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Ep 880 - Google Drive __HOT__

The ACS880 single drives offers a wide range of standard interfaces. In addition the drive has three option slots that can be used for extensions including fieldbus adapter modules, input/output extension modules, feedback modules and a safety functions module.

Ep 880 - Google Drive

I want to import my csv as a 2d array within appscript, I don't want to export it to sheets, I just want to use the data to create google forms.The csv is located on the google drive so I want to import from my google drive into a 2d array variable.

AirPrint is a technology built into most popular printer models, including the printers and print servers listed here. To use AirPrint, you don't need to install an app, additional drivers, or other software.

USB-only devices Similar to AirPrint printers, these USB devices allow you to print or scan without having to install additional drivers. Because they require a USB connection, they support driverless printing or scanning only from Mac computers.

Exploiting genetic systems that link desired traits to chromosomes or genetic elements with a positive transmission bias (that is, >50%) dates back to the potential uses of chromosomal translocations by Serebrovski1, which was further generalized and articulated by Curtis in the 1960s for spreading a desired trait throughout a target population2. These so-called gene-drive systems or selfish genes3 are abundant in nature. Driving elements can bias the transmission of sex chromosomes or autosomes (meiotic drive)4,5,6,7,8,9,10,11 or only themselves, as exemplified by the diverse families of transposable elements12,13 (for example, P-elements in fruitflies14,15,16 or retrotransposons in humans17). Such super-Mendelian genetic entities have been implicated in the evolution of genome architectures in plants and animals17,18,19,20,21.

Homing endonuclease genes (HEGs)36,37 are an example of low-threshold selfish genetic elements that are found in a variety of microorganisms. These elements encode highly sequence-specific endonucleases that cut a naive homologous chromosome at the site where they are inserted into the genome and are copied into the DNA breaks they create by homology-directed repair (HDR) pathways. HEGs provided the first practical tools for building and testing synthetic gene-drive systems in strains of Drosophila38,39 or Anopheline mosquitoes40 engineered to carry a HEG recognition site.

I begin by discussing full gene-drive systems that carry linked transgenes expressing Cas9 in the germline and a gRNA-directing DNA cleavage at the site where the gene-drive cassette is inserted into the genome45,53. These drive elements can be used to reduce mosquito populations (suppression) or to render them incapable of transmitting pathogens (modification; for example, by including cargo genes encoding anti-malarial effectors46). For modification systems, incorporating functional recoded versions of genes into drives can greatly improve their performance54,55,56,57.

Mathematical modelling of suppression drives with differing fitness costs by Burt63 (Fig. 1h) predicted that they should reach an equilibrium level in populations of an infinite size determined by the copying efficiency of the drive element. Generational delays in incurring fitness costs improved the suppressive performance of drives (for example, grandchildless > sterile > lethal phenotypes). The main virtue of suppression drives is that, if successful, they eliminate or greatly reduce the transmission of all diseases vectored by a given insect. For example, suppression of Anopheline mosquitoes would reduce malaria caused by all malarial parasites, most notably the main pathogens of concern Plasmodium falciparum and Plasmodium vivax. Likewise, suppression of Aedes mosquitoes, such as Aedes aegypti, would greatly reduce the transmission of all arboviruses vectored by this species, including those causing dengue fever, yellow fever, chikungunya and Zika. The primary challenge of this approach, however, is the possible failure of the drive to achieve its goal of suppression owing to it generating (or the pre-existing presence of) functional cleavage-resistant alleles in the population that cannot be converted by the gene-drive. Such functional drive-resistant alleles would be positively selected, leading to the disappearance of the suppression drive and rebound of drive-resistant vector-competent mosquitoes. Additionally, local elimination of a mosquito species (although modelling suggests this is very unlikely on a global scale64,65; Fig. 2) might result in other species filling in the empty niche66,67, which could have unintended ecological consequences.

Given the many parameters that need to be known to calculate R0, it is difficult to estimate precisely the effect of introducing a gene-drive system (either suppression or modification), particularly given seasonal cycles of mosquito breeding and the considerable variability of environmental and human factors in both space and time contributing to this calculation64,65,70,114,115,170,171,172. Nonetheless, certain general principles can be underscored regarding the potential beneficial impacts of gene drives when layered on top of existing interventions (for example, insecticide-impregnated bed nets, indoor residual spraying with insecticides, anti-malarial drugs and sanitation measures to reduce breeding capacity such as draining standing water). Given the substantial progress that has been made over the past decade in reducing malarial prevalence and deaths (by 50% globally167), one can infer that R0 must be somewhere near 1 in many regions and that additional reductions could help drop it below 1, at least in some of these locations.

First-generation suppression drives developed in the Crisanti laboratory47 (Fig. 2a) performed comparably to the proof-of-principle modification drives46. However, suppression drives, by their intended design, suffer a greater impact from imperfect copying when transmitted through females71. The problem stems from non-copying events in which the target site is cleaved and, instead of the break being repaired by HDR-mediated directional gene conversion72,73,74,75 (resulting in copying of the drive element), the site is mutated by the competing non-homologous end-joining (NHEJ) pathway to generate drive-resistant insertion/deletion (indel) alleles45,46,47,49,60,76,77. Most of such NHEJ-induced indel alleles are non-functional (for example, out-of-frame or deleterious to protein function) and contribute passively to suppression of the target population71. However, a fraction of in-frame indels can retain target gene function and such alleles will rapidly take over the population owing to the strong positive selective advantage associated with fertility (Fig. 2b).

Another potential suppression tactic is to destroy (or shred) X chromosomes in males so that only the Y chromosome is transmitted79. A key aim for this approach is to destroy79 or mutate80 the X chromosome prior to fertilization of the egg to avoid reducing total progeny output. Note that one could also express the X-shredder from an autosome to generate daughterless fathers, however, as this sterilizing trait would be inherited in only a Mendelian fashion, such elements would rapidly decrease in frequency in the population in contrast to exhibiting drive when linked to the Y chromosome. Proof-of-principle X-shredders using either HEG or CRISPR systems targeting repeated X-linked ribosomal RNA genes showed promise81,82; however, it proved difficult to express the nucleases from the Y chromosome, most likely owing to the phenomenon of meiotic sex chromosome inactivation83. Another general concern for these and other suppression drives is to minimize any dominant fitness costs associated with being heterozygous for the drive element.

Although the dsx-drive very effectively suppressed laboratory cage populations without generating functional drive-resistant alleles48, there was the lingering concern that such alleles might arise very rarely in large natural populations. One way to reduce this possibility is to impose female sterility by two independent mechanisms. The Crisanti group created such a dual sterilization drive by mounting a HEG X-shredder under the control of a male-specific promoter (beta2-tubulin) on the dsx-drive84 (Fig. 2c). In the process, they also optimized regulatory sequences to minimize the heterozygous fitness costs of the drive element. Both mathematical modelling and cage experiments confirmed that the composite dsx-shredder drove more quickly than the parent dsx-drive (Fig. 2d).

There are three general solutions to drive attenuation in females. One solution is to restrict drive to males, thereby not generating any DNA cleavage in the female germline that could damage paternal alleles. Although simple in principle, this strategy requires the identification of suitable male-specific regulatory elements to control Cas9 expression, which remain to be characterized. The second solution is to limit the expression of the Cas9 nuclease to the period of germline development (for example, meiosis) when HDR takes place and then shut it off abruptly prior to the stages at which it would accumulate in the egg (for example, in nurse cells)85,91. Such restricted Cas9 expression should, in principle, result in a drive that is transmitted 100% of the time through both male and female lineages (see A clean drive below). The third solution is to eliminate individuals carrying non-drive NHEJ events, that is, to kill or sterilize all the mistakes. This latter strategy, which can be highly effective and offers a general solution to the drive-resistance problem, depends on a phenomenon referred to as lethal or sterile mosaicism (see below and Box 2).

A broadly transferable system for eliminating non-functional drive-resistant alleles, present either as sequence variants in a population78,92,93,94,95 or arising during the gene-drive process45,46,47,49,60,76,77, is to insert the drive into an essential gene and endow it with a recoded cDNA-restoring gene function53,54,55,56,57,61. Such recoded-drive elements can survive when homozygous. However, non-functional alleles resulting from non-homologous end-joining (NHEJ) will be eliminated by a combination of dominantly acting lethal or sterile mosaicism (see below) and standard negative selection. Furthermore, if one chooses a functionally critical site in a target gene, such as a catalytic centre in an essential enzyme54,56,57 or in a signal required for cellular trafficking such as a membrane tethering motif57, the likelihood of potentially competing functional NHEJ alleles arising is greatly diminished. 041b061a72

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