Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Basis for Ebolavirus VP35 Suppression of Human Dendritic Cell Maturation

ABSTRACT Zaire ebolavirus (EBOV) VP35 is a double-stranded RNA (dsRNA)-binding protein that inhibits RIG-I signaling and alpha/beta interferon (IFN-α/β) responses by both dsRNA-binding-dependent and -independent mechanisms. VP35 also suppresses dendritic cell (DC) maturation. Here, we define the pathways and mechanisms through which VP35 impairs DC maturation. Wild-type VP35 (VP35-WT) and two well-characterized VP35 mutants (F239A and R322A) that independently ablate dsRNA binding and RIG-I inhibition were delivered to primary human monocyte-derived DCs (MDDCs) using a lentivirus-based expression system. VP35-WT suppressed not only IFN-α/β but also proinflammatory responses following stimulation of MDDCs with activators of RIG-I-like receptor (RLR) signaling, including RIG-I activators such as Sendai virus (SeV) or 5′-triphosphate RNA, or MDA5 activators such as encephalomyocarditis virus (EMCV) or poly(I·C). The F239A and R322A mutants exhibited greatly reduced suppression of IFN-α/β and proinflammatory cytokine production following treatment of DCs with RLR agonists. VP35-WT also blocked the upregulation of DC maturation markers and the stimulation of allogeneic T cell responses upon SeV infection, whereas the mutants did not. In contrast to the RLR activators, VP35-WT and the VP35 mutants impaired IFN-β production induced by Toll-like receptor 3 (TLR3) or TLR4 agonists but failed to inhibit proinflammatory cytokine production induced by TLR2, TLR3, or TLR4 agonists. Furthermore, VP35 did not prevent lipopolysaccharide (LPS)-induced upregulation of surface markers of MDDC maturation and did not prevent LPS-triggered allogeneic T cell stimulation. Therefore, VP35 is a general antagonist of DC responses to RLR activation. However, TLR agonists can circumvent many of the inhibitory effects of VP35. Therefore, it may be possible to counteract EBOV immune evasion by using treatments that bypass the VP35-imposed block to DC maturation. IMPORTANCE The VP35 protein, which is an inhibitor of RIG-I signaling and alpha/beta interferon (IFN-α/β) responses, has been implicated as an EBOV-encoded factor that contributes to suppression of dendritic cell (DC) function. We used wild-type VP35 and previously characterized VP35 mutants to clarify VP35-DC interactions. Our data demonstrate that VP35 is a general inhibitor of RIG-I-like receptor (RLR) signaling that blocks not only RIG-I- but also MDA5-mediated induction of IFN-α/β responses. Furthermore, in DCs, VP35 also impairs the RLR-mediated induction of proinflammatory cytokine production, upregulation of costimulatory markers, and activation of T cells. These inhibitory activities require VP35 dsRNA-binding activity, an activity previously correlated to VP35 RIG-I inhibitory function. In contrast, while VP35 can inhibit IFN-α/β production induced by TLR3 or TLR4 agonists, this occurs in a dsRNA-independent fashion, and VP35 does not inhibit TLR-mediated expression of proinflammatory cytokines. These data suggest strategies to overcome VP35 inhibition of DC function.
Colour normalisation based on background information

This paper proposes an improvement on a well-known colour normalisation by the introduction of some knowledge on background. Comprehensive normalisation gives an invariant representation of the image colour. This invariant representation can be considered a canonical representation whenever image content is preserved and changes are only due to illuminant conditions. One of the steps of the normalisation is based on the grey-world normalisation that removes colour changes on each channel. Because a diagonal model is assumed, the independence of chromatic variations is also achieved if the channel normalisation is applied only with background mean in spite of image mean. This will allow one to remove illuminant effects meanwhile no influence from the foreground is introduced on the normalised coordinates. It will provide an almost canonical colour space without an explicit estimation of the scene illuminant.
Streaming Elements for FPGA Signal and Image Processing Accelerators

Field-programmable gate array (FPGA) devices boast abundant resources with which custom accelerator components for signal, image, and data processing may be realized; however, realizing high-performance, low-cost accelerators currently demands manual register transfer level design. Software-programmable soft processors have been proposed as a way to reduce this design burden, but they are unable to support performance and cost comparable to custom circuits. This paper proposes a new soft processing approach for FPGA that promises to overcome this barrier. A high-performance, fine-grained streaming processor, known as a streaming accelerator element, is proposed, which realizes accelerators as large-scale custom multicore networks. By adopting a streaming execution approach with advanced program control and memory addressing capabilities, typical program inefficiencies can be almost completely eliminated to enable performance and cost, which are unprecedented among software-programmable solutions. When used to realize accelerators for fast Fourier transform, motion estimation, matrix multiplication, and sobel edge detection, it is shown how the proposed architecture enables real-time performance and with performance and cost comparable with hand-crafted custom circuit accelerators and up to two orders of magnitude beyond existing soft processors.
Regulation of Immune Response and Inflammatory Reactions against Viral Infection by VCAM-1

ABSTRACT The migration of activated antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during viral infection. The ablation of VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of antigen-specific T cells during a systemic infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in VCAM-1 mutant mice compared to B6 controls suggest a significant role for VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8+ T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of infection in VCAM-1 mutant mice. Thus, these results underscore the potential role of VCAM-1 in regulating the immune response and inflammatory reactions against viral infections.
Fixation Ratio of Error Location-Aware Strategy for Increased Reliable Retention Time of Flash Memory

The lifetime of NAND flash is highly restricted by the bit error rate (BER), while error-correcting codes (ECC) can provide only limited error correction capability to tolerate increasing bit errors. In this paper, a novel fixation ratio of error locations aware (FRELA) strategy is proposed to prolong the reliable retention time of flash memory. The concept of FRELA is motivated by following two observations obtained from our real hardware experimental platform: first, the increasing trend of average BER with the retention time and the program/erase cycles can be easily modeled; second, there is a great possibility that an error bit of flash memory remains wrong after a certain retention time. The key purpose of FRELA is to flip the corresponding data bits according to the locations recording of error bits prior to operating ECC. By virtue of the BER prediction model, the required storage space of FRELA is effectively reduced because it avoids updating the information of locations frequently. The experimental results show that FRELA can prolong the reliable retention time of 2×-nm NAND flash by more than 60% without stronger ECC, while experiencing at most 1.03% degradation in writing speed and 0.79% degradation in reading speed, respectively.
Bayesian structure from motion using inertial information

A novel approach to Bayesian structure from motion (SfM) using inertial information and sequential importance sampling (SIS) is presented. The inertial information is obtained from camera-mounted inertial sensors and is used in the Bayesian SfM approach as prior knowledge of the camera motion in the sampling algorithm. Experimental results using both synthetic and real images show that, when inertial information is used, more accurate results can be obtained or the same estimation accuracy can be obtained at a lower cost.
Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

ABSTRACT Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. IMPORTANCE Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.
Tibiotalocalcaneal Nailing: Indications and Technique

Tibiotalocalcaneal fusion is a salvage procedure for severe arthrosis and deformity of both the tibiotalar and subtalar joints. The use of an intramedullary nail for this procedure has the advantages of providing immediate rigid internal fixation and compression at the fusion site, and offers load-sharing capacity. Tibiotalocalcaneal nailing can be used to reduce pain and improve function in patients with posttraumatic arthrosis, avascular necrosis, neuropathic arthropathy, and neuromuscular disease, and in revision situations such as nonunion and failed total ankle arthroplasty. Despite this, tibiotalacalcaneal fusion has limited indications as a result of the morbidity associated with having fused subtalars and tibiotalar joints. Results with this procedure are more often considered satisfactory rather than excellent, and it should be considered an alternative to amputation. The history, indications, contraindications, technique, and results of tibiotalocalcaneal nailing are discussed.
Unsupervised segmentation of multispectral images using edge progression and cost function

The paper is concerned with the development of an unsupervised segmentation algorithm for multispectral images. Due to the high dimensionality of these images, the underlining motivation of this work is on how to build up a robust unsupervised segmentation algorithm with acceptable computational complexity. After an initial approximate segmentation using the EM algorithm, a cost function associated to each pixel is proposed. This function includes a term that measures how close the pixel at hand is to the region's distribution centroids, and another term that measures the local homogeneity in the pixel's neighborhood. In addition, an edge progression technique is used to re-label pixels optimally. Extensive experiments have been carried out on many multispectral images and quantitative results have shown the efficiency of the approach.
A new image retrieval system supporting query by semantics and example

We propose a new image retrieval system that provides users with both semantics based query and visual features based query. Our system has several advantages. First, it integrates visual features and semantics seamlessly. Second, it uses some effective techniques, such as image classification and relevance feedback, to bridge the gap between visual features and semantics. Third, it proposes several ways to obtain the semantic information of the image, which reduces manual labor and reduces the "subjectivity" of semantics by human. Fourth, it can update the semantics of the image by human intervention, which makes the image retrieval more flexible. We have implemented an image retrieval system based on our proposed approach. Experiments on an image database containing 22,000 items show that our scheme can achieve high efficiency.
A 100-mA, 99.11% Current Efficiency, 2-mVpp Ripple Digitally Controlled LDO With Active Ripple Suppression

Digital low-dropout (DLDO) regulators are gaining attention due to their design scalability for distributed multiple voltage domain applications required in state-of-the-art system-on-chips. Due to the discrete nature of the output current and the discrete-time control loop, the steady-state response of the DLDO has inherent output voltage ripple. A hybrid DLDO (HD-LDO) with fast response and stable operation across a wide load range while reducing the output voltage ripple is proposed. In the HD-LDO, a DLDO and a low current analog ripple cancelation amplifier (RCA) work in parallel. The output dc of the RCA is sensed by a 2-bit analog-to-digital converter, and the digitized linear stage current is fed into the DLDO as an error signal. During load transients, a gear-shift controller enables fast transient response using dynamic load estimation. The DLDO suppresses the output dc of the RCA within its current resolution. With this arrangement, a majority of the dc load current is provided by the DLDO and the RCA supplies ripple cancelation current. The HD-LDO is designed and fabricated in a 180-nm CMOS technology, and occupies 0.697 mm2 of the die area. The HD-LDO operates with an input voltage range of 1.43–2.0 V and an output voltage range of 1.0–1.57 V. At 100-mA load current, the HD-LDO achieves a current peak efficiency of 99.11% and a settling time of 15 clock periods with a 0.5-MHz clock for a current switching between 10 and 90 mA. The RCA suppresses fundamental, second, and third harmonics of the switching frequency by 13.7, 13.3, and 14.1 dB, respectively.
A Structurally Unresolved Head Segment of Defined Length Favors Proper Measles Virus Hemagglutinin Tetramerization and Efficient Membrane Fusion Triggering

