Information-Based Physics: An Observer-Centric Foundation

It is generally believed that physical laws, reflecting an inherent order in the universe, are ordained by nature. However, in modern physics the observer plays a central role raising questions about how an observer-centric physics can result in laws apparently worthy of a universal nature-centric physics. Over the last decade, we have found that the consistent apt quantification of algebraic and order-theoretic structures results in calculi that possess constraint equations taking the form of what are often considered to be physical laws. I review recent derivations of the formal relations among relevant variables central to special relativity, probability theory and quantum mechanics in this context by considering a problem where two observers form consistent descriptions of and make optimal inferences about a free particle that simply influences them. I show that this approach to describing such a particle based only on available information leads to the mathematics of relativistic quantum mechanics as well as a description of a free particle that reproduces many of the basic properties of a fermion. The result is an approach to foundational physics where laws derive from both consistent descriptions and optimal information-based inferences made by embedded observers.Comment: To be published in Contemporary Physics. The manuscript consists of 43 pages and 9 Figure

Quantum Experimental Data in Psychology and Economics

We prove a theorem which shows that a collection of experimental data of probabilistic weights related to decisions with respect to situations and their disjunction cannot be modeled within a classical probabilistic weight structure in case the experimental data contain the effect referred to as the 'disjunction effect' in psychology. We identify different experimental situations in psychology, more specifically in concept theory and in decision theory, and in economics (namely situations where Savage's Sure-Thing Principle is violated) where the disjunction effect appears and we point out the common nature of the effect. We analyze how our theorem constitutes a no-go theorem for classical probabilistic weight structures for common experimental data when the disjunction effect is affecting the values of these data. We put forward a simple geometric criterion that reveals the non classicality of the considered probabilistic weights and we illustrate our geometrical criterion by means of experimentally measured membership weights of items with respect to pairs of concepts and their disjunctions. The violation of the classical probabilistic weight structure is very analogous to the violation of the well-known Bell inequalities studied in quantum mechanics. The no-go theorem we prove in the present article with respect to the collection of experimental data we consider has a status analogous to the well known no-go theorems for hidden variable theories in quantum mechanics with respect to experimental data obtained in quantum laboratories. For this reason our analysis puts forward a strong argument in favor of the validity of using a quantum formalism for modeling the considered psychological experimental data as considered in this paper.Comment: 15 pages, 4 figure

Probabilistic time

The concept of time emerges as an ordering structure in a classical statistical ensemble. Probability distributions $p_\tau(t)$ at a given time $t$ obtain by integrating out the past and future. We discuss all-time probability distributions that realize a unitary time evolution as described by rotations of the real wave function $q_\tau(t)=\pm \sqrt{p_\tau(t)}$. We establish a map to quantum physics and the Schr\"odinger equation. Suitable classical observables are mapped to quantum operators. The non-commutativity of the operator product is traced back to the incomplete statistics of the local-time subsystem. Our investigation of classical statistics is based on two-level observables that take the values one or zero. Then the wave functions can be mapped to elements of a Grassmann algebra. Quantum field theories for fermions arise naturally from our formulation of probabilistic time.Comment: new references, 30 page

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Progress toward a malaria vaccine: Efficient induction of protective anti-malaria immunity

Malaria can be a very severe disease, particularly in young children, pregnant women (mostly in primipara), and malaria naive adults, and currently ranks among the most prevalent infections in tropical and subtropical areas throughout the world. the widespread occurrence and the increased incidence of malaria in many countries, caused by drug-resistant parasites (Plasmodium falciparum and P. vivax) and insecticide-resistant vectors (Anopheles mosquitoes), indicate the need to develop new methods of controlling this disease.Experimental vaccination with irradiated sporozoites can protect animals and humans against the disease, demonstrating the feasibility of developing an effective malaria vaccine. However, developing a universally effective, long lasting vaccine against this parasitic disease has been a difficult task, due to several problems. One difficulty stems from the complexity of the parasite's life cycle. During their life cycle, malaria parasites change their residence within the host, thus avoiding being re-exposed to the same immunological environment. These parasites also possess some distinct antigens, present at different life stages of the parasite, the so-called stage-specific antigens, While some of the stage-specific antigens can induce protective immune responses in the host, these responses are usually genetically restricted, this being another reason for delaying the development of a universally effective vaccine. the stage-specific antigens must be used as immunogens and introduced into the host by using a delivery system that should efficiently induce protective responses against the respective stages. Here we review several research approaches aimed at inducing protective anti-malaria immunity, overcoming the difficulties described above.NYU, Sch Med, Dept Med & Mol Parasitol, New York, NY 10010 USAUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilWeb of Scienc

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease