cssi/SciSciGPT-SciSciNet huggingface dataset:
High affinity interactions of Pb2+ with synaptotagmin I

Lead (Pb) is a potent neurotoxin that disrupts synaptic neurotransmission. We report that Synaptotagmin I (SytI), a key regulator of Ca2+-evoked neurotransmitter release, has two high-affinity Pb2+ binding sites that belong to its cytosolic C2A and C2B domains. The crystal structures of Pb2+-complexed C2 domains revealed that protein-bound Pb2+ ions have holodirected coordination geometries and all-oxygen coordination spheres. The on-rate constants of Pb2+ binding to the C2 domains of SytI are comparable to those of Ca2+ and are diffusion-limited. In contrast, the off-rate constants are at least two orders of magnitude smaller, indicating that Pb2+ can serve as both a thermodynamic and kinetic trap for the C2 domains. We demonstrate, using NMR spectroscopy, that population of these sites by Pb2+ ions inhibits further Ca2+ binding despite the existing coordination vacancies. Our work offers a unique insight into the bioinorganic chemistry of Pb(ii) and suggests a mechanism by which low concentrations of Pb2+ ions can interfere with the Ca2+-dependent function of SytI in the cell.
Experiments in Fast, Autonomous, GPS-Denied Quadrotor Flight

High speed navigation through unknown environments is a challenging problem in robotics. It requires fast computation and tight integration of all the subsystems on the robot such that the latency in the perception-action loop is as small as possible. Aerial robots add a limitation of payload capacity, which restricts the amount of computation that can be carried onboard. This requires efficient algorithms for each component in the navigation system. In this paper, we describe our quadrotor system which is able to smoothly navigate through mixed indoor and outdoor environments and is able to fly at speeds of more than 18 m/s. We provide an overview of our system and details about the specific component technologies that enable the high speed navigation capability of our platform. We demonstrate the robustness of our system through high speed autonomous flights and navigation through a variety of obstacle rich environments.
Inflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate

Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation. ER stress is increased with aging and other pathological stimuli. We hypothesized that age and mechanical stretch increase alveolar epithelial cells’ proinflammatory responses that are mediated by ER stress. Furthermore, we believed that inhibition of this upstream mechanism with 4PBA, an ER stress reducer, alleviates subsequent inflammation and monocyte recruitment. Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 2 months (young) and 20 months (old) of age. The cells were cyclically stretched at 15% change in surface area for up to 24 h. Prior to stretch, groups were administered 4PBA or vehicle as a control. Mechanical stretch and age upregulated ER stress and proinflammatory MCP-1/CCL2 and MIP-1β/CCL4 chemokine expression in ATIIs. Age-matched and mismatched monocyte recruitment by ATII conditioned media was also quantified. Age increases susceptibility to stretch-induced ER stress and downstream inflammatory gene expression in a primary ATII epithelial cell model. Administration of 4PBA attenuated the increased ER stress and proinflammatory responses from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media.
Mapping problem and requirements to final solution: A document analysis of capstone design projects:

Formulating and solving engineering problems and designing solutions that meet the established requirements are important skills that graduating engineering students need to possess. However, there...
Design of a Multi-Color Plenoptic Camera for Snapshot Hyperspectral Imaging

The design of a custom camera lens including: a two-lens optical system, filter array, and iris has been developed enabling a greyscale plenoptic camera to acquire full field-of-view, 2D, instantaneous hyperspectral measurements. This work focuses on the use of 7 discrete color filters and their effect on the image quality. It was determined that the placement of the filters inside the aperture plane of the camera was paramount to mitigating image artifacts. In addition, design rules were developed such that the optimal optical parameters (image distance, working distance, and focal length) can be easily determined from a few charts.
An anionic 3+2 cyclization-elimination route to cyclopentenes

Abstract Anionic 3+2 cyclization-elimination reactions between 1-benzenesulfonyl-2-( N,N -diisopropyl)carboxamidoallyllithium (2) and electron-deficient olefins provide the 4-substituted- N,N -diisopropylcyclopent-1-ene carboxamides 3–8 in yields of 22–89%.
Identifying errors in Freesurfer automated skull stripping and the incremental utility of manual intervention

Quality assurance (QA) is vital for ensuring the integrity of processed neuroimaging data for use in clinical neurosciences research. Manual QA (visual inspection) of processed brains for cortical surface reconstruction errors is resource-intensive, particularly with large datasets. Several semi-automated QA tools use quantitative detection of subjects for editing based on outlier brain regions. There were two project goals: (1) evaluate the assumption that statistical outliers are related to errors of cortical extension, and (2) examine whether error identification and correction significantly impacts estimation of cortical parameters and established brain-behavior relationships. T1 MPRAGE images (N = 530) of healthy adults were obtained from the NKI-Rockland Sample and reconstructed using Freesurfer 5.3. Visual inspection of T1 images was conducted for: (1) participants (n = 110) with outlier values (z scores ±3 SD) for subcortical and cortical segmentation volumes (outlier group), and (2) a random sample of remaining participants (n = 110) with segmentation values that did not meet the outlier criterion (non-outlier group). The outlier group had 21% more participants with visual inspection-identified errors than participants in the non-outlier group, with a medium effect size (Φ = 0.22). Nevertheless, a considerable portion of images with errors of cortical extension were found in the non-outlier group (41%). Although nine brain regions significantly changed size from pre- to post-editing (with effect sizes ranging from 0.26 to 0.59), editing did not substantially change the correlations of neurocognitive tasks and brain volumes (ps > 0.05). Statistically-based QA, although less resource intensive, is not accurate enough to supplant visual inspection. We discuss practical implications of our findings to guide resource allocation decisions for image processing.
Fast plane-wave reverse time migration

ABSTRACTPlane-wave reverse time migration (RTM) could potentially provide quick subsurface images by migrating fewer plane-wave gathers than shot gathers. However, the time delay between the first ...
Temporal resolution of single-photon responses in primate rod photoreceptors and limits imposed by cellular noise.

Many studies have focused on the visual system’s ability to detect photons, but not on its ability to encode the relative timing of detected photons. Timing is essential for computations such as de...
Talk to Me: A Case Study on Coordinating Expertise in Large-Scale Scientific Software Projects

Large-scale collaborative scientific software projects require more knowledge than any one person typically possesses. This makes coordination and communication of knowledge and expertise a key factor in creating and safeguarding software quality, without which we cannot have sustainable software. However, as researchers attempt to scale up the production of software, they are confronted by problems of awareness and understanding. This presents an opportunity to develop better practices and tools that directly address these challenges. To that end, we conducted a case study of developers of the Trilinos project. We surveyed the software development challenges addressed and show how those problems are connected with what they know and how they communicate. Based on these data, we provide a series of practicable recommendations, and outline a path forward for future research.
Early Identification of Pathogenic Social Media Accounts

Pathogenic Social Media (PSM) accounts such as terrorist supporters exploit large communities of supporters for conducting attacks on social media. Early detection of these accounts is crucial as they are high likely to be key users in making a harmful message “viral”. In this paper, we make the first attempt on utilizing causal inference to identify PSMs within a short time frame around their activity. We propose a time-decay causality metric and incorporate it into a causal community detection-based algorithm. The proposed algorithm is applied to groups of accounts sharing similar causality features and is followed by a classification algorithm to classify accounts as PSM or not. Unlike existing techniques that take significant time to collect information such as network, cascade path, or content, our scheme relies solely on action $\log$ of users. Results on a real-world dataset from Twitter demonstrate effectiveness and efficiency of our approach. We achieved precision of 0.84 for detecting PSMs only based on their first 10 days of activity; the misclassified accounts were then detected 10 days later.
Parametrically Robust Dynamic Speed Estimation Based Control for Doubly Fed Induction Generator

This paper presents a speed estimation based vector control architecture for doubly fed induction generator (DFIG). The main advantage of the proposed architecture is that with this methodology the generator can be operated without a speed sensor and position encoder. The method calculates the machine parameters online using a recursive least square (RLS) technique based on identifying the transfer function relating to rotor speed and position error. Minimum variance controller (MVC) ensures that the position error is minimum by proper estimation of the speed. For illustration, first, the small signal model of the machine and the regulator design is discussed. Then, a methodology is proposed, in which machine's mutual inductance is estimated online, so that the estimation approach is robust to changes in the machine parameters. Second, the control architecture with the speed estimation technique is discussed. The proposed approach is validated using a real-time simulation platform for a GE 1.5 MW wind turbine (both for steady-state operations and grid disturbance conditions) and with hardware in the loop (HIL) experimental setup for a 2-kW doubly fed induction machine (DFIM). Simulation results demonstrate desired steady-state and dynamic performance of this sensorless control approach for DFIG-based variable-speed wind turbines.
Evolution-Guided Policy Gradient in Reinforcement Learning

Deep Reinforcement Learning (DRL) algorithms have been successfully applied to a range of challenging control tasks. However, these methods typically suffer from three core difficulties: temporal credit assignment with sparse rewards, lack of effective exploration, and brittle convergence properties that are extremely sensitive to hyperparameters. Collectively, these challenges severely limit the applicability of these approaches to real world problems. Evolutionary Algorithms (EAs), a class of black box optimization techniques inspired by natural evolution, are well suited to address each of these three challenges. However, EAs typically suffer from high sample complexity and struggle to solve problems that require optimization of a large number of parameters. In this paper, we introduce Evolutionary Reinforcement Learning (ERL), a hybrid algorithm that leverages the population of an EA to provide diversified data to train an RL agent, and reinserts the RL agent into the EA population periodically to inject gradient information into the EA. ERL inherits EA's ability of temporal credit assignment with a fitness metric, effective exploration with a diverse set of policies, and stability of a population-based approach and complements it with off-policy DRL's ability to leverage gradients for higher sample efficiency and faster learning. Experiments in a range of challenging continuous control benchmarks demonstrate that ERL significantly outperforms prior DRL and EA methods.
Cyberbullying Detection System with Multiple Server Configurations

Due to the proliferation of online networking, friendships and relationships - social communications have reached a whole new level. As a result of this scenario, there is an increasing evidence that social applications are frequently used for bullying. State-of-the-art studies in cyberbullying detection have mainly focused on the content of the conversations while largely ignoring the users involved in cyberbullying. To encounter this problem, we have designed a distributed cyberbullying detection system that will detect bullying messages and drop them before they are sent to the intended receiver. A prototype has been created using the principles of NLP, Machine Learning and Distributed Systems. Preliminary studies conducted with it, indicate a strong promise of our approach.
Change in future climate due to Antarctic meltwater

Meltwater from the Antarctic Ice Sheet is projected to cause up to one metre of sea-level rise by 2100 under the highest greenhouse gas concentration trajectory (RCP8.5) considered by the Intergovernmental Panel on Climate Change (IPCC). However, the effects of meltwater from the ice sheets and ice shelves of Antarctica are not included in the widely used CMIP5 climate models, which introduces bias into IPCC climate projections. Here we assess a large ensemble simulation of the CMIP5 model ‘GFDL ESM2M’ that accounts for RCP8.5-projected Antarctic Ice Sheet meltwater. We find that, relative to the standard RCP8.5 scenario, accounting for meltwater delays the exceedance of the maximum global-mean atmospheric warming targets of 1.5 and 2 degrees Celsius by more than a decade, enhances drying of the Southern Hemisphere and reduces drying of the Northern Hemisphere, increases the formation of Antarctic sea ice (consistent with recent observations of increasing Antarctic sea-ice area) and warms the subsurface ocean around the Antarctic coast. Moreover, the meltwater-induced subsurface ocean warming could lead to further ice-sheet and ice-shelf melting through a positive feedback mechanism, highlighting the importance of including meltwater effects in simulations of future climate. Accounting for meltwater from the Antarctic Ice Sheet in simulations of global climate leads to substantial changes in future climate projections and identifies a potential feedback mechanism that exacerbates melting.
Point cloud processing via recurrent set encoding

We present a new permutation-invariant network for 3D point cloud processing. Our network is composed of a recurrent set encoder and a convolutional feature aggregator. Given an unordered point set, the encoder firstly partitions its ambient space into parallel beams. Points within each beam are then modeled as a sequence and encoded into subregional geometric features by a shared recurrent neural network (RNN). The spatial layout of the beams is regular, and this allows the beam features to be further fed into an efficient 2D convolutional neural network (CNN) for hierarchical feature aggregation. Our network is effective at spatial feature learning, and competes favorably with the state-of-the-arts (SOTAs) on a number of benchmarks. Meanwhile, it is significantly more efficient compared to the SOTAs.
International Standardization of Base Line Tapes and Wires

The International Bureau of Weights and Measures has sent a group of invar base-line wires for standardization to several of the national laboratories. Twenty-four-meter invar wires are used rather generally in Eruope for geodetic base-line work instead of the 50-meter base-line tapes used by the United States Coast and Geodetic Survey. These wires are described in “La mesure rapide des bases geodesiques” by J. R. Benoit and C. E. Guillaume. The standardization of these wires at the International Bureau is carried out in a basementroom in the main laboratory building. The new equipment, Installed a few years ago, is described by Dr. Guillaume in an article entitled “La nouvelle base edifiee au Bureau International,” published in the “Proces-verbaux des seances” of the International Committee for the session of 1925. The working standard for the measurements is an H-shaped four-meter invar bar.
Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel

Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic β-cell function. Despite the significance of estrogen hormones for regulation of glucose metabolism, little is known about the roles of endogenous estrogen metabolites in modulating pancreatic β-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic β-cells. We show that catechol estrogens, hydroxylated at positions C2 and C4 of the steroid A ring, rapidly potentiated glucose-induced insulin secretion via a nongenomic mechanism. 2-Hydroxyestrone, the most abundant endogenous estrogen metabolite, was more efficacious in stimulating insulin secretion than any other tested catechol estrogens. In insulin-secreting cells, catechol estrogens produced rapid activation of calcium influx and elevation in cytosolic free calcium. Catechol estrogens also generated sustained elevations in cytosolic free calcium and evoked inward ion current in HEK293 cells expressing the transient receptor potential A1 (TRPA1) cation channel. Calcium influx and insulin secretion stimulated by estrogen metabolites were dependent on the TRPA1 activity and inhibited with the channel-specific pharmacological antagonists or the siRNA. Our results suggest the role of estrogen metabolism in a direct regulation of TRPA1 activity with potential implications for metabolic diseases.
Nudging: A Very Short Guide

This brief essay offers a general introduction to the idea of nudging, along with a list of ten of the most important “nudges.” It also provides a short discussion of the question whether to create a separate “behavioral insights unit” or instead to rely on existing institutions.
Prosecutorial Discretion, Drug Case Selection, and Inequality in Federal Court

In this article, I explore variations in prosecutors’ discretionary case selection practices by drawing on findings from a comparative field research project of drug prosecutions conducted in four ...
Computer-Aided Diagnosis †

A provider's ability to make correct decisions regarding patient care is predicated on the correct identification of a patient's diagnoses. However, the process of developing diagnostic certainty remains a challenging task despite an increasingly sophisticated array of available diagnostic modalities and techniques. Clinicians need support to integrate a broad range of findings from these tools along with a patient's symptoms and signs. This chapter discusses the evolution and utility of computer-aided diagnostic decision support systems including recent developments in neural networks, microarray technology, and syndromic surveillance. Keywords: diagnostic decision support; Bayesian analysis; belief networks; decision trees; neural networks; microarray technology; syndromic surveillance
Matrix Completion as a Post-Processing Technique for Probabilistic Roadmaps

This paper describes a novel post-processing algorithm for probabilistic roadmaps (PRMs), inspired by the recent literature on matrix completion. We argue that the adjacency matrix associated with real roadmaps can be decomposed into the sum of low-rank and sparse matrices. Our method, based on Robust Principal Component Analysis (RPCA), numerically computes a relaxation of this decomposition by solving a convex optimization problem–even when most of the entries in the adjacency matrix are unknown. Given a PRM with n vertices and only \(O(n log^2 n)\) collision-checked candidate edges, the algorithm estimates the status of all \(n(n - 1)/2\) possible edges in the full road map with high accuracy, without performing any additional collision checks. Numerical experiments on problems from the Open Motion Planning Library indicate that they posses the requisite low-rank plus sparse structure; and that after checking 5% of the possible edges, the algorithm estimates the full visibility graph with 96% accuracy. Based on numerical experiments, we propose sharper estimates of the error as a function of number of edge checks than what is previously reported. The practical utility of the algorithm is that average path length across the resulting denser edge set is significantly shorter (at the cost of somewhat increased spatial complexity and query times). An ancillary benefit is that the resulting low-rank plus sparse decomposition readily reveals information about that would be otherwise difficult to compute, such as the number of convex cells in free configuration space and the number of vertices in each.We believe that this novel connection between motion planning and matrix completion–two previously disparate lines of research–provides a new perspective on sampling-based motion planning and may guide future algorithm development.
Near-Optimal Design for Fault-Tolerant Systems with Homogeneous Components under Incomplete Information

In this paper, we study a fault-tolerant control for systems consisting of multiple homogeneous components such as parallel processing machines. This type of system is often more robust to uncertainty compared to those with a single component. The state of each component is either in the operating mode or faulty. At any time instant, each component may independently become faulty according to a Bernoulli probability distribution. If a component is faulty, it remains so until it is fixed. The objective is to design a fault-tolerant system by sequentially choosing one of the following three options: (a) do nothing at zero cost; b) detect the number of faulty components at the cost of inspection, and c) fix the system at the cost of repairing faulty components. A Bellman equation is developed to identify a near-optimal solution for the problem. The efficacy of the proposed solution is verified by numerical simulations.
A Note on Pricing With Market Power: Third-Degree Price Discrimination With Quality-Differentiated Demand:

The article points up limitations in the standard undergraduate treatment of third-degree price discrimination by monopolists. While such treatments allude to qualitative distinctions between highe...
Improving Safety in Reinforcement Learning Using Model-Based Architectures and Human Intervention

This work is supported by U.S. Army Research Laboratory under Cooperative Agreement Number W911NF-10-2-0022
Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation.

Purpose To determine whether trypan blue (TB) reduces canine lens epithelial cell (LEC) or corneal endothelial cell (CEC) viability in vitro; if cell death is noted, to subsequently evaluate the molecular mechanism. Methods Cellular viability was determined using a lactate dehydrogenase (LDH) assay. In TB-treated LECs, caspase 3/7 activity was assessed to evaluate apoptosis; autophagy was evaluated using immunoblotting against LC3 and p62. To evaluate the effects of TB on ex vivo posterior capsule opacification (PCO), following mock cataract surgery, lens capsules were treated with TB and subsequently maintained in culture to determine LEC migration and proliferation. Results Following acute exposure, TB did not significantly reduce LEC or CEC viability at any of the concentrations tested. Increased caspase 3/7 activity was found in LEC cultures treated with TB for an extended period of time; no change in LC3 or p62 expression was noted. Ex vivo PCO formation was not significantly altered by TB treatment. Conclusions Acute exposure to TB did not reduce LEC or CEC viability, and only longer exposure to TB was able to initiate apoptosis. Treatment with intraocular TB at the time of cataract surgery is likely safe to the CECs but will not prevent PCO formation.
Enhancing keV high harmonic signals generated by long-wave infrared lasers

It is indicated by single-atom simulations that the intensity of a single isolated X-ray pulse in the 3.4 to 4 keV region from an 8 micron laser driven high harmonic generation can be increased by more than two orders of magnitude when a single-cycle pulse centered at 800 nm is added. The ionization probability of a helium atom by the two-pulse field is set to $4.56 \times {10^{ - 5}}$4.56×10−5, which is needed for balancing the index of refraction of free electrons with that of neutral helium atoms to achieve phase matching.
Dynamic Mechanism Design with Budget-Constrained Buyers Under Limited Commitment

We study the dynamic mechanism design problem of a seller who repeatedly auctions independent items over a discrete time horizon to buyers who face a cumulative budget constraint. A driving motivat...
Oceans on Mars: The possibility of a Noachian groundwater-fed ocean in a sub-freezing martian climate

Abstract The Noachian climate of Mars is thought by many to have been “warm and wet”, characterized by a global mean annual temperature (MAT) >273 K and abundant rainfall infiltrating into the groundwater system. In this “warm and wet” scenario, when the groundwater system was in contact with the surface in the northern lowlands, a groundwater-fed ocean could form. In contrast, 1-dimensional climate models and 3-dimensional general circulation models (GCMs) are unable to reproduce long-lived, continuous “warm and wet” conditions due to the influence of the faint young Sun when considering a pure CO2-H2O atmosphere; these models instead predict “cold and icy” conditions, characterized by MAT ~225 K and water trapped as snow and ice in the southern highlands. Furthermore, a kilometers-thick globally continuous cryosphere is predicted in this “cold and icy” scenario, precluding direct connection of the groundwater system and the surface, and disfavoring a Noachian northern lowlands ocean. However, global MAT values lack information about regional and seasonal temperature variations, which may vary significantly from global MAT. In this work, we explore whether regional or seasonal temperature variations could permit the formation of a Noachian ocean in a climate with global MAT 273 K. If the long-lived Noachian global MAT was >255 K (~30 K above the nominal ambient “cold and icy” climate) and the subsurface contained >63 m global equivalent layer (GEL) of groundwater, then groundwater could be released onto the surface and pond on the floor of the Hellas basin; global MAT >258 K and a subsurface water inventory of >170 m GEL are required for release of groundwater into the topographically lowest regions of Utopia Planitia. If a subsurface water reservoir of ≥770 m GEL existed and local MAT was ≥273 K at Utopia, groundwater release could occur at Utopia and lead to flooding of the northern lowlands and formation of an ocean up to the level of Contact 1. Further, in a “cold and icy” MAT 225 K climate, short-term punctuated heating that raised global MAT to >255 K for at least a few thousand years could lead to groundwater release and flooding of the lowest points on Mars. Under the influence of these very cold climates (global MAT ~255–260 K), these bodies of water would remain ice-free for a geologically short period of time, possibly only a few hundred days, and would completely freeze and sublime in only a few thousand years.
Resource abundance, market size, and the choice of technology

How resource abundance and market size affect the choice of increasing returns technologies is studied in an overlapping-generations general equilibrium model in which manufacturing firms engage in oligopolistic competition. The model is surprisingly tractable. First, for the steady state, the wage rate, the level of technology, and capital stock are not affected by the amount of natural resources. An increase in the share of agricultural revenue going to natural resources leads to a lower wage rate and firms choose less advanced technologies. Second, an increase in market size increases the equilibrium wage rate, level of technology, and capital stock. Finally, other things equal, a country with a lower endowment of natural resources or a higher market size has a comparative advantage in producing the manufactured good.
A catalytic, highly stereoselective aldehyde olefination reaction

Abstract A catalytic aldehyde olefination reaction has been discovered. A Cu(II) complex (5 mol %) derived from a salen-quinine mixed ligand catalyzed the reaction between aldehydes and two molecules of acetyl chloride to produce trans C–C double bonds exclusively. The new catalytic aldehyde alkenation reaction presumably goes through a C-3 acylated β-lactone intermediate that loses one molecule of CO 2 .
Highly enantioselective Ru-catalyzed hydrogenation of β-keto esters using electron-donating bis(trialkylphosphine) ligand-TangPhos

Highly electron-donating bis(trialkylphosphine) TangPhos and its corresponding ruthenium complexes provided high enantioselectivities for the hydrogenation of β-keto esters. Up to 99.8% and 99.5% ee have been achieved in hydrogenation of β-alkyl and β-aryl substituted β-keto esters, respectively. Asymmetric hydrogenation of ethyl 4-chloro acetoacetate in 98.2% ee is also reported.
Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging.

A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an in situ polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell-interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.
Synthesis and resolution of a new chiral C2-symmetric bisphenol: trans-1,2-bis(2-hydroxyphenyl)cyclopentane

Abstract The title compound was prepared in six steps from dicumarol. Subsequent resolution with O-methylmandelic acid gave either enantiomer in ≥98% ee.
Conjugate reduction of polyfunctional α,β-unsaturated carbonyl compounds using [(Ph3P)CuH]6. Compatibility with halogen, sulfonate, and γ-oxygen and sulfur substituents

Abstract In contrast to organocuprate conjugate addition and standard methods for conjugate reduction, use of the stable copper(I) hydride cluster, [(Ph3P)CuH]6, allows chemoselective conjugate reduction of α,β-unsaturated carbonyl compounds substituted at the γ-position with leaving groups. In addition, the compatibility of the conjugate reduction with organic halides and sulfonate groups is demonstrated.
Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor

A short and effective synthesis of N-linked di- and trisaccharides is described. In a high-yielding reaction sequence, the glucosamine derivative 1 was transformed to the 3-azido-2,3-dideoxy sugar ...
Highly Fluorinated Cyclopentanones and Their Enols

2H-Perfluorocyclopentanone (1k) and its enol (1e) have been independently synthesized and equilibrated. In carbon tetrachloride, the enol is the only detectable form at equilibrium. In addition to its high relative stability, this enol displays interesting reactivity, including reversible bromination and hydrolysis reactions. Replacing the vinyl fluorine of 1e with hydrogen changes the relative enol stability dramatically as the enol is only present to the extent of 13% in carbon tetrachloride under equilibrating conditions. In Lewis basic solvents, however, the enol is the only detectable form because of its strength as a hydrogen bond donor. Quantum mechanical calculations on both systems suggest that ketone destabilization, but not enol stabilization, by fluorination is responsible for the remarkable relative stability of the enols.
A computational solution to improve biomarker reproducibility during long-term projects.

Biomarkers are fundamental to basic and clinical research outcomes by reporting host responses and providing insight into disease pathophysiology. Measuring biomarkers with research-use ELISA kits is universal, yet lack of kit standardization and unexpected lot-to-lot variability presents analytic challenges for long-term projects. During an ongoing two-year project measuring plasma biomarkers in cancer patients, control concentrations for one biomarker (PF) decreased significantly after changes in ELISA kit lots. A comprehensive operations review pointed to standard curve shifts with the new kits, an analytic variable that jeopardized data already collected on hundreds of patient samples. After excluding other reasonable contributors to data variability, a computational solution was developed to provide a uniform platform for data analysis across multiple ELISA kit lots. The solution (ELISAtools) was developed within open-access R software in which variability between kits is treated as a batch effect. A defined best-fit Reference standard curve is modelled, a unique Shift factor “S” is calculated for every standard curve and data adjusted accordingly. The averaged S factors for PF ELISA kit lots #1–5 ranged from -0.086 to 0.735, and reduced control inter-assay variability from 62.4% to <9%, within quality control limits. S factors calculated for four other biomarkers provided a quantitative metric to monitor ELISAs over the 10 month study period for quality control purposes. Reproducible biomarker measurements are essential, particularly for long-term projects with valuable patient samples. Use of research-use ELISA kits is ubiquitous and judicious use of this computational solution maximizes biomarker reproducibility.
Microbial Communities Are Well Adapted to Disturbances in Energy Input.

ABSTRACT Although microbial systems are well suited for studying concepts in ecological theory, little is known about how microbial communities respond to long-term periodic perturbations beyond diel oscillations. Taking advantage of an ongoing microcosm experiment, we studied how methanotrophic microbial communities adapted to disturbances in energy input over a 20-day cycle period. Sequencing of bacterial 16S rRNA genes together with quantification of microbial abundance and ecosystem function were used to explore the long-term dynamics (510 days) of methanotrophic communities under continuous versus cyclic chemical energy supply. We observed that microbial communities appeared inherently well adapted to disturbances in energy input and that changes in community structure in both treatments were more dependent on internal dynamics than on external forcing. The results also showed that the rare biosphere was critical to seeding the internal community dynamics, perhaps due to cross-feeding or other strategies. We conclude that in our experimental system, internal feedbacks were more important than external drivers in shaping the community dynamics over time, suggesting that ecosystems can maintain their function despite inherently unstable community dynamics. IMPORTANCE Within the broader ecological context, biological communities are often viewed as stable and as only experiencing succession or replacement when subject to external perturbations, such as changes in food availability or the introduction of exotic species. Our findings indicate that microbial communities can exhibit strong internal dynamics that may be more important in shaping community succession than external drivers. Dynamic “unstable” communities may be important for ecosystem functional stability, with rare organisms playing an important role in community restructuring. Understanding the mechanisms responsible for internal community dynamics will certainly be required for understanding and manipulating microbiomes in both host-associated and natural ecosystems.
Diastereo- and Enantiodifferentiation in Indium-Promoted Allylations of 2,3-Azetidinediones in Water. Definition of Long-Range Stereocontrol Elements on π-Facial Selectivity for β-Lactam Synthesis

The stereochemical course of the reactions of N-benzyl-2,3-azetidinedione with six differently functionalized allylic bromides, as promoted by indium metal in 1:1 H2O−THF, were initially examined. ...
Growth and characterization of heavily doped silicon crystals

Silicon crystals grown with the Czochralski method are still the most common material used for the production of electronic devices. In recent years, a growing need of large diameter crystals with increasingly higher doping levels is observed, especially to support the expanding market of discrete devices and its trend towards lower and lower resistivity levels for the silicon substrate. The growth of such heavily doped, large-diameter crystals poses several new challenges to the crystal grower, and the presence of a high dopant concentration in the crystal affects significantly its main properties, requiring also the development of dedicated characterization techniques. This paper illustrates the recent advances in the growth and characterization of silicon crystals heavily doped with antimony, arsenic, phosphorus and boron. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Intramolecular cyclization manifolds of 4-alkylpyridines bearing ambiphilic side chains: construction of spirodihydropyridines or benzylic cyclization via anhydrobase intermediates.

4-Alkylpyridines possessing nucleophilic β-dicarbonyl side chains have been converted to spirodihydropyridines upon treatment with ethyl chloroformate and sub-stoichiometric amounts of Ti(OiPr)4. Alternatively, inclusion of mild base in the reaction medium was found to facilitate generation of anhydrobase intermediates. Subsequent aldol-like condensations with electrophilic side chain moieties followed by hydrolysis delivered benzylically cyclized pyridines in good yield. In situ hydrogenation of cyclized anhydrobase intermediates afforded 4-substituted piperidines.
Syntheses of β- and γ-fluorophenyl cis- and trans-α-methylene-γ-butyrolactones

Abstract Preparation of a series of cis -γ-fluorophenyl-β-phenyl-α-methylene-γ-butyrolactones is reported via ‘allylboration’ of fluorobenzaldehydes with ( E )-methyl 3-phenyl-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)acrylate. The corresponding trans-γ-fluorophenyl lactones were prepared either (i) via ‘allylboration’ using the ( Z )-reagents or (ii) via an indium triflate-mediated isomerization of the cis -products. The difficulty in isomerizing difluorinated cis -products confirms the probable intermediacy of carbocations. Finally, the synthesis of cis -β-fluorophenyl-γ-phenyl-α-methylene-γ-butyrolactones was achieved via an indium-catalyzed allylation–lactonization of aldehydes with ( Z )-2-(bromomethyl)-3-(fluorophenyl)acrylates.
ResistanceGA: An R package for the optimization of resistance surfaces using genetic algorithms

1. Understanding how landscape features affect functional connectivity among populations is a cornerstone of landscape genetic analyses. However, parameterization of resistance surfaces that best describe connectivity is largely a subjective process that explores a limited parameter space. 2. ResistanceGA is a new R package that utilizes a genetic algorithm to optimize resistance surfaces based on pairwise genetic distances and either CIRCUITSCAPE resistance distances or cost distances calculated along least cost paths. Functions in this package allow for the optimization of both categorical and continuous resistance surfaces, as well as the simultaneous optimization of multiple resistance surfaces. 3. There is considerable controversy concerning the use of Mantel tests to accurately relate pairwise genetic distances with resistance distances. Optimization in ResistanceGA uses linear mixed effects models with the maximum likelihood population effects parameterization to determine AICc, which is the fitness function for the genetic algorithm. 4. ResistanceGA fills a void in the landscape genetic toolbox, allowing for unbiased optimization of resistance surfaces and for the simultaneous optimization of multiple resistance surfaces to create a novel composite resistance surface.
AIControl: replacing matched control experiments with machine learning improves ChIP-seq peak identification

ChIP-seq is a technique to determine binding locations of transcription factors, which remains a central challenge in molecular biology. Current practice is to use a 'control' dataset to remove background signals from a immunoprecipitation (IP) 'target' dataset. We introduce the AIControl framework, which eliminates the need to obtain a control dataset and instead identifies binding peaks by estimating the distributions of background signals from many publicly available control ChIP-seq datasets. We thereby avoid the cost of running control experiments while simultaneously increasing the accuracy of binding location identification. Specifically, AIControl can (i) estimate background signals at fine resolution, (ii) systematically weigh the most appropriate control datasets in a data-driven way, (iii) capture sources of potential biases that may be missed by one control dataset and (iv) remove the need for costly and time-consuming control experiments. We applied AIControl to 410 IP datasets in the ENCODE ChIP-seq database, using 440 control datasets from 107 cell types to impute background signal. Without using matched control datasets, AIControl identified peaks that were more enriched for putative binding sites than those identified by other popular peak callers that used a matched control dataset. We also demonstrated that our framework identifies binding sites that recover documented protein interactions more accurately.
Palladium-catalyzed cross-coupling reaction of alkynylzincs with benzylic electrophiles

Abstract The reaction of alkynylzinc bromides with benzyl bromides or chlorides in the presence of a catalytic amount of Pd(DPEphos)Cl2 in THF at 23 °C cleanly produces the corresponding benzylated alkynes in 73–97% yields. With 10−3 mol % of Pd(DPEphos)Cl2, the maximum turnover number of 7.1 × 104 has been observed for the formation of PhC CCH2Ph.
Samarium-promoted coupling of pyridine-based heteroaryl analogues of benzylic acetates with carbonyl compounds.

2-Substituted pyridine, quinoline, isoquinoline, bipyridine, and 1,10-phenanthroline analogues of benzylic acetates undergo SmI2-promoted coupling with aldehydes and ketones to afford (2-hydroxyalkyl)heteroaromatics.
Synthesis of prodrug candidates: conjugates of amino acid with nucleoside boranophosphate.

Preparation of antiviral and anticancer prodrug candidates, P-tyrosinyl(P-O)-5‘-P-nucleosidyl boranophosphates, is described. One-pot synthesis via a phosphoramidite method resulted in the title compounds with good yields. The P-boranophosphate diastereomers were separated by RP-HPLC, and their structures were confirmed by 1H and 31P NMR spectroscopy and MS analysis.
Communication and quorum sensing in non-living mimics of eukaryotic cells

Cells in tissues or biofilms communicate with one another through chemical and mechanical signals to coordinate collective behaviors. Non-living cell mimics provide simplified models of natural systems; however, it has remained challenging to implement communication capabilities comparable to living cells. Here we present a porous artificial cell-mimic containing a nucleus-like DNA-hydrogel compartment that is able to express and display proteins, and communicate with neighboring cell-mimics through diffusive protein signals. We show that communication between cell-mimics allows distribution of tasks, quorum sensing, and cellular differentiation according to local environment. Cell-mimics can be manufactured in large quantities, easily stored, chemically modified, and spatially organized into diffusively connected tissue-like arrangements, offering a means for studying communication in large ensembles of artificial cells.
The synthesis of biologically relevant 4(5)‐phosphono‐5(4)‐aminoimidazoles using a Pd‐catalyzed coupling reaction

Regiochemically defined 1-benzyl-4-phosphono-5-carboalkoxyimidazoles were synthesized from the corresponding 4-bromoimidazoles using a tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling reaction with diethyl phosphite. The corresponding Michaelis-Arbusov reaction failed to give a phospho-nylated product. The carbomethoxy moiety was converted to an amino group using a Curtius rearrangement to afford 1-benzyl-4-phosphono-5-amino-imidazoles. Following deprotection and hydrolysis, phos-phonic acid-linked aminoimidazoles were accessed that resemble intermediates formed during purine biosynthesis.
An intersection of privatization and public utility regulation: The Ohio State University's energy concession agreement

Abstract U.S. colleges and universities have for some time joined the privatization movement where university functions and assets are turned over to private contractors. Here we present a case of a 50-year comprehensive energy concession agreement by The Ohio State University that generated an up-front payment exceeding a billion dollars. The agreement, with many principles and design practices borrowed directly from economic regulation of public utilities and against the backdrop of the literature on privatization and contract theory, provides an insightful case that informs these literature, as well as future privatization efforts by universities and other large-scale public organizations.
The Enantiospecific Synthesis of an Isoxazoline. A RGD Mimic Platelet GPIIb/IIIa Antagonist.

A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and >99.6% optical purity, starting from l-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of Nα-n-Boc-l-asparagine with iodosobenzene diacetate provides optically pure Nα-n-Boc-l-α,β-diaminopropionic acid (8) in 75% yield. A process of lipase resolution−base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.