Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.

Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from the milk thistle seed, Silybum marianum, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, despite clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.

Fluctuation theorems are a class of equalities each of which links a thermodynamic path functional such as heat and work to a state function such as entropy and free energy. Jinwoo and Tanaka [L. Jinwoo and H. Tanaka, Sci. Rep. 5, 7832 (2015)] have shown that each microstate of a fluctuating system can be regarded as an ensemble (or a 'macrostate') if we consider trajectories that reach each microstate. They have revealed that local forms of entropy and free energy are true thermodynamic potentials of each microstate, encoding heat, and work, respectively, within an ensemble of paths that reach each state. Here we show that information that is characterized by the local form of mutual information between two subsystems in a heat bath is also a true thermodynamic potential of each coupled state and encodes the entropy production of the subsystems and heat bath during a coupling process. To this end, we extend the fluctuation theorem of information exchange [T. Sagawa and M. Ueda, Phys. Rev. Lett. 109, 180602 (2012)] by showing that the fluctuation theorem holds even within an ensemble of paths that reach a coupled state during dynamic co-evolution of two subsystems.

Designing motion representations for the problem of 3D human action recognition from skeleton sequences is an important yet challenging task. An effective representation should be robust to noise, invariant to viewpoint changes and result in a good performance with low-computational demand. Two main challenges in this task include how to efficiently represent spatio-temporal patterns of skeletal movements and how to learn their discriminative features for classification task. This paper presents a novel skeleton-based representation and a deep learning framework for 3D action recognition using RGB-D sensors. We propose to build an action map called SPMF (Skeleton Posture-Motion Feature), which is a compact image representation built from skeleton poses and their motions. An Adaptive Histogram Equalization (AHE) algorithm is then applied on the SPMF to enhance their local patterns and form an enhanced action map, namely Enhanced-SPMF. For learning and classification tasks, we exploit Deep Convolutional Neural Networks based on the DenseNet architecture to learn directly an end-to-end mapping between input skeleton sequences and their action labels via the Enhanced-SPMFs. The proposed method is evaluated on four challenging benchmark datasets, including both individual actions, interactions, multiview and large-scale datasets. The experimental results demonstrate that the proposed method outperforms previous state-of-the-art approaches on all benchmark tasks, whilst requiring low computational time for training and inference.

Water soluble polymers have gained an increasing interest in enhanced oil recovery (EOR) processes, especially as polymer flooding. Despite the fact that the flow of polymer in porous medium has been a research subject for many decades with numerous publications, there are still some research areas that need progress. The prediction of polymer injectivity remains elusive. Polymers with similar shear viscosity might have different in-situ rheological behaviors and may be exposed to different extent of mechanical degradation. Hence, determining polymer in-situ rheological behavior is of great significance for defining its utility. In this study, an investigation of rheological properties and mechanical degradation of different HPAM (partially hydrolyzed polyacrylamide) polymers was performed using Bentheimer sandstone outcrop cores. Results show that, HPAM in-situ rheology is different from bulk rheology measured in rheometer. Specifically, shear thickening behavior occurs at high rates, and near-Newtonian behavior is measured at low rates in porous media. This deviates strongly from measurements in the rheometer. Polymer molecular weight and concentration influence its viscoelasticity and subsequently its flow characteristics in porous media. Exposure to mechanical degradation by flow at high rate through porous media leads to significant reduction in shear thickening and thereby improved injectivity. More importantly, the degraded polymer maintained in-situ viscosity at low flow rates indicating that improved injectivity can be achieved without compromising viscosity at reservoir flow rates. This is explained by reduction in viscoelasticity. Mechanical degradation also leads to reduced residual resistance factor (RRF), especially for high polymer concentrations. For some of the polymer injections, successive degradation (increased degradation with transport length in porous media) was observed. The results presented here may be used to optimize polymer injectivity.

