Darwinian Evolution of Intelligence.

Intelligence is often discussed in terms of neural networks in the cerebral cortex, whose evolution has presumably been influenced by Darwinian selection. Here we present molecular evidence that one of the many kinesin motors, KIF14, has evolved to exhibit a special feature in its amino acid sequence that could improve neural networks. The improvement is quantified by comparison of NIF14 sequences for 12 species. The special feature is level sets of synchronized hydrophobic extrema in water wave profiles based on several hydropathic scales. The most effective scale is a new one based on fractals indicative of approach of globular curvatures to self-organized criticality, which summarizes evolutionary trends based on intelligent design.

Phase transitions may explain why SARS-CoV-2 spreads so fast and why new variants are spreading faster.

The novel coronavirus SARS CoV-2 responsible for the COVID-19 pandemic and SARS CoV-1 responsible for the SARS epidemic of 2002-2003 share an ancestor yet evolved to have much different transmissibility and global impact 1. A previously developed thermodynamic model of protein conformations hypothesized that SARS CoV-2 is very close to a new thermodynamic critical point, which makes it highly infectious but also easily displaced by a spike-based vaccine because there is a tradeoff between transmissibility and robustness 2. The model identified a small cluster of four key mutations of SARS CoV-2 that predicts much stronger viral attachment and viral spreading compared to SARS CoV-1. Here we apply the model to the SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2)3 and predict, using no free parameters, how the new mutations will not diminish the effectiveness of current spike based vaccines and may even further enhance infectiousness by augmenting the binding ability of the virus.

A data-driven model for COVID-19 pandemic - Evolution of the attack rate and prognosis for Brazil.

We introduce a compartmental model SEIAHRV (Susceptible, Exposed, Infected, Asymptomatic, Hospitalized, Recovered, Vaccinated) with age structure for the spread of the SARAS-CoV virus. In order to model current different vaccines we use compartments for individuals vaccinated with one and two doses without vaccine failure and a compartment for vaccinated individual with vaccine failure. The model allows to consider any number of different vaccines with different efficacies and delays between doses. Contacts among age groups are modeled by a contact matrix and the contagion matrix is obtained from a probability of contagion p c per contact. The model uses known epidemiological parameters and the time dependent probability p c is obtained by fitting the model output to the series of deaths in each locality, and reflects non-pharmaceutical interventions. As a benchmark the output of the model is compared to two good quality serological surveys, and applied to study the evolution of the COVID-19 pandemic in the main Brazilian cities with a total population of more than one million. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of We also estimate the attack rate, the total proportion of cases (symptomatic and asymptomatic) with respect to the total population, for all Brazilian states since the beginning of the COVID-19 pandemic. We argue that the model present here is relevant to assessing present policies not only in Brazil but also in any place where good serological surveys are not available.

Synchronized attachment and the Darwinian evolution of coronaviruses CoV-1 and CoV-2.

CoV2019 has evolved to be much more dangerous than CoV2003. Experiments suggest that structural rearrangements dramatically enhance CoV2019 activity. We identify a new first stage of infection that precedes structural rearrangements by using biomolecular evolutionary theory to identify sequence differences enhancing viral attachment rates. We find a small cluster of mutations which show that CoV-2 has a new feature that promotes much stronger viral attachment and enhances contagiousness. The extremely dangerous dynamics of human coronavirus infection is a dramatic example of evolutionary approach of self-organized networks to criticality. It may favor a very successful vaccine. The identified mutations can be used to test the present theory experimentally.

Self-organized networks: Darwinian evolution of dynein rings, stalks, and stalk heads.

Cytoskeletons are self-organized networks based on polymerized proteins: actin, tubulin, and driven by motor proteins, such as myosin, kinesin, and dynein. Their positive Darwinian evolution enables them to approach optimized functionality (self-organized criticality). Dynein has three distinct titled subunits, but how these units connect to function as a molecular motor is mysterious. Dynein binds to tubulin through two coiled coil stalks and a stalk head. The energy used to alter the head binding and propel cargo along tubulin is supplied by ATP at a ring 1,500 amino acids away. Here, we show how many details of this extremely distant interaction are explained by water waves quantified by thermodynamic scaling. Water waves have shaped all proteins throughout positive Darwinian evolution, and many aspects of long-range water-protein interactions are universal (described by self-organized criticality). Dynein water waves resembling tsunami produce nearly optimal energy transport over 1,500 amino acids along dynein's one-dimensional peptide backbone. More specifically, this paper identifies many similarities in the function and evolution of dynein compared to other cytoskeleton proteins such as actin, myosin, and tubulin.

Thermodynamic Scaling of Interfering Hemoglobin Strain Field Waves.

Hemoglobin (Hgb) forms tetramers (dimerized α-ß dimers), which enhance its globular stability and may also facilitate small gas molecule transport, as shown by recent all-atom Newtonian solvated simulations. Hydropathic bioinformatic thermodynamic scaling enables close comparisons of hemoglobin dimers with myoglobin and neuroglobin, and reveals many nonlocal wave-like features of strained Hgb structures at the coarse-grained amino acid level. The thermodynamic analysis employs two hydropathic scales, one describing abrupt first-order unfolding transitions, the other continuous second-order transitions. Small molecule exchange at hemes is a first-order process. Wave-like collective tetrameric features appropriate to ligand absorption and release, seen in optical experiments (short times), are identified thermodynamically at long times. Strain fields localized near hemes interfere with extended strain fields associated with dimer interfacial misfit, resulting in novel wavelength dependent dimer correlation function Fano antiresonances.

Scalable Molecular Dynamics with NAMD on the Summit System.

NAMD (NAnoscale Molecular Dynamics) is a parallel molecular dynamics application that has been used to make breakthroughs in understanding the structure and dynamics of large biomolecular complexes, such as viruses like HIV and various types of influenza. State-of-the-art biomolecular simulations often require integration of billions of timesteps, computing all interatomic forces for each femtosecond timestep. Molecular dynamics simulation of large biomolecular systems and long-timescale biological phenomena requires tremendous computing power. NAMD harnesses the power of thousands of heterogeneous processors to meet this demand. In this paper, we present algorithm improvements and performance optimizations that enable NAMD to achieve high performance on the IBM Newell platform (with POWER9 processors and NVIDIA Volta V100 GPUs) which underpins the Oak Ridge National Laboratory's Summit and Lawrence Livermore National Laboratory's Sierra supercomputers. The Top-500 supercomputers June 2018 list shows Summit at the number one spot with 187 Petaflop/s peak performance and Sierra third with 119 Petaflop/s. Optimizations for NAMD on Summit include: data layout changes for GPU acceleration and CPU vectorization, improving GPU offload efficiency, increasing performance with PAMI support in Charm++, improving efficiency of FFT calculations, improving load balancing, enabling better CPU vectorization and cache performance, and providing an alternative thermostat through stochastic velocity rescaling. We also present performance scaling results on early Newell systems.

Stress partition and microstructure in size-segregating granular flows.

When a granular mixture involving grains of different sizes is shaken, sheared, mixed, or left to flow, grains tend to separate by sizes in a process known as size segregation. In this study, we explore the size segregation mechanism in granular chute flows in terms of the pressure distribution and granular microstructure. Therefore, two-dimensional discrete numerical simulations of bidisperse granular chute flows are systematically analyzed. Based on the theoretical models of J. M. N. T. Gray and A. R. Thornton [Proc. R. Soc. A 461, 1447] and K. M. Hill and D. S. Tan [J. Fluid Mech. 756, 54 (2014)], we explore the stress partition in the phases of small and large grains, discriminating between contact stresses and kinetic stresses. Our results support both gravity-induced and shear-gradient-induced segregation mechanisms. However, we show that the contact stress partition is extremely sensitive to the definition of the partial stress tensors and, more specifically, to the way mixed contacts (i.e., involving a small grain and a large grain) are handled, making conclusions on gravity-induced segregation uncertain. By contrast, the computation of the partial kinetic stress tensors is robust. The kinetic pressure partition exhibits a deviation from continuum mixture theory of a significantly higher amplitude than the contact pressure and displays a clear dependence on the flow dynamics. Finally, using a simple approximation for the contact partial stress tensors, we investigate how the contact stress partition relates to the flow microstructure and suggest that the latter may provide an interesting proxy for studying gravity-induced segregation.

Proteinquakes in the evolution of influenza virus hemagglutinin (A/H1N1) under opposing migration and vaccination pressures.

Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on shifting sialic acid interactions are required for optimal balance between the receptor-binding and receptor-destroying activities of HA and NA for efficient virus replication. Our comprehensive results present a historical (1945-2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains.

Thermodynamic description of Beta amyloid formation using physicochemical scales and fractal bioinformatic scales.

Protein function depends on both protein structure and amino acid (aa) sequence. Here we show that modular features of both structure and function can be quantified economically from the aa sequences alone for the small (40,42 aa) plaque-forming (aggregative) amyloid beta fragments. Some edge and center features of the fragments are predicted. Bioinformatic scales based on ß strand formation propensities and the thermodynamically second order fractal hydropathicity scale based on evolutionary optimization (self-organized criticality) are contrasted with the standard first order physicochemical scale based on complete protein (water-air) unfolding. The results are consistent with previous studies of these physicochemical factors that show that aggregative properties, even of beta fragments, are driven primarily by near-equilibrium hydropathic forces.

Mechlorethamine, vincristine, melphalan and prednisone (MOMP) for the treatment of relapsed lymphoma in dogs.

Eighty-eight dogs with relapsed lymphoma were treated with the MOMP (mechlorethamine, vincristine, melphalan and prednisone) protocol on a 28-day treatment cycle. The overall response rate (ORR) to the MOMP protocol was 51.1% for a median of 56 days (range 7-858 days). Twelve percent of dogs experienced a complete response for a median of 81 days (range 42-274 days) and 38.6% experienced a partial response for a median of 49 days (range 7-858 days). Dogs with T-cell lymphoma had an ORR of 55% for a median of 60 days (range 49-858 days) while those with B-cell lymphoma had an ORR of 57% for a median of 81 days (range 7-274 days) (P = 0.783). The overall survival time for all dogs was 183 days (range 17-974 days). Fifty-four percent of dogs experienced toxicity with the majority classified as grade I. The MOMP protocol seems well-tolerated and is an option for dogs with relapsed lymphoma.

Punctuated evolution of influenza virus neuraminidase (A/H1N1) under opposing migration and vaccination pressures.

Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945-2011) Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC). Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains.

Depressive symptoms, self-esteem, HIV symptom management self-efficacy and self-compassion in people living with HIV.

The aims of this study were to examine differences in self-schemas between persons living with HIV/AIDS with and without depressive symptoms, and the degree to which these self-schemas predict depressive symptoms in this population. Self-schemas are beliefs about oneself and include self-esteem, HIV symptom management self-efficacy, and self-compassion. Beck's cognitive theory of depression guided the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico. Sixty-five percent of the sample reported depressive symptoms. These symptoms were significantly (p ≤ 0.05), negatively correlated with age (r = -0.154), education (r = -0.106), work status (r = -0.132), income adequacy (r = -0.204, self-esteem (r = -0.617), HIV symptom self-efficacy (r = - 0.408), and self-kindness (r = - 0.284); they were significantly, positively correlated with gender (female/transgender) (r = 0.061), white or Hispanic race/ethnicity (r = 0.047) and self-judgment (r = 0.600). Fifty-one percent of the variance (F = 177.530 (df = 1524); p < 0.001) in depressive symptoms was predicted by the combination of age, education, work status, income adequacy, self-esteem, HIV symptom self-efficacy, and self-judgment. The strongest predictor of depressive symptoms was self-judgment. Results lend support to Beck's theory that those with negative self-schemas are more vulnerable to depression and suggest that clinicians should evaluate PLHIV for negative self-schemas. Tailored interventions for the treatment of depressive symptoms in PLHIV should be tested and future studies should evaluate whether alterations in negative self-schemas are the mechanism of action of these interventions and establish causality in the treatment of depressive symptoms in PLHIV.

A multinational study of self-compassion and human immunodeficiency virus-related anxiety.

AIM: This study represents an initial effort at examining the association between the construct of self-compassion and human immunodeficiency virus (HIV)-related anxiety in a multinational population with HIV disease. BACKGROUND: Previous studies have found that self-compassion is a powerful predictor of mental health, demonstrating positive and consistent linkages with various measures of affect, psychopathology and well-being, including anxiety. METHODS: Cross-sectional data from a multinational study conducted by the members of the International Nursing Network for HIV Research (n = 1986) were used. The diverse sample included participants from Canada, China, Namibia, the United States of America and the territory of Puerto Rico. Study measures included the anxiety subscale of the Symptom Checklist-90 instrument, the Brief Version Self-Compassion Inventory and a single item on anxiety from the Revised Sign and Symptom Checklist. FINDINGS: Study findings show that anxiety was significantly and inversely related to self-compassion across participants in all countries. We examined gender differences in self-compassion and anxiety, controlling for country. Levels of anxiety remained significantly and inversely related to self-compassion for both males (P = 0.000) and females (P = 0.000). Levels of self-compassion and anxiety varied across countries. CONCLUSIONS: Self-compassion is a robust construct with cross-cultural relevance. A culturally based brief treatment approach aimed at increasing self-compassion may lend itself to the development of a cost effective adjunct treatment in HIV disease, including the management of anxiety symptoms.

Performance characteristics of a conformal ultra-wideband multilayer applicator (CUMLA) for hyperthermia in veterinary patients: a pilot evaluation of its use in the adjuvant treatment of non-resectable tumours.

Performance and clinical characteristics of a novel hyperthermia antenna operating at 434 MHz were evaluated for the adjuvant treatment of locally advanced superficial tumours in cats, dogs and horses. Electromagnetic simulations were performed to determine electric field characteristics and compared to simulations for a flat microwave antenna with similar dimensions. Simulation results show a reduced skin surface and backfield irradiation and improved directional irradiation (at broadside) compared to a flat antenna. Radiated power and penetration is notably increased with a penetration depth of 4.59 cm compared to 2.74 cm for the flat antenna. Clinical use of the antenna was then evaluated in six animals with locoregionally advanced solid tumours receiving adjuvant chemotherapy. During clinical applications, therapeutic temperatures were achieved at depths ≥4 cm. Objective responses were seen in all patients; tissue toxicity in one case limited further therapy. This antenna provides compact, efficient, focused and deep-penetrating clinical hyperthermia for the treatment of solid tumours in veterinary patients.

Mediators of antiretroviral adherence: a multisite international study.

The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country.

Hydropathic self-organized criticality: a magic wand for protein physics.

Self-organized criticality (SOC) is a popular concept that has been the subject of more than 3000 articles in the last 25 years. The characteristic signature of SOC is the appearance of self-similarity (power-law scaling) in observable properties. A characteristic observable protein property that describes protein-water interactions is the water-accessible (hydropathic) interfacial area of compacted globular protein networks. Here we show that hydropathic power-law (size- or length-scale-dependent) exponents derived from SOC enable theory to connect standard Web-based (BLAST) short-range amino acid (aa) sequence similarities to long-range aa sequence hydropathic roughening form factors that hierarchically describe evolutionary trends in water - membrane protein interactions. Our method utilizes hydropathic aa exponents that define a non-Euclidean metric realistically rooted in the atomic coordinates of 5526 protein segments. These hydropathic aa exponents thereby encapsulate universal (but previously only implicit) non-Euclidean long-range differential geometrical features of the Protein Data Bank. These hydropathic aa exponents easily organize small mutated aa sequence differences between human and proximate species proteins. For rhodopsin, the most studied transmembrane signaling protein associated with night vision, analysis shows that this approach separates Euclidean short- and non-Euclidean long-range aa sequence properties, and shows that they correlate with 96% success for humans, monkeys, cats, mice and rabbits. Proper application of SOC using hydropathic aa exponents promises unprecedented simplifications of exponentially complex protein sequence-structure-function problems, both conceptual and practical.

Percolative theories of strongly disordered ceramic high-temperature superconductors.

Optimally doped ceramic superconductors (cuprates, pnictides, etc.) exhibit transition temperatures T(c) much larger than strongly coupled metallic superconductors like Pb (T(c) = 7.2 K, E(g)/kT(c) = 4.5) and exhibit many universal features that appear to contradict the Bardeen, Cooper, and Schrieffer theory of superconductivity based on attractive electron-phonon pairing interactions. These complex materials are strongly disordered and contain several competing nanophases that cannot be described effectively by parameterized Hamiltonian models, yet their phase diagrams also exhibit many universal features in both the normal and superconductive states. Here we review the rapidly growing body of experimental results that suggest that these anomalously universal features are the result of marginal stabilities of the ceramic electronic and lattice structures. These dual marginal stabilities favor both electronic percolation of a dopant network and rigidity percolation of the deformed lattice network. This "double percolation" model has previously explained many features of the normal-state transport properties of these materials and is the only theory that has successfully predicted strict lowest upper bounds for T(c) in the cuprate and pnictide families. Here it is extended to include Coulomb correlations and percolative band narrowing, as well as an angular energy gap equation, which rationalizes angularly averaged gap/T(c) ratios, and shows that these are similar to those of conventional strongly coupled superconductors.

Universal non-Landau, self-organized, lattice disordering percolative dopant network sub-T(c) phase transition in ceramic superconductors.

Ceramic superconductors (cuprates, pnictides, etc.) exhibit universal features in both T(c)(max) and in their planar lattice disordering measured by EXAFS, as reflected by three phase transitions. The two highest temperature transitions are known to be associated with formation of Jahn-Teller pseudogaps and superconductive gaps, with corresponding Landau order parameters, but no new gap is associated with the third transition below T(c), and its origin is mysterious. It is argued that the third subT(c) transition is a dopant glass transition, which is remarkably similar to topological transitions previously observed in chalcogenide and oxide alloy network glasses (like window glass).