arXiv subjects

J. C. Phillips

Publications and source records attributed to J. C. Phillips.

At least 55 records · Page 3Linked to original sources

arXiv2014

Similarity Is Not Enough: Tipping Points of Ebola Zaire Mortalities

In early 2014 an outbreak of a slightly mutated Zaire Ebola subtype appeared in West Africa which is less virulent than 1976 and 1994 strains. The numbers of cases per year appear to be ~ 1000 times larger than the earlier strains, suggesting a greatly enhanced transmissibility. Although the fraction of the 2014 spike glycoprotein mutations is very small (~3%), the mortality is significantly reduced, while the transmission appears to have increased strongly. Bioinformatic scaling had previously shown similar inversely correlated trends in virulence and transmission in N1 (H1N1) and N2 (H3N2) influenza spike glycoprotein mutations. These trends appear to be related to various external factors (migration, availability of pure water, and vaccination programs). The molecular mechanisms for Ebola's mutational response involve mainly changes in the disordered mucin-like domain (MLD) of its spike glycoprotein amino acids. The MLD has been observed to form the tip of an oligomeric amphiphilic wedge that selectively pries apart cell-cell interfaces via an oxidative mechanism.

q-bio.OT↗

arXiv2014

Filovirus Glycoprotein Sequence, Structure and Virulence

Leading Ebola subtypes exhibit a wide mortality range, here explained at the molecular level by using fractal hydropathic scaling of amino acid sequences based on protein self-organized criticality. Specific hydrophobic features in the hydrophilic mucin-like domain suffice to account for the wide mortality range. Significance statement: Ebola virus is spreading rapidly in Africa. The connection between protein amino acid sequence and mortality is identified here.

q-bio.BM↗

arXiv2014

Hydropathic evolution of hemagglutinin and neuraminidase glycoproteins of A(H1N1 and H3N2) viruses

More virulent strains of influenza virus subtypes H1N1 appeared in 2007 and H3N2 in 2011. The amino acid differences from prior less virulent strains appear to be small when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for globular compaction and modularity quantifies the mutational origins of increased virulence, and also analyzes receptor sites and N-linked glycan accretion.

q-bio.BM↗

arXiv2014

Fractal Scaling of Cortical Matter, Amyloid Fragmentation and Plaque Formation across Rodents and Primates

Thermodynamic tools are well suited to connecting evolution of protein functionalities to mutations of amino acid sequences, especially for neuronal network structures. These tools enable one to quantify changes in modular structure and correlate them with corresponding changes in observable properties. Here we quantify modular rodent-primate changes in amyloid precursor protein A4 and \b{eta} amyloid fragments. These are related to changes in cortical connectivity and to the presence (absence) of plaque formation in primates (rodents). Two thermodynamic scales are used, descriptive of water/air protein unfolding (old), or fractal conformational restructuring (new). These describe complementary aspects of protein activity, at respectively higher and lower effective temperatures.

q-bio.BM↗

arXiv2014

A Cubic Equation of State for Amyloid Plaque Formation

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 from the aa sequence alone for the amyloid 770 aa precursor protein A4. Both the new second order hydropathicity scale, based on evolutionary optimization (self-organized criticality), and the standard first order scale, based on complete protein (water-air) unfolding, yield thermodynamically significant features of amyloid function related to spinodal decomposition into modules. Spinodal crossings are marked by breaks in slope of algebraic functions of aa sequences. The new scale is associated with a lower effective temperature than the standard scale.

q-bio.BM↗

arXiv2014

Thermodynamic Description of Beta Amyloid Formation

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 from the aa sequences alone for the small (40,42 aa) plaque-forming amyloid beta fragments. Some edge and center features of the fragments are predicted. Contrasting results from the second order hydropathicity scale based on evolutionary optimization (self-organized criticality) and the first order scale based on complete protein (water-air) unfolding show that fragmentation has mixed first- and second-order character.

q-bio.BM↗

arXiv2013

Hierarchical hydropathic evolution of influenza glycoproteins (N2, H3, A/H3N2) under relentless vaccination pressure

Hemagglutinin (HA) and neuraminidase (NA) are highly variable envelope glycoproteins. Here hydropathic analysis, previously applied to quantify common flu (H1N1) evolution (1934-), is applied to the evolution of less common but more virulent (avian derived) H3N2 (1968-), beginning with N2. Whereas N1 exhibited opposing migration and vaccination pressures, the dominant N2 trend is due to vaccination, with only secondary migration interactions. Separation and evaluation of these effects is made possible by the use of two distinct hydropathic scales representing first-order and second-order thermodynamic interactions. The evolutions of H1 and H3 are more complex, with larger competing migration and vaccination effects. The linkages of H3 and N2 evolutionary trends are examined on two modular length scales, medium (glycosidic) and large (corresponding to sialic acid interactions). The hierarchical hydropathic results complement and greatly extend advanced phylogenetic results obtained from similarity studies. They exhibit simple quantitative trends that can be transferred to engineer oncolytic properties of other viral proteins to treat recalcitrant cancers.

