The architecture of multivalent polymers exerts an amplified interaction between attached ligands and targets. In current research, we reveal that a dendronized polymer augments the efficacy of an ...oncolytic peptide (OP; KKWWKKWDipK) for immunotherapy by exploiting (i) “flexible” linear polymer backbone to facilitate interactions with biomembrane systems, and (ii) “rigid” dendronized side chains to enhance the membrane lytic property. We show that a dendronized N-(2-hydroxypropyl)methacrylamide (HPMA) polymer-OP conjugate (PDOP) adopts α-helix secondary structure and induces robust immunogenic cell death (ICD) in cancer cells as characterized by multiple damage-associated molecular patterns (DAMPs) which include intracellular formation of reactive oxygen species (ROS) and surface exposure of calreticulin (CRT). These events convert immunosuppressive 4T1 tumor to an immunoresponsive one by recruiting CD8+ cytotoxic T cells into tumor beds. Combination of PDOP with anti-PD-L1 immune checkpoint blockade (ICB) increases the number of effector memory T cells and completely eradicates 4T1 tumors in mice. Our findings suggest that PDOP is a promising platform for oncolytic immunotherapy.
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The recent SARS-CoV-2 pandemic has brought many questions over the origin of the virus, the threat it poses to animals both in the wild and captivity, and the risks of a permanent viral reservoir ...developing in animals. Animal experiments have shown that a variety of animals can become infected with the virus. While coronaviruses have been known to infect animals for decades, the true intermediate host of the virus has not been identified, with no cases of SARS-CoV-2 in wild animals. The screening of wild, farmed, and domesticated animals is necessary to help us understand the virus and its origins and prevent future outbreaks of both COVID-19 and other diseases. There is intriguing evidence that farmed mink infections (acquired from humans) have led to infection of other farm workers in turn, with a recent outbreak of a mink variant in humans in Denmark. A thorough examination of the current knowledge and evidence of the ability of SARS-CoV-2 to infect different animal species is therefore vital to evaluate the threat of animal to human transmission and reverse zoonosis.
Robust evidence supporting strategies for companion animal antimicrobial stewardship is limited, despite frequent prescription of highest priority critically important antimicrobials (HPCIA). Here we ...describe a randomised controlled trial where electronic prescription data were utilised (August 2018-January 2019) to identify above average HPCIA-prescribing practices (n = 60), which were randomly assigned into a control group (CG) and two intervention groups. In March 2019, the light intervention group (LIG) and heavy intervention group (HIG) were notified of their above average status, and were provided with educational material (LIG, HIG), in-depth benchmarking (HIG), and follow-up meetings (HIG). Following notification, follow-up monitoring lasted for eight months (April-November 2019; post-intervention period) for all intervention groups, though HIG practices were able to access further support (i.e., follow-up meetings) for the first six of these months if requested. Post-intervention, in the HIG a 23.5% and 39.0% reduction in canine (0.5% of total consultations, 95% confidence interval, 0.4-0.6, P = 0.04) and feline (4.4%, 3.4-5.3, P < 0.001) HPCIA-prescribing consultations was observed, compared to the CG (dogs: 0.6%, 0.5-0.8; cats: 7.4%, 6.0-8.7). The LIG was associated with a 16.7% reduction in feline HPCIA prescription (6.1% of total consultations, 5.3-7.0, P = 0.03). Therefore, in this trial we have demonstrated effective strategies for reducing veterinary HPCIA prescription.
We report on several features in the energy spectrum from an ultralow-noise germanium detector operated deep underground. By implementing a new technique able to reject surface events, a number of ...cosmogenic peaks can be observed for the first time. We discuss an irreducible excess of bulklike events below 3 keV in ionization energy. These could be caused by unknown backgrounds, but also dark matter interactions consistent with DAMA/LIBRA. It is not yet possible to determine their origin. Improved constraints are placed on a cosmological origin for the DAMA/LIBRA effect.
Metal foam projectiles are used to generate dynamic pressure–time histories representative of shock loading in water and air. A 1D plastic shock wave analysis is performed for a foam projectile ...impacting a free but rigid mass. It is shown that the pressure versus time pulse exerted on the mass and the shock arrest distance within the foam depend upon the ratio of foam mass to impacted mass, and upon the ratio of quasi-static to hydrodynamic strength of the foam. The theory is supported by two sets of experiments, one where Alporas foam impacts an instrumented Kolsky pressure bar, and one where the foam is fired at a free mass. It is demonstrated that the magnitude and duration of the pressure pulse can be controlled by suitable adjustment of the velocity, length and density of the foam projectile.
African swine fever is widespread in Africa but has occasionally been introduced into other continents. In June 2007, African swine fever was isolated in the Caucasus Region of the Republic of ...Georgia and subsequently in neighboring countries (Armenia, Azerbaijan, and 9 states of the Russian Federation). Previous data for sequencing of 3 genes indicated that the Georgia 2007/1 isolate is closely related to isolates of genotype II, which has been identified in Mozambique, Madagascar, and Zambia. We report the complete genomic coding sequence of the Georgia 2007/1 isolate and comparison with other isolates. A genome sequence of 189,344 bp encoding 166 open reading frames (ORFs) was obtained. Phylogeny based on concatenated sequences of 125 conserved ORFs showed that this isolate clustered most closely with the Mkuzi 1979 isolate. Some ORFs clustered differently, suggesting that recombination may have occurred. Results provide a baseline for monitoring genomic changes in this virus.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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