cssi/SciSciGPT-SciSciNet huggingface dataset:
A convex optimization approach to radiation treatment planning with dose constraints

We present a method for handling dose constraints as part of a convex programming framework for inverse treatment planning. Our method uniformly handles mean dose, maximum dose, minimum dose, and dose-volume (i.e., percentile) constraints as part of a convex formulation. Since dose-volume constraints are non-convex, we replace them with a convex restriction. This restriction is, by definition, conservative; to mitigate its impact on the clinical objectives, we develop a two-pass planning algorithm that allows each dose-volume constraint to be met exactly on a second pass by the solver if its corresponding restriction is feasible on the first pass. In another variant, we add slack variables to each dose constraint to prevent the problem from becoming infeasible when the user specifies an incompatible set of constraints or when the constraints are made infeasible by our restriction. Finally, we introduce ConRad, a Python-embedded open-source software package for convex radiation treatment planning. ConRad implements the methods described above and allows users to construct and plan cases through a simple interface.
Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.

Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and...
Robust Genome Editing with Short Single-Stranded and Long, Partially Single-Stranded DNA Donors in Caenorhabditis elegans .

CRISPR-based genome editing using ribonucleoprotein complexes and synthetic single-stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs—such as green fluorescent protein tags remains challenging in many systems. Here, we describe a streamlined and optimized editing protocol for the nematode Caenorhabditis elegans. We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging 14 Argonaute proteins in C. elegans using ssODN donors. In addition, we describe a novel PCR-based, partially single-stranded, “hybrid” donor design that yields high efficiency editing with large (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent protein tags into multiple loci, achieving editing efficiencies that approach those previously obtained only with much shorter ssODN donors. The principals and strategies described here are likely to translate to other systems, and should allow researchers to reproducibly and efficiently obtain both long and short precision genome edits.
Thanks but no thanks: State-owned multinationals from emerging markets and host-country policies

I study the impact of the internationalization of state-owned companies from emerging markets on host-country government policy. Whereas the literature commonly recommends that host-country governments design policies to attract foreign direct investment, governments instead question or block investments by state-owned firms from emerging markets. I address this conflict between theory and practice by separating the causes of this behavior into six types depending on the characteristics of the firm (i.e., state ownership and emerging market origin) and the logic (i.e., economics, politics, and psychology). I suggest the development of ex-ante rule-based policies that provide clarity, address concerns, and support the benefits of inward investments, while limiting state capture by domestic interests. Thus, I explain how economic concerns over national security sectors and strategic technologies can be dealt with via exclusion, the political worries over opacity and weak governance can be addressed through monitoring, and the psychological anxieties of unfriendly governments and loss of relative status can be ameliorated using controls.
Genome-Wide Quantitation of Protein Synthesis Rates in Bacteria.

Abstract Bacteria produce different amounts of their proteins in response to different conditions. The ability to accurately quantitate the rates of protein synthesis across the genome is an important step toward understanding both underlying regulation and bacterial physiology at a systems level. Ribosome profiling (deep sequencing of ribosome-protected mRNA fragments) enables accurate and high-throughput measurement of such synthesis rates. Ribosomes protect RNAs from nuclease digestion; thus, by collecting and sequencing protected footprints, one can obtain information on the position of every ribosome at the time of cell collection. Assuming ribosomes go on to translate full-length proteins, the density of ribosomes across an ORF can be used to determine protein synthesis rates. Here we outline a step-by-step protocol and discuss the steps where variability and bias may be introduced, including ways to minimize it.
The Drivers and Impacts of Water Infrastructure Reliability : A Global Analysis of Manufacturing Firms

Inadequate infrastructure impedes the productivity of manufacturing firms, with negative consequences for the wider economy. This study examines how water infrastructure copes with severe weather fluctuations and analyzes the effect of unreliable water supplies on the productivity of manufacturing firms, focusing predominately on firms in developing economies. This is achieved using firm-level data from World Bank Enterprise Surveys covering more than 16,000 manufacturing firms in a cross-section of 103 countries between 2009 and 2015. The study finds that periods of significantly low rainfall lead to higher water outages, and that the overall impact is driven by the effects of drought on low-income and lower-middle-income economies, with upper-middle-income and high-income economies benefitting from more resilient water infrastructure. Furthermore, the study finds that incidents of water outages lead to lower firm productivity for firms in less developed economies. For the average firm located in a low-income or lower-middle-income economy, one additional water outage incident per day in a typical month can lead to losses of approximately 8.2 percent of annual sales. This finding calls for increased policy focus on water infrastructure services, particularly in poorer countries where water infrastructure and firms seem to be particularly vulnerable to the vagaries of rainfall.
Clinical characterization of host response to simian hemorrhagic fever virus infection in permissive and refractory hosts: A model for determining mechanisms of VHF pathogenesis

Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. Unlike the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viral RNA was measurable in circulating blood 2 days after exposure, and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of livers from terminal monkeys and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host response suggests that relatively small subsets of a host’s response to infection may be responsible for driving hemorrhagic fever pathogenesis. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host–response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.
Parametric demand learning with limited price explorations in a backlog stochastic inventory system

We study a multi-period stochastic inventory system with backlogs. Demand in each period is random and price sensitive, but the firm has little or no prior knowledge about the demand distribution a...
Patent policy and American innovation after eBay: An empirical examination

Abstract The 2006 Supreme Court ruling in eBay vs. MercExchange removed the presumption of injunctive relief from infringement and marked a sea change in U.S. patent policy. Subsequent legal and policy changes reduced the costs of challenging patent validity and narrowed the scope of patentable subject matter. Proponents of these changes argue that they have made the U.S. patent system more equitable, particularly for sectors such as information technology, where patent ownership is fragmented and innovation highly cumulative. Opponents suggest the same reforms have weakened intellectual property rights and curtailed innovation. After reviewing the legal background and relevant economic theory, we examine patenting, R&D spending, venture capital investment and productivity growth in the wake of the eBay decision. Overall, we find no evidence that changes in patent policy have harmed the American innovation system.
Quantitative analysis of desomorphine in blood and urine using solid phase extraction and gas chromatography-mass spectrometry.

Abstract Desomorphine, a semi-synthetic opioid, is a component of the street drug Krokodil. Despite continued reports of Krokodil use, confirmation via toxicological testing remains scarce. The lack of confirmed desomorphine reports may be in part due to the limited published analytical methodology capable of detecting desomorphine at forensically relevant concentrations. In an effort to assist with identification efforts, a robust analytical method was developed and validated. Solid phase extraction (SPE) and gas chromatography–mass spectrometry (GC–MS) were used to determine desomorphine in blood and urine using a deuterated analog as the internal standard. Data was acquired using selected ion monitoring (SIM) mode. Extraction efficiencies in blood and urine were 69% and 90%, respectively. The limits of quantitation in blood and urine were 5 ng/mL and 8 ng/mL, ten-fold lower than previously published methods. Intra- and inter-assay CVs were 2–4% (n = 3) and 3–7% (n = 15), respectively. The method was fully validated in accordance with published guidelines for forensic use. Furthermore, it provides a means by which desomorphine can be identified in toxicology specimens at forensically relevant concentrations, without the need for derivatization.
Exploring the Challenges and Coping Strategies in Households Relying on SNAP and Food Pantries

Food insecurity is a substantial and persistent problem in the United States. This paper explores key challenges experienced by households relying on the Supplemental Nutrition Assistance Program (...
From the Fringe to the Fore: Labor Unions and Employee Compensation

Conventional wisdom suggests that labor unions raise worker wages, while the newer empirical literature finds only negligible earnings effects. I reconcile this apparent contradiction by arguing th...
An analytic physically motivated model of the mammalian cochlea

In this paper, an analytic model of the mammalian cochlea is developed. A mixed physical-phenomenological approach by utilizing existing work on the physics of classical box-representations of the cochlea and behavior of recent data-derived wavenumber estimates is used. Spatial variation is incorporated through a single independent variable that combines space and frequency. This paper arrives at closed-form expressions for the organ of Corti velocity, its impedance, the pressure difference across the organ of Corti, and its wavenumber. Model tests using real and imaginary parts of chinchilla data from multiple locations and for multiple variables are performed. The model also predicts impedances that are qualitatively consistent with current literature. For implementation, the model can leverage existing efforts for both filter bank or filter cascade models that target improved algorithmic or analog circuit efficiencies. The simplicity of the cochlear model, its small number of model constants, its ability to capture the variation of tuning, its closed-form expressions for physically-interrelated variables, and the form of these expressions that allows for easily determining one variable from another make the model appropriate for analytic and digital auditory filter implementations as discussed here, as well as for extracting macromechanical insights regarding how the cochlea works.
Robust Text Classifier on Test-Time Budgets

We design a generic framework for learning a robust text classification model that achieves high accuracy under different selection budgets (a.k.a selection rates) at test-time. We take a different approach from existing methods and learn to dynamically filter a large fraction of unimportant words by a low-complexity selector such that any high-complexity state-of-art classifier only needs to process a small fraction of text, relevant for the target task. To this end, we propose a data aggregation method to train the classifier, allowing it to achieve competitive performance on fractured sentences. On four benchmark text classification tasks, we demonstrate that the framework gains consistent speedup with little degradation in accuracy on various selection budgets.
Using Referenda to Improve Targeting and Decrease Costs of Conditional Cash Transfers

Cost-effective allocation of conditional cash transfers (CCT) requires identifying recipients with low opportunity costs who might change behavior. This paper develops a low-cost approach for improving program implementation by using a stated preference, referendum-style survey question to calculate willingness to accept (WTA) for CCT contracts. This is illustrated in the context of Mexico's Payments for Ecosystem Services Program, with the paper finding that the estimated social cost based on WTA is substantially lower than actual payments. Simulation of three geographic targeting approaches shows that joint selection using deforestation risk and WTA could increase program impact under the same budget. The paper also simulates modified payment schedules based on predicted WTA and demonstrates that these could reduce program cost.
Productivity Measurement: Racing to Keep Up

This article provides a nontechnical review of the literature and issues related to the measurement of aggregate productivity. I begin with a discussion of productivity measures, their performance ...
Top Management Team Characteristics and Financial Reporting Quality

ABSTRACT The accounting literature often views managers as individuals whose financial reporting decisions are determined by their economic incentives and individual characteristics. However, manag...
Studying the effect of bioswales on nutrient pollution in urban combined sewer systems

The objective of this study was to evaluate the impact of bioswales on nutrient pollution in an urban combined sewershed. This evaluation was based on two criteria: the ability of bioswales to (1) remove nutrient pollution from stormwater runoff directly and (2) decrease sewer overflow volumes, which indirectly reduces total sewershed nutrient pollution during a storm event. Bioswales' direct nutrient removal was determined by analyzing nitrogen and phosphorus levels in water samples at seven bioswales located in the Bronx, New York City (NYC) over 42 storm events, while a bioswale's indirect nutrient removal through combined sewer overflow reduction was estimated by quantifying water retention at one of the bioswales. The study results indicated that: 1) the bioswale retained about 40% of stormwater conveyed to it from a drainage area 231 times its size, 2) bioswales leach nutrients into the subsurface, and 3) nitrogen leaching from bioswales varied seasonally, while phosphorus leaching decreased steadily over the study period. Although the studied bioswales leached a median 1.3 kg nitrogen per year into the subsurface, they provided an aggregate decrease in watershed nutrient pollution, from 7.7 to 6 kg nitrogen per year, due to their reduction of combined sewer overflow via stormwater retention.
Grouped Survival Times

The grouped survival data consists of occurrence and exposure data over given time intervals and possible covariate strata. Grouping data from such large sample sizes into tabular presentations (life tables) often provides a convenient format for presenting and summarizing life information. Grouped survival data can involve censored data (right censoring, left censoring, or double censoring) and/or truncated data. Moreover, the exact censoring or truncation times may be unknown for grouped data. In this article, we provide the literature on analyzing grouped survival data, and discuss the estimating procedure for the hazard function and survival function under nonparametric or parametric models, test statistics for comparing the survival probabilities among different population groups, and large sample properties for these estimators and test statistics. Keywords: Aalen's additive model; Cox's regression model; counting process; grouped survival data; life tables; maximum likelihood; Sheppard correction
On the expected diameter, width, and complexity of a stochastic convex hull

We investigate several computational problems related to the stochastic convex hull (SCH). Given a stochastic dataset consisting of n points in \(\mathbb {R}^d\) each of which has an existence probability, a SCH refers to the convex hull of a realization of the dataset, i.e., a random sample including each point with its existence probability. We are interested in computing certain expected statistics of a SCH, including diameter, width, and combinatorial complexity. For diameter, we establish the first deterministic 1.633-approximation algorithm with a time complexity polynomial in both n and d. For width, two approximation algorithms are provided: a deterministic O(1)-approximation running in \(O(n^{d+1} \log n)\) time, and a fully polynomial-time randomized approximation scheme (FPRAS). For combinatorial complexity, we propose an exact \(O(n^d)\)-time algorithm. Our solutions exploit many geometric insights in Euclidean space, some of which might be of independent interest.
On the robustness of linear stabilizing feedback control for linear uncertain systems

We investigate linear time-invariant scalar-input systems with constant uncertainties that are not required to satisfy matching conditions. In a previous paper, the existence of stabilizing discontinuous controllers is established under three assumptions for such systems. The first assumption requires controllability of the system for each uncertainty. The second is a condition on an uncertain Lyapunov equation, and the third is a boundedness condition related to the controllability matrix. In this paper, using the same assumptions, we show the existence of a linear stabilizing control. Our result is related to the high-gain theorem of classical control.
Idiosyncratic Information, Moral Hazard, and the Cost of Capital

This paper examines the effects of idiosyncratic accounting information on a firm's cost of capital. By embedding a moral hazard problem into a multi‐firm asset pricing model, I show that moral hazard distorts the sharing of idiosyncratic risk but does not affect the sharing of systematic risk in the economy. A firm‐level improvement in idiosyncratic information reduces the firm's cost of capital even though it does not affect the implied cost of capital inferred from publicly traded shares. Moreover, an economy‐level improvement in idiosyncratic information reduces the risk premium for idiosyncratic risk but increases the risk premium for systematic risk, resulting in an ambiguous net effect on the firm's cost of capital. These results provide alternative explanations for the mixed empirical evidence on the relation between information quality and the cost of capital.
Non-monotone Submodular Maximization with Nearly Optimal Adaptivity and Query Complexity

Submodular maximization is a general optimization problem with a wide range of applications in machine learning (e.g., active learning, clustering, and feature selection). In large-scale optimization, the parallel running time of an algorithm is governed by its adaptivity, which measures the number of sequential rounds needed if the algorithm can execute polynomially-many independent oracle queries in parallel. While low adaptivity is ideal, it is not sufficient for an algorithm to be efficient in practice---there are many applications of distributed submodular optimization where the number of function evaluations becomes prohibitively expensive. Motivated by these applications, we study the adaptivity and query complexity of submodular maximization. In this paper, we give the first constant-factor approximation algorithm for maximizing a non-monotone submodular function subject to a cardinality constraint $k$ that runs in $O(\log(n))$ adaptive rounds and makes $O(n \log(k))$ oracle queries in expectation. In our empirical study, we use three real-world applications to compare our algorithm with several benchmarks for non-monotone submodular maximization. The results demonstrate that our algorithm finds competitive solutions using significantly fewer rounds and queries.
Rethinking therapeutic action

Like other core psychoanalytic constructs, the theory of therapeutic action is currently in flux, as theorists of differing persuasions propose different mechanisms. In this article, the authors attempt to integrate developments within and without psychoanalysis to provide a working model of the multifaceted processes involved in producing change in psychoanalysis and psychoanalytic psychotherapy. A theory of therapeutic action must describe both what changes (the aims of treatment) and what strategies are likely to be useful in facilitating those changes (technique). The authors believe that single-mechanism theories of therapeutic action, no matter how complex, are unlikely to prove useful at this point because of the variety of targets of change and the variety of methods useful in effecting change in those targets (such as techniques aimed at altering different kinds of conscious and unconscious processes). Interventions that facilitate change may be classified into one of three categories: those that foster insight, those that make use of various mutative aspects of the treatment relationship and a variety of secondary strategies that can be of tremendous importance. They propose that, in all forms of psychoanalytic treatment, we would be more accurate to speak of the therapeutic actions, rather than action.
Novel zafirlukast derivatives exhibit selective antibacterial activity against Porphyromonas gingivalis

Periodontal disease is an oral chronic immune-inflammatory disease highly prevalent worldwide that is initiated by specific oral bacterial species leading to local and systemic effects. The development of new preventive/therapeutic strategies to specifically target oral periodontopathogens without perturbing oral microbiome species normally colonizing the oral cavity is needed. The fast and affordable strategy of repositioning of already FDA-approved drugs can be an answer to the development of novel treatments against periodontal pathogens such as Porphyromonas gingivalis. Herein, we report the synthesis and antibacterial activity of novel zafirlukast derivatives, their bactericidal effect, and their cytotoxicity against oral epithelial cell lines. Many of these derivatives exhibited superior antibacterial activity against P. gingivalis compared to the parent drug zafirlukast. The most promising compounds were found to be selective against P. gingivalis and they were bactericidal in their activity. Finally, we demonstrated that these potent derivatives of zafirlukast provided a better safety profile against oral epithelial cells compared to zafirlukast.
A new terpyrrolic analogue of dipyrrolylquinoxalines: an efficient optical-based sensor for anions in organic media

Abstract The synthesis and X-ray structural characterization of a new terpyrrolic analog of dipyrrolylquinoxaline (DPQ) is described that contains two pyrrole anion recognition groups bridged by a central 1,2-linked pyrrole. Relative to the ‘parent’ DPQ system, this new terpyrrolic scaffold acts as an improved colorimetric and fluorescent sensor for halide and dihydrogen phosphate anions in organic media. This enhancement is particularly dramatic in the case of H2PO4− (studied as its tetrabutylammonium salt); in CH2Cl2 it is bound with an affinity constant, K, of 17,500 M−1 by the terpyrrole of this report vs. 80 M−1 in the case of DPQ. The present findings thus support the emerging notion that a range of pyrrole-based anion recognition and sensing systems may be produced by replacing the central quinoxaline spacer in DPQs by other bridging subunits and that these new receptors may have properties that differ dramatically from their DPQ ‘parents’.
Ruthenium(III) Chloride–Catalyzed Ring Opening of Epoxides with Aromatic Amines

Abstract Ruthenium(III) chloride catalyzes the nucleophilic opening of epoxides by anilines, leading to the efficient synthesis of β‐amino alcohols. High regioselectivity can be considered as a noteworthy advantage of this method.
Enantioselective Deprotonative Ring Contraction of N1-Methyl-N4-Boc-benzo[e][1,4]diazepine-2,5-diones

N1-Methyl-N4-Boc-benzo[e][1,4]diazepine-2,5-diones were prepared in good yield and high stereochemical purity from five amino acids. Upon deprotonation, these compounds undergo ring contraction to the corresponding quinolone-2,4-diones with high enantioselectivity, providing efficient entry to a potentially useful drug scaffold. Mechanistic commentary and comparisons to related reactions are provided.
Synthesis and reactions of lithio derivatives of 1-allenylbenzotriazole

1-(2-Chloropropen-2-yl)benzotriazole (6) is converted by heating with sodium hydroxide or by lithium diisopropylamide at -78° into 1-allenylbenzotriazole (1) in high yield. Allene 1 undergoes in situ lithiation at the α-carbon and subsequent reactions with iodomethane or carbonyl compounds to produce 1-(1-substituted allenyl)benzotriazoles 9 and 2a-c, respectively. Three equivalents of lithium diisopropylamide dilithiated 1 and afforded symmetrical 1-(1,3-disubstituted allenyl)benzotriazoles 11a,b upon reaction with ketones. The unsymmetrical 1-(1,3-disubstituted allenyl)benzotriazole 5 was obtained via a stepwise addition of benzophenone to the lithio derivative of 1 followed by a second lithiation and quenching with acetone. Monosubstituted allenes 2a and 8 were cyclized into the benzotriazolyl substituted dihydrofuran 3 and dihydropyrrole 4 respectively.
Spatial Structure of Synchronized Inhibition in the Olfactory Bulb.

Olfactory sensory input is detected by receptor neurons in the nose which then send information to the olfactory bulb, the first brain region for processing olfactory information. Within the olfactory bulb, many local circuit interneurons, including axonless granule cells, function to facilitate fine odor discrimination. How interneurons interact with principal cells to affect bulbar processing is not known though the mechanism is likely to be different than in sensory cortical regions since the olfactory bulb lacks an obvious topographical organization; neighboring glomerular columns, representing inputs from different receptor neuron subtypes, typically have different odor tuning. Determining the spatial scale over which interneurons such as granule cells can affect principal cells is a critical step towards understanding how the olfactory bulb operates. We addressed this question by assaying inhibitory synchrony using intracellular recordings from pairs of principal cells with different inter-somatic spacing. We find that in acute rat olfactory bulb slices from both sexes, inhibitory synchrony is evident in the spontaneous synaptic input in mitral cells separated up to 220 [graphic1]m (300 [graphic2]m with elevated K + ). At all inter-somatic spacing assayed, inhibitory synchrony was dependent on Na + channels, suggesting that action potentials in granule cells function to coordinate GABA release at relatively distant dendrodendritic synapses formed throughout the the dendritic arbor. Our results suggest that individual granule cells are able to influence relatively large groups of mitral and tufted cells belonging to clusters of at least 15 glomerular modules, providing a potential mechanism to integrate signals reflecting a wide variety of odorants. SIGNIFICANCE STATEMENT Inhibitory circuits in the olfactory bulb play a major role in odor processing, especially during fine odor discrimination. How inhibitory networks enhance olfactory function, and over what spatial scale they operate, is not known. Interneurons are potentially able to function on both a highly localized, synapse-specific level as well as on a larger, spatial scale that encompasses many different glomerular channels. While recent indirect evidence has suggested a relatively localized functional role for most inhibition in the olfactory bulb, in the present study we used paired intracellular recordings to directly demonstrate that inhibitory local circuits operate over large spatial scales by using fast action potentials to link GABA release at many different synaptic contacts formed with principal cells.
Intramolecular ketene-allene cycloadditions.

This report describes intramolecular thermal [2 + 2] cycloadditions between ketenes and allenes. The formation of ketenes and the subsequent cycloadditions occurred under a variety of conditions, affording 7-methylidinebicyclo[3.2.0]heptanones and 7-methylidinebicyclo[3.1.1]heptanones in 45−78% yields. The regioselectivity of the cycloaddition varied with the substitution of the allene, and the yield of cyclized products varied with reaction conditions.
Density dependence in demography and dispersal generates fluctuating invasion speeds

Density dependence plays an important role in population regulation and is known to generate temporal fluctuations in population density. However, the ways in which density dependence affects spatial population processes, such as species invasions, are less understood. Although classical ecological theory suggests that invasions should advance at a constant speed, empirical work is illuminating the highly variable nature of biological invasions, which often exhibit nonconstant spreading speeds, even in simple, controlled settings. Here, we explore endogenous density dependence as a mechanism for inducing variability in biological invasions with a set of population models that incorporate density dependence in demographic and dispersal parameters. We show that density dependence in demography at low population densities-i.e., an Allee effect-combined with spatiotemporal variability in population density behind the invasion front can produce fluctuations in spreading speed. The density fluctuations behind the front can arise from either overcompensatory population growth or density-dependent dispersal, both of which are common in nature. Our results show that simple rules can generate complex spread dynamics and highlight a source of variability in biological invasions that may aid in ecological forecasting.
Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches

Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this programming commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood. Here, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression. A total of 9,439 differentially methylated regions (DMRs) associated with augmented maternal care were identified in male offspring hypothalamus, as well as a modest but significant decrease in global DNA methylation. Differentially methylated and expressed genes were enriched for functions in neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation, as well as known stress response genes. Twenty prioritized genes were identified as highly relevant to the stress resiliency phenotype. This combined unbiased approach enabled the discovery of novel genes and gene pathways that advance our understanding of the epigenomic mechanisms underlying the effects of maternal care on the developing brain.
Research Highlights from the U.S. Department of Energy’s Working Group on Photoelectrochemical Hydrogen Production

The US Department of Energy (DOE) hydrogen production research and development portfolio focuses on low-cost, highly efficient and environmentally friendly production technologies based on diverse, domestic resources. Within the DOE, work on hydrogen production technologies integrates basic and applied research, as well as technology development and demonstration. The integration of basic and applied research is of particular importance in “transformational” production technologies, such as photoelectrochemical (PEC) hydrogen production, where scientific advances are needed for achieving the long-term DOE performance and cost targets. In the case of renewable hydrogen production via PEC solar water splitting, high solar-to-hydrogen conversion efficiency has been demonstrated to date on the laboratory scale, but only with high-cost, low-durability material systems. In order to identify and develop the appropriate high-efficiency, low-cost, durable and scalable PEC material systems, research and development efforts in the DOE EERE (Energy Efficiency and Renewable Energy) Office have keyed in on specific focus areas, including: 1) the engineering of solar energy absorption properties in PEC semiconductor materials, such as the bandgap lowering in stable metal oxides as well as bandgap raising in nanostructured sulfide catalysts; 2) the engineering of PEC solid-liquid interfaces for optimal reaction rates and stability, such as surface nitrogenation in III-V semiconductor systems; 3) the standardization of PEC measurement and reporting methodologies, using national and international peer-review process, for facilitating research progress; and 4) the design and analysis of integrated PEC device and system configurations for scalable hydrogen production. As described in this presentation, all of these research and development areas rely heavily on collaborative efforts among academia, industry and national laboratory partners, utilizing state of the art resources in materials theory, synthesis, characterization and analysis. The collaboration extends nationally among research programs supported by the DOE EERE as well as Office of Science; and internationally via networking through the International Energy Agency’s Hydrogen Implementation Agreement Annex-26. Key and encouraging accomplishments resulting from the collaborative work are highlighted in this presentation.
Simultaneous Ribosome Profiling of Human Host Cells Infected with Toxoplasma gondii

ABSTRACT Toxoplasma gondii is a ubiquitous obligate intracellular parasite that infects the nucleated cells of warm-blooded animals. From within the parasitophorous vacuole in which they reside, Toxoplasma tachyzoites secrete an arsenal of effector proteins that can reprogram host gene expression to facilitate parasite survival and replication. Gaining a better understanding of how host gene expression is altered upon infection is central for understanding parasite strategies for host invasion and for developing new parasite therapies. Here, we applied ribosome profiling coupled with mRNA measurements to concurrently study gene expression in the parasite and in host human foreskin fibroblasts. By examining the parasite transcriptome and translatome, we identified potential upstream open reading frames that may permit the stress-induced preferential translation of parasite mRNAs. We also determined that tachyzoites reduce host death-associated pathways and increase survival, proliferation, and motility in both quiescent and proliferative host cell models of infection. Additionally, proliferative cells alter their gene expression in ways that are consistent with massive transcriptional rewiring, while quiescent cells were best characterized by reentry into the cell cycle. We also identified a translational control regimen consistent with mechanistic target of rapamycin (mTOR) activation in quiescent cells and, to a lesser degree, in proliferative cells. This study illustrates the utility of the method for dissection of gene expression programs simultaneously in the parasite and host. IMPORTANCE Toxoplasma gondii is a single-celled parasite that has infected up to one-third of the world’s population. Significant overhauls in gene expression in both the parasite and the host cell accompany parasite invasion, and a better understanding of these changes may lead to the development of new therapeutic agents. In this study, we employed ribosome profiling to determine the changes that occur at the levels of transcription and translation in both the parasite and the infected host cell at the same time. We discovered features of Toxoplasma mRNAs that suggest a means for controlling parasite gene expression under stressful conditions. We also show that differences in host gene expression occur depending on whether they are confluent or not. Our findings demonstrate the feasibility of using ribosomal profiling to interrogate the host-parasite dynamic under a variety of conditions.
Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion of Lysis by Human Serum.

We previously showed that Entamoeba histolytica kills human cells through a mechanism that we termed trogocytosis ("trogo-" means "nibble"), due to its resemblance to trogocytosis in other organisms. In microbial eukaryotes like E. histolytica, trogocytosis is used to kill host cells. In multicellular eukaryotes, trogocytosis is used for cell killing and cell-cell communication in a variety of contexts. Thus, nibbling is an emerging theme in cell-cell interactions both within and between species. When trogocytosis occurs between mammalian immune cells, cell membrane proteins from the nibbled cell are acquired and displayed by the recipient cell. In this study, we tested the hypothesis that through trogocytosis, amoebae acquire and display human cell membrane proteins. We demonstrate that E. histolytica acquires and displays human cell membrane proteins through trogocytosis and that this leads to protection from lysis by human serum. Protection from human serum occurs only after amoebae have undergone trogocytosis of live cells but not phagocytosis of dead cells. Likewise, mutant amoebae defective in phagocytosis, but unaltered in their capacity to perform trogocytosis, are protected from human serum. Our studies are the first to reveal that amoebae can display human cell membrane proteins and suggest that the acquisition and display of membrane proteins is a general feature of trogocytosis. These studies have major implications for interactions between E. histolytica and the immune system and also reveal a novel strategy for immune evasion by a pathogen. Since other microbial eukaryotes use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.IMPORTANCE Entamoeba histolytica causes amoebiasis, a potentially fatal diarrheal disease. Abscesses in organs such as the liver can occur when amoebae are able to breach the intestinal wall and travel through the bloodstream to other areas of the body. Therefore, understanding how E. histolytica evades immune detection is of great interest. Here, we demonstrate for the first time that E. histolytica acquires and displays human cell membrane proteins by taking "bites" of human cell material in a process named trogocytosis ("trogo-" means "nibble"), and that this allows amoebae to survive in human serum. Display of acquired proteins through trogocytosis has been previously characterized only in mammalian immune cells. Our study suggests that this is a more general feature of trogocytosis not restricted to immune cells and broadens our knowledge of eukaryotic biology. These findings also reveal a novel strategy for immune evasion by a pathogen and may apply to the pathogenesis of other infections.
Facet Formation in Submicron Selective Growth of Si/SiGe

The paper reviews the work in mostly Si and SiGe epitaxy and some III-V work on patterned substrates. Results of metalorganic chemical vapor deposition (MOCVD), low pressure chemical vapor deposition (LPCVD), gas source molecular beam epitaxy (GSMBE), and solid source molecular beam epitaxy (MBE) were discussed in the context of facet formation and mass accumulation. A model was shown to explain the facet formation and its evolution in the process of growth. Further work on surface diffusion and nucleation processes as functions of temperature and other growth parameters will provide needed information for accurate modeling of the facet growth process.
A HIGHLY STEREOCONTROLLED FORMAL SYNTHESIS OF RAC-CHOKOLS A AND G FROM A COMMON GEM-BORAZIRCONOCENE INTERMEDIATE

Abstract The stereoselective synthesis of rac-chokols A and G precursors described herein proceeds from the readily available gem-borazirconocene 2 by conjugate addition to 2-methylcyclopentenone to give the common intermediate 3, which is then transformed in a series of reactions to provide the chokols in overall yields of 16 and 17 % respectively.
Multi-task Learning with Sample Re-weighting for Machine Reading Comprehension.

We propose a multi-task learning framework to learn a joint Machine Reading Comprehension (MRC) model that can be applied to a wide range of MRC tasks in different domains. Inspired by recent ideas of data selection in machine translation, we develop a novel sample re-weighting scheme to assign sample-specific weights to the loss. Empirical study shows that our approach can be applied to many existing MRC models. Combined with contextual representations from pre-trained language models (such as ELMo), we achieve new state-of-the-art results on a set of MRC benchmark datasets. We release our code at https://github.com/xycforgithub/MultiTask-MRC.
Total synthesis of the formamicin aglycon, formamicinone.

The total synthesis of formamicinone (2), the aglycone of formamicin (1), has been accomplished via the late-stage Suzuki cross-coupling of fragments 5 and 6, the macrolactonization of seco ester 14, and the Mukaiyama aldol reaction of aldehyde 3 and methyl ketone 4. An efficient and highly stereoselective second generation synthesis of vinyl iodide 6 is also described.
Semiconductor physics: Dark spins come to light

The spin of a photoluminescent nitrogen centre in diamond has a long life-time that could be useful as a qubit, for example. It's difficult enough to image such a single spin — imagine using that bright spin to detect nearby invisible 'dark' spins.
Development of a liquid chromatography-tandem mass spectrometry assay of six antimicrobials in plasma for pharmacokinetic studies in premature infants.

This method provides a simple extraction procedure, as well as a validated, sensitive, and specific liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of ampicillin, piperacillin, tazobactam, meropenem, acyclovir, and metronidazole in human plasma. The method was validated over concentration ranges specific for each compound, with a lower limit of quantification of 50-300 ng/mL and a sample volume of 50 µL. The method is accurate and precise, with within- and between-day accuracy ranging from 85 to 110% and 92 to 110%, respectively, and within- and between-day precision of 89-111% and 91-109%, respectively. Simplicity, low plasma volume, and high throughput make this method suitable for clinical pharmacokinetic studies in premature infants.
The first practical asymmetric synthesis of R and S-Warfarin

Abstract A highly efficient synthesis of both enantiomers of warfarin Ia and Ib has been developed by using a novel two step “chiral switch” strategy and a DuPHOS-Rh(I) catalyzed asymmetric hydrogenation.
Coupling of Fischer Carbene Complexes with o-Alkynylbenzamides

The coupling of 2-alkynylbenzamide derivatives with carbene complexes has been examined for systems that contain remote alkene functionality tethered either to the starting carbene complex or to the nitrogen of the amide. In most cases the reaction proceeds via alkyne insertion, followed by isobenzofuran formation, followed by intramolecular Diels−Alder reaction, followed by dehydration to afford aminonaphthalene derivatives. In examples using carbene complex tethered alkenes, intramolecular cyclopropanation is a competing reaction process.
Binuclear iron(III) phthalocyanine(μ-oxodimer)/tetrabutylammonium oxone: a powerful catalytic system for oxidation of hydrocarbons in organic solution

Abstract Binuclear iron(III) phthalocyanine-(μ-oxodimer) complex was tested in catalytic oxygenation reactions of several hydrocarbons using tetrabutylammonium oxone as the oxidant in dichloromethane solution at room temperature. Results of the study demonstrate that this is an extremely powerful catalytic system for oxidative conversion of aromatic hydrocarbons (anthracene, 2-tert-butylanthracene, 2-methylnaphthalene, 9,10-dihydroanthracene, 1,2,3,4-tetrahydronaphthalene, indane, ethylbenzene, toluene, and benzene) to the respective p-quinones in high yields in 5–30 min. Under these conditions, adamantane is oxidized with 71% conversion after 10 min affording a mixture of 1-adamantanol, 2-adamantanone, 1-hydroxy-2-adamantanone, and 4-protoadamantanone.
Cis-regulatory elements and human evolution

Modification of gene regulation has long been considered an important force in human evolution, particularly through changes to cis-regulatory elements (CREs) that function in transcriptional regulation. For decades, however, the study of cis-regulatory evolution was severely limited by the available data. New data sets describing the locations of CREs and genetic variation within and between species have now made it possible to study CRE evolution much more directly on a genome-wide scale. Here, we review recent research on the evolution of CREs in humans based on large-scale genomic data sets. We consider inferences based on primate divergence, human polymorphism, and combinations of divergence and polymorphism. We then consider 'new frontiers' in this field stemming from recent research on transcriptional regulation.
The beckmann rearrangement of cyclohex‐2‐enone oximes. Synthesis of 4,5‐diphenyl‐2,3,4,5‐tetrahydro‐1H‐azepin‐2‐one

The Beckmann rearrangement of either syn or anti 3,4-diphenyl-cyclohexenone oxime 2a,b in polyphosphoric acid produces only one of the two possible isomeric unsaturated caprolactams 1. Under neutral conditions, only the syn oxime tosylate 9b rearranges to lactam 1, the anti oxime tosylate 9a remains unchanged. These results support earlier reports that alkyl migration is preferred over vinyl migration in the Beckmann rearrangement of unsaturated cyclic ketoximes. Structure proof of the lactam was made using deuterium exchange and HMQC nmr experiments.