Nanotechnology-Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial-loaded nanocarriers are avidly taken up by macrophages, the main cells hostingMycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment

ASTRA: ASTrometry and phase-Referencing Astronomy on the Keck interferometer

ASTRA (ASTrometric and phase-Referencing Astronomy) is an upgrade to the existing Keck Interferometer which aims at providing new self-phase referencing (high spectral resolution observation of YSOs), dual-field phase referencing (sensitive AGN observations), and astrometric (known exoplanetary systems characterization and galactic center general relativity in strong field regime) capabilities. With the first high spectral resolution mode now offered to the community, this contribution focuses on the progress of the dual field and astrometric modes.Comment: 10 pages, 6 figures, 2 tables, SPIE 201

Detection and Preservation of Biosignatures in Mars Analogs Hot Spring Deposits from the Taupo Volcanic Zone, New Zealand

Characterizing the preservation potential of biosignatures in martian analogs is essential in the quest for biosignatures with martian rovers. Hot spring silica deposits are part of the minerals with a high preservation potential. As part of an ongoing study, we are characterizing the nature and distribution of organic molecules including lipid biomarkers in a range of analog hot spring deposits, evaluating their preservation potential, and determining the potential signals from flight-like experiments. We are focusing on various geothermal fields in the New Zealand Taupo Volcanic Zone with physical and chemical variabilities. Samples are being extracted for lipid biomarker characterization as well as analysis using flight-like experiments from the current and future pyrolyzer-gas chromatographmass spectrometer instruments SAM and MOMA on the Curiosity and Exomars2020 rovers. The aim of work is to improve our knowledge of the detection and preservation of biosignatures in different hot spring lithologies while simultaneously evaluating the potential limits and biases of flight experiments.Fil: Millan, Maëva. University Of Georgetown; Estados Unidos. National Aeronautics and Space Administration; Estados UnidosFil: Campbell, Kathleen A.. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Van Kranendonk, Martin J.. University of New South Wales; AustraliaFil: Sriaporn, Chanenath. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Handley, Kim M.. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Dobson, Michaela. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Camp, Sîan. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Teece, Bonnie. University of New South Wales; AustraliaFil: Guido, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Recursos Minerales. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto de Recursos Minerales; ArgentinaFil: Djokic, Tara. University of New South Wales; AustraliaFil: Farmer, Jack D.. Arizona State University; Estados UnidosFil: Stewart Johnson, Sarah. University Of Georgetown; Estados UnidosEPSC-DPS Joint Meeting 2019GenevaSuizaEuropean Process Safety Centr

Reducing Uncertainties in Carbonate Clumped Isotope Analysis Through Consistent Carbonate-Based Standardization

About a decade after its introduction, the field of carbonate clumped isotope thermometry is rapidly expanding because of the large number of possible applications and its potential to solve long‐standing questions in Earth Sciences. Major factors limiting the application of this method are the very high analytical precision required for meaningful interpretations, the relatively complex sample preparation procedures, and the mass spectrometric corrections needed. In this paper we first briefly review the evolution of the analytical and standardization procedures and discuss the major remaining sources of uncertainty. We propose that the use of carbonate standards to project the results to the carbon dioxide equilibrium scale can improve interlaboratory data comparability and help to solve long‐standing discrepancies between laboratories and temperature calibrations. The use of carbonates reduces uncertainties related to gas preparation and cleaning procedures and ensures equal treatment of samples and standards. We present a set of carbonate standards of diverse composition, discuss how they can be used to correct for mass spectrometric biases, and demonstrate that their use significantly improves the comparability among four laboratories. We propose that the use of these standards or of a similar set of carbonate standards will improve the comparability of data across laboratories.publishedVersio

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing.

Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO