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Atomic structure prediction and associated property calculations are the bedrock of chemical physics. Since high-fidelity ab initio modeling techniques for computing the structure and properties can be prohibitively expensive, this motivates the development of machine-learning (ML) models that make these predictions more efficiently. Training graph neural networks over large atomistic databases introduces unique computational challenges, such as the need to process millions of small graphs with variable size and support communication patterns that are distinct from learning over large graphs, such as social networks. We demonstrate a novel hardware–software codesign approach to scale up the training of atomistic graph neural networks (GNN) for structure and property prediction. First, to eliminate redundant computation and memory associated with alternative padding techniques and to improve throughput via minimizing communication, we formulate the effective coalescing of the batches of variable-size atomistic graphs as the bin packing problem and introduce a hardware-agnostic algorithm to pack these batches. In addition, we propose hardware-specific optimizations, including a planner and vectorization for the gather-scatter operations targeted for Graphcore’s Intelligence Processing Unit (IPU), as well as model-specific optimizations such as merged communication collectives and optimized softplus. Putting these all together, we demonstrate the effectiveness of the proposed codesign approach by providing an implementation of a well-established atomistic GNN on the Graphcore IPUs. We evaluate the training performance on multiple atomistic graph databases with varying degrees of graph counts, sizes, and sparsity. We demonstrate that such a codesign approach can reduce the training time of atomistic GNNs and can improve their performance by up to 1.5× compared to the baseline implementation of the model on the IPUs. Additionally, we compare our IPU implementation with a Nvidia GPU-based implementation and show that our atomistic GNN implementation on the IPUs can run 1.8× faster on average compared to the execution time on the GPUs.

Although the MYC oncogenic network represents an attractive therapeutic target for lymphoma, MYC inhibitors have been difficult to develop. Alternatively, inhibitors of epigenetic/ transcriptional regulators, particularly the bromodomain and extraterminal (BET) family, have been used to modulate MYC. However, current benzodiazepine-derivative BET inhibitors (BETi) elicit disappointing responses and dose-limiting toxicity in relapsed/refractory lymphoma, potentially because of enrichment of high-risk molecular features and chemical backbone-associated toxicities. Consequently, novel nonbenzodiazepine BETi and improved mechanistic understanding are required. Here we characterize the responses of aggressive MYC-driven lymphomas to 2 nonbenzodiazepine BETi: PLX51107 and PLX2853. Both invoked BIM-dependent apoptosis and in vivo therapy, associated with miR-17∼92 repression, in murine Eµ-myc lymphomas, with PLX2853 exhibiting enhanced potency. Accordingly, exogenous BCL-2 expression abrogated these effects. Because high BCL-2 expression is common in diffuse large B-cell lymphoma (DLBCL), BETi were ineffective in driving apoptosis and in vivo therapy of DLBCL cell lines, mirroring clinical results. However, BETi-mediated BIM upregulation and miR-17∼92 repression remained intact. Consequently, coadministration of BETi and ABT199/venetoclax restored cell death and in vivo therapy. Collectively, these data identify BIM-dependent apoptosis as a critical mechanism of action for this class of BETi that, via coadministration of BH3 mimetics, can deliver effective tumor control in DLBCL.

Although the MYC oncogenic network represents an attractive therapeutic target for lymphoma, MYC inhibitors have been difficult to develop. Alternatively, inhibitors of epigenetic/ transcriptional regulators, particularly the bromodomain and extraterminal (BET) family, have been used to modulate MYC. However, current benzodiazepine-derivative BET inhibitors (BETi) elicit disappointing responses and dose-limiting toxicity in relapsed/refractory lymphoma, potentially because of enrichment of high-risk molecular features and chemical backbone-associated toxicities. Consequently, novel nonbenzodiazepine BETi and improved mechanistic understanding are required. Here we characterize the responses of aggressive MYC-driven lymphomas to 2 nonbenzodiazepine BETi: PLX51107 and PLX2853. Both invoked BIM-dependent apoptosis and in vivo therapy, associated with miR-17∼92 repression, in murine Eµ-myc lymphomas, with PLX2853 exhibiting enhanced potency. Accordingly, exogenous BCL-2 expression abrogated these effects. Because high BCL-2 expression is common in diffuse large B-cell lymphoma (DLBCL), BETi were ineffective in driving apoptosis and in vivo therapy of DLBCL cell lines, mirroring clinical results. However, BETi-mediated BIM upregulation and miR-17∼92 repression remained intact. Consequently, coadministration of BETi and ABT199/venetoclax restored cell death and in vivo therapy. Collectively, these data identify BIM-dependent apoptosis as a critical mechanism of action for this class of BETi that, via coadministration of BH3 mimetics, can deliver effective tumor control in DLBCL.

The article "Who Invented Combined Arms?" by David T. Zabecki discusses the development and use of combined arms in military history. The author argues that Spain, during the last phases of the Reconquista in 1482-1492, was the first to develop combined arms with the creation of the tercios, which consisted of pikemen, swordsmen, and harquebusiers. The tercios were highly disciplined and skilled, making them the dominant European fighting force for a century and a half. However, their preeminence ended in 1658. The author also acknowledges that no commander in history has invented a tactical system from scratch, and all innovations are improvements on past practices. The article concludes by stating that the tactical systems on today's battlefields have their roots in the methods of Gustavus II Adolphus of Sweden, who introduced artillery that maneuvered with the infantry and revived shock action in heavy cavalry. [Extracted from the article]

Racial disparities in heart transplantation (HT) outcomes are suspected but uncertain. The additional impact of a recent change in donor allocation on disparities in HT in the United States (US) is unknown. We hypothesize racial disparities in HT are present and may be worsened by new allocation practices.

Several letters to the editor are presented in response to articles in previous issues, including an article about reincarnation, investigation on the lives of animals, future of feminism and religion.

The article explores that tradeoffs between generality/power and simplicity/usability in authoring tools for advanced and adaptive learning environments (LEs) in the U.S. Advanced and adaptive learning environments are those computer-based LEs that include advancements over traditional courseware, multimedia and educational simulations. Authoring tools relieve the designer of the task of programming by providing suitably generic and flexible building blocks and customization parameters. The teachers and other subject matter experts play an important role in the design process of LEs.

Presents letters to the editor referencing topics discussed in previous issues. Article on collective intelligence by Craig Hamilton in the spring issue; Feature on group mind; Guru/Pandit talk by Andrew Cohen.

MetaLinks, an authoring tool and web server for adaptive hyperbooks, is described. MetaLinks hyperbooks provide textbook-like content in a flexible manner that supports opportunistic processes of active reading and learning. Through adaptive methods a single on-line artifact can address the diverse needs of a variety of user goals and backgrounds. The system is designed to support inquiry, exploratory, or curiosity-driven learning in richly interconnected material and to ameliorate a number of usability issues that arise in such open ended learning environments. Chief among the usability issues addressed are the potential for discontinuous conceptual and narrative flow as users navigate flexibly and idiosyncratically through hyperbook content. Our goals are addressed through a number of interface features and adaptive methods including narrative smoothing, custom depth control, and thematic links. In this paper we describe the MetaLinks system, discuss a number of hyperbook design issues, and give the results of two formative evaluations of a MetaLinks Hyperbook.

Seismicity is one of the most commonly monitored phenomena used to determine the state of a volcano and for the prediction of volcanic eruptions. Although several real-time earthquake-detection and data acquisition systems exist, few continuously measure seismic amplitude in circumstances where individual events are difficult to recognize or where volcanic tremor is prevalent. Analog seismic records provide a quick visual overview of activity; however, continuous rapid quantitative analysis to define the intensity of seismic activity for the purpose of predicing volcanic eruptions is not always possible because of clipping that results from the limited dynamic range of analog recorders. At the Cascades Volcano Observatory, an inexpensive 8-bit analog-to-digital system controlled by a laptop computer is used to provide 1-min average-amplitude information from eight telemetered seismic stations. The absolute voltage level for each station is digitized, averaged, and appended in near real-time to a data file on a multiuser computer system. Raw realtime seismic amplitude measurement (RSAM) data or transformed RSAM data are then plotted on a common time base with other available volcano-monitoring information such as tilt. Changes in earthquake activity associated with dome-building episodes, weather, and instrumental difficulties are recognized as distinct patterns in the RSAM data set. RSAM data for domebuilding episodes gradually develop into exponential increases that terminate just before the time of magma extrusion. Mount St. Helens crater earthquakes show up as isolated spikes on amplitude plots for crater seismic stations but seldom for more distant stations. Weather-related noise shows up as low-level, long-term disturbances on all seismic stations, regardless of distance from the volcano. Implemented in mid-1985, the RSAM system has proved valuable in providing up-to-date information on seismic activity for three Mount St. Helens eruptive episodes from 1985 to 1986 (May 1985, May 1986, and October 1986). Tiltmeter data, the only other telemetered geophysical information that was available for the three dome-building episodes, is compared to RSAM data to show that the increase in RSAM data was related to the transport of magma to the surface. Thus, if tiltmeter data is not available, RSAM data can be used to predict future magmatic eruptions at Mount St. Helens. We also recognize the limitations of RSAm data. Two examples of RSAM data associated with phreatic or shallow phreatomagmatic explosions were not preceded by the same increases in RSAM data or changes in tilt associated with the three dome-building eruptions.

This research addresses the widening gap between research in intelligent tutoring systems and practical use of this technology by the educational community. In order to insure that intelligent tutoring systems (ITSs) are effective, teachers must be involved in their design and evaluation. We have followed a user participatory design process to build a set of ITS knowledge acquisition tools tailored for usability by teachers. The system facilitates rapid prototyping and testing of curriculum and multiple tutoring strategies. Teachers use the system to create, modify, and test the system's domain content and tutoring strategy knowledge bases. The design includes novel methodologies for strategy representation and overlay student modeling, and incorporates considerations from instructional design theory. Tools have been designed to provide the user with visual models of the concepts and structures of the underlying framework. In close collaboration with a veteran high school teacher, we have used the interface to design a tutor for statics (part of a high school physics course). In this paper we describe the system (called KAFITS), report on our experience involving educators in ITS development, discuss issues of ITS knowledge representation and acquisition, and compare the system with related research in generic tutoring systems and knowledge acquisition.

We describe a computer tutor designed to help students understand physics concepts. The tutor uses a teaching strategy called "bridging analogies" that previous research has demonstrated to be successful in one-on-one tutoring. The strategy is designed to remedy misconceptions by appealing to existing correct intuitions, and extending these intuitions by encouraging analogical thinking. Students were videotaped while using the program and were encouraged to think aloud. The strategy was successful in changing beliefs for some students. We outline suggestions for improving the tutor using artificial intelligence technology.

KRAEMER, W. J., S. J. FLECK, R. CALLISTER, M. SHEALY, G. A. DUDLEY, C. M. MARESH, L. MARCHITELLI, C. CRUTHIRDS, T. MURRAY, and J. E. FALKEL. Training responses of plasma beta-endorphin, adrenocorticotropin, and cortisol. Med. Sci. Sports Exerc, Vol. 21, No. 2, pp. 146–153, 1989. The purpose of this study was to examine the effects of three different run training programs on plasma responses of beta-endorphin (β-EP), adrenocorticotropin (ACTH), and cortisol to maximal treadmill exercise. Subjects were randomly assigned to one of three training groups: sprint intervals (SI) (N= 8), endurance (E) (N= 10), or combination (C) (N= 7). Training was monitored for 10 wk, and maximal treadmill exercise tests were administered pre-training and after 2, 4, 6, 8, and 10 wk of training. Blood samples were obtained (pre-training and after 10 wk) before, immediately after, and 5 and 15 min following the maximal exercise tests. All groups significantly (P< 0.05) increased maximal oxygen consumption values at 8 and 10 wk of the training period. Significant exercise-induced increase in plasma β-EP, ACTH, cortisol, and blood lactate were observed for both pre- and post-training tests in all training groups. The SI group demonstrated significant post-training increases in β-EP, ACTH, cortisol, and 5 min post-exercise blood lactate concentrations in response to maximal exercise. No training-induced hormonal changes were observed for the E group. While exercise-induced increases were observed, the C group exhibited significant post-training reductions in plasma responses ofβ-EP, ACTH, and blood lactate concentrations in response to maximal exercise. Still, resting and post-exercise increases in plasma cortisol concentrations were significantly higher in magnitude in the post-training test. Lactate was significantly correlated with β-EP (r = 0.72), ACTH (r = 0.70), and cortisol (r = 0.64). These data suggest that different run training programs produce differential effects on plasma β-EP, ACTH, and cortisol in response to maximal exercise and that these responses may be linked to anaerobic metabolic factors.

The article presents the conference of the American Conference on Oriental Rugs (ACOR) 4 at the Westin Hotel, Denver, Colorado in May 1998 mounted by the Colorado Textile Group. Michael Rothberg in the Focus Sessions surveyed the Baluch prayer rugs. Jim Dixon presented Islamic cosmology and number symbolisms. The ACOR exhibit was mounted by Sharon and Rex Brown. The Navajo child's blanket collected in 1847 in Vera Cruz, Mexico is included.

A reprint of the article "The Bar for Corporate Leadership on Climate Has Been Raised" by Tom Murray, which appeared on the website EDF.org on April 1, 2016, is presented.

We report the use of broth simulation as a means of validating the practice of sub-dispensing from stock vials of long-lived sterile radiopharmaceuticals. ‘Matched’ vials of nutrient broth accompanied the stock vials of long-lived sterile radiopharmaceuticals during their time in use and were subject to the same handling and storage procedures. At the end of the life of each radiopharmaceutical stock vial, the matching broth residue was sent for incubation and reporting. The results to date have yielded no reports of microbial contamination in any of the simulated broths (0 in 256).

Shares opinions on the development of a community collaboration Web site for improvisation dance sector. Development of a Web site that provides region-specific and aggregate collaboration facilities;Possibility of providing online article editing and publishing; Ideas for how online collaboration can be structured in a way that promotes consciousness, multiple perspectives and transparency.

The article offers the author's view on the establishment of a smart regulatory policy by sustainable leadership. He mentions the support of most business enterprises on reforming the policy which will benefit both the economy and the environment. An overview of the sustainable chemicals policy of retail firm Wal-Mart Stores Inc. is also presented.

The article discusses the successes and future plans of the Environmental Defense Fund (EDF) in regards to its work with the corporate sector in social responsibility of businesses. Information is presented about the EDF's work with McDonald's, Walmart, FedEx Corp., and KKR to integrate sustainability into their operations, strategy, and supply chain management. Need for more aggressive private sector leadership to align corporate sustainability operations and strategy is emphasized.

Several letters to the editor are presented in response to articles in previous issues including "The Business of Being Henry" and "A Fish Out of Time" in the Special 2013 issue and "Open Season" in the Spring 2013 issue.

The poem "Love Poems," by Tom Murray is presented. First Line: I don't understand them; Last Line: They are because of.

Several letters to the editor are presented in response to articles in previous issues including an article by Nick Hart in the August 15, 2007 issue, comments on censorship and public scrutiny by Eric Hayman and the advantages of photojournalism.