Molecular Biology at the Quantum Level: Can Modern Density Functional Theory Forge the Path?

Recent years have seen vast improvements in the ability of rigorous quantum-mechanical methods to treat systems of interest to molecular biology. In this review article, we survey common computational methods used to study such large, weakly bound systems, starting from classical simulations and reaching to quantum chemistry and density functional theory. We sketch their underlying frameworks and investigate their strengths and weaknesses when applied to potentially large biomolecules. In particular, density functional theory---a framework that can treat thousands of atoms on firm theoretical ground---can now accurately describe systems dominated by weak van der Waals interactions. This newfound ability has rekindled interest in using this tried-and-true approach to investigate biological systems of real importance. In this review, we focus on some new methods within density functional theory that allow for accurate inclusion of the weak interactions that dominate binding in biological macromolecules. Recent work utilizing these methods to study biologically-relevant systems will be highlighted, and a vision for the future of density functional theory within molecular biology will be discussed

Landscape Predictions for the Higgs Boson and Top Quark Masses

If the Standard Model is valid up to scales near the Planck mass, and if the cosmological constant and Higgs mass parameters scan on a landscape of vacua, it is well known that the observed orders of magnitude of these quantities can be understood from environmental selection for large-scale structure and atoms. If in addition the Higgs quartic coupling scans, with a probability distribution peaked at low values, environmental selection for a phase having a scale of electroweak symmetry breaking much less than the Planck scale leads to a most probable Higgs mass of 106 GeV. While fluctuations below this are negligible, the upward fluctuation is 25/p GeV, where p measures the strength of the peaking of the a priori distribution of the quartic coupling. If the top Yukawa coupling also scans, the most probable top quark mass is predicted to lie in the range (174--178) GeV, providing the standard model is valid to at least 10^{17} GeV. The downward fluctuation is 35 GeV/ \sqrt{p}, suggesting that p is sufficiently large to give a very precise Higgs mass prediction. While a high reheat temperature after inflation could raise the most probable value of the Higgs mass to 118 GeV, maintaining the successful top prediction suggests that reheating is limited to about 10^8 GeV, and that the most probable value of the Higgs mass remains at 106 GeV. If all Yukawa couplings scan, then the e,u,d and t masses are understood to be outliers having extreme values induced by the pressures of strong environmental selection, while the s, \mu, c, b, \tau Yukawa couplings span only two orders of magnitude, reflecting an a priori distribution peaked around 10^{-3}. Extensions of these ideas allow order of magnitude predictions for neutrino masses, the baryon asymmetry and important parameters of cosmological inflation.Comment: 41 pages; v4: threshold corrrections for top Yukawa are correcte

Density Perturbations and the Cosmological Constant from Inflationary Landscapes

An anthropic understanding of the cosmological constant requires that the vacuum energy at late time scans from one patch of the universe to another. If the vacuum energy during inflation also scans, the various patches of the universe acquire exponentially differing volumes. In a generic landscape with slow-roll inflation, we find that this gives a steeply varying probability distribution for the normalization of the primordial density perturbations, resulting in an exponentially small fraction of observers measuring the COBE value of 10^-5. Inflationary landscapes should avoid this "\sigma problem", and we explore features that can allow them to do that. One possibility is that, prior to slow-roll inflation, the probability distribution for vacua is extremely sharply peaked, selecting essentially a single anthropically allowed vacuum. Such a selection could occur in theories of eternal inflation. A second possibility is that the inflationary landscape has a special property: although scanning leads to patches with volumes that differ exponentially, the value of the density perturbation does not vary under this scanning. This second case is preferred over the first, partly because a flat inflaton potential can result from anthropic selection, and partly because the anthropic selection of a small cosmological constant is more successful.Comment: 23 page

Group Prenatal Care Attendance and Women's Characteristics Associated with Low Attendance: Results from Centering and Racial Disparities (CRADLE Study).

ObjectivesGroup prenatal care (GPC), an alternative to individual prenatal care (IPC), is becoming more prevalent. This study aimed to describe the attendance and reasons of low attendance among pregnant women who were randomly assigned to receive GPC or IPC and explore the maternal characteristics associated with low-attendance.MethodsThis study was a descriptive study among Medically low risk pregnant women (N = 992) who were enrolled in an ongoing prospective study. Women were randomly assigned to receive CenteringPregnany GPC (N = 498) or IPC (N = 994) in a single clinical site The attendance frequency and reason for low-attendance (i.e. ≤ 5/10 sessions in GPC or ≤ 5 visits in IPC) were described separately in GPC and IPC. Multivariable logistic regressions were performed to explore the associations between maternal characteristics and low-attendance.ResultsOn average, women in GPC attended 5.32 (3.50) sessions, with only 6.67% attending all 10 sessions. Low-attendance rate was 34.25% in GPC and 10.09% in IPC. The primary reasons for low-attendance were scheduling barriers (23.19%) and not liking GPC (16.43%) in GPC but leaving the practice (34.04%) in IPC. In multivariable analysis, lower perceived family support (P = 0.01) was positively associated with low-attendance in GPC, while smoking in early pregnancy was negatively associated low-attendance (P = 0.02) in IPC.Conclusions for practiceScheduling challenges and preference for non-group settings were the top reasons for low-attendance in GPC. Changes may need to be made to the current GPC model in order to add flexibility to accommodate women's schedules and ensure adequate participation.Trial registrationNCT02640638 Date Registered: 12/20/2015

