text:
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Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric
disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific
hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the
burst spikes, known to depend on T-type Ca2?channels, were increased in MD neurons. In vivo knockout or knockdown of the T-type
locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a
the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of
Abnormal oscillations or excitability has been a key neurological
sign for frontal lobe dysfunction in neurological and psychiatric
disorders (McAllister and Price, 1987; Barry et al., 2003; Gucuy-
Beleza et al., 2009); for example, the 1–7 Hz oscillations seen in
attention deficit hyperactivity disorder (ADHD) (Barry et al.,
2003), and the frontal lobe-specific paroxysms in frontal lobe
hood (Hernandez et al., 2001; Gonzalez-Heydrich et al., 2007)
and schizophrenia-like symptoms in adults (Adachi et al., 2000;
Helmstaedter, 2001; Patrikelis et al., 2009).
Considering the critical role of thalamic neurons in controlling
1994; Steriade and Contreras, 1995; Steriade, 2006; Ernst et al.,
tal lobe dysfunction could be attributed to the thalamus. This hy-
Price, 1987; Stuss and Gow, 1992; Paradiso et al., 1999; Kellinghaus
andLu ¨ders,2004;Maxetal.,2005;Millichap,2008).
oxia (Ishige et al., 1987; Choi, 1990), has been one of the most
tions (Damasio and Anderson, 1985; Owen et al., 1990, 1993; Shal-
lice and Burgess, 1991; Stuss and Gow, 1992; Pigula et al., 1993;
Ho ¨ckel and Vaupel, 2001). Based on the fact that cobalt (Co) ions
trigger signaling pathways which are activated by hypoxia (Piret et
implanting a wire made of Co in the prefrontal cortex (PFC) and
demonstrate how the role of the thalamus is involved in the devel-
Animal care and handling were performed according to the directives of
the Animal Care and Use Committee of Korea Advanced Institute of
Science and Technology. The CaV3.1?/? and wild-type littermate con-
Mid-Career Researcher Program of the National Research Foundation of Korea funded by the Korea government
Copyright©2011theauthors 0270-6474/11/314063-11$15.00/0
TheJournalofNeuroscience,March16,2011 • 31(11):4063–4073 • 4063
Page 2
trol mice were generated by mating heterozygotes from C57BL/6J back-
a 12 h light/dark cycle.
Mouse model of FLE generated using a wire form of cobalt
C57BL/6J male and female mice (10–20 weeks old) were prepared for
Co-wire implantation. Under avertin (0.2%) anesthesia (tribromoetha-
Alfa Aesar) with the radial orientation (vertical to the cortical surface)
ventral, 1.3 mm) using a stereotaxic device (David Kopf Instruments).
An epidural electrode for EEG recordings was implanted in the right
frontal cortex, where the cobalt was implanted, and another electrode
was implanted in the left frontal and temporal cortexes (right frontal:
anteroposterior, 2.8 mm; lateral, 0.8 mm; left frontal: anteroposterior,
2.8 mm; lateral, 0.8 mm; right temporal: anteroposterior, ?2.4 mm;
lateral, ?2.4 mm; left temporal: anteroposterior; ?2.4 mm, lateral, 2.4
skull. After 3 d of recovery, the EEG signal and video recording were
ber (a square-floor rectangular box). EEG signals were amplified (model
7H polygraph, Grass Technologies) and digitized at a sampling rate of
500 Hz (DIGIDATA 1320A, Molecular Devices). pClamp9.2 software
(Molecular Devices) was used for data acquisition. To induce secondary
jected intraperitoneally (550 mg/kg), 7 d after Co-wire implantation
(7.0 ? 0.8 d on average) (Walton and Treiman, 1988).
Magnetic resonance imaging
For magnetic resonance imaging (MRI), mice with Co-wire implanta-
tion (5 d after Co-wire implantation) were anesthetized and set into an
MR compatible cradle. During MRI, the animals were anesthetized by
breathing 2% isoflurane into oxygen-enriched air with a facemask. The
The MRI acquisitions were performed on a 4.7 T horizontal MRI (Bio-
spec, Bruker) with a shielded gradient coil 65 mm in diameter. The
experiments were performed using a 38 mm internal diameter birdcage
coil (Bruker). The measurements were performed using the parameters
given below. T1-weighted images were obtained using a fast spin-echo
sequence with the following parameters: pulse repetition time (TR) ?
(FOV) ? 25 mm; slice thickness (ST) ? 1 mm; pixel resolution ? 100
?100 ?m; and acquisition time for one set ? 6.7 min.
T2-weighted images were obtained using a fast spin-echo sequence
and acquisition time for one set ? 11.5 min.
Histology and immunoblotting
buffered 4% formalin for 24 h and embedded in paraffin for sectioning
on a microtome into 5 ?m slices, which were stained with hematoxylin
and eosin after deparaffination. The brain slices were visualized under a
bright-field microscope (Olympus). For immunoblotting, brains were
isolated on ice and cut into 1 mm slices using a brain matrix (RBMA-
tungsten-implanted group) with morphologically normal neurons in the surrounding area (image 2 in tungsten-implanted group). Left, Ipsilateral PFC (100?); middle, magnified image 1 of
4064 • J.Neurosci.,March16,2011 • 31(11):4063–4073Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction
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atlas, were separately removed and sonicated
in homogenization buffer containing protease
phosphatase inhibitor (Phostop, Roche). Pro-
teins (30–50 ?g) were loaded onto 10% poly-
acrylamide Tris-HCl gel and transferred to a
nitrocellulose membrane (Protran, Whatman).
The following antibodies used: ?-actin (sc-
47778, Santa Cruz Biotechnology), VEGFa (sc-
507, Santa Cruz Biotechnology). Anti-mouse
(Abcam) and anti-rabbit secondary antibodies
Behavioral analysis
Open-field test. Each mouse was gently placed at
the center of the open-field test arena (a square-
40 ? 50 cm) in a dark room. The distance of
spontaneous movement during a 1.5 h time pe-
riod was monitored at 5 min intervals by digital
6:00 P.M. and 10:00 P.M. EthoVision (Noldus)
Fear-conditioning test. Fear conditioning
was conducted in conditioning chambers
(acrylic test station, dim light, metal grid floor;
San Diego Instruments) and a testing chamber
(a white plastic, circular cylinder). A video
camera was mounted on top of the chambers.
The fear-conditioning procedure was con-
ducted over 2 d. On day 1, each mouse was
acclimated to the conditioning chamber (4
min, 40 s) and then given three pairs of a con-
coterminated with an unconditional stimulus
(foot shock, 2 s, 0.7 mA). The trial interval was
60 s. On the day of testing, the freezing re-
sponses to the conditional stimulus were mea-
sured in the testing chamber with test tones
(180 s). To test contextual conditioning, the
mice were placed in the conditioning chamber
and were allowed to explore for 5 min. Behav-
ioral freezing was manually counted by an ob-
server blinded to the previous treatments.
Electrolytic lesions
C57BL/6J male and female mice (10–20 weeks
ethanol, 20 mg/ml) and placed in a stereotaxic
was made in the skull with a dental drill. Elec-
trolytic lesions were made in the mediodorsal
thalamus (MD) (anteroposterior, ?1.46; lat-
eral, ?0.25; ventral, 3.3 mm) with monopolar
electrodes (stainless steel insulated with Ep-
oxylite, Am Systems). Electrolytic lesions were
made by passing a DC current (10 mA; A365,
World Precision Instruments) for 15 s. A piece
of Co-wire (Alfa Aesar) was then implanted in
planted as described for the cobalt model of
PFC damage. After 4 d of recovery, the EEG
dose of avertin and fixed with 10% formalin.
Brain slices (40 ?M) were cut on a cryostat and
stained with cresyl violet.
Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunctionJ.Neurosci.,March16,2011 • 31(11):4063–4073 • 4065
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Pharmacological analyses
Bicuculline methobromide test. C57BL/6J male
and female mice (10–20 weeks old) were pre-
pared for injection of bicuculline methobro-
mide (BMB). Under avertin (0.2%) anesthesia
(tribromoethanol, 20 mg/ml, i.p.), electrolytic
lesions were made in the contralateral and ip-
silateral sides of the MD thalamus. After 4 d of
recovery, the EEG signal was acquired for 2 h,
during which BMB (30 mg/kg) was injected
Antiepileptic drug test. C57BL/6J male and
female mice (10–20 weeks old) were pre-
pared for injection of ethosuximide (Coulter
et al., 1989). Basal EEG activity was recorded
for 8 ? 1.1 d after Co-wire implantation.
for 2 h. Zonisamide (60 mg/kg)and phenyt-
oin (100 mg/kg) were injected to test the ef-
fect on frontal seizure spikes.
Multiunit recording
C57BL/6J male and female mice (10–20 weeks
ethanol, 20 mg/ml) and placed in a stereotaxic
device (David Kopf instruments). A piece of
mm; ventral, 1.3 mm). After 4.2 ? 0.2 d, and
9.2 ? 0.2 d after cobalt implantation, mice
were anesthetized by intraperitoneal injection
of urethane (under light anesthesia; 1.35 g/kg)
and placed in a stereotaxic device (Thomas
RECORDING). The temperature was main-
tained at 37°C using a homothermic blanket
system (Harvard Apparatus). A single incision
above the region where the MD nuclei are located. Quartz-coated te-
trodes (0.5–2 M?; Thomas RECORDING) were positioned in the MD
mm). Signals were amplified ?95-fold and bandpass filtered at 300–
5000 Hz (for the measurement of multiunit activity) or at 0.50–50 Hz
[for the measurement of local field potential (LFP)] by an AC amplifier
(PGMA, Thomas RECORDING) digitized at the 10 kHz sampling rate
(DT3010, Neuralynx). A burst was defined by the following criteria in
interspike interval within a burst) must be ?6 ms; maximum interval to
end burst, 10 ms; minimum interval between bursts, 200 ms; minimum
duration of burst, 4 ms; and minimum number of spikes within a burst,
?100 ms, high-frequency spikes of 200–400 Hz with more than two
spikes, a shortening of the first interspike interval (1–4 ms), and a pro-
viously (Guido et al., 1992; Kim et al., 2003).
In vivo transduction of lentivirus
A lentiviral vector expressing short hairpin RNA (shRNA) to target the
CaV3.1 T-type calcium channel was constructed. A synthetic double-
oligonucleotide (5?–CGGAATTCCGGGAAGATCGTAGATA GCAAA-
was inserted into the shLentisyn3.4G lentiviral vector. The shLentisyn3.4G
National Center for Biotechnology Information, other than CaV3.1. A
CGGGTAAGTGAA CTGACAAGAAttcaagaga TTCTTGTCAGTTCACT-
TACT TTTTGATATCTAGACA–3?) was also inserted into the
shLentisyn3.4G vector and used as a control. This sequence did not have
anol, 20 mg/ml) and perfused transcardially with heparin solution (10
units/ml) followed by 4% formaldehyde dissolved in PBS. For CaV3.1
?m) were incubated with CaV3.1 primary antibody (Alomone Labs),
Seven to 10 d after infection with lentiviruses harboring shC or sh3.1,
ascorbate acid, and 3.0 mM pyruvate (bubbled with 95% O2/5% CO2).
The brain was then rapidly removed, and slices (350 ?m thick) were
made with a vibratome (Leica Microsystems). After incubation for at
least 45 min in 32°C, slices were kept at room temperature in a holding
chamber until they were transferred to a submersion-type recording
chamber held at room temperature. The solution used for slice incuba-
the MD neurons, cells were maintained at ?60 mV and the recording
4066 • J.Neurosci.,March16,2011 • 31(11):4063–4073 Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction
Page 5
solution was substituted with Ca2?current recording solution com-
posed of 115 mM NaCl, 3.0 mM KCl, 10 mM sucrose, 10 mM glucose, 26
mM NaHCO3, 2 mM MgCl2, 2.5 mM CaCl2, 0.5 mM 4-aminopyridine, 5
impermeant), 0.5 mM CaCl2, 1.0 mM MgCl2, 4 mM Mg-ATP, 0.3 mM
TEA-Cl, pH 7.3 (titrated with CsOH). Standard voltage protocols for
inducing T-currents were applied (Perez-Reyes, 2003). Only cells with
low membrane capacitance (40–100 pF) and high membrane resistance
(?400 M?) were included in the analysis.
Data analysis
Coherence analysis. The signals ?600 s were analyzed to measure the
analyzed using the higher-order spectral analysis toolbox and Matlab
R2008a (Chua et al., 2007).
right frontal cortex (FR) and MD thalamus. The GC analysis uses the
prediction error in autoregressive (AR) modeling of the signal. It can be
determined whether signal y influences signal x by comparing the pre-
diction error of x obtained from AR modeling with the prediction error
of x obtained from joint AR modeling of x and y. That is, when y influ-
ences x, the prediction error is significantly decreased for the joint AR
modeling. This is quantified by the following relative prediction im-
provement, called the Granger–Sargent statistic:
2? ?xy
Here, ?x
of the univariate AR model of x, and ?xy
multivariate mean error of predicting x ob-
tained from the joint AR model of x and y.
signal y influences signal x. The AR model or-
der was determined from Bayesian informa-
tion criteria considering the tradeoff between
racy of prediction (Pereda et al., 2005). For the
GC analysis, it is essential to determine the ep-
och in which the signal can be assumed to be
stationary (Granger, 1969). We could verify
this and obtained reliable AR models using 5 s
segmentation of our data. Therefore, the sig-
nals within 600 s were segmented into 5 s ep-
ochs (Sitnikova et al., 2008).
Event detection. For detection of spikes,
Clampfit 9.2 (Molecular Devices) was used.
number and property of each spike.
of knockdown after transfection of shRNA, a
Positive Pixel Count Algorithm (Aperio) was
used. All data were analyzed using the t test,
ANOVA, and the SigmaStat 3.1 software pack-
2is the mean-squared prediction error
2is the
2becomes large, and it can be assumed that
lesionsbyCo-wire implantation
To induce frontal lobe-specific damage,
we implanted a Co-wire into the right
PFC of adult mice. After 5 d of implanta-
tion, a bloody scar reflecting angiogenesis
was formed where Co-wire had been im-
(MRI) showed that Co-wire implantation led to more profound
n ? 4). Such damage was limited to the right frontal cortex,
while no damage signals were found in the left frontal cortex
www.jneurosci.org as supplemental material). The damaged
area detected in MR images was further characterized by he-
matoxylin/eosin staining, and we found that Co-wire implan-
tation resulted in clear signs of hypoxic damage as measured
by the increase of ghost cells (Ito et al., 2006) and inflamma-
tory angiogenesis (Sharp and Bernaudin, 2004) visualized by
blood vessels filled with red blood cells (RBCs) (Fig. 1b,c;
supplemental Fig. S2a, available at www.jneurosci.org as sup-
plemental material) (nonlesion control, n ? 3; tungsten, n ?
3; cobalt, n ? 4; p ? 0.05).
To measure the Co-wire-induced damage at molecular level,
we examined vascular endothelial growth factor (VEGF), a key
angiogenic modulator in response to hypoxia (Sharp and Ber-
naudin, 2004) and found that VEGF proteins were significantly
increased in the PFC 5 d after Co-wire implantation when com-
pared with tungsten-wire-implanted groups (Fig. 1d; supple-
mental Fig. S2b, available at www.jneurosci.org as supplemental
material) (nonlesion control, n ? 2; tungsten, n ? 4, cobalt, n ?
3). These results suggest that Co-wire led to a hypoxia-like dam-
age in the PFC.
injection. c, *Co: comparison of the effects of contralateral and ipsilateral MD lesions on spike generation, 6 d after Co-wire
Lesions in the ipsilateral MD thalamus abolish frontal lobe-specific spikes in the cobalt-implanted group. a,
Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunctionJ.Neurosci.,March16,2011 • 31(11):4063–4073 • 4067
Page 6
stereotypic circling
Next, we wondered whether the Co-wire-
induced PFC damage caused behavioral
abnormalities known to be reported in
patients with PFC dysfunctions (Benson,
2009). An open-field test revealed a pro-
gressive development of hyperactivity
(Fig. 2a,c) (control, n ? 6; cobalt ?6 d,
n ? 5; cobalt ?14 d, n ? 5; cobalt ?28 d,
n ? 9; two-way ANOVA, F(3,192) ?
30.018, p ? 0.001; two-tailed t test, p ?
0.05) when compared with control mice.
In addition, they showed a decreased ex-
ploration in center areas of an open-field
due to their stereotypic circling behaviors
along the wall of test box (Fig. 2b,e) (two-
tailed t test, p ? 0.05). The abnormal
hyperactivity and stereotypic behaviors
have been associated with attention prob-
lems in patients with PFC dysfunctions
(McGuire and Sylvester, 1987; Gainetdi-
nov et al., 2001; Kates et al., 2005; Gilby,
2008). Consistently, they also showed re-
duced learning in a fear-conditioning ex-
periment (supplemental Fig. S3, available
at www.jneurosci.org as supplemental
material) (two-tailed t test, context, p ?
0.01; cue, p ? 0.05), which requires care-
ful attention to cue or contextual stimuli
(Armony and Dolan, 2002; Han et al.,
2003). These results suggest that the im-
behavioral abnormalities similar to those
found in ADHD (Davids et al., 2003) and
FLE childhood (Hernandez et al., 2001;
Gonzalez-Heydrich et al., 2007).
leadstofrontallobe epilepsy
Since frontal lobe dysfunctions are associated with abnormal
frontal lobe rhythms (Elbert et al., 1992; Barry et al., 2003) we
tried to examine cortical electroencephalogram (EEG) and
LFPs of MD thalamus (supplemental Fig. S4a, available at
www.jneurosci.org as supplemental material). Approximately
5 to 6 d after Co-wire implantation in the right PFC (5.8 ?
0.7 d on average), the right frontal lobe showed single spike
activities (Fig. 3a). However, other wires, made with metals
such as tungsten, copper, and aluminum, did not induce sei-
zure spikes when implanted in the PFC during the whole re-
cording period (supplemental Figs. S4c, Fig. S5a, available at
www.jneurosci.org as supplemental material) (cobalt, n ? 10;
after (9.0 ? 1.2 d on average), the frontal seizure spikes were
propagated to the left frontal lobe and to the MD thalamus
(Fig. 3a). The frontal lobe-specific spikes were continuously
examined during the whole recording period (Fig. 4a), al-
though the peak frequency of single-spike activities became
faster as time passed by (supplemental Fig. S5b, available at
30 d postimplantation, mice intermittently showed a second-
ary generalization of single spikes (onset, 11.2 ? 1.4 d on
average) or ictal discharges with whole-body convulsions (on-
set, 18.1 ? 2.5 d on average) (Fig. 3a).
By administration of HT (Walton and Treiman, 1988) at a
subconvulsive dose (550 mg/kg), the corticothalamic and corti-
mittent secondary generalizations was facilitated within an hour
with a similar pattern (Figs. 3b, 4b) (n ? 12). At that dose of HT,
mice without Co-wire implantation did not show any seizure
spikes (supplemental Fig. S6, available at www.jneurosci.org as
lobe seizures in the Co-wire model seems to be activity- and
neural pathway-dependent but not due to the time-dependent
diffusion of Co ions from the PFC to the MD or other brain
Since frontal lobe-specific seizure with secondary general-
ization is a well known symptom found in patients with FLE
(KellinghausandLu ¨ders,2004),wetestedwhethertheCo-wire-
induced seizures could be inhibited by anti-FLE drugs including
Hz) during development of frontal lobe spikes. contr, Contralateral; ipsi, ipsilateral. *p ? 0.05, **p ? 0.01. Data represent
4068 • J.Neurosci.,March16,2011 • 31(11):4063–4073 Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction
Page 7
zonisamide and phenytoin. Systemic administration of FLE
drugs robustly abolished the Co-wire-induced seizures (Fig.
4c,d). In addition, we found that ethosuximide, a drug for ab-
al., 1989), also suppressed the Co-wire-induced seizure spikes
(8 ? 1.1 d after Co-wire implantation) (Fig. 4d) (vehicle group,
n ? 4; zonisamide group, n ? 3; phenytoin group, n ? 3; etho-
suximide group, n ? 5; p ? 0.05) (Frampton and Scott, 2005).
These results suggest that the PFC damage by Co-wire leads to
temporally associated with the progressive increase of abnormal
hyperactivities in this model (Fig. 2). Consistently, the abnormal
ter, 2001).
lobe-specific spikes
The propagation of seizure spikes to the MD and the suppres-
sion of seizures by ethosuximide suggested a possibility that
the thalamus is involved in the development of FLE. To ad-
dress this issue, we examined the Co-wire-induced FLE in
mice with a right lesion in the MD (Fig. 5a) and found that
they were resistant to the generation of frontal spikes (Fig.
5b,c) (6 d after Co-wire implantation; contralateral, n ? 5;
ipsilateral, n ? 5; two-tailed t test, p ? 0.01) and secondary
generalizations when compared with the left MD lesion. The
right MD lesion, however, showed no effects on cortical sei-
induces cortical seizures through thalamus-independent mecha-
nisms (Steriade and Contreras, 1998) (Fig. 5b,c) (two-tailed t
test, p ? 0.05). These results suggest that the development of
Co-wire-induced FLE demands the role of thalamic neurons.
The hemisphere-specific interactions between the MD and
PFC neurons through reciprocal connections (Kuroda et al.,
1993) seem to be critical.
frontal-lobe-specific spikes
To probe the PFC–MD interactions, we
tween the two nuclei during the develop-
ment of frontal spikes. The bicoherence
between the two regions reached a peak
around theta frequencies before the onset
of seizure spikes (4.2 ? 0.3 d on average)
two-tailed t test, p ? 0.05). As frontal
spikes were initiated and their interevent
interval (IEI) was increased, the theta co-
herence between the two regions was de-
creased (IEI ?2, 5.8 ? 0.2 d on average;
IEI ?1.5, 7.6 ? 0.5 d on average) (Fig.
of the thalamocortical feedback in re-
and after the onset of frontal spikes,
Granger causality analysis was performed
between MD and PFC. Consistent with
coherence analysis, the MD–PFC interac-
tion was increased before the onset of
frontal spikes (4.2 ? 0.3 d after Co-wire
implantation) (Fig. 6c; supplemental Ta-
and the PFC at theta frequencies preceded the onset of frontal
lobe spikes.
FLE-like symptoms
Considering a previous study that thalamic burst firings are in-
volved in the generation of thalamocortical interactions (Jean-
monod et al., 1996, 2001), we examined the firing mode of MD
neurons in our model by in vivo extracellular recordings of the
MD under partial urethane anesthesia (1.35 mg/kg). Before the
onset of frontal lobe spikes (4.2 ? 0.2 d after Co-wire implanta-
tion), low-threshold burst spikes known to depend on the acti-
vationofT-typeCa2?channels(Perez-Reyesetal.,1998;Llina ´set
al., 1999) significantly increased in the MD without changes in
tonic spike activity (Fig. 7). In the period when the faster frontal
spikes fully developed (9.0 ? 0.2 d after Co-wire implantation),
[control, n ? 14; before, n ? 18; spike (IEI ?1.5), n ? 12; one-
way ANOVA: burst, p ? 0.05; tonic, p ? 0.05]. These results
suggest that burst firings of MD neurons support the PFC–MD
of frontal spikes (Fig. 6).
Considering that CaV3.1 is the major T-type Ca2?channel sub-
unit that supports burst firings in the thalamocortical relay neu-
rons (Crunelli et al., 1989), we introduced lentiviruses harboring
CaV3.1-specific shRNA into the MD; this infection significantly
reduced CaV3.1 proteins and T-type Ca2?currents in the MD
neurons (Fig. 8a,b; supplemental Table S2, available at www.
jneurosci.org as supplemental material) [lentivirus harboring
shRNA-Control (shC), n ? 5; lentivirus harboring shRNA
Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction J.Neurosci.,March16,2011 • 31(11):4063–4073 • 4069
Page 8
Cav3.1 (sh3.1), n ? 5; two-tailed ? test,
p ? 0.05]. Knockdown of CaV3.1 in the
MD also significantly ameliorated neu-
rological and behavioral abnormalities
found in this model. The PFC power at
theta range and MD–PFC cross talk was
significantly decreased before spiking
(4.6 ? 0.2 d) (Fig. 8c,d; supplemental Fig.
S7, available at www.jneurosci.org as sup-
plemental material) (shC, n ? 5; sh3.1,
n ? 3; two-tailed t test, p ? 0.01), com-
pared with the control group. The num-
two-tailed t test, p ? 0.05). MD-specific
knockdown of the CaV3.1 gene also ame-
liorated the locomotor hyperactivity seen
n ? 5; two-tailed t test, p ? 0.01).
In addition, the therapeutic effect of
the MD-specific knockdown of the
CaV3.1 gene on FLE-like symptoms was
also observed after knockout of the gene
(CaV3.1?/?), which is known to abolish
burst spikes in the thalamus (Kim et al.,
2001). CaV3.1?/?mice showed reduced
(supplemental Fig. S8a, available at www.
jneurosci.org as supplemental material)
(CaV3.1?/?, n ? 6; CaV3.1?/?, n ? 5;
two-tailed t test, p ? 0.01), a lack of fron-
tal lobe-specific spikes after the onset of
spiking, and an absence of locomotor hy-
peractivity (6 d after Co-wire implanta-
www.jneurosci.org as supplemental ma-
4; two-way ANOVA, p ? 0.001).
Since the first report on Phineas Gage,
who suffered a severe frontal lobe injury
in 1848 (Damasio et al., 1994; Macmillan, 2002), frontal lobe
dysfunction characterized by a spectrum of cognitive impair-
ments such as hyperactivity, inattention, impulsiveness, and, in
severe cases, personality changes (Mateer and Williams, 1991;
(Levin, 1984; Benson, 1991; Gedye, 1991; Shue and Douglas,
1992;Niedermeyer,1998;KellinghausandLu ¨ders,2004;Yoonet
in the PFC in mice leads to neurological and behavioral abnor-
malities that have been reported in patients with FLE (Helms-
taedter, 2001; Kellinghaus and Lu ¨ders, 2004).
FLE does not usually cause severe convulsions, despite frontal-
lobe-specific spikes. Instead, patients with FLE show cognitive dys-
functions that have been reported in other neuropsychiatric
initiated in the frontal cortex and then leads to complex behavioral
the lack of robust experimental models that allow researchers to
induce frontal-lobe-specific spikes. In this study, we established a
Co-wire model of PFC damage, which leads to neurological and
behavioral symptoms that have been reported in patients with FLE
(Figs. 2, 3), and found that the activation of thalamic T-type Ca2?
PFC damage by Co-wire implantation mimics hypoxic condi-
tions including increased neuronal death, ghost cells (Fig. 1b; sup-
plemental Fig. S2a, available at www.jneurosci.org as supplemental
material), and enhanced VEGF expression (Fig. 1d). In addition to
VEGF, hypoxia induces many other molecules including Hif-1,
has been well known that hypoxic stress on brain slices increases a
Heinemann, 1992; Jensen et al., 1998). Those molecular and physi-
In this model, our results suggest that the activation of tha-
lamic T-type Ca2?channels within the MD is critical for the
showed decreased hyperactivity, compared with shC group (6 d after cobalt wire was implanted). *p ? 0.05. Data represent
4070 • J.Neurosci.,March16,2011 • 31(11):4063–4073 Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction
Page 9
onset of FLE (Figs. 5–8). In contrast to our results, other studies
show that the involvement of thalamic T-type Ca2?channels in
cortically induced seizures is not required, since the induction of
cortical seizures by local injection of BMB is not associated with
thalamic functions (Neckelmann et al., 1998; Steriade and Con-
treras, 1998; Destexhe et al., 1999). This difference can be ex-
plained, in part, by the capacity of BMB to directly increase the
synchronous seizure spikes in cortical neurons (Gutnick et al.,
1982). PFC damage caused by Co-wire, however, may not be
enough to induce cortical synchrony, but may also require tha-
lamic bursting activity modulated by T-type Ca2?channels.
How can PFC damage cause activation of thalamic T-type
Ca2?channels? From an anatomical perspective, PFC neurons
can stimulate two types of thalamic neurons [thalamocortical
through reciprocal connections (Groenewegen, 1988; Hugue-
neurotransmitter released into the MD by nRT neurons may be
involved in de-inactivation mechanisms that allow T-type Ca2?
channels to be easily activated in response to excitatory inputs
(Crunelli and Leresche, 1991; Cox et al., 1997). Consistent with
this idea, both the corticothalamic and thalamocortical drives
increased together (Fig. 6c) and at the same time as the low-
threshold burst spikes of MD neurons were enhanced (Fig. 7),
which reflects the activation of T-type Ca2?channels (Hugue-
nard, 1996; Kim et al., 2001; Crunelli and Leresche, 2002; Lee et
al., 2004; Ernst et al., 2009). Since the thalamic burst spikes are
known to be efficient in stimulating postsynaptic neurons (Lis-
man, 1997), the activation of T-type Ca2?channels in the MD
PFC cross talk and leading to frontal lobe-specific seizures at the
EEG level (Fig. 6).
In addition, thalamic burst spiking is thought to be a sensory
gating mechanism, which can terminate the relay of sensory in-
formation to the cortex (McCormick and Bal, 1994). In this re-
gard, it is plausible that the selective increases in burst spikes in
tion in the MD–PFC pathways, leading to frontal lobe dysfunc-
(Fig. 8) or drugs that weaken the thalamocortical interactions
may be a novel option for preventing further cognitive dysfunc-
this, ethosuximide, a T-type Ca2?channel blocker used to treat
absence seizures, efficiently abolished the onset of FLE in our
model (Fig. 4d) (ethosuximide, n ? 5; p ? 0.01).
Finally, our results suggest a two-step model of PFC dysfunc-
mal thalamocortical feedback driven by thalamic T-type Ca2?
channels, which, in turn, leads to the onset of neurological and
behavioral abnormalities. This model neatly explains why the
progressive development of cortical dysfunction in patients with
a lesion in the PFC takes time (Grattan and Eslinger, 1992; An-
derson et al., 2000; McKinlay et al., 2002; Englander et al., 2003)
and how the thalamus contributes to attention span when pa-
tients are awake, which is a controversial issue (Crick, 1984; Ste-
riade et al., 1993; Sherman, 2001).
(2000) Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a ret-
rospective comparison with psychoses in temporal lobe epilepsy. Seizure
Anderson SW, Damasio H, Tranel D, Damasio AR (2000) Long-term se-
ropsychol 18:281–296.
Armony JL, Dolan RJ (2002) Modulation of spatial attention by fear-
conditioned stimuli: an event-related fMRI study. Neuropsychologia
Barry RJ, Clarke AR, Johnstone SJ (2003) A review of electrophysiology in
attention-deficit/hyperactivity disorder: I. Qualitative and quantitative
electroencephalography. Clin Neurophysiol 114:171–183.
BelezaP,BilginO,NoachtarS (2009) Interictalrhythmicalmidlinetheta
differentiates frontal from temporal lobe epilepsies. Epilepsia
BensonDF (1991) Theroleoffrontaldysfunctioninattentiondeficithyper-
activity disorder. J Child Neurol 6:S9–12.
Choi DW (1990) Cerebral hypoxia: some new approaches and unanswered
questions. J Neurosci 10:2493–2501.
Chua CK, Chandran V, Acharya R, Lim CM (2007) Higher order spectral
CoulterDA,HuguenardJR,PrinceDA (1989) Characterizationofethosux-
imide reduction of low-threshold calcium current in thalamic neurons.
Ann Neurol 25:582–593.
Cox CL, Huguenard JR, Prince DA (1997) Nucleus reticularis neurons me-
diate diverse inhibitory effects in thalamus. Proc Natl Acad Sci U S A
Crick F (1984) Function of the thalamic reticular complex: the searchlight
hypothesis. Proc Natl Acad Sci U S A 81:4586–4590.
CrunelliV,LerescheN (1991) AroleforGABABreceptorsinexcitationand
inhibition of thalamocortical cells. Trends Neurosci 14:16–21.
CrunelliV,LerescheN (2002) Childhoodabsenceepilepsy:genes,channels,
neurons and networks. Nat Rev Neurosci 3:371–382.
Crunelli V, Lightowler S, Pollard CE (1989) A T-type Ca2?current under-
lies low-threshold Ca2?potentials in cells of the cat and rat lateral genic-
ulate nucleus. J Physiol 413:543–561.
Daffner KR, Mesulam MM, Holcomb PJ, Calvo V, Acar D, Chabrerie A,
Kikinis R, Jolesz FA, Rentz DM, Scinto LF (2000) Disruption of atten-
tion to novel events after frontal lobe injury in humans. J Neurol Neuro-
surg Psychiatry 68:18–24.
Damasio A, Anderson S (1985) The frontal lobes. Clin Neuropsychol
DamasioH,GrabowskiT,FrankR,GalaburdaAM,DamasioAR (1994) The
return of Phineas Gage: clues about the brain from the skull of a famous
patient. Science 264:1102–1105.
Davids E, Zhang K, Tarazi FI, Baldessarini RJ (2003) Animal models of
attention-deficit hyperactivity disorder. Brain Res Rev 42:1–21.
Destexhe A, Contreras D, Steriade M (1999) Cortically-induced coherence
of a thalamic-generated oscillation. Neuroscience 92:427–443.
Elbert T, Lutzenberger W, Rockstroh B, Berg P, Cohen R (1992) Physical
aspects of the EEG in schizophrenics. Biol Psychiatry 32:595–606.
Bergman W (2003) Analyzing risk factors for late posttraumatic sei-
zures: a prospective, multicenter investigation. Arch Phys Med Rehabil
Ernst WL, Zhang Y, Yoo JW, Ernst SJ, Noebels JL (2009) Genetic enhance-
voltage-activated calcium current induces pure absence epilepsy.
J Neurosci 29:1615–1625.
FramptonJE,ScottLJ (2005) Zonisamide:areviewofitsuseinthemanage-
ment of partial seizures in epilepsy. CNS Drugs 19:347–367.
Gainetdinov RR, Mohn AR, Caron MG (2001) Genetic animal models: fo-
cus on schizophrenia. Trends Neurosci 24:527–533.
Gedye A (1991) Frontal lobe seizures in autism. Med Hypotheses
Gilby KL (2008) A new rat model for vulnerability to epilepsy and autism
spectrum disorders. Epilepsia 49 [Suppl 8]:108–110.
Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D, Faraone
SV, Boyer K, Mrakotsky C, DeMaso D, Bourgeois B, Biederman J (2007)
Psychiatric disorders and behavioral characteristics of pediatric patients
with both epilepsy and attention-deficit hyperactivity disorder. Epilepsy
Behav 10:384–388.
Granger CWJ (1969) Investigating causal relations by econometric models
and cross-spectral methods. Econometrica 37:424–438.
Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunctionJ.Neurosci.,March16,2011 • 31(11):4063–4073 • 4071
Page 10
Grattan LM, Eslinger PJ (1992) Long-term psychological consequences of
childhood frontal lobe lesion in patient DT. Brain Cogn 20:185–195.
Groenewegen HJ (1988) Organization of the afferent connections of the
mediodorsal thalamic nucleus in the rat, related to the mediodorsal-
prefrontal topography. Neuroscience 24:379–431.
Gucuyener K, Erdemoglu AK, Senol S, Serdaroglu A, Soysal S, Kockar AI
(2003) Use of methylphenidate for attention-deficit hyperactivity disor-
der in patients with epilepsy or electroencephalographic abnormalities.
J Child Neurol 18:109–112.
Guido W, Lu SM, Sherman SM (1992) Relative contributions of burst and
tonic responses to the receptive field properties of lateral geniculate neu-
rons in the cat. J Neurophysiol 68:2199–2211.
Gutnick MJ, Connors BW, Prince DA (1982) Mechanisms of neocortical
epileptogenesis in vitro. J Neurophysiol 48:1321–1335.
Han CJ, O'Tuathaigh CM, van Trigt L, Quinn JJ, Fanselow MS, Mongeau R,
Koch C, Anderson DJ (2003) Trace but not delay fear conditioning re-
quires attention and the anterior cingulate cortex. Proc Natl Acad Sci
Helmstaedter C (2001) Behavioral aspects of frontal lobe epilepsy. Epilepsy
Behav 2:384–395.
bergM (2007) Thefrequency,complicationsandaetiologyofADHDin
new onset paediatric epilepsy. Brain 130:3135–3148.
Hernandez MT, Sauerwein HC, de Guise E, Lortie A, Jambaque ´ I, Dulac O,
Lassonde M (2001) Neuropsychology of frontal lobe epilepsy in chil-
dren. Adv Behav Biol 50:103–111.
Ho ¨ckel M, Vaupel P (2001) Tumor hypoxia: definitions and current clini-
cal, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276.
Huguenard JR (1996) Low-threshold calcium currents in central nervous
system neurons. Annu Rev Physiol 58:329–348.
Huguenard JR, Prince DA (1994) Intrathalamic rhythmicity studied in
J Neurosci 14:5485–5502.
Ishige N, Pitts LH, Hashimoto T, Nishimura MC, Bartkowski HM (1987)
Effect of hypoxia on traumatic brain injury in rats. Part 1: changes in
rosurgery 20:848–853.
Ito U, Kuroiwa T, Nagasao J, Kawakami E, Oyanagi K (2006) Temporal
of the cerebral cortex: ultrastructure of neuronal remodeling. Stroke
Jeanmonod D, Magnin M, Morel A (1996) Low-threshold calcium spike
bursts in the human thalamus. Common physiopathology for sensory,
motor and limbic positive symptoms. Brain 119:363–375.
JeanmonodD,MagninM,MorelA,SiegemundM,CancroA,LanzM,Llina ´s
R, Ribary U, Kronberg E, Schulman J, Zonenshayn M (2001) Thalamo-
JensenFE,WangC,StafstromCE,LiuZ,GearyC,StevensMC (1998) Acute
and chronic increases in excitability in rat hippocampal slices after peri-
natal hypoxia in vivo. J Neurophysiol 79:73–81.
JobstBC,WilliamsonPD (2005) Frontallobeseizures.PsychiatrClinNorth
Am 28:635–651.
Kates WR, Lanham DC, Singer HS (2005) Frontal white matter reductions
in healthy males with complex stereotypies. Pediatr Neurol 32:109–112.
Kellinghaus C, Lu ¨ders HO (2004) Frontal lobe epilepsy. Epileptic Disord
Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW, Shin HS
(2001) Lack of the burst firing of thalamocortical relay neurons and re-
sistance to absence seizures in mice lacking ?1G T-type Ca2?channels.
Neuron 31:35–45.
Kim D, Park D, Choi S, Lee S, Sun M, Kim C, Shin HS (2003) Thalamic
control of visceral nociception mediated by T-type Ca2?channels. Sci-
ence 302:117–119.
Kuroda M, Murakami K, Oda S, Shinkai M, Kishi K (1993) Direct synaptic
sal thalamic nucleus (MD) and corticothalamic neurons the MD in the
prefrontal cortex. Brain Res 612:339–344.
Lee J, Kim D, Shin HS (2004) Lack of delta waves and sleep disturbances
during nonrapid eye movement sleep in mice lacking ?1G-subunit of
T-type calcium channels. Proc Natl Acad Sci U S A 101:18195–18199.
Levin S (1984) Frontal lobe dysfunctions in schizophrenia–II. Impairments
of psychological and brain functions. J Psychiatr Res 18:57–72.
Lisman JE (1997) Bursts as a unit of neural information: making unreliable
synapses reliable. Trends Neurosci 20:38–43.
Llina ´sRR,RibaryU,JeanmonodD,KronbergE,MitraPP (1999) Thalamo-
cortical dysrhythmia: a neurological and neuropsychiatric syndrome
characterized by magnetoencephalography. Proc Natl Acad Sci U S A
Luhmann HJ, Heinemann U (1992) Hypoxia-induced functional altera-
tions in adult rat neocortex. J Neurophysiol 67:798–811.
Luria A, Pribram K, Homskaya E (1964) An experimental analysis of the
behavioral disturbance produced by a left frontal arachnoidal endotheli-
oma (meningioma). Neuropsychologia 2:257–280.
Macmillan M (2002) An odd kind of fame: stories of Phineas Gage: MIT.
MateerC,WilliamsD (1991) Effectsoffrontallobeinjuryinchildhood.Dev
Neuropsychol 7:359–376.
Max JE, Manes FF, Robertson BA, Mathews K, Fox PT, Lancaster J (2005)
Prefrontal and executive attention network lesions and the development
of attention-deficit/hyperactivity symptomatology. J Am Acad Child
Adolesc Psychiatry 44:443–450.
McAllister TW, Price TR (1987) Aspects of the behavior of psychiatric in-
patients with frontal lobe damage: some implications for diagnosis and
treatment. Compr Psychiatry 28:14–21.
McCormick DA, Bal T (1994) Sensory gating mechanisms of the thalamus.
Curr Opin Neurobiol 4:550–556.
McGuire TL, Sylvester CE (1987) Neuropsychiatry evaluation and treat-
ment of children with head injury. J Learn Disabil 20:590–595.
McKinlay A, Dalrymple-Alford JC, Horwood LJ, Fergusson DM (2002)
Long term psychosocial outcomes after mild head injury in early child-
hood. J Neurol Neurosurg Psychiatry 73:281–288.
Millichap JG (2008) Etiologic classification of attention-deficit/hyperactiv-
ity disorder. Pediatrics 121:e358–e365.
Neckelmann D, Amzica F, Steriade M (1998) Spike-wave complexes and
fast components of cortically generated seizures. III. Synchronizing
mechanisms. J Neurophysiol 80:1480–1494.
Niedermeyer E (1998) Frontal lobe functions and dysfunctions. Clin Elec-
troencephalogr 29:79–90.
Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins TW (1990) Plan-
ning and spatial working memory following frontal lobe lesions in man.
Neuropsychologia 28:1021–1034.
Owen AM, Roberts AC, Hodges JR, Summers BA, Polkey CE, Robbins TW
(1993) Contrasting mechanisms of impaired attentional set-shifting in
patients with frontal lobe damage or Parkinson's disease. Brain
Paradiso S, Chemerinski E, Yazici KM, Tartaro A, Robinson RG (1999)
Frontal lobe syndrome reassessed: comparison of patients with lateral or
Patrikelis P, Angelakis E, Gatzonis S (2009) Neurocognitive and behavioral
functioning in frontal lobe epilepsy: a review. Epilepsy Behav 14:19–26.
Pereda E, Quiroga RQ, Bhattacharya J (2005) Nonlinear multivariate anal-
ysis of neurophysiological signals. Prog Neurobiol 77:1–37.
Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type
calcium channels. Physiol Rev 83:117–161.
Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP,
FoxM,ReesM,LeeJH (1998) Molecularcharacterizationofaneuronal
low-voltage-activated T-type calcium channel. Nature 391:896–900.
Pigula FA, Wald SL, Shackford SR, Vane DW (1993) The effect of hypoten-
sion and hypoxia on children with severe head injuries. J Pediatr Surg
Piret JP, Mottet D, Raes M, Michiels C (2002) CoCl2, a chemical inducer of
hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in
hepatoma cell line HepG2. Ann NY Acad Sci 973:443–447.
RollsET,HornakJ,WadeD,McGrathJ (1994) Emotion-relatedlearningin
patients with social and emotional changes associated with frontal lobe
damage. J Neurol Neurosurg Psychiatry 57:1518–1524.
Andermann F, Desbiens R, Keene D, Cendes F (1995) Autosomal dom-
Shallice T, Burgess PW (1991) Deficits in strategy application following
frontal lobe damage in man. Brain 114:727–741.
4072 • J.Neurosci.,March16,2011 • 31(11):4063–4073Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunction
Page 11
Sharp FR, Bernaudin M (2004) HIF1 and oxygen sensing in the brain. Nat
Rev Neurosci 5:437–448.
Sherman SM (2001) Tonic and burst firing: dual modes of thalamocortical
relay. Trends Neurosci 24:122–126.
ShueKL,DouglasVI (1992) Attentiondeficithyperactivitydisorderandthe
frontal lobe syndrome. Brain Cogn 20:104–124.
Sitnikova E, Dikanev T, Smirnov D, Bezruchko B, van Luijtelaar G (2008)
Granger causality: cortico-thalamic interdependencies during absence
seizures in WAG/Rij rats. J Neurosci Methods 170:245–254.
Steriade M (2006) Grouping of brain rhythms in corticothalamic systems.
Neuroscience 137:1087–1106.
Steriade M, Contreras D (1995) Relations between cortical and thalamic
cellular events during transition from sleep patterns to paroxysmal activ-
ity. J Neurosci 15:623–642.
Steriade M, Contreras D (1998) Spike-wave complexes and fast compo-
nents of cortically generated seizures. I. Role of neocortex and thalamus.
J Neurophysiol 80:1439–1455.
Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscilla-
tions in the sleeping and aroused brain. Science 262:679–685.
Stores G, Zaiwalla Z, Bergel N (1991) Frontal lobe complex partial seizures
Child Neurol 33:998–1009.
Stuss DT, Gow CA (1992) "Frontal dysfunction" after traumatic brain in-
jury. Cogn Behav Neurol 5:272–282.
Tan M, Appleton R (2005) Attention deficit and hyperactivity disorder,
methylphenidate, and epilepsy. Arch Dis Child 90:57–59.
Walton NY, Treiman DM (1988) Experimental secondarily generalized
convulsive status epilepticus induced by d,l-homocysteine thiolactone.
Epilepsy Res 2:79–86.
Wienbruch C, Moratti S, Elbert T, Vogel U, Fehr T, Kissler J, Schiller A,
Rockstroh B (2003) Source distribution of neuromagnetic slow wave
activity in schizophrenic and depressive patients. Clin Neurophysiol
Ragland JD, Carter CS (2008) Association of dorsolateral prefrontal
cortex dysfunction with disrupted coordinated brain activity in schizo-
phrenia: relationship with impaired cognition, behavioral disorganiza-
tion, and global function. Am J Psychiatry 165:1006–1014.
ZikopoulosB,BarbasH (2006) Prefrontalprojectionstothethalamicretic-
Kimetal.•ThalamicFeedbackMediatesPrefrontalDysfunctionJ.Neurosci.,March16,2011 • 31(11):4063–4073 • 4073


text:
Confined Space Entry
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Confined spaces are significantly more hazardous than normal workplaces. The hazards involved may not be unique to confined spaces, but are always exacerbated by the enclosed nature of the confined space. The resulting injuries are potentially fatal. A seemingly insignificant error or oversight while working in a confined space can result in a tragic accident. This one day course will enable participants to work safely in confined spaces.
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Rev 5

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See how osteoarthritis eats away at the protective cushioning in the knee, causing pain, swelling, and stiffness. And learn how a knee replacement can renew your quality of life.
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Donahue is working with those patients and doctors to carve out a compromise, one that reforms the treatment rather than sees the status quo as immutable or seeks to ban it. "I was being told from all the research that my experience of loss doesn't exist. Yet I know without question what happened to me," she explains. "I also was discovering this opposite view that said, 'This deliberate and knowing fraud on innocent psychiatric patients who are having their brains destroyed by the evil kingdom.' I am not the kind of person who can believe that, either. I don't believe in massive conspiracies."
It is not an exaggeration to say that electroconvulsive therapy has opened a new reality for me. I used to deny when a depressive episode was coming on. knew how much it would hurt, how long the darkness would last. Now I know there is something that will work and work quickly. It takes away the anticipation and the fear. I also used to be unable to shake the dread even when I was feeling good, because I knew the bad feelings would return. ECT has wiped away that foreboding. It has given me a sense of control, of hope.
That does not mean I look forward to the treatments. Who would? But when I lie down, I know that within seconds I'll be asleep - and that this process going to make me better. I also know that like many patients today, I can go home after each treatment rather than stay overnight in the hospital.
I have had seven more sets of ECT since the first in 2001. All my treatments have been unilateral, which means the electrodes go on just one side of my head in positions aimed at minimizing memory loss. The same concern led them to gradually lower the intensity of the stimulus they give me, to a level the doctors say one-10th of what Stelian Dukakis probably got in the 1950s. I generally need treatment every seven or eight months, my timeline for depression returning.
A nun who contacted me after a story on my ECT appeared in the newspaper described how afraid she had been to have ECT. She said, "This is the way would feel going in for a root canal." As for me, I hate fillings, and don't like to go to the dentist, period. I happened to have had a root canal not long before my first electroconvulsive therapy. In some ways ECT is less traumatic for me than going to the dentist, and certainly less frightening than the root canal. Lots of doctors say I am crazy for thinking something like that, but I don't think negatively about the treatment.
Excerpted from Shock: The Healing Power of Electroconvulsive Therapy, published this month by Penguin. Copyright 2006 by Kitty Dukakis and Larry Tye.


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great video.. i hope hey post the next one..
Inside MMA Episode 12 which includes Sean Sherk. Sherk learns today his faith, when the California State Athletic Commission (CSAC) rules on his testing positive for steroids.
UFC president Dana White has already stated that Sherk will not be striped of his title regardless of the CSAC ruling. Sherk will face the winner of BJ Penn and Joe Stevenson in 2008.
great video.. i hope hey post the next one..
I dont get this. Say Sherk was aquitted…then there is still an interim champion. Now he is guilty…there is still an interim champion. Doesn't this guy get any type of punishment for disgracing the sport. To me it seems pretty obvious that if you are found guilty, you should be stripped and have to work back up again. Not getting a title shot as soon as you are cleared to fight. Dana is pissing people off now with this interim Champion shit. I know I'm getting pissed off.
Yeah great show. When I saw it was an hour I didn't think I would make it past 5 minutes but it kept my attention. Sherk looked a little guilty to me with all of his "uhhh uhhhh uhhh's" and looking away from the guys when he was talking about his appeal. In my opinion, he got caught, he had to do something to get to that level, it wasnt just a coincidence. I think he should have to fight two fights before returing to the title picture.
These guys hyped up Soku so much that I'm really looking foward to see him fight.


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Before, I would get up at eight in the morning, go to work, go to school, go to the gym, come home, have sex with my girlfriend. I had a lot of ambition, I had career goals...Now basically I just sit in my room all day and don't talk to anyone." -- Kevin Malley
Soul Food Junkies Trailer
Written by Hezekial Hiram Zillerman On Thursday, January 05, 2012
One of my favorite blogs on the web is Barclay.TV. You'll see us link to Barclay from time to time. As he finds some of the greatest gems on the innanet. Namely, this teaser clip for "Soul Food Junkies". Directed by Byron Hurt, "Soul Food Junkies" aims to bring more awareness to the health crisis on plaguing communities of color, its history and how it's become part of our cultural identity. Below the cut, he explains his mission. Please check out the trailer as well.
"Minorities contract diabetes and suffer from heart diseases in disproportionate numbers. That alone costs the American economy enough to be concerned about what people eat and why." -- Stanley Crouch
Tags: entertainment, health, videos
This Guy: CJ Senter
Written by Hezekial Hiram Zillerman On Thursday, October 20, 2011
When I was in first grade, I was on a stage in the cafetornasium singing off key to "We Are The World (we aww duh chirren)". I followed that up with a mastery and addiction to Super Mario Bros. An addiction I enjoy today. The next generation of kids, raised themselves because we were too busy going to clubs and getting pregnant. But the kids after that? They are preparing for war. They are getting in shape and getting strong to destroy us. Yes, I said it. These kids are making sure that they don't have to deal with type II diabetes and obesity so when they are ready to whoop our ass, they will have no problem. We'll probably die from the shame of being so out of shape compared to them before they actually land a punch, but I digress. Below watch as CJ Senter, the 10 year old fitness guru, trains his troops for the first wave of shock and awe.
After the cut, more CJ. And meet the generals of the upcoming war. Including a 9 year old girl that squats 180 lbs. 5 times and another who deadlifts 195 lbs. Where's Richard Simmons when you need him?
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Happy Birthday Broadway!
Happy Birthday Broadway!
Well I was born in a small town
And I can breathe in a small town
Gonna die in this small town
And that's prob'ly where they'll bury me
Happy Birthday, Broadway!
If you type "google" into google you can break the internet.
HAPPY BIRTHDAY you two!! Special shout-out to Broadway!!
"I'm telling you - it's a madhouse out there. I feel like Charlton Heston waking up in the field and seeing the chimp on top of the pony." ~ Dennis Miller
Happy Birthday
HAPPY BIRTHDAY BROADWAY!!!!! New York misses you! Hope you are still having a wonderful birthday!!
Hey... thanks, everyone!!!
I did have a wonderful day and was able to forget just how old I'm getting. ACK! But now that picture of NYC is making me *home*sick.
*Runs in late to the party*
Happy Birthday Broadway!
Last edited by Unklescott; 07-22-2006 at 11:35 PM.
Happy Birthday allybug :happybirthdy
Special birthday shout out to BROADway!
"Among the blind, the squinter rules." ~ Gerard Didier Erasmus
I didn't have computer access yesterday so belated happy birthday to Broadway and allybug47150!


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The salvage of Ohio's oldest iron foundry is one of Reclaimed Cleveland longest and most labor-intensive undertakings to date. These relics of Cleveland's mid-century manufacturing boom are prime for second life in a domestic setting. This mirror was found amid the remnants of the 300-year old foundry's cavernous production floors.
This product is crafted from repurposed vintage materials.
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Hang tight!
Recipe by Reynolds Wrap® Heavy Duty Aluminum Foil
"Foil packets make these ribs fall-off-the-bone tender and keep all the savory flavor inside."
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1 tablespoon
packed brown sugar
1 tablespoon
1 tablespoon
chili powder
1 teaspoon
1 teaspoon
garlic powder
4 pounds
beef short ribs (bone-in), trimmed of fat
Ice cubes
1/2 cup
barbecue sauce, plus additional for serving
Excellent - they were "fall off the bone" good.
Well I used the aluminum foil, but that is it!!! I used 2 slabs of baby back ribs and cut into 4 sections. I removed the membrane! Brushed with Baby Rays Barbecue Sauce and put each section into aluminum foil in the fridge over night! Next day I put the ribs in the oven for 2.5 hrs on 300 degrees on a cookie sheet! When done, I simply put them on the grill for 5 minutes to give that barbecued flavor! Simply fell off the bone! And absolutely no mess!! Soo good!!!
8 Ratings
YUM!!!! I Don't have time to cook during the week so I used this rub on 4 meaty boneless chuck ribs & let them rest on the counter for about 15 minutes. Then I cooked them with olive oil on the George Foreman Grill. They cooked to perfection in about 15 minutes or so. I served them with our favorite BBQ sauce on the side but they were juicy, tender, & delicious on their own.
My husband has not stopped raving about this recipe! The ribs were melt-in-your-mouth tender. The rub was not overpowering and added just the right amount of kick. You knocked this out of the park! Will definitely make this again!!!!
Delish! Followed the recipe to a T and the result was a tender, moist "fall off the bone" tasty short rib! Perfectly seasoned. The foil pockets made clean up super easy! Can't wait to show off at the next office luncheon, this recipe will have them bowing down callling me MasterChef!
Amazing! We applied the dry rub in the morning...Letting it sit the entire day in the fridge. We then cooked it according to the original recipe instructions. ..however, we added a little beer to our barbecue sauce & grilled them directly on the grill. They were the best ribs I have ever had!
Very good! Some of the best I've had, or made. I followed the recipe almost exactly. Changes I made as follows: hot smoked paprika and chipotle chili powder were substituted. Also, the recipe didn't specify but I cooked mine over lump charcoal, two towers of coals each an hour apart.
I burned thenm, by accident, but they were still really good :)
* Percent Daily Values are based on a 2,000 calorie diet.
Grilled BBQ Short Ribs with Dry Rub
Serving Size: 1/4 of a recipe
Servings Per Recipe: 4
Amount Per Serving
Calories: 1007
Calories from Fat: 755
Memorial Day is a time to get together with friends and family for food, fun, and memories.
Nothing beats a big bowl of cool, creamy potato salad at your cookout.
Delicious recipes, party ideas, and cooking tips! Get a year of Allrecipes magazine for $7.99!
Discover the secret to incredibly tender grilled ribs with almost no cleanup.
See how to make a quick-and-easy rub for grilled short ribs.
See how to make Korean-style grilled short ribs.


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Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/13965
|Adi Shankara at Mandhata and Mahishmati
|Canestraight, Linda; Nagar, Murari Lal
|Adi Shankara
|Columbia, MO: Om Shanti Mandiram
|Series/Report no.:
|Om Holy Book; 8
|This piece is a collection of select email messages exchanged among some OM devotees on the subject for more than a decade. These have been presented here in their natural order and sequence as they occurred just to show the natural development of thought. No attempt has been made to bring any order or system. The subject and object treated in this publication is the first attempt ever made in the history of Vedic Civilization as far as the divine life of Jagadguru Adi Shankara Bhagvatpada is concerned. We thought of giving the title to this publication as Adi Shankara Goes to School, but the subject covered here is much more intensive as well as extensive. Shankaracharya acquired his basic knowledge at the feet of his Gurudeva Shri Govinda-Bhagavatpada. Govindeshvara Gupha served as Shankara's Gurukulam at Mount Mandhata. And Mahishmati (today's Maheshvara) emerged as his Advaita-Vedanta-Vijaya-Vaijayanti. The full history of this revolutionary occurrence is yet to be written.
Items in MOspace are protected by copyright, with all rights reserved, unless otherwise indicated.


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Arcadja Auctions >Artists Database >S >School I-Schrote >Adolf Schreyer
Adolf SchreyerTweet (Frankfurt/main 1828 - Kronberg 1899 ) - Artworks Wikipedia® - Adolf Schreyer
Christie's /Oct 27, 2014
€25,962.47 - €33,380.31
Not Sold
Find artworks, auction results, sale prices and pictures of Adolf Schreyer at auctions worldwide.Go to the complete price list of works Follow the artist with our email alert
Variants on Artist's name :
Schreyer Adolphe
Along with Adolf Schreyer, our clients also searched for the following authors:
Florentine School, Francesco Paolo Michetti, Filippo De Pisis, Antonio Possenti, Umberto Boccioni, Pier Francesco Mola, Ubaldo Gandolfi, Pablo Picasso, Roberto Gaetano Crippa, Caspar Netscher, Juan De Arellano Y Francisco Camilo
Florentine School, Francesco Paolo Michetti, Filippo De Pisis, Antonio Possenti, Umberto Boccioni, Pier Francesco Mola, Ubaldo Gandolfi, Pablo Picasso, Roberto Gaetano Crippa, Caspar Netscher, Juan De Arellano Y Francisco Camilo
Artworks in Arcadja325
Some works of Adolf SchreyerExtracted between 325 works in the catalog of Arcadja
Adolf Schreyer - Horse Drawn Wagon
Other WORKS AT AUCTION
Adolf Schreyer (German, 1828-1899) Horse Drawn Wagon oil on panel signed Ad. Schreyer (lower left) 12 1/2 x 17 inches. Property from a Private Collection Provenance: Sold: Selkirk Winter Gallery Auction, St. Louis, December 4, 1989, Lot 525 Dr. Christoph Andreas has kindly confirmed the authenticity of this work. Please contact us for a complete condition report.
Adolf Schreyer - The Encounter
Original 1861
Auction: Christie's -Nov 25, 2014 - AmsterdamLot number: 231
Other WORKS AT AUCTION
Lot Description Adolf Schreyer (Frankfurt am Main 1828-1899 Cronenberg) The encounter signed and dated 'Ad Schreyer. 1861.' (lower right) oil on canvas, unframed 70 x 138.5 cm. Painted in 1861. Lot Condition Report I confirm that I have read this Important Notice and agree to its terms. View Condition Report
Adolf Schreyer - Bedouins Taking Aim
Auction: Bonhams -Nov 5, 2014 - New YorkLot number: 12
Other WORKS AT AUCTION
Adolf Schreyer (German, 1828-1899) Bedouins taking aim signed 'Ad. Schreyer' (lower right) oil on canvas 21 1/4 x 29in (54 x 73.8cm) Footnotes Provenance Ralph Hopkins Watson, Greenwich, Connecticut (Vice President of U.S. Steel). Bequeathed to the mother of the present owners, circa 1963. Thence by descent to the present owners. Adolf Schreyer was without doubt one of the most successful German orientalist painters of the 19th century. Celebrated during his lifetime, Schreyer was born in Frankfurt on the Main to wealthy parents who encouraged his education at the Städelsches Kunstinstitut and later at the Düsseldorf Academy. He later settled in Vienna, specializing in landscapes and military subjects, a genre much in demand at the time and which qualified him to accompany Maximilian Karl, the 6th Prince of Thurn und Taxis, on his campaigns through Hungary, Wallachia, Russia and Turkey. In 1854 he was following the Austrian army as an artist-reporter assigned to cover the Crimean War (1854-1857). In the following years, Schreyer traveled to Syria, Egypt and, by 1861, to Algeria. It was the sojourn in Algeria that determined the future course of Schreyer's career. Fascinated by the local culture, he spent time learning the local dialects and riding with Bedouin horsemen, making them his perpetual subject for the rest of his long career. In 1862 he established himself in Paris, where he was highly praised by the art critic Theophile Gautier and embraced by his contemporaries. The French went so far as to claim him as one of their own, as his art recalled both Delacroix and Fromentin. Another critic praised his dramatic and realistic subjects steeped in the pervasive Romanticism of the day: "His canvases seem to make you shiver with the intense coldness of the atmosphere when he paints a winter scene, while you languish under the burning sun when he conveys you to the arid atmosphere of the desert." ( Le Courrier artistique , Paris, 1865). Schreyer exhibited his pictures of Eastern European peasants and soldiers alongside countless variations on the theme of the Arab horseman at the Paris Salon and across Europe, garnering him numerous medals and honors. During the course of Schreyer's long career, violent, even frenzied depictions of Algerian horsemen at battle gave way to more calculated compositions, in which elaborately dressed Arab figures ride through rough terrain, either singly or in groups. The present painting demonstrates Schreyer's mastery of subject and color with great bravura. Horsemen engaged in a frontal gallop toward the viewer lend a unique dynamism to the scene, making this one of the most spectacular painting by Schreyer to come to the market in recent years. We would like to thank Dr. Christoph Andreas for confirming the authenticity of this painting by photographs.
Adolf Schreyer - Arab Horsemen In A Mountainous Landscape
Auction: Christie's -Oct 27, 2014 - New YorkLot number: 76
Other WORKS AT AUCTION
Adolf Schreyer (German, 1828-1899) Arab Horsemen in a Mountainous Landscape signed 'ad. Schreyer' (lower right) oil on canvas 23¾ x 31½ in. (60.3 x 80 cm.) Anonymous sale; Bonham's, New York, 21 April 2009, lot 113. Acquired at the above sale by the present owner. Property From An Important California Collection
Adolf Schreyer - Le Porte-étendard
Auction: Sotheby's -Oct 23, 2014 - ParisLot number: 93
Other WORKS AT AUCTION
Adolf Schreyer FRANCFORT 1828 - 1899 CRONBERG, ÉCOLE ALLEMANDE LE PORTE-ÉTENDARD ADOLF SCHREYER ; THE STANDARD BEARER ; OIL ON CANVAS ; SIGNED LOWER RIGHT Signé ad Schreyer en bas à droite Huile sur toile 70 x 100 cm., 27 ½ by 39 ½ in. Read Condition Report Read Condition Report Register or Log-in to view condition report Saleroom Notice Authentication Nous remercions le Docteur Christoph Andreas qui a confirmé l'authenticité de ce tableau Provenance Tedesco Frères, Paris (probablement acquis auprès de l'artiste) ; M. Knoedler & Co., Paris (acquis du précédent autour de 1900) ; John Levy, Paris (acquis du précédent vers 1925) ; Edward A. Langenbach, Ohio ; Resté chez les descendants du précédent The canvas has been relined. Under ultraviolet light the varnish fluoresces opaquely in places making the surface difficult to read, however retouchings are visible notably: strokes in the three foreground horses, areas in the ground below the rightmost horse, in the lower-left and upper-right corners, and strengthening to the signature. The artist's pentimenti are visible near the leftmost grouping of figures. Held in a decorative gilt frame. "In response to your inquiry, we are pleased to provide you with a general report of the condition of the property described above. Since we are not professional conservators or restorers, we urge you to consult with a restorer or conservator of your choice who will be better able to provide a detailed, professional report. Prospective buyers should inspect each lot to satisfy themselves as to condition and must understand that any statement made by Sotheby's is merely a subjective, qualified opinion. Prospective buyers should also refer to any Important Notices regarding this sale, which are printed in the Sale Catalogue. NOTWITHSTANDING THIS REPORT OR ANY DISCUSSIONS CONCERNING A LOT, ALL LOTS ARE OFFERED AND SOLD AS IS" IN ACCORDANCE WITH THE CONDITIONS OF BUSINESS PRINTED IN THE SALE CATALOGUE."


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Patients in a vegetative state appear to awaken after a coma but show no signs of awareness of self or their environment. Though their eyes are open, they have no purposeful actions, explained Dr. Allan Ropper, a neurologist at Brigham and Women's Hospital in Boston, who wrote an accompanying editorial. Their behavior is limited to reflexive behaviors, such as roving eye movements, swallowing or yawning.
The minimally conscious state is a newer term that describes patients with very limited and erratic verbal or motor responses to a spoken voice or other external stimuli.
The research raises provocative questions about the nature of consciousness and self-awareness, Ropper said.
Even if brain scans show hints of residual consciousness, "the question is, what does it mean? That is what people are going to have to grapple with," Ropper said. "It has to do with what you think life is and what is a meaningful life. Those are social, cultural and theological questions."
Ropper also cautioned against families gleaning a false sense of hope. Evidence of consciousness was found in only a small percentage of patients. And all of those were patients who had suffered traumatic brain injury, not "anoxic" brain injury caused by a lack of oxygen from, say, cardiac arrest.
The ultimate hope is that brain scans could one day enable some level of communication, said Dr. Joseph Fins, a professor of medicine and public health and chief of the division of medical ethics at Weill Cornell Medical College in New York City.
"Restoring communication is the holy grail," Fins said. "The thing that families overwhelmingly want is for their loved one to be able to express their wishes, and to know that their loved one is not in pain. These are things that could profoundly impact the decisions of families found in the difficult situation of caring for someone who is veget
|Copyright©2010 ScoutNews,LLC.
All rights reserved


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Amateur Racing On Deck at '14 Indiana MX
Wednesday, August 13, 2014
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This Saturday, August 16, the world's fastest professional dirt-bike racers will descend upon the brand new Ironman Raceway in Crawfordsville, Indiana for the inaugural Thor Indiana National. In conjunction with round eleven of the Lucas Oil Pro Motocross Championship, sanctioned by AMA Pro Racing, Ironman Raceway will host an entire weekend of amateur racing as part of the Great Lakes Motocross (GLMX) series.
The Amateur program kicks off this Friday, August 15, with open practice from 10 a.m. - 3 p.m. Weather permitting, Amateurs will receive three rotations on the new Ironman Raceway motocross track just one day before the pros go to battle.
Amateur racers and their families are encouraged to stick around for Saturday's first-ever Thor Indiana National, where Red Bull KTM's Ken Roczen and Ryan Dungey will continue fighting for a championship in the 450 Class. The KTM duo will be joined by GEICO Honda's Eli Tomac and Team Honda Muscle Milk's Trey Canard, who have made this 2014 season one of the most exciting in recent history.
In the 250 Class, the Midwest's very own Jeremy Martin continues to lead the championship chase with his Yamalube/Star Racing/Yamaha teammate Cooper Webb and Monster Energy/Pro Circuit/Kawasaki's Blake Baggett on his heels. Add in the most recent winner, Valli Motorsports Yamaha's Christophe Pourcel, and the stage is set for a great day of racing in Crawfordsville.
One day after the biggest names in motocross attempt to conquer the new Ironman racetrack, amateurs will line the fresh gate for a full day of racing action. Sunday's amateur race will follow the GLMX class structure, offering classes for 65cc machines all the way to 60+ Vet classes, Women and various age and skill levels. There will not be classes for 50cc machines this year. Don't miss the chance to also earn great contingency money from Yamaha, Suzuki, Kawasaki and Honda!
Registration for Sunday's racing takes place on Friday from 1 - 5 p.m. and again on Sunday at 7 a.m. The fee is $40 per class and an AMA membership is required to race, but not for practice. For Indiana and Michigan residents only, a GLMX membership is also required.
Practice begins at 8 a.m. on Sunday and racing will immediately follow. For complete details on Ironman Raceway's amateur program, please click HERE. For more information on the Indiana National, please click HERE.
Action for the Thor Indiana National on Saturday, August 16, begins at 8:30 a.m. ET with timed practice. Opening ceremonies get underway at 12:25 p.m. ET, with the first gate drop scheduled for 1:05 p.m. ET.
MX Sports Pro Racing
MX Sports Pro Racing manages and produces the world's most prestigious professional motocross series - the Lucas Oil Pro Motocross Championship, sanctioned by AMA Pro Racing. The industry leader in off road power sport event production and management, its mission is to showcase the sport of professional motocross competition at events throughout the United States. Through its various racing properties, partnerships and affiliates, MX Sports Pro Racing organizes events for thousands of action sports athletes each year and attracts millions of motorsports spectators. Visit
Alli Sports
Alli Sports is a media, event and branded content company that specializes in action, adventure, and adrenaline based sports. Alli Properties include the Dew Tour, Lucas Oil Pro Motocross Championship, the Red Bull Signature Series and World of Adventure Sports presented by Go Pro. Alli Sports is a division of the NBC Sports Group. More information can be found at
AMA Pro Racing
AMA Pro Racing is the premier professional motorcycle racing organization in North America, operating a full schedule of events and championships for a variety of motorcycle disciplines. Learn more about AMA Pro Racing at
Lucas Oil Products
Based in Corona, Calif., Lucas Oil Products, Inc is the world leader of High Performance Lubricants and Problem Solving Additives and produces and markets 272 unique formulations in thirty four countries around the globe and is growing country by country, market by market every year. Through innovative product research and development, along with progressive marketing programs, Lucas Oil Products has established itself as the top-selling additive line in the American truck-stop industry. Lucas Oil is involved in an array of motorsports sponsorships, including the "Official Motor Oil of the Lucas Oil Pro Motocross Championship." Visit:
MAVTV is a television network with its roots deep in the automotive world. With an unparalleled line-up of motorsports events and exclusive automotive reality shows, MAVTV is the answer for motor-heads from all walks of life. But MAVTV is much more than a motorsports destination, with original action/adventure programming, live MMA and an unbelievable library of blockbuster movies - MAVTV is a network the whole family can enjoy. A network by the people and for the people, made in America and American Real. Visit:
2014 AMA Motocross Gallery
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Chad Reed
Learn everything you need to know about MX / SX champ Chad Reed. Check out Motorcycle USA's Chad Reed bio page for career highlights, pictures, and news.
James Stewart
A front runner from day one, James "Bubba" Stewart is one of the fastest supercross racers around. Check out Motorcycle USA's James Stewart bio for career highlights, full biography, interviews, and news.
Ryan Villopoto
Get to know supercross and motocross champion Ryan Villopoto in his full bio at Motorcycle-USA.com. Get full career highlights, a complete Villopoto bio, pictures, and the latest news.
Ryan Dungey
While still wet behind the ears Ryan Dungey, has managed to accomplish what many riders spend years chasing. Get to know Dungey in his full bio at Motorcycle-USA.com with career highlights, racer biography, pictures, and the latest news.
Trey Canard
Get to know Trey Canard in his full biography at Motorcycle-USA.com. Full career highlights, a complete Trey Canard racer bio, pictures, and the latest news.
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DanaFitz DanaFollow DanaFitz
Female living in CA USA
Level 1 Traveler
1 tour
2 countries
Level 1 Traveler
1 tour
2 countries
Following 1 person
Followed by 1 person
Dana is now following Andrew
MikeFromCA posted on Dana's (DanaFitz) profile
Hey Dana, Welcome to the group! Nice to see another CA person on the trip. When are you flying out?
Posted over 2 years ago
over 2 years ago
Hey! I'm not flying out until Saturday morning from SFO. Fingers crossed that there isn't fog delaying flights
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Pakistan Foreign Secretary Salman Bashir is expected to travel to the U.S. over the weekend for talks with his Indian counterpart Nirupama Rao on the sidelines of the U.N. General Assembly session though a date for their meeting is yet to be finalised.
Mr. Bashir and other senior officials of the Foreign Office are expected to leave for New York during the weekend, official sources said. "The delegation could leave on Saturday," a source told PTI.
Foreign Minister Shah Mahmood Qureshi recently said that the two Foreign Secretaries are expected to meet ahead of a meeting of the Foreign Ministers of India and Pakistan on September 26.
Though Mr. Qureshi has said he is not expecting any "major breakthrough" in his talks with his Indian counterpart S.M. Krishna, Foreign Office spokesman Abdul Basit did not rule out the possibility of a positive outcome to the talks next week.
Pakistan will approach the talks with an "open mind", Mr. Basit said. "When we approach the talks with an open mind, there is the possibility of something positive coming out of the meeting," he added.
During their meeting in the Egyptian resort of Sharm El-Sheikh in July, the Prime Ministers of the two countries had decided that the Foreign Secretaries should meet "as often as necessary."
However, the two sides have been unable to schedule a meeting of the Foreign Secretaries due to Pakistan's stand that Foreign Secretary Nirupama Rao should visit Islamabad for the parleys. The Foreign Office has pointed out that Bashir visited New Delhi for the last round of talks and it was the turn of his counterpart to come to Islamabad for the next meeting.
Pakistan is also not keen on talks between the Foreign Secretaries being held in a third country on the sidelines of international events as the Foreign Office believes such meetings are difficult to schedule.
Keywords: Pakistan Foreign Minister, Shah Mahmood Qureshi, Salman Bashir, Nirupama Rao, Mumbai attacks, unconditional talks, composite dialogue, Lahore, Sharm el-Sheikh, Balochistan


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The U.S. Department of the Treasury and the Internal Revenue Service have published proposed rules establishing reporting requirements for employers and insurers under the Affordable Care Act ("ACA"), or Obamacare.
Under the ACA, employers with 50 or more full-time employees must offer health insurance or pay a penalty. The new proposed rules flesh out how employers must report information to the IRS with respect to their employees' enrollment in qualified health plans.
The rules cover a broad range of topics, including the information to be reported, the forms that must be used for returns, the time and manner of filing tax documents and penalties for failing to comply. In addition the rules provide that an employer must provide a statement to covered employees identifying the policy number and other coverage-related information.
The regulations are proposed to apply for calendar years beginning after December 31, 2014. Employers, however, would not be subject to penalties for failure to comply with requirements for the 2014 tax year.
In other words, employers would be given one year to voluntarily comply. An employer would not face penalties if it first reports in 2016 for the 2015 tax year.
The Department of the Treasury is accepting public comment on the proposed rules through November.
DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.
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