High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics.

High-frequency conductivity of optically excited charge carriers in hydrogenated nanocrystalline silicon investigated by spectroscopic femtosecond pump-probe reflectivity measurements

We report an investigation into the high-frequency conductivity of optically excited charge carriers far from equilibrium with the lattice. The investigated samples consist of hydrogenated nanocrystalline silicon films grown on a thin film of silicon oxide on top of a silicon substrate. For the investigation, we used an optical femtosecond pump-probe setup to measure the reflectance change of a probe beam. The pump beam ranged between 580 and 820nm, whereas the probe wavelength spanned 770 to 810nm. The pump fluence was fixed at 0.6mJ/cm2. We show that at a fixed delay time of 300fs, the conductivity of the excited electron-hole plasma is described well by a classical conductivity model of a hot charge carrier gas found at Maxwell-Boltzmann distribution, while Fermi-Dirac statics is not suitable. This is corroborated by values retrieved from pump-probe reflectance measurements of the conductivity and its dependence on the excitation wavelength and carrier temperature. The conductivity decreases monotonically as a function of the excitation wavelength, as expected for a nondegenerate charge carrier gas.

High stress monitoring of prestressing tendons in nuclear concrete vessels using fibre-optic sensors

Maintaining the structural health of prestressed concrete nuclear containments is a key element in ensuring nuclear reactors are capable of meeting their safety requirements. This paper discusses the attachment, fabrication and characterisation of optical fibre strain sensors suitable for the prestress monitoring of irradiated steel prestressing tendons. The all-metal fabrication and welding process allowed the instrumented strand to simultaneously monitor and apply stresses up to 1300 MPa (80% of steel's ultimate tensile strength). There were no adverse effects to the strand's mechanical properties or integrity. After sensor relaxation through cyclic stress treatment, strain transfer between the optical fibre sensors and the strand remained at 69%. The fibre strain sensors could also withstand the non-axial forces induced as the strand was deflected around a 4.5 m bend radius. Further development of this technology has the potential to augment current prestress monitoring practices, allowing distributed measurements of short- and long-term prestress losses in nuclear prestressed-concrete vessels. © 2014 Elsevier B.V.

Effects of grain size and microstructure on threshold values and near threshold crack growth in powder-formed Ni-base superalloy

Threshold stress intensity values, ranging from ∼6 to 16 MN m −3/2 can be obtained in powder-formed Nimonic AP1 by changing the microstructure. The threshold and low crack growth rate behaviour at room temperature of a number of widely differing API microstructures, with both ‘necklace’ and fully recrystallized grain structures of various sizes and uniform and bimodal γ′-distributions, have been investigated. The results indicate that grain size is an important microstructural parameter which can control threshold behaviour, with the value of threshold stress intensity increasing with increasing grain size, but that the γ′-distribution is also important. In this Ni-base alloy, as in many others, near threshold fatigue crack growth occurs in a crystallographic manner along {111} planes. This is due to the development of a dislocation structure involving persistent slip bands on {111} planes in the plastic zone, caused by the presence of ordered shearable precipitates in the microstructure. However, as the stress intensity range is increased, a striated growth mode takes over. The results presented show that this transition from faceted to striated growth is associated with a sudden increase in crack propagation rate and occurs when the size of the reverse plastic zone at the crack tip becomes equal to the grain size, independent of any other microstructural variables.

High-pressure XPS of crotyl alcohol selective oxidation over metallic and oxidized Pd(111)

Here, we report on the first application of high-pressure XPS (HP-XPS) to the surface catalyzed selective oxidation of a hydrocarbon over palladium, wherein the reactivity of metal and oxide surfaces in directing the oxidative dehydrogenation of crotyl alcohol (CrOH) to crotonaldehyde (CrHCO) is evaluated. Crotonaldehyde formation is disfavored over Pd(111) under all reaction conditions, with only crotyl alcohol decomposition observed. In contrast, 2D Pd5O4 and 3D PdO overlayers are able to selectively oxidize crotyl alcohol (1 mTorr) to crotonaldehyde in the presence of co-fed oxygen (140 mTorr) at temperatures as low as 40 °C. However, 2D Pd5O4 ultrathin films are unstable toward reduction by the alcohol at ambient temperature, whereas the 3D PdO oxide is able to sustain catalytic crotonaldehyde production even up to 150 °C. Co-fed oxygen is essential to stabilize palladium surface oxides toward in situ reduction by crotyl alcohol, with stability increasing with oxide film dimensionality.

High accuracy interrogation of a WDM FBG sensor array using radiation modes from a B-FBG

We report the development of a WDM optical sensor array interrogation system using the radiation modes from a BFBG. We present results indicating 70nm bandwidth, with 0.2um RMS noise and a minimum WDM spacing of 30um. We further show the system to be polarization independent.

Super-high temperature sensitivity of long-period gratings in B/Ge co-doped fiber

Long period fiber grating (LPFG) can be used as active gain controlling device in EDFA. However, LPFGs fabricated in the standard telecom fiber only have a typical temperature sensitivity of 3-10nm/100°C, which may not be sufficient for implementing tuneable filters capable of wide tuning range and high tuning efficiency. In this paper, we report a theoretical and experimental investigation of thermal properties of LPFGs fabricated in B/Ge co-doped optical fiber. We have found that the temperature sensitivity of the LPFGs in the B/Ge fiber is considerably increased compared with those produced in the standard fiber. The LPFGs written in the B/Ge fiber have achieved, on average, one order of magnitude higher sensitivity than that of the LPFGs produced in the standard telecom fiber. We have also identified that the thermal response of LPFG is strongly dependent on the order of the coupled resonant cladding mode. The maximum sensitivity of 1.75nm/°C achieved by the 10th cladding mode of the 240μm LPFG is nearly 24 times that of the minimum value (0.075nm/C) exhibited by the 30th mode of the 34μm LPFG. Such devices may lead to high-efficiency and low-cost thermal/electrical tunable loss filters or sensors with extremely high temperature resolution.

High-temperature sensitivity of long-period gratings in B-Ge codoped fiber

We report an investigation of thermal properties of long-period fiber gratings (LPFGs) of various periods fabricated in the conventional B-Ge codoped fiber. It has been found that the temperature sensitivity of the LPFGs produced in the B-Ge fiber can be significantly enhanced as compared with the standard telecom fiber. A total of 27.5-nm spectral shift was achieved from only 10 °C change in temperature for an LPFG with 240-μm period, demonstrating a first ever reported high sensitivity of 2.75 nm/°C. Such an LPFG may lead to high-efficiency and low-cost thermal/electrical tunable loss filters or sensors with extremely high-temperature resolution. The nonlinear thermal response of the supersensitive LPG was also reported and first explained.

Nondestructive measurement of water content and moisture migration of unsaturated red clays in South China

To reveal the moisture migration mechanism of the unsaturated red clays, which are sensitive to water content change and widely distributed in South China, and then rationally use them as a filling material for highway embankments, a method to measure the water content of red clay cylinders using X-ray computed tomography (CT) was proposed and verified. Then, studies on the moisture migrations in the red clays under the rainfall and ground water level were performed at different degrees of compaction. The results show that the relationship between dry density, water content, and CT value determined from X-ray CT tests can be used to nondestructively measure the water content of red clay cylinders at different migration time, which avoids the error reduced by the sample-to-sample variation. The rainfall, ground water level, and degree of compaction are factors that can significantly affect the moisture migration distance and migration rate. Some techniques, such as lowering groundwater table and increasing degree of compaction of the red clays, can be used to prevent or delay the moisture migration in highway embankments filled with red clays.

High accuracy discrimination of Parkinson's disease participants from healthy controls using smartphones

The aim of this study is to accurately distinguish Parkinson's disease (PD) participants from healthy controls using self-administered tests of gait and postural sway. Using consumer-grade smartphones with in-built accelerometers, we objectively measure and quantify key movement severity symptoms of Parkinson's disease. Specifically, we record tri-axial accelerations, and extract a range of different features based on the time and frequency-domain properties of the acceleration time series. The features quantify key characteristics of the acceleration time series, and enhance the underlying differences in the gait and postural sway accelerations between PD participants and controls. Using a random forest classifier, we demonstrate an average sensitivity of 98.5% and average specificity of 97.5% in discriminating PD participants from controls. © 2014 IEEE.

High-power operation of quantum-dot semiconductor disk laser at 1180 nm

In this letter, we report on a high-power operation of an optically pumped quantum-dot semiconductor disk laser designed for emission at 1180 nm. As a consequence of the optimization of the operation conditions, a record-high continuous-wave output power exceeding 7 W is obtained for this wavelength at a heat-sink temperature of 2 °C. A wavelength tuning over a range of 37 nm is achieved using a birefringent filter inside the cavity.

On some Sufficient Conditions for High Breakdown Point of ML Estimators

High breakdown point estimators LME(k) and LT E(k) for location and scale are obtained for symmetrical exponentially decreasing density family.

High-accuracy discrimination of Parkinson’s Disease participants from healthy controls using smartphones

Objective: To test the practicality and effectiveness of cheap, ubiquitous, consumer-grade smartphones to discriminate Parkinson’s disease (PD) subjects from healthy controls, using self-administered tests of gait and postural sway. Background: Existing tests for the diagnosis of PD are based on subjective neurological examinations, performed in-clinic. Objective movement symptom severity data, collected using widely-accessible technologies such as smartphones, would enable the remote characterization of PD symptoms based on self-administered, behavioral tests. Smartphones, when backed up by interviews using web-based videoconferencing, could make it feasible for expert neurologists to perform diagnostic testing on large numbers of individuals at low cost. However, to date, the compliance rate of testing using smart-phones has not been assessed. Methods: We conducted a one-month controlled study with twenty participants, comprising 10 PD subjects and 10 controls. All participants were provided identical LG Optimus S smartphones, capable of recording tri-axial acceleration. Using these smartphones, patients conducted self-administered, short (less than 5 minute) controlled gait and postural sway tests. We analyzed a wide range of summary measures of gait and postural sway from the accelerometry data. Using statistical machine learning techniques, we identified discriminating patterns in the summary measures in order to distinguish PD subjects from controls. Results: Compliance was high all 20 participants performed an average of 3.1 tests per day for the duration of the study. Using this test data, we demonstrated cross-validated sensitivity of 98% and specificity of 98% in discriminating PD subjects from healthy controls. Conclusions: Using consumer-grade smartphone accelerometers, it is possible to distinguish PD from healthy controls with high accuracy. Since these smartphones are inexpensive (around $30 each) and easily available, and the tests are highly non-invasive and objective, we envisage that this kind of smartphone-based testing could radically increase the reach and effectiveness of experts in diagnosing PD.

