Neuraghe: Exploiting CPU-FPGA synergies for efficient and flexible CNN inference acceleration on zynQ SoCs

Deep convolutional neural networks (CNNs) obtain outstanding results in tasks that require human-level understanding of data, like image or speech recognition. However, their computational load is significant, motivating the development of CNN-specialized accelerators. This work presents NEURAghe, a flexible and efficient hardware/software solution for the acceleration of CNNs on Zynq SoCs. NEURAghe leverages the synergistic usage of Zynq ARM cores and of a powerful and flexible Convolution-Specific Processor deployed on the reconfigurable logic. The Convolution-Specific Processor embeds both a convolution engine and a programmable soft core, releasing the ARM processors from most of the supervision duties and allowing the accelerator to be controlled by software at an ultra-fine granularity. This methodology opens the way for cooperative heterogeneous computing: While the accelerator takes care of the bulk of the CNN workload, the ARM cores can seamlessly execute hard-to-accelerate parts of the computational graph, taking advantage of the NEON vector engines to further speed up computation. Through the companion NeuDNN SW stack, NEURAghe supports end-to-end CNN-based classification with a peak performance of 169GOps/s and an energy efficiency of 17GOps/W. Thanks to our heterogeneous computing model, our platform improves upon the state-of-the-art, achieving a frame rate of 5.5 frames per second (fps) on the end-to-end execution of VGG-16 and 6.6fps on ResNet-18

A comparative study of WASP-67b and HAT-P-38b from WFC3 data

Atmospheric temperature and planetary gravity are thought to be the main parameters affecting cloud formation in giant exoplanet atmospheres. Recent attempts to understand cloud formation have explored wide regions of the equilibrium temperature-gravity parameter space. In this study, we instead compare the case of two giant planets with nearly identical equilibrium temperature ($T_\mathrm{eq}$ $\sim 1050 \, \mathrm{K}$) and gravity ($g \sim 10 \, \mathrm{m \, s}^{-1})$. During $HST$ Cycle 23, we collected WFC3/G141 observations of the two planets, WASP-67 b and HAT-P-38 b. HAT-P-38 b, with mass 0.42 M$_\mathrm{J}$ and radius 1.4 $R_\mathrm{J}$, exhibits a relatively clear atmosphere with a clear detection of water. We refine the orbital period of this planet with new observations, obtaining $P = 4.6403294 \pm 0.0000055 \, \mathrm{d}$. WASP-67 b, with mass 0.27 M$_\mathrm{J}$ and radius 0.83 $R_\mathrm{J}$, shows a more muted water absorption feature than that of HAT-P-38 b, indicating either a higher cloud deck in the atmosphere or a more metal-rich composition. The difference in the spectra supports the hypothesis that giant exoplanet atmospheres carry traces of their formation history. Future observations in the visible and mid-infrared are needed to probe the aerosol properties and constrain the evolutionary scenario of these planets.Comment: 16 pages, 17 figures, 8 tables, accepted for publication in The Astronomical Journa

Criteria for effective design, construction, and gene knockdown by shRNA vectors

BACKGROUND: RNA interference (RNAi) technology is a powerful methodology recently developed for the specific knockdown of targeted genes. RNAi is most commonly achieved either transiently by transfection of small interfering (si) RNA oligonucleotides, or stably using short hairpin (sh) RNA expressed from a DNA vector or virus. Much controversy has surrounded the development of rules for the design of effective siRNA oligonucleotides; and whether these rules apply to shRNA is not well characterized. RESULTS: To determine whether published algorithms for siRNA oligonucleotide design apply to shRNA, we constructed 27 shRNAs from 11 human genes expressed stably using retroviral vectors. We demonstrate an efficient method for preparing wild-type and mutant control shRNA vectors simultaneously using oligonucleotide hybrids. We show that sequencing through shRNA vectors can be problematic due to the intrinsic secondary structure of the hairpin, and we determine a strategy for effective sequencing by using a combination of modified BigDye chemistries and DNA relaxing agents. The efficacy of knockdown for the 27 shRNA vectors was evaluated against six published algorithms for siRNA oligonucleotide design. Our results show that none of the scoring algorithms can explain a significant percentage of variance in shRNA knockdown efficacy as assessed by linear regression analysis or ROC curve analysis. Application of a modification based on the stability of the 6 central bases of each shRNA provides fair-to-good predictions of knockdown efficacy for three of the algorithms. Analysis of an independent set of data from 38 shRNAs pooled from previous publications confirms these findings. CONCLUSION: The use of mixed oligonucleotide pairs provides a time and cost efficient method of producing wild type and mutant control shRNA vectors. The addition to sequencing reactions of a combination of mixed dITP/dGTP chemistries and DNA relaxing agents enables read through the intrinsic secondary structure of problematic shRNA vectors. Six published algorithms for siRNA oligonucleotide design that were tested in this study show little or no efficacy at predicting shRNA knockdown outcome. However, application of a modification based on the central shRNA stability should provide a useful improvement to the design of effective shRNA vectors

Yellow and Red Supergiants in the Large Magellanic Cloud

Due to their transitionary nature, yellow supergiants provide a critical challenge for evolutionary modeling. Previous studies within M31 and the SMC show that the Geneva evolutionary models do a poor job at predicting the lifetimes of these short-lived stars. Here we extend this study to the LMC while also investigating the galaxy's red supergiant content. This task is complicated by contamination by Galactic foreground stars that color and magnitude criteria alone cannot weed out. Therefore, we use proper motions and the LMC's large systemic radial velocity (\sim278 km/s) to separate out these foreground dwarfs. After observing nearly 2,000 stars, we identified 317 probable yellow supergiants, 6 possible yellow supergiants and 505 probable red supergiants. Foreground contamination of our yellow supergiant sample was \sim80%, while that of the the red supergiant sample was only 3%. By placing the yellow supergiants on the H-R diagram and comparing them against the evolutionary tracks, we find that new Geneva evolutionary models do an exemplary job at predicting both the locations and the lifetimes of these transitory objects.Comment: Accepted for publication in the Ap

Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)

PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window

Single MHC Mutation Eliminates Enthalpy Associated with T Cell Receptor Binding

The keystone of the adaptive immune response is T cell receptor (TCR) recognition of peptide presented by Major Histocompatibility Complex (pMHC) molecules. The co-crystal structure of AHIII TCR bound to the MHC, HLA-A2, showed a large interface with an atypical binding orientation. MHC mutations in the interface of the proteins were tested for changes in TCR recognition. From the range of responses observed, three representative HLA-A2 mutants, T163A, W167A, and K66A, was selected for further study. Binding constants and co-crystal structures of the AHIII TCR and the three mutants were determined. K66 in HLA-A2 makes contacts with both peptide and TCR and previously has been identified as a critical residue for recognition by numerous TCR. The K66A mutation resulted in the lowest AHIII T cell response and the lowest binding affinity, which suggests T cell response may correlate with affinity. Importantly, the K66A mutation does not affect the conformation of the peptide. The change in affinity appears to be due to a loss in hydrogen bonds in the interface as a result of a conformational change in the TCR complementarity-determining region 3 (CDR3) loop. Isothermal titration calorimetry confirmed the loss of hydrogen bonding by a large loss in enthalpy. Our findings are inconsistent with the notion that the CDR1 and CDR2 loops of the TCR are responsible for MHC restriction, while the CDR3 loops interact solely with the peptide. Instead, we present here a MHC mutation that does not change the conformation of the peptide, yet results in an altered conformation of a CDR3

Leucine-rich repeats of the class II transactivator control its rate of nuclear accumulation

ABSTRACT: Activation of class II major histocompatibility complex (MHC) gene expression is regulated by a master regulator, class II transcriptional activator (CIITA). Transactivation by CIITA requires its nuclear import. This study will address a mechanistic role for the leucine-rich repeats (LRR) of CIITA in regulating nuclear translocation by mutating 12 individual consensus-motif "leucine" residues in both its ␣-motifs and ␤-motifs. While some leucine mutations in the LRR motif of CIITA cause congruent loss of transactivation function and nuclear import, other alanine substitutions in both the ␣-helices and the ␤-sheets have normal transactivation function but a loss of nuclear accumulation (i.e., functional mutants). This seeming paradox is resolved by the observations that nuclear accumulation of these functional mutants does occur but is significantly less than wild-type. This difference is revealed only in the presence of leptomycin B and actinomycin D, which permit examination of nuclear accumulation unencumbered by nuclear export and new CIITA synthesis. Further analysis of these mutants reveals that at limiting concentrations of CIITA, a dramatic difference in transactivation function between mutants and wild-type CIITA is easily detected, in agreement with their lowered nuclear accumulation. These experiments reveal an interesting aspect of LRR in controlling the amount of nuclear accumulation

CATERPILLER 16.2 (CLR16.2), a Novel NBD/LRR Family Member That Negatively Regulates T Cell Function

The newly discovered mammalian CATERPILLER (NOD, NALP, PAN) family of proteins share similarities with the NBD-LRR superfamily of plant disease resistance (R) proteins and are predicted to mediate important immune regulatory function. This report describes the first cloning and characterization of a novel CATERPILLER gene, CLR16.2 that is located on human chromosome 16. The protein encoded by this gene has a typical NBD-LRR configuration. Analysis of CLR16.2 suggests the highest expression among T lymphocytes. Cellular localization studies of CLR16.2 revealed that it is a cytoplasmic protein. Querying microarray studies in the public data base showed that CLR16.2 was significantly (>90%) down-regulated 6 h after anti-CD3 and anti-CD28 stimulation of primary T lymphocytes. Its reduction upon T cell stimulation is consistent with a potential negative regulatory role. Indeed CLR16.2 decreased NF-kappaB, NFAT, and AP-1 induction of reporter gene constructs in response to T cell activation by anti-CD3 and anti-CD28 antibodies or PMA and ionomycin. Following T cell stimulation, the presence of CLR16.2 reduced the levels of the endogenous transcripts for the IL-2 and CD25 proteins that are central in maintaining T cell activation and preventing T cell anergy. This reduction was accompanied by a delay of IkappaBalpha degradation. We propose that CLR16.2 serves to attenuate T cell activation via TCR and co-stimulatory molecules, and its reduction during T cell stimulation allows the ensuing cellular activation