cssi/SciSciGPT-SciSciNet huggingface dataset:
Extreme copy number variation at a tRNA ligase gene affecting phenology and fitness in yellow monkeyflowers.

Copy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness-relevant, CNV within an annual population of the yellow monkeyflower Mimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate-frequency three-copy variants of RLG1a (trip+; 5/35 = 14%), and trip+ lines exhibited elevated RLG1a expression under multiple conditions. trip+ carriers, in addition to being over-represented in late-flowering and large-flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (p < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+) that carries 250-300 copies of RLG1a totalling ~5.7 Mb (20-40% of a chromosome). In the progeny of a high+ carrier, Mendelian segregation of diagnostic alleles and qPCR-based copy counts indicate that high+ is a single tandem array unlinked to the single-copy RLG1a locus. In the wild, high+ carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single-copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress-responsive life-history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification.
Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning.

Summary C. elegans vulval precursor cell (VPC) fates are patterned by an epidermal growth factor (EGF) gradient. High-dose EGF induces 1° VPC fate, and lower dose EGF contributes to 2° fate in support of LIN-12/Notch. We previously showed that the EGF 2°-promoting signal is mediated by LET-60/Ras switching effectors, from the canonical Raf-MEK-ERK mitogen-activated protein (MAP) kinase cascade that promotes 1° fate to the non-canonical RalGEF-Ral that promotes 2° fate. Of oncogenic Ras effectors, RalGEF-Ral is by far the least well understood. We use genetic analysis to identify an effector cascade downstream of C. elegans RAL-1/Ral, starting with an established Ral binding partner, Exo84 of the exocyst complex. Additionally, RAL-1 signals through GCK-2, a citron-N-terminal-homology-domain-containing MAP4 kinase, and PMK-1/p38 MAP kinase cascade to promote 2° fate. Our study delineates a Ral-dependent developmental signaling cascade in vivo , thus providing the mechanism by which lower EGF dose is transduced.
The Social Cost of Strategic Classification

Consequential decision-making typically incentivizes individuals to behave strategically, tailoring their behavior to the specifics of the decision rule. A long line of work has therefore sought to counteract strategic behavior by designing more conservative decision boundaries in an effort to increase robustness to the effects of strategic covariate shift. We show that these efforts benefit the institutional decision maker at the expense of the individuals being classified. Introducing a notion of social burden, we prove that any increase in institutional utility necessarily leads to a corresponding increase in social burden. Moreover, we show that the negative externalities of strategic classification can disproportionately harm disadvantaged groups in the population. Our results highlight that strategy-robustness must be weighed against considerations of social welfare and fairness.
The Current State of the Pediatric Emergency Medicine Workforce and Innovations to Improve Pediatric Care

Abstract Many hospitals and emergency departments lack resources to optimally care for ill and injured children, perpetuating risks of receiving fragmented and “uneven” care. In this article, we describe the present state of our pediatric emergency medicine workforce as well as the impact that different innovations could have on the future of pediatric emergency care. Many innovative initiatives, including physician and advanced practice provider education and training, pediatric readiness recognition programs, telemedicine and in-situ simulation outreach, and community paramedicine are being utilized to help bridge access gaps and augment the reach of the pediatric emergency medicine workforce. Advocacy for reimbursement for novel care delivery models, such as community paramedicine and telemedicine, and funding for outreach education is essential. Also, better understanding of our current training models for and utilization of advanced practice practitioners in pediatric emergency medicine is crucial to understanding the diversity of workforce growth and opportunity.
Non-linear pricing and optimal shipping policies

Abstract A monopolist produces a good for sale to a buyer with uncertain valuation. The seller seeks to implement a profit-maximizing non-linear pricing scheme, which includes the time at which the good is shipped to the consumer. If the buyer discounts future payoffs and the seller does not, then delayed shipments act as an almost-perfect substitute for complete information and the monopolist can extract almost all of the surplus from trade. Shipping policies thus serve as a powerful tool of enhancing price discrimination. However, if the seller is as patient as, or even only slightly more patient than, the buyer, then she cannot benefit from delaying allocations.
The state of the art of electrostatic discharge protection: physics, technology, circuits, design, simulation, and scaling

This paper discusses state-of-the-art electrostatic discharge (ESD) protection in advanced semiconductor technologies and emerging technologies. ESD physics, semiconductor process issues, device and circuit simulation, circuits, and devices are examined.
Interval Estimation of Individual-Level Causal Effects Under Unobserved Confounding

We study the problem of learning conditional average treatment effects (CATE) from observational data with unobserved confounders. The CATE function maps baseline covariates to individual causal effect predictions and is key for personalized assessments. Recent work has focused on how to learn CATE under unconfoundedness, i.e., when there are no unobserved confounders. Since CATE may not be identified when unconfoundedness is violated, we develop a functional interval estimator that predicts bounds on the individual causal effects under realistic violations of unconfoundedness. Our estimator takes the form of a weighted kernel estimator with weights that vary adversarially. We prove that our estimator is sharp in that it converges exactly to the tightest bounds possible on CATE when there may be unobserved confounders. Further, we study personalized decision rules derived from our estimator and prove that they achieve optimal minimax regret asymptotically. We assess our approach in a simulation study as well as demonstrate its application in the case of hormone replacement therapy by comparing conclusions from a real observational study and clinical trial.
Validated Prediction Models for Macular Degeneration Progression and Predictors of Visual Acuity Loss Identify High-Risk Individuals

Purpose To determine predictive factors and risk scores for conversion to overall advanced age-related macular degeneration (AMD), geographic atrophy (GA), neovascular disease (NV), and loss of vision, and to validate the model for AMD in an external cohort. Methods Progression to advanced AMD was evaluated using stepwise survival analysis. Risk scores including genetic, demographic, behavioral, and ocular factors were derived for 3 AMD endpoints and were validated and calibrated in a large independent cohort. Vision loss of 15 or more letters was evaluated as a new endpoint in genetic analyses. Results Eight common and rare variants in genes CFH, C3, ARMS2, COL8A1, and HSPH1/B3GALTL conferred a significantly higher risk of transition to advanced AMD. Three loci (C2, CFB, RAD51B) were associated with lower rate of progression. A protective effect was suggested for CTRB1 and PELI3. The age-adjusted area under the curve (AUC) for the composite model including 13 loci model was 0.900 over 12 years (0.896 in the validation cohort). Generally, progressors had a higher risk category and nonprogressors had a lower risk category when genetic factors were considered. Furthermore, there was heterogeneity between models for GA and NV. The model was calibrated in the validation cohort. Determinants of visual loss included age, education, body mass index, smoking, and several common and rare genetic variants. Conclusion Eyes with the same baseline macular grade had a wide range of estimated probability of subsequent progression and visual loss based on the validated risk score. Identifying high-risk individuals at an earlier stage using predictive modeling could lead to improved preventive and therapeutic strategies in the era of precision medicine.
Anderson localization for two interacting quasiperiodic particles

We consider a system of two discrete quasiperiodic 1D particles as an operator on $$\ell^2(\mathbb Z^2)$$ and establish Anderson localization at large disorder, assuming the potential has no cosine-type symmetries. In the presence of symmetries, we show localization outside of a neighborhood of finitely many energies. One can also add a deterministic background potential of low complexity, which includes periodic backgrounds and finite range interaction potentials. Such background potentials can only take finitely many values, and the excluded energies in the symmetric case are associated to those values.
Computing Robust Principal Components by A* Search

Principal Component Analysis (PCA) is a classical dimensionality reduction technique that computes a low rank representation of the data. Recent studies have shown how to compute this low rank repr...
The Academic Success of African American Males at a Maryland Community College

The purpose of this qualitative study is to examine the perception of African American males participating in one 4A program at a Mid-Atlantic community college. Twenty African American males, along with six staff members were selected to participate in the study. The study used focus groups to investigate students’ interactions with academic advisors and counselors and the impact of those interactions on students’ academic success. The nigrescence theory of evolving cultural identity served as the framework, as it emphasizes the role and impact of cultural identity as a driver for successful academic performance (Cross, 1991). The study revealed that these African American males had positive perceptions of their experiences in the program and with their mentors, advisors, and counselors.
Food Deserts and the Causes of Nutritional Inequality

We study the causes of “nutritional inequality”: why the wealthy eat more healthfully than the poor in the United States. Exploiting supermarket entry and household moves to healthier neighborhoods, we reject that neighborhood environments contribute meaningfully to nutritional inequality. We then estimate a structural model of grocery demand, using a new instrument exploiting the combination of grocery retail chains’ differing presence across geographic markets with their differing comparative advantages across product groups. Counterfactual simulations show that exposing low-income households to the same products and prices available to high-income households reduces nutritional inequality by only about 10%, while the remaining 90% is driven by differences in demand. These findings counter the argument that policies to increase the supply of healthy groceries could play an important role in reducing nutritional inequality.
Robust inference in models identified via heteroskedasticity

Identification via heteroskedasticity exploits variance changes between regimes to identify parameters in simultaneous equations. Weak identification occurs when shock variances change very little ...
Atomistic Study of the Effect of Magnesium Dopants on the Strength of Nanocrystalline Aluminum

Atomistic simulations have been used to study the deformation mechanisms of nanocrystalline pure Al and Al-Mg binary alloys. Voronoi tessellation was used to fully create a three-dimensional polycrystalline model with a grain size of 10 nm, while hybrid Monte Carlo and molecular dynamic simulations were used to achieve both mechanical and chemical equilibriums in nanocrystalline Al-5 at.%Mg. The results of tensile tests show an improved strength, including the yield strength and ultimate strength, through doping 5 at.%Mg into nanocrystalline aluminum. The results of atomic structures clearly reveal the multiple strengthening mechanisms related to doping in Al-Mg alloys. At the early deformation stage, up to an applied strain of 0.2, the strengthening mechanism of the dopants exhibits as dopant pinning grain boundary (GB) migration. However, at the late deformation stage, which is close to failure of nanocrystalline materials, dopants can prohibit the initiation of intergranular cracks and also impede propagation of existing cracks along the GBs, thus improving the flow stress of Al-Mg alloys.
Resampling Procedures for Sample Surveys

This entry discusses the two basic resampling techniques that have found widespread application in survey sampling: Jackknife Repeated Replication (JRR) and Balanced Repeated Replication (BRR). To date, resampling methods based on the bootstrap have found only limited application in samples, which involve complex (stratified and clustered) sample design. Keywords: resampling; replication; Jackknife repeated replication; balanced repeated replication; variance estimation; standard error estimation; complex survey samples
Ectopic Germ Cells Can Induce Niche-like Enwrapment by Neighboring Body Wall Muscle.

Summary Niche cell enwrapment of stem cells and their differentiating progeny is common and provides a specialized signaling and protective environment. Elucidating the mechanisms underlying enwrapment behavior has important basic and clinical significance in not only understanding how niches are formed and maintained but also how they can be engineered and how they are misregulated in human pathologies, such as cancer. Previous work in C. elegans found that, when germ cells, which are enwrapped by somatic gonadal niche cells, are freed into the body cavity, they embed into other tissues. We investigated this phenomenon using live-cell imaging and discovered that ectopic germ cells preferentially induce body-wall muscle to extend cellular processes that enwrap the germ cells, the extent of which was strikingly similar to the distal tip cell (DTC)-germ stem cell niche. Enwrapment was specific for escaped germ cells, and genetic analysis revealed it did not depend on pathways that control cell death and engulfment or muscle arm extension. Instead, using a large-scale RNAi screen and GFP knockin strains, we discovered that the enwrapping behavior of muscle relied upon the same suite of cell-cell adhesion molecules that functioned in the endogenous niche: the C. elegans E-cadherin HMR-1, its intracellular associates α-catenin (HMP-1) and β-catenin (HMP-2), and the L1CAM protein SAX-7. This ectopic niche-like behavior resembles the seed-and-soil model of cancer metastasis and offers a new model to understand factors regulating ectopic niche formation.
Directed, Palladium(II)-Catalyzed Enantioselective anti-Carboboration of Alkenyl Carbonyl Compounds.

A substrate-directed enantioselective anti-carboboration reaction of alkenes has been developed, wherein a carbon-based nucleophile and a boron moiety are installed across the C═C bond through a five-membered palladacycle intermediate. A preliminary result also shows it is possible to extend this reaction to alkenes that are more distal from the directing group and react via a six-membered palladacycle. The reaction is promoted by a palladium(II) catalyst and a monodentate oxazoline ligand. A range of enantioenriched secondary alkylboronate products were obtained with moderate to high enantioselectivity that could be further upgraded by recrystallization. This work represents an efficient method to synthesize versatile and valuable alkylboronate building blocks. Building on an earlier mechanistic proposal by He, Peng, and Chen, a revised model is proposed to account for the stereoconvergent nature of this transformation.
Fusion, Magnetic Confinement

An overview is presented of the principles of magnetic confinement of plasmas for the purpose of achieving controlled fusion conditions. Sec. 1 discusses the different nuclear fusion reactions which can be exploited in prospective fusion reactors and explains why special technologies need to be developed for the supply of tritium or {sup 3}He, the probable fuels. In Sec. 2 the Lawson condition, a criterion that is a measure of the quality of confinement relative to achieving fusion conditions, is explained. In Sec. 3 fluid equations are used to describe plasma confinement. Specific confinement configurations are considered. In Sec. 4 the orbits of particle sin magneti and electric fields are discussed. In Sec. 5 stability considerations are discussed. It is noted that confinement systems usually need to satisfy stability constraints imposed by ideal magnetohydrodynamic (MHD) theory. The paper culminates with a summary of experimental progress in magnetic confinement. Present experiments in tokamaks have reached the point that the conditions necessary to achieve fusion are being satisfied.
A rate-based equation-oriented parallel column model: Application to dividing wall columns

Abstract This paper describes a rate-based parallel column model, which, via the CAPE-OPEN framework, can be used in any CAPE-OPEN compliant process flowsheet simulation package and can be used to model dividing wall columns of arbitrary configuration. Heat transfer across the dividing wall can be modelled in a straightforward way. Vapour split ratios are determined during the solution of the model equations by requiring the pressure on both sides of the dividing wall(s) to be equal. We compare the predictions of the rate-based model to experimental data from the University of Texas at Austin. There is good agreement between model and measured data. A design case study demonstrates the versatility of our method of calculating vapour splits from a pressure balance.
KNOWLEDGE AND CONFIDENCE IN PERFORMING THE PUDENDAL BLOCK: AN ASSESSMENT OF NEWFOUNDLAND OBGYN RESIDENTS AND PHYSICIANS

Objectives The objectives of this study are to assess the knowledge of both OBGYN physicians and residents in Newfoundland on the utilization and administration of the pudendal block. Moreover, the participants attitude and confidence for this procedure will be explored. Finally, the barriers of performing the pudendal block in labor will be identified. Methods A prospective audit of residents and physicians of Newfoundland was conducted during April and May of 2018. The physicians and residents were invited to participate in a paper-based survey. The data was analyzed with SAS software. Results The results of the study showed no statistical significance between staff and residents in their knowledge of the labor pudendal block technique. However, 88% of residents believed that this topic was not covered well in the residency curriculum. Moreover, 94% of residents felt that they were not adequately prepared to provide the pudendal block as an option for labor analgesia in their practice. Conclusions While the textbook knowledge between staff and residents is similar, the practical training of pudendal block administration is lacking in residents. Moreover, there is a decline in the provision of the pudendal block for labor analgesia in Newfoundland which may partly be due to the staff physicians’ perception of its effectiveness. As a result, residents are not receiving adequate exposure to this in their training. A final consequence is the decrease in the confidence of trainees to perform the pudendal block in their future practices. From this study, it appears that a curriculum change is necessary.
Sentimental mutual fund flows

We show that many stylized empirical patterns for mutual fund flows are driven by investor sentiment. Specifically, when sentiment is high, investors exhibit a stronger tendency of chasing past fund performance; fund flows are less sensitive to fund expenses; and investors are attracted more to funds with sheer visibility. Moreover, the well‐documented positive relation between fund flows and future fund performance is significant only during high sentiment periods and is mainly driven by expected component of fund flows. Finally, we show that mutual fund investors exhibit a significantly negative timing ability at the individual fund level when sentiment is high.
Do foreign aid donors reward recipients for improving gender outcomes

ABSTRACTWe investigate whether developing nations are rewarded by donor countries and multilateral aid organizations for improving women’s outcomes. If donors reallocate accordingly, their decision...
Awake hippocampal-prefrontal replay mediates spatial learning and decision making

SUMMARY Spatial learning requires remembering and choosing paths to goals. Hippocampal place cells replay spatial paths during immobility in reverse and forward order, offering a potential mechanism. However, how replay mediates both goal-directed learning and memory-guided decision making is unclear. We therefore continuously tracked replay in the same hippocampal-prefrontal ensembles throughout learning of a spatial alternation task. We found that during pauses between behavioral trajectories, awake reverse and forward hippocampal replay consistently mediated an internal cognitive search of all available past and future possibilities, and exhibited opposing learning gradients for prediction of past and future behavioral paths, respectively. Coordinated hippocampal-prefrontal replay mediated recall of correct past paths and selection of future choices leading to reward based on the hippocampal cognitive search, executing spatial working memory rules. Our findings reveal a learning shift from hippocampal reverse-replay-based retrospective evaluation to forward-replay-based prospective planning, with prefrontal filtering of memory-guided paths for learning and decision-making.
Δ2-Isoxazolines from β,γ-unsaturated oximes

3,5-Disubstituted Δ2-isoxazolines can be prepared using the palladium-mediated nucleometalation / methoxycarbonylation of β,γ-unsaturated oximes. This novel route to this class of compounds is tolerant of a wide variety of functionality in the starting material, and provides a rapid route to highly functionalized isoxazolines.
Does Rainfall Matter for Economic Growth? Evidence from Global Sub-National Data (1990-2014)

Much micro-econometric evidence suggests that precipitation has wide ranging impacts on vital economic indicators such as agricultural yields, human capital, and even conflict. And yet paradoxically most macro-econometric evidence (especially in the climate economy literature) finds that precipitation has no robust and significant impact on various measures of aggregate economic output. This paper argues that spatial aggregation of weather at the country level explains this result. The paper uses annual subnational gross domestic product data to show a concave relationship between precipitation and local gross domestic product growth between 1990 and 2014. It then demonstrates that when the data are aggregated at larger spatial scales, the impact decreases and eventually vanishes. The impact of precipitation on aggregate economic activity is predominantly felt in developing countries; it is insignificant in developed countries. Agriculture is found to be the dominant pathway. The results have significant consequences for measuring the economic impacts of climate change.
Palladium-catalyzed ortho-halogenation of diaryl oxime ethers

Abstract The palladium-catalyzed ortho monobromination and iodination of single E or Z geometric isomers of substituted diaryl ketoxime ethers [Ar 1 C(Ar 2 ) = N–OCH 3 ] have been accomplished in good yield (64–82% isolated yield). A minor amount of di- ortho -halogenation side product is produced in this reaction (0–10%). The aromatic ring that is halogenated is the one ‘ trans ’ to the OCH 3 group, indicating that there is no isomerization about the C N bond during the reaction. Further, the site of functionalization is presumably controlled by the lone pair electrons on nitrogen. This study is the first to demonstrate the ability of the geometry of the oxime ether group to target the functionalization of only one aromatic ring when there are two aromatic rings directly attached to the carbon of the C N bond of the oxime ether. Electron-withdrawing substituents on either ring decrease reaction rate and diminish the amount of di- ortho -bromination side product.
An Open Library of Human Kinase Domain Constructs for Automated Bacterial Expression

Kinases play a critical role in cellular signaling and are dysregulated in a number of diseases, such as cancer, diabetes, and neurodegeneration. Therapeutics targeting kinases currently account for roughly 50% of cancer drug discovery efforts. The ability to explore human kinase biochemistry and biophysics in the laboratory is essential to designing selective inhibitors and studying drug resistance. Bacterial expression systems are superior to insect or mammalian cells in terms of simplicity and cost effectiveness but have historically struggled with human kinase expression. Following the discovery that phosphatase coexpression produced high yields of Src and Abl kinase domains in bacteria, we have generated a library of 52 His-tagged human kinase domain constructs that express above 2 μg/mL of culture in an automated bacterial expression system utilizing phosphatase coexpression (YopH for Tyr kinases and lambda for Ser/Thr kinases). Here, we report a structural bioinformatics approach to identifying kinase domain constructs previously expressed in bacteria and likely to express well in our protocol, experiments demonstrating our simple construct selection strategy selects constructs with good expression yields in a test of 84 potential kinase domain boundaries for Abl, and yields from a high-throughput expression screen of 96 human kinase constructs. Using a fluorescence-based thermostability assay and a fluorescent ATP-competitive inhibitor, we show that the highest-expressing kinases are folded and have well-formed ATP binding sites. We also demonstrate that these constructs can enable characterization of clinical mutations by expressing a panel of 48 Src and 46 Abl mutations. The wild-type kinase construct library is available publicly via Addgene.
Structures and bonding in K0.91U1.79S6 and KU2Se6.

The compounds K 0.91 U 1.79 S 6 and KU 2 Se 6 , members of the AAn 2 Q 6 actinide family (A = alkali metal or Tl; An = Th or U; Q = S, Se, or Te), have been synthesized from US 2 , K 2 S, and S at 1273 K and U, K 2 Se, and Se at 1173 K, respectively. KU 2 Se 6 shows Curie-Weiss behavior above 30 K and no magnetic ordering down to 5 K. The value of μ eff is 2.95(1) μ B /U. Its electronic spectrum shows the peaks characteristic of 5f-5f transitions. It is a semiconductor with an activation energy of 0.27 eV for electrical conduction. Both K 0.91 U 1.79 S 6 and KU 2 Se 6 crystallize in space group Immm of the orthorhombic system and are of the KTh 2 Se 6 structure type. Both contain infinite one-dimensional linear Q-Q chains characteristic of the AAn 2 Q 6 family. Typical of the known AAn 2 Q 6 compounds, in KU 2 Se 6 , there are two alternating Se-Se distances of 2.703(2) and 2.855(2) A, both much longer than an Se-Se single bond. In contrast, in K 0.91 U 1.79 S 6 , the first sulfide of this family to be characterized structurally, there are alternating normal S 2 2- pairs 2.097(5) A in length. In K 0.91 U 1.79 S 6 , the formal oxidation state of U is 4+.
An efficient synthesis of 3,3-difluoro-pyrrolidine hydrochloride starting with 2-chloro-2,2-difluoroacetic acid

Abstract A facile and fluorination-free synthesis of 3,3-difluoropyrrolidine hydrochloride (3), an important synthon in the synthesis of biologically active compounds, is reported. The seven-step synthesis starts from the commercially available 2-chloro-2,2-difluoroacetic acid (1) in a three-step telescoped process that produces crystalline N,N-diethyl-2,2-difluoro-3-hydroxy-4-nitrobutanamide (2). A convenient and high-yielding reductive nitromethylation of 2 followed by a catalytic hydrogenation/cyclization sequence and borane reduction affords 3 in good yield and purity.
Deconstructing multivariate decoding for the study of brain function

Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function.
Multiiron Polyoxoanions. Syntheses, Characterization, X-ray Crystal Structures, and Catalysis of H2O2-Based Hydrocarbon Oxidations by [FeIII4(H2O)2(P2W15O56)2]12-

The reaction of [P2W15O56]12- and aqueous Fe3+ forms two ferric polytungstophosphate derivatives that have been isolated, purified, and characterized by X-ray crystallography and several physical methods. At pH ∼3 and [Na+] = 2 M, needles of Na12[FeIII4(H2O)2(P2W15O56)2]·58H2O, Na-1, form, in which the conventional ion packing arrangement in solid heteropoly acids is observed: each polyanion, [FeIII4(H2O)2(P2W15O56)2]12- (1), is well separated by the cations (Na+). At pH ∼1 and [Na+] = 1 M, however, elongated prisms of H3Na9[FeIII4(H2O)2(P2W15O56)2]·62H2O, (Na-1)n, form. (Na-1)n is a novel one-dimensional inorganic polymer composed of 1 linked via ion pairing with strongly associated hydrated sodium cations. Both Na-1 and (Na-1)n display identical characteristics in H2O solution. Seven lines of evidence are consistent with the FeIII4 oxidation state in 1: (1) the synthesis itself (only Fe3+ used); (2) bond-length-based valence sum calculations based on the two X-ray structures; (3) the electrochemical b...
Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection

The Mre11-Rad50-Xrs2NBS1 complex plays important roles in the DNA damage response by activating the Tel1ATM kinase and catalyzing 5′–3′ resection at DNA double-strand breaks (DSBs). To initiate resection, Mre11 endonuclease nicks the 5′ strands at DSB ends in a reaction stimulated by Sae2CtIP. Accordingly, Mre11-nuclease deficient (mre11-nd) and sae2Δ mutants are expected to exhibit similar phenotypes; however, we found several notable differences. First, sae2Δ cells exhibit greater sensitivity to genotoxins than mre11-nd cells. Second, sae2Δ is synthetic lethal with sgs1Δ, whereas the mre11-nd sgs1Δ mutant is viable. Third, Sae2 attenuates the Tel1-Rad53CHK2 checkpoint and antagonizes Rad953BP1 accumulation at DSBs independent of Mre11 nuclease. We show that Sae2 competes with other Tel1 substrates, thus reducing Rad9 binding to chromatin and to Rad53. We suggest that persistent Sae2 binding at DSBs in the mre11-nd mutant counteracts the inhibitory effects of Rad9 and Rad53 on Exo1 and Dna2-Sgs1–mediated resection, accounting for the different phenotypes conferred by mre11-nd and sae2Δ mutations. Collectively, these data show a resection initiation independent role for Sae2 at DSBs by modulating the DNA damage checkpoint.
Synthesis of (+/-) mappicine and mappicine ketone

Mappicine and mappicine ketone are camptothecin analogs of interest as antiviral agents. A novel synthesis of these compounds is described using a Friedlander condensation. The requisite ketone is prepared via a regioselective ortho-directed metallation/alkylation of a trisubstituted pyridine. This is condensed with N-t-butyloxycarbonyl-o-aminobenzaldehyde as a convenient, stable o-aminobenzaldehyde equivalent in the Friedlander condensation.
N-Substituted tertiary and O-substituted quaternary carbon stereogenic centers by site-, diastereo- and enantioselective vinylogous Mannich reactions

A readily accessible small-molecule phosphine, derived from commercially available starting materials such as an enantiomerically pure amino acid, serves as the precursor to a Ag-based chiral complex that can be prepared and used in situ to promote a variety of enantioselective vinylogous Mannich (EVM) reactions that involve siloxypyrroles as reaction partners. Transformations with unsubstituted nucleophilic components proceed efficiently and with exceptional site- (γ vs α-addition), diastereo- and enantioselectivity [up to 98% yield, generally >98:2 γ/α and diastereomeric ratio (dr) and up to 99:1 enantiomeric ratio (er)]. The first examples of efficient, diastereo- and enantioselective vinylogous Mannich additions with 5-methyl-substituted siloxyfuran, resulting in the formation of O-substituted quaternary carbon stereogenic centers are presented as well. Appreciable efficiency and diastereo- and enantioselectivity (up to >98:2 dr and >99:1 er) is accompanied by formation of α-addition products that can be oxidatively removed.
Phenotypes associated with genes encoding drug targets are predictive of clinical trial side effects.

Only a small fraction of early drug programs progress to the market, due to safety and efficacy failures, despite extensive efforts to predict safety. Characterizing the effect of natural variation in the genes encoding drug targets should present a powerful approach to predict side effects arising from drugging particular proteins. In this retrospective analysis, we report a correlation between the organ systems affected by genetic variation in drug targets and the organ systems in which side effects are observed. Across 1819 drugs and 21 phenotype categories analyzed, drug side effects are more likely to occur in organ systems where there is genetic evidence of a link between the drug target and a phenotype involving that organ system, compared to when there is no such genetic evidence (30.0 vs 19.2%; OR = 1.80). This result suggests that human genetic data should be used to predict safety issues associated with drug targets. Safety issues including side effects are one of the major factors causing failure of clinical trials in drug development. Here, the authors leverage information about phenotypes associated with variation in genes encoding drug targets to predict drug-treatment-related side effects.
Synthesis and Properties of Conjugated Hybrid Tetrathiafulvalene Dimers

The synthesis of new hybrid tetrathiafulvalene (TTF) dimers (11a-c) has been carried out by a Wittig-Horner reaction of the respective phosphonate esters (10a-c) with 2-(tetrathiafulvalenylvinyl)-9, 10-anthraquinone (9) prepared by olefination of formyltetrathiafulvalene (7) and the phosphonium salt of anthraquinone 8. Electrochemical studies show that the dimers 11a-c mainly retain the electrochemical properties of both TTF and the pi-extended TTF components, and most importantly, intramolecular electronic interactions between the two moieties are observed by cyclic voltammetry and Osteryoung square wave voltammetry. Semiempirical PM3 calculations reveal an almost planar geometry for the TTF and the benzene ring connected through the vinyl spacer. These compounds can form stable charge-transfer complexes with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) showing a stoichiometry of 1:3 (D:A). Attempts to electrocrystallize the dimeric donors with different counteranions are discussed.
Total synthesis of fostriecin (CI-920).

The first total synthesis of the potent antitumor agent fostriecin (CI-920) is described, confirming the relative and absolute stereochemistry assignments. Fostriecin is a unique phosphate monoester which exhibits weak topoisomerase II inhibition (IC50 = 40 μM) and more potent and selective protein phosphatase 2A and 4 (PP2A and PP4) inhibition (IC50 = 40−3 nM and 1.5 nM), resulting in mitotic entry checkpoint inhibition. Phase I clinical trials with fostriecin, which were the first to explore the potential of this novel mechanism of action, were halted even before therapeutic concentrations were reached or dose-limiting toxicity established due to problems of drug stability observed during storage of naturally derived material. The synthesis of fostriecin detailed herein is the first stage of efforts that may serve to address these limitations to the clinical examination of this or related promising new antitumor agents.
Move Together, Communicate Together: Supporting Preschoolers’ Communication Skills Through Physical Activities

During the preschool years, children develop several inter-related skills including motor skills and communication skills. In this article, we highlight several communication teaching strategies and describe how practitioners can promote communication skills of preschoolers with disabilities by providing them with multiple opportunities to practice these skills during motor activities. The following strategies are described: arrange the physical environment, model motor vocabulary, ask motor related questions, use a fill in the blank strategy, and reinforce/prompt child communication. The use of these strategies during large and small group motor activities is illustrated with vignettes. We present strategies for creating an engaging environment and providing meaningful opportunities so that children can learn important communication skills while also developing critical motor skills.
Polymerization of vinyl derivatives of the main group elements

A survey of selected novel hybrid organic-inorganic polymers obtained by polymerization and copolymerzation of main group compounds containing vinyl groups is presented. Examples from groups 13 through 16 are discussed with an emphasis on synthesis and quantitative reactivity studies.
Domain-general brain regions do not track linguistic input as closely as language-selective regions

Language comprehension engages a cortical network of left frontal and temporal regions. Activity in this network is language-selective, showing virtually no modulation by non-linguistic tasks. In addition, language comprehension engages a second network consisting of bilateral frontal, parietal, cingulate, and insular regions. Activity in this “Multiple Demand (MD)” network scales with comprehension difficulty, but also with cognitive effort across a wide range of non-linguistic tasks in a domain-general fashion. Given the functional dissociation between the language and MD networks, their respective contributions to comprehension are likely distinct, yet such differences remain elusive. Prior neuroimaging studies have suggested that activity in each network co-varies with some linguistic features that, behaviorally, influence on-line processing and comprehension. This sensitivity of the language and MD networks to local input characteristics has often been interpreted — implicitly or explicitly — as evidence that both networks track linguistic input closely, and in a manner consistent across individuals. Here, we used fMRI to directly test this assumption by comparing the BOLD signal time-courses in each network across different people ( n =45, men and women) listening to the same story. Language network activity showed fewer individual differences, indicative of closer input tracking, whereas MD network activity was more idiosyncratic and, moreover, showed lower reliability within an individual across repetitions of a story. These findings constrain cognitive models of language comprehension by suggesting a novel distinction between the processes implemented in the language and MD networks. SIGNIFICANCE STATEMENT Language comprehension recruits both language-specific mechanisms and domain-general mechanisms that are engaged in many cognitive processes. In the human cortex, language-selective mechanisms are implemented in the left-lateralized “core language network”, whereas domain-general mechanisms are implemented in the bilateral “Multiple Demand (MD)” network. Here, we report the first direct comparison of the respective contributions of these networks to naturalistic story comprehension. Using a novel combination of neuroimaging approaches we find that MD regions track stories less closely than language regions. This finding constrains the possible contributions of the MD network to comprehension, contrasts with accounts positing that this network has continuous access to linguistic input, and suggests a new typology of comprehension processes based on their extent of input tracking.
Use of Metalated Enecarbamates in the Squarate Cascade. Direct Access to Highly Functionalized 2,4-Cyclooctadienones by Intramolecular Interception of the Mesocyclic Dienolates.

Abstract A new method for constructing highly functionalized eight-membered ring ketones, fused to one or two additional rings as desired, is reported.
AN EVOLUTIONARY RESOLUTION OF MANIPULATION CONFLICT

Individuals can manipulate the behavior of social partners. However, manipulation may conflict with the fitness interests of the manipulated individuals. Manipulated individuals can then be favored to resist manipulation, possibly reducing or eliminating the manipulated behavior in the long run. I use a mathematical model to show that conflicts where manipulation and resistance coevolve can disappear as a result of the coevolutionary process. I find that while manipulated individuals are selected to resist, they can simultaneously be favored to express the manipulated behavior at higher efficiency (i.e., providing increasing fitness effects to recipients of the manipulated behavior). Efficiency can increase to a point at which selection for resistance disappears. This process yields an efficient social behavior that is induced by social partners, and over which the inducing and induced individuals are no longer in conflict. A necessary factor is costly inefficiency. I develop the model to address the evolution of advanced eusociality via maternal manipulation (AEMM). The model predicts AEMM to be particularly likely in taxa with ancestrally imperfect resistance to maternal manipulation. Costly inefficiency occurs if the cost of delayed dispersal is larger than the benefit of exploiting the maternal patch. I discuss broader implications of the process.
First open-framework zinc germanates by a molecular templating route

Despite the recent progress in the synthesis of new germanates, no zinc germanate has been synthesized by using a molecular templating route. A unique type of zincogermanate framework has now been prepared by using ethylenediamine as the structure-directing agent. The three-dimensional framework can be simply described as the face-centered packing of an elongated neutral cluster unit, Ge9O18.
Asymmetric indium-mediated Barbier-type allylation reactions with ketones to form homoallylic alcohol products

Abstract We report a general method for the enantioselective allylation of both aromatic and aliphatic ketones under indium-mediated Barbier-type conditions. Using 2 equiv of a commercially available amino alcohol, either (1 S ,2 R )-(+)-2-amino-1,2-diphenylethanol ((+)- 1 ) or (1 R ,2 S )-(−)-2-amino-1,2-diphenylethanol ((−)- 1 ) as the chiral auxiliary, good yields and enantioselectivities were achieved. To our knowledge, the enantioselectivities reported herein are the highest obtained for the indium-mediated allylations of ketones, specifically the homoallylic alcohol product obtained from the addition to α,α,α-trifluoroacetophenone provided 80% enantiomeric excess.
Preparation and activity of recyclable polymer-supported ruthenium olefin metathesis catalysts

The ruthenium catalysts (PCy3)2Ru(C(H)Ph)Cl2 (1), (PCy3)Ru(IMes)(C(H)Ph)Cl2 (2), (PCy3)Ru(SIMes)(C(H)Ph)Cl2 (3), (PCyp3)Ru(IMes)(CHCHC(CH3)2)Cl2 (4), and (PCy3)Ru(IPr)(3-phenylindenylid-1-ene)Cl2 (5), where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, Cy = cyclohexyl, and Cpy = cyclopentyl, have been grafted to polymer supports and found to be effective heterogeneous catalysts for ring-closing metathesis. In some cases, they are recyclable, show comparable reactivity to their homogeneous counterparts, tolerate functional groups, and perform very well with unsubstituted dienes.
A Comparative Analysis of 5-Azacytidine- and Zebularine-Induced DNA Demethylation

The nonmethylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity and reduce genomic DNA methylation. In this study, whole-genome bisulfite sequencing is used to construct maps of DNA methylation with single base pair resolution in Arabidopsis thaliana seedlings treated with each demethylating agent. We find that both inhibitor treatments result in nearly indistinguishable patterns of genome-wide DNA methylation and that 5-azacytidine had a slightly greater demethylating effect at higher concentrations across the genome. Transcriptome analyses revealed a substantial number of upregulated genes, with an overrepresentation of transposable element genes, in particular CACTA-like elements. This demonstrates that chemical demethylating agents have a disproportionately large effect on loci that are otherwise silenced by DNA methylation.
Syntheses of dispiro[2.1.4.1]decane and dispiro[2.0.3.3]decane

Abstract Efficient syntheses of the hitherto unknown hydrocarbons dispiro[2.1.4.1]decane and dispiro[2.0.3.3]decane have been realized through reaction sequences involving spiro[3.4]octan-2-one and spiro[3.4]octan-5-one as key intermediates.
Samarium-mediated Barbier reaction of carbonyl compounds

Abstract Samarium metal in the presence of catalytic amounts of iodine was found to be effective for the Barbier reaction of carbonyl compounds.
The development of N-aryl trifluoroacetimidate-based benzyl and allyl protecting group reagents

Abstract An exploration of the role of para -substituents on the balance between stability and reactivity of N -phenyl trifluoroacetimidates prompted the discovery of new reagents for the addition of allyl and benzyl protecting groups, namely O -allyl and O -benzyl N -( p- nitrophenyl)trifluoroimidates. These compounds are stable and crystalline at ambient temperature, making them ideal alternatives to existing benzylating and allylating reagents used under acidic conditions.