568 research outputs found
A systematic analysis on the clinical safety and efficacy of onco-virotherapy
Several onco-virotherapy candidates have been developed and clinically evaluated for the treatment of cancer, and several are approved for clinical use. In this systematic review we explored the clinical impact of onco-virotherapy compared to other cancer therapies by analyzing factors such as trial design, patient background, therapy design, delivery strategies, and study outcomes. For this purpose, we retrieved clinical studies from three platforms: ClinicalTrials.gov, PubMed, and EMBASE. We found that most studies were performed in patients with advanced and metastatic tumors, using a broad range of genetically engineered vectors and mainly administered intratumorally. Therapeutic safety was the most frequently assessed outcome, while relatively few studies focused on immunological antitumor responses. Moreover, only 59 out of 896 clinical studies were randomized controlled trials reporting comparative data. This systemic review thus reveals the need of more, and better controlled, clinical studies to increase our understanding on the application of onco-virotherapy either as a single treatment or in combination with other cancer immunotherapies
Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: Proof of principle
Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium
The effect of metabolic phenotype on sociability and social group size preference in a coral reef fish
Although individuals within social groups experience reduced predation risk and find food patches more consistently, there can be competition for food among groupmates. Individuals with a higher standard metabolic rate (SMR) may be less social, to prioritize food acquisition over defense, while a greater maximum metabolic rate (MMR) may modulate sociability through increased competitive ability. Therefore, in theory, individuals with a higher SMR may prefer smaller groups and those with greater MMR may prefer larger groups. We examined links among metabolic phenotype, sociability, and choice of group size in the redbelly yellowtail fusilier Caesio cuning. Individuals were exposed to three association tests: (a) a choice between two fish or zero fish; (b) a choice between five fish or zero fish; and (c) a choice between two fish and five fish. The first two tests quantified sociability while the third measured relative group size choice. Although there was no link between SMR and sociability, fish with a higher MMR were more social than those individuals with a lower MMR. While no correlation was found between MMR and group size choice, there was weak evidence that, if anything, individuals with a higher SMR preferred larger groups, contrary to our hypothesis. As C. cuning is an active fish that spends a large proportion of time operating above SMR, this result could suggest that the links between sociability and SMR may shift depending on a speciesâ routine behavior. Links between sociability and MMR may arise if competitive ability allows individuals to obtain resources within groups. Although metabolic traits had no significant influence on group size choice, variation in food availability or predation risk could alter the effects of metabolism on group size choice
The theory of canonical perturbations applied to attitude dynamics and to the Earth rotation. Osculating and nonosculating Andoyer variables
The Hamiltonian theory of Earth rotation, known as the Kinoshita-Souchay
theory, operates with nonosculating Andoyer elements. This situation parallels
a similar phenomenon that often happens (but seldom gets noticed) in orbital
dynamics, when the standard Lagrange-type or Delaunay-type planetary equations
unexpectedly render nonosculating orbital elements. In orbital mechanics,
osculation loss happens when a velocity-dependent perturbation is plugged into
the standard planetary equations. In attitude mechanics, osculation is lost
when an angular-velocity-dependent disturbance is plugged in the standard
dynamical equations for the Andoyer elements. We encounter exactly this
situation in the theory of Earth rotation, because this theory contains an
angular-velocity-dependent perturbation (the switch from an inertial frame to
that associated with the precessing ecliptic of date).
While the osculation loss does not influence the predictions for the figure
axis of the planet, it considerably alters the predictions for the
instantaneous spin-axis' orientation. We explore this issue in great detail
Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease
The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site
Medical treatment of pediatric urolithiasis
In recent years the incidence of pediatric stone disease has increased several fold, mostly due to hypercalciuria and hypocitraturia. The goal of medical treatment is to protect the patient from formation of new stones and expansion of existing ones. The non-pharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. The pharmacological treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. This review discusses the current options of medical treatment of pediatric urolithiasis
Lorentz Covariant Theory of Light Propagation in Gravitational Fields of Arbitrary-Moving Bodies
The Lorentz covariant theory of propagation of light in the (weak)
gravitational fields of N-body systems consisting of arbitrarily moving
point-like bodies with constant masses is constructed. The theory is based on
the Lienard-Wiechert presentation of the metric tensor. A new approach for
integrating the equations of motion of light particles depending on the
retarded time argument is applied. In an approximation which is linear with
respect to the universal gravitational constant, G, the equations of light
propagation are integrated by quadratures and, moreover, an expression for the
tangent vector to the perturbed trajectory of light ray is found in terms of
instanteneous functions of the retarded time. General expressions for the
relativistic time delay, the angle of light deflection, and gravitational red
shift are derived. They generalize previously known results for the case of
static or uniformly moving bodies. The most important applications of the
theory are given. They include a discussion of the velocity dependent terms in
the gravitational lens equation, the Shapiro time delay in binary pulsars, and
a precise theoretical formulation of the general relativistic algorithm of data
processing of radio and optical astrometric measurements in the non-stationary
gravitational field of the solar system. Finally, proposals for future
theoretical work being important for astrophysical applications are formulated.Comment: 77 pages, 7 figures, list of references is updated, to be published
in Phys. Rev. D6
Astrometry and geodesy with radio interferometry: experiments, models, results
Summarizes current status of radio interferometry at radio frequencies
between Earth-based receivers, for astrometric and geodetic applications.
Emphasizes theoretical models of VLBI observables that are required to extract
results at the present accuracy levels of 1 cm and 1 nanoradian. Highlights the
achievements of VLBI during the past two decades in reference frames, Earth
orientation, atmospheric effects on microwave propagation, and relativity.Comment: 83 pages, 19 Postscript figures. To be published in Rev. Mod. Phys.,
Vol. 70, Oct. 199
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