Autophagy and Cell Death in Alzheimer’s, Parkinson’s and Prion Diseases

Neurodegenerative brain disorders (NBD) impair brain cells’ proteostasis with the accumulation of normal, mutant, misfolded or unfolded proteins in the endoplasmic reticulum (ER). The increased ER burden of these proteins elicits the unfolded protein response (UPR) and stimulates autophagy (AUT). In the short term, UPR and AUT attenuate ER’s burden. With prolonged ER stress, the UPR changes from supporting cell survival to promoting apoptosis. The failure of the UPR, to meet the increased protein burden, leads to an increase in cytosolic protein accumulation that initially further stimulates AUT. Over time, the accumulated proteins in the cytosol undergo post-translational changes into toxic monomers and oligomers that repress AUT at multiple levels and promote cell death. This review describes the interlinked signalling pathways of AUT, apoptosis and necroptosis and their modulation by Alzheimer’s, Parkinson’s and prion diseases and outlines the pharmacological strategies for targeting AUT, apoptosis and necroptosis signalling pathways

Postavka konačne inačne teorije kvantnoj teoriji polja

The proposed framework is intended to faciliate the search for Lagrangian-based regularizations that introduce only such coefficients which are not regarded as formal auxiliary parameters that will eventually be disposed of during renormalization. Using the path-integral formalism, we put forward a new framework for such finite, alternative quantum theories to a given quantum field theory that have no formal auxiliary parameters. The corresponding alternative, perturbative Green functions are acceptably regularized perturbative expansions of the original Green functions, causal and imply no unphysical free particles. To demonstrate that the proposed framework is feasible, we provide an alternative to the quantum field theory with the φ4 interaction.Predlažu se postavke čiji je cilj olakšanje traženja regularizacija uz primjenu samo onih koeficijenata koji se ne smatraju formalnim pomoćnim parametrima, a koji se kasnije odbacuju renormalizacijom. Rabeći formalizam integrala po putevima, izlažemo novu postavku za takve konačne, inačne kvantne teorije danoj kvantnoj teoriji polja koja nema formalne pomoćne parametre. Odgovarajuće inačne perturbativne Greeenove funkcije su prihvatljivo regulirani perturbativni razvoji izvornih Greenovih funkcija, kauzalni su i ne uključuju nefizikalne slobodne čestice. Radi pokazivanja da je predložena postavka ostvariva, izlažemo inačicu kvantnoj teoriji polja s φ4 interakcijom

Dva temeljna problema kvantnog raspršenja osnovnih čestica

We put forward a finite theory of quantum scattering of fundamental particles without using auxiliary particles. It suggests that to avoid ultraviolet divergencies and model faster-than-light effects it suffices to appropriately change only the free-field Lagrangians while retaining their locality in space-time and Lorentz invariance. Using functions of two independent four-vector variables, we base this finite theory on the path-integral formalism in the four-dimensional space-time and the Lehmann-Symanzik-Zimmermann reduction formula.Izlažemo konačnu teoriju kvantnog raspršenja osnovnih čestica bez uvođenja pomoćnih čestica. Ona ukazuje da se mogu izbjeći ultraljubičaste divergencije i izraziti učinci nadsvjetlosnih brzina za što je dovoljna odgovarajuća promjena Lagrangiana bez polja, a zadržava se lokalnost u prostoru-vremenu i Lorentzova invarijantnost. Primjenom funkcija dviju četiri-vektorskih varijabla, zasnivamo tu konačnu teoriju na formalizmu integrala po putevima u četiri-dimenzijskom prostoru-vremenu i na Lehmann-Symanzik-Zimmermannovom sažetom izrazu

Dva temeljna problema kvantnog raspršenja osnovnih čestica

We put forward a finite theory of quantum scattering of fundamental particles without using auxiliary particles. It suggests that to avoid ultraviolet divergencies and model faster-than-light effects it suffices to appropriately change only the free-field Lagrangians while retaining their locality in space-time and Lorentz invariance. Using functions of two independent four-vector variables, we base this finite theory on the path-integral formalism in the four-dimensional space-time and the Lehmann-Symanzik-Zimmermann reduction formula.Izlažemo konačnu teoriju kvantnog raspršenja osnovnih čestica bez uvođenja pomoćnih čestica. Ona ukazuje da se mogu izbjeći ultraljubičaste divergencije i izraziti učinci nadsvjetlosnih brzina za što je dovoljna odgovarajuća promjena Lagrangiana bez polja, a zadržava se lokalnost u prostoru-vremenu i Lorentzova invarijantnost. Primjenom funkcija dviju četiri-vektorskih varijabla, zasnivamo tu konačnu teoriju na formalizmu integrala po putevima u četiri-dimenzijskom prostoru-vremenu i na Lehmann-Symanzik-Zimmermannovom sažetom izrazu

Okvir teorije koja je osnova standardnog modela

We put forward the following, physically motivated premiss for constructing a theory that underlies the standard model in four-dimensional space-time: The Euler-Lagrange equations of such a theory formally resemble some equations of motion underlying fluid-dynamics equations in the kinetic theory of gases. In support of this premiss, we point out local and covariant Lagrangians whose Euler-Lagrange equations contain a subsystem equivalent to the Euler-Lagrange equations of the standard model with covariantly regularized propagators, and a subsystem describing faster-than-light effects.Predlažemo novu, fizički motiviranu postavku za razvijanje teorije koja je osnova standardnog modela u četiri-dimenzijskom prostoru–vremenu: Euler-Lagrangeove jednadžbe te teorije formalno sliče osnovnim jednadžbama dinamike tekućina u kinetičkoj teoriji plinova. Kao podršku toj postavci ističemo lokalnu i kovarijantnu Lagrangeovu funkciju čije Euler-Lagrangeove jednadžbe sadrže podsustav koji je jednakovrijedan Euler-Lagrangeovim jednadžbama standardnog modela s kovarijantno sređenim propagatorima i podsustav koji opisuje učinke iznad brzine svjetlosti

Okvir teorije koja je osnova standardnog modela

We put forward the following, physically motivated premiss for constructing a theory that underlies the standard model in four-dimensional space-time: The Euler-Lagrange equations of such a theory formally resemble some equations of motion underlying fluid-dynamics equations in the kinetic theory of gases. In support of this premiss, we point out local and covariant Lagrangians whose Euler-Lagrange equations contain a subsystem equivalent to the Euler-Lagrange equations of the standard model with covariantly regularized propagators, and a subsystem describing faster-than-light effects.Predlažemo novu, fizički motiviranu postavku za razvijanje teorije koja je osnova standardnog modela u četiri-dimenzijskom prostoru–vremenu: Euler-Lagrangeove jednadžbe te teorije formalno sliče osnovnim jednadžbama dinamike tekućina u kinetičkoj teoriji plinova. Kao podršku toj postavci ističemo lokalnu i kovarijantnu Lagrangeovu funkciju čije Euler-Lagrangeove jednadžbe sadrže podsustav koji je jednakovrijedan Euler-Lagrangeovim jednadžbama standardnog modela s kovarijantno sređenim propagatorima i podsustav koji opisuje učinke iznad brzine svjetlosti

Osnova za konačne inačne teorije kvantnoj teoriji polja. II – Unitarnost

We generalized the \u27t Hooft-Veltman method of unitary regulators to put forward a path-integral framework for finite, alternative theories to a given quantum field theory. We demonstrated that the proposed framework is feasible by providing a finite alternative to the quantum field theory of a single, self-interacting real scalar field. Here we give two properties of self-energy that make the corresponding scattering matrix unitary. We show that the perturbative self-energy has these two properties at least up to the second order in the coupling constant.Poopćili smo ’t Hooft-Veltmanovu metodu unitarnih regulatora radi postavljanja osnove za integrale po putevima za konačne, inačne teorije dane kvantne teorije polja. Pokazali smo da je predložena osnova moguća jer se nalazi konačna inačica kvantnoj teoriji izdvojenog, samodjelujućeg realnog skalarnog polja. Dajemo dva svojstva svojstvene energije koja čine odnosnu matricu raspršenja unitarnom. Pokazujemo da svojstvena energija smetnje ima ta dva svojstva barem do drugog reda stalnice vezanja

Postavka konačne inačne teorije kvantnoj teoriji polja

The proposed framework is intended to faciliate the search for Lagrangian-based regularizations that introduce only such coefficients which are not regarded as formal auxiliary parameters that will eventually be disposed of during renormalization. Using the path-integral formalism, we put forward a new framework for such finite, alternative quantum theories to a given quantum field theory that have no formal auxiliary parameters. The corresponding alternative, perturbative Green functions are acceptably regularized perturbative expansions of the original Green functions, causal and imply no unphysical free particles. To demonstrate that the proposed framework is feasible, we provide an alternative to the quantum field theory with the φ4 interaction.Predlažu se postavke čiji je cilj olakšanje traženja regularizacija uz primjenu samo onih koeficijenata koji se ne smatraju formalnim pomoćnim parametrima, a koji se kasnije odbacuju renormalizacijom. Rabeći formalizam integrala po putevima, izlažemo novu postavku za takve konačne, inačne kvantne teorije danoj kvantnoj teoriji polja koja nema formalne pomoćne parametre. Odgovarajuće inačne perturbativne Greeenove funkcije su prihvatljivo regulirani perturbativni razvoji izvornih Greenovih funkcija, kauzalni su i ne uključuju nefizikalne slobodne čestice. Radi pokazivanja da je predložena postavka ostvariva, izlažemo inačicu kvantnoj teoriji polja s φ4 interakcijom