This paper utilizes dynamic panel threshold technology to conduct a nonlinear test on the direct effect between environmental regulation and economic fluctuations and the effect of industrial structure upgrading by taking 35 industrial sectors in China from 2003 to 2016 . The research has found that there is an inverted "U" relationship between environmental regulation and economic fluctuations, with the enhancement of environmental regulations, the economic fluctuation increases first and then decreases. The cross-terms of environmental regulation and industrial structure rationalization or industrial structure upgrading are significantly negative, which indicates that the enhancement of environmental regulation is conducive to promoting industrial structure upgrading and reducing the economic fluctuations. While the rationalization factors of industrial structure and advanced industrial structure are significantly negative, indicating that both forms of industrial structure upgrading are conducive to reducing the economic fluctuations. Environmental regulation has technical innovation thresholds for industrial structure upgrading and economic fluctuations, but there are no human capital or FDI thresholds. In the rationalization model of industrial structure, there is a nonlinear "U" relationship between environmental regulation and economic fluctuations when the proportion of scientific research expenditure is more than 1.35%. With the enhancement of environmental regulation, the economic fluctuation reduces first and then increases, and the corresponding inflection point value is 2.398% of the environmental regulation level. At the same time, the environmental regulation can indirectly reduce economic fluctuations by pushing down the industrial structure upgrades. In the advanced model of industrial structure, there is a “U” relationship between environmental regulation and economic fluctuation when the proportion of scientific research expenditure is greater than 1.26%. With continuous enhancement of environmental regulation, the economic fluctuation reduces first and then increases. The corresponding inflection point value is 1.78% of the environmental regulation level, and environmental regulation can indirectly reduce economic fluctuations by promoting the industrial structure at the same time.

Speech/music classification that facilitates optimized signal processing from classification results has been extensively adapted as an essential part of various electronics applications, such as multi-rate audio codecs, automatic speech recognition, and multimedia document indexing. In this paper, a new technique to improve the robustness of speech/music classifier for 3GPP enhanced voice service (EVS) using long short-term memory (LSTM) is proposed. For effective speech/music classification, feature vectors implemented with the LSTM are chosen from the features of the EVS. Experiments show that LSTM-based speech/music classification produces better results than conventional EVS under a variety of conditions and types of speech/music data.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

To understand functions of biomolecules such as proteins, not only structures but their conformational change and kinetics are important to be characterized but its atomistic details are hard to obtain both experimentally and computationally. We review our recent computational studies using novel enhanced sampling techniques for conformational sampling of biomolecules and calculations of their kinetics. For efficiently characterizing the free energy landscape of a biomolecule, we introduce the multiscale enhanced sampling method, which uses a combined system of atomistic and coarse-grained models. Based on the idea of Hamiltonian replica exchange, we can recover the statistical properties of the atomistic model without any biases. We next introduce the string method as a path search method to calculate the minimum free energy pathways along a multidimensional curve in high dimensional space. Finally we introduce novel methods to calculate kinetics of biomolecules based on the ideas of path sampling: One is the Onsager-Machlup action method, and the other is the weighted ensemble method. Some applications of above methods to biomolecular systems are also discussed and illustrated.

Optofluidics, a research discipline combining optics with microfluidics, currently aspires to revolutionize the analysis of biological and chemical samples e.g. for medicine, pharmacology, or molecular biology. In order to detect low concentrations of analytes in water, we developed an optofluidic device containing a nanostructured substrate for surface enhanced Raman spectroscopy (SERS). The geometry of the gold surface allows localized plasmon oscillations to give rise to the SERS effect, in which the Raman spectral lines are intensified by the interaction of the plasmonic field with the electrons in the molecular bonds. The SERS substrate was enclosed in a microfluidic system, which allowed transport and precise mixing of the analyzed fluids, while preventing contamination or abrasion of the highly sensitive substrate. To illustrate its practical use, we employed the device for quantitative detection of persistent environmental pollutant 1,2,3-trichloropropane in water in submillimolar concentrations. The developed sensor allows fast and simple quantification of halogenated compounds and it will contribute towards the environmental monitoring and enzymology experiments with engineered haloalkane dehalogenase enzymes.

Based on author's previous work [Sun, B. The Reynolds Navier-Stokes Turbulence Equations of Incompressible Flow Are Closed Rather Than Unclosed. Preprints 2018, 2018060461 (doi: 10.20944/preprints201806.0461.v1)], this paper proposed an explicit representation of velocity fluctuation and formulated the Reynolds stress tensor in terms of the mean velocity field. The proposed closed Reynolds Navier-Stokes turbulence formulations reveal that the mean vorticity is the key source of producing turbulence.

The vibration signal of heavy gearbox presents non-stationary and nonlinear characteristics, which increases the difficulty to extract the fault feature. When the gear has a subtle fault, it may cause a perceptible change of local fluctuation rather than the large scale fluctuation. Therefore, the feature parameters extracted from local fluctuation can effectively improve the recognition performance of the gear fault. In this paper, a novel signal processing method based on variational mode decomposition (VMD) and detrended fluctuation analysis (DFA) is proposed to identify the gear fault of heavy gearbox. Firstly, the raw vibration signal is decomposed several mode components by VMD, which is an adaptive and non-recursive signal decomposition method. Next, the sensitive mode component is selected by a maximal indicator, which is composed of kurtosis and correlation coefficient of relative higher frequency mode components corresponding to local fluctuation of raw vibration signal. Finally, the characteristics of the double-scales feature parameters of selected sensitive mode are extracted by DFA. In addition, the position of turning point of double scales is estimated by sliding windowing algorithm. The proposed method is evaluated through its application to gear fault classification using vibration signal. The results demonstrates that the recognization rate of gear faults condition have marked improvement by proposed method than the DFA of Small Time Scale (STS-DFA) method.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

Understanding the chalk-fluid interactions and the associated mineralogical and mechanical alteration at sub-micron scale are major goals in Enhanced Oil Recovery. Mechanical strength, porosity, and permeability of chalk are linked to mineral dissolution that occurs during brine injections, and affect the reservoir potential. This paper presents a novel "single grain" methodology to recognize the varieties of carbonates in rocks and loose sediments: Raman spectroscopy is a non-destructive, quick, and user-friendly technique representing a powerful tool to identify minerals down to 1 µm. An innovative working technique for oil exploration is proposed, as the mineralogy of micron-sized crystals grown in two flooded chalk samples (Liége, Belgium) was successfully investigated by Raman spectroscopy. The drilled chalk cores were flooded with MgCl₂ for c. 1.5 (Long Term Test) and 3 years (Ultra Long Term Test) under North Sea reservoir conditions (Long Term Test: 130°C, 1 PV/day, 9.3 MPa effective stress; Ultra Long Term Test: 130°C, varying between 1-3 PV/day, 10.4 MPa effective stress). Raman spectroscopy was able to identify the presence of recrystallized magnesite along the core of the Long Term Test up to 4 cm from the injection surface, down to the crystal size of 1-2 µm. In the Ultra Long Term Test core the growth of MgCO₃ affected nearly the entire core (7 cm). In both samples, no dolomite or high-magnesium calcite secondary growth could be detected when analysing 557 and 90 Raman spectra on the Long and Ultra Long Term Test, respectively. This study can offer Raman spectroscopy as a breakthrough tool in petroleum exploration of unconventional reservoirs, due to its quickness, spatial resolution, and non-destructive acquisition of data. These characteristics would encourage its use coupled with electron microscopes and energy dispersive systems or even electron microprobe studies.

Radar transmit signal design is a critical factor for the radar performance. In this paper, we investigate the problem of radar signal waveform design under the small signal power conditions for detecting a doubly spread target, whose impulse response can be modeled as a random process, in a colored noise environment. The doubly spread target spans multiple range bins (range-spread) and its impulse response is time-varying due to fluctuation (hence also Doppler-spread), such that the target impulse response is both time-selective and frequency-selective. Instead of adopting the conventional assumption that the target is wide-sense stationary uncorrelated scattering,we assume that the target impulse response is both wide-sense stationary in range and in time to account for the possible correlation between the impulse responses corresponding to close range intervals. The locally most powerful detector, which is asymptotically optimal for small signal cases, is then derived for detecting such targets. The signal waveform is optimized to maximizing the detection performance of the detector or equivalently maximizing the Kullback-Leibler divergence. Numerical simulations validate the effectiveness of the proposed waveform design for the small signal power conditions and performance of optimum waveform design are shown in comparison to the frequency modulated waveform.

Most of existing fuzzy forecasting models partition historical training time series into fuzzy time series and build fuzzy-trend logical relationship groups to generate forecasting rules. The determination process of intervals is complex and uncertainty. In this paper, we present a novel fuzzy forecasting model based on high-order fuzzy-fluctuation trends and the fuzzy-fluctuation logical relationships of the training time series. Firstly, we compare each data with the data of its previous day in historical training time series to generate a new fluctuation trend time series(FTTS). Then, fuzzify the FTTS into fuzzy-fluctuation time series(FFTS) according to the up, equal or down range and orientation of the fluctuations. Since the relationship between historical FFTS and the fluctuation trend of future is nonlinear, Particle Swarm Optimization (PSO) algorithm is employed to estimate the required parameters. Finally, use the acquired parameters to forecast the future fluctuations. In order to compare the performance of the proposed model with that of the other models, we apply the proposed method to forecast the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) time series datasets. The experimental results and the comparison results show that the proposed method can be successfully applied in stock market forecasting or such kinds of time series. We also apply the proposed method to forecast Shanghai Stock Exchange Composite Index (SHSECI) to verify its effectiveness and universality.

The optimization of guide vane closing schemes (OGVCS) of pumped storage hydro unit (PSHU) is the research field of cooperative control and optimal operation of pumped storage, wind power and solar power generation. This paper presents a OGVCS model of PSHU considering the rise rate of the unit rotational speed and the specific node pressure of each hydraulic unit, as well as various complicated hydraulic and mechanical constraints. OGVCS model is formulated as a multi-objective optimization problem to optimize conflictive objectives, i.e., unit rotational speed and water hammer pressure criteria. In order to realize the efficient solution of the OGVCS model, an enhanced multi-objective bacterial-foraging chemotaxis gravitational search algorithm (EMOBCGSA) is proposed to solve this problem, which adopts population reconstruction, adaptive selection chemotaxis operator of local searching strategy and Elite archive set to efficiently solve the multi-objective problem. Especially, novel constraints-handling strategy with eliminating and local search based on violation ranking is used to balance various hydraulic and mechanical constraints. Finally, simulation cases of complex extreme operating conditions (i.e., load rejection and pump outage) of ‘single tube-double units’ type PSHU system are conducted to verify the feasibility and effectiveness of the proposed EMOBCGSA in solving OGVCS problem. The simulation results indicate that the proposed EMOBCGSA can provide lower rise rate of the unit rotational speed and smaller water hammer pressure than other method established recently while considering various complex constraints in OGVCS problem.

We report magnetic silver nanoshells (M AgNSs) that have both magnetic and SERS properties for SERS-based detection. The M AgNSs are composed of hundreds of Fe3O4 nanoparticles for rapid accumulation and bumpy silver shell for sensitive SERS detection by near-infrared laser excitation. The intensity of the SERS signal from the M AgNSs was strong enough to provide single particle-level detection. We obtained much stronger SERS signal intensity from the aggregated M AgNSs than from the non-aggregated AgNSs. 4-Fluorothiophenol was detected at concentrations as low as 1 nM, which corresponds to 0.16 ppb. The limit of detection for tetramethylthiuram disulfide was 10 μM, which corresponds to 3 ppm. The M AgNSs can be used to detect trace amounts of organic molecules using a portable Raman system.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Special preparation of SBA-15 materials has been carried out for creating adsorbents exhibiting an enhanced and selective adsorption toward CO2. This creation starts from an adequate conditioning of the silica surface, via a thermo-alkaline treatment to increase the population of silanol species on it. CO2 adsorption is only reasonably achieved when the SiO2 surface becomes aminated after put in contact with a solution of an amino alkoxide compound in the right solvent. Unfunctionalized and amine-functionalized substrates were characterized through X-ray diffraction, N2 sorption, Raman spectroscopy, electron microscopy, 29Si solid-state NMR, and NH3 thermal programmed desorption. These analyses proved that the thermo-alkaline procedure desilicates the substrate and eliminates the micropores (without affecting the SBA-15 capillaries), present in the original solid. NMR analysis confirms that the hydroxylated solid anchors more amino functionalizing molecules than the unhydroxylated material. The SBA-15 sample subjected to hydroxylation and amino- functionalization displays a high enthalpy of interaction, a reason why this solid is suitable for a strong deposition of CO2 but with the possibility of observing a low-pressure hysteresis phenomenon. Contrastingly, CH4 adsorption on amino-functionalized, hydroxylated SBA-15 substrates becomes almost 5 times lesser than the CO2 one, thus giving proof of their selectivity toward CO2.

Using coherent optical detection and digital signal processing, laser phase noise and equalization enhanced phase noise can be effectively mitigated using the feed-forward and feed-back carrier phase recovery approaches. In this paper, theoretical analyses of feed-back and feed-forward carrier phase recovery methods have been carried out in the long-haul high-speed n-level phase shift keying (n-PSK) optical fiber communication systems, involving a one-tap normalized least-mean-square (LMS) algorithm, a block-wise average algorithm, and a Viterbi-Viterbi algorithm. The analytical expressions for evaluating the estimated carrier phase and for predicting the bit-error-rate (BER) performance (such as the BER floors) have been presented and discussed in the n-PSK coherent optical transmission systems by considering both the laser phase noise and the equalization enhanced phase noise. The results indicate that the Viterbi-Viterbi carrier phase recovery algorithm outperforms the one-tap normalized LMS and the block-wise average algorithms for small phase noise variance (or effective phase noise variance), while the one-tap normalized LMS algorithm shows a better performance than the other two algorithms for large phase noise variance (or effective phase noise variance). In addition, the one-tap normalized LMS algorithm is more sensitive to the level of modulation formats.