Harnessing recombinase polymerase amplification for rapid multi-gene detection of SARS-CoV-2 in resource-limited settings

The COVID-19 pandemic is challenging diagnostic testing capacity worldwide. The mass testing needed to limit the spread of the virus requires new molecular diagnostic tests to dramatically widen access at the point-of-care in resource-limited settings. Isothermal molecular assays have emerged as a promising technology, given the faster turn-around time and minimal equipment compared to gold standard laboratory PCR methods. However, unlike PCR, they do not typically target multiple SARS-CoV-2 genes, risking sensitivity and specificity. Moreover, they often require multiple steps thus adding complexity and delays. Here we develop a multiplexed, 1-2 step, fast (20-30 minutes) SARS-CoV-2 molecular test using reverse transcription recombinase polymerase amplification to simultaneously detect two conserved targets - the E and RdRP genes. The agile multi-gene platform offers two complementary detection methods: real-time fluorescence or dipstick. The analytical sensitivity of the fluorescence test was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick was 130 (95% CI: 82-500) RNA copies per reaction. High specificity was found against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing in decentralised settings, with minimal or equipment-free incubation methods and a user-friendly prototype smartphone application. This rapid, simple, ultrasensitive and multiplexed molecular test offers valuable advantages over gold standard tests and in future could be configurated to detect emerging variants of concern

Electrical characterization of the soft breakdown failure mode in MgO layers

The soft breakdown (SBD) failure mode in 20 nm thick MgO dielectric layers grown on Si substrates was investigated. We show that during a constant voltage stress, charge trapping and progressive breakdown coexist, and that the degradation dynamics is captured by a power-law time dependence. We also show that the SBD current-voltage (I-V) characteristics follow the power-law model I = aVb typical of this conduction mechanism but in a wider voltage window than the one reported in the past for SiO2. The relationship between the magnitude of the current and the normalized differential conductance was analyzed

Hashimoto’s thyroiditis and acute chest syndrome revealing sickle cell anemia in a 32 years female patient

Sickle cell anemia results from a single amino acid substitution in the gene encoding the 4-globin subunit. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. Hashimoto's thyroiditis is a common thyroid disease now recognized as an autoimmune thyroid disorder, it is usually thought to be haemolytic autoimmune anemia. We report the case of a 32 years old women admitted for chest pain and haemolysis anemia in which Hashimoto's thyroiditis and sickle cell anemia were found. In our observation the patient is a young woman whose examination did not show signs of goitre but the analysis of thyroid function tests performed before an uto-immune hemolytic anemia (confirmed by a high level of unconjugated bilirubin and a Coombs test positive for IgG) has found thyroid stimulating hormone (TSH) and positive thyroid antibody at rates in excess of 4.5 times their normal value. In the same period, as the hemolytic anemia, and before the atypical chest pain and anguish they generated in the patient, the search for hemoglobinopathies was made despite the absence of a family history of haematological disease or painful attacks in childhood. Patient electrophoresis's led to research similar cases in the family. The mother was the first to be analyzed with ultimately diagnosed with sickle cell trait have previously been ignored. This case would be a form with few symptoms because the patient does not describe painful crises in childhood or adolescence

Seismic risk in the city of Al Hoceima (north of Morocco) using the vulnerability index method, applied in Risk-UE project

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-016-2566-8Al Hoceima is one of the most seismic active regions in north of Morocco. It is demonstrated by the large seismic episodes reported in seismic catalogs and research studies. However, seismic risk is relatively high due to vulnerable buildings that are either old or don’t respect seismic standards. Our aim is to present a study about seismic risk and seismic scenarios for the city of Al Hoceima. The seismic vulnerability of the existing residential buildings was evaluated using the vulnerability index method (Risk-UE). It was chosen to be adapted and applied to the Moroccan constructions for its practicality and simple methodology. A visual inspection of 1102 buildings was carried out to assess the vulnerability factors. As for seismic hazard, it was evaluated in terms of macroseismic intensity for two scenarios (a deterministic and probabilistic scenario). The maps of seismic risk are represented by direct damage on buildings, damage to population and economic cost. According to the results, the main vulnerability index of the city is equal to 0.49 and the seismic risk is estimated as Slight (main damage grade equal to 0.9 for the deterministic scenario and 0.7 for the probabilistic scenario). However, Moderate to heavy damage is expected in areas located in the newer extensions, in both the east and west of the city. Important economic losses and damage to the population are expected in these areas as well. The maps elaborated can be a potential guide to the decision making in the field of seismic risk prevention and mitigation strategies in Al Hoceima.Peer ReviewedPostprint (author's final draft

Analysis of electron mobility in HfO2/TiN gate metal-oxide-semiconductor field effect transistors: The influence of HfO2 thickness, temperature, and oxide charge

We report a new analysis of electron mobility in HfO2/TiN gate metal-oxide-semiconductor field effect transistors (MOSFETs) by investigating the influence of HfO2 thickness (1.6-3 nm), temperature (50-350 K), and oxide charge (similar to 1x10(11)-8x10(12) cm(-2)) in the high inversion charge region. The fixed oxide charge and interface state densities are deliberately increased using negative-bias-temperature stress, allowing the determination of the Coulomb scattering term as a function of temperature for various oxide charge levels. The temperature dependence of the Coulomb scattering term is consistent with the case of a strongly screened Coulomb potential. Using the experimentally determined temperature dependence of Coulomb scattering term, a model is developed for the electron mobility, including the effects oxide charge (mu(C)), high-k phonon (mu(Ph-Hk)), silicon phonon (mu(Ph-Si)), and surface roughness scattering (mu(SR)). The model provides an accurate description of the experimental data for variations in HfO2 thickness, temperature, and oxide charge. Using the model the relative contributions of each mobility component are presented for varying oxide charge and high-k thickness. Scaling of the HfO2 physical thickness provided a reduction in the oxide charge and high-k phonon scattering mechanisms, leading to an increase in electron mobility in HfO2/TiN gate MOSFETs

Augmentation of Bone Tunnel Healing in Anterior Cruciate Ligament Grafts: Application of Calcium Phosphates and Other Materials

Bone tunnel healing is an important consideration after anterior cruciate ligament (ACL) replacement surgery. Recently, a variety of materials have been proposed for improving this healing process, including autologous bone tissue, cells, artificial proteins, and calcium salts. Amongst these materials are calcium phosphates (CaPs), which are known for their biocompatibility and are widely commercially available. As with the majority of the materials investigated, CaPs have been shown to advance the healing of bone tunnel tissue in animal studies. Mechanical testing shows fixation strengths to be improved, particularly by the application of CaP-based cement in the bone tunnel. Significantly, CaP-based cements have been shown to produce improvements comparable to those induced by potentially more complex treatments such as biologics (including fibronectin and chitin) and cultured cells. Further investigation of CaP-based treatment in the bone tunnels during ACL replacement is therefore warranted in order to establish what improvements in healing and resulting clinical benefits may be achieved through its application

Tilt order parameters, polarity and inversion phenomena in smectic liquid crystals

The order parameters for the phenomenological description of the smectic-{\it A} to smectic-{\it C} phase transition are formulated on the basis of molecular symmetry and structure. It is shown that, unless the long molecular axis is an axis of two-fold or higher rotational symmetry, the ordering of the molecules in the smectic-{\it C} phase gives rise to more than one tilt order parameter and to one or more polar order parameters. The latter describe the indigenous polarity of the smectic-{\it C} phase, which is not related to molecular chirality but underlies the appearance of spontaneous polarisation in chiral smectics. A phenomenological theory of the phase transition is formulated by means of a Landau expansion in two tilt order parameters (primary and secondary) and an indigenous polarity order parameter. The coupling among these order parameters determines the possibility of sign inversions in the temperature dependence of the spontaneous polarisation and of the helical pitch observed experimentally for some chiral smectic-{\it $C^{\ast}$} materials. The molecular interpretation of the inversion phenomena is examined in the light of the new formulation.Comment: 12 pages, 5 figures, RevTe

