cssi/SciSciGPT-SciSciNet huggingface dataset:
Explaining Aviation Safety Incidents Using Deep Temporal Multiple Instance Learning

Although aviation accidents are rare, safety incidents occur more frequently and require a careful analysis to detect and mitigate risks in a timely manner. Analyzing safety incidents using operational data and producing event-based explanations is invaluable to airline companies as well as to governing organizations such as the Federal Aviation Administration (FAA) in the United States. However, this task is challenging because of the complexity involved in mining multi-dimensional heterogeneous time series data, the lack of time-step-wise annotation of events in a flight, and the lack of scalable tools to perform analysis over a large number of events. In this work, we propose a precursor mining algorithm that identifies events in the multidimensional time series that are correlated with the safety incident. Precursors are valuable to systems health and safety monitoring and in explaining and forecasting safety incidents. Current methods suffer from poor scalability to high dimensional time series data and are inefficient in capturing temporal behavior. We propose an approach by combining multiple-instance learning (MIL) and deep recurrent neural networks (DRNN) to take advantage of MIL's ability to learn using weakly supervised data and DRNN's ability to model temporal behavior. We describe the algorithm, the data, the intuition behind taking a MIL approach, and a comparative analysis of the proposed algorithm with baseline models. We also discuss the application to a real-world aviation safety problem using data from a commercial airline company and discuss the model's abilities and shortcomings, with some final remarks about possible deployment directions.
What Makes a Good Endoscopic Teacher: A Qualitative Analysis.

Objective Teaching learners to perform endoscopic procedures is challenging, yet effective endoscopy teaching practices are not well-described in the literature, and prior studies have focused on perspectives of supervising physicians rather than learners. We sought to characterize, from the perspective of endoscopy learners, endoscopic teaching behaviors perceived as beneficial and detrimental to learning using qualitative methods. Design This is a prospective qualitative content analysis. Gastroenterology fellows from 2 tertiary care centers anonymously provided feedback regarding supervising physicians’ teaching behaviors during endoscopic training between March 2016 and December 2016. Preprinted cards were completed at the conclusion of procedures to document behaviors that fellows perceived as enhancing or hampering their learning. Two investigators performed content analysis of written comments; each identified behavior was assigned positive or negative valence. Setting Mount Sinai Hospital in New York, New York and University of California San Francisco in San Francisco, California. Both institutions are academic tertiary care centers. Participants A total of 19 gastroenterology fellows at 2 training institutions participated. Results A total of 239 teaching behaviors were identified by 19 fellows who worked with 31 supervising physicians; 29 unique behaviors were identified and organized into 7 themes: teaching, learning environment, autonomy, communication, coaching, feedback, and professionalism. Of all, 185 (77.4%) behaviors were reported as beneficial, and 54 (22.6%) as detrimental to the learning experience. Behaviors related to teaching were most often perceived as beneficial, while behaviors related to professionalism and communication were most often perceived as detrimental to learning. Conclusions Specific teaching behaviors may help or hinder learning of endoscopic skills. These behaviors may be useful for efforts related to teaching evaluation, faculty development, and direct teaching.
Near-Global Covariability of Hourly Precipitation in Space and Time

AbstractA detailed analysis of hourly precipitation from 60°N to 60°S for the covariability is performed at 0.25° resolution using the new CMORPH dataset. For all points, correlations are computed ...
Visualizing Angle-Independent Principal Strains in the Longitudinal View of the Carotid Artery: Phantom and In Vivo Evaluation.

Abstract Non-invasive vascular elastography can evaluate the stiffness of the carotid artery by visualizing the vascular strain distribution. Axial strain estimates of the longitudinal cross section of the carotid artery are sensitive to the angle between the artery and the transducer. Anatomical variations in branching and arching of the carotid artery can affect the assessment of arterial stiffness. In this study, we hypothesized that principal strain elastograms computed using compounded plane wave imaging can reliably visualize the strain distribution in the carotid artery, independent of the transducer angle. We corroborated this hypothesis by conducting phantom and in vivo studies using a commercial ultrasound scanner (Sonix RP, Ultrasonix Medical Corp., Richmond, BC, Canada). The phantom studies were conducted using a homogeneous cryogel vessel phantom. The goal of the phantom study was to assess the feasibility of visualizing the radial deformation in the longitudinal plane of the vessel phantom, independent of the transducer angle (±30°, ±20°, ±10° and 0°). The in vivo studies were conducted on 20 healthy human volunteers in the age group 50–60 y. All echo imaging was performed at a transmit frequency of 5 MHz and sampling frequency of 40 MHz. The elastograms obtained from the phantom study revealed that for straight vessels, which had their lumen parallel to the transducer, principal strains were similar to axial strains. At non-parallel configurations (angles ±30°, ±20° and ±10°), the magnitudes of the mean principal strains were within 2.5% of the parallel configuration (0° angle) estimates and, thus, were observed to be relatively unaffected by change in angle. However, in comparison, the magnitude of the axial strain decreased with increase in angle because of coordinate dependency. Further, the pilot in vivo study indicated that the principal and axial strain elastograms were similar for subjects with relatively straight arteries. However, for arteries with arched geometry, axial strains were significantly lower (p
The association between discrimination and health: findings on Russian, Somali and Kurdish origin populations in Finland.

Background The Second European Union Minorities and Discrimination Survey recently demonstrated widespread discrimination across EU countries, with high discrimination rates observed in countries like Finland. Discrimination is known to negatively impact health, but fewer studies have examined how different types of perceived discrimination are related to health. Methods This study examines (i) the prevalence of different types of perceived discrimination among Russian, Somali and Kurdish origin populations in Finland, and (ii) the association between different types of perceived discrimination (no experiences; subtle discrimination only; overt or subtle and overt discrimination) and health (self-rated health; limiting long-term illness (LLTI) or disability; mental health symptoms). Data are from the Finnish Migrant Health and Wellbeing Study (n = 1795). Subtle discrimination implies reporting being treated with less courtesy and/or treated with less respect than others, and overt discrimination being called names or insulted and/or threatened or harassed. The prevalence of discrimination and the associations between discrimination and health were calculated with predicted margins and logistic regression. Results Experiences of subtle discrimination were more common than overt discrimination in all the studied groups. Subtle discrimination was reported by 29% of Somali origin persons and 35% Russian and Kurdish origin persons. The prevalence of overt discrimination ranged between 22% and 24%. Experiences of discrimination increased the odds for poor self-reported health, LLTI and mental health symptoms, particularly among those reporting subtle discrimination only. Conclusions To promote the health of diverse populations, actions against racism and discrimination are highly needed, including initiatives that promote shared belonging.
Staff auditors' proclivity for computer-mediated communication with clients and its effect on skeptical behavior

Abstract A questioning nature and professional skepticism are fundamental requirements for auditors to conduct high quality audits and facilitate appropriate financial reporting. This study considers whether computer-mediated communication (CMC) reduces auditors' questioning during interactions with the client, compared to face-to-face (FTF) communication. We also examine how nonverbal cues commonly associated with deception affect auditors' skeptical behavior. Based on partner interviews and a survey comparing partners/managers with staff, we find that partners are concerned with the increased use of CMC for a variety of reasons, and that staff are more comfortable using CMC in a wider array of audit settings than are managers and partners. Experimental results based on Social Presence Theory (SPT) demonstrate that FTF interactions include more content and follow-up questions (a key aspect of skepticism) than CMC. Additionally, auditors engage in fewer relationship-building statements when communicating electronically. Also consistent with SPT, auditors communicating electronically request more documentation, though they ask fewer questions in general. Finally, using a unique measure of auditor skepticism based on revealed behavior, we find that auditors were more skeptical if the controller displayed nonverbal cues associated with deception, than when these specific cues were not present or not observable (CMC). Our findings suggest that communication mediums with reduced channels (e.g., no audio or visual channels), such as CMC, are less appropriate for complex and unique problem solving tasks. When paired with the concern that younger staff auditors are more likely to engage in CMC, skeptical behavior could be stunted in the modern audit environment, impacting financial statement quality.
DeepFense: online accelerated defense against adversarial deep learning

Recent advances in adversarial Deep Learning (DL) have opened up a largely unexplored surface for malicious attacks jeopardizing the integrity of autonomous DL systems. With the wide-spread usage of DL in critical and time-sensitive applications, including unmanned vehicles, drones, and video surveillance systems, online detection of malicious inputs is of utmost importance. We propose DeepFense, the first end-to-end automated framework that simultaneously enables efficient and safe execution of DL models. DeepFense formalizes the goal of thwarting adversarial attacks as an optimization problem that minimizes the rarely observed regions in the latent feature space spanned by a DL network. To solve the aforementioned minimization problem, a set of complementary but disjoint modular redundancies are trained to validate the legitimacy of the input samples in parallel with the victim DL model. DeepFense leverages hardware/software/algorithm co-design and customized acceleration to achieve just-in-time performance in resource-constrained settings. The proposed countermeasure is unsupervised, meaning that no adversarial sample is leveraged to train modular redundancies. We further provide an accompanying API to reduce the non-recurring engineering cost and ensure automated adaptation to various platforms. Extensive evaluations on FPGAs and GPUs demonstrate up to two orders of magnitude performance improvement while enabling online adversarial sample detection.
Optimal fiscal and monetary policy under imperfect competition

