Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies

The observation showing that Lewy type synucleinopathy (LTS), the pathological hallmark of Parkinson’s disease (PD), is found in the gut of almost all PD subjects led to a substantial amount of research to develop a diagnostic procedure in living patients based on endoscopically obtained gastrointestinal biopsies. However, the existing studies have provided conflicting results regarding the sensitivity and specificity of gastrointestinal biopsies for the detection of LTS. We therefore undertook a multi-center staining and blinded judging of a common set of slides from colonic biopsies to determine the optimal protocol for the detection of LTS. Four different immunohistochemical methods, developed in four separate expert laboratories, were evaluated for their sensitivity and specificity to detect enteric LTS. Test sets of formalin-fixed, paraffin-embedded sections from biopsies of 9 PD subjects and 3 controls were stained with the 4 methods and graded by 4 different observers. Four types of staining morphology (granular staining in the lamina propria, perivascular/vascular wall staining in the submucosa, lacy-granular pattern in the submucosa and epithelial cell nuclear staining) were variably observed in the slides stained by the 4 methods. Positive alpha-synuclein staining was observed by all 5 judges in most of the slides from control cases, regardless of the staining methods that were used. Moreover, none of the tested method or staining pattern had a specificity and sensitivity more than 80 % regarding to PD. Overall, our study suggest that the tested methods are not adequate for the prediction of PD using gastrointestinal biopsies. Future studies are warranted to test new immunostaining methods

Theoretical predictions for the direct detection of neutralino dark matter in the NMSSM

We analyse the direct detection of neutralino dark matter in the framework of the Next-to-Minimal Supersymmetric Standard Model. After performing a detailed analysis of the parameter space, taking into account all the available constraints from LEPII, we compute the neutralino-nucleon cross section, and compare the results with the sensitivity of detectors. We find that sizable values for the detection cross section, within the reach of dark matter detectors, are attainable in this framework. For example, neutralino-proton cross sections compatible with the sensitivity of present experiments can be obtained due to the exchange of very light Higgses with m_{h_1^0}\lsim 70 GeV. Such Higgses have a significant singlet composition, thus escaping detection and being in agreement with accelerator data. The lightest neutralino in these cases exhibits a large singlino-Higgsino composition, and a mass in the range 50\lsim m_{\tilde\chi_1^0}\lsim 100 GeV.Comment: Final version to appear in JHEP. References added. LaTeX, 53 pages, 23 figure

Postmortem examination of vascular lesions in cognitive impairment: A survey among neuropathological services

Background and Purpose - A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients. Methods - Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed. Results - A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline. Conclusions - The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment

Fermion Masses and Mixing in Intersecting Branes Scenarios

We study the structure of Yukawa couplings in intersecting D6-branes wrapping a factorizable 6-torus compact space T^6. Models with MSSM-like spectrum are analyzed and found to fail in predicting the quark mass spectrum because of the way in which the family structure for the left-handed, right-handed quarks and, eventually, the Higgses is `factorized' among the different tori. In order to circumvent this, we present a model with three supersymmetric Higgs doublets which satisfies the anomaly cancellation condition in a more natural way than the previous models, where quarks were not treated universally regarding their branes assignments, or some particular branes were singled out being invariant under orientifold projection. In our model, the family structures for the left, right quarks, left leptons and the Higgses arise from one of the tori and can naturally lead to universal strength Yukawa couplings which accommodate the quark mass hierarchy and the mixing angles.Comment: 21 pages, latex, matches the Phys. Rev. D versio

Constraints on the Nucleon Strange Form Factors at Q^2 ~ 0.1 GeV^2

We report the most precise measurement to date of a parity-violating asymmetry in elastic electron-proton scattering. The measurement was carried out with a beam energy of 3.03 GeV and a scattering angle =6 degrees, with the result A_PV = -1.14 +/- 0.24 (stat) +/- 0.06 (syst) parts per million. From this we extract, at Q^2 = 0.099 GeV^2, the strange form factor combination G_E^s + 0.080 G_M^s = 0.030 +/- 0.025 (stat) +/- 0.006 (syst) +/- 0.012 (FF) where the first two errors are experimental and the last error is due to the uncertainty in the neutron electromagnetic form factor. This result significantly improves current knowledge of G_E^s and G_M^s at Q^2 ~0.1 GeV^2. A consistent picture emerges when several measurements at about the same Q^2 value are combined: G_E^s is consistent with zero while G_M^s prefers positive values though G_E^s=G_M^s=0 is compatible with the data at 95% C.L.Comment: minor wording changes for clarity, updated references, dropped one figure to improve focu

Relating the CMSSM and SUGRA models with GUT scale and Super-GUT scale Supersymmetry Breaking

While the constrained minimal supersymmetric standard model (CMSSM) with universal gaugino masses, m_{1/2}, scalar masses, m_0, and A-terms, A_0, defined at some high energy scale (usually taken to be the GUT scale) is motivated by general features of supergravity models, it does not carry all of the constraints imposed by minimal supergravity (mSUGRA). In particular, the CMSSM does not impose a relation between the trilinear and bilinear soft supersymmetry breaking terms, B_0 = A_0 - m_0, nor does it impose the relation between the soft scalar masses and the gravitino mass, m_0 = m_{3/2}. As a consequence, tan(\beta) is computed given values of the other CMSSM input parameters. By considering a Giudice-Masiero (GM) extension to mSUGRA, one can introduce new parameters to the K\"ahler potential which are associated with the Higgs sector and recover many of the standard CMSSM predictions. However, depending on the value of A_0, one may have a gravitino or a neutralino dark matter candidate. We also consider the consequences of imposing the universality conditions above the GUT scale. This GM extension provides a natural UV completion for the CMSSM.Comment: 16 pages, 11 figures; added erratum correcting several equations and results in Sec.2, Sec.3 and 4 remain unaffected and conclusions unchange

Towards a resolution of the proton form factor problem: new electron and positron scattering data

There is a significant discrepancy between the values of the proton electric form factor, $G_E^p$, extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of $G_E^p$ from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization ($\varepsilon$) and momentum transfer ($Q^2$) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing $\varepsilon$ at $Q^2 = 1.45 \text{ GeV}^2$. This measurement is consistent with the size of the form factor discrepancy at $Q^2\approx 1.75$ GeV$^2$ and with hadronic calculations including nucleon and $\Delta$ intermediate states, which have been shown to resolve the discrepancy up to $2-3$ GeV$^2$.Comment: 6 pages, 4 figures, submitted to PR

Photoproduction of K+K− meson pairs on the proton

The exclusive reaction γp→pK+K− was studied in the photon energy range 3.0–3.8  GeV and momentum transfer range 0.6<−t<1.3  GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. In this kinematic range the integrated luminosity was approximately 20  pb−1. The reaction was isolated by detecting the K+ and the proton in CLAS, and reconstructing the K− via the missing-mass technique. Moments of the dikaon decay angular distributions were extracted from the experimental data. Besides the dominant contribution of the ϕ meson in the P wave, evidence for S−P interference was found. The differential production cross sections dσ/dt for individual waves in the mass range of the ϕ resonance were extracted and compared to predictions of a Regge-inspired model. This is the first time the t-dependent cross section of the S-wave contribution to the elastic K+K− photoproduction has been measured

Demonstration of a novel technique to measure two-photon exchange effects in elastic e±pe^\pm p scattering

The discrepancy between proton electromagnetic form factors extracted using unpolarized and polarized scattering data is believed to be a consequence of two-photon exchange (TPE) effects. However, the calculations of TPE corrections have significant model dependence, and there is limited direct experimental evidence for such corrections. We present the results of a new experimental technique for making direct $e^\pm p$ comparisons, which has the potential to make precise measurements over a broad range in $Q^2$ and scattering angles. We use the Jefferson Lab electron beam and the Hall B photon tagger to generate a clean but untagged photon beam. The photon beam impinges on a converter foil to generate a mixed beam of electrons, positrons, and photons. A chicane is used to separate and recombine the electron and positron beams while the photon beam is stopped by a photon blocker. This provides a combined electron and positron beam, with energies from 0.5 to 3.2 GeV, which impinges on a liquid hydrogen target. The large acceptance CLAS detector is used to identify and reconstruct elastic scattering events, determining both the initial lepton energy and the sign of the scattered lepton. The data were collected in two days with a primary electron beam energy of only 3.3 GeV, limiting the data from this run to smaller values of $Q^2$ and scattering angle. Nonetheless, this measurement yields a data sample for $e^\pm p$ with statistics comparable to those of the best previous measurements. We have shown that we can cleanly identify elastic scattering events and correct for the difference in acceptance for electron and positron scattering. The final ratio of positron to electron scattering: $R=1.027\pm0.005\pm0.05$ for $=0.206$ GeV$^2$ and $0.830\leq \epsilon\leq 0.943$