Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions

The internally electrodynamic (IED) particle model was derived based on overall experimental observations, with the IED process itself being built directly on three experimental facts, a) electric charges present with all material particles, b) an accelerated charge generates electromagnetic waves according to Maxwell's equations and Planck energy equation and c) source motion produces Doppler effect. A set of well-known basic particle equations and properties become predictable based on first principles solutions for the IED process; several key solutions achieved are outlined, including the de Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass, Einstein mass-energy relation, Newton's law of gravity, single particle self interference, and electromagnetic radiation and absorption; these equations and properties have long been broadly experimentally validated or demonstrated. A specific solution also predicts the Doebner-Goldin equation which emerges to represent a form of long-sought quantum wave equation including gravity. A critical review of the key experiments is given which suggests that the IED process underlies the basic particle equations and properties not just sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200

An orphan gene is necessary for preaxial digit formation during salamander limb development

Limb development in salamanders differs from other tetrapods in that the first digits to form are the two most anterior (preaxial dominance). This has been proposed as a salamander novelty and its mechanistic basis is unknown. Salamanders are the only adult tetrapods able to regenerate the limb, and the contribution of preaxial dominance to limb regeneration is unclear. Here we show that during early outgrowth of the limb bud, a small cohort of cells express the orphan gene Prod1 together with Bmp2, a critical player in digit condensation in amniotes. Disruption of Prod1 with a gene-editing nuclease abrogates these cells, and blocks formation of the radius and ulna, and outgrowth of the anterior digits. Preaxial dominance is a notable feature of limb regeneration in the larval newt, but this changes abruptly after metamorphosis so that the formation of anterior and posterior digits occurs together within the autopodium resembling an amniote-like pattern

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

Staff Perceptions of Risk for Prison Rape Perpetration and Victimization

Copyright © 2012 SAGE Publications, http://tpj.sagepub.com Used by permission

Pharmacokinetic Modeling to Guide Preclinical Development of an Islatravir-Eluting Reservoir-Style Biodegradable Implant for Long-Acting HIV PrEP

Long-acting injectable cabotegravir is more effective than daily oral PrEP at preventing HIV transmission due to improved adherence, but requires bi-monthly large-volume intramuscular injections. Subcutaneous (SC) contraceptive implants can be formulated with antiretrovirals for extended-duration HIV PrEP. Islatravir (ISL) is a first-in-class, investigational antiretroviral with pharmacologic properties well-suited for implant delivery. We performed preclinical studies for the development of a reservoir-style, poly(ε-caprolactone) ISL-eluting implant by conducting a single-dose SC ISL dose-ranging pharmacokinetic (PK) study of 0.1, 0.3, and 1 mg/kg in adult Wistar rats. Non-compartmental analysis was conducted, and dose proportionality assessed for ISL plasma and intracellular islatravir-triphosphate (ISL-tp). Population PK models estimated ISL's unit impulse response to deconvolve ISL-implant in vivo absorption rate (mg/day) and cumulative mass (mg) from published rat plasma PK (n> = 10). Drug release was interpreted using four kinetic models. Dose proportionality was affirmed for ISL and ISL-tp. A first-order, two-compartment model fitted the SC ISL bolus data. Mean (SD) absorption rate from 0 to 154 days was 0.072 ± 0.024 mg/day, and cumulative mass at 154 days was 8.67 ± 3.22 mg. ISL absorption was well-described by zero-order (r2 = 0.95) and Ritger-Peppas (r2 = 0.98). Our zero-order ISL-release poly(ε-caprolactone) implant is projected to achieve clinical PK above ISL-tp's PrEP efficacy threshold. Continued development for HIV PrEP applications is warranted

Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration

This secondary analysis explored changes in protein-unbound concentrations of lopinavir and amprenavir when co-administered in HIV-infected subjects. Total and unbound pharmacokinetic parameters were calculated and compared between subjects receiving each agent alone, and co-administration. When co-administered, unbound and total concentrations decrease. Co-administration significantly increased lopinavir unbound clearance, while significant changes in fraction unbound (fu) were not detected. For amprenavir, significant increases in fu and unbound clearance occurred with co-administration. This demonstrates the complex nature of drug-drug interactions between highly protein-bound, CYP-metabolized drugs, and the need to measure unbound concentrations in disease states like hepatitis C, where such agents are co-administered

Lifelong testicular differentiation in Pleurodeles waltl (Amphibia, Caudata)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Leftovers: The presence of manufacture-derived aquatic lipids in Alaskan pottery

Lipids preserved within the walls of ancient pottery vessels are routinely analysed to reveal their original contents. The provenience of aquatic lipids in pottery is generally connected to vessel function (e.g., for cooking or storing fish, shellfish and aquatic mammals). However, ethnographic reports from early historic Alaska mention the use of aquatic oils for waterproofing low-fired pottery. Results of lipid residue studies on Alaskan pottery reflect an exclusive function of pottery to process aquatic resources. However, can one be sure these residues are the product of vessel function and not a remnant of the manufacturing process? The study presents the results of an experiment where the preservation of aquatic lipids during the firing process at different temperatures was measured. It was found that nearly all lipids were removed at firing temperatures of ≥ 400°C. Petrographic analysis of Alaskan pottery samples indicates that firing temperatures were generally > 550°C but <800°C. The contribution of pre-firing manufacture-derived lipids to samples fired at these temperatures may be regarded as negligible. While the possible presence of aquatic lipids from post-firing surface treatments cannot be excluded, such treatments appear unnecessary for well-fired pottery