N′-[(E)-2-Hydroxy­benzyl­idene]-5-methyl­isoxazole-4-carbohydrazide monohydrate

In the structure of the title compound, C12H11N3O3·H2O, the dihedral angle formed by the benzene and isoxazole rings is 2.03 (8)°. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯N hydrogen bond. In the crystal structure, mol­ecules are linked into a three-dimesional network by inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds, and by π–π stacking inter­actions involving adjacent benzene and isoxazole rings [centroid–centroid separation = 3.663 (2) Å]

The association of a single nucleotide polymorphism in the promoter region of the LAMA1 gene with susceptibility to Chinese high myopia

Purpose: High myopia is a severe hereditary ocular disease leading to blindness. LAMA1 (alpha subunit of laminin) is a promising candidate gene for high myopia present in the MYP2 (myopia 2) region. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in LAMA1 in Chinese subjects. Methods: Ninety-seven Chinese subjects with high myopia and ethnically and sexually matched 103 normal controls were enrolled. Genomic DNA was prepared from peripheral blood. The 5 SNPs of LAMA1 were analyzed using PCR and SNaPshot. Allele frequencies were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using the χ2 tests or the Fisher exact tests. Results: One of the 5 SNPs showed a significant difference between patients and control subjects (rs2089760: pgenotype=0.005, pallel=0.003). There were no statistically significant differences between patients and control subjects for the other four SNPs: rs566655, rs11664063, rs607230, and rs3810046. Conclusions: Our results indicate that the polymorphism of rs2089760, located in the promoter region of LAMA1, may be associated with high myopia in the Chinese population and should be investigated further. © 2011 Molecular Vision.link_to_subscribed_fulltex

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection

BACKGROUND: Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. RESULTS: In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. CONCLUSIONS: Our result demonstrates that metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture. Comparing with other existing methods, LPFS shows better performance to select a small set of key molecules. In addition, LPFS is a general methodology and can be applied to other high-dimensional data analysis, for example cancer genomics

Quantum size effects on the perpendicular upper critical field in ultra-thin lead films

We report the thickness-dependent (in terms of atomic layers) oscillation behavior of the perpendicular upper critical field $H_{c2\perp}$ in the ultra-thin lead films at the reduced temperature ($t=T/T_c$). Distinct oscillations of the normal-state resistivity as a function of film thickness have also been observed. Compared with the $T_c$ oscillation, the $H_{c2\perp}$ shows a considerable large oscillation amplitude and a $\pi$ phase shift. The oscillatory mean free path caused by quantum size effect plays a role in $H_{c2\perp}$ oscillation.Comment: 4 pages, 4 figure

Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer\u27s disease.

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer\u27s disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD-C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid-β1-42 (Aβ 1-42 ), Tau protein phosphorylation (P-tau) and β-site APP-cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD-C10 administration boosted the expression of synapse-associated proteins, such as postynaptic density protein 95, synaptophsin, α-amino 3-hydroxy-5-methyl-4-isoxa-zolep-propionate receptor and neurotrophic factors, e,g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Taken together, our results demonstrate that FSD-C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ 1-42 and P-tau, and promoting the generation of synapse-associated proteins and neurotrophic factors

FSD-C10: A more promising novel ROCK inhibitor than Fasudil for treatment of CNS autoimmunity.

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and vasodilation between Fasudil and FSD-C10. The results demonstrated that FSD-C10, like Fasudil, induced neurite outgrowth of neurons and dendritic formation of BV-2 microglia and enhanced the production of neurotrophic factor brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3). However, the cell cytotoxicity and vasodilation of FSD-C10 were relatively small compared with Fasudil. Although Fasudil inhibited both ROCK I and ROCK II, FSD-C10 more selectively suppressed ROCK II, but not ROCK I, which may be related to vasodilation insensitivity and animal mortality. Thus, FSD-C10 may be a safer and more promising novel ROCK inhibitor than Fasudil for the treatment of several neurological disorders

Comprehensive analysis of passive generation of parabolic similaritons in tapered hydrogenated amorphous silicon photonic wires

Parabolic pulses have important applications in both basic and applied sciences, such as high power optical amplification, optical communications, all-optical signal processing, etc. The generation of parabolic similaritons in tapered hydrogenated amorphous silicon photonic wires at telecom (λ~1550 nm) and mid-IR (λ≥2100 nm) wavelengths is demonstrated and analyzed. The self-similar theory of parabolic pulse generation in passive waveguides with increasing nonlinearity is presented. A generalized nonlinear Schrödinger equation is used to describe the coupled dynamics of optical field in the tapered hydrogenated amorphous silicon photonic wires with either decreasing dispersion or increasing nonlinearity. The impacts of length dependent higher-order effects, linear and nonlinear losses including two-photon absorption, and photongenerated free carriers, on the pulse evolutions are characterized. Numerical simulations show that initial Gaussian pulses will evolve into the parabolic pulses in the waveguide taper designed

Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids

SummarySpinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the μ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCβ3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization

Mid-Infrared Self-Similar Compression of Picosecond Pulse in an Inversely Tapered Silicon Ridge Waveguide

On chip high quality and high degree pulse compression is desirable in the realization of integrated ultrashort pulse sources, which are important for nonlinear photonics and spectroscopy. In this paper, we design a simple inversely tapered silicon ridge waveguide with exponentially decreasing dispersion profile along the propagation direction, and numerically investigate self-similar pulse compression of the fundamental soliton within the mid-infrared spectral region. When higher-order dispersion (HOD), higher-order nonlinearity (HON), losses (α), and variation of the Kerr nonlinear coefficient γ(z) are considered in the extended nonlinear Schrödinger equation, a 1 ps input pulse at the wavelength of 2490 nm is successfully compressed to 57.29 fs in only 5.1-cm of propagation, along with a compression factor Fc of 17.46. We demonstrated that the impacts of HOD and HON are minor on the pulse compression process, compared with that of α and variation of γ(z). Our research results provide a promising solution to realize integrated mid-infrared ultrashort pulse sources