bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Film Die Flow Uniformity Using Optimization Methods Coupled with Finite Element Computational Fluid Dynamics (CFD) Analysis
Authors: Lee P. C. , Dietsche L. , Dooley J. , Parashar S. 
Published: March 2015

Abstract
The aim of this study was to evaluate various optimization strategies to be used with computational fluid dynamics (CFD), in order to optimize the geometry for a polymer die to meet the dual objectives of uniform flow at the exit with minimal pressure drop. 3D finite element simulations using the numerically optimized geometry predict a more uniform flow than simulations using the baseline geometry. However, some of the initial optimized results yielded die geometries that would be impractical to fabricate. Additional constraints were placed on the allowable geometric parameters and solution space to push the optimization towards more feasible optimal solutions. Thus we have shown how CFD-based optimization methods, coupled with knowledge of die design technology and fabrication techniques can lead to the design of better performing polymer dies.
UV-Curable Technique of Magnetic Roller Soft Mold and Microstructure Pattern Replication
Authors: Weng Y. J. 
Published: March 2015

Abstract
This study adopted the novel magnetic roller soft mold embossing technique of the soft mold preparation method, embossing, combined with the existing gas-assisted UV-curable technique, to develop an innovative magnetic-assisted continuous roller platform. Using the advantages of uniform and accurate control of applied pressure of the magnetic disk, this study used the magnetic roller soft mold embossing and UV-curable technique for replicating microstructure patterns, resulting in a more mature micro-nano embossing technology and application. The experimental results showed that the new magnetic roller soft mold preparation method can accurately cast and replicate micro-nano structures of Polydimethylsiloxane (PDMS) composite magnetic iron powder, and the magnetic disk can impose uniform pressure to effectively implement complete filling during the rolling process. This innovative process provides a simple and rapid molding mechanism, which significantly improves the microstructure pattern replication technique.
Measurement and Numerical Simulation of Void and Warpage in Glass Fiber Reinforced Molded Chunky Parts
Authors: Kleindel S. , Salaberger D. , Eder R. , Schretter H. , Hochenauer C. 
Published: March 2015

Abstract
The aim of this paper is to determine the reason for the large warpage of an injection molded chunky part made of glass fiber reinforced polyamide 6. State of the art commercial 3D injection molding simulation software was used to predict the warpage of the part. While the simulation predicted a product virtually free of warpage the molded parts showed a large deformation. Several molding experiments and X-ray computed tomography (μCT) scans of the moldings have been performed to figure out the reason for this. The μCT scans revealed voids in the thick walls of the part. It was found that these defects were the main cause of the unreliable simulation results. Therefore it is concluded that voids can have a major influence on the reliability of numerical warpage predictions. This paper shows a simplified method to determine the zones were voids will appear and shows the comparison with μCT-data.
Slip Heating in Die Drool with Viscous Dissipation
Authors: Gilbert P. H. , Giacomin A. J. 
Published: March 2015

Abstract
Plastics can build-up on the die lip during extrusion. This phenomenon is called die drool and can be costly for plastics producers, requiring periodic shutdowns for die cleaning. Die drool has been attributed to the cohesive fracture of the melt into a drool layer and a bulk layer. The bulk layer slips on the drool layer after fracture, resulting in heating at the slip interface, called slip heating. The heat generated through slip heating can contribute to polymer thermal degradation, and to the die drool degradation. The impact of slip heating on die temperature rise has been investigated by neglecting viscous dissipation (Gilbert and Giacomin, 2014). This work considers viscous dissipation and its importance to slip heating. We find that viscous dissipation and slip heating contribute equally to the melt temperature rise, and we conclude with a worked example showing the importance of these two heating sources during polymer processing. We also develop two sufficient conditions for the accurate use of our results, Pé ≤ 1 and ∂Θ/∂ς ≪ ∂2Θ/∂ζ2.
Cost-effectiveness Analysis with Influence Diagrams
Authors: Arias M. , Díez F. J. 
Published: March 2015

