vulnerable plaque (VP). Although this murine model offers the opportunity to study the different molecular biological pathways that regulate plaque destabilization, the size of the animals severely limits the use of the model for in vivo diagnostics and percutaneous interventions. This study aimed to create a VP model in the rabbit, based on the murine model, to aid the assessment and development of novel diagnostic and interventional tools. New Zealand white rabbits were fed on a 2% cholesterol diet. After 1 week, a shear stress-altering device was implanted around the right carotid artery. Twelve weeks after cast placement, the carotid artery was isolated and processed for (immuno-)histological analysis to evaluate the presence of a VP phenotype. Atherosclerotic plaques with high lipid and macrophage content, low vascular smooth muscle cell content and intimal neovascularization were located upstream and downstream of the cast. The plaques lacked a significant necrotic core. In conclusion, we were able to create atherosclerotic plaques with a phenotype beyond that of a fatty streak, with a high percentage of lipids and macrophages, a thick cap with some vascular smooth muscle cells and neovascularization. However, as there was only a small necrotic core, the overall phenotype seems less vulnerable as compared to the thin fibrous cap atheroma in patients.
Of mushrooms and method: History and the family in Hobbes’s science of politics
Authors: Sagar Paul
Published: May 2014

Hobbes’s account of the commonwealth is standardly interpreted to be primarily a theory of contract, whereby the archetypal manner of forming a political community is via an act of mutual agreement between suspicious individuals of equal power. By examining Hobbes’s theories of the pre-political family, and what he says about the role of real history in the development of political societies, I conclude that this standard interpretation is untenable. Rather, Hobbes’s conception of commonwealth ‘by institution’ is a hypothetical model used to illustrate the mechanics of sovereignty, and to reconcile men to the conditions of subjection to absolute political power. In practice, all sovereignty is originally by ‘acquisition’. Realizing this casts serious doubt on the possibility that Hobbes is a fundamentally democratic thinker. In turn, we are invited to reconsider the history of political thought after Hobbes, in particular by seeing his theory of the family and of history as a genealogical ancestor of Scottish Enlightenment political theory.
Minimal mutual advantage: How the social contract can do justice to the disabled
Authors: Sisson Melanie , DeNicolo Martin
Published: May 2014

In this work we address the proposition that because it emerges from the contract tradition and so relies upon the assumption of mutual advantage, John Rawls' theory of “Justice as Fairness” cannot accommodate persons with severe mental and/or physical impairments. We respond to this criticism by proposing a revision to Rawls' contracting situation, the Original Position (OP). Specifically, we propose to supplant the traditional understanding of mutual advantage—which we agree does constitute the necessary and sufficient condition for deliberation to come about in the OP, as it stands—with a more modest alternative: a Hobbes-inspired concept that we call minimal mutual advantage. We argue that when this revision is introduced into Justice as Fairness, it reconciles admirably the seeming tension between contractarianism’s insistence on the rational, self-interested actor and the reality of societies in which not all members are capable of meeting a standard of reciprocity understood in terms of productive contributions to the general well-being. In so doing, minimal mutual advantage renders indistinguishable the disabled from the able in the OP, allowing Justice as Fairness to capture successfully problems of disability while leaving intact the more appealing aspects of liberalism that other approaches would dismiss.
Berlin and Bosanquet: True self and positive freedom
Authors: Simhony Avital
Published: May 2014

Is the Idealist conception of positive freedom doomed as politically dangerous? Decidedly yes, Berlin famously argues. The danger lies with manipulating positive freedom into a political tool of tyranny, coercing individuals to be free. The vehicle of manipulation is a conception of a divided self that underpins positive freedom. For, Berlin argues, conceptions of freedom derive directly from views of what constitutes a self. He cites the British Idealists as evidence for his criticism. The case for Green’s immunity to Berlin’s criticism is now well established. Bosanquet, in particular, however, is a sitting duck to Berlin’s fire. Berlin’s fire, however, misses its target. Not only is Bosanquet immune to Berlin’s criticism, but Berlin’s criticism obscures the extent to which Bosanquet shares Berlin’s worry about the danger of concentrated political power. Moreover, Bosanquet institutionalizes positive freedom into a bulwark against political tyranny in a fashion that Berlin’s wholesale criticism of positive freedom forecloses. Bosanquet’s true self is equipped to resist being coerced to be free. Indeed, Berlin’s divided self ill-describes Bosanquet’s conception of self which being, instead, complex/dynamic/integrated, is at once spontaneous/energetic and habitual/automatic. Moreover, whereas he recognizes with Bosanquet that positive freedom is not merely an internal condition of the true self, but takes shape in society, Berlin’s holistic interpretation of the organic metaphor of society means that he sees only the “dark” side of that connection. Consequently, he misses the affirmative link, the “bright” side, that Bosanquet, employing a relational interpretation of the organic metaphor, forges between positive freedom and social institutions. Ultimately, engaging Berlin and Bosanquet unveils the complexity of political theory.
Modeling the visibility of the stroboscopic effect occurring in temporally modulated light systems
Authors: Perz M , Vogels IMLC , Sekulovski D , Wang L , Tu Y , Heynderickx IEJ
Published: May 2014

Three perception experiments were conducted to develop a measure for predicting the visibility of the stroboscopic effect occurring in temporally modulated light systems. In the first experiment, different methodologies were evaluated for their measurement error. In the second experiment, the visibilities of the stroboscopic effect for square wave and sine wave light modulations were measured and the results were found to be consistent with previous findings for flicker perception. In the third experiment, specifically crafted, complex waveforms were used to test the theory of frequency summation. Based on the results of these three experiments, a new measure for the visibility of the stroboscopic effect was developed, consisting of a summation of the energy in all frequency components, normalized for human sensitivity.
Fuel efficiency assessment with Data Envelopment Analysis
Authors: Kiymaz Evren , Johnson Alan W , Cunningham William
Published: May 2014

Military air forces have a significant demand for fuel, but increasing costs force them to use their fuel as efficiently as possible. We investigated the suitability of Data Envelopment Analysis (DEA) to measure C-17 airlift fuel efficiency for the United States Air Mobility Command (AMC). Airlift missions constitute the decision-making units in our study. Seven respective inputs and outputs were used and three different DEA models were contrasted. The results show that DEA provides an effective ability to identify fuel usage inefficiencies. A slack-based DEA measure proved superior at differentiating inefficiencies to an established index in use by AMC planners.
Predictors of Insulin Initiation in Metformin and Sulfonylurea Users in Primary Care Practices
Authors: Kostev Karel , Dippel Franz-Werner , Rathmann Wolfgang
Published: May 2014

Aims:

The aims were to investigate predictors of insulin initiation in new users of metformin or sulfonylureas in primary care practices, in particular, its association with decreased renal function.

Methods:

Data from 9103 new metformin and 1120 sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 from 1072 practices were retrospectively analyzed (Disease Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score matching was used to adjust for confounders (age, sex, practice characteristics, comorbidity).

Results:

Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years ( P < .001). Kaplan-Meier curves (propensity score matched patients) showed that the metformin group was at a lower risk of insulin initiation compared to sulfonylurea users throughout the study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m2) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users.

Conclusions:

New users of sulfonylurea monotherapy in primary care practices in Germany were about 3-fold more likely to start insulin therapy than those with metformin. Kidney function decline was associated with earlier insulin initiation in metformin but not in sulfonylurea users.
How Political and Media System Characteristics Moderate Interactions between Newspapers and Parliaments
Authors: Vliegenthart Rens , Mena Montes Noemi
Published: May 2014

This paper investigates the multidirectional causal relationships between negative economic coverage in two national newspapers and parliamentary questions addressing the economic crisis in Spain and the Netherlands, while controlling for the “real” economy as portrayed by stock market indices. Weekly level vector autoregression (VAR) analyses demonstrate for both countries that newspaper coverage is affected by stock market ratings and parliamentary questions. In Spain, newspaper coverage also affects parliament. A more detailed analysis shows that in Spain, the newspaper that is close to the government is ignored by the opposition as a source for parliamentary questions, while this newspaper also ignores the attention the opposition pays to negative economic developments in its parliamentary questions. In the Netherlands, we do not find any differences across newspapers. These findings reflect the differences in political and media systems and specifically the differences in the levels of consensus-orientation and political parallelism between the two countries.
Effects of dilution and baseplate strength on stress distributions in multipass welds deposited using low transformation temperature filler alloys
Authors: Ramjaun T. I. , Stone H. J. , Karlsson L. , Kelleher J. , Ooi S. W. , Dalaei K. , Rebelo Kornmeier J. , Bhadeshia H. K. D. H.
Published: May 2014

Transformation plasticity can be utilised to control residual stresses in steel welds. This requires special filler alloys that transform at a sufficiently low temperature to compensate for accumulated thermal contraction strains. However, the welding parameters needed to optimise the effect in multipass joints have yet to be established. This topic has been investigated by characterising the residual stress distribution in multipass welds fabricated with different welding alloys and baseplates using neutron diffraction to assess the effects of dilution and baseplate strength. While the use of richly alloyed weld metal does enhance fatigue performance in single pass joints, the extent of stress relief that can be derived from transformation plasticity is reduced due to incomplete martensitic transformation when further layers are deposited. For all cases studied, compressive stresses were measured in the weld metal with balancing tensile stress in the heat affected zone of the plate. The magnitude of the tension was observed to be a function of the strength of the baseplate. Recommendations are also presented for the combination of welding and material parameters that lead to the optimum exploitation of transformation plasticity as a method for boosting the fatigue performance of multipass welded joints.
Novel soft variable polarity plasma arc and its influence on keyhole in horizontal welding of aluminium alloys
Authors: Zhang Q. L. , Fan C. L. , Lin S. B. , Yang C. L.
Published: May 2014

A novel soft variable polarity plasma arc has been proposed to solve the problems in horizontal welding of aluminium alloys (in 2G position). It is defined as an arc with reduced arc pressure while retaining the ability to maintain a stable keyhole. In this paper, its characteristics were studied and its influence on the stability of keyhole was investigated. The results indicate that it has been changed in the energy and pressure distribution compared with ordinary variable polarity plasma arc. It is beneficial for the stability of keyhole especially for the stability of keyhole shrinking process. The keyhole can be established easily. It can also improve the wetting and spreading of molten metal in weld pool. The reason for a stable keyhole is that the soft variable polarity plasma can provide a suitable heat input and a suitable arc pressure.
Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells
Authors: Sherman Alexandra , Su Jin , Lin Shina , Wang Xiaomei , Herzog Roland W. , Daniell Henry
Published: May 2014

Key Points

Factor VIII antigens can be expressed in chloroplasts and bioencapsulated in plant cells. Oral delivery of plant cells expressing FVIII domains suppresses and reverses inhibitor formation in mice with hemophilia A by induction of CD4+ regulatory T cells.
Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia
Authors: Kiel Mark J. , Velusamy Thirunavukkarasu , Rolland Delphine , Sahasrabuddhe Anagh A. , Chung Fuzon , Bailey Nathanael G. , Schrader Alexandra , Li Bo , Li Jun Z. , Ozel Ayse B. , Betz Bryan L. , Miranda Roberto N. , Medeiros L. Jeffrey , Zhao Lili , Herling Marco , Lim Megan S. , Elenitoba-Johnson Kojo S. J.
Published: May 2014

Key Points

We identify gain-of-function mutations involving IL2RG, JAK1/3, and STAT5B as well as deleterious mutations affecting EZH2, FBXW10, and CHEK2 in T-PLL. Pharmacologic targeting of primary T-PLL cells with the STAT5 inhibitor pimozide leads to apoptosis.
Some results on zero points of m-accretive operators in reflexive Banach spaces
Authors: Wu Chang Qun , Lv Songtao , Zhang Yunpeng
Published: May 2014

A modified proximal point algorithm is proposed for treating common zero points of a finite family of m-accretive operators. A strong convergence theorem is established in a reflexive, strictly convex Banach space with the uniformly Gâteaux differentiable norm.
Cardan angle rotation sequence effects on first‐metatarsophalangeal joint kinematics: implications for measuring hallux valgus deformity
Authors: Glasoe Ward M , Pena Fernando A , Phadke Vandana
Published: May 2014

Background

There currently are no recommended standards for reporting kinematics of the first‐metatarsophalangeal joint. This study compared 2 different rotation sequences of Cardan angles, with implications for understanding the measurement of hallux valgus deformity.

Methods

Thirty‐one women (19 hallux valgus; 12 controls) participated. All were scanned in an open‐upright magnetic resonance scanner, their foot posed to simulate the gait conditions of midstance, heel‐off, and terminal stance. Using computer processes, selected tarsals were reconstructed into virtual bone models and embedded with principal‐axes coordinate systems, from which the rotation matrix between the hallux and first metatarsal was decomposed into Cardan angles. Joint angles were then compared using a within factors (rotation sequence and gait condition) repeated‐measures analysis of variance (ANOVA).

Results

Only the transverse plane‐first sequence consistently output incremental increases of dorsiflexion and abduction across gait events in both groups. There was an interaction (F ≥ 25.1; p < 0.001). Follow‐up comparisons revealed angles were different (p < 0.05) at terminal stance.

Conclusions

Different rotation sequences yield different results. Extracting the first rotation in the transverse plane allows for the resting alignment of the hallux to deviate from the sagittal plane. Therefore, representing first‐metatarsophalangeal joint kinematics with the transverse plane‐first rotation sequence may be preferred, especially in cases of hallux valgus deformity.
QSAR DataBank - an approach for the digital organization and archiving of QSAR model information
Authors: Ruusmann Villu , Sild Sulev , Maran Uko
Published: May 2014

Background

Research efforts in the field of descriptive and predictive Quantitative Structure-Activity Relationships or Quantitative Structure–Property Relationships produce around one thousand scientific publications annually. All the materials and results are mainly communicated using printed media. The printed media in its present form have obvious limitations when they come to effectively representing mathematical models, including complex and non-linear, and large bodies of associated numerical chemical data. It is not supportive of secondary information extraction or reuse efforts while in silico studies poses additional requirements for accessibility, transparency and reproducibility of the research. This gap can and should be bridged by introducing domain-specific digital data exchange standards and tools. The current publication presents a formal specification of the quantitative structure-activity relationship data organization and archival format called the QSAR DataBank (QsarDB for shorter, or QDB for shortest).

Results

The article describes QsarDB data schema, which formalizes QSAR concepts (objects and relationships between them) and QsarDB data format, which formalizes their presentation for computer systems. The utility and benefits of QsarDB have been thoroughly tested by solving everyday QSAR and predictive modeling problems, with examples in the field of predictive toxicology, and can be applied for a wide variety of other endpoints. The work is accompanied with open source reference implementation and tools.

Conclusions

The proposed open data, open source, and open standards design is open to public and proprietary extensions on many levels. Selected use cases exemplify the benefits of the proposed QsarDB data format. General ideas for future development are discussed.
Joint assembly and genetic mapping of the Atlantic horseshoe crab genome reveals ancient whole genome duplication
Authors: Nossa Carlos W , Havlak Paul , Yue Jia-Xing , Lv Jie , Vincent Kimberly Y , Brockmann H Jane , Putnam Nicholas H
Published: May 2014

Background

Horseshoe crabs are marine arthropods with a fossil record extending back approximately 450 million years. They exhibit remarkable morphological stability over their long evolutionary history, retaining a number of ancestral arthropod traits, and are often cited as examples of “living fossils.” As arthropods, they belong to the Ecdysozoa, an ancient super-phylum whose sequenced genomes (including insects and nematodes) have thus far shown more divergence from the ancestral pattern of eumetazoan genome organization than cnidarians, deuterostomes and lophotrochozoans. However, much of ecdysozoan diversity remains unrepresented in comparative genomic analyses.

Results

Here we apply a new strategy of combined de novo assembly and genetic mapping to examine the chromosome-scale genome organization of the Atlantic horseshoe crab, Limulus polyphemus. We constructed a genetic linkage map of this 2.7 Gbp genome by sequencing the nuclear DNA of 34 wild-collected, full-sibling embryos and their parents at a mean redundancy of 1.1x per sample. The map includes 84,307 sequence markers grouped into 1,876 distinct genetic intervals and 5,775 candidate conserved protein coding genes.

Conclusions

Comparison with other metazoan genomes shows that the L. polyphemus genome preserves ancestral bilaterian linkage groups, and that a common ancestor of modern horseshoe crabs underwent one or more ancient whole genome duplications 300 million years ago, followed by extensive chromosome fusion. These results provide a counter-example to the often noted correlation between whole genome duplication and evolutionary radiations. The new, low-cost genetic mapping method for obtaining a chromosome-scale view of non-model organism genomes that we demonstrate here does not require laboratory culture, and is potentially applicable to a broad range of other species.
Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans
Authors: Jeon Ja-Young , Nam Jin-Young , Kim Hyoun-Ah , Park Yong-Beom , Bae Sang-Cheol , Suh Chang-Hee
Published: May 2014

Introduction

Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses. We attempted to identify single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the susceptibility to systemic lupus erythematosus (SLE).

Methods

SNPs were genotyped using SNaPSHOT assay in 300 Korean patients with SLE and 217 normal controls (NC), and in replication samples (160 SLE patients and 143 NC). Also, the functional effects of NR1H3 gene promoter polymorphisms were analyzed using a luciferase assay, real-time polymerase chain reaction, B cell proliferation assay and an electrophoretic mobility shift assay.

Results

We identified five polymorphisms: -1851 T > C (rs3758673), -1830 T > C (rs3758674), -1003 G > A (new), -840 C > A (rs61896015) and -115 G > A (rs12221497). There was a significant and reproducible difference in the -1830 T > C, -1003 G > A and -115 G > A polymorphisms between the SLE and the NC. Luciferase activity of the structure containing -1830 C was less enhanced compared to the structure containing -1830 T in basal, GW3965 and T0901317 treated Hep3B cells (P = 0.009, P = 0.034 and P <0.001, respectively). Proliferation of the -1830 TC type was increased compared to the -1830 TT type in basal, GW3965 and T0901317 treated B cells from SLE patients (P = 0.011, P = 0.040 and P = 0.017, respectively). Transcription factor GATA-3 preferentially bound the -1830 T allele in the promoter.

Conclusions

NR1H3 genetic polymorphisms may be associated with disease susceptibility and clinical manifestations of SLE. Specifically, -1830 T > C polymorphism within NR1H3 promoter region may be involved in regulation of NR1H3 expression.
Inflammation programs self-reactive CD8+ T cells to acquire T-box-mediated effector function but does not prevent deletional tolerance
Authors: Jackson Stephanie R , Yuan Jinyun , Berrien-Elliott Melissa M , Chen Collin L , Meyer Jennifer M , Donlin Maureen J , Teague Ryan M
Published: May 2014

CD8+ T cells must detect foreign antigens and differentiate into effector cells to eliminate infections. But, when self-antigen is recognized instead, mechanisms of peripheral tolerance prevent acquisition of effector function to avoid autoimmunity. These distinct responses are influenced by inflammatory and regulatory clues from the tissue environment, but the mechanism(s) by which naive T cells interpret these signals to generate the appropriate immune response are unclear. The identification of the molecules operative in these cell-fate decisions is crucial for developing new treatment options for patients with cancer or autoimmunity, where manipulation of T cell activity is desired to alter the course of disease. With the use of an in vivo murine model to examine CD8+ T cell responses to healthy self-tissue, we correlated self-tolerance with a failure to induce the T-box transcription factors T-bet and Eomes. However, inflammation associated with acute microbial infection induced T-bet and Eomes expression and promoted effector differentiation of self-reactive T cells under conditions that normally favor tolerance. In the context of a Listeria infection, these functional responses relied on elevated T-bet expression, independent of Eomes. Alternatively, infection with LCMV induced higher Eomes expression, which was sufficient in the absence of T-bet to promote effector cytokine production. Our results place T-box transcription factors at a molecular crossroads between CD8+ T cell anergy and effector function upon recognition of peripheral self-antigen, and suggest that inflammation during T cell priming directs these distinct cellular responses.
Technical Advance: Liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease
Authors: Burwitz Benjamin J , Reed Jason S , Hammond Katherine B , Ohme Merete A , Planer Shannon L , Legasse Alfred W , Ericsen Adam J , Richter Yoram , Golomb Gershon , Sacha Jonah B
Published: May 2014

Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease.
Lyrical Philosophy, or How to Sing with Mind
Authors: Epstein Mikhail
Published: May 2014

