Localized and controlled delivery of nitric oxide to the conventional outflow pathway via enzyme biocatalysis: towards therapy for Glaucoma

Nitric oxide (NO) has been shown to lower intraocular pressure (IOP), however its therapeutic effects on outflow physiology are location- and dose-dependent. Here, a NO delivery platform that directly targets the resistance-generating region of the conventional outflow pathway and locally liberates a controlled dose of NO is reported. An increase in outflow facility (decrease in IOP) is demonstrated in mouse model

Norcantharidin (NCTD) induces mitochondria mediated apoptosis in human HepG2 cells

Norcantharidin (NCTD), a demethylated form of cantharidin, is now in used as a routine anticancer drug. However, the detailed mechanisms underlying this process are generally unclear. The aims of this study were to evaluate the apoptotic effects and molecular mechanisms of NCTD. MTT assay was used to determine the cell growth inhibitory rate. Flow cytometry were used to detect the apoptosis and the loss of mitochondrial membrane potential (Δψm) induced by NCTD. Caspase detection kit were used to detect the activity of caspase-3 -9. Western-blot was used to detect the expression of Bcl-2, Bax and cytochrome C (cyt C). Our results indicated that, treatment of NCTD resulted in significant decrease in cell viability in a dose-and time-dependent manner. A dose-dependent apoptosis was also observed by flow cytometery analysis. Molecular mechanistic studies of apoptosis revealed that, NCTD treatment resulted in a significant loss of Δψm, release of cyt C, enhanced expression of pro-apoptotic protein Bax and suppression of anti-apoptotic protein Bcl-2. These were followed by activation of caspases-9 and -3, subsequently leading to cell apoptosis. These results indicate that, NCTD induced cytotoxicity in HepG2 cells by apoptosis, which is mediated through mitochondrial pathway.Key words: Norcantharidin, apoptosis, caspase, Bax/Bcl-2, cyto C, HepG2 cells

Search for the Elusive Higgs Boson Using Jet Structure at LHC

We consider the production of a light non-standard model Higgs boson of order 100~\GEV with an associated $W$ boson at CERN Large Hadron Collider. We focus on an interesting scenario that, the Higgs boson decays predominately into two light scalars $\chi$ with mass of few GeV which sequently decay into four gluons, i.e. $h\to 2\chi \to 4g$. Since $\chi$ is much lighter than the Higgs boson, it will be highly boosted and its decay products, the two gluons, will move close to each other, resulting in a single jet for $\chi$ decay in the detector. By using electromagnetic calorimeter-based and jet substructure analyses, we show in two cases of different $\chi$ masses that it is quite promising to extract the signal of Higgs boson out of large QCD background.Comment: 20 pages, 7 figure

Mild Reinforcement Learning Deficits in Patients With First-Episode Psychosis

Numerous studies have identified reinforcement learning (RL) deficits in schizophrenia. Most have focused on chronic patients with longstanding antipsychotic treatment, however, and studies of RL in early-illness patients have produced mixed results, particularly regarding gradual/procedural learning. No study has directly contrasted both rapid and gradual RL in first-episode psychosis (FEP) samples. We examined probabilistic RL in 34 FEP patients and 36 controls, using Go/NoGo (GNG) and Gain vs Loss-Avoidance (GLA) paradigms. Our results were mixed, with FEP patients exhibiting greater impairment in the ability to use positive, as opposed to negative, feedback to drive rapid RL on the GLA, but not the GNG. By contrast, patients and controls showed similar improvement across the acquisition. Finally, we found no significant between-group differences in the postacquisition expression of value-based preference in both tasks. Negative symptoms were modestly associated with RL measures, while the overall bias to engage in Go-responding correlated significantly with psychosis severity in FEP patients, consistent with striatal hyperdopaminergia. Taken together, FEP patients demonstrated more circumscribed RL impairments than previous studies have documented in chronic samples, possibly reflecting differential symptom profiles between first-episode and chronic samples. Our finding of relatively preserved gradual/procedural RL, in briefly medicated FEP patients, might suggest spared or restored basal ganglia function. Our findings of preserved abilities to use representations of expected value to guide decision making, and our mixed results regarding rapid RL, may reflect a lesser degree of prefrontal cortical functional impairment in FEP than in chronic samples. Further longitudinal research, in larger samples, is required.postprin

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

Superfluid vs Ferromagnetic Behaviour in a Bose Gas of Spin-1/2 Atoms

We study the thermodynamic phases of a gas of spin-1/2 atoms in the Hartree-Fock approximation. Our main result is that, for repulsive or weakly-attractive inter-component interaction strength, the superfluid and ferromagnetic phase transitions occur at the same temperature. For strongly-attractive inter-component interaction strength, however, the ferromagnetic phase transition occurs at a higher temperature than the superfluid phase transition. We also find that the presence of a condensate acts as an effective magnetic field that polarizes the normal cloud. We finally comment on the validity of the Hartree-Fock approximation in describing different phenomena in this system.Comment: 10 pages, 2 figure

Observation of spin Coulomb drag in a two-dimensional electron gas

An electron propagating through a solid carries spin angular momentum in addition to its mass and charge. Of late there has been considerable interest in developing electronic devices based on the transport of spin, which offer potential advantages in dissipation, size, and speed over charge-based devices. However, these advantages bring with them additional complexity. Because each electron carries a single, fixed value (-e) of charge, the electrical current carried by a gas of electrons is simply proportional to its total momentum. A fundamental consequence is that the charge current is not affected by interactions that conserve total momentum, notably collisions among the electrons themselves. In contrast, the electron's spin along a given spatial direction can take on two values, "up" and "down", so that the spin current and momentum need not be proportional. Although the transport of spin polarization is not protected by momentum conservation, it has been widely assumed that, like the charge current, spin current is unaffected by electron-electron (e-e) interactions. Here we demonstrate experimentally not only that this assumption is invalid, but that over a broad range of temperature and electron density, the flow of spin polarization in a two-dimensional gas of electrons is controlled by the rate of e-e collisions

Sharp Global Bounds for the Hessian on Pseudo-Hermitian Manifolds

We find sharp bounds for the norm inequality on a Pseudo-hermitian manifold, where the L^2 norm of all second derivatives of the function involving horizontal derivatives is controlled by the L^2 norm of the sub-Laplacian. Perturbation allows us to get a-priori bounds for solutions to sub-elliptic PDE in non-divergence form with bounded measurable coefficients. The method of proof is through a Bochner technique. The Heisenberg group is seen to be en extremal manifold for our inequality in the class of manifolds whose Ricci curvature is non-negative.Comment: 13 page

See-saw neutrino masses and large mixing angles in the vortex background on a sphere

In the vortex background on a sphere, a single 6-dimensional fermion family gives rise to 3 zero-modes in the 4-dimensional point of view, which may explain the replication of families in the Standard Model. Previously, it had been shown that realistic hierarchical mass and mixing patterns can be reproduced for the quarks and the charged leptons. Here, we show that the addition of a single heavy 6-dimensional field that is gauge singlet, unbound to the vortex, and embedded with a bulk Majorana mass enables to generate 4D Majorana masses for the light neutrinos through the see-saw mechanism. The scheme is very predictive. The hierarchical structure of the fermion zero-modes leads automatically to an inverted pseudo-Dirac mass pattern, and always predicts one maximal angle in the neutrino see-saw matrix. It is possible to obtain a second large mixing angle from either the charged lepton or the neutrino sector, and we demonstrate that this model can fit all observed data in neutrino oscillations experiments. Also, U_{e3} is found to be of the order ~0.1.Comment: 23 pages, 1 figur

An archival case study : revisiting the life and political economy of Lauchlin Currie

This paper forms part of a wider project to show the significance of archival material on distinguished economists, in this case Lauchlin Currie (1902-93), who studied and taught at Harvard before entering government service at the US Treasury and Federal Reserve Board as the intellectual leader of Roosevelt's New Deal, 1934-39, as FDR's White House economic adviser in peace and war, 1939-45, and as a post-war development economist. It discusses the uses made of the written and oral material available when the author was writing his intellectual biography of Currie (Duke University Press 1990) while Currie was still alive, and the significance of the material that has come to light after Currie's death