Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV):use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV

Reversible suppression of an essential gene in adult mice using transgenic RNA interference

RNAi has revolutionized loss-of-function genetics by enabling sequence-specific suppression of virtually any gene. Furthermore, tetracycline response elements (TRE) can drive expression of short hairpin RNAs (shRNAs) for inducible and reversible target gene suppression. Here, we demonstrate the feasibility of transgenic inducible RNAi for suppression of essential genes. We set out to directly target cell proliferation by screening an RNAi library against DNA replication factors and identified multiple shRNAs against Replication Protein A, subunit 3 (RPA3). We generated transgenic mice with TRE-driven Rpa3 shRNAs whose expression enforced a reversible cell cycle arrest. In adult mice, the block in cell proliferation caused rapid atrophy of the intestinal epithelium which led to weight loss and lethality within 8-11 d of shRNA induction. Upon shRNA withdrawal, villus atrophy and weight loss were fully reversible. Thus, shRpa3 transgenic mice provide an interesting tool to study tissue maintenance and regeneration. Overall, we have established a robust system that serves the purpose of temperature-sensitive alleles in other model organisms, enabling inducible and reversible suppression of essential genes in a mammalian system

The Real (Social) Experience of Monetary Policy

This paper takes a socio-economic approach to considering money in relation to real experience, focusing on the real effects of monetary policy. While most of the economics literature focuses on interest-rate setting as the core tool of monetary policy, we focus here instead on signalling by the central bank as a mechanism for influencing expectations and behaviour in conditions of uncertainty. This involves addressing the social-conventional expectations among different groups (a mechanism for dealing with uncertainty) applied to their particular ways of framing the real and financial sectors. Actual credit conditions faced by borrowers in turn are the outcome of the conventional view among banks as a result of their framing and the influence of central bank signalling. These relations between central banks, banks and the non-bank public in turn normally rest on long-established relations of trust. We consider the real effects of monetary policy in circumstances where trust has broken down

Critical Velocity of Vortex Nucleation in Rotating Superfluid 3He-A

We have measured the critical velocity v_c at which 3He-A in a rotating cylinder becomes unstable against the formation of quantized vortex lines with continuous (singularity-free) core structure. We find that v_c is distributed between a maximum and minimum limit, which we ascribe to a dependence on the texture of the orbital angular momentum l(r) in the cylinder. Slow cool down through T_c in rotation yields l(r) textures for which the measured v_c's are in good agreement with the calculated instability of the expected l texture.Comment: 4 pages, 3 figure

The Causal Structure of Emotions in Aristotle: Hylomorphism, Causal Interaction between Mind and Body, and Intentionality

Recently, a strong hylomorphic reading of Aristotelian emotions has been put forward, one that allegedly eliminates the problem of causal interaction between soul and body. Taking the presentation of emotions in de An. I 1 as a starting point and basic thread, but relying also on the discussion of Rh. II, I will argue that this reading only takes into account two of the four causes of emotions, and that, if all four of them are included into the picture, then a causal interaction of mind and body remains within Aristotelian emotions, independent of how strongly their hylomorphism is understood. Beyond the discussion with this recent reading, the analysis proposed of the fourfold causal structure of emotions is also intended as a hermeneutical starting point for a comprehensive analysis of particular emotions in Aristotle. Through the different causes Aristotle seems to account for many aspects of the complex phenomenon of emotion, including its physiological causes, its mental causes, and its intentional object

A Comparison of Polarization Observables in Electron Scattering from the Proton and Deuteron

Recoil proton polarization observables were measured for both the p($\vec {\rm e}$,e$^\prime\vec{\rm p}\,$) and d($\vec {\rm e}$,e$^\prime\vec{\rm p}\,)$n reactions at two values of Q$^2$ using a newly commissioned proton Focal Plane Polarimeter at the M.I.T.-Bates Linear Accelerator Center. The hydrogen and deuterium spin-dependent observables $D_{\ell\ell}$ and $D_{{\ell}t}$, the induced polarization $P_n$ and the form factor ratio $G^p_E/G^p_M$ were measured under identical kinematics. The deuterium and hydrogen results are in good agreement with each other and with the plane-wave impulse approximation (PWIA).Comment: 9 pages, 1 figure; accepted by Phys. Rev. Let

A unified approach for the solution of the Fokker-Planck equation

This paper explores the use of a discrete singular convolution algorithm as a unified approach for numerical integration of the Fokker-Planck equation. The unified features of the discrete singular convolution algorithm are discussed. It is demonstrated that different implementations of the present algorithm, such as global, local, Galerkin, collocation, and finite difference, can be deduced from a single starting point. Three benchmark stochastic systems, the repulsive Wong process, the Black-Scholes equation and a genuine nonlinear model, are employed to illustrate the robustness and to test accuracy of the present approach for the solution of the Fokker-Planck equation via a time-dependent method. An additional example, the incompressible Euler equation, is used to further validate the present approach for more difficult problems. Numerical results indicate that the present unified approach is robust and accurate for solving the Fokker-Planck equation.Comment: 19 page

The Charge Form Factor of the Neutron at Low Momentum Transfer from the 2H⃗(e⃗,e′n)p^{2}\vec{\rm H}(\vec{\rm e},{\rm e}'{\rm n}){\rm p} Reaction

We report new measurements of the neutron charge form factor at low momentum transfer using quasielastic electrodisintegration of the deuteron. Longitudinally polarized electrons at an energy of 850 MeV were scattered from an isotopically pure, highly polarized deuterium gas target. The scattered electrons and coincident neutrons were measured by the Bates Large Acceptance Spectrometer Toroid (BLAST) detector. The neutron form factor ratio $G^{n}_{E}/G^{n}_{M}$ was extracted from the beam-target vector asymmetry $A_{ed}^{V}$ at four-momentum transfers $Q^{2}=0.14$, 0.20, 0.29 and 0.42 (GeV/c)$^{2}$.Comment: 5 pages, 3 figures, submitted to Phys. Rev. Let

Measurement of the proton electric to magnetic form factor ratio from \vec ^1H(\vec e, e'p)

We report the first precision measurement of the proton electric to magnetic form factor ratio from spin-dependent elastic scattering of longitudinally polarized electrons from a polarized hydrogen internal gas target. The measurement was performed at the MIT-Bates South Hall Ring over a range of four-momentum transfer squared $Q^2$ from 0.15 to 0.65 (GeV/c)$^2$. Significantly improved results on the proton electric and magnetic form factors are obtained in combination with previous cross-section data on elastic electron-proton scattering in the same $Q^2$ region.Comment: 4 pages, 2 figures, submitted to PR

Measurement of the Proton's Neutral Weak Magnetic Form Factor

We report the first measurement of the parity-violating asymmetry in elastic electron scattering from the proton. The asymmetry depends on the neutral weak magnetic form factor of the proton which contains new information on the contribution of strange quark-antiquark pairs to the magnetic moment of the proton. We obtain the value $G_M^Z= 0.34 \pm 0.09 \pm 0.04 \pm 0.05$ n.m. at $Q^2=0.1$ (GeV/c)${}^2$.Comment: 4 pages TEX, text available at http://www.krl.caltech.edu/preprints/OAP.htm