cssi/SciSciGPT-SciSciNet huggingface dataset:
Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease

Summary The etiology of non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is poorly understood. To understand the causal mechanisms underlying NAFLD, we conducted a multi-omics, multi-tissue integrative study using the Hybrid Mouse Diversity Panel, consisting of ∼100 strains of mice with various degrees of NAFLD. We identified both tissue-specific biological processes and processes that were shared between adipose and liver tissues. We then used gene network modeling to predict candidate regulatory genes of these NAFLD processes, including Fasn , Thrsp , Pklr , and Chchd6 . In vivo knockdown experiments of the candidate genes improved both steatosis and insulin resistance. Further in vitro testing demonstrated that downregulation of both Pklr and Chchd6 lowered mitochondrial respiration and led to a shift toward glycolytic metabolism, thus highlighting mitochondria dysfunction as a key mechanistic driver of NAFLD.
Confidence structures in decision making

Decision making is defined in terms of four elements: the set of decisions, the set of outcomes for each decision, a set-valued criterion function, and the decision maker's value judgment for each outcome. Various confidence structures are defined, which give the decision maker's confidence of a given decision leading to a particular outcome. The relation of certain confidence structures to Bayesian decision making and to membership functions in fuzzy set theory is established. A number of schemes are discussed for arriving atbest decisions, and some new types of domination structures are introduced.
Experiments and models of MHD jets and their relevance to astrophysics and solar physics

Magnetohydrodynamic (MHD)-driven jets involve poloidal and toroidal magnetic fields, finite pressure gradients, and unbalanced forces. The mechanism driving these jets is first discussed qualitatively by decomposing the magnetic force into a curvature and a gradient component. The mechanism is then considered quantitatively by consideration of all terms in the three components of the MHD equation of motion and in addition, the implications of Ampere's law, Faraday's law, the ideal Ohm's law, and the equation of continuity. The analysis shows that jets are self-collimating with the tip of the jet moving more slowly than the main column of the jet so there is a continuous stagnation near the tip in the jet frame. Experiments supporting these conclusions are discussed and it is shown how this mechanism relates to jets in astrophysical and solar corona contexts.
MATIC: Learning around errors for efficient low-voltage neural network accelerators

As a result of the increasing demand for deep neural network (DNN)-based services, efforts to develop dedicated hardware accelerators for DNNs are growing rapidly. However, while accelerators with high performance and efficiency on convolutional deep neural networks (Conv-DNNs) have been developed, less progress has been made with regards to fully-connected DNNs (FC-DNNs). In this paper, we propose MATIC (Memory Adaptive Training with In-situ Canaries), a methodology that enables aggressive voltage scaling of accelerator weight memories to improve the energy-efficiency of DNN accelerators. To enable accurate operation with voltage overscaling, MATIC combines the characteristics of destructive SRAM reads with the error resilience of neural networks in a memory-adaptive training process. Furthermore, PVT-related voltage margins are eliminated using bit-cells from synaptic weights as in-situ canaries to track runtime environmental variation. Demonstrated on a low-power DNN accelerator that we fabricate in 65 nm CMOS, MATIC enables up to 60–80 mV of voltage overscaling (3.3× total energy reduction versus the nominal voltage), or 18.6× application error reduction.
Local correctability of expander codes

In this work, we present the first local-decoding algorithm for expander codes. This yields a new family of constant-rate codes that can recover from a constant fraction of errors in the codeword symbols, and where any symbol of the codeword can be recovered with high probability by reading N e symbols from the corrupted codeword, where N is the block-length of the code.Expander codes, introduced by Sipser and Spielman, are formed from an expander graph G = ( V , E ) of degree d, and an inner code of block-length d over an alphabet Σ. Each edge of the expander graph is associated with a symbol in Σ. A string in Σ E will be a codeword if for each vertex in V, the symbols on the adjacent edges form a codeword in the inner code.We show that if the inner code has a smooth reconstruction algorithm in the noiseless setting, then the corresponding expander code has an efficient local-correction algorithm in the noisy setting. Instantiating our construction with inner codes based on finite geometries, we obtain novel locally decodable codes with rate approaching one. This provides an alternative to the multiplicity codes of Kopparty, Saraf and Yekhanin (STOC '11) and the lifted codes of Guo, Kopparty and Sudan (ITCS '13).
Prophylactic mesh augmentation: Patient selection, techniques, and early outcomes.

Abstract Background Incisional hernias (IH) following abdominal surgery are frequent and morbid. Prophylactic mesh augmentation (PMA) has emerged as a technique to reduce IH formation. We aim to report patient selection, techniques and early outcomes after PMA. Methods Retrospective chart review identified descriptive characteristics, risk factors, operative technique, and early post-operative outcomes for PMA patients and matched non-PMA patients between January 1, 2016 and October 31, 2017. Results 18 consecutive PMA cases were performed (55.6% female, mean age 54.3 years and mean BMI = 29.5 kg/m2). 88.9% of patients had at least two high-risk features for IH. Zero PMA patients developed IH compared to 5.3% non-PMA patients (p = 0.314) (6-months mean follow-up). No difference in surgical site occurrences (SSO) were identified between the two groups. Conclusions Early results are encouraging, demonstrating PMA is safe with equivocal SSO. Further studies are needed to assess if the reduction in IH formation is statistically significant with longer follow-up.
The puzzle of missing female engineers: Academic preparation, ability beliefs, and preferences

Abstract This paper uses administrative North Carolina data linked from high school to college and national surveys to characterize the largest contributor to the STEM gender gap: engineering. Disparities are the result of differential entry during high school or earlier rather than postsecondary exit. Differences in pre-college academic preparation account for 5 to 7% of the gap. Females’ relative lack of academic self-confidence explains 8%, while other-regarding preferences and professional goals capture a further 14%. Empirical evidence using identifying variation in the gender composition of twins in North Carolina shows that opposite-sex pairs are more likely to pursue gender-stereotypical majors.
Educational approach to cyber foundations in an undergraduate core program

Maximizing a student's learning in a general education information technology course is critical when teachers have only a little time to cover numerous topics within the discipline. It is therefore paramount that programs utilize the most effective pedagogical approach to educating students on these topics. This allows teachers to take full advantage of this limited time per topic. The principal contribution of this paper is a statistical analysis of student performance in an intermediate-level information technology course when exposed to two popular methods of teaching information technology concepts. This course is part of the larger cyber education model at the United States Military Academy. Our study implemented and analyzed the results from a control group educated with systematic, skills-based instruction versus a treatment group where a problemcentered learning approach was utilized. Our experimental results provide statistically significant reinforcement of the idea that problem-centered learning is superior to skills-based instruction for educating students in information technology topics as a part of their cyber education.
MEDICAID AND THE LABOR SUPPLY OF SINGLE MOTHERS: IMPLICATIONS FOR HEALTH CARE REFORM

The Medicaid expansions and health insurance subsidies of the Affordable Care Act (ACA) change work incentives for single mothers. To evaluate the employment effects of these policies ex ante, I estimate a model of labor supply and health insurance choice exploiting variation in pre‐ACA Medicaid policies. Simulations show that single mothers increase their labor supply at the extensive and intensive margin by 12% and 7%, respectively, uninsurance rates decline by up to 40%, and an average family's welfare improves by 1,600 dollars per year. Health insurance subsidies and not Medicaid expansions mostly drive these effects.
Speaking up to the “emotional vampire”: A conservation of resources perspective

Abstract Although narcissists are commonly compared to “emotional vampires” who drain others of their energy, research examining the impact of narcissistic leadership on employee well-being and outcomes remain scant. Drawing from conservation of resources (COR) theory, we theorize that narcissistic leadership consumes employees' emotional and cognitive resources, thus negatively affecting their work energy, and voice behavior. Moreover, we further investigate how leader team-oriented accountability, which helps to reduce narcissistic leaders' self-serving tendencies, moderates this negative indirect effect. Three-wave survey data collected from 357 employees working at a large consulting firm (Study 1) and experimental data collected from 129 working professionals (Study 2) both provided support for the negative indirect effect of narcissistic leadership on employees' voice via their work energy. Additionally, this negative indirect effect is significant only when leaders are not accountable towards their team and that such negative indirect effect becomes non-significant when leaders exhibit high team-oriented accountability.
Explicit binary tree codes with polylogarithmic size alphabet

This paper makes progress on the problem of explicitly constructing a binary tree code with constant distance and constant alphabet size. We give an explicit binary tree code with constant distance and alphabet size poly(logn), where n is the depth of the tree. This is the first improvement over a two-decade-old construction that has an exponentially larger alphabet of size poly(n). At the core of our construction is the first explicit tree code with constant rate and constant distance, though with non-constant arity - a result of independent interest. This construction adapts the polynomial interpolation framework to the online setting.
Molecular search with conformational change: One-dimensional discrete-state stochastic model

Molecular search phenomena are observed in a variety of chemical and biological systems. During the search, the participating particles frequently move in complex inhomogeneous environments with random transitions between different dynamic modes. To understand the mechanisms of molecular search with alternating dynamics, we investigate the search dynamics with stochastic transitions between two conformations in a one-dimensional discrete-state stochastic model. It is explicitly analyzed using the first-passage time probability method to obtain a full dynamic description of the search process. A general dynamic phase diagram is developed. It is found that there are several dynamic regimes in the molecular search with conformational transitions, and they are determined by the relative values of the relevant length scales in the system. Theoretical predictions are fully supported by Monte Carlo computer simulations.
Unet++: A nested u-net architecture for medical image segmentation

In this paper, we present UNet++, a new, more powerful architecture for medical image segmentation. Our architecture is essentially a deeply-supervised encoder-decoder network where the encoder and decoder sub-networks are connected through a series of nested, dense skip pathways. The re-designed skip pathways aim at reducing the semantic gap between the feature maps of the encoder and decoder sub-networks. We argue that the optimizer would deal with an easier learning task when the feature maps from the decoder and encoder networks are semantically similar. We have evaluated UNet++ in comparison with U-Net and wide U-Net architectures across multiple medical image segmentation tasks: nodule segmentation in the low-dose CT scans of chest, nuclei segmentation in the microscopy images, liver segmentation in abdominal CT scans, and polyp segmentation in colonoscopy videos. Our experiments demonstrate that UNet++ with deep supervision achieves an average IoU gain of 3.9 and 3.4 points over U-Net and wide U-Net, respectively.
Studying Preferences and Concerns about Information Disclosure in Email Notifications

People receive dozens, or hundreds, of notifications per day and each notification poses some risk of accidental information disclosure in the presence of others; onlookers may see notifications on a mobile phone lock screen, on the periphery of a desktop or laptop display. We quantify the prevalence of these accidental disclosures in the context of email notifications, and we study people's relevant preferences and concerns. Our results are compiled from a retrospective survey of 131 respondents, and a contextual-labeling study where 169 participants labeled 1,040 meeting-email pairs. We find that, for 53% of people, at least 1 in 10 email notifications poses an information disclosure risk, and the real or perceived severity of these risks depend both on user characteristics and the meeting or email attributes. We conclude by exploring machine learning for predicting people's comfort levels, and we present implications for the design of future social-context aware notification systems.
Serotonin regulates dynamics of cerebellar granule cell activity by modulating tonic inhibition.

Serotonin (5-hydroxytryptamine, 5-HT) regulates synaptic integration at the input stage of cerebellar processing by increasing tonic inhibition of granule cells. This circuit mechanism reduces the ...
A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate Type II Topoisomerases and Enable DNA Replication

Summary When DNA is unwound during replication, it becomes overtwisted and forms positive supercoils in front of the translocating DNA polymerase. Unless removed or dissipated, this superhelical tension can impede replication elongation. Topoisomerases, including gyrase and topoisomerase IV in bacteria, are required to relax positive supercoils ahead of DNA polymerase but may not be sufficient for replication. Here, we find that GapR, a chromosome structuring protein in Caulobacter crescentus, is required to complete DNA replication. GapR associates in vivo with positively supercoiled chromosomal DNA, and our biochemical and structural studies demonstrate that GapR forms a dimer-of-dimers that fully encircles overtwisted DNA. Further, we show that GapR stimulates gyrase and topo IV to relax positive supercoils, thereby enabling DNA replication. Analogous chromosome structuring proteins that locate to the overtwisted DNA in front of replication forks may be present in other organisms, similarly helping to recruit and stimulate topoisomerases during DNA replication.
Spin readout via spin-to-charge conversion in bulk diamond nitrogen-vacancy ensembles

We demonstrate the optical readout of ensembles of nitrogen-vacancy (NV) center spins in a bulk diamond sample via spin-to-charge conversion. A high power 594 nm laser is utilized to selectively ionize these paramagnetic defects in the mS=0 spin state with a contrast of up to 12%. In comparison to the conventional 520 nm spin readout, the spin-to-charge-conversion-based readout provides a higher signal-to-noise ratio, with tenfold sensing measurement speedup for millisecond long pulse sequences. This level of performance was achieved for an NV− ionization of only 25%, limited by the ionization and readout laser powers. These observations pave the way to a range of high-sensitivity metrology applications where the use of NV− ensembles in bulk diamond has proven useful, including sensing and imaging of target materials overlaid on the diamond surface.
An interaction-based model for neuropsychiatric features of copy-number variants

Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features.
Coordinated Control Strategy of a Battery Energy Storage System to Support a Wind Power Plant Providing Multi-Timescale Frequency Ancillary Services

