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At least 397 records · Page 22

Application health monitoring for extreme-scale resiliency using cooperative fault management

Resiliency is and will be a critical factor in determining scientific productivity on current and exascale supercomputers, and beyond. Applications oblivious to and incapable of handling transient soft and hard errors could waste supercomputing resources or, worse, yield misleading scientific insights. In this work, we introduce a novel application-driven silent error detection and recovery strategy based on application health monitoring. Our methodology uses application output that follows known patterns, as indicators of an application's health and knowledge that violation of these patterns could be indication of faults. Information from system monitors that report hardware and software health status is used to corroborate faults. Collectively, this information is used by a fault coordinator agent to take preventive and corrective measures by applying computational steering to an application between checkpoints. This cooperative fault management system uses the Fault Tolerance Backplane as a communication channel. The benefits of this framework are demonstrated with two real application case studies, molecular dynamics, and quantum chemistry simulations, on scalable clusters with simulated memory and I/O corruptions. Lastly, the developed approach is general and can be easily applied to other applications.

97 MATHEMATICS AND COMPUTING↗

Bulk locality and cooperative flows

We use the ‘bit thread’ formulation of holographic entanglement entropy to highlight the distinction between the universally-valid strong subadditivity and the more restrictive relation called monogamy of mutual information (MMI), known to hold for geometrical states (i.e. states of holographic theories with gravitational duals describing a classical bulk geometry). In particular, we provide a novel proof of MMI, using bit threads directly. To this end, we present an explicit geometrical construction of cooperative flows which we build out of disjoint thread bundles. We conjecture that our method applies in a wide class of configurations, including ones with non-trivial topology, causal structure, and time dependence. The explicit nature of the construction reveals that MMI is more deeply rooted in bulk locality than is the case for strong subadditivity.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

TANDEM: a mutual cooperation effort for transactinide nuclear data evaluation and measurement

Here, the need for accurate nuclear reaction data of actinides is well documented and several initiatives from international organizations for improvement have been initiated in the past. This need, particularly in view of method development for non-destructive assay of nuclear waste, has generated a joint effort to use prompt and delayed neutron activation techniques to enhance nuclear capture data of some long lived actinides such as 237 Np, 242 Pu and 241 Am in the frame of a multilateral cooperation. This research initiative is targeted to lay grounds for the development of a non-destructive active neutron interrogation technique to quantify actinides in mixed waste and residues from decommissioning of nuclear installations for safe treatment and storage of such materials.

42 ENGINEERING↗

Five amino acid mismatches in the zinc-finger domains of Cellulose Synthase 5 and Cellulose Synthase 6 cooperatively modulate their functional properties by controlling homodimerization in Arabidopsis

Cellulose synthase 5 (CESA5) and CESA6 are known to share substantial functional overlap. In the zinc-finger domain (ZN) of CESA5, there are five amino acid (AA) mismatches when compared to CESA6. These mismatches in CESA5 were replaced with their CESA6 counterparts one by one until all were replaced, generating nine engineered CESA5s. Each N-terminal enhanced yellow fluorescent protein-tagged engineered CESA5 was introduced to prc1-1, a cesa6 null mutant, and resulting mutants were subjected to phenotypic analyses. For this work, we found that five single AA-replaced CESA5 proteins partially rescue the prc1-1 mutant phenotypes to different extents. Multi-AA replaced CESA5s further rescued the mutant phenotypes in an additive manner, culminating in full recovery by CESA5 G43R + S49T+S54P+S80A+Y88F . Investigations in cellulose content, cellulose synthase complex (CSC) motility, and cellulose microfibril organization in the same mutants support the results of the phenotypic analyses. Bimolecular fluorescence complementation assays demonstrated that the level of homodimerization in every engineered CESA5 is substantially higher than CESA5. The mean fluorescence intensity of CSCs carrying each engineered CESA5 fluctuates with the degree to which the prc1-1 mutant phenotypes are rescued by introducing a corresponding engineered CESA5. Taken together, these five AA mismatches in the ZNs of CESA5 and CESA6 cooperatively modulate the functional properties of these CESAs by controlling their homodimerization capacity, which in turn imposes proportional changes on the incorporation of these CESAs into CSCs.

59 BASIC BIOLOGICAL SCIENCES↗

Cooperative Formation of Icosahedral Proline Clusters from Dimers

Ion mobility spectrometry-mass spectrometry and Fourier transform infrared spectroscopy (FTIR) techniques were combined with quantum chemical calculations to examine the origin of icosahedral clusters of the amino acid proline. When enantiopure proline solutions are electrosprayed (using nanospray) from 100 mM ammonium acetate, only three peaks are observed in the mass spectrum across a concentration range of five orders of magnitude: a monomer [Pro+H]{sup +} species, favored from 0.001 to 0.01 mM proline concentrations; a dimer [2Pro+H]{sup +} species, the most abundant species for proline concentrations above 0.01 mM; and, the dimer and dodecamer [12Pro+2H]{sup 2+} for 1.0 mM and more concentrated proline solutions. Electrospraying racemic D/L-proline solutions from 100 mM ammonium acetate leads to a monomer at low proline concentrations (0.001 to 0.1 mM), and a dimer at higher concentrations (>0.09 mM), as well as a very small population of 8 to 15 Pro clusters that comprise <0.1% of the total ion signals even at the highest proline concentration. Solution FTIR studies show unique features that increase in intensity in the enantiopure proline solutions, consistent with clustering, presumably from the icosahedral geometry in bulk solution. When normalized for the total proline, these results are indicative of a cooperative formation of the enantiopure 12Pro species from 2Pro. .

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A cooperative conjugate gradient method for linear systems permitting efficient multi-thread implementation

This paper revisits, in a multi-thread context, the so-called multi-parameter or block conjugate gradient (B-CG) methods, first proposed as sequential algorithms by O’Leary and Brezinski, for the solution of the linear system Ax=b, for an n-dimensional symmetric positive definite matrix A. Instead of the scalar parameters of the classical CG algorithm, which minimizes a scalar functional at each iteration, multiple descent and conjugate directions are updated simultaneously. Implementation involves the use of multiple threads and the algorithm is referred to as cooperative CG (CCG) to emphasize that each thread now uses information that comes from the other threads. It is shown that for a sufficiently large matrix dimension n, the use of an optimal number of threads results in a worst case flop count of O(n{sup 7/3}) in exact arithmetic. Numerical experiments on a multi-core, multi-thread computer, for synthetic and real matrices, illustrate the theoretical results.

97 MATHEMATICS AND COMPUTING↗

STAT3 stimulates adipogenic stem cell proliferation and cooperates with HMGA2 during the early stage of differentiation to promote adipogenesis

Signal transducer and activator of transcription 3 (STAT3) is abundantly expressed in the adipose tissue of obese mice and humans, but the role of STAT3 in adipogenesis is still not fully understood. In the present study, we discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. Moreover, accumulation of lipid droplets was inhibited by Stat3 knockdown. Importantly, in the nucleus of early differentiating cells, we demonstrated that STAT3 protein co-localized with high-mobility-group protein AT-hook 2 (HMGA2), which was reported to promote adipogenesis in a previous study. Taken together, our data indicate that STAT3 and HMGA2 cooperatively promote adipogenesis which highlight a more detail understanding of STAT3 related transcription factor network during adipogenesis. - Highlights: • We discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. • Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. • Accumulation of lipid droplets was inhibited by Stat3 knockdown. • STAT3 protein co-localized with HMGA2, which was reported to promote adipogenesis in a previous study.

60 APPLIED LIFE SCIENCES↗

WDR74 participates in an early cleavage of the pre-rRNA processing pathway in cooperation with the nucleolar AAA-ATPase NVL2

Highlights: • WDR74, along with NVL2, participates in the cleavage of pre-rRNA ITS1 at site 2. • NVL2 strips WDR74 away from the MTR4-exosome to relocate it in the nucleolus. • MTR4-bound WDR74 accumulates in the nucleoplasm of NVL2-deficient cells. • WDR74-MTR4 interaction is regulated by NVL2 during ribosome biogenesis. WD repeat-containing protein 74 (WDR74), a nucleolar-localized protein, is the mammalian ortholog of Nsa1, a 60S ribosome assembly factor in yeast. We previously showed that WDR74 associates with MTR4, the nuclear exosome-assisting RNA helicase, whose dissociation is prohibited by an ATPase-deficient mutant of the AAA-type chaperone NVL2. However, the functions and regulation of WDR74 during ribosome biogenesis in cooperation with NVL2 remains unknown. Here, we demonstrated that knockdown of WDR74 leads to significant defects in the pre-rRNA cleavage within the internal transcribed spacer 1 (ITS1), occurring in an early stage of the processing pathway. Interestingly, when the dissociation of WDR74 from the MTR4-containing exonuclease complex was impaired upon expression of the mutant NVL2, the same processing defect, with partial migration of WDR74 from the nucleolus towards the nucleoplasm, was observed. In the nucleoplasm, an increased interaction between WDR74 and MTR4 was detected by in situ proximity ligation assay. Therefore, the dissociation of WDR74 from MTR4 in a late stage of rRNA synthesis is thought to be required for appropriate maturation of the pre-60S particles. These results suggest that the spatiotemporal regulation of ribosome biogenesis in the nucleolus is mediated by the ATPase activity of NVL2.

60 APPLIED LIFE SCIENCES↗

Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression

Highlights: • HOTTIP is required for activation of distal HOXA genes but its role is restricted by CTCF boundary. • HOTTIP and CTCF coordinate to specify the pattern of histone modifications on HOXA genes in foreskin fibroblasts. • HOTTIP RNA acts as a new interaction partner of CTCF. The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5′ edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts. Our results reveal the functional connection of HOTTIP and CTCF, and shed light on lincRNAs in gene activation and CTCF mediated chromatin organization.

60 APPLIED LIFE SCIENCES↗

Optimizing the surface distribution of acid sites for cooperative catalysis in condensation reactions promoted by water

Addition of small amounts of water to the organic solvent may result in different promoting or inhibiting effects in aldol condensation reactions depending on the distribution of active sites on the surface. In a combination of liquid-phase catalytic activity measurements, spectroscopies and theoretical calculations, we have shown that water clusters around the acid site can form bridges with a ketone molecule located close to the activated carbonyl, on another site. When the distance between the two acid sites is greater than a distance corresponding to about 2 water molecules, the efficiency of the bond polarization of the ketone by a remotely located acid site decreases significantly, and the presence of water no longer promotes the reaction. Furthermore, this work provides a quantitative assessment of how solvent molecules can bridge isolated active sites to enable cooperative catalysis, which offers an additional dimension for engineering catalysis at the nanoscale.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Solving the duck curve in a smart grid environment using a non-cooperative game theory and dynamic pricing profiles

With the intermittency that comes with electricity generation from renewables, utilizing dynamic pricing will encourage the demand-side to respond in a smart way that would minimize the electricity costs and flatten the net electricity demand curve. Determining the optimal dynamic pricing profile that would leverage distributed storage to flatten the curve is a novel idea that needs to be studied. Moreover, the economic feasibility of utilizing distributed electrical energy storage is still not given in the literature. Therefore, in this paper, a novel way of solving a citywide dynamic model using a bilevel programming algorithm is introduced. The problem is developed as a novel non-cooperative Stackelberg game that utilizes air-conditioning systems and electrical storage through the end-users to determine the optimal dynamic pricing profile. The results show that the combined effect of utilizing demand-side air-conditioning systems and distributed storage together can flatten the curve while employing the optimal dynamic pricing profile. An economic study is performed to determine the economic feasibility of 20 different cases with different battery designs and the level of solar penetration. Three metrics were used to evaluate the economic performance of each case: the levelized cost of storage, the levelized cost of energy, and the simple payback period. Most cases had levelized cost of storage values lower than 0.457 $/kWh, which is the lower bound available in the literature. Seven out of 16 cases have a simple payback period shorter than the lifetime of the system (25 years). The case with a 100 MW PV power plant and a battery storage of size 597 MWh, was found to be the most promising case with a simple payback period of 12.71 years for the photovoltaic plant and 19.86 years for the demand-side investments.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Cooperation or Rivalry? Impact of alternative development pathways on India's long-term electricity generation and associated water demands

The world has witnessed a significant shift in the last decade in the way countries interact with each other. A cooperation based international paradigm is being challenged by countries engaging in rivalry with each other in the name of their national interests. What developmental pathway the world charts in the future is going to be path defining for global energy and emissions use. India, expected to play a critical role in the emissions mitigation debate, would contribute to and would be impacted by these pathways. In India specific literature, however, little attention has been paid to development pathways related uncertainties and their impact on energy futures. We seek to address this gap by modelling India's electricity futures and associated water demands under different development pathways. Our analysis shows that alternative development pathways would have significantly different implications for the energy access, electricity generation mix, associated water withdrawals, and carbon dioxide emissions in India. We conclude by arguing that energy, emissions and water policies should be conceived with an explicit understanding of uncertainties related to potential development pathways that the world and India can chart.

India, Electricity-Water Nexus, Development Pathwa↗

Time-Varying Output Delay Compensation-A Model-Free Approach and its Application on Cooperative On-Ramp Merging

This paper presents a model-free approach to compensate for time-varying output delay in networked control systems. The proposed architecture combines a model-free observer and the Smith predictor. The model-free observer estimates the current state while handling modeling errors and uncertainties of the system. The Smith predictor moves the effect of time delay outside the control closed-loop using the estimated delayed output and the actual output of the plant. The proposed method is applied to a cooperative on-ramp merging problem. First, an ultra-local model predictive control is implemented to provide a computationally efficient online speed planner agnostic to the vehicle dynamics. After that, a model-free observer is designed to estimate the current state. Finally, the proposed architecture is tested against a time-varying output delay with an upper bound of 200 milliseconds. The results demonstrate the effectiveness of the proposed method with improved tracking of intervehicle distance.

Waleed khan, Muhammad [The University of Texas at ↗

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Energy-efficient cooperative resource allocation and task scheduling for Internet of Things environments

Offloading Internet of Things (IoT) tasks to the cloud for further processing might not always lead to an optimal execution time, particularly in situations such as resource contention, under-provisioning, over-provisioning, and fragmentation. In addition, dynamically optimizing the number of Virtual Machines (VMs) for resource scheduling in order to meet application requirements remains a major research challenge. Further, existing resource scheduling algorithms focus primarily on minimizing operational costs while maximizing resource sharing and utilization. Considering energy utilization as part of the resource allocation and scheduling process as an optimization objective for maintaining load balancing has often been neglected. To address these challenges and more, we propose a cooperative energy-aware resource allocation and scheduling strategy based on a Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) multi-criteria decision-making method. Here we used the Grid Workloads Archive dataset to evaluate our proposed approach named TOPREAL. Experimental results with respect to the allocation of VM resources when considering processing a large segment of tasks indicate that TOPREAL outperforms existing algorithms in terms of energy savings, with an average improvement of 40.25%, while maintaining an average improvement of 16.21% when it comes to execution time. Results also demonstrate that our method can save an average of 78.06 processing hours and 63,215kJ of energy when compared to existing scheduling algorithms. These results demonstrate the effectiveness of our proposed model and the viability of using multi-criteria decision-making techniques such as TOPSIS to solve the resource allocation and scheduling problem in edge environments.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Modeling the effects of carbon payments and forest owner cooperatives on carbon storage and revenue in Pacific Northwest forestlands

The forestlands of the Pacific Northwest store a significant amount of carbon, provide wildlife habitat, generate revenue for forestland owners, and provide for sustainable generation of forest products. Promoting forest carbon storage is increasingly recognized as a key management objective to mitigate climate change. We developed an agent-based model to examine the effectiveness of current land management practices in sustaining forest carbon storage and revenue flows, and the utility of market-based carbon payments in improving carbon storage while also improving revenue generation in the Pacific Northwest. We find that while market based incentives can improve both forest carbon storage and revenue, they are limited in their benefit to small forest owners. Our results highlight the crucial need for additional policy interventions to reduce barriers to market access for small private owners and ensure sustainable forest management in this region. We further show that a forest owners’ cooperative, which aggregates small owners to reduce the costs of participating in a carbon market, can help overcome these barriers and result in both greater carbon storage and a more equitable benefit from carbon payments.

54 ENVIRONMENTAL SCIENCES↗

Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases

N 6 -methyladenosine (m 6 A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m 6 A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. Here, we present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs, constitutes the minimally required regions for creating m 6 A modifications in vitro. We also show that Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