SummaryBackground: Cost-effectiveness analysis (CEA) is used increasingly in medicine to determine whether the health benefit of an intervention is worth the economic cost. Decision trees, the standard decision modeling technique for non-temporal domains, can only perform CEA for very small problems.Objective: To develop a method for CEA in problems involving several dozen variables.Methods: We explain how to build influence diagrams (IDs) that explicitly represent cost and effectiveness. We propose an algorithm for evaluating cost-effectiveness IDs directly, i.e., without expanding an equivalent decision tree.Results: The evaluation of an ID returns a set of intervals for the willingness to pay – separated by cost-effectiveness thresholds – and, for each interval, the cost, the effectiveness, and the optimal intervention. The algorithm that evaluates the ID directly is in general much more efficient than the brute-force method, which is in turn more efficient than the expansion of an equivalent decision tree. Using OpenMarkov, an open-source software tool that implements this algorithm, we have been able to perform CEAs on several IDs whose equivalent decision trees contain millions of branches.Conclusion: IDs can perform CEA on large problems that cannot be analyzed with decision trees.
An ultraviolet floral polymorphism associated with life history drives pollinator discrimination inMimulus guttatus
Authors: DeMarche Megan L. , Miller Timothy J. , Kay Kathleen M. 
Published: March 2015

•Premise of the study:Ultraviolet (UV) floral patterns are common in angiosperms and mediate pollinator attraction, efficiency, and constancy. UV patterns may vary within species, yet are cryptic to human observers. Thus, few studies have explicitly described the distribution or ecological significance of intraspecific variation in UV floral patterning. Here, we describe the geographic distribution and pattern of inheritance of a UV polymorphism in the model plant speciesMimulus guttatus(Phrymaceae). We then test whether naturally occurring UV phenotypes influence pollinator interactions withinM. guttatus.•Methods:We document UV patterns in 18 annual and 19 perennial populations and test whether UV pattern is associated with life history. To examine the pattern of inheritance, we conducted crosses within and between UV phenotypes. Finally, we tested whether bee pollinators discriminate among naturally occurring UV phenotypes in two settings: wild bee communities and captiveBombus impatiens.•Key results:WithinM. guttatus, perennial populations exhibit a small bulls‐eye pattern, whereas a bilaterally symmetric runway pattern occurs mainly in annual populations. Inheritance of UV patterning is consistent with a single‐locus Mendelian model in which the runway phenotype is dominant. Bee pollinators discriminate against unfamiliar UV patterns in both natural and controlled settings.•Conclusions:We describe a widespread UV polymorphism associated with life history divergence withinMimulus guttatus. UV pattern influences pollinator visitation and should be considered when estimating reproductive barriers between life history ecotypes. This work develops a new system to investigate the ecology and evolution of UV floral patterning in a species with extensive genomic resources.
Coexpression of TIGIT and FCRL3 Identifies Helios+ Human Memory Regulatory T Cells
Authors: Bin Dhuban Khalid , d’Hennezel Eva , Nashi Emil , Bar-Or Amit , Rieder Sadiye , Shevach Ethan M. , Nagata Satoshi , Piccirillo Ciriaco A. 
Published: March 2015

Abstract
Two distinct subsets of CD4+Foxp3+ regulatory T (Treg) cells have been described based on the differential expression of Helios, a transcription factor of the Ikaros family. Efforts to understand the origin and biological roles of these Treg populations in regulating immune responses have, however, been hindered by the lack of reliable surface markers to distinguish and isolate them for subsequent functional studies. Using a single-cell cloning strategy coupled with microarray analysis of different Treg functional subsets in humans, we identify the mRNA and protein expression of TIGIT and FCRL3 as a novel surface marker combination that distinguishes Helios+FOXP3+ from Helios−FOXP3+ memory cells. Unlike conventional markers that are modulated on conventional T cells upon activation, we show that the TIGIT/FCRL3 combination allows reliable identification of Helios+ Treg cells even in highly activated conditions in vitro as well as in PBMCs of autoimmune patients. We also demonstrate that the Helios−FOXP3+ Treg subpopulation harbors a larger proportion of nonsuppressive clones compared with the Helios+FOXP3+ cell subset, which is highly enriched for suppressive clones. Moreover, we find that Helios− cells are exclusively responsible for the productions of the inflammatory cytokines IFN-γ, IL-2, and IL-17 in FOXP3+ cells ex vivo, highlighting important functional differences between Helios+ and Helios− Treg cells. Thus, we identify novel surface markers for the consistent identification and isolation of Helios+ and Helios− memory Treg cells in health and disease, and we further reveal functional differences between these two populations. These new markers should facilitate further elucidation of the functional roles of Helios-based Treg heterogeneity.
NF-κB Downregulates Cbl-b through Binding and Suppressing Cbl-b Promoter in T Cell Activation
Authors: Liu Yong , Li Yao , Zhang LiMin , Li MingQiang , Li Chao , Xue ChengBiao , Huang Xia , Zhou Ping 
Published: March 2015

AbstractT cell activation causes the translocation of NF-κB dimers from the cytoplasm into the nucleus where NF-κB regulates inflammatory and immune response genes. Cbl-b is a negative regulator of T cell activation. However, the correlation between NF-κB activity and Cbl-b expression remains unclear. We showed that IκBαΔN-Tg T cells exhibited less NF-κB activity but higher levels of Cbl-b when compared with wild-type T cells. Furthermore, ursolic acid suppressed NF-κB activation and inhibited the downregulation of Cbl-b in wild-type T cells. NF-κBp65 specifically bound to an 11-bp NF-κB consensus sequence (gcaggaagtcc) in the Cbl-b promoter. Binding of NF-κB to this sequence suppressed Cbl-b transcription, thereby resulting in the negative regulation of Cbl-b expression. In addition, Cbl-b knockout led to the loss of cardiac allograft tolerance in IκBαΔN-Tg mice. These results indicated that NF-κB downregulated Cbl-b by binding and suppressing Cbl-b promoter in T cell activation. Our findings provide a novel role for NF-κB signaling in T cell activation.
Deficiency of MALT1 Paracaspase Activity Results in Unbalanced Regulatory and Effector T and B Cell Responses Leading to Multiorgan Inflammation
Authors: Bornancin Frédéric , Renner Florian , Touil Ratiba , Sic Heiko , Kolb Yeter , Touil-Allaoui Ismahane , Rush James S. , Smith Paul A. , Bigaud Marc , Junker-Walker Ursula , Burkhart Christoph , Dawson Janet , Niwa Satoru , Katopodis Andreas , Nuesslein-Hildesheim Barbara , Weckbecker Gisbert , Zenke Gerhard , Kinzel Bernd , Traggiai Elisabetta , Brenner Dirk , Brüstle Anne , St. Paul Michael , Zamurovic Natasa , McCoy Kathy D. , Rolink Antonius , Régnier Catherine H. , Mak Tak W. , Ohashi Pamela S. , Patel Dhavalkumar D. , Calzascia Thomas 
Published: March 2015

AbstractThe paracaspase MALT1 plays an important role in immune receptor-driven signaling pathways leading to NF-κB activation. MALT1 promotes signaling by acting as a scaffold, recruiting downstream signaling proteins, as well as by proteolytic cleavage of multiple substrates. However, the relative contributions of these two different activities to T and B cell function are not well understood. To investigate how MALT1 proteolytic activity contributes to overall immune cell regulation, we generated MALT1 protease-deficient mice (Malt1PD/PD) and compared their phenotype with that of MALT1 knockout animals (Malt1−/−). Malt1PD/PD mice displayed defects in multiple cell types including marginal zone B cells, B1 B cells, IL-10–producing B cells, regulatory T cells, and mature T and B cells. In general, immune defects were more pronounced in Malt1−/− animals. Both mouse lines showed abrogated B cell responses upon immunization with T-dependent and T-independent Ags. In vitro, inactivation of MALT1 protease activity caused reduced stimulation-induced T cell proliferation, impaired IL-2 and TNF-α production, as well as defective Th17 differentiation. Consequently, Malt1PD/PD mice were protected in a Th17-dependent experimental autoimmune encephalomyelitis model. Surprisingly, Malt1PD/PD animals developed a multiorgan inflammatory pathology, characterized by Th1 and Th2/0 responses and enhanced IgG1 and IgE levels, which was delayed by wild-type regulatory T cell reconstitution. We therefore propose that the pathology characterizing Malt1PD/PD animals arises from an immune imbalance featuring pathogenic Th1- and Th2/0-skewed effector responses and reduced immunosuppressive compartments. These data uncover a previously unappreciated key function of MALT1 protease activity in immune homeostasis and underline its relevance in human health and disease.
K+ Efflux Agonists Induce NLRP3 Inflammasome Activation Independently of Ca2+ Signaling
Authors: Katsnelson Michael A. , Rucker L. Graham , Russo Hana M. , Dubyak George R. 
Published: March 2015

Abstract
Perturbation of intracellular ion homeostasis is a major cellular stress signal for activation of NLRP3 inflammasome signaling that results in caspase-1–mediated production of IL-1β and pyroptosis. However, the relative contributions of decreased cytosolic K+ concentration versus increased cytosolic Ca2+ concentration ([Ca2+]) remain disputed and incompletely defined. We investigated roles for elevated cytosolic [Ca2+] in NLRP3 activation and downstream inflammasome signaling responses in primary murine dendritic cells and macrophages in response to two canonical NLRP3 agonists (ATP and nigericin) that facilitate primary K+ efflux by mechanistically distinct pathways or the lysosome-destabilizing agonist Leu-Leu-O-methyl ester. The study provides three major findings relevant to this unresolved area of NLRP3 regulation. First, increased cytosolic [Ca2+] was neither a necessary nor sufficient signal for the NLRP3 inflammasome cascade during activation by endogenous ATP-gated P2X7 receptor channels, the exogenous bacterial ionophore nigericin, or the lysosomotropic agent Leu-Leu-O-methyl ester. Second, agonists for three Ca2+-mobilizing G protein–coupled receptors (formyl peptide receptor, P2Y2 purinergic receptor, and calcium-sensing receptor) expressed in murine dendritic cells were ineffective as activators of rapidly induced NLRP3 signaling when directly compared with the K+ efflux agonists. Third, the intracellular Ca2+ buffer, BAPTA, and the channel blocker, 2-aminoethoxydiphenyl borate, widely used reagents for disruption of Ca2+-dependent signaling pathways, strongly suppressed nigericin-induced NLRP3 inflammasome signaling via mechanisms dissociated from their canonical or expected effects on Ca2+ homeostasis. The results indicate that the ability of K+ efflux agonists to activate NLRP3 inflammasome signaling can be dissociated from changes in cytosolic [Ca2+] as a necessary or sufficient signal.
IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection
Authors: Heim Cortney E. , Vidlak Debbie , Scherr Tyler D. , Hartman Curtis W. , Garvin Kevin L. , Kielian Tammy 
Published: March 2015

Abstract
Staphylococcus aureus is a leading cause of human prosthetic joint infections (PJIs) typified by biofilm formation. We recently identified a critical role for myeloid-derived suppressor cells (MDSCs) in S. aureus biofilm persistence. Proinflammatory signals induce MDSC recruitment and activation in tumor models; however, the mechanisms responsible for MDSC homing to sites of biofilm infection are unknown. In this study, we report that several cytokines (IL-12p40, IL-1β, TNF-α, and G-CSF) and chemokines (CXCL2, CCL5) were significantly elevated in a mouse model of S. aureus PJI. This coincided with significantly increased MDSC infiltrates concomitant with reduced monocyte, macrophage, and T cell influx compared with uninfected animals. Of the cytokines detected, IL-12 was of particular interest based on its ability to possess either pro- or anti-inflammatory effects mediated through p35-p40 heterodimers or p40 homodimers, respectively. MDSC recruitment was significantly reduced in both p40 and p35 knockout mice, which resulted in enhanced monocyte and neutrophil influx and bacterial clearance. Adoptive transfer of wild-type MDSCs into infected p40 knockout animals worsened disease outcome, as evidenced by the return of S. aureus burdens to levels typical of wild-type mice. Tissues obtained from patients undergoing revision surgery for PJI revealed similar patterns of immune cell influx, with increased MDSC-like cells and significantly fewer T cells compared with aseptic revisions. These findings reveal a critical role for IL-12 in shaping the anti-inflammatory biofilm milieu by promoting MDSC recruitment.
HkRP3 Is a Microtubule-Binding Protein Regulating Lytic Granule Clustering and NK Cell Killing
Authors: Ham Hyoungjun , Huynh Walter , Schoon Renee A. , Vale Ronald D. , Billadeau Daniel D. 
Published: March 2015

Abstract
NK cells provide host defense by killing viral-infected and cancerous cells through the secretion of preformed lytic granules. Polarization of the lytic granules toward the target cell is dependent on an intact microtubule (MT) network as well as MT motors. We have recently shown that DOCK8, a gene mutated in a primary immunodeficiency syndrome, is involved in NK cell killing in part through its effects on MT organizing center (MTOC) polarization. In this study, we identified Hook-related protein 3 (HkRP3) as a novel DOCK8- and MT-binding protein. We further show that HkRP3 is present in lytic granule fractions and interacts with the dynein motor complex and MTs. Significantly, depletion of HkPR3 impaired NK cell cytotoxicity, which could be attributed to a defect in not only MTOC polarity, but also impaired clustering of lytic granules around the MTOC. Our results demonstrate an important role for HkRP3 in regulating the clustering of lytic granules and MTOC repositioning during the development of NK cell–mediated killing.
Planning and Guidance of Cardiac Resynchronization Therapy–Lead Implantation by Evaluating Coronary Venous Anatomy Assessed with Multidetector Computed Tomography
Authors: Catanzaro John N. , Makaryus John N. , Jadonath Ram , Makaryus Amgad N. 
Published: March 2015

Objectives We sought to evaluate the utility of multidetector computed tomography (MDCT) in preoperative planning of cardiac resynchronization therapy (CRT) device implantation. Background Variation in coronary venous anatomy can affect optimal lead placement and may warrant preimplantation visualization prior to CRT lead placement. Methods Prospective randomized enrollment of 29 patients (17 males; mean age at implant 66.7 ± 12.8 years) was undertaken. Patients were randomized to preimplantation MDCT (GE® 64-detector Lightspeed, n = 16) or no MDCT. Implantation was planned based on three-dimensional coronary venous reconstruction as visualized in the CT group. Measurement of coronary sinus (CS) angulation, CS ostial (os) diameter, right atrial (RA) width, volume, and height was undertaken prior to implant. Intraoperative CS lead implantation times (introduction, cannulation, and left ventricular [LV] lead positioning), procedure time, fluoroscopy time, and venogram contrast volume were measured to determine if there was a difference between patients who underwent preimplant CT scan and those who did not. Results CS os diameter (mean = 13.8 ± 2.9 cm) was inversely correlated with total fluoroscopy time ( r = -0.57, P = .008), and total procedure time, but this correlation was not statistically significant ( r = - 0.36, P = 0.12). RA width (mean = 52.8 ± 9.9 cm) was associated with a shorter total procedure time ( r = −0.44, P = .047) and LV lead positioning time ( r = −0.33, P = .012). There were no statistically significant differences between the CT group and the non-CT group with respect to total intraoperative and fluoroscopy times or venogram contrast volumes. Total procedure time was longer in the CT group but the difference was not statistically significant (94 ± 27.2 vs. 74.7 ± 26.6; P = .065). Conclusion Noninvasive visualization of the coronary venous anatomy before CRT implantation can be used as a guide for lead placement. While no significant differences were noted between the two groups with respect to intraoperative variables, CS os diameter and RA width inversely correlated to a shorter procedure time and LV lead positioning time, respectively. Further clinical trials regarding the utility of MDCT to visualize coronary venous anatomy prior to CRT implantation for procedural planning and lead placement guidance are warranted.
Sex-Related Differences in Self-Reported Neurocognitive Impairment among High-Risk Cocaine Users in Methadone Maintenance Treatment Program
Authors: Shrestha Roman , Huedo-Medina Tania B. , Copenhaver Michael M. 
Published: March 2015

Background Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. Methods The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients’ awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. Results Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. Conclusions These findings suggest that cocaine users enter into treatment with a range of NCI – with women having significantly more neurocognitive deficits than men – that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients.