Grand Challenges and Opportunities for Molecular Psychiatry Research: A Perspective

Molecular psychiatry is a still nascent field, aspiring to imitate the great development of revolutionary tools and techniques achieved elsewhere. The rapid development of new methods such as high-throughput genomic and bioinformatics technologies has greatly advance our understanding of the pathology and etiology of most, if not all, psychiatric disorders, far beyond what we would have expected a few years ago. Although these great advances have brought us closer to understanding the development of many psychiatric disorders, the majority of the questions about their origins remain. Many of thes

Interaction of the phencyclidine model of schizophrenia and nicotine on total and categorized ultrasonic vocalizations in rats

Patients with schizophrenia smoke cigarettes at a higher rate than the general population. We hypothesized that a factor in this comorbidity is sensitivity to the reinforcing and reinforcement- enhancement effects of nicotine. Phencyclidine (PCP) was used to model behavioral changes resembling negative symptoms of schizophrenia in rats. USVs in rats have been used to measure emotional states, with 50 kHz USVs indicating positive states and 22 kHz indicating negative. Total and categorized numbers of 22 and 50 kHz ultrasonic vocalizations (USVs) and USVs during a visual stimulus (e.g. a potential measure of reinforcement-enhancement) were examined in rats following .injection ofh PCP (2.0 mg/kg), and/or nicotine (0.2 or 0.4 mg/kg) daily for 7 days. PCP was then discontinued and all rats received nicotine (0.2 mg/kg and 0.4 mg/kg) and PCP (2.0 mg/kg) on 3 challenge days. PCP acutely decreased 50 kHz vocalizations while repeated nicotine potentiated rates of vocalizations, with similar patterns during light presentations. Rats in the PCP and nicotine combination groups made more 50 kHz vocalizations compared to control groups on challenge days. We conclude that PCP may produce a reward deficit that is shown by decreased 50 kHz USVs, and behaviors post-PCP exposure may best model the comorbidity between schizophrenia and nicotine

Matched filter optimization of kSZ measurements with a reconstructed cosmological flow field

We develop and test a new statistical method to measure the kinematic Sunyaev-Zel'dovich (kSZ) effect. A sample of independently detected clusters is combined with the cosmic flow field predicted from a galaxy redshift survey in order to derive a matched filter that optimally weights the kSZ signal for the sample as a whole given the noise involved in the problem. We apply this formalism to realistic mock microwave skies based on cosmological $N$-body simulations, and demonstrate its robustness and performance. In particular, we carefully assess the various sources of uncertainty, cosmic microwave background primary fluctuations, instrumental noise, uncertainties in the determination of the velocity field, and effects introduced by miscentring of clusters and by uncertainties of the mass-observable relation (normalization and scatter). We show that available data (\plk\ maps and the MaxBCG catalogue) should deliver a $7.7\sigma$ detection of the kSZ. A similar cluster catalogue with broader sky coverage should increase the detection significance to $\sim 13\sigma$. We point out that such measurements could be binned in order to study the properties of the cosmic gas and velocity fields, or combined into a single measurement to constrain cosmological parameters or deviations of the law of gravity from General Relativity.Comment: 17 pages, 10 figures, 3 tables. Submitted to MNRAS. Comments are welcome

High-energy behavior of the nuclear symmetry potential in asymmetric nuclear matter

Using the relativistic impulse approximation with empirical NN scattering amplitude and the nuclear scalar and vector densities from the relativistic mean-field theory, we evaluate the Dirac optical potential for neutrons and protons in asymmetric nuclear matter. From the resulting Schr\"{o}% dinger-equivalent potential, the high energy behavior of the nuclear symmetry potential is studied. We find that the symmetry potential at fixed baryon density is essentially constant once the nucleon kinetic energy is greater than about 500 MeV. Moreover, for such high energy nucleon, the symmetry potential is slightly negative below a baryon density of about $$ fm$^{-3}$ and then increases almost linearly to positive values at high densities. Our results thus provide an important constraint on the energy and density dependence of nuclear symmetry potential in asymmetric nuclear matter.Comment: 6 pages, 5 figures, revised version, to appear in PR

Heavy-tailed distributions in fatal traffic accidents: role of human activities

Human activities can play a crucial role in the statistical properties of observables in many complex systems such as social, technological and economic systems. We demonstrate this by looking into the heavy-tailed distributions of observables in fatal plane and car accidents. Their origin is examined and can be understood as stochastic processes that are related to human activities. Simple mathematical models are proposed to illustrate such processes and compared with empirical results obtained from existing databanks.Comment: 10 pages, 5 figure

Study of axial strain induced torsion of single wall carbon nanotubes by 2D continuum anharmonic anisotropic elastic model

Recent molecular dynamic simulations have found chiral single wall carbon nanotubes (SWNTs) twist during stretching, which is similar to the motion of a screw. Obviously this phenomenon, as a type of curvature-chirality effect, can not be explained by usual isotropic elastic theory of SWNT. More interestingly, with larger axial strains (before buckling), the axial strain induced torsion (a-SIT) shows asymmetric behaviors for axial tensile and compressing strains, which suggests anharmonic elasticity of SWNTs plays an important role in real a-SIT responses. In order to study the a-SIT of chiral SWNTs with actual sizes, and avoid possible deviations of computer simulation results due to the finite-size effect, we propose a 2D analytical continuum model which can be used to describe the the SWNTs of arbitrary chiralities, curvatures, and lengths, with the concerning of anisotropic and anharmonic elasticity of SWNTs. This elastic energy of present model comes from the continuum limit of lattice energy based on Second Generation Reactive Empirical Bond Order potential (REBO-II), a well-established empirical potential for solid carbons. Our model has no adjustable parameters, except for those presented in REBO-II, and all the coefficients in the model can be calculated analytically. Using our method, we obtain a-SIT responses of chiral SWNTs with arbitrary radius, chiralities and lengthes. Our results are in reasonable agreement with recent molecular dynamic simulations. [Liang {\it et. al}, Phys. Rev. Lett, ${\bf 96}$, 165501 (2006).] Our approach can also be used to calculate other curvature-chirality dependent anharmonic mechanic responses of SWNTs.Comment: 14 pages, 2 figure

Analysis of rare variations reveals roles of amino acid residues in the N-terminal extracellular domain of nicotinic acetylcholine receptor (nAChR) alpha6 subunit in the functional expression of human alpha6*-nAChRs

BACKGROUND: Functional heterologous expression of naturally-expressed and apparently functional mammalian α6*-nicotinic acetylcholine receptors (nAChRs; where ‘*’ indicates presence of additional subunits) has been difficult. Here we wanted to investigate the role of N-terminal domain (NTD) residues of human (h) nAChR α6 subunit in the functional expression of hα6*-nAChRs. To this end, instead of adopting random mutagenesis as a tool, we used 15 NTD rare variations (i.e., Ser43Pro, Asn46Lys, Asp57Asn, Arg87Cys, Asp92Glu, Arg96His, Glu101Lys, Ala112Val, Ser156Arg, Asn171Lys, Ala184Asp, Asp199Tyr, Asn203Thr, Ile226Thr and Ser233Cys) in nAChR hα6 subunit to probe for their effect on the functional expression of hα6*-nAChRs. RESULTS: N-terminal α-helix (Asp(57)); complementary face/inner β-fold (Arg(87) or Asp(92)) and principal face/outer β-fold (Ser(156) or Asn(171)) residues in the hα6 subunit are crucial for functional expression of the hα6*-nAChRs as variations in these residues reduce or abrogate the function of hα6hβ2*-, hα6hβ4- and hα6hβ4hβ3-nAChRs. While variations at residues Ser(43) or Asn(46) (both in N-terminal α-helix) in hα6 subunit reduce hα6hβ2*-nAChRs function those at residues Arg(96) (β2-β3 loop), Asp(199) (loop F) or Ser(233) (β10-strand) increase hα6hβ2*-nAChR function. Similarly substitution of NTD α-helix (Asn(46)), loop F (Asp(199)), loop A (Ala(112)), loop B (Ala(184)), or loop C (Ile(226)) residues in hα6 subunit increase the function of hα6hβ4-nAChRs. All other variations in hα6 subunit do not affect the function of hα6hβ2*- and hα6hβ4*-nAChRs. Incorporation of nAChR hβ3 subunits always increase the function of wild-type or variant hα6hβ4-nAChRs except for those of hα6(D57N, S156R, R87C or N171K)hβ4-nAChRs. It appears Asp57Lys, Ser156Arg or Asn171Lys variations in hα6 subunit drive the hα6hβ4hβ3-nAChRs into a nonfunctional state as at spontaneously open hα6(D57N, S156R or N171K)hβ4hβ3(V9’S)-nAChRs (V9’S; transmembrane II 9’ valine-to-serine mutation) agonists act as antagonists. Agonist sensitivity of hα6hβ4- and/or hα6hβ4hβ3-nAChRs is nominally increased due to Arg96His, Ala184Asp, Asp199Tyr or Ser233Cys variation in hα6 subunit. CONCLUSIONS: Hence investigating functional consequences of natural variations in nAChR hα6 subunit we have discovered additional bases for cell surface functional expression of various subtypes of hα6*-nAChRs. Variations (Asp57Asn, Arg87Cys, Asp92Glu, Ser156Arg or Asn171Lys) in hα6 subunit that compromise hα6*-nAChR function are expected to contribute to individual differences in responses to smoked nicotine

The SU(3) bosons and the spin nematic state on the spin-1 bilinear-biquadratic triangular lattice

A bond-operator mean-field theory in the SU(3) bosons representation is developed to describe the antiferro-nematic phase of the spin-1 bilinear-biquadratic model. The calculated static structure factors reveal delicately that the antiferro-nematic state may exhibit both the ferro- and antiferro-quadruple long-range orders, which is reminiscent of the ferrimagnets or the canted antiferromagnets. This result may influence the spin wave theory concerned with this phase. Possible relevance of this unconventional state to the quasi-two-dimensional triangular material NiGa2S4 is addressed.Comment: 8pages, 6figure

Yukawa Corrections from Four-Point Functions in Intersecting D6-Brane Models

We discuss corrections to the Yukawa matrices of the Standard Model (SM) fermions in intersecting D-brane models due to four-point interactions. Recently, an intersecting D-brane model has been found where it is possible to obtain correct masses and mixings for all quarks as well as the tau lepton. However, the masses for the first two charged leptons come close to the right values but are not quite correct. Since the electron and muon are quite light, it is likely that there are additional corrections to their masses which cannot be neglected. With this in mind, we consider contributions to the SM fermion mass matrices from four-point interactions. In an explicit model, we show that it is indeed possible to obtain the SM fermion masses and mixings which are a better match to those resulting from experimental data extrapolated at the unification scale when these corrections are included. These corrections may have broader application to other models.Comment: 24 pages, 4 figure

Quantum-defect theory of resonant charge exchange

We apply the quantum-defect theory for $-1/R^4$ potential to study the resonant charge exchange process. We show that by taking advantage of the partial-wave-insensitive nature of the formulation, resonant charge exchange of the type of $^1$S+$^2$S can be accurately described over a wide range of energies using only three parameters, such as the \textit{gerade} and the \textit{ungerade} $s$ wave scattering lengths, and the atomic polarizability, even at energies where many partial waves contribute to the cross sections. The parameters can be determined experimentally, without having to rely on accurate potential energy surfaces, of which few exist for ion-atom systems. The theory further relates ultracold interactions to interactions at much higher temperatures.Comment: 8 pages, 7 figure