cssi/SciSciGPT-SciSciNet huggingface dataset:
Inferring Parsimonious Migration Histories for Metastatic Cancers

Metastasis is the migration of cancerous cells from a primary tumor to other anatomical sites. Although metastasis was long thought to result from monoclonal seeding, or single cellular migrations, recent phylogenetic analyses of metastatic cancers have reported complex patterns of cellular migrations between sites, including polyclonal migrations and reseeding. However, accurate determination of migration patterns from somatic mutation data is complicated by intratumor heterogeneity and discordance between clonal lineage and cellular migration. We introduce MACHINA, a multi-objective optimization algorithm that jointly infers clonal lineages and parsimonious migration histories of metastatic cancers from DNA sequencing data. MACHINA analysis of data from multiple cancers shows that migration patterns are often not uniquely determined from sequencing data alone and that complicated migration patterns among primary tumors and metastases may be less prevalent than previously reported. MACHINA's rigorous analysis of migration histories will aid in studies of the drivers of metastasis.
Pre-synaptic Muscarinic Excitation Enhances the Discrimination of Looming Stimuli in a Collision-Detection Neuron.

Summary Visual neurons that track objects on a collision course are often finely tuned to their target stimuli because this is critical for survival. The presynaptic neural networks converging on these neurons and their role in tuning them remain poorly understood. We took advantage of well-known characteristics of one such neuron in the grasshopper visual system to investigate the properties of its presynaptic input network. We find the structure more complex than hitherto realized. In addition to dynamic lateral inhibition used to filter out background motion, presynaptic circuits include normalizing inhibition and excitatory interactions mediated by muscarinic acetylcholine receptors. These interactions preferentially boost responses to coherently expanding visual stimuli generated by colliding objects, as opposed to spatially incoherent controls, helping to discriminate between them. Hence, in addition to active dendritic conductances within collision-detecting neurons, multiple layers of inhibitory and excitatory presynaptic connections are needed to finely tune neural circuits for collision detection.
How a data-driven course planning tool affects college students' GPA: evidence from two field experiments

College students rely on increasingly data-rich environments when making learning-relevant decisions about the courses they take and their expected time commitments. However, we know little about how their exposure to such data may influence student course choice, effort regulation, and performance. We conducted a large-scale field experiment in which all the undergraduates at a large, selective university were randomized to an encouragement to use a course-planning web application that integrates information from official transcripts from the past fifteen years with detailed end-of-course evaluation surveys. We found that use of the platform lowered students' GPA by 0.28 standard deviations on average. In a subsequent field experiment, we varied access to information about course grades and time commitment on the platform and found that access to grade information in particular lowered students' overall GPA. Our exploratory analysis suggests these effects are not due to changes in the portfolio of courses that students choose, but rather by changes to their behavior within courses.
Visualizing electronic excitations with the particle-hole map: orbital localization and metric space analysis

The particle-hole map (PHM) is a computational tool to visualize electronic excitations–calculated using time-dependent density-functional theory–based on representations in canonical molecular orbital transition space. Beyond the standard canonical representation, transformation to localized orbitals is a common technique in electronic structure theory. We analyze the PHM as a visualization tool for both canonical and localized orbital representations and give numerical examples for simple one-dimensional model systems. We show that the localized PHMs can be used to construct simple descriptors of the charge-transfer character of an excitation through metric space analysis, and that it can improve the clarity of the visualization provided by the canonical PHM.
Investor Relations and Information Assimilation

ABSTRACT This paper examines whether investor relations (IR) officers provide value by facilitating the assimilation of firm information by the market. We find that firms with IR officers have lowe...
Improved Signature Schemes for Secure Multi-party Computation with Certified Inputs

The motivation for this work comes from the need to strengthen security of secure multi-party protocols with the ability to guarantee that the participants provide their truthful inputs in the computation. This is outside the traditional security models even in the presence of malicious participants, but input manipulation can often lead to privacy and result correctness violations. Thus, in this work we treat the problem of combining secure multi-party computation (SMC) techniques based on secret sharing with signatures to enforce input correctness in the form of certification. We modify two currently available signature schemes to achieve private verification and efficiency of batch verification and show how to integrate them with two prominent SMC protocols.
Evaporation from the human tear film studied by interferometry.

Previous measurements of evaporation from the human tear film have been based on measuring humidity in an open chamber1,2 or a closed chamber.3–5 The presence of the chamber restricts natural air and convection currents, and therefore the measured evaporation rate may be less than in unobstructed conditions.
Property and Its Rule (in Late Indo-Islamicate and Early Colonial) South Asia: What’s in a Name?

This article sets out a framework for understanding two key issues in the history of early modern and modern South Asia. First, it addresses the vexed question of the generalizability of the “Western” concept of property to Indo-Islamicate land systems. Rather than beginning from the idea of ‘Islamic property law/relations’ it proposes that we reconstruct concepts relating to the control of the earth’s material substrate in terms of four modes of idiomizing land in the Islamicate tradition. In light of how the latter reconstruction suggests that (Indo-)Islamicate modes of idiomization focused on the produce of land more than land itself, the article then turns to a second issue. This concerns the similarities and differences between the deontic cultures of rights and responsibilities that characterized early modern polities (both in Mughal India and England) and nineteenth-century ones (like metropolitan Britain’s and that emerging from the East India Company’s so-called rule of property in the subcontinent).
How Do Countries Use an Asset and Liability Management Approach ? A Survey on Sovereign Balance Sheet Management

This paper summarizes and discusses the results of a survey on country practices in the management of sovereign assets and liabilities. Twenty-eight countries, mostly high-income economies, responded to the questionnaire. The survey responses provide detailed information about various approaches to the sovereign asset and liability management framework in terms of balance sheet production as well as objectives, priority areas, and challenges associated with integrated management. In addition to the survey results, where possible and relevant, this paper provides insight through prominent country examples. The survey results confirm that the number of countries that have developed such a framework is limited. Although most of the respondents indicated that they regularly produce an accounting balance sheet, the objective of this exercise is often limited to monitoring sovereign assets and liabilities rather than determining mismatches between them. In the cases where a sovereign asset and liability management framework is implemented, there are significant differences across countries. Most countries include state-owned enterprises in the sovereign balance sheet, but only a minority also considers central banks, in some cases only international reserves and sovereign funds. The challenges cited include institutional arrangements, uncertain or lacking mandate, coordination between institutions, data availability, and valuation of assets. Most of these challenges are related to the implementation of the approach. The development of sound practices for sovereign asset and liability management could benefit governments and facilitate the implementation of a holistic approach to manage their balance sheets and related risks, increasing their resilience to shocks.
Simultaneous inhibition of MEK and Hh signaling reduces pancreatic cancer metastasis

Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal cancer types, with an estimated 44,330 death in 2018 in the US alone. While targeted therapies and immune checkpoint inhibitors have significantly improved treatment options for patients with lung cancer and renal cell carcinomas, little progress has been made in pancreatic cancer, with a dismal 5-year survival rate currently at ~8%. Upon diagnosis, the majority of pancreatic cancer cases (~80%) are already metastatic. Thus, identifying ways to reduce pancreatic cancer metastasis is an unmet medical need. Furthermore, pancreatic cancer is notorious resistant to chemotherapy. While Kirsten RAt Sarcoma virus oncogene (K-RAS) mutation is the major driver for pancreatic cancer, specific inhibition of RAS signaling has been very challenging, and combination therapy is thought to be promising. In this study, we report that combination of hedgehog (Hh) and Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) signaling inhibitors reduces pancreatic cancer metastasis in mouse models. In mouse models of pancreatic cancer metastasis using human pancreatic cancer cells, we found that Hh target gene Gli1 is up-regulated during pancreatic cancer metastasis. Specific inhibition of smoothened signaling significantly altered the gene expression profile of the tumor microenvironment but had no significant effects on cancer metastasis. By combining Hh signaling inhibitor BMS833923 with RAS downstream MEK signaling inhibitor AZD6244, we observed reduced number of metastatic nodules in several mouse models for pancreatic cancer metastasis. These two inhibitors also decreased cell proliferation significantly and reduced CD45⁺ cells (particularly Ly6G⁺CD11b⁺ cells). We demonstrated that depleting Ly6G⁺ CD11b⁺ cells is sufficient to reduce cancer cell proliferation and the number of metastatic nodules. In vitro, Ly6G⁺ CD11b⁺ cells can stimulate cancer cell proliferation, and this effect is sensitive to MEK and Hh inhibition. Our studies may help design novel therapeutic strategies to mitigate pancreatic cancer metastasis.
Heterogeneous Photonic Integration on Silicon

We review recent advances in heterogeneous silicon photonic integration technology and components and describe progress in silicon photonic integrated circuits. Techniques for laser integration and the impact of active silicon photonic integrated circuits could have on interconnects, telecommunications and silicon electronics are reviewed. A variety of materials are being heterogeneously integrated, including arsenides for short wavelength lasers, phosphides for infrared lasers, QCLs for long wavelengths, LiNbO 3 and GaAs for nonlinear applications and YIG for isolators and circulators.
Generating highly specific spectra and identifying thermal decomposition products via Gas Chromatography / Vacuum Ultraviolet Spectroscopy (GC/VUV): Application to nitrate ester explosives

Abstract Gas chromatography/mass spectrometry (GC/MS) is a "workhorse" instrument for chemical analysis, but it can be limited in its ability to differentiate structurally similar compounds. The coupling of GC to vacuum ultraviolet (VUV) spectroscopy is a recently developed technique with the potential for increased detection specificity. To date, GC/VUV has been demonstrated in the analysis of volatile organic compounds, petroleum products, aroma compounds, pharmaceuticals, illegal drugs, and lipids. This paper is the first to report on the utility of GC/VUV for explosives analysis in general, and the first to report on thermal degradation within the VUV cell and its analytical utility. The general figures of merit and performance of GC/VUV were evaluated with authentic standards of nitrate ester explosives (e.g., nitroglycerine (NG), ethylene glycol dinitrate (EGDN), pentaerythritol tetranitrate (PETN), and erythritol tetranitrate (ETN)). In addition, the explosive analytes were thermally degraded in the VUV cell, yielding reproducible, complex and characteristic mixtures of gas phase products (e.g., nitric oxide, carbon monoxide, and formaldehyde). The relative amounts of the degradation products were estimated via spectral subtraction of library spectra. Lastly, GC/VUV was used to analyze milligram quantities of intact and burned samples of double-base smokeless powders containing nitroglycerine, diphenylamine, ethyl centralite, and dibutylphthalate
Is the credit spread puzzle a myth

Abstract We revisit Feldhutter and Schaefer (FS, 2018), who report evidence of a “credit spread puzzle” for high-yield but not investment-grade bonds. We show their results are reversed when their model is calibrated to market values of debt (as required by theory) rather than book values. We then demonstrate that using credit spreads rather than historical default rates to identify the default boundary provides the statistical power necessary to reject their assumption that firm dynamics follow geometric Brownian motion. A large market price of jump risk is required to match historical default rates, which generates a credit spread puzzle for investment-grade but not high-yield bonds.
A geometric setting for quantum osp(1|2)

A geometric categorification is given for arbitrary-large-finite-dimensional quotients of quantum osp(1|2) and the tensor product of its simple modules. The modified quantum osp(1|2) of Clark-Wang, a new version in this paper and the modified quantum sl(2) are isomorphic to each other over a field containing Q(v) and a root of -1.
Gradient Descent with Identity Initialization Efficiently Learns Positive-Definite Linear Transformations by Deep Residual Networks

We analyze algorithms for approximating a function f(x)=Φx mapping ℜd to ℜd using deep linear neural networks, that is, that learn a function h parameterized by matrices Θ1,…,ΘL and defined by h(x)...
Tunable Fabry-Pérot Filter for Optical Glucose Monitoring

This paper presents a Tunable MEMS Fabry-Perot (FP) filter for the application of optical glucose sensor in Long-Wave Infrared (LWIR) range. The structure design, simulation, fabrication process and testing system are reported. The spectral wavelength tuning range from 10.9 I¼m to 12.19 I¼m was designed for the transmission peak which is related to the glucose concentration. A tuning distance between top and bottom reflector of 2.25µm has been achieved, while maintaining a relatively low tuning voltage of 20V. The Tunable FP filter is the core part of glucose sensor and has other applications in Bio-sensor, hyperspectral imaging and tunable lasers, etc.
5 – Muscle proteins

Proteins within the muscle matrix play an essential role in the quality attributes of cooked meat, such as tenderness, juiciness, and mouthfeel. In processed meats, salt- and phosphate-extracted myofibrillar proteins, which are superior gelling, fat-emulsifying, and water-binding agents, are largely responsible for the product textural properties. A single most important functional protein is myosin. For intact muscle cuts, the enhanced meat tenderness during postmortem aging is due to the proteolytic actions of various endogenous proteases. Apart from their in situ functionality, muscle proteins, including fish surimi, collagen, plasma protein, and other meat by-product proteins, have been prepared and utilized as functional food ingredients.
Anisotropic quadrangulation

Quadrangulation methods aim to approximate surfaces by semiregular meshes with as few extraordinary vertices as possible. A number of techniques use the harmonic parameterization to keep quads close to squares, or fit parametrization gradients to align quads to features. Both types of techniques create near-isotropic quads; feature-aligned quadrangulation algorithms reduce the remeshing error by aligning isotropic quads with principal curvature directions. A complementary approach is to allow for anisotropic elements, which are well-known to have significantly better approximation quality. In this work we present a simple and efficient technique to add curvature-dependent anisotropy to harmonic and feature-aligned parameterization and improve the approximation error of the quadrangulations. We use a metric derived from the shape operator which results in a more uniform error distribution, decreasing the error near features.
Schubert polynomial analogues for degenerate involutions

We survey the recent study of involution Schubert polynomials and a modest generalization that we call degenerate involution Schubert polynomials. We cite several conditions when (degenerate) involution Schubert polynomials have simple factorization formulae. Such polynomials can be computed by traversing through chains in certain weak order posets, and we provide explicit descriptions of such chains in weak order for involutions and degenerate involutions. As an application, we give several examples of how certain multiplicity-free sums of Schubert polynomials factor completely into very simple linear factors.
Socioeconomic factors and happiness: evidence from self-reported mental health data

This study investigates socioeconomic and health-related factors that contribute to well-being in America, partially replicating the analysis of Oswald and Wu (Rev Econ Stat 93(4):1118–1134, 2011) using many more years’ worth of data. In particular, data from more than 2 decades of Behavioral Risk Factor Surveillance System surveys were used to investigate to what degree various factors explain the self-reported number of bad mental health days in the past month. We find that self-reported mental health changes most with age, employment situation, and marital status. Mental health was worse when income was less than peer group average or weight was more than peer group average, and the strength of these effects differed by gender. Because data spanned several decades, we were able to estimate generational effects and time trends, unlike otherwise similar analyses of BRFSS data.
An oTree-based flexible architecture for financial market experiments

Abstract This document presents an architecture for experiments in finance. The architecture builds on oTree, a modern platform for behavioral experiments, allowing for sophisticated economic environments, market institutions, and trader strategies. The system supports both continuous-and discrete-time markets, and allows for communication latencies at time resolutions of 10–20 ms. Such precise communication latencies facilitate the experimental study of high-frequency trading. The architecture also modularizes its main components, which makes the system flexible, portable, and scalable.
Postoperative Opioid Prescribing Practices and Evidence-Based Guidelines in Bariatric Surgery.

Excessive opioid prescribing creates risk for abuse and adverse effects, but must be balanced against individualized pain control. Minimal literature exists to guide providers in the postoperative bariatric surgical setting. We compare opioid prescribing practice for minimally invasive bariatric surgery in a university hospital with self-reported patient use and satisfaction. This data is used to create practice guidelines for postoperative prescriptions. A 10-question survey was administered at the first postoperative office visit. All patients at this visit were eligible. None declined or excluded. We analyzed 115 patients for 3 procedures: laparoscopic sleeve gastrectomy (LSG; n = 53), laparoscopic roux-en-Y gastric bypass (LRYGB; n = 50), and laparoscopic adjustable gastric band removal (LAGBR; n = 12). Outcomes included number of pills prescribed (verified), proportion used, duration of use, satisfaction with pain control, and non-narcotic analgesic use. An average of 27 ± 10 pills were dispensed for LSG, average 4.1 days of use; 28 ± 7 pills for LRYGB, 4.6 days; and16 ± 9 pills for LAGBR, 2.6 days. Fifty to 74% retained more than half or all of their opioids at 2 weeks. Fifty-four percent utilized non-narcotic analgesics. Overall, 91.3% reported adequate pain control. For each procedure, average number of pills used was calculated with representative values for “less than half left” (75% of average number of pills prescribed) and “more than half left” (25% of average number of pills prescribed). For LSG, an average of 9 pills were used; LRYGB 14 pills, and LAGBR 7 pills. Opioids are overprescribed following most common surgical procedures, but only one study has evaluated patterns after bariatric surgery. Our survey-based tool examines prescribing, utilization and satisfaction following common minimally invasive bariatric procedures. Opioid prescriptions were variable, and excessive for most patients. We now recommend prescribing no more than 15 pills after these operations.
Physics at a Photon Collider

A Photon Collider will provide unique opportunities to study the SM Higgs boson and to determine its properties. MSSM Higgs bosons can be discovered at the Photon Collider for scenarios where they might escape detection at the LHC. As an example for the many other physics topics which can be studied at a Photon Collider, recent results on Non-Commutative Field Theories are also discussed.
Regressive Sin Taxes, With an Application to the Optimal Soda Tax

A common objection to “sin taxes”—corrective taxes on goods that are thought to be overconsumed, such as cigarettes, alcohol, and sugary drinks—is that they often fall disproportionately on low-income consumers. This paper studies the interaction between corrective and redistributive motives in a general optimal taxation framework and delivers empirically implementable formulas for sufficient statistics for the optimal commodity tax. The optimal sin tax is increasing in the price elasticity of demand, increasing in the degree to which lower-income consumers are more biased or more elastic to the tax, decreasing in the extent to which consumption is concentrated among the poor, and decreasing in income effects, because income effects imply that commodity taxes create labor supply distortions. Contrary to common intuitions, stronger preferences for redistribution can increase the optimal sin tax, if lower-income consumers are more responsive to taxes or are more biased. As an application, we estimate the optimal nationwide tax on sugar-sweetened beverages, using Nielsen Homescan data and a specially designed survey measuring nutrition knowledge and self-control. Holding federal income tax rates constant, our estimates imply an optimal federal sugar-sweetened beverage tax of 1 to 2.1 cents per ounce, although optimal city-level taxes could be as much as 60% lower due to cross-border shopping.
Direct synthesis of methyl 2-diazo-4-aryl-3-butenoates and their application to the enantioselective synthesis of 4 -aryl -4 -(1 -naphthyl ) -2 -butenoates

Abstract An improved one-flask synthesis of various methyl 2-diazo-4-aryl and 4-heteroaryl-3-butenoates, precursors to donor/acceptor substituted carbenoids, is described. Their Rh 2 ( S -DOSP) 4 catalyzed reaction with 1-acetoxy-3,4-dihydronaphthalene, via a combined C–H activation/Cope rearrangement pathway followed by elimination of acetic acid affords a highly enantioselective (98–99% ee) entry to methyl 4-aryl- and 4-heteroaryl-4-(1-naphthyl)-2-butenoates.
Co-regulation of transcription by BRG1 and BRM, two mutually exclusive SWI/SNF ATPase subunits

SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity. However, it remains unknown how loss of the catalytic subunit(s) affects the binding and genome-wide occupancy of the remainder complex and how changes in occupancy affect transcriptional output. We addressed this gap by depleting BRG1 and BRM, the two ATPase subunits in SWI/SNF, and characterizing the changes to chromatin occupancy of the remaining subunit and related this to transcription changes induced by loss of the ATPase subunits. We show that depletion of one subunit frequently leads to loss of the remaining subunit. This could cause either positive or negative changes in gene expression. At a subset of sites, the sibling subunit is either retained or gained. Additionally, we show genome-wide that BRG1 and BRM have both cooperative and antagonistic interactions with respect to transcription. Importantly, at genes where BRG1 and BRM antagonize one another we observe a nearly complete rescue of gene expression changes in the combined BRG/BRM double knockdown. This series of experiments demonstrate that mutually exclusive SWI/SNF complexes have heterogeneous functional relationships and highlight the importance of considering the role of the remaining SWI/SNF complexes following loss or depletion of a single subunit.
Disentangling bacterial invasiveness from lethality in an experimental host‐pathogen system

Quantifying virulence remains a central problem in human health, pest control, disease ecology, and evolutionary biology. Bacterial virulence is typically quantified by the LT50 (i.e., the time taken to kill 50% of infected hosts); however, such an indicator cannot account for the full complexity of the infection process, such as distinguishing between the pathogen's ability to colonize versus kill the hosts. Indeed, the pathogen needs to breach the primary defenses in order to colonize, find a suitable environment to replicate, and finally express the virulence factors that cause disease. Here, we show that two virulence attributes, namely pathogen lethality and invasiveness, can be disentangled from the survival curves of a laboratory population of Caenorhabditis elegans nematodes exposed to three bacterial pathogens: Pseudomonas aeruginosa, Serratia marcescens, and Salmonella enterica We first show that the host population eventually experiences a constant mortality rate, which quantifies the lethality of the pathogen. We then show that the time necessary to reach this constant mortality rate regime depends on the pathogen growth rate and colonization rate, and thus determines the pathogen invasiveness. Our framework reveals that Serratia marcescens is particularly good at the initial colonization of the host, whereas Salmonella enterica is a poor colonizer yet just as lethal once established. Pseudomonas aeruginosa, on the other hand, is both a good colonizer and highly lethal after becoming established. The ability to quantitatively characterize the ability of different pathogens to perform each of these steps has implications for treatment and prevention of disease and for the evolution and ecology of pathogens.
The crystal growth and characterization of the lanthanide-containing double perovskites Ln2NaIrO6 (Ln=La, Pr, Nd)

Abstract Single crystals of a series of double perovskite oxides Ln2NaIrO6 (Ln=La, Pr, Nd) have been synthesized in acidic molten NaOH fluxes. They crystallize in the monoclinic space group P21/n, forming a distorted 1:1 ordered rock salt lattice of the Na+ and Ir5+ cations. Magnetic susceptibility measurements show paramagnetic behavior, with no evidence of magnetic order down to 2 K.
Comments on quasicrystals and their potential use as catalysts

Recent findings suggest that quasicrystalline materials may make better catalysts than their crystalline counterparts. On the other hand, detailed surface science studies suggest that the surfaces of Al-based quasicrystals behave as if they are chemically similar to pure Al. In this paper, we discuss these results along with the unique thermodynamic and electronic properties of quasicrystals which could affect their catalytic nature.
Monetary Policy in Fossil Fuel Exporters : The Curse of Horizons

This paper examines the role of monetary policy in fossil fuel exporters at different horizons. The main argument is that central banks in these economies need to look beyond the horizon of the business cycle. In the short run, (independent) monetary policy should flexibly target inflation. In the medium run, central banks need to coordinate with fiscal authorities to ensure that monetary policy operates around a credible and sustainable fiscal anchor. In the long run, central banks should beware of the existential threats posed by new risks related to stranded assets.
Homomorphic Signatures for Polynomial Functions.

We construct the first homomorphic signature scheme that is capable of evaluating multivariate polynomials on signed data. Given the public key and a signed data set, there is an efficient algorithm to produce a signature on the mean, standard deviation, and other statistics of the signed data. Previous systems for computing on signed data could only handle linear operations. For polynomials of constant degree, the length of a derived signature only depends logarithmically on the size of the data set. Our system uses ideal lattices in a way that is a “signature analogue” of Gentry’s fully homomorphic encryption. Security is based on hard problems on ideal lattices similar to those in Gentry’s system.
Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons

Hippocampus, granular retrosplenial cortex (RSCg), and anterior thalamic nuclei (ATN) interact to mediate diverse cognitive functions. To identify cellular mechanisms underlying hippocampo-thalamo-retrosplenial interactions, we investigated the potential circuit suggested by projections to RSCg layer 1 (L1) from GABAergic CA1 neurons and ATN. We find that CA1→RSCg projections stem from GABAergic neurons with a distinct morphology, electrophysiology, and molecular profile. Their long-range axons inhibit L5 pyramidal neurons in RSCg via potent synapses onto apical tuft dendrites in L1. These inhibitory inputs intercept L1-targeting thalamocortical excitatory inputs from ATN to coregulate RSCg activity. Subicular axons, in contrast, excite proximal dendrites in deeper layers. Short-term plasticity differs at each connection. Chemogenetically abrogating CA1→RSCg or ATN→RSCg connections oppositely affects the encoding of contextual fear memory. Our findings establish retrosplenial-projecting CA1 neurons as a distinct class of long-range dendrite-targeting GABAergic neuron and delineate an unusual cortical circuit specialized for integrating long-range inhibition and thalamocortical excitation.
Antagonist muscle activity during reactive balance responses is elevated in Parkinson's disease and in balance impairment.

Background Abnormal antagonist leg muscle activity could indicate increased muscle co-contraction and clarify mechanisms of balance impairments in Parkinson’s disease (PD). Prior studies in carefully selected patients showed PD patients demonstrate earlier, longer, and larger antagonist muscle activation during reactive balance responses to perturbations. Research question Here, we tested whether antagonist leg muscle activity was abnormal in a group of PD patients who were not selected for phenotype and most of whom had volunteered for exercise-based rehabilitation. Methods We compared antagonist activation during reactive balance responses to multidirectional support-surface translation perturbations in 31 patients with mild-moderate PD (age 68±9; HY UPDRS-III 32±10) and 13 matched individuals (age 65±9). We quantified modulation of muscle activity (i.e., the ability to activate and inhibit muscles appropriately according to the perturbation direction) using modulation indices (MI) derived from minimum and maximum EMG activation levels observed across perturbation directions. Results Antagonist leg muscle activity was abnormal in unselected PD patients compared to controls. Linear mixed models identified significant associations between impaired modulation and PD (P<0.05) and PD severity (P<0.01); models assessing the entire sample without referencing PD status identified associations with balance ability (P<0.05), but not age (P = 0.10). Significance Antagonist activity is increased during reactive balance responses in PD patients who are not selected on phenotype and are candidates for exercise-based rehabilitation. This activity may be a mechanism of balance impairment in PD and a potential rehabilitation target or outcome measure.
Increased temperatures may safeguard the nutritional quality of crops under future elevated CO2 concentrations.

Iron (Fe) and zinc (Zn) deficiencies are a global human health problem that may worsen by the growth of crops at elevated atmospheric CO2 concentration (eCO2 ). However, climate change will also involve higher temperature, but it is unclear how the combined effect of eCO2 and higher temperature will affect the nutritional quality of food crops. To begin to address this question, we grew soybean (Glycine max) in a Temperature by Free-Air CO2 Enrichment (T-FACE) experiment in 2014 and 2015 under ambient (400 μmol mol-1 ) and elevated (600 μmol mol-1 ) CO2 concentrations, and under ambient and elevated temperatures (+2.7°C day and +3.4°C at night). In our study, eCO2 significantly decreased Fe concentration in soybean seeds in both seasons (-8.7 and -7.7%) and Zn concentration in one season (-8.9%), while higher temperature (at ambient CO2 concentration) had the opposite effect. The combination of eCO2 with elevated temperature generally restored seed Fe and Zn concentrations to levels obtained under ambient CO2 and temperature conditions, suggesting that the potential threat to human nutrition by increasing CO2 concentration may not be realized. In general, seed Fe concentration was negatively correlated with yield, suggesting inherent limitations to increasing seed Fe. In addition, we confirm our previous report that the concentration of seed storage products and several minerals varies with node position at which the seeds developed. Overall, these results demonstrate the complexity of predicting climate change effects on food and nutritional security when various environmental parameters change in an interactive manner.
Lewis Acid-Promoted Reactions of 3-Methoxy-N-(benzenesulfonyl)-1,4-benzoquinone Monoimine with Propenylbenzenes.

BF3·OEt2-promoted reactions of 4-N-(benzenesulfonyl)-3-methoxy-1,4-benzoquinone monoimine (5) with (E)-propenylbenzenes bearing strong electron-donating groups on their aromaric rings produce 2-aryl-6-methoxy-3-methyl-5-[N-(benzenesulfonyl)amino]-2,3-diydrobenzofurans (6). With neutral propenylbenzenes, either the dihydrobenzofurans, bicyclo[3.2.1]octenediones 17, or products of tandem cycloaddition (7−9) are formed depending upon reaction conditions. In the latter, molecules with seven to eight asymmetric centers are formed in a single reaction from achiral starting materials. Thus, these seemingly simple reactions yield products of remarkable complexity, and with a high degree of stereoselectivity.
Aqueous medium effects on multi-component reactions

The effect of aqueous media on many organic reactions has been studied, and often those reactions exhibiting pressure acceleration are also accelerated in water. Because some specific examples of the Ugi and Passerini reactions that are inefficient under conventional conditions have been accelerated by pressure, we examined Ugi and Passerini reactions in aqueous solutions, where significant increases in efficiency were observed. These effects were correlated to the cohesive energy density of aqueous solutions.
Sequence Specific Modeling of E. coli Cell-Free Protein Synthesis.

Cell-free protein synthesis (CFPS) is a widely used research tool in systems and synthetic biology. However, if CFPS is to become a mainstream technology for applications such as point of care manufacturing, we must understand the performance limits and costs of these systems. Toward this question, we used sequence specific constraint based modeling to evaluate the performance of E. coli cell-free protein synthesis. A core E. coli metabolic network, describing glycolysis, the pentose phosphate pathway, energy metabolism, amino acid biosynthesis, and degradation was augmented with sequence specific descriptions of transcription and translation and effective models of promoter function. Model parameters were largely taken from literature; thus the constraint based approach coupled the transcription and translation of the protein product, and the regulation of gene expression, with the availability of metabolic resources using only a limited number of adjustable model parameters. We tested this approach by s...
The feature-weighted receptive field: an interpretable encoding model for complex feature spaces

Abstract We introduce the feature-weighted receptive field (fwRF), an encoding model designed to balance expressiveness, interpretability and scalability. The fwRF is organized around the notion of a feature map—a transformation of visual stimuli into visual features that preserves the topology of visual space (but not necessarily the native resolution of the stimulus). The key assumption of the fwRF model is that activity in each voxel encodes variation in a spatially localized region across multiple feature maps. This region is fixed for all feature maps; however, the contribution of each feature map to voxel activity is weighted. Thus, the model has two separable sets of parameters: “where” parameters that characterize the location and extent of pooling over visual features, and “what” parameters that characterize tuning to visual features. The “where” parameters are analogous to classical receptive fields, while “what” parameters are analogous to classical tuning functions. By treating these as separable parameters, the fwRF model complexity is independent of the resolution of the underlying feature maps. This makes it possible to estimate models with thousands of high-resolution feature maps from relatively small amounts of data. Once a fwRF model has been estimated from data, spatial pooling and feature tuning can be read-off directly with no (or very little) additional post-processing or in-silico experimentation. We describe an optimization algorithm for estimating fwRF models from data acquired during standard visual neuroimaging experiments. We then demonstrate the model’s application to two distinct sets of features: Gabor wavelets and features supplied by a deep convolutional neural network. We show that when Gabor feature maps are used, the fwRF model recovers receptive fields and spatial frequency tuning functions consistent with known organizational principles of the visual cortex. We also show that a fwRF model can be used to regress entire deep convolutional networks against brain activity. The ability to use whole networks in a single encoding model yields state-of-the-art prediction accuracy. Our results suggest a wide variety of uses for the feature-weighted receptive field model, from retinotopic mapping with natural scenes, to regressing the activities of whole deep neural networks onto measured brain activity.
MOLECULAR STRUCTURE OF THE GEH2...OH2 COMPLEX

Hartree−Fock and post-Hartree−Fock (density functional DFT, many-body perturbation theory MP2 and MP4(SDTQ), and coupled-cluster CCSD, and CCSD[T]) quantum-mechanical methods were applied to establish molecular structures and interaction energies of the GeH2···OH2 complex. Molecular geometries of nonplanar and planar conformers were optimized at the Hartree−Fock, DFT, and MP2 levels of theory using triple-ζ-quality (TZP) augmented by sets of polarization functions (TZP(2d,2p) and TZP(2df,2pd)) basis sets. The optimized nonplanar structures correspond to minimum-energy species at all applied levels of theory. Calculated interaction energies (corrected for the basis set superposition error, CP) are relatively large and amount to −9.43 kcal/mol (MP4(CP)(SDTQ)/TZP(2df,2pd)//MP2/TZP(2df,2pd)), −9.77 kcal/mol (DFT(CP)/TZP(2df,2pd)//DFT/TZP(2df,2pd)), −8.16 kcal/mol (CCSD(CP)/TZP(2df,2pd)//MP2/TZP(2df,2pd)), and −8.90 kcal/mol at the CCSD[T](CP)/TZP(2df,2pd) levels. The optimized planar molecular structure of th...
Relaxed Two-to-one Recoding Schemes.

A two-to-one recoding (TOR) scheme is a new cryptographic primitive, proposed in the recent work of Gorbunov, Vaikuntanathan, and Wee (GVW), as a means to construct attribute-based encryption (ABE) schemes for all boolean circuits. GVW show that TOR schemes can be constructed assuming the hardness of the learning-with-errors (LWE) problem. We propose a slightly weaker variant of TOR schemes called correlation-relaxed two-to-one recoding (CR-TOR). Unlike the TOR schemes, our weaker variant does not require an encoding function to be pseudorandom on correlated inputs. We instead replace it with an indistinguishability property that states a ciphertext is hard to decrypt without access to a certain encoding. The primary benefit of this relaxation is that it allows the construction of ABE for circuits using the TOR paradigm from a broader class of cryptographic assumptions. We show how to construct a CR-TOR scheme from the noisy cryptographic multilinear maps of Garg, Gentry, and Halevi as well as those of Coron, Lepoint, and Tibouchi. Our framework leads to an instantiation of ABE for circuits that is conceptually different from the existing constructions.
Type I procollagen heterotrimer assembly is linked to subtle differences in the structures of the pro-α1(I) and pro-α2(I)-carboxyl-propeptides

The assembly of the type I procollagen heterotrimer is initiated by an interaction between the carboxyl propeptides, with triple helix folding proceeding in the C→N direction. The pro-α1-(I)-C-propeptides can interact with self to form the homotrimer or with pro-α2(I)-C-propeptide to establish the heterotrimer. The two propeptides are similar in length and have about 65% identity in sequence. Nevertheless, we proposed that differences in interaction between propeptides might account for thein vivo selection of heterotrimer formation rather than homotrimer formation. To test this hypothesis we have determined the probable structures of the human C-propeptides by molecular modeling and energy minimization using Molecular Simulations Insight, Discover 95.0/3.0, and Biopolymer programs. The propeptide structures were constrained with the two known intrachain disulfide bonds in each case. The two structures were globally similar, with three distinct structural domains (G-I, L, G-II) in each case. A few crucial Pro residues and other sequence differences, however, produced different structures in each domain. The different interaction profiles of the three domains may be of crucial importance for heterotrimer selection.
Titanium-Mediated [2 + 2 + 2] Coupling of Diynes with Homoallylic Alcohols

In connection with the known diyne-ene [2 + 2 + 2] cycloaddition reactions mediated by titanium aryloxides, the ability of titanium alkoxides to promote coupling of a titanacyclopentadiene with an alkene has been assessed for the isomerization-free preparation of 1,3-cyclohexadienes. The successful cycloaddition by titanium alkoxides is predicated on the use of homoallylic alcohols as the olefin component. With secondary homoallylic alcohols, high 1,3-diastereoselectivity is observed, which lends itself to enantioselective preparation of functionalized 1,3-cyclohexadienes.
Centrifuge: rapid and sensitive classification of metagenomic sequences

Centrifuge is a novel microbial classification engine that enables rapid, accurate, and sensitive labeling of reads and quantification of species on desktop computers. The system uses an indexing scheme based on the Burrows-Wheeler transform (BWT) and the Ferragina-Manzini (FM) index, optimized specifically for the metagenomic classification problem. Centrifuge requires a relatively small index (4.2 GB for 4078 bacterial and 200 archaeal genomes) and classifies sequences at very high speed, allowing it to process the millions of reads from a typical high-throughput DNA sequencing run within a few minutes. Together, these advances enable timely and accurate analysis of large metagenomics data sets on conventional desktop computers. Because of its space-optimized indexing schemes, Centrifuge also makes it possible to index the entire NCBI nonredundant nucleotide sequence database (a total of 109 billion bases) with an index size of 69 GB, in contrast to k-mer-based indexing schemes, which require far more extensive space.
Biomimetic Syntheses of the Flindersial Alkaloids

The flindersial alkaloids have a potentially novel mechanism for antimalarial activity. The recently disclosed flinderoles were postulated to be derived through dimerization of the natural product borrerine in a manner similar to their structural isomers, the borreverines. Recent work by the authors has shown that the flindersial alkaloids share a common biosynthetic origin to that of borrerine. The application of this insight has resulted in the synthesis of naturally occurring flindersial alkaloids with controlled formation of the structural isomer. Only three synthetic steps from tryptamine are needed for any of the natural products.
Preferential Targeting of Lateral Entorhinal Inputs onto Newly Integrated Granule Cells.

Mature dentate granule cells in the hippocampus receive input from the entorhinal cortex via the perforant path in precisely arranged lamina, with medial entorhinal axons innervating the middle molecular layer and lateral entorhinal cortex axons innervating the outer molecular layer. Although vastly outnumbered by mature granule cells, adult-generated newborn granule cells play a unique role in hippocampal function, which has largely been attributed to their enhanced excitability and plasticity (Schmidt-Hieber et al., 2004; Ge et al., 2007). Inputs from the medial and lateral entorhinal cortex carry different informational content, thus the distribution of inputs onto newly integrated granule cells will affect their function in the circuit. Therefore we examined the functional innervation and synaptic maturation of newly-generated dentate granule cells in the mouse hippocampus using retroviral labeling in combination with selective optogenetic activation of medial or lateral entorhinal inputs. Our results indicate that lateral entorhinal inputs provide the majority of functional innervation of newly integrated granule cells at 21 day post-mitosis. Despite preferential functional targeting, the dendritic spine density of immature granule cells was similar in the outer and middle molecular layers, which we speculate could reflect an unequal distribution of shaft synapses. However, chronic blockade of neurotransmitter release of medial entorhinal axons with tetanus toxin disrupted normal synapse development of both medial and lateral entorhinal inputs. Our results support a role for preferential lateral perforant path input onto newly generated neurons in mediating pattern separation, but also indicates that medial perforant path input is necessary for normal synaptic development. SIGNIFICANCE STATEMENT The formation of episodic memories involves the integration of contextual and spatial information. Newly-integrated neurons in the dentate gyrus of the hippocampus play a critical role in this process, despite constituting only a minor fraction of the total number of granule cells. Here we demonstrate that these neurons preferentially receive information thought to convey the context of an experience - a unique role that each newly integrated granule cell serves for about a month before reaching maturity.