This paper studies optimal fiscal and monetary policy under imperfect competition in a stochastic, flexible-price, production economy without capital. It shows analytically that in this economy the nominal interest rate acts as an indirect tax on monopoly profits. Unless the social planner has access to a direct 100% tax on profits, he will always find it optimal to deviate from the Friedman rule by setting a positive and time-varying nominal interest rate. The dynamic properties of the Ramsey allocation are characterized numerically. As in the perfectly competitive case, the labor income tax is remarkably smooth, whereas inflation is highly volatile and serially uncorrelated. An exact numerical solution method to the Ramsey conditions is proposed.
Paternalism and Psychology

Does bounded rationality make paternalism more attractive? This Essay argues that errors will be larger when suppliers have stronger incentives or lower costs of persuasion and when consumers have weaker incentives to learn the truth. These comparative statics suggest that bounded rationality will often increase the costs of government decisionmaking relative to private decisionmaking, because consumers have better incentives to overcome errors than government decisionmakers, consumers have stronger incentives to choose well when they are purchasing than when they are voting, and it is more costly to change the beliefs of millions of consumers than a handful of bureaucrats. As such, recognizing the limits of human cognition may strengthen the case for limited government.
Underwater Surveying via Bearing Only Cooperative Localization

Bearing only cooperative localization has been used successfully on aerial and ground vehicles. In this paper we present an extension of the approach to the underwater domain. The focus is on adapting the technique to handle the challenging visibility conditions underwater. Furthermore, data from inertial, magnetic, and depth sensors are utilized to improve the robustness of the estimation. In addition to robotic applications, the presented technique can be used for cave mapping and for marine archeology surveying, both by human divers. Experimental results from different environments, including a fresh water, low visibility, lake in South Carolina; a cavern in Florida; and coral reefs in Barbados during the day and during the night, validate the robustness and the accuracy of the proposed approach.
Toward Identifying Subnetworks from FBF Binding Landscapes in Caenorhabditis Spermatogenic or Oogenic Germlines

Metazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In Caenorhabditis elegans, FBF (fem-3 Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to "disentangle" these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a fem-3(gf) mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target fog-3, while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets gld-1 and htp-1 We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.
Interrelationships between Violent crime, demographic and socioeconomic factors: a preliminary analysis between Central-Northern European countries and Mediterranean countries

Abstract. The paper here investigates possible relationships between violent crime, migration and unemployment. Results seem to show an association between some crimes - such as theft, assaults and sexual violence- and immigration but not between intentional homicides and immigration. Preliminary evidence also suggests that intentional homicides are associated with high rates of unemployment, linking this violent crime to socioeconomic and situational factors within countries. In addition, unlike commonplace opinions, statistical evidence here reveals that rich countries have levels of violent crime higher than poor countries. Especially, violent crime in central-northern European regions (geo-economic areas with high GDP per capita, e.g., Germany, Finland, Norway, etc.) is higher than Mediterranean countries with lower GDP per capita (e.g., Greece, Italy, Spain, etc.). These conclusions are of course tentative. There is need for much more detailed research into the relations between unemployment, immigration and violent crime to explain general causes of these social issues in modern economies. This study concludes with some socioeconomic implications and explanations. Keywords. Violent crime, Violence, Theft, Sexual violence, Intentional homicides, Immigrants, Migration, Unemployment, Europe, Poverty, Mediterranean countries. JEL. C10, I30, J10, J11, J15, J20, J60, J61, J62, O15.
FlashProfile: a framework for synthesizing data profiles

We address the problem of learning a syntactic profile for a collection of strings, i.e. a set of regex-like patterns that succinctly describe the syntactic variations in the strings. Real-world datasets, typically curated from multiple sources, often contain data in various syntactic formats. Thus, any data processing task is preceded by the critical step of data format identification. However, manual inspection of data to identify the different formats is infeasible in standard big-data scenarios. Prior techniques are restricted to a small set of pre-defined patterns (e.g. digits, letters, words etc.), and provide no control over granularity of profiles. We define syntactic profiling as a problem of clustering strings based on syntactic similarity, followed by identifying patterns that succinctly describe each cluster. We present a technique for synthesizing such profiles over a given language of patterns, that also allows for interactive refinement by requesting a desired number of clusters. Using a state-of-the-art inductive synthesis framework, PROSE, we have implemented our technique as FlashProfile. Across 153 tasks over 75 large real datasets, we observe a median profiling time of only ∼ 0.7s. Furthermore, we show that access to syntactic profiles may allow for more accurate synthesis of programs, i.e. using fewer examples, in programming-by-example (PBE) workflows such as Flash Fill.
North Atlantic Summertime Anticyclonic Rossby Wave Breaking: Climatology, Impacts, and Connections to the Pacific Decadal Oscillation

AbstractAnticyclonic Rossby wave breaking (RWB) is characterized by the rapid and irreversible deformation of potential vorticity (PV) contours on isentropic surfaces manifesting as a pair of merid...
Vigilance and control

We sometimes fail unwittingly to do things that we ought to do. And we are, from time to time, culpable for these unwitting omissions. We provide an outline of a theory of responsibility for unwitting omissions. We emphasize two distinctive ideas: (1) many unwitting omissions can be understood as failures of appropriate vigilance, and; (2) the sort of self-control implicated in these failures of appropriate vigilance is valuable. We argue that the norms that govern vigilance and the value of self-control explain culpability for unwitting omissions.
In symbio biopoiesis as model of evolved Alife (400 PPM Microbiome)

Artificial life techniques are illustrative at exploring the wisdom of natural living systems. Genetic algorithms, cellular automatons are computativily complex and visually seductive with Alife in silico. Robotic artists, creating Alife installations experience design challenges more akin to works created in vivo. Robotic works function both in silico and in vivo, with the virtual spaces of computer code and unpredictable environment of the real world. With robotic Alife installations, things like; will the interactant test the system with muscle or try to defeat the code, are design challenges forcing evolution. Interactive artists have pioneered behavior based works conceived with the current understanding of living systems, such as bottom up emergent behaviors, subsumption architectures (Autopoiesis, Fusiform Polyphony), parallel processing (Paparazzi Bots), distributed intelligences and energy autonomy (400 PPM Microbiome & Autotelematic Spider Bots). Still, in silco / in vivo works within the Alife ...
Proceedings of the Third Workshop on LLVM Compiler Infrastructure in HPC

LLVM, winner of the 2012 ACM Software System Award, has become an integral part of the software-development ecosystem for optimizing compilers, dynamic-language execution engines, source-code analysis and transformation tools, debuggers and linkers, and a whole host of programming-language and toolchain-related components. Now heavily used in both academia and industry, where it allows for rapid development of production-quality tools, LLVM is increasingly used in work targeted at high-performance computing. Research in, and implementation of, programming-language analysis, compilation, execution, and profiling has clearly benefited from the availability of a high-quality, freely-available infrastructure on which to build.
Persistent Scatterer Density by Image Resolution and Terrain Type

Persistent scatterer interferometry is a powerful time-series technique which uses the most temporally stable pixels (denoted persistent scatterers, or PS), to enable measurement of deformation in decorrelation-prone data sets. System performance depends heavily on the density of identified PS, which is influenced by two factors: image resolution and terrain type. In this work, we establish a quantitative link between PS density and these factors. First, we present a simple theoretical framework for predicting PS density by estimating the change in the pixel signal-to-clutter ratio (SCR) as a function of bandwidth for several different terrain types. Then, we analyze the behavior of PS density for three terrain types at different image resolutions. The model agrees with empirical results within 50% error, and rather closer for the high SCR points that form the desired network of PS points. Additionally, we find that the probability density functions of PS occurrence with respect to SCR for each region are approximately independent of system bandwidth. Thus, the increase in PS density is roughly proportional to increased bandwidth due to a higher pixel density in finer resolution images. We note that there is a slight increase in PS detectability with increasing bandwidth beyond the bandwidth scaling, but the gain is small compared to the bandwidth factor. These results form a model with a more quantitative understanding of the relationship between PS density and by extension, PS system performance, and image resolution and terrain.
Validity and Generalizability in Epidemiologic Studies

The validity of a study of humans is often separated into two components: the validity of the inferences as they pertain to members of the source population (internal validity), and the validity of the inferences as they pertain to people outside that population (external validity). Scientific generalization extends beyond statistical generalization of study results to the formulation of abstract concepts relating the study factors. Internal validity is a prerequisite for the study to contribute usefully to this process of abstraction, but the generalization process is otherwise separate from the concerns of internal validity and the mechanics of the study design. Keywords: internal validity; external validity; generalization; scientific inference; bias; confounding; misclassification
Cooperative Cancer Trials

