bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptual Design of Schoenflies Motion Generators Based on the Wrench Graph
Authors: Amine Semaan , Nurahmi Latifah , Wenger Philippe , Caro Stéphane 
Published: February 2014

The subject of this paper is about the conceptual design of parallel Schoenflies motion generators based on the wrench graph.
By using screw theory and Grassmann geometry, some conditions on both the constraint and the actuation wrench systems are generated for the assembly of limbs of parallel Schoenflies motion generators, i.e., 3T1R parallel manipulators. Those conditions are somehow related to the kinematic singularities of the manipulators. Indeed, the parallel manipulator should not be in a constraint singularity in the starting configuration for a valid architecture, otherwise it cannot perform the required motion pattern. After satisfying the latter condition, the parallel manipulator should not be in an actuation singularity in a general configuration, otherwise the obtained parallel manipulator is permanently singular.
Based on the assembly conditions, six types of wrench graphs are identified and correspond to six typical classes of 3T1R parallel manipulators. The geometric properties of these six classes are highlighted. A simplified expression of the superbracket decomposition is obtained for each class, which allows the determination and the comparison of the singularities of 3T1R parallel manipulators at their conceptual design stage. The methodology also provides new architectures of parallel Schoenflies motion generators based on the classification of wrench graphs and on their singularity conditions.
A Three-Dimensional Musculoskeletal Driver Model to Study Steering Tasks
Authors: Mehrabi Naser , Razavian Reza Sharif , McPhee John 
Published: February 2014

Realistic driver models can play an important role in developing new driver assistance technologies. A realistic driver model can reduce the time-consuming trial and error process of designing and testing products, and thereby reduce the vehicle’s development time and cost. A realistic model should provide both driver path planning and arm motions that are physiologically possible. The interaction between a driver’s hand and steering wheel can influence control performance and steering feel.
The aim of this work is to develop a comprehensive yet practical model of the driver and vehicle. Consequently, a neuro-muscular driver model in conjunction with a high-fidelity vehicle model is developed to learn and understand more about the driver’s performance and preferences, and their effect on vehicle control and stability. This driver model can provide insights into task performance and energy consumption of the driver, including fatigue and co-contraction dynamics of a steering task. In addition, this driver model in conjunction with a high-fidelity steering model can be used to develop new steering technologies such as Electric Power Steering.
First-Order Reliability Analysis of Vehicle Safety in Highway Horizontal Curves
Authors: Shin Jaekwan , Lee Ikjin 
Published: February 2014

This study presents a reliability analysis of vehicle sideslip and rollover in highway horizontal curves, mainly focusing on exit ramps and interchanges. To accurately describe failure modes of a ground vehicle, analytic models for sideslip and rollover are derived considering nonlinear characteristics of vehicle behavior using the commercial software, TruckSim®, with high fidelity. Then, the probability of accident is evaluated using the First-Order Reliability Method (FORM). Furthermore, sensitivity functions of each failure mode are analytically derived to apply FORM.
Numerical studies are conducted using a single-unit truck model. The results show that a truck is more likely to rollover than to slip at dry load. To propose practical application of the study, the reliability analysis for the minimum radius recommended by American Association of State Highway and Transportation Officials (AASHTO) at various speeds and bank angles is conducted. The reliability analysis of current design method shows that the method cannot provide the sufficient margin of safety against both of rollover and sideslip when there are deviations from assumed conditions, especially at low speed of vehicles.
The Impact of Asynchronous GPGPU Behaviors on Stochastic Simulation
Authors: Steuben John C. , Turner Cameron J. 
Published: February 2014

This work examines the effect of one key aspect of General Purpose Graphics Processing Unit (GPGPU) computing on the realism and fidelity of stochastic simulations. In particular it is shown that the asynchronous nature of GPGPU computing can be leveraged to produce increased fidelity and realism, compared to conventional computing methods, when applied to probabilistic or stochastic simulations. This is a multifaceted argument that shows:
1) Asynchronous behaviors are essential to produce high computational throughput on GPGPU devices, and thus allow more rigorous sampling, which in turn enables a deeper understanding of the underlying stochastic processes.
2) Asynchronous GPGPU computing can eliminate the “global clock” present in simulations and potentially produce a better representation of the underlying process.
This paper also attempts to give a working introduction to GPGPU computing, and to the applications of this technology in the field of stochastic simulation. A range of literature regarding these simulations is also surveyed, in order to provide context. A demonstration of synchronous versus asynchronous algorithms for robot swarm path planning is used to illustrate this discussion. Several notes on the limitations of GPGPU computing in this field are also made, along with remarks regarding future development of GPGPU-accelerated stochastic simulations.
Unbalance Identification in Large Steam Turbo-Generator Unit Using a Model-Based Method
Authors: Pennacchi Paolo , Vania Andrea , Chatterton Steven , Nistor Ionel , Voinis Philippe , Ricci Roberto , Borghesani Pietro 
Published: February 2014

