Simultaneous Manipulation Research Articles

Simultaneous generation and focus of radially polarized light with metal-dielectric grating metasurface

Simultaneous manipulation of light polarization and phase possesses great significance for modern optical technologies. Here we propose metal-dielectric gratings capable of tailoring the polarization and phase of light based on polarization filtering with the polarization extinction ratio exceeding 10dB and the transmittance higher than 65%. The standard radially polarized (RP) light with axially symmetric polarization distribution can be generated by using arrayed grating with gradient phase under the illumination of circularly polarized (CP) light. Besides, a RP metasurface lens with high numerical aperture is presented, which can convert the CP light into the focused radially polarized light at wavelength of 632.8nm. This compact and efficient approach would have potential applications in beam manipulation, super-resolution imaging and integrated optics system.

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data.

Auto-Ignition Control in Spark-Ignition Engines Using Internal Model Control Structure

This paper analyzes the feasibility of applying model predictive control strategies for mitigation of the auto-ignition phenomenon, which affects the performance of spark-ignition internal combustion engines. The first part of this paper shows the implementation and experimental validation of a two-dimensional model, based on thermodynamic equations, to simulate operating conditions in engines fueled with natural gas. Over this validated model, several control strategies are studied in order to evaluate, through simulation analysis, which of these offer the best handling capacity of the auto-ignition phenomenon. In order to achieve this goal, multivariate control strategies are implemented for a simultaneous manipulation of the fuel/air ratio, the crank angle at ignition, and the inlet pressure. The controlled variable in this research is the temperature at the ignition point. This temperature is obtained through an estimation based on pressure in the combustion chamber at that point, which is located toward the end zone of the compression stroke. If the ignition temperature of the fuel–air mixture is reached during the compression process, then auto-ignition takes place. Proposed control strategies consist of maintaining the temperature in the ignition point below the fuel–air mixture auto-ignition temperature. The results show that auto-ignition is difficult to avoid using a single input–single output (SISO) strategy. However, a multiple input–single output (MISO) approach avoids the influence of the phenomenon without a significant impact over the engine's performance. Among the developed strategies, an approach based on model predictive control and feedforward control strategy shows the best performance, measured through the integral absolute error (IAE) index. These results open the possibility of new ways for improving the control capacity of auto-ignition phenomenon in engines compared to currently available feedback control systems.

Diversity-Oriented Polymerization: One-Shot Synthesis of Library of Graft and Dendronized Polymers by Cu-Catalyzed Multicomponent Polymerization.

Graft and dendronized polymers have attracted much attention in the polymer community, and there have been significant efforts to develop better synthetic methods. Herein, we report the highly efficient synthesis of graft and dendronized polymers by using Cu-catalyzed multicomponent polymerization (MCP). Based on diversity-oriented synthesis, we prepared a library of various graft and dendronized polymers from combinations of three types of monomers (mono-functionalized alkynes, bis-sulfonyl azides, and diamines/diols) that are bench stable and readily accessible. After reaction optimization, 54 samples of high-molecular-weight graft and dendronized polymers were prepared, the MCP method allowing simultaneous manipulation of the structures of both the main chains and the side chains. Moreover, because of the severe steric hindrance of the side chains, these polymers adopted extended conformations, as shown by the large shape parameter in solution. Also, the extended morphology of the single polymer chains was directly visualized by atomic force microscopy and transmission electron microscopy in the solid state. Most importantly, this diversity-oriented polymerization became possible because of highly step-economical and efficient one-step MCP, paving the way toward the easily tunable synthesis of graft and dendronized polymers.

On the relevance of using laboratory selection to study the adaptive value of circadian clocks

AbstractThe phrase ‘as sure as night comes after day’ highlights the most conspicuous phenomenon on earth (i.e. the daily cycling of geophysical factors). It is hypothesized that life‐forms on earth have evolved timekeeping mechanisms (circadian clocks) as adaptations to cope with such cyclic variations in their environment and, to test this hypothesis, diverse strategies have been employed. In this review, these different approaches, including comparative, clinal, ecology and/or trait manipulation and laboratory selection strategies are discussed, aiming to evaluate the adaptive value of circadian clocks. The limitations of each of these methods are assessed, and it is suggested that laboratory selection is an ideal, potent and suitable strategy for examining whether circadian clocks are indeed adaptations. In support of this, laboratory selection strategies are highlighted and critically reviewed in a discussion of studies that demonstrate the evolution of circadian clocks and life‐history traits in response to selection for the timing of rhythmic behaviours, as well as those studies that demonstrate the evolution of circadian clocks in response to selection for life‐history traits. Finally, newer approaches are proposed that involve the use of mutants, simultaneous manipulation of multiple environmental factors and genomic technologies in conjunction with laboratory selection to further explore the adaptive significance of circadian clocks.

