There is a widespread consensus in the research community that reading instruction in English should first focus on teaching letter (grapheme) to sound (phoneme) correspondences rather than adopt ...meaning-based reading approaches such as whole language instruction. That is, initial reading instruction should emphasize systematic phonics. In this systematic review, I show that this conclusion is not justified based on (a) an exhaustive review of 12 meta-analyses that have assessed the efficacy of systematic phonics and (b) summarizing the outcomes of teaching systematic phonics in all state schools in England since 2007. The failure to obtain evidence in support of systematic phonics should not be taken as an argument in support of whole language and related methods, but rather, it highlights the need to explore alternative approaches to reading instruction.
Recent events have pushed RNA research into the spotlight. Continued discoveries of RNA with unexpected diverse functions in healthy and diseased cells, such as the role of RNA as both the source and ...countermeasure to a severe acute respiratory syndrome coronavirus 2 infection, are igniting a new passion for understanding this functionally and structurally versatile molecule. Although RNA structure is key to function, many foundational characteristics of RNA structure are misunderstood, and the default state of RNA is often thought of and depicted as a single floppy strand. The purpose of this perspective is to help adjust mental models, equipping the community to better use the fundamental aspects of RNA structural information in new mechanistic models, enhance experimental design to test these models, and refine data interpretation. We discuss six core observations focused on the inherent nature of RNA structure and how to incorporate these characteristics to better understand RNA structure. We also offer some ideas for future efforts to make validated RNA structural information available and readily used by all researchers.
In this Perspective, we evaluate current progress in understanding how the brain encodes our sense of direction, within the context of parallel work focused on how early vestibular pathways encode ...self-motion. In particular, we discuss how these systems work together and provide evidence that they involve common mechanisms. We first consider the classic view of the head direction cell and results of recent experiments in rodents and primates indicating that inputs to these neurons encode multimodal information during self-motion, such as proprioceptive and motor efference copy signals, including gaze-related information. We also consider the paradox that, while the head-direction network is generally assumed to generate a fixed representation of perceived directional heading, this computation would need to be dynamically updated when the relationship between voluntary motor command and its sensory consequences changes. Such situations include navigation in virtual reality and head-restricted conditions, since the natural relationship between visual and extravisual cues is altered.
Non-volatile memory (NVM) devices, such as Flash, phase change RAM, spin transfer torque RAM, and resistive RAM, offer several advantages and challenges when compared to conventional memory ...technologies, such as DRAM and magnetic hard disk drives (HDDs). In this paper, we present a survey of software techniques that have been proposed to exploit the advantages and mitigate the disadvantages of NVMs when used for designing memory systems, and, in particular, secondary storage (e.g., solid state drive) and main memory. We classify these software techniques along several dimensions to highlight their similarities and differences. Given that NVMs are growing in popularity, we believe that this survey will motivate further research in the field of software technology for NVMs.
Pain is an immense clinical and societal challenge, and the key to understanding and treating it is variability. Robust interindividual differences are consistently observed in pain sensitivity, ...susceptibility to developing painful disorders, and response to analgesic manipulations. This review examines the causes of this variability, including both organismic and environmental sources. Chronic pain development is a textbook example of a gene-environment interaction, requiring both chance initiating events (e.g., trauma, infection) and more immutable risk factors. The focus is on genetic factors, since twin studies have determined that a plurality of the variance likely derives from inherited genetic variants, but sex, age, ethnicity, personality variables, and environmental factors are also considered.
Recent advances in single molecule real-time (SMRT) and nanopore sequencing technologies have enabled high-quality assemblies from long and inaccurate reads. However, these approaches require high ...coverage by long reads and remain expensive. On the other hand, the inexpensive short reads technologies produce accurate but fragmented assemblies. Thus, a hybrid approach that assembles long reads (with low coverage) and short reads has a potential to generate high-quality assemblies at reduced cost.
We describe hybridSPAdes algorithm for assembling short and long reads and benchmark it on a variety of bacterial assembly projects. Our results demonstrate that hybridSPAdes generates accurate assemblies (even in projects with relatively low coverage by long reads) thus reducing the overall cost of genome sequencing. We further present the first complete assembly of a genome from single cells using SMRT reads.
hybridSPAdes is implemented in C++ as a part of SPAdes genome assembler and is publicly available at http://bioinf.spbau.ru/en/spades
d.antipov@spbu.ru
supplementary data are available at Bioinformatics online.
Bacteria often live in dynamic fluid environments and flow can affect fundamental microbial processes such as nutrient uptake and infection. However, little is known about the consequences of the ...forces and torques associated with fluid flow on bacteria. Through microfluidic experiments, we show that fluid shear produces strong spatial heterogeneity in suspensions of motile bacteria, characterized by up to 70% cell depletion from low-shear regions due to 'trapping' in high-shear regions. Two mathematical models and a scaling analysis accurately capture these observations, including the maximal depletion at mean shear rates of 2.5-10 s super(-1), and reveal that trapping by shear originates from the competition between the cell alignment with the flow and the stochasticity in the swimming orientation. We show that this shear-induced trapping directly impacts widespread bacterial behaviours, by hampering chemotaxis and promoting surface attachment. These results suggest that the hydrodynamic environment may directly affect bacterial fitness and should be carefully considered in the study of microbial processes.
•We provide a comprehensive review of articles involving simulation in manufacturing.•Comparison of results from 2002 to 2013 with previous review results.•The results show a general shift in the ...application of discrete event simulation from manufacturing system design to operation.
This paper provides a comprehensive review of discrete event simulation publications published between 2002 and 2013 with a particular focus on applications in manufacturing. The literature is classified into three general classes of manufacturing system design, manufacturing system operation, and simulation language/package development. The paper further categorizes the literature into 11 subclasses based on the application area. The current review contributes to the literature in three significant ways: (1) it provides a wide coverage by reviewing 290 papers; (2) it provides a detailed analysis of different aspects of the literature to identify research trends through innovative data mining approaches as well as insights derived from the review process; and (3) it updates and extends the existing classification schemes through identification and inclusion of recently emerged application areas and exclusion of obsolete categories. The results of the literature analysis are then used to make suggestions for future research.
We report a novel model in which remote activation of peripheral nociceptive pathways in transgenic mice is achieved optogenetically, without any external noxious stimulus or injury. Taking advantage ...of a binary genetic approach, we selectively targeted Nav1.8(+) sensory neurons for conditional expression of channelrhodopsin-2 (ChR2) channels. Acute blue light illumination of the skin produced robust nocifensive behaviors, evoked by the remote stimulation of both peptidergic and nonpeptidergic nociceptive fibers as indicated by c-Fos labeling in laminae I and II of the dorsal horn of the spinal cord. A non-nociceptive component also contributes to the observed behaviors, as shown by c-Fos expression in lamina III of the dorsal horn and the expression of ChR2-EYFP in a subpopulation of large-diameter Nav1.8(+) dorsal root ganglion neurons. Selective activation of Nav1.8(+) afferents in vivo induced central sensitization and conditioned place aversion, thus providing a novel paradigm to investigate plasticity in the pain circuitry. Long-term potentiation was similarly evoked by light activation of the same afferents in isolated spinal cord preparations. These findings demonstrate, for the first time, the optical control of nociception and central sensitization in behaving mammals and enables selective activation of the same class of afferents in both in vivo and ex vivo preparations. Our results provide a proof-of-concept demonstration that optical dissection of the contribution of specific classes of afferents to central sensitization is possible. The high spatiotemporal precision offered by this non-invasive model will facilitate drug development and target validation for pain therapeutics.
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