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Viral rebound following antiretroviral therapy (ART) discontinuation in HIV-1-infected individuals is believed to originate from a small pool of CD4+ T cells harboring replication-competent provirus. However, the origin and nature of the rebound virus has remained unclear. Recent studies have suggested that rebound virus does not originate directly from individual latent proviruses but rather from recombination events involving multiple proviruses. Here we evaluate the origin of rebound virus in 16 ART-suppressed, chronically SIV-infected rhesus monkeys following ART discontinuation. We sequence viral RNA and viral DNA in these animals prior to ART initiation, during ART suppression, and following viral rebound, and we compare rebound viral RNA after ART discontinuation with near full-length viral DNA from peripheral blood and lymph node mononuclear cells (PBMC and LNMC) during ART suppression. Sequences of initial rebound viruses closely match viral DNA sequences in PBMC and LNMC during ART suppression. Recombinant viruses are rare in the initial rebound virus populations but arise quickly within 2–4 weeks after viral rebound. These data suggest that intact proviral DNA in PBMC and LNMC during ART suppression is likely the direct origin of viral rebound in chronically SIV-infected rhesus monkeys following ART discontinuation., The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.

The main purpose of this research was to evaluate and analyze the economic value of the meteorological information services (MIS) provided by the Central Weather Bureau (CWB) when applied to aquaculture in Taiwan. In this research, a contingent valuation method (CVM) was used to inquire about the subjective rating given to the CWB’s meteorological information services based on the responses to a national level questionnaire distributed among aquaculture farmers. The subjective rating revealed how the aquaculture farmers rated the accuracy of the MIS provided by the CWB and how they recognized the impact of the MIS on their aquaculture output. On this basis, this research determined the economic value brought about by the application of the meteorological information services. In order to understand the main factors affecting the respondents’ willingness-to-pay (WTP) for the MIS, this research also conducted an empirical estimation of the bid function. The results indicated that the main factors affecting the WTP were found to include the respondents’ subjective rating of the meteorological information services (including the accuracy rating and the effect rating), traditional social and economic background variables such as income and education level, as well as fish species. In addition, through testing the estimation of the bid function, it was also found that the survey sample used in this research had a significant starting point bias effect, which needed to be corrected using econometric methods. According to the empirical results, the median willingness-to-pay (WTP) of aquaculture farmers in Taiwan was 3544 New Taiwan Dollars (NTD)/person/year and the total economic value at the national level ranged from 157 million to 209 million NTD per year. Since the MIS service users have often lacked sufficient knowledge and ability to interpret the weather forecasts, how to strengthen the capabilities of service users in using MIS through the promotion of training programs and improve the value of the MIS may be an important policy insight.

This review briefly summarizes the situation regarding food security in East and Southeast Asia. In accordance with the World Food Summit definition and 2009 Declaration of the World Summit on Food Security, the four pillars of food security—food availability, access to food, the stability of food supplies, and food utilization—are closely scrutinized along with the characteristics of food security at the sub-regional level. Historical trends for the agricultural economy and the food trade, such as food imports and exports, production and consumption, and the food price index in the sub-region, are presented and statistically analysed. Additionally, because agricultural industry in this region is vulnerable to climate change, issues about how climate change affects food security in food production systems, agricultural livelihoods, nutrition, and food policy making, which can be linked to the four pillars in different ways, are also discussed.

In this paper, we explore the effect of using different convolutional layers, batch normalization and the global average pooling layer upon a convolutional neural network (CNN) based gaze tracking system. A novel method is proposed to label the participant&rsquo, s face images as gaze points retrieved from eye tracker while watching videos for building a training dataset that is closer to human visual behavior. The participants can swing their head freely, therefore, the most real and natural images can be obtained without too many restrictions. The labeled data are classified according to the coordinate of gaze and area of interest on the screen. Therefore, varied network architectures are applied to estimate and compare the effects including the number of convolutional layers, batch normalization (BN) and the global average pooling (GAP) layer instead of the fully connected layer. Three schemes, including the single eye image, double eyes image and facial image, with data augmentation are used to feed into neural network to train and evaluate the efficiency. The input image of the eye or face for an eye tracking system is mostly a small-sized image with relatively few features. The results show that BN and GAP are helpful in overcoming the problem to train models and in reducing the amount of network parameters. It is shown that the accuracy is significantly improved when using GAP and BN at the mean time. Overall, the face scheme has a highest accuracy of 0.883 when BN and GAP are used at the mean time. Additionally, comparing to the fully connected layer set to 512 cases, the number of parameters is reduced by less than 50% and the accuracy is improved by about 2%. A detection accuracy comparison of our model with the existing George and Routray methods shows that our proposed method achieves better prediction accuracy of more than 6%.

In this paper, the use of the rotary prism eye exercise device combined with dynamic modified eye charts to establish the children myopia control method by rotating prism speed with changing. In this program, clients typically range in age from 12 to 18 years of age. The eye exercise was performed on Saturday and Sunday of each week for three months. The visual acuity was measured by the use of an auto refraction device before and after two weeks of eye exercises. After three months, the improvement in visual acuity was average of 0.20D of both right and left eyes decreasing an indicating that eye exercises as vision training-based program could improve visual acuity for children with myopia.

We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus., Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1. IMPORTANCE We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus.

The precise time when the viral reservoir is seeded during acute HIV-1 infection remains unclear. We previously demonstrated that the viral reservoir was seeded by day 3 following SIVmac251 infection in rhesus monkeys. Here we report the impact of initiating ART on day 0 (6 h), 1, 2, or 3 following intrarectal SIVmac251 infection in 20 rhesus monkeys (N = 5/group). After 6 months of daily suppressive ART, antiretroviral drugs were discontinued, and viral rebound was monitored. 0% (0 of 5), 20% (1 of 5), 60% (3 of 5), and 100% (5 of 5) of animals that initiated ART on days 0 (6 h), 1, 2, or 3, respectively, showed viral rebound following ART discontinuation and correlated with integrated viral DNA in lymph node CD4+ T cells. These data demonstrate that the viral reservoir is seeded within the first few days of infection and that early ART initiation limits the viral reservoir., The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4+ T cells is seeded within the first 2 days after infection.

The cellular endosomal sorting complex required for transport (ESCRT) was recently found to mediate important morphogenesis processes at the nuclear envelope (NE). We previously showed that the Epstein-Barr virus (EBV) BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress. Here, we uncover new cellular factors and mechanisms involved in this process. BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. BFRF1 is ubiquitinated, and elimination of possible ubiquitination by either lysine mutations or fusion of a deubiquitinase hampers NE-derived vesicle formation and virus maturation. While it interacts with multiple Nedd4-like ubiquitin ligases, BFRF1 preferentially binds Itch ligase. We show that Itch associates with Alix and BFRF1 and is required for BFRF1-induced NE vesicle formation. Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE and EBV maturation, uncovering novel regulatory mechanisms of nuclear egress of viral nucleocapsids. IMPORTANCE The nuclear envelope (NE) of eukaryotic cells not only serves as a transverse scaffold for cellular processes, but also as a natural barrier for most DNA viruses that assemble their nucleocapsids in the nucleus. Previously, we showed that the cellular endosomal sorting complex required for transport (ESCRT) machinery is required for the nuclear egress of EBV. Here, we further report the molecular interplay among viral BFRF1, the ESCRT adaptor Alix, and the ubiquitin ligase Itch. We found that BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. The lysine residues and the ubiquitination of BFRF1 regulate the formation of BFRF1-induced NE-derived vesicles and EBV maturation. During the process, a ubiquitin ligase, Itch, preferably associates with BFRF1 and is required for BFRF1-induced NE vesicle formation. Therefore, our data indicate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE, suggesting novel regulatory mechanisms for ESCRT-mediated NE modulation.

Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo . Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice.

HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in the majority of HIV-1 infected individuals and can lead to viral escape following bNAb monotherapy in humans. In this study, we show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of pre-existing viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in SHIV-SF162P3-infected rhesus monkeys. We then show that the V3 glycan-dependent antibody PGT121 alone and the V2 glycan-dependent antibody PGDM1400 alone both fail to protect against a mixed challenge with SHIV-SF162P3 and SHIV-325C. In contrast, the combination of both bNAbs provides 100% protection against this mixed SHIV challenge. These data reveal that single bNAbs efficiently select resistant viruses from a diverse challenge swarm to establish infection, demonstrating the importance of bNAb cocktails for HIV-1 prevention.

The implications of the international demonstration effect (IDE) for the development of underdeveloped economies have long been studied and debated. Yet few formal analyses exist in the literature, especially regarding its implications for the growth of domestic markets and the division of labour in developing economies. We offer an analysis of endogenous specialization under IDE, the first of its kind, showing that, far more complicated than the scenario held by conventional wisdom, IDE makes more difficult the emergence of the market underpinning the domestic division of labour, but facilitates the expansion of the market once the market has been developed.

Recently, heterogeneous system architectures are becoming a mainstream for achieving high performance and power efficiency. In particular, many-core graphics processing units (GPUs) have started to play an important role for computing in heterogeneous architectures. However, for application designers, computational workload still needs to be distributed among heterogeneous GPUs manually and remains inefficient. In this work, we propose a MINLP-based method for efficient workload distribution among GPUs by considering the capabilities of GPUs for various applications. Experimental results demonstrate the performance of our proposed method.

Owing to the rising awareness of environment protection, high performance is not the only aim in system design, energy efficiency has increasingly become an important goal. In accordance with this goal, heterogeneous systems which are more efficient than CPU-based homogeneous systems, and occupying a growing proportion in the Top500 and the Green500 lists. Nevertheless, heterogeneous system design being more complex presents greater challenges in achieving a good tradeoff between performance and energy efficiency for applications running on such systems. To address the performance energy tradeoff issue in CPU-GPU heterogeneous systems, we propose a novel feedback control optimization (FCO) method that alternates between frequency scaling of device and division of kernel workload between CPU and GPU. Given a kernel and a workload division, frequency scaling involves finding near-optimal core frequency of the CPU and of the GPU. Further, an iterative algorithm is proposed for finding a near-optimal workload division that balance workload between CPU and GPU at a frequency that was optimal for the previous workload division. The frequency scaling phase and workload division phase are alternatively performed until the proposed FCO method converges and finds a configuration including core frequency for CPU, core frequency for GPU, and the workload division. Experiments show that compared with the state-of-the-art GreenGPU method, performance can be improved by 7.9%, while energy consumption can be reduced by 4.16%.

A miniaturized C-band multiple-input-multiple-output (MIMO) antenna with good isolation and gain enhancement is investigated. Based on the reaction theorem, an equivalent magnetic current is introduced to decrease the effect caused by the electric current source, contributing to wideband isolation enhancement. Such a miniaturized antenna usually suffers from gain deterioration. Therefore, a three stacked superstrates with the metal strips are proposed for wideband gain enhancement. Good S 11 ( 21 (

The cellular endosomal sorting complex required for transport (ESCRT) machinery participates in membrane scission and cytoplasmic budding of many RNA viruses. Here, we found that expression of dominant negative ESCRT proteins caused a blockade of Epstein-Barr virus (EBV) release and retention of viral BFRF1 at the nuclear envelope. The ESCRT adaptor protein Alix was redistributed and partially colocalized with BFRF1 at the nuclear rim of virus replicating cells. Following transient transfection, BFRF1 associated with ESCRT proteins, reorganized the nuclear membrane and induced perinuclear vesicle formation. Multiple domains within BFRF1 mediated vesicle formation and Alix recruitment, whereas both Bro and PRR domains of Alix interacted with BFRF1. Inhibition of ESCRT machinery abolished BFRF1-induced vesicle formation, leading to the accumulation of viral DNA and capsid proteins in the nucleus of EBV-replicating cells. Overall, data here suggest that BFRF1 recruits the ESCRT components to modulate nuclear envelope for the nuclear egress of EBV., Author Summary Herpesviruses are large DNA viruses associated with human and animal diseases. After viral DNA replication, the herpesviral nucleocapsids egress through the nuclear membrane for subsequent cytoplasmic virion maturation. However, the mechanism by which the virus regulates the nuclear membrane and cellular machinery involved in this process remained elusive. The cellular endosomal sorting complex required for transport (ESCRT) machinery is known to participate in the biogenesis of multivesicular bodies, cytokinesis and the release of enveloped viruses from cytoplasmic membranes. Here, we show that functional ESCRT machinery is required for the maturation of Epstein-Barr virus (EBV). ESCRT proteins are redistributed close to the nucleus-associated membrane through interaction with the viral BFRF1 protein, leading to vesicle formation and structural changes of the nuclear membrane. Remarkably, inhibition of ESCRT machinery abolishes BFRF1-induced vesicle formation, and leads to the accumulation of viral DNA and capsid proteins in the nucleus. Specific interactions between BFRF1 and Alix are required for BFRF1-derived vesicle formation and crucial for the nuclear egress of EBV.

Advanced ischemic heart disease is usually accompanied by left ventricular (LV) myocardial volume loss and an abnormal enhancing pattern on delayed phase of multi-detector row computed tomography (MDCT). To assist radiologists and physicians in estimating the LV myocardial volume on delayed phase, this paper proposes an adaptive segmentation method for contouring the myocardial region in the delayed-phase MDCT and for computing the volume. The proposed method uses an anisotropic diffusion filter as a preprocessing procedure to enhance contrast and reduce specks in MDCT imaging. This work picks the middle of mid-ventricular level image slices as the lead slice. The proposed method develops two contouring modes to sketch the myocardium contour on the lead slice. By establishing the obtained contours as the initial contours, the region-growing method is employed to identify the contour of the myocardial region for each slice. The convex-hull finding algorithm is then used to refine the extracted contour. Finally, the width properties of the myocardial region and the morphological operators are used to obtain the entire LV myocardial volume. Twenty-seven healthy patients who had no symptoms of ischemic heart disease are examined to evaluate the performance of the proposed method. Compared with manual contours delineated by two experienced experts, the contouring results using computer simulation reveal that the proposed method reliably identifies contours similar to those obtained using manual sketching. The proposed method provides robust contouring for the LV myocardium on delayed-phase MDCT. The potential role of this technique may substantially reduce the time required to sketch manually a precise contour with high stability.

Indirect immunofluorescence (IIF) with HEp-2 cells is used for the detection of antinuclear autoantibodies (ANAs) in systemic autoimmune diseases. The ANA testing allows to scan a broad range of autoantibody entities and to describe them by distinct fluorescence patterns. The identification of patterns has recently by a human inspecting the slides with a microscope. The lacking automation of this technique has resulted in the development of alternative techniques based on chemical reactions, which have not the discrimination power of the ANA testing. An automatic system would pave the way for a wider use of ANA testing. An automatic inspection system for ANA testing can be divided into HEp-2 cell detection, fluorescence pattern classification and computer-aided diagnosis phases. This study focused on the first phase of cell detection that utilized the circle Hough transformation to separate connected cell in IIF images. The proposed method evaluated 7614 cells with six distinct fluorescence patterns from 113 images. Such a method provided a robust and fast automatic segmentation of HEp-2 fluorescent patterns in ANA testing.

Angiogenesis is a popular issue and indicator in the assessment of tumor's growth and metastasis. Three-dimensional (3-D) power Doppler ultrasound images could characterize benign and malignant breast masses. Therefore, this study extracts the features vascularization from 3-D ultrasound images and selects seven morphological features to diagnose benign and malignant breast tumors by using support vector machine (SVM). These features are trained by the Az value under the receiver operating characteristic (ROC) curve to distinguish the more important features from others. The simulations evaluate 30 benign and 30 malignant breast tumor cases by using the morphological features. The classification performance of the proposed method in term of Az value for the ROC curve of the features derived from 3-D power Doppler is 0.8423. The result shows that the vascular morphology in 3-D power Doppler ultrasound images could be used to diagnose benign and malignant breast tumors.

A significant, if not the major, characteristic of environmental protection is that its effect is largely worldwide. On the other hand, the world consists of hundreds of independent countries and regions. Therefore, an important problem in the protection of the global environment is that of the free-rider or public-goods problem. Pursuing its own interest, each country, state or region has insufficient incentive to safeguard global environment. This paper proposes a solution to this public-goods problem by enriching the United Nations with sufficient funds to subsidise abatement and empowering it with sharp enough teeth (through cooperation with the World Trade Organisation) to penalise non-compliance, including the failure to contribute the proposed higher contributions to the United Nations.