The clinical trials cooperative group program was established by the US National Cancer Institute in 1955. The number of groups increased to 18 by 1985 and then decreased to 11. This article describes the work of the groups since the mid-1980s. It covers Phase I, II, and III studies, in a range of histologic groups, including breast, colorectal, lung, ovary, central nervous system, and prostate. Developments include intergroup studies, formalized interim monitoring systems, and increased emphasis on pediatric cancer and cancer prevention and control. Various methodologic developments are summarized. Keywords: National Cancer Institute; Phases I–III; interim analysis; data monitoring; Bayesian; surrogate; prognostic; quality of life; cure model
Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex

Background: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean ± standard deviation of 19.8 ± 6.3 vs. 16.6 ± 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2. Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.
White Knighting: How Help Reinforces Gender Differences between Men and Women

Individuals often prize helping behaviors in the workplace, but these behaviors can potentially be harmful to those who receive help. Two online experiments were conducted to determine whether dependency-oriented help, which consists of solving a problem for the beneficiary (Nadler 2002), has negative consequences for female beneficiaries and positive consequences for male helpers (Studies 1 and 2: 100 and 203 U.S. MTurk respondents respectively). I found that observers perceived women who received dependency-oriented help from men as being lower in status (Study 2), competence (Studies 1 and 2), and promotability (Studies 1 and 2) than women who received autonomy-oriented help from men. Contrary to expectations, observers’ endorsement of benevolent sexism moderated these effects such that their evaluations of female beneficiaries of dependency-oriented help was more negative the less they endorsed benevolent sexism (Studies 1 and 2). Finally, observers evaluated helpers who gave dependency-oriented help as lower in status and competence than helpers who give autonomy-oriented help (Study 2). Overall, the present findings suggest ways in which helping behaviors can have harmful effects on both helpers and beneficiaries of help in the workplace.
The duality gap for two-team zero-sum games

Abstract We consider multiplayer games in which the players fall in two teams of size k, with payoffs equal within, and of opposite sign across, the two teams. In the classical case of k = 1 , such zero-sum games possess a unique value, independent of order of play. However, this fails for all k > 1 ; we can measure this failure by a duality gap, which quantifies the benefit of being the team to commit last to its strategy. We show that the gap equals 2 ( 1 − 2 1 − k ) for m = 2 and 2 ( 1 − m − ( 1 − o ( 1 ) ) k ) for m > 2 , with m being the size of the action space of each player. Extensions hold also for different-size teams and players with various-size action spaces. We further study the effect of exchanging order of commitment among individual players (not only among the entire teams). The class of two-team zero-sum games is motivated from the weak selection model of evolution, and from considering teams such as firms in which independent players (ideally) have shared utility.
Dumping and Antidumping Duties

Abstract The majority of the world's countries have antidumping (AD) statutes in place, hundreds of AD actions occur annually across these countries, and AD criteria and procedures have been codified in the General Agreement on Tariffs and Trade and its successor, the World Trade Organization. AD's unique characteristics along with its high incidence of use make it a particularly apt policy for studying numerous trade theories and political economy models. We review the economics literature on dumping and antidumping activity, with particular emphasis on the evolution of the literature and the most recent contributions. We also point the reader to resources and rich data available to study AD, as well as our thoughts (in a concluding section) on where scholars should next focus their attention in this literature.
Stability of nitroxide biradical TOTAPOL in biological samples.

Abstract We characterize chemical reduction of a nitroxide biradical, TOTAPOL, used in dynamic nuclear polarization (DNP) experiments, specifically probing the stability in whole-cell pellets and lysates, and present a few strategies to stabilize the biradicals for DNP studies. DNP solid-state NMR experiments use paramagnetic species such as nitroxide biradicals to dramatically increase NMR signals. Although there is considerable excitement about using nitroxide-based DNP for detecting the NMR spectra of proteins in whole cells, nitroxide radicals are reduced in minutes in bacterial cell pellets, which we confirm and quantify here. We show that addition of the covalent cysteine blocker N-ethylmaleimide to whole cells significantly slows the rate of reduction, suggesting that cysteine thiol radicals are important to in vivo radical reduction. The use of cell lysates rather than whole cells also slows TOTAPOL reduction, which suggests a possible role for the periplasm and oxidative phosphorylation metabolites in radical degradation. Reduced TOTAPOL in lysates can also be efficiently reoxidized with potassium ferricyanide. These results point to a practical and robust set of strategies for DNP of cellular preparations.
Integrality gap of the vertex cover linear programming relaxation

