Optically programmable gate array

The Optically Programmable Gate Array (OPGA), an optical version of a conventional FPGA, benefits from a direct parallel interface between an optical memory and a logic circuit. The OPGA utilizes a holographic memory accessed by an array of VCSELs to program its logic. An active pixel sensor array incorporated into the OPGA chip makes it possible to optically address the logic in a very short time allowing for rapid dynamic reconfiguration. Combining spatial and shift multiplexing to store the configuration pages in the memory, the OPGA module can be made compact. The reconfiguration capability of the OPGA can be applied to solve more efficiently problems in pattern recognition and database search

Optically programmable gate array

The Optically Programmable Gate Array (OPGA), an optical version of a conventional FPGA, benefits from a direct parallel interface between an optical memory and a logic circuit. The OPGA utilizes a holographic memory accessed by an array of VCSELs to program its logic. An active pixel sensor array incorporated into the OPGA chip makes it possible to optically address the logic in a very short time allowing for rapid dynamic reconfiguration. Combining spatial and shift multiplexing to store the configuration pages in the memory, the OPGA module can be made compact. The reconfiguration capability of the OPGA can be applied to solve more efficiently problems in pattern recognition and database search

Real-Time Gait Phase Detection on Wearable Devices for Real-World Free-Living Gait

Detecting gait phases with wearables unobtrusively and reliably in real-time is important for clinical gait rehabilitation and early diagnosis of neurological diseases. Due to hardware limitations of microcontrollers in wearable devices (e.g., memory and computation power), reliable real-time gait phase detection on the microcontrollers remains a challenge, especially for long-term real-world free-living gait. In this work, a novel algorithm based on a reduced support vector machine (RSVM) and a finite state machine (FSM) is developed to address this. The RSVM is developed by exploiting the cascaded K-means clustering to reduce the model size and computation time of a standard SVM by 88% and a factor of 36, with only minor degradation in gait phase prediction accuracy of around 4%. For each gait phase prediction from the RSVM, the FSM is designed to validate the prediction and correct misclassifications. The developed algorithm is implemented on a microcontroller of a wearable device and its real-time (on the fly) classification performance is evaluated by twenty healthy subjects walking along a predefined real-world route with uncontrolled free-living gait. It shows a promising real-time performance with an accuracy of 91.51%, a sensitivity of 91.70%, and a specificity of 95.77%. The algorithm also demonstrates its robustness with varying walking conditions

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

System size and centrality dependence of the balance function in A + A collisions at sqrt s NN = 17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si and centrality selected Pb+Pb collisions at sqrt s_NN = 17.2$ GeV with the NA49 large acceptance detector at the CERN-SPS. In particular, long range pseudo-rapidity correlations of oppositely charged particles were measured using the Balance Function method. The width of the Balance Function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

Kailo: a systemic approach to addressing the social determinants of young people’s mental health and wellbeing at the local level [version 1; peer review: awaiting peer review]

The mental health and wellbeing of children and young people is deteriorating. It is increasingly recognised that mental health is a systemic issue, with a wide range of contributing and interacting factors. However, the vast majority of attention and resources are focused on the identification and treatment of mental health disorders, with relatively scant attention on the social determinants of mental health and wellbeing and investment in preventative approaches. Furthermore, there is little attention on how the social determinants manifest or may be influenced at the local level, impeding the design of contextually nuanced preventative approaches. This paper describes a major research and design initiative called Kailo that aims to support the design and implementation of local and contextually nuanced preventative strategies to improve children's and young people’s mental health and wellbeing. The Kailo Framework involves structured engagement with a wide range of local partners and stakeholders - including young people, community partners, practitioners and local system leaders - to better understand local systemic influences and support programmes of youth-centred and evidence-informed co-design, prototyping and testing. It is hypothesised that integrating different sources of knowledge, experience, insight and evidence will result in better embedded, more sustainable and more impactful strategies that address the social determinants of young people’s mental health and wellbeing at the local level

Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia

B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4

The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the target cell surface to induce the co-receptor binding site on gp120 as the initial step in the entry process. The binding site is comprised of a highly conserved region on the gp120 core, as well as elements of the third variable region (V3). Antibodies against the co-receptor binding site are abundantly elicited during natural infection of humans, but the mechanism of elicitation has remained undefined. In this study, we investigate the requirements for elicitation of co-receptor binding site antibodies by inoculating rabbits, monkeys and human-CD4 transgenic (huCD4) rabbits with envelope glycoprotein (Env) trimers possessing high affinity for primate CD4. A cross-species comparison of the antibody responses showed that similar HIV-1 neutralization breadth was elicited by Env trimers in monkeys relative to wild-type (WT) rabbits. In contrast, antibodies against the co-receptor site on gp120 were elicited only in monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the detection of high-titer co-receptor antibodies in all sera from a set derived from human volunteers inoculated with recombinant gp120. These findings strongly suggest that complexes between Env and (high-affinity) primate CD4 formed in vivo are responsible for the elicitation of the co-receptor-site-directed antibodies. They also imply that the naïve B cell receptor repertoire does not recognize the gp120 co-receptor site in the absence of CD4 and illustrate that conformational stabilization, imparted by primary receptor interaction, can alter the immunogenicity of a type 1 viral membrane protein

Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region

Cell-Type Independent MYC Target Genes Reveal a Primordial Signature Involved in Biomass Accumulation

The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells