In just a few days, at the Society for Neuroscience meeting in Chicago, we will be unveiling SLICE – our new affordable light sheet microscope that truly redefines what’s possible in imaging technology. SLICE is the result of our collaboration with leading microscopy researchers at Columbia University, embodying our mission to support “Big Science in labs of all sizes”.

What makes SLICE extraordinary and such a transformative technology? Let me share some key points:

• Performance on par with systems costing ten times as much
• Resolution of ~1 μm laterally and ~5 μm axially, resolves cells and neuronal processes throughout the brain
• Three-wavelength imaging capability
• Compatible with iDISCO, CLARITY, SHANEL, BINAREE and other optical clearing techniques

Most importantly, we’re offering SLICE at an introductory price under $50,000 for a limited time, including lasers and a computer workstation. This is not just a price point; it’s a statement of our commitment to democratizing access to advanced research tools.

I personally invite you to visit us at Booth 781 during SfN to learn about our exclusive conference offers designed to make this innovative technology even more accessible. See SLICE in action, and let’s discuss how it can propel your research forward. If you can’t make it to SfN, please visit our website SLICE for detailed information.

In my 30 years in this field, I’ve seen many advances, but SLICE stands out as a true game-changer. It has the potential to accelerate research across multiple disciplines, and I couldn’t be more excited to share it with you.

We pride ourselves in helping scientists make new discoveries, which is why we are determined to do things that allow more researchers to make more discoveries.

I look forward to your feedback and to seeing the groundbreaking research that SLICE will enable in your labs.

Sincerely,

Jack Glaser

President, MBF Bioscience

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Since their inception, NIMH’s SBIR/STTR programs have been a catalyst for numerous small businesses, propelling them to become global leaders or attractive acquisition targets. Notable early beneficiaries include Acadia Pharmaceuticals, Alkermes, and Neurocrine Biosciences, among others.

MBF Bioscience, originally known as MicroBrightField, stands out as a shining example of NIMH’s successful investment in innovation. As a pioneer in developing cutting-edge microscopy and image analysis software for neuroscience research, MBF has transformed the landscape of brain structure and function studies. Our state-of-the-art tools have become indispensable to researchers worldwide, significantly advancing our collective understanding of neurological and psychiatric disorders. The impact of MBF’s contributions is evidenced by the impressive tally of nearly 20,000 peer-reviewed publications that have utilized our products in their research.

In recognition of its outstanding contributions, MBF Bioscience, along with several other NIMH-funded businesses, has been honored with the prestigious Tibbetts Award from the U.S. Small Business Administration. This accolade celebrates companies that exemplify the spirit of the SBIR/STTR programs through their economic, technical, and societal impact.

The success stories of MBF Bioscience and other NIMH-supported companies underscore the institute’s vital role in identifying and nurturing groundbreaking ideas from their inception. NIMH’s early-stage funding has been instrumental in bringing a multitude of innovative technologies and treatments to fruition, ultimately benefiting millions of individuals affected by mental health conditions.

As NIMH charts its course for the future, its ongoing support for small businesses through the SBIR and STTR programs promises to fuel the next wave of innovations in mental health technology and care delivery. The remarkable achievements of the past 75 years, exemplified by companies like MBF Bioscience, lay a solid foundation for continued growth and breakthroughs in this critical field.

The feature of MBF Bioscience in NIMH’s anniversary blog not only highlights our company’s achievements but also reinforces the importance of continued investment in mental health research and technology. As we move forward, we remain committed to pushing the boundaries of neuroscience research tools, inspired by NIMH’s enduring support and the potential to make a lasting impact on mental health care.

Read the article here: https://www.nimh.nih.gov/about/director/messages/2024/driving-innovation-in-mental-health-technology-through-small-business-programs 

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For example, one of our current customers said to me, “you folks are like pond larvae, you are small…but you’re always there, adapting, changing, and evolving.”

It’s true, I guess. From the very beginning of MBF Bioscience, my father and I were dedicated to illuminating the discoveries in the neuroscience world using a rigorous, methodical approach. It’s what’s led to our award-winning group of products. We take great pride in serving the needs of researchers with real insights, in real life, and in real time.

But, our company…like bioscience…never stands still. Yesterday’s insights led to today’s insights. Today’s insights will lead to greater insights tomorrow. And, like a living organism, we must evolve to get better. Our products like Neurolucida and Stereo Investigator, have evolved and expanded. That’s why three years ago we added Vidrio Technologies into the MBF fold. We recognized that multi-photon imaging would not only improve our business, but it would grow more scientific insights as well.

That evolution of MBF has continued this year with adding Neurophotometrics to the MBF Family, completed just weeks ago. We’re thrilled that Sage Aronson and his team at NPM will be continuing their commitment to emerging researchers, and joining with us to see how we can raise the bar together.

The post Letter from the President: Why Getting Compared to Larvae is the Best Thing that Happened at SfN appeared first on MBF Bioscience.

The authors obtained post-mortem human brain samples from the Brodmann area 28 (BA28) entorhinal cortex (EC) of subjects exhibiting a range of Alzheimer’s disease (AD) pathology and categorized into 3 groups based on cognition and AD pathology: normal cognition, noAD pathology; normal cognition with moderate to severe AD pathology, and definite AD cases. Synaptosome fractions were characterized biochemically, and proteomic profiles were determined using liquid chromatography coupled to mass spectrometry. Weighted gene co-expression network analysis was used to generate a protein co-expression network and identify protein modules (co-expressed proteins) that were present in the different cognition/AD pathology categories.

In parallel, tissue samples from the same brain area were fixed and processed for dendrite imaging using Golgi-Cox staining. Dendritic segments of pyramidal neurons from layers 2 and 3 of BA28 from each category of cognition/AD pathology were imaged with a 60X/1.40 NA oil-immersion objective using a brightfield microscope. The resulting 3D image stacks were opened in Neurolucida 360 and dendrite and dendritic spine morphologies were reconstructed using semi-automatic and automatic functions. Spines were automatically classified as stubby, mushroom, or filopodia. Volumetric measurements of the spine, as well as the density of each spine type per dendrite length were extracted with Neurolucida Explorer.

Figure: Overview of workflow. Synaptosomes were isolated from postmortem human BA28 entorhinal cortex (EC) and subjected to liquid chromatography tandem mass spectrometry-based proteomics. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to generate a network of protein co-expression modules. BA28 EC samples were also Golgi stained and z-stacks of dendritic segments were imaged and digitally reconstructed to obtain measurements of dendritic spine density and morphology. Module eigenprotein values were correlated with dendritic spine metrics. The hub protein of a module significantly correlated with a dendritic spine metric would be selected for functional validation by CRISPR activation in rat primary hippocampal neurons.

The authors then correlated dendritic spine measurements with module eigenprotein expression from the proteomic analysis to integrate the two data categories. Among the results, one particular protein module stood out; it was consistently present in both AD and non-AD tissue, and was positively correlated with thin dendritic spine length, especially thin spines. Twinfilin2, the hub protein within this module, has a well-established role in modulating the cytoskeleton, specifically the protein actin. When the authors looked at neurons from rats grown in culture with different amounts of TWF2, they found those with more TWF2 grew longer thin-spines. This was the only type of spine affected by TWF2, demonstrating what the authors call a remarkable specificity regarding the ability of their cross-platform analysis to identify the functions of proteins.

Looking ahead, the researchers have identified many proteins organized in modules with hub-proteins, some that are expressed equally in AD and non-AD cases, and some that are not. They are in a good position to determine which of these hub proteins merit further study using functional analyses.

The comprehensive workflow employed by the researchers opens up new possibilities for unraveling the mysteries of neuronal function and holds immense potential for advancing our knowledge of diverse neurological conditions. As we delve deeper into the complex world of neuroscience, the connection between technology and scientific inquiry continues to illuminate the path towards groundbreaking discoveries.

Reference:

Walker, C. K., Greathouse, K. M., Tuscher, J. J., Dammer, E. B., Weber, A. J., Liu, E., Curtis, K. A., Boros, B. D., Freeman, C. D., Seo, J. V., Ramdas, R., Hurst, C., Duong, D. M., Gearing, M., Murchison, C. F., Day, J. J., Seyfried, N. T., & Herskowitz, J. H. (2023). Cross-platform synaptic network analysis of human entorhinal cortex identifies TWF2 as a modulator of dendritic spine length. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.2102-22.2023

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MBF Bioscience Announces the Acquisition of Neurophotometrics

Williston, VT – 10.26.2023 — MBF Bioscience, a leading provider of cutting-edge solutions in the field of bioscience, is pleased to announce the latest addition to its family – Neurophotometrics (NPM). This acquisition is a significant milestone in our commitment to advancing scientific research and innovation.

The acquisition of NPM combines two companies with a shared deep passion for helping scientists bring new insights and discoveries to the future of bioscience. MBF and NPM will work closely together to develop new products and bridge technologies to advance bioscience.

 “We are thrilled to welcome NPM to the MBF Bioscience family,” said Jack Glaser, president of MBF Bioscience. “NPM’s expertise in developing optical equipment for neuroscience research, and its commitment to innovation complement our own mission and values perfectly. Together, we can build a new generation of exceptional tools to support the future of scientific research.”

“We are excited to join forces with MBF Bioscience,” said Sage Aronson, Neurophotometrics. “MBF’s global reach and resources will enable us to bring our products and services to more scientists around the world. We share MBF’s commitment to providing the highest quality technical support, and we look forward to working together to create a brighter future for bioscience.”

MBF is committed to providing our customers with the best possible products and services, and the acquisition of NPM will further strengthen MBF’s ability to do so.

Please don’t hesitate to reach out to us at the contact number below. We continue to rely on your insight, perspective, and advice about how we can serve you better today to enable exciting discoveries tomorrow.

Thanks for being part of this amazing journey.

###

Contact Information: MBF Bioscience | 1-802-288-9290 | info@mbfbioscience.com

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At MBF Bioscience, democratizing neuroscience has been part of our DNA since our founding 35 years ago when we launched Neurolucida. Our goal was to provide affordable, cutting-edge technology to neuroscience laboratories in every institution worldwide so that neuroscientists could make discoveries without having huge research budgets or having computer programmers on staff.

When we started MBF, advances in Neuroscience research were driven by individual investigators.  More and more “big science” is having a greater impact on the field.  This transition began around the turn of the century, with the discovery that there are more than 20,000 unique genes in the brain. Advances in molecular biologic, neuroanatomical, neurophysiologic and computational techniques employed by teams of researchers at research institutes or by networked labs at multiple universities have analyzed the complexity of the brain’s neural circuits comprised of thousands of unique neuron subtypes.  Amongst “big science” projects are those that produced whole brain maps of the expression of 20,000 genes, the connectome of hundreds of neuron subtypes, the axonal projections of thousands of individual neurons and the physiologic characteristics of hundreds of genetically unique neuron subtypes.  Typically, publication of these projects includes upwards of 50 authors, indicative of the effort required.  The value of these large-scale databases and data sets is the ability to extract information about specific brain circuits to understand how their function generates behavior.   This is the work still primarily driven by individual investigators, who continue to make conceptual advances in the field now aided by the resources provided by “big science”. 

One of our long-time users, Dr. Charles Gerfen, has been involved in several “big science” projects, including the GENSAT project at NIMH/NINDS with Dr. Nat Heintz at Rockefeller University that generated 300 Cre-expressing transgenic mouse lines, the Allen Institute’s Mouse Connectome study that mapped the projections of neuron subtypes from 1000 brain areas, and the HHMI Janelia Mouse Light Project that traced the axonal projections of 900 individual cortical neurons.  With teams of researchers these projects each mapped the distribution and connections of diverse subtypes of neurons into a standard whole brain atlas to provide a searchable “google map-like” database of brain circuits. 

With advice from Dr. Gerfen, MBF developed a new software platform called NeuroInfo, that incorporates functions to allow individual researchers to map their neuroanatomical data into a standard atlas framework.  NeuroInfo is becoming a widely used platform for individual researchers to use a “big science” approach to study their specific biologic questions of interest to understand how neural circuits are related to neurologic and mental disorders. 

