Use of a tissue clearing technique combined with retrograde trans-synaptic viral tracing to evaluate changes in mouse retinorecipient brain regions following optic nerve crush.

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

How to Promote Urban Intelligent Transportation: A Fuzzy Cognitive Map Study.

As an important part of smart city, intelligent transportation is an critical breakthrough to solve urban traffic congestion, build an integrated transportation system, realize the intelligence of traffic infrastructure and promote sustainable development of traffic. In order to investigate the construction of intelligent transportation in cities, 20 initial affecting variables were determined in this study based on literature analysis. A questionnaire collected from professionals in intelligent transportation was conducted, and a total of 188 valid responses were received. Then the potential grouping was revealed through exploratory factor analysis. Finally, a causal model containing seven concepts was established using the practical experience and knowledge of the experts. A root cause analysis method based on fuzzy cognitive map (FCM) was also proposed to simulate intelligent transportation construction (ITC). The results indicate:(1) The 20 variables can be divided into six dimensions: policy support (PS), traffic sector control (TSC), technical support (TS), communication foundation (CF), residents' recognition (RR), and talent quality (TQ); and (2) In the FCM model, all six concept nodes (PS, TSC, TS, CF, RR, and TQ) have a significant positive correlation with the target concept node ITC. The rank of the six dimensions according to correlation strength is TS, CF, PS, TSC, RR, and TQ. The findings of this paper can help academics and practitioners understand the deep-seated determinants of urban intelligent transportation construction more comprehensively, and provide valuable suggestions for policy makers. And thus, the efficiency of intelligent transportation construction can be improved.

An integrated single- and two-photon non-diffracting light-sheet microscope.

We describe a fluorescence optical microscope with both single-photon and two-photon non-diffracting light-sheet excitations for large volume imaging. With a special design to accommodate two different wavelength ranges (visible: 400-700 nm and near infrared: 800-1200 nm), we combine the line-Bessel sheet (LBS, for single-photon excitation) and the scanning Bessel beam (SBB, for two-photon excitation) light sheet together in a single microscope setup. For a transparent thin sample where the scattering can be ignored, the LBS single-photon excitation is the optimal imaging solution. When the light scattering becomes significant for a deep-cell or deep-tissue imaging, we use SBB light-sheet two-photon excitation with a longer wavelength. We achieved nearly identical lateral/axial resolution of about 350/270 nm for both imagings. This integrated light-sheet microscope may have a wide application for live-cell and live-tissue three-dimensional high-speed imaging.

Mirrorless Optical Parametric Oscillation with Tunable Threshold in Cold Atoms.

We report the demonstration of a mirrorless optical parametric oscillator with a tunable threshold in laser-cooled atoms with four-wave mixing (FWM) using electromagnetically induced transparency. Driven by two classical laser beams, the generated Stokes and anti-Stokes fields counterpropagate and build up efficient intrinsic feedback through the nonlinear FWM process. This feedback does not involve any cavity or spatially distributed microstructures. We observe the transition of photon correlation properties from the biphoton quantum regime (below the threshold) to the oscillation regime (above the threshold). The pump threshold can be tuned by varying the operating parameters. We achieve the oscillation with a threshold as low as 15 µW.

Shaping the Biphoton Temporal Waveform with Spatial Light Modulation.

We demonstrate a technique for shaping the temporal wave function of biphotons generated from spatially modulated spontaneous four-wave mixing in cold atoms. We show that the spatial profile of the pump field can be mapped onto the biphoton temporal wave function in the group delay regime. The spatial profile of the pump laser beam is shaped by using a spatial light modulator. This spatial-to-temporal mapping enables the generation of narrow-band biphotons with controllable temporal waveforms.

Efficiently loading a single photon into a single-sided Fabry-Perot cavity.

We demonstrate that a single photon with an optimal temporal waveform can be efficiently loaded into a cavity. Using heralded narrow-band single photons with exponential growth wave packet shaped by an electro-optical amplitude modulator, whose time constant matches the photon lifetime in the cavity, we demonstrate a loading efficiency of (87±2)% from free space to a single-sided Fabry-Perot cavity. We further demonstrate directly loading heralded single Stokes photons into the cavity with an efficiency of (60±5)% without the electro-optical amplitude modulator and verify the time reversal between the frequency-entangled paired photons. Our result and approach may enable promising applications in realizing large-scale quantum networks based on cavity quantum electrodynamics.

Differential-phase-shift quantum key distribution using heralded narrow-band single photons.

We demonstrate the first proof of principle differential phase shift (DPS) quantum key distribution (QKD) using narrow-band heralded single photons with amplitude-phase modulations. In the 3-pulse case, we obtain a quantum bit error rate (QBER) as low as 3.06% which meets the unconditional security requirement. As we increase the pulse number up to 15, the key creation efficiency approaches 93.4%, but with a cost of increasing the QBER. Our result suggests that narrow-band single photons maybe a promising source for the DPS-QKD protocol.

Developing early formulations: practice and perspective.

Early formulations are prepared mostly for drug compounds at both discovery and preclinical stages and are used to animals via various routes such as oral and intravenous dosing. They serve the purpose of evaluating these compounds on a broad range of pharmaceutical interests, notably pharmacology (activity/efficacy), pharmacokinetics (PK), and toxicology. It is estimated that approx. 40% of all drug compounds discovered have certain delivery limitations due to poor solubility or poor bioavailability. This brings tremendous challenges to the scientists working in the field of early formulations. This study intends to cover a broad spectrum of early formulations including basic aspect and development aspect. On basic aspect, it summarized early formulation study purpose, objectives, dosing route, animal species, etc. It then evaluated a variety of dosage forms and solubility enhancement approaches including various solutions, suspensions, lipid-based formulations, solid dispersions, etc. On development aspect, this study broadly reviewed literatures and current practice in the field, the issues and challenges. It offered authors' own approaches and strategies including general development schemes for oral and for i.v., recommended excipient use range for oral and for i.v., experimental procedures for vitro serial dilution method, for kinetic solubility, etc. The study also discussed a number of case analyses and emphasized scientific rationales and experimental approaches in each of them. The study concluded with authors' summary and some comments on early formulation practice, thoughts and perspectives on its future trend. The study is a mixture of literature review and investigational research. It provides many useful information, practical procedures, and recommendations. It is expected that the study will fill the void of literature of such kind, and provide direct benefit to everyday practitioners in the field.

Solubilization of flurbiprofen in pH-surfactant solutions.

Based on an investigation on furbiprofen solubilization in polysorbate 80 solutions at different pH, this study proposed an equilibrium-based model to characterize the drug-surfactant interactions in pH controlled system. The model reflected both interactions and interdependence among all drug-containing species: unionized drug in water D(u), ionized drug in water D(i), unionized drug in micelles D(u)M, and ionized drug in micelles D(i)M. The micelles were defined and quantitated as the micellized surfactants, so both D(u)M and D(i)M were also seen as unionized and ionized drug associated with micellized surfactants. This mathematical treatment enables the modeling of the drug solubilization in pH-surfactant solutions without making unsound approximations. Using a separate set of solubility data at a different pH, a comparison was conducted between experimental data and the solubility estimated by this model, and by the partition model proposed by Rippie et al. It was found that both models yielded reasonably good estimation compared with experimental data. It was also found that the solubility data estimated by the proposed model were more reliable especially when the surfactant concentration was high in the system. This suggests that the consideration of interrelations and interdependence of all drug species in pH-surfactant solutions by this model is justified and appropriate.

Cosolubilization of non-polar drugs in polysorbate 80 solutions.

This study investigated the cosolubilization phenomenon of three non-polar drugs (hydrocortisone, beta-estradiol, and ethynylestradiol) in polysorbate 80 solutions. It was found that the solubility of any drug decreased in the presence of other steroidal compounds. In an attempt to understand the observation, the author proposed a model to describe and to predict the drug solubility in the presence of other non-polar drugs in a non-ionic surfactant. The model indicates that, in a non-ionic surfactant solution that contains both drugs D(a) and D(b), the total solubility [D(a)(tot)] is related not only to the physical chemical properties of D(a) (micellar equilibrium constant K(a), the intrinsic solubility [D(a)]), as well as the total surfactant concentration [S(tot)], it is also related to the physical chemical properties of the D(b). Mathematically, the [D(a)(tot)] decreases as the product of the micellar equilibrium constant K(b) and the intrinsic solubility [D(b)] increases. The model was also put to the test by comparing the cosolubilization data obtained experimentally with the data calculated from the proposed model. The fact that these two sets of data were in good agreement lent strong support to the newly proposed model.

Predicting solubility in multiple nonpolar drugs-cyclodextrin system.

This study presents a model to predict the solubility of a nonpolar drug D(A) in the presence of other nonpolar drugs D(1) em leader D(n) in a complexing ligand L system such as hydroxypropyl-beta-cyclodextrin (HPbetaCD). Using an equilibrium approach, the model describes the molecular interactions among these drug species and the ligand. The model indicates that the solubility of D(A) invariably decreases as a result of the presence of D(1) em leader D(n). Furthermore, the decrease in D(A) solubility is related to the sum of the products of the intrinsic solubilities of the other drugs and drug-ligand complexation constants. To test the model, three steroids (prednisolone, 17alpha-hydroxyprogesterone, and progesterone) were used as model compounds in HPbetaCD solutions. The experimental data showed that the solubility of any particular drug decreased in the presence of other drugs. At all tested HPbetaCD concentrations, these experimental solubility data were in good agreement with the predicted solubility data. This result lends strong support to the reliability and effectiveness of the proposed model.