bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel E2 Glycoprotein Tetramer Detects Hepatitis C Virus–Specific Memory B Cells
Authors: Boisvert Maude , Zhang Wanrui , Elrod Elizabeth J. , Bernard Nicole F. , Villeneuve Jean-Pierre , Bruneau Julie , Marcotrigiano Joseph , Shoukry Naglaa H. , Grakoui Arash 
Published: November 2016

Abstract
Acute hepatitis C virus (HCV) infection culminates in viral persistence in the majority of cases. Abs that recognize the envelope glycoproteins E1 and E2 are generated during the late stages of acute infection, yet their contribution to spontaneous viral clearance remains controversial. Investigation of the humoral responses during acute HCV infection have been limited by the inability to directly identify and characterize HCV-specific B cells. In this study we describe the development of a novel tetramer of the E2 glycoprotein ectodomain (J6, genotype 2a strain), which allowed us to visualize E2-specific B cells longitudinally in the peripheral blood of HCV-infected individuals. HCV-specific class-switched memory B cells were detected in 3 out of 7 participants during late acute infection, with a mean frequency of 0.63% for positive samples (range 0.16–0.67%) and in 7 out of 7 participants with chronic infection with a mean frequency of 0.47% (range 0.20–0.78%). In a cross-sectional study, E2 tetramer positive population was detected in 28 out of 31 chronically infected individuals. Deep sequencing of the BCR from E2-specific class-switched memory B cells sorted from two independent participants revealed a focused repertoire suggestive of clonal selection. Tetramer-specific B cells exhibited skewed CDR3 length distribution and increased mutation frequency compared with naive B cells. This BCR profile is indicative of clonal expansion and affinity maturation. E2 tetramer allows for specific and sensitive ex vivo characterization of rare HCV-specific B cells in infected individuals, and will enable researchers to gain a better understanding of humoral immunity in HCV infection.
Mechanisms of Acute Toxicity in NKG2D Chimeric Antigen Receptor T Cell–Treated Mice
Authors: Sentman Marie-Louise , Murad Joana M. , Cook W. James , Wu Ming-Ru , Reder Jake , Baumeister Susanne H. , Dranoff Glenn , Fanger Michael W. , Sentman Charles L. 
Published: November 2016

Abstract
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed. Injection of very high numbers of activated T cells expressing CARs based on murine NKG2D or DNAM1 resulted in increased serum cytokines (IFN-γ, IL-6, and MCP-1) and acute toxicity similar to cytokine release syndrome. Acute toxicity required two key effector molecules in CAR T cells—perforin and GM-CSF. Host immune cells also contributed to this toxicity, and mice with severe immune cell defects remained healthy at the highest CAR T cell dose. These data demonstrate that specific CAR T cell effector mechanisms and the host immune system are required for this cytokine release–like syndrome in murine models.
The Nuclear Receptor AhR Controls Bone Homeostasis by Regulating Osteoclast Differentiation via the RANK/c-Fos Signaling Axis
Authors: Izawa Takashi , Arakaki Rieko , Mori Hiroki , Tsunematsu Takaaki , Kudo Yasusei , Tanaka Eiji , Ishimaru Naozumi 
Published: November 2016

Abstract
The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)–mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow–derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, bone marrow macrophages isolated from AhR−/− mice exhibited impaired phosphorylation of Akt and MAPK as well as NF-κB, whereas their response to M-CSF remained unchanged. Osteoclast differentiation mediated by the AhR signaling pathway was also regulated in an RANKL/c-Fos–dependent manner. Furthermore, ligand activation of AhR by the smoke toxin benzo[a]pyrene accelerated osteoclast differentiation in a receptor-dependent manner, and AhR-dependent regulation of mitochondrial biogenesis in osteoclasts was observed. Moreover, AhR−/− mice exhibited impaired bone healing with delayed endochondral ossification. Taken together, the present results suggest that the RANKL/AhR/c-Fos signaling axis plays a critical role in osteoclastogenesis, thereby identifying the potential of AhR in treating pathological, inflammatory, or metabolic disorders of the bone.
HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism
Authors: Bradley Todd , Yang Guang , Ilkayeva Olga , Holl T. Matt , Zhang Ruijun , Zhang Jinsong , Santra Sampa , Fox Christopher B. , Reed Steve G. , Parks Robert , Bowman Cindy M. , Bouton-Verville Hilary , Sutherland Laura L. , Scearce Richard M. , Vandergrift Nathan , Kepler Thomas B. , Moody M. Anthony , Liao Hua-Xin , Alam S. Munir , McLendon Roger , Everitt Jeffrey I. , Newgard Christopher B. , Verkoczy Laurent , Kelsoe Garnett , Haynes Barton F. 
Published: November 2016

Abstract
The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cross-reactive with the HIV broadly neutralizing Ab (bnAb) 2F5. Molecular mimicry of host proteins by pathogens can lead to autoimmune disease. In this article, we demonstrate that neither the 2F5 bnAb nor HIV MPER-KYNU cross-reactive Abs elicited by immunization with an MPER peptide-liposome vaccine in 2F5 bnAb VHDJH and VLJL knock-in mice and rhesus macaques modified KYNU activity or disrupted tissue tryptophan metabolism. Thus, molecular mimicry by HIV-1 Env that promotes the evasion of host anti–HIV-1 Ab responses can be directed toward nonfunctional host protein epitopes that do not impair host protein function. Therefore, the 2F5 HIV Env gp41 region is a key and safe target for HIV-1 vaccine development.
Feasibility Studies on Selective Laser Melting of Copper Powders for the Development of High-temperature Circuit Carriers
Authors: Syed-Khaja Aarief , Kaestle Christopher , Franke Joerg 
Published: November 2016

Abstract
Additive manufacturing (AM) has the potential to lead significant changes in the present state-of-the-art production processes. This provides tool-free and direct manufacturing of complex geometries simultaneously integrating various functions into components. Though AM techniques are widely used in various sectors, the application into electronics production has been not yet explored. In electronics production, substrate development has high relevance due to their multi-functionality in giving the mechanical support and electrically connecting electronic components. This contribution introduces an innovative approach in the development of high-temperature substrates through additive layered manufacturing. The technique used in the investigations was selective laser melting (SLM) of copper based powder materials mainly bronze alloy and pure copper, for the generation of conductive patterns on ceramic surfaces. The process parameters for the SLM technique and the influential factors in the generation of conductive structures are discussed in detail.
Introduction to a new silicone adhesive designed for wearables technologies
Authors: Poliskie Michelle , Fregoso Javier , Krizan Robert 
Published: November 2016

Abstract
Wearables for accessing the web (e.g., glasses and watches) have been slow to infiltrate the market; however, those used to monitor real-time biometric activity (e.g., thermometers, glucose meters) have found feverish interest by both consumers and insurance companies. Therefore, the wearables market is expected to grow from 20 billion in 2015 to an approximate 135 billion in 2019 [1]. These new applications require adhesives that are biocompatible, strong and flexible. These material attributes are commonly considered agnostic properties and; therefore, require special design consideration in order to optimize all attributes simultaneously. In this report, it was demonstrated that EPM2-2412, a new silicone adhesive from NuSil, outperformed other commercially available adhesives by more than two order-of-magnitudes, as measured by peel strength. These mechanical properties, as well as the inherent biocompatibility and chemical durability of silicone, make possible enhanced designs in wearables technology.
High Speed Fluorescent Inspection of Non-visible defects
Authors: Singh Gurvinder , Suresh Chet , Thornell John , Han Woo Young 
Published: November 2016

Abstract
The semiconductor industry continues to drive down defectivity rates, especially as the liability to ship replacement parts for field failures is pushed back into the supply chain. As dimensions are driven down to finer pitch, there are a certain class of defects that are caused by organic residue. Inspection using white light for advanced packaging is well known. However, organic residue defects appear transparent to white light but can be the root cause of field reliability issues. Residue on top of a bump, as an example, could cause damage to the part when operating at high temperatures in the field. Up until now, such an inspection would have been performed either using a manual fluorescent microscope or not at all. A well understood capability gap in the industry, defects due to organic residue are present in copper pillar bump and wafer level chip scale packages – both fan-in and fan-out, as well as packages based on organic substrate. This paper presents data from high-speed fluorescent inspection that could address this problem in a unique way that was not possible up until now.
Ultrasonic System Normalization on Wedge Bonders
Authors: Niayesh Omid , Svendsen Vaughn , Chen Raymond , Fu Jason , Seppaenen Henri , Luechinger Christoph 
Published: November 2016

Abstract
Operators of ultrasonic wedge bonders desire that bonders using the same process inputs achieve identical process outputs. In practice, it has been found that process outputs can differ between bonders operating with the same inputs. A common practice to bring the performance of bonders into closer agreement is to make small adjustments to the input parameters. These adjustments are looked upon unfavorably because they are typically determined using non-standardized, non-automated procedures, and further, the process inputs for each bonder then need to be tracked separately. Therefore, there is a strong desire to normalize the performance of one bonder to another using an automated procedure.
This paper presents a method to normalize the performance of a number of bonders based upon bond deformation measurements taken automatically by the bonder. Several case studies are presented that demonstrate the effectiveness of this normalization procedure in improving the similarity of process outcomes across a group of bonders. The results show that bonders after Ultrasonic Normalization make bonds with more similar end deformation, shear strength and bond width than the bonders before Ultrasonic Normalization.
Consumable and Process Improvement for Large Copper Wire Bonding
Authors: Xu Tao , Walker Todd , Poncelet Bernard , Fu Jason , Luechinger Christoph 
Published: November 2016

Abstract
Aluminum (Al) wire has certain limitations and cannot satisfy the increased demands for power electronics interconnects. Copper (Cu) wire has many benefits and is replacing Al wire in high power, high temperature applications. Cu wire is much harder and wears the bond tool much faster than Al wire. Consumable lifetime and process stability have to be improved so that Cu wire interconnect can be accepted for mass production. The bond tool wear mechanism is investigated. Bond process parameter, bond tool tip geometry, and bond tool material affect bond tool lifetime and bond performance. By combining the bond tool tip design and bond process optimization, an ultra-shallow groove bond tool that has a groove depth (GD) of 40% wire diameter achieved producing 260,000 Cu wire bonds. The groove opening angle (GOA) affects wire confine capability of a bond tool and a larger GOA is preferred for bond tools with a shallower GD. Alternative bond tool material shows benefits of improving bond appearance and further extending bond tool lifetime.
Temporary Wafer Bonding Materials with Mechanical and Laser Debonding Technologies for Semiconductor Device Processing
Authors: Liu Xiao , Wu Qi , Bai Dongshun , Stanley Trevor , Lee Alvin , Su Jay , Huang Baron 
Published: November 2016

Abstract
Advanced wafer-level packaging (WLP) techniques, mainly driven by high performance applications in memory and mobile market, have been adopted for large-scale manufacturing in recent years. Temporary wafer bonding and debonding technology has been widely studied and developed over the last decade for use in various WLP technologies, such as package-on-package (PoP), fan-out integration, and 2.5-D and 3-D integration using through-silicon-via (TSV). Temporary bonding technology enables handling of thinned substrates (&lt;100 μm), which can no longer self-support during backside processing and packaging. Moreover, some applications require the temporary bonding materials to withstand temperatures up to 250°C in high-vacuum conditions, and even up to 350°C or higher during the dopant activation step required for manufacturing power devices. Therefore, a simple yet effective temporary bonding process and material that can survive all the backside processes is highly desired.
In this study, a series of formulations based on polar thermoplastics were developed for temporary wafer bonding applications. These materials target high temperature survivability and improved adhesion to prevent the premature delamination during downstream wafer processing. All of these materials provide high thermal stability up to 250°C or higher, and are able to be bonded to carrier wafers treated with release layers, which can be selectively debonded by either mechanical or laser release after backside processing. The material left on device wafer after debonding can be easily cleaned using common industrial solvents. Wafers bonded with these materials demonstrate lower overall stack total thickness variation (TTV &lt; 5 μm) after grinding and have successfully passed a 200°C PECVD process without any delamination during grinding and PECVD processes.
Behaviors of QFN Packages on a Leadframe Strip
Authors: Ouyang Eric , Ahn Billy , Chow Seng Guan , Dexter Anonuevo , Gu SeonMo , Jeong YongHyuk , Kim JaeMyong 
Published: November 2016

Abstract
To lower the manufacturing cost of quad flat no-lead (QFN) packages, the number of QFN packages on a leadframe must be increased. However, the increased number of packages or changes to the layout of QFN packages on the leadframe can impact the mold compound flow behavior, which will, in turn, affect warpage, and the generation of voids inside the mold compound. In this paper, both simulation and experimental approaches were conducted to study the behaviors of QFN packages on a leadframe strip. For simulation, we will demonstrate and present an analysis methodology to account for the in-line processing parameters, especially the step of manufacturing and processing the mold compound material to form the QFN packages on a leadframe strip. The in-line manufacturing parameters, such as pressure, temperature, shrinkage, and processing timing, were all considered and modeled. A commercial finite element tool was used. For the experiment, we measured the warpages and the voids of QFN packages as a function of the package location on the leadframe. The warpage of the package, and the voids generation of QFN packages at different locations on the leadframe strip were studied. In conclusion, the experiment vs. modeling data was correlated, and the study proved to be very useful for the prediction of warpage, and void generations.
Optimizing Board Level Reliability of a Novel LGA Package for IoT Applications
Authors: Assi Tara , Galles Paul , Mawer Andrew , Uehling Trent , Safai Steve 
Published: November 2016

Abstract
Technology development for Internet of Things applications is growing astronomically, increasing the demand for smaller, faster, and lower power solutions to run and power a vast array of connected machines and objects. The LS1012A is the smallest 64-bit processor on the market today, with a novel 211 LGA package that creates a mechanically robust and space efficient component. However, excellent board level reliability is required in order to meet the various IoT application needs. This study evaluates the board level reliability of the 211 LGA by performing single chamber thermomechanical cycling, monotonic bend testing, and JEDEC drop testing. The objective of this study is to fully optimize the board level performance of the 211 LGA without dramatically altering the package design. Two significant board level changes were applied to achieve significant board level performance, exceeding all projected application uses.
Understanding Whisker Growth: Effect of Substrate and Underlayer
Authors: Jagtap Piyush , Kumar Praveen 
Published: November 2016

Abstract
The fundamentals of whiskering in pure Sn coatings electrodeposited on pure Cu and brass (65 wt. % Cu: 35 wt. % Zn) substrates with and without electrodeposited Ni underlayer was studied. These coatings were subjected to isothermal aging at 50 °C to accelerate the whisker growth, and whisker growth was studied using scanning electron microscope (SEM) equipped with focused ion imaging. Texture characterization was conducted using X-rays and electron backscatter diffraction (EBSD). It was observed that whisker growth was more accelerated in case of brass substrate compared to pure Cu substrate. No whisker growth was observed in coatings with Ni underlayer. It was observed that diffusion of substrate atoms along Sn grain boundaries plays major role in whiskering. Ni underlayer inhibited diffusion of Cu and Zn atoms into Sn coating and hence was very effective in mitigating whisker growth.
A Comparison of Immersion Gold and Tin Surface Finishes on Sensing Electrodes for PCB Environmental Saltwater Concentration Sensors
Authors: Dean Robert N. , Werner Frank T. , Bozack Michael J. 
Published: November 2016

Abstract
Printed circuit board (PCB) sensors using low-cost commercial printed circuit board fabrication processes have been demonstrated for environmental sensing applications. One configuration of these sensors uses exposed electrodes to measure saltwater concentration in freshwater/seawater mixtures, through monitoring the resistance between the electrodes when they are immersed in the saltwater/freshwater solution. The lowest cost commercial PCB processes use an immersion Sn HASL surface finish on exposed copper cladding, including the sensing electrodes. This commercial PCB process has been demonstrated to make an effective, low-cost, short-lifetime sensor for saltwater concentration testing. The Sn finish, however, may not be optimal for this application. Sn oxidizes, which can interfere with sensor performance. Additionally, Sn and Sn oxides are potentially reactive with chemical constituents in seawater and seawater/freshwater solutions. An immersion Au (ENIG) surface finish is certainly less reactive with the atmosphere and chemicals likely present in the testing environment. However, an immersion Au finish increases the cost of the sensors by 30% to 40%. To investigate if the possible benefits of the more expensive Au surface finish are worth the extra expense, a study was performed where identical PCB sensors were procured from a commercial vendor with their standard low-cost Sn HASL finish and with their standard ENIG surface finish. Both sets of sensors were then evaluated in concentrations of seawater and freshwater, from 0% to 100% seawater concentration, using freshwater samples from a natural freshwater source near the coast where the seawater was obtained. Testing demonstrated an insignificant difference in sensor performance between the Sn HASL and the ENIG coated sensing electrodes. The results of this investigation indicated that for applications where the sensors will not be used for long periods of time, the added expense of an immersion Au surface finish is not worth the added cost.
Measurement and Modeling of Nuclear Waste in the Double Shell Tanks at Hanford Nuclear Waste Site Using Miniature Sensors
Authors: Aravelli Aparna , McDaniel Dwayne , Abrahao Anthony , Awwad Amer , Davila Clarice 
Published: November 2016

Abstract
Double Shell Tanks (DST's) at the Hanford Site in Washington store nuclear waste and require an understanding of tank integrity. Depending on the chemical composition and pH of the waste, certain temperature requirements are specified. However, the DST's are complex tanks and the methods used to find the temperature data, chemical composition, and other parameters provide results that are often uncertain. Temperature measurements are usually recorded more than 10 feet away from the walls primarily because of technical constraints. Results are fed into basic simulation models to get an estimation of the wall conditions. Hence, there exists a need to accurately measure and model the wall and inside temperatures. To resolve the issue, the authors attempt the use of a miniature pyrometer (Infrared (IR) temperature sensor) to be deployed into the annulus of the DST's. The IR sensor can be mounted on an annulus inspection camera or an ultrasonic testing crawler for temperature measurement of the outer wall for the DSTs. Further, advanced heat transfer based thermal models are developed using the software Solid works 2013 (simulation application) for accurate prediction of the nuclear waste temperatures in the tanks. Successful implementation of the pilot scale testing would result in the deployment of the technology for testing the nuclear waste storage tanks at the Hanford Site in Washington.