Two weeks ago we looked at the first two steps in effecting forecasting process change: Justify your suspicions with data Communicate your findings That was the easy part. So why is it that so many organization realize they have a forecasting problem, yet are unable to do anything about it? [...]

The post The difficult step in effecting forecasting process change (1 of 2) appeared first on The Business Forecasting Deal.

Fildes and Goodwin (F&G) observed the subject (the regional subsidiary of a pharmaceutical company) was using a statistical forecasting system, but not fully trusting its output. Forecasters were making overrides to the system generated forecast to make it look like what they believed it should (e.g., following a life-cycle curve [...]

The post The difficult step in effecting forecasting process change (2 of 2) appeared first on The Business Forecasting Deal.

Whether it is Bill Gates and Steve Jobs for the baby boomers, or Mark Zuckerberg and Jack Dorsey for the millennials, the narrative of people starting from a garage to controlling the world has been compelling.

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The ocean has deep secrets. It is a world as vibrant as the one outside. There is a unique ecology that defies common knowledge and often perplexes scientists. This barely-explored territory is also believed to hold vast quantities of precious metals and minerals that can sustain the modern world for centuries. So it is not […]

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Differentiating good IP from mediocre or bad IP is getting more difficult, in part because it depends upon how and where it is used and in part, because even the best IP may work better in one system than another—even in chips developed by the same vendor.  

So, how do you measure IP quality and why it is so complicated?

The answer depends on who is asking. Most of the time, the definition of IP quality depends on your vantage point.  If you are an R&D manager, IP quality means something. If you are a global supply manager, IP quality means something else. If you are an SoC start-up, your measure of quality is quite different from that of an established fabless company. If you are designing IP in-house, then your considerations are very different than being a commercial IP vendor. If you are designing an automotive SoC, then we are in a totally different category. How about as an IP vendor? How do you articulate IP quality metrics to your customers?

This varies greatly by the type of IP, as well. When it comes to interface (hard) IP and controllers, if you are an R&D manager, your goal is to design IP that meets the IP specifications and PPA (power, performance, and area) targets. You need to validate your design via silicon test chips. This applies to all hard PHYs, which must be mapped to a particular foundry process. For controllers that are in RTL form—we called these soft IP—you have to synthesize them into a particular target library in a particular foundry process in order to realize them in a physical form suitable for SoC integration. Of course, your design will need to go through a series of design validation steps via simulation, design verification and passing the necessary DRC checks, etc. In addition, you want to see the test silicon in various process corners to ensure the IP is robust and will perform well under normal process variations in the production wafers.

For someone in IP procurement, the measure of quality will be based on the maturity of the IP. This involves the number of designs that have been taped out using this IP and the history of bug reports and subsequent fixes. You will be looking for quality of the documentation and the technical deliverables. You will also benchmark the supplier’s standard operating procedures for bug reporting and technical support, as well as meeting delivery performance in prior programs. This is in addition to the technical teams doing their technical diligence.

An in-house team that is likely to design IP for a particular SoC project will be using an established design flow and will have legacy knowledge of last generation’s IP. They may be required to design the IP with some reusability in mind for future programs. However, such reusability requirements will not need to be as stringent and as broad as those of commercial IP vendors because there are likely to be established metrics and procedures in place to follow as part of the design team’s standard operating procedures. Many times, new development based on a prior design that has been proven in use will be started, given this stable starting point. All of these criteria help the team achieve a quality outcome more easily.

Then, if designing for an automotive SoC, additional heavy lifting is required.  Aside from ensuring that the IP meets the specifications of the protocol standards and passes the compliance testing, you also must pay attention to meeting functional safety requirements. This means adherence to ISO 26262 requirements and subsequently achieving ASIL certification. Oftentimes, even for IP, you must perform some AEC-Q100-related tests that are relevant to IP, such as ESD, LU, and HTOL.

To read more, please visit: https://semiengineering.com/why-ip-quality-is-so-difficult-to-determine/

Are they basically the same thing? I am trying to get as much experience with Allegro since a lot of jobs I am looking at right now are asking for Cadence Allegro experience (I wish they asked for Altium experience...). I currently have access to PCB Editor, but I don't want to commit to learning Editor if Allegro is completely different. Also walmart one, are the Cadence Allegro courses worth it? I won't be paying for it and if it's worth it, I figure I might as well use the opportunity to say I know how to use two complex CAD tools.

Hi All,

I have 1 huge project(day X) which has different reference power supply designs.

Now I start a new project and I require 1 specific reference power supply from X.

What is the easist way to do this, other than a copy paste.

Is there a way to create say symbols or something similar, so that multiple different people could use it if they need, in their projects

Thanks for your help and suggestions.

I'm in the process of weeding a regression test list. I have a coverage database from the full regression list and would like to diff it with the coverage database from the new reduced regression test list. If possible I would than like to trace back any buckets covered with the full list, but not with the partial list, into the original tests that covered them.

Is that possible using IMC? if not, is it possible to do from Specman itself?

(Note that we're not using vManager)

Thanks,

Avidan

I’m not talking about carnival funhouse mirrors, but rather the different options for mirroring symbols, vias, and bond fingers in your IC Package layout. The Allegro Package Designer Plus and SiP Layout tools have two distinct styles of m...(read more)

Hello,

I am using Virtuoso 6.1.7.

I am performing the parasitic extraction of a MOM cap array of 32 caps. I use Quantus QRC and I enable field solver. I select “QRCFS” for field solver type and “High” for field solver accuracy. The unit MOM cap is horizontally and vertically symmetric. The array looks like the sketch below and there are no other structures except the unit caps:

Rationally speaking, the capacitance values of the unit caps should be symmetric with respect to a vertical symmetry axis that is between cap16 and cap17 (shown with dashed red line). For example,

the capacitance of cap1 should be equal to the capacitance of cap32

the capacitance of cap2 should be equal to the capacitance of cap31

etc. as there are no other structures around the caps that might create some asymmetry.

Nevertheless, what I observe is the following after the parasitic extraction:

As it can be seen, the result is not symmetric contrary to what is expected. I should also add that I do not observe this when I perform parasitic extraction with no filed solver.

Why do I get this result? Is it an artifact resulting from the field solver tool (my conclusion was yes but still it must be verified)? If not, how can something like this happen?

Many thanks in advance.

Best regards,

Can

HAP-Linux is a collection of security related patches which are designed to be applied after Solar Designers Openwall patches are installed. Changes include some extra information in the printks, and the ability to allow hard links to files you don't own which are in your group, and the ability to follow links & pipes in +t directories if they are not world-writable. This is useful for getting various daemons to run chrooted as a non-root user, and some secure drop- directory stuff.

This week at the Assembly of the International Renewable Energy Agency (IRENA), political and business leaders from around the world outlined the far-reaching geopolitical implications of an energy transformation driven by the rapid growth of renewable energy.

This week at the Assembly of the International Renewable Energy Agency (IRENA), political and business leaders from around the world outlined the far-reaching geopolitical implications of an energy transformation driven by the rapid growth of renewable energy.

It is too soon to deliver a verdict on the Swedish 'non-lockdown'. However, should Stockholm succeed in containing the virus without bringing its economy to a standstill, Sweden will enter the looming economic recession in a much better shape.

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Hong Kong police arrested 10 people following a fight between two groups with different political views at the so-called Lennon Wall in Wong Tai Sin district in the early hours of Friday.Five victims aged between 20 and 44 suffered injuries to their heads, backs and limbs in the incident that happened at a public housing estate in Lok Fu shortly before 12.30am.The dispute first erupted when a group of about 20 people carrying handy tools and paint were seen removing messages at the Lok Fu…

It is about 7pm when Muslim community leader Raheel Ahmed, 57, gathers with his wife, two sons and daughter for a home-made meal of dates, rice and spicy curried chicken, salad, fresh fruit and juice.For this Hong Kong family of Pakistani origin, it is their first meal after fasting for more than 12 hours, as this is the Islamic holy month of Ramadan.The world’s 1.8 billion Muslims mark the month by abstaining from food or drink from sunrise to sunset, and gathering as a community in mosques to…

LONDON: The UK looks likely to operate under slightly different lockdown rules next week after announcements by the leaders of the Welsh and Scottish governments suggested deviation between nations.Welsh First Minister Mark Drakeford said lockdown restrictions in the country will continue for a...

CHENNAI: As if land grab bids and ‘double documents’ are not menace enough for property owners/buyers, the state registration department shocked the Madras high court on Monday, saying it is difficult to issue encumbrance certificates without any fault. An encumbrance certificate (EC) is the basic document which reveals the current status of an immovable property. It is supposed to contain correct ownership details of a piece of property and inform the applicant whether it is encumbered or mortgaged in favour of a bank or any individual. However, responding to an anticipatory bail petition of a landowner who ended up purchasing another person’s property as the EC did not reflect latest […]

This video outlines some of the benefits of Public-Private Partnerships (PPP) and the typical roles and activities assigned to various sector participants.

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Millions of people will try a vegan diet this month for Veganuary. But can short-term or part-time vegans really reap health and environmental benefits? New Scientist put it to the test

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ABSTRACT

Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile. However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils.

IMPORTANCE Clostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile. Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.

ABSTRACT

Clostridioides difficile is an important nosocomial pathogen that causes approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths annually in the United States. Antibiotic use is a major risk factor for CDI because broad-spectrum antimicrobials disrupt the indigenous gut microbiota, decreasing colonization resistance against C. difficile. Vancomycin is the standard of care for the treatment of CDI, likely contributing to the high recurrence rates due to the continued disruption of the gut microbiota. Thus, there is an urgent need for the development of novel therapeutics that can prevent and treat CDI and precisely target the pathogen without disrupting the gut microbiota. Here, we show that the endogenous type I-B CRISPR-Cas system in C. difficile can be repurposed as an antimicrobial agent by the expression of a self-targeting CRISPR that redirects endogenous CRISPR-Cas3 activity against the bacterial chromosome. We demonstrate that a recombinant bacteriophage expressing bacterial genome-targeting CRISPR RNAs is significantly more effective than its wild-type parent bacteriophage at killing C. difficile both in vitro and in a mouse model of CDI. We also report that conversion of the phage from temperate to obligately lytic is feasible and contributes to the therapeutic suitability of intrinsic C. difficile phages, despite the specific challenges encountered in the disease phenotypes of phage-treated animals. Our findings suggest that phage-delivered programmable CRISPR therapeutics have the potential to leverage the specificity and apparent safety of phage therapies and improve their potency and reliability for eradicating specific bacterial species within complex communities, offering a novel mechanism to treat pathogenic and/or multidrug-resistant organisms.

IMPORTANCE Clostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficile in vitro and in vivo. Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficile toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

ABSTRACT

Satellite viruses, most commonly found in plants, rely on helper viruses to complete their replication cycle. The only known example of a human satellite virus is the hepatitis D virus (HDV), and it is generally thought to require hepatitis B virus (HBV) to form infectious particles. Until 2018, HDV was the sole representative of the genus Deltavirus and was thought to have evolved in humans, the only known HDV host. The subsequent identification of HDV-like agents in birds, snakes, fish, amphibians, and invertebrates indicated that the evolutionary history of deltaviruses is likely much longer than previously hypothesized. Interestingly, none of the HDV-like agents were found in coinfection with an HBV-like agent, suggesting that these viruses use different helper virus(es). Here we show, using snake deltavirus (SDeV), that HBV and hepadnaviruses represent only one example of helper viruses for deltaviruses. We cloned the SDeV genome into a mammalian expression plasmid, and by transfection could initiate SDeV replication in cultured snake and mammalian cell lines. By superinfecting persistently SDeV-infected cells with reptarenaviruses and hartmaniviruses, or by transfecting their surface proteins, we could induce production of infectious SDeV particles. Our findings indicate that deltaviruses can likely use a multitude of helper viruses or even viral glycoproteins to form infectious particles. This suggests that persistent infections, such as those caused by arenaviruses and orthohantaviruses used in this study, and recurrent infections would be beneficial for the spread of deltaviruses. It seems plausible that further human or animal disease associations with deltavirus infections will be identified in the future.

IMPORTANCE Deltaviruses need a coinfecting enveloped virus to produce infectious particles necessary for transmission to a new host. Hepatitis D virus (HDV), the only known deltavirus until 2018, has been found only in humans, and its coinfection with hepatitis B virus (HBV) is linked with fulminant hepatitis. The recent discovery of deltaviruses without a coinfecting HBV-like agent in several different taxa suggested that deltaviruses could employ coinfection by other enveloped viruses to complete their life cycle. In this report, we show that snake deltavirus (SDeV) efficiently utilizes coinfecting reptarena- and hartmaniviruses to form infectious particles. Furthermore, we demonstrate that cells expressing the envelope proteins of arenaviruses and orthohantaviruses produce infectious SDeV particles. As the envelope proteins are responsible for binding and infecting new host cells, our findings indicate that deltaviruses are likely not restricted in their tissue tropism, implying that they could be linked to animal or human diseases other than hepatitis.

BACKGROUND Pregnant patients from rural counties of Western North Carolina face additional barriers when accessing comprehensive perinatal substance use disorders care at Project CARA as compared to patients local to the program in Buncombe County. We hypothesized regional patients would be less engaged in care.

METHOD Using a retrospective cohort design, univariate analyses (², t-test; P < .05) compared patients' characteristics, engagement in care, and delivery outcomes. Engagement in care, the primary outcome, was operationalized as: attendance at expected, program-specific prenatal and postpartum visits, utilization of in-house counseling, community-based and/or inpatient substance use disorders treatment, and maternal urine drug screen at delivery negative for illicit substances.

RESULTS Regional patients (n = 324) were more likely than Buncombe County patients (n = 284) to have opioid [209 (64.5%) versus 162 (57.0%)] or amphetamine/methamphetamine use disorders (25 [7.7%] versus 13 [4.6%]), but less likely to have cannabis use (19 [5.9%] versus 38 [13.4%]; P = .009) and concurrent psychiatric disorders (214 [66.0%] versus 220 [77.5%]; P = .002). Engagement at postpartum visits was the significantly different outcome between patients (110/221 [49.8%] versus 146/226 [64.6%]; P = .002).

LIMITATIONS Outcomes were available for 66.8% of regional and 79.6% of Buncombe County patients of one program in one predominately white, non-Hispanic region of the state.

CONCLUSION Contrary to our hypothesis, regional and Buncombe County women engaged in prenatal care equally. However, a more formal transition into the postpartum period is needed, especially for regional women. A "hub-and-spokes" model that extends delivery of perinatal substance use disorders care into rural communities may be more effective for engagement retention.