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

The acridonecarboxamide GF120918 potently reverses P-glycoprotein-mediated resistance in human sarcoma MES-Dx5 cells

The doxorubicin-selected, P-glycoprotein (P-gp)-expressing human sarcoma cell line MES-Dx5 showed the following levels of resistance relative to the non-P-gp-expressing parental MES-SA cells in a 72 h exposure to cytotoxic drugs: etoposide twofold, doxorubicin ninefold, vinblastine tenfold, taxotere 19-fold and taxol 94-fold. GF120918 potently reversed resistance completely for all drugs. The EC50s of GF120918 to reverse resistance of MES-Dx5 cells were: etoposide 7 ± 2 nM, vinblastine 19 ± 3 nM, doxorubicin 21 ± 6 nM, taxotere 57 ± 14 nM and taxol 91 ± 23 nM. MES-Dx5 cells exhibited an accumulation deficit relative to the parental MES-SA cells of 35% for [3H]-vinblastine, 20% for [3H]-taxol and [14C]-doxorubicin. The EC50 of GF120918, to reverse the accumulation deficit in MES-Dx5 cells, ranged from 37 to 64 nM for all three radiolabelled cytotoxics. [3H]-vinblastine bound saturably to membranes from MES-Dx5 cells with a KD of 7.8 ± 1.4 nM and a Bmax of 5.2 ± 1.6 pmol mg–1 protein. Binding of [3H]-vinblastine to P-gp in MES-Dx5 membranes was inhibited by GF120918 (Ki = 5 ± 1 nM), verapamil (Ki = 660 ± 350 nM) and doxorubicin (Ki = 6940 ± 2100 nM). Taxol, an allosteric inhibitor of [3H]-vinblastine binding to P-gp, could only displace 40% of [3H]-vinblastine (Ki = 400 ± 140 nM). The novel acridonecarboxamide derivative GF120918 potently overcomes P-gp-mediated multidrug resistance in the human sarcoma cell line MES-Dx5. Detailed analysis revealed that five times higher GF120918 concentrations were needed to reverse drug resistance to taxol in the cytotoxicity assay compared to doxorubicin, vinblastine and etoposide. An explanation for this phenomenon had not been found. © 1999 Cancer Research Campaig

Within- and across-breed genomic prediction using whole-genome sequence and single nucleotide polymorphism panels

International audienceBackground Currently, genomic prediction in cattle is largely based on panels of about 54k single nucleotide polymorphisms (SNPs). However with the decreasing costs of and current advances in next-generation sequencing technologies, whole-genome sequence (WGS) data on large numbers of individuals is within reach. Availability of such data provides new opportunities for genomic selection, which need to be explored.MethodsThis simulation study investigated how much predictive ability is gained by using WGS data under scenarios with QTL (quantitative trait loci) densities ranging from 45 to 132 QTL/Morgan and heritabilities ranging from 0.07 to 0.30, compared to different SNP densities, with emphasis on divergent dairy cattle breeds with small populations. The relative performances of best linear unbiased prediction (SNP-BLUP) and of a variable selection method with a mixture of two normal distributions (MixP) were also evaluated. Genomic predictions were based on within-population, across-population, and multi-breed reference populations.ResultsThe use of WGS data for within-population predictions resulted in small to large increases in accuracy for low to moderately heritable traits. Depending on heritability of the trait, and on SNP and QTL densities, accuracy increased by up to 31 %. The advantage of WGS data was more pronounced (7 to 92 % increase in accuracy depending on trait heritability, SNP and QTL densities, and time of divergence between populations) with a combined reference population and when using MixP. While MixP outperformed SNP-BLUP at 45 QTL/Morgan, SNP-BLUP was as good as MixP when QTL density increased to 132 QTL/Morgan.ConclusionsOur results show that, genomic predictions in numerically small cattle populations would benefit from a combination of WGS data, a multi-breed reference population, and a variable selection method

Determination of the Molecular Basis for a Limited Dimorphism, N417K, in the Plasmodium vivax Duffy-Binding Protein

Invasion of human red blood cells by Plasmodium merozoites is vital for replication and survival of the parasite and, as such, is an attractive target for therapeutic intervention. Merozoite invasion is mediated by specific interactions between parasite ligands and host erythrocyte receptors. The P. vivax Duffy-binding protein (PvDBP) is heavily dependent on the interaction with the human Duffy blood group antigen/receptor for chemokines (DARC) for invasion. Region II of PvDBP contains many allelic polymorphisms likely to have arisen by host immune selection. Successful vaccine development necessitates a deeper understanding of the role of these polymorphisms in both parasite function and evasion of host immunity. A 3D structure of the homologous P. knowlesi DBP predicts that most variant residues are surface-exposed, including N417K, which is a dimorphic residue change that has previously been shown to be part of a linked haplotype that alters DBP sensitivity to inhibitory antibody. In natural isolates only two residues are found at this site, asparagine (N) and lysine (K). Site-directed mutagenesis of residue 417 was used to create a panel of 20 amino acid variants that were then examined for their binding phenotype and response to immune sera. Our results suggest that the observed dimorphism likely arose due to both structural requirements and immune selection pressure. To our knowledge, this is the first exhaustive examination of this kind of the role of a single amino acid residue in antigenic character and binding ability. Our results demonstrate that a single amino acid substitution can dramatically alter both the ability of the PvDBP to bind to human erythrocytes and its antigenic character

Heavy metals in the irrigation water, soils and vegetables in the Philippi horticultural area in the Western Cape Province of South Africa

The aims of this study were to investigate the extent of heavy metal contamination in the Philippi horticultural area in the Western Cape Province, South Africa. Concentrations of Cd, Cr, Cu, Mn, Ni, Pb and Zn were determined in the irrigation water, soils and vegetables in both winter and summer cropping seasons with an ICP-AES and tested against certified standards. Differences were found in heavy metal concentrations between the winter and summer cropping seasons in the irrigation water, soils and vegetables. Certain heavy metals exceeded the maximum permissible concentrations in the irrigation water, soils and vegetables produced in South Africa. These toxic concentrations were predominantly found in the summer cropping season for the soils and in the crops produced in winter. It is thus suggested that further studies are carried out in the Philippi horticultural area to determine the sources of the heavy metals to try and mitigate the inputs thereof and therefore reduce the amount of heavy metals entering the human food chain.ISI & Scopu

Head Exposure to Cold during Whole-Body Cryostimulation: Influence on Thermal Response and Autonomic Modulation

Recent research on whole-body cryotherapy has hypothesized a major responsibility of head cooling in the physiological changes classically reported after a cryostimulation session. The aim of this experiment was to verify this hypothesis by studying the influence of exposing the head to cold during whole-body cryostimulation sessions, on the thermal response and the autonomic nervous system (ANS). Over five consecutive days, two groups of 10 participants performed one whole-body cryostimulation session daily, in one of two different systems; one exposing the whole-body to cold (whole-body cryostimulation, WBC), and the other exposing the whole-body except the head (partial-body cryostimulation, PBC).10 participants constituted a control group (CON) not receiving any cryostimulation. In order to isolate the head-cooling effect on recorded variables, it was ensured that the WBC and PBC systems induced the same decrease in skin temperature for all body regions (mean decrease over the 5 exposures: -8.6°C±1.3°C and -8.3±0.7°C for WBC and PBC, respectively), which persisted up to 20-min after the sessions (P20). The WBC sessions caused an almost certain decrease in tympanic temperature from Pre to P20 (-0.28 ±0.11°C), while it only decreased at P20 (-0.14±0.05°C) after PBC sessions. Heart rate almost certainly decreased after PBC (-8.6%) and WBC (-12.3%) sessions. Resting vagal-related heart rate variability indices (the root-mean square difference of successive normal R-R intervals, RMSSD, and high frequency band, HF) were very likely to almost certainly increased after PBC (RMSSD:+49.1%, HF: +123.3%) and WBC (RMSSD: +38.8%, HF:+70.3%). Plasma norepinephrine concentration was likely increased in similar proportions after PBC and WBC, but only after the first session. Both cryostimulation techniques stimulated the ANS with a predominance of parasympathetic tone activation from the first to the fifth session and in slightly greater proportion with WBC than PBC. The main result of this study indicates that the head exposure to cold during whole-body cryostimulation may not be the main factor responsible for the effects of cryostimulation on the ANS

Development of the infant foot as a load bearing structure : study protocol for a longitudinal evaluation (the Small Steps study)

Background An improved understanding of the structural and functional development of the paediatric foot is fundamental to a strong theoretical framework for health professionals and scientists. An infant’s transition from sitting, through crawling and cruising, to walking is when the structures and function of the foot must adapt to bearing load. The adaptation of skin and other hard and soft tissue, and foot and gait biomechanics, during this time is poorly understood. This is because data characterising the foot tissue and loading pre-walking onset does not exist. Of the existing kinematic and plantar pressure data, few studies have collected data which reflects the real-life activities of infants with modern equipment. Methods This is a longitudinal study and part of the Great Foundations Initiative, a collaborative project between the University of Brighton and the University of Salford, which is seeking to improve foot health in children. Two cohorts of 50 infants will be recruited at the two sites (University of Brighton, Eastbourne, UK and University of Salford, Salford, UK). Infants will be recruited when they first reach for their feet and attend four laboratory visits at milestones related to foot loading, with experienced independent walking being the final milestone. Data collection will include tissue characteristics (skin thickness, texture, elasticity, pH and tendon thickness and cross-sectional area), plantar pressures and kinematics captured during real world locomotion tasks. Discussion This study will provide a database characterising the development of the infant foot as it becomes a weight bearing structure. The data will allow effective comparison and quantification of changes in structure and function due to maturation and loading by measuring pre and post established walking. Additional variables which impact on the development of the foot (gender, ethnicity and body weight) will also be factored into our analysis. This will help us to advance understanding of the determinants of foot development in early childhood

Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand

Plasmodium vivax Duffy binding protein region II (DBPII) is an important vaccine candidate for antibody-mediated immunity against vivax malaria. A significant challenge for vaccine development of DBPII is its highly polymorphic nature that alters sensitivity to neutralizing antibody responses. Here, we aim to characterize naturally-acquired neutralizing antibodies against DBPII in individual Thai residents to give insight into P. vivax vaccine development in Thailand. Anti-DBPII IgG significantly increased in acute vivax infections compared to uninfected residents and naive controls. Antibody titers and functional anti-DBPII inhibition varied widely and there was no association between titer and inhibition activity. Most high titer plasmas had only a moderate to no functional inhibitory effect on DBP binding to erythrocytes, indicating the protective immunity against DBPII binding is strain specific. Only 5 of 54 samples were highly inhibitory against DBP erythrocyte-binding function. Previously identified target epitopes of inhibitory anti-DBPPII IgG (H1, H2 and H3) were localized to the dimer interface that forms the DARC binding pocket. Amino acid polymorphisms (monomorphic or dimorphic) in H1 and H3 protective epitopes change sensitivity of immune inhibition by alteration of neutralizing antibody recognition. The present study indicates Thai variant H1.T1 (R308S), H3.T1 (D384G) and H3.T3 (K386N) are the most important variants for a DBPII candidate vaccine needed to protect P. vivax in Thai residents