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What is representation in the human brain and AI systems? | OUPblog – OUPblog

You know the way Google search will sometimes finish your sentences for you? Or, when youre typing an email, theres some ghostly predictive text that floats just in front of your cursor? Well, theres a new kid on the block that makes these gadgets look like toy tricks out of a Christmas cracker. Give it a sentence of Jane Austen and it will finish the paragraph in the same style. Give it a philosophical conjecture and it will fill the page with near-coherent academic ruminations.GPT-3is essentially just predicting what words should come next, following on from the prompt its been given. That the machine does so well is partly because its been trained on an unimaginably huge database of samples of English (reputedly, $13 million worth of training). A similar machine can predict, from a sequence of amino acids, how the resulting protein will fold, short-cutting months of lab work and in some cases years of human ingenuity (AlphaFold). But what is going on inside the machine? What is it keeping track of inside its huge neural network brain?

We face the same question, of course, when we look at the human braina seemingly inscrutable organ of even greater complexity. Yet neuroscience is beginning to make sense of whats going on inside: of patterns of activity distributed across millions of neurons, flowing into other patterns; coupling and modulating; unfolding in a way that opens the organism to the world outside, projected through its inner space of needs and drives, bathed in the wash of past experience, reaching out to control and modify that world to its own agenda. We can now see what some of these patterns of activity are, and we have an inkling of what they are doing, of how they track the environment, and subserve behaviour.

Neuroscientists are recording these patterns with new techniques. But what do the patterns mean? How should they be understood? Neuroscience is increasingly tackling these questions by asking what the activation patternsrepresent. For example,representational similarity analysis(RSA) is used to ask whether the human brain processes images in the same way as the brain of the macaque monkey. Surprisingly,similar techniquescan be used to compare the human brain to an AI computer system trained to perform the same task. These AIs are deep neural networks, cousins of the seemingly unfathomable GPT-3 and AlphaFold brains we met at the start. Astoundingly, it turns out that sometimes the deep neural network is processing images in roughly the same way as the human brain. In a general sense, both are performing the same computations en route to working out that they are looking at a picture of two cats on a sofa. In other cases, we see the brain using ahexagonal codeto represent physical spaceand more abstract conceptual spacesand to reason about them.

All of this means that representation has become something of a hot topic in cognitive neuroscience. Representation has always been around, of course, working away in the foundations ever since the cognitive revolution showed that we could explain behaviour in terms of internal processing without having to feel embarrassed about intelligent homunculi or ghosts in the machine. What we have now are much better ways to see those representations in the brain and to marry them up with the computational story about how the organism intelligently deals with its environment.

representation is the crucial link for connecting brain activity with functional, adaptive behaviour

What we still need is a proper understanding of what representation isan understanding of how there come to be things in the head which stand in for, and allow creatures to deal with, things in their environment. A once-unconventional idea in contemporary philosophy (originating with Ruth Millikan, David Papineau, and Karen Neander) is that this is intimately tied up with functionbiological functions based on natural selection. Although a connection to function may have always been implicit in some scientific practice, it is now being recognised explicitly (Hunt et al. 2012,Richards et al. 2019). For example, in a recent manifesto for the role of representation in computational cognitive neuroscience, Kriegeskorte and Diedrichsen (2019) argue that representation is the crucial link for connecting brain activity with functional, adaptive behaviour. Meanwhile in philosophy, appealing to natural teleology to explain representation has moved into the mainstream, being embraced by researchers from diverse disciplinary starting points (David Haig,Robert Williams), alongside recent landmark contributions from early advocates (Karen Neander,Ruth Millikan).

The devil is in the details, of course, but it is beginning to look as if we have the main ingredients in place: internal states that stand in useful relations to things in the environment, internal processing which relies on those relations, and the functions that serves for the organism. Just as the cognitive sciences come to lean on representation ever more heavily, it seems that we now have the resources to understand this foundational notion.

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What is representation in the human brain and AI systems? | OUPblog - OUPblog

HistoIndex Explores the Clinical Utility of Stain-free AI Digital Pathology Platform in 388 Patients with Triple-Negative Breast Cancer (TNBC) – The…

Assessing Collagen Features at a Finer Level of Detail

In a collaborative study involving scientists from the Institute of Molecular and Cell Biology (IMCB) in Singapore and TNBC pathologists from the Singapore General Hospital (SGH), unstained biopsies from 388 TNBC patients were scanned using HistoIndex's AI-based SHG platform and analyzed to extract different collagen features from the SHG images at a finer level of detail. Findings published in the leading peer-reviewed oncology journal, Breast Cancer Research [3], showed a strong correlation between several imaging features and clinicopathological characteristics. Aggregation of collagen fibers, collagen fiber density and the length of dispersed thin collagen fibers were key collagen-associated parameters revealed to be of prognostic value based on the patient cohort and clinical outcomes. Furthermore, analyzing the aggregated thick collagen (ATC) fibers and dispersed thin collagen (DTC) fibers (as shown in Figure 1) provided a novel understanding of collagen remodeling during cancer progression.

Says Professor Tan Puay Hoon, Chairman, Division of Pathology, and Senior Consultant, Department of Anatomical Pathology, SGH, and lead pathologist of the study, "Critical biomarkers in TNBC are needed to stratify patients and predict clinical outcomes. Technological advances in pathology such as SHG assessment may improve the characterization of detailed and minute changes in important collagen features within the tumor stromal microenvironment such as the collagen structure, density and length. These are important parameters that could possibly enhance pathological assessment and allow for a clearer understanding of the relationship between collagen features and tumor progression."

Evaluating Therapeutic Efficacy with Key Collagen Parameters

The advantages of these novel collagen parameters make the platform a valuable asset in existing and future TNBC studies that are currently monitoring therapeutic responses in their exploration of targeted treatments. For instance, an ongoing collaboration between HistoIndex and a team at the Memorial Sloan Kettering Cancer Center (MSK), led by Professor Linda Vahdat, Chief of Medical Oncology and Clinical Director of Cancer Services at the MSK Physicians at Norwalk Hospital, is currently investigating influencing the tumor microenvironment with anti-copper therapy (copper depletion) for patients with breast cancer who are at a high risk of a relapse.

Copper encourages the growth of the blood vessels that feed dormant, and later active, cancer cells, and is also needed by certain cancer molecules to communicate with and influence the tumor microenvironment. Subsequently, this element is a necessary resource to build a collagen scaffolding that cancer cells populate as they become aggressive. Having spent many years examining copper depletion in TNBC studies, Prof. Vahdat has previously explained the role of copper in triggering metastasis, and how the collagen scaffolding that houses the tumor breaks down once copper is pulled out of the system [4].

Says Prof. Vahdat, "Collagen within the tumor microenvironment represents an under-explored predictor of treatment outcome. Preliminary data from our group suggests that we can normalize the collagen microenvironment with a copper depletion strategy rendering an inhospitable environment for metastases. With this collaboration with HistoIndex, we hope to be able to predict those primary tumors that are amenable to this treatment strategy."

About TNBC

The term Triple-Negative Breast Cancer refers to the fact that the cancer cells do not possess estrogen or progesterone receptors and also do not overexpress the protein called HER2. A patient is diagnosed with this form of breast cancer when the cells test "negative" for all three receptors. TNBC differs from other types of invasive breast cancer as they progress faster, have limited targeted treatments, and a generally bleak prognosis. According to the American Cancer Society, TNBC accounts for about 10-15% of all breast cancers and is more common in women younger than the age 40, who are African-American, or women who have a BRCA1 mutation [5].

References

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HistoIndex Explores the Clinical Utility of Stain-free AI Digital Pathology Platform in 388 Patients with Triple-Negative Breast Cancer (TNBC) - The...

Organoids give insight into the development of cervical cancer – BioNews

25 January 2021

Molecular changes that give rise to cervical cancer have been identified using novel 'organoid' models.

Published in Nature Cell Biology, researchers in Germany have developed an organoid model of the cervix, providing them with a unique way to study its normal biology and better understand why cancers develop.

'These fundamental findings form a basis for further understanding of the mechanisms involved in carcinogenesis at these metaplastic sites. To study how human papillomavirus (HPV), together with superseding bacterial infections, plays a key role in transforming cells to malignancy,' said Dr Cindrilla Chumduri from the Biocentre at the University of Wrzburg, who led the study.

Organoids are tiny 3D structures made of cells just a few millimetres in size that are artificially developed to closely resemble whole organs. They are increasingly used in medical research to allow scientists to study life processes and the effect of drugs.

Prior to this new study, it was known that the cervix has two regions covered by two different types of epithelial cells so called 'squamous epithelia' and 'columnar epithelia'. The boundaries between these two different cell types are called transition zones, and 90 perecent of cervical cancers originate at these sites. However, it was not known exactly how these two cell populations and their boundaries are ordinarily kept distinct in a healthy cervix, or why this is a hotspot for cancer development.

Using the organoid structures, the researchers discovered that instead of the two different epithelial cell types developing from the same stem cells, they are in fact derived from two discrete stem cell populations.

Complex interactions between these stem cells and their surrounding microenvironment were found to be important for keeping the two types of cells separate and for ensuring a healthy cervical architecture. This is achieved using the Wnt signaling pathway proteins known for their role in cellular differentiation, among other processes.

The researchers also showed that disrupting Wnt signalling can alter the homeostasis seen in the cervix, allowing one type of epithelium cell to replace the other an early event in cancer development termed metaplasia. Different types of cervical cancers can develop depending on which epithelial cell population is displaced.

It is hoped that this improved understanding of the fundamental biology of the cervix and the molecular changes seen in cervical metaplasia will help improve our understanding of how certain viral and bacterial infections principally HPV cause cervical cancer.

Dr Chumduri also added, 'these critical insights can help to develop diagnostics for the early detection of these two tumour forms and new therapeutic strategies'.

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Organoids give insight into the development of cervical cancer - BioNews

Role of Antizyme Inhibitor Proteins in Cancers and Beyond | OTT – Dove Medical Press

Vennela Tulluri, Venkatesh V Nemmara

Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA

Correspondence: Venkatesh V NemmaraDepartment of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USATel +1 856-256-5460Email nemmara@rowan.edu

Abstract: Polyamines are multivalent organic cations essential for many cellular functions, including cell growth, differentiation, and proliferation. However, elevated polyamine levels are associated with a slew of pathological conditions, including multiple cancers. Intracellular polyamine levels are primarily controlled by the autoregulatory circuit comprising two different protein types, Antizymes (OAZ) and Antizyme Inhibitors (AZIN), which regulate the activity of the polyamine biosynthetic enzyme ornithine decarboxylase (ODC). While OAZ functions to decrease the intracellular polyamine levels by inhibiting ODC activity and exerting a negative control of polyamine uptake, AZIN operates to increase intracellular polyamine levels by binding and sequestering OAZ to relieve ODC inhibition and to increase polyamine uptake. Interestingly, OAZ and AZIN exhibit autoregulatory functions on polyamine independent pathways as well. A growing body of evidence demonstrates the dysregulation of AZIN expression in multiple cancers. Additionally, RNA editing of the Azin1 transcript results in a gain-of-function phenotype, which is shown to drive aggressive tumor types. This review will discuss the recent advances in AZINs role in cancers via aberrant polyamine upregulation and its polyamine-independent protein regulation. This report will also highlight AZIN interaction with proteins outside the polyamine biosynthetic pathway and its potential implication to cancer pathogenesis. Finally, this review will reveal the protein interaction network of AZIN isoforms by analyzing three different interactome databases.

Keywords: polyamine, ornithine decarboxylase, antizyme inhibitor, antizyme, putrescine, spermine, spermidine, mRNA editing, 26S proteasome, degradation, ubiquitin-independent, protein interactome

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Role of Antizyme Inhibitor Proteins in Cancers and Beyond | OTT - Dove Medical Press

Bio-Based Itaconic Acid Market 2020 Global Industry Analysis Size Share Growth Trends and Forecast Thermo Fisher Scientific., Itaconix Corporation,…

This Bio-Based Itaconic Acid Market research report is a careful examination of variables affecting the organization is additionally given which estimates looming chances to the organizations and builds up the methodologies to lift return of investment. This Global Bio-Based Itaconic Acid Industry examination puts a light on different sections that are depended upon to observe the fastest business advancement in the midst of the estimated time-frame. In no uncertainty, the present organizations need to consider this market research before taking any decision about the items. Besides, it makes clients aware about the various strategies that are used by key players of the market.

This Bio-Based Itaconic Acid Market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localized market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographical expansions, technological innovations in the market. To gain more info on industrial enzymes market contact Data Bridge Market Research for an Analyst Brief, our team will help you take an informed market decision to achieve market growth.

Market Insights

Bio-based itaconic acidmarketis expected to grow at a rate of 5.50% for the forecast period of 2020 to 2027. Data Bridge Market Research report on bio-based itaconic acid market provides analysis and insights regarding the various factors expected to be prevalent throughout the forecasted period while providing their impacts on the markets growth.

This Global Bio-Based Itaconic Acid Market Report Will Provide:

The changing trend towards eco-friendly products due to growing awareness regardinggreen house emissionswill help impact the bio-based itaconic acidmarket growth in the forecast period of 2020 to 2027. The rising incidence for bio-based unsaturated polyester resin, growing awareness concerning the benefits ofitaconic acidand rising application scope in manufacturing adhesives and sealants are some of the factors that will fuel the growth of the market. Moreover, technological advancements in bio-based pmma and increasing R& D investmentwill cater ample opportunities that will lead to the growth of the market in the above mentioned forecast period.

Availability of low cost substitutes is expected to be as the restraining factorto the growth of bio-based itaconic acidmarket in the forecast period of 2020 to 2027.

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Major Market Players Covered in The Bio-Based Itaconic Acid Market Are:

The major players covered in the bio-based itaconic acid market report are Thermo Fisher Scientific., Itaconix Corporation, Qingdao Kehai Biochemistry Co., LTD., AEKYUNG PETROCHEMICAL Co., Ltd, Zhejiang Guoguang Biochemistry Co.,Ltd., Spectrum Ultimate Chem India Pvt. Ltd, Alpha Chemika, Haihang Industry Co., Ltd, Ronas Chemicals Ind. Co., Ltd., Hefei TNJ Chemical Industry Co.,Ltd., Alfa Aesar, Merck KGaA, Choice Organochem Llp., FUSO CHEMICAL CO., LTD., Henan Haofei Chemical Co.,Ltd., Chemical Manufacturing Corp and FUJIFILM Wako Pure Chemical Corporation, among other domestic and global players. Market share data is available for global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

Asia- Pacific dominates the bio-based itaconic acidmarket due to the large market share in the itaconic acid market due to rising regulatory expenditure on infrastructure improvement in India and China.

Global Bio-Based Itaconic Acid MarketScope and Segments

Bio-based itaconic acidmarket is segmented on the basis of derivative and application. The growth amongst the different segments helps you in attaining the knowledge related to the different growth factors expected to be prevalent throughout the market and formulate different strategies to help identify core application areas and the difference in your target markets.

Based on regions, the Bio-Based Itaconic Acid Market is classified into North America, Europe, Asia- Pacific, Middle East & Africa, and Latin America

Middle East and Africa (GCC Countries and Egypt)

North America (United States, Mexico, and Canada)

South America (Brazil, Argentina etc.)

Europe (Turkey, Germany, Russia UK, Italy, France, etc.)

Asia-Pacific (Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia, and Australia)

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Strategic Points Covered in Table of Content of Global Bio-Based Itaconic Acid Market:

Chapter 1: Introduction, market driving force product Objective of Study and Research Scope Bio-Based Itaconic Acid market

Chapter 2: Exclusive Summary the basic information of Bio-Based Itaconic Acid Market.

Chapter 3: Displaying the Market Dynamics- Drivers, Trends and Challenges of Geotextile Tube

Chapter 4: Presenting Bio-Based Itaconic Acid Market Factor Analysis Porters Five Forces, Supply/Value Chain, PESTEL analysis, Market Entropy, Patent/Trademark Analysis.

Chapter 5: Displaying the by Type, End User and Region 2013-2018

Chapter 6: Evaluating the leading manufacturers of Bio-Based Itaconic Acid market which consists of its Competitive Landscape, Peer Group Analysis, BCG Matrix & Company Profile

Chapter 7: To evaluate the market by segments, by countries and by manufacturers with revenue share and sales by key countries in these various regions.

Chapter 8 & 9: Displaying the Appendix, Methodology and Data Source

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Bio-Based Itaconic Acid Market 2020 Global Industry Analysis Size Share Growth Trends and Forecast Thermo Fisher Scientific., Itaconix Corporation,...

Automatic Biochemistry Analyzers Market Size By Analysis, Key Vendors, Regions, Type and Application, and Forecasts to 2027 – NeighborWebSJ

Fort Collins, Colorado: Reports Globe has published the latest study on Automatic Biochemistry Analyzers Market Report Analysis by Size with Future Outlook, Key Players SWOT Analysis and Forecast to 2026. It uses exploratory techniques such as qualitative and quantitative analysis to identify and present data on the target market. Successful sales strategies have been mentioned that will help you do business in record time and multiply customers.

This report is presented clearly and concisely to help you better understand the structure and dynamics of the market. The trends and recent developments in the Automatic Biochemistry Analyzers market were analyzed. The opportunities that lead to the growth of the market were analyzed and presented. Focusing on the global market, the report provides answers to the key questions stakeholders are facing today around the world. Information on market size raises the problem of increasing competitiveness and hampering market-leading sectors and market growth.

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Automatic Biochemistry Analyzers market research report provides detailed information on the following aspects: Industry Size, Market Share, Growth, Segmentation, Manufacturers and Advancement, Key Trends, Market Drivers, Challenges, Standardization, Deployment Models, Opportunities, Strategies, Future Roadmaps and Annual Forecasts to 2027, etc. The report will help you also in understanding the dynamic structure of the Automatic Biochemistry Analyzers market by identifying and analyzing market segments. The Global Automatic Biochemistry Analyzers 2021 Industry Research Report has given the expected compound annual growth rate (CAGR) as a% of value for a given period of time and clearly helps the user make their decision based on the futuristic chart of the key players on the global Automatic Biochemistry Analyzers market. The report introduces some of the major players in the global Automatic Biochemistry Analyzers market and offers insightful information about the Automatic Biochemistry Analyzers industry such as Business Overview, Automatic Biochemistry Analyzers Market Product Segmentation, Revenue Segmentation, and the Latest Information. Developments.

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1. What is the overall structure of the market?2. What was the historical value and what is the forecasted value of the market?3. What are the key product level trends in the market?4. What are the market level trends in the market?5. Which of the market players are leading and what are their key differential strategies to retain their stronghold?6. Which are the most lucrative regions in the market space?

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Global Automatic Biochemistry Analyzers market is segmented based by type, application and region.

Automatic Biochemistry Analyzers Market Segmentation, By Type

Automatic Biochemistry Analyzers Market Segmentation, By Application

The prime objective of this report is to help the user understand the market in terms of its definition, segmentation, market potential, influential trends, and the challenges that the market is facing. Deep researches and analysis were done during the preparation of the report. The readers will find this report very helpful in understanding the market in depth. The data and the information regarding the market are taken from reliable sources such as websites, annual reports of the companies, journals, and others and were checked and validated by the industry experts. The facts and data are represented in the report using diagrams, graphs, pie charts, and other pictorial representations. This enhances the visual representation and also helps in understanding the facts much better.

Global Automatic Biochemistry Analyzersmarket Key Report Highlights:

This in-depth research documentation offers an illustrative overview of the entire market outlook with details on scope, executive summary, and market segments The report also includes sections on the competitive spectrum, highlighting major players, with a detailed assessment of supply chain management, competition dynamics, and growth objectives. Other crucial details on Porters Five Forces assessment, SWOT analysis, and data triangulation methods have also been included in the report. Other relevant details on production patterns, growth rate, market share of each of the segments have also been pinned in the report. The report also houses crucial analytical details on revenue share and sales projections, besides volumetric estimations of each of the product segments have also been highlighted in the report to encourage unfaltering market decisions and sustainable revenue streams in the global Automatic Biochemistry Analyzers market.A dedicated chapter on COVID-19 analysis has therefore been included in this versatile report to encourage future-ready business discretion aligning with post-COVID-19 market environment.

Major Points from Table of Content:

1. Executive Summary2. Assumptions and Acronyms Used3. Research Methodology4. Automatic Biochemistry Analyzers Market Overview5. Automatic Biochemistry Analyzers Supply Chain Analysis6. Automatic Biochemistry Analyzers Pricing Analysis7. Global Automatic Biochemistry Analyzers Market Analysis and Forecast by Type8. Global Automatic Biochemistry Analyzers Market Analysis and Forecast by Application9. Global Automatic Biochemistry Analyzers Market Analysis and Forecast by Sales Channel10. Global Automatic Biochemistry Analyzers Market Analysis and Forecast by Region11. North America Automatic Biochemistry Analyzers Market Analysis and Forecast12. Latin America Automatic Biochemistry Analyzers Market Analysis and Forecast13. Europe Automatic Biochemistry Analyzers Market Analysis and Forecast14. Asia Pacific Automatic Biochemistry Analyzers Market Analysis and Forecast15. Middle East & Africa Automatic Biochemistry Analyzers Market Analysis and Forecast16. Competition Landscape

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Automatic Biochemistry Analyzers Market Size By Analysis, Key Vendors, Regions, Type and Application, and Forecasts to 2027 - NeighborWebSJ

Genetics of Smoking and Risk of Atherosclerotic Cardiovascular Diseases: A Mendelian Randomization Study – DocWire News

JAMA Netw Open. 2021 Jan 4;4(1):e2034461. doi: 10.1001/jamanetworkopen.2020.34461.

ABSTRACT

IMPORTANCE: Smoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.

OBJECTIVE: To determine the association between genetic liability to smoking and risk of CAD, PAD, and large-artery stroke.

DESIGN, SETTING, AND PARTICIPANTS: Mendelian randomization study using summary statistics from genome-wide associations of smoking (UK Biobank; up to 462 690 individuals), CAD (Coronary Artery Disease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; up to 60 801 cases, 123 504 controls), PAD (VA Million Veteran Program; up to 24 009 cases, 150 983 controls), and large-artery stroke (MEGASTROKE; up to 4373 cases, 406 111 controls). This study was conducted using summary statistic data from large, previously described cohorts. Review of those publications does not reveal the total recruitment dates for those cohorts. Data analyses were conducted from August 2019 to June 2020.

EXPOSURES: Genetic liability to smoking (as proxied by genetic variants associated with lifetime smoking index).

MAIN OUTCOMES AND MEASURES: Risk (odds ratios [ORs]) of CAD, PAD, and large-artery stroke.

RESULTS: Genetic liability to smoking was associated with increased risk of PAD (OR, 2.13; 95% CI, 1.78-2.56; P = 3.6 10-16), CAD (OR, 1.48; 95% CI, 1.25-1.75; P = 4.4 10-6), and stroke (OR, 1.40; 95% CI, 1.02-1.92; P = .04). Genetic liability to smoking was associated with greater risk of PAD than risk of large-artery stroke (ratio of ORs, 1.52; 95% CI, 1.05-2.19; P = .02) or CAD (ratio of ORs, 1.44; 95% CI, 1.12-1.84; P = .004). The association between genetic liability to smoking and atherosclerotic cardiovascular diseases remained independent from the effects of smoking on traditional cardiovascular risk factors.

CONCLUSIONS AND RELEVANCE: In this mendelian randomization analysis of data from large studies of atherosclerotic cardiovascular diseases, genetic liability to smoking was a strong risk factor for CAD, PAD, and stroke, although the estimated association was strongest between smoking and PAD. The association between smoking and atherosclerotic cardiovascular disease was independent of traditional cardiovascular risk factors.

PMID:33464320 | DOI:10.1001/jamanetworkopen.2020.34461

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Genetics of Smoking and Risk of Atherosclerotic Cardiovascular Diseases: A Mendelian Randomization Study - DocWire News

Assistant Professor in Stem Cell Biology or Regenerative Biology job with University of California, Irvine | 312638 – The Chronicle of Higher…

Assistant Professor in Stem Cell Biology or RegenerativeBiology

Applications are invited for a tenure-track faculty position at thelevel of Assistant Professor in the Department of Developmental andCell Biology. We seek candidates with an interest in stem cell orregeneration biology, broadly defined. Applicants should pursueresearch in the major areas of interest of the department,including, but not limited to developmental biology, stem celland/or niche biology, regeneration and cancer stem cells. Prioritywill be given to candidates whose research will benefit frominterdisciplinary collaborations, interactions with members of thedepartment (http://devcell.bio.uci.edu), andfrom affiliation with campus centers and institutes.

The successful applicant is expected to conduct a vibrant researchprogram, contribute to the teaching and service missions of theUniversity of California, and share our commitment to diversity,equity and inclusion. Please send a curriculum vitae, 3-pagesummary of research accomplishments and goals, 1-page statement ofteaching and mentoring experience and philosophy, 1-page statementhighlighting past and/or potential contributions to diversity,equity and inclusion, and at least three letters of reference viathe online recruitment URL: https://recruit.ap.uci.edu/apply/JPF06561. Evaluation criteria for the research, teaching, and diversitystatements are provided at the online recruitment URL. Applicationscompleted by March 7, 2021 will be granted full consideration. Anyquestions about the suitability of an applicant for thisopportunity can be directed to the search chair, Peter Donovanpdonovan@uci.edu.

The UCI School of Biological Sciences is recognized as a nationalleader in the development of programs designed to increase theparticipation of underrepresented groups in the biomedical sciencesand is firmly committed to the ideals of equity, diversity, andinclusion (https://port.bio.uci.edu/about/,https://equity.bio.uci.edu). UCIis an Hispanic-Serving Institution, an Asian American and NativeAmerican Pacific Islander Serving Institution, and a chartermember of the AAAS SEA Change initiative that supportsinstitutional efforts to increase access and success for students,faculty and staff from groups marginalized in STEMM (https://www.aaas.org/news/four-new-charter-members-join-sea-change).Programs are available to meet the needs of dual-career academicpartners. Faculty are eligible for subsidized housing and aMortgage Origination Program. UC Irvine (https://uci.edu) is located 10 minutes fromthe coast (https://www.youtube.com/watch?v=82ARz3B60pU),is consistently ranked among the nations top 10 publicuniversities, and has recently been designated the #1 universitydoing the most for the American dream. The city of Irvine is hometo excellent parks, schools, entertainment opportunities, and adiverse citizenry.

The University of California, Irvine is an EqualOpportunity/Affirmative Action Employer advancing inclusiveexcellence. All qualified applicants will receive consideration foremployment without regard to race, color, religion, sex, sexualorientation, gender identity, national origin, disability, age,protected veteran status, or other protectedcategories covered by the UC nondiscrimination policy. A recipientof an NSF ADVANCE award for gender equity, UCI is responsive to theneeds of dual career couples, supports work-life balance through anarray of family-friendly policies, and is dedicated to broadeningparticipation in higher education.

The University of California is committed to creating andmaintaining a community dedicated to the advancement, application,and transmission of knowledge and creative endeavors throughacademic excellence, where all individuals who participate inUniversity programs and activities can work and learn together in asafe and secure environment, free of violence, harassment,discrimination, exploitation, or intimidation. With thiscommitment, as well as a commitment to addressing all forms ofacademic misconduct, UC Irvine conducts institutional referencechecks for candidate finalists to whom the department or otherhiring unit would like to extend a formal offer of appointment intoLadder Rank Professor or Professor of Teaching series, at all ranks(i.e., assistant, associate, and full). The institutional referencechecks involve contacting the administration of the applicantsprevious institution(s) to ask whether there have beensubstantiated findings of misconduct that would violate theUniversitys Faculty Code of Conduct. To implement this process, UCIrvine requires all candidates of Ladder Rank Professor orProfessor of Teaching series, at all ranks (i.e., assistant,associate, and full) to complete, sign, and upload the formentitled Authorization to Release Information into AP RECRUIT aspart of their application. If the candidate does not include thesigned authorization to release information with the applicationmaterials, the application will be considered incomplete. As withany incomplete application, the application will not receivefurther consideration. Although all applicants for facultyrecruitments must complete the entire application, only finalists(i.e., those to whom the department or other hiring unit would liketo extend a formal offer) considered for Ladder Rank Professor orProfessor of Teaching series, at all ranks (i.e., assistant,associate, and full) positions will be subject to institutionalreference checks.

REQUIREMENTS Curriculum Vitae Cover Letter Three letters of Reference Statement of Research Three pages.1. One page describing the significance and impact of your graduateand postdoctoral research.2. Two pages providing a plan for your future independent researchprogram that indicates how your research program will synergizewith the research environment at UCI (see e.g., https://www.bio.uci.edu/centers-institutes) Statement of Teaching One page.1. Describe any experience teaching/lecturing toundergraduates/graduate students or other populations and mentoringothers.2. Explain your teaching philosophy and describe how you willengage in teaching strategies that are effective in diversepopulations. Statement of Contributions to Diversity(http://www.uci.edu/diversity) One page.1. Indicate how you have demonstrated awareness of the issues facedby historically underrepresented or economically disadvantagedgroups and the benefits of a diverse and inclusive faculty.2. Provide evidence (if any) of your track record and success inactivities aimed at reducing barriers in education or research forunderrepresented or disadvantaged groups.3. Detail your specific plans (if any) to contribute through campusprograms, new activities, or through national or off-campusorganizations.

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Assistant Professor in Stem Cell Biology or Regenerative Biology job with University of California, Irvine | 312638 - The Chronicle of Higher...

RNA ties itself in knots, then unties itself in mesmerizing video – Livescience.com

Striking new videos show how RNA the genetic molecule that tells cells how to build proteins tangles up in insane knots as it forms, only to disentangle itself at the last second, and in a way that took scientists by surprise.

The high-resolution videos depict a bouncing conga line of nucleotides, the building blocks of RNA; as the single strand of RNA grows longer, these nucleotides dance and twist into different three-dimensional shapes, wiggling first into one conformation and then another. Once fully assembled, the RNA assumes its final shape, which dictates how it can interact with other molecules and proteins in the cell.

But on the way, the RNA can get trapped in "knots" that must be undone for this final shape to emerge.

"So the RNA has to get out of it," said study author Julius Lucks, an associate professor of chemical and biological engineering and a member of the Center for Synthetic Biology at Northwestern University. The RNA won't function correctly if it remains trapped in the wrong knot, meaning a knot that gets in the way of its final shape, he said. "What was surprising is how it got out of that trap. This was only discovered when we had the high-resolution videos."

Related: Genetics by the numbers: 10 tantalizing tales

In the new study, published Jan. 15 in the journal Molecular Cell, Lucks and his colleagues generated their videos of RNA using experimental data and a computer algorithm. The goal was to zoom in on how RNA forms, both to better understand basic cell biology and to pave the way to better treatments for RNA-related diseases.

In the experiments, the team used a specific kind of RNA called signal recognition particle (SNP) RNA, an evolutionarily ancient molecule found across all kingdoms of life. They used this RNA as a model since it serves a fundamental function in many kinds of cells.

To zoom in on how cells build this RNA, the team used chemicals to pause the construction process. So as new nucleotides got added to the RNA, the researchers hit pause and then recorded how those nucleotides interacted with others already in the lineup, and what shapes they all formed together. By capturing the data from many individual RNA molecules, the team developed snapshots of how RNA generally builds itself through time.

These snapshots served as individual frames in what would become their final videos of RNA formation. That's where the computer model came in. The algorithm essentially strung together the individual frames into mini-movies and filled in the gaps between frames with the most likely nucleotide interactions. In these videos, the team noticed how the RNA got tangled into complex knots that, if left tied, would render the whole molecule useless.

"It folds into this trap state, and it kind of stays there," Lucks said. SNP RNA is meant to form in a signature "hairpin-like" shape, and these traps seem to get in the way. But as more nucleotides get added to the sequence, the new nucleotides swoop in to unravel the knot by displacing the nucleotides tangled up inside.

"That last little nucleotide is like a trigger" that allows the whole RNA to pop into the correct conformation, Lucks said. Think of the last fold in an origami project, which suddenly transforms a crinkly piece of paper into a lovely butterfly. In the videos, the nucleotides highlighted in dark purple knot themselves up, and the dark pink nucleotides help free them, Lucks noted.

Learning how RNA tangles and untangles is key to understanding how cells function and how proteins form; the research can also help address diseases where RNA doesn't function properly or a specific protein can't form, such as spinal muscular atrophy, and infectious diseases such as COVID-19 that are caused by RNA viruses, according to a statement.

A big question is whether RNA can mostly untangle itself from these knots, or whether it sometimes needs helper proteins to ease the process. It's possible that some proteins act as so-called "RNA chaperones" and help sculpt the molecule into its final form, Lucks said. He added that it may be a combination of both, although at this point, that's speculative.

Originally published on Live Science.

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RNA ties itself in knots, then unties itself in mesmerizing video - Livescience.com

HistoIndex Explores the Clinical Utility of Stain-free AI Digital Pathology Platform in 388 Patients with Triple-Negative Breast Cancer (TNBC) -…

TNBC is an incredibly challenging and aggressive form of breast cancer compared to other subtypes and holds a relatively poor prognosis primarily due to a lack of targeted treatments. In cancer, collagen fibers play a significant role in the tumor microenvironment, with remodeling of the extracellular matrix (ECM) that is often more collagen-rich with increased 'stiffness' [1]. As a component of the ECM, collagen may also influence cancer cell behavior[2]. Particularly in TNBC, collagen remodeling is seen in the stromal compartment [3].

Assessing Collagen Features at a Finer Level of Detail

In a collaborative study involving scientists from the Institute of Molecular and Cell Biology (IMCB) in Singapore and TNBC pathologists from the Singapore General Hospital (SGH), unstained biopsies from 388 TNBC patients were scanned using HistoIndex's AI-based SHG platform and analyzed to extract different collagen features from the SHG images at a finer level of detail. Findings published in the leading peer-reviewed oncology journal, Breast Cancer Research [3], showed a strong correlation between several imaging features and clinicopathological characteristics. Aggregation of collagen fibers, collagen fiber density and the length of dispersed thin collagen fibers were key collagen-associated parameters revealed to be of prognostic value based on the patient cohort and clinical outcomes. Furthermore, analyzing the aggregated thick collagen (ATC) fibers and dispersed thin collagen (DTC) fibers (as shown in Figure 1) provided a novel understanding of collagen remodeling during cancer progression.

Says Professor Tan Puay Hoon, Chairman, Division of Pathology, and Senior Consultant, Department of Anatomical Pathology, SGH, and lead pathologist of the study, "Critical biomarkers in TNBC are needed to stratify patients and predict clinical outcomes. Technological advances in pathology such as SHG assessment may improve the characterization of detailed and minute changes in important collagen features within the tumor stromal microenvironment such as the collagen structure, density and length. These are important parameters that could possibly enhance pathological assessment and allow for a clearer understanding of the relationship between collagen features and tumor progression."

Evaluating Therapeutic Efficacy with Key Collagen Parameters

The advantages of these novel collagen parameters make the platform a valuable asset in existing and future TNBC studies that are currently monitoring therapeutic responses in their exploration of targeted treatments. For instance, an ongoing collaboration between HistoIndex and a team at the Memorial Sloan Kettering Cancer Center (MSK), led by Professor Linda Vahdat, Chief of Medical Oncology and Clinical Director of Cancer Services at the MSK Physicians at Norwalk Hospital, is currently investigating influencing the tumor microenvironment with anti-copper therapy (copper depletion) for patients with breast cancer who are at a high risk of a relapse.

Copper encourages the growth of the blood vessels that feed dormant, and later active, cancer cells, and is also needed by certain cancer molecules to communicate with and influence the tumor microenvironment. Subsequently, this element is a necessary resource to build a collagen scaffolding that cancer cells populate as they become aggressive. Having spent many years examining copper depletion in TNBC studies, Prof. Vahdat has previously explained the role of copper in triggering metastasis, and how the collagen scaffolding that houses the tumor breaks down once copper is pulled out of the system [4].

Says Prof. Vahdat, "Collagen within the tumor microenvironment represents an under-explored predictor of treatment outcome. Preliminary data from our group suggests that we can normalize the collagen microenvironment with a copper depletion strategy rendering an inhospitable environment for metastases. With this collaboration with HistoIndex, we hope to be able to predict those primary tumors that are amenable to this treatment strategy."

About TNBC

The term Triple-Negative Breast Cancer refers to the fact that the cancer cells do not possess estrogen or progesterone receptors and also do not overexpress the protein called HER2. A patient is diagnosed with this form of breast cancer when the cells test "negative" for all three receptors. TNBC differs from other types of invasive breast cancer as they progress faster, have limited targeted treatments, and a generally bleak prognosis. According to the American Cancer Society, TNBC accounts for about 10-15% of all breast cancers and is more common in women younger than the age 40, who are African-American, or women who have a BRCA1 mutation [5].

References

SOURCE Histoindex Pte. Ltd.

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HistoIndex Explores the Clinical Utility of Stain-free AI Digital Pathology Platform in 388 Patients with Triple-Negative Breast Cancer (TNBC) -...