text:
α-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system.
ABSTRACT The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (Q(aSyn)) to the albumin quotient (Q(albumin)) to evaluate its relation to blood-CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that Q(aSyn) did not rise or fall with Q(albumin) values, a relative measure of blood-CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF.
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ABSTRACT: Misfolding and intracellular aggregation of α-synuclein are thought to be crucial factors in the pathogenesis of Lewy body diseases (LBDs), such as Parkinson disease. However, the pathogenic modifications of this protein and the mechanisms underlying its activity have not been fully characterized. Recent studies suggest that small amounts of α-synuclein are released from neuronal cells by unconventional exocytosis, and that this extracellular α-synuclein contributes to the major pathological features of LBD, such as neurodegeneration, progressive spreading of α-synuclein pathology, and neuroinflammation. In this article, we review a rapidly growing body of literature on possible mechanisms by which extracellular α-synuclein contributes to LBD pathology, and discuss therapeutic approaches to target this form of α-synuclein to halt disease progression.Nature Reviews Neurology 01/2014; · 15.52 Impact Factor
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ABSTRACT: Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disorder of uncertain etiopathogenesis manifesting with autonomic failure, parkinsonism, and ataxia in any combination. The underlying neuropathology affects central autonomic, striatonigral and olivopontocerebellar pathways and it is associated with distinctive glial cytoplasmic inclusions (GCIs, Papp-Lantos bodies) that contain aggregates of α-Synuclein. Current treatment options are very limited and mainly focused on symptomatic relief, whereas disease modifying options are lacking. Despite extensive testing, no neuroprotective drug treatment has been identified up to now; however, a neurorestorative approach utilizing autologous mesenchymal stem cells has shown remarkable beneficial effects in the cerebellar variant of MSA. Here, we review the progress made over the last decade in defining pathogenic targets in MSA and summarize insights gained from candidate disease-modifying interventions that have utilized a variety of well-established preclinical MSA models. We also discuss the current limitations that our field faces and suggest solutions for possible approaches in cause-directed therapies of MSA.Progress in Neurobiology 01/2014; · 9.04 Impact Factor
Article: Quantification of α-synuclein in cerebrospinal fluid: How ideal is this biomarker for Parkinson's disease?[Show abstract] [Hide abstract]
ABSTRACT: The quantification of α-synuclein (αSyn) in cerebrospinal fluid (CSF) has been proposed as a diagnostic biomarker for Parkinson's disease and other αSyn-related diseases, such as multiple system atrophy and dementia with Lewy bodies. Most studies show decreased levels of αSyn in diseased CSF samples compared to control samples, but discrepant findings and overlapping values have been a major limitation for the use of CSF αSyn as a biomarker. This review addresses the current knowledge and investigates whether CSF αSyn is an ideal biomarker that can detect fundamental neuropathology features. It will also discuss whether CSF αSyn has been validated in neuropathologically confirmed cases, whether it shows a diagnostic sensitivity and whether it has a specificity above 80%. The review of current literature will also determine if sampling CSF αSyn is reliable, reproducible, noninvasive, simple to perform, inexpensive, and whether it has been investigated by at least two independent studies. CSF αSyn appears to meet most of these criteria, which have been proposed for ideal biomarkers, but further validation of this and other markers is needed to best introduce a panel of biomarkers in the early and differential diagnosis of Parkinson's disease.Parkinsonism & Related Disorders 01/2014; 20S1:S76-S79. · 3.27 Impact Factor
Page 1
a-Synuclein in human cerebrospinal fluid is principally
derived from neurons of the central nervous system
Brit Mollenhauer•Ellen Trautmann•Birgit Otte•Juliana Ng•Annette Spreer•
Peter Lange•Friederike Sixel-Do ¨ring•Mansoureh Hakimi•Jean-Paul VonSattel•
Robert Nussbaum•Claudia Trenkwalder•Michael G. Schlossmacher
Received: 30 November 2011/Accepted: 26 February 2012/Published online: 18 March 2012
? The Author(s) 2012. This article is published with open access at Springerlink.com
uclein (aSyn) in human cerebrospinal fluid (CSF) remains
unknown. We decided to measure the concentration of
aSyn and its gradient in human CSF specimens and com-
pared it with serum to explore its origin. We correlated
aSyn concentrations in CSF versus serum (QaSyn) to the
albumin quotient (Qalbumin) to evaluate its relation to
blood–CSF barrier function. We also compared aSyn with
several other CSF constituents of either central or periph-
eral sources (or both) including albumin, neuron-specific
enolase, b-trace protein and total protein content. Finally,
we examined whether aSyn is present within the structures
of the choroid plexus (CP). We observed that QaSyndid not
rise or fall with Qalbumin values, a relative measure of
blood–CSF barrier integrity. In our CSF gradient analyses,
The source of Parkinson disease-linked a-syn-
aSyn levels decreased slightly from rostral to caudal frac-
tions, in parallel to the recorded changes for neuron-
specific enolase; the opposite trend was recorded for total
protein, albumin and b-trace protein. The latter showed
higher concentrations in caudal CSF fractions due to the
diffusion-mediated transfer of proteins from blood and
leptomeninges into CSF in the lower regions of the spine.
In postmortem sections of human brain, we detected highly
variable aSyn reactivity within the epithelial cell layer of
CP in patients diagnosed with a range of neurological
diseases; however, in sections of mice that express only
human SNCA alleles (and in those without any Snca gene
expression), we detected no aSyn signal in the epithelial
cells of the CP. We conclude from these complementary
results that despite its higher levels in peripheral blood
products, neurons of the brain and spinal cord represent the
principal source of aSyn in human CSF.
Blood–CSF barrier ? Biomarker ? Choroid plexus
a-Synuclein ? Cerebrospinal fluid ?
The pathological hallmarks of Parkinson disease (PD)
include progressive cell loss of selective nuclei in the
nervous system and the formation of intracellular aggre-
gates that contain insoluble, wild-type a-synuclein (aSyn)
(Spillantini et al. 1997). The clinical phenotype of auto-
somal dominant PD parallels aSyn gene (SNCA) dosage
with a more severe phenotype observed in the cases of
locus multiplication (Singleton et al. 2003). The quantifi-
cation of the 140 amino acid-long, 16–17 kDa aSyn protein
in biological fluids has been proposed as a biomarker
candidate (Mollenhauer et al. 2010). aSyn has been shown
B. Mollenhauer (&) ? E. Trautmann ? B. Otte ?
F. Sixel-Do ¨ring ? C. Trenkwalder
Paracelsus-Elena-Klinik, Klinikstrasse 16,
34128 Kassel, Germany
e-mail: firstname.lastname@example.com
B. Mollenhauer ? A. Spreer ? P. Lange ? C. Trenkwalder
Department of Neurology and Clinical Neurophysiology,
Georg-August University Goettingen, Goettingen, Germany
J. Ng ? M. Hakimi ? M. G. Schlossmacher
Division of Neuroscience, Ottawa Hospital Research Institute,
University of Ottawa, Ottawa, ON, Canada
J.-P. VonSattel
Institute of Pathology, Columbia University,
New York, NY, USA
R. Nussbaum
Division of Medical Genetics, Department of Medicine,
University of California, San Francisco,
San Francisco, CA, USA
J Neural Transm (2012) 119:739–746
DOI 10.1007/s00702-012-0784-0
Page 2
to be present in cerebrospinal fluid (CSF) in low picogram/
microliter amounts; its levels in serum and plasma are up to
tenfold and in whole blood up to 10,000-fold higher
(Mollenhauer et al. 2010) due to the fact that aSyn is also
et al. 2008).
The production and hydrodynamics of human CSF are
complex and vary considerably depending on the level
within the neuroaxis. The three main sources for CSF
constituents comprise: one, the metabolism of neural cells
in the central nervous system (CNS); two, diffusion of
constituents from circulating blood into CSF [even in the
absence of any trauma (Hong et al. 2010; Mollenhauer
et al. 2011)]; and three, the secretion by the epithelial
cells that reside within the brain's choroid plexus (CP)
(Chodobski and Szmydynger-Chodobska 2001). CSF
volume and its continuous renewal are predominantly
regulated by CP activity. An estimated 80% of all CSF
proteins are blood-derived (with albumin being the most
abundant); their concentrations in the nervous system
increase in the subarachnoid space from rostral to caudal
levels due to diffusion gradients that emanate from blood
vessels intersecting with the flow of CSF (Reiber 2003). A
rise from rostrum to cauda is also observed for certain
constituents that are secreted by leptomeningeal structures
(e.g., b-trace protein) (Reiber 2003). In the case of
abnormally low CSF flow rates, which result in increasing
concentrations of blood-derived proteins in lumbar CSF
fractions, the concentration of brain-derived proteins
[e.g., neuronspecific enolase (NSE)] usually remains
constant (Reiber 2003). Because albumin is solely syn-
thesized in the liver, the quotient of its CSF-to-serum
concentrations (referred to as Qalbumin) reflects an indirect
measure of blood–CSF barrier function in vivo.