Ab initio energetics and kinetics study of H2 and CH4 in the SI clathrate hydrate

We present ab initio results at the density functional theory level for the energetics and kinetics of H2 and CH4 in the SI clathrate hydrate. Our results complement a recent article by some of the authors [G.Román-Pérez et.al., Phys.Rev.Lett. 105, 145901 (2010)] in that we show additional results of the energy landscape of H2 and CH 4 in the various cages of the host material, as well as further results for energy barriers for all possible diffusion paths of H2 and CH4 through the water framework. We also report structural data of the low-pressure phase SI and the higher-pressure phases SII and S

Simultaneous Solutions of the Strong CP and Mu Problems

The \mu parameter of the supersymmetric standard model is replaced by \lambda S, where S is a singlet chiral superfield, introducing a Peccei--Quinn symmetry into the theory. Dynamics at the electroweak scale naturally solves both the strong CP and \mu problems as long as \lambda is of order \sqrt{M_Z /M_pl} or smaller, and yet this theory has the same number of relevant parameters as the supersymmetric standard model. The theory will be tested at colliders: the \mu parameter is predicted and there are long-lived superpartners that decay to gravitinos or axinos at separated vertices. To avoid too much saxion cold dark matter, a large amount of entropy must be produced after the electroweak phase transition. If this is accomplished by decays of a massive particle, the reheat temperature should be no more than a GeV, strongly constraining baryogenesis. Cold dark matter may be composed of both axions, probed by direct detection, and saxions, probed by a soft X-ray background arising from decays to \gamma \gamma. There are two known possibilities for avoiding problematic axion domain walls: the introduction of new colored fermions or the assumption that the Peccei--Quinn symmetry was already broken during inflation. In the first case, in our theory the colored particles are expected to be at the weak scale, while in the second case it implies a good chance of discovering isocurvature perturbations in the CMB radiation and a relatively low Hubble parameter during inflation.Comment: 14 pages; v2. references added and typos correcte

Ecosystem-scale measurements of biomass water using cosmic ray neutrons

Accurate estimates of biomass are imperative for understanding the global carbon cycle. However, measurements of biomass and water in the biomass are difficult to obtain at a scale consistent with measurements of mass and energy transfer, ~1 km, leading to substantial uncertainty in dynamic global vegetation models. Here we use a novel cosmic ray neutron method to estimate a stoichiometric predictor of ecosystem-scale biomass and biomass water equivalent over tens of hectares. We present two experimental studies, one in a ponderosa pine forest and the other in a maize field, where neutron-derived estimates of biomass water equivalent are compared and found consistent with direct observations. Given the new hectometer scale of nondestructive observation and potential for continuous measurements, we anticipate this technique to be useful to many scientific disciplines

Genome-Wide Association Studies for Yield-Related Traits in Soft Red Winter Wheat Grown in Virginia

Grain yield is a trait of paramount importance in the breeding of all cereals. In wheat (Triticum aestivum L.), yield has steadily increased since the Green Revolution, though the current rate of increase is not forecasted to keep pace with demand due to growing world population and increasing affluence. While several genome-wide association studies (GWAS) on yield and related component traits have been performed in wheat, the previous lack of a reference genome has made comparisons between studies difficult. In this study, a GWAS for yield and yield-related traits was carried out on a population of 322 soft red winter wheat lines across a total of four rain-fed environments in the state of Virginia using single-nucleotide polymorphism (SNP) marker data generated by a genotyping-by-sequencing (GBS) protocol. Two separate mixed linear models were used to identify significant marker-trait associations (MTAs). The first was a single-locus model utilizing a leave-one-chromosome-out approach to estimating kinship. The second was a sub-setting kinship estimation multi-locus method (FarmCPU). The single-locus model identified nine significant MTAs for various yield-related traits, while the FarmCPU model identified 74 significant MTAs. The availability of the wheat reference genome allowed for the description of MTAs in terms of both genetic and physical positions, and enabled more extensive post-GWAS characterization of significant MTAs. The results indicate a number of promising candidate genes contributing to grain yield, including an ortholog of the rice aberrant panicle organization (APO1) protein and a gibberellin oxidase protein (GA2ox-A1) affecting the trait grains per square meter, an ortholog of the Arabidopsis thaliana mother of flowering time and terminal flowering 1 (MFT) gene affecting the trait seeds per square meter, and a B2 heat stress response protein affecting the trait seeds per head

Representing Global Reactive Potential Energy Surfaces Using Gaussian Processes

This article presents a detailed study on constructing potential energy surfaces using a machine learning method, namely, Gaussian process regression