Fault identification in industrial machine is a topic of major importance under engineering point of view. In fact, the possibility to identify not only the type, but also the severity and the position of a fault occurred along a shaft-line allows quick maintenance and shorten the downtime. This is really important in the power generation industry where the units are often of several tenths of meters long and where the rotors are enclosed by heavy and pressure-sealed casings.
In this paper, an industrial experimental case is presented related to the identification of the unbalance on a large size steam turbine of about 1.3 GW, belonging to a nuclear power plant. The case history is analyzed by considering the vibrations measured by the condition monitoring system of the unit. A model-based method in the frequency domain, developed by the authors, is introduced in detail and it is then used to identify the position of the fault and its severity along the shaft-line. The complete model of the unit (rotor – modeled by means of finite elements, bearings – modeled by linearized damping and stiffness coefficients and foundation – modeled by means of pedestals) is analyzed and discussed before being used for the fault identification. The assessment of the actual fault was done by inspection during a scheduled maintenance and excellent correspondence was found with the identified one by means of authors’ proposed method.
Finally a complete discussion is presented about the effectiveness of the method, even in presence of a not fine tuned machine model and considering only few measuring planes for the machine vibration.
Consideration of Assistive Devices in the Gait Analysis of Spinal Cord–Injured Subjects
Authors: Lugrís Urbano , Carlín Jairo , Luaces Alberto , Cuadrado Javier 
Published: February 2014

The gait of spinal cord–injured subjects can be improved by means of properly designed active orthoses. Since the gait pattern varies greatly among different patients, the orthoses and their corresponding controllers must be carefully customized, and the joint motor torques obtained from inverse dynamic analysis constitute a useful input for this task.
Nowadays, the analysis of standard gait by using motion capture data is a mature discipline. However, the problem becomes more complex in the case of spinal cord–injured subjects wearing active orthoses: in addition to the presence of the orthoses, these patients always require the help of supplementary assistive devices, such as crutches, in order to stabilize their gait.
In this work, the gait analysis of a subject walking with the aid of crutches and active knee–ankle–foot orthoses is performed, by introducing the assistive devices both at the experimental and computational levels. The required sensors and actuators are incorporated to the system, and the measurements are used to solve the inverse dynamics problem in order to calculate the joint motor torques produced by the subject during gait.
Online Implementation of the Delta Design Game for Analyzing Collaborative Team Practices
Authors: Oberoi Sharad , Finger Susan , Rosé Eric 
Published: February 2014

Over the past four years the authors have developed an online version of the Delta Design game, a board game which was developed by Bucciarelli (1) to teach students design collaboration skills. In the online version, players move tiles on a shared virtual board and communicate only through text chat. In addition, the objective functions are computed automatically each time a tile is moved, so the focus of the game changes from rapid number-crunching to negotiation. Since every state of the board, along with micro-level team performance and chat data, are captured, the resulting corpus from 38 four-player team games provides a rich resource to explore different aspects of collaborative team practices.
This paper gives an overview of the online implementation of Delta Design and discusses the findings from user studies including several undergraduate capstone design classes. Observations of the board-moving tactics show that teams planning a strategy before starting the game or players sharing details about their role’s constraints with other team members do not have much effect on the game’s outcome. Finally, this paper demonstrates that the complex rules of the Delta Design game make it a suitable candidate for analyzing collaboration strategies in team-based design projects.
Magnetic Actuation of Meso-Scale Mechanisms
Authors: Moore P. M. , Modica F. , Wiens G. J. , Fassi I. 
Published: February 2014

This paper discusses the applications and development of magnetic actuators for meso-scale mechanisms. Due to their small sizes, meso-scale parts cannot be actuated using techniques typical of macro-scale mechanisms, such as servos or ball screws. Similarly, the techniques used in micro-actuation, such as the use of electrostatic force in MEMS devices, cannot be easily scaled up to the meso-scale. As a result, the use of magnetic forces for actuating meso-scale mechanisms may be capable of filling this void of actuation methods.
A case study of a fixturing mechanism meant for meso-scale end-milling was analyzed. This mechanism uses two fixed-fixed beams in order to actively tune the harmonic modes of the machining operation in order to improve the stability of the cutting. It also uses magnetic forces to actuate the fixturing platform in order to provide close-loop feedback of cutting force.
Posttranscriptional Regulation of the Yersinia pestis Cyclic AMP Receptor Protein Crp and Impact on Virulence
Authors: Lathem Wyndham W. , Schroeder Jay A. , Bellows Lauren E. , Ritzert Jeremy T. , Koo Jovanka T. , Price Paul A. , Caulfield Adam J. , Goldman William E. 
Published: February 2014

ABSTRACT

The cyclic AMP receptor protein (Crp) is a transcriptional regulator that controls the expression of numerous bacterial genes, usually in response to environmental conditions and particularly by sensing the availability of carbon. In the plague pathogen
Yersinia pestis
, Crp regulates the expression of multiple virulence factors, including components of the type III secretion system and the plasminogen activator protease Pla. The regulation of Crp itself, however, is distinctly different from that found in the well-studied
Escherichia coli
system. Here, we show that at physiological temperatures, the synthesis of Crp in
Y. pestis
is positively regulated at the posttranscriptional level. The loss of the small RNA chaperone Hfq results in decreased Crp protein levels but not in steady-state Crp transcript levels, and this regulatory effect occurs within the 5′ untranslated region (UTR) of the Crp mRNA. The posttranscriptional activation of Crp synthesis is required for the expression of
pla
, and decoupling
crp
from Hfq through the use of an exogenously controlled promoter and 5′ UTR increases Pla protein levels as well as partially rescues the growth defect associated with the loss of Hfq. Finally, we show that both Hfq and the posttranscriptional regulation of Crp contribute to the virulence of
Y. pestis
during pneumonic plague. The Hfq-dependent, posttranscriptional regulation of Crp may be specific to
Yersinia
species, and thus our data help explain the dramatic growth and virulence defects associated with the loss of Hfq in
Y. pestis
.

IMPORTANCE
The Crp protein is a major transcriptional regulator in bacteria, and its synthesis is tightly controlled to avoid inappropriate induction of the Crp regulon. In this report, we provide the first evidence of Crp regulation in an Hfq-dependent manner at the posttranscriptional level. Our discovery that the synthesis of Crp in
Yersinia pestis
is Hfq dependent adds an additional layer of regulation to catabolite repression in this bacterium. Our work provides a mechanism by which the plague pathogen links not just the sensing of glucose or other carbon sources but also other signals that influence Crp abundance via the expression of small RNAs to the induction of the Crp regulon. In turn, this allows
Y. pestis
to fine-tune Crp levels to optimize virulence gene expression during plague infection and may allow the bacterium to adapt to its unique environmental niches.
Structural and Functional Insights into Peptidoglycan Access for the Lytic Amidase LytA of Streptococcus pneumoniae
Authors: Mellroth Peter , Sandalova Tatyana , Kikhney Alexey , Vilaplana Francisco , Hesek Dusan , Lee Mijoon , Mobashery Shahriar , Normark Staffan , Svergun Dmitri , Henriques-Normark Birgitta , Achour Adnane 
Published: February 2014

ABSTRACT

The cytosolic
N
-acetylmuramoyl-
l
-alanine amidase LytA protein of
Streptococcus pneumoniae
, which is released by bacterial lysis, associates with the cell wall via its choline-binding motif. During exponential growth, LytA accesses its peptidoglycan substrate to cause lysis only when nascent peptidoglycan synthesis is stalled by nutrient starvation or β-lactam antibiotics. Here we present three-dimensional structures of LytA and establish the requirements for substrate binding and catalytic activity. The solution structure of the full-length LytA dimer reveals a peculiar fold, with the choline-binding domains forming a rigid V-shaped scaffold and the relatively more flexible amidase domains attached in a
trans
position. The 1.05-Å crystal structure of the amidase domain reveals a prominent Y-shaped binding crevice composed of three contiguous subregions, with a zinc-containing active site localized at the bottom of the branch point. Site-directed mutagenesis was employed to identify catalytic residues and to investigate the relative impact of potential substrate-interacting residues lining the binding crevice for the lytic activity of LytA.
In vitro
activity assays using defined muropeptide substrates reveal that LytA utilizes a large substrate recognition interface and requires large muropeptide substrates with several connected saccharides that interact with all subregions of the binding crevice for catalysis. We hypothesize that the substrate requirements restrict LytA to the sites on the cell wall where nascent peptidoglycan synthesis occurs.

