Using Numerical Simulation to Better Understand Fixation Rates, and Establishment of a New Principle: Haldane’s Ratchet

In 1957, Haldane first described a fundamental problem with evolutionary theory. This problem eventually became widely known as “Haldane’s Dilemma”. The essence of this problem is that even given a steady supply of beneficial mutations plus deep time, the rate that such mutations reach fixation is too slow to achieve meaningful evolution. After more than 50 years, this fundamental problem remains unresolved. ReMine has gone far beyond Haldane’s original mathematical analysis, and has developed “cost theory analysis” which strongly supports Haldane’s thesis. Here we examine this long-standing problem using an entirely different approach. We employ advanced numerical simulation of the mutation/selection process to empirically measure the fixation rates of beneficial, neutral, and deleterious mutations. We do this employing both realistic and optimized population parameters. In our numerical simulations, each new mutation is tracked through time until it is either lost due to drift or becomes fixed in the population. We first confirm that our numerical simulations correctly tallying the fixation of neutral mutations. We show that neutral mutations go to fixation just as predicted by conventional theory (i.e., over deep time the fixation rate approached the gametic mutation rate). We also show that the reason the vast majority of neutral mutant alleles fail to go to fixation, is because they lost due to drift, and this rate of loss rapidly approached 100% as population size is increased. We then show that given realistic distributions of mutation fitness affects, the vast majority of all mutations (including deleterious and beneficial mutations), are similarly lost due to random drift. In terms of fixations, deleterious mutations went to fixation only slightly slower, while beneficial mutations went to fixation only slightly faster, than neutral mutations. We then perform large-scale experiments to examine the feasibility of the ape-to-man scenario over a six million year period. We analyze neutral and beneficial fixations separately (realistic Proceedings of the Seventh International Conference on Creationism. Pittsburgh, PA: Creation Science Fellowship rates of deleterious mutations could not be studied in deep time due to extinction). Using realistic parameter settings we only observe a few hundred selection-induced beneficial fixations after 300,000 generations (6 million years). Even when using highly optimal parameter settings (i.e., favorable for fixation of beneficials), we only see a few thousand selection-induced fixations. This is significant because the ape-to-man scenario requires tens of millions of selective nucleotide substitutions in the human lineage. Our empirically-determined rates of beneficial fixation are in general agreement with the fixation rate estimates derived by Haldane and ReMine using their mathematical analyses. We have therefore independently demonstrated that the findings of Haldane and ReMine are for the most part correct, and that the fundamental evolutionary problem historically known as “Haldane’s Dilemma” is very real. Previous analyses have focused exclusively on beneficial mutations. When deleterious mutations were included in our simulations, using a realistic ratio of beneficial to deleterious mutation rate, deleterious fixations vastly outnumbered beneficial fixations. Because of this, the net effect of mutation fixation should clearly create a ratchet-type mechanism which should cause continuous loss of information and decline in the size of the functional genome. We name this phenomenon “Haldane’s Ratchet”

Immunologic Status of Uremic Patients

The immunologic status of 25 uremic patients was studied with a battery of tests evaluating the humoral and cytological aspects of immunity. The individual\u27s humoral immune status was evaluated as follows: quantitation of the three major serum immunoglobulins (IgG, IgA and IgM) expressed in mg/100 ml of serum and compared to established normal clinical standards (±2 SD/mean); qualitation of IgG and IgM evaluated by specific virus antibody titers and antitoxin values associated with IgG and by isoagglutinin tilers of the ABO blood groups associated with IgM. Immunoglobulin status is grouped into hyper- and hypo-immunoglobulin variations from normal and correlated with serum complement values (Beta 1C/1A and hemolytic activity). The cytological status in the evaluation consists of assaying the individual\u27s ability to produce interferon by the Sendai-Sindbis virus system in peripheral blood leukocytes. Results of the study emphasize the need for individual evaluation of uremic patients to enable more effective immuno- depressive therapy before and after renal transplantation

Osteoradionecrosis of the jaws due to teeth extractions during and after radiotherapy: A systematic review

Teeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. Methods: This systematic review was conducted according to PRISMA protocol, and the PROSPERO registration number was CRD42018079986. An electronic search was performed on the following search engines: PubMed, Scopus, and Web of Science. A cumulative meta‐analysis was performed. Results: Two thousand two hundred and eighty‐one records were screened, and nine were finally included. This systematic review revealed an ORN incidence of 5.8% (41 patients out of 462, 95% CI = 2.3–9.4); 3 ORN developed in the maxilla. No other clinical risk factors were detected. Conclusion: Post‐RT teeth extractions represent a major risk factor for ORN development, especially in the mandible, with a diminishing trend in the last years. Further research on other possible risk factors might improve this evidence

Soybean cultivar UA 5213C

Disclosed a soybean cultivar designated UA 5213C. The invention relates to the seeds of this cultivar, to the plants, to the plant parts, and to methods for producing progeny of the cultivar. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. The invention also relates to soybean cultivars or breeding cultivars, and plant parts derived from this cultivar, and to methods for producing other soybean cultivars, lines, or plant parts derived from it. The invention further relates to hybrid soybean seeds, plants, and plant parts produced by crossing this cultivar with another soybean cultivar

Soybean cultivar UA Kirksey

The soybean cultivar UA Kirksey is disclosed. The invention relates to the seeds of the cultivar , to the plants of cultivar, to the plant parts of cultivar, and to methods for producing progeny of it. Methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods are described. The invention also relates to: soybean cultivars or breeding cultivars, and plant parts derived from the cultivar; to methods for producing other soybean cultivars, lines, or plant parts derived from it, and to the soybean plants, varieties, and their parts derived from use of those methods. The invention also relates to hybrid soybean seeds, plants, and plant parts produced by crossing cultivar UA Kirksey with another soybean cultivar

Local Causal States and Discrete Coherent Structures

Coherent structures form spontaneously in nonlinear spatiotemporal systems and are found at all spatial scales in natural phenomena from laboratory hydrodynamic flows and chemical reactions to ocean, atmosphere, and planetary climate dynamics. Phenomenologically, they appear as key components that organize the macroscopic behaviors in such systems. Despite a century of effort, they have eluded rigorous analysis and empirical prediction, with progress being made only recently. As a step in this, we present a formal theory of coherent structures in fully-discrete dynamical field theories. It builds on the notion of structure introduced by computational mechanics, generalizing it to a local spatiotemporal setting. The analysis' main tool employs the \localstates, which are used to uncover a system's hidden spatiotemporal symmetries and which identify coherent structures as spatially-localized deviations from those symmetries. The approach is behavior-driven in the sense that it does not rely on directly analyzing spatiotemporal equations of motion, rather it considers only the spatiotemporal fields a system generates. As such, it offers an unsupervised approach to discover and describe coherent structures. We illustrate the approach by analyzing coherent structures generated by elementary cellular automata, comparing the results with an earlier, dynamic-invariant-set approach that decomposes fields into domains, particles, and particle interactions.Comment: 27 pages, 10 figures; http://csc.ucdavis.edu/~cmg/compmech/pubs/dcs.ht

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine)

Background Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. Methods 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. Results The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). Conclusions Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP