Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

BACKGROUND: Anti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice. METHODS: We investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing. RESULTS: After 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy. CONCLUSIONS: The cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage

SARS CoV subunit vaccine: Antibodymediated neutralisation and enhancement

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation)

Large-Scale Structure at z~2.5

We have made a statistically complete, unbiased survey of C IV systems toward a region of high QSO density near the South Galactic Pole using 25 lines of sight spanning $1.5<z<2.8$. Such a survey makes an excellent probe of large-scale structure at early epochs. We find evidence for structure on the $15-35h^{-1}$ proper Mpc scale ($H_0 \equiv 100$ km $s^{-1}$ Mpc${-1}$) as determined by the two point C IV - C IV absorber correlation function, and reject the null hypothesis that C IV systems are distributed randomly on such scales at the $\sim 3.5\sigma$ level. The structure likely reflects the distance between two groups of absorbers subtending $\sim~ 13 \times 5 \times 21h^{-3}$ and $\sim 7 \times 1 \times 15h^{-3}$ Mpc$^3$ at $z\sim 2.3$ and $z \sim 2.5$ respectively. There is also a marginal trend for the association of high rest equivalent width C IV absorbers and QSOs at similar redshifts but along different lines of sight. The total number of C IV systems detected is consistent with that which would be expected based on a survey using many widely separated lines of sight. Using the same data, we also find 11 Mg II absorbers in a complete survey toward 24 lines of sight; there is no evidence for Mg II - Mg II or Mg II - QSO clustering, though the sample size is likely still small to detect such structure if it exists.Comment: 56 pages including 32 of figures, in gzip-ed uuencoded postscript format, 1 long table not included, aastex4 package. Accepted for publication in ApJ Supplement

The Near-Infrared Number Counts and Luminosity Functions of Local Galaxies

This study presents a wide-field near-infrared (K-band) survey in two fields; SA 68 and Lynx 2. The survey covers an area of 0.6 deg.$^2$, complete to K=16.5. A total of 867 galaxies are detected in this survey of which 175 have available redshifts. The near-infrared number counts to K=16.5 mag. are estimated from the complete photometric survey and are found to be in close agreement with other available studies. The sample is corrected for incompleteness in redshift space, using selection function in the form of a Fermi-Dirac distribution. This is then used to estimate the local near-infrared luminosity function of galaxies. A Schechter fit to the infrared data gives: M$^\ast_K = -25.1 \pm 0.3$, $\alpha = -1.3\pm 0.2$ and $\phi^\ast =(1.5\pm 0.5)\times 10^{-3}$ Mpc$^{-3}$ (for H$_0=50$ Km/sec/Mpc and q$_0=0.5$). When reduced to $\alpha=-1$, this agrees with other available estimates of the local IRLF. We find a steeper slope for the faint-end of the infrared luminosity function when compared to previous studies. This is interpreted as due to the presence of a population of faint but evolved (metal rich) galaxies in the local Universe. However, it is not from the same population as the faint blue galaxies found in the optical surveys. The characteristic magnitude ($M^\ast_K$) of the local IRLF indicates that the bright red galaxies ($M_K\sim -27$ mag.) have a space density of $\le 5\times 10^{-5}$ Mpc$^{-3}$ and hence, are not likely to be local objects.Comment: 24 pages, 8 figures, AASTEX 4.0, published in ApJ 492, 45

Electronic Structure and Valence Band Spectra of Bi4Ti3O12

The x-ray photoelectron valence band spectrum and x-ray emission valence-band spectra (Ti K _beta_5, Ti L_alpha, O K_alpha) of Bi4Ti3O12 are presented (analyzed in the common energy scale) and interpreted on the basis of a band-structure calculation for an idealized I4/mmm structure of this material.Comment: 6 pages + 7 PostScript figures, RevTex3.0, to be published in Phys.Rev.B52 (Oct.95). Figures also available via anonymous ftp at ftp://ftp.physik.uni-osnabrueck.de/pub/apostnik/BiTiO

UNRESTRAINED MEASUREMENT OF ARM MOTION BASED ON A WEARABLE WIRELESS SENSOR NETWORK

Techniques that could precisely monitor human motion are useful in applications such as rehabilitation, virtual reality, sports science, and surveillance. Most of the existing systems require wiring that restrains the natural movement. To overcome this limitation, a wearable wireless sensor network using accelerometers has been developed in this paper to determine the arm motion in the sagittal plane. The system provides unrestrained movements and improves its usability. The lightweight and compact size of the developed sensor node makes its attachment to the limb easy. Experimental results have shown that the system has good accuracy and response rate when compared with a goniometer

On Witten multiple zeta-functions associated with semisimple Lie algebras IV

In our previous work, we established the theory of multi-variable Witten zeta-functions, which are called the zeta-functions of root systems. We have already considered the cases of types $A_2$, $A_3$, $B_2$, $B_3$ and $C_3$. In this paper, we consider the case of $G_2$-type. We define certain analogues of Bernoulli polynomials of $G_2$-type and study the generating functions of them to determine the coefficients of Witten's volume formulas of $G_2$-type. Next we consider the meromorphic continuation of the zeta-function of $G_2$-type and determine its possible singularities. Finally, by using our previous method, we give explicit functional relations for them which include Witten's volume formulas.Comment: 22 pag