Controllable nonreciprocal phonon laser in a hybrid photonic molecule based on directional quantum squeezing.

Here, a scheme for a controllable nonreciprocal phonon laser is proposed in a hybrid photonic molecule system consisting of a whispering-gallery mode (WGM) optomechanical resonator and a χ(2)-nonlinear WGM resonator, by directionally quantum squeezing one of two coupled resonator modes. The directional quantum squeezing results in a chiral photon interaction between the resonators and a frequency shift of the squeezed resonator mode with respect to the unsqueezed bare mode. We show that the directional quantum squeezing can modify the effective optomechanical coupling in the optomechanical resonator, and analyze the impacts of driving direction and squeezing extent on the phonon laser action in detail. Our analytical and numerical results indicate that the controllable nonreciprocal phonon laser action can be effectively realized in this system. The proposed scheme uses an all-optical and chip-compatible approach without spinning resonators, which may be more beneficial for integrating and packaging of the system on a chip. Our proposal may provide a new route to realize integratable phonon devices for on-chip nonreciprocal phonon manipulations, which may be used in chiral quantum acoustics, topological phononics, and acoustical information processing.

Heralded high-fidelity quantum hyper-CNOT gates assisted by charged quantum dots inside single-sided optical microcavities.

Photonic hyper-parallel quantum information processing (QIP) can simplify the quantum circuit and improve the information-processing speed, as well as reduce the quantum resource consumption and suppress the photonic dissipation noise. Here, utilizing the singly charged semiconductor quantum dot (QD) inside single-sided optical microcavity as the potentially experimental platform, we propose five schemes for heralded four-qubit hyper-controlled-not (hyper-CNOT) gates, covering all cases of four-qubit hyper-CNOT gates operated on both the polarization and spatial-mode degrees of freedom (DoFs) of a two-photon system. The novel heralding mechanism improves the fidelity of each hyper-CNOT gate to unity in principle without the strict restriction of strong coupling. The adaptability and scalability of the schemes make the hyper-CNOT gates more accessible under current experimental technologies. These heralded high-fidelity photonic hyper-CNOT gates can therefore have immense utilization potentials in high-capacity quantum communication and fast quantum computing, which are of far-reaching significance for QIP.

Complete and faithful hyperentangled-Bell-state analysis of photon systems using a failure-heralded and fidelity-robust quantum gate.

Hyperentangled-Bell-state analysis (HBSA) represents a key step in many quantum information processing schemes that utilize hyperentangled states. In this paper, we present a complete and faithful HBSA scheme for two-photon quantum systems hyperentangled in both the polarization and spatial-mode degrees of freedom, using a failure-heralded and fidelity-robust quantum swap gate for the polarization states of two photons (P-SWAP gate), constructed with a singly charged semiconductor quantum dot (QD) in a double-sided optical microcavity (double-sided QD-cavity system) and some linear-optical elements. Compared with the previously proposed complete HBSA schemes using different auxiliary tools such as parity-check quantum nondemonlition detectors or additional entangled states, our scheme significantly simplifies the analysis process and saves the quantum resource. Unlike the previous schemes based on the ideal optical giant circular birefringence induced by a single-electron spin in a double-sided QD-cavity system, our scheme guarantees the robust fidelity and relaxes the requirement on the QD-cavity parameters. These features indicate that our scheme may be more feasible and useful in practical applications based on the photonic hyperentanglement.

Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.

The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of γ-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate γ-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia.

[Investigation on Spectral Characteristics of Micro-Gap Dielectric Barrier Uniform Discharge in Air].

The plasmas generated by dielectric barrier discharge in atmospheric pressure air have wide application prospect in industry. In order to study generation condition and mechanism, the dielectric barrier uniform discharge in atmospheric pressure air has been studied experimentally with a micro-gap discharge device. Results of electrical characteristics indicate that it exist several current pulses with short width in half period of the applied voltage at a low voltage, a large number of micro-discharge filaments are observed. The discharge power increases with increasing peak value of applied voltage, the micro-discharge filaments increase meanwhile. When the peak of applied voltage reaches to 9.2 kV, only a discharge hump with a width of about 5.5 µs appears in a half period of the applied voltage, micro-discharge filaments cannot be discerned. The uniform discharge has been obtained finally as the micro-discharge filaments extend and superimpose randomly. The emission spectrum of dielectric barrier discharge scanning from 330 to 420 nm is collected. It is found that the intensity of 337.1 nm is stronger than that of 391.4 nm. If the intensity of 337.1 nm is considered as the datum reference, the intensity of 391.4 nm shows the magnitude of electron average energy. The molecule internal energy is evaluated by vibration temperature. The electron average energy and molecule internal energy have been investigated by optical emission spectra. It is found that both of them decrease with increasing the applied voltage. Results indicate that it is not easy to form filamentary discharge when the electrical energy is lower. The average electron energy of uniform discharge is lower than that of the filamentary discharge. These results are of great significance to the application of dielectric barrier uniform discharge obtained in air at atmospheric pressure.

Glu-333 of nicastrin directly participates in gamma-secretase activity.

gamma-Secretase is a proteolytic membrane complex that processes a variety of substrates including the amyloid precursor protein and the Notch receptor. Earlier we showed that one of the components of this complex, nicastrin (NCT), functions as a receptor for gamma-secretase substrates. A recent report challenged this, arguing instead that the Glu-333 residue of NCT predicted to participate in substrate recognition only participates in gamma-secretase complex maturation and not in activity per se. Here, we present evidence that Glu-333 directly participates in gamma-secretase activity. By normalizing to the active pool of gamma-secretase with two separate methods, we establish that gamma-secretase complexes containing NCT-E333A are indeed deficient in intrinsic activity. We also demonstrate that the NCT-E333A mutant is deficient in its binding to substrates. Moreover, we find that the cleavage of substrates by gamma-secretase activity requires a free N-terminal amine but no minimal length of the extracellular N-terminal stub. Taken together, these studies provide further evidence supporting the role of NCT in substrate recognition. Finally, because gamma-secretase cleaves itself during its maturation and because NCT-E333A also shows defects in gamma-secretase complex maturation, we present a model whereby Glu-333 can serve a dual role via similar mechanisms in the recruitment of both Type 1 membrane proteins for activity and the presenilin intracellular loop during complex maturation.

Two different groups of signal sequence in M-superfamily conotoxins.

M-superfamily conotoxins can be divided into four branches (M-1, M-2, M-3 and M-4) according to the number of amino acid residues in the third Cys loop. In general, it is widely accepted that the conotoxin signal peptides of each superfamily are strictly conserved. Recently, we cloned six cDNAs of novel M-superfamily conotoxins from Conus leopardus, Conus marmoreus and Conus quercinus, belonging to either M-1 or M-3 branch. These conotoxins, judging from the putative peptide sequences deducted from cDNAs, are rich in acidic residues and share highly conserved signal and pro-peptide region. However, they are quite different from the reported conotoxins of M-2 and M-4 branches even in their signal peptides, which in general are considered highly conserved for each superfamily of conotoxins. The signal sequences of M-1 and M-3 conotoxins composed of 24 residues start with MLKMGVVL-, while those of M-2 and M-4 conotoxins composed of 25 residues start with MMSKLGVL-. It is another example that different types of signal peptides can exist within a superfamily besides the I-conotoxin superfamily. In addition to the different disulfide connectivity of M-1 conotoxins from that of M-4 or M-2 conotoxins, the sequence alignment, preferential Cys codon usage and phylogenetic tree analysis suggest that M-1 and M-3 conotoxins have much closer relationship, being different from the conotoxins of other two branches (M-4 and M-2) of M-superfamily.

Confining Mn2+-Doped Lead Halide Perovskite in Zeolite-Y as Ultrastable Orange-Red Phosphor Composites for White Light-Emitting Diodes.

CsPbX3 (X = Cl, Br, I) perovskite quantum dots (QDs) have emerged as competitive candidate luminescent materials in the photoelectric fields due to their superior luminescence properties. However, the major drawback such as poor resistance to temperature, moisture, and irradiation of light, especially for the red QDs with I-, hinders their practical applications. Herein, we synthesized Mn2+-doped CsPbCl3 embedded in the cage of zeolite-Y as a new orange-red phosphor for the white light-emitting diode (WLED). The composites have significantly improved resistance to both elevated temperature and water over the bare Mn2+-doped QDs. The former exhibits little degradation whereas the latter shows apparent decline upon the irradiation of lights in the orange LED devices, which are fabricated by employing each material as a color-conversion phosphor coated on a 365 nm UV chip. A WLED is also achieved with a 365 nm UV chip coated with a CsPb(Cl0.5,Br0.5)3-Y blue phosphor and a CsPb0.75Mn0.25Cl3-Y orange phosphor. The device possesses a Commission Internationale de l'Éclairage coordinate of (0.34, 0.36), a correlated color temperature of 5336 K and a color rendering index of 81.

Molecular cloning, expression and characterization of protein disulfide isomerase from Conus marmoreus.

The oxidative folding of disulfide-rich conotoxins is essential for their biological functions. In vivo, disulfide bond formation is mainly catalyzed by protein disulfide isomerase. To elucidate the physiologic roles of protein disulfide isomerase in the folding of conotoxins, we have cloned a novel full-length protein disulfide isomerase from Conus marmoreus. Its ORF encodes a 500 amino acid protein that shares sequence homology with protein disulfide isomerases from other species, and 70% homology with human protein disulfide isomerase. Enzymatic analyses of recombinant C. marmoreus protein disulfide isomerase showed that it shared functional similarities with human protein disulfide isomerase. Using conotoxins tx3a and sTx3.1 as substrate, we analyzed the oxidase and isomerase activities of the C. marmoreus protein disulfide isomerase and found that it was much more efficient than glutathione in catalyzing oxidative folding and disulfide isomerization of conotoxins. We further demonstrated that macromolecular crowding had little effect on the protein disulfide isomerase-catalyzed oxidative folding and disulfide isomerization of conotoxins. On the basis of these data, we propose that the C. marmoreus protein disulfide isomerase plays a key role during in vivo folding of conotoxins.

Solution structure of an M-1 conotoxin with a novel disulfide linkage.

The M-superfamily of conotoxins has a typical Cys framework (-CC-C-C-CC-), and is one of the eight major superfamilies found in the venom of the cone snail. Depending on the number of residues located in the last Cys loop (between Cys4 and Cys5), the M-superfamily family can be divided into four branches, namely M-1, -2, -3 and -4. Recently, two M-1 branch conotoxins (mr3e and tx3a) have been reported to possess a new disulfide bond arrangement between Cys1 and Cys5, Cys2 and Cys4, and Cys3 and Cys6, which is different from those seen in the M-2 and M-4 branches. Here we report the 3D structure of mr3e determined by 2D (1)H NMR in aqueous solution. Twenty converged structures of this peptide were obtained on the basis of 190 distance constraints obtained from NOE connectivities, as well as six varphi dihedral angle, three hydrogen bond, and three disulfide bond constraints. The rmsd values about the averaged coordinates of the backbone atoms were 0.43 +/- 0.19 A. Although mr3e has the same Cys arrangement as M-2 and M-4 conotoxins, it adopts a distinctive backbone conformation with the overall molecule resembling a 'flying bird'. Thus, different disulfide linkages may be employed by conotoxins with the same Cys framework to result in a more diversified backbone scaffold.

From the identification of gene organization of alpha conotoxins to the cloning of novel toxins.

In the venoms of cone snails, alpha conotoxins are competitive antagonists of nicotinic acetylcholine receptors. Eleven novel cDNA and eight partial gene sequences (including two pseudogenes) of alpha conotoxins were identified from five species of cone snail. As expected, every cDNA encodes a precursor of prepropeptide. In all the partial genes of alpha conotoxins identified, there is a long intron inserted at a fixed position in the pro-region, dividing the encoding region into two exons. The mutation rate in exon I (encoding the signal peptide and a part of pro-region) is much lower than that in exon II (encoding the other part of pro-region, the mature peptide and 3' untranslational region). Interestingly, the sequences at the 5' and 3' end of introns are highly conserved. In addition, in the identified introns exist long dinucleotide (e.g. "GT", "CA") or trinucleotide ("CAT") repeats. In the special case of Pu 1.1, there are five almost identical repeats of a 150 bp sequence in the long intron. Taking advantage of the conserved 3' end sequence of intron, 16 alpha conotoxins, as well as a pseudogene and three kappa A conotoxins, were identified from their genomic DNAs. Based on the comparison of these cDNA and gene sequences, a hypothesis of the alpha conotoxin evolution was proposed.

Characterization of novel M-superfamily conotoxins with new disulfide linkage.

The M-superfamily with the typical Cys framework (-CC-C-C-CC-) is one of the seven major superfamilies of conotoxins found in the venom of cone snails. Based on the number of residues in the last Cys loop (between C4 and C5), M-superfamily conotoxins can be provisionally categorized into four branches (M-1, M-2, M-3, M-4) [Corpuz GP, Jacobsen RB, Jimenez EC, Watkins M, Walker C, Colledge C, Garrett JE, McDougal O, Li W, Gray WR, et al. (2005) Biochemistry44, 8176-8186]. Here we report the purification of seven M-superfamily conotoxins from Conus marmoreus (five are novel and two are known as mr3a and mr3b) and one known M-1 toxin tx3a from Conus textile. In addition, six novel cDNA sequences of M-superfamily conotoxins have been identified from C. marmoreus, Conus leopardus and Conus quercinus. Most of the above novel conotoxins belong to M-1 and M-2 and only one to M-3. The disulfide analyses of two M-1 conotoxins, mr3e and tx3a, revealed that they possess a new disulfide bond arrangement (C1-C5, C2-C4, C3-C6) which is different from those of the M-4 branch (C1-C4, C2-C5, C3-C6) and M-2 branch (C1-C6, C2-C4, C3-C5). This newly characterized disulfide connectivity was confirmed by comparing the HPLC profiles of native mr3e and its two regioselectively folded isoforms. This is the first report of three different patterns of disulfide connectivity in conotoxins with the same cysteine framework.

Sequence diversity of T-superfamily conotoxins from Conus marmoreus.

Remarkable sequence diversity of T-superfamily conotoxins was found in a mollusk-hunting cone snail Conus marmoreus. The sequence of mr5a purified from the snail venom was determined, while six other sequences of Mr5.1a, Mr5.1b, Mr5.2, Mr5.3, Mr5.4a, and Mr5.4b were deduced from their corresponding cDNA cloned by RACE approach. mr5a of 10 amino acid residues is one of the shortest T-superfamily conotoxins ever found. They all share a typical (-CC-CC-) Cys pattern, a conserved signal peptide and a long 3'-untranslated region. A consensus Glu residue is preceded by the second two adjacent cysteines in all these toxins except in mr5a, whereas Mr5.1a, Mr5.1b, Mr5.4a and Mr5.4b are abundant in Trp residues. The identification of these highly divergent T-superfamily conotoxins will facilitate the understanding the relationship of their structure and function.

[Effect of alkaline and ultrasonic pretreatment on the sludge disintegration].

In order to enhance the efficiency of anaerobic digestion, the effects of ultrasonic pretreatment, alkaline pretreatment and the combination of these two methods have been studied on sludge disintegration by using multifrequency ultrasonic batch. The results showed that the combining of ultrasonic and alkaline treatment was more effective than alkaline or ultrasonic treatment alone in releasing SCOD and VSS solubilization. The VSS reduction rate was 15.98% with ultrasonic pretreatment alone, 22.12% with alkaline pretreatment alone(NaOH/TS = 0.04). When the sludge was pretreated by the alkaline treatment (NaOH/TS = 0.04) for 24 h followed by ultrasonic vibration for 60 min, and simultaneous ultrasonic (60 min) and alkaline( NaOH/TS = 0.04) treatment, the VSS reduction rate could reach 51.45% and 54.45% respectively. Two distinct phases of hydrolysis were observed. The first phase was a very rapid increase in solubilization, followed by a much slower second phase. According to kinetic analysis for first rapid phase, the simultaneous alkaline and ultrasonic treatment could not only get the highest hydrolysis rate among these methods, but also reduce the pretreatment time in ultrasonic pretreatment and alkaline dose in alkaline treatment.

cDNA cloning of two novel T-superfamily conotoxins from Conus leopardus.

The full-length cDNAs of two novel T-superfamily conotoxins, Lp5.1 and Lp5.2, were cloned from a vermivorous cone snail Conus leopardus using 3'/5'-rapid amplification of cDNA ends. The cDNA of Lp5.1 encodes a precursor of 65 residues, including a 22-residue signal peptide, a 28-residue propeptide and a 15-residue mature peptide. Lp5.1 is processed at the common signal site-X-Arg- immediately before the mature peptide sequences. In the case of Lp5.2, the precursor includes a 25-residue signal peptide and a 43-residue sequence comprising the propeptide and mature peptide, which is probably cleaved to yield a 29-residue propeptide and a 14-residue mature toxin. Although these two conotoxins share a similar signal sequence and a conserved disulfide pattern with the known T-superfamily, the pro-region and mature peptides are of low identity, especially Lp5.2 with an identity as low as 10.7% compared with the reference Mr5.1a. The elucidated cDNAs of these two toxins will facilitate a better understanding of the species distribution, the sequence diversity of T-superfamily conotoxins, the special gene structure and the evolution of these peptides.

BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch.

BmBKTx1 is a novel short chain toxin purified from the venom of the Asian scorpion Buthus martensi Karsch. It is composed of 31 residues and is structurally related to SK toxins. However, when tested on the cloned rat SK2 channel, it only partially inhibited rSK2 currents, even at a concentration of 1 microm. To screen for other possible targets, BmBKTx1 was then tested on isolated metathoracic dorsal unpaired median neurons of Locusta migratoria, in which a wide variety of ion channels are expressed. The results suggested that BmBKTx1 could specifically block voltage-gated Ca(2+)-activated K(+) currents (BK-type). This was confirmed by testing the BmBKTx1 effect on the alpha subunits of BK channels of the cockroach (pSlo), fruit fly (dSlo), and human (hSlo), heterologously expressed in HEK293 cells. The IC(50) for channel blocking by BmBKTx1 was 82 nm for pSlo and 194 nm for dSlo. Interestingly, BmBKTx1 hardly affected hSlo currents, even at concentrations as high as 10 microm, suggesting that the toxin might be insect specific. In contrast to most other scorpion BK blockers that also act on the Kv1.3 channel, BmBKTx1 did not affect this channel as well as other Kv channels. These results show that BmBKTx1 is a novel kind of blocker of BK-type Ca(2+)-activated K(+) channels. As the first reported toxin active on the Drosophila Slo channel dSlo, it will also greatly facilitate studying the physiological role of BK channels in this model organism.