With increasing penetrations of wind generation on electric grids, wind power plants (WPPs) are encouraged to provide frequency ancillary services (FAS); however, it is a challenge to ensure that variable wind generation can reliably provide these ancillary services. This paper proposes using a battery energy storage system (BESS) to ensure theWPPs’ commitment to FAS. This method also focuses on reducing the BESS’s size and extending its lifetime. In this paper, a state-machine-based coordinated control strategy is developed to utilize a BESS to support the obliged FAS of a WPP (including both primary and secondary frequency control).This method takes into account the operational constraints of theWPP (e.g., real-time reserve) and the BESS (e.g., state of charge [SOC], charge and discharge rate) to provide reliable FAS. Meanwhile, an adaptive SOC-feedback control is designed to maintain SOC at the optimal value as much as possible, and, thus, reduce the size and extend the lifetime of the BESS. The effectiveness of the control strategy is validated with an innovative multi-area interconnected power system simulation platform that can mimic realistic power systems operation and control by simulating realtime economic dispatch, regulating reserve scheduling, multi-area automatic generation control, and generators’ dynamic response.
Proceedings of the 2013 conference on Computer supported cooperative work companion

It is our great pleasure to welcome you to the 2013 ACM Computer Supported Cooperative Work -- CSCW'13. This year's conference continues its tradition of being the premier forum for research on online collaboration, social computing, and social media studies. CSCW meets a wide range of research interests, from technical communication systems building to ethnographic studies of computer-mediated collaboration in the wild. The mission of the conference is to share novel research in these domains of interest in order to advance the state of the art in CSCW. CSCW is committed to innovation in all aspects of research. This year's conference marks the second year in which the conference used a revision cycle in the paper reviewing process. The goal of this process is to increase quality of accepted papers and grow the program to better reflect the richness of our field. 390 paper submissions were received, 139 of which were accepted for publication after going through two rigorous review cycles. This year also marks the first year in which page length limits and the Papers/Notes distinction were eliminated, resulting in an overall modest increase in the length of papers. In all, the changes to the authoring and reviewing process have generated more papers of higher quality. CSCW '13 also has tracks for posters, demos, videos, workshops, panels, and a doctoral consortium, all of which are seeing tremendous participation. The workshops alone, for instance, have attracted almost 150 participants. For the first time, CSCW this year will have an open format "unconference" track where attendees can explore ideas in greater depth. We will also have a fitness track to start each day with some collaborative healthy activity. In addition to the stellar technical program, CSCW'13 hosts two exciting keynote speakers, Ron Burt and Jascha Franklin-Hodge. Ron will open the conference with a discussion of his research on volatility and advantage in networks, while Jascha will close the conference with an in-thetrenches look at modern digital democracy. Other highlights outside the papers program include a posters and videos reception and the main conference reception, both of which should provide time to connect with your fellow CSCW researchers.
Risk analysis beyond vulnerability and resilience – characterizing the defensibility of critical systems

Abstract A common problem in risk analysis is to characterize the overall security of a system of valuable assets (e.g., government buildings or communication hubs), and to suggest measures to mitigate any hazards or security threats. Currently, analysts typically rely on a combination of indices, such as resilience, robustness, redundancy, security, and vulnerability. However, these indices are not by themselves sufficient as a guide to action; for example, while it is possible to develop policies to decrease vulnerability, such policies may not always be cost-effective. Motivated by this gap, we propose a new index, defensibility. A system is considered defensible to the extent that a modest investment can significantly reduce the damage from an attack or disruption. To compare systems whose performance is not readily commensurable (e.g., the electrical grid vs. the water-distribution network, both of which are critical, but which provide distinct types of services), we defined defensibility as a dimensionless index. After defining defensibility quantitatively, we illustrate how the defensibility of a system depends on factors such as the defender and attacker asset valuations, the nature of the threat (whether intelligent and adaptive, or random), and the levels of attack and defense strengths and provide analytical results that support the observations arising from the above illustrations. Overall, we argue that the defensibility of a system is an important dimension to consider when evaluating potential defensive investments, and that it can be applied in a variety of different contexts.
Leveraging Motifs to Model the Temporal Dynamics of Diffusion Networks

Information diffusion mechanisms based on social influence models are mainly studied using likelihood of adoption when active neighbors expose a user to a message. The problem arises primarily from the fact that for the most part, this explicit information of who-exposed-whom among a group of active neighbors in a social network, before a susceptible node is infected is not available. In this paper, we attempt to understand the diffusion process through information cascades by studying the temporal network structure of the cascades. In doing so, we accommodate the effect of exposures from active neighbors of a node through a network pruning technique that leverages network motifs to identify potential infectors responsible for exposures from among those active neighbors. We attempt to evaluate the effectiveness of the components used in modeling cascade dynamics and especially whether the additional effect of the exposure information is useful. Following this model, we develop an inference algorithm namely InferCut, that uses parameters learned from the model and the exposure information to predict the actual parent node of each potentially susceptible user in a given cascade. Empirical evaluation on a real world dataset from Weibo social network demonstrate the significance of incorporating exposure information in recovering the exact parents of the exposed users at the early stages of the diffusion process.
Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states

Abstract Objectives Rates of hospitalization with sepsis/septicemia and associated mortality in the US have risen significantly during the last two decades. Antibiotic resistance may contribute to the rates of sepsis-related outcomes through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. However, there is limited information about the relationship between prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes. Methods For different age groups of adults (18-49y, 50-64y, 65-74y, 75-84y, 85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections (CAUTIs) in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014, and rates of hospitalization with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) reported to the Healthcare Cost and Utilization Project (HCUP), as well as rates of mortality with sepsis (ICD-10 codes A40-41.xx present on death certificate). Results Among the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones in Escherichia coli had the strongest association with septicemia hospitalization rates for individuals aged over 50y, and with sepsis mortality rates for individuals aged 18-84y. There were several positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults. Conclusions These findings, and those from work on the relationship between antibiotic use and sepsis rates, support the association between use of/resistance to certain antibiotics and rates of sepsis-related outcomes, indicating the potential utility of antibiotic replacement.
Payoff information and learning in signaling games

Abstract We add the assumption that players know their opponents' payoff functions and rationality to a model of non-equilibrium learning in signaling games. Agents are born into player roles and play against random opponents every period. Inexperienced agents are uncertain about the prevailing distribution of opponents' play, but believe that opponents never choose conditionally dominated strategies. Agents engage in active learning and update beliefs based on personal observations. Payoff information can refine or expand learning predictions, since patient young senders' experimentation incentives depend on which receiver responses they deem plausible. We show that with payoff knowledge, the limiting set of long-run learning outcomes is bounded above by rationality-compatible equilibria (RCE), and bounded below by uniform RCE. RCE refine the Intuitive Criterion ( Cho and Kreps, 1987 ) and include all divine equilibria ( Banks and Sobel, 1987 ). Uniform RCE sometimes but not always exists, and implies universally divine equilibrium.
Risk and Reward in the Orphan Drug Industry

Thanks to a combination of scientific advances and economic incentives, the development of therapeutics to treat rare or orphan diseases has grown dramatically in recent years. With the advent of Food and Drug Administration–approved gene therapies and the promise of gene editing, many experts believe we are at an inflection point in dealing with these afflictions. In this article, the authors propose to document this inflection point by measuring the risk and reward of investing in the orphan drug industry. They construct a stock market index of 39 publicly traded companies that specialize in developing drugs for orphan diseases and compare the financial performance of this index, which they call ORF, to the broader biopharmaceutical industry and the overall stock market from 2000 to 2015. Although the authors report that ORF underperformed other biopharma companies and the overall stock market in the early 2000s, its performance has improved over time: from 2010 to 2015, ORF returned 608%, far exceeding the 317%, 320%, and 305% returns of the S&P, NASDAQ, and NYSE ARCA Biotech indexes, respectively, and the 83% of the S&P 500. ORF does have higher volatility than the other indexes but still outperforms even on a risk-adjusted basis, with a Sharpe ratio of 1.24 versus Sharpe ratios of 1.17, 1.14, and 1.05, respectively, for the other three biotech indexes and 0.71 for the S&P 500. However, ORF has a market beta of 1.16, which suggests significant correlation to the aggregate stock market and less diversification benefits than traditional pharmaceutical investments. TOPICS:Mutual funds/passive investing/indexing, security analysis and valuation, performance measurement
Dirac's Magnetic Monopoles (Again)

Dirac's quantization of magnetic monopole strength is derived without reference to a (singular, patched) vector potential.
Recent demography drives changes in linked selection across the maize genome.

A study using population genomic data of domesticated and wild maize shows that purifying selection plays a major role in shaping maize diversity, and the efficacy of purifying selection increased following post-domestication population expansion.
Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[1,2-c]pyridine-9-ols

Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinolinones 6, 10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and l-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a−7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction−methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551−4554) have been developed. Tetracycle 24 is isomeric with the potent an...
Genomic characterization of six virus-associated cancers identifies changes in the tumor immune microenvironment and altered genetic programs

Viruses affect approximately 20% of all human cancers and induce expression of immunogenic viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas and other genomic datasets to define how virus infection shapes the tumor immune microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with virus-positive tumors often exhibiting increased infiltration of cytolytic cell types compared to their virus-negative counterparts. Analyses of the infiltrating T cell receptor repertoire in these patients revealed that Epstein-Barr virus infection was associated with decreased receptor diversity in multiple cancers, suggesting an antigen-driven clonal T cell response. Tissue-specific gene expression signatures capturing virus-associated transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of patient prognosis. Together, the analyses presented suggest viruses have distinct effects in different tumors, with implications for immunotherapy.
The effect of ocean warming on black sea bass (Centropristis striata) aerobic scope and hypoxia tolerance.

Over the last decade, ocean temperature on the U.S. Northeast Continental Shelf (U.S. NES) has warmed faster than the global average and is associated with observed distribution changes of the northern stock of black sea bass (Centropristis striata). Mechanistic models based on physiological responses to environmental conditions can improve future habitat suitability projections. We measured maximum, standard metabolic rate, and hypoxia tolerance (Scrit) of the northern adult black sea bass stock to assess performance across the known temperature range of the species. Two methods, chase and swim-flume, were employed to obtain maximum metabolic rate to examine whether the methods varied, and if so, the impact on absolute aerobic scope. A subset of individuals was held at 30°C for one month (30chronic°C) prior to experiments to test acclimation potential. Absolute aerobic scope (maximum–standard metabolic rate) reached a maximum of 367.21 mgO2 kg-1 hr-1 at 24.4°C while Scrit continued to increase in proportion to standard metabolic rate up to 30°C. The 30chronic°C group exhibited a significantly lower maximum metabolic rate and absolute aerobic scope in relation to the short-term acclimated group, but standard metabolic rate or Scrit were not affected. This suggests a decline in performance of oxygen demand processes (e.g. muscle contraction) beyond 24°C despite maintenance of oxygen supply. The Metabolic Index, calculated from Scrit as an estimate of potential aerobic scope, closely matched the measured factorial aerobic scope (maximum / standard metabolic rate) and declined with increasing temperature to a minimum below 3. This may represent a critical threshold value for the species. With temperatures on the U.S. NES projected to increase above 24°C in the next 80-years in the southern portion of the northern stock’s range, it is likely black sea bass range will continue to shift poleward as the ocean continues to warm.
Protection of poorly nucleophilic pyrroles

A method for the introduction of carbamate protecting groups on the ring nitrogen of electron-deficient pyrroles has been developed using the commercially available chloroformates and stoichiometric tetrabutylammonium iodide. The method is postulated to generate the more reactive iodoformates in situ to facilitate these protection reactions.
Dioxolane-to-Bridged Acetal-to-Spiroketal via Ring-Closing Metathesis and Rearrangement: A Novel Route to 1,7- Dioxaspiro[5.5]undecanes

Several examples of 1,7-dioxaspiro[5.5]undecane spiroketal systems have been synthesized from the common bicyclic intermediate 1 via acid-catalyzed rearrangement. Intermolecular ketalization of C2 symmetric diene diol 3 with ketone 9 and then desymmetrization by ring-closing metathesis rapidly constructs bicyclic acetal 1. The locked conformation and steric bias of 1 allow stereoselective functionalization of one or both double bonds before spiroketalization.
Origin of slow spontaneous resting-state neuronal fluctuations in brain networks

Resting- or baseline-state low-frequency (0.01-0.2 Hz) brain activity is observed in fMRI, EEG, and local field potential recordings. These fluctuations were found to be correlated across brain regions and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow resting-state fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (<0.05 Hz) activity could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra- and extracellular K+ and Na+ and intracellular Cl- ions, Na+/K+ exchange pump, and KCC2 cotransporter. In the network model simulating resting awake-like brain state, we observed infra-slow fluctuations in the extracellular K+ concentration, Na+/K+ pump activation, firing rate of neurons, and local field potentials. Holding K+ concentration constant prevented generation of the infra-slow fluctuations. The amplitude and peak frequency of this activity were modulated by the Na+/K+ pump, AMPA/GABA synaptic currents, and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state activity observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are reported as the resting-state fluctuations in fMRI and EEG recordings.
Photochemical rearrangements of quinone monoketals

Abstract We have studied the photochemistry of over 15 quinone cyclic monoketals, which were prepared by diol exchange from the dimethyl ketals, Swenton oxidation/hydrolysis, or direct ketalization. Their reactions in acidic media are generally explained by the classical mechanism for cyclohexadienone photochemical (di-π-methane) rearrangements: photocyclization to a cyclopropane-oxyallylcation that is protonated, followed by solvolysis. This reaction pathway provides, after hydrolysis, β-carboxy-substituted cyclopentenones. With a substituent at the β-position of the quinone monoketal, rearrangement selectivity is modestly in favor of the more substituted alkene product. With a substituent at the α-position of the quinone monoketal, rearrangement selectivity is strongly in favor of the less substituted alkene product. Possible mechanistic reasoning to explain these observations is offered. We have studied the photochemistry of > 15 quinone cyclic monoketals. Their reactions in acidic media are explained by photocyclization to a cyclopropane-oxyallylcation that is protonated, followed by solvolysis. This reaction pathway provides, after hydrolysis, β-carboxy-substituted cyclopentenones. Download : Download full-size image
Asymmetric Synthesis of 4-Hydroxy-3-phenyltetrahydroisoquinoline Derivatives Using Enantiopure Sulfinimines (N-Sulfinyl Imines)

Addition of lateral lithiated amides and phthalide anions to enantiopure sulfinimines (N-sulfinyl imines) represents a new approach for the asymmetric synthesis of 3-substituted isoquinolones and 3-substituted 4-hydroxy isoquinolones, respectively, important chiral building blocks for isoquinoline alkaloid synthesis. In one example 3-phenylisoquinolone (−)-15b was prepared in >95% ee by treatment of amide ion 10b with sulfinimine (S)-(+)-11 and subsequent deprotection of the N-sulfinyl auxiliary and cyclization. Oxaziridine-mediated hydroxylation of the anion of 16 afforded 4-hydroxy isoquinolone 19, which was transformed into 4-hydroxy-3-phenyltetrahydroisoquinoline (−)-22. In another approach 22 was prepared more directly by addition of phthalide ion 26 to (S)-(+)-11, creating the two stereogenic centers simultaneously. The selectivity proved to be highly counterion dependent.
Palladium-Catalyzed Hydroarylation of Propiolamides. A Regio- and Stereocontrolled Method for Preparing 3,3-Diarylacrylamides

A general regio- and stereoselective synthesis of 3,3-diarylacrylamides is reported. Palladium-catalyzed coupling reactions of propiolamides with aryl halides provide arylpropiolamides. A subsequent hydroarylation reaction of these arylpropiolamides with aryl halides, catalytic palladium, an amine base, and formic acid in refluxing ethyl acetate provides 3,3-diarylacrylamides regio- and stereoselectively. The unique stereo- and regiocontrol is presumed to proceed through careful reaction parameters that allow intramolecular coordination of the propiolamide amide functionality to the transient palladium−alkyne complex. Palladium-catalyzed hydroarylation of propiolamides has not been studied; however, preliminary results from related systems suggest that regioselective addition can be achieved. The methodology as a synthesis tool is demonstrated in an efficient route to previously difficult-to-prepare potent, benzimidazole antiviral targets. In addition, the synthesis scope is explored where, by judicious c...
Synthesis of Bulk and Alumina-Supported Bimetallic Carbide and Nitride Catalysts

A new synthesis for the preparation of the bimetallic carbide, Co3Mo3C, as well as syntheses for the preparation of alumina-supported Ni2Mo3N, Co3Mo3N, and Co3Mo3C are described. The syntheses utilize the temperature-programmed reduction (TPR) method in which solid-state precursors are converted to the desired products in the presence of gas-phase reactants. Bulk and alumina-supported Co3Mo3C is prepared in a two-step synthesis in which oxide precursors are converted to Co3Mo3N, which is subsequently carburized to give the bimetallic carbide. Alumina-supported Ni2Mo3N and Co3Mo3N are prepared from supported oxide precursors via nitridation in flowing NH3, while the carburization of bulk and alumina-supported Co3Mo3N utilizes a CH4/H2 mixture to yield the bimetallic carbide products. Elemental analysis of a 22.5 wt % Co3Mo3C/Al2O3 catalyst suggests incomplete replacement of N with C under the synthesis conditions employed. The alumina-supported carbide and nitride materials have high surface areas and O2 c...
Wewakazole, a novel cyclic dodecapeptide from a Papua New Guinea Lyngbya majuscula.

Phytochemical examination of a Papua New Guinea collection of Lyngbya majuscula resulted in the discovery of wewakazole (1), a novel cyclic dodecapeptide containing an unprecedented six five-membered heterocycles. Multiple NMR experiments and MS/MS data were required to assemble its planar structure because of its extensively signal-overlapped NMR spectra. In particular, a 1D HMBC was utilized to orient a three amino acid fragment that could not be placed by standard spectroscopic methods.
Total synthesis of (+/-)-deoxypenostatin A. Approaches to the syntheses of penostatins A and B.

A short synthesis of (±)-deoxypenostatin A (28) has been carried out using the convergent coupling of dienal 11, epoxide 13, and methylenetriphenylphosphorane (17) to prepare trienol 19 in only two steps. The key step is the Yb(OTf)3-catalyzed intramolecular Diels−Alder reaction of hydrated trienyl glyoxylate 23, which gives lactone 24 stereoselectively. Elaboration of lactone 24 to enone 27 by an intramolecular Horner−Emmons Wittig reaction and epimerization completes the synthesis of 28. Modest yields of Diels−Alder adducts 45a and 46a could be prepared analogously from MEM ether 44c, but the sensitivity of several of the intermediates precluded the elaboration of 45a to penostatin A (1).
Flash sintering activated by bulk phase and grain boundary complexion transformations

Abstract A naturally-occurring coupled thermal and electric runaway, resulted from an Arrhenius temperature-dependent specimen conductivity, can trigger flash sintering in many ceramics. This study reveals another possibility to activate flash sintering: a bulk phase transformation or a grain boundary (phase-like) complexion transition can cause an abrupt rise in the specimen conductivity to jump start flash sintering (prior to the occurrence of a natural thermal runaway). In undoped and Al2O3-doped ZnO, the flash sintering is activated by natural thermal runways that can be quantitively predicted from an Arrhenius extrapolation of low-temperature specimen conductivity. In contrast, a bulk eutectic reaction and the associated formation of premelting-like intergranular films (IGFs) in Bi2O3-doped ZnO can lead to a nonlinear rise in the specimen conductivity (above the Arrhenius extrapolation) to trigger flash sintering prior to the occurrence of the predicted natural thermal runaway. Yet, a natural thermal runaway can still take place in Bi2O3-doped ZnO before the occurrence of the interfacial and bulk transformation if the initial electric field is increased to a sufficiently high level. All five cases can be fully explained in a consistent framework so that this set of experiments systematically validate our theory of flash initiation. This work uncovers the roles of the bulk phase and interfacial (phase-like) complexion transformations in initiating flash sintering, thereby suggesting a new direction to understand and tailor the flash sintering process. An observation of ultra-fast field-induced migration of aliovalent cations during the flash sintering of Al2O3-doped ZnO is also reported.
1,3-Dipolar cycloaddition of 2- and 3-nitroindoles with azomethine ylides. A new approach to pyrrolo[3,4-b]indoles

Abstract The 1,3-dipolar cycloaddition of unstabilized azomethine ylides with 2- and 3-nitroindoles furnishes the expected hexahydropyrrolo[3,4-b]indole cycloadducts in good to excellent yields. The cycloadducts can be denitrated with Bu3SnH/AIBN, and cycloadduct 5 was oxidized with MnO2 to yield the known pyrrolo[3,4-b]indole 13.
Synthesis, Structure, and Reactivity of a Palladium Hydrazonato Complex: A New Type of Reductive Elimination Reaction To Form C-N Bonds and Catalytic Arylation of Benzophenone Hydrazone.

A rare, structurally characterized μ1 ,η1 -hydrazonato complex is a probable intermediate in the Pd-catalyzed N-arylation of hydrazones. Starting from aryl halides the reaction proceeds efficiently and under mild conditions with chelating phosphane ligands (L2 ); even Cs2 CO3 can be used as the base [Eq. (a)]. R=alkyl, aryl, MeCO, MeO; X=Br, I.
Incorporating Priors with Feature Attribution on Text Classification

Feature attribution methods, proposed recently, help users interpret the predictions of complex models. Our approach integrates feature attributions into the objective function to allow machine learning practitioners to incorporate priors in model building. To demonstrate the effectiveness our technique, we apply it to two tasks: (1) mitigating unintended bias in text classifiers by neutralizing identity terms; (2) improving classifier performance in scarce data setting by forcing model to focus on toxic terms. Our approach adds an L2 distance loss between feature attributions and task-specific prior values to the objective. Our experiments show that i) a classifier trained with our technique reduces undesired model biases without a tradeoff on the original task; ii) incorporating prior helps model performance in scarce data settings.
Magnetic thin films for data storage

Abstract Applications of magnetic thin films in data storage technology and areas for future research on thin films are discussed. Recent work at various laboratories indicates that magnetic recording densities of at least two orders of magnitude greater than those of today will be achieved. Among the advances in thin film technology which are needed to make this possible are the following: improved wear resistant overcoats for magnetic media; higher coercivity thin film media with isolated grain structure and multilayers to achieve low noise; high magnetization, high permeability multilayer thin film materials for advanced recording heads; giant magnetoresistive materials for advanced read heads. Although magnetic recording is expected to continue to dominate the data storage industry for the next two decades, magnetic-optic recording is likely to play an increasingly large role as a removable storage medium for large files of data involving images and multimedia. For increased storage density in magneto-optic recording, new magneto-optic thin film materials which are sensitive in the blue (or shorter) wavelength spectrum are needed. These films must not only provide large magneto-optic coefficients, but must also have the proper microstructure so that noise is low during readback. In order for these advances to be possible, new materials, new processing techniques, improved models and improved resolution imaging systems for studying both the magnetic and physical microstructure of thin films are needed.