Structure and dynamics of liquid water from ab initio simulations: adding Minnesota density functionals to Jacob's ladder.

The accurate representation of the structural and dynamical properties of water is essential for simulating the unique behavior of this ubiquitous solvent. Here we assess the current status of describing liquid water using ab initio molecular dynamics, with a special focus on the performance of all the later generation Minnesota functionals. Findings are contextualized within the current knowledge on DFT for describing bulk water under ambient conditions and compared to experimental data. We find that, contrary to the prevalent idea that local and semilocal functionals overstructure water and underestimate dynamical properties, M06-L, revM06-L, and M11-L understructure water, while MN12-L and MN15-L overdistance water molecules due to weak cohesive effects. This can be attributed to a weakening of the hydrogen bond network, which leads to dynamical fingerprints that are over fast. While most of the hybrid Minnesota functionals (M06, M08-HX, M08-SO, M11, MN12-SX, and MN15) also yield understructured water, their dynamical properties generally improve over their semilocal counterparts. It emerges that exact exchange is a crucial component for accurately describing hydrogen bonds, which ultimately leads to corrections in both the dynamical and structural properties. However, an excessive amount of exact exchange strengthens hydrogen bonds and causes overstructuring and slow dynamics (M06-HF). As a compromise, M06-2X is the best performing Minnesota functional for water, and its D3 corrected variant shows very good structural agreement. From previous studies considering nuclear quantum effects (NQEs), the hybrid revPBE0-D3, and the rung-5 RPA (RPA@PBE) have been identified as the only two approximations that closely agree with experiments. Our results suggest that the M06-2X(-D3) functionals have the potential to further improve the reproduction of experimental properties when incorporating NQEs through path integral approaches. This work provides further proof that accurate modeling of water interactions requires the inclusion of both exact exchange and balanced (non-local) correlation, highlighting the need for higher rungs on Jacob's ladder to achieve predictive simulations of complex biological systems in aqueous environments.

Plane Waves Versus Correlation-Consistent Basis Sets: A Comparison of MP2 Non-Covalent Interaction Energies in the Complete Basis Set Limit.

Second-order Møller-Plesset perturbation theory (MP2) is the most expedient wave function-based method for considering electron correlation in quantum chemical calculations and, as such, provides a cost-effective framework to assess the effects of basis sets on correlation energies, for which the complete basis set (CBS) limit can commonly only be obtained via extrapolation techniques. Software packages providing MP2 energies are commonly based on atom-centered bases with innate issues related to possible basis set superposition errors (BSSE), especially in the case of weakly bonded systems. Here, we present noncovalent interaction energies in the CBS limit, free of BSSE, for 20 dimer systems of the S22 data set obtained via a highly parallelized MP2 implementation in the plane-wave pseudopotential molecular dynamics package CPMD. The specificities related to plane waves for accurate and efficient calculations of gas-phase energies are discussed, and results are compared to the localized (aug-)cc-pV[D,T,Q,5]Z correlation-consistent bases as well as their extrapolated CBS estimates. We find that the BSSE-corrected aug-cc-pV5Z basis can provide MP2 energies highly consistent with the CBS plane wave values with a minimum mean absolute deviation of ∼0.05 kcal/mol without the application of any extrapolation scheme. In addition, we tested the performance of 13 different extrapolation schemes and found that the X-3 expression applied to the (aug-)cc-pVXZ bases provides the smallest deviations against CBS plane wave values if the extrapolation sequence is composed of points D and T, while (X+12)-4 performs slightly better for TQ and Q5 extrapolations. Also, we propose A(X-12)-3+B(X+12)-4 as a reliable alternative to extrapolate total energies from the DTQ, TQ5, or DTQ5 data points. In spite of the general good agreement between the values obtained from the two types of basis sets, it is noticed that differences between plane waves and (aug-)cc-pVXZ basis sets, extrapolated or not, tend to increase with the number of electrons, thus raising the question of whether these discrepancies could indeed limit the attainable accuracy for localized bases in the limit of large systems.

Efficient Treatment of Correlation Energies at the Basis-Set Limit by Monte Carlo Summation of Continuum States.

The calculation of electron correlation is vital for the description of atomistic phenomena in physics, chemistry, and biology. However, accurate wavefunction-based methods exhibit steep scaling and often sluggish convergence with respect to the basis set at hand. Because of their delocalization and ease of extrapolation to the basis-set limit, plane waves would be ideally suited for the calculation of basis-set limit correlation energies. However, the routine use of correlated wavefunction approaches in a plane-wave basis set is hampered by prohibitive scaling due to a large number of virtual continuum states and has not been feasible for all but the smallest systems, even if substantial computational resources are available and methods with comparably beneficial scaling, such as the Møller-Plesset perturbation theory to second order (MP2), are used. Here, we introduce a stochastic sampling of the MP2 integrand based on Monte Carlo summation over continuum orbitals, which allows for speedups of up to a factor of 1000. Given a fixed number of sampling points, the resulting algorithm is dominated by a flat scaling of ∼O(N2). Absolute correlation energies are accurate to <0.1 kcal/mol with respect to conventional calculations for several hundreds of electrons. This allows for the calculation of unbiased basis-set limit correlation energies for systems containing hundreds of electrons with unprecedented efficiency gains based on a straightforward treatment of continuum contributions.

Extreme Scalability of DFT-Based QM/MM MD Simulations Using MiMiC.

We present a highly scalable DFT-based QM/MM implementation developed within MiMiC, a recently introduced multiscale modeling framework that uses a loose-coupling strategy in conjunction with a multiple-program multiple-data (MPMD) approach. The computation of electrostatic QM/MM interactions is parallelized exploiting both distributed- and shared-memory strategies. Here, we use the efficient CPMD and GROMACS programs as QM and MM engines, respectively. The scalability is demonstrated through large-scale benchmark simulations of realistic biomolecular systems employing non-hybrid and hybrid GGA exchange-correlation functionals. We show that the loose-coupling strategy adopted in MiMiC, with its inherent high flexibility, does not carry any significant computational overhead compared to a tight-coupling scheme. Furthermore, we demonstrate that the adopted parallelization strategy enables scaling up to 13,000 CPU cores with efficiency above 70%, thus making DFT-based QM/MM MD simulations using hybrid functionals at the nanosecond scale accessible.

MiMiC: A Novel Framework for Multiscale Modeling in Computational Chemistry.

We present a flexible and efficient framework for multiscale modeling in computational chemistry (MiMiC). It is based on a multiple-program multiple-data (MPMD) model with loosely coupled programs. Fast data exchange between programs is achieved through the use of MPI intercommunicators. This allows exploiting the existing parallelization strategies used by the coupled programs while maintaining a high degree of flexibility. MiMiC has been used in a new electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) implementation coupling the highly efficient CPMD and GROMACS programs, but it can also be extended to use other programs. The framework can also be utilized to extend the partitioning of the system into several domains that can be treated using different models, such as models based on wave function or density functional theory as well as coarse-graining and continuum models. The new QM/MM implementation treats long-range electrostatic QM-MM interactions through the multipoles of the QM subsystem which substantially reduces the computational cost without loss of accuracy compared to an exact treatment. This enables QM/MM molecular dynamics (MD) simulations of very large systems.

Shedding Light on the Basis Set Dependence of the Minnesota Functionals: Differences Between Plane Waves, Slater Functions, and Gaussians.

The Minnesota family of exchange-correlation (xc) functionals are among the most popular, accurate, and abundantly used functionals available to date. However, their use in plane-wave based first-principles MD has been limited by their sparse availability. Here, we present an implementation of the M05, M06, and M11 families of xc functionals within a plane wave/pseudopotential framework allowing for a comprehensive analysis of their basis set dependence. While it has been reported that in Gaussian bases some members of the Minnesota family only converge slowly to the basis set limit, (1) we show that converged energies can be conveniently obtained from plane waves if sufficiently dense integration meshes are used. Based on the HC7/11 database, we assess the influence of basis set type on the calculation of reaction enthalpies and show that complete basis set values obtained in plane waves may occasionally differ notably from their atom-centered counterparts. We provide an analysis of the origin of these differences and discuss implications on practical usage.