Abstract We give a characterization result for the integrality gap of the natural linear programming relaxation for the vertex cover problem. We show that integrality gap of the standard linear programming relaxation for any graph G equals 2 − 2 χ f ( G ) where χ f ( G ) denotes the fractional chromatic number of G .
Acute myeloid/T-lymphoblastic leukaemia (AMTL): A distinct category of acute leukaemias with common pathogenesis in need of improved therapy

Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia (AML) harbour hallmarks of T cell development, such as T-cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T-ALL), including WT1, PHF6, RUNX1 and BCL11B. This proposed diagnostic entity overlaps with early T cell precursor (ETP) T-ALL and T cell/myeloid mixed phenotype acute leukaemias (MPALs), and also includes a subset of leukaemias currently classified as AML with features of T-lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches.
trans-3-Ethyl-cis-2,6,6-trimethyl-4-oxocyclohexanecarboxylic acid: an intermediate in the synthesis of a highly potent estrogen.

The title compound, C12H20O3, (IV), the ethyl ester of which is an intermediate in the synthesis of a compound reported to be highly estrogenic, has been prepared. After the initial steps reported for the synthesis of this ester intermediate were followed, it was converted into the crystalline acid, (IV), for X-ray analysis. It was verified that (IV) was racemic when prepared. X-ray analysis showed that anti-hydrogenation of the double bond had occurred in the synthesis, making the orientation of the carboxyl group cis to the 2-methyl group and trans to the 3-ethyl group. NMR spectroscopy showed that the stereochemistry of (IV) was identical with that of its ester precursor. While the earlier report did not note the stereochemistry of this ester, it pointed out that the estrogenic product derived from it possessed the opposite carboxyl-2-methyl orientation, i.e. trans, although no X-ray analysis was performed. In the light of these results and the importance of correlating biological activity with compound structure, the unequivocal characterization of the highly estrogenic compound is warranted.
A Simple and Convenient Method for the Synthesis of N,N-Diaryl Tertiary Amines

Direct preparation of tertiary amines in which two substituents are aromatic is described. In the presence of either the inorganic base sodium tert -butoxide or the sterically hindered organic base diisopropylethylamine, the alkylation of secondary diarylamines is achieved smoothly. In contrast to methods previously reported in the literature, this procedure is high-yielding and does not require the use of transition-metal catalysts or functional-group-intolerant hydride reductants.
Syntheses and characterization of the new homoleptic indium-polysulfide complexes [In2S27]4-, [In2S14]2-, and [In2S16]2-

The reaction of InCl 3 with K 2 S 5 and Ph 4 PCl in a 2:5:4 mole ratio in DMF afforded thin pale yellow crystals of (Ph 4 P) 4 [In 2 S 27 ] (1). I crystallizes in the triclinic space group P1
Phage-encoded LuxR-type receptors responsive to host-produced bacterial quorum-sensing autoinducers

Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. QS relies on the cell-density-dependent production, accumulation, and receptor-mediated detection of extracellular signaling molecules called autoinducers (AIs). Gram-negative bacteria commonly use N-acyl homoserine lactones (AHLs) as their AIs, and they are detected by LuxR-type receptors. Often, LuxR-type receptors are insoluble when not bound to a cognate AI. In this report, we show that LuxR-type receptors are encoded on phage genomes, and in the cases we tested, the phage LuxR-type receptors bind to and are solubilized specifically by the AHL AI produced by the host bacterium. We do not yet know the viral activities that are controlled by these phage QS receptors; however, our observations, coupled with recent reports, suggest that their occurrence is more widespread than previously appreciated. Using receptor-mediated detection of QS AIs could enable phages to garner information concerning the population density status of their bacterial hosts. We speculate that such information can be exploited by phages to optimize the timing of execution of particular steps in viral infection.IMPORTANCE Bacteria communicate with chemical signal molecules to regulate group behaviors in a process called quorum sensing (QS). In this report, we find that genes encoding receptors for Gram-negative bacterial QS communication molecules are present on genomes of viruses that infect these bacteria. These viruses are called phages. We show that two phage-encoded receptors, like their bacterial counterparts, bind to the communication molecule produced by the host bacterium, suggesting that phages can "listen in" on their bacterial hosts. Interfering with bacterial QS and using phages to kill pathogenic bacteria represent attractive possibilities for development of new antimicrobials to combat pathogens that are resistant to traditional antibiotics. Our findings of interactions between phages and QS bacteria need consideration as new antimicrobial therapies are developed.
Synthesis of functionalized oxacalix[4]arenes.

Tetranitrooxacalix[4]arenes are generated in high yield by the room-temperature SNAr reaction of 1,3-dihydroxybenzenes with 1,5-difluoro-2,4-dinitrobenzene. The reaction is tolerant to a range of functionality on the nucleophilic component, including hydroxyl-substitution at the 2- and 5-positions, which yields previously unknown 26,28- and 5,17-dihydroxyoxacalix[4]arenes.
Asymmetric synthesis of (+)-(S,S)-reboxetine via a new (S)-2-(hydroxymethyl)morpholine preparation.

(S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99% ee in eight steps. Key steps were selective oxidation of an N-protected hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic substitution.
Processing of eukaryotic Okazaki fragments by redundant nucleases can be uncoupled from ongoing DNA replication in vivo.

Prior to ligation, each Okazaki fragment synthesized on the lagging strand in eukaryotes must be nucleolytically processed. Nuclease cleavage takes place in the context of 5' flap structures generated via strand-displacement synthesis by DNA polymerase delta. At least three DNA nucleases: Rad27 (Fen1), Dna2 and Exo1, have been implicated in processing Okazaki fragment flaps. However, neither the contributions of individual nucleases to lagging-strand synthesis nor the structure of the DNA intermediates formed in their absence have been fully defined in vivo. By conditionally depleting lagging-strand nucleases and directly analyzing Okazaki fragments synthesized in vivo in Saccharomyces cerevisiae, we conduct a systematic evaluation of the impact of Rad27, Dna2 and Exo1 on lagging-strand synthesis. We find that Rad27 processes the majority of lagging-strand flaps, with a significant additional contribution from Exo1 but not from Dna2. When nuclease cleavage is impaired, we observe a reduction in strand-displacement synthesis as opposed to the widespread generation of long Okazaki fragment 5' flaps, as predicted by some models. Further, using cell cycle-restricted constructs, we demonstrate that both the nucleolytic processing and the ligation of Okazaki fragments can be uncoupled from DNA replication and delayed until after synthesis of the majority of the genome is complete.
Two case studies detailing Bayesian parameter inference for dynamic energy budget models

Abstract Mechanistic representations of individual life-history trajectories are powerful tools for the prediction of organismal growth, reproduction and survival under novel environmental conditions. Dynamic energy budget (DEB) theory provides compact models to describe the acquisition and allocation of energy by organisms over their full life cycle. However, estimating DEB model parameters, and their associated uncertainties and covariances, is not trivial. Bayesian inference provides a coherent way to estimate parameter uncertainty, and propagate it through the model, while also making use of prior information to constrain the parameter space. We outline a Bayesian inference approach for energy budget models and provide two case studies – based on a simplified DEBkiss model, and the standard DEB model – detailing the implementation of such inference procedures using the open-source software package deBInfer. We demonstrate how DEB and DEBkiss parameters can be estimated in a Bayesian framework, but our results also highlight the difficulty of identifying DEB model parameters which serves as a reminder that fitting these models requires statistical caution.
Double Annulation Route to Fused Bicyclic Compounds with Three Contiguous Quaternary Centers

Fused bicyclic and tricyclic compounds featuring two or three new CC σ bonds, two new rings, two or three new stereocenters, and three new contiguous quaternary centers can be prepared stereoselectively, atom-economically, and in one synthetic operation via a cascade reaction of two nonstereogenic, readily available starting materials: a tethered bis(malononitrile) and an internal alkynone. The course of the “double annulation” changes drastically with the structure of the starting materials, alternately affording trans-decalins or cis-fused unsaturated lactones.
An efficient and convenient synthesis of enantiopure 4-(t-butyldimethylsilyloxy)-cyclohex-2-en-1-one: a formal synthesis of (±)-mesembranol

Abstract Inexpensive enantiopure (+)-limonene oxide 1 is converted to 4-(R)-(t-butyldimethylsilyloxy)-cyclohex-2-en-1-one 2a . All isolated intermediates can be distilled obviating the need for chromatography. With 2a,b in hand, a formal synthesis of (±)-mesembranol 17 using vinyl triflate methodology is high yielding.
Efficient assembly of the phomactin core via two different macrocyclization protocols.

The core structure of phomactins C and D was assembled by an efficient strategy starting from 3,4-dimethylcyclohexen-2-one. Key reactions include (1) a high yielding and highly diastereoselective Michael addition of a mixed cuprate, (2) a carbonylative alkyne−enoltriflate coupling or an intramolecular addition of an acetylide onto an aldehyde to form the macrocycle, (3) chemoselective Michael addition of a cuprate to an enynone, to give the carbon framework of desformyl phomactin C or D, and finally (4) regioselective addition of a thia-nucleophile to the more reactive β-position of the resulting dienone.
Selective reduction of α,β-epoxyketones to β-hydroxyketones using silyllithium reagents

Abstract 2,3-Epoxy-1-phenyl-1-propanone was reduced to 3-hydroxy-1-phenyl-1-propanone using dimethylphenyl-, methyldiphenyl- or triphenylsilyllithium in THF at −40 °C. The methyldiphenylsilyllithium reagent was superior, providing the product in 70% yield. The reaction is believed to proceed via an epoxide ring-opening assisted Brook rearrangement. A number of α,β-epoxyketones underwent reduction with methyldiphenylsilyllithium to form the corresponding β-hydroxyketones in moderate to good yield.
Palladium–NHC catalyzed formation of cyclopenta[b]benzofurans and their subsequent modification

Abstract A palladium NHC complex is used to catalyze the addition of ortho iodophenols to diazabicyclic alkenes. The product cyclopenta[ b ]benzofurans are then derivatized by the Suzuki reaction, and reduction of the N N bond and followed by conversion of the amines into amides.
An improved procedure for the synthesis of 4,4-disubstituted-3-oxo-1,2,5-thiadiazolidine 1,1 -dioxides

An improved synthesis for the preparation of 3-oxo-1,2,5-thiadiazolidine 1,1-dioxides has been developed. This facile two-step procedure fromα-amino acid esters and chlorosulfonyl isocyanate results in excellent yields of products.
Reaction of antitumor hydroxymethylacylfulvene (HMAF) with thiols

Abstract Hydroxymethylacylfulvene (HMAF) is a semisynthetic derivative of the toxic sesquiterpene illudin S. HMAF (also designated MGI-114) has potent antitumor properties and is currently in clinical trials. It reacts with thiols at neutral and acidic pH forming novel products in which the primary allylic hydroxyl is displaced by thiol. These derivatives retain antitumor activity.
Computational design of small transcription activating RNAs for versatile and dynamic gene regulation

A longstanding goal of synthetic biology has been the programmable control of cellular functions. Central to this is the creation of versatile regulatory toolsets that allow for programmable control of gene expression. Of the many regulatory molecules available, RNA regulators offer the intriguing possibility of de novo design—allowing for the bottom-up molecular-level design of genetic control systems. Here we present a computational design approach for the creation of a bacterial regulator called Small Transcription Activating RNAs (STARs) and create a library of high-performing and orthogonal STARs that achieve up to ~ 9000-fold gene activation. We demonstrate the versatility of these STARs—from acting synergistically with existing constitutive and inducible regulators, to reprogramming cellular phenotypes and controlling multigene metabolic pathway expression. Finally, we combine these new STARs with themselves and CRISPRi transcriptional repressors to deliver new types of RNA-based genetic circuitry that allow for sophisticated and temporal control of gene expression.
Syntheses and Structural Characterizations of Sheet- and Column-like Lanthanide−Transition Metal Arrays: The Effect of Hydrogen Bonding on the Structure When K+ Is Replaced by [NH4]+

Sheet- and column-like cyanide bridged lanthanide−transition metal arrays were synthesized through metathesis reactions between anhydrous LnCl3 (Ln = Eu, Yb) and A2[M(CN)4] (A = K+, NH4+; M = Ni, Pt) in a 1:2 molar ratio in DMF (DMF = N,N-dimethylformamide) solution. Single-crystal X-ray analysis revealed that complexes of formula {K(DMF)7Ln[M(CN)4]2}∞ (Ln = Eu, M = Ni, 1; Ln = Yb, M = Pt, 2) consist of infinite layers of neutral, puckered sheets that contain hexagonal rings of composition {(DMF)10Ln2[M(CN)4]3}6 with interstitial (DMF)4K2[M(CN)4] units located between the layers. The sheet structure is generated through the repeating (DMF)10Ln2[M(CN)4]3 unit with trans cyanide ligands in [M(CN)4]2- serving as bridges. The column-like complex {(NH4)(DMF)4Yb[Pt(CN)4]2}∞, 3, is formed when NH4+ replaces K+. It consists of infinite, negatively charged, square, parallel columns bundled through N−H···NC hydrogen bonds between NH4+ and terminal CN from the columns. Cis cyanide ligands in [Pt(CN)4]2- units serve ...
Pure tones modulate the representation of orientation and direction in the primary visual cortex

The primary visual cortex (V1) receives direct inputs from the primary auditory cortex. Yet, the impact of sounds on visual processing in V1 remains controverted. We show that the modulation by pur...