Robust Digital Molecular Design of Binarized Neural Networks

Molecular programming - a paradigm wherein molecules are engineered to perform computation - shows great potential for applications in nanotechnology, disease diagnostics and smart therapeutics. A key challenge is to identify systematic approaches for compiling abstract models of computation to molecules. Due to their wide applicability, one of the most useful abstractions to realize is neural networks. In prior work, real-valued weights were achieved by individually controlling the concentrations of the corresponding "weight" molecules. However, large-scale preparation of reactants with precise concentrations quickly becomes intractable. Here, we propose to bypass this fundamental problem using Binarized Neural Networks (BNNs), a model that is highly scalable in a molecular setting due to the small number of distinct weight values. We devise a noise-tolerant digital molecular circuit that compactly implements a majority voting operation on binary-valued inputs to compute the neuron output. The network is also rate-independent, meaning the speed at which individual reactions occur does not affect the computation, further increasing robustness to noise. We first demonstrate our design on the MNIST classification task by simulating the system as idealized chemical reactions. Next, we map the reactions to DNA strand displacement cascades, providing simulation results that demonstrate the practical feasibility of our approach. We perform extensive noise tolerance simulations, showing that digital molecular neurons are notably more robust to noise in the concentrations of chemical reactants compared to their analog counterparts. Finally, we provide initial experimental results of a single binarized neuron. Our work suggests a solid framework for building even more complex neural network computation

Isoleeritud suure pöörli murru mõju suremusele on võrreldav reieluu proksimaalse osa murruga

Eesti Arst 2022; 101(11):64

Does Screening in the Emergency Department Hurt or Help Victims of Intimate Partner Violence?

Study objective: Recent systematic reviews have noted a lack of evidence that screening for intimate partner violence does more good than harm. We assess whether patients screened for intimate partner violence on a computer kiosk in the emergency department (ED) experienced any adverse events during or subsequent to the ED visit and whether computer kiosk identification and referral of intimate partner violence in the ED setting resulted in safety behaviors or contact with referrals. Methods: We conducted a prospective, observational study in which a convenience sample of male and female ED patients triaged to the waiting room who screened positive (on a computer kiosk-based questionnaire) for intimate partner violence in the past year were provided with resources and information and invited to participate in a series of follow-up interviews. At 1-week and 3-month follow-up visits, we assessed intimate partner violence, safety issues, and use of resources. In addition, to obtain an objective measure of safety, we assessed the number of violence-related 911 calls to participant addresses within a call district 6 months before and 6 months after the index ED visit. Results: Of the 2,134 participants in a relationship in the last year, 548 (25.7%) screened positive for intimate partner violence. No safety issues, such as calling security or a partner’s interference with the screening, occurred during the ED visit for any patient who disclosed intimate partner violence. Of the 216 intimate partner violence victims interviewed in person and 65 contacted by telephone 1 week later, no intimate partner violence victims reported any injuries or increased intimate partner violence resulting from participating in the study. For the sample in the local police district, there was no increase in the number of intimate partner violence victims who called 911 in the 6 months after the ED visit. Finally, 35% (n131) reported they had contacted community resources during the 3-month follow-up period. Conclusion: Among patients screening positive for intimate partner violence, there were no identified adverse events related to screening, and many had contacted community resources

A DNA-Based Archival Storage System

Abstract Demand for data storage is growing exponentially, but the capacity of existing storage media is not keeping up. Using DNA to archive data is an attractive possibility because it is extremely dense, with a raw limit of 1 exabyte/mm 3 (10 9 GB/mm 3 ), and long-lasting, with observed half-life of over 500 years. This paper presents an architecture for a DNA-based archival storage system. It is structured as a key-value store, and leverages common biochemical techniques to provide random access. We also propose a new encoding scheme that offers controllable redundancy, trading off reliability for density. We demonstrate feasibility, random access, and robustness of the proposed encoding with wet lab experiments involving 151 kB of synthesized DNA and a 42 kB randomaccess subset, and simulation experiments of larger sets calibrated to the wet lab experiments. Finally, we highlight trends in biotechnology that indicate the impending practicality of DNA storage for much larger datasets

Zooming in and out : studying practices by switching theoretical lenses and trailing connections

This paper contributes to re-specifying a number of the phenomena of interest to organisational studies in terms of patterns of socio-material practices and their effects. It does so by outlining a vocabulary and strategy that make up a framework for theorising work and organisational practices. The vocabulary is based on number of sensitising concepts that connote practice as an open-ended, heterogeneous accomplishment which takes place within a specific horizon of sense and a set of concerns which the practice itself brings to bear. The strategy is based on the metaphorical movement of "zooming in" and "zooming out of" practice. The zooming in and out are obtained through switching theoretical lenses and repositioning in the field, so that certain aspects of the practice are fore-grounded while others are bracketed. Building on the results of an extended study of telemedicine, the paper discusses in detail the different elements of the framework and how it enhances our capacity to re-present practice. The paper concludes with some considerations on how the proposed approach can assist us in advancing the research agenda of organizational and work studies

DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access

In support of the publication "DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access" we share the following datasets and code: AutoCAD drawing of the microfluidic trapping device. Sequences of the DNA used to encode the 25 files used in the current study. FASTQ-files of the sequencing experiments of Figures 5b and d. Python scripts that allow for the reproduction of our sequencing data analysis. The code has been tested on MacOS 13.0.1, Python 3.7.13, samtools 1.16.1 and BWA 0.7.17

Structural basis for VIPP1 oligomerization and maintenance of thylakoid membrane integrity

Vesicle-inducing protein in plastids 1 (VIPP1) is essential for the biogenesis and maintenance of thylakoid membranes, which transform light into life. However, it is unknown how VIPP1 performs its vital membrane-remodeling functions. Here, we use cryo-electron microscopy to determine structures of cyanobacterial VIPP1 rings, revealing how VIPP1 monomers flex and interweave to form basket-like assemblies of different symmetries. Three VIPP1 monomers together coordinate a non-canonical nucleotide binding pocket on one end of the ring. Inside the ring's lumen, amphipathic helices from each monomer align to form large hydrophobic columns, enabling VIPP1 to bind and curve membranes. In vivo mutations in these hydrophobic surfaces cause extreme thylakoid swelling under high light, indicating an essential role of VIPP1 lipid binding in resisting stress-induced damage. Using cryo-correlative light and electron microscopy (cryo-CLEM), we observe oligomeric VIPP1 coats encapsulating membrane tubules within the Chlamydomonas chloroplast. Our work provides a structural foundation for understanding how VIPP1 directs thylakoid biogenesis and maintenance

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

Purpose: Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods: We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results: The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions: Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model