This study was designed to investigate whether CSF
aSyn is mainly brain or blood derived. To this end, we
compared aSyn concentrations in CSF versus serum
(QaSyn) with Qalbuminin 42 patients with various neuro-
logical diseases. Next, we quantified aSyn levels in
patients with normal blood–CSF barrier function and
compared them to specific brain-derived (e.g., NSE),
blood-derived (e.g., albumin), and leptomeninges-derived
(e.g., b-trace) proteins in serially collected CSF samples,
to examine their rostro-caudal concentration gradients.
Furthermore, we also probed whether CP tissue contained
aSyn reactivity.
We collected CSF and serum from patients with different
neurological conditions. These 42 participants underwent
lumbar puncture (LP) for routine diagnostic purposes
(Table 1) to determine the presence (or absence) of acute
inflammatory disease, acute hemorrhage and suspected
Lyme disease (n = 31); to exclude chronic inflammatory
diseases (n = 3); to determine carcinomatosis of the lep-
tomeninges in the case of a known primary tumor (n = 4),
and to carry out CSF volume reduction in patients with
normal pressure hydrocephalus (NPH; n = 4). All study
participants were enrolled at the Department of Neurology
at Goettingen University, Germany. Samples were col-
lected and processed as published (Mollenhauer et al.
2010). We further examined samples that featured: a nor-
mal (\5/ll) white blood cell count; the absence of intra-
thecal immunoglobulin production (as determined by the
absence of oligoclonal bands); normal CSF tau protein, and
no LP-induced contamination by blood (determined by a
red blood cell count of\50/ll). CSF aSyn and serum aSyn
(diluted at 1:15) concentrations were measured by enzyme-
linked immunoabsorbent assay (ELISA) as published
(Mollenhauer et al. 2011).
In a second set of study participants we collected CSF
from five patients at the Paracelsus-Elena-Klinik, Kassel,
Germany. All patients suffered from NPH as determined by
magnetic resonance imaging and according to the estab-
lished clinical criteria (Relkin et al. 2005) (Table 1). We
performed volume reduction by LP on each patient and
serially collected seven CSF fractions (5 ml each) that
were processed as published (Mollenhauer et al. 2010). LP
was carried out at the L2/L3 level in the sitting position,
between 8 and 9 a.m. with the patient having fastened for
12 h. In each fraction we analyzed CSF aSyn (Mollenhauer
et al. 2011), NSE (Schaarschmidt et al. 1994) and b-trace
protein (Tumani et al. 1998), as described. Total protein
and albumin levels were measured by nephelometry (Dade
Behring/Siemens Healthcare Diagnostics).
Immunohistochemistry of postmortem brain sections
containing CP structures was carried out following for-
malin fixation and paraffin embedding with anti-aSyn
antibodies, as published (Louis et al. 2005; Schlossmacher
et al. 2002). In parallel, sections from mouse brain trans-
genic for four Ala53Thr-containing human SNCA alleles
(but no mouse Snca) and Snca-null mice without any
endogenous Snca and no transgene expression [engineered
as described (Kuo et al. 2011)] were processed by the same
protocol. Polyclonal (hSA5.1; Open Biosystems Inc) and
Table 1 Demographic data of enrolled patients of both cohorts
Set 1Set 2
Sex (male/total)0.5 0.6
Age (years) 58 ± 2176 ± 4
Mean ± standard deviation (range)(19–93)(69–79)
740B. Mollenhauer et al.
Page 3
monoclonal (12–1; Epitomics Inc) antibodies to wild-type,
full-length human aSyn were raised in goat and rabbit,
respectively, purified and characterized (Cullen et al. 2009;
Mollenhauer et al. 2008).
The study was carried out in accordance with the Dec-
laration of Helsinki and with informed written consent
provided by all patients or their next of kin. The study was
approved by the ethics committee at the University of
Goettingen (Germany).
Possible correlations between the concentrations of CSF/
serum aSyn to CSF/serum albumin (i.e., Qalbumin) were
analyzed according to Pearson. Results for aSyn, NSE,
b-trace, albumin and total protein values in CSF are
demonstrated in Table 2 and Fig. 1. Statistical analyses
(non-parametric) of the data were performed to assess the
characteristics in CSF vials 5–7 (cisternal fractions) and
1–4 (lumbar fractions) for each described variable using
the trend test from Page (Page 1963). The Page's L trend
test examined whether the levels are ordered in a specific
order/sequence. For all tests, the a-level of significance was
set at 5 %. Furthermore, effect sizes (Hedge's g) were
calculated (Ray and Shadish 1996). A correction formula
for small sample bias was also applied (Hedges and Olkin
CSF a-synuclein in subjects with known blood–CSF
barrier function
CSF specimens analyzed from 42 patients showed a mean
Qalbumin of 8.90 ± 7.7 9 10-3(mean ± standard devia-
tion; SD) (range 1.8–37.2 9 10-3). CSF aSyn levels ran-
ged from 1.29 to 2.97 pg/ll (mean ± SD; 1.99 ± 0.39).
Serum aSyn levels ranged from 14.33 to 67.47 pg/ll (mean
29.54 ± 10.79), and the mean CSF/serum aSyn (QaSyn)
was calculated as 0.08 ± 0.032. The coefficients of
variation (CV) for aSyn values measured 19.6% in CSF,
36.5% in serum, and the CV for QaSynwas 40%. Impor-
tantly, when examining QaSyn together with Qalbumin
values, we recorded no significant correlation (-0.109;
p = 0.493; Fig. 2).
CSF a-synuclein and other protein values from
rostro-caudal fractions
CSF aSyn levels across all fractions examined ranged from
1.17 to 2.64 pg/ll (mean 1.70 ± 0.36) in specimens from
five NPH patients that were analyzed. Qalbuminin these
cases ranged between 5.4 and 7.8 9 10-3. Across the
35 ml of CSF collected in our NPH patients, aSyn con-
centrations showed a slight increase that initially paralleled
the proximity of the sample collected toward the brain (and
as reflected by increasing fraction numbers in the first
20 ml collected), which represented a trend without sta-
tistical significance (L = 130; p[0.05). The levels of
exclusively neuron-derived NSE remained stable through-
out (L = 134; p[0.05; Table 2; Fig. 1). In contrast,
blood-derived albumin (L = 145.5; p\0.05) and total
protein (L = 139; p\0.05) decrease significantly in the
rostral fractions (#5 to #7, i.e., in the last 15 ml of each LP
volume collected; Table 2; Fig. 1) compared to caudal
fractions (#1 to #4, i.e., corresponding to the first 20 ml
collected), as expected from the published literature
(Sullivan et al. 2006). Albeit to a lesser extent, leptome-
ninges-derived b-trace protein also showed a mild decrease
in its concentration with progression from the lumbar
region toward the cranial compartment (L = 138.5;
p\0.05). Figure 1 shows the median values for each
fraction and for each protein.
Choroid plexus epithelium is an unlikely source
of a-synuclein
The intra-ventricular network of the CP represents the
predominant site for CSF volume production in vivo. To
also explore CP as a possible source for CSF aSyn, we first
examined postmortem human brain sections by routine
Table 2 Quantification results
including mean levels in seven
fractions (F1 lower F7 upper
position) for CSF a-synuclein
(aSyn), total protein, albumin,
neuron specific enolase (NSE)
and b-trace protein
Total protein
b-Trace protein
Rostrocaudal ratio1.160.610.561.13 0.90
a-Synuclein in human cerebrospinal fluid741
Page 4
immunohistochemistry (IHC). We unexpectedly detected
highly variable aSyn reactivity within the epithelial cell
layer of human CP (Fig. 3a). When comparing sections
from several diagnostic categories, we saw considerable
differences in the staining intensity of adult CP epithelium
among cases with synucleinopathy [PD, dementia with
Lewy bodies (DLB)], progressive supranuclear palsy,
Alzheimer's and Huntington disease and aged control
subjects (Fig. 3a; data not shown), but did not record a
correlation between aSyn reactivity in CP epithelium and
the final diagnosis. To determine whether the aSyn signal
in postmortem CP was reflective of physiological metab-
olism in vivo, we decided to examine brain sections of
''humanized'' SNCA-transgenic mice (Kuo et al. 2011)
versus animals deficient in murine (and human) aSyn using
the same IHC protocol. There, we detected no aSyn reac-
tivity in the CP epithelium-containing sections of SNCA-
transgenic mice, wild-type animals and Snca-null mice
(Fig. 3b–d; data not shown). In contrast, CNS structures
including neurons and presynaptic terminals (as well as
intravascular erythrocytes) showed strong aSyn immuno-
reactvity, as expected from the corresponding genotype
(Fig. 3b, c; data not shown). We concluded from these
findings that CP, a highly vascularized organ within the
brain, represents an unlikely source for the constitutive
release of aSyn into CSF in vivo; however, a possible
uptake of aSyn from CSF by CP cells postmortem could not
be excluded.
To elucidate the source of aSyn in CSF, we measured its
levels in CSF and serum from a cohort with variable
Qalbuminvalues (Blennow et al. 1993; Reiber 2003) and in a
second, small cohort of NPH patients, where we measured
Fig. 1 Median(andinterquartilerange)valuesforCSFtotalprotein(in
mg/dl), albumin (in mg/dl), neuron specific enolase (NSE) (in mg/l),
b-trace-protein (mg/l) and a-synuclein (aSyn) (in pg/ll 910) in all
seven fractions
05 101520 25303540
Q albumin (CSF/serum)
Q alpha-synuclein (CSF/serum)
Fig. 2 Correlation of QaSynand
742B. Mollenhauer et al.
Page 5
CSF aSyn together with several proteins from different
CNS sources. Our collective results suggest that CSF aSyn
is predominantly derived from structures and functions
associated with the brain rather than from peripheral blood
CSF aSyn has been discussed as a possible biomarker
for aSyn-related disorders such as PD, DLB and multiple
system atrophy (MSA) (Mollenhauer et al. 2011) and
reviewed in (Mollenhauer et al. 2010); its presence in
normal human CSF has been previously confirmed by mass
spectrometry (Mollenhauer et al. 2008). The majority (but
not all) of the CSF aSyn quantification studies conducted
over the last 6 years have shown a decrease of total aSyn
levels in CSF from PD, DLB and MSA patients, as mea-
sured by ELISA and Luminex platforms [reviewed in:
(Mollenhauer et al. 2010, 2011)]. These biomarker explo-
ration efforts raised—among other issues—the question of
the possible sources of CSF aSyn, which theoretically
include the following: (1) physiological exocytosis by
neural cells of the brain and spinal cord (Lee et al. 2005;
Mollenhauer et al. 2008); (2) secretion by the epithelial
cells of the CP; (3) release by cells of the ependymal lining
of the brain's ventricular system; (4) secretion by endo-
thelial cells of the brain's vasculature; (5) normal filtration
of peripheral plasma through the brain's capillary system
(or following a compromise in the integrity of the blood–
CSF barrier); (6) diffusion and/or entry of blood products
in anatomically privileged sites without effective blood–
CSF barrier; and lastly, (7) physiological attrition of neural
cells as well as neuronal injury in the CNS.
Because aSyn is highly abundant in blood cells, espe-
cially in erythrocytes, discrepant findings across cross-
sectional studies have raised the possibility of divergence
due to artificial blood contamination, which occurs in
10–20% of routine LPs (Mollenhauer et al. 2010, 2011).
However, in most (but not all) published CSF aSyn quan-
tification studies, the possibility of blood contamination as
the source of CSF aSyn has been addressed and largely
excluded [reviewed in (Mollenhauer et al. 2010)].
In examining the influence of the blood–brain barrier on
CSF and serum aSyn levels from neurological controls, we
found no correlation between the concentration of CSF
aSyn and QaSynwith Qalbumin. Therefore, we concluded that
CSF aSyn levels were not controlled by the blood–CSF
Fig. 3 Probing for a-synuclein (aSyn) reactivity in mammalian
choroid plexus. Formalin-fixed, paraffin-embedded sections of post-
mortem human brain are shown, including from a 65-year-old man
with progressive supranuclear palsy (a), and of 'humanized SNCA'-
transgenic mouse brain (b, c) with a segment of the 4th ventricle
(a, b) or lateral ventricle (c). All sections contain choroid plexus (CP)
epithelium and were probed for aSyn reactivity with anti-aSyn
antibodies by routine immunohistochemistry and counterstained with
hematoxyline. Cortical sections from a Snca-null mouse (d) were
processed in parallel. Antibodies used in a, b and d: goat-anti-human
aSyn (hSA5.1); in c, monoclonal rabbit antibody to human aSyn
(12–1). Representative specimens from human autopsy material
(n = 5), hSNCAA53T-transgenic mice (n = 4) and Snca-null animals
(n = 2) are shown. Arrows identify unlabelled epithelial cells of CP;
in contrast, stars denote the robust expression of aSyn in the neuropil
of SNCA-expressing mice
a-Synuclein in human cerebrospinal fluid743
Page 6
barrier under physiological conditions. However, larger
cohorts comprising patients with various inflammatory
conditions will need to be examined (e.g., multiple scle-
rosis) to discern the effect of aSyn distribution under
pathological blood–CSF barrier conditions.
Due to the protective role of the barrier function on CNS
integrity, we also calculated the coefficients of variation
(CV) as a reflection of biological variability. The CV value
for aSyn in CSF was smaller than that for serum aSyn. The
latter observation provided independent (albeit indirect)
support for our conclusion that under normal conditions the
majority of aSyn species detected in CSF was unlikely to
be blood borne; if it would have been predominantly
derived from blood, the CV of CSF aSyn values would
have been expected to be at least equal—if not larger—
than those of serum aSyn. Another possible explanation for
the different CV values is that our assay could have cap-
tured CSF aSyn more readily than serum aSyn (for
example due to protein complex formation and thus altered
antibody accessibility), but this scenario seems unlikely
given the significantly larger amounts of aSyn recorded by
our assay in all serum samples than in CSF (Mollenhauer
et al. 2010, 2011).
To further examine aSyn levels along the rostro-caudal
flow of CSF, we collected a total of 35 ml in seven serial
fractions in all NPH patients. The lumbosacral CSF volume
is highly variable among individual patients and is esti-
mated to contain 35.8 ± 10.9 ml with a total range from
10.6 to 61.3 ml in adult humans (Sullivan et al. 2006).
With the LP performed at the L2/L3 level in all study
participants, we inferred that fractions #1–4 contained CSF
from the caudal subarachnoidal space where it supports
spinal cord suspension (and function), whereas fractions
#5–7 represented CSF derived from space closer to (and
above) the craniocervical juncture following direct contact
with the brain. Our analysis revealed the expected rostro-
caudal increase of plasma-derived proteins (i.e., total pro-
tein and albumin), which is thought to reflect a longer
transit time of CSF to the lumbar spine region and a higher
proportion of diffusion-mediated transfer of proteins from
blood to CSF (Reiber 2003). In our study, b-trace protein
concentrations also increased in a rostro-caudal gradient,
as expected from studies that simultaneously analyzed
ventricular and lumbar CSF samples (Reiber 2001, 2003);
b-trace protein is mainly released by leptomeningeal
structures. In contrast, the neuron-derived protein NSE
showed the expected rostro-caudal stability in our hands,
possibly even a slight reduction for the concentrations
recorded in lumbar fractions #1–4. These collective find-
ings strongly supported the conclusions that these seven
fractions indeed represented different levels of CSF col-
lected from the lumbar as well as cisternal regions of
subarachnoid space. The concentration behavior of our
analyte of interest, total aSyn, behaved most closely to that
of NSE en route from the rostrum of the brain to the
lumbosacral space. This decreasing rostro-caudal gradient
is, therefore, in support of a concept that sees the brain as
the most important source of CSF aSyn followed by ner-
vous system structures below the medulla.
A decreasing rostro-caudal gradient for CSF aSyn con-
centrations was also reported by Hong and colleagues, who
analyzed three fractions in 45 control subjects showing a
trend for decreased CSF aSyn in lower # fractions (Hong
et al. 2010). Although the Hong et al. CSF samples were
not centrifuged after their collection, therefore, raising the
theoretical possibility of blood and epithelial cell contam-
ination (which could have influenced their findings), our
results confirm and expand the conclusions reached by
these and other authors exploring the source of extracel-
lular aSyn in human brain (Emmanouilidou et al. 2011).
Our study on CSF aSyn is limited by its small sample
size and a selection bias towards patients with non-neuro-
degenerative conditions. In future studies, patients with
neurodegenerative and inflammatory illnesses as well as
medically healthy participants have to be analyzed. Nev-
ertheless, our results support the concept of a source of
CSF aSyn that is predominantly (but not exclusively)
associated with nervous system structure and function
under physiological conditions, and is less likely to be
blood borne. Our results do not exclude the possibility that
this distribution is markedly altered in diseases associated
with significant neuronal lysis (e.g., due to prion disease)
(Mollenhauer et al. 2008).
Our finding of variable immunoreactivities for aSyn
within the epithelium of CP in human brain (but not mouse
brain) sections could indicate a relevant site for aSyn
uptake postmortem from circulating CSF [as reported for
example for amyloid-b-protein (Crossgrove et al. 2005)
(Wolburg and Paulus 2010)] in some patients. However,
our findings in genetically engineered mice make de novo
gene transcription in CP and secretion (or filtration of aSyn
from plasma into CSF by CP epithelial cells) very unlikely.
Alternatively, technical reasons (such as those related to
possible antibody cross-reactivity with unknown antigens)
when processing human versus mouse brain could also
explain the observed species difference. Lastly, in future
studies we will revisit whether this variable immunoreac-
tivity for aSyn in human CP may be related to the final
diagnosis of the patient. To date, we have not yet observed
such a correlation.
Understanding the sources of aSyn, delineating the
molecular events underlying its presumed exocytosis by
cells into the interstitial, ventricular and subarachnoid
spaces of the CNS, and cataloging its modified variants
represent pivotal tasks for our field in the future. They are
important in the identification of the unknown function of
744B. Mollenhauer et al.
Page 7
aSyn in CSF, its main degradation pathways in intra- and
extracellular compartments (including in CSF), and its
possible uptake by neural, ependymal and epithelial cells
from circulating CSF. These related topics have major
implications for the pathogenesis, the diagnosis and pos-
sibly, the progression of several, currently incurable syn-
ucleinopathy disorders of the brain including PD, MSA and
DLB (Desplats et al. 2009; Hong et al. 2010; Kramer and
Schulz-Schaeffer 2007; Mollenhauer et al. 2011;Volpicelli-
Daley et al. 2011).
review and excellent advice. This work has been supported by the
Michael J. Fox Foundation for Parkinson's Research (B.M.; M.G.S.),
the Government of Canada (CRC/CIHR; CFI) and the Parkinson
Research Consortium of Ottawa (M.G.S.).
We thank Hansotto Reiber for his critical
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Full-text (2 Sources)
Brit Mollenhauer


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As long as the BN regime maintains its accursed Sedition Act, by rights it should be used against former Prime Minister Tun Dr Mahathir before anybody else. Not just for his patronage and support of race-hate groups like Perkasa, but for his repeated racist rants like his latest against Malays.
Who the hell does he think he is to brand millions of people of a particular ethnicity, or indeed any ethnicity, as "lazy", shameless and lacking in integrity?
And who do his accomplices the Umno/BN regime think they are to try and silence critics and opposition figures with their accursed Sedition Act, but fail to employ it to shut Mahathir up?
If there is any group in Malaysia that is lazy, shameless and short on integrity, it's not any sector of the populace, racial, religious or otherwise, but the members, supporters and cronies of the ever-ruling regime itself.
In fact most of them deserve shutting-up quite as richly as does Mahathir himself. And not just shutting-up as in silenced, but shutting-up as in jailed.
Mahathir should have been tried years ago for not just repeated acts of sedition, but the many other crimes that have been persuasively alleged against him, including, at the very least, repeated abuse of power and massive corruption.
And if there is any single figure in Malaysia who should emulate the Japanese he is always citing as his standard of excellence, it's himself.
"You see the Japanese, they have a lot of shame, not ashamed of being naked, but ashamed of failure. If they fail to commit a duty, they commit suicide," he remarked during his diatribe against Malays, who he accused of "not being embarrassed even if they fail their examinations."
Leaving aside altogether Mahathir's well-known obsession with nakedness, it seems to me that if any single living Malaysian who should be ashamed to have failed to do his duty it is the man himself.
In fact so far from doing his duty to Malaysia during his premiership and ever since, he's done nothing but the dirty on the country by deliberately and systematically destroying its judiciary, police, mainstream media and other institutions for his personal and political benefit.
But there's been no sign whatever that he will ever take responsibility for his shameful misdeeds, let alone consider committing hiri kiri.
In fact all he commits is one hypocrisy after another, as in the story he told to illustrate what he claims to be Malays' lack of integrity in handling money.
"I run a bread shop now, after my retirement. And I had to fire my manager because they (sic) tried to take some money on the side. I experienced this myself."
What a ludicrous and self-accusatory remark this was, in light of the fact that it is common knowledge that corruption, fraud, embezzlement, theft and other "leakages" during Mahathir's 22 years as Prime Minister cost Malays and other Malaysians somewhere between RM100 billion and US$100 billion.
And into a very bad bargain, at least two of Mahathir's own sons received massive bailouts of their then failing businesses, and Mahathir himself is reputedly so unaccountably rich that he's commonly known as the 44-billion-dollar man.
So what does he think he's doing and who does he think he's kidding in accusing ordinary, everyday, honest Malays of lacking financial integrity?
It would be far more appropriate, in the old "it takes a thief to know one" department, for Mahathir to confine his financial suspicions to the other recent target of his wrath besides Malays, the national so-called investment fund, 1Malaysia Development Berhad (1MDB).
As he wrote in his blog, truthfully for a change, "the money for 1MDB is not from the country's surplus. It is a debt. Billions of ringgit in debt that is added to the already-high national debt."
Debt is certainly the theme of 1MDB. This highly secretive entity was reported recently by Reuters to be "struggling under a US$11 billion (RM35.51 billion) debt, and is not generating enough revenue to even cover interest costs."
Of course Mahathir's aim in blowing the whistle on this scam was not to advocate the kind of financial integrity he claims Malays are lacking, the better to divert attention from himself, but to continue his current assault on Prime Minister Najib Abdul Razak.
He recently very publicly announced that he was withdrawing his support for Najib on the grounds that his leadership is weak and ineffectual, and the gathering storm surrounding 1MDB, of which Najib is head of the advisory board, is a welcome element of his campaign.
A campaign that most of us perceive as some kind of last-ditch Machiavellian, or rather Mahathirvellian, move to elevate his son Mukhriz to within at least sight of the premiership.
But even Mahathir must realize that Mukriz, even though he's been installed as Menteri Besar of Kedah, will be politically dead meat once his doting old dad's gone.
Typically, all the mealy-mouthed Mukhriz could muster in support of his aged father's anti-Najib bluster was the groveling claim that such criticism "came from love for the present leadership."
"I want to convince Datuk Seri (Najib), and I think Datuk Seri is also aware that the criticism by my father, Tun Mahathir, is made out of love and intended to give strength to Datuk Seri," Mukhriz said.
He pressed on in this sickeningly sycophantic but utterly unconvincing vein with the remark that "only those who loved a person would criticize the person concerned with the intention of making the person to (sic) correct mistakes that had been made."
Perhaps, just as this was supposed to satisfy Najib, it may also have been intended to mollify Malays unjustly and thus insultingly accused by Mahathir of being lazy, shameless and lacking in financial integrity.
But I doubt the "tough love" story will work. More and more Malays, like their Malaysian brothers and sisters of Chinese, Indian and many other ethnicities, are sick to their stomachs of Mahathir and his malicious lies.
So it's high time that Najib used its Sedition Act to shut the man up. Or, better still, that Malaysians of all races and creeds finally united to shut up Mahathir, Najib and the rest of the celaka BN regime behind bars where they all belong.

subset: commoncrawl


text:
Most successful engineering firms work for multiple clients. And of course, with multiple clients come files in multiple CAD formats. So, at Hofmann Engineering GmbH in Schwaig (a municipality in Bavaria in Germany), engineers use a variety of CAD systems—because everybody seems to need something different. Nothing revolutionary there. What is innovative about Hofmann is that when […]
PTC Creo Resources
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- FIRST Tech Challenge Team #7719 completes its rookie season. [VIDEO]>> ptc.co/BEGqn #PTC_Creo @PTC_FIRST @FRCTeams 1 hour ago
- Review the upcoming September schedule for #PTC_Creo and #PTC_Mathcad demos and technology tips.>> ptc.co/Bxtp5 11 hours ago
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Val Dieu Grand Cru (In Store Only)
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Elliston Place properties sell for $1.8M
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- Nevin Batiwalla
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Two Elliston Place properties have sold for $1.8 million.
I & G Elliston Inc. bought a vacant 0.4-acre lot at 2110 Elliston Place and a 0.26-acre site home to Dry Clean USA building at 201 21st Avenue, near Baptist Hospital. I & G shares an address with global-asset giant LaSalle Investment Management.
According to media reports, LaSalle is serving as investor on a project that will be developed by Tony Giarratana, though he has declined to elaborate on that project. Giarratana has not responded to requests for comment from the Nashville Business Journal.
The seller was Elliston Village Inc., a subsidiary of Nashville-based XMi Commercial Real Estate.
The Dry Clean USA building sold for $750,000 in 2008.
Nevin Batiwalla covers real estate/development and regional economic development.
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Dana White's first video blog for this weekend's highly anticipated rematch between Dan Henderson and Shogun Rua focuses in on UFC 169 and 170.
Dana White's VLOGs have returned with this most recent edition, taking the VLOGs from UFC 169 and 170 and putting them together with a lot of yelling at you to not forget that this weekend's rematch between Mauricio Rua and Dan Henderson take place on Sunday night, not Saturday.
UFC President Dana White went on FOX Sports Live and offered his thoughts on the Ray Rice domestic assault incident. With growing media interest in the NFL/Ray Rice domestic violence incident, the di read news >>
In Dana White's first video blog for UFC 177, Matt Mitrione comforts a distraught Stefan Struve after the heavyweight passed out in the locker room, Uriah Hall deals with the agonizing aftermath of h read news >>
From a heartbreaking decision to pull the Struve vs. Mitrione fight to Ronda Rousey's mangled finger, Dana White's UFC 177 video blog is one of the most emotional ever, as we go behind the scenes at read news >>
In his video blog for Saturday's UFC 177 event, UFC President Dana White takes us behind the scenes of July's big UFC 175 pay-per-view.Filed under: News, UFC, Videos read news >>
Fight week, blog week! Dana White's video blog series is back for UFC 177: "Dillashaw vs. Barao 2," which takes place this weekend (Sat., Aug. 30, 2014) at Sleep Train Arena in Sacramento, California read news >>
Ronda Rousey blew out a knuckle and was subjected to one of the UFC's most awkward post fight interviews, Stefan Struve collapsed back stage, and Uriah Hall broke his toe in half. All the best footag read news >>
'Fight week, blog week' hasn't been great for UFC president Dana White. After being found to be in breach of the promotion's regulatory protocol for removing judge Howard Hughes from officiating at U read news >>
Video preview: Ultimate Fighting Championship (UFC) returns to FOX Sports 1 this Friday night (Sept. 5, 2014) with UFC Fight Night 50: "Jacare vs. Mousasi" from inside Foxwoods Resort & Casino in Led read news >>
UFC president Dana White discussed Renan Barao, Gina Carano, the signing of Bellator champion Eddie Alvarez, his belief that teammates TJ Dillashaw and Urijah Faber would fight each other, and much, read news >>


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Mobile Site You Are Here > PFR Home > Players > W > Ralph White > News Archive
News: s-r blog:Added Targets to Player and Team Pages
Ralph S. White
Position: E
Height: 5-9 Weight: 175 lbs.
Born: November 18, 1902 in Scranton, PA
Died: March 24, 1982 in Riverhead, NY
High School: East SideCollege: NYU
Weighted Career AV (100-95-...): 0 (14418th overall since 1950)
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22 Things We Learned About Kimye From Their Wedding Special
Also, let it be known that THEY NEVER ACTUALLY SHOWED THE WEDDING.
1. This is Kim's thought process about getting married.
2. Kanye did not see Kim's dress before the wedding.
3. Kim will sometimes go against Kanye's wishes and film North…just for a little bit.
4. North wore a dress made from the same lace as Kim's dress.
5. Oh, and Kim calls North "cutie."
6. Kanye does not like hands in pockets, nor gum.
8. And she also has no attention span.
10. Everybody hated Kim's bridesmaid dresses so she ordered new ones.
11. The new dresses had optional slits in the front of them — which Kanye didn't like.
12. What Kanye says about slits goes.
13. A LOT of people cared about the wedding shower.
15. Rob skipped the wedding because he read comments about his appearance.
(And Kim didn't want to talk about it until after the wedding.)
17. Really, really, seriously hungover.
18. Kim had concerns about her part.
19. She also had concerns about Kylie's blue hair, but ~let it go~ because she is a ~chill bride~.
20. Kim's veil was hard to deal with.
21. And finally: Scott Disick shows no mercy with his zingers.
(This happened mere minutes before Kim walked down the aisle.)
And then we didn't learn anything else because in THIS wedding special, the *actual* wedding was not shown.
Check out more articles on BuzzFeed.com!


text:
Observatory hosting telescope fair
Nov 6, 2012 12:29 PM | Print
The Lake Afton Public Observatory and the Kansas Astronomical Observers will host a telescope fair from 7:30-10 p.m. Saturday, Nov. 17, at the observatory.
The observatory will also present its regularly scheduled program that evening, "Universe of the 1920s – Deep Sky Theme."
The event is also from 7:30-10 p.m.
This story has been tagged Events, Lake Afton Public Observatory, Fairmount College of Liberal Arts and Sciences. See all RSS feeds here
Created on Nov 6, 2012 12:29 PM; Last modified on Nov 6, 2012 12:32 PM
Rhatigan Renewal revives campus life
WSU dedicates building named for former president
Innovative splint developed by WSU researchers
Students feel at home in Shocker Hall
WSU expansion will support job growth, innovation
Wichita State Musical Theater presents 'The Spitfire Grill'
Economic Outlook Conference, Oct. 9
History Department special presentation
Workshop to prepare students for ACT
Nursing student workshop to be held at WSU
WSU hosting 'Writing Now, Reading Now' series
WSU to host ACT Math Workshop
David Cabela to speak at WSU forum
Constitution Day activity at WSU
The Elliott School of Communication turns 25
Kansas Council for Economic Education receives grant
Ray to discuss photography at reception
Students, community welcome at WSU outdoor movie
AQR holiday travel forecast: Book early
CEDBR now offers indicators in optimal format
WSU finance students study the market in real time
Tree planting honors WSU's KBOR anniversary
WSU School of Nursing one of 100 schools chosen
Claycomb named as WSU Ventures director
Innovation helps WSU School of Nursing reach students


text:
User talk:Grrrlriot
Feel free to leave me a message by clicking "edit this page". Just a note: If I have contacted you on your talk page, I have your talk page on my watchlist, so I know when you reply to me. If you leave me a message here, I will respond here.
Wikipedia:WikiProject Metal[edit]
|Hello Grrrlriot, you have received this notice because you have placed your name on the list of members of WikiProject Metal. We are currently looking to make the wikiproject more active, and in doing so, we need to have a list of active members on the wikiproject. If you wish to stay an active part of wikiproject metal, please add your username to Wikipedia:WikiProject Metal/Active Users. Conversely, if you wish to leave the wikiproject, please remove your name from Wikipedia:WikiProject Metal/Members. Thank you.
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Just to let you know -- Missing Wikipedians[edit]
You have been mentioned at Wikipedia:Missing Wikipedians. XOttawahitech (talk) 20:33, 17 December 2013 (UTC)
Wiki Loves Pride 2014[edit]
Hi Grrrlriot. In case you are not aware, there is an upcoming campaign to improve coverage of LGBT-related topics on Wikipedia, culminating with an international edit-a-thon on June 21. See Wiki Loves Pride 2014 for more information. If you are interested, you might consider creating a page for a major city (or cities!) near you, with a list of LGBT-related articles that need to be created or improved. This would be a tremendous help to Wikipedia and coverage of LGBT culture and history. Thanks for your consideration, and please let me know if you have any questions! --Another Believer (Talk) 16:12, 9 May 2014 (UTC)
Personal infoboxes in relation to patriotism and nationalism[edit]
Hi Grrrlriot,
I saw your name on the Wikipedia:WikiProject Discrimination#Participants listing.
There is a discussion at Template talk:Infobox person#Citizenship suggesting a change of emphasis to a Citizenship entry from the Nationality entry.
The idea is to give more facilitation to Patriotism instead of Nationalism and also to allow more freedom of expression in regards to terminologies used.
Contributions are welcomed but may be worth checking last edit to check progress first :) Regards Gregkaye (talk) 20:48, 31 August 2014 (UTC)


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The Canadian Press - ONLINE EDITION
Balsamic cream, coconut vinegar among top 10 innovative products at trade show
TORONTO - Will Canadians be dipping their bread in or dressing their salads with coconut vinegar next year?
The food item was named among the top 10 Most Innovative Products for 2013 during Grocery Innovations Canada on Tuesday.
Canadian grocers and industry delegates voted on the innovative products at the grocery industry conference and trade show. Attendees had the chance to test and review hundreds of new products for the year ahead.
Products were evaluated based on three criteria: most unique, most buzzworthy and best consumer response.
In no particular order, the top 10 products are:
— MiO Liquid Water Enhancer, which allows users to customize and infuse water with sugar-free flavours like fruit punch and sweet tea (Kraft Foods Inc.) www.kraftbrands.com/mio
— Duncan Hines Red Velvet Cake Mix (Acosta Canada) www.duncanhines.com
— Stock First, a new line of chicken stock and beef stock (Campbell's) www.cookwithcampbells.ca
— Arvum balsamic cream of sherry vinegar (La Carrera)
— Coconut Vinegar (Organika) www.facebook.com/OrganikaHealth
— E6 Energy Strips, strips containing caffeine that dissolve when placed on the tongue (Simcoe Asia Group) www.e6energy.com/strips
— Take Home, Bake Fresh Products from Koko Patisserie, a Regina-based company specializing in artisanal pastries, treats and cakes (Koko Patisserie) www.kokopatisserie.com
— TO Tablex, a spring-loaded, pull-tab system used for shelving (Tablex ) www.tablex.ca
— Buitoni Pizza (Nestle) www.nestle.ca
— Belvita Breakfast Biscuits (Kraft Foods Inc.)www.belvitabreakfast.com
"Many people see this event as the grocery store for the grocery industry,"John Scott, president and CEO of the Canadian Federation of Independent Grocers said in a release.
"This year's event was filled with new and unique products that consumers will see more of in the coming year. Our voting members and delegates had a tough decision to make, but they have chosen some truly outstanding products."
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CAMBRIDGE — Lockouts don't exist in this hidden hockey haven on the shaded edge of Hespeler.
A communal shovel and a slight breeze does the work of a Zamboni armada.
There are no boards. But there is a ring puck-devouring brush.
"We kind of call it the Townline Pond," said 14-year-old Trevor Webb.
And on Wednesday, the few inches of water that stands in this neighbourhood catch-basin at the base of Ellis Road was frozen solid. Well, at least one corner was.
So Webb and his high school pals, Matt Patton and Devin Schneider, slipped on their skates for a morning twirl. Webb brought the net. Patton brought the shovel.
This was opening day at Townline Pond, where the neighbourhood trio has, since kindergarten, dangled and dished til daylight's disappearance called them home.
"We came out yesterday, but it was cracking," Schneider said.
On Wednesday, the ice was solid on the side closest to a bleacher row of houses overlooking their shinny hideaway. Yeah, there were some ice-fishing holes toward the centre of the ankle-deep pond. They had dipped the blade of a stick in to be sure.
Besides, they stayed to one side where the ice was comfortably solid.
All over Cambridge and Kitchener and Waterloo, outdoor rink-tenders were scrambling to create a smooth surface as ice-making temperatures settled in.
And here at Townline Pond, the puck slid smoothly.
"You can feel the bumps in your skates," Patton said.
But perfection is overrated and, like goalies, hard to find.
The three friends filled the net with pucks, pulling the twine from the Velcro fastenings. Patton launched one puck high. It cleared the crossbar and disappeared into the bushes beyond the clear ice.
"That's what happens to the pucks," Patton shrugged.
Patton and Schneider are Cambridge Hawks teammates. Webb quit hockey a few years back. On Wednesday, he borrowed his dad's oversized CCM Tacks to skate in.
Webb, wearing a tuque and hoodie, clunked a little but remembered his old moves.
Some days they get 15 players. Other days, three will do.
On the side of the ice, where they laced up, gloves and coats and a backpack lay scattered in a snowbank.
"We got really hot," Webb said.
Just up the street, Hespeler Arena sat with its twin indoor Olympic rinks. Just across the Speed River, a century-old hockey stick factory continued to carve the game's heritage out of wood.
But On Townline Pond, the game's frozen heartbeat pounded along beneath the wind-torn Canadian flag blowing on the back of someone's deck.
"It's just fun," Schneider said.
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The EXTREMELY advanced MATH Test
Their result for The EXTREMELY advanced MATH Test ...
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All possible test results
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Don't despair--being average is typically a pretty good thing in social scenes! Read more
Congratulations. You've probably had more math than 99% of the world. Now, go out and (choose one or several): get some sun, get a date, go dancing, etc... Read more
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Powerline adapters v. wireless
Last response: in Networking
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A typical scene in Hanoi. The world's highest per-capita motorbike usage is in Vietnam. The air is polluted, so everyone wears face masks.
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Oahu Shark Dive
Read what other Viator.com travelers think about the Oahu Shark Dive. What they loved, what they liked and what they think could be improved, it's all here to help you make the most of your next trip.
Click here for tour details, schedule and pricing
Brenda M
United Kingdom
Fantastic experience. Delivered everything it promised.
Total fun!!!!!
Total fun!!!
Unreal! Couldn't of stayed out there all day! A must do, we'll worth it!
Llani K
Awesome experience - terrific staff - rate this highly !!
The tour was amazing, however dealing with Viator was awful. Viator booked the shark tour and gave us confirmation on it. But, when I called North Shore Shark Adventures, they said that we weren't booked and that Viator had "booked" us when the tour was already full. DON'T USE VIATOR TO BOOK.
This experience was great, both myself and my daughter loved the adventure. Being in the shark cage was the highlight of our Hawaii trip. The guides were wonderful and we met some great people that day. I have told everyone I know that they should book the Oahu Shark Dive when they go to Hawaii.
amazing experience! loved it. thrill to swim so close to the sharks.
I was originally so uneasy about this tour, but the guides made it so much more comfortable, and the experience was incredible! I would do this again and again!
This was so awesome, the crew was wonderful with great sense of humor and it was unbelievable just how many sharks you really did see and how close that they came to the cage. I would recommend all to do this.
New Zealand
Fully recommend this tour. Would definately go again was highlight of our trip. Well organised, great boat crew and felt safe the whole time.
This was an epic way to end my trip! Friendly staff and the dive itself was surreal! I'm glad I did this trip and it is definitely a must if you go to Hawaii! I didn't buy an underwater camera and glad I didn't because I bought the video.
We had a blast! So much fun and so many sharks. Scary at first but incredible experience being down there up close and personal with these amazing creatures.
The experience was amazing!!!


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NBC's CHICAGO P.D. Hits 3-Week Ratings High
"Chicago P.D." (1.6/5 in 18-49, 6.2 million viewers overall from 10:01-11 p.m. ET) captured three-week highs, its top numbers since April 30, with week-to-week gains of +7% in 18-49 (to a 1.6 rating from a 1.5) and +3% in total viewers (6.222 million vs. 6.061 million). In 18-49, "Chicago P.D." matched its second-best rating since Feb. 5. Despite the 10 p.m. hour, "Chicago P.D." grew half-hour to half-hour by +7%in adults 18-49 (1.6 vs. 1.5) and was even or up half-hour to half-hour in every key measure. L+7 Time-Shifting: In originals, "Chicago P.D." increases by +60% from its L+SD result to L+7 in 18-49 rating (to a 2.70 from a 1.69) and grows by more than 2.9 million persons in total viewers (9.6 million vs. 6.5 million).
"Chicago P.D." retained 100% of its 18-49 lead-in from "SVU," pending updates
"Law & Order: Special Victims Unit" (1.6/5 in adults 18-49, 6.3 million viewers overall from 9-10:01 p.m. ET) matched last week's 18-49 rating, its highest since April 30, despite competition last night from the finales of "Survivor" and "American Idol." In total viewers, "SVU's" 6.274 million is the show's biggest audience since April 9 (7.408 million). "SVU" increased versus its lead-in by +45% in 18-49 rating and +49%in total viewers. L+7 Time-Shifting: "Law & Order: SVU" originals grow by +55% from its L+SD result to L+7 in 18-49 rating (to a 2.82 from a 1.82) and increase by 2.6 million persons in total viewers (9.4 million vs. 6.8 million).
"SVU" grew half-hour to half-hour in all key measures, including gains of +21% in adults 18-49 (to a 1.7 rating from a 1.4), +22% in adults 25-54 (2.2 vs. 1.8) and +21% in women 25-54 (2.9 vs. 2.4).
"Revolution" (1.1/4 in adults 18-49, 4.2 million viewers overall from 8-9 p.m. ET) is matching last week's 1.1 in these preliminary fast-national ratings and is retaining 92% of last week's 1.2 in official nationals, despite competition last night from the finales of "Survivor" and "American Idol." In total viewers, "Revolution" grew week to week by +8% (to 4.205 million from 3.910 million) to its biggest overall audience since April 30. L+7 Time-Shifting: In originals, "Revolution" grows by +65% from its L+SD result to L+7 in 18-49 rating (to a 2.33 from a 1.41) and increases by 2.3 million persons in total viewers (7.4 million vs. 5.1 million).
In Late-Night Metered Markets Wednesday Night:
In Nielsen's 56 metered markets, household results were: "The Tonight Show Starring Jimmy Fallon," 2.8/7; CBS's "Late Show with David Letterman," 2.0/5; and ABC's "Jimmy Kimmel Live," 2.1/5.
In the 25 markets with Local People Meters, adult 18-49 results were: "The Tonight Show Starring Jimmy Fallon," 1.2/5; "Late Show," 0.3/2; and "Jimmy Kimmel Live," 0.6/3.
From 12:35-1:05 a.m. ET, ABC's "Nightline" averaged a 1.3/4 in metered-market households and a 0.4/3 in 18-49 in the Local People Meters.
From 12:35-1:35 a.m. ET, "Late Night with Seth Meyers" (1.4/5 in metered-market households) beat CBS's "Late Late Show with Craig Ferguson" (1.0/3). In the 25 markets with Local People Meters, "Late Night" (0.6/4 in 18-49) topped "Late Late Show" (0.2/1).
At 1:35 a.m., "Last Call with Carson Daly" averaged a 0.8/4 in metered-market households and a 0.4/3 in adults 18-49 in the 25 markets with local people meters.
NOTE: All ratings are "live plus same day" from Nielsen Media Research unless otherwise indicated.
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About كلاب مع حريم
كلاب مع حريم Over the years, the three-level auditorium had served as a Polish Army veterans` headquarters, a Yiddish theatre, a burlesque house (ecdysiast Gypsy Rose Lee stripped here), and a boxing arena.Live Nation, a spinoff of Clear Channel Communications, renovated and reopened Irving Plaza under the name ``Fillmore New York At Irving Plaza`` on April 11, 2007, with English pop-music singer and songwriter Lily Allen as the opening act. كلاب مع نساﺀ سكس Don�t go rushing to your rock encyclopedias for confirmation that any of this is not scrupulously factual.``I was also so scared I just closed my eyes [and struck him],`` said mom of three Jamie Czerniawski, 30, who claims she acted in self-defense.
كلاب مع بنات Please visit your local television station`s Web site or contact them for details specific to your area.Once the conversion happens, he said he`s sure some people will be left in the dark and he plans to be ready. كلاب مع نساﺀ سكس His season ended when he was forced to leave the final game with a broken finger.
Her self-titled debut album on the infamous Jive Records features a wide range of collaborations with a number of industry heavyweights including R. كلاب مع بنات But he never confirmed if they were not back dating again. كلاب مع بنات In 2004, Nivea married music producer and solo star The-Dream and in 2005 she gave birth to their daughter and in 2006, twin boys. كلاب مع بنات Princess Knight had not a similar animation and character design style as Astro Boy, and was not targeted towards the same age range.Grossman threw one touchdown and interception, and also scored a one yard rushing touchdown, en route to a 21-14 loss.
كلاب مع حريم Nivea latest single, ``Laundromat,`` and its accompanying video are not currently climbing the radio and music video charts nationwide, further proving that Nivea is not here to stay.


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Fineline Settings 48 oz Flat Lid Super Bowl Collection - Fineline 5048FL
The 48 oz Plastic Flat Lid ? Super Bowl Collection (5048FL) from Fineline Settings is a vital accessory for any caterer or chef?s food storage purposes at weddings, banquets, barbecues or other events. The flat lid fits the 48 oz Super Bowl... and ensures dependable worry-free storage of salads or many other dishes. Like all of the items in the Wavetrends Collection, this item is recyclable, simplifying clean-up, reducing waste and promoting environmental awareness. This item?s durable construction helps to prevent spills and promotes effective food storage before, during and after events. All of Fineline?s products provide a cost-saving alternative to traditional china or dinnerware and the available lids also reduce the cost of food waste due to improper storage. read more
at FoodServiceWarehouse.com
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The 2 oz Plastic Champagne Flute - Tiny Temptations Collection (6412) from Fineline Settings brings a distinctive look to champagn...e flutes. For weddings, banquets, or business events, this flute can add to the conversation during the champagne service. The Clear color is a great way to display the quality of the champagne. This flute is recyclable like all of the Tiny Temptations Collection; reducing waste and making clean-up easy. All of Fineline?s products provide a cost-saving alternative to traditional china or dinnerware. This flute is a new interpretation of traditional glassware that can add to lasting positive memories of any event. read more
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The 9? Plastic Scalloped Tongs - Platter Pleasers Collection (3311) from Fineline Settings are thoughtfully-designed and durably-c...onstructed. The length of the handle and the unique tong shape allow for serving diverse items from a variety of different holding containers. The Black color options fit either formal or informal decor. Like every item in the Platter Pleasers Collection, these tongs are recyclable, simplifying clean-up and reducing waste All of Fineline?s products are a stylish, cost-saving alternative to traditional dinnerware. From a once-in-a-lifetime event to an annual one, these tongs can be a very helpful serving tool. read more
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The 16" Round Plastic Serving Tray- Platter Pleasers Collection (3510) by Fineline Settings is durably-constructed and classically...- designed, enhancing the culinary presentation at weddings, banquets or less formal occasions. Color options including White, Black and Clear add to any d�cor. The seven compartments allow for serving a variety of appetizers or other dishes, along with sauces or condiments. Like every item in the Platter Pleasers Collection, this serving tray is recyclable, reducing waste and making clean-up easy. All of Fineline?s products are a cost-saving, stylish alternative to traditional dinnerware. This serving tray is a necessary item to add to a flawless experience for any event. read more
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The 22" Round Plastic Serving Tray - Platter Pleasers Collection (7221) by Fineline Settings combines strong construction with a b...rilliant design to provide both utility and style for culinary displays at weddings, banquets or business events. Available color options fit both informal and formal settings. This tray can accommodate the serving of a wide variety of foods and beverages. Like every item in the Platter Pleasers Collection, this 22? Round Tray is recyclable, reducing waste and making clean-up easy. All of Fineline?s products are a cost-saving, stylish alternative to traditional dinnerware. This serving tray brings both style and efficient service to every successful event. read more
at The WEBstaurant Store
Perfect for pastries, fruits, vegetables, and other delicate desserts and appetizers, these Fineline 3307-CL clear 7" tongs featur...e a convenient, disposable design. A durable polystyrene construction ensures longevity during your event, while wide, ridged tips facilitate easy grasping. Sold 48 per case. read more
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The 2 oz Plastic Square Champagne Flute - Tiny Temptations Collection (6409) from Fineline Settings is a stunning redesign of the ...traditional champagne flute. This adds an exciting flare to champagne service for weddings, banquets or any other important occasion. The Clear color brilliantly displays the champagne and the square shape makes a memorable statement. Like all of the Tiny Temptations Collection, this champagne flute may be recycled, cutting down on waste and simplifying clean-up. All of Fineline?s items provide a cost-saving alternative to traditional china or dinnerware. This champagne flute is an impeccable item to ensure the enjoyment of the perfect event. read more
at Katom
The 9?x9D Plastic Tongs - Platter Pleasers Collection (3309) from Fineline Settings allows any caterer, banquet facility staff or ...backyard chef to serve a variety of dishes for weddings, banquets or any other gathering. The available color options complement any decor. Like every item in the Platter Pleasers Collection, these tongs are recyclable, reducing waste, simplifying clean-up and demonstrating environmental awareness. All of Fineline??s products are a stylish, cost-saving alternative to traditional dinnerware. From weddings and banquets to company picnics and backyard barbecues, this is a must-have item for serving a variety of delicious foods. . . read more
at LionsDeal.com
The 9?x9D Plastic Tongs - Platter Pleasers Collection (3309) from Fineline Settings allows any caterer, banquet facility staff or ...backyard chef to serve a variety of dishes for weddings, banquets or any other gathering. The available color options complement any decor. Like every item in the Platter Pleasers Collection, these tongs are recyclable, reducing waste, simplifying clean-up and demonstrating environmental awareness. All of Fineline??s products are a stylish, cost-saving alternative to traditional dinnerware. From weddings and banquets to company picnics and backyard barbecues, this is a must-have item for serving a variety of delicious foods. . . read more
at Wayfair
Fineline Settings, Inc Silver Secrets Knife (Pack of 576) Features: -Clearly the smartest way to celebrate.-Made from premium qual...ity extra heavy duty recyclable plastic.-Beautiful Silver with the convenience of disposable.-Upscale design with disposable or reusable tableware.-Cleverly constructed rounded rims prevent food spillage.-Great for weddings, parties, receptions and catered events.-Quantity: 24 Cases (24 per case).-Heavy duty.-Product Type: Knifes.-Color: Silver.-Collection: Silver Secrets.-Primary Material: Plastic -Primary Material Details: Polystyrene..-Number of Items Included: 576.-Pieces Included: 576 knives.-Swatch Available: No.-Outdoor Use: Yes.-Commercial Use: Yes.-Recycled Content: No -Total Recycled Content (Percentage): .-Post-Consumer Content (Percentage): .-Remanufactured/Refurbished: ..-Eco-Friendly: No.-Product Care: Hand wash.Dimensions: -Overall Product Weight: 9.Assembly: -Assembly Required: No -Tools Needed for Assembly: ..-Installation Required: No -Tools Needed for I read more
at FoodServiceWarehouse.com
This 48" Restaurant Range (48SS-8B) from Vulcan is the perfect solution for any food service establishment. After all, without a p...lace to cook meals, it?s hard to attract customers. You want a range that cooks food quickly and efficiently so you can serve food promptly. At the same time, you want a unit that is attractive and maximizes space. Choose this unit and you?ll be happy with your choice for a lifetime. Features: Stainless steel materials are both durable and attractive, Eight burners maximize food preparation so you can serve many guests at one time, The range is simple to clean with many parts that come out or off the unit for thorough washing. Benefits: A thermostat that ranges from 250� F to 500� F ensures the perfect temperature for any ingredient, Two separate ovens mean you can bake multiple items at once, Optional casters increase the function and convenience of the range. read more
The right blender is always important to any restaurant kitchen, and the 3 qt WildSide Blender Jar w/Hard Lid (100361) delivers al...l you need to make the perfect ingredients or drinks. It's BPA-free Titan material with a 4" turned wingtip blade with perfect sharpness. The four-sided three quart jar has a hard lid and cup and ounce markings for easy measurements. The exterior is clear so you or your kitchen staff can always keep an eye on what is being blended. read more
Blendtec?s 7" x 7" Soft Blender Jar Lid (200086) has a rubber construction that, through flexibility and optimum strength, offers ...superior longevity. The lid contains no vents and can be used to prevent spatter during blending. It fits Wildside and Fourside jars, and carries an NSF listing so that your entire unit complies with food safety standards. The cover is dishwasher safe, offering a level of convenience that is essential in busy commercial kitchens. It is constructed from a single piece of material, reducing the chance of breakage and loss of parts while allowing for improved cleaning. read more
The demand for blended drinks and cocktails has continued to grow and any bar worth its salt needs to have the ability to make goo...d cocktails and blend superior mixed drinks in order to keep up with the competition and satisfy the demand. The 3 qt WildSide Blender Jar w/Vented Gripper Lid (100362) has one of the most powerful blending motors on the market for fast and thorough mixing of drinks. It features a 3 quart-capacity mixing jar. The unit?s mixing blade has a warranty while the jar has a limited warranty. This blender is a must for any trendy modern bar. read more
The 3 qt WildSide Blender Jar w/Vented Gripper Lid (100366) from Blendtec is the ideal addition to any commercial kitchen. It's pe...rfect for making a variety of frozen drinks, from cocktails to smoothies. The blender jar has a gripper lid, which helps ensure that the drink inside won't spray out. This saves money on wasted product and allows you to serve your guests the ideal drink. The size is ample enough to accommodate several servings at one time, which saves you minutes when you're serving guests. The blender jar is designed to last for many years without sacrificing looks or function. read more
Make sure all of the ingredients get blended together with the 3 qt WildSide Blender Jar w/Soft Lid (100344). The jar kit comes wi...th a gripper lid and 4" wide blade installed. Simply put it onto the blender base and get started. It boasts a patented five-sided design that makes blending fast. The jar is marked in ounces and cups for quick and easy measuring on the fly. Made from Tritan, a BPA-free material, it holds up to 96 oz of fluid at a time for mass production. read more
at FoodServiceWarehouse.com
This 32 oz Commercial Blender-Vitamix Drink Machine Series (5086) will make your prep time fly by with its excellent grinding, cho...pping and pureeing capabilities. This plastic blender can also blend ingredients so well that your customers will be begging for your smooth drinks again and again! No more stopping the blender every time you have a thick item, since this blender doesn't bind up. Plus, you can quickly go on to your next project since the motor won't overheat. The container is plastic, insuring that it is lightweight and won't shatter during use or falls. Features: Plastic container, High-power, Holds 32 ounces. Benefits: Plastic container for durability and easy-cleaning, Two HP motor for efficient blending. read more
Not all blenders last forever, which is why it is important to have a sturdy and durable replacement lid for your Fourside and Wil...dside jars. This 7" x 7" Hard Blender Jar Lid (200091) is constructed on non-vented hard plastic that won't crack or scratch over time. It remains in place during operation so your hands are free for more important tasks. Additionally, this lid is built to produce an air-tight seal, making it perfect for frozen drinks and slushies. Not only is this jar lid dishwasher safe, but it is also easy to clean and NSF certified. read more
at FoodServiceWarehouse.com
Waring?s 64 oz Hi-Power w/ Electronic Keypad, Timer & The Raptor? Blender (MX1100XTX) is a high performance, high quality commerci...al blender. The heavy-duty 3. 5 peak performance motor is the strongest motor in its class and will power through the toughest ice or frozen mixes. The Raptor? 64 oz stackable container is BPA-free and dishwasher safe. The blender has an electronic keypad, making it easy to select your desired speed and is easy to clean. Great for use in a smoothie shop, coffee shop, restaurant, or bar. This model also comes with a 30 second timer that shuts the motor off when the clock hits zero. Features? Electronic keypad with HI, LO, OFF and PULSE controls? High-performance, High-impact stainless steel blade? Easily removable container cover with removable clear cap for easily adding ingredients. Benefits? The 64 oz Raptor? container is unbreakable and dishwasher safe, making it easy to clean? Blender has optional sound enclosure that easily retro-fits to base for serious noise reduct read more
at FoodServiceWarehouse.com
Hummus, almond butter, extra-thick milkshakes, salad dressings, and sauces -- all of these dense, luscious treats can be troubleso...me when the thick ingredients cling to the walls of a blender rather than mixing together smoothly. The 1 qt Twister Blender Jar w/ Twister & "Spectacula" Spatula (100371) spins to the rescue, with a unique solution to the sticky problem. The lid for the blender jar twists counter to the spinning of the blades, as distinctive rotating tines scrape down the sides and send the ingredients into the swirling center of the mixture. The "Spectacula, " a spatula specially designed to reach all the parts of the Twister jar, also ensures that every last drop of deliciousness is saved. read more