IMPORTANCE
Streptococcus pneumoniae
is a human respiratory tract pathogen responsible for millions of deaths annually. Its major pneumococcal autolysin, LytA, is required for autolysis and fratricidal lysis and functions as a virulence factor that facilitates the spread of toxins and factors involved in immune evasion. LytA is also activated by penicillin and vancomycin and is responsible for the lysis induced by these antibiotics. The factors that regulate the lytic activity of LytA are unclear, but it was recently demonstrated that control is at the level of substrate recognition and that LytA required access to the nascent peptidoglycan. The present study was undertaken to structurally and functionally investigate LytA and its substrate-interacting interface and to determine the requirements for substrate recognition and catalysis. Our results reveal that the amidase domain comprises a complex substrate-binding crevice and needs to interact with a large-motif epitope of peptidoglycan for catalysis.
Novel Mechanistic Insights into Ectodomain Shedding of EGFR Ligands Amphiregulin and TGF-α: Impact on Gastrointestinal Cancers Driven by Secondary Bile Acids
Authors: Nagathihalli Nagaraj S. , Beesetty Yugandhar , Lee Wooin , Washington M. Kay , Chen Xi , Lockhart A. Craig , Merchant Nipun B. 
Published: February 2014

Abstract
Secondary bile acids (BA) such as deoxycholic acid (DCA) promote the development of several gastrointestinal malignancies, but how they mediate this effect is unclear. In this study, we offer evidence of a mechanism involving ectodomain shedding of the EGFR ligands amphiregulin (AREG) and TGF-α, which rely upon the cell surface protease TACE/ADAM-17. Specifically, we show that AREG participates in DCA-induced EGFR and STAT3 signaling, cell-cycle progression, and tumorigenicity in human colorectal cancer and pancreatic ductal adenocarcinoma (PDAC). TACE and AREG, but not TGF-α, were overexpressed in both colorectal cancer and PDAC tissues compared with normal tissues. Exposure of colorectal cancer and PDAC cells to DCA resulted in colocalization of Src and TACE to the cell membrane, resulting in AREG-dependent activation of EGFR, mitogen-activated protein kinase (MAPK), and STAT3 signaling. Src or TACE inhibition was sufficient to attenuate DCA-induced AREG, but not TGF-α shedding. We also examined a role for the BA transporter TGR5 in DCA-mediated EGFR and STAT3 signaling. RNA interference-mediated silencing of TGR5 or AREG inhibited DCA-induced EGFR, MAPK, and STAT3 signaling, blunted cyclin D1 expression and cell-cycle progression, and attenuated DCA-induced colorectal cancer or PDAC tumorigenicity. Together, our findings define an AREG-dependent signaling pathway that mediates the oncogenic effects of secondary BAs in gastrointestinal cancers, the targeting of which may enhance therapeutic responses in their treatment. Cancer Res; 74(7); 2062–72. ©2014 AACR.
LRH-1 Governs Vital Transcriptional Programs in Endocrine-Sensitive and -Resistant Breast Cancer Cells
Authors: Bianco Stéphanie , Brunelle Mylène , Jangal Maïka , Magnani Luca , Gévry Nicolas 
Published: February 2014

AbstractTumor characteristics are decisive in the determination of treatment strategy for patients with breast cancer. Patients with estrogen receptor α (ERα)–positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in antiestrogen-sensitive and -resistant breast cancer cells. We identified genome-wide LRH-1–binding sites using ChIP-seq (chromatin immunoprecipitation sequencing), uncovering preferential binding to regions distal to transcriptional start sites. We further characterized these LRH-1–binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1–binding sites are active and could be involved in long-range enhancer–promoter looping. Combined with transcriptome analysis of LRH-1–depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein, we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies. Cancer Res; 74(7); 2015–25. ©2014 AACR.
The PAM50 Risk-of-Recurrence Score Predicts Risk for Late Distant Recurrence after Endocrine Therapy in Postmenopausal Women with Endocrine-Responsive Early Breast Cancer
Authors: Filipits Martin , Nielsen Torsten O. , Rudas Margaretha , Greil Richard , Stöger Herbert , Jakesz Raimund , Bago-Horvath Zsuzsanna , Dietze Otto , Regitnig Peter , Gruber-Rossipal Christine , Müller-Holzner Elisabeth , Singer Christian F. , Mlineritsch Brigitte , Dubsky Peter , Bauernhofer Thomas , Hubalek Michael , Knauer Michael , Trapl Harald , Fesl Christian , Schaper Carl , Ferree Sean , Liu Shuzhen , Cowens J. Wayne , Gnant Michael ,   for the Austrian Breast and Colorectal Cancer Study Group
Published: February 2014

AbstractPurpose: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients.Experimental Design: The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.Results: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ2 15.32, P &lt; 0.001; ROR-based risk groups: ΔLRχ2 14.83, P &lt; 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease.Conclusion: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors. Clin Cancer Res; 20(5); 1298–305. ©2014 AACR.