q-bio.BM↗

arXiv2012

Self-Organized Criticality: A Prophetic Path to Curing Cancer

While the concepts involved in Self-Organized Criticality have stimulated thousands of theoretical models, only recently have these models addressed problems of biological and clinical importance. Here we outline how SOC can be used to engineer hybrid viral proteins whose properties, extrapolated from those of known strains, may be sufficiently effective to cure cancer.

q-bio.BM↗

arXiv2012

Punctuated 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). 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. Previously we identified much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. We showed that these smaller changes can be monitored very accurately across many Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages, which increases gradually due to migration, but decreases abruptly under large-scale vaccination pressures. Here we show that, while HA evolution is much more complex, it still shows abrupt punctuation changes linked to those of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on 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 an 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. While the common influenza virus discussed here has been rendered almost harmless by decades of vaccination programs, the sequential decoding lessons learned here are applicable to other viruses that are emerging as powerful weapons for controlling and even curing common organ cancers. Those engineered oncolytic drugs will be discussed in future papers.

q-bio.BM↗

arXiv2012

Punctuated evolution of influenza virus neuraminidase (A/H1N1) under 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 on much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. We show that very small amino acid changes can be monitored very accurately across many Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the differential hydropathicity scale based on protein self-organized criticality (SOC). NA exhibits punctuated evolution at the molecular scale, millions of times smaller than the more familiar species scale, and thousands of times smaller than the genomic scale. Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in influenza severity in the last century, a reduction which is hidden from short-term studies of vaccine effectiveness. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses.

q-bio.BM↗

arXiv2012

Self-Organized Criticality: A Guide to Water-Protein Landscape Evolution

We focus here on the scaling properties of small interspecies differences between red cone opsin transmembrane proteins, using a hydropathic elastic roughening tool previously applied to the rhodopsin rod transmembrane proteins. This tool is based on a non-Euclidean hydropathic metric realistically rooted in the atomic coordinates of 5526 protein segments, which thereby encapsulates universal non-Euclidean long-range differential geometrical features of water films enveloping globular proteins in the Protein Data Bank. Whereas the rhodopsin blue rod water films are smoothest in humans, the red cone opsins' water films are optimized in cats and elephants, consistent with protein species landscapes that evolve differently in different contexts. We also analyze red cone opsins in the chromatophore-containing family of chameleons, snakes, zebrafish and goldfish, where short- and long-range (BLAST and hydropathic) aa correlations are found with values as large as 97-99%. We use hydropathic amino acid (aa) optimization to estimate the maximum number Nmax of color shades that the human eye can discriminate, and obtain 10^6 < Nmax < 10^7, in good agreement with experiment.

cond-mat.soft↗

arXiv2012

Frequency-Rank Correlations of Rhodopsin Mutations with Tuned Hydropathic Roughness Based on Self-Organized Criticality

The behavior of disease-linked mutations of membrane proteins is especially simple in rhodopsin, where they are well-studied, as they are responsible for retinitis pigmentosa, RP (retinal degeneration). Here we show that the frequency of occurrence of single RP mutations is strongly influenced by their posttranslational survival rates, and that this survival correlates well (82%) with a long-range, non-local hydropathic measure of the roughness of the water interfaces of ex-membrane rhodopsin based on self-organized criticality (SOC). It is speculated that this concept may be generally useful in studying survival rates of many mutated proteins.

cond-mat.soft↗

arXiv2011

Bifurcation of Stretched Exponential Relaxation in Microscopically Homogeneous Glasses

Measured exponents associated with Stretched Exponential Relaxation (SER) are widely scattered in microscopically inhomogeneous glasses, but accurately bifurcate into two "magic" values, 3/5 and 3/7, in a wide variety of microscopically homogeneous glasses. These bifurcated values are derived here from a statistical product model that involves diffusion of excitations to native traps in the presence of short-range forces only, or combined short- and long- range forces, respectively. Bifurcated SER can be used to monitor sample homogeneity. It explains a wide range of experimental data, and even includes multiple aspects of the citation distributions of 20th century science, involving 25 million papers and 600 million citations, and why these changed radically in 1960. It also shows that the distribution of country population sizes has compacted glassy character, and is strongly influenced by migration.