High-resolution cyclostratigraphy of the Cenomanian-Turonian interval: Paleoceanographic implications, a comparison between deep sea drilling project site 386 and 144

The purpose of this study was to determine the extent to which oceanic anoxic events (OAE's) are recorded in deep-water deposits of the former western Tethyan Sea, by investigating the Cenomanian-Turonian time interval characterized by the worldwide OAE 2 event. The study improved our knowledge of the possible controlling mechanisms that triggered this event at these sites, and furthered our understanding of this global phenomenon. This was examined by high-resolution, multi-proxy analyses of sediments at DSDP Sites 386 and 144, including sedimentology, scanning electron microscopy, stable isotopes, bulk and clay mineralogy, major and trace element geochemistry, biomarkers, and paleontological data. ^ The results provide a better stratigraphic resolution for the Cenomanian-Turonian, which allowed for more precise determination of chronologic boundaries, sedimentation rates at DSDP Site 386, and a more accurate calculation of the frequency of the cycles recorded in the sequence, which fall predominantly within the precession (∼23 kyr) and short eccentricity (∼100 kyr) ranges. The combined proxies allow assessment of the correlation of δ13Corg, and major and trace elements with the predominance of cyanobacteria. These organisms were the main producers of the organic matter during the dysoxic and euxinic conditions of OAE 2 at DSDP Site 386. A huge amount of microcrystalline quartz of eolian origin is also associated with OAE 2. The geochemical proxies further provide evidence that OAE 2 was linked to increased volcanism outside the deep water of the proto-Atlantic Ocean. The clays in the Turonian sediments are terrigenous and derived predominantly from eolian transport. Comparing DSDP Site 386 and 144 with stratotype sections, the δ13C org and TOC data indicate that OAE 2 seems diachronous throughout the proto-Atlantic Ocean. ^ This study concludes that the development of anoxic conditions in the deep water of the Atlantic during the latest Cenomanian-Turonian resulted from a combination of factors related to local oceanic setting and mitigated by global tectonism and climate. The data provide a more comprehensive view of the interacting factors that led to sustained high productivity of the cyanobacteria and photosynthetic protists that produced organic-carbon-rich deposits in the world's oceans. ^

Archaeological otoliths as environmental recorders: high resolution sampling of pacific cod (Gadus macrocephalus) otoliths from Kiska Island, Alaska

Archaeological fish otoliths have the potential to serve as proxies for both season of site occupation and palaeoclimate conditions. By sampling along the distinctive sub-annual seasonal bands of the otolith and completing a stable isotope (δ¹⁸O, δ¹³C) analysis, variations within the fish’s environment can be identified. Through the analysis of cod otoliths from two archaeological sites on Kiska Island, Gertrude Cove (KIS-010) and Witchcraft Point (KIS-005), this research evaluates a micromilling methodological approach to extracting climatic data from archaeological cod otoliths. In addition, δ¹⁸Ootolith data and radiocarbon dates frame a discussion of Pacific cod harvesting, site occupation, and changing climatic conditions on Kiska Island. To aid in the interpretation of the archaeological Pacific cod results, archaeological and modern Atlantic cod otoliths were also analyzed as a component of this study to develop. The Atlantic cod otoliths provided the methodological and interpretative framework for the study, and also served to assess the efficacy of this sampling strategy for archaeological materials and to add time-depth to existing datasets. The δ¹⁸Ootolith values successfully illustrate relative variation in ambient water temperature. The Pacific cod δ¹⁸O values demonstrate a weak seasonal signal identifiable up to year 3, followed by relatively stable values until year 6/7 when values continuously increase. Based on the δ¹⁸O values, the Pacific cod were exposed to the coldest water temperatures immediately prior to capture. The lack of a clear cycle of seasonal variation and the continued increase in values towards the otolith edge obscures the season of capture, and indicates that other behavioural, environmental, or methodological factors influenced the otolith δ¹⁸O values. It is suggested that Pacific cod would have been harvested throughout the year, and the presence of cod remains in Aleutian archaeological sites cannot be used as a reliable indicator of summer occupation. In addition, when the δ¹⁸O otolith values are integrated with radiocarbon dates and known climatic regimes, it is demonstrated that climatic conditions play an integral role in the pattern of occupation at Gertrude Cove. Initial site occupation coincides with the end of a neoglacial cooling period, and the most recent and continuous occupation coincides with the end of a localized warming period and the onset of the Little Ice Age (LIA).