Normal mode analysis of macromolecular systems with the mobile block Hessian method

Until recently, normal mode analysis (NMA) was limited to small proteins, not only because the required energy minimization is a computationally exhausting task, but also because NMA requires the expensive diagonalization of a 3N(a) x 3N(a) matrix with N-a the number of atoms. A series of simplified models has been proposed, in particular the Rotation-Translation Blocks (RTB) method by Tama et al. for the simulation of proteins. It makes use of the concept that a peptide chain or protein can be seen as a subsequent set of rigid components, i.e. the peptide units. A peptide chain is thus divided into rigid blocks with six degrees of freedom each. Recently we developed the Mobile Block Hessian (MBH) method, which in a sense has similar features as the RTB method. The main difference is that MBH was developed to deal with partially optimized systems. The position/orientation of each block is optimized while the internal geometry is kept fixed at a plausible - but not necessarily optimized - geometry. This reduces the computational cost of the energy minimization. Applying the standard NMA on a partially optimized structure however results in spurious imaginary frequencies and unwanted coordinate dependence. The MBH avoids these unphysical effects by taking into account energy gradient corrections. Moreover the number of variables is reduced, which facilitates the diagonalization of the Hessian. In the original implementation of MBH, atoms could only be part of one rigid block. The MBH is now extended to the case where atoms can be part of two or more blocks. Two basic linkages can be realized: (1) blocks connected by one link atom, or (2) by two link atoms, where the latter is referred to as the hinge type connection. In this work we present the MBH concept and illustrate its performance with the crambin protein as an example

Dimensions of fluvial-tidal meanders: Are they disproportionally large?

This is the final version. Available from Geological Society of America via the DOI in this record.GSA Data Repository item 2018343, supplementary figures, tables, and a .kml file with the recorded polygons of fluvial-tidal meanders, is available online at http://www.geosociety.org/datarepository/2018/ or on request from [email protected] of the world’s major river systems seemingly have one or a few disproportionally large meanders, with tight bends, in the fluvial-tidal transition (e.g., the Thames in the UK, and the Salmon River in Canada). However, quantitative studies on meanders have so far primarily focused on rivers without tidal influence or on small tidal meanders without river inflow, providing relations between channel geometry and meander characteristics (length, amplitude, and sinuosity). Physics-based predictions of meander size and shape for the fluvial-tidal transition zone remain untested for a lack of data. Therefore, it remains unclear whether the dimensions of meanders in the fluvial-tidal transition zone are indeed disproportionally large, and whether meander characteristics can be used as an indicator for tidal influence. Here, data from 823 meanders in 68 fluvial-tidal transition zones worldwide are presented that reveal broad-brush relations between channel geometry and meander dimensions. Our results show that fluvial-tidal meanders indeed become larger in the seaward direction, but the dimensions are proportional to local channel width, as in rivers. Sinuosity maxima are an exception, rather than the rule, in the fluvial-tidal transition zone. Surprisingly, the width of the upstream river correlates with estuarine channel width and tidal meander size even though river discharge constitutes only a fraction of the tidal prism. The new scaling relations can be used to constrain dimensions of rivers and estuaries and their meanders.Dutch Technology Foundation Toegepaste en Technische Wetenschappe

The effects of tannin-containing ground pine bark diet upon nutrient digestion, nitrogen balance, and mineral retention in meat goats

Background Pine bark is a rich source of phytochemical compounds including tannins, phenolic acids, anthocyanins, and fatty acids. These phytochemicals have potential to significantly impact on animal health and animal production. The goal of this work is to measure the effects of tannins in ground pine bark as a partial feed replacement on feed intake, dietary apparent digestibility, nitrogen balance, and mineral retention in meat goats. Results Eighteen Kiko cross goats (initial BW = 31.8 ± 1.49 kg) were randomly assigned to three treatment groups (n = 6). Dietary treatments were tested: control (0 % pine bark powder (PB) and 30 % wheat straw (WS)); 15 % PB and 15 % WS, and 30 % PB and 0 % WS. Although dry matter (DM) intake and digestibility were not affected (P > 0.10) by feeding PB, neutral detergent fiber (linear; P = 0.01), acid detergent fiber (linear; P = 0.001) and lignin digestibility (linear; P = 0.01) decreased, and crude protein (CP) digestibility tended to decrease (P = 0.09) as PB increased in the diet, apparent retention of Ca (P = 0.09), P (P = 0.03), Mg (P = 0.01), Mn (P = 0.01), Zn (P = 0.01) and Fe (P = 0.09) also increased linearly. Nitrogen intake and fecal N excretion were not affected (P > 0.05) by addition of PB in the diet, but N balance in the body was quadratically increased (P < 0.01) in the 15 % PB diet compared to other diets. This may be due to more rumen escape protein and less excreted N in the urine with the 15 % PB diet. The study showed that a moderate level of tannin-containing pine bark supplementation could improve gastrointestinal nitrogen balance with the aim of improving animal performance. Conclusion These results suggest that tannin-containing PB has negative impact on fiber, lignin, and protein digestibility, but positively impacted on N-balance

Assimilation in Multilingual Cities

We characterise how the assimilation patterns of minorities into the strong and the weak language differ in a situation of asymmetric bilingualism. Using large variations in language composition in Canadian cities from the 2001 and 2006 Censuses, we show that the differences in the knowledge of English by immigrant allophones (i.e. the immigrants with a mother tongue other than English and French) in English-majority cities are mainly due to sorting across cities. Instead, in French-majority cities, learning plays an important role in explaining differences in knowledge of French. In addition, the presence of large anglophone minorities deters much more the assimilation into French than the presence of francophone minorities deters the assimilation into English. Finally, we find that language distance plays a much more important role in explaining assimilation into French, and that assimilation into French is much more sensitive to individual characteristics than assimilation into English. Some of these asymmetric assimilation patterns extend to anglophone and francophone immigrants, but no evidence of learning is found in this case

Pathwise Accuracy and Ergodicity of Metropolized Integrators for SDEs

Metropolized integrators for ergodic stochastic differential equations (SDE) are proposed which (i) are ergodic with respect to the (known) equilibrium distribution of the SDE and (ii) approximate pathwise the solutions of the SDE on finite time intervals. Both these properties are demonstrated in the paper and precise strong error estimates are obtained. It is also shown that the Metropolized integrator retains these properties even in situations where the drift in the SDE is nonglobally Lipschitz, and vanilla explicit integrators for SDEs typically become unstable and fail to be ergodic.Comment: 46 pages, 5 figure

Cost-effectiveness of laparoscopic versus open distal pancreatectomy for pancreatic cancer

BACKGROUND: A recent Cochrane review compared laparoscopic versus open distal pancreatectomy for people with for cancers of the body and tail of the pancreas and found that laparoscopic distal pancreatectomy may reduce the length of hospital stay. We compared the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer. METHOD: Model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service. A decision tree model was constructed using probabilities, outcomes and cost data from published sources. A time horizon of 5 years was used. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: The probabilistic sensitivity analysis showed that the incremental net monetary benefit was positive (£3,708.58 (95% confidence intervals (CI) -£9,473.62 to £16,115.69) but the 95% CI includes zero, indicating that there is significant uncertainty about the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy. The probability laparoscopic distal pancreatectomy was cost-effective compared to open distal pancreatectomy for pancreatic cancer was between 70% and 80% at the willingness-to-pay thresholds generally used in England (£20,000 to £30,000 per QALY gained). Results were sensitive to the survival proportions and the operating time. CONCLUSIONS: There is considerable uncertainty about whether laparoscopic distal pancreatectomy is cost-effective compared to open distal pancreatectomy for pancreatic cancer in the NHS setting

Posterior Bearing Overhang Following Medial and Lateral Mobile Bearing Unicompartmental Knee Replacements

This study explores the extent of bearing overhang following mobile bearing Oxford unicompartmental knee replacement (OUKR) (Oxford Phase 3, Zimmer Biomet). The Oxford components are designed to be fully congruent, however knee movements involve femoral rollback, which may result in bearing overhang at the posterior margin of the tibial implant, with potential implications for; pain, wear, and dislocation. Movement is known to be greater, and therefore posterior overhang more likely to occur, with; lateral compared to medial implants, anterior cruciate ligament deficiency, and at extremes of movement. 24 medial, and 20 domed lateral, OUKRs underwent sagittal plane knee fluoroscopy during step‐up and forward lunge exercises. The bearing position was inferred from the relative position of the femoral and tibial components. Based on the individual component sizes and geometry the extent the posterior part of the bearing which overhung the posterior part of the tibial component was calculated. There was no significant posterior overhang in knees with medial implants. Knees with lateral domed implants exhibited overhang at flexion angles beyond 60°, the magnitude of which increased with increasing flexion angle, reaching a maximum of 50% of the bearing length at 140° (range 0‐140°). This demonstrates a clear difference between the kinematics, and prevalence and extent of posterior bearing overhang between medial and lateral OUKRs