cond-mat.soft↗

arXiv2011

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. Here we show that SOC may enable theory to connect standard Web-based (BLAST) short-range amino acid (aa) similarities to long-range aa roughening form factors that accurately describe evolutionary trends in water-membrane protein interactions. Our method utilizes a hydropathic aa metric based on 5526 protein segments and thereby encapsulates differential geometrical features of the Protein Data Bank. It easily organizes small aa sequence differences between humans and proximate species. For rhodopsin, the most studied transmembrane signaling protein associated with night vision, it shows that short- and long-range aa sequence properties correlate with 96% success for humans, monkeys, cats, mice and rabbits. Proper application of SOC promises unprecedented simplifications of exponentially complex protein sequence-structure-function problems, both conceptual and practical.

cond-mat.soft↗

arXiv2011

Protein Adaptive Plasticity and Night Vision

Proteins appear to be the most dramatic natural example of self-organized network criticality (SONC), a concept that explains many otherwise apparently exponentially unlikely phenomena. Adaptive plasticity is a term which has become much more specific as a result of recent physiological and genetic studies. Here we show that the molecular properties of rhodopsin, the transmembrane protein associated with night vision, can be quantified species by species using the Moret-Zebende hydropathicity scale based on SONC. The results show that long-range adaptive plasticity optimizes proximate species molecular functionality far more effectively than one would infer using only standard amino acid sequence (local similarity) tools such as BLAST for multiple alignments. These results should be universal, and they suggest new paths for analyzing and predicting protein functionality from amino acid sequences alone.

cond-mat.soft↗

arXiv2010

Self-Organized Criticality in Proteins: Hydropathic Roughening Profiles of G-Protein Coupled Receptors

Proteins appear to be the most dramatic natural example of self-organized criticality (SOC), a concept that explains many otherwise apparently unlikely phenomena. Protein conformational functionality is often dominated by long-range hydro(phobic/philic) interactions which both drive protein compaction and mediate protein-protein interactions. Superfamily transmembrane GPCR are the largest family of proteins in the human genome; their amino acid sequences form the largest data base for protein-membrane interactions. While there are now structural data on the heptad transmembrane structures of representatives of several heptad families, here we show that fresh insights into global and some local chemical trends in GPCR properties can be obtained accurately from sequences alone, especially by separating the extracellular and cytoplasmic loops from transmembrane segments. The global mediation of long-range water-protein interactions occurs in conjunction with modulation of these interactions by roughened interfaces. Hydropathic roughening profiles are defined here solely in terms of amino acid sequences, and knowledge of protein coordinates is not required. Roughening profiles both for GPCR and some simpler protein families display accurate and transparent connections to protein functionality.

cond-mat.soft↗

arXiv2010

Internal Stresses and Formation of Switchable Nanowires at Thin Silica Film Edge

At vertical edges, thin films of silicon oxide (SiO_{2-x}) contain semiconductive c-Si layered nanocrystals (Si NC) embedded in and supported by an insulating g-SiO2 matrix. Tour et al. have shown that a trenched thin film geometry enables the NC to form switchable nanowires (SNW) when trained by an applied field. The field required to form SNW decreases rapidly within a few cycles, or by annealing at 600 C in even fewer cycles, and is stable to 700C. Here we describe the intrinsic evolution of Si NC and SNW in terms of the competition between internal stresses and electro-osmosis. The analysis relies heavily on experimental data from a wide range of thin film studies, and it explains why a vertical edge across the planar Si-SiOx interface is necessary to form SNW. The discussion also shows that the formation mechanisms of Si NC and Si/SiO_{2-x} SNW are intrinsic and result from optimization of nanowire conductivity in the presence of residual host misfit stresses.

cond-mat.mtrl-sci↗

arXiv2010

Elastic Barriers and Formation of Nanoscale Switching Networks

Thin films of silicon oxide (SiOx) are mixtures of semiconductive c-Si nanoclusters (NC) embedded in an insulating g-SiO2 matrix. Tour et al. have shown that a trenched thin film geometry enables the NC to form semiconductive filamentary arrays when driven by an applied field. The field required to form reversible nanoscale switching networks (NSN) decreases rapidly within a few cycles, or by annealing at 600 C in even fewer cycles, and is stable to 700C. Here we discuss an elastic mechanism that explains why a vertical edge across the planar Si-SiOx interface is necessary to form NSN. The discussion shows that the formation mechanism is intrinsic and need not occur locally at the edge, but can occur anywhere in the SiOx film, given the unpinned nanoscale vertical edge geometry.

cond-mat.soft↗