Miracle-dz/UniFAR-FTUs huggingface dataset:
The N-terminal Domain of Mammalian Lysyl-tRNA Synthetase Is a Functional tRNA-binding Domain*

Lysyl-tRNA synthetase from higher eukaryotes possesses a lysine-rich N-terminal polypeptide extension appended to a classical prokaryotic-like LysRS domain. Band shift analysis showed that this extra domain provides LysRS with nonspecific tRNA binding properties. A N-terminally truncated derivative of LysRS, LysRS-ΔN, displayed a 100-fold lower apparent affinity for tRNA3 Lys and a 3-fold increase inK m for tRNA3 Lys in the aminoacylation reaction, as compared with the native enzyme. The isolated N-domain of LysRS also displayed weak affinity for tRNA, suggesting that the catalytic and N-domains of LysRS act synergistically to provide a high affinity binding site for tRNA. A more detailed analysis revealed that LysRS binds and specifically aminoacylates an RNA minihelix mimicking the amino acid acceptor stem-loop structure of tRNA3 Lys, whereas LysRS-ΔN did not. As a consequence, merging an additional RNA-binding domain into a bacterial-like LysRS increases the catalytic efficiency of the enzyme, especially at the low concentration of deacylated tRNA prevailing in vivo. Our results provide new insights into tRNALys channeling in eukaryotic cells and shed new light on the possible requirement of native LysRS for triggering tRNA3 Lys packaging into human immunodeficiency virus, type 1 viral particles.
A mycobacterial extracytoplasmic function sigma factor involved in survival following stress

The extracytoplasmic function (ECF) sigma factors constitute a diverse group of alternative sigma factors that have been demonstrated to regulate gene expression in response to environmental conditions in several bacterial species. Genes encoding an ECF sigma factor of Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium smegmatis, designated sigE, were cloned and analyzed. Southern blot analysis demonstrated the presence of a single copy of this gene in these species and in Mycobacterium bovis BCG, Mycobacterium leprae, and Mycobacterium fortuitum. Sequence analysis showed the sigE gene to be highly conserved among M. tuberculosis, M. avium, M. smegmatis, and M. leprae. Recombinant M. tuberculosis SigE, when combined with core RNA polymerase from M. smegmatis, reconstituted specific RNA polymerase activity on sigE in vitro, demonstrating that this gene encodes a functional sigma factor. Two in vivo transcription start sites for sigE were also identified in M. smegmatis and M. bovis BCG. Comparison of wild-type M. smegmatis with a sigE mutant strain demonstrated decreased survival of the mutant under conditions of high-temperature heat shock, acidic pH, exposure to detergent, and oxidative stress. An inducible protective response to oxidative stress present in the wild type was absent in the mutant. The mycobacterial SigE protein, although nonessential for viability in vitro, appears to play a role in the ability of these organisms to withstand a variety of stresses.
Destabilized lysosomes and elimination of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in eastern oysters (Crassostrea virginica)

Contaminated oysters from near the Galveston Bay Ship Channel ([GBSC], TX, USA) were transplanted into clean aquariums in order to investigate the recovery of their lysosomal health. Destabilized lysosomes in the oyster hemocytes recovered from 81% to 34% after 23 d of elimination. Chemical analyses showed that transplanted oysters eliminated organic chemicals they had accumulated in their tissue. Enhanced lysosomal health (i.e., decreased lysosomal destabilization) was correlated positively with lower tissue concentrations of chemicals. This study indicates that lysosomal destabilization is a transient biomarker, which indicates only the current status (e.g., within one month) of chemical exposure and potential adverse biological effects. Analytical measurements revealed that polycyclic aromatic hydrocarbons (PAHs) generally were eliminated faster than polychlorinated biphenyls (PCBs) by a factor of 5 to 7. Body burdens of PCBs decreased exponentially, while the elimination pattern of PAHs were biphasic, representing a faster elimination during the early phase of elimination and, subsequently, a much slower elimination. This indicates that elimination of PAHs in the oysters is more complex and may include additional mechanisms compared to the uptake and elimination of PCBs.
Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC. Several imaging modalities including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and angiography are used in evaluating patients with chronic liver disease and suspected HCC. CT, MRI and contrast-enhanced US have replaced biopsy for diagnosis of HCC. Dynamic multiphase contrast-enhanced CT or MRI is the current standard for imaging diagnosis of HCC. Functional imaging techniques such as perfusion CT and diffusion-weighted MRI provide additional information about tumor angiogenesis that may be useful for treatment. Techniques evaluating tissue mechanical properties such as magnetic resonance elastography, and acoustic radiation force impulse imaging are being explored for characterizing liver lesions. The role of PET in the evaluation of HCC is evolving with promise seen especially with the use of a hepatocyte-specific PET tracer. Imaging is also critical for assessment of treatment response and detection of recurrence following locoregional treatment. Knowledge of the post-treatment appearance of HCC is essential for correct interpretation. This review article provides an overview of the role of imaging in the diagnosis, staging and post-treatment follow-up of HCC.
Inactivation of Pde8b enhances memory, motor performance, and protects against age‐induced motor coordination decay

Phosphodiesterases (PDEs) are critical regulatory enzymes in cyclic nucleotide signaling. PDEs have diverse expression patterns within the central nervous system (CNS), show differing affinities for cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and regulate a vast array of behaviors. Here, we investigated the expression profile of the PDE8 gene family members Pde8a and Pde8b in the mouse brain. We find that Pde8a expression is largely absent in the CNS; by contrast, Pde8b is expressed in select regions of the hippocampus, ventral striatum, and cerebellum. Behavioral analysis of mice with Pde8b gene inactivation (PDE8B KO) demonstrate an enhancement in contextual fear, spatial memory, performance in an appetitive instrumental conditioning task, motor‐coordination, and have an attenuation of age‐induced motor coordination decline. In addition to improvements observed in select behaviors, we find basal anxiety levels to be increased in PDE8B KO mice. These findings indicate that selective antagonism of PDE8B may be an attractive target for enhancement of cognitive and motor functions; however, possible alterations in affective state will need to be weighed against potential therapeutic value.
Improving the performance of speculatively parallel applications on the Hydra CMP

Hydra is a chip multiprocessor (CMP) with integrated support for thread-level speculation. Thread-level speculation provides a way to parallelize sequential programs without the need for data dependence analysis or synchronization. This makes it possible to parallelize applications for which static memory dependence analysis is difficult or impossible. While performance of the baseline Hydra system on applications with significant amounts of medium to large grain parallelism is good, the performance on integer applications with fine-grained parallelism can be poor. In this paper, we describe a collection of software and hardware techniques for improving speculation performance of the Hydra CMP. These techniques focus on reducing the overheads associated with speculation and improving the speculation behavior of the applications using code restructuring. When these techniques are applied to a set of ten integer, multimedia and floating-point benchmarks, significant performance improvements result.
Expresso : A user-friendly GUI for designing, training and using Convolutional Neural Networks

With a view to provide a user-friendly interface for designing, training and developing deep learning frameworks, we have developed Expresso, a GUI tool written in Python. Expresso is built atop Caffe, the open-source, prize-winning framework popularly used to develop Convolutional Neural Networks. Expresso provides a convenient wizard-like graphical interface which guides the user through various common scenarios -- data import, construction and training of deep networks, performing various experiments, analyzing and visualizing the results of these experiments. The multi-threaded nature of Expresso enables concurrent execution and notification of events related to the aforementioned scenarios. The GUI sub-components and inter-component interfaces in Expresso have been designed with extensibility in mind. We believe Expresso's flexibility and ease of use will come in handy to researchers, newcomers and seasoned alike, in their explorations related to deep learning.
Dynamic tracking line: feasible tracking region of a robot in conveyor systems

The concept of dynamic tracking line is proposed as the feasible tracking region for a robot in a robot-conveyor system, which takes the conveyor speed into consideration. This paper presents an effective method to find the dynamic tracking line in a robotic workcell. The maximum permissible line-speed which is a quantitative measure of the robot capability for conveyor tracking, is defined on the basis of the relation between the end effector speed and the bounds on the joint velocities, accelerations, and torques. This measure is derived in an analytic form using the parameterized dynamics and kinematics of the manipulator, and some of its properties are established mathematically. The problem of finding the dynamic tracking line is then formulated as a root-solving problem for a single-variable equation, and solved by the use of a simple numerical technique. Finally, numerical examples are presented to demonstrate the methodology and its applications in workspace specification.
DESTINY: A tool for modeling emerging 3D NVM and eDRAM caches

The continuous drive for performance has pushed the researchers to explore novel memory technologies (e.g. nonvolatile memory) and novel fabrication approaches (e.g. 3D stacking) in the design of caches. However, a comprehensive tool which models both conventional and emerging memory technologies for both 2D and 3D designs has been lacking. We present DESTINY, a microarchitecture-level tool for modeling 3D (and 2D) cache designs using SRAM, embedded DRAM (eDRAM), spin transfer torque RAM (STT-RAM), resistive RAM (ReRAM) and phase change RAM (PCM). DESTINY facilitates design-space exploration across several dimensions, such as optimizing for a target (e.g. latency or area) for a given memory technology, choosing the suitable memory technology or fabrication method (i.e. 2D v/s 3D) for a desired optimization target etc. DESTINY has been validated against industrial cache prototypes. We believe that DESTINY will drive architecture and system-level studies and will be useful for researchers and designers.
SWORD: scalable workload-aware data placement for transactional workloads

In this paper, we address the problem of transparently scaling out transactional (OLTP) workloads on relational databases, to support database-as-a-service in cloud computing environment. The primary challenges in supporting such workloads include choosing how to partition the data across a large number of machines, minimizing the number of distributed transactions, providing high data availability, and tolerating failures gracefully. Capturing and modeling the transactional workload over a period of time, and then exploiting that information for data placement and replication has been shown to provide significant benefits in performance, both in terms of transaction latencies and overall throughput. However, such workload-aware data placement approaches can incur very high overheads, and further, may perform worse than naive approaches if the workload changes. In this work, we propose SWORD, a <u>s</u>calable <u>wor</u>kload-aware <u>d</u>ata partitioning and placement approach for OLTP workloads, that incorporates a suite of novel techniques to significantly reduce the overheads incurred both during the initial placement, and during query execution at runtime. We model the workload as a hypergraph over the data items, and propose using a hypergraph compression technique to reduce the overheads of partitioning. To deal with workload changes, we propose an incremental data repartitioning technique that modifies data placement in small steps without resorting to complete workload repartitioning. We have built a workload-aware active replication mechanism in SWORD to increase availability and enable load balancing. We propose the use of fine-grained quorums defined at the level of groups of tuples to control the cost of distributed updates, improve throughput, and provide adaptability to different workloads. To our knowledge, SWORD is the first system that uses fine-grained quorums in this context. The results of our experimental evaluation on SWORD deployed on an Amazon EC2 cluster show that our techniques result in orders-of-magnitude reductions in the partitioning and book-keeping overheads, and improve tolerance to failures and workload changes; we also show that choosing quorums based on the query access patterns enables us to better handle query workloads with different read and write access patterns.
Triangle reordering for reduced overdraw in animated scenes

We introduce an automatic approach for optimizing the triangle rendering order of animated meshes with the objective of reducing overdraw while maintaining good post-transform vertex cache efficiency. Our approach is based on prior methods designed for static meshes. We propose an algorithm that clusters the space of viewpoints and key frames. For each cluster, we generate a triangle order that exhibits satisfactory vertex cache efficiency and low overdraw. Results show that our approach significantly improves overdraw throughout the entire animation sequence while only requiring a few index buffers. We expect that this approach will be useful for games and other real-time rendering applications that involve complex shading of articulated characters.
p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis

Apical constriction (AC) is a widely utilized mechanism of cell shape change whereby epithelial cells transform from a cylindrical to conical shape, which can facilitate morphogenetic movements during embryonic development. Invertebrate epithelial cells undergoing AC depend on the contraction of apical cortex-spanning actomyosin filaments that generate force on the apical junctions and pull them toward the middle of the cell, effectively reducing the apical circumference. A current challenge is to determine whether these mechanisms are conserved in vertebrates and to identify the molecules responsible for linking apical junctions with the AC machinery. Utilizing the developing mouse eye as a model, we have uncovered evidence that lens placode AC may be partially dependent on apically positioned myosin-containing filaments associated with the zonula adherens. In addition we found that, among several junctional components, p120-catenin genetically interacts with Shroom3, a protein required for AC during embryonic morphogenesis. Further analysis revealed that, similar to Shroom3, p120-catenin is required for AC of lens cells. Finally, we determined that p120-catenin functions by recruiting Shroom3 to adherens junctions. Together, these data identify a novel role for p120-catenin during AC and further define the mechanisms required for vertebrate AC.
“ Easy ” Parameterized Verification of Cross Clock Domain Protocols

This paper demonstrates how an off-the-shelf model checker that utilizes a Satisfiability Modulo Theories decision procedure and kinduction can be used for verification applications that have traditionally required special purpose hybrid model checkers and/or theorem provers. We present fully parameterized proofs of two types of protocols designed to cross synchronous boundaries: a simple data synchronization circuit and a serial communication protocol used in UARTs (8N1). The proofs were developed using the SAL model checker and its ICS decision procedures.
Conversion of pBR 322-Based Plasmids into Broad-Host-Range Vectors by Using the Tn 3 Transposition Mechanism

We constructed a series of transposon vectors which allow efficient in vitro gene manipulation and subsequent introduction of cloned DNA into a variety of gram-negative bacteria. Transfer of the cloned fragment from these multicopy plasmids into self-transmissible broad-host-range vectors is achieved in vivo, using the Tn3 transposition mechanism. Transposition into a variety of broad-host-range plasmids proceeds efficiently, and the resulting recombinant plasmids can be readily transferred and maintained in a variety of gram-negative bacteria. The utility of the transposable vectors was demonstrated by the introduction and expression of the lacIPOZY sequences of Escherichia coli into Pseudomonas putida strains, allowing them to utilize lactose as a sole source of carbon and energy.
High-capacity reversible multi-layer watermarking for H.264/AVC video

Watermarking any digital content usually leads to irreversible changes in the host. This can be unacceptable in certain application areas and due to a number of reasons such as legal issues. To satisfy these requirements, the paradigm of reversible watermarking was developed. This paper proposes a reversible watermarking technique based on the difference expansion technique. The watermark so embedded is fragile in nature and is useful for authentication systems. The proposed algorithm utilizes the IPCM macroblocks in an H.264/AVC bitstream to embed a high-capacity watermark. The performance of the proposed technique is evaluated for a variety of video samples and for a variety of encoding parameters. The results show that the technique is capable of embedding a high payload in the H.264/AVC bitstream with a negligible effect on the rate-distortion characteristics while at the same time being completely reversible.
C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth Muscle

Background—Accumulating evidence suggests that C-reactive protein (CRP), in addition to predicting vascular disease, may actively facilitate lesion formation by inciting endothelial cell activation. Given the central importance of angiotensin type 1 receptor (AT1-R) in the pathogenesis of atherosclerosis, we examined the effects of CRP on AT1-R expression and kinetics in vascular smooth muscle (VSM) cells. In addition, the effects of CRP on VSM migration, proliferation, and reactive oxygen species (ROS) production were evaluated in the presence and absence of the angiotensin receptor blocker, losartan. Lastly, the effects of CRP (and losartan) on neointimal formation were examined in vivo in a rat carotid angioplasty model. Methods and Results—The effects of human recombinant CRP (0 to 100 &mgr;g/mL) on AT1-R transcript, mRNA stability, and protein expression were studied in cultured human VSM cells. AT1-R binding was assessed with 125I-labeled angiotensin II (Ang II). VSM migration was assessed with wound cell migration assays, whereas VSM proliferation was determined with [3H]-incorporation and cell number. The effects of CRP (and losartan) on Ang II–induced ROS production were evaluated by 2′,7′-dichlorofluorescein fluorescence. Lastly, the effects of CRP (and losartan) on neointimal formation, VSM cell migration, proliferation, and matrix formation were studied in vivo in a rat carotid artery balloon injury model. CRP markedly upregulated AT1-R mRNA and protein expression and increased AT1-R number on VSM cells. CRP promoted VSM migration and proliferation in vitro and increased ROS production. Furthermore, CRP potentiated the effects of Ang II on these processes. In the rat carotid artery angioplasty model, exposure to CRP resulted in an increase in cell migration and proliferation, collagen and elastin content, and AT1-R expression, as well as an increase in neointimal formation; these effects were attenuated by losartan. Conclusions—CRP, at concentrations known to predict cardiovascular events, upregulates AT1-R–mediated atherosclerotic events in vascular smooth muscle in vitro and in vivo. These data lend credence to the notion that CRP functions as a proatherosclerotic factor as well as a powerful risk marker.
A journey towards inclusive education; a case study from a ‘township’ in South Africa

The purpose of this case study was to relate part of the journey to appropriate education for two young children with physical disabilities in a low socio-economic peri-urban informal settlement – or ‘township’ – in South Africa. The part of the on-going journey described here spanned four-and-a-half years and included the two children, their families, their teachers, their community and a small team of rehabilitation professionals working for a non-profit organisation in the area. The rehabilitation professionals’ goals were to provide support for the children, their families, their current special care centre and the school(s) they would attend in the future. The steps from the special care centre, to a mainstream early childhood development (ECD) centre for both of them, and then on to (a) a school for learners with special educational needs (LSEN) for one child and (b) a mainstream primary school for the other, are described. Challenges encountered on the way included parental fears, community attitudes and physical accessibility. Practical outcomes included different placements for the two children with implications and recommendations for prioritised parent involvement, individual approaches, interdisciplinary and community-based collaborations. Recommendations are given for clinical contexts, curricula and policy matters; for research and for scaling up such a programme through community workers.
Learning to Play the Violin: Motor Control by Freezing, Not Freeing Degrees of Freedom

Playing a violin requires precise patterns of limb coordination that are acquired over years of practice. In the present study, the authors investigated how motion at proximal arm joints influenced the precision of bow movements in novice learners and experts. The authors evaluated the performances of 11 children (4-12 years old), 3 beginning-to-advanced level adult players, and 2 adult concert violinists, using a musical work that all had mastered as their first violin piece. The authors found that learning to play the violin was not associated with a release or freeing of joint degrees of freedom. Instead, learning was characterized by an experience-dependent suppression of sagittal shoulder motion, as documented by an observed reduction in joint angular amplitude. This reduction in the amplitude of shoulder flexion-extension correlated highly with a decrease of bow-movement variability. The remaining mechanical degrees of freedom at the elbow and shoulder showed patterns of neither suppression nor freeing. Only violinists with more than 700 practice hr achieved sagittal shoulder range of motion comparable to experts. The findings imply that restricting joint amplitude at selected joint degrees of freedom, while leaving other degrees of freedom unconstrained, constitutes an appropriate strategy for learning complex, high-precision motor patterns in children and adults. The findings also highlight that mastering even seemingly simple bowing movements constitutes a prolonged learning process.