At MBF Bioscience, we’re committed to providing the best products and value to neuroscientists in labs of all sizes. We’re focused on making our products something that labs can rely on for years to come at a reasonable cost with great support. We’re proud of our own accomplishments and how we’ve adapted and evolved over the years to bring the most advanced technology at affordable prices to labs around the world.

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Light Beads Microscopy is a new method of two-photon microscopy optimized for volume imaging. It enables investigators to scan an entire volume in the rate that other conventional mesoscopes records just a single plane. This new technique makes use of columns of “Light Beads”, individual beams which are distinguishable in time and focus to different depths in the sample. Their novel approach uses 30 multiplexed beams, roughly an order of magnitude higher than any other previous temporal multiplexing approach demonstrated in vivo.  This quantum leap in imaging efficiency makes Light Beads Microscopy well suited for studying multi-regional encoding of sensory information and the dynamic interaction of brain networks at the single-neuron level.

Using Light Beads Microscopy and genetically encoded calcium indicators, Demas and colleagues imaged calcium transients in hundreds of thousands of cells in vivo, in portions of somatosensory-, visual-, posterior parietal-, and retro splenial–cortex, contained in a 3 mm X 5 mm area and a depth of 0.5 mm. The sampling rate of 5 Hz was per volume, not per plane. Stimuli used were whiskers perturbation and visual presentation of high-contrast drifting grates. Three sub-populations of neurons were identified that respond to whiskers stimuli, visual stimuli, or are spontaneously active. They also found evidence of mixed-selectivity in four anatomically separate clusters of cells, and of neurons that undergo distinct types of response modulation to one stimulus by the other located in separate anatomical locations.

To make the multiplexing happen, the laser light pulse is sent through two series of optical cavities that contain convex mirrors. The first cavity lets a small fraction of the energy of the laser pulse escape to the second cavity through a partially reflecting mirror (PRM) but sends the bulk of the laser energy back into the first cavity through a delay line loop created by the convex mirrors until it encounters the PRM again. The second cavity, which functions mainly as a delay line, splits the incoming pulse into two pulses. The first pulse is directed to the sample, while the second is delayed by the cavity before also being sent to the microscope. By travelling over and over in the first cavity and dividing pulses in the second one as described, a 90fs laser pulse is split into thirty ‘sub- pulses’ that occur only about 7ns apart from each other, with all 30 sub-pulses delivered to the sample in ~200ns.  MBF Bioscience engineers created the software for the Light Beads Microscope using ScanImage. This software was used to control the hardware and to receive and assemble the signals multiplexed in time and space from the photomultiplier tube.

Here at MBF Bioscience, thanks to a Small Business Innovation Research Grant from the NIMH, we are now working to commercialize this technology. We plan to optimize the hardware that creates the lights beads to reduce the overall microscope-system footprint and make it more versatile and easily adaptable to other laser-scanning microscopes and/or excitation wavelengths.

Light Beads Microscopy represents a major breakthrough in our ability to study the activity of large cell populations in the brain, and has the potential to revolutionize our understanding of how the brain encodes information.

Learn more about ScanImage and how it can help your research at: https://www.mbfbioscience.com/products/scanimage.

Reference:

Demas, J., Manley, J., Tejera, F. et al. High-speed, cortex-wide volumetric recording of neuroactivity at cellular resolution using light beads microscopy. Nat Methods 18, 1103–1111 (2021). https://doi.org/10.1038/s41592-021-01239-8

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In a study published in 2015, Bansel et al. found that long-lived C. elegans mutants exhibited a higher proportion of life in an unhealthy state compared to non-mutants. In their 2017 publication, Rollins et al. sought to better understand the relationship between lifespan and quality of life in C. elegans mutants. The authors used two models to assess health span in short-lived mutants: one focused on age-dependent factors such as locomotion, maximum bending amplitude, and thermo-tolerance; the other examined the effects of extrinsic forces over time, including accumulation of autofluorescence and pharyngeal pumping.

To track the worms and obtain data on size and behavior including speed of locomotion and bending angle, the researchers utilized WormLab® software. They found that short-lived mutants spent less time in a healthy state compared to non-mutants, when locomotion markers were used for the evaluation.   Unexpectedly, however, short-lived mutants exhibited thermo-tolerance for a longer percentage of life span than wild-type worms, suggesting that these mutants may have an advantage in this particular measure of health span.

The authors propose a new metric that combines survival rate and health performance to more accurately score health, taking into account both age-dependent and time-dependent factors. This approach could help to better understand the relationship between lifespan and quality of life in model organisms and could have implications for future research on aging and longevity.

In conclusion, the study of short-lived C. elegans mutants provides valuable insights into the relationship between life span and quality of life. The use of two models to assess health and the proposal of a new metric to score health highlight the complexity of this relationship and the need for further research to fully understand it. As we continue to strive for longer, healthier lives, the use of model organisms like C. elegans will undoubtedly remain essential to this research as we aim to promote healthy aging and unlock the secrets of aging.

Learn more about the WormLab software

Reference:

Rollins, J. A., Howard, A. C., Dobbins, S. K., Washburn, E. H., & Rogers, A. N. (2017). Assessing health span in Caenorhabditis elegans: Lessons from short-lived mutants. The Journals of Gerontology: Series A, 72(4), 473–480. https://doi.org/10.1093/gerona/glw248

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The radical new advantage of the Mini2P microscope is its light weight and the flexibility of its laser-cable. With heavier microscopes, for instance when used for imaging neurons in the striatum (Maltese et al. 2021), animals are restricted to less active behaviors such as walking on a treadmill, but with the extremely light weight Mini2P, in-vivo imaging, for instance of ‘place-cells’ in the hippocampus, can be done on animals engaging in much more active behaviors, such as finding their way through a maze (Zong et al.).

ScanImage software gives efficient control of the Mirrorcle (Mirrorcle Technologies, Inc., Richmond CA) MEM scanner for XY imaging, the electronically-tunable µTlens for focusing, and laser beam power. ScanImage receives the resulting data from photo-multiplier-tubes (PMTs) and assembles images of functioning neurons. The input and output signals for this in-vivo imaging are controlled with and exchanged between ScanImage and the hardware via the VDAQ card and breakout board.

Proof of concept is shown in, ‘Large-scale two-photon calcium imaging in freely moving mice,’ by Zong et al., published this year: ScanImage … fully supports the hardware control and data acquisition of MINI2P. Following the wiring illustration and the operation manual in Methods S1, Section 9, the system can be run directly without further modification. (Zong et al., Control and Acquisition, p. e9)

The just three-gram 2P miniscope with its flexible fiber laser cable attached was shown to be light enough for active behavorial experiments. Three-dimensional imaging of fluorescence indicating cellular calcium concentration in visual cortex, hippocampus archicortex, and hippocampus was done at 7.5 Hz. The mice were so unencumbered as to be considered freely moving, and ‘place-cells’ in the hippocampus were seen to undergo changes in calcium concentration correlated with the animals’ position in the maze.

How does ScanImage accomplish control and acquisition? The mirrorcle resonant scanner driver is intended for use with a MEMS mirror device. This driver enables one of the axes, the X axis, of the mirror to be used in resonant scanning mode. To use the second axis, the Y axis, of the mirror, an Analog Galvo device is added to ScanImage. ScanImage takes the information about the fast X axis mirror position and uses it to calculate and send the signal for the relatively slow Y axis mirror. Two analog outputs of vDAQ send the MEMS scanning control signal (fast axial and slow axial) to the mirror device. A third analog output sends the control signal to the µTlens driver (Thorlabs, Newton, NJ). A fourth analog output sends the laser power control signal to the laser controller. The laser source was a compact, single-wavelength, fiber-based femtosecond laser (FemtoFiber Ultra 920, Toptica, Munich, Germany). For acquisition, the signals from two-channel PMTs are connected to two high-speed (125 MHz) analog inputs of the vDAQ card. A maximum of 4 channels can be acquired simultaneously. ScanImage organizes the PMT data to form the images.

The process of imaging functioning neurons in freely behaving animals is incredibly powerful, but also exceedingly complex. ScanImage software can simplify these procedures and make the control of in-vivo image acquisition easily executable.

To learn more about how ScanImage controls the Mini2P, click here to see the workshop given by ScanImage product manager, Mitchell Sandoe.

Reference:

Maltese, Marta, Jeffrey R March, Alexander G Bashaw, Nicolas X Tritsch, 2021, Dopamine differentially modulates the size of projection neuron ensembles in the intact and dopamine-depleted striatum.  https://doi.org/10.7554/eLife.68041

Zong, Weijian, Horst A Obenhaus , Emilie R Skytøen, Hanna Eneqvist, Nienke L de Jong, Ruben Vale, Marina R Jorge, May-Britt Moser, Edvard I Moser, 2022, Large-scale two-photon calcium imaging in freely moving mice. Cell, 185(7):1240-1256.e30. doi: 10.1016/j.cell.2022.02.017. Epub 2022 Mar 18.

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The facial nucleus, present in vertebrate animals, is a group of neurons in the brainstem that receives instructions from neurons in the cortex to direct movement of the muscles of the face. For this paper, the authors characterized the facial nucleus of two similar species, African and Asian elephants, with muscular, dexterous trunks. These species’ faces share many similarities, but have distinctly different ear size and trunk morphology—areas controlled by the facial nucleus. The authors used varied methods, matched to the available elephant material, including Nissl staining, cell counting, axonal osmium tetroxide stains, somata drawings, cell fiber counting, and nerve tracing to examine the facial nucleus in specimens from African (n=4) and Asian elephants (n=4 elephants). Stereo Investigator^® software was used to acquire images of thin sections, conduct stereological procedures, and measure cell size and axon diameter.

Two methods were used to quantify cell populations in the elephant facial nucleus, an unbiased stereology approach and a model-based stereology strategy that consisted of complete counts of cell pieces in every tenth section were used. Using unbiased stereology, the researchers counted ~200-300 cells per specimen with the Stereo Investigator optical fractionator probe. To confirm their results, the research team next counted ~5000–8,000 cells and cell fragments per specimen, then corrected for double-counted cells. The results were equivalent; however, the unbiased stereology approach was much less time consuming.

The researchers found that the facial nucleus in elephants is much larger than in most mammals and it is comprised of approximately five-fold more neurons, but at significantly lower neuronal density. African elephants were found to have more neurons in the medial facial subnucleus than Asian elephants, consistent with their much larger and more expressive ears. Dorsal and lateral facial subnuclei, which control movement of the trunk, were elongated compared to other vertebrate mammals and contained many more neurons than land-based species. Interestingly, these regions had a distinct proximal-to-distal cells size increase. Comparison with other species and between newborn and adult elephants suggest that this increase in size is needed for to support the extreme axonal volumes associated with trunk innervation. These cell-size gradients were found to be a unique feature of the elephant facial nucleus. Finally, the research team identified a high-density motor fovea that they believe are associated with the tip of the trunk in African elephants. Asian and African elephants’ trunks differ in that Asian elephants have one dorsal trunk finger and they tend to engage much of their trunk in grasping objects by wrapping them in their trunks, whereas African elephants’ trunks have dorsal and ventral fingers that are often used to pinch objects. Their work suggests that African elephants have more neurons associated with the trunk tip than do Asian elephants and that control of African elephants’ trunk fingers resides in the motor foveae they identified.

The research described here relied heavily on cell-count data that was most efficiently obtained using the optical fractionator probe in Stereo Investigator^®. The authors found strong relationships between the number, density, and size of neurons and the position and function of elephant facial morphology. Their results pose interesting avenues for future research, including the role of ear movement in “auditory and infrasound perception” and follow-up studies on the cell-size differences found in the putative trunk representation in the facial nucleus and how these differences may be involved with elephants’ presumed need to compensate for inherent nerve conduction delays associated with their large size.

Learn more about industry-leading Stereo Investigator^® systems for image acquisition and stereological studies.

View our webinar that introduces Stereo Investigator^® and unbiased stereology.

Reference:

Kaufmann, L. V., Schneeweiß, U., Maier, E., Hildebrandt, T., & Brecht, M. (2022). Elephant Facial Motor Control. Science Advances, 8(43). https://doi.org/10.1126/sciadv.abq2789

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