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In a recent work [P. Baudin and K. Kristensen, J. Chem. Phys. 144, 224106 (2016)], we introduced a local framework for calculating excitation energies (LoFEx), based on second-order approximated coupled cluster (CC2) linear-response theory. LoFEx is a black-box method in which a reduced excitation orbital space (XOS) is optimized to provide coupled cluster (CC) excitation energies at a reduced computational cost. In this article, we present an extension of the LoFEx algorithm to the calculation of CC2 oscillator strengths. Two different strategies are suggested, in which the size of the XOS is determined based on the excitation energy or the oscillator strength of the targeted transitions. The two strategies are applied to a set of medium-sized organic molecules in order to assess both the accuracy and the computational cost of the methods. The results show that CC2 excitation energies and oscillator strengths can be calculated at a reduced computational cost, provided that the targeted transitions are local compared to the size of the molecule. To illustrate the potential of LoFEx for large molecules, both strategies have been successfully applied to the lowest transition of the bivalirudin molecule (4255 basis functions) and compared with time-dependent density functional theory.

We report porting of the Divide-Expand-Consolidate Resolution of the Identity second-order Møller-Plesset perturbation (DEC-RI-MP2) method to the graphic processing units (GPUs) using OpenACC compiler directives. It is shown that the OpenACC compiler directives implementation efficiently accelerates the rate-determining step of the DEC-RI-MP2 method with minor implementation effort. Moreover, the GPU acceleration results in a better load balance and thus in an overall scaling improvement of the DEC algorithm. The resulting cross-platform hybrid MPI/OpenMP/OpenACC implementation has scalable and portable performance on heterogeneous HPC architectures. The GPU-enabled code was benchmarked using a reduced version of the S12L test set of Stefan Grimme (Grimme, Chem. Eur. J. 2012, 18, 9955) consisting of supramolecular complexes up to 158 atoms and 4292 contracted basis functions (cc-pVTZ). The test set results demonstrate the general applicability of the DEC-RI-MP2 method showing results consistent with the DEC-RI-MP2 introductory paper (Baudin et al., J. Chem. Phys. 2016, 144, 054102) on molecules of complicated electronic structures. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation (DEC-RI-MP2) theory method introduced in Baudin et al. [J. Chem. Phys. 144, 054102 (2016)] is significantly improved by introducing the Laplace transform of the orbital energy denominator in order to construct the double amplitudes directly in the local basis. Furthermore, this paper introduces the auxiliary reduction procedure, which reduces the set of the auxiliary functions employed in the individual fragments. The resulting Laplace transformed divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation method is applied to the insulin molecule where we obtain a factor 9.5 speedup compared to the DEC-RI-MP2 method.

An atomic orbital density matrix based response formulation of the nuclei-selected approach of Beer, Kussmann, and Ochsenfeld [J. Chem. Phys. 134, 074102 (2011)] to calculate nuclear magnetic resonance (NMR) shielding tensors has been developed and implemented into LSDalton allowing for a simultaneous solution of the response equations, which significantly improves the performance. The response formulation to calculate nuclei-selected NMR shielding tensors can be used together with the density-fitting approximation that allows efficient calculation of Coulomb integrals. It is shown that using density-fitting does not lead to a significant loss in accuracy for both the nuclei-selected and the conventional ways to calculate NMR shielding constants and should thus be used for applications with LSDalton.

The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2016 The Histochemical Society.)

We report an implementation of the molecular gradient using the divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation theory (DEC-RI-MP2). The new DEC-RI-MP2 gradient method combines the precision control as well as the linear-scaling and massively parallel features of the DEC scheme with efficient evaluations of the gradient contributions using the RI approximation. We further demonstrate that the DEC-RI-MP2 gradient method is capable of calculating molecular gradients for very large molecular systems. A test set of supramolecular complexes containing up to 158 atoms and 1960 contracted basis functions has been employed to demonstrate the general applicability of the DEC-RI-MP2 method and to analyze the errors of the DEC approximation. Moreover, the test set contains molecules of complicated electronic structures and is thus deliberately chosen to stress test the DEC-RI-MP2 gradient implementation. Additionally, as a showcase example the full molecular gradient for insulin (787 atoms and 7604 contracted basis functions) has been evaluated.

We present the DEC-RIMP2-F12 method where we have augmented the Divide Expand-Consolidate resolution-of-the-identity second-order Møller-Plesset perturbation theory method (DEC-RIMP2) [P. Baudin et al., J. Chem. Phys. 144, 054102 (2016)] with an explicitly correlated (F12) correction. The new method is linear-scaling, massively parallel, and it corrects for the basis set incompleteness error in an efficient manner. In addition, we observe that the F12 contribution decreases the domain error of the DEC-RIMP2 correlation energy by roughly an order of magnitude. An important feature of the DEC scheme is the inherent error control defined by a single parameter, and this feature is also retained for the DEC-RIMP2-F12 method. In this paper we present the working equations for the DEC-RIMP2-F12 method and proof of concept numerical results for a set of test molecules.

We augment the recently introduced same number of optimized parameters (SNOOP) scheme [K. Kristensen et al., J. Chem. Phys. 142, 114116 (2015)] for calculating interaction energies of molecular dimers with an F12 correction and generalize the method to enable the determination of interaction energies of general molecular clusters. The SNOOP, uncorrected (UC), and counterpoise (CP) schemes with/without an F12 correction are compared for the S22 test set of Jurečka et al. [Phys. Chem. Chem. Phys. 8, 1985 (2006)]-which consists of 22 molecular dimers of biological importance-and for water and methane molecular clusters. The calculations have been performed using the Resolution of the Identity second-order Møller-Plesset perturbation theory method. We conclude from the results that the SNOOP scheme generally yields interaction energies closer to the complete basis set limit value than the UC and CP approaches, regardless of whether the F12 correction is applied or not. Specifically, using the SNOOP scheme with an F12 correction yields the computationally most efficient way of achieving accurate results at low basis set levels. These conclusions hold both for molecular dimers and more general molecular clusters.

The theoretical foundation for solving coupled cluster singles and doubles (CCSD) amplitude equations to a desired precision in terms of independent fragment calculations using restricted local orbital spaces is reinvestigated with focus on the individual error sources. Four different error sources are identified theoretically and numerically and it is demonstrated that, for practical purposes, local orbital spaces for CCSD calculations can be identified from calculations at the MP2 level. The development establishes a solid theoretical foundation for local CCSD calculations for the independent fragments, and thus for divide-expand-consolidate coupled cluster calculations for large molecular systems with rigorous error control. Based on this theoretical foundation, we have developed an algorithm for determining the orbital spaces needed for obtaining the single fragment energies to a requested precision and numerically demonstrated the robustness and precision of this algorithm.

The Resolution of the Identity second-order Møller-Plesset perturbation theory (RI-MP2) method is implemented within the linear-scaling Divide-Expand-Consolidate (DEC) framework. In a DEC calculation, the full molecular correlated calculation is replaced by a set of independent fragment calculations each using a subset of the total orbital space. The number of independent fragment calculations scales linearly with the system size, rendering the method linear-scaling and massively parallel. The DEC-RI-MP2 method can be viewed as an approximation to the DEC-MP2 method where the RI approximation is utilized in each fragment calculation. The individual fragment calculations scale with the fifth power of the fragment size for both methods. However, the DEC-RI-MP2 method has a reduced prefactor compared to DEC-MP2 and is well-suited for implementation on massively parallel supercomputers, as demonstrated by test calculations on a set of medium-sized molecules. The DEC error control ensures that the standard RI-MP2 energy can be obtained to the predefined precision. The errors associated with the RI and DEC approximations are compared, and it is shown that the DEC-RI-MP2 method can be applied to systems far beyond the ones that can be treated with a conventional RI-MP2 implementation.

We propose a reformulation of the traditional (T) triples correction to the coupled cluster singles and doubles (CCSD) energy in terms of local Hartree-Fock (HF) orbitals such that its structural form aligns with our recently developed linear-scaling divide-expand-consolidate (DEC) coupled cluster family of local correlation methods. In a DEC-CCSD(T) calculation, a basis of local occupied and virtual HF orbitals is used to partition the correlated calculation on the full system into a number of independent atomic fragment and pair fragment calculations, each performed within a truncated set of the complete orbital space. In return, this leads to a massively parallel algorithm for the evaluation of the DEC-CCSD(T) correlation energy, which formally scales linearly with the size of the full system and has a tunable precision with respect to a conventional CCSD(T) calculation via a single energy-based input threshold. The theoretical developments are supported by proof of concept DEC-CCSD(T) calculations on a series of medium-sized molecular systems.

ZFR is an ancient and highly conserved chromosome-associated protein from nematodes to mammals, embryologically expressed in most species, with the exception of the nematode Caenorhabditis elegans. The ZFR encodes zinc and RNA binding protein, and in rat, the nuclear-cytoplasmic shuttling ZFR has been found with transport and translation-associated RNA granule-like structures in the somatodendritic compartments of hippocampal neurons. The majority of axons cross the midline before projecting to their contralateral synaptic target and this crossing decision is under tight control. Molecular factors contributing to these processes have been identified, although the mechanisms are not fully understood. In this study, we tested the role of ceZFR in axon guidance using ceZfr RNAi-treated animals to analyse axon midline crossing, axon fasciculation and cord commissures. In adult stages, RNAi-induced depletion of the ceZfr transcript leads to several phenotypes related to axon guidance. A midline crossing defect was observed in the ventral nerve cord (VNC) in axon type D, DD/VD motoneuron axons and axon type 1, interneuron axons. We further detected a dorsal nerve cord (DNC) axon fasciculation. Some ceZfr RNAi-treated animals revealed that cord commissures fail to reach their synaptic target. We provide evidence that ceZFR has a role in axon guidance. When Zfr was depleted by RNAi, the phenotypes are characterized by defects in axon midline crossing, axon defasciculation and cord commissures. Our results thus support the hypothesis that ZFR has essential roles during neurogenesis, and could support early steps of RNA transport and localization through RNA granule formation in the nucleus and/or to their nucleo-cytoplasmic shuttling., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Three new variants of the auxiliary-density-matrix method (ADMM) of Guidon, Hutter, and VandeVondele [J. Chem. Theory Comput. 6, 2348 (2010)] are presented with the common feature that they have a simplified constraint compared with the full orthonormality requirement of the earlier ADMM1 method. All ADMM variants are tested for accuracy and performance in all-electron B3LYP calculations with several commonly used basis sets. The effect of the choice of the exchange functional for the ADMM exchange-correction term is also investigated.

The incidence of head and neck squamous cell carcinoma has risen steadily over the past decade due to the increase in cancers associated with the human papillomavirus (HPV). The prognosis for the treatment of this type of cancer with radiotherapy and chemoradiotherapy is good. However, because these treatments can have detrimental effects on organ function and quality of life, researchers are looking into transoral robotic surgery (TORS) as a possible alternate therapy. TORS might have a positive effect on postoperative function and quality of life for cancer survivors. The aim of this review is to report on the current situation regarding the treatment of oropharyngeal cancer with TORS, with a focus on the long-term oncologic and functional outcomes of this strategy. The articles cited in this review were selected from the PubMed and MEDLINE database. They contain study results pertaining to TORS implementation, complications, oncologic and functional outcomes, and the implications of HPV-associated cancer. We found that while TORS has some clear advantages and strengths and almost certainly a permanent place in future treatment, further research is necessary to correctly evaluate the role it will play in the complete management of oropharyngeal cancer.

Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, Møller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from http://www.daltonprogram.org for a number of UNIX platforms.

Using the coupled cluster Lagrangian technique, we have determined perturbative corrections to the coupled cluster singles and doubles (CCSD) energy that converge towards the coupled cluster singles, doubles, and triples (CCSDT) and coupled cluster singles, doubles, triples, and quadruples (CCSDTQ) energies, considering the CCSD state as the unperturbed reference state and the fluctuation potential as the perturbation. Since the Lagrangian technique is utilized, the energy corrections satisfy Wigner's 2n + 1 rule for the cluster amplitudes and the 2n + 2 rule for the Lagrange multipliers. The energy corrections define the CCSD perturbation series, CCSD(T-n) and CCSD(TQ-n), which are term-wise size extensive to any order in the perturbation. A detailed comparison of the CCSD(TQ-n) series and the CC(2)PT(n) series of Hirata et al. [J. Chem. Phys. 114, 3919 (2001)] has been performed, revealing some deficiencies of the latter related to the target energy of the series and its lack of size extensivity.

Hyposmia is often undiagnosed despite the known negative effect on taste, appetite and life quality. However, a new focus on the first cranial nerve has emerged as a consequence of a discovered connection between neurodegenerative disorders and hyposmia. In Parkinson's disease and Alzheimer's disease hyposmia is not only one of the earliest clinical presentations, the degree of hyposmia also correlates with the later progression of these two conditions. Hyposmia should not be ignored nor accepted; instead it should be integrated in any neurological examination, especially in elderly patients.

An analysis of Dunlap's robust fitting approach reveals that the resulting two-electron integral matrix is not manifestly positive semidefinite when local fitting domains or non-Coulomb fitting metrics are used. We present a highly local approximate method for evaluating four-center two-electron integrals based on the resolution-of-the-identity (RI) approximation and apply it to the construction of the Coulomb and exchange contributions to the Fock matrix. In this pair-atomic resolution-of-the-identity (PARI) approach, atomic-orbital (AO) products are expanded in auxiliary functions centered on the two atoms associated with each product. Numerical tests indicate that in 1% or less of all Hartree-Fock and Kohn-Sham calculations, the indefinite integral matrix causes nonconvergence in the self-consistent-field iterations. In these cases, the two-electron contribution to the total energy becomes negative, meaning that the electronic interaction is effectively attractive, and the total energy is dramatically lower than that obtained with exact integrals. In the vast majority of our test cases, however, the indefiniteness does not interfere with convergence. The total energy accuracy is comparable to that of the standard Coulomb-metric RI method. The speed-up compared with conventional algorithms is similar to the RI method for Coulomb contributions; exchange contributions are accelerated by a factor of up to eight with a triple-zeta quality basis set. A positive semidefinite integral matrix is recovered within PARI by introducing local auxiliary basis functions spanning the full AO product space, as may be achieved by using Cholesky-decomposition techniques. Local completion, however, slows down the algorithm to a level comparable with or below conventional calculations., (Copyright © 2013 Wiley Periodicals, Inc.)

Large-scale on-the-fly Born-Oppenheimer molecular dynamics simulations using recent advances in linear scaling electronic structure theory and trajectory integration techniques have been performed for protonated water clusters around the magic number (H(2)O)(n)H(+) , for n = 20 and 21. Besides demonstrating the feasibility and efficiency of the computational approach, the calculations reveal interesting dynamical details. Elimination of water molecules is found to be fast for both cluster sizes but rather insensitive to the initial geometry. The water molecules released acquire velocities compatible with thermal energies. The proton solvation shell changes between the well-known Eigen and Zundel motifs and is characterized by specific low-frequency vibrational modes, which have been quantified. The proton transfer mechanism largely resembles that of bulk water but one interesting variation was observed., (Copyright © 2012 Wiley Periodicals, Inc.)

Divide-Expand-Consolidate (DEC) is a local correlation method where the inherent locality of the electron correlation problem is used to express the correlated calculation on a large molecular system in terms of small independent fragment calculations employing small subsets of local HF orbitals. A crucial feature of the DEC scheme is that the sizes of the local orbital spaces are determined in a black box manner during the calculation. In this way it is ensured that the correlation energy has been determined to a predefined precision compared to a conventional calculation. In the present work we apply the DEC scheme to calculate the correlation energy as well as the electron density matrix for the insulin molecule using second order Møller-Plesset (MP2) theory. This is the first DEC calculation on a molecular system which is too large to be treated using a conventional MP2 implementation. The fragmentation errors for the insulin DEC calculation are carefully analyzed using internal consistency checks. It is demonstrated that size-intensive properties are determined to the same precision for small and large molecules. For example, the percentage of correlation energy recovered and the error per electron in the correlated density matrix depend only on the predefined precision and not on the molecular size.

We demonstrate that the divide-expand-consolidate (DEC) scheme--which has previously been used to determine the second-order Møller-Plesset (MP2) correlation energy--can be applied to evaluate the MP2 molecular gradient in a linear-scaling and embarrassingly parallel manner using a set of local Hartree-Fock orbitals. All manipulations of four-index quantities (describing electron correlation effects) are carried out using small local orbital fragment spaces, whereas two-index quantities are treated for the full molecular system. The sizes of the orbital fragment spaces are determined in a black-box manner to ensure that the error in the DEC-MP2 correlation energy compared to a standard MP2 calculation is proportional to a single input threshold denoted the fragment optimization threshold (FOT). The FOT also implicitly controls the error in the DEC-MP2 molecular gradient as substantiated by a theoretical analysis and numerical results. The development of the DEC-MP2 molecular gradient is the initial step towards calculating higher order energy derivatives for large molecular systems using the DEC framework, both at the MP2 level of theory and for more accurate coupled-cluster methods.

Though some data indicate an association between gastroesophageal reflux disease (GERD) and upper airway inflammatory disease, a connection between GERD and chronic rhinosinusitis (CRS) is a matter of controversy in today's medicine. The aim of this study was to examine whether patients with GERD have a different nose- and sinus-related quality of life compared to a control group. A total of 77 patients with GERD diagnosed by gastroscopy were evaluated according to their nose- and sinus-related quality of life. It was scored using the Sino-Nasal Outcome Test-20 (SNOT-20). Total SNOT-20 score was compared with a control group consisting of 480 teachers. The average total SNOT-20 score in patients with GERD was 22.1, and in the control group 9.4 (p < 0.005). In the patient group, the median was 17.0 and standard deviation 18.4 corresponding to 5.0 and 11.5 in the controls. The 95% confidence interval in the patient group was (18.0, 26.3), and (8.3, 10.4) in the control group. Patients with GERD have a reduced nose- and sinus-related quality of life compared to a control group based on the fact that they have a significantly higher total SNOT-20 score than the controls. Accordingly, this study indicates that there is a causal relationship between GERD and CRS.

We apply damped response theory to the phenomenon of magnetic circular dichroism (MCD), and we investigate how the numerical instability associated with the simulation of the MCD spectrum from individually calculated A and B terms for close lying states can be remedied by the use of damped response theory. We also present a method for calculating the Faraday A term, formulated as a double residue of the quadratic response function.

We present a thorough locality analysis of the divide-expand-consolidate amplitude equations for second-order Møller-Plesset perturbation theory and the coupled cluster singles doubles (CCSD) model, which demonstrates that the amplitude equations are local when expressed in terms of a set of local occupied and local unoccupied Hartree-Fock orbitals, such as the least-change molecular basis. The locality analysis thus shows that a CC calculation on a large molecular system may be carried out in terms of CC calculations on small orbital fragments of the total molecular system, where the sizes of the orbital fragment spaces are determined in a black box manner to ensure that the CC correlation energy is calculated to a preset energy threshold. A practical implementation of the locality analysis is described, and numerical results are presented, which demonstrate that both the orbital fragment sizes and the relative energy error compared to a full CC calculation are independent of the molecular system size.

Damped response theory is applied to the calculation of two-photon absorption (TPA) spectra, which are determined directly, at each frequency, from a modified damped cubic response function. The TPA spectrum may therefore be evaluated for selected frequency ranges, making the damped TPA approach attractive for calculations on large molecules with a high density of states, where the calculation of TPA using standard theory is more problematic. Damped response theory can also be applied to the case of intermediate state resonances, where the standard TPA expression is divergent. Both exact damped response theory and its application within density functional theory are discussed. The latter is implemented using an atomic-orbital based density matrix formulation, which makes the approach especially suitable for studies on large systems. A test preliminary study is presented for the TPA spectrum of R-(+)-1,1'-bi(2-naphtol)., (© 2011 American Institute of Physics)

Habitual smoking represents a chronic insult to the airway. However, the effects of smoking on upper airway health remains poorly described. Our objective was to examine the relationship between cigarette smoking and self-assessed upper airway health and evaluate dose-response relationships between exposure and complaints in a sample of 2,523 patients. Eligible subjects were adults referred to ENT specialist for evaluation of chronic nasal or sleep-related complaints. Thirteen specific symptoms and conditions, mainly related to the upper airway, were graded based on visual analog scales (VAS). Smokers, representing 33% of the sample, were more likely to report severe upper airway complaints compared to non-smokers (odds ratio 1.31-2.08) and exhibited significantly higher visual analog scale scores than non-smokers for 9 out of 13 outcome variables (p < 0.001-0.007). Further, significant associations were found between cigarette consumption and severity of complaints (p < 0.001-0.01), heavy smokers generally being more likely to exhibit high VAS scores than light smokers. In several cases smoking status and self-reported asthma/allergy had similar impact on subjective outcomes. Cigarette smoking was clearly associated with impaired upper airway health and seemed to be an important determinant in subjects seeking medical attention due to chronic nasal or sleep-related complaints. Both threshold and dose-response like relationships were evident between cigarette consumption and the outcome measures.

In mouse, knock-out of the Zfr gene encoding the zinc finger RNA-binding protein (ZFR) is associated with early lethality during gastrulation, suggesting that a pool of maternally contributed Zfr mRNA might compensate to allow development. ZFR is an ancient and highly conserved chromosome-associated protein from nematodes to mammals. We characterized expression of the Zfr transcript during early development in Mus musculus, Danio rerio, and Caenorhabditis elegans by quantitative real-time polymerase chain reaction. Mouse Zfr mRNA was detected in all stages tested during mouse preimplantation, with higher levels at the 1-cell stage that includes the maternal contribution of Zfr mRNA. In D. rerio, Zfr mRNA expression was highest in unfertilized eggs and declines throughout development. In C. elegans, Zfr mRNA expression was barely detectable in the fertilized egg and the L1 stage, but increased in the adult organism. Microinjections of green fluorescent protein (GFP)-tagged versions of in vitro-transcribed mouse and C. elegans Zfr mRNAs into early mouse embryos allowed analysis of the intracellular localization of the protein. Mouse ZFR-GFP was localized in the nucleus in 2-cell stage embryos although absent from nucleoli. Deletion studies revealed that this nuclear localization required the C-terminal part of ZFR, as deletion of the C-terminal resulted in the localization to the nuclear membrane. Despite the lack of a conserved nuclear localization signal, the C. elegans ZFR-GFP fusion protein also displayed an intranuclear localization in the 2-cell mouse embryo.

Coupled cluster calculations can be carried out for large molecular systems via a set of calculations that use small orbital fragments of the full molecular orbital space. The error in the correlation energy of the full molecular system is controlled by the precision in the small fragment calculations. The determination of the orbital spaces for the small orbital fragments is black box in the sense that it does not depend on any user-provided molecular fragmentation, rather orbital spaces are carefully selected and extended during the calculation to give fragment energies of a specified precision. The computational method scales linearly with the size of the molecular system and is massively parallel.

Objectives/hypothesis: The effects of smoking on endonasal geometry and airflow remain largely unknown. Our study examined the relationship between smoking status and objective measures of nasal cavity dimensions, nasal congestion, and nasal airflow, using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF)., Study Design: Cross-sectional study., Methods: Included in the study were 2,523 consecutive patients referred for evaluation of chronic nasal or sleep-related complaints. Smoking history was recorded, and AR and PNIF were measured at baseline and after decongestion of the nasal mucosa. Minimal cross-sectional areas (MCA), nasal cavity volumes (NCV), and PNIF, as well as quantified reversible mucosal congestion based on nasal congestion indexes (NCI) were analyzed to reveal possible associations with smoking status. Linear and logistic regressions were applied adjusting for possible confounders., Results: Smokers exhibited lower values of MCA, NCV, and PNIF than nonsmokers, both at baseline and after decongestion. Further, smokers had a lower decongestive capacity of the nasal mucosa, reflected by lower NCI for AR measures. Cigarette consumption, expressed as either pack-years or cigarettes smoked per day, showed a similar inverse relationship with the rhinometric measures even though a linear dose-response relationship could not be established., Conclusions: We have clearly demonstrated that smokers exhibit lower MCA and NCV, achieve lower PNIF values, and have a less-compliant nasal mucosa than nonsmokers. Our results are unique, and provide evidence that smoking has adverse effects on the nasal airway, possibly due to mucosal inflammation. This might have further implications because altered nasal function could compromise the lower airways.

Objectives: The relationship between congestion of the nasal mucosa and subjective nasal obstruction remains poorly defined. Applying the novel Nasal Congestion Index (NCI), we compared subjective nasal obstruction with objective measures for reversible congestion of the nasal mucosa., Study Design: A total of 2,523 consecutive patients were included in this cross-sectional study. Eligible subjects were adults referred to the ENT department, Sørlandet Hospital, Kristiansand, Norway, for evaluation of chronic nasal or sleep-related complaints., Methods: Subjects underwent acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) at baseline and after decongestion of the nasal mucosa. Based on these registrations, an NCI was calculated for minimal cross-sectional area (MCA), nasal cavity volume (NCV), and PNIF, and employed for quantification of reversible mucosal congestion. Subjective nasal obstruction was measured by nasal obstruction visual analogue scales (NO-VAS). Statistical analyses were based on ANOVA and multiple linear and logistic regression, adjusting for age, gender, body mass index, asthma, allergy, smoking history, and type of planned intervention., Results: Crude estimates indicated that the NCIs were significantly higher in subjects with severe complaints of nasal obstruction compared with subjects with lesser symptoms (P < .001). These associations were confirmed by linear and logistic regression analyses. NCI for MCA, NCV, and PNIF showed highly significant associations with subjective nasal obstruction (P < .001)., Conclusions: We have clearly demonstrated an association between subjective nasal obstruction and reversible congestion of the nasal mucosa by employing the NCI. The measure has proven to be useful for evaluating patients with complaints of nasal obstruction.

We present a quasienergy-based formulation of damped response theory where a common effective lifetime parameter has been introduced for all excited states in terms of complex excitation energies. The introduction of finite excited state lifetimes leads to a set of (complex) damped response equations, which have the same form to all orders in the perturbation. An algorithm is presented for solving the damped response equations in Hartree-Fock theory and Kohn-Sham density functional theory. The use of the quasienergy formulation allows us to obtain directly the computationally simplest expressions for damped response functions by applying a set of response parameter elimination rules, which minimize the total number of damped response equations to be solved. In standard response theory broadened absorption spectra are obtained by ad hoc superimposing lineshape functions onto the absorption stick spectra, whereas an empirical lineshape function common to all excitations is an integrated part of damped response theory. By superimposing the lineshape functions inherent in damped response theory onto the stick spectra of standard response theory, we show that the absorption spectra obtained in standard and damped response theory calculations are identical. We demonstrate that damped response theory may be applied to obtain absorption spectra in all frequency ranges, also those that are not readily addressed using standard response theory. This makes damped response theory an effective tool, e.g., for determining absorption spectra for large molecules, where the density of the excited states may be very high, and where standard response theory therefore is not applicable in practice. A thorough comparison is given between our formulation of damped response theory and the formulation by Norman et al. [J. Chem. Phys. 123, 194103 (2005)].

Density fitting is an important method for speeding up quantum-chemical calculations. Linear-scaling developments in Hartree-Fock and density-functional theories have highlighted the need for linear-scaling density-fitting schemes. In this paper, we present a robust variational density-fitting scheme that allows for solving the fitting equations in local metrics instead of the traditional Coulomb metric, as required for linear scaling. Results of fitting four-center two-electron integrals in the overlap and the attenuated Gaussian damped Coulomb metric are presented, and we conclude that density fitting can be performed in local metrics at little loss of chemical accuracy. We further propose to use this theory in linear-scaling density-fitting developments.

We present a second-quantization based atomic-orbital method for the computation of time-dependent response functions within Hartree-Fock and Kohn-Sham density-functional theories. The method is suited for linear scaling. Illustrative results are presented for excitation energies, one- and two-photon transition moments, polarizabilities, and hyperpolarizabilities for hexagonal BN sheets with up to 180 atoms.

A computational study of the Faraday B term of magnetic circular dichroism at the coupled cluster singles and doubles level is presented for pyridine, pyrazine, pyrimidine, and phosphabenzene. Gauge-origin independence is obtained by expressing the B term as a total derivative of the one-photon dipole transition strength and using London orbitals. The high quality of the coupled cluster singles and doubles (CCSD) B terms makes these useful for the assignment of experimental spectra. Previous assignments of the experimental spectra based on the qualitative perimeter model are confirmed by the CCSD results for the three azines, while a reassignment is proposed for phosphabenzene. For non-overlapping bands, the B terms calculated at the equilibrium geometries are in good agreement with the experimental values. For overlapping bands, large deviations occur. Attributing a line width to the calculated equilibrium B terms leads to a large cancellation of positive and negative contributions. This cancellation may result in a large displacement of the band center maximum, leading to a large uncertainty in the assignments of "vertical experimental excitation energies" (pyridine). Bands may also completely vanish due to such cancellation (phosphabenzene). Explicit consideration of the cancellation yields simulated theoretical spectra that are in good agreement with experiment once the theoretical spectra are parallel displaced. A major contribution for this parallel displacement is the shift in the excitation energies due to correlation beyond CCSD, as seen when comparing vertical CCSD and CC3 equilibrium-geometry excitation energies.