Radical chain repair: The hydroalkylation of polysubstituted unactivated alkenes.

The concept of repair is widely used by nature to heal molecules such as proteins, lipids, sugars, and DNA that are damaged by hydrogen atom abstraction resulting from oxidative stress. We show that this strategy, rather undocumented in the field of synthetic organic chemistry, can be used in a radical chain reaction to enable notoriously intractable transformations. By overcoming the radical chain inhibitor properties of substituted alkenes, the radical-mediated hydroalkylation of mono-, di-, tri-, and even tetrasubstituted unactivated olefins could be performed under mild conditions. With a remarkable functional group tolerance, this reaction provides a general coupling method for the derivatization of olefin-containing natural products.

Exploiting Coordinate Scaling Relations To Accelerate Exact Exchange Calculations.

Exact exchange is an important constituent in many state-of-the-art approximations to the exchange-correlation (xc) functional of Kohn-Sham DFT. However, its evaluation can be computationally intensive, which can be particularly prohibitive in DFT-based molecular dynamics (MD) simulations, often restricted to semilocal functionals. We derive a scheme based on the formal coordinate scaling properties of the exact xc functional that allows for a substantial reduction of the cost of the evaluation of both the exact exchange energy and potential. We show that within a plane-wave/pseudopotential framework, excellent accuracy is retained, while speed ups from up to ∼6 can be reached. The coordinate scaling thus accelerates hybrid-functional-based first-principles MD simulations by nearly one order of magnitude.

Plane-Wave Implementation and Performance of à-la-Carte Coulomb-Attenuated Exchange-Correlation Functionals for Predicting Optical Excitation Energies in Some Notorious Cases.

Linear-response time-dependent density functional theory (LR-TD-DFT) has become a valuable tool in the calculation of excited states of molecules of various sizes. However, standard generalized-gradient approximation and hybrid exchange-correlation (xc) functionals often fail to correctly predict charge-transfer (CT) excitations with low orbital overlap, thus limiting the scope of the method. The Coulomb-attenuation method (CAM) in the form of the CAM-B3LYP functional has been shown to reliably remedy this problem in many CT systems, making accurate predictions possible. However, in spite of a rather consistent performance across different orbital overlap regimes, some pitfalls remain. Here, we present a fully flexible and adaptable implementation of the CAM for Γ-point calculations within the plane-wave pseudopotential molecular dynamics package CPMD and explore how customized xc functionals can improve the optical spectra of some notorious cases. We find that results obtained using plane waves agree well with those from all-electron calculations employing atom-centered bases, and that it is possible to construct a new Coulomb-attenuated xc functional based on simple considerations. We show that such a functional is able to outperform CAM-B3LYP in some cases, while retaining similar accuracy in systems where CAM-B3LYP performs well.

Nonadiabatic effects in electronic and nuclear dynamics.

Due to their very nature, ultrafast phenomena are often accompanied by the occurrence of nonadiabatic effects. From a theoretical perspective, the treatment of nonadiabatic processes makes it necessary to go beyond the (quasi) static picture provided by the time-independent Schrödinger equation within the Born-Oppenheimer approximation and to find ways to tackle instead the full time-dependent electronic and nuclear quantum problem. In this review, we give an overview of different nonadiabatic processes that manifest themselves in electronic and nuclear dynamics ranging from the nonadiabatic phenomena taking place during tunnel ionization of atoms in strong laser fields to the radiationless relaxation through conical intersections and the nonadiabatic coupling of vibrational modes and discuss the computational approaches that have been developed to describe such phenomena. These methods range from the full solution of the combined nuclear-electronic quantum problem to a hierarchy of semiclassical approaches and even purely classical frameworks. The power of these simulation tools is illustrated by representative applications and the direct confrontation with experimental measurements performed in the National Centre of Competence for Molecular Ultrafast Science and Technology.

Treatment of Acetabular Fractures in Adolescents.

Although the treatment of acetabular fractures in adults has evolved substantially, treatment of these injuries in adolescents remains primarily nonoperative. We performed a retrospective review to evaluate outcomes of treatment of adolescent acetabular fractures. We identified 38 adolescent acetabular fractures (patient ages, 11-18 years), all treated by an experienced trauma surgeon. Open reduction and internal fixation (ORIF) was performed in 37 cases, and 1 case was treated nonoperatively. Mean follow-up was 38.2 months. All fractures healed. Reduction was anatomical in 30 cases, imperfect in 7. One patient had surgical secondary congruence, 1 had preoperative deep vein thrombosis, 1 developed a deep infection, and 2 had femoral head avascular necrosis and developed posttraumatic arthritis (both had hip dislocations). Of the 38 patients, 34 returned to full activity. At latest follow-up, 29 had no pain, and 6 had mild intermittent pain not limiting activity. ORIF was found to be safe and to result in predictable union. We therefore advocate a more aggressive strategy. Given our low complication rate, we recommend nonoperative management only for stable, minimally displaced fractures (<1 mm). Unstable fractures, fractures with any hip subluxation, and fractures displaced more than 1 mm should be managed with ORIF. As reported in adults, articular injury often is associated with secondary degenerative arthritis. This association is expected in adolescents as well. Given adolescents' life expectancy subsequent to injury and surgery, any late posttraumatic arthritis will have a significant impact on quality of life over the long term, with increased duration compared with adults.

Human infrared vision is triggered by two-photon chromophore isomerization.

Vision relies on photoactivation of visual pigments in rod and cone photoreceptor cells of the retina. The human eye structure and the absorption spectra of pigments limit our visual perception of light. Our visual perception is most responsive to stimulating light in the 400- to 720-nm (visible) range. First, we demonstrate by psychophysical experiments that humans can perceive infrared laser emission as visible light. Moreover, we show that mammalian photoreceptors can be directly activated by near infrared light with a sensitivity that paradoxically increases at wavelengths above 900 nm, and display quadratic dependence on laser power, indicating a nonlinear optical process. Biochemical experiments with rhodopsin, cone visual pigments, and a chromophore model compound 11-cis-retinyl-propylamine Schiff base demonstrate the direct isomerization of visual chromophore by a two-photon chromophore isomerization. Indeed, quantum mechanics modeling indicates the feasibility of this mechanism. Together, these findings clearly show that human visual perception of near infrared light occurs by two-photon isomerization of visual pigments.

A quinoxaline-fused tetrathiafulvalene-based sensitizer for efficient dye-sensitized solar cells.

A new quinoxaline-fused tetrathiafulvalene-based sensitizer has been prepared and characterized. The resulting power conversion efficiency of 6.47% represents the best performance to date for tetrathiafulvalene-sensitized solar cells.

The development and nature of femoral head cam lesions following acetabular fractures.

The aim of acetabular fracture fixation is to restore joint congruity with restoration of the articular surface. Poor outcomes are seen where this has not been achieved. Letournel reported a collarette osteophyte seen postoperatively in a proportion of patients, which he suggested was an early precursor to the development of osteoarthritis. This is a retrospective study of patients treated at a tertiary referral unit who developed this lesion. The triangular index was measured in 48 of these patients and then correlated with their clinical findings, Oxford Hip Score and the presence of osteoarthritis. Length of follow-up, fracture classification, and joint congruency were also recorded. Results showed a statistically significant relationship between cam lesion size and the development of osteoarthritis (P = 0.008), cam lesion size and length of follow-up (P = 0.01), and between groin pain and postoperative joint congruency (LR = 0.035). These findings suggest that the appearance of a cam lesion is a poor long-term prognostic marker for the development of osteoarthritis in patients with an acetabular fracture.

The reconstruction of periprosthetic pelvic discontinuity.

The surgical techniques and outcomes of acetabular reconstruction for periprosthetic pelvic discontinuity cases are reported. The mean time to surgery for 9 patients with acute pelvic discontinuity was 16.3 days, with 8 patients (88%) having posterior column plating and a porous metal acetabular cup. No cases required revision surgery, with a mean follow-up of 34 months (range, 24-67 months). Of the 62 chronic pelvic discontinuity cases, 20 had an ilioischial cage, with a revision rate of 29%. There were 42 cup-cage reconstructions with an 8-year survivorship of 86.3%, with a mean follow-up of 35 months (range, 24-93 months). Stable reconstruction of chronic pelvic discontinuity was achievable by distraction using a cup-cage acetabular reconstruction; however, satisfactory stability of acute pelvic discontinuity was achieved with compression of the posterior column using screw augmentation of the acetabular shell supplemented by posterior column plating.

Thrombo-prophylaxis in pelvic and acetabular trauma patients: a UK consensus?

AIMS: The incidence of deep vein thrombosis, non-fatal pulmonary embolism and fatal pulmonary embolism may be as high as 61%, 10% and 2%, respectively, in patients with pelvic and acetabular injuries. A survey of the pelvic and acetabular units across the United Kingdom was performed to ascertain the thrombo-prophylaxis policy for these patients. In particular, questions were asked about different regimes on post-operative patients, conservatively managed patients and those simply discussed over the telephone. We enquired about their known rates of DVT and PE and their methods of data collection. METHODS: Postal questionnaires were sent to 22 pelvic and acetabular trauma centres around the United Kingdom. RESULTS: Replies from 18 units were received in which a total of 837 operations are performed per year. Forty-five percent of pelvic and acetabular units do not routinely prescribe chemical prophylaxis for post-operative patients and 56% do not prescribe prophylaxis for conservatively managed patients. The policy of the remaining units showed no consistency in duration or agent. Fifty-three percent of units use a database to collect information related to the numbers of patients operated up on. Forty-seven percent have no defined method for collecting DVT and PE numbers. For this reason, reported rates of proximal DVT, non-fatal PE and fatal PE were below that expected at 2.5%, 0.8% and 0.1%, respectively. CONCLUSIONS: Despite high rates of thrombo-embolic complications in patients with pelvic and acetabular injuries there is no UK consensus on prescribing prophylaxis.

Perineal hygiene in patients with pelvic fractures.

At the tertiary referral Orthopaedic Unit of St. Georges Hospital, it was noted that there was an unacceptably high number of soiled perinea in patients transferred from Base Hospitals. This not only exposed the patients to increased infection [Jepsen O. The effectiveness of preoperative skin preparations: an integrated review of the literature. AORN J 1993;58:477-82; and Nix D, Ermer-Seltun J. A review of perineal skin care protocols and skin barrier product use. Ostomy Wound Manage 2004;50:59-67] but was also undignified and unacceptable for them. We decided to audit the problem with a view to finding out why this was happening and to improve the situation. A 2-year study was carried out over three distinct phases (phase 1: February-June 2004, phase 2: July-November 2004, phase 3: February-November 2005). Observations of soiling were recorded in a questionnaire by the surgeon prior to surgery. Key system and clinical guidelines were implemented during the second phase, and the audit process was repeated. The percentage of clean perinea in phase 1 was 32%, phase 2 68% and phase 3 99.5% indicating a clear improvement in the overall system.

Avulsion injuries of the hamstring origin - a series of 12 patients and management algorithm.

INTRODUCTION: Injuries to the origin of the hamstring muscles usually occur in athletes and can result in an avulsion fracture of the ischium, an avulsion of the ischial apophysis, or a pure avulsion of the hamstring tendons themselves, depending on the patient's age. These are rare injuries in the general population and are often initially misdiagnosed as a simple 'hamstring pull', leading to the development of chronic pain and disability. PATIENTS AND METHODS: We present a retrospective case series of the 12 patients with such injuries who presented or were referred consecutively to the senior author between 1997 and 2006. RESULTS: There was a significant delay (5 months to 12 years) in the diagnosis of the injury in 8 of the 12 patients. Five of these 8 patients required more extensive surgery than would otherwise have been required as a result of this delay, but all recovered well. The sporting career of one of the remaining three patients had already been brought to an end by her injury and the subsequent disability, and she elected not to have surgery. Of the four patients who were diagnosed acutely, three required surgery, and all four had an excellent result. CONCLUSIONS: Injuries to the hamstring origin are rare and are often initially misdiagnosed as a simple 'hamstring pull', leading to the development of chronic pain and disability. Displaced injuries of the ischial apophysis and pure tendon avulsions are probably best treated surgically in the acute setting. As a result of our experience with these patients, we have produced a management algorithm.