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Stimulation of ABCB4/MDR3 ATPase activity requires an intact phosphatidylcholine lipid [Research Articles]

ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of the phospholipids are members of the PC family, but only a subset of mainly 16.0-18:1 PC and 16:0-18:2 PC variants are present. To elucidate whether ABCB4 is the key discriminator in this enrichment of specific PC lipids, we used in vitro studies to identify crucial determinants in substrate selection. We demonstrate that PC-lipid moieties alone are insufficient for stimulating ABCB4 ATPase activity, and that at least two acyl chains and the backbone itself are required for a productive interaction. The nature of the fatty acids, like length or saturation has a quantitative impact on the ATPase activity. Our data demonstrate a two-step enrichment and protective function of ABCB4 to mitigate the harsh detergent effect of the bile salts, because ABCB4 can translocate more than just the PC-lipid variants found in bile.




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FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family [Research]

The Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family consists of two type-I transmembrane scaffolding receptors, DCBLD1 and DCBLD2, which play important roles in development and cancer. The nonreceptor tyrosine kinases FYN and ABL are known to drive phosphorylation of tyrosine residues in YXXP motifs within the intracellular domains of DCBLD family members, which leads to the recruitment of the Src homology 2 (SH2) domain of the adaptors CT10 regulator of kinase (CRK) and CRK-like (CRKL). We previously characterized the FYN- and ABL-driven phosphorylation of DCBLD family YXXP motifs. However, we have identified additional FYN- and ABL-dependent phosphorylation sites on DCBLD1 and DCBLD2. This suggests that beyond CRK and CRKL, additional DCBLD interactors may be regulated by FYN and ABL activity. Here, we report a quantitative proteomics approach in which we map the FYN- and ABL-regulated interactomes of DCBLD family members. We found FYN and ABL regulated the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2.




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Blake Shelton, Taylor Sheridan working on a singing competition series for CBS

Country music star Blake Shelton and writer-producer Taylor Sheridan are working on a new reality competition series for CBS called "The Road."




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CBT: How Checking Contributes to Mental Health Problems (Eating Disorders, Depression, Anxiety)

Although common ‘disorders’ (e.g., eating disorders, anxiety, and depression) look different on the surface, there are some common underlying mechanisms. One of these is checking. I’m going to go explain the role of checking in a selection of common mental health problems. Checking in Health Anxiety Examples: – Person goes to the Dr for blood […]

The post CBT: How Checking Contributes to Mental Health Problems (Eating Disorders, Depression, Anxiety) appeared first on Dr Alice Boyes.




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How To Change Negative Core Beliefs: A Straightforward Guide to Cognitive Behavioral Therapy (CBT)

The core beliefs that cause the most common problems fall into the following 3 categories. These core beliefs commonly underlie depression and anxiety. Helpless Core Beliefs such as: “I’m incompetent” “I’m needy” “I’m weak” “I’m defective, I don’t measure up” “I’m a failure” Unlovable Core Beliefs such as: “I’m unlovable” “I’m different” “I’m bound to […]

The post How To Change Negative Core Beliefs: A Straightforward Guide to Cognitive Behavioral Therapy (CBT) appeared first on Dr Alice Boyes.




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CBC Nova Scotia News - November 11, 2024

The only daily TV news package to focus on Nova Scotians and their stories




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CBC Nova Scotia News - November 12, 2024

The only daily TV news package to focus on Nova Scotians and their stories




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CBRM to seek new CAO, but not before municipality's financial situation is known

The new mayor and council are planning big changes for the Cape Breton Regional Municipality, and one of those is at the top of the staff organizational chart now that chief administrative officer Marie Walsh is set to retire.



  • News/Canada/Nova Scotia

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CBC in Minnesota: What are voters saying after Trump win?

CBC News reporter Sarah Law reports from Duluth, Minn., early Wednesday after Donald Trump defeated Kamala Harris to secure his second term as U.S. president.




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CBC | MLB News




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CBC Winnipeg News - November 12, 2024

Our community. Our neighbourhoods. The news of our city.




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CBC Kitchener-Waterloo Make The Season Kind 2024

Make The Season Kind is a month of giving in support of The Food Bank of Waterloo Region. Join CBC K-W for a kick-off show on Friday, Dec. 6 at TheMuseum in downtown Kitchener with performances by I, The Mountain, singer-songwriter Mandippal, local chef Terry Salmond and more.



  • News/Canada/Kitchener-Waterloo

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'There is stigma, but there is help:' Death of CBSA officer shines light on mental health in profession

Details remain scarce surrounding the death of a Canada Border Services Agency (CBSA) officer at the Ambassador Bridge on Saturday. The border authority and union said an employee died by suicide while on the job on the Windsor, Ont., side of the border. 



  • News/Canada/Windsor

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CBC | NBA News




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CBC | NFL News




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CBC | CFL News




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CME Group Announces First Trades of CBL Australian Carbon Credit Unit (ACCU) Futures

CME Group, the world's leading derivatives marketplace, today announced its new CBL Australian Carbon Credit Unit (ACCU) futures have launched and are available for trading. A total of five...




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Early Black Friday deals: save up to $300 on every M4 MacBook Pro 14-inch & 16-inch

Early Black Friday deals are in effect on Apple's 2024 MacBook Pro M4, with every configuration — retail and CTO — eligible for a coupon discount.


Save up to $300 on Apple's new MacBook Pro M4 - Image credit: Apple

Unlock savings of up to $300 off the configuration of your choosing with promo code APINSIDER at Apple Authorized Reseller Adorama. These deals offer aggressive discounts ahead of Black Friday, taking the stress out of holiday shopping.

Use code APINSIDER


Continue Reading on AppleInsider | Discuss on our Forums




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Amazon drops early Black Friday deals on M4 MacBook Pro, Mac mini, iMac, MacBook Air 16GB

Apple's 1TB M4 MacBook Pro 14-inch is eligible for a material early Black Friday discount at Amazon, along with savings on the 2024 Mac mini M4 and a record low price on the 13-inch MacBook Air 16GB.


Amazon slashed prices on Apple's current Macs - Image credit: Apple

In what is the steepest price drop we've seen on the 14-inch M4 / 16GB RAM / 1TB SSD spec, Amazon has shaved $145 off MSRP when you order the laptop in the Silver colorway.


Continue Reading on AppleInsider | Discuss on our Forums




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MacBook Air 16GB models are on sale from $749.99 right now on Amazon

The lowest prices of the year are here well before Black Friday, with MacBook Air models with 16GB RAM dropping to as low as $749.99.


MacBook Air models with 16GB RAM are priced as low as $749 - Image credit: Apple

Amazon's aggressive early Black Friday deals on current MacBook Air models deliver rock-bottom pricing on specs that include 16GB unified memory.

Buy from $749.99


Continue Reading on AppleInsider | Discuss on our Forums




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Holiday 2024 MacBook Buyer's Guide -- Which Mac laptop you should buy?

Apple's late 2024 update to its Mac and MacBook ranges has brought M4 to the product line. Here's how to choose the best portable Mac for your budget for the 2024 holiday season.


MacBook Air and MacBook Pro

Apple's fall product updates covered many areas, but for the Mac product category, it meant an update to M4. Following the introduction of the chip in the iPad Pro lineup earlier in the year, the MacBook Pro now uses the speedy chip.

Even better, Apple didn't stop at just M4, as it brought out M4 Pro and M4 Max variants as well. These additions offer a lot more performance options, and in the case of the M4 Max, more performance than an M2 Ultra in some benchmarks.


Continue Reading on AppleInsider | Discuss on our Forums




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CBSE To Conduct Workshop On Effective Collaboration In Parenting And Education

The workshops will equip school leaders with necessary skills to assist parents in guiding their children's academic, social, and emotional growth.




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Pakistan Government Takes Firm Stance On Champions Trophy, PCB Told To...

While the PCB wants to organise all ICC Champions Trophy matches at home, the BCCI has refused to send the Indian team across the border.




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AG Jennings sues Monsanto for PCB contamination

Claims include public nuisance, trespass and unjust enrichment Delaware Attorney General Kathy Jennings filed a lawsuit Wednesday against agrochemical giant Monsanto and two of its corporate spinoffs for long-lasting damage to Delaware’s natural resources. The lawsuit seeks to recover damages and clean-up costs associated with polychlorinated biphenyls (PCBs), extremely toxic and persistent chemicals which Monsanto […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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Apple MacBook Pro 16-inch Review

Read the in depth Review of Apple MacBook Pro 16-inch Laptops. Know detailed info about Apple MacBook Pro 16-inch configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.




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Redmi SonicBass Wireless Earphones Review

Read the in depth Review of Redmi SonicBass Wireless Earphones Audio Video. Know detailed info about Redmi SonicBass Wireless Earphones configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.




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Apple Macbook Pro 13-inch 2020 Review

Read the in depth Review of Apple Macbook Pro 13-inch 2020 Laptops. Know detailed info about Apple Macbook Pro 13-inch 2020 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.




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Carvaan Musicbar CBWY121 Review

Read the in depth Review of Carvaan Musicbar CBWY121 Audio Video. Know detailed info about Carvaan Musicbar CBWY121 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.





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BoardSurfers: Optimizing RF Routing and Impedance Using Allegro X PCB Editor

Achieving optimal power transfer in RF PCBs hinges on meticulously routed traces that meet specific impedance requirements. Impedance matching is essential to ensure that traces have the same impedance to prevent signal reflection and inefficient pow...(read more)




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OrCAD X – The Anytime Anywhere PCB Design Platform

OrCAD X is the next-generation integrated PCB design platform. It brings to you a powerful cloud-enabled design solution that includes design and library data management integrated with the proven PCB design and analysis product portfolio of Cad...(read more)




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BoardSurfers: Optimizing Designs with PCB Editor-Topology Workbench Flow

When it comes to system integration, PCB designers need to collaborate with the signal analysis or integrity team to run pre-route or post-route analysis and modify constraints, floorplan, or topology based on the results. Allegro PCB Edito...(read more)




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Accelerate PCB Documentation in OrCAD X Presto with Live Doc

Live Doc is an advanced automated PCB documentation generation tool integrated with OrCAD X Presto designed to streamline the creation of PCB documentation. By automating the generation of PCB fabrication and assembly drawings, Live Doc significantly...(read more)




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How to transfer etch/conductor delays from Allegro Package Designer (APD) to pin delays in Allegro PCB Editor

The packaging group has finished their design in Allegro Package Designer (APD) and I want to use the etch/conductor delay information from the mcm file in the board design in Allegro PCB Designer. Is there a method to do this?

This can be done by exporting the etch/conductor data from APD and importing it as PIN_DELAY information into Allegro PCB Editor.

If you are generating a length report for use in Allegro Pin Delay, you should consider changing the APD units to Mils and uncheck the Time Delay Report.

In Allegro Package Designer:

  1. Select File > Export > Board Level Component.
  2. Select HDL for the Output format and select OK.

       3. Choose a padstack for use when generating the component and select OK.

This will create a file, package_pin_delay.rpt, in the component subdirectory of the current working directory. This file will contain the etch/conductor delay information that can be imported into Allegro.

In Allegro PCB Editor:

  1. Make sure that the device you want to import delays to is placed in your board design and is visible.
  2. Select File > Import > Pin delay.
  3. Browse to the component directory and select package_pin_delay.rpt. The browser defaults to look for *.csv files so you will need to change the Files of type to *.* to select the file.
  4. You may be prompted with an error message stating that the component cannot be found and you should select one. If so, select the appropriate component.
  5. Select Import.
  6. Once the import is completed, select Close.

Note: It is important that all non-trace shapes have a VOLTAGE property so they will not be processed by the the 2D field solver. You should run Reports > Net Delay Report in APD prior to generating the board-level component. This will display the net name of each net as it is processed. If you miss a VOLTAGE property on a net, the net name will show in the report processing window, and you will know which net needs the property.




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PCB Chamfering Board edge connectors

Hi 

I am looking into chamfering the edge of PCB for Board edge connectors. I have performed fillet command earlier but new to chamfering.

Below is the description :

As seen above, the PCB edge are chamfered in thickness as well as at the corners.

Using OrCAD PCB hotfix S023.




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10 Layer PCB project won't generate Gerber's completely for middle layers

Hello Fellow PCB Designers,

We have a 10 layer PCB design that originated in Pads and was converted over to Allegro 17.4, this is an old design but is manufacturable and works perfectly fine.  When I try to generate a Gerber for the Top or Bottom layers

the Gerber comes out fine.  But Most of the middle layers are Etch's and via's for power and grounds, but the Gerber's come mostly blank, there might be some details, but in the Gerber view everything is displayed correctly.

The design does have many close spacings, I have not changed anything in the constrains manager yet, turned off a lot of the DRC's, but thinking there might be something wrong with the constrains.

  I find that the CSet is set to 2_18, not sure yet what this means, also there are many of these definitions, PCS 3,4,5,ect, are the same as CSet 2_18 any suggestions would be great, we are currently looking into this, have seen

that even small change in constraint manager can cause long processing and even Allegro crashing, this is a large project.

Thanks Much, Thanks, Mike Pollock.




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How to transfer custom title block from Orcad Capture to PCB Editor

Hi,

So I was trying to update the title block of a schematic that I have. The title block that was on there was out of date . I clicked on place --> title block and was able to find the title block that I need. I also have a .OLB file that contains that title block. Then I created a Netlist with the old BRD file as the input file (To keep it as is but modify changes) but when I do that I still do not see / cannot place the title block that I need. Under Place --> format symbols in Allegro , I do see a title block that is coming from the database (But it's the old one). I don't know what to do at this point and would appreciate any tips. I did make sure that the path to where the library is , is defined in the user preferences. 
I also tried copying the title block under the library folder in capture before creating my Netlist and that did not work either.

Thank you all.




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Purging duplicate vias in pcb editor

How do we purge/remove the duplicated vias in the same location of the PCB editor? These vias are not the one stacked and they are just blind vias running in internal layers 12-14. I find there is an additional copy of the blind via at the same location. Not sure what caused this issue.




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Launch footprint editor from Capture or PCB Editor?

I'd like to be able to edit a footprint for a part in my design without needing to find the footprint filepath and directly open that file in PCB Editor. I see that I can view footprints from Capture, and that doing so shows me the footprint path, but I can't find any way to launch the editor. Is there any way to go directly from a part in a Capture schematic or a placed part in a PCB Editor board design to editing that part's footprint?




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Orcad PCB (allegro) not using GPU over USB

Hi,

I have a monitor plugged to my laptop using a HDMI to USB adapter. When using this adapter, Allegro runs very slowly. It seems that it is not using my video card.

Is this a known issue with a workaround I can try?

Thanks,

Michael




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datasheets for difference of Allegro PCB and OrCAD Professional

Hi All

I am looking for the functions which are different about OrCAD Professional and Allegro tier.

is there any resource?

regard




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Allegro PCB Design Link issue

Hi All

I followed tutorial video below for using Design link

https://www.youtube.com/watch?v=f9JmFF8lqA0

and I followed the video with embedded board design file which should be same one on video

I did every set. but  at 2:55 of video, Steve have the tabs of both design names on top of Constraint Manager in video

but my one didn't exist them

which one would be different?

there was some comment on command windows but I think they would not be problem here

regard




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UI issues of PCB Environment Editor 17.4

Hi,

I found that under the Dark Theme of PCB Environment Editor 17.4,

the window background is not all dark, resulting in unclear text display。

As shown in the figure below:




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BoardSurfers: Training Insights: What’s New in the Allegro PCB Editor Basic Techniques Course

The Allegro PCB Editor Basic Techniques course provides all the essential training required to start working with Allegro® PCB Editor. The course covers all the design tasks, including padstack and symbol creation, logic import, constraints setup...(read more)




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How to perform the EMI / EMC analysis on the PCB layout

Hai Community,

I have a PCB board which has multiple high speed nets and I want to perform the EMI and EMC checking.

Which Cadence tool should I use for checking the EMI and EMC coupling?

Regards,

Rohit Rohan




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Optimizing PCB design for thermal performance

Optimizing PCB thermal performance is essential in today’s high-density designs, as it ensures stability, prolongs component life, and prevents potential thermal issues. One of the first steps to achieving this is with strategic component placement. Positioning high-power components—such as regulators, power transistors, or processors—away from heat-sensitive parts can prevent thermal interference, and placing them near the edges of the PCB often helps dissipate heat more effectively. It’s also beneficial to group components by their heat generation, creating dedicated thermal zones that can manage localized heating and reduce impact on other areas of the board.

 

Using thermal vias is another effective technique. By placing thermal vias under components like BGAs or power ICs, heat can be transferred from the surface to internal layers or ground planes. Increasing the size and number of these vias, or using thicker plating, enhances heat conductivity and helps manage heat more evenly across layers in multilayer boards. Increasing copper thickness on the PCB also has a major impact. Opting for thicker copper layers (e.g., 2 oz or even 3 oz copper) significantly boosts the heat dissipation capabilities of power planes and traces, especially in high-current areas. Large copper planes, such as dedicated ground or power planes, are equally effective in spreading heat efficiently. Adding thermal pads directly beneath heat-generating components improves this heat distribution.

 

Thermal relief pads help regulate heat flow for through-hole components by controlling heat transfer, which reduces thermal stress during soldering and prevents excessive heat spread to nearby sensitive areas. Performing thermal analysis with software tools like Celsius can be invaluable, as it allows you to simulate and model heat distribution, spot potential thermal issues, and refine your design before finalizing it.

 

Using heat sinks and thermal pads provides a direct way to draw heat from high-power components. Heat sinks can be attached with thermal adhesives, screws, or clamps, while thermal interface materials (TIMs), such as thermal pads or conductive adhesives, further reduce thermal resistance, enhancing heat-transfer efficiency. Optimizing the PCB layer stackup is also a key factor. Dedicated ground and power layers improve heat conduction across the PCB, enabling heat transfer between layers, particularly in high-density and multilayer PCBs.

 

In designs with high power requirements, active cooling options like fans, blowers, or heat pipes can be essential, helping to direct airflow across the PCB and further improving heat dissipation. Adding ventilation slots around hot zones and considering passive cooling paths enhance natural airflow, making the design more thermally efficient. By combining several of these techniques, you can create a PCB that handles heat effectively, resulting in a robust, long-lasting, and reliable product.

 

Let us know if you’ve had any challenges with thermal management in your designs—I’d be glad to discuss further!




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Allegro PCB Router quit unexpectedly with an exit code of -1073741701. Also, nothing is logged in log file.

Has anyone experienced the same situation?




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ECCB governor hopes for digital currency boost

The Eastern Caribbean Central Bank is to launch a digital currency for the benefit of its dispersed island economies – essential to a region that has been disproportionately affected by climate change-induced disasters, governor Timothy Antoine tells fDi.




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Save $200 on Apple’s 2024 MacBook Air with M3 chip before Black Friday

As of Nov. 12, Apple’s 2024 MacBook Air with the new M3 chip is $200 off at Amazon, priced at $899.




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CBN launches initiatives to drive financial inclusion

The Central Bank of Nigeria has officially launched three initiatives to drive financial inclusion in the country. The initiatives were launched at the second edition of the International Financial Inclusion Conference, which was held in Lagos on Tuesday under the theme, ‘Inclusive Growth: Harnessing Inclusion for Economic Development’. Speakers at the event highlighted the fact


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  • Business & Economy