Revisiting special relativity: A natural algebraic alternative to Minkowski spacetime

Minkowski famously introduced the concept of a space-time continuum in 1908, merging the three dimensions of space with an imaginary time dimension $i c t$, with the unit imaginary producing the correct spacetime distance $x^2 - c^2 t^2$, and the results of Einstein's then recently developed theory of special relativity, thus providing an explanation for Einstein's theory in terms of the structure of space and time. As an alternative to a planar Minkowski space-time of two space dimensions and one time dimension, we replace the unit imaginary $i = \sqrt{-1}$, with the Clifford bivector $\iota = e_1 e_2$ for the plane that also squares to minus one, but which can be included without the addition of an extra dimension, as it is an integral part of the real Cartesian plane with the orthonormal basis $e_1$ and $e_2$. We find that with this model of planar spacetime, using a two-dimensional Clifford multivector, the spacetime metric and the Lorentz transformations follow immediately as properties of the algebra. This also leads to momentum and energy being represented as components of a multivector and we give a new efficient derivation of Compton's scattering formula, and a simple formulation of Dirac's and Maxwell's equations. Based on the mathematical structure of the multivector, we produce a semi-classical model of massive particles, which can then be viewed as the origin of the Minkowski spacetime structure and thus a deeper explanation for relativistic effects. We also find a new perspective on the nature of time, which is now given a precise mathematical definition as the bivector of the plane.Comment: 29 pages, 2 figure

Treatment Preferences of Adult Patients with Attention-Deficit/Hyperactivity Disorder – A Discrete Choice Experiment

Jeff Schein,1 Martin Cloutier,2 Marjolaine Gauthier-Loiselle,2 Maryaline Catillon,3 Yan Meng,4 Beatrice Libchaber,2 Fanny Jiang,2 Ann Childress5 1Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 2Analysis Group, Inc, Montréal, QC, Canada; 3Analysis Group, Inc, New York, NY, USA; 4Analysis Group, Inc, London, UK; 5Center for Psychiatry and Behavioral Medicine, Las Vegas, NV, USACorrespondence: Maryaline Catillon, Analysis Group, Inc, 151 West 42nd Street, 23rd Floor, New York, NY, 10036, USA, Tel +1 857 222 6863, Email [email protected]: Understanding patient preferences for treatments may facilitate shared decision-making. This study assessed adult patient preferences for attention-deficit/hyperactivity disorder (ADHD) treatments in a sample of 600 patients in the United States (US).Methods: A web-based discrete choice experiment (DCE) survey was conducted among treated adults with ADHD. Participants were recruited from Dynata’s US panel (06/22/2023-07/06/2023). Attributes and levels, identified based on clinical inputs and published data, included efficacy and safety. Participants’ preferences were estimated using conditional logistic regression. Willingness to trade-off and attributes’ relative importance were calculated. Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities. Results were stratified by current treatment status. Sensitivity analyses including participants who passed validity tests were conducted.Results: Among the 600 participants (mean age 37.9 years; 66.2% female; 50.8% treated), all attributes had a statistically significant impact on preferences for ADHD treatments (p 60% of relative importance in decision-making. Participants were willing to forgo 0.59, 0.57, 0.49, 0.32, and 0.17 percentage points of symptom improvement to achieve one-percentage-point reduced risk of insomnia, nausea, anxiety, feeling jittery, and dry mouth, respectively. Centanafadine profile had consistently higher adjusted total utilities than its comparators. Similar results were obtained in the subgroup and sensitivity analyses.Conclusion: Efficacy was the most important attribute for patients when making treatment decision, but taken together, AEs had greater relative importance than efficacy alone. Accordingly, a profile resembling that of centanafadine would be preferred by an average patient compared to key competitors due to its favorable safety profile. These findings may help improve treatment decision-making, enhance treatment satisfaction, and foster adherence.Keywords: ADHD, decision-making, discrete choice experiment, patient-centered care, patient satisfaction, patient preference, utilit

PDE6D Inhibitors with a New Design Principle Selectively Block K‑Ras Activity

peer reviewe

Compact Time and Determinism for Bosons: foundations

Free bosonic fields are investigated at a classical level by imposing their characteristic de Broglie periodicities as constraints. In analogy with finite temperature field theory and with extra-dimensional field theories, this compactification naturally leads to a quantized energy spectrum. As a consequence of the relation between periodicity and energy arising from the de Broglie relation, the compactification must be regarded as dynamical and local. The theory, whose fundamental set-up is presented in this paper, turns out to be consistent with special relativity and in particular respects causality. The non trivial classical dynamics of these periodic fields show remarkable overlaps with ordinary quantum field theory. This can be interpreted as a generalization of the AdS/CFT correspondence.Comment: For editorial reasons the present version (0903.3680v5 accepted for publication in Found. Phys.) is focused on the foundational points of 0903.3680v4 (par.1, par.2 and par.3.2). The remaining parts (par.3.1, app.A and app.B) will be extended and published in dedicated papers. 28 pages, 3 figure

PDE6D Inhibitors with a New Design Principle Selectively Block K-Ras Activity

The trafficking chaperone PDE6D (also referred to as PDE delta) has been nominated as a surrogate target for K-Ras4B (hereafter K-Ras). Arl2-assisted unloading of K-Ras from PDE6D in the perinuclear area is significant for correct K-Ras localization and therefore activity. However, the unloading mechanism also leads to the undesired ejection of PDE6D inhibitors. To counteract ejection, others have recently optimized inhibitors for picomolar affinities; however, cell penetration generally seems to remain an issue. To increase resilience against ejection, we engineered a "chemical spring" into prenyl-binding pocket inhibitors of PDE6D. Furthermore, cell penetration was improved by attaching a cell-penetration group, allowing us to arrive at micromolar in cellulo potencies in the first generation. Our model compounds, Deltaflexin-1 and -2, selectively disrupt K-Ras, but not H-Ras membrane organization. This selectivity profile is reflected in the antiproliferative activity on colorectal and breast cancer cells, as well as the ability to block sternness traits of lung and breast cancer cells. While our current model compounds still have a low in vitro potency, we expect that our modular and simple inhibitor redesign could significantly advance the development of pharmacologically more potent compounds against PDE6D and related targets, such as UNC119 in the future

On the Physiological and Therapeutical Properties of Glycerine

n/

Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats.

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7-36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7-36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7-36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats

Experimental observation compatible with the particle internal clock

The particle internal clock conjectured by L. de Broglie in 1924 was looked for in a channeling experiment with ∼80 MeV electrons traversing a 1-μm thick silicon crystal aligned along the 〈110〉 direction. Part of them undergo what is called the rosette motion, in which they interact with a single atomic row. When the electron energy is finely varied, the rate of electron transmission at 0° shows an 8% dip within 0.5% of the resonance energy, 80.874 MeV, for which the frequency of atomic collisions matches the internal clock frequency. Our observation is compatible with the de Broglie hypothesis

Étude de la diffusion inélastique de particules alpha de 44,4 MeV sur 58Ni, 60Ni, 64Ni

Using the 44.4 MeV alpha particle beam of the Saclay cyclotron, a study of the states preferentially excited in (α, α') experiments was made. The energies of these states and the angular distributions of the inelastically scattered α particles leaving the nucleus in these excited states are given. The application of the Blair inelastic diffractional calculations allows us to give parity assignment to some of the levels.Utilisant le faisceau analysé de particules α de 44,4 MeV du cyclotron de Saclay, une recherche des niveaux préférentiellement excités lors de la diffusion inélastique de ces particules sur 58Ni. 60Ni, 64Ni a été effectuée. Le dispositif expérimental de détection et sélection de particules est celui décrit par M. Chaminade. Le spectre énergétique des particules émises montre l'excitation préférentielle de niveaux vers 1,4 ; 4 ; 5 ; 6 et 10 MeV. Les courbes de distributions angulaires de particules α émises abandonnant le noyau dans ces différents états d'excitation sont données. Ces courbes présentent des oscillations caractéristiques de l'interaction de surface. Une interprétation préliminaire selon le modèle de Blair est donnée