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Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke
Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.
Here, we demonstrate that minocycline attenuates both
The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.
Cerebral ischemia triggers a cascade of pathophysiological events including excitotoxicity, ionic imbalance, oxidative and nitrosative stresses and apoptotic-like cell death mechanisms
Cell death associated with the initial blood flow interruption and the immediately ensuing excitotoxity is abrupt, while inflammation occurs over a long period of time from stroke onset. Accordingly, anti-inflammatory treatment is likely to extend the therapeutic window allowing improved intervention in stroke. Indeed, minocycline, a common tetracycline antibiotic, has been demonstrated to provide neuroprotection against ischemic brain via the inhibition of the inflammatory cascade
In this study, we examined direct protective effects of minocycline on neurons and astrocytes, and also determined minocycline's toxicity profile in both
Minocycline improves cell viability of neurons, but not astrocytes
Based on ATP activities (MTT assay), minocycline, at low doses, maintained cell viability of primary cultured neurons exposed to OGD (0.001 μM: 85.9 ± 13.1%, 0.01 μM: 94.4 ± 7.2%, 0.1 μM: 90.4 ± 13.0%, 1 μM: 88.2 ± 13.8%; values hereon are expressed relative to non-OGD exposed group) compared to vehicle treated group (0 μM: 67.1 ± 10.3%), but was toxic at high dose (100 μM: 55.1 ± 8.4%) (F7,32 = 14.775, p < 0.0001) (Figure
Figure 1
ATP activity and trypan blue assay in cultured neurons and astrocytes
ATP activity and trypan blue assay in cultured neurons and astrocytes. ATP activity was measured to reveal cell viability with varying concentrations of minocycline or vehicle. OGD condition reduced ATP activity of cultured neurons to 40% of non-OGD control group (A). Low doses of minocycline (0.001 to 10 μM) preserved cell viability of neurons (A), but not astrocytes (B). In contrast, high dose of minocycline (100 μM) displayed toxicity to both neurons and astrocytes (A, B). In parallel with ATP assay, Trypan blue assay revealed that low doses of minocycline (0.001-10 μM) exerted neuroprotective effects on cultured neurons, but not astrocytes (C-G: neurons, H-L: astrocytes, C, H: non-OGD control, D, I: 0 μM, E, J: 1 μM, F, K: 100 μM of minocycline). High dose of minocycline (100 μM) displayed toxicity for both neurons and astrocytes. Data are shown as mean values ± SEM (*p < 0.05 increase and **p < 0.05 decrease vs. vehicle-treated cultured neurons or astrocytes; A, G: neurons, B, L: astrocytes). Scale bar: 25 μm.
Minocycline alters OGD-induced apoptotic cell death
The cell death of neurons and astrocytes under OGD condition represents apoptotic-like cell damage as revealed by caspase 3/7 assay (neurons: 29927.5 ± 6365.4/well; astrocytes: 17758.5 ± 5.78.9 well) (Figure
Figure 2
Caspase3/7 activity and tunel staining in cultured neurons and astrocytes
Caspase3/7 activity and tunel staining in cultured neurons and astrocytes. Low dose minocycline (1 μM) reduced caspase3/7 activity of neurons (A), but not of astrocytes (B). In contrast, high dose minocycline (100 μM) displayed no suppressive effects on caspase 3/7 activity of neurons and increased that of astrocytes (A, B). Similarly, low dose minocycline reduced, whereas high dose minocycline increased the number of TUNEL positive neurons compared to vehicle-treated cultured neurons (OGD-exposed neurons treated with 0, 1 and 100 μM of minocycline; panels C, D and E, respectively). On the other hand, minocycline at all doses did not reduce the number of TUNEL positive astrocytes (OGD-exposed astrocytes treated with 0, 1 and 100 μM of minocycline; panels F, G and H, respectively). Data are shown as mean values ± SEM (*p < 0.05. A, I: neurons, B, J: astrocytes). Scale bar: 50 μm.
Under OGD condition, increased Bcl-2 expression was induced by low dose minocycline in cultured neurons (0 μM: 1.25 ± 0.48, 1 μM: 18.9 ± 2.16 cells/0.05 mm2), but not at a high dose (100 μM: 2.21 ± 1.10 cells/0.05 mm2) (F2,12 = 15.288; p = 0.004) (Figure
Figure 3
Bcl-2 expression and cytochrome c release in cultured neurons and astrocytes
Bcl-2 expression and cytochrome c release in cultured neurons and astrocytes. Western blotting revealed that low dose minocycline upregulated Bcl-2 expression of neurons (A: lysates from 0, 1 and 100 μM of minocycline-treated neurons correspond to lanes 1, 2, and 3, respectively) with subsequent inhibition cytochrome c release from mitochondria to cytosol (B: lysates from 0, 1 and 100 μM of minocycline-treated neurons correspond to lanes 7, 8, and 9, respectively). In contrast, minocycline at all doses did not upregulate Bcl-2 expression in astrocytes (A: lysates from 0, 1 and 100 μM of minocycline-treated astrocytes correspond to lanes 4, 5, and 6, respectively). Immunocytochemical analysis revealed that minocycline low dose (D: 1 μM) significantly increased the number of Bcl-2 positive neurons compared to vehicle-treated (C: 0 μM) or high dose-treated neurons (E: 100 μM). In contrast, minocycline at all doses did not alter the number of Bcl-2 positive astrocytes (F: 0 μM, G: 1 μM and H: 100 μM). Quantitative analyses of Bcl-2 positive cells are shown in panels I and J. Data represent mean values ± SEM (* p < 0.05. I: neurons, J: astrocytes). Scale bar: 25 μm.
Minocycline ameliorates stroke-induced behavioral deficits
At three days post-stroke, the typical motor and neurological dysfunctions produced by MCAo were significantly blocked by minocycline when intravenously administrated at a low dose (20 mg/kg) starting at 60 minutes after reperfusion, as revealed by EBST (0 mg/kg: 88 ± 12.5%, 20 mg/kg: 68.3 ± 15%) (F2,27 = 10.439; p = 0.0004) (Figure
Figure 4
Motor and neurological performance of stroke rats
Motor and neurological performance of stroke rats. Both motor and neurological dysfunctions were significantly ameliorated by low dose minocycline (20 mg/kg, i.v.), as revealed by elevated body swing test (EBST; A) and Bederson test (B). In contrast, high dose minocycline (100 mg/kg, i.v.) significantly exacerbated neurological deficits and slightly worsened motor deficits. Data are shown as the mean values ± SEM (*p < 0.05).
Minocycline reduces cerebral infarcts
Following behavioral testing at three days post-stroke, TTC staining revealed that the infarct volume was significantly reduced by low dose minocycline (80.1 ± 41.7 mm3) relative to vehicle-treated stroke group (138.5 ± 48.8 mm3) (F2,27 = 9.552; p = 0.0007) (Figure
Figure 5
Cerebral infarct analysis of stroke brains
Cerebral infarct analysis of stroke brains. TTC staining revealed that low dose minocycline (20 mg/kg; B) significantly reduced cerebral infarct volumes compared to the vehicle group (A). In particular, the striatal infarct volumes in the low dose group were significantly smaller than the vehicle group. In contrast, high dose minocycline (100 mg/kg; C) significantly increased the infarct volumes compared to those in the vehicle group. Quantitative analyses are shown in panel D. Data represent mean values ± SEM (*p < 0.05).
Minocycline abrogates MCAo-mediated apoptotic cell death
A new set of animals (n = 18) underwent MCAo, randomly assigned to similar minocycline treatment as described above, and euthanized at three days post-stroke for immunohistochemical analyses of apoptotic cell death. Results revealed that Bcl-2 immunoreactivity was significantly increased in the brains of stroke animals that were treated with low dose minocycline, especially within the striatum ipsilateral to the occluded MCA (20 mg/kg: 9.83 ± 1.50 density/0.05 mm2) relative to vehicle-treated stroke animals (0.235 ± 0.112 cells/0.05 mm2) (F2,15 = 37.151; p < 0.0001) (Figure
Figure 6
Tunel staining in the ischemic peri-infarct area
Tunel staining in the ischemic peri-infarct area. Low dose significantly decreased (B), whereas high dose significantly increased (C) the number of TUNEL positive cells in the ischemic striatal peri-infarct area of minocycline-treated stroke rats compared to the vehicle-treated stroke rats (A). Quantitative analyses of Bcl-2 positive cells are shown in panel D. Data are shown as mean values ± SEM (*p < 0.05). Four representative ischemic striatal peri-infarct areas (+0.2 mm anterior to the bregma), in which TUNEL positive cells were counted (data in panel D), are shown in panel E (square boxes labeled 1-4 correspond to areas 1-4 in panel D). Scale bar: 25 μm.
In addition, whereas TUNEL-positive cells with agglutinated nuclei highly populated the striatal peri-infarct area of high dose minocycline treated or vehicle treated animals, there were significantly fewer TUNEL-positive cells in animals treated with low dose minocycline (F2,15 = 35.411; p < 0.0001) (Figure
Figure 7
Bcl-2 expression in the ischemic peri-infarct area
Bcl-2 expression in the ischemic peri-infarct area. Low dose (B) significantly upregulated, whereas high dose (C) significantly suppressed the Bcl-2 expression in the ischemic peri-infarct area of minocycline-treated rats compared to that in the vehicle-treated rats (A). Quantitative analyses of Bcl-2 positive cells are shown in panel D. Data are shown as mean values ± SEM (*p < 0.05). Two representative ischemic striatal peri-infarct areas (+0.2 mm anterior to the bregma), in which Bcl-2 positive cells were counted (data in panel D), are shown in panel E (square boxes). Co-localization of Bcl-2 and MAP2 was found in ischemic striatal peri-infarct area, suggesting anti-apoptotic effects of minocycline via Bcl-2 upregulation in ischemic neurons (F-H). In contrast, GFAP positive astrocytes did not express Bcl-2 (I-K). Scale bar: 25 μm (A-C), 12.5 μm (F-K); asterisks (*): merged cell; green and red immunofluorescent markers correspond to Bcl-2 and MAP2, respectively.
Minocycline rescues neurons in the peri-infarct area
To determine the effect of minocycline on neurons
Figure 8
Neuronal survival in the ischemic peri-infarct area
Neuronal survival in the ischemic peri-infarct area. Neuronal survival in the ischemic striatal peri-infarct area, visualized with cresyl violet stain, was significantly preserved by low dose minocycline (A: intact control, B: vehicle, C: 20 mg/kg, D: 100 mg/kg). In contrast, high dose minocycline resulted in the collapse of fundamental neuroarchitecture of the striatum accompanied by severe edema. Data are shown as mean values ± SEM (*p < 0.05). Scale bar: 25 μm.
The present study demonstrates that minocycline exerted direct protection on neurons, in the absence of astrocyte participation, against ischemic stroke. An equally important finding is that minocycline not only promoted dose-dependent neuroprotective effects, but also induced toxicity at a high dose for both neurons and astrocytes. Both sets of
To date, the primary CNS mechanism implicated in minocycline neuroprotection is the drug's highly potent inhibitory effect on microglial activation, which is achieved by blocking the phosphorylation of p38 and the translocation of 5-Lipoxygenase into the nucleus, thereby preventing the release of cytokines and the induction of inflammation
In stroke brains, increased chemokine mRNA expression displays a biphasic profile, being found initially in neurons, then subsequently in astrocytes
To further clarify the anti-apoptotic features of minocycline, we examined the alterations in expression of apoptosis-related components, specifically the cell survival-enhancing Bcl-2/cytochrome c pathway. Our results revealed that low dose minocycline protected again neurons, but not astrocytes against OGD by elevating Bcl-2 expression and consequently strengthening the anchor of cytochrome c to the mitochondria. We extend here the participation of Bcl-2/cytochrome c pathway in minocycline's direct protection of OGD-exposed neurons, previously shown in ischemic kidney cells
To reveal the possible toxic side effects of minocycline, we similarly examined cell survival and apoptosis in OGD-exposed cultured neurons and astrocytes treated with high dose (100 μM) minocycline. Minocycline at a high dose was toxic as revealed by markedly reduced cell survival of both OGD-exposed neurons and astrocytes compared to vehicle treated OGD-exposed cells. Moreover, relative to vehicle treated OGD exposed cells, high dose minocycline did not elevate Bcl-2 expression, but increased caspase 3/7 activity, as well as the number of TUNEL positive cells in the ischemic striatum.
In parallel to the toxicity profile of minocycline observed in the
In previous reports, therapeutic efficacy in different animal models of neurological disorders was consistently observed when minocycline was administered 3 mg/kg-45 mg/kg either intravenously or intraperitoneally
The observed dose-dependent protection of neurons over astrocytes by low dose minocycline, and the neurotoxic effects of high dose minocycline provide guidance in designing the clinical protocol for stroke patients. Because astrocytes play a crucial role in blood brain barrier maintenance, a perturbed astrocyte viability, as seen with high dose minocycline, may compromise the barrier that could allow inflammatory cells to penetrate the CNS and exacerbate the stroke deficits. Indeed, most of the animals that received high dose minocycline exhibited severe edema. The establishment of an effective dose range that confers protection on neurons, while not disrupting astrocytes, would perhaps lead to improved therapeutic outcome of minocycline.
Minocycline's inability to protect astrocytes or to increase Bcl-2 expression in these cells
In conclusion, the safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy. The implication of the present direct minocycline protection of neurons, as opposed to the reported inhibition of microglial activity, can be best appreciated by the fact that stroke triggers abrupt neuronal cell death that would require immediate intervention to rescue ischemic cells. A delay in abrogating the primary stroke-induced cell death could result in "fixed" or devastating histological and functional deficits that will be difficult to repair. Coupled with the ability of minocycline to block the microglial activation occurring at later post-stroke periods, we now provide evidence that minocycline is also able to achieve an expedited direct neuroprotection against ischemia at early time points. To our knowledge, such two-pronged neuroprotective approach targeting both primary and secondary cell death processes associated with stroke has not been shown with monotherapy. Minocycline stands as a multiple site of action therapeutic drug, which clinically should be effective in treating neurological diseases, like stroke, characterized by many facets of cell death cascades.
The present experimental research and relevant ethical issues were approved by Veterans Affair Medical Center Institutional Animal Care and Use Committee, and adhered to National Institutes of Health guidelines.
In vitro study
Cell culture
Primary cultures of neurons and astrocytes were derived from the rat (Sprague-Dawley) striatum and maintained in culture following the supplier's protocol (CAMBREX, MD). Briefly, immediately after thawing, cells (4 × 104 cells/well) were seeded and grown in 96-well plate coated by poly-l lysine in Neurobasal media (GIBCO, CA) containing 2 mM L-glutamine, 2% B27 (GIBCO, CA) and 50 U/ml penicillin and streptomycin for 7-10 days at 37°C in humidified atmosphere containing 5% CO2. Purity of the cells were immunocytochemically determined to be > 99% for both neuronal and astrocytic cell population as revealed by DARPP-32 and GFAP immunostaining, respectively. Moreover, we confirmed that these cells were appropriate for the oxygen glucose deprivation (OGD) injury model, where glutamate excitotoxicity plays an important role, as revealed by expression of glutamate receptors (determined immunocytochemically using vesicular glutamate transpoter-1) in 50% of the neuronal and astrocytic cell population.
Oxygen-glucose deprivation (OGD)
Cultured cells were exposed to the OGD injury model as described previously
Cell viability
Cell viability was evaluated by ATP activity following the supplier's protocol (Promega, WI) and by Trypan blue (Sigma, MO). Briefly, MTT assay was carried out by adding MTT assay solution immediately after OGD. The intensities of chemiluminescence of ATP activity were measured and calculated by Image station 2000R system (Kodak, NY). In addition, Trypan blue exclusion method was conducted and mean viable cell counts were calculated in three randomly selected areas (0.2 mm2) in each well (n = 5 per treatment condition) to reveal the cell viability for each treatment condition.
Caspase 3/7 assay
For caspase assay, the same number of cells (40,000 cells/well) was seeded in 96-well plate and maintained as described above. After OGD treatment for 2 hours, caspase 3/7 assay was examined following the manufacturer's protocol (Promega, WI). Briefly, examination of caspase activity was performed by adding caspase assay solution immediately after OGD. Following incubation at room temperature, the intensities of chemiluminescence were measured and calculated following the procedures mentioned above. The intensities were compared between minocycline-treated and vehicle-treated OGD groups after subtracting the mean of no OGD control group.
For Western blot of Bcl-2, cultured cells were extracted and homogenized by solution containing 20 mM Tris-HCl (7.6), 150 mM NaCl, 1% NP40, 1 mM PMSF, 1 μg/ml leupeptin, 1 μg/ml TPCK and 1 μg/ml TLCK. For cytochrome c assay, cultured cells were extracted following the manufacturer's protocol (BioVision, CA). Briefly, cells were homogenized in ice-cold buffer containing protease inhibitors. After centrifugation at 700 g for 10 minutes at 4°C, the supernatant was further centrifuged at 12,000 g for 40 minutes at 4°C. Thereafter, the supernatant was collected as cytosol fraction, and the pellet was resuspended with mitochondria extraction buffer containing DTT and protease inhibitor, and stored as mitochondria fraction. Collected samples (50 μg) were loaded into 12.5% SDS-PAGE electrophoresis and transferred to a nitrocellulose membrane. After blocking by 3% skim milk in 10 mM Tris-HCl (pH 7.6), 150 mM NaCl and 0.3% TritonX at room temperature for one hour, the blot was probed with a monoclonal antibody against Bcl-2 (1:2000, Chemicon, CA), and cytochrome c (1:500, Pharmigen, CA), and visualized using a HRP-conjugated anti-mouse IgG antibody and chemiluminescence system (Amersham, UK).
Each 1 × 105 cells were plated on 8 well Permanox® slides (Nalge Nunc Int, IL) at two days before fixation. Cultured cells were treated with 4% paraformaldehyde (PFA) for 10 minutes at room temperature after rinsing with phosphate buffered saline (PBS). After blocking reaction with 10% normal goat serum (Vector, CA), cells were incubated overnight at 4°C with an anti-Bcl-2 monoclonal antibody (1:100, Chemicon, CA), or anti-MAP2 polyclonal antibody (1:1000, Chemicon) with 10% normal goat serum. After several rinses in PBS, cells were incubated for 45 minutes at room temperature in FITC-conjugated anti-mouse IgG (1:1000, Molecular probe, CA), or Rhodamine-conjugated anti-rabbit IgG (1:2000, Molecular probe, CA) for visualization. Cells were processed for DAPI. immunostaining then subsequently embedded with mounting medium. Immunofluorescent images were visualized using Zeiss Axiophot 2 and the number of immunopositive cells was counted per high power field view selected at random (50,000 μm2). In addition, control studies included exclusion of primary antibody and substituted with 10% normal goat serum in PBS. No immunoreactivity was observed in these controls. All studies were conducted in quadruplicates, with n = 100 per treatment condition. Assessments were performed blindly by an independent investigator.
TUNEL staining
Cultured cells were washed with PBS. As described in our previous report
In vivo study
Stroke surgery
Sprague-Dawley, male 10-week old rats, weighing about 250 g, were anesthetized with gas inhalation composed of 30% oxygen (0.3 L/min) and 70% nitrous oxide (0.7 L/min) mixture. The gas was passed through an isoflurane vaporizer set to deliver 3% to 4% isoflurane during initial induction and 1.5% to 2% during surgery. Transient unilateral focal ischemia was produced using a well-established middle cerebral artery occlusion (MCAo) using the intraluminal suture model as previously described
Behavioral tests
Behavioral estimation was performed by using semi quantitative analysis of motor asymmetry (elevated body swing test, EBST) and neurological function (Bederson test) at 72 hours just prior to euthanasia as previously described
Infarct estimation via 2,3,5-triphenyltetrazolium chloride (TTC) staining
After behavioral testing at 72 hours post stroke, animals were anesthetized with a lethal dose of equithesin (500 mg/kg, i.p.), decapitated and the brains harvested. Histological determination of infarct volume was performed using standard TTC staining, and quantitative image analysis was carried out as previously described
Under deep anesthesia, rats were sacrificed at 72 hours after reperfusion, and perfused through the ascending aorta with 200 ml of cold PBS, followed by 100 ml of 4% PFA in PBS. Brains were removed and post-fixed in the same fixative for 3 days followed by 30% sucrose in phosphate buffer (PB) for 1 week. Six series of coronal sections were cut at a thickness of 30 μm by cryostat and stored at -20°C. Free floating sections for immunohistochemistry were incubated overnight at 4°C with an anti-Bcl-2 monoclonal antibody (1:50, Chemicon), anti-MAP2 polyclonal antibody (1:500, Chemicon), or anti-GFAP polyclonal antibody (1:500, Chemicon, CA) with 10% normal goat serum. After several rinses in PBS, the sections were visualized following the method described above with modification to accelerate FITC with biotin conjugated anti-mouse IgG antibody and FITC conjugated streptoavidin (1:500, Sigma, MO). Control studies included exclusion of primary antibody substituted with 10% normal goat serum in PBS. No immunoreactivity was observed in these controls. Furthermore, TUNEL staining was performed as described in
Morphological Analysis
The density of the Bcl-2 positive cells and TUNEL positive cells in the ischemic peri-infarct area (determined by cresyl violet stain using consecutive sections) was estimated and analyzed as described previously
In order to determine significant differences in cerebral infarcts, motor deficits, the number of TUNEL positive cells and Bcl-2 positive cells were analyzed using Repeated Measures of ANOVA followed by post hoc Scheffe's test. For Bederson neurological deficits, the non-parametric Kruskal-Wallis test was performed. Statistical significance was preset at p < 0.05.
Authors' contributions
NM assisted in study conceptualization, design and coordination, and also carried out the histological and molecular assays and drafted the manuscript. TY performed the behavioral tests and immunohistochemical analyses. KH assisted in stroke surgeries and histological procedures. LX performed the stroke surgeries and assisted in histological analyses. MM assisted in the molecular assays and analyses. GY assisted in behavioral, surgical and histological assays. YK assisted in molecular analyses. KO participated in data analyses and manuscript write-up. DCH assisted in study design and manuscript write-up. CVB conceived the study, supervised its design and coordination, and led the manuscript write-up. All authors read and approved the final manuscript.
This project was funded by MCG Department of Neurology Funds. The authors thank the technical assistance of Ms. Eunkyung 'Cate' Bae and Dr. Seong Jin Yu in the final preparation of the manuscript.
Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative diseases
Reducing calcium overload in the ischemic brain
Role of calcium in neuronal cell injury: which subcellular compartment is involved?
Apoptosis in the nervous system
Reactive oxygen radicals in signaling and damage in the ischemic brain
Calcium antagonists for ischemic stroke: a systematic review
Ions, cell volume, and apoptosis
Mechanisms, challenges and opportunities in stroke
The complexity of tissue-type plasminogen activator: can serine protease inhibitors help in stroke management?
Hypothermia and hyperbaric oxygen as treatment modalities for severe head injury
Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling
Mechanisms of hyperbaric oxygen and neuroprotection in stroke
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia
A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window
Neuroprotection by tetracyclines
Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease
Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice
Rise and fall of minocycline in neuroprotection: need to promote publication of negative results
Minocycline protects basal forebrain cholinergic neurons from mu p75-saporin immunotoxic lesioning
Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis
The promise of minocycline in neurology
The potential of minocycline for neuroprotection in human neurologic disease
Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination
Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia
Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia
Minocycline blocks nitric oxide-induced neurotoxicity by inhibition p38 MAP kinase in rat cerebellar granule neurons
Inocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by differential regulation of p38 and Akt pathways
Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria
Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline
Nitric oxide-induced apoptosis is mediated by Bax/Bcl-2 gene expression, transition of cytochrome c, and activation of caspase-3 in rat vascular smooth muscle cells
Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice
Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury
Delayed minocycline but not delayed mild hypothermia protects against embolic stroke
Effects of minocycline alone and in combination with mild hypothermia in embolic stroke
Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats
Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease
Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection
Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation
Minocycline enhances MPTP toxicity to dopaminergic neurons
Minocycline worsens hypoxic-ischemic brain injury in a neonatal mouse model
5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases
Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity
The yin and the yang of 5-lipoxygenase pathway activation
Prolonged expression of interferon-inducible protein-10 in ischemic cortex after permanent occlusion of the middle cerebral artery in rat
Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3
Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients
Regulation of chemokine receptor expression in human microglia and astrocytes
Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion
Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes
Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases
Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia
Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species
Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity
Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro
Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial
Histamine H2-receptor antagonist ranitidine protects against neural death induced by oxygen-glucose deprivation
Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease
Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats
Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination
Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats
Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats
Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase
Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury
Quantitative histology of Wallerian degeneration I. Nuclear population in rabbit sciatic nerve
Increased expression of hippocampal cholinergic neurostimulating peptide-related components and their messenger RNAs in the hippocampus of aged senescence-accelerated mice
The Rat Brain in Stereotaxic Coordinates


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- Bo Ran, Xiang-yang Chen, +11 authors Ming Li
- 2014
After publication of this work [1], we noted that we inadvertently failed to include the complete list of all co-authors, and they were not listed in the correct order. In addition, we have provided updated Authors' Contributions and Competing interests sections. We apologize for any inconvenience these oversights may have caused. Competing interests The… (More)
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Retraction The Publisher and Editor regretfully retract this article [1] because the peer-review process was inappropriately influenced and compromised. As a result, the scientific integrity of the article cannot be guaranteed. A systematic and detailed investigation suggests that a third party was involved in supplying fabricated details of potential peer… (More)
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- Journal of orthopaedic surgery and research
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BACKGROUND Previous studies have demonstrated that pelvic incidence and sacral slope are significantly greater in idiopathic scoliosis patients compared with normal adolescents. However, whether these sagittal parameters are related to the progression of scoliosis remain unknown. The present was designed to determine the differences in the sagittal profiles… (More)
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If I try to run
wmic /user:username /password:password /node:ipaddress systemenclosure get serialnumber
I get an error on the PC's that SW wont log into.
Node - 192.168.202.142
Code = 0x80070005
Description = Access is denied.
Facility = Win32
This is the same error I get if I inentially use the wrong credentials on the PC that it normally works for. But I have triple checked the credentials and I know that they are correct.
Any Idea's?
(I was having problems before this -- but seem to have gotten the original problems worked out. --- You can check out this thread for some additional information. http:/
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Dec 10, 2008 at 6:02 UTC
If I run WMIdiag.vbs on one of the clients I am unable to connect to, here is what I get. It says there are error's but I don't understand this. Can anyone shed some light on this?


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Courtroom Etiquette
Making a good impression in court is very important. Below is a list of things to remember before you go to court:
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It's a good idea to be represented by an attorney when you appear in court. Sometimes, the judge will even REQUIRE that you have an attorney! Being well informed of your charges, potential fines and sentencing possibilities is also important. Your attorney will help you to have a better understanding of these things. Hiring a good attorney is also important to defend your rights, argue your case, file motions and negotiate with the District Attorney.


text:
The Second Test
My mouth dropped open in disbelief. However, at the time I was only concerned with getting my pants back. Standing in my boxers in a busy airport terminal wasn't exactly boosting my self-esteem. "Can you give me my pants please?" I asked.
"Oh, right, here you go" she said while handing over my khakis. "Now that you've passed the first test, you'll have to continue to the second. It won't be quite as fun."
"What am i being tested for in the first place?"
"I can't tell you now, all I can say is that Inetec isn't exactly what you thought it was."
I was lead down the terminal, taken out of the airport, and told to sit in the backseat of a car. The car stopped at an office building and I was to a desk upstairs. On the desk sat a sheet of questions, a scantron, and a pencil. "Ahh I hate these things," I mumbled.


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Sea Rowing Club.
Studland Bay, Dorset.
Make time for life.
Sea Rowing Club Blog Share Sea Rowing Locations
"here's my quote" supports sea rowing - heresmyquote.com
Sea Rowing Club aims to encourage more people to make time to go sea rowing and share the great sea rowing places they know.
"Free yourself from the shackles of daily life and do something that makes you feel great everyday." - Bob


text:
First, here's the http://grfx.cstv.com/photos/schools/ariz/sports/m-baskbl/auto_pdf/2011-12/misc_non_event/Red-Blue_box_10-22-11.pdf" target="_blank">official box score from the Red-Blue Game and a link to the UA http://www.arizonawildcats.com/allaccess/?media=272744" target= "_blank">archived webcast of it.
Our coverage today: A http://azstarnet.com/sports/basketball/college/wildcats/arizona-basketball-final-score-red-blue/article_5660e0b6-fcfa-11e0-88bd-001cc4c002e0.html" target="_blank">main story on the Red-Blue Game and atmosphere around it, a http://azstarnet.com/sports/basketball/college/wildcats/arizona-basketball-redshirt-unlikely-as-parrom-progresses/article_6e126c9a-863f-5aac-9c52-28bf055625e1.html" target="_blank">sidebar on Kevin Parrom's progress, and a http://azstarnet.com/sports/basketball/college/wildcats/photo-gallery-red-blue-scrimmage-game/collection_fb09a91c-fd0a-11e0-8fbc-001cc4c002e0.html" target="_blank">photo gallery. (Greg Hansen's column is not immediately available online).
Some more notes from the game:
Sean Miller made several references to how important the atmosphere was to recruiting. Arizona hosted already committed players Gabe York, Grant Jerrett and Brandon Ashley, while 2012 target Kaleb Tarczewski was on hand as well as some key younger players.
"Today obviously means so much more than the game," Miller said. "The former teams' players and coaches, and our current team...and obviously a big part of our future was sitting here as well.
"I'd like to thank our fans and the people in our ticket office working as hard as they did. There was a combination of energy and atmosphere that not many college basketball program enjoy. That's why we all came to Arizona and that's what makes us so special. It was just really a great afternoon."
Miller told the fans when he took the microphone before the game that "we have our future here" and alluded to the Nov. 9 fall signing date when he thanked fans for showing up during his postgame news conference.
"They did their job and hopefully over these the next couple of weeks we can feel the impact," Miller said.
Solomon Hill thought it should help, too.
"Seeing as many guys back, seeing the team, the four freshmen go out there and jell ... If I had gone on my trip seeing the No. 1 recruiting class and the NBA players, it would be hard to pass this up," Hill said. "It should have a great deal to do with the recruiting in the future."
Miller said that only Hill and Kyle Fogg are starters at this point. "Beyond that there's two weeks of practice to really figure out who the others are and those guys have to keep working hard as well."
Jason Terry said he was surprised how quickly Sean Miller has revived the UA program.
"I had my doubts," he said. "I was ready to hang it up and come back and coach myself. One day, hopefully, I will. But they picked the right man for the job. The direction this school is in, it's only going to go up.
"By him bringing us back, he realized what it means to be an Arizona Wildcat. When I first stepped foot on campus, I was greeted by Sean Elliott, Steve Kerr, Jud Bueschler, Damon Stoudamire -- all those guys in a pickup game. I knew then it was a brotherhood and it meants a lot to wear Arizona across your chest."
The way Miller sees it, the Red-Blue Game won't be the only time this season that six guys score in double figures.
"I do think we have a lot of different players who can make plays on offense and defense, and balance has to be our cornerstone this year," Miller said. "We will have a lot of games with four or five players in double figures and same thing on defense, we'll have to have a lot of contributions from a lot of players. It'll be a fun team to watch from that perspective. And especially as the year grows our younger players will be more comfortable."
Chase Budinger was asked to reflect back on his tenure at UA. He played for three coaches in three years during UA's transition years.
"I had a different college experience but it's like a brotherhood," Budinger said. "We're a family and coach Olson did a great job for 20 something years that he was here of creating that and Sean is doing the same moving forward. It's nice to see."
Jordin Mayes said he is recovering well after having surgery to repair a stress fracture in his foot over the summer. He had two points, two rebounds and three assists in 21 minutes for the Blue team.
"I feel like I'm about to 100 percent," Mayes said. "I have no pain in it. I'm running well. I'm working hard, lifting with my feet well so everything's doing good."


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September 12, 1999
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New Braunfels Herald Zeitung (Newspaper) - September 12, 1999, New Braunfels, Texas WAI U/Herald-Zertung Chance Lowry, store manager at Home Depot, 1360 Interstate 35 North, displays some fire ant repellent products. Fall an ideal time to fight fire antsFire Ant Awareness Week lets Texans coordinate efforts By Erin Magruder Staff Writer Anyone who has ever encountered fire ants knows they give a very painful connotation to the phrase, "Ants in Your Pants." Now is the time for Comal County residents to do something to take the sting out of spring — by treating their yards for fire ants in the fall. This week has been designated "Fire Ant Awareness Week" by the Texas Agricultural Extension Service and the Texas A&M University System. The campaign is designed to motivate neighborhood residents to coordinate their efforts to manage the fire ant population, Comal County Extension Agent Marty Gibbs said. "lf only one resident treats their yard," Gibbs said. "The fire ants will simply pick up and move to another yard that does not have an insecticide." Gibbs said fall was an ideal time to treat fire ants because it eliminates % percent of the population by spring. Fire ant control is important because they can be much more than just a nuisance, Gibbs said. "Fire ants tend to get where they don't belong," he said. "They can ground out electrical equipment, cause damage to farmlands and in rare cases kill someone." However, only a small portion of the population experience severe allergic reactions.See FIRE ANTS/5 A Meeting WHO: Comal Independent School District board of trustees WHEN: 7 p.m. Monday WHERE: Bill Brown Elementary School, 20410 Texas 46 West WHY: Public hearing on proposed 1999-2000 tax rate J0A. New i&SUJNFEL 20332 nni)9 10/22/00 7.6 SO - WEST MI CRO PU BL I SHING 2627 E YftNDFLL DR EL POSO, TX 79903-L3Herald-ZeitungVol. 148, No. 212 54 pages in 5 sections September 12, 1999 Serving ^omal CountY since 1852 $1.00 City council listens as residents share views on proposed projects September is here, but the summer heat will continue this week. See page 2A.Index Abby.............................................2C Business....................... 7-8C Classified................................1-1 OD Crossword....................................2C Forum...........................................6A Local/Metro...................................4A Movies..........................................2C Obituaries.................................3A Sports....................................1-4B Today............................................2A Television............................Montagewww.herald-zeltung.com Key code 77 Grand jury indicts two for blaze By Heather Tood Staff Writer A Comal County grand jury indicted two New Braunfels residents this past Wednesday on a number of charges related to a Feb. 3 blaze that damaged four downtown businesses. Leticia Gonzalez, 26, and Andrew Ortiz, 36, are accused of starting an early morning fire in the IOO block of North Castell Avenue. No one was injured. New Braunfels Fire Marshal Elroy Friesen-hahn said Gonzalez and Ortiz were indicted on charges of arson, tampering w ith physical evidence and theft. The indictments ended a seven-month investigation that involved city, state and federal fire officials. Damage to the building, on the east side of North Castell Avenue, was estimated between $ 100,000 and $ 150,000. Friesenhahn said Gonzalez was the manager of one of the businesses destroyed by the fire, First Plaza Finance at 140 N. Castell Ave., at the time of the blaze. Ortiz was Gonzalez's boy friend at the time. If convicted of the arson charge, the pair could face two to 20 years in prison and a fine up to $ 10,000. Jim Noble, Comal County assistant district attorney, said the theft charge was raised to third-degree felony because it earned a charge of engaging in organized cnme. "Organized crime is not its own offense, but if you commit a crime w ith two or more other people, it's considered an organized crime," he said. Noble said the value of the theft ranged between S1.500 and $20,000, which was normally a state jail felony. But, w ith the oiganized crime charge, the theft charge would be bumped to a three-degree felony, which carries a pnson term of two to 10 years and a fine up to $ 10,000. Tampering w ith evidence also is a third-degree felony. Noble said persons can be indicted for a crime based on a grand jury 's finding of probable cause. At least nine people on the 12- See BLAZE/11 A Bond workshop WAI Ll/Herald-Zeitung New Braunfels resident Vance Langley addresses New Braunfels City Council during Saturday's bond election workshop at the municipal building, 424 S. Castell Ave. By Peri Stone-Palmquist Staff Writer New Braunfels voters could have a lot to chose from in a future city bond election. In a workshop Saturday, New Braunfels City Council listened to and discussed five hours worth of ideas for bond issues, ranging from streets and drainage to recreation to public safety projects. Council did not accept or reject any ideas, or start prioritizing the project list. Ultimately, any projects they do chose will be put before voters in a bond election, although an election date has not been set. City manager Mike Shands said, "By passing a bond, the voters are voluntarily imposing additional property taxes on themselves to repay the debt. We are saying that we agree to higher taxes for the bend improvements." The property tax increase per $100,000 valuation would be about $83 per year, for instance, for a $10 million bond financed over 15 years. "We all have to pay taxes," Mayor Stoney Williams said. "It's hitting us, See BOND WORKSHOP/10A WAI U/Herald-Zeitung New Braunfels Mayor Stoney Williams (left) and District 3 councilman Randy Vanstory listen as District 3 councilwoman Jan Kotylo speaks at the bond forum. Inside ► Skat players explain the game Skat, a card game that was brought to the United States — and New Braunfels — Germany, requires a quick mind and plenty of concentration. Discover what this popular pastime is all about. /IC ► Business fills renovated home Gallagher Real Estate found new office space in an old house. Owner Charlie Gallagher recently moved his business into a remodeied and renovated Langston House, which dates back to the 1850s. IIC Weather CISD tax By Heather Todd Staff Writer Comal Independent School District patrons can give their two cents Monday about a proposed tax rate increase that could raise the average bill by more than $100. A public hearing on the 1999-2000 tax rate will begin at 7 p.m. at Bill Brown Elementary School, 20410 Texas 46 West. Abel Campos, business manager for CISD, said the administration proposed a $1.88 tax rate next year, with a 38-cent debt service rate and a $ 1.50 maintenance and operations rate. ^ Rangers win in a thriller Smithson Valley passed its first test of the 1999 football season with flying colors. The Rangers improved to 2-0 with a dramatic 10-7 win over San Antonio O'Connor this past Friday. New Braunfels also pushed its record to 2-0, but the No. 4 Canyon Cougars lost to No. 8 Schertz Clemens. /1B rate hearing set for Monday The district's current $1,768 per $100 valuation tax rate is based on a $ 1.50 maintenance and operations rate and a 26.8-cent debt service rate. The 11 -cent increase on the 1999-2000 tax rate would mean the average homeowner would pay $108 more in school taxes next year. Officials with the Comal Appraisal District said based on preliminary figures, the average home in CISD would be valued at $97,189 next year. The average home value in CISD this year was about $94,472. The $1.88 tax rate would translate into a $ 1, 179 tax bill next year, $ 108 more than the average tax bill of $1,071 this past year. CISD patrons receive a $ 15,000 exemption from the state and a 20 percent home stead exemption from the district. A tax relief provision in Senate Bill 4, passed by state lawmakers during the 1999 legislative session, actually will save local taxpayers some money on their tax bills this year. Campos said the district initially was looking at a 15-cent increase on the debt service rate to fund bond projects, or a total $ 1.92 tax rate. But additional funding from the state based on a tax relief measure allowed the district to divert those funds to debt service and lower the tax rate by four cents. See TAX RATE/5A ;
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Man Group is the most phenomenal money machine the City has seen for decades. Its trick was to catch the rise of hedge funds at their outset in the 1980s and pursue the growth of these "alternative" investments at a pace few rivals have been able to match.
The result is a FTSE 100 company worth £5bn, managing assets of £25bn. The sheer size of the business is also testament to Man's reputation as a professional operator with strict internal controls that is happy to accept scrutiny by regulators.
Investors do not expect to hear allegations such as those being aired in the US district court for the eastern district of Pennsylvania. Man is an establishment firm that can count five of the City's richest individuals among its shareholders and directors. Chairman Harvey McGrath has company shares worth £100m and his chief executive, Stanley Fink, son of a lampshade maker, is worth about £75m.
On top, Mr Fink has collected about £10m in salary in the last three years and his personal investments include a hotel in the Alpine ski resort of Courchevel.
The term hedge funds covers a wide variety of investment techniques, and Man's contribution was to popularise momentum-following. Its involvement arose almost by accident. Until the 1980s, ED&F Man was primarily a trader in commodities such as cocoa, sugar and coffee. It found itself increasingly trying to use financial instruments to protect itself against the fluctuations in the prices of these commodities. In other words, it wanted to hedge its risk.
That led it into the game of trying to predict price movements. In 1984, it entered a partnership with a statistician who claimed to have developed a system of following trends in market prices.
Man liked the results and in 1989 it bought a little-known investment management firm named Adam, Harding & Lueck that was employing a similar trend-following model. It was the deal that would see ED&F Man jettison its dull past in commodities and enter the go-go world of hedge funds.
The appeal of hedge funds is the promise of consistent returns. Traditional fund managers too often fail to beat the general stock market, and the switch towards hedge funds has transformed the business of money management. There are about 8,000 hedge funds in the world and they are reckoned to account for about half the volume of shares traded daily on the London Stock Exchange.
Man has developed a long way from its original techniques. It now owns a fund-of-fund business which invests in both its own and third-party hedge funds. But the most rapid growth has been seen at Man Financial, the broking division named in the Pennsylvania court case.
The primary case is an action by the Commodities Futures Trading Commission (CFTC), a regulatory body, against Paul Eustace, who set up the Philadelphia Alternative Asset Management Company (PAAM).
The explosive allegations against Man Financial are made in a motion to the court by the receiver to Eustace's fund. The receiver is trying to uncover the full story of the collapse and is thought to have recovered only about $75m so far for investors.
"Man Financial has hindered the receiver's investigation by refusing to turn over relevant documents, and this motion seeks to correct Man Financial's misconduct," says the motion to the court.
While Man says it has provided "over 4,200 pages of documentation", the receiver says this is still less than full disclosure. In particular, he says the documents do not explain why details of the "50 account", which was allegedly used to disguise losses, was not made available to investors or to UBS, the other broker to the Eustace fund.
Man, saying it is "surprised and disappointed by the actions of the receiver", added: "The receiver's actions are at odds with public statements he has made to the effect that he has received a high degree of cooperation from most parties involved and no one has yet refused to provide documents requested. Man Financial has a demonstrable record of cooperation and compliance with regulatory bodies in all the jurisdictions in which it operates. In this case, we have complied with all requests for information from our regulator, the CFTC. We remain committed to working closely and constructively with both the CFTC and the receiver to PAAM.
"Since this issue is still subject to legal and regulatory investigation, we have no comment to make on the broader content of the receiver's motion."


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Manifestprograms.com is a 1 year old domain, situated in Australia. The domain is linked to the IP address 126.96.36.199 which is provided by the hosting company Early registration addresses.
It was registered by Alec Courtright . Registration details show that it was registered on 09 Jan 2016 through Go Daddy and will expire on 09 Jan 2017.
The site is being served through DPS/0.2.2.


text:
Anyway, it was quite an eventful night at the departures. We "abused" the baggage weighing scale at the entrance by measuring our own mass instead... lol... Then I was stopped short by a Chinese couple seeking directions and had to act like some interpreter between the airport staff and them for a while. I realised I was Vocab-limited. Blah!
My sis and her mates got into some overloading problem at the check in point. They were off-scale by 8kgs in total. It ended up with them unpacking stuff which was really kinda funny. Every luggage was packed full with food items. It looked like they were all prepared to go to some war zone.
Then someone's backpack had to burst at its seam which got everyone stumped. Thankfully, there was a "heroine" to the rescue. While everyone was fretting what can be done, I was quick-witted enough to think of removing the rubber strings lacing the front to tie around the bag. I supposed that will hold it well till they reach their place in Beijing. I think I impressed brother with my crisis management skills. He muttered a "Great thinking sis". *proudz
Never forgetting some last moment pictures.
I cannot recall what we were laughing at.
Presenting the Sim siblings.
Aren't very good with self taken shots.
Had to resort to a 3rd party help for the perfect sibling shot.
Papi and Mami
Already missing us. Went through the gates and still wanna take pictures.


text:
Writing on Windows Once More
I have a fascination with windows.
This is a sudden realization, and it comes to me, of course, while sitting in front of a window. It's only one of those small ones, nothing grand. The window, I mean, not the realization. Though I guess there's nothing amazing about a window obsession, either.
Shaking the circles of words from my head I go to stand, wanting to see if the coffee has finished brewing. The machine isn't roaring or belching as it tends to do while brewing coffee, a developing problem that I keep forgetting to look into. It'll probably need to be fixed, I expect.
A second realization: I'm fixed.
No, not like that. I'm fixed to the spot. I've sunk so far into this chair that it refuses to release me, refuses to allow my warm body to be removed from its upholstered embrace. I wiggle a bit, hoping to loosen myself from the cushioned clutches, and find myself oddly, well, able. There's nothing holding me, nothing keeping me down.
Realization number three: my legs have betrayed me. Those two fleshy limbs that have supported me all my life, save for the times my arms lent a hand or two, are now revolting. I've read about things like this, so I search my mind for clues to coerce my legs into cooperating. Somehow, I don't believe letting them eat cake will help.
But it'd probably make me feel better: cake with my coffee. Coffeecake? Or is that something different entirely? Baking was never my forte: just eating baking.
I sigh. I slump. I'm pretty much just a sagging lump in this chair, defeated by my own body: double-crossed by my own legs.
Double-crossed? I look down at my legs again. Or just crossed?
With a little effort I unfold them, and a painful tingling races from my toes to my thighs. Good gawd, I'm being eaten alive by invisible termites from the waist down, like I'm stuck in their big invisible termite nest. Termite hill? Termite… lair?
By the time I've exhausted my vocabulary of termite domiciles they've left, and in fact haven't taken anything with them. Unless I had some sort of invisible legs that they have stolen from me: the legs of my soul. Or something like that.
Finally, I stand. I stumble over to the coffee machine on shaking legs (the soul parts of the legs were obviously integral to their use, it seems) and pour myself a cup. Or a mug, rather. Two spoons of sugar go in, followed by the spoon. I spin the dark liquid in a quick circle, admiring the whirlpool I've created: Charybdis would be proud.
I pull the cup to my waiting lips, and soon make the fourth realization of the day: I really am fascinated with windows.
The coffee is cold, almost unbearably so. I squish and contort my face as the bitter liquid passes my lips, the sugar having not dissolved with the lack of heat. Blegh. The girls never say it, but they all know the fourth criteria: strong, black, rich, and hot. Very hot.
Disappointed, I sit back down on my chair. It has a comforting warmth, almost as if I belonged there, sitting before the window. Of course, that warmth can be explained by the concept of residual body heat, but there's nothing poetic or romantic in that.
And there's so little that's romantic these days.
So I sit still: warmed by my past and gazing out that small, squat window.
I really am fascinated.


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November 07, 1938
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Abilene Reporter News (Newspaper) - November 7, 1938, Abilene, Texas Million Parade Before Stalin as Soviet, 21 Years Old, Hears Fascist Attack Predicted-See Page 3 I WEST TEXAS'■ ll ||||g I NEWSPAPER ll VOL. LV III, NO. 160. W)t Abilene Reporter "WITHOUT. OR WITH OFFENSE TO FRIENDS OR FOES WE SKE I VII YOUR WORLD EXACTLY AS IT COES,"-Byton (MM PNM (DP) ABILENE, TEXAS, MONDAY EVENING, NOVEMBER 7, 1938—TEN PAGES AmmIiM PRM (AT) PRICE FIVE CENTS 'to avenge evicted jews— Polish Youth Shoots, Gravely Wounds Nazi Embassy Aide PARIS, Nov. 7.—(AP)—A 17-year-old Folish Jew. declaring he had come to avenge his countrymen who have been expelled from Germany, I today shot and gravely wounded a secretary of the German embassy. The secretary, Ernst von Rath, 32-yemr-old nephew of the late Roland Koester, former German ambassador to France, was taken to a hospital where he underwent an oper-aton for remova' of bullets from his abdomen and one shoulder. The assailant, who gave his name as Herschel Grynszpan, formerly of Hanover, Germany, was captured by embassy attaches after a brief scuffle and handed over to the French police. The embassy spokesman said the youth who fired the shot declared he "wanted to avenge his Polish brethren." (Germany last week sent back to Poland several thousand resident Polish Jews, fearing new Polish passport regulations might deprive them of citizenship and leave them In Germany as German charges.) The youth entered the embassy at 9:35 o'clock. He was taken to the office of von Rath, who is attached to German legation service as well other attarr.es came on the run. Both shots struck von Rath and wounded him gravely. He was taken to a nearby hospital. Embassy authorities held the ms to the embassy. Two pistol sluts rang out, and youth until French police arrived. The embassy spokesman charged that the youth w s "excited by Jews in France" and indicated his belief the shooting was inspired by the recent mass expulsion of Polish Jews from Germany. —Animals In Hie News— Chums They're Good Pals In Spite Of Language Barriers MERCURY DOWN TO 28 Abilene Shivers in Earliest Snow of History I Inch on Ground 9 HUSKY HUSKER ! Windsor's Brother to Visit— RECONCILIATION FORESEEN BETWEEN DUKEAND WALLY AND BRITISH ROYAL FAMILY LONDON, Nov. 7.—(UP)—The first actual stop toward restoration of normal relations between the Duke and Duchess of Windsor and the rest, of Britain's royal family will occur Armistice day, sources close to Buckingham palace reported today. On that day, the Duke and Duchess of Gloucester, en route home from Kenja colony, will visit Edward ani his American-born wife in Paris—with the approval of King George and Queen Elizabeth. Whether the visit means that some day the woman for whom Edward gave up the British throne will be accorded a place in the royal scheme oi things was uncertain, but at least it was considered that plans for the visit were a first step toward restoring normal relations of the royal family with the duke and duchess. The visit of the Duchess of Gloucester to the Windsors will be the first time that any woman member of the British royal family has met the former Wallis Warfield of Baltimore since her marriage to the duke. It will also be the first time that the Duke of Gloucester has seen his brother since Edward's abdication to marry "the woman I love." The Windsors recently have rented a large new house on a quiet Paris boulevard and the duchess has been busy for the past two weeks directing painters, carpenters and others lr redecorating and furnishing it. The Gloucester*! are scheduled to arrive at Mar-eilles on Friday and to take an airplane to Paris Immediately for a visi' with the Windsors. They probably will spend one night there before speeding on to London. Some well-informed sources expressed belief that the visit would be a fore-runner to a visit of the Windsors to Eng-lan * in 1939. Since his abdication, the duke of Windsor has been virtually in exile from England. The government controls his income and thus is able to persuade him to live abroad, which he has done. It als( was understood that a projected visit by the Windsors to the United States next spring has been delayed as a result of the British government's opposition. JUDGE SIGNS INJUNCTION— CIO Wins Equal Rights on Jersey Streets Ruling Defeats Hague's 'War' X-Ray Effects Johnny's Cure # Two-time champ is Ted Bal-ko, pictured in action as he won the national cornhusking championship at Dell Rapids, S. D. His score of 22.24 bushels husked In 80 minutes was short of the 25.78 bushels that won him the title in 1934. Balko, 33 years old, is from Redwood Falls, Minn. .Court Rules on Minor Cases m WASHINGTON. Nov. 7.—The "Supreme court delivered 13 opinions today, but left for later determination cases involving powers of the National Labor Relations board and the status of the proposed child labor amendment to the constitution. Cases decided by the court today after a two-week recess were of minor importance. Justice Black twice added to his long string of lone dissents. In one instance he contended an attack on "a Florida statute requiring citrus fruit canners to stamp on containers the name of the state in which the product was grown should be directed at the Florida legislature rather than the courts. His fellow pjustices returned the case for trial. He differed also with another rul-* ing setting aside a $188,108 deficiency tax levied by the treasury against an estate. Left for a decision by the justices next Monday or later was litigation ^'involving the labor board's power to regulate a local company which sells its product to other