Integrated magnetic tweezers and single-molecule FRET for investigating the mechanical properties of nucleic acid

Many enzymes promote structural changes in their nucleic acid substrates via application of piconewton forces over nanometer length scales. Magnetic tweezers (MT) is a single molecule force spectroscopy method widely used for studying the energetics of such mechanical processes. MT permits stable application of a wide range of forces and torques over long time scales with nanometer spatial resolution. However, in any force spectroscopy experiment, the ability to monitor structural changes in nucleic acids with nanometer sensitivity requires the system of interest to be held under high degrees of tension to improve signal to noise. This limitation prohibits measurement of structural changes within nucleic acids under physiologically relevant conditions of low stretching forces. To overcome this challenge, researchers have integrated a spatially sensitive fluorescence spectroscopy method, single molecule-FRET, with MT to allow simultaneous observation and manipulation of nanoscale structural transitions over a wide range of forces. Here, we describe a method for using this hybrid instrument to analyze the mechanical properties of nucleic acids. We expect that this method for analysis of nucleic acid structure will be easily adapted for experiments aiming to interrogate the mechanical responses of other biological macromolecules.

Simultaneous Bilateral Endoscopic Manipulation for Bilateral Renal Stones

To report the first performance of simultaneous bilateral percutaneous nephrolithotomy and flexible ureteroscopy carried out in tandem by 2 different surgeons in a patient with bilateral medium-sized renal calculi, describing step-by-step details of the surgical technique. A 46-year-old man, affected with hyperparathyroidism, was diagnosed with asymptomatic bilateral medium-sized renal stones. An abdominal noncontrast computed tomography scan revealed a left single kidney stone with a maximum diameter of 16 mm and 2 right renal stones located in the pelvis and in the lower calyx, of 21 and 19 mm in maximum diameter, respectively. A bilateral simultaneous percutaneous nephrolithotomy on the right side and flexible ureteroscopy on the left side were therefore carried out. The total operative time was 80 minutes. No intra- or postoperative complications were experienced. On postoperative day 1, the creatinine serum level was stable (0.7 mg/dL); he was discharged home 48 hours later. Ureteral stents were removed 7 days after the procedure. At 2 weeks follow-up, an abdominal noncontrast computed tomography scan showed a stone-free status and no changes in renal function were detected. A simultaneous bilateral endoscopic manipulation is feasible and safe and it can be offered in the presence of medium-sized bilateral renal stones in high-volume centers by experienced surgeons.

Stokes trap for multiplexed particle manipulation and assembly using fluidics

The ability to confine and manipulate single particles and molecules has revolutionized several fields of science. Hydrodynamic trapping offers an attractive method for particle manipulation in free solution without the need for optical, electric, acoustic, or magnetic fields. Here, we develop and demonstrate the Stokes trap, which is a new method for trapping multiple particles using only fluid flow. We demonstrate simultaneous manipulation of two particles in a simple microfluidic device using model predictive control. We further show that this approach can be used for fluidic-directed assembly of multiple particles in solution. Overall, this technique opens new vistas for fundamental studies of particle-particle interactions and provides a new method for the directed assembly of colloidal particles.

Mastoid Vibration Affects Dynamic Postural Control During Gait

Our objective was to investigate how manipulating sensory input through mastoid vibration (MV) could affect dynamic postural control during walking, with and without simultaneous manipulation of the visual and the somatosensory systems. We used three levels of MV (none, unilateral, and bilateral) via vibrating elements placed on the mastoid processes. We combined this with the six conditions of the Locomotor Sensory Organization Test (LSOT) paradigm to challenge the visual and somatosensory systems. We hypothesized that MV would affect both amount and temporal structure measures of sway variability during walking and that, in combination with manipulations of the visual and the somatosensory inputs, MV would augment the effects previously observed. The results confirmed that MV produced a significant increase in the amount of sway variability in both anterior-posterior and medial-lateral directions. Significant changes in the temporal structure of sway variability were only observed in the anterior-posterior direction. Bilateral MV produced larger effects than unilateral stimulation. We concluded that sensory input while walking could be affected using MV. Combining MV with manipulations of visual and somatosensory input could allow us to better understand the contributions of the sensory systems during locomotion.

Expression of a mutant prohibitin from the aP2 gene promoter leads to obesity-linked tumor development in insulin resistance-dependent manner.

A critical unmet need for the study of obesity-linked cancer is the lack of preclinical models that spontaneously develop obesity and cancer sequentially. Prohibitin (PHB) is a pleiotropic protein that has a role in adipose and immune functions. We capitalized on this attribute of PHB to develop a mouse model for obesity-linked tumor. We achieved this by expressing Y114F-PHB (m-PHB) from the aP2 gene promoter for simultaneous manipulation of adipogenic and immune signaling functions. The m-PHB mice develop obesity in a sex-neutral manner, but only male mice develop impaired glucose homeostasis and hyperinsulinemia similar to transgenic mice expressing PHB. Interestingly, only male m-PHB mice develop histiocytosis with lymphadenopathy, suggesting that metabolic dysregulation or m-PHB alone is not sufficient for the tumor development and that both are required for tumorigenesis. Moreover, ovariectomy in female m-PHB mice resulted in impaired glucose homeostasis, hyperinsulinemia and consequently tumor development similar to male m-PHB mice. These changes were not observed in sham-operated control m-Mito-Ob mice, further confirming the role of obesity-related metabolic dysregulation in tumor development in m-PHB mice. Our data provide a proof-of-concept that obesity-associated hyperinsulinemia promotes tumor development by facilitating dormant mutant to manifest and reveals a sex-dimorphic role of PHB in adipose-immune interaction or immunometabolism. Targeting PHB may provide a unique opportunity for the modulation of immunometabolism in obesity, cancer and in immune diseases.

Optogenetic Approaches for Mesoscopic Brain Mapping.

Recent advances in identifying genetically unique neuronal proteins has revolutionized the study of brain circuitry. Researchers are now able to insert specific light-sensitive proteins (opsins) into a wide range of specific cell types via viral injections or by breeding transgenic mice. These opsins enable the activation, inhibition, or modulation of neuronal activity with millisecond control within distinct brain regions defined by genetic markers. Here we present a useful guide to implement this technique into any lab. We first review the materials needed and practical considerations and provide in-depth instructions for acute surgeries in mice. We conclude with all-optical mapping techniques for simultaneous recording and manipulation of population activity of many neurons in vivo by combining arbitrary point optogenetic stimulation and regional voltage-sensitive dye imaging. It is our intent to make these methods available to anyone wishing to use them.

A novel approach for metabolic pathway optimization: Oligo-linker mediated assembly (OLMA) method.

BackgroundImbalances in gene expression of a metabolic pathway can result in less-yield of the desired products. Several targets were intensively investigated to balance the gene expression, such as promoter, ribosome binding site (RBS), the order of genes, as well as the species of the enzymes. However, the capability of simultaneous manipulation of multiple targets still needs to be explored.ResultsWe reported a new DNA assembling method to vary all the above types of regulatory targets simultaneously, named oligo-linker mediated assembly (OLMA) method, which can incorporate up to 8 targets in a single assembly step. Two experimental cases were used to demonstrate the capability of the method: (1) assembly of multiple pieces of lacZ expression cassette; (2) optimization of four enzymes in lycopene biosynthetic pathway. Our results indicated that the OLMA method not only exploited larger combinatorial space, but also reduced the inefficient mutants.ConclusionsThe unique feature of oligo-linker mediated assembly (OLMA) method is inclusion of a set of chemically synthetic double-stranded DNA oligo library, which can be designed as promoters and RBSs, or designed with different overhang to bridge the genes in different orders. The inclusion of the oligos resulted in a PCR-free and zipcode-free DNA assembly reaction for OLMA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13036-015-0021-0) contains supplementary material, which is available to authorized users.

Tunable Nanochannels along Graphene Oxide/Polymer Core–Shell Nanosheets to Enhance Proton Conductivity

Simultaneous manipulation of topological and chemical structures to induce ionic nanochannel formation within solid electrolytes is a crucial but challenging task for the rational design of high‐performance electrochemical devices including proton exchange membrane fuel cell. Herein, a novel generic approach is presented for the construction of tunable ion‐conducting nanochannels via direct assembly of graphene oxide (GO)/poly(phosphonic acid) core–shell nanosheets prepared by surface‐initiated precipitation polymerization. Using this simple and rapid approach to engineer GO/polymer nanosheets at the molecular‐level, ordered and continuous nanochannels with interconnected hydrogen‐bonded networks having a favorable water environment can be created. The resulting membranes exhibit proton conductivities up to 32 mS cm−1 at 51% relative humidity, surpassing state‐of‐the‐art Nafion membrane and all previously reported GO‐based materials.

Band renormalization and spin polarization of MoS2 in graphene/MoS2 heterostructures

Transition metal dichalcogenides exhibit spin–orbit split bands at the K-point that become spin polarized for broken crystal inversion symmetry. This enables simultaneous manipulation of valley and spin degrees of freedom. While the inversion symmetry is broken for monolayers, we show here that spin polarization of the MoS2 surface may also be obtained by interfacing it with graphene, which induces a space charge region in the surface of MoS2. Polarization induced symmetry breaking in the potential gradient of the space charge is considered to be responsible for the observed spin polarization. In addition to spin polarization we also observe a renormalization of the valence band maximum (VBM) upon interfacing of MoS2 with graphene. The energy difference between the VBM at the Γ-point and K-point shifts by ∼150 meV between the clean and graphene covered surface. (© 2015 WILEY-VCH Verlag GmbH &Co. KGaA, Weinheim)

All-Optical Interrogation of Neural Circuits.

This review describes the nexus of dramatic recent developments in optogenetic probes, genetically encoded activity sensors, and novel microscopies, which together allow the activity of neural circuits to be recorded and manipulated entirely using light. The optical and protein engineering strategies that form the basis of this "all-optical" approach are now sufficiently advanced to enable single-neuron and single-action potential precision for simultaneous readout and manipulation from the same functionally defined neurons in the intact brain. These advances promise to illuminate many fundamental challenges in neuroscience, including transforming our search for the neural code and the links between neural circuit activity and behavior.

Effect of increasing amounts of straw on pigs’ explorative behaviour

According to European legislation, pigs must have permanent access to sufficient quantity of material to enable manipulation activities. However, few studies have quantified how much straw is needed to fulfil the requirements of growing pigs. We investigated the effect of increasing amount of straw on pigs’ manipulation of the straw, and hypothesised that after a certain point increasing straw amount will no longer increase oral manipulation further. From 30 to 80kg live weight, pigs were housed in 90 groups of 18 pigs in pens (5.48m×2.48m) with partly slatted concrete floor and daily provided with fresh uncut straw onto the solid part of the floor. Experimental treatments were 10, 80, 150, 220, 290, 360, 430 or 500g straw per pig and day. At 40 and 80kg live weight, the time spent in oral manipulation of the straw by three focal pigs per pen (large, medium and small sized) were recorded along with the percentage of pigs manipulating straw simultaneously. This was recorded in three 1-h intervals (1h before and 1h after straw allocation in the morning, as well as from 17 to 18h in the afternoon). With increasing quantity of straw provided, we found a curvilinear (P<0.01) increase in the time spent in oral manipulation of the straw. Smaller pigs spent more time manipulating straw than larger and medium sized pigs (367, 274 and 252s/h for small, medium and large sized pigs, respectively; P<0.001), and pigs spent more time manipulating straw at 40kg than 80kg live weight (356 vs. 250s/h; P<0.001). At both live weights, pigs spent most time manipulating straw during the hour after allocation of straw. Similar effects of increasing amounts of straw were found for the percentage of pigs engaged in simultaneous manipulation of the straw. Post hoc analyses were applied to estimate the point, after which additional straw did not increase manipulation of straw any further. For the time spent manipulating straw the estimated change point was 253 (approx. 95% confidence limits (CL) 148–358) g straw per pig and day. For the number of pigs simultaneously manipulating straw the change point was 248 (CL 191–304) g straw per pig and day. These results show that increasing the quantity of straw from minimal to approximately 250g per pig and day increased the time spent in oral manipulation of the straw, as well as the occurrence of simultaneous straw manipulation.Hence, data from the current experiment identified 250g straw per pig per day as the amount of straw where a further increase in straw provision did not further increase neither time spent on oral manipulation of straw, nor the percentage of pigs simultaneously manipulating straw. This suggests that, within the current housing system and using this criterion, this amount of straw may be the biological turning point for increasing oral manipulation of straw.

Simultaneous morphology manipulation and upconversion luminescence enhancement of β-NaYF4:Yb3+/Er3+ microcrystals by simply tuning the KF dosage.

A strategy has been adopted for simultaneous morphology manipulation and upconversion luminescence enhancement of β-NaYF4:Yb3+/Er3+ microcrystals by simply tuning the KF dosage. X-ray power diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and photoluminescence spectra (PL) were used to characterize the samples. The influence of molar ratio of KF to Y3+ on the crystal phase and morphology has been systematically investigated and discussed. It is found that the molar ratio of KF to Y3+ can strongly control the morphology of the as-synthesized β-NaYF4 samples because of the different capping effect of F− ions on the different crystal faces. The possible formation mechanism has been proposed on the basis of a series of time-dependent experiments. More importantly, the upconversion luminescence of β-NaYF4:Yb3+/Er3+ was greatly enhanced by increasing the molar ratio of KF to RE3+ (RE = Y, Yb, Er), which is attributed to the distortion of local crystal field symmetry around lanthanide ions through K+ ions doping. This synthetic methodology is expected to provide a new strategy for simultaneous morphology control and remarkable upconversion luminescence enhancement of yttrium fluorides, which may be applicable for other rare earth fluorides.

Unconventional Magnetic and Resistive Hysteresis in an Iodine-Bonded Molecular Conductor.

Simultaneous manipulation of both spin and charge is a crucial issue in magnetic conductors. We report on a strong correlation between magnetism and conductivity in the iodine-bonded molecular conductor (DIETSe)2 FeBr2 Cl2 [DIETSe=diiodo(ethylenedithio)tetraselenafulvalene], which is the first molecular conductor showing a large hysteresis in both magnetic moment and magnetoresistance associated with a spin-flop transition. Utilizing a mixed-anion approach and iodine bonding interactions, we tailored a molecular conductor with random exchange interactions exhibiting unforeseen physical properties.

Erratum: Corrigendum: Simultaneous all-optical manipulation and recording of neural circuit activity with cellular resolution in vivo

Nat. Methods 12, 140–146 (2015); published online 22 December 2014; corrected after print 6 February 2015 In the version of this article initially published, the size of the scale bar reported in the legend of Figure 3a was incorrect. The correct size is 100 μm, not 50 μm. In addition, the volume ofinjected virus in the Online Methods section “Titration of calcium indicator expression” had the incorrect unit.

Developing a New Biophysical Tool to Combine Magneto-Optical Tweezers with Super-Resolution Fluorescence Microscopy

We present a novel experimental setup in which magnetic and optical tweezers are combined for torque and force transduction onto single filamentous molecules in a transverse configuration to allow simultaneous mechanical measurement and manipulation. Previously we have developed a super-resolution imaging module which, in conjunction with advanced imaging techniques such as Blinking assisted Localisation Microscopy (BaLM), achieves localisation precision of single fluorescent dye molecules bound to DNA of ~30 nm along the contour of the molecule; our work here describes developments in producing a system which combines tweezing and super-resolution fluorescence imaging. The instrument also features an acousto-optic deflector that temporally divides the laser beam to form multiple traps for high throughput statistics collection. Our motivation for developing the new tool is to enable direct observation of detailed molecular topological transformation and protein binding event localisation in a stretching/twisting mechanical assay that previously could hitherto only be deduced indirectly from the end-to-end length variation of DNA. Our approach is simple and robust enough for reproduction in the lab without the requirement of precise hardware engineering, yet is capable of unveiling the elastic and dynamic properties of filamentous molecules that have been hidden using traditional tools.