ABSTRACT Paramyxoviruses include several insidious and ubiquitous pathogens of humans and animals, with measles virus (MeV) being a prominent one. The MeV membrane fusion apparatus consists of a receptor binding protein (hemagglutinin [H]) tetramer and a fusion (F) protein trimer. Four globular MeV H heads are connected to a tetrameric stalk through flexible linkers. We sought here to characterize the function of a 17-residue H-head segment proximal to the stalk that was unresolved in all five MeV H-head crystal or cocrystal structures. In particular, we assessed whether its primary sequence and length are critical for proper protein oligomerization and intracellular transport or for membrane fusion triggering. Extensive alanine substitutions had no effect on fusion triggering, suggesting that sequence identity is not critical for this function. Excessive shortening of this segment reduced or completely abrogated fusion trigger function, while length compensation restored it. We then characterized the mechanism of function loss. Mutated H proteins were efficiently transported to the cell surface, but certain alterations enhancing linker flexibility resulted in accumulation of high-molecular-weight H oligomers. Some oligomers had reduced fusion trigger capacity, while others retained this function. Thus, length and rigidity of the unresolved head segment favor proper H tetramerization and counteract interactions between subunits from different tetramers. The structurally unresolved H-head segment, together with the top of the stalk, may act as a leash to provide the right degree of freedom for the heads of individual tetramers to adopt a triggering-permissive conformation while avoiding improper contacts with heads of neighboring tetramers. IMPORTANCE Understanding the molecular mechanism of membrane fusion triggering may allow development of new antiviral strategies. The fusion apparatus of paramyxoviruses consists of a receptor binding tetramer and a fusion protein trimer. Structural analyses of the receptor binding hemagglutinin-neuraminidases of certain paramyxoviruses suggest that fusion triggering is preceded by relocation of its head domains, facilitated by flexible linkers. Having noted a structurally unresolved 17-residue segment linking the globular heads to the tetrameric stalk of the measles virus hemagglutinin (H), we asked whether and how it may facilitate membrane fusion triggering. We conclude that, together with the top of the stalk, the flexible linker keeps H heads on a leash long enough to adopt a triggering-permissive conformation but short enough to limit roaming and improper contacts with heads of neighboring tetramers. All morbillivirus H-protein heads appear to be connected to their stalks through a “leash,” suggesting a conserved triggering mechanism.
Casting and Splinting Management for Hand Injuries in the In-Season Contact Sport Athlete

Context: Upper extremity injuries are extremely common in contact sports such as football, soccer, and lacrosse. The culture of competitive athletics provides an environment where hand injuries are frequently downplayed in an effort to prevent loss of game time. However, studies have shown that many sport-induced hand injuries do not actually require immediate surgical attention and can be safely treated through immobilization so that the athlete may complete the athletic season. In these cases, appropriate casting and splinting measures should be taken to ensure protection of the injured player and the other competitors without causing loss of game time. Evidence Acquisition: Articles published between 1976 and 2015 were reviewed to capture historical and current views on the treatment of hand injuries in the in-season athlete. Study Design: Clinical review. Level of Evidence: Level 5. Results: Although traditionally many sports-induced traumatic injuries to the hand held the potential to be season-ending injuries, experience has shown that in-season athletes do not necessarily need to lose game time to receive appropriate treatment. A thorough knowledge of converting everyday splints and casts into game day, sport-approved protective immobilization devices is key to safely allowing athletes with select injuries to play while injured. Conclusion: Protective techniques allow for maximum functionality during gameplay while safely and effectively protecting the injury from further trauma while bony healing takes place.
Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

ABSTRACT Alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. Western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense. However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigen-nucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.
New DCT-domain transcoding using split and merge technique

For the conventional downscaling video transcoder, the video server would be to first decompress the video, perform the downscaling operation in the pixel domain, and then recompress it. This is computational intensive. However, it is difficult to perform video downscaling in the DCT-domain since the prediction errors of each frame are computed from its immediate past higher resolution frames. Besides, the motion vector need to resample due to the size of the video is changed. Due to the mismatch of the resampled motion vector with the incoming DCT coefficients, the video transcoder need to recalculate the new DCT coefficient with lower resolution in pixel domain; this can create undesirable complexity as well as introduce re-encoding error. In this paper, we propose a new architecture to obtain the new DCT coefficients and the new motion vector by reuse the incoming motion vector and DCT coefficients. Since our proposed transcoder is mainly performing in DCT domain, low computational complexity can be achieved as well as the re-encoding can be reduced. Experimental result show that our proposed video downscaling transcoder can lead to significant computational savings as well as provide a high video quality compared to the conventional approach.