cssi/SciSciGPT-SciSciNet huggingface dataset:
Static Condensation Optimal Port/Interface Reduction and Error Estimation for Structural Health Monitoring

Having the application in structural health monitoring in mind, we propose reduced port spaces that exhibit an exponential convergence for static condensation procedures on structures with changing geometries for instance induced by newly detected defects. Those reduced port spaces generalize the port spaces introduced in [K. Smetana and A.T. Patera, SIAM J. Sci. Comput., 2016] to geometry changes and are optimal in the sense that they minimize the approximation error among all port spaces of the same dimension. Moreover, we show numerically that we can reuse port spaces that are constructed on a certain geometry also for the static condensation approximation on a significantly different geometry, making the optimal port spaces well suited for use in structural health monitoring.
Gain-of-function Shh mutants activate Smo cell-autonomously independent of Ptch1/2 function

Sonic Hedgehog (Shh) signaling is characterized by non-cell autonomy; cells expressing Shh do not respond to the ligand. Here, we identify several Shh mutations that can activate the Hedgehog (Hh) pathway cell-autonomously. Cell-autonomous pathway activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of the Shh receptors Patched1 and -2. Many of the Shh mutants that gain activity fail to undergo auto processing resulting in the perdurance of the Shh pro-peptide, a form of Shh that is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smoothened, independently of Patched1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the Shh response.
What information matters to investors at different stages of a firm's life cycle?

Abstract We examine the role of reported accounting information (e.g., earnings and book values) relative to analysts' earnings forecasts to determine what information is most relevant for explaining market value conditional on a firm's life cycle stage. Using the life cycle measure developed in Dickinson (2011), we find that accounting information and analysts' earnings forecasts are each informative for market values, but in differing ways conditional on a firm's life cycle stage. In both returns and price specifications, we find that for growth and mature firms, investors put relatively more weight on analysts' forecasts. Conversely, for introduction and decline firms, investors find accounting information more relevant for stock price and stock returns. However, consistent with Burgstahler and Dichev (1997), we find that book values are more relevant than earnings for firms that are more likely to exercise an abandonment option (i.e., introduction and decline firms). Overall, our findings are also consistent with our predictions derived from a simple learning model by Pastor and Veronesi (2009).
The shape of the orbit in FLRW spacetimes

The shape of the orbit of a free particle is examined in Friedmann-Lemaitre-Robertson-Walker (FLRW) cosmologies. The spatial projection of the orbit is time-independent and has a simple geometric description. We relate this description to the expression in terms of standard FLRW coordinates.
Unraveling the inner workings of respiratory arsenate reductase.

It began back in 1994 with a short note in the journal Nature , about a curious bacterium from the Aberjona watershed, strain MIT-13, that could grow on arsenic (1). Arsenic resistance had been well established, as it had been found in many clinical species like Staphylococcus aureus and Escherichia coli . Arsenite oxidation linked to resistance was also known. However, this was different—the organism, later to be named Sulfurospirillum arsenophilum (2), could couple the oxidation of lactate to the reduction of arsenate [As(V)] for growth. More significantly, incubation experiments revealed dissolution and reduction of arsenic from the sediments. This suggested that such organisms could be responsible for mobilizing arsenic in aquifers, resulting in the poisoning of millions of people worldwide. As more researchers began investigating microbial arsenic metabolism, it became apparent that not only was there a robust biogeochemical cycle, but arsenic played a role in the evolution of life on Earth (3). Thus began the journey to decipher how these organisms were capable of harnessing the energy from arsenic oxyanions. Now, Glasser et al. (4) have found the holy grail by solving the crystal structure of the respiratory arsenate reductase, Arr, from Shewanella sp. ANA-3. In doing so, they answer several questions, including the type of iron sulfur clusters in both ArrA and ArrB, the coordinating ligand to the molybdenum (cysteine, as had been predicted), the nature of the catalytic pocket, the binding of arsenic to the reaction site, and the mechanism of substrate transformation. Furthermore, they propose a reasonable solution to the preferred electron flow in these bidirectional enzymes. The respiratory arsenate reductase, Arr, was established both biochemically and through gene knockout studies (5⇓–7). Once key conserved regions in the protein sequence were recognized, more examples were found in both Bacteria and Archaea. Although … [↵][1]1To whom correspondence may be addressed. Email: stolz{at}duq.edu or basup{at}iupui.edu. [1]: #xref-corresp-1-1
Efficient transposon mutagenesis mediated by an IPTG-controlled conditional suicide plasmid

Transposon mutagenesis is highly valuable for bacterial genetic and genomic studies. The transposons are usually delivered into host cells through conjugation or electroporation of a suicide plasmid. However, many bacterial species cannot be efficiently conjugated or transformed for transposon saturation mutagenesis. For this reason, temperature-sensitive (ts) plasmids have also been developed for transposon mutagenesis, but prolonged incubation at high temperatures to induce ts plasmid loss can be harmful to the hosts and lead to enrichment of mutants with adaptive genetic changes. In addition, the ts phenotype of a plasmid is often strain- or species-specific, as it may become non-ts or suicidal in different bacterial species. We have engineered several conditional suicide plasmids that have a broad host range and whose loss is IPTG-controlled. One construct, which has the highest stability in the absence of IPTG induction, was then used as a curable vector to deliver hyperactive miniTn5 transposons for insertional mutagenesis. Our analyses show that these new tools can be used for efficient and regulatable transposon mutagenesis in Escherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa. In P. aeruginosa PAO1, we have used this method to generate a Tn5 insertion library with an estimated diversity of ~ 108, which is ~ 2 logs larger than the best transposon insertional library of PAO1 and related Pseudomonas strains previously reported. We have developed a number of IPTG-controlled conditional suicide plasmids. By exploiting one of them for transposon delivery, a highly efficient and broadly useful mutagenesis system has been developed. As the assay condition is mild, we believe that our methodology will have broad applications in microbiology research.
A Demonstration of Implication Logic Based on Volatile (Diffusive) Memristors

Implication logic gates that are based on volatile memristors are demonstrated experimentally with the use of relay-based volatile memristor emulators of an original design. The fabricated logic circuit involves two volatile memristors and it is capable of performing four fundamental logic functions (two types of material implication and the negations thereof). Moreover, current-voltage characteristics of individual emulators are recorded and self-sustained oscillations in a resistor-volatile memristor circuit are found. The developed emulator offers a great potential for memristive circuit experiments because of its simplicity, similarity of response with volatile memristors, and low cost. Our findings, which are based on emulators, can easily be reproduced with physical volatile memristors and, thus, open up possibilities for emerging in-memory computing architectures.
Has Trump Damaged the U.S. Image Abroad? Decomposing the Effects of Policy Messages on Foreign Public Opinion

The U.S. President Donald Trump has frequently made foreign countries central to his political messages, often conveying animosity. But do foreign citizens react more to the speaker of these messages—Trump himself—or their content? More generally, when people are exposed to messages sent from foreign countries, are their attitudes influenced by information heuristics or information content in messages? Although related studies are abundant in the literature of American public opinion, these questions are not fully examined in the literature of foreign public opinion. To address them, we used Japan as a case and fielded a survey experiment exposing citizens to U.S. policy messages that varied by source, policy content, and issue salience. Results suggest that while the source cue (Trump attribution) causes negative perceptions of the U.S., the policy content (cooperative vs. uncooperative) has a larger effect in shaping opinion of the U.S. Furthermore, analysis of interaction effects shows that only when U.S. policy approach is uncooperative does the Trump attribution have significantly negative and large effects. We conclude that foreign citizens rely more on policy content in transnational opinion formation—an aspect that past research in this area has overlooked. Substantively, these findings may demonstrate that even under a presidency that has alienated foreign countries and seemingly undermined U.S. stature in the world, foreign opinion toward the U.S. does not hinge entirely on its political leader. In short, Trump has not irreparably damaged the U.S. image abroad.
Modern data analytics approach to predict creep of high-temperature alloys

Abstract A breakthrough in alloy design often requires comprehensive understanding in complex multi-component/multi-phase systems to generate novel material hypotheses. We introduce a modern data analytics workflow that leverages high-quality experimental data augmented with advanced features obtained from high-fidelity models. Herein, we use an example of a consistently-measured creep dataset of developmental high-temperature alloy combined with scientific alloy features populated from a high-throughput computational thermodynamic approach. Extensive correlation analyses provide ranking insights for most impactful alloy features for creep resistance, evaluated from a large set of candidate features suggested by domain experts. We also show that we can accurately train machine learning models by integrating high-ranking features obtained from correlation analyses. The demonstrated approach can be extended beyond incorporating thermodynamic features, with input from domain experts used to compile lists of features from other alloy physics, such as diffusion kinetics and microstructure evolution.
Gender, genetics, and analgesia: understanding the differences in response to pain relief

Genetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and neuropathic pain models, females have been reported to have more pain than males. This review focuses on literature evidence of differences in pain relief due to multiple genetic variations and gender of the patient.
Elaborate pupils in skates may help camouflage the eye

The skate Leucoraja erinacea is a bottom-dweller that buries into the substrate with its eyes protruding, revealing elaborately shaped pupils. It has been suggested that such pupil shapes may camouflage the eye, yet this has never been tested. Here, we asked whether skate pupils dilate or constrict depending on background spatial frequency. In experiment 1, the skates' pupillary response to three artificial checkerboards of different spatial frequencies was recorded. Results showed that pupils did not change in response to spatial frequency. In experiment 2, in which skates buried into three natural substrates of different spatial frequencies, such that their eyes protruded, pupils showed a subtle but statistically significant response to changes in substrate spatial frequency. Although light intensity is the primary factor determining pupil dilation, our results show that pupils also change depending on the spatial frequency of natural substrates, which suggests that pupils may aid in camouflaging the eye.
Quantification and Analysis of Scientific Language Variation Across Research Fields

Quantifying differences in terminologies from various academic domains has been a longstanding problem yet to be solved. We propose a computational approach for analyzing linguistic variation among scientific research fields by capturing the semantic change of terms based on a neural language model. The model is trained on a large collection of literature in five computer science research fields, for which we obtain field-specific vector representations for key terms, and global vector representations for other words. Several quantitative approaches are introduced to identify the terms whose semantics have drastically changed, or remain unchanged across different research fields. We also propose a metric to quantify the overall linguistic variation of research fields. After quantitative evaluation on human annotated data and qualitative comparison with other methods, we show that our model can improve cross-disciplinary data collaboration by identifying terms that potentially induce confusion during interdisciplinary studies.
Retirement plans for contingent workers: issues and options

This paper examines retirement saving policy for independent – or contingent – workers, a growing segment of the workforce. Because few of these workers are covered by employer-sponsored retirement plans, they often do not benefit from payroll deduction, employer matching contributions, automatic enrollment, and other provisions that encourage retirement saving. Better use of fintech, judicious changes to tax policy, and expanded Automatic IRAs would help independent workers save for retirement. In addition, we propose the creation of retirement saving accounts that attach to the worker as a supplement to, and possible replacement for, the current system of employer-sponsored accounts.
Sublinear Time Numerical Linear Algebra for Structured Matrices

We show how to solve a number of problems in numerical linear algebra, such as least squares regression, lp-regression for any p ≥ 1, low rank approximation, and kernel regression, in time T(A)poly(log(nd)), where for a given input matrix A ∈ Rn×d, T(A) is the time needed to compute A · y for an arbitrary vector y ∈ Rd. Since T(A) ≤ O(nnz(A)), where nnz(A) denotes the number of non-zero entries of A, the time is no worse, up to polylogarithmic factors, as all of the recent advances for such problems that run in input-sparsity time. However, for many applications, T(A) can be much smaller than nnz(A), yielding significantly sublinear time algorithms. For example, in the overconstrained (1+e)-approximate polynomial interpolation problem, A is a Vandermonde matrix and T(A) = O(n log n); in this case our running time is n · poly (log n) + poly (d/e) and we recover the results of Avron, Sindhwani, and Woodruff (2013) as a special case. For overconstrained autoregression, which is a common problem arising in dynamical systems, T(A) = O(n log n), and we immediately obtain n· poly (log n) + poly(d/e) time. For kernel autoregression, we significantly improve the running time of prior algorithms for general kernels. For the important case of autoregression with the polynomial kernel and arbitrary target vector b ∈ Rn, we obtain even faster algorithms. Our algorithms show that, perhaps surprisingly, most of these optimization problems do not require much more time than that of a polylogarithmic number of matrix-vector multiplications.
Auditor Reporting and Regulatory Sanctions in the Broker‐Dealer Industry: From Self‐Regulation to PCAOB Oversight

The financial security of the investing public relies on high quality service by broker-dealers (BDs), investors’ gateway to the financial markets. The Securities and Exchange Commission (SEC) has long required auditors to attest to BDs’ internal controls and compliance with regulations (including those privately owned). Following the unravelling of the Madoff Ponzi scheme in 2008, the SEC required auditors of all BDs to register with the Public Company Accounting Oversight Board (PCAOB), and Congressional initiatives signaled imminent transition from private (American Institute of Certified Public Accountants; AICPA) to public (PCAOB) oversight. We investigate whether audit quality increased following this transition by measuring whether auditors report material internal control and compliance problems for BD clients where a deficiency presumably existed (i.e., BDs sanctioned by the Financial Industry Regulatory Authority (FINRA) for transgressions against stakeholders). Overall, we do not find increased reporting quality following the regulatory shift, but do observe variation by auditor group and BD ownership. While reporting quality for global network firms (GNFs) increases slightly, lower reporting quality observed prior to the regulatory shift for Specialist audit firms (having large BD portfolios but small overall size) is exacerbated afterward. This finding complements results of PCAOB inspections and other research identifying audit quality problems among small, industry-specialized firms in non-public client settings. Focusing on deficiencies likely more difficult to detect, we find lower reporting quality for private relative to publicly-affiliated BDs prior to PCAOB oversight, and lower reporting quality for very small audit firms relative to GNFs following the regulatory shift.
Global existence of weak solutions for strongly damped wave equations with nonlinear boundary conditions and balanced potentials

We demonstrate the global existence of weak solutions to a class of semilinear strongly damped wave equations possessing nonlinear hyperbolic dynamic boundary conditions. The associated linear operator is is the Wentzell–Laplacian. A balance condition is assumed to hold between the nonlinearity defined on the interior of the domain and the nonlinearity on the boundary. This allows for arbitrary (supercritical) polynomial growth of each potential, as well as mixed dissipative/antidissipative behaviour.
Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis.

Objective To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols. Data Sources PubMed, Embase, and the Cochrane library searched up to July 2018. Study Eligibility Criteria Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols. Study Appraisal and Synthesis Methods Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias. Results The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, −12.2, −3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, −1.3; 95% CI, −5.4, 2.7) were similar. Conclusion The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Perfect Bayesian Equilibria in repeated sales

Abstract A special case of Myerson's classic result describes the revenue-optimal equilibrium when a seller offers a single item to a buyer. We study a repeated sales extension of this model: a seller offers to sell a single fresh copy of an item to the same buyer every day via a posted price. The buyer's private value for the item is drawn initially from a publicly known distribution F and remains the same throughout. A key aspect of this game is that the seller might try to learn the buyer's private value to extract more revenue, while the buyer is motivated to hide it. We study the Perfect Bayesian Equilibria (PBE) in this setting with varying levels of commitment power to the seller. We find that the seller having the commitment power to not raise prices subsequent to a purchase significantly improves revenue in a PBE.
Aggregate Worker Reallocation and Occupational Mobility in the United States: 1976-2000

We investigate the evolution and the sources of aggregate employment reallocation in the United States in the 1976-2000 March files of the Current Population Survey. We focus on the annual flows of male workers across occupations at the Census 3-digit level, the finest disaggregation at which a moving worker changes career and relocates to an observationally different technology. The total reallocation of employment across occupations is strongly procyclical and mildly declining until the early 1990s, and then relatively flat. The negative trend is entirely due to younger workers, as it is reversed for men over age 40. To reveal the sources of these patterns, while correcting for possible worker selection into employment, we construct a synthetic panel based on birth cohorts, and estimate various models of worker occupational mobility. We find that the cross-occupation dispersion in labor demand, as measured by an index of net employment reallocation, has a strong association with total reallocation. The demographic composition of employment, more specifically the increasing average age and college attainment level, explains some of the trend and cycles in worker flows. High unemployment reduces the level of mobility directly. However, more strikingly, the level of unemployment also influences the magnitude and the sign of the education effect. As predicted by job-matching theory, occupational mobility has residual persistence, so shocks to aggregate employment reallocation propagate through time. Finally, cohorts born after the mid-1950's have increasingly low occupational mobility beyond what can be explained by their observable characteristics
Early detection of cryostorage tank failure using a weight-based monitoring system.

To study the relationship between liquid nitrogen loss and temperature in cryostorage dewars and develop an early-warning alarm for impending tank failure. Cryostorage dewars were placed on custom-engineered scales, and weight and temperature data were continuously monitored in the setting of slow, medium, and fast rate-loss of LN2 to simulate three scenarios of tank failure. LN2 Tank weights and temperatures were continuously monitored and recorded, with a calculated alarm trigger set at 10% weight loss and temperature of − 185 °C. With an intact tank, a 10% loss in LN2 occurred in 4.2–4.9 days. Warming to − 185 °C occurred in 37.8–43.7 days, over 30 days after the weight-based alarm was triggered. Full evaporation of LN2 required ~ 36.8 days. For the medium rate-loss simulation, a 10% loss in LN2 occurred in 0.8 h. Warming to − 185 °C occurred in 3.7–4.8 h, approximately 3 h after the weight-based alarm was triggered. For the fast rate-loss simulation, a 10% weight loss occurred within 15 s, and tanks were depleted in under 3 min. Tank temperatures began to rise immediately and at a relatively constant rate of 43.9 °C/h and 51.6 °C/h. Temperature alarms would have sounded within 0.37 and 0.06 h after the breech. This study demonstrates that a weight-based alarm system can detect tank failures prior to a temperature-based system. Weight-based monitoring could serve as a redundant safety mechanism for added protection of cryopreserved reproductive tissues.
The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair

P53-binding protein 1 (53BP1) mediates DNA repair pathway choice and promotes checkpoint activation. Chromatin marks induced by DNA double-strand breaks and recognized by 53BP1 enable focal accumulation of this multifunctional repair factor at damaged chromatin. Here, we unveil an additional level of regulation of 53BP1 outside repair foci. 53BP1 movements are constrained throughout the nucleoplasm and increase in response to DNA damage. 53BP1 interacts with the structural protein NuMA, which controls 53BP1 diffusion. This interaction, and colocalization between the two proteins in vitro and in breast tissues, is reduced after DNA damage. In cell lines and breast carcinoma NuMA prevents 53BP1 accumulation at DNA breaks, and high NuMA expression predicts better patient outcomes. Manipulating NuMA expression alters PARP inhibitor sensitivity of BRCA1-null cells, end-joining activity, and immunoglobulin class switching that rely on 53BP1. We propose a mechanism involving the sequestration of 53BP1 by NuMA in the absence of DNA damage. Such a mechanism may have evolved to disable repair functions and may be a decisive factor for tumor responses to genotoxic treatments.
Nanostructuring of laser textured surface to achieve superhydrophobicity on engineering metal surface

Superhydrophobic metal alloy surfaces are increasingly employed in aerospace and naval applications for anti-icing, drag reduction, self-cleaning, and high-efficiency light absorption capabilities. Emerging laser-based surface texturing methods demonstrate significant potential for manufacturing these surfaces, with the advantages of high processing precision and flexibility. In this research, superhydrophobicity is achieved on engineering metal surfaces using a novel nanosecond Laser-based High-throughput Surface Nanostructuring process. First, a high-energy nanosecond pulse laser scans the metal surface submerged in water using a large spatial increment and a fast processing speed. After that, the laser-textured surface is further treated by immersion in a chlorosilane reagent for a specific period of time. As a result of these two processes, micro- and nano-scale surface features are generated on the metal surface. These features are measured on AISI 4130 steel workpieces through scanning electron microscopy. The surface chemistry is characterized by x-ray photoelectron spectroscopy and correlated with processing conditions. The features are also compared after completion of each process step to understand their individual and cumulative effect on the textured surface. It is found that utilizing a high laser power intensity during the laser texturing process phase will significantly enhance surface nanostructuring effects after the chlorosilane treatment, resulting in feature size decrease and increase in feature density.Superhydrophobic metal alloy surfaces are increasingly employed in aerospace and naval applications for anti-icing, drag reduction, self-cleaning, and high-efficiency light absorption capabilities. Emerging laser-based surface texturing methods demonstrate significant potential for manufacturing these surfaces, with the advantages of high processing precision and flexibility. In this research, superhydrophobicity is achieved on engineering metal surfaces using a novel nanosecond Laser-based High-throughput Surface Nanostructuring process. First, a high-energy nanosecond pulse laser scans the metal surface submerged in water using a large spatial increment and a fast processing speed. After that, the laser-textured surface is further treated by immersion in a chlorosilane reagent for a specific period of time. As a result of these two processes, micro- and nano-scale surface features are generated on the metal surface. These features are measured on AISI 4130 steel workpieces through scanning electron micr...
Atmospheric blocking and intercomparison of objective detection methods: flow field characteristics

Objective methods for identifying and quantifying atmospheric blocking have been developed over recent decades, primarily targeting North Atlantic blocks. Differences arise from these methods, leading to changes in the resultant blocking climatology. To understand these differences, and better inform future assessments built on quantitative detection of blocks, this paper examines blocking properties produced by three different objective detection algorithms over the global extratropics. Blocking criteria examined include 500 hPa geopotential height anomaly ( Z∗ ), column-averaged potential vorticity anomaly ( PV∗ ), and 500 hPa geopotential height gradient (AGP). Results are analyzed for blocking climatologies and for instantaneous blocking patterns, as well as distributions of block size, speed, duration, and distance traveled. The results emphasize physical characteristics of the flow field and the subsequent blocking regions that emerge; overall, PV∗ and Z∗ blocked regions often have higher pattern correlation and spatial similarity, though these two methods also display high agreement with AGP in some instances. Z∗ finds the largest (and greatest number of) blocked regions, while PV∗ -detected regions are smallest in all instances except Southern Hemisphere winter. In some cases, PV∗ tracks a nearby jet streak, leading to differences with height-based algorithms. All three algorithms detect some questionable low-latitude blocks that are stationary and persist but do not impair zonal flow, although at different times. Therefore, careful consideration of the algorithm biases is important in future blocking studies. For example, linking extreme weather to detected blocking could vary substantially depending on the algorithm used.
Whole transcriptome analysis identifies upregulated genes and pathways in ductal carcinoma in situ mimicking usual ductal hyperplasia

Ductal carcinoma in situ (DCIS) and usual ductal hyperplasia (UDH) represent two extremes on the spectrum of intraductal proliferative lesions of the breast with corresponding differences in invasive carcinoma risk, molecular alteration and therapeutic management. In cases with overlapping morphology, the distinction between DCIS and UDH can be challenging. We performed whole transcriptome analysis on laser-capture microdissected samples from formalin-fixed, paraffin-embedded (FFPE) tissue in two cases of DCIS with UDH-like morphology (DUM) and their corresponding UDH. Of the top 10 genes differentially up/down regulated in DUM compared to UDH, we selected cyclin D1 (upregulated in DUM) and CD117 (c-kit) (down regulated in DUM) and performed immunohistochemical studies using clinically validated antibodies for cyclin D1 and CD117, respectively. Our results showed that both DUM lesions showed strong and diffuse (>50%) nuclear positivity for cyclin D1 antibody. The corresponding foci of UDH showed no reactivity to weak and sparse (<1%) staining for cyclin D1 antibody. Conversely, UDH expressed patchy CD117 (c-kit) positivity, while DUM lesion was completely negative. We also demonstrated that DUM lesions are enriched for genes associated with invasive ducal carcinoma, luminal subtype and brain metastasis. In summary, despite morphological similarities, DUM and UDH are molecularly distinct. Our study showed that whole transcriptome analysis of morphologically distinct lesions from the same FFPE sample isolated by laser capture microdissection provides a powerful tool to identify novel biomarkers in breast cancer.
Homomorphic ZW chromosomes in a wild strawberry show distinctive recombination heterogeneity but a small sex-determining region.

Recombination in ancient, heteromorphic sex chromosomes is typically suppressed at the sex-determining region (SDR) and proportionally elevated in the pseudoautosomal region (PAR). However, little is known about recombination dynamics of young, homomorphic plant sex chromosomes. We examine male and female function in crosses and unrelated samples of the dioecious octoploid strawberry Fragaria chiloensis in order to map the small and recently evolved SDR controlling both traits and to examine recombination patterns on the incipient ZW chromosome. The SDR of this ZW system is located within a 280 kb window, in which the maternal recombination rate is lower than the paternal one. In contrast to the SDR, the maternal PAR recombination rate is much higher than the rates of the paternal PAR or autosomes, culminating in an elevated chromosome-wide rate. W-specific divergence is elevated within the SDR and a single polymorphism is observed in high species-wide linkage disequilibrium with sex. Selection for recombination suppression within the small SDR may be weak, but fluctuating sex ratios could favor elevated recombination in the PAR to remove deleterious mutations on the W. The recombination dynamics of this nascent sex chromosome with a modestly diverged SDR may be typical of other dioecious plants.
Artefactual formation of pyruvate from in-source conversion of lactate.

RATIONALE Lactate and pyruvate are high abundance products of glucose metabolism. Analysis of both molecules as part of metabolomics studies in cellular metabolism and physiology have been aided by advances in liquid chromatography-mass spectrometry (LC-MS). METHODS We used ion pairing-chromatography and negative ion mode ESI on an QExactive HF to perform stable isotope assisted metabolomics profiling of lactate and pyruvate metabolism. RESULTS Using an LC-MS method for polar metabolite analysis we discovered an artefactual formation of pyruvate from in-source fragmentation of lactate. Surprisingly, this in-source fragmentation has not been previously described, thus we report this identification to warn other investigators. This artefact was detected by baseline chromatographic resolution of lactate and pyruvate by LC with confirmation of this artefact by stable isotope labeling of lactate and pyruvate. CONCLUSIONS These findings have immediate implications for metabolomics studies by LC-MS and direct infusion MS, especially in negative ion mode, whereby users should resolve lactate from pyruvate or robustly quantify the potential formation of pyruvate from higher abundance lactate in their assays.
The synthesis of highly reactive, multi-functional α,β-epoxy- and α-acetoxy-nitrosamines

