cssi/SciSciGPT-SciSciNet huggingface dataset:
From genome to drug lead: identification of a small-molecule inhibitor of the SARS virus.

Abstract Virtual screening, a fast, computational approach to identify drug leads [Perola, E.; Xu, K.; Kollmeyer, T. M.; Kaufmann, S. H.; Prendergast, F. G. J. Med. Chem. 2000, 43, 401; Miller, M. A. Nat. Rev. Drug Disc. 2002, 1 220], is limited by a known challenge in crystallographically determining flexible regions of proteins. This approach has not been able to identify active inhibitors of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using solely the crystal structures of a SARS-CoV cysteine proteinase with a flexible loop in the active site [Yang, H. T.; Yang, M. J.; Ding, Y.; Liu, Y. W.; Lou, Z. Y. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 13190; Jenwitheesuk, E.; Samudrala, R. Bioorg. Med. Chem. Lett. 2003, 13, 3989; Rajnarayanan, R. V.; Dakshanamurthy, S.; Pattabiraman, N. Biochem. Biophys. Res. Commun. 2004, 321, 370; Du, Q.; Wang, S.; Wei, D.; Sirois, S.; Chou, K. Anal. Biochem. 2005, 337, 262; Du, Q.; Wang, S.; Zhu, Y.; Wei, D.; Guo, H. Peptides 2004, 25, 1857; Lee, V.; Wittayanarakul, K.; Remsungenen, T.; Parasuk, V.; Sompornpisut, P. Science (Asia) 2003, 29, 181; Toney, J.; Navas-Martin, S.; Weiss, S.; Koeller, A. J. Med. Chem. 2004, 47, 1079; Zhang, X. W.; Yap, Y. L. Bioorg. Med. Chem. 2004, 12, 2517]. This article demonstrates a genome-to-drug-lead approach that uses terascale computing to model flexible regions of proteins, thus permitting the utilization of genetic information to identify drug leads expeditiously. A small-molecule inhibitor of SARS-CoV, exhibiting an effective concentration (EC50) of 23 μM in cell-based assays, was identified through virtual screening against a computer-predicted model of the cysteine proteinase. Screening against two crystal structures of the same proteinase failed to identify the 23-μM inhibitor. This study suggests that terascale computing can complement crystallography, broaden the scope of virtual screening, and accelerate the development of therapeutics to treat emerging infectious diseases such as SARS and Bird Flu.
Kinetics of oxide film growth on metal crystals—III. Perturbation treatment of space charge fields

Abstract A perturbation analysis of the effects of diffusing space charge on rate of oxide film growth is developed by considering small deviations C″1(x) from homogeneous field distributions C′1(x). The ratio C″1 (extremum)/C1(max) is found to be proportional to Ck(max) L(t) 2 T in zero surface charge field E0, where L(t) is the oxide film thickness, T is the temperature, and Ck(max) is the maximum boundary concentration of the diffusing species k producing the space charge. The ratio of particle perturbation current J″1 to unperturbed current J′1 is also proportional to Ck(max) L(t) 2 T for zero E0; J″1 is positive for k = 1 but negative for k = 2, assuming species 2 to be oppositely charged from species 1. This result for J″ 1 J′ 1 also holds when E0 is large and inversely proportional to L(t), which is the case whenever the surface charge density is determined by the interplay of two diffusion currents. These results show that space charge causes deviations from the parabolic growth law which increase in importance with decreasing temperature. Space charge also modifies the logarithmic-type growth law obtained for E0 independent of L(t). For this case, J″ 1 J′ 1 varies exponentially with E 0 L(t) T .
A hybrid inventory policy with split delivery under regular and surge demand

Abstract This paper proposes a hybrid inventory policy with split delivery under regular and surge demand. The combination of regular and surge demand can be observed in many areas, such as healthcare inventory and humanitarian supply chain management. The arrival rate of regular demand is typically higher than the arrival rate of surge demand, whereas the volume of regular demand is typically lower than the volume of surge demand. This paper proposes an inventory management model that considers both emergency and regular replenishments corresponding to both demand patterns. The equilibrium equations developed for this model are based on the level crossing theory. These equations are used to develop a search-based heuristics to identify near optimal inventory management policies. Numerical results show that the proposed hybrid inventory policy with split delivery outperforms similar hybrid inventory policy without split delivery when holding and shortage costs are relatively low.
Magic in Western Culture: From Antiquity to the Enlightenment

The story of the beliefs and practices called 'magic' starts in ancient Iran, Greece, and Rome, before entering its crucial Christian phase in the Middle Ages. Centering on the Renaissance and Marsilio Ficino - whose work on magic was the most influential account written in premodern times - this groundbreaking book treats magic as a classical tradition with foundations that were distinctly philosophical. Besides Ficino, the premodern story of magic also features Plotinus, Iamblichus, Proclus, Aquinas, Agrippa, Pomponazzi, Porta, Bruno, Campanella, Descartes, Boyle, Leibniz, and Newton, to name only a few of the prominent thinkers discussed in this book. Because pictures play a key role in the story of magic, this book is richly illustrated.
Roles of blood flow in platelet adhesion and aggregation.

The investigations described in this review concern platelet adhesion and aggregation as blood flow-dependent phenomena. The experimental approach utilizes a chamber in which are controlled both blood flow and, in aggregation studies, the rate at which ADP enters flowing blood by localized diffusion through a Cuprophan membrane. Videomicroscopy and densitometry of video recordings allow quantification of the in situ growth of surface-adherent platelet aggregates. Platelet adhesion is studied separately using phase contrast microscopy. As a result, with the present method one can distinguish adhesion from aggregation, utilize whole blood, simulate arterial (or extracorporeal) shear rate conditions, independently vary ADP entry rate, and quantify aggregate growth in situ continuously.
Perceived size of off-size familiar objects under normal and degraded viewing conditions

To examine the effect of familiar (assumed) size on perceived size Ss judged the heights of off-size chain under normal and degraded viewing conditions. Judgments of an enlarged chair regressed toward the familiar size and regression increased as visual information was degraded. Judgments of a reduced chair failed to show regression, apparently because that object was recognized as a nonrepresentative stimulus.
Representative Hyphomycetes have regions of DNA homologous to Aspergillus nidulans developmental genes.

Thousands of fungal species are classified as hyphomycetes. Many of these species have a significant impact on moder society as pathogens, both plant and animal, as producers ofmycotoxins, as food spoilage and fermentation organisms, and as potential candidates for manipulation in the biotechnological industries. However, with few exceptions, i.e., Aspergillus nidulans and the anamorph of Neurospora crassa, little genetic information is available on the majority of filamentous fungi. Several developmentally regulated genes have been cloned from A. nidulans including SpoCI (Timberlake and Barnard, 1981; Gwynne et al., 1984) and tubC (May et al., 1985). SpoCI is a gene cluster that codes for several poly(A) + RNAs that are preferentially expressed during conidiophore development. Beta3-tubulin (tubC) functions in the development of microtubules during conidial mitosis and is either absent or found in only trace levels in the vegetative state. The non-developmentally regulated (i.e., is present in vegetative cultures) benA gene codes for two other beta-tubulin polypeptides, betal and beta2, in A. nidulans. Except for a survey of representatives of the genus Aspergillus (Mullaney and Klich, 1987), no information exists regarding the analogous genes in other filamentous fungi. The widespread distribution of similar genes outside the aspergilli would enhance the use of A. nidulans as a model to study other fungal species. Such a model would facilitate developmental regulation studies in many economically important hyphomycetes. As an initial step in determining if other filamentous fungi have similar developmental genes to those of A. nidulans, several hyphomycetes
Effect of meningococcal endotoxin on the immune response.

Summary1. The enhancement of antibody production against crystalline bovine serum albumin by the simultaneous injection of meningococcal endotoxin is reported. 2. An optimum dosage of endotoxin for production of the adjuvant effect is approximately the same as that required to prepare rabbits for the generalized Shwartzman reaction or to provoke the local Shwartzman phenomenon. 3. Failure of inhibition of antibody production by dosages of endotoxin capable of producing delayed uptake of radio active colloidal gold by the reticuloendothelial system is mentioned. 4. Possible mechanisms responsible for the adjuvant phenomenon are discussed.
Annealing of Kovar in Pakaging

The importance and aim of the Kovar’s annealing are introduced.The best annealing temperature and atmosp here are analyzed.
Filtration coefficient in cat hindlimb using protein concentration changes.

The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the in...
Biomaterials: Impact on Keratoprosthesis Implantation

The increasing demand for corneal tissue and clinical circumstances of severe corneal scarring and vascularization have stimulated a continued interest in developing an artificial cornea from innovative biomaterials. We review the latest findings on the variety of materials used for artificial corneas and keratoprostheses, focusing most heavily on the Boston keratoprosthesis, the AlphaCor, and the Osteo-odonto Keratoprosthesis. Advancement of keratoprosthesis design has largely focused on surface modification of established materials and surveying new materials. Techniques such as modifying the PMMA surface in the Boston keratoprosthesis with PEG and RGD peptide conjugation are targeted towards decreasing the formation of RPM and improving biointegration respectively. Similar efforts have been undertaken to improve biocompatibility for various AlphaCor prototypes with integration of novel procedures such as photolithographic patterning and microcontact printing. New materials, such as titanium, interpenetrating polymer networks, and bioactive glass composites, have also been investigated to improve the functionality of the Boston keratoprosthesis, AlphaCor, and Osteo-odonto Keratoprosthesis. Severe corneal injury necessitates the use of keratoprostheses and artificial corneas. These have utilized a variety of materials in their development and construction including biologic, nonbiologic and even electronic solutions. The type of material used is of critical importance to the biocompatibility and long-term success of these corneal implants. However, a keratoprosthesis able to restore vision in the long term remains a challenge.
Pattern recognition with “materials that compute”

