Bioengineered fluorescent nanoprobe conjugates for tracking human bone cells: In vitro biocompatibility analysis

Herein, we validated novel functionalized hybrid semiconductor bioconjugates made of fluorescent quantum dots (QD) with the surface capped by chitosan (polysaccharide) and chemically modified with O-phospho-L-serine (OPS) that are biocompatible with different human cell sources. The conjugation with a directing signaling molecule (OPS) allows preferential accumulation in human bone mesenchymal stromal cells (HBMSC). The chitosan (Chi) shell with the fluorescent CdS core was characterized by spectroscopical (UV spectrophotometry and photoluminescence), by morphological techniques (Transmission Electron Microscopy (TEM)) and showed small size (ø 2.3 nm) and a stable photoluminescence emission band. The in vitro biocompatibility results were not dependent on the polysaccharide chain length (Chi with higher and lower molecular weight) but were remarkably affected by the surface modification (Chi or Chi-OPS). In addition, the efficiency of nanoparticles uptake by the cells was dependent on cells nature (human primary cells or cell lines) and tissue source (bone or skin) in the presence or absence of the OPS modification. The complex cellular uptake pathways involved in the cell labeling with the nanoparticles do not interfere on the normal cellular biology (adhesion and proliferation), osteogenic differentiation, and gene expression. The bone cells particles uptake evaluation showed a possible pathway by Caveolin-1 that regulates cell transduction in the membrane’s Caveolae. Caveolae mediates non-specific endocytosis, and it is upregulated in HBMSC. The OPS-modified nanoparticles promoted an intense intracellular trafficking by the HBMSCs that showed late-osteoblast phenotype with an increase of extracellular matrix (ECM) mineralization (Alizarin red and Von Kossa staining for calcium phosphate crystals). In this work, the OPS modified bioconjugated QD proved to be a reliable and stable fluorescent bioprobe for cell imaging and targeting research that could also help in clarifying some cellular mechanisms of particles intracellular traffic through the cytoplasmic membrane and osteogenic differentiation induction. The in vitro HBMSC’s biocompatibility responses indicated that the OPS-modified chitosan QDs have a prospective future in laboratory and pre-clinical applications such as bioimaging analysis and for ex-vivo cellular evaluation of biomedical implants.This work was supported by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) (POCI/01/0145/FEDER/007265) and the project NORTE-01-0145-FEDER-000012, supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). In addition, it was supported by Portuguese funds through FCT/MCTES in the framework of the project UID/BIM/04293/2019 and Christiane Salgado contract (CEECINST/00091/2018)

An instability of higher-dimensional rotating black holes

We present the first example of a linearized gravitational instability of an asymptotically flat vacuum black hole. We study perturbations of a Myers-Perry black hole with equal angular momenta in an odd number of dimensions. We find no evidence of any instability in five or seven dimensions, but in nine dimensions, for sufficiently rapid rotation, we find perturbations that grow exponentially in time. The onset of instability is associated with the appearance of time-independent perturbations which generically break all but one of the rotational symmetries. This is interpreted as evidence for the existence of a new 70-parameter family of black hole solutions with only a single rotational symmetry. We also present results for the Gregory-Laflamme instability of rotating black strings, demonstrating that rotation makes black strings more unstable.Comment: 38 pages, 13 figure

Ultraspinning instability: the missing link

We study linearized perturbations of Myers-Perry black holes in d=7, with two of the three angular momenta set to be equal, and show that instabilities always appear before extremality. Analogous results are expected for all higher odd d. We determine numerically the stationary perturbations that mark the onset of instability for the modes that preserve the isometries of the background. The onset is continuously connected between the previously studied sectors of solutions with a single angular momentum and solutions with all angular momenta equal. This shows that the near-extremality instabilities are of the same nature as the ultraspinning instability of d>5 singly-spinning solutions, for which the angular momentum is unbounded. Our results raise the question of whether there are any extremal Myers-Perry black holes which are stable in d>5.Comment: 19 pages. 1 figur

Ultraspinning instability of anti-de Sitter black holes

Myers-Perry black holes with a single spin in d>5 have been shown to be unstable if rotating sufficiently rapidly. We extend the numerical analysis which allowed for that result to the asymptotically AdS case. We determine numerically the stationary perturbations that mark the onset of the instabilities for the modes that preserve the rotational symmetries of the background. The parameter space of solutions is thoroughly analysed, and the onset of the instabilities is obtained as a function of the cosmological constant. Each of these perturbations has been conjectured to represent a bifurcation point to a new phase of stationary AdS black holes, and this is consistent with our results.Comment: 22 pages, 7 figures. v2: Reference added. Matches published versio

Thermodynamic instability of doubly spinning black objects

We investigate the thermodynamic stability of neutral black objects with (at least) two angular momenta. We use the quasilocal formalism to compute the grand canonical potential and show that the doubly spinning black ring is thermodynamically unstable. We consider the thermodynamic instabilities of ultra-spinning black objects and point out a subtle relation between the microcanonical and grand canonical ensembles. We also find the location of the black string/membrane phases of doubly spinning black objects.Comment: 25 pages, 7 figures v2: matches the published versio

A cross-sectional study of vascular risk factors in a rural South African population : data from the Southern African Stroke Prevention Initiative (SASPI)

Background: Rural sub-Saharan Africa is at an early stage of economic and health transition. It is predicted that the 21st century will see a serious added economic burden from non-communicable disease including vascular disease in low-income countries as they progress through the transition. The stage of vascular disease in a population is thought to result from the prevalence of vascular risk factors. Already hypertension and stroke are common in adults in sub-Saharan Africa. Using a multidisciplinary approach we aimed to assess the prevalence of several vascular risk factors in Agincourt, a rural demographic surveillance site in South Africa. Methods: We performed a cross sectional random sample survey of adults aged over 35 in Agincourt (population ≈ 70 000). Participants were visited at home by a trained nurse who administered a questionnaire, carried out clinical measurements and took a blood sample. From this we assessed participants' history of vascular risk, blood pressure using an OMRON 705 CP monitor, waist circumference, body mass index (BMI), ankle brachial index (ABI), and total and HDL cholesterol. Results: 402 people (24% men) participated. There was a high prevalence of smoking in men, but the number of cigarettes smoked was small. There was a striking difference in mean BMI between men and women (22.8 kg/m2 versus 27.2 kg/m2), but levels of blood pressure were very similar. 43% of participants had a blood pressure greater than 140/90 or were on anti-hypertensive treatment and 37% of participants identified with measured high blood pressure were on pharmacological treatment. 12% of participants had an ABI of < 0.9, sugesting the presence of sub-clinical atheroma. 25.6% of participants had a total cholesterol level > 5 mmol/l. Conclusion: We found a high prevalence of hypertension, obesity in women, and a suggestion of subclinical atheroma despite relatively favourable cholesterol levels in a rural South African population. South Africa is facing the challenge of an emerging epidemic of vascular disease. Research to establish the social determinates of these risk factors and interventions to reduce both individual and population risk are required

Intense violet–blue emission and paramagnetism of nanocrystalline Gd3+ doped ZnO ceramics

Nanocrystalline Zn1-xGdxO (x = 0, 0.02, 0.04, 0.06, and 0.08) ceramics were synthesized by ball milling and subsequent solid-state reaction. The transmission electron microscopy (TEM) micrograph of as synthesized samples revealed the formation of crystallites with an average diameter of 60 nm, and the selected area electron diffraction (SAED) pattern confirmed the formation of wurtzite structure. A red shift in the band gap was observed with increasing Gd3+ concentration. The photoluminescence of nanocrystalline Gd3+ doped ZnO exhibited a strong violet–blue emission. Concentration dependence of the emission intensity of Gd3+ in ZnO was studied, and the critical concentration was found to be 4 mol% of Gd3+. The Gd3+ doped ZnO exhibited paramagnetic behavior at room temperature, and the magnetic moment increased with Gd3+ concentration