Self-consistent implementation of meta-GGA functionals for the ONETEP linear-scaling electronic structure package

Accurate and computationally efficient exchange-correlation functionals are critical to the successful application of linear-scaling density functional theory (DFT). Local and semi-local functionals of the density are naturally compatible with linear-scaling approaches, having a general form which assumes the locality of electronic interactions and which can be efficiently evaluated by numerical quadrature. Presently, the most sophisticated and flexible semi-local functionals are members of the meta-generalized-gradient approximation (meta-GGA) family, and depend upon the kinetic energy density, tau, in addition to the charge density and its gradient. In order to extend the theoretical and computational advantages of tau-dependent meta-GGA functionals to large-scale DFT calculations on thousands of atoms, we have implemented support for tau-dependent meta-GGA functionals in the ONETEP program. In this paper we lay out the theoretical innovations necessary to implement tau-dependent meta-GGA functionals within ONETEP's linear-scaling formalism. We present expressions for the gradient of the tau-dependent exchange-correlation energy, necessary for direct energy minimization. We also derive the forms of the tau-dependent exchange-correlation potential and kinetic energy density in terms of the strictly localized, self-consistently optimized orbitals used by ONETEP. To validate the numerical accuracy of our self-consistent meta-GGA implementation, we performed calculations using the B97M-V and PKZB meta-GGAs on a variety of small molecules. Using only a minimal basis set of self-consistently optimized local orbitals, we obtain energies in excellent agreement with large basis set calculations performed using other codes. Finally, to establish the linear-scaling computational cost and applicability of our approach to large-scale calculations, we present the outcome of self-consistent meta-GGA calculations on amyloid fibrils of increasing size, up to tens of thousands of atoms

Towards eco-efficient lean production systems

Lean Production has proved itself a worthwhile production strategy in many distinct industries across all regions of the planet by achieving higher levels of production efficiency. Several authors identified that Lean inadvertently has had significant environmental gains. Such achievements are considered of special relevance in a global and highly competitive economy which is progressively both tied-up and driven by an environmental agenda. The main goal of the present study is to enlighten the contribution of Lean for achieving a better environmental performance of production systems and identify this as an emergent business model for supporting eco-efficiency

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial.

Lessons learnedThe addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation.BackgroundThis randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer.MethodsPatients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS).ResultsOne hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen.ConclusionAddition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup

A high resolution RH map of the bovine major histocompatibility complex

<p>Abstract</p> <p>Background</p> <p>The cattle MHC is termed the bovine leukocyte antigen (BoLA) and, along with the MHCs of other ruminants, is unique in its genomic organization. Consequently, correct and reliable gene maps and sequence information are critical to the study of the BoLA region. The bovine genome sequencing project has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from each other and from conventional gene maps in the BoLA region. To independently compare the accuracies of the different sequence assemblies, we have generated a high resolution map of BoLA using a 12,000_radradiation hybrid panel. Seventy-seven unique sequence tagged site (STS) markers chosen at approximately 50 kb intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions of the bovine MHC were mapped on a 12,000_radbovine radiation hybrid (RH) panel to evaluate the different assemblies of the bovine genome sequence.</p> <p>Results</p> <p>Analysis of the data generated a high resolution RH map of BoLA that was significantly different from the Btau_3.1 assembly of the bovine genome but in good agreement with the Btau_4.0 assembly. Of the few discordancies between the RH map and Btau_4.0, most could be attributed to closely spaced markers that could not be precisely ordered in the RH panel. One probable incorrectly-assembled sequence and three missing sequences were noted in the Btau_4.0 assembly. The RH map of BoLA is also highly concordant with the sequence-based map of HLA (NCBI build 36) when reordered to account for the ancestral inversion in the ruminant MHC.</p> <p>Conclusion</p> <p>These results strongly suggest that studies using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of the Btau_4.0 assembly and indicate that additional research is needed to produce a complete assembly of the BoLA genomic sequences.</p

State-of-the-art in lean design engineering:a literature review on white collar lean

Lean is usually associated with the ‘operations’ of a manufacturing enterprise; however, there is a growing awareness that these principles may be transferred readily to other functions and sectors. The application to knowledge-based activities such as engineering design is of particular relevance to UK plc. Hence, the purpose of this study has been to establish the state-of-the-art, in terms of the adoption of Lean in new product development, by carrying out a systematic review of the literature. The authors' findings confirm the view that Lean can be applied beneficially away from the factory; that an understanding and definition of value is key to success; that a set-based (or Toyota methodology) approach to design is favoured together with the strong leadership of a chief engineer; and that the successful implementation requires organization-wide changes to systems, practices, and behaviour. On this basis it is felt that this review paper provides a useful platform for further research in this topic

The chemical evolution of the solar neighbourhood for planet-hosting stars

Theoretical physical-chemical models for the formation of planetary systems depend on data quality for the Sun's composition, that of stars in the solar neighbourhood, and of the estimated "pristine" compositions for stellar systems. The effective scatter and the observational uncertainties of elements within a few hundred parsecs from the Sun, even for the most abundant metals like carbon, oxygen and silicon, are still controversial. Here we analyse the stellar production and the chemical evolution of key elements that underpin the formation of rocky (C, O, Mg, Si) and gas/ice giant planets (C, N, O, S). We calculate 198 galactic chemical evolution (GCE) models of the solar neighbourhood to analyse the impact of different sets of stellar yields, of the upper mass limit for massive stars contributing to GCE ($M_{\rm up}$) and of supernovae from massive-star progenitors which do not eject the bulk of the iron-peak elements (faint supernovae). Even considering the GCE variation produced via different sets of stellar yields, the observed dispersion of elements reported for stars in the Milky Way disk is not reproduced. Among others, the observed range of super-solar [Mg/Si] ratios, sub-solar [S/N], and the dispersion of up to 0.5 dex for [S/Si] challenge our models. The impact of varying $M_{\rm up}$ depends on the adopted supernova yields. Thus, observations do not provide a constraint on the M$_{\rm up}$ parametrization. When including the impact of faint supernova models in GCE calculations, elemental ratios vary by up to 0.1-0.2 dex in the Milky Way disk; this modification better reproduces observations.Comment: 36 pages, 26 figures, 1 Table, 1 Appendix, Accepted for publication in MNRA

The Japanese model in retrospective : industrial strategies, corporate Japan and the 'hollowing out' of Japanese industry

This article provides a retrospective look at the Japanese model of industrial development. This model combined an institutional approach to production based around the Japanese Firm (Aoki's, J-mode) and strategic state intervention in industry by the Japanese Ministry of International Trade and Industry (MITI). For a long period, the alignment of state and corporate interests appeared to match the wider public interest as the Japanese economy prospered. However, since the early 1990s, the global ambitions of the corporate sector have contributed to a significant 'hollowing out' of Japan's industrial base. As the world today looks for a new direction in economic management, we suggest the Japanese model provides policy-makers with a salutary lesson in tying the wider public interest with those of the corporate sector

The chemical evolution of the solar neighbourhood for planet-hosting stars

Theoretical physical-chemical models for the formation of planetary systems depend on data quality for the Sun’s composition, that of stars in the solar neighbourhood, and of the estimated ”pristine” compositions for stellar systems. The effective scatter and the observational uncertainties of elements within a few hundred parsecs from the Sun, even for the most abundant metals like carbon, oxygen and silicon, are still controversial. Here we analyse the stellar production and the chemical evolution of key elements that underpin the formation of rocky (C, O, Mg, Si) and gas/ice giant planets (C, N, O, S). We calculate 198 galactic chemical evolution (GCE) models of the solar neighbourhood to analyse the impact of different sets of stellar yields, of the upper mass limit for massive stars contributing to GCE (Mup) and of supernovae from massive-star progenitors which do not eject the bulk of the iron-peak elements (faint supernovae). Even considering the GCE variation produced via different sets of stellar yields, the observed dispersion of elements reported for stars in the Milky Way disk is not reproduced. Among others, the observed range of super-solar [Mg/Si] ratios, sub-solar [S/N], and the dispersion of up to 0.5 dex for [S/Si] challenge our models. The impact of varying Mup depends on the adopted supernova yields. Thus, observations do not provide a constraint on the Mup parametrization. When including the impact of faint supernova models in GCE calculations, elemental ratios vary by up to 0.1-0.2 dex in the Milky Way disk; this modification better reproduces observations