Writing at @readmargins
Building agentic things for enterprises @GetWriter
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Articles by Ranjan Roy
Protective or Pathogenic? Microglial Responses at the Intersection of Amyloid-β, Tau, and Neuroinflammation in Alzheimer’s Disease
Submitted: 15 October 2026 You are already at the latest version Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, pathological tau aggregation, and neuronal loss. Neuroinflammation is increasingly recognized as a contributor to disease progression, with microglia playing a central and context-dependent role.
Heart failure-induced reprogramming of salt-evoked neurovascular coupling in the rat hypothalamus
Introduction Neurovascular coupling (NVC) is a well-established phenomenon in the brain that involves a tight coupling between neuronal activity and increased cerebral blood flow (CBF) (Iadecola, 2017; Urban et al., 2017). This activity-dependent increase in CBF (also known as functional hyperaemia) occurs rapidly (<2 s) and in a spatially restricted manner (Li et al., 2009; Silva et al., 2000), ensuring the optimal delivery of glucose and oxygen to brain areas with increased metabolic demand.
Isosmotic hypovolemia preserves inverse neurovascular coupling in the supraoptic nucleus during heart failure
CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. REFERENCES 1. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci. 2008; 9(7): 519-531. 2, , , . Somato-dendritic vasopressin and oxytocin secretion in endocrine and autonomic regulation. J Neuroendocrinol. 2020; 32(6):e12856. 3, , , et al.
Ranjan Roy: SpaceX’s pivot to AI transforms its market identity, IPO volatility is on the horizon, and retail investors are taking on new risks | Big Technology
Key takeaways SpaceX’s strategic pivot towards AI has significantly altered its market perception. Elon Musk’s acquisition of X.ai has transformed SpaceX into a formidable AI player. The inclusion of AI in SpaceX’s valuation has driven up its IPO value. SpaceX’s IPO is expected to experience high volatility in the coming months. OpenAI’s current valuation is not supported by its earnings, raising concerns. Retail investors are increasingly taking on risks traditionally borne by VCs and governments.
Ranjan Roy: Apple’s iPhone sales drive current success, AI integration faces significant challenges, and the tech industry lacks revolutionary AI devices | Big Technology
Key Takeaways Apple’s current success is primarily driven by iPhone sales, with AI not yet significantly impacting their business. Despite a lack of genuine product innovation, Apple’s business model remains healthy. There are currently no revolutionary AI computing devices available in the market. Apple is transforming Siri into a more capable assistant by leveraging Google’s Gemini model. Apple’s approach to AI integration reflects their focus on user experience and interface advantage.
Ranjan Roy: Corporate America is rationing AI as costs skyrocket, the hype around generative AI is hindering meaningful development, and 82% of token spending fails to yield productive outcomes | Big Technology
Key takeaways Corporate America is reducing AI usage due to rising costs. AI spending may be driven by irrational behaviors rather than genuine value. Rapid shifts in AI’s perceived value reflect a lack of cost understanding. Companies are now recognizing hidden AI costs previously overlooked. Skepticism exists about widespread AI-related issues in the industry. Wasteful spending in cloud code is a significant industry issue. AI spending patterns influence fundraising and market behavior.
Ranjan Roy: SpaceX’s partnership with Anthropic boosts AI compute capabilities, growing skepticism about tech transformation, and the crucial need for model efficiency | Big Technology
Key takeaways The partnership between SpaceX and Anthropic highlights the evolving dynamics in the AI sector. Anthropic faces significant challenges in securing enough computing power to meet demand. SpaceX’s shift to providing compute capacity marks a strategic pivot in its business model. Anthropic’s new data center partnership significantly boosts its compute capabilities. Skepticism is growing about the transformative potential of technology in enterprises.
Ranjan Roy: OpenAI’s billion-user goal remains unmet, consumer sentiment towards AI is extremely negative, and crypto app growth is slowing in a saturated market | Big Technology
Key Takeaways OpenAI’s ambitious goal to reach a billion ChatGPT users by 2025 remains unmet, indicating challenges in scaling consumer growth. A strategic pivot towards enterprise solutions might be necessary for OpenAI to maintain its competitive edge. Consumer sentiment towards AI is notably negative, which could be impacting the growth of AI applications. Daily active user growth for AI apps has stagnated, with a decline noted in recent months.
Ranjan Roy: Nvidia faces fierce competition from Google and Amazon, the significance of GPUs in AI model training, and the geopolitical risks of export controls | Big Technology
Key takeaways Nvidia is currently facing significant challenges due to increased competition and export controls. The competition from tech giants like Google and Amazon is threatening Nvidia’s dominance in the AI chip market. GPUs are considered ideal for AI model training due to their parallel processing capabilities. Nvidia’s competitive advantage is not just in its chips but in its entire ecosystem and capacity.
Ranjan Roy: AI is shifting towards consumption-based models, public fear stems from rapid advancements, and large language models are often overhyped | Big Technology
Key takeaways The shift towards consumption-based models in AI is a natural progression in the industry. AI services might soon be monetized similarly to utilities, with usage-based payment models. Public negativity towards AI often stems from fear of its rapidly advancing capabilities. Societal unease with AI tools reflects broader concerns about tech industry figures. The economic implications of AI, particularly around data compensation, are significant.
Ranjan Roy: AI marketing hype often overshadows substance, concerns about AI exploiting software vulnerabilities, and the significance of scaling laws in model performance | Big Technology
Key Takeaways The marketing of AI models often involves more hype than actual substance. There is significant concern about AI’s potential to exploit software vulnerabilities. Anthropic’s recent AI developments hint at a breakthrough, though specifics are unclear. Scaling laws suggest larger AI models can lead to significant improvements. Hype around AI security vulnerabilities often lacks substantive evidence. Most reported software exploits are theoretical, not practically executable.
Ranjan Roy: The appeal of video AI is waning, OpenAI shifts focus to powerful models, and SaaS companies are embracing AI integration | Big Technology
Key Takeaways The appeal of video AI may be waning as users prefer consuming content over creating it. AI-generated videos risk losing utility if they become too similar and average out. OpenAI is shifting focus from video generation to more powerful AI models that understand physics. Asura models differ significantly from GPT series, posing challenges for simultaneous development. OpenAI’s decision to deprioritize world models signals a strategic focus amidst competition.
Ranjan Roy: OpenAI’s revenue could reach $284 billion by 2030, skepticism surrounds sustainability of growth projections, and Amazon’s retail model faces critical challenges | Big Technology
Key Takeaways OpenAI’s revenue has surged to $25 billion annually, reflecting robust growth in AI adoption. There is skepticism about the sustainability of revenue projections for companies like Anthropic. OpenAI’s future revenue is projected to hit $284 billion by 2030, raising questions about feasibility. Significant financial losses are expected for OpenAI as it scales its operations. OpenAI’s revenue growth is impressive but may falter without competition.
Ranjan Roy: OpenAI shifts focus to core business, generative AI set for mainstream by 2025, and data privacy concerns hinder enterprise entry | Big Technology
Key takeaways OpenAI is shifting its focus to core business areas, moving away from numerous side projects. Generative AI is expected to enter the mainstream by 2025. OpenAI’s approach to data privacy and security may hinder its transition to enterprise markets. The consumer AI market has not materialized as expected, prompting a shift towards enterprise applications. Google remains dominant in the search market, highlighting challenges for consumer AI.
Ranjan Roy: AI's role in military operations is exaggerated, ethical implications of autonomous warfare are significant, and cultural clashes hinder tech-defense collaborations | Big Technology
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Technology and Grieving Original
It's been a while since we've last posted here at Margins. My co-host Can has been busy with his startup Felt, and I ended up on an incredible startup/acquisition journey with a DTC intimate apparel company called Adore Me. That's right, Can is selling maps and I'm selling bras. That’s how we keep this newsletter free! Today, I'm going to be writing about something a bit different than our usual content.
Angiotensin-II drives changes in microglia–vascular interactions in rats with heart failure - Communications Biology
Abstract Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist.
Impaired oxytocin signalling in the central amygdala in rats with chronic heart failure
Supporting Information Filename Description tjp16364-sup-0001-PeerReview.pdf378.8 KB Peer Review History References , , , , , , , & (2020). Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats. Journal of Neuroinflammation, 17(1), 221. , , , , , , & (2022).
Impaired oxytocin signalling in the central amygdala in rats with chronic heart failure
Supporting Information Filename Description tjp16364-sup-0001-PeerReview.pdf378.8 KB Peer Review History References , , , , , , , & (2020). Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats. Journal of Neuroinflammation, 17(1), 221. , , , , , , & (2022).
Coastal Farmers’ Attitude Towards Climate Smart Agriculture In Bangladesh
License Copyright (c) 2024 SAARC Agriculture Centre This work is licensed under a Creative Commons Attribution 4.0 International License. © SAARC Agricultural Centre Copyright on any research article is transferred in full to SAARC Journal of Agriculture upon publication in the journal. The copyright transfer includes the right to reproduce and distribute the article in any form of reproduction (printing, electronic media or any other form).
Blood flows from the SCN toward the OVLT within a new brain vascular portal pathway
Abstract The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature.
The Panel Reacts: Is the Vision Pro for Everyone, or Just Enthusiasts?
I put on Apple’s Vision Pro headset for the first time this weekend. The technology was even better than I expected. The device’s mixed reality passthrough was near-perfect, blending the physical and digital worlds seamlessly. And it wasn’t too heavy either. If I hadn’t found the $3,500 price tag impossible to justify, I might’ve just been one of the guys using it in the crosswalk. But after seeing the Vision Pro’s debut, I’ve wondered just who it is for. Is it for developers? Enterprise users?
The Panel Reacts: Google Introduces Gemini, Its Answer To OpenAI’s GPT-4
On Wednesday, Google finally introduced Gemini, its answer to OpenAI’s GPT-4. Gemini will power Google’s Bard chatbot and become available to software developers building generative AI applications. The model is multimodal — meaning it can read and analyze words, shapes, and sounds — and Google shared several impressive demos with reporters yesterday.
Impaired oxytocin signaling in the central amygdala in rats with chronic heart failure
Abstract Abstract Aims Heart failure (HF) patients often suffer from cognitive decline, depression, and mood impairments, but the molecular signals and brain circuits underlying these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT) is critically involved in the regulation of mood, and OTergic signaling in the central amygdala (CeA) is a key mechanism controlling emotional responses including anxiety-like behaviors.
Big Technology Is Going Paid With Deeper Coverage and New Features
Discover more from Big Technology A newsletter about big tech and society by independent journalist Alex Kantrowitz. Over 145,000 subscribers Three years ago, I founded Big Technology with a dream that independent tech reporting might find an audience. My hope was that tech journalism outside the big newsrooms could challenge narratives, look where others weren’t, and take swings others wouldn’t. Being nimble, a bit like a startup, might help me take on the incumbents. It seemed worth trying.
Blood flow directionality establishes the SCN as source and OVLT as target within a new vascular portal pathway
New Results doi: https://doi.org/10.1101/2023.06.20.545729 Abstract The suprachiasmatic nucleus (SCN) is the locus of a brain clock that sets the phase of oscillation in cells throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the OVLT (here termed SCN-OVLTp). This discovery begs the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature.
Uncovering the role of Lewis and Brønsted acid sites in perforated SAPO-34 with an enhanced lifetime in methanol conversion to light olefins
Uncovering the role of Lewis and Brønsted acid sites in perforated SAPO-34 with an enhanced lifetime in methanol conversion to light olefins Mohammad Ghavipour, Tiago J. Goncalves, Ralph Al Hussami, Ranjan Roy, Samira Siahrostami and Jan Kopyscinski Abstract Although the micropores of SAPO-34 (the catalyst in the conversion of methanol to light olefins) favor higher light olefins selectivity, they are vulnerable to blockage by coke, which can result in fast catalyst deactivation.
SVB and the Wealth Creation Flywheel
Ranjan here, just back from SXSW and oh what a few days. This week I’ll be writing about, yes, you guessed it, Silicon Valley Bank. On Friday morning, I was on the Big Technology podcast with Alex Kantrowitz, along with Dan Primack, discussing SVB. About 15 minutes after we finished recording, the news came out that SVB had gone into receivership. On Sunday, I took a break from the SXSW hoopla to write and just as I was about finished, the rescue was announced.
Alexa, what happened?
Ranjan here. This week I'll be writing about Amazon's Alexa, voice as a platform, and what it takes to realize the potential of an innovation. I have four Echo devices in my household.
FTX and How to Lose Money
Ranjan here and in today’s post I’m going to try to write about FTX. As readers have likely noticed, we haven’t been writing very much, but I’ve probably received more requests to help make sense of the FTX debacle than any other topic, even Elon. Here goes. If you follow Can or me, you probably have a sense of where we stand on crypto (not exactly bullish). My longtime gripe has been a lack of normie utility for crypto, while Can questioned the technology underlying Web3 (Note 1).
What's it, Why and How to Make It?
Like evergreen songs, there is a crucial aspect in the SEO world, and we call it “Evergreen Content.” If you want to rank on the top of Search Engines, selecting these content topics can always be a great choice. Crafting Evergreen Content is no rocket science. You have to consider and implement a few points while curating the content. And through this blog, you will learn how you can make it. What Is Evergreen Content?
Shein and the Tech Cold War
Ranjan here, it’s been a while and Can and I miss you! This week I’ll be writing about Shein, its relationship to TikTok, and the US-China tech cold war. I’m sure most Margins readers have heard of the Chinese ecommerce juggernaut Shein (I’d be more curious how many have actually shopped on the site). For the uninitiated, Shein is a Chinese ecommerce site that receives accolades like being the “world’s largest online retailer” and the “3rd most valuable private company”.
Margins by Ranjan Roy and Can Duruk
Ranjan here. This week I’ll be writing about the Tiger Global venture model and late-stage private markets. It’s becoming more clear there will be many more tides washed out and emperors de-robed in the coming months. I’m convinced some of the most intriguing stories yet to be written will come out of the world of Tiger-style late-stage private startup funding (not that there’s any shortage of interesting in the markets right now).
Elon's Giant Package
Ranjan here. As we enter what seems to be week 6,942 of the Musk-Twitter reality show, I’m going to try to present a theory on what he’s really up to. I’ll admit, when this saga started I assumed Elon’s intentions were just shitpost performance art. However, the more you look at the Twitter take-private in the context of Tesla, the SEC, and the current overall market, it does feel like it’s part of a bigger plan. As I go to publish, I see Twitter-Elon might be a done deal.
9.2% and the Master of Twitter
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9.2% and the Master of Twitter
I woke up yesterday to the headlines: Elon Musk buys 9.2% stake in Twitter, making him the largest shareholder. It’s 2022 and the Fed has hiked, but we have a long way to go before the absurdity ends. Before I get into a theory on why I think he did it (because, c’mon, we all need a theory) it’s important to understand the context of Elon’s battle with the SEC over the past few years and, more importantly, how he’s spent the last six weeks escalating things.
Robinhood and Democracy Promotion
Ranjan here. Today I’m writing about Robinhood, early access to IPOs, and the “democratization of finance”. Now that my co-host Can is back, I once again feel pressured to write on time. This makes me happy. Writing about Robinhood also makes me happy. In March 2021, Robinhood announced they (Note 1) would be building a platform to give everyday investors access to IPOs. It really was the perfect ‘democratizing finance’ story.
Who is Web3 Really Good for?
Hi! Can here. Long time, no see! I started a company. It’s called Felt and it is about maps. And yes, we are hiring! Scroll to the end to learn more. For a long time, I resisted opining on crypto, even though I had a lot of early exposure to it. My roommate circa 2011~2012 was really into Bitcoin.
Peloton, Valuations, and Innovation
Ranjan here with a warning: Today's newsletter has a Sex and the City spoiler. This will likely be the only time this happens in a Margins piece, but, hey, it's 2021. Things still don’t make sense. Let's talk about Peloton, valuations, and innovation. You may have seen the Sex and the City character Mr. Big died after riding a Peloton in the premiere episode of the show's reboot.
Inverse neurovascular coupling contributes to positive feedback excitation of vasopressin neurons during a systemic homeostatic challenge
Highlights • Salt loading evokes activity-dependent vasoconstrictions in the SON • Activity-dependent vasoconstrictions are mediated by dendritically released VP • Vasoconstrictions reduce blood flow and generate a local hypoxia microenvironment • Salt-loading vasoconstrictions evoke positive feedback excitation of VP neurons Summary Neurovascular coupling (NVC), the process that links neuronal activity to cerebral blood flow changes, has been mainly studied in superficial brain areas, namely...
The Teenager Economy
Ranjan here. We've kept Margins free, both to spread our ideas as wide as possible and so we don't feel overly stressed about writing regularly. However, if you've ever enjoyed our writing, I'd love if you could donate to a fundraiser I'm working on with the American Cancer Society for Breast Cancer Awareness Month. Okay, on to the post: I bought my first pair of Allbirds in Feb 2020.
Memestocks and Reddit redesigns
Ranjan here. This post will be a bit of a love letter to Reddit as well as a theory on how a 2017 funding round and key hire laid the seeds for the memestock craziness of 2021. Reddit is probably the social platform that has brought me the most uncomplicated joy over the past decade (Note 1). I gauge the quality of a movie or TV show if the first thing I do after watching it is spend hours dissecting it on Reddit.
Advertising Stagflation
Ranjan here. This week I’m writing about inflationary dynamics and digital marketing. Everyone seems to be talking about inflation, but I’m still having a lot of trouble imagining what non-transitory inflation looks and feels like in real life. As an econ undergrad, sure, I get the technical definitions and feedback loops. As someone who worked in emerging market finance, I’ve certainly watched other countries experience inflation through a terminal screen.
Doordash and Pizza Arbitrage
Editor’s Note: As this post has gotten a bit of attention, we wanted to add in the name of my friend’s restaurants. They’re fighting the good fight right now, so if you happen to be in the Kansas area, please support Aj’s NY Pizzeria (it’s NY-style pizza based in Manhattan and Topeka, Kansas, and while I’m biased, it’s good). If capitalism is driven by a search for profit, the food delivery business confuses the hell out of me. Every platform loses money.
Substack got lucky, and so did Margins
Hi. It’s Can, on Substack about Substack. Saving the world, one mail at a time It's been around a year and a half since Ranjan and I started this Substack. It was before when newsletters, at least in our small corner of the internet, were called Substacks. Ranjan and I met in New York City after my cold email and we hit it off immediately. A couple of months later, as the tech two dudes we are, we started a podcast and even recorded two episodes.
The first phygital coup
Ranjan here. Today I’m writing about how a lot of the absurd visuals from the invasion of the Capitol were, rather than jokes, a very 2021 version of modern warfare. Also to note, I hate the word phygital, which travels in thought leader-y circles as the confluence of our physical and digital worlds, but it kinda fits here. Please recommend any better terms to describe that concept.
Ape Armies and Investor Relations
On January 28th, when Gamestop stock hit a high of $483 a share, I wrote, "when the tourists leave, Gamestop's stock will come crashing down." I was temporarily right (GME fell to the 30s), and then proven completely wrong: the tourists never left. There have been so many times over the past decade Iâve thought, âthings canât get weirder and stupider.â And then they do.
The Internet is for Porn
Hi. This post is written by a friend of Margins, who happens to be a product executive at a public tech company. He wrote this initially in September 2020, but we were hesitant to publish it anonymously. Nevertheless, our friend turned out to be very insightful and we thought it’d be a shame (hah!) not to share his wisdom. It’s not like we’ve never written about it before.
Game. Stop.
Ranjan here. Yeah, writing about that. A year ago I wrote about how ZIRP, or cheap capital, had completely distorted financial markets at all levels. Last summer, I wrote about how Robinhood sells order flow to giants like Citadel and its traders are "the gravy". I theorized how people sitting at home, spending more time on social media, was adding a new level of distortion into financial markets.
Exasperated Exuberance
Ranjan here. Today I'll be writing on the current market mania and what comes next. It was quite something to watch this moment: Even Brian Chesky seems flummoxed. You can almost see him making a wealth calculation in his head, and full credit he handles it masterfully, but my god, what a crazy moment we’re in. On Wednesday, I took part in a panel covering the Doordash S-1 + IPO, organized by Mario Gabriele (definitely check out his publication The Generalist).
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