Driven by advances in materials and computer science, researchers are attempting to design systems where the computer and material are one and the same entity. Using theoretical and computational modeling, we design a hybrid material system that can autonomously transduce chemical, mechanical, and electrical energy to perform a computational task in a self-organized manner, without the need for external electrical power sources. Each unit in this system integrates a self-oscillating gel, which undergoes the Belousov-Zhabotinsky (BZ) reaction, with an overlaying piezoelectric (PZ) cantilever. The chemomechanical oscillations of the BZ gels deflect the PZ layer, which consequently generates a voltage across the material. When these BZ-PZ units are connected in series by electrical wires, the oscillations of these units become synchronized across the network, where the mode of synchronization depends on the polarity of the PZ. We show that the network of coupled, synchronizing BZ-PZ oscillators can perform pattern recognition. The “stored” patterns are set of polarities of the individual BZ-PZ units, and the “input” patterns are coded through the initial phase of the oscillations imposed on these units. The results of the modeling show that the input pattern closest to the stored pattern exhibits the fastest convergence time to stable synchronization behavior. In this way, networks of coupled BZ-PZ oscillators achieve pattern recognition. Further, we show that the convergence time to stable synchronization provides a robust measure of the degree of match between the input and stored patterns. Through these studies, we establish experimentally realizable design rules for creating “materials that compute.”
Association between Laryngeal Airway Aperture and the Discharge Rates of Genioglossus Motor Units

We know very little about how muscles and motor units in one region of the upper airway are impacted by adjustments in an adjacent airway region. In this case, the focus is on regulation of the expiratory airstream by the larynx and how changes in laryngeal aperture impact muscle motor unit activities downstream in the pharynx. We selected sound production as a framework for study as it requires i) sustained expiratory airflow, ii) laryngeal airway regulation for production of whisper and voice and iii) pharyngeal airway regulation for production of different vowel sounds. We used these features as the means of manipulating expiratory airflow, pharyngeal and laryngeal airway opening to compare the effect of each on the activation of genioglossus (GG) muscle motor units in the pharynx. We show that some GG muscle motor units a) discharge stably on expiration associated with production of vowel sounds, b) are exquisitely sensitive to subtle alterations in laryngeal airflow and c) discharge at higher firing rates in high flow vs. low flow conditions even when producing the same vowel sound. Our results reveal subtle changes in GG motor unit discharge rates that correlate with changes imposed at the larynx, and which may contribute to the regulation of the expiratory airstream.
Facilitating Trade and Peace Relations: Challenges of the Present U.S Government and Impact on U.S – China and Global Relations

The Trans Pacific Partnership, however, is not the only trade agreement facing dangers of being finalized or even implemented. Other protectionist waves – namely those arising in relation to Europe, have witnessed growing difficulties, protests and challenges to efforts aimed at mitigating barriers through the Transatlantic Trade and Investment Partnership (TTIP) between the United States and the European Union. Should markets be allowed to regulate themselves – or interventionist measures embraced when these appear to be necessary? If so, under what circumstances? Should the failure to evenly distribute the benefits and income derived from globalization be left to monetary policy – rather than protectionist measures? These constitute some vital questions which this paper aims to address. The central theme of this paper – as with other papers published by the author in relation to Free Trade Agreements is namely: That Free Trade Agreements, on their own, are intended to be beneficial to any economy. It ceases to be beneficial for a number of reasons, most notably, when they have been badly negotiated and lacking of essential provisions. Therefore, there should be every opportunity to renegotiate badly negotiated Free Trade Agreements which may have been attributed to previous or present administrations – as well as ensuring that future agreements are not lacking when it comes to essential provisions.
Abstract P288: ATP Signaling Stimulates Fibroblast Activation: The Role of Pannexin1 Channels in Fibrosis

BACKGROUND-We have shown that Pannexin1 (Panx1), a novel ATP channel, is found in ventricular cardiac myocytes and upregulated on myocyte sarcolemmal membranes during acute ischemia. We hypothesize that the channel is part of a protein complex that plays a role in downstream cell signaling post myocardial infarction (MI). METHODS-Using a canine model of MI, where the left anterior descending coronary artery is occluded (CO) we examined epicardial tissue from hearts subjected to 0–3 hrs of CO. Immunoprecipitation (IP) with subsequent silver stain studies revealed novel binding partners for Panx1. Co-immunoprecipitation studies (Co-IP) were performed to confirm Panx1 binding partners. In vitro dye uptake studies and ATP assays were used to determine the function of Panx1 channels under hypoxic conditions. RESULTS-IP followed by silver staining revealed multiple potential binding partners for Panx1 in the heart. Following 3 hrs CO some interactions increased while others decreased. Co-immunoprecipitation identified one of these partners for Panx1 as the MAGUK scaffolding protein SAP97, an interaction that is significantly increased following 3 hr CO (n=3, p<0.05). Immunostaining showed that CO increased trafficking and stabilization of Panx1 channels at the cell membranes. In vitro dye uptake studies show that cells increase dye uptake following hypoxia, an event that is blocked by the Panx1 channel blocker, Probenecid. Hypoxia also causes increased ATP release likely due to opening of Panx1 channels. ATP release activated fibroblasts and stimulated early fibrosis signaling. CONCLUSIONS-Our data show the presence of a Panx1 protein complex in cardiac myocytes that is scaffolded at the cell membranes by SAP97. Under cellular stress Panx1 channels release ATP to induce early fibrotic events. We We conclude that Panx1 plays a key functional role in ATP signaling and formation of fibrosis in the post-MI heart.
Software tools for high-throughput CALPHAD from first-principles data

Abstract We present a set of software tools that largely automate the process of converting ab initio data into thermodynamic databases that can readily be imported into standard thermodynamic modeling softwares. These tools are based on the Special Quasirandom Structures (SQS) formalism, extended to transparently handle, not only traditional fcc, bcc and hcp solid solutions, but also multiple-sublattice structures with possible sublattice disorder. A large database of pre-generated SQS is provided that covers over 30 of the most common multi-sublattice structures and spans the composition ranges of each of their sublattices. In addition, we exploit a theoretically justified and robust method to address the issue of assigning free energies to mechanically unstable “virtual” phases, thus providing a compelling solution to a long-standing problem in CALPHAD modeling, especially in the context of ab initio data. We also propose a simple low-order approximation scheme to include short-range order effects that requires no additional ab initio input. The resulting thermodyamic database seamlessly combines ab initio data (formation energies and, optionally, vibrational free energies) with elemental Scientific Group Thermodata Europe (SGTE) data. The proposed tools provide a clear path to expand the coverage of high-throughput efforts towards non-stoichiometric phases and non-zero temperatures. The generated free energy models can also provide very good starting points to perform complex thermodynamic assessments, especially in cases where the available experimental data poorly constrain some thermodynamic parameters. The Cu-Pt-W phase diagram is calculated as an example.
Optimal Intensity of Warfarin Therapy in Patients With Mechanical Aortic Valves.

Objective:To review the current guidelines and published literature in order to identify the evidence-based international normalized ratio (INR) goal in patients with a mechanical aortic valve.Data...
Characterization and fine mapping of qPE12, a new locus controlling rice panicle exsertion

Panicle exsertion is an important agronomic trait involved in pollination and hybrid rice seed production. The identification of genes controlling panicle exsertion will play a central role in hybrid rice breeding. C115, a chromosome segment substitution line carrying introgression segments of Nipponbare in genetic background of indica variety 9311, had significantly shortened panicle exsertion, uppermost internode length and plant height. Genetic analysis in F2 and F3 populations derived from a cross of C115 and 9311 indicated that the shortened panicle exsertion of C115 was recessive and controlled by a single Medelian factor, and the allele from Nipponbare decreased the phenotypic value. Primary mapping suggested qPE12, the Nipponbare introgression segment locating on the long arm of chromosome 12, was responsible for this phenotypic variation. Based on map-based cloning strategy, fine mapping was carried out with a total of 1130 recessive individuals selected from F2 and F3 populations, delimiting qPE12 to a 190-kb region. This result provides important information for isolation of a new gene controlling panicle exsertion in the future.
Immigrant Worker Centers, Technologies of Citizenship, and the Duty to Be Well:

Although worker centers have reenergized immigrant labor movements in the U.S., recent research points to their potential deradicalization as they expand and institutionalize. This article builds o...
Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.

OBJECTIVE There are variable reports of risk of concordance for progression to islet autoantibodies (Ab+) and type 1 diabetes in identical twins (IT) after one twin is diagnosed. We examined development of Ab+ and type 1 diabetes and the effects of genetic factors and common environment on Ab+ in IT, nonidentical twins (NT), and full siblings (FS). RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study ( N = 48,026) were screened from 2004 to 2015 for Ab+ (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these, 17,226 (157 IT, 283 NT, and 16,786 FS) were followed for Ab+ or type 1 diabetes for a median of 2.1 years. RESULTS At screening, IT were more likely to have positive GADA, IA-2A, and IAA than NT or FS (all P P ≤ 0.03). Initially, Ab+ IT had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody negative (b−) IT. In NT, type 1 diabetes risk by 3 years was 72% for initially multiple Ab+, 13% for single Ab+, and 0% for initially Ab− NT. FS had a 3-year type 1 diabetes risk of 47% for multiple Ab+, 12% for single Ab+, and 0.5% for initially Ab− subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.
Molecular characterization and prevalence of Halarachne halichoeri in threatened southern sea otters (Enhydra lutris nereis).

Parasitism, particularly in concert with other sublethal stressors, may play an important, yet underappreciated role in morbidity and mortality of threatened species. During necropsy of southern sea otters (Enhydra lutra nereis) from California submitted to the Marine Wildlife Veterinary Care and Research Center's Sea Otter Necropsy Program between 1999 and 2017, pathologists occasionally observed nasopulmonary mites infesting the respiratory tracts. Infestation was sometimes accompanied by lesions reflective of mite-associated host tissue damage and respiratory illness. Our objectives were to estimate prevalence of nasopulmonary mites, determine the taxonomic identity of the observed mites, and create a DNA reference for these organisms in southern sea otters as an aid in population management. Using unique morphological characteristics discerned via light and scanning electron microscopy (SEM), we identified the mites as Halarachne halichoeri, a species typically associated with harbor seals (Phoca vitiluna). The 18S, 16S, 28S and ITS1-2 genetic regions were sequenced and submitted to GenBank. We observed H. halichoeri mites in 25.6% (95% CI 19.9-33.4%). of southern sea otters from a subset of necropsies performed between 2012 and 2017. This is the first documentation of H. halichoeri in southern sea otters and is suggestive of parasite exchange between sea otters and harbor seals.
Augmenting Policy Making for Autonomous Vehicles Through Geoinformatics and Psychographics

Data-driven policy making has been on the rise in research, industry, and government; but especially for novel areas such as Artificial Intelligence and Autonomous Vehicles (AVs). Few studies on AVs' performance and feasibility are performed through demographic, geographic, and psychographic data. In this manuscript, descriptive and predictive analytics are presented to evaluate (and partly defy) the most commonplace beliefs for AVs safety, and vehicle collision causes. The goals of this manuscript include: identifying the context for which an accident occurs, defining the factors that feed into that context, and migrating that knowledge to AVs policy making. Policy makers around the world are being forced to re-defining policies for new technologies that effect our everyday life. Multiple aspects can influence such policy making process; the challenge exacerbates when the technology hasn't been used prior (such as AVs). AVs are coming to all roads in the US and around the world. It is very important therefore to understand the factors contributing to this major change. In this paper, machine learning models are trained, tested, and developed (in R) based on locations (longitudes and latitudes) of accidents, driver-pedestrian interactions, and driver's behavior (through three studies). After analyzing demographical data, no major pointers were found that could be used in deriving rules & regulations for the mentioned upcoming change in transport. Therefore, this paper shifts the focus to geographic and psychographic data (which had stronger correlations to safety and other car accident schemes). Additionally, technologies like Vissim and the Traffic Simulator are suggested to generate driver's scenarios, and to simulate certain cases where there can be multiple outcomes. The National Highway Traffic and Safety Administration (NHTSA) is a pioneer in the car safety industry and one of the main data collectors. The work presented in this manuscript uses data (72 datasets, and almost 9200000 data points) from NHTSA. Experimental work is presented, results are recorded, evaluated, and used to define conclusions and future directions.
NRF2-dependent metabolic reprogramming is required for tumor recurrence following oncogene inhibition

Summary Oncogenic signaling pathways both directly and indirectly regulate anabolic metabolism, and this is required for tumor growth. Targeted therapies that inhibit oncogenic signaling have dramatic impacts on cellular metabolism. However, it is not known whether the acquisition of resistance to these therapies is associated with – or driven by – alterations in cellular metabolism. To address this, we used a conditional mouse model of Her2-driven breast cancer to study metabolic adaptations following Her2 inhibition, during residual disease, and after tumor recurrence. We found that Her2 downregulation caused widespread changes in cellular metabolism, culminating in oxidative stress. Tumor cells adapted to this metabolic stress by upregulation of the antioxidant transcription factor, NRF2. Constitutive NRF2 expression persisted during residual disease and tumor recurrence, and NRF2 was both sufficient to promote tumor recurrence, and necessary for recurrent tumor growth. These results are supported by clinical data showing that the NRF2 transcriptional program is activated in recurrent breast tumors, and that NRF2 is associated with poor prognosis in patients with breast cancer. Mechanistically, NRF2 signaling in recurrent tumors induced metabolic reprogramming to re-establish redox homeostasis and upregulate de novo nucleotide synthesis. Finally, this NRF2-driven metabolic state rendered recurrent tumor cells sensitive to glutaminase inhibition, suggesting that NRF2-high recurrent tumors can be therapeutically targeted. Together, these data provide evidence that NRF2-driven metabolic reprogramming is required for breast cancer recurrence following oncogene inhibition. Significance Although tumor recurrence is the leading cause of mortality in breast cancer, the cellular properties that allow tumor cells to evade therapy and form recurrent tumors remain largely uncharacterized. Similarly, very little is known about how tumor metabolism changes following therapy, or whether alterations in cellular metabolism drive tumor recurrence. In this study, we identify the antioxidant transcription factor NRF2 as a critical positive regulator of breast cancer recurrence. We find that NRF2-dependent metabolic reprogramming is both sufficient and required to promote tumor recurrence. Additionally, we demonstrate that the NRF2-driven metabolic state renders recurrent tumors sensitive to glutaminase inhibitors, suggesting a novel therapeutic approach for the treatment of recurrent breast cancer.
The use of anna specification technology in ada software development

Sections of this paper are reprinted from David C. Luckham. Programming with Specifications: An Introduction to ANNA, a language for Specifying Ada Programs (Texts and Monographs in Computer Science). Copyright 1990, Springer-Verlag.
A Reply to “I Hope You Will Let Flynn Go”

Capone and Bucca offer a socio-pragmatic analysis of President Trump’s utterance, ‘I hope you will let Flynn go’ to show that Trump illicitly tried to persuade Comey to drop the investigation of Flynn. I do not dispute that claim. Instead, I offer an overview of their argument—with one potential point of disagreement. Capone and Bucca assume, As pragmatic investigators typically do, that speakers have determinate intentions and reason in complex ways about how to realize those intentions. I suggest that speakers may not have determinate intentions and may not engage in the complex types of reasoning pragmatics typically attributes to them. I do not suggest that this point undercuts Capone and Bucca’s claims; rather, it suggests that their emphasis on a normative component in pragmatic analysis is correct, and suggests that a focus on the normative component supports their claims.
Review: Sentimentality Reloaded. Reconsiderations of Romantic Sentimentality in Nineteenth-century Bolivia Today.

Book Review of Leonardo Garcia Pabon. El cuento sentimental romantico en Bolivia (siglo XIX). La Paz: Plural Editores, 2017. 457 pp.
Neighborhood-level stroke hot spots within major United States cities.

Abstract Objective Identifying communities at high risk of stroke is an important step in improving systems of stroke care. Stroke is known to show spatial clustering at the state and county levels, but it is not known if clusters are present within city boundaries. Methods We performed a geospatial analysis of the prevalence of stroke within 500 major cities in the United States using the Centers for Disease Control and Prevention 500 Cities Project. For each city, we calculated the Moran's I statistic, which looks for evidence of spatial clustering, and used Monte Carlo simulation to assess for clustering significance. Results The mean overall crude prevalence of self-reported history of stroke at the city level was 2.8% (IQR 2.4–3.2%). Monte Carlo simulations of spatial patterns of stroke were successfully performed for 497 cities, of which 136 (27.3%) showed significant spatial clustering at the neighborhood level. All nine cities with more than one million inhabitants in 2010 showed significant spatial clustering. Conclusions This is the first study to demonstrate that stroke shows clustering at the neighborhood level within many major cities in the United States and within all of the largest cities. Understanding where stroke clusters exist within cities can form the basis of optimizing emergency medical services deployment and improving systems of stroke care.
Measurement of Radio-Frequency Radiation Pressure

In this work we perform measurements of the radiation pressure of a radio-frequency (RF) electromagnetic field which will lead to a new SI traceable power calibration. There are several groups around the world investigating methods to perform more direct SI traceable measurement of RF power (where RF is defined to range from 100s of MHz to THz). A measurement of radiation pressure offers the possibility for a measure traceable to the kilogram and to Planck's constant through the redefined SI. Towards this goal, we demonstrate the ability to measure the radiation pressure/force carried in a field at 15 GHz.
Attitudes toward business ethics: empirical investigation on different moral philosophies among business students in Vietnam

The purpose of this study is to investigate the attitudes toward business ethics of Vietnamese business students based on the five moral philosophies including Machiavellianism, Moral objectivism, legalism, ethical relativism and social Darwinism. Using the 30-item attitudes towards business ethics questionnaire (ATBEQ) developed by Neumann and Reichel (1987) based on the work of Stevens (1979), the authors examined the attitudes toward business ethics of 282 business students at a public university in Ho Chi Minh City in Vietnam. It appeared that there was a significant difference between all five philosophies except legalism. Legalism was found only significantly different from moral objectivism. The respondents scored highest for moral objectivism, followed by ethical relativism, social Darwinism, legalism and Machiavellianism. We found a significant difference between male and female business students for Machiavellianism and ethical relativism, and a partially significant difference for legalism. Finally, we found that code of ethics only made a significant difference for only Machiavellianism and social Darwinism.
Paradoxical Changes Underscore Epigenetic Reprogramming During Adult Zebrafish Extraocular Muscle Regeneration

Purpose Genomic reprogramming and cellular dedifferentiation are critical to the success of de novo tissue regeneration in lower vertebrates such as zebrafish and axolotl. In tissue regeneration following injury or disease, differentiated cells must retain lineage while assuming a progenitor-like identity in order to repopulate the damaged tissue. Understanding the epigenetic regulation of programmed cellular dedifferentiation provides unique insights into the biology of stem cells and cancer and may lead to novel approaches for treating human degenerative conditions. Methods Using a zebrafish in vivo model of adult muscle regeneration, we utilized chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to characterize early changes in epigenetic signals, focusing on three well-studied histone modifications-histone H3 trimethylated at lysine 4 (H3K4me3), and histone H3 trimethylated or acetylated at lysine 27 (H3K27me3 and H3K27Ac, respectively). Results We discovered that zebrafish myocytes undergo a global, rapid, and transient program to drive genomic remodeling. The timing of these epigenetic changes suggests that genomic reprogramming itself represents a distinct sequence of events, with predetermined checkpoints, to generate cells capable of de novo regeneration. Importantly, we uncovered subsets of genes that maintain epigenetic marks paradoxical to changes in expression, underscoring the complexity of epigenetic reprogramming. Conclusions Within our model, histone modifications previously associated with gene expression act for the most part as expected, with exceptions suggesting that zebrafish chromatin maintains an easily editable state with a number of genes paradoxically marked for transcriptional activity despite downregulation.
‘The role of percolation in hydrogel-based tissue engineering and bioprinting’

Abstract Hydrogels provide an excellent material platform to be used as a structural scaffold in tissue engineering or as a bioink for bioprinting. Their mechanical and degradation properties must however be very well tuned so that they can simultaneously provide a continuous mechanical support to embedded cells and promote the growth of a new tissue. This constitutes a significant challenge that can be addressed by using a rational approach combining experiments and simulations. We show here that the solution to achieving continuous integrity during the hydrogel-to-tissue transition relies on the concept of mechanical percolation in an interpenetrating network made of hydrogel and neo-tissue. We particularly discuss how percolation theory predicts that the hydrogel must possess some heterogeneities, which may be achieved via localized modes of degradation and nonuniform cell seeding.
Implementing and Maintaining the Program

The ultimate worth of staff training and program development rests on whether the newly developed rehabilitation strategy is ever implemented and whether the implemented program is truly effective for the consumer and user-friendly to the staff. Therefore, the moment of truth for interactive staff training (IST) occurs when the program committee tries out the rehabilitation strategy that they drafted on paper. Very often, newly developed programs are abruptly introduced into a rehabilitation milieu, met with disapproval by staff and consumers, and quickly discarded. IST includes several recommendations about how to introduce the newly developed program in such a way that widespread adoption of the program is likely.
Robot Gaze Behaviors in Human-to-Robot Handovers

We present the results of two studies investigating gaze behaviors of a robot receiving an object from a human. Robot gaze is an important nonverbal behavior during human-robot handovers, yet prior work has only studied robots as givers. From a frame-by-frame video analysis of human-human handovers, we identified four receiver gaze behaviors: gazing at the giver's hand, gazing at their face, and two kinds of face-hand transition gazes. We implemented these behaviors on a robot arm equipped with an anthropomorphic head. In Study 1, participants compared videos of a handover from a human actor to a robot exhibiting these four gaze behaviors. We found that when the robot transitions its head gaze from the giver's face to the giver's hand, participants consider the handover to be more likable, anthropomorphic, and communicative of timing ($p<; 0.0001$). In Study 2, participants physically performed object handovers with the robot and rated their experiences of the handovers for each of the four gaze behaviors of the robot. We found weaker effects with face gaze rated the most likable ($p=0.01$) and anthropomorphic ($p=0.03$) behavior. In contrast to previous studies, we found no evidence that the robot's gaze affected the start time of the human's handover.
Examples of asymptotically conical Ricci-flat Kähler manifolds

Previously the author has proved that a crepant resolution π : Y → X of a Ricci-flat Kahler cone X admits a complete Ricci-flat Kahler metric asymptotic to the cone metric in every Kahler class in \({H^2_c(Y,\mathbb R)}\). These manifolds can be considered to be generalizations of the Ricci-flat ALE Kahler spaces known by the work of P. Kronheimer, D. Joyce and others. This article considers further the problem of constructing examples. We show that every 3-dimensional Gorenstein toric Kahler cone admits a crepant resolution for which the above theorem applies. This gives infinitely many examples of asymptotically conical Ricci-flat manifolds. Then other examples are given of which are crepant resolutions hypersurface singularities which are known to admit Ricci-flat Kahler cone metrics by the work of C. Boyer, K. Galicki, J. Kollar, and others. We concentrate on 3-dimensional examples. Two families of hypersurface examples are given which are distinguished by the condition b3(Y) = 0 or b3(Y) ≠ 0.
Search for new mechanism of CP violation through tau decay and semileptonic decay of hadrons

If CP is violated in any decay process involving leptons it will signify the existence of a new force (called the X boson) responsible for CP violation that may be the key to understanding matter-antimatter asymmetry in the universe. We discuss the signatures of CP violation in (1) the decay of tau lepton, and (2) the semileptonic decay of π, K, D, B and t particles by measuring the polarization of the charged lepton in the decay. We discuss how the coupling constants and their phases of the coupling of the X boson to 9 quark vertices and 3 lepton vertices can be obtained through 12 decay processes.
Retromolar intubation for severe trismus: a less invasive alternative to tracheostomy and submental intubation.

A 67-year-old woman with renal cell cancer metastatic to the paranasal sinuses presented for nasal endoscopy and palliative debridement. The extensive sinonasal mass was a contraindication to transnasal intubation. Tumour invasion into the lateral and medial pterygoid muscles as well as prior
Voltage-driven polyelectrolyte complexation inside a nanopore

We have investigated how a pair of oppositely charged macromolecules can be driven by an electric field to form a polyelectrolyte complex inside a nanopore. To observe and isolate an individual complex pair, a model protein nanopore, embedded in artificial phospholipid membrane, allowing compartmentalization (cis/trans) is employed. A polyanion in the cis and a polycation in the trans compartments are subjected to electrophoretic capture by the pore. We find that the measured ionic current across the pore has a distinguishable signature of complex formation, which is different from the signature of the passage of individual molecules through the pore. The ionic current signature allows us to detect the interaction between the two oppositely charged macromolecules and thus, enables us to measure the lifetime of the complex inside the nanopore. After showing that we can isolate a complex pair in the nanopore, we studied the effects of molecular identity on the nature of interaction in different complex pairs. In contrast to the irreversible conductance state of the alpha hemolysin (alpha HL) channel in the complexation of poly-styrene sulfonate (PSS) and poly L lysine (PLL), a reversible conductance state is observed during complexation between single stranded DNA (ssDNA) and PLL. This suggests that there is a weak interaction between ssDNA and PLL, when compared to the interaction in a PSS PLL complex. Analysis of the PSS-PLL complexation events and its lifetime inside the nanopore supports a four step mechanism: (i) The polyanion is captured by the pore, (ii) the polyanion starts threading through the pore. (iii) The polycation is captured, a complex pair is formed in the pore, and the polyanion slides along the polycation. (iv) The complex pair can be pulled through the pore into the trans compartment or it can dissociate. Additionally, we have developed a simple theoretical model, which describes the lifetime of the complex inside the pore. The observed reversible two-state conductance across alpha HL channel during ssDNA PLL complexation, is described as the binding/unbinding of PLL during the translocation of ssDNA. This enables us to evaluate the apparent rate constants for association/dissociation and equilibrium dissociation constants for the interaction of PLL with ssDNA. This work throws light on the behavior of polyelectrolyte complexes in an electric field and enhances our understanding of the electrical aspects of inter-macromolecular interactions, which plays an extremely important role in the organization of macromolecules in the crowded and confined cellular environment.
When the lights go out: Californians’ experience with wildfire-related public safety power shutoffs increases intention to adopt solar and storage

Abstract As wildfire risk in the western U.S. grows due to climate change, the frequency and duration of public safety power shutoffs (PSPSs) are expected to increase. Surveying California residents (n = 804), we identify four respondent groupings based on PSPS experience and concern about future power outages. We find that those with higher levels of experience/concern express higher levels of intention to adopt solar and/or storage, even after controlling for factors such as socio-demographics, climate change concern, and existing adoption of smart technology within the home. Such findings have implications for areas where residents have experienced and/or are concerned about future power outages, suggesting that motivations for solar and storage adoption can go beyond financial considerations and environmental attitudes, and may include a desire to lessen impacts from power disruptions. In this Perspective, we argue that experience with and concern about extreme events, especially those that have the potential to result in power disruptions, should be incorporated into research about residential solar and storage adoption, and will likely become more important as extreme weather, climate change, and other aspects of an evolving electricity grid impact future power system reliability.
Preclinical Studies of Preactivated Merocyanine 540 and Merodantoin

It is apparent from the discussion in the previous chapters that photoproducts in pMC540 display a significant toxicity against cultured tumor cells and enveloped viruses but are only minimally cytotoxic to normal cells. A question of obvious significance is whether these findings from in vitro studies have any relevance to cancer or viral infections in humans. In this chapter, we shall examine the data obtained from studies utilizing in vivo models that support further development of these compounds for ultimate clinical use.
Life-on-a-chip.

Mechanistic studies of cellular processes are usually carried out with large populations of cells. However, parameters that are measured as averages of large populations can be misleading. For instance, an apparently linear response to a signal could, in fact, reflect an increasing number of cells in the population that have switched from 'off' to 'on', rather than a graded increase in response by all the cells. At present, the study of single cells is challenging, but new technologies mean it might soon be a reality.
Functional Analysis of Protein Targets by Metabolomic Approaches

Proteomics methods, such as activity-based protein profiling, can be used to connect proteins to biology and disease. Some proteins found through unbiased methods are not well characterized, which makes it difficult to ascertain the role of these proteins. Metabolomics approaches are useful in characterizing proteins that regulate or bind metabolites. Here, we provide examples of the development and use of metabolomics approaches to elucidate protein–metabolite interactions.
Collision and Collusion: Artists, Academics, and Activists in Dialogue with the University of California and Critical Disability Studies

This essay recounts two interconnected collaborative disability studies projects. Because of every person’s complex relationship to their own embodiment and that of others, disability beckons us to a realm beyond abstraction, even as the field becomes ever more theoretical. We describe how disability shaped what we did and how we did it; description is a key term here. Conversations such as the ones we had in 2010 and 2012 pave the way for new ideas by offering concrete examples of disability as a generative force. Through risk taking and creative practice, the best academics and artists challenge the status quo, maybe serving as translators for people not in the habit of giving disability or disabled people much thought. The more people come to associate disability with positive ideas, the more we can imagine changing those hardwired negative, pitying forces that dominate approaches to policy, practices, and encounters in daily life. Keywords: access, arts, audio description, critical disability studies, collaboration, curation, design, distance learning.