The article suggests that, contrary to widespread opinions and standard encyclopedic definitions, philosophy is a domain not only of thoughts and ideas but also of feelings. Philosophy as (etymologically) love for wisdom includes emotions in both of its components. Among the many various feelings that we experience, there is a discrete group that, thanks to their involvement with universals, may be regarded as philosophical. Wonder, grief, compassion, tenderness, hope, despair, and delight are philosophical if they are experienced on behalf of humankind and addressed to the world as a whole. The vocation of philosophy is to expand the realm of feelings through the generalizing capacity of the reason, so that love, joy, and pain can be experienced in a noble way, on a maximally global scale, not reducible to private or practical situations. Emotions of philosophical cast affect the world more powerfully than metaphysical ideas and logical propositions. Revolutions are driven less by ideas than by philosophical wrath, exasperation with the existing order of things, and the feeling that the world is unjust.

It is in this context that Epstein's essay defines the genre of lyric philosophy as a direct self-expression of the thinking subject in the process of attaining self-cognition — as represented, for instance, in the work of Augustine, Montaigne, Kierkegaard, Emerson, and Nietzsche. Philosophical subjecthood as a means of self-expression for the transcendental subject (in the Kantian sense) should be distinguished from the purely personal subjectivity inherent to empirical individuals, in the same way and to the same extent as philosophical feelings should be distinguished from mundane ones experienced in everyday situations. Since the subject focused on itself is essential to lyricism, we may even speak of the generic, inescapable lyricism of philosophy per se.
The Approach of a Lyricist
Authors: Hagberg Garry L.
Published: May 2014

As part of a Common Knowledge colloquium on “lyric philosophy,” this essay considers (a) some of the connections between linguistic and nonlinguistic meaning (and the nature of that distinction), (b) the connection between linguistic meaning and what Wittgenstein called aspect perception or imagination-enriched perception, (c) issues in the analysis of meaning down to constituent parts and the problematic legacy of atomistic approaches to word-meaning, (d) the inflection of experience across time and across context and the role of sensibility in both perception and linguistic meaning, and (e) the larger problem of what Simone Weil called “enslavement to one's own method.” What Jan Zwicky urges, and philosophically as well as poetically works toward, is, in Wittgenstein's terms, “a changed way of seeing,” though in her work the focus is specifically on a changed way of seeing the long-established question of linguistic meaning. Hagberg's essay seeks to specify or at least to intimate the form of human mutual understanding that, while too easily missed by traditionally entrenched approaches, Zwicky's approach nicely captures.
The Aleatory Genre
Authors: Roberts M. F. Simone
Published: May 2014

The philosophy suggested by Jan Zwicky's expanded understanding of lyric and use of the fragment-as-method inspired this notebook of misunderstanding. Seeking to read Zwicky in the tradition of the aleatory genre and its basic form, the fragment, Roberts finds that her own sense of poetics and ethics (feminist, poststructural, phenomenological) accords generally with Zwicky's lyric philosophy and epistemology of imagination. Roberts's resonance with Zwicky's theory is conflicted by Zwicky's choice to isolate her fragment-method from the larger history of the aleatory genre and its complex political evolution. Misunderstandings are compounded by Zwicky's disengagement from her contemporaries in the aleatory genre, the instability of her definitions by way of gestalt, and the impossible scale of her “ontological imperative.” In the end, Roberts is disappointed by this tempting but failed affinity.
Beyond Pointing and Hoping
Authors: Allen Danielle
Published: May 2014

Jan Zwicky's fertile essays expose by contrast the aridity of much contemporary writing about the point of humanistic endeavor and intellectual life. Thinking, in her account, is importantly the work of imagination. The more common focus on critical thinking, in arguments on behalf of liberal arts pedagogy, does put a salutary emphasis on some aspects of thoughtfulness, for instance, use of evidence and argumentation, but Zwicky is right that this approach fails to articulate a standard for synthetic, imaginative discernment that meaningfully grasps the world. Zwicky usefully provides an account of just such a standard. Yet her argument that “other than pointing and hoping, there are no rules, no algorithms, by which human perception of a gestalt may be facilitated” sells the work of teachers short. An alternative case is made by Plato in his representation of Socrates-as-teacher, and most of this article is a case study of passages from the Republic.