Abstract The synthesis of the reactive acetates, trans -3-acetoxy-2-hydroxy- N -nitrosomorpholine 3 and N -(1-acetoxy-2-hydroxyethyl)- N -nitrosoethanolamine 12, of two α-hydroxynitrosamines has been accomplished through the ring opening of the corresponding epoxides, NEMOR and 10 which were prepared by dimethyldioxirane oxidation of the vinyl nitrosamines.
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes

Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7. We show that expression of the MHC class I genes is downregulated in HPV-positive keratinocytes in an E7-dependent manner. Methylome analysis revealed hypermethylation at a distal CpG island (CGI) near the HLA-E gene in NIKS-16 cells compared to either NIKS cells or NIKS-16∆E7 cells, which lack E7 expression. The HLA-E CGI functions as an active promoter element which is dramatically repressed by DNA methylation. HLA-E protein expression on cell surface is downregulated by high-risk HPV16 and HPV18 E7 expression, but not by low-risk HPV6 and HPV11 E7 expression. Conversely, demethylation at the HLA-E CGI restores HLA-E protein expression in HPV-positive keratinocytes. Because HLA-E plays an important role in antiviral immunity by regulating natural killer and CD8+ T cells, epigenetic downregulation of HLA-E by high-risk HPV E7 may contribute to virus-induced immune evasion during HPV persistence.
Salience-Driven Value Construction for Adaptive Choice under Risk.

Decisions we face in real life are inherently risky and can result in one of many possible outcomes. However, most of what we know about choice under risk is based on studies that use options with only two possible outcomes (simple gambles), so it remains unclear how the brain constructs reward values for more complex risky options faced in real life. To address this question, we combined experimental and modeling approaches to examine choice between pairs of simple gambles and pairs of three-outcome gambles in male and female human subjects. We found that subjects evaluated individual outcomes of three-outcome gambles by multiplying functions of reward magnitude and probability. To construct the overall value of each gamble, however, most subjects differentially weighted possible outcomes based on either reward magnitude or probability. These results reveal a novel dissociation between how reward information is processed when evaluating complex gambles: valuation of each outcome is based on a combination of reward information whereas weighting of possible outcomes mainly relies on a single piece of reward information. We show that differential weighting of possible outcomes enabled subjects to make decisions more easily and quickly. Together, our findings reveal a plausible mechanism for how salience, in terms of possible reward magnitude or probability, can influence the construction of subjective values for complex gambles. They also point to separable neural mechanisms for how reward value controls choice and attention in order to allow for more adaptive decision making under risk. SIGNIFICANCE STATEMENT Real-life decisions are inherently risky and can result in one of many possible outcomes, but how does the brain integrate information from all these outcomes to make decisions? To address this question, we examined choice between pairs of gambles with multiple outcomes using various computational models. We found that subjects evaluated individual outcomes by multiplying functions of reward magnitude and probability. To construct the overall value of each gamble, however, they differentially weighted possible outcomes based on either reward magnitude or probability. By doing so, they were able to make decisions more easily and quickly. Our findings illustrate how salience, in terms of possible reward magnitude or probability, can influence the construction of subjective values for more adaptive choice.
Aromatic Borataheterocycles: Surrogates for Cyclopentadienyl in Transition-Metal Complexes

This review describes the syntheses and coordination chemistry of selected unsaturated borataheterocycles. These compounds are formally derived from common heteroaromatic rings by the isoelectronic substitution of an anionic BH− group for a neutral CH group. Specifically included are the five-membered rings 1,2- and 1,3-thiaborolyls, derived from thiophene, 1,2-oxaborolyl, derived from furan, and 1,2-azaborolyl, derived from pyrrole. Also included is the six-membered ring 1,2-azaboratabenzene, derived from pyridine. These anionic rings can serve as surrogates for cyclopentadienyl in organometallic compounds.
Rapid Bursts from GRS 1915+105 with RXTE

The light curves of GRS 1915+105 observed with RXTE on 1996 October 15 reveal a wide range of transient activity, including regular bursts with a recurrence time of about 1 minute, irregular bursts, and dips. In contrast to bursts from other sources, a secondary (and a tertiary) weaker burst immediately following the primary burst are observed. Detailed energy spectra indicate that the source softens during the main outburst and successively hardens during the secondary and tertiary bursts. This may imply that the accretion flow has a corona-disk configuration and that the relative contribution of the hot corona decreases during the primary bursts and increases during the secondary and tertiary bursts. The primary burst profile resembles the bursts produced in the time-dependent evolutions of accretion disks, which are thermally and viscously unstable. The secondary burst may reflect an inward shift of the inner edge of the disk, which results in a greater release of gravitational binding energy.
BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud.

Summary BioJupies is a web application that enables the automated creation, storage, and deployment of Jupyter Notebooks containing RNA-seq data analyses. Through an intuitive interface, novice users can rapidly generate tailored reports to analyze and visualize their own raw sequencing files, gene expression tables, or fetch data from >9,000 published studies containing >300,000 preprocessed RNA-seq samples. Generated notebooks have the executable code of the entire pipeline, rich narrative text, interactive data visualizations, differential expression, and enrichment analyses. The notebooks are permanently stored in the cloud and made available online through a persistent URL. The notebooks are downloadable, customizable, and can run within a Docker container. By providing an intuitive user interface for notebook generation for RNA-seq data analysis, starting from the raw reads all the way to a complete interactive and reproducible report, BioJupies is a useful resource for experimental and computational biologists. BioJupies is freely available as a web-based application from http://biojupies.cloud .
Proton-Conducting Films of Nanoscale Ribbons Formed by Exfoliation of the Layer Perovskite H2SrTa2O7

Thin films of nanoscale ribbons derived from the layer perovskite H2SrTa2O7 were grown and characterized as solid-state proton conductors. The ribbons, made by exfoliation of the parent solid with ...
Existing Host Range Mutations Constrain Further Emergence of RNA Viruses.

ABSTRACT RNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the double-stranded RNA (dsRNA) bacteriophage φ6 (wild type and two isogenic host range mutants) on the novel host Pseudomonas syringae pv. atrofaciens. Both Sanger sequencing of 50 P. syringae pv. atrofaciens mutant clones for each genotype and population Illumina sequencing revealed the same high-frequency mutations allowing infection of P. syringae pv. atrofaciens. Wild-type φ6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wild-type clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wild-type φ6 clones had nonsynonymous mutations in p12, and 2 others had point mutations in p9 and p5. None of these genes had previously been associated with host range expansion in φ6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion. IMPORTANCE RNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system ( Pseudomonas phage φ6), we studied the impact of preexisting host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show that extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to that of wild-type φ6. This research suggests that serial host-shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified new genes involved in φ6 host range expansion, expanding our knowledge of this important model system in experimental evolution.
Design, Synthesis, and Self-Assembly of “Artificial Dinucleotide Duplexes”

The synthesis of the A−U and G−C functionalized systems 1, 2, 3, and 4 has been accomplished using palladium-mediated cross-coupling reactions. These systems undergo self-association in nonpolar solvents such as CDCl3 as judged from FABMS and NMR spectroscopic analyses.
Diversity-generation from an allenoate–enone coupling: syntheses of azepines and pyrimidones from common precursors

Abstract Amine-catalyzed coupling reactions of allenoate esters and α,β-unsaturated carbonyls lead to a diverse range of α,α′-disubstituted allenoates. With appropriately substituted monomers, intermolecular reactions can lead to pyrimidone products. Alternatively, with amine substituted allenoates, a 7-endo-dig cyclization can be carried out such that a divergent pathway is observed that leads to azepine scaffolds.
A novel sequential aminodiene Diels-Alder strategy for the rapid construction of substituted analogues of Kornfeld's ketone.

Through a novel sequence of aminodiene Diels−Alder reactions, amidofurans 18a−c were converted to tricyclic ketones 21a−c in moderate to good yields. Ketone 21a could be converted to Uhle's ketone ...
New isomeric analogues of anti-HIV active azidonucleosides

Abstract Synthesis and antiviral studies of novel 2′-isomeric dideoxynucleosides of the D-related class are described. The target compounds are analogues of anti-HIV active 4′-azido-2′-deoxynucleosides.
Contact Structures of Sasaki Type and Their Associated Moduli

This article is based on a talk at the RIEMain in Contact conference in Cagliari, Italy in honor of the 78th birthday of David Blair one of the founders of modern Riemannian contact geometry. The present article is a survey of a special type of Riemannian contact structure known as Sasakian geometry. An ultimate goal of this survey is to understand the moduli of classes of Sasakian structures as well as the moduli of extremal and constant scalar curvature Sasaki metrics, and in particular the moduli of Sasaki-Einstein metrics.
A total synthesis of (+/-)-trans-kumausyne.

A short total synthesis of (±)-trans-kumausyne is reported. Key steps include a tandem ring-opening−ring-closing metathesis and the effective introduction of the pentenyl side chain by allylation−cross metathesis.