Observation of peripheral charge induced low frequency capacitance-voltage behaviour in metal-oxide-semiconductor capacitors on Si and GaAs substrates

We report on experimental observations of room temperature low frequency capacitance-voltage (CV) behaviour in metal oxide semiconductor (MOS) capacitors incorporating high dielectric constant (high-k) gate oxides, measured at ac signal frequencies (2 kHz to 1 MHz), where a low frequency response is not typically expected for Si or GaAs MOS devices. An analysis of the inversion regions of the CV characteristics as a function of area and ac signal frequency for both n and p doped Si and GaAs substrates indicates that the source of the low frequency CV response is an inversion of the semiconductor/high-k interface in the peripheral regions outside the area defined by the metal gate electrode, which is caused by charge in the high-k oxide and/or residual charge on the high-k oxide surface. This effect is reported for MOS capacitors incorporating either MgO or GdSiOx as the high-k layers on Si and also for Al2O3 layers on GaAs(111B). In the case of NiSi/MgO/Si structures, a low frequency CV response is observed on the p-type devices, but is absent in the n-type devices, consistent with positive charge (>8 x 10(10) cm(-2)) on the MgO oxide surface. In the case of the TiN/GdSiOx/Si structures, the peripheral inversion effect is observed for n-type devices, in this case confirmed by the absence of such effects on the p-type devices. Finally, for the case of Au/Ni/Al2O3/GaAs(111B) structures, a low-frequency CV response is observed for n-type devices only, indicating that negative charge (> 3 x 10(12) cm(-2)) on the surface or in the bulk of the oxide is responsible for the peripheral inversion effect. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4729331

In situ H(2)S passivation of In(0.53)Ga(0.47)As/InP metal-oxide-semiconductor capacitors with atomic-layer deposited HfO(2) gate dielectric

We have studied an in situ passivation of In(0.53)Ga(0.47)As, based on H(2)S exposure (50-350 degrees C) following metal organic vapor phase epitaxy growth, prior to atomic layer deposition of HfO(2) using Hf[N(CH(3))(2)](4) and H(2)O precursors. X-ray photoelectron spectroscopy revealed the suppression of As oxide formation in air exposed InGaAs surfaces for all H(2)S exposure temperatures. Transmission electron microscopy analysis demonstrates a reduction of the interface oxide between the In(0.53)Ga(0.47)As epitaxial layer and the amorphous HfO(2) resulting from the in situ H(2)S passivation. The capacitance-voltage and current-voltage behavior of Pd/HfO(2)/In(0.53)Ga(0.47)As/InP structures demonstrates that the electrical characteristics of samples exposed to 50 degrees C H(2)S at the end of the metal-organic vapor-phase epitaxy In(0.53)Ga(0.47)As growth are comparable to those obtained using an ex situ aqueous (NH(4))(2)S passivation. (c) 2008 American Institute of Physics. (DOI: 10.1063/1.2829586

Temperature and frequency dependent electrical characterization of HfO2/InxGa1-xAs interfaces using capacitance-voltage and conductance methods

Electrical properties of metal-oxide-semiconductor capacitors using atomic layer deposited HfO2 on n-type GaAs or InxGa1-xAs (x=0.53, 0.30, 0.15) epitaxial layers were investigated. Capacitance-voltage (CV) measurements indicated large temperature and frequency dispersion at positive gate bias in devices using n-type GaAs and low In content (x=0.30, 0.15) InxGa1-xAs layers, which is significantly reduced for devices using In0.53Ga0.47As. For In0.53Ga0.47As devices, the CV response at negative gate bias is most likely characteristic of an interface state response and may not be indicative of true inversion. The conductance technique on Pd/HfO2/In0.53Ga0.47As/InP shows reductions in interface state densities by In0.53Ga0.47As surface passivation and forming gas annealing (325 degrees C). (C) 2009 American Institute of Physics. (DOI: 10.1063/1.3089688