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Age-dependent molecular alterations in the autophagy pathway in HIVE patients and in a gp120 tg mouse model: reversal with beclin-1 gene transfer
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DOI: 10.1007/s13365-012-0145-7
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- Fields, J., Dumaop, W., Rockenstein, E. et al. J. Neurovirol. (2013) 19: 89. doi:10.1007/s13365-012-0145-7
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Aged (>50 years old) human immunodeficiency virus (HIV) patients are the fastest-growing segment of the HIV-infected population in the USA and despite antiretroviral therapy, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group. Autophagy is an intracellular clearance pathway for aggregated proteins and aged organelles; dysregulation of autophagy is implicated in the pathogenesis of Parkinson's disease, Alzheimer's disease, and HAND. Here, we hypothesized that dysregulated autophagy may contribute to aging-related neuropathology in HIV-infected individuals. To explore this possibility, we surveyed autophagy marker levels in postmortem brain samples from a cohort of well-characterized <50 years old (young) and >50 years old (aged) HIV+ and HIV encephalitis (HIVE) patients. Detailed clinical and neuropathological data showed the young and aged HIVE patients had higher viral load, increased neuroinflammation and elevated neurodegeneration; however, aged HIVE postmortem brain tissues showed the most severe neurodegenerative pathology. Interestingly, young HIVE patients displayed an increase in beclin-1, cathepsin-D and light chain (LC)3, but these autophagy markers were reduced in aged HIVE cases compared to age-matched HIV+ donors. Similar alterations in autophagy markers were observed in aged gp120 transgenic (tg) mice; beclin-1 and LC3 were decreased in aged gp120 tg mice while mTor levels were increased. Lentivirus-mediated beclin-1 gene transfer, that is known to activate autophagy pathways, increased beclin-1, LC3, and microtubule-associated protein 2 expression while reducing glial fibrillary acidic protein and Iba1 expression in aged gp120 tg mice. These data indicate differential alterations in the autophagy pathway in young versus aged HIVE patients and that autophagy reactivation may ameliorate the neurodegenerative phenotype in these patients.
KeywordsAging HIV Autophagy gp120 Beclin-1
Currently, over 30 million people live with human immunodeficiency virus (HIV) worldwide. In the USA, the aging population represents one of the fastest-growing groups with HIV (Scott et al. 2011). The Center for Disease Control (CDC) estimates that by the year 2015, half of all Americans living with HIV will be over the age of 50 (Smith 2005). In the central nervous system (CNS), microglial cells have been identified as a primary reservoir for HIV infection (Gendelman et al. 1997; Gonzalez-Scarano and Martin-Garcia 2005; Haas et al. 2000; Wiley et al. 1996) with productive infection also detected in astrocytes (Carroll-Anzinger and Al-Harthi 2006). Modern treatments with highly active antiretroviral therapy regimens result in HIV suppression and immune recovery, however the prevalence of HIV-associated neurocognitive disorders (HAND) and neurodegeneration (Budka et al. 1987; Cherner et al. 2007; Gendelman et al. 1997; Heaton et al. 2010, 2011; Wiley and Achim 1994) has remained the same or increased (Joska et al. 2010) in particular among people over the age of 50.
The mechanisms of neurodegeneration in aged individuals with HAND are not completely understood; however, HIV activates apoptotic pathways (Kaul et al. 2001), dysregulates calcium homeostasis (Lipton 1994; Nath et al. 2000, 2002) and promotes oxidative stress (Norman et al. 2008). Moreover, recent studies have shown that HIV proteins might interfere with clearance pathways such as autophagy (Alirezaei et al. 2008a, b; Zhou et al. 2011), a pathway necessary for protein quality control and elimination of defective older intracellular organelles (Cuervo 2004). Autophagy is a complex process that involves nucleation, initiation, elongation, and termination proteins. Initially, a phagophore forms and develops into the autophagosome, a double-membrane sac that delivers cytoplasmic material to the lysosomal compartment for degradation (Codogno et al. 2012). During the aging process, deficits in autophagy have been described in Alzheimer's disease (AD; Nixon et al. 2005; Pickford et al. 2008), Parkinson's disease (PD; Crews et al. 2010; Cuervo et al. 2004), and other aging-related disorders (Cuervo 2004). Specifically, the autophagy nucleation protein beclin-1 and closure protein light chain (LC)3 have been implicated in human disease (Crews et al. 2010; Gozuacik and Kimchi 2004; Jaeger and Wyss-Coray 2010). Similarly, neurodegeneration has been linked to defects in autophagy in patients with HIV (Alirezaei et al. 2008a, b; Zhou et al. 2011).
We have recently shown that in the CNS of young HIV human cases and in young transgenic (tg) mice expressing HIV-gp120 protein (gp120 tg; Toggas et al. 1994), abnormal functioning of the autophagy pathway (Zhou et al. 2011) is associated with progressive accumulation of amyloid-beta (Aβ; Achim et al. 2009), α-synuclein (α-syn; Ebrahimi-Fakhari et al. 2011; Everall et al. 2009; Khanlou et al. 2009), and tau (Patrick et al. 2011). In contrast, activation of autophagy by gene therapy recovers the deficits in autophagy observed in α-syn tg mice (Spencer et al. 2009). However, the mechanisms by which HIV proteins might interfere with autophagy during aging are unknown. Here, we postulate that dysfunctional autophagy activity may contribute to HAND progression in aged individuals. In this report, we extend our past studies by characterizing differences in viral load (VL), CNS immune activation and expression of autophagy-related proteins among <50 years old (young) and >50 years old (aged) HIV-infected individuals. Our results indicate that while autophagy was upregulated in the brains of young HIVE patients, it was downregulated in the brains of aged HIVE patients. Similarly, autophagy was downregulated in aged gp120 tg mice and activation with beclin-1 gene transfer ameliorated the neurodegenerative phenotype. These findings provide novel insight and potentially important targets to combat HAND in the aging population.
Study population
Summary of subject demographic and brain pathology information
Gender F/M
PMI (h)
Brain weight (g)
Brain pathology
Under 50 (young)
39.2 ± 6.04
14.0 ± 12.13
1317 ± 131.3
20 Normal, 1 Alzheimer type II gliosis, 6 microglial nodule encephalitis, 17 HIV encephalitis, 6 other
50 and older (aged)
55.2 ± 5.51
23.6 ± 24.49
1336 ± 176.5
13 Normal, 6 Alzheimer type II gliosis, 1 microglial nodule encephalitis, 8 HIV encephalitis, 5 other
Determination of HIV p24 levels in postmortem samples
HIV-1 p24 levels in postmortem tissues were determined using a commercially available p24 enzyme-linked immunosorbent assay (ELISA; NEK050001KT, PerkinElmer, Waltham, MA, USA). In brief, as previously described (Hashimoto et al. 2002), tissues from human brain samples (0.1 g) were homogenized in 0.7 mL of fractionation buffer containing phosphatase and protease inhibitor cocktails (Calbiochem, San Diego, CA, USA). Samples were precleared by centrifugation at 5,000×g for 5 min at room temperature. Homogenate was analyzed for protein quantity by BCA assay (Thermo Scientific) and then 100 μg of protein from each sample was assayed for p24 using the manufacturer's protocol.
Generation of gp120 tg mice
For studies of autophagy function, an animal model of HIV protein-mediated neurotoxicity, aged (12 months) tg mice expressing high levels of gp120 under the control of the glial fibrillary acidic protein (GFAP) promoter were used (Toggas et al. 1994). These mice develop neurodegeneration accompanied by astrogliosis, microgliosis, and memory deficits in the water maze test (Toggas et al. 1994). The mice were sacrificed within 1 week of behavioral testing and brains were removed for biochemical analyses of frozen or fixed brain tissues.
Construction of lentivirus vectors
The mouse beclin-1 cDNA (Open Biosystems) was PCR amplified and cloned into the third-generation self-inactivating lentivirus vector (Naldini et al. 1996a, b) with the CMV promoter driving expression producing the vector LV-beclin-1. Lentiviruses expressing beclin-1, luciferase or empty vector (as controls) was prepared by transient transfection in 293 T cells (Naldini et al. 1996a, b; Tiscornia et al. 2006; Spencer et al. 2009).
Mouse lines and intracerebral injections of lentiviral vectors
A cohort of aged (12 months) mice (n = 20), gp120 tg (n = 10), and control mice (n = 10) were injected with 3 μl of the lentiviral preparations (2.5 × 107 TU) into the temporal cortex (using a 5 μl Hamilton syringe). Briefly, as previously described (Marr et al. 2003), mice were placed under anesthesia on a Koft stereotaxic apparatus and coordinates (hippocampus: AP, 2.0 mm; lateral, 1.5 mm; depth, 1.3 mm and cortex: AP, 0.5 mm; lateral, 1.5 mm; depth, 1.0 mm) were determined as per the Franklin and Paxinos (1997) atlas. The lentiviral vectors were delivered using a Hamilton syringe connected to a hydraulic system to inject the solution at a rate of 1 μl every 2 min. To allow diffusion of the solution into the brain tissue, the needle was left for an additional 5 min after the completion of the injection. Mice received unilateral injections (right side) to allow comparisons against the contralateral side, with either LV-beclin-1 (n = 5) or LV-control (n = 5). Additional controls were performed by injecting non-tg littermates with either LV-beclin-1 (n = 5) or LV-control (n = 5). Mice survived for 3 months after the lentiviral injection. As an additional control for LV injection, age-matched littermates were injected with LV-luciferase.
Since no differences were observed between the LV-control and the LV-luciferase, all data presented in this paper are shown with the LV-control vector. Following National Institutes of Health (NIH) guidelines for the humane treatment of animals, mice were anesthetized with chloral hydrate and flush-perfused transcardially with 0.9 % saline. Brains and peripheral tissues were removed and divided in sagittal sections. The right hemibrain was post-fixed in phosphate-buffered 4 % PFA (pH 7.4) at 4 °C for 48 h for neuropathological analysis, while the left hemibrain was snap-frozen and stored at −70 °C for subsequent RNA and protein analysis.
For western blot and immunohistochemical analysis of the autophagy pathway, polyclonal antibodies against GFAP (MAB3402, dilution 1:500, Millipore), cathepsin-D (1:500, Calbiochem, San Diego, CA, USA), Iba-1 (1:1,000, Wako Corp., Japan), microtubule-associated protein (MAP) 2 (MAP378, 1:250, Millipore), LC3 (1:1,000, Abcam), mTor (1:1,000, Sigma), beclin-1 (1:1,000, Novus Biologicals, Littleton, CO, USA).
Immunoblot analysis
Frontal cortex tissues from human and mouse brains were homogenized and fractionated using a buffer that facilitates separation of the membrane and cytosolic fractions (1.0 mmol/L HEPES, 5.0 mmol/L benzamidine, 2.0 mmol/L 2-mercaptoethanol, 3.0 mmol/L EDTA, 0.5 mmol/L magnesium sulfate, 0.05 % sodium azide; final pH, 8.8). In brief, as previously described (Hashimoto et al. 2002), tissues from human and mouse brain samples (0.1 g) were homogenized in 0.7 mL of fractionation buffer containing phosphatase and protease inhibitor cocktails (Calbiochem, San Diego, CA, USA). Samples were precleared by centrifugation at 5,000×g for 5 min at room temperature. Supernatants were retained and placed into appropriate ultracentrifuge tubes and were centrifuged at 436,000×g for 1 h at 4 °C in a TL-100 rotor (Beckman Coulter, Brea, CA, USA). This supernatant was collected as representing the cytosolic fraction, and the pellets were resuspended in 0.2 mL of buffer and rehomogenized for the membrane fraction.
After determination of the protein content of all samples by BCA protein assay (Thermo Fisher Scientific, Rockford, IL, USA), homogenates were loaded (20 μg total protein/lane), separated on 4–12 % Bis-Tris gels and electrophoresed in 5 % HEPES running buffer, and blotted onto Immobilon-P 0.45 μm membrane using NuPage transfer buffer. The membranes were blocked in either 5 % nonfat milk/1 % BSA in phosphate-buffered saline (PBS) + 0.05 % Tween-20 (PBST) or in 5 % BSA in PBST for 1 h. Membranes were incubated overnight at 4 °C with primary antibodies. Following visualization, blots were stripped and probed with a mouse monoclonal antibody against Actin (1:2,000, mab1501, Millipore, Billerica, MA, USA) as a loading control. All blots were then washed in PBS, 0.05 % tween-20 and then incubated with secondary species-specific antibodies (American Qualex, 1:5,000 in BSA-PBST) and visualized with enhanced chemiluminescence reagent (Perkin-Elmer). Images were obtained and semiquantitative analysis was performed with the VersaDoc gel imaging system and Quantity One software (Bio-Rad).
immunohistochemistry, image analysis, and laser scanning confocal microscopy
Briefly, as previously described (Masliah et al. 2003), free-floating 40 μm thick vibratome sections were washed with Tris-buffered saline (TBS, pH 7.4), pretreated in 3 % H2O2, and blocked with 10 % serum (Vector Laboratories, Burlingame, CA, USA), 3 % bovine serum albumin (Sigma), and 0.2 % gelatin in TBS-Tween. For human brains, sections from the midfronal cortex were used; for the mice, sagittal sections from the complete brain were studied. Sections were incubated at 4 °C overnight with the primary antibodies. Sections were then incubated in secondary antibody (1:75, Vector), followed by Avidin d-horseradish peroxidase (HRP, ABC Elite, Vector) and reacted with diaminobenzidine (0.2 mg/ml) in 50 mM Tris (pH 7.4) with 0.001 % H2O2. Control experiments consisted of incubation with pre-immune rabbit serum. To investigate the effects of postmortem delay and fixation on the levels of mTor immunoreactivity, preliminary studies were performed in a subset of cases (n = 5) with postmortem delay ranging from 4 to 48 h. In addition, double immunolabeling studies were performed as previously described (Spencer et al. 2009) to determine the cellular localization of the autophagy markers. For this purpose, vibratome sections from the young and aged HIV+ and HIVE+ cases as well as of the non-tg and gp120 tg mice were immunostained with antibodies against the neuronal marker MAP2 (mouse monoclonal) and antibodies against either LC3, mTor, or Cathepsin-D (rabbit polyclonal). Sections were then reacted with secondary antibodies tagged with FITC to detect MAP2 and mTor and with the tyramide Red amplification system (Perkin-Elmer) to detect Cathepsin-D. Conversely for the experiments analyzing LC3, this autophagy marker was detected with FITC while MAP2 was detected with the tyramide Red amplification system (Perkin-Elmer). Sections were mounted on superfrost slides (Fisher) and coverslipped with media containing DAPI. Double-immunolabeled sections were imaged with the laser scanning confocal microscope as described below.
Immunostained sections were imaged with a digital Olympus microscope and assessment of levels of GFAP, Iba1, beclin-1, Cathepsin-D, and mTor immunoreactivity was performed utilizing the Image-Pro Plus program (Media Cybernetics, Silver Spring, MD, USA). For each case, a total of three sections (10 images per section) were analyzed in order to estimate the average number of immunolabeled cells per unit area (square millimeter) and the average intensity of the immunostaining (corrected optical density).
For confocal images (LC3 and MAP2), all sections were processed simultaneously under the same conditions and experiments were performed twice for reproducibility. Sections were imaged with a Zeiss 63× (N.A. 1.4) objective on an Axiovert 35 microscope (Zeiss, Germany) with an attached MRC1024 laser scanning confocal microscope system (BioRad, Hercules, CA, USA).
Analysis of neurodegeneration
Neuronal structural integrity was evaluated as previously described (Rockenstein et al. 2005a, b). In brief, blind-coded, 40 μm thick microtome sections from human and mouse brains fixed in 4 % paraformaldehyde were immunolabeled with mouse monoclonal antibodies against MAP2 (1:200). After overnight incubation, sections were incubated with fluorescein isothiocyanate-conjugated secondary antibodies (1:75; Vector Laboratories, Burlingame, CA, USA), transferred to SuperFrost slides (Fisher Scientific, Tustin, CA, USA), and mounted under glass coverslips with antifading medium (Vector Laboratories). All sections were processed under the same standardized conditions. The immunolabeled blind-coded sections were serially imaged with a laser scanning confocal microscope (MRC-1024; Bio-Rad) and analyzed with ImageJ v1.43 software (NIH, Bethesda, MD, USA), as previously described (Crews et al. 2010). For each mouse, a total of three sections were analyzed; for each section, four fields in the frontal cortex and hippocampus were examined. Results were expressed as percent area of the neuropil occupied by immunoreactive signal. All sections were processed under the same standardized conditions. Immunostained sections were imaged with a digital Olympus microscope and the Image-Pro Plus program (version 4.5.1, Media Cybernetics).
Statistical analysis
All the analyses were conducted on blind-coded samples. After the results were obtained, the code was broken and data were analyzed with the StatView program (SAS Institute, Inc., Cary, NC, USA). Comparisons among groups were performed with one-way ANOVA, unpaired Student's t test and Chi-square analysis. All results were expressed as mean ± SEM. The differences were considered to be significant if p values were <0.05.
Role of the funding source
The funding source had no role in the study design, data collection, data analysis, data interpretation or writing of this report. The corresponding author had full access to all the data and had final responsibility for the decision to submit the paper for publication.
Clinical and neuropathological characteristics of young and aged donors with and without HIVE
CD4+ cell count, plasma VL, presence of neuropsychological impairment, and CSF VL in the young and aged HIV+ cohort
Log plasma VL*
Log CSF VL
Under 50 (young)
70.2 ± 151.9 (n = 29)
4.53 ± 1.39 (n = 29)
3.14 ± 1.35 (n = 30)
9 HAD, 9 MCMD, 3 NPI, 10 NPI-O, 5 unable, 2 normal
50 and older (aged)
241.2 ± 325.4 (n = 25)
3.64 ± 1.70 (n = 23)
2.64 ± 1.25 (n = 21)
1 HAD, 2 MCMD, 3 NPI, 7 NPI-O, 2 NPI-U, 4 unable, 6 normal
HIV capsid protein, p24, levels are increased in aged and neuropsychological impaired patients
Neuroinflammation and neuropathology were increased in postmortem brains from aged HIVE patients
Autophagy markers are reduced in aged HIVE patients compared to young HIVE patients
Autophagy markers are reduced in aged gp120-tg mice; lentivirus delivery of beclin-1 restores autophagy marker expression
LV-mediated beclin-1 delivery reduces neuroinflammation and neurodegeneration in aged gp120 tg mice brains
In the current study, we show for the first time differential levels of autophagy proteins in postmortem brain tissue samples from aged HIVE and young HIVE patients. While the young HIVE group display increased autophagy markers, the aged HIVE group showed reduced autophagy pathway proteins. Viral protein and inflammatory marker levels were increased while autophagy proteins beclin-1, LC3 and the neuronal marker MAP2 were reduced in HIVE brain tissues from aged donors compared to those from young donors. Similarly, analysis of aged gp120 tg mouse brains showed reduced autophagy marker expression and increased neurodegeneration compared to aged non-tg mice. LV-beclin-1 gene transfer restored autophagy markers and reduced neuroinflammation and neurodegeneration in aged gp120 tg mouse brains. Previous studies have shown that HIV can alter the autophagy pathway, but these studies show possible reduced autophagy function in aged HIVE patients and increased inflammation markers accompanied with simplified neuronal synaptic complexity compared to young HIVE donors. Furthermore, LV-mediated beclin-1 gene transfer restores autophagy function and reduces neurodegeneration in aged gp120 tg mice. HIV infection in young patients may differ markedly to that in aged patients with respect to autophagy and neuronal injury; these data corroborate evidence that HIV infection may exacerbate consequences of normal aging and may provide a potential therapy for aged HAND patients.
The present studies are consistent with recent findings that suggest the autophagy pathway is dysregulated during AD, PD, and HIV (Ebrahimi-Fakhari et al. 2011; Pickford et al. 2008; Zhou et al. 2011); however, this is the first report of distinct differences in autophagy marker expression among young and aged HIVE patients. A survey of HIV patients showed overall autophagy markers are increased in postmortem samples from HIV-infected individuals (Zhou et al. 2011). By further categorizing patients according to age and HIVE status, the current studies revealed distinct differences in aged and young HIVE brains. These differences in autophagy function among young and aged HIVE patients may contribute to the growing list of chronic comorbidities among aged HIV patients. The differences observed in brains from deceased young versus aged HIVE patients suggest that two distinct types of infection may be responsible for the differences observed between young and aged HIVE patients: (1) viremia is robust and infiltrates the CNS leading to early neural complications and death (young) or (2) viremia is subdued throughout infection, the CNS is not dramatically affected early on, yet long-term infection gradually increases neuroinflammation and neurodegeneration (aged). HIV patients that live over 50 years may harbor a low but chronic viral burden that can limit normal autophagy function and lead to proteinopathies such as seen in AD and PD. Another alternative is that HIV infection progresses similarly in most patients but some patients escape the battery of opportunistic infections to live a longer life. The compensatory autophagy response seen in young patients may be meant to clear excessive toxic molecule build up until the system is overwhelmed and the molecular recycling system fails. Reduced autophagy marker levels detected in aged HIVE samples may represent less viable cells with reduced capacity to perform normal physiological processes, such as autophagy. Consistent with this notion, Aβ expression correlates with age in postmortem samples from HIVE patients, and in the second scenario this may be a natural occurrence of most chronic HIV infections (Achim et al. 2009; Khanlou et al. 2009). In either case, understanding how HIV affects neuronal autophagy may lead to therapies that slow down neurodegeneration. Importantly, neither of these scenarios considers those individuals who contract HIV infection after turning 50, for which alternative patterns of disease have been reported (Erlandson et al. 2012). Additional studies using samples from large cohorts of HIV patients combined with animal models and cellular-based studies will prove valuable in dissecting the complications of aging with neuroAIDS.
Beclin-1 and LC3 are essential proteins in the autophagy pathway, and interference at either level may result in cellular toxicity (Kragh et al. 2012). Beclin-1 mediates autophagosome nucleation and LC3 is an integral autophagy protein that facilitates autophagosome elongation and closure and may also be involved in disease (Dinkins et al. 2010; Gannage et al. 2010; Kyei et al. 2009). Despite increased autophagy machinery, HIV patients have increased Aβ and α-synuclein accumulation in the brain (Achim et al. 2009; Khanlou et al. 2009). These and other reports suggest that dysfunctional autophagy is associated with neurodegenerative diseases and may exacerbate problems associated with HIV infection of the CNS. In this context, it may be possible to reintroduce functional autophagy by gene transfer to ameliorate HIVE phenotypes.
It was recently reported that HIV-1 infection inhibits autophagy pathways in monocytes, but no direct effect on neurons has been shown (Van Grol et al. 2010). Kyei et al. showed that the HIV-1 protein Nef interacts with autophagy pathways in macrophages (Kyei et al. 2009). In subsequent findings, groups have shown that HIV-1 may highjack the autophagy pathway to promote replication (Gregoire et al. 2011; Killian 2012). Despite these advances, it is not known if HIV directly or indirectly affects neuronal autophagy and ultimately contributes to neurodegeneration. Our current studies show aged HIVE patients express increased neuroinflammatory markers and reduced neuronal markers, indicating progressed neurodegeneration, and loss of synaptic processes may be associated with decreased autophagy-related proteins (beclin-1 and LC3). The gp120 tg mouse serves as a model for HIV-1-protein mediated neurotoxicity and the mice present neuropathology and behavioral deficits similar to those seen in HAND patients (Toggas et al. 1994). Furthermore, in the α-syn tg mouse model for PD, LV-mediated delivery of beclin-1 to the CNS reversed neuropathology and reduced the accumulation of α-syn (Spencer et al. 2009). The current studies further support the hypothesis that proteinopathies may be due to dysfunctional autophagy and that normal molecular recycling may be restored via LV-mediated beclin-1 gene transfer. Indeed, LV-beclin-1 ameliorated astrogliosis, microgliosis, and neurodegeneration in the gp120 tg mouse model and may serve as a therapy for aged HAND patients.
Impetus has been placed on understanding how aging may exacerbate HAND. Healthy individuals >65 are designated elderly by the Centers for Disease Control, but HIV infected individuals are designated "aged" HIV patients at >50, due to progressed signs of aging. It is predicted that by 2015, over 50 % of AIDS cases in the USA, and 15 % of newly diagnosed cases will be >50 (Erlandson et al. 2012; Watkins and Treisman 2012). Reports have demonstrated that aged HIV patients have increased risk of severe depression and cognitive impairment, less time between infection and AIDS diagnosis and reduced T-lymphocyte proliferation (Watkins and Treisman 2012). Further studies are needed to characterize and combat HIV in this particularly vulnerable group. Our data support the hypothesis that HIV exacerbates the effects of aging and implicate dysregulated autophagy as a possible cause of HAND.
Studies on mechanisms of HIV pathogenesis in aged patients are lacking; aging with HIV is a relatively novel problem. Most studies consider neuroAIDS with respect to the HIV-infected population as a whole, yet physicians and the CDC note stark differences in the progression of disease between young and aged groups (Erlandson et al. 2012; Watkins and Treisman 2012). In an effort to understand differences in HIV pathogenesis between young and aged patients, we surveyed 83 HIV patients, 33 of which were >50 years old. Among the young and aged groups, 40 % of each group was classified as normal brain pathology; however, 18 % of the aged group presented with Alzheimer type II gliosis in contrast to only one patient from the young group. Also noteworthy, 34 % of the young group had encephalitis versus 24 % of the aged group. High VL and encephalitis may have contributed to the premature demise of young patients, whereas persistent low-level infection, as seen in aged patients, may contribute to the Alzheimer-like pathology. In contrast to past reports, the current studies indicate that CD4+ cell count was higher in aged brains, and CNS plasma viral burden is reduced in aged HIV patients; yet, p24 and inflammatory markers are increased compared to their younger counterparts. Chronic inflammation may promote long-term deleterious changes in gene expression in aged HIV infected individuals, which may explain how aged HIV patients suffer increased morbidity despite higher CD4+ cell counts. Cohort size and population dynamics all contribute to data variability.
The proportion of HIV-1-infected individuals over the age of 50 is rapidly increasing, yet therapies to prevent or treat HAND remain scant (Erlandson et al. 2012; Watkins and Treisman 2012). Furthermore, the HIV-infected population is not alone as the average age of the general population is increasing along with the prevalence of age-associated neurodegenerative diseases. These studies implicate autophagy as a novel target for preventing and treating HAND, AD, PD, and possibly other neurodegenerative disorders. Importantly, this report suggests that young and aged HIV patients may require unique drug regimens to combat progression in these two distinct stages of disease.
We thank the National Institutes of Aging (AG043384) and the National Institutes of Mental Health for (MH062962, MH5974 and MH83506) funding this work.
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~ The Story ~
I'm not sure. Yet. Check the guidance and comments for updates.....SORRY!!!
My alarm woke me up at 6:02am and I got up right away and looked out my window. My dad pulled out of the driveway and drove off to work. My mom was with him, so she must be going to work early. I walked downstairs. Good, I thought. The house to myself. I'll be able to blow dry my hair without waking anybody up. I sat down at my computer and logged on. Right away my two best friends popped up.
Welcome Zoey_coolkid154948309. You have 2 messages.
Tori: Yay! You're on! Ugh! I was waiting for you for like, 10 minutes Zoey!!!
James: I thought you might be on :) Hey Zo.
I rolled my eyes. Of course these two were on. Tori is constantly on, and James always seems like he knows right when I'm going to be on and logs on the instant I do. I sighed. I'd better respond to Tori first. Before she wonders where I am because I didn't respond within 2 seconds.
Zoey: Hey Tori!
Tori: Hey girl!
Zoey: What's up?
Tori: Not much. But I can see James is on ;)
Zoey: *sighs dramatically* Uh-huh....
Tori: LOL Kay, I'll leave you for a bit.
Zoey: <3 Thanks!!
I closed the chat box and clicked on James' name.
James: I'm assuming Tori is on? :)
Zoey: Yeah, but she signed off for a bit, haha. Said she was gonna leave for a bit.
James: So....how are you?
Zoey: Pretty good. You?
James: Fine. OMG Can you believe the new piece for band?!? Mr. D is pushing us to the limit!
Zoey: I know! He expects the flutes to hit all these notes that are like, 2 octaves higher than what we normally play!
James: Aw, you can do it though. He expects the most out of the french horns though! We're hitting all these notes in 6/8 time and he's whining that our notes are a bit pitchy!!!
Zoey: Hey, I'll talk to you later, okay? I should get ready for school.
James: At 6:15am?!?
Zoey: I'm a girl :)
James: Ugh. Makeup, outfit, hair. I'm so glad I'm not a girl. I just have to find a shirt without a stain on it, shower, and eat something. :) So much easier.
Zoey: Lucky you <3 Alrightee...I gtg!!! Byee!
James: Byee! See you at school...
I signed off and went back upstairs. Turning the shower on, I started singing at the top of my lungs. After all, no one was home to hear me. A defiant meow came from behind me. I turned around to find my ridiculously stubborn calico cat, S'mores, glaring at me from a loveable kitten face. I reached down and scratched her behind the ears. "Hullo baby girl...." I crooned. She meowed at me again. "Oh, well, excuse me, I forgot that there was still someone to be woken up, S'moresie...." She purred and stalked away. I snorted. You'd think she owned the place. I got in the shower, and as soon as I did, the phone rang. AUGH!!! I got back out and wrapped a towel around me. I ran into my adjoining bedroom and picked up the phone. "Hello?" I asked impatiently.
"Zoey?" Tori's voice asked on the other end of the phone.
"No, she got in the shower." I replied.
"Zoey, please stop with the jokes. I know you lied to us. To me and James."
My blood ran cold. Crap.
"Why wouldn't you tell us about you going to that special arts school? Why would you lie to us about going with us?" Her voice was thick with tears.
"I-I....Who told you?" I asked.
"I found your acceptance letter in your binder. You know, the one you gave to me to borrow?" She was sobbing now. "Do you have any idea what this does to me? What it does to James?"
"Tori, James will be fine. He has his girlfriend. We'll talk durning the summer or something." My voice shook as I said it. I had kept this from both of them. This was something major that I should've told them months ago.
"I can't believe you wouldn't tell me!" She was yelling now.
"Tori--" I started.
"No, Zoey, shut up. Don't talk to me, because I don't know if I can trust you anymore." She hung up, and I was left alone, my shocked silence broken only by the busy signal.

subset: commoncrawl


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Why not review Sumvision cyclone HD2 1080p Divx & ISO HDMI USB/SD Media Player and Recorder with built in DVBT tuner which has a built-in freeview recorder?
@james1000: Jees, you're obsessed! USB 3.0 is far from ubiquitous so it's fair to assume that any device that we don't explicitly mention has USb 3.0, doesn't.
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Pedroia returns to lineup as Sox look to extend winning streak to six
Pedroia returns to lineup as Sox look to extend winning streak to six
After leaving Thursday night's game in the fifth inning and missing Friday night's game, Dustin Pedroia is back in the Red Sox lineup Saturday as they look to extend their winning streak to six in a 4:05 game against the Seattle Mariners.
Pedroia felt pain his left knee Thursday night and was taken out of the game by manager John Farrell as a precaution. The rainy conditions and wet field were also factors in keeping the second baseman out Thursday and Friday.
Pedroia (.288, two homers, 21 RBI) had surgery on the knee in October. It's the same leg that was hurt when Manny Machado slid into Pedroia at second base in April, the slide that sparked various confrontations between the Orioles and Red Sox.
Left-hander Brian Johnson (1-0, 7.20 ERA) was called up from Triple-A Pawtucket to make his second start of the season for Boston and right-handed reliever Ben Taylor was optioned to the PawSox. Right-hander Rob Whalen, 23, comes up from Triple-A Tacoma to make his first start of the season for the Mariners.
The lineups:
Jean Segura SS
Danny Valencia 1B
Robinson Canó 2B
Nelson Cruz DH
Kyle Seager 3B
Taylor Motter LF
Guillermo Heredia RF
Mike Zunino C
Jarrod Dyson CF
Rob Whalen RHP
Mookie Betts RF
Dustin Pedroia 2B
Xander Bogaerts SS
Andrew Benintendi LF
Hanley Ramirez DH
Mitch Moreland 1B
Jackie Bradley Jr. CF
Sandy Leon C
Deven Marrero 3B
Brian Johnson LHP


text:
|430 sq. ft.
|Property type
|Minimum Stay
|2 - 7 nights
In the heart of the small village of Saint-Pargoire, in the Herault valley, surrounded by a countryside made of garrigue, pine trees and vineyards, this very nice apartment offers a complete open view to the surrounding landscape from its terrace that overlooks the 10x5 m swimming pool (The heating system guarantees 27 degrees from May to September). South-west oriented, it is fully furnished and equipped. Bbq in the garden. Very quiet area.
All facilities in the village (2 Bakeries, 2 Groceries, Newsdealer, Pharmacy, Butcher, Doctors...). Supermarkets and all kinds of shops in Pezenas and Clermont l'Hérault (15 km both).
Good restaurants and wine cellars everywhere in the region. Seafood restaurants in Sète, Mèze, Bouzigues and Balaruc. Numerous local markets in the villages and many interesting sites to visit around: Montpellier, Pézénas, Béziers, Sète, Saint-Guilhem-le-Désert, Salagou lake, Clamouse caves, and the cirques de Mourèze and Navacelles...
Swimming Pool: The 5x10 m private pool with additional 1.5 m roman stairs (Depth from 1 m to 1.8 m) is heated at 27 degrees with a Heat pump pool heater. We use Salt water Electrolyser which gives a cleaner and softer water and eliminates inconveniences, such as eyes irritation, dry skin, unpleasant taste…
Shops in the village: All facilities (2 Bakeries, 2 Groceries, 1 Newsdealer, 1 Pharmacy, 1 Butcher, 1 Bar, 1 Pizzeria, 1 Restaurant, 1 Caterer...) are located at 200 m from the apartment.
June & September: Dear All, I would like to inform / remind you that June & September Months (even May actually) are quite pleasant in South of France. The weather is warm and the nights cooler than in July & August. There are less tourists, as kids are at school. The swimming pool will be at 27 degrees ! Therefore, do not hesitate to take your holidays off-season.
To reply to the most frequently asked questions. There is no additional cost for whatsoever related to the apartment rental (Parking, water, electricity, cleaning at the end of the stay, access to the pool,… are included.). There is only one apartment for rent (Upper level with the terrace on the pictures). The apartment is adjacent to my parents' house, and except both of them, there will be no more people/families at the address during your stay.
Can only echo all the other excellent reviews of this property. Not only are Marie-Claude and Gabriel great hosts, they are also great company, we really loved getting to know them. Also, Patrick was the epitome of efficiency and helpfulness during the booking process, promptly answering any question we threw at him!
St Pargoire itself is a delightful village, a fair selection of shops and a weekly market just a 2 minute walk away. Both Boulangeries are superb, with a wide selection of fresh breads, pastries, cakes etc and friendly service. We couldn't choose between them, so alternated between them! The staff in both of the small grocery stores are also very helpful and friendly and between them offer a wide range of good quality merchandise.
We have no hesitation in recommending this property to other travellers.
Just back from a wonderful stay in Saint Pargoire with my husband and nineteen month old son. Marie Claude and Gabriel are excellent hosts, wonderful hospitality, and really made us feel so welcome. We had the wonderful pool all to ourselves and the location is ideal. Our little boy is asking to go back to the pool everyday. Highly recommend this property, and check out the local restaurant Lou Regalou. We will definitely be back.
An excellent location for a quiet break away from it all. The apartment is comfortable and well equipped and the pool is very well maintained. The owners were very helpful and welcoming. The village facilities are close at hand and the restaurant is definitely worth a visit. I'm sure we will return.
Was it as lovely as last time? Yes Where the owners as friendly and helpful? Yes Did we enjoy it as much? Yes.
What can I say that I did not say last time? The pool house. This is fitted out with a table and chairs, a ceiling fan and lights. A perfect place to catch some lunchtime shade if you can not tear yourself away from the pool. The poolside furniture. There are tables and chairs. Trolleys for your drinks. There are reclining chairs, sun beds and reclining sun beds and all fitted out with comfortable cushions. The quantity, quality and diversity of the poolside furniture would put many a so called "luxury" villa to shame.
This place is a must for pool and sun lovers.
Will we be coming back? Try and stop us!
Edward and Lynne. England
We, my husband and 10 year old son have just returned from a wonderful stay in St Pargoire. The apartment is exactly like the description and photos, really clean with a superb pool and has everything you need plus it's in a great location in the village, walking distance from the shop, restaurant, bar, post office and weekly market. The reservation process was very smooth and any questions answered promptly. We were welcomed by the owners who were lovely and immediately made us feel at home and yet left us to relax and enjoy our holiday. The terrace is great for breakfast and evening meals and has a great view of the countryside.... Saint Pargoire is in a great location for the sites of caves, lakes, rivers for canoeing, Abbeys, wine tasting, art and pretty villages so much to see and with the beach at Meze only 20 minutes away..with all the delicious sea food (the oysters are a must) one week is not enough. We will be back and would recommend this "gem" for all who would like to relax in village life knowing that the sites and cities of Beziers and Montpellier are not far with stunning scenery en route...
In 32 years of renting properties from large villas to flats, this was the nicest cleanest pool in all that time. Worth it for the pool alone. The small private balconey was ideal for breakfast and evening meals alike. The view over the open fields was lovely, and one morning we watched 5 Kestrels (probably a family) working these fields and flying to within 20 feet of us The apartment contained just about everything you could require and was ample for a couple. To also have all the village amenities within a short walk (and I do mean short) was a bonus. Add to that the warm welcome we recieved and that fact that despite being left to enjoy the peace and quiet we knew there was help at hand if we needed it, it made a perfect holiday.
Marks out of 10 - 10
Perfect for - all the above.
Would we return - you bet
Regrets - We only had a week there.
Edward and Lynne - Kent - England
Very close are the cities of Montpelier, Pézénas, Béziers, Sète, Saint-Guilhem-le-Désert, Salagou lake, Clamouse caves, and the cirques de Mourèze and Navacelles ... One hour drive away are the Haut Languedoc natural park with its lakes and forests, the famous Millau bridge, la Couvertoirade, a small secluded village built by the Templar knights. Numerous festivals all summer long in the region.
Access : A75 motorway at 5 km, Paulhan exit.
Airport and TGV high speed train at 40 km in Montpellier.
|Rental Period
|Minimum Price
|Additional Nights
|Weekend Night
|Event Price
Rate 3
1 Oct 2016 - 26 May 2017
2 night minimum stay
for 2 nights
Rate 2
27 May 2017 - 23 Jun 2017
Changeover Day: Saturday
7 night minimum stay
for 7 nights
Rate 1
24 Jun 2017 - 1 Sep 2017
7 night minimum stay
for 7 nights
Rate 2
2 Sep 2017 - 29 Sep 2017
7 night minimum stay
for 7 nights
Rate 3
30 Sep 2017 - 25 May 2018
Changeover Day: Saturday
2 night minimum stay
for 2 nights
|No additional mandatory fees
50% down payment required at the time of booking, 50% balance to be paid 3 months before stay.
Save 100 Euros if you rent 2 weeks in June & September. Pay 700 instead of 800. And the water of the swimming pool will still be at 27 degrees !


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Chapter 4
They were at a dead run now, Lando panting to keep up with Chewie and Luke. Leia? Luke called as he felt a massive disturbance in the Force. There was a moment of silence. Then a quiet answer. I'm finished. He... He's gone Luke. Luke didn't know what to do. He couldn't bring himself to laugh. Leia would hate him if he wept. Luke didn't even try to check if his father lived through the force. He knew if he attempted he would not be able to stop the tears.
Someday perhaps his sister would understand what he had lost. Someday her bitterness would die, and take her lack of remorse with it. He only hoped that one day she would morn him. They screeched to a halt at the doors of his father's personal shuttle bay. He ran his ID card through quickly.
"Leia, where are you?" He muttered. The door's gaudy light flashed red. "Entrance denied." Chirped the unfeeling monotone. Luke went pale. He had though that, like every other door on the ship, the bay would open with a clearance as high as his. But if it opened only to his father... Luke began to panic, pacing.
"Will blaster bolts overload the door controls?" Lando asked, trying to help. Luke shook his head. "That only works on the cheap stuff, this is high grade. We can't even get in! And where's Leia? What else could possibly go wrong?" Visions of being executed for killing the Dark Lord filled his head. Palpatine turning out himself to make surely it was fittingly full of agony. Shoved into space without suits to freeze or asphyxiate, whichever came first. Stop it. He ordered his frantic mind. This won't help you.
Leia rounded the corner, in extreme disarray and heaving a blaster over each shoulder. She tossed one to Chewie. "I ran into a squad of troopers." She said by way of explanation. "There were about twelve of them, I fired from behind cover and barley made it." She smirked. "They look worse than I do, though."
She looked over his shoulder at the door. "Having trouble?" She asked, voice mild but face intent with worry. "The controls won't give us clearance. We're having lots of trouble." She scrutinized it carefully. "I can handle it." Get them out of here, I'll have to use my saber pretty precisely, I can't risk telling you what to do on a thing this complex and explanations to Chewie for that one would take too long. She thought.
"Chewie, Lando, run up and scout for troopers coming our way." They nodded curtly and walked cautiously, guns at the ready, out of the alcove. Leia took her light saber out of her carrying pack, gingerly slicing off the covering, exposing a maze of wire. She studied it carefully.
"I think I can keep it from killing us as we go through If I trip this. But with the computers dead, I don't know how we'll budge it open." "Leave that to me." Luke said calmly. She nodded. She trusted Luke. If he said he could do something, then she respected his judgment. Taking her blaster, she fired through the wires and cut the safeties. Pulling off another panel, she cut the backup flows.
"Thank the maker we planned for this and studied systems." She muttered just to break the tense, worried silence. With a final violent buzz and snap of energy, the door lost power. Leia tucked her saber back in her bag before Lando and Chewie, returning at an ominously fast pace from their watch, saw it and asked questions about its origin.
"We don't have much time, there's two squads approaching from the bridge, and they've spotted us. They're on their way." Without pretence, Luke smoothly cut around the doors edges and pushed it in. A shot rang close, and the group hurried to the lone ship. With a show of telekinesis Luke heaved the slab back into place.
Throwing herself through the door, Leia sat in the navigator's chair. Luke seated himself as the pilot and started punching at the controls. A look of horror swept his face. "Leia, Leia, nothing is working!" Chewie growled darkly upon hearing the dire words. "What?" She screeched. "That's impossible, it's supposed to be ready to fly at all times! He executes the staff if it isn't! I checked it! I checked everything!"
"Whether he does or not, I still can't get power!" They swung their chairs to face each other. "You don't think he-" "Survived? That's impossible! But-" They swung back to the controls, Leia trying aimlessly to find the malfunction, Luke testing the Force. Lando and Chewie looked on in bemusement. Luke and Leia had always worked well together, but now it was like they were different sides of the same person. They never had to ask what to do next, or what the other thought. It was an unnerving, implacable similarity.
"Someone go check the drive, the thrusters, someone do something! Anything!" Leia shouted. She'd never felt like this. Hysterical, lost, and above all afraid. In a sadistic way it reminded her of the death emotions. Almost as if they were connected. Chewie and Lando pushed and scrambled to get out of her way.
Leia looked up. "It's no normal malfunction, but there's defiantly something wrong in the ion drive. I've never heard of anything remotely like this before. Have you?" He shook his head, raised his eyes, and took a deep breath.
"Leia, you must know why that is, there's no other explanation." "No." She whimpered. "Please tell me that's not what you found! Luke, tell me!" He didn't speak, just looked at her face, which she turned sideways so her features could not be seen, his steely blue eyes unreadable. "He's alive." He finally spoke. She turned, slowly, farther away from his emotionless, accusing eyes. She hung her head.
"We lost. I failed." No one spoke, she didn't seem to care. "I can't believe this, I won't believe any of it." She was frightening now, her control having gone the way of their ion drive. "It isn't true. And nothing was ever true." "Truth," Luke said quietly, "Is only some twisted soul's point of view." Leia looked up at him, saddened by his loss of faith.
"You believe that? You used to be so idealistic, you always believed in people! I've never realized how young you were, how very young we all are. We are children, fighting this war, killing other children. Forgive us." She whispered to the air. He stood, and she grabbed his hand. "I'm not going out there." She said through gritted teeth. "He can not be right. He hasn't come, he's forcing us to crawl back to his darkness. I will not." "Leia, we have to come out some time-" "It doesn't have to be now!" He sighed. "What will this accomplish?" "We'll have a small victory, everything counts. He'll be forced to come in here and fetch us. Luke, I know you. You have pride, and you want to give in?"
She was determined. She was always determined. And if his father had a mind to execute them for their insolence, he would at least humor her one last time before she died.
It had been four hours. The storm troopers stranding outside the door with him were fidgeting. One started to sit down in the middle of the corridor, but a cutting glance from his lordship sent him back to his feet with a jaunty salute. Watching this through the opened door, Lando and Chewie chuckled. The sergeant of the small force fumed as the Rebel alien and human made unseemly rude gestures at him form the ship's protection, almost willing to risk his superiors wrath to respond in kind.
An hour later found the four run always seated in the control room, tense and not speaking. Lando, wanting to meet his fate and be done with it, crept towards the door. "Don't even think about it!" Leia shrieked and the leather chair creaked ever so slightly at his movement. Chastised, Lando moved away from the door. "Leia, maybe we should just-" Luke began. "No one is going anywhere! Except the Sith, and he'll be breaking very soon indeed." Chewie growled something mutinous, but his life debut, which included the great Princess along with his fondness for her kept him from fulfilling that promise.
Outside the officers still stood, now milling around bored. Vader was not patient. He never had been. But this was a battle of sorts, and no matter the battleground, he did not loose. He had lost once, and the price still left a tangible durasteel weight to bear. He would not make that mistake again.
It was morning. Chewie had long since abandoned his post to sleep at Luke's insistence, but Leia's red-rimmed eyes struggled to retain alertness. Finally Luke snapped. "This is ridiculous!" Storm troopers awoke from their standing sleep, intrigued by the loud argument. Vader smiled. So much for sibling tolerance. "How long are you going to have us sit here and delay the inevitable? I've had it, I'm going out there, and if I were you I'd keep my further dark side symbolisms to my self!"
"DON'T YOU DARE GO OUT THERE!" She screeched." "Watch me!" He stomped through the shuttle, ignored the door, slammed through the durasteel wall beside it with a hand motion and an angry thought, and, marching up to his father, yelled "I've had it! You're the parent, DEAL with this!"
"Certainly." The Dark Lord answered with irritating calm. "LEIA!" He bellowed, vocal tuners at their loudest. Troopers started to rub their helmets, ears pained by this rude interruption from their tired haze. "What? You wish to gloat, no doubt." Snapped Leia, flanked by an extremely nervous Calrissian, mumbling apologies, and a chortling wookie who could appreciate irony on the worst of situations.
"Of course not." Vader supplied, as if his dignity had been offended. "Have a pleasant flight, little one?" Her face turned fuchsia. she had failed and he dared to throw it in her face. She shook with rage, and he observed her. She glowed, literally emanating a light haze of power from her body.
Luke looked ashamed. He was a poor student, he could not be light nor dark, was forever pursuing emotion and the wills of others when he should be acting on the Force. He was furious with no one, save himself, the stupid, gawky, unwanted young man. And there is no hatred like self-hatred. The enmity of a galaxy cannot compare to the utter loathing of despising oneself. He missed the motion swirling in the corner of his eye. Leia had swung with all her tiny might at her tormentor, actually forcing the distracted Dark Lord back a pace.
She was proud of herself for the fleeting moment before her unconsciousness, as the thought of how futile that had been crept in with the blackness of unconsciousness. Luke dived under his sister as she fell, cushioning her descent. Her hand was an unpleasant sight; reopened scar from previous torture, charred burns of a scabbed, mangled tissue and exposed bone. That was the natural reaction, even for Jedi, to punching multiple inch durasteel with bare hands. The troopers were plainly in shock.
"Take the two prisoners back to their cells, select double shifts of guards, and find someone to fix this damn door!" He shouted them into action, hefting Leia into his arms. "Come." He snapped to Luke, and the younger man walked twice his normal speed to follow his father.
Inside the Medical Bay, Officer Dran gazed at the Princess' folly in horror. "What in all- and she- she did this how?" He sputtered.
"Let me elaborate. There is a new fissure in my durasteel mask." Luke gave a low whistle.
"She cracked the thing? I never knew she packed such a punch." Luke paused. "Then again, I've seldom seen anyone that angry." Leia made a small noise, and they rushed to the cot. Her eyes opened on her brother.
"What happened?" She looked curious about the change of scenery and her oddly bent limb, but little more in her delirium.
"You hurt your arm." The drowsy girl frowned.
"Obviously, my darling astute brother. To him, I mean?"
"Ummm, not all that much. I think I can see a little crack in the mask though..." He added perkily to bolster her falling face.
"Oh good." She murmured happily, dreamily. "Now I can-" And she was asleep again.
"She held off exhaustion to ask you that?" Vader questioned, bewildered.
"Apparently," Luke countered defensively as he smoothed a light blanket over her, "It was important."
She was swirling, falling short distances over and over, not in short jolts but in unending pattern. The only concrete thing was the feeling in her sword arm. Something was wrong.
It was very late when he stirred. The devoted Officer Dran fetched everything for her, fretting over his daughter. It wasn't easy to miss his admiration of her, Dran's, as Amidala would have termed it, innocent affection. Infatuation, more like it. Had she had this affect on Rebel crew? No wonder they were so fiercely loyal under interrogation. They placed all hope in her, their living goddess who fiercely believed they could win this war.
Standing and taking a step towards the door, her hand shot out and firmly clutched his arm. She writhed uncomfortably in sleep. "Stay." She begged, fear of unknown shadows taking over her rational mind, and perhaps his. He sat back down, fully aware that she was delusional and still asleep. That didn't matter; she needed him, pleaded with him to help her. A smile flitted across sleeping lips, and her pale hand drew cryptic circles on the black leather of his palm. "Thank you Daddy." She murmured to the apparition in her head and the touch at once. That sealed his fate. He stayed all through the night at the side of a girl recovering from trying to kill him. Irony, Amidala was fond of saying, is everywhere.
When she recovered all words were brief. He almost longed for her to sleep, for her unconscious released her essentially kind nature. He just happened not to be on the receiving end of it. The girl he had met that night gave him hope that one day he could speak to his daughter with her eyes firmly open in all ways.
Luke had been as eager to please as Dran. Seldom did a twenty year old bring breakfast in bed to his sister instead of his love. That had begun to worry Vader. Luke had been popular with the females of Rebellion. Leia taunted to her shamefaced sibling frequently, recalling several lovely young techs and pilots sobbing over Luke's gentle 'We just aren't cut out for each other.'
"Luke was always heart breaker. Every woman wanted to date the conquering hero, and he had a talent for picking the shallow ones that lasted, say, five minutes. He finally figured out he wasn't the meaningless fling type, but it took him long enough."
Do not break people as if they don't exist, Luke, he thought fiercely, it would always end in them breaking something precious to you in return. Believe me, I've learned. What he took from this was that Luke wasn't likely to have any long-term relationship interrupted by his abduction. If there been, of course, he would have fetched the girl. A prospective bride to be could certainly be treated to this lavish and empowered captivity. He respected Luke's wishes, though he couldn't bring himself to extend that to Solo, The lack of such a girl wasn't normal. Vader was interested in beginning the production of Skywalkers as soon as possible, so Luke's lack of ties was beneficial. It meant no capturing a certain soldier he had his heart set on, and he could form an alliance in court.
He'd enjoy seeing the twins settled, in love, as happy as he had been, even, he supposed, if she insisted on dragging home that damn smuggler. But whereas Leia had erected a Corellian blockade to be overcome, he was sure, with a suitable partner, Luke would be less difficult. Vader knew several young women who would gladly be introduced.
"Sir, we've made conduct with Priority One Orbital Docking Facility. Bay 6 is clear for our arrival. The Lieutenant's voice emerged from the corner of the room, his face obscured by a large headset used for communication through the heavy broadcast interference that shielded the planet. The Emperor's palace had a system engineered to utilize the clearest path available, but the rest of the military had not been so lucky.
"Excellent." Leia crossed her legs, hiding her nervousness. She occupied a chair that the pit crew had placed for her, long hair captured in a single braid. Silently she informed her family that they had arrived. Cutting off this communiqué, she spoke to Piett. "I presume they won't divert more than a few shuttles for a hours?" He sighed.
"They never do, it's priority based. Don't worry your highness, you'll get a speedy transport." "I realized that. I'm sorry to delay your shore leave, actually. After such a long run, I understand your eagerness to be home." He blushed slightly at her bridging an unmilitary topic. "Yes, your highness."
"Do you have any family, Admiral?" She asked, in an offhand way but appearing concerned with his answer. "I am married, my lady. I have two children, daughters. One six, the second three." She smiled at him. "You must be proud. Having a brother, I'm of the opinion that daughters are far superior." He was taken aback. Here he was having a casual conversation with the Princess of the Empire.
"Being a son, I'm not sure I agree." She laughed quietly. She had a lovely laugh, high and reminiscent of the bells his rural church had once been so proud of. That was before a rebel raiding group, desperate for food, had chosen the sleepy town and it's defensible stone sanctuary as their headquarters and burned the Imperial loyalist priest for his objections. How he would have loved for his daughters and wife to see the Amirta he was raised in, but he was ashamed of the fire burned rubble, riddled with bullet holes that it now was.
Leia heard this. The admiral was no longer a faceless enemy, over her short spans of commanding this bridge she had been shown he was a good man, hadn't joined the Empire for meaningless reasons at all. Everyone has a story, she thought, giving him a mournful sigh. "I'm sorry for your loss, Admiral." She murmured so that no one overheard.
Of course she knew, Piett fought shock. The Princess was, after all, not quite human. Many on the ship were of the opinion that her family were mythical creatures, returned from the graves of the past to wield power. "It's nothing, my Lady." He shut his eyes. "Everything," she corrected, "Is something. Every man is something. I hope you build a new Amirta in this life, Piett. Your children deserve to see it."
With that she turned back, and announced that all personnel were free to travel with the extent of at least a month's leisure, and not to return until receiving further orders under the heading of new code Blue Rendezvous. Yes, he thought distractedly, now totally loyal to the woman in front of him even if hell itself dared to touch her, no one can take from me the memories I hold.
Luke shoved his things inside the leather satchel while Jemmis was admiring the collection of exotic parts on the dresser. "In a month you managed to amass more rare junk on this thing than I have on mine in a year. Good work!" He broke into tears. "My widdle Imperial heir, I'm so proud!"
"My eyes will not bestow the benefit of a role." He pronounced formally, flicking his hand at the offender. "What do you think? That sounded emperor worthy to you, right?" He hated Palpatine, of course, but that didn't require him making an idiot of himself in front of court. And his father…
He hadn't believed Leia had been allowed to dock the Executor. He'd gladly relinquished the opportunity after manning the nightshifts in space, but this was more complicated. If she returned to the self destructive frenzy that reigned when her goal slipped away, Lelian Vader would rid the world of her enemies, and her self, and take the whole vessel with her. Luke knew better, she wouldn't endanger the lives of innocents except in utmost desperation, or spend so much time that went unobserved and unreported to her father gaining the trust and learning the expertise of the crew.
He extended his hand to Jemmis. "Will I see you again?" He asked softly. Jemmis grinned. Unless you intend on never setting foot off the planet. I've been promoted. You have the privilege of gazing on the personal pilot of the esteemed Prince Lucian. I know, I know, you're honored." Jemmis bowed mockingly. "Your father asked, and I jumped at it. I mean, now this is prestige! Plus, he liked that we're already friends, though he mentioned you could fly whenever you wished." "It's only prestigious if ye live, Jemmis." Luke corrected. "The Emperor may dislike my hair or something and 'puftg!'" "'Puftg?'" "Yes, Jem. That would be the sound of a Prince going splat." "Too good for regular splat, are we? I'm not worried. Your parlor tricks are nothing compared to the things you do with a saber, and the tricks were amazing. What would he do with Vader? You think a father remains loyal when his legacy dies? Guess again. I think I'll be about for a while Luke." Skywalker shook his head at his friend. "Believe me, I hope you're right."
"All personnel, this is your commanding officer. We are soon to loose our tow ship crew and be inserted into the Maglocks. Please brace if necessary, and enjoy your leave." Leia's calm voice cut through normal operation like butter. Determined to do this by the book to be completely right, Leia had performed by the book. What she had hated to factor was their surprise over a female voice. As long as no one was curious enough to annoy the bridge crew into talking, they should remain fine.
"I can't stress enough," she advised, flicking off the intercom with an elegant hand, "How important to me your secrecy is. To All of us. To your Empire." She hated using that word, but loyal high officers and technicians nodded solemnly, convinced that they had single handedly saved the world by tightly sealing their lips. "Thank you, oh how I would hate to be disappointed by such fine soldiers." Appealing to their pride, fear and chivalry all at once, she was masterful in the art of command, subtle and layered.
As the shuttle scraped against the landing pad of Vader's intimidating home, Luke was thankful for his father's slight squeeze on his shoulder. It brought the paranoid son to Earth. Quite simply, they were Skywalkers. If his father sent that all would be right then it would be. Perhaps this, if only for a while, was a home to be proud to return to. It wasn't how he'd expected to go to Coruscant, it wasn't what a farm boy, pilot or Jedi had glimpsed in his life. But as the razor reflection of a metal building caught and held Leia's slight smile, he knew that it couldn't be all that bad.


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Meant to Be
(HannaKingdom and I ONLY! :])
What would you give for love? Your life? What if you've already paid that price, even before you made the wish. Before you even wanted that life to end?
But what if you changed for the better? Would you be happy then? Probably not without love. But when you find it, hold onto it, because you can only feel it once...
Jay and Asha Hale, the newish wedded couple have left Vampire Mansion, and are living in their own home. Their child has born, and their lives are
It was perfect. We were perfect. Perfectly happy; content with our lives. We were in love. And we still are; we always will be!
Asha and I were meant to be together, and we always loved each other, even though we didn't even know who we were falling for...until the Mansion
We didn't really meet, but glimpsed each other. I know I instantly fell in love, and I hope Asha did too.
But we've left the Mansion, having nothing to do there. And we have new lives together...


text:
The Office of First-Year Experience and Student Retention is working to create a culture where every UVU employee recognizes that he/she has an important role in retaining students and helping them to succeed. Our goal is to increase awareness of and commitment to this role. In support of this goal, the Student Advocate Award is given annually to one faculty member and one staff member who have demonstrated outstanding commitment to student success.
Outstanding Staff Advocate:
Rebecca Disrud
For the past five years, Rebecca has focused on creating and expanding Writing Center programs to support all writers at UVU, including the Graduate Writing Center to support the work of emerging researchers in UVU's graduate programs and GRE preparation workshops. She mentors her undergraduate peer tutors with an eye toward their academic and professional development, helping them design projects that both mesh with their career goals and expand Writing Center resources for other UVU students. Rebecca has also supervised numerous student research projects and secured funding for students to present their work at national and international conferences. Rebecca strongly believes in supporting long-term student success through writing development and strives to make the Writing Center a place where all writers come to succeed.
Congratulations to Marinda and Rebecca. Thank you for your continuing commitment to student success!


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Louis Vuitton Damier Ebene Passport Case Pre Owned
Product Details
Authenticity code: Louis Vuitton CA3078
Authentic: Pre-Owned
This authentic Louis Vuitton Damier Ebene Passport Case is Beautiful! This passport holder in Damier canvas features various compartments to hold business cards and papers.
- Exterior: Excellent
- Interior: Excellent
- Description of Interior: Leather Lined
- Interior Pockets: Six open interior pockets
- Color: Brown
- Hardware Description: Silver Hardware
- Material: Canvas
- Width: 3.7 in.
- Height: 5.3 in.
Product Code: 2305010
Read more about Louis Vuitton Date Code here.
All photos are of actual item being sold. This Louis Vuitton® item is guaranteed to be authentic. Louis Vuitton is a registered trademark of Louis Vuitton. LuxeDH is not affiliated with or represents Louis Vuitton in any way or form.


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London has the best 4G coverage in the UK but also the slowest download speeds, according to a new report.
Mobile users in the capital can access the most powerful wireless networks almost 70% of the time, reveals consumer Watchdog Which?
This is streaks ahead of the rest of the country, with people in Wales only able to connect to 4G 35% of the time. The next best after London is Yorkshire and Humberside on 61.3%.
However, it's not all good news for Londoners, as the city's population density means download speeds are considerably worse than everywhere else in the UK.
Northern Ireland has the highest 4G download speed with 23.3Mbps, found the report, produced n conjunction with mobile coverage company OpenSignal.The capital's residents have to make do with an average 4G speed of 18.8Mbps while their Welsh counterparts enjoy 21.7Mbps.
In terms of 4G providers, EE was top for availability and download speeds. All said they were investing in their mobile networks though.
Alex Neill, Which? managing director of home and legal, said: "It's clear mobile providers must do much more to improve their networks if they are to provide greater access to their customers."
Regulator Ofcom is currently compiling a coverage map by asking the UK's 20 million Android users to download an app that automatically measures signal strength and download speeds.Reuse content


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Dawns secretsMature
"Dawn?" Gabriel asked recognizing Dawn's voice instantly shock and fury tinted his voice, "put me down."
"No" Dawn's voice almost purred in his ear.
"Now Dawn" Gabriel could smell the unmistakeable smell of Jack Daniels, he twisted in Dawn's vice like grip. "What is your problem?" the little vampyre shouted, his voice echoed through the trees
"My problem?" Dawn sounded slightly amused, "I'm drunk you're sexy. Why what's your problem"
"Right now, my problem is you" Gabriel snarled, he kicked back and swore as he realized that Dawn like him had boots that ended just below his knees, the leather protecting his skin. "Put me down" Gabriel tried one last time.
"Why?" Dawn asked, Gabriel used his only option, he slammed his head back into Dawn's face, the back of his skull met Dawn's mouth. The daemons dropped him and he scurried to a safe distance away turning to look at Dawn, Dawn didn't look like he was in pain but there was a steady flow of blood running down his chin, he touched his lip gently looking at the red stain on his fingers. Gabriel waited ready for him to do something. But the daemon looked up his eyes met Gabriel's then he twisted round, spitting a mouthful of blood onto the ground behind him, then he straightened up again.
"I suppose I deserved that" he said nodding slightly, he looked at Gabriel again. A slight smile touched his mouth and then he vanished leaving Gabriel alone.
Gabriel stormed into the house. He slammed his bedroom door shut. He rested his back on the door as he breathed to calm down. Then he stripped off and climbed in the shower the hot water scorching his skin. He made sure he got Dawn's blood out of the back of his hair before climbing out again. He shivered as he wrapped the towel around his thin waist. Then stepping out into his bedroom, he pulled off the towel got into the tracksuit bottoms that he slept in and still furious climbed into bed it was hours before he fell asleep.
The next morning he woke up he had a banging headache, he climbed out of bed rubbing his head, as he went to the wardrobe he saw a piece of paper that had been slipped under his door. Picking it up he put it on the bed, it was a letter. He recognized a few of the letters but the rest were a jumble to him, and he growled.
He pulled the red shirt back on and un-tucked his hair. Then grabbed a pair of black cotton combat style trousers and tugged those on too. Then grabbing the letter he went to find Daryll.
The small vampyre read the note out to Gabriel;
Dear Gabriel,
I cannot apologize enough for what I have done. I do not expect you to forgive this. i have decided to go back to the underworld and leave you in a bit of peace. It seems I was wrong about you, you don't need my help and I shall not give it where it's not wanted. Thank you for being in my life again, if only for a short while. I will miss you a great deal.
Daryll looked at him,
"What does he mean 'again'?" Gabriel frowned
"No idea" he left the letter with Daryll as he ran down the hall to the front door "thanks" he called back, Daryll grinned to himself and looked at the letter again.


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Pro Stock Report From the NHRA Lucas Oil Nationals
In Pro Stock Motorcycle action at the NHRA Lucas Oil Nationals, Hector Arana Jr. defended his Chicago win from last season with a 6.918 at 194.66 on his Lucas Oil Buell, defeating two-time world champ Matt Smith (6.957 at 190.24) in the final. The win was Aranas 10th career victory, first of the season and second at Route 66 Raceway. He defeated LE Tonglet, Jerry Savoie, and Chaz Kennedy before taking Smith out in the final. Arana sits second in points.
This is one of my favorite tracks, Arana Jr. said. We had the bike and I knew we had the bike all weekend, but we couldnt get it to leave the line well, and we finally figured it out for the last session. We made a change, and we felt good about it, so we didnt change anything for the first round, and from then on out we didnt touch it. We just went consistently down the track.
Number one qualifier at the Lucas Oil Nationals was Chip Ellis on the Piranaz Buell Pro Stock Motorcycle entry.
Smith, piloting the new Victory Motorcycles Gunner entry, was looking to win his first race since the 2013 fall event in Las Vegas. He advanced to the final round after defeating then events number one qualifier, Chip Ellis on the Piranaz Buell. In the final, despite getting the Gunner to a head start on the starting line against Aranas Buell, Smith was unable to claim the win when Arana powered by him on the top end. Despite the loss, it was a positive points day for Smith, who moves into the top 10 in the PSM standings at No. 8 with four Pro Stock Motorcycle events remaining before the Countdown to the Championship.
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|[issues] New comment: (FOR-18) support mulitple languages
|Thu, 01 Jan 1970 00:00:00 GMT
The following comment has been added to this issue: Author: Juan Jose Pablos Created: Tue, 16 Sep 2003 6:38 PM Body: OK, I got a first version: Allows menu labels to be displayed in another language out of a catalog. Currently there is two languages Spanish [es] and Italian [it] It works but forrest needs are a bit further. It has been added to CVS for a demostration: add project.i18n=true to forrest.properties run: forrest seed forrest run --------------------------------------------------------------------- View the issue: http://issues.cocoondev.org/jira//secure/ViewIssue.jspa?key=FOR-18 Here is an overview of the issue: --------------------------------------------------------------------- Key: FOR-18 Summary: support mulitple languages Type: New Feature Status: Assigned Priority: Critical Project: Forrest Component: None Assignee: Juan Jose Pablos Reporter: Ralf Hauser Created: Sat, 11 Jan 2003 2:27 AM Updated: Tue, 16 Sep 2003 6:35 PM Description: In my current environment to develop static mulitlingual web-sites, I use an ant build.xml and the m4 macro preprocessor to achieve the following (sample): 1) index.en.m4 gets converted to index.en.html The *.en.m4 contains all language dependent text (similarly *.de.m4 for German) and includes index.m4 that contains the page's content layout. [(^\.)+].m4 includes sitedef.m4 where I define all global parts of the website (e.g. navigation structure, unique content e.g. phone numbers, filenames, etc.). This in turn includes a sitedefs.en or sitedef.de, ... respectively for global, language dependent definitions. 2) Dependencies a) upon change of [(^\.)+].m4, all depending *.*LANG*.html get rebuilt b) upon change of sitedef.m4, build.xml, and alike all *.html gets rebuilt c) upon change of sitedefs.en all *.en.html get rebuilt. Obviously, I could use the exact same approach to create .xml whereever I created .html before, but my long-term goal is to get rid of m4. Has anybody already put some thought into how this would be done with forrest? --------------------------------------------------------------------- JIRA INFORMATION: This message is automatically generated by JIRA. If you think it was sent incorrectly contact one of the administrators: http://issues.cocoondev.org/jira//Administrators.jspa If you want more information on JIRA, or have a bug to report see: http://www.atlassian.com/software/jira
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Ever notice when you're out at a club, you miraculously know how to sing like a pro after your fourth drink? That principle can apply to painting, as well! Explore your creativity during this painting class where you'll create your own masterpiece with the expert guidance of a professional artist. Sip on a beverage of your choosing while enjoying a relaxed, pressure-free atmosphere to create your work of art. Whether you want to practice your brush strokes, or take a break from your monotonous nighttime schedule of bars, bars, and more bars, this class is a great way to unwind and spend a memorable night with friends!
Note: All supplies are provided, including a 16x20 canvas you can take home. Food and drink are not included, but are available for purchase at the venue before, during and after class.
Painting Evening in Japantown Restaurant
What to expect
- Unleash your creativity during this painting workshop where you'll be taken step by step through artistic discovery
- Enjoy the drink of your choice in a relaxed, pressure-free atmosphere, while creating your own masterpiece
- Learn valuable techniques to reveal your artistic genius
About this Activity
Key Highlights
|$35.00 per guest
|Duration / Session
|3 hours
|# Sessions
About the Teacher
Bret is an internationally represented artist. Educated at UCLA, he has exhibited in Paris, San Francisco, and Los Angeles. He is passionate about sharing his creative knowledge with others. A life time teacher of the arts, he has taught groups of all ages art & music in the Bay Area for over 10 years.
Cancellation Policy
Cancellation notice must be provided at least 48 hours in advance in order to receive a full refund. Notice provided up to 24 hours before the event have the option of rescheduling to a future date.


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All reader reviews by Simon
Soho Japan
Great Great Great! nice food, great customer service. Very reasonably priced(lunchtimes)
Thursday, February 02, 2006
Overall rating
Food 9 | Service 10 | Atmosphere 9 | Value for money 10
Very Expensive and not great. Bigest problem is they try to offer all types of food but don't do any of it very well. If you order from a place that charges £2.80 for Steamed Rice then you'll accept anything!
Thursday, February 02, 2006
Overall rating
Food 2 | Service 3 | Atmosphere 0 | Value for money 1
Elena's L'Etoile
I'll keep this short and (not so) sweet. 1. Friendly service (if you are with the right people).
2. Unfriendly if you are in a group of people under the age of 30.
4.Bland food.
Lots of better places to go.
Thursday, January 12, 2006
Overall rating
Food 4 | Service 5 | Atmosphere 6 | Value for money 0


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Remember what we said about 3D displays being well on their way to becoming the next mainstream display of choice for the average consumer? Well it seems that 3D technology's slow but gradual invasion into consumer-grade electronic devices has just been given a huge boost recently, especially if Hitachi's announcement of its success in the creation of a 4.5-inch display that is reportedly capable of high-definition resolutions is of any indication.
With all the signs pointing towards what seems to be a slow but steady push by various OEMs and manufacturers to make 3D displays the new mainstream in digital entertainment, it should be of little surprise that what was once considered a "novel" technology is starting to make inroads into the consumer electronic devices which we make use of on an everyday basis. And apparently, it seems that Hitachi is all set to "Inspire the Next", at least where 3D technology is concerned, and the latest announcement of its new 3D display is probably the best proof of that.
According to Hitachi, the new 3D display makes use of a certain "liquid crystal lens system", which is also known as the lenticular lens approach, to produce its 3D effects. This is different from the technology used by Hitachi's older 3D mobile display, which utilizes the "parallax barrier method". Hitachi claims that the new approach is capable of bringing about improved display quality..
In addition, Hitachi has also claimed that its new 4.5-inch, glasses-free 3D display will be capable of displaying digital content at a high-definition resolution of 1280 x 720, and that it will also boast a brightness of 400cd/m2 in 2D mode, and up to 470cd/m2 when set to 3D mode, as show in the specifications list below.
Hitachi has not announced any major plans for its new display, although the company has claimed that it expects to see the display being used in a variety of mobile devices such as mobile phones, portable television sets and handheld gaming consoles.
Source: Hitachi Japan via TechCrunch


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Amcor jobs under threat
Amcor will close its Fairfield paper mill in Melbourne's north-east, which employs about 90 people.
The packaging products giant is shifting operations to Botany in New South Wales in 2010.
Amcor says it will try to relocate the 90 workers.
Amcor's Managing Director, Greg Beatty says some workers will be offered positions in other parts of the company.
But he admits others may lose their jobs.
Amcor says the new site will be more environmentally friendly than the Fairfield plant.
The Forestry Union's Victorian president, Alex Miller says the Fairfield workers were told of the planned closure at a meeting this morning.
"Disappointment, but in some cases resignation. They've understood that for some time that there was a threat hanging over the mill. I think it will take a few days for the shock to set in", he said.
The closure won't take affect for another three years.
Topics: company-news, business-economics-and-finance, fairfield-3078


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#241 "Red Dawn"
From a stranger in an unknown location
A wolf pictured in his natural environment is always a breathtaking sight, but something about this particular illustration seems to deliver discomfort as opposed to tranquility. I don't mean to say that this illustration is unattractive or is not artfully rendered. I believe just the opposite is true. Only an illustration that is drawn with great skill could induce an intense emotional reaction, whether it be negative or positive. But what is it that delivers to me feelings of discomfort? Let's examine the physical environment first. While the landscape in the picture is beautiful, it is also barren and harsh. The craggy surfaces of a rocky mountain face rise up in opposition to the earth below and block out the final rays of the autumnal sun. A few sparse trees dot the landscape, offering little comfort or shade to a weary traveler seeking shelter. The river, the source of life, seems to be not only flowing but running away, fleeing from this land without promise. And then there is the wolf itself. The creature is majestic and dignified, but there's something in the eyes that sends a message of pain and vexation, something in the ragged fur that speaks of hardship.
However, even though this picture suggests thoughts of adversity and austerity, there is also a memory of one of my favorite films that I have somehow tied to this illustration and that I just can't seem to shake. The movie is called "Red Dawn," and like the illustration above, the movie paints a picture of the hardships and trials that are faced when living in an unforgivable natural environment. But at the same time, the movie (like this picture again) delivers themes of perseverance, determination and the magnificent power of a strong will to survive. The obvious disconnect between the two is that there are no Russians taking over the United States in this stranger's picture, but overall, I still thought the movie was applicable enough to warrant the connection. If you haven't seen the movie, send it to the top of your Netflix queue today; it's a true classic. Before you view, check out the trailer below.


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Well, if you are among the elderly that have an iPhone, and you have a collection of old tapes that you were reluctant to get rid of for some reason, and the tapes are still playable, you can now convert them directly to your iPhone or iPod.
The Tape Dock by Ion is one way to convert your audio cassette content directly to digital tracks on your iPhone. The Tape Dock is similar to Ion's Tape 2 Go product, but with the Tape Dock, you connect your iPhone or iPod directly to the unit. The Tape Dock works with the company's EZ Vinyl/Tape Converter software and will work with either Windows or OS X.
However, if you are nostalgic to hear that gentle, subtle tape-hiss during playback of your favorite big-hair rock band from the 1980s, this is your ticket.
source: B&H Photo via CNET


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Sales & Marketing Executive Job - International
Job Title: Sous Chef
Region: International
Salary: £Competitive HOURLY - Hotel - South Wales
Sous Chef Job Description
Relief Chefs De Partie / Banqueting Chefs – Vale of Glamorgan
The Package
Competitive hourly pay
Holiday pay
Travelling expenses (where applicable)
Enhanced fees for certain days
Company pension scheme
The Company
Catering Services International has been established for over 25 years and boasts ex industry consultants, who regularly work shifts alongside you. We have a tonnes of work in and around the south Wales areas and we pride ourselves on being an agency that truly cares.
The Role
We are currently recruiting Chefs from CDP level up to head chef to work shifts within an hotels for the Christmas period. These vacancies are also ongoing well into the new year so this is the perfect time to secure work when January is usually quiet.
We have lots of work – much of it full time and ongoing in a large hotel near Cowbridge and should you really like the role we can place you there permanently.
Your own transport is highly desirable due to the location of the work. We pay generous rates per hour, time and a half on Sundays and travel costs where applicable. UNACPPED EARNINGS.
What We Are Looking For
Successful Chefs will preferably possess / be able to demonstrate the following:
Previous experience in high quality, rosette or volume catering to at least a Chef de Partie level.
A current food hygiene qualification.
Ability to maintain the highest standards at all times and a keen eye for detail.
Organised and hands-on to ensure optimal service to customers and staff.
Great team player and motivator with the passion for creativity.
Your own transport and a good attitude are highly advantageous due to the nature of the work
Excellent working references / recommendations from previous employers.
What Next ?
If you would like to know more or you would like to apply for this opportunity pick up the phone and call 02920 394777 or simply e-mail your CV to firstname.lastname@example.com
Apply for this Sous Chef Vacancy (International)
Enter your details below to apply for this job. We will also match you to any other existing vacancies we hold in our database.


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The North Face Girls' Reversible Down Moondoggy Jacket - $89.88
Keep her warm, comfortable and looking her best, even in winter's worst. The 100% nylon body has a durable water-repellent finish for wet-weather comfort. The jacket's interior is filled with 550-fill-down insulation for toasty, heat-trapping warmth. Zip-in and snap-in compatible. Welt handwarmer pockets. Elastic cuffs, hood and hem. Jacket reverses to plaid body. Imported.Sizes: XS-XL.Colors: Fusion Pink, Gravity Purple, Kokomo Green. - $89.88


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Added on 01-Jul-2005
The Darkness Follow Up Hyde Park With Queen+Paul Rodgers With Release Of Their Queen Influenced New AlbumNME.com reports that The Darkness's vocalist Justin Hawkins and his brother, guitarist Dan Hawkins will be performing this Friday, July 8, 2005 on a joint collabortion of 2 songs with Queen+Paul Rodgers at the Hyde Park, London concert that is perhaps the most greatly anticipated, and largest capacity crowd, gig of the Internationally acclaimed sellout Queen+Paul Rodgers tour.Following up the gig, the Hawkins brothers and their band The Darkness, will be releasing their new album and single. The album is The Darkness's sophomore effort on the heels of their debut album, ''Permission To Land''. The album has the added Queen influence and touch in that renowned Queen Producer, Roy Thomas Baker, lended his talents on this album, which also was recorded in the same studio that Queen also recorded their legendary ''Bohemian Rhapsody'' in. As an extra tip of the hat to Queen, Justin Hawkins had the immense pleasure, and honor..of playing one of Freddie Mercury's pianos on the record. The Darkness have regularly cited Queen as one of their primary artistic, musical inspirations and influences.The new as yet untitled album from The Darkness has an expected tentative release date of October 17, 2005, with the single set to drop tentatively on October 3, 2005.Justin Hawkins has his own solo single , ''This Town Ain't Big Enough For The Both Of Us'', a cover of the classic Sparks tune, due out on August 8.Sources:http://www.nme.com/news/112876.htmhttp://www.nme.com/news/111739.htm
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text: Can it get any worse for Jonathan Ross? Suspended from the BBC for three months, sales of his biography have tanked and now a further humiliation. Madame Tussauds has put Ross's waxwork into storage because of the Sachsgate row - even though it cost in the region of £150,000 to make.


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You missed it This great deal for J. Design Studios is over. But don't despair, we've got more great deals every day.
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J. Design Studios
On-Location Photo Shoot for Two or More with Access to an Online Gallery of Digital Images
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Choose a special location in the Springfield area, and whether it's a family portrait or otherwise, an expert photographer will make the most of your time to capture as many stunning photos of candid, intimate moments as possible:
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