We show that the Modified Newtonian Dynamics (MOND) regime can be fully recovered as the weak-field limit of a particular theory of gravity formulated in the metric approach. This is possible when Milgrom's acceleration constant is taken as a fundamental quantity which couples to the theory in a very consistent manner. As a consequence, the scale invariance of the gravitational interaction is naturally broken. In this sense, Newtonian gravity is the weak-field limit of general relativity and MOND is the weak-field limit of that particular extended theory of gravity. We also prove that a Noether's symmetry approach to the problem yields a conserved quantity coherent with this relativistic MONDian extension.
In the pursuit of a general formulation for a modified gravitational theory at the non-relativistic level and as an alternative to the dark matter hypothesis, we construct a model valid over a wide variety of astrophysical scales. Through the inclusion of Milgrom's acceleration constant into a gravitational theory, we show that very general formulae can be constructed for the acceleration felt by a particle. Dimensional analysis shows that this inclusion naturally leads to the appearance of a mass-length scale in gravity, breaking its scale invariance. A particular form of the modified gravitational force is constructed and tested for consistency with observations over a wide range of astrophysical environments, from Solar system to extragalactic scales. We show that over any limited range of physical parameters, which define a specific class of astrophysical objects, the dispersion velocity of a system must be a power law of its mass and size. These powers appear linked together through a natural constraint relation of the theory. This yields a generalized gravitational equilibrium relation valid for all astrophysical systems. A general scheme for treating spherical symmetrical density distributions is presented, which in particular shows that the Fundamental Plane of elliptical galaxies, the Newtonian virial equilibrium, the Tully-Fisher and the Faber-Jackson relations, as well as the scalings observed in local dwarf spheroidal galaxies, are nothing but particular cases of that relation when applied to the appropriate mass-length scales. We discuss the implications of this approach for a modified theory of gravity and emphasize the advantages of working with the force, instead of altering Newton's second law of motion, in the formulation of a gravitational theory.
Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.
In this article we perform a second order perturbation analysis of the gravitational metric theory of gravity f (χ) = χ 3/2 developed by . We show that the theory accounts in detail for two observational facts: (1) the phenomenology of flattened rotation curves associated to the Tully-Fisher relation observed in spiral galaxies, and (2) the details of observations of gravitational lensing in galaxies and groups of galaxies, without the need of any dark matter. We show how all dynamical observations on flat rotation curves and gravitational lensing can be synthesised in terms of the empirically required metric coefficients of any metric theory of gravity. We construct the corresponding metric components for the theory presented at second order in perturbation, which are shown to be perfectly compatible with the empirically derived ones. It is also shown that under the theory being presented, in order to obtain a complete full agreement with the observational results, a specific signature of Riemann's tensor has to be chosen. This signature corresponds to the one most widely used nowadays in relativity theory. Also, a computational program, the MEXICAS (Metric EXtended-gravity Incorporated through a Computer Algebraic System) code, developed for its usage in the Computer Algebraic System (CAS) Maxima for working out perturbations on a metric theory of gravity, is presented and made publicly available.
Multi-tyrosine kinase inhibitors (MTKIs) have thus far had limited success in the treatment of castration-resistant prostate cancer (CRPC). Here, we report a phase I-cleared orally bioavailable MTKI, ESK981, with a novel autophagy inhibitory property that decreased tumor growth in diverse preclinical models of CRPC. The anti-tumor activity of ESK981 was maximized in immunocompetent tumor environments where it upregulated CXCL10 expression through the interferon gamma pathway and promoted functional T cell infiltration, which resulted in enhanced therapeutic response to immune checkpoint blockade. Mechanistically, we identify the lipid kinase PIKfyve as the direct target of ESK981. PIKfyve-knockdown recapitulated ESK981’s anti-tumor activity and enhanced the therapeutic benefit of immune checkpoint blockade. Our study reveals that targeting PIKfyve via ESK981 turns tumors from cold into hot through inhibition of autophagy, which may prime the tumor immune microenvironment in advanced prostate cancer patients and be an effective treatment strategy alone or in combination with immunotherapies.
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