Archive for category: Reveryplay

The reporter construct, the control plasmid, and a transformation marker plasmid were coinjected into worms to generate the extrachromosomal arrays for analysis. Elegans and Caenorhabditis briggsae, leading us to focus further analyses on these two genes. We further examined the functional relationship between miR-71 and DAF-16, a FOXO transcription factor acting critically and negatively downstream of AGE-1/PI3K in the InsR pathway. Because the InsR pathway was previously shown to play a prominent role in L1 diapause (2, 3), we examined genetic interactions between miR-71 and different components of the InsR pathway.

A recent study showed that the expression of miR-71 was significantly increased relative to other miRNAs in starved L1 worms (15). However, miR-71 does not appear to regulate all postembryonic development during L1 diapause recovery. Unlike classical heterochronic miRNAs such as lin-4 and let-7, the role of miR-71 in vulval cell division is essential in animals recovering from starvation-induced L1 diapause, but not in animals hatched on plates with food. As pointed out above, multiple miRNAs in addition to miR-71 and the let-7 family miRNAs have roles in L1 diapause, and they may regulate the expression of many diverse targets that may include, but are not limited to, factors involved in UNC-31–InsR-signaling activities.

We further examined worms recovering from 4 d of L1 starvation and found that around 90% of the mir-71(lf) mutants displayed retarded vulval precursor cell (VPC) division, compared with less than 5% in wild type (Fig. 4A). We found that the 3′UTRs of several genes of the InsR pathway, including unc-31, age-1, pdk-1, akt-2, and sgk-1, contain predicted miR-71 targeting sites (as predicted by TargetScan revery play login and mirWIP). (H and I) Fluorescence images (H) and statistical data (I) showing that the M cell diveded in fed animals but remained undivided in 4-, 7-, or 11-d–starved L1 wild-type and mir-71(lf) worms. (E) Fluorescence and DIC images showing that the unc-31 3′UTR reporter was repressed in mir-71(+)worms (2/2 transgenic lines) but not in mir-71(lf) worms (4/4 transgenic lines). We found that the poor survival rate of daf-16(mu86)(lf) was further decreased by mir-71(lf) (Fig. 2C), consistent with the notion that a portion of miR-71 activities regulate genes that act in parallel to UNC-31–mediated InsR/PI3K signaling for long-term survival during L1 diapause. Mutating miR-71 drastically reduces the survival rate of animals in L1 diapause, and the effect can be suppressed by mutations of insulin receptor pathway genes age-1 and unc-31.

These results compelled us to examine specific interactions between individual miRNAs and their targets to gain mechanistic insights. This result suggests that miR-71 likely functions upstream of, or in parallel to, HBL-1 in regulating VPC timing. Moreover, the expression of hbl-1 is repressed by let-7 family miRNAs at L3 during normal development, and the hyperactivity of hbl-1 caused by failure of miRNA regulation leads to retarded development (26).

The numbers on each image indicate how many worms of the examined ones displayed the indicated phenotype. (Right panels) The gonad of the same animals in the Left panels to indicate the similar developmental stage. (A) Differential interference contrast (DIC) images showing L4 worms recovered from 4-d–starved L1 worms.

Among short-lived miRNA mutants, a mir-71 deletion mutant, mir-71(n4115) (referred to as mir-71(lf) hereafter), displayed a severe reduction in L1 starvation survival rate (Table S1 and Fig. 2A). We found that the reduced survival rate of ain-1 was suppressed by either reduction of age-1 function or loss of unc-31 function (Fig. 1 B and C), suggesting that a significant portion of the overall miRNA functions in L1 diapause is upstream of, or in parallel to, the InsR pathway. In this study, we addressed the questions of whether and how miRNAs impact developmental arrest and the long-term survival of early L1 stage worms in response to food starvation.

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We then compared the expression of a hbl-1 3′UTR reporter (18) in the mir-71(lf) mutants with that in wild type and found that the expression of this reporter was slightly derepressed at L3 in the mir-71 mutant (Fig. 4 F and G). (D) Bar graph showing that the delayed VPC timing defect of mir-71(lf) worms was enhanced by daf-16(lf) after 1 or 3 d of L1 starvation. (B) Bar graph showing the correlation between the severity of the retarded vulval precursor cell (VPC) timing defect of mir-71(lf) mutants and the duration of L1 starvation.

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On the other hand, the role of a particular miRNA (miR-71) is executed by repressing the expression of many genes in multiple pathways. On one hand, we showed that deletions of a good number of miRNAs have varying impacts on the L1 diapause survival rate, although they may effect the rate through different mechanisms. Instead, many specific physiological functions, such as the starvation-induced stress response, are regulated by a miRNA-target network, often involving multiple miRNAs and a large number of their targets. We found that the known developmental timing genes, hbl-1, lin-42, and lit-1, were at the top of the list (TargetScan). To understand how miR-71 affects VPC division, we searched its predicted targets for potential genes involved in regulating developmental timing. These results indicate that miR-71 plays a significant role in larval development of animals recovering from L1 diapause and likely does so by regulating the expression of components of the insulin receptor/DAF-16 pathway, as well as factors acting downstream, or in parallel to, DAF-16.

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To investigate the roles of miRNAs in animal survival during starvation-induced L1 diapause, we impaired the overall miRISC function with loss-of-function (lf) mutants of ain-1 (ku322, ku425, and tm3681) and ain-2(tm2432) and examined their L1 starvation survival rate (Materials and Methods). The strong suppression of the mir-71(lf) defect by hbl-1(RNAi), and the relatively weak effect of miR-71 on hbl-1 expression, are consistent with the idea that miR-71 exerts its role by modulating activities of multiple genes related to hbl-1 function in developmental timing. In contrast, the nuclear-localized GFP expression under the control of the 3′UTR of age-1(Fig. 3 C and D) or unc-31 (Fig. 3 E and F) was strongly repressed in the control worms, but prominently derepressed in mir-71(lf) mutant worms. If the 3′UTR of age-1 or unc-31 is repressed by miR-71, the GFP expression will be repressed in tissues where miR-71 is expressed in wild-type worms, but derepressed in the same tissues of mir-71(lf) worms. (A) The mir-71(n4115, lf) mutant displayed severe reduction in L1 starvation survival rate, and the reduced survival rate of mir-71(lf) was suppressed by a reduction-of-function allele of age-1(hx546). (C) The reduced L1 starvation survival rate of ain-1(lf) mutants was significantly suppressed by a null allele of unc-31.

When late, first larval stage (L1) worms sense unfavorable conditions, they enter an alternative and long-lived larval stage called dauer larvae (or dauer diapause). The nematode Caenorhabditis elegans responds to starvation by entering developmental arrest at multiple stages of its life cycle (1). Extreme climate events such as droughts and heatwaves are intensifying under climate change, yet their combined effects on plant recovery remain unclear. These pages contain all relevant country-specific information, including the recovery and resilience plans, the Commission’s assessment of the plans as well as information on payments requested by the Member States and funds paid out by the Commission.

Elegans Genetic Center (reference 257) and an N2 strain from the laboratory stock, respectively. Wild-type strains A and B are an N2 strain recently obtained from the C. (A) Survival rate curves of wild-type and mutant strains, as indicated. This is consistent with the previous reports that AIN-1 and AIN-2 are functional homologs with overlapping biochemical roles (16, 17). The roles of InsRs have also been implicated in arresting the cell cycle in germ cells and a portion of somatic cells during L1 diapause (2, 4). Contributed new reagents/analytic tools; X.Z., R.Z., and M.H.

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This result is consistent with the observation that miR-71 is specifically required for the starvation-induced stress response (Fig. S5). For example, we observed a robust retarded mutant phenotype in the vulval lineage but did not see obvious defects in seam cell differentiation or alae formation. It seems plausible that miRNAs that control developmental timing are also involved in regulating the metabolic rate through repressing the InsR pathway activity.

The primers that were used to amplify the 3′UTR of candidate genes are available upon request. 3′UTRs of genes of interest were cloned into the modified pPD129.57 vector as described previously (18). The data for 3′UTR expression and for VPC timing were analyzed using χ2 test.

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• Unlike dauer diapause, L1 diapause is not accompanied by life cycle changes and has not been shown to require certain signaling pathways that control the formation of dauer diapause such as TGF-β signaling (daf-1, daf-7) and nuclear hormone receptor (daf-12) (2, 3).
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• DAF-16 (the FOXO homolog in C. elegans) has been shown to play an important role in cell cycle arrest and developmental progression partly by promoting cki-1 expression in some somatic cells during L1 arrest (2).
• To test whether the activity of the InsR pathway was down-regulated by miR-71, we first examined the endogenous expression of components of the InsR pathway in mir-71(lf).
• However, the mechanisms that coordinate the long-term survival, overall developmental arrest, and reinitiation remain to be investigated.

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• (D) Bar graph showing that the delayed VPC timing defect of mir-71(lf) worms was enhanced by daf-16(lf) after 1 or 3 d of L1 starvation.
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• We found that the reduced survival rate of ain-1 was suppressed by either reduction of age-1 function or loss of unc-31 function (Fig. 1 B and C), suggesting that a significant portion of the overall miRNA functions in L1 diapause is upstream of, or in parallel to, the InsR pathway.
• For example, we observed a robust retarded mutant phenotype in the vulval lineage but did not see obvious defects in seam cell differentiation or alae formation.
• Compromising overall miRNA function dramatically reduces the survival rate of L1 worms in starvation-induced diapause, and the effect can be significantly suppressed by an age-1/PI3K mutation.
• Note that there are extra GFP-positive cells (red arrows) in mir-71(lf) mutants.

S1A indicated a dominant role of intestinal miRNAs in regulating L1 starvation survival. We used a dual-color 3′UTR reporter system (18) to test the computational, prediction-based hypothesis that the 3′UTRs of age-1 and unc-31 are directly regulated by miR-71 (Fig. 3B and Materials and Methods). Among these potential miRNA targets, the predicted miR-71–targeting sites in the 3′UTRs of age-1 and unc-31 are conserved between C.

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Here we show that compromising overall microRNA (miRNA) functions or mutating certain individual miRNAs impairs the long-term survival of nematodes during starvation-induced L1 diapause. Third-party accounts will also be restored if third-party backup was enabled on the old device. If you become locked out of those services and don’t have a backup of your accounts in Duo Mobile, you’ll need to contact the support team for that application (or perform the account recovery process for each of those third-party applications). However, whether an account can be restored depends upon Duo Restore being enabled by the administrator in the Duo Admin Panel or whether you’ve set a recovery password for reconnecting third-party accounts.

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Unnamed devices can be specified by their specific SES device and element number. This greatly reduces the chance of getting it wrong when you (or the datacenter technician) physically pulls the disk. You can also reboot, and GEOM will pick up the multipath when it first tastes the disks during boot.

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Direct Attached deployments require a bit more hardware and cabling. The NVMe interface is also extensible to allow operating over the network (where it is known as NVMe Over Fabric or NVMe-oF). NVMe on the other hand, supports multiple queues (often 64 queues, but the official specification allows for up to 65,536 queues) allowing for many commands to be run concurrently. While both SATA and SAS allow multiple commands to be issued at once to the device, these commands cannot actually be executed concurrently—instead, they are queued for sequential operation.

• In addition to the above query types, SES also supports a number of commands, including activating the “locate” and “fault” LEDs if present, and the ability to individually power off drives.
• While I have been aware of this in my home server as well, it is easy to forget to ensure that disks are not silently killing themselves by cycling the heads.
• An eight lane controller can only directly attach to 8 disks, requiring more controllers (consuming additional PCI-E slots) to connect more drives.
• My Seagate Exos enterprise drives make almost 0 noise actually.
• SATA+AHCI improved data transfer speeds, simplicity of communication, and included abilities that we today take for granted, such as “hot swap” and command queueing.
• The settings you mentioned are already set this way.
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My question is – is there a way to tell if a certain disk suffers from the issue prior to purchasing? For the system I’m monitoring here, the SSD that it boots from has a wearout indicator sitting on 95 of 100 (only 5% of the rated life consumed), visibly unchanged for a long time so it’s not very interesting as an example. (The properties like ID_SERIAL_SHORT can be queried on a running system using udevadm info, such as udevadm info /dev/sdd to get the properties of the disk currently assigned ID sdd.) Somewhat more useful for monitoring is the smartmon_load_cycle_count_raw_value, which provides the actual number of load cycles that have been done. Secondly what are your disk monitoring refresh intervals and what do you use on your system to monitor SMART disk health?

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The timer values specified are in milliseconds, so this example will park the disk heads after 30 minutes of inactivity. If we wanted to allow the disk to still park its heads but at minimum frequency, setting the APM value to 7Fh (hdparm -B 127) seems to be the correct choice. Of the three disks that I decided need some attention, I have one Western Digital disk and two Seagate ones.

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Obligatory word of warning – mucking with low-level drive settings like this can cause issues. Has anyone found a tool that can use EPC to change the Idle_b and Idle_c values for Exos drives? View an ad to download for free It’s self-hosted and self-managed, so data remains within your company network.Bank-Level EncryptionBanking-standard TLS 1.2 technology protects your computer from unauthorized access. Unparalleled PerformanceOur proprietary video-codec, DeskRT, compresses image data to reduce bandwidth and latency to a level imperceptible to the human eye. With decades of experience in IT management and later as a writer and tutor, she combines technical knowledge with a passion for clear communication.
The APM specification dating from 1992 includes some controls for hard drives, allowing a host system to specify the desired performance level of a disk and whether standby is permitted by sending commands to a disk. In addition to the above query types, SES also supports a number of commands, including activating the “locate” and “fault” LEDs if present, and the ability to individually power off drives. The first step is to map out the relationship between the physical chassis where the disks reside, and the logical devices enumerated by the operating system.
Unfortunately, APM settings don’t persist between power cycles so if we wanted to change disk settings with APM they would need to be reapplied on every boot. Advanced power management levels80h and higher do not permit the device to spin down to save power. For example, a device may implement one power management method from 80h to A0h and a higherperformance, higher power consumption method from level A1h to FEh. To prevent parking more often that is useful (for a server, usually that choice would be “very rarely”), there are a couple ways to do it and which apply will depend on what the hard drive vendor’s firmware supports. With the SMART metrics captured by Prometheus, it’s fairly easy to write a query that will show how often a given disk is parking its heads. Since I use Prometheus to capture information on the server’s operation however, I can use that to monitor that my hard drives are doing well.

Western Digital idle3

Other interfaces for remote storage include iSCSI, Fiber-Channel, Infiniband, RoCE, and others, reveryplay but those specialized solutions are beyond the scope of this article. Serial Attached SCSI (SAS) is the most common interface for enterprise storage, first appearing in 2004. Serial ATA (SATA) is the familiar interface used for non-enterprise storage, and is an extension of the original ATA interface dating from the 1980s. In this article we will discuss some strategies and tools to make managing disk arrays on FreeBSD (and related platforms like TrueNAS Core) much easier. It may be what you want is to enable HDD standby, which will “spin down” the drives when not in use
I will optimize settings later for the security/quietness tradeoff however, I’m very pleased with it for now. How can I set this value on the Truenas interface? Keeping it spinning but not accessing data is safer. I would still recommend against idling your drive as that reduces longevity. I also set the tunable vfs.zfs.txg.timeout to a somewhat large value so the regular syncs don’t happen every 5 seconds.
It is fairly well-known among techies that hard drives used in server-like workloads can suffer from poor configuration by default such that they frequently load and unload their heads, which can cause disks to fail much faster than they otherwise would. My Seagate Archive SMR disk (which began life as an external hard drive and was retired from that role when it became too small to hold as much as I wanted to back up to it) apparently doesn’t support reporting EPC settings (since asking for them says so), and initially didn’t accept new values for the idle timers either. The Prometheus Node Exporter is the canonical tool for capturing machine metrics like utilization and hardware information with Prometheus, but it alone does not support probing SMART data from storage drives. While SSDs don’t have any heads to park, most do report a media_wearout_indicator that represents the amount of data written to the device in relation to the amount that it’s specified to accept before the Flash storage medium wears out.

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Once you’ve done so, you must test delivery to your “real” inbox—you don’t want to learn that delivery isn’t working after your storage has already become unavailable! If you’d feel safer with a team of experts monitoring your storage, consider a ZFS Support Subscription. If you rely on manually checking on your storage periodically, you will regret it. Another important aspect of managing your storage system is configuring notifications. Klara recommends embedding these details directly into the ZFS vdev properties of each disk—a feature Klara created, which will become generally available in the upcoming OpenZFS 2.2 release. In these configurations, your system may or may not support features like individual “locate” and “fault” LEDs.

Using the no-op true command on other paths to that disk, will cause GEOM to re-”taste” the disk and see the label and automatically add the additional paths to the existing multipath. This will write a GEOM Multipath label to the last sector of the disk. Each SAS Expander will present as a new /dev/ses# device, so your system may have more than one.
Sounds like the drives being woken for the ZIL to flush writes to the ZFS pool and then going back to idle/sleep every 5 seconds. Enable the checkmark for the Syslog and choose a pool that is not based on hard drives. I had this same problem, using HGST data center refurb drives.
I moved the system dataset to the boot pool. I don’t move any data, no apps are running, this is a vanilla Scale install so far, yet the HDD is in constant work. 1 SSD to boot and 1 HDD to store data. Agree, I have used SeaChest with good results for this same issue on scale plus drive cache. If you do it on a live pool, I’d back up your data first.

• Yeah, it’s not helping, thanks.
• While SSDs don’t have any heads to park, most do report a media_wearout_indicator that represents the amount of data written to the device in relation to the amount that it’s specified to accept before the Flash storage medium wears out.
• I would still recommend against idling your drive as that reduces longevity.
• Since I use Prometheus to capture information on the server’s operation however, I can use that to monitor that my hard drives are doing well.
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• Replacing the drive is financially out of the question.

SATA disks plugged directly into the motherboard use an interface called AHCI which does not provide much in the way of advanced management features. For smaller numbers of drives, and for most home systems, the most common way the disks are attached is to the SATA controllers built into the motherboard. Non-Volatile Memory Express (NVMe) is a newer storage interface that is becoming very popular for flash storage devices. Just download the executable file on both devices and run it to open the tool. At a glance, changing idle3 and EPC settings seems to have done the job nicely; here is the same graph of head park rates per disk as before, but on a smaller timescale that makes individual head parks visible. Seagate provide a “Seachest” collection of tools for manipulating their drives, but rather more usefully to users of non-Windows operating systems like Linux they also offer an open-source openSeaChest.
When it comes to long-term data storage, there are several strategies and media types that Redditors recommend. It refreshes the disks SMART information every 5 min. ZFS and Btrfs both aim to modernize storage by combining filesystems and volume management, but… Monitoring and maintaining your storage media is one of the most important parts of keeping your data safe.
For ZFS users, automating fault responses with tools like ZED (ZFS Event Daemon) can simplify disk replacement and minimize downtime. Configuring your system to notify you when a disk has errors, or when the filesystem reports a degraded device, will ensure your system gets prompt attention when something goes wrong. Experienced enterprise storage managers also keep extensive notes including the model number, SKU and/or URL for reordering, purchase order information, warranty end date, warranty URL, and any other useful information about each drive. While the operating system typically provides device aliases based on the disk’s serial number, WWN, or some other static identifier, this does not provide all of the information you might want.
We can also see that the disk in Slot07 was recently swapped, and that Slot08 does not contain a disk and its locate LED is activated. SES provides a mechanism to query information from the enclosure, including temperature, fan speed, and status of power supplies. Many backplanes include support for SCSI Enclosure Services (SES).

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Craig starred opposite Nicole Kidman in the science fiction horror film The Invasion in 2007, the fourth film adaptation of the novel The Body Snatchers by Jack Finney, which was met with a negative reception. The other actor to have previously played Bond, George Lazenby, has also since voiced his approval of Craig. Also in 2005, Craig starred in the BBC television film Archangel – based on Robert Harris’ novel – as an English academic who stumbles upon a notebook believed to have belonged to Joseph Stalin. Craig appeared in three theatrical films in 2005, all of which were supporting roles.

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Despite this, Craig supported Barack Obama in the 2008 and 2012 US presidential elections. The role involves raising awareness for the UN Mine Action Service (UNMAS), and political and financial support for the cause. Craig participated in the Broadway Cares/Equity Fights AIDS fundraising 8 December 2009, raising $1,549,953 in the 21st annual Gypsy of the Year competition, from six weeks of curtain appeals at their hit Broadway drama, A Steady Rain. In 2024, he starred as William Lee in Luca Guadagnino’s adaptation of William S. Burroughs novel Queer. In 2022, Craig starred in a contemporary revival of Macbeth opposite Ruth Negga on Broadway.
First things first, you’ll need to create an account with us. I wish for you guys not to devalue player points like this. I thought it was against the rules to link player points to purchases in any way? This is not what techteam is suggesting. In my opinion, if you reward the player with PP and some more chips, it’ll make them more inclined to try.
Two days before the film’s release in the US, Craig was awarded a star on the Hollywood Walk of Fame which is located at 7007 Hollywood Boulevard (referring to Bond’s code number “007”), and next to the star of fellow Bond actor Roger Moore. After delays due to the COVID-19 pandemic, Craig’s fifth and final Bond film, No Time to Die, was released in September 2021 and received favourable reviews. In 2019, Craig starred in Rian Johnson’s black comedy murder-mystery Knives Out as Benoit Blanc, a detective investigating the sudden death of a family patriarch. The film premiered in September 2017 and was distributed by the Orchard the following year. In 2017, Craig co-starred in Steven Soderbergh’s comedy Logan Lucky, about two brothers who pull off a heist during a NASCAR race.