Nanomedicines as cancer therapeutics: Current status

As of 21st century, cancer is arguably the most complex and challenging disease known to mankind and an inevitable public health concern of this millennium. Nanotechnology, suitably amalgamated with cancer research, has ushered an era of highly personalized and safer medicines which can improve cancer diagnosis and therapy. A wide variety of nanomedicines are currently under investigation, including polymeric/non-polymeric nanoparticles, dendrimers, quantum dots, carbon nanotubes, lipid- and micelle-based nanoparticles. The bases of these nanomedicines in reducing toxicity associated with cancer therapy are their ability to carry a large payload and multivalent-ligand targeting. This imparts specificity for targeting the tissues as well as bypass resistance mechanisms. The major hurdles on these future medicines are potential toxicity of nanoparticles, which imposes the need of extensive regulatory evaluation before nanomedicines could be utilized as cancer therapeutics. This review highlights nanopharmaceuticals that have been investigated in oncology for various applications (diagnosis, therapeutic delivery and theranostics). It also discusses the effects of nano-sized materials on tissues/organ functions, the possibility of overcoming multi-drug resistance by using nanomedicines and their current clinical status

Xanthine oxidase-derived reactive oxygen metabolites contribute to liver necrosis: protection by 4-hydroxypyrazolo[3,4-d]pyrimidine

AbstractXanthine oxidase (XO) generates reactive oxygen metabolites (ROM) as a by-product while catalyzing their reaction. The present study implicates these ROM in the pathogenesis of liver necrosis produced in rats by the intraperitoneal administration of thioacetamide (TAA; 400 mg/kg b.wt.). After 16 h of TAA administration, the activity of rat liver XO increased significantly compared to that of the control group. At the same time, the level of serum marker enzymes of liver necrosis (aminotransferases and alkaline phosphatase) and tissue malondialdehyde content also increased in TAA treated rats. Tissue malondialdehyde concentration is an indicator of lipid peroxidation and acts as a useful marker of oxidative damage. Pretreatment of rats with XO inhibitor (4-hydroxypyrazolo[3,4-d]pyrimidine; allopurinol (AP)) followed by TAA could lower the hepatotoxin-mediated rise in malondialdehyde level as well as the level of marker enzymes associated with liver necrosis. The survival rate also increased in rats given AP followed by the lethal dose of TAA. In either case, the effect of AP was dose-dependent. Results presented in the paper indicate that increased production of XO-derived ROM contributes to liver necrosis, which can be protected by AP

The second and third Sonine coefficients of a freely cooling granular gas revisited

In its simplest statistical-mechanical description, a granular fluid can be modeled as composed of smooth inelastic hard spheres (with a constant coefficient of normal restitution $\alpha$) whose velocity distribution function obeys the Enskog-Boltzmann equation. The basic state of a granular fluid is the homogeneous cooling state, characterized by a homogeneous, isotropic, and stationary distribution of scaled velocities, $F(\mathbf{c})$. The behavior of $F(\mathbf{c})$ in the domain of thermal velocities ($c\sim 1$) can be characterized by the two first non-trivial coefficients ($a_2$ and $a_3$) of an expansion in Sonine polynomials. The main goals of this paper are to review some of the previous efforts made to estimate (and measure in computer simulations) the $\alpha$-dependence of $a_2$ and $a_3$, to report new computer simulations results of $a_2$ and $a_3$ for two-dimensional systems, and to investigate the possibility of proposing theoretical estimates of $a_2$ and $a_3$ with an optimal compromise between simplicity and accuracy.Comment: 12 pages, 5 figures; v2: minor change

Radiative corrections to low energy neutrino reactions

We show that the radiative corrections to charged current (CC) nuclear reactions with an electron(positron) in the final state are described by a universal function. The consistency of our treatment of the radiative corrections with the procedure used to extract the value of the axial coupling constant $g_A$ is discussed. To illustrate we apply our results to (anti)neutrino deuterium disintegration and to $pp$ fusion in the sun. The limit of vanishing electron mass is considered, and a simple formula valid for E_{obs}\gsim 1 MeV is obtained. The size of the nuclear structure-dependent effects is also discussed. Finally, we consider CC transitions with an electron(positron) in the initial state and discuss some applications to electron capture reactions.Comment: 23 pages, 5 figure

Supernova Neutrinos and the LSND Evidence for Neutrino Oscillations

The observation of the $\bar{\nu}_e$ energy spectrum from a supernova burst can provide constraints on neutrino oscillations. We derive formulas for adiabatic oscillations of supernova antineutrinos for a variety of 3- and 4-neutrino mixing schemes and mass hierarchies which are consistent with the LSND evidence for $\bar{\nu}_{\mu}\to \bar{\nu}_e$ oscillations. Finally, we explore the constraints on these models and LSND given by the supernova SN1987A $\bar{\nu}_e$'s observed by the Kamiokande-2 and IMB-3 detectors.Comment: 8 pages, 3 figures. Changes with respect to original version: appendix added; minor changes in text, figures, reference

Innovative Overheating solution for solar thermal collector using a reflective surface included in the air gap

In this work, a new solution to prevent the overheating of solar collectors in the case of stagnation is presented. The solution proposed consists of inserting a reflective sheet inside the solar collector between the absorber and the glass cover to reduce the incoming energy by reflecting solar radiation. This protection is switched ON or OFF according to the absorber temperature. A prototype has been manufactured and tested in outside conditions and in laboratory. A numerical model of the solar collector with the protection was developed and has been validated. The calculated temperature values are very close to the measured data. The experimental and numerical results showed the good behaviour of the proposed solution

Generalized Parton Distributions from Hadronic Observables: Non-Zero Skewness

We propose a physically motivated parametrization for the unpolarized generalized parton distributions, H and E, valid at both zero and non-zero values of the skewness variable, \zeta. Our approach follows a previous detailed study of the \zeta=0 case where H and E were determined using constraints from simultaneous fits of the experimental data on both the nucleon elastic form factors and the deep inelastic structure functions in the non singlet sector. Additional constraints at \zeta \neq 0 are provided by lattice calculations of the higher moments of generalized parton distributions. We illustrate a method for extracting generalized parton distributions from lattice moments based on a reconstruction using sets of orthogonal polynomials. The inclusion in our fit of data on Deeply Virtual Compton Scattering is also discussed. Our method provides a step towards a model independent extraction of generalized distributions from the data. It also provides an alternative to double distributions based phenomenological models in that we are able to satisfy the polynomiality condition by construction, using a combination of experimental data and lattice, without resorting to any specific mathematical construct.Comment: 29 pages, 8 figures; added references, changed text in several place

Reexamining nonstandard interaction effects on supernova neutrino flavor oscillations

Several extensions of the standard electroweak model allow new four-fermion interactions (nu_a nu_b * ff) with strength eps_ab*G_F, where (a,b) are flavor indices. We revisit their effects on flavor oscillations of massive (anti)neutrinos in supernovae, in order to achieve, in the region above the protoneutron star, an analytical treatment valid for generic values of the neutrino mixing angles (omega,phi,psi)=(theta_12,theta_13,theta_23). Assuming that eps_ab<<1, we find that the leading effects on the flavor transitions occurring at high (H) and low (L) density along the supernova matter profile can be simply embedded through the replacements phi-->phi+eps_H and omega-->omega+eps_L, respectively, where eps_H and eps_L are specific linear combinations of the eps_ab's. Similar replacements hold for eventual oscillations in the Earth matter. From a phenomenological point of view, the most relevant consequence is a possible uncontrolled bias (phi-->phi+eps_H) in the value of the mixing angle phi inferred by inversion of supernova neutrino data. Such a drawback, however, does not preclude the discrimination of the neutrino mass spectrum hierarchy (direct or inverse) through supernova neutrino oscillations.Comment: Text clarified, one figure added. To appear in PR

Sum rules and dualities for generalized parton distributions: is there a holographic principle?

To leading order approximation, the physical content of generalized parton distributions (GPDs) that is accessible in deep virtual electroproduction of photons or mesons is contained in their value on the cross-over trajectory. This trajectory separates the t-channel and s-channel dominated GPD regions. The underlying Lorentz covariance implies correspondence between these two regions through their relation to GPDs on the cross-over trajectory. This point of view leads to a family of GPD sum rules which are a quark analogue of finite energy sum rules and it guides us to a new phenomenological GPD concept. As an example, we discuss the constraints from the JLab/Hall A data on the dominant u-quark GPD H. The question arises whether GPDs are governed by some kind of holographic principle.Comment: 45 pages, 4 figures, Sect. 2 reorganized for clarity. Typos in Eq. (20) corrected. 4 new refs. Matches published versio