cssi/SciSciGPT-SciSciNet huggingface dataset:
Influential Parameters for the Analysis of Intracellular Parasite Metabolomics.

ABSTRACT Metabolomics is increasingly popular for the study of pathogens. For the malaria parasite Plasmodium falciparum, both targeted and untargeted metabolomics have improved our understanding of pathogenesis, host-parasite interactions, and antimalarial drug treatment and resistance. However, purification and analysis procedures for performing metabolomics on intracellular pathogens have not been explored. Here, we purified in vitro -grown ring-stage intraerythrocytic P. falciparum parasites for untargeted metabolomics studies; the small size of this developmental stage amplifies the challenges associated with metabolomics studies as the ratio between host and parasite biomass is maximized. Following metabolite identification and data preprocessing, we explored multiple confounding factors that influence data interpretation, including host contamination and normalization approaches (including double-stranded DNA, total protein, and parasite numbers). We conclude that normalization parameters have large effects on differential abundance analysis and recommend the thoughtful selection of these parameters. However, normalization does not remove the contribution from the parasite’s extracellular environment (culture media and host erythrocyte). In fact, we found that extraparasite material is as influential on the metabolome as treatment with a potent antimalarial drug with known metabolic effects (artemisinin). Because of this influence, we could not detect significant changes associated with drug treatment. Instead, we identified metabolites predictive of host and medium contamination that could be used to assess sample purification. Our analysis provides the first quantitative exploration of the effects of these factors on metabolomics data analysis; these findings provide a basis for development of improved experimental and analytical methods for future metabolomics studies of intracellular organisms. IMPORTANCE Molecular characterization of pathogens such as the malaria parasite can lead to improved biological understanding and novel treatment strategies. However, the distinctive biology of the Plasmodium parasite, including its repetitive genome and the requirement for growth within a host cell, hinders progress toward these goals. Untargeted metabolomics is a promising approach to learn about pathogen biology. By measuring many small molecules in the parasite at once, we gain a better understanding of important pathways that contribute to the parasite’s response to perturbations such as drug treatment. Although increasingly popular, approaches for intracellular parasite metabolomics and subsequent analysis are not well explored. The findings presented in this report emphasize the critical need for improvements in these areas to limit misinterpretation due to host metabolites and to standardize biological interpretation. Such improvements will aid both basic biological investigations and clinical efforts to understand important pathogens.
Research Design Issues in Studies Using Discretionary Accruals

Because discretionary accruals are known to be noisy proxies of earnings management that often produce biased results, we argue that a correlation between discretionary accruals and a hypothesized factor is generally not an adequate basis for valid inferences about earnings management. In this commentary, we propose and discuss a set of suggestions for improving the research design of studies on earnings management that use discretionary accruals. Specifically, we discuss suggestions for developing predictions about earnings management, choosing among discretionary accrual proxies, estimating discretionary accruals, addressing potential bias in the estimates, and critically evaluating the results obtained. [ABSTRACT FROM AUTHOR]
Laser-induced electron emission from Au nanowires: A probe for orthogonal polarizations

Photoelectron field emission, induced by femtosecond laser pulses focused on metallic nanotips, provides spatially coherent and temporally short electron pulses. The properties of the photoelectron yield give insight into both the material properties of the nanostructure and the exciting laser focus. Ultralong nanoribbons, grown as a single crystal attached to a metallic taper, are sources of electron field emission that have not yet been characterized. In this report, photoemission from gold nanoribbon samples is studied and compared to emission from tungsten and gold tips. We observe that the emission from sharp tips generally depends on one transverse component of the exciting laser field, while the emission of a blunted nanoribbon is found to be sensitive to both components. We propose that this property makes photoemission from nanoribbons a candidate for position-sensitive detection of the longitudinal field component in a tightly focused beam.
Verbal learning and memory in prelingually deaf children with cochlear implants

AbstractObjective: Deaf children with cochlear implants (CIs) show poorer verbal working memory compared to normal-hearing (NH) peers, but little is known about their verbal learning and memory (VLM) processes involving multi-trial free recall.Design: Children with CIs were compared to NH peers using the California Verbal Learning Test for Children (CVLT-C).Study sample: Participants were 21 deaf (before age 6 months) children (6–16 years old) implanted prior to age 3 years, and 21 age-IQ matched NH peers.Results: Results revealed no differences between groups in number of words recalled. However, CI users showed a pattern of increasing use of serial clustering strategies across learning trials, whereas NH peers decreased their use of serial clustering strategies. In the CI sample (but not in the NH sample), verbal working memory test scores were related to resistance to the build-up of proactive interference, and sentence recognition was associated with performance on the first exposure to the word list ...
The aggregate income losses from childhood stunting and the returns to a nutrition intervention aimed at reducing stunting

This paper undertakes two calculations, one for all developing countries, the other for 34 developing countries that together account for 90 percent of the world's stunted children. The first calculation asks how much lower a country's per capita income is today as a result of some of its workers having been stunted in childhood. The analysis uses a development accounting framework, relying on micro-econometric estimates of the effects of childhood stunting on adult wages, through the effects on years of schooling, cognitive skills, and height, parsing out the relative contribution of each set of returns to avoid double counting. The estimates show that, on average, the per capita income penalty from stunting is around 7 percent. The second calculation estimates the economic value and the costs associated with scaling up a package of nutrition interventions using the same methodology and set of assumptions used in the first calculation. The analysis considers a package of 10 nutrition interventions for which data are available on the effects and costs. The estimated rate-of-return from gradually introducing this program over a period of 10 years in the 34 countries is17 percent, and the corresponding benefit-cost ratio is 15:1.
Metrics for Signal Temporal Logic Formulae

Signal Temporal Logic (STL) is a formal language for describing a broad range of real-valued, temporal properties in cyber-physical systems. While there has been extensive research on verification and control synthesis from STL requirements, there is no formal framework for comparing two STL formulae. In this paper, we show that under mild assumptions, STL formulae admit a metric space. We propose two metrics over this space based on i) the Pompeiu-Hausdorff distance and ii) the symmetric difference measure and present algorithms to compute them. Alongside illustrative examples, we present an application of these metrics as design quality measures where they are used to compare all the temporal behaviors of a designed system, such as a synthetic genetic circuit, with the “desired” specification.
Vertebrate myosin 1d regulates left-right organizer morphogenesis and laterality.

Establishing left–right asymmetry is a fundamental process essential for arrangement of visceral organs during development. In vertebrates, motile cilia-driven fluid flow in the left–right organizer (LRO) is essential for initiating symmetry breaking event. Here, we report that myosin 1d (myo1d) is essential for establishing left–right asymmetry in zebrafish. Using super-resolution microscopy, we show that the zebrafish LRO, Kupffer’s vesicle (KV), fails to form a spherical lumen and establish proper unidirectional flow in the absence of myo1d. This process requires directed vacuolar trafficking in KV epithelial cells. Interestingly, the vacuole transporting function of zebrafish Myo1d can be substituted by myosin1C derived from an ancient eukaryote, Acanthamoeba castellanii, where it regulates the transport of contractile vacuoles. Our findings reveal an evolutionary conserved role for an unconventional myosin in vacuole trafficking, lumen formation, and determining laterality.
Observation-Informed Generalized Hybrid Error Covariance Models

AbstractBecause of imperfections in ensemble data assimilation schemes, one cannot assume that the ensemble-derived covariance matrix is equal to the true error covariance matrix. Here, we describe...
Efficient data ingestion and query processing for LSM-based storage systems

In recent years, the Log Structured Merge (LSM) tree has been widely adopted by NoSQL and NewSQL systems for its superior write performance. Despite its popularity, however, most existing work has focused on LSM-based key-value stores with only a single LSM-tree; auxiliary structures, which are critical for supporting ad-hoc queries, have received much less attention. In this paper, we focus on efficient data ingestion and query processing for general-purpose LSM-based storage systems. We first propose and evaluate a series of optimizations for efficient batched point lookups, significantly improving the range of applicability of LSM-based secondary indexes. We then present several new and efficient maintenance strategies for LSM-based storage systems. Finally, we have implemented and experimentally evaluated the proposed techniques in the context of the Apache AsterixDB system, and we present the results here.
How Do Right-To-Carry Laws Affect Crime Rates? Coping With Ambiguity Using Bounded-Variation Assumptions

Despite dozens of studies, research on crime has struggled to reach consensus about the impact of right-to-carry (RTC) gun laws. With this in mind, we formalize and apply a class of bounded variation assumptions that flexibly restrict the degree to which outcomes may vary across time and space. Using these assumptions, we present empirical analysis of the effect of RTC laws on violent and property crimes in Virginia, Maryland and Illinois. Imposing specific assumptions that we believe worthy of consideration, we find that RTC laws increase some crimes, decrease other crimes, and have effects that vary over time for others.
Muscle-specific regulation of right ventricular transcriptional responses to chronic hypoxia-induced hypertrophy by the muscle ring finger-1 (MuRF1) ubiquitin ligase in mice

We recently identified a role for the muscle-specific ubiquitin ligase MuRF1 in right-sided heart failure secondary to pulmonary hypertension induced by chronic hypoxia (CH). MuRF1−/− mice exposed to CH are resistant to right ventricular (RV) dysfunction whereas MuRF1 Tg + mice exhibit impaired function indicative of heart failure. The present study was undertaken to understand the underlying transcriptional alterations in the RV of MuRF1−/− and MuRF1 Tg + mice. Microarray analysis was performed on RNA isolated from the RV of MuRF1−/−, MuRF1 Tg+, and wild-type control mice exposed to CH. MuRF1−/− RV differentially expressed 590 genes in response to CH. Analysis of the top 66 genes (> 2-fold or 3-fold or < − 3-fold) revealed significant associations with oxidoreductase-metabolic, glycoprotein-transmembrane-integral proteins, and alternative splicing/splice variant annotations. The significant genes were enriched for promoters with ZIC1 protein transcription factor binding sites. The differentially expressed genes in MuRF1−/− and MuRF1 Tg + RV after CH have common functional annotations related to oxidoreductase (including antioxidant) and transmembrane component functions. Moreover, the functionally-enhanced MuRF1−/− hearts regulate genes related to transcription, homeobox proteins, and kinases/phosphorylation. These studies also reveal potential indirect effects of MuRF1 through regulating Rreb-1, and they reveal mechanisms by which MuRF1 may transcriptionally regulate anti-oxidant systems in the face of right heart failure.
Predicting Division Planes of Three-Dimensional Cells by Soap-Film Minimization

One key aspect of cell division in multicellular organisms is the orientation of the division plane. Proper division plane establishment contributes to normal plant body organization. To determine the importance of cell geometry in division plane orientation, we designed a three-dimensional probabilistic mathematical model to directly test the century-old hypothesis that cell divisions mimic soap-film minima. According to this hypothesis, daughter cells have equal volume and the division plane occurs where the surface area is at a minimum. We compared predicted division planes to a plant microtubule array that marks the division site, the preprophase band (PPB). PPB location typically matched one of the predicted divisions. Predicted divisions offset from the PPB occurred when a neighboring cell wall or PPB was directly adjacent to the predicted division site to avoid creating a potentially structurally unfavorable four-way junction. By comparing divisions of differently shaped plant cells (maize [Zea mays] epidermal cells and developing ligule cells and Arabidopsis thaliana guard cells) and animal cells (Caenorhabditis elegans embryonic cells) to divisions simulated in silico, we demonstrate the generality of this model to accurately predict in vivo division. This powerful model can be used to separate the contribution of geometry from mechanical stresses or developmental regulation in predicting division plane orientation.
Greedyflow: Distributed greedy packet routing between landmarks in DTNs

Abstract Delay Tolerant Networks (DTNs) have attracted much research interest recently due to its adaptability in areas without infrastructures. In such scenarios, moving data from one place (landmark) to another place (landmark) is essential for data communication between different areas. However, current DTN routing algorithms either fail to fully utilize node mobility or have additional requirements that cannot be satisfied easily in DTNs. Therefore, in this paper, we propose a distributed greedy routing algorithm, namely GreedyFlow, for efficient packet routing between landmarks in DTNs. GreedyFlow builds a local traffic map and a global landmark map on each node. The local traffic map indicates the node’s knowledge about the amount of traffic (node transition) between landmarks in the area where it primarily visits. The global landmark map shows the distribution of landmarks in the system and is built offline. In packet routing, the global landmark map shows the general packet forwarding direction, while the local traffic map helps determine the next-hop landmark on the fastest path in the forwarding direction. As a result, packets are greedily forwarded toward their destination landmarks. We also propose advanced components to enhance the consistency of local traffic maps and exploit node-based forwarding, both of which help improve the packet routing efficiency. Extensive real trace driven experiments demonstrate the high efficiency of GreedyFlow.
A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila

Summary Steroid hormones are a group of lipophilic hormones that are believed to enter cells by simple diffusion to regulate diverse physiological processes through intracellular nuclear receptors. Here, we challenge this model in Drosophila by demonstrating that Ecdysone Importer (EcI), a membrane transporter identified from two independent genetic screens, is involved in cellular uptake of the steroid hormone ecdysone. EcI encodes an organic anion transporting polypeptide of the evolutionarily conserved solute carrier organic anion superfamily. In vivo, EcI loss of function causes phenotypes indistinguishable from ecdysone- or ecdysone receptor (EcR)-deficient animals, and EcI knockdown inhibits cellular uptake of ecdysone. Furthermore, EcI regulates ecdysone signaling in a cell-autonomous manner and is both necessary and sufficient for inducing ecdysone-dependent gene expression in culture cells expressing EcR. Altogether, our results challenge the simple diffusion model for cellular uptake of ecdysone and may have wide implications for basic and medical aspects of steroid hormone studies.
From Machine to Machine: An OCT-Trained Deep Learning Algorithm for Objective Quantification of Glaucomatous Damage in Fundus Photographs

Purpose Previous approaches using deep learning (DL) algorithms to classify glaucomatous damage on fundus photographs have been limited by the requirement for human labeling of a reference training set. We propose a new approach using quantitative spectral-domain (SD) OCT data to train a DL algorithm to quantify glaucomatous structural damage on optic disc photographs. Design Cross-sectional study. Participants A total of 32 820 pairs of optic disc photographs and SD OCT retinal nerve fiber layer (RNFL) scans from 2312 eyes of 1198 participants. Methods The sample was divided randomly into validation plus training (80%) and test (20%) sets, with randomization performed at the patient level. A DL convolutional neural network was trained to assess optic disc photographs and predict SD OCT average RNFL thickness. Main Outcome Measures The DL algorithm performance was evaluated in the test sample by evaluating correlation and agreement between the predictions and actual SD OCT measurements. We also assessed the ability to discriminate eyes with glaucomatous visual field loss from healthy eyes with area under the receiver operating characteristic (ROC) curves. Results The mean prediction of average RNFL thickness from all 6292 optic disc photographs in the test set was 83.3±14.5 μm, whereas the mean average RNFL thickness from all corresponding SD OCT scans was 82.5±16.8 μm (P = 0.164). There was a very strong correlation between predicted and observed RNFL thickness values (Pearson r = 0.832; R2 = 69.3%; P Conclusions We introduced a novel DL approach to assess fundus photographs and provide quantitative information about the amount of neural damage that can be used to diagnose and stage glaucoma. In addition, training neural networks to predict SD OCT data objectively represents a new approach that overcomes limitations of human labeling and could be useful in other areas of ophthalmology.
Search for parking: A dynamic parking and route guidance system for efficient parking and traffic management

Parking space is a scarce resource in today’s cities. Travelers often spend a sizable amount of time searching for available parking spaces. This increases travelers’ overall travel cost and causes...
Were They Joking? Depends on Social Dominance Orientation

This investigation was conducted to determine how social dominance orientation (SDO) influences perceptions of race related comments. We discovered that individuals that were high in SDO perceive that a White authority figure was joking when a derogatory race related comment was made about White students, but they did not believe that a Black authority figure was joking when the same comment was made toward White students. This study further demonstrates that SDO plays a vital role in how individuals perceive interactions that involve race related bias.
The New Muon g 2 Experiment at Fermilab

Precision measurements of fundamental quantities have played a key role in pointing the way forward in developing our understanding of the universe. Though the enormously successful Standard Model (SM) describes the breadth of both historical and modern experimental particle physics data, it is necessarily incomplete. The muon $g-2$ experiment executed at Brookhaven concluded in 2001 and measured a discrepancy of more than three standard deviations compared to the Standard Model calculation. Arguably, this remains the strongest hint of physics beyond the SM. A new initiative at Fermilab is under construction to improve the experimental accuracy four-fold. The current status is presented here.
Broken symmetry in the human BK channel

ABSTRACT Voltage-gated and ligand-modulated ion channels play critical roles in excitable cells. To understand the interplay among voltage-sensing, ligand-binding and channel opening, the structures of ion channels in various functional states need to be determined. Here, the “random spherically constrained” (RSC) single-particle cryo-EM method was employed to study the human large conductance voltage- and calcium-activated potassium (hBK or hSlo1) channels reconstituted into liposomes. The hBK structure has been determined at 3.5 A resolution in the absence of Ca2+. Instead of the common four-fold symmetry observed in ligand-modulated ion channels, a two-fold symmetry was observed in hBK. Two opposing subunits in the Ca2+ sensing gating ring rotate around the center of each subunit, which results in the movement of the assembly and flexible interfaces and Ca2+ binding sites. Despite the significant movement, the local conformation of the assembly interfaces and Ca2+ binding sites remains the same among the four subunits.
Clarifying relative plausibility: A rejoinder:

This rejoinder replies to the twenty published commentaries on our article, “Relative Plausibility and Its Critics.” Our response has four objectives: 1) presenting further details regarding relati...
Temporal Logic Task Planning and Intermittent Connectivity Control of Mobile Robot Networks

In this paper, we develop a distributed intermittent communication and task planning framework for mobile robot teams. The goal of the robots is to accomplish complex tasks, captured by local linear temporal logic formulas, and share the collected information with all other robots and possibly also with a user. Specifically, we consider situations where the robot communication capabilities are not sufficient to form reliable and connected networks, while the robots move to accomplish their tasks. In this case, intermittent communication protocols are necessary that allow the robots to temporarily disconnect from the network in order to accomplish their tasks free of communication constraints. We assume that the robots can only communicate with each other when they meet at common locations in space. Our distributed control framework jointly determines local plans that allow all robots to fulfill their assigned temporal tasks, sequences of communication events that guarantee information exchange infinitely often, and optimal communication locations that minimize a desired distance metric. Simulation results verify the efficacy of the proposed controllers.
Effect of biopsy on the MRI radiomics classification of benign lesions and luminal A cancers

Radiomic features extracted from magnetic resonance (MR) images have potential for diagnosis and prognosis of breast cancer. However, presentation of lesions on images may be affected by biopsy. Thirty-four nonsize features were extracted from 338 dynamic contrast-enhanced MR images of benign lesions and luminal A cancers (80 benign/34 luminal A prebiopsy; 46 benign/178 luminal A postbiopsy). Feature value distributions were compared by biopsy condition using the Kolmogorov–Smirnov test. Classification performance was assessed by biopsy condition in the task of distinguishing between lesion types using the area under the receiver operating characteristic curve (AUCROC) as performance metric. Superiority and equivalence testing of differences in AUCROC between biopsy conditions were conducted using Bonferroni–Holm-adjusted significance levels. Distributions for most nonsize features for each lesion type failed to show a statistically significant difference between biopsy conditions. Fourteen features outperformed random guessing in classification. Their differences in AUCROC by biopsy condition failed to reach statistical significance, but we were unable to prove equivalence using a margin of ΔAUCROC = ± 0.10. However, classification performance for lesions imaged either prebiopsy or postbiopsy appears to be similar when taking into account biopsy condition.
Private Information Retrieval with Sublinear Online Time.

We present the first protocols for private information retrieval that allow fast (sublinear-time) database lookups without increasing the server-side storage requirements. To achieve these efficiency goals, our protocols work in an offline/online model. In an offline phase, which takes place before the client has decided which database bit it wants to read, the client fetches a short string from the servers. In a subsequent online phase, the client can privately retrieve its desired bit of the database by making a second query to the servers. By pushing the bulk of the server-side computation into the offline phase (which is independent of the client’s query), our protocols allow the online phase to complete very quickly—in time sublinear in the size of the database. Our protocols can provide statistical security in the two-server setting and computational security in the single-server setting. Finally, we prove that, in this model, our protocols are optimal in terms of the trade-off they achieve between communication and running time.
Semi-nonparametric modeling of topological domain formation from epigenetic data

Hi-C experiments capturing the 3D genome architecture have led to the discovery of topologically-associated domains (TADs) that form an important part of the 3D genome organization and appear to play a role in gene regulation and other functions. Several histone modifications have been independently associated with TAD formation, but their combinatorial effects on domain formation remain poorly understood at a global scale. We propose a convex semi-nonparametric approach called nTDP based on Bernstein polynomials to explore the joint effects of histone markers on TAD formation as well as predict TADs solely from the histone data. We find a small subset of modifications to be predictive of TADs across species. By inferring TADs using our trained model, we are able to predict TADs across different species and cell types, without the use of Hi-C data, suggesting their effect is conserved. This work provides the first comprehensive joint model of the effect of histone markers on domain formation. Our approach, nTDP, can form the basis of a unified, explanatory model of the relationship between epigenetic marks and topological domain structures. It can be used to predict domain boundaries for cell types, species, and conditions for which no Hi-C data is available. The model may also be of use for improving Hi-C-based domain finders.
Fluxonic Processing of Photonic Synapse Events

Much of the information processing performed by a biological neuron occurs in the dendritic tree. For artificial neural systems using light for communication, it is advantageous to convert signals to the electronic domain at synaptic terminals, so dendritic computation can be performed with electrical circuits. Here, we present circuits based on Josephson junctions and mutual inductors that act as dendrites, processing signals from synapses receiving single-photon communication events with superconducting detectors. We show simulations of circuits performing basic temporal filtering, logical operations, and nonlinear transfer functions. We further show how the synaptic signal from a single photon can fan out locally in the electronic domain to enable the dendrites of the receiving neuron to process a photonic synapse event or pulse train in multiple different ways simultaneously. Such a technique makes efficient use of photons, energy, space, and information.
Effect of Nanoparticle Shape on the Electrical and Thermal Properties of Solid Polymer Electrolytes

The effect of nanoparticle shape on the ionic conductivity and thermal properties of solid polymer electrolytes is reported. Poly(ethylene oxide) (PEO) and LiClO4 electrolytes with an ether oxygen to Li+ molar ratio of 10:1 are filled with TiO2 nanorods and elliptical-shaped fillers in the concentration ranges of 1–2.5 and 1–10 wt %, respectively. The filler concentration that provides the maximum improvement in the ionic conductivity scales inversely with aspect ratio (AR): 10 wt % for spherical nanoparticles (AR = 1), 5 wt % for ellipses (AR ≈ 4.4), and 1–2 wt % for nanorods (AR ≈ 6.6). The same trend is true for Fe2O3 nanofillers, suggesting that the observation is independent of the chemical identity of the metal oxide filler. While the filler concentration required to maximize the conductivity improvement is correlated to the nanofiller shape, the magnitude of the improvement is correlated to the surface-to-volume ratio of the filler. Specifically, the conductivity increases 1 order of magnitude by i...
EUS-Guided Pancreatic Cyst Ablation: a Clinical and Technical Review

Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined. Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm.
On the Convergence of Approximate Message Passing With Arbitrary Matrices

Approximate message passing (AMP) methods and their variants have attracted considerable recent attention for the problem of estimating a random vector x observed through a linear transform A. In the case of large i.i.d. zero-mean Gaussian A, the methods exhibit fast convergence with precise analytic characterizations on the algorithm behavior. However, the convergence of AMP under general transforms A is not fully understood. In this paper, we provide sufficient conditions for the convergence of a damped version of the generalized AMP (GAMP) algorithm in the case of quadratic cost functions (i.e., Gaussian likelihood and prior). It is shown that, with sufficient damping, the algorithm is guaranteed to converge, although the amount of damping grows with peak-to-average ratio of the squared singular values of the transforms A. This result explains the good performance of AMP on i.i.d. Gaussian transforms A, but also their difficulties with ill-conditioned or non-zero-mean transforms A. A related sufficient condition is then derived for the local stability of the damped GAMP method under general cost functions, assuming certain strict convexity conditions.
A Low-Power, Single-Chip Electronic Skin Interface for Prosthetic Applications

A low-power, single-chip electronic skin interface is presented. Its small size and reduced battery requirements are ideal for advanced prosthetic limbs that utilize electronic skin to provide their user tactile feedback. The architecture consists of multiple charge-sensitive analog front ends (AFEs) interfaced to a central, 16-bit microcontroller core which is capable of processing the sensory information in real-time. Event-driven operation allows the chip to monitor all input channels while idle and consuming minimal energy. A test chip has been fabricated in a 0.13 µm CMOS technology and implements 13 AFE channels. Its functionality is demonstrated by interfacing the chip to a prototype electronic skin based on polyvinylidene fluoride (PVDF) piezoelectric sensors. Signals from the sensors are captured by the presented chip and processed to calculate the corresponding charge. This is accomplished by programming the microcontroller with a custom software algorithm implemented in C, granting the system the flexibility to interface to different types of sensors. The single-chip electronic skin system consumes 7.0 µW per channel and 76.5 µW in the example application, making it suitable for use with battery-powered prosthetics.
Antiproton flux and properties of elementary particle fluxes in primary cosmic rays measured with the Alpha Magnetic Spectrometer on the International Space Station

Abstract Precision measurements by AMS of the antiproton flux and the antiproton-to-proton flux ratio in primary cosmic rays in the absolute rigidity range from 1 to 525 GV is presented, together with the fluxes and flux ratios of charged elementary particles in cosmic rays up to 1 TV. In the absolute rigidity range 60–500 GV, the antiproton p ¯ , proton p and positron e + fluxes are found to have nearly identical rigidity dependence and the electron e - flux exhibits different rigidity dependence. From 60GV to 500 GV, the p ¯ / p , p ¯ / e + and p / e + flux ratios are rigidity independent. These AMS measurements continue to reveal important properties of cosmic ray elementary particle fluxes and provide invaluable input towards understanding the origin of many observed unexpected phenomena.
A coupled manifold optimization framework to jointly model the functional connectomics and behavioral data spaces

The problem of linking functional connectomics to behavior is extremely challenging due to the complex interactions between the two distinct, but related, data domains. We propose a coupled manifold optimization framework which projects fMRI data onto a low dimensional matrix manifold common to the cohort. The patient specific loadings simultaneously map onto a behavioral measure of interest via a second, non-linear, manifold. By leveraging the kernel trick, we can optimize over a potentially infinite dimensional space without explicitly computing the embeddings. As opposed to conventional manifold learning, which assumes a fixed input representation, our framework directly optimizes for embedding directions that predict behavior. Our optimization algorithm combines proximal gradient descent with the trust region method, which has good convergence guarantees. We validate our framework on resting state fMRI from fifty-eight patients with Autism Spectrum Disorder using three distinct measures of clinical severity. Our method outperforms traditional representation learning techniques in a cross validated setting, thus demonstrating the predictive power of our coupled objective.
Conceptual Issues in Calibrating the Basel III Countercyclical Capital Buffer

This paper discusses issues in calibrating the countercyclical capital buffer (CCB) based on a sample of EU countries. It argues that the main indicator for buffer decisions under the Basel III framework, the credit-to-GDP gap, does not always work best in terms of covering bank loan losses that go beyond what could be expected from economic downturns. Instead, in the case of countries with short financial cycles and/or low financial deepening such as transition and developing economies, the Basel gap is shown to work best when computed with a low, smoothing factor and adjusted for the degree of financial deepening. The paper also analyzes issues in calibrating an appropriate size of the CCB and, using a loss function approach, points to a tradeoff between stability of the buffer size and cost efficiency considerations.
Data Poisoning Attacks on Stochastic Bandits.

Stochastic multi-armed bandits form a class of online learning problems that have important applications in online recommendation systems, adaptive medical treatment, and many others. Even though potential attacks against these learning algorithms may hijack their behavior, causing catastrophic loss in real-world applications, little is known about adversarial attacks on bandit algorithms. In this paper, we propose a framework of offline attacks on bandit algorithms and study convex optimization based attacks on several popular bandit algorithms. We show that the attacker can force the bandit algorithm to pull a target arm with high probability by a slight manipulation of the rewards in the data. Then we study a form of online attacks on bandit algorithms and propose an adaptive attack strategy against any bandit algorithm without the knowledge of the bandit algorithm. Our adaptive attack strategy can hijack the behavior of the bandit algorithm to suffer a linear regret with only a logarithmic cost to the attacker. Our results demonstrate a significant security threat to stochastic bandits.
Clinicopathological characteristics of ypT0N0 urothelial carcinoma following neoadjuvant chemotherapy and cystectomy.

Aims To describe a large tertiary care academic centre’s experience with patients who achieve a complete pathological response (ie, ypT0N0) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with emphasis on morphological features present in the RC and clinical outcome. Methods 41 patients with ypT0N0 disease following transurethral resection of bladder tumour (TURBT), NAC and RC with available clinical follow-up information were analysed. Slides from all RCs were reviewed to confirm pathological stage and assess for morphological parameters (eg, foreign body giant cell reaction, dystrophic calcification, scar and fat necrosis). Results With median follow-up of 32.8 months, the recurrence-free survival at 1 and 5 years was 97.4% and 93.5%, while the overall survival at 3 and 5 years was 94.2% and 88.6%, respectively. No patients died of urothelial carcinoma. Stage assigned at TURBT was 1 pTa (2%), 1 pT1 (2%), 38 pT2 (93%) and 1 pT3a (2%). 17 TURBTs demonstrated variant histology, with the majority of these being squamous (65%). The most common morphological features present at RC were scar (100%), foreign body giant cell reaction (80%), chronic inflammation within lamina propria (68%) and dystrophic calcifications (39%). Other morphological features were less common or absent. Conclusion ypT0N0 disease at RC portends an excellent prognosis, regardless of stage or variant histology in the TURBT; scar, foreign body giant cell reaction, chronic inflammation and dystrophic calcifications are often present.
Alkali metals plus complexants: From alkalides and electrides to aromatic anions

Electron transfer from an alkali metal to a suitable complexant for the cation can yield crystalline ionic solids that contain the complexed cation and either an alkali metal anion (alkalide) or a trapped electron (electride). The nature and properties of electrides are emphasized in this paper. When the organic complexant contains aromatic groups, the anionic species is an aromatic radical anion. Preliminary work on the addition of alkali metals to LOGEAs (large organic globular electron acceptors) is described and strategies for the synthesis of mixed electride-anion compounds are considered.
New chiral synthons for efficient introduction of bispropionates via stereospecific oxonia-cope rearrangements.

Compounds 1 and 2 are novel synthons for bispropionate synthesis, undergoing stereospecific Lewis acid-catalyzed transfer of the bispropionate unit with a variety of aldehydes, including α-chiral aldehydes. Thus 1 leads to the E-alkene bispropionate 3 with anti-stereochemistry, whereas diastereomer 2 gives the Z-alkene product 4, under mild conditions and with complete stereospecificity. The efficacy of this methodology is demonstrated in a short synthesis of invictolide beginning with 2 and (R)-2-methylpentanal.
High-resolution cryo-EM structures of outbreak strain human norovirus shells reveal size variations.

Noroviruses are a leading cause of foodborne illnesses worldwide. Although GII.4 strains have been responsible for most norovirus outbreaks, the assembled virus shell structures have been available in detail for only a single strain (GI.1). We present high-resolution (2.6- to 4.1-A) cryoelectron microscopy (cryo-EM) structures of GII.4, GII.2, GI.7, and GI.1 human norovirus outbreak strain virus-like particles (VLPs). Although norovirus VLPs have been thought to exist in a single-sized assembly, our structures reveal polymorphism between and within genogroups, with small, medium, and large particle sizes observed. Using asymmetric reconstruction, we were able to resolve a Zn2+ metal ion adjacent to the coreceptor binding site, which affected the structural stability of the shell. Our structures serve as valuable templates for facilitating vaccine formulations.
Synthesis of thieno[3,4-d]-1,3-dithiol-2-one derivatives

Abstract A series of mono-substituted and bis-substituted derivatives of thieno [3,4- d ]-1,3-dithiol-2-one were prepared through halogenation, chloromethylation, and subsequent nucleophilic substitution reactions. Compounds were characterized by NMR, FT-IR, and HRMS.
Inferring Demographic History Using Two-Locus Statistics

Population demographic history may be learned from contemporary genetic variation data. Methods based on aggregating the statistics of many single loci into an allele frequency spectrum (AFS) have proven powerful, but such methods ignore potentially informative patterns of linkage disequilibrium (LD) between neighboring loci. To leverage such patterns, we developed a composite-likelihood framework for inferring demographic history from aggregated statistics of pairs of loci. Using this framework, we show that two-locus statistics are more sensitive to demographic history than single-locus statistics such as the AFS. In particular, two-locus statistics escape the notorious confounding of depth and duration of a bottleneck, and they provide a means to estimate effective population size based on the recombination rather than mutation rate. We applied our approach to a Zambian population of Drosophila melanogaster. Notably, using both single- and two-locus statistics, we inferred a substantially lower ancestral effective population size than previous works and did not infer a bottleneck history. Together, our results demonstrate the broad potential for two-locus statistics to enable powerful population genetic inference.
The Interaction between ORF18 and ORF30 Is Required for Late Gene Expression in Kaposi's Sarcoma-Associated Herpesvirus

In the beta- and gammaherpesviruses, a specialized complex of viral transcriptional activators (vTAs) coordinate to direct expression of virus-encoded late genes, which are critical for viral assembly and whose transcription initiates only after the onset of viral DNA replication. The vTAs in Kaposi's sarcoma-associated herpesvirus (KSHV) are ORF18, ORF24, ORF30, ORF31, ORF34, and ORF66. While the general organization of the vTA complex has been mapped, the individual roles of these proteins and how they coordinate to activate late gene promoters remain largely unknown. Here, we performed a comprehensive mutational analysis of the conserved residues in ORF18, which is a highly interconnected vTA component. Surprisingly, the mutants were largely selective for disrupting the interaction with ORF30 but not the other three ORF18 binding partners. Furthermore, disrupting the ORF18-ORF30 interaction weakened the vTA complex as a whole, and an ORF18 point mutant that failed to bind ORF30 was unable to complement an ORF18 null virus. Thus, contacts between individual vTAs are critical as even small disruptions in this complex result in profound defects in KSHV late gene expression.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma and other B-cell cancers and remains a leading cause of death in immunocompromised individuals. A key step in the production of infectious virions is the transcription of viral late genes, which generates capsid and structural proteins and requires the coordination of six viral proteins that form a complex. The role of these proteins during transcription complex formation and the importance of protein-protein interactions are not well understood. Here, we focused on a central component of the complex, ORF18, and revealed that disruption of its interaction with even a single component of the complex (ORF30) prevents late gene expression and completion of the viral lifecycle. These findings underscore how individual interactions between the late gene transcription components are critical for both the stability and function of the complex.
PREPARATION OF AN o-SUBSTITUTED BENZAMIDINE BY THE PINNER METHOD. A LITERATURE CLARIFICATION

(1990). PREPARATION OF AN o-SUBSTITUTED BENZAMIDINE BY THE PINNER METHOD. A LITERATURE CLARIFICATION. Organic Preparations and Procedures International: Vol. 22, No. 5, pp. 643-645.
Cell-type and region-specific nucleus accumbens AMPAR plasticity associated with morphine reward, reinstatement, and spontaneous withdrawal

Despite evidence that morphine-related pathologies reflect adaptations in NAc glutamate signaling, substantial gaps in basic information remain. The current study examines the impact of non-contingent acute, repeated, and withdrawal-inducing morphine dosing regimens on glutamate transmission in D1- or D2-MSNs in the nucleus accumbens shell (NAcSh) and core (NAcC) sub-regions in hopes of identifying excitatory plasticity that may contribute to unique facets of opioid addiction-related behavior. Following an acute morphine injection (10 mg/kg), average miniature excitatory postsynaptic current (mEPSC) amplitude mediated by AMPA-type glutamate receptors was increased at D1-MSNs in the both the NAcShl and NAcC, whereas only the frequency of events was elevated at D2-MSNs in the NAcSh. In contrast, spontaneous somatic withdrawal induced by escalating dose of repeated morphine twice per day (20, 40, 60, 80, 100 mg/kg) enhanced mEPSC frequency specifically at D2-MSNs in the NAcSh. Similar to previous findings, excitatory drive was elevated at NAcSh D1-MSNs after 10–14 days home cage abstinence. Following abstinence, an acute drug re-exposure produced a rapid and enduring endocytosis of GluA2-containing AMPARs at D1-MSNs in the shell, that when blocked by an intra-NAc shell infusion of the Tat-GluA23Y peptide, increased reinstatement of morphine place preference—a phenomenon distinctly different than effects previously found with cocaine. The present study is the first to directly identify unique circuit specific adaptations in NAc glutamate synaptic transmission associated with morphine-related acute reward and somatic withdrawal as well as post-abstinence short-term plasticity. Moreover, while differing classes of abused drugs (i.e., psychostimulants and opioids) produce seemingly similar bidirectional plasticity in the NAc following drug re-exposure, our findings indicate this plasticity has distinct behavioral consequences.
Lewis acid promoted conjugate addition of vinylmagnesium bromide to chiral α,β-unsaturated N-acyl oxazolidinones

Abstract Lewis acid promoted conjugated additions of vinylmagnesium bromide to chiral α,β-unsaturated N-acyl oxazolidinones are described. A series of enatiomerically pure β-branched 4-pentenoic acid derivatives have been synthesized with high diastereoselectivity.