Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they ...could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.
Carbon-based quantum dots (CBQDs), sulfur-doped carbon-based quantum dots (S-CBQDs), and nitrogen-doped carbon-based quantum dots (N-CBQDs) have strong potential for drug delivery platforms. They ...were conjugated with andrographolide, a well-known hydrophobic drug, to study the concomitant changes in hydrophilicity. The interactions between these nanomaterials and the drug were studied by characterizing the optical and structural properties of the nanoparticles before and after coupling with the drug. It was found that the interaction of the drug with these nanomaterials produced noticeable changes in their optical and structural properties. Moreover, the partition coefficient for the nanocomposites was determined by NMR. The results indicate that conjugating the drug with the nanoparticles significantly enhanced its affinity for the aqueous phase, from 2.632 to 0.1117, thereby opening the possibility of using this approach for developing an effective drug delivery platform for this hydrophobic drug.
This study aimed to analyze epidemiological indicators related to seroprevalent and seroincident cases of spotted fever group rickettsiae (SFGR) and to identify housing conditions related to tick ...infestation. A prospective study (2016-2018) was conducted to examine rickettsial seropositivity in humans, domestic animals, and wild mammals in the municipality of Uramita, Antioquia, Colombia, where a previous Rickettsia rickettsii outbreak was reported from 2014 to 2015. The seroprevalence and its associated factors were estimated at baseline, and the seroincidence and its risk factors for humans were estimated 20 months later. A cross-sectional analysis was performed to evaluate the housing conditions linked to tick infestation. The SFGR seroprevalence was 26.70% (95% confidence interval CI, 20.79-31.37), and the factors associated with SFGR seropositivity were male sex (adjusted prevalence ratio PRa, 1.67; 95% CI, 1.19-2.32), age (evaluated in 5-year increments) (PRa, 1.05; 95% CI, 1.01-1.09), and household proximity (PRascattered vs. very near=3.87; 95% CI, 1.12-8.66). The overall seroincidence was 7.40% (95% CI, 4.71-11.06), and the factors associated with SFGR seroincident cases were the presence of wild animals (adjusted relative risk RRa, 2.46; 95% CI, 1.06-4.72) and the presence of trees in the peri-domiciliary area (RRa, 0.47; 95% CI, 0.23-0.94). The prevalence of house tick infestation was 27.81% (95% CI, 21.93-34.80), and the factors associated with infestation were dirt floors (PRa, 5.88; 95% CI, 2.28-10.31), fiber cement roofs (PRa, 1.76; 95% CI, 1.07-2.83), and the presence of canines in peri-domiciliary or intra-domiciliary areas (PRa, 5.05; 95% CI, 3.31-7.19). Seropositivity rates for canines and opossums were 35.62% (26/73) and 100% (6/6), respectively. Identification of these factors will help to implement efficient surveillance programs in Colombia.
ABSTRACT Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for ...neutrino events with deposited energies TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, -induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index −2.50 0.09 and a flux at 100 TeV of . Under the same assumptions, an unbroken power law with index −2 is disfavored with a significance of 3.8 (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 (p = 1.7%) if instead we compare the best fit to a spectrum with index −2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a e fraction of 0.18 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 (p = 0.014%).
We present results on searches for point-like sources of neutrinos using four years of IceCube data, including the first year of data from the completed 86 string detector. The total livetime of the ...combined data set is 1373 days. For an E super(-2) spectrum, the observed 90% C.L. flux upper limits are ~10 super(-12) TeV super(-1) cm super(-2) s super(-1) for energies between 1 TeV and 1 PeV in the northern sky and ~10 super(-11) TeV super(-1) cm super(-2) s super(-1) for energies between 100 TeV and 100 PeV in the southern sky. This represents a 40% improvement compared to previous publications, resulting from both the additional year of data and the introduction of improved reconstructions. In addition, we present the first results from an all-sky search for extended sources of neutrinos. We update the results of searches for neutrino emission from stacked catalogs of sources and test five new catalogs; two of Galactic supernova remnants and three of active galactic nuclei. In all cases, the data are compatible with the background-only hypothesis, and upper limits on the flux of muon neutrinos are reported for the sources considered.
ABSTRACT In this paper searches for flaring astrophysical neutrino sources and sources with periodic emission with the IceCube neutrino telescope are presented. In contrast to time-integrated ...searches, where steady emission is assumed, the analyses presented here look for a time-dependent signal of neutrinos using the information from the neutrino arrival times to enhance the discovery potential. A search was performed for correlations between neutrino arrival times and directions, as well as neutrino emission following time-dependent light curves, sporadic emission, or periodicities of candidate sources. These include active galactic nuclei, soft γ-ray repeaters, supernova remnants hosting pulsars, microquasars, and X-ray binaries. The work presented here updates and extends previously published results to a longer period that covers 4 years of data from 2008 April 5 to 2012 May 16, including the first year of operation of the completed 86 string detector. The analyses did not find any significant time-dependent point sources of neutrinos, and the results were used to set upper limits on the neutrino flux from source candidates.
We present the results of the first IceCube search for dark matter annihilation in the center of the Earth. Weakly interacting massive particles (WIMPs), candidates for dark matter, can scatter off ...nuclei inside the Earth and fall below its escape velocity. Over time the captured WIMPs will be accumulated and may eventually self-annihilate. Among the annihilation products only neutrinos can escape from the center of the Earth. Large-scale neutrino telescopes, such as the cubic kilometer IceCube Neutrino Observatory located at the South Pole, can be used to search for such neutrino fluxes. Data from 327 days of detector livetime during 2011/2012 were analyzed. No excess beyond the expected background from atmospheric neutrinos was detected. The derived upper limits on the annihilation rate of WIMPs in the Earth and the resulting muon flux are an order of magnitude stronger than the limits of the last analysis performed with data from IceCube's predecessor AMANDA. The limits can be translated in terms of a spin-independent WIMP-nucleon cross section. For a WIMP mass of 50 GeV this analysis results in the most restrictive limits achieved with IceCube data.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Milky Way is expected to be embedded in a halo of dark matter particles, with the highest density in the central region, and decreasing density with the halo-centric radius. Dark matter might be ...indirectly detectable at Earth through a flux of stable particles generated in dark matter annihilations and peaked in the direction of the Galactic Center. We present a search for an excess flux of muon (anti-) neutrinos from dark matter annihilation in the Galactic Center using the cubic-kilometer-sized IceCube neutrino detector at the South Pole. There, the Galactic Center is always seen above the horizon. Thus, new and dedicated veto techniques against atmospheric muons are required to make the southern hemisphere accessible for IceCube. We used 319.7 live-days of data from IceCube operating in its 79-string configuration during 2010 and 2011. No neutrino excess was found and the final result is compatible with the background. We present upper limits on the self-annihilation cross-section, , for WIMP masses ranging from 30 GeV up to 10 TeV, assuming cuspy (NFW) and flat-cored (Burkert) dark matter halo profiles, reaching down to cm s , and cm s for the channel, respectively.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by ...an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The nu(mu) energy unfolding described in this paper is based on data taken with IceCube in its 79-string ...configuration. A sample of muon neutrino charged-current interactions with a purity of 99.5% was selected by means of amultivariate classification process based on machine learning. The subsequent unfolding was performed using the software TRUEE. The resulting spectrum covers an E-nu-range of more than four orders of magnitude from 125 GeV to 3.2 PeV. Compared to the Honda atmospheric neutrino flux model, the energy spectrum shows an excess of more than 1.9 sigma in four adjacent bins for neutrino energies E-nu >= 177.8 TeV. The obtained spectrum is fully compatible with previous measurements of the atmospheric neutrino flux and recent IceCube measurements of a flux of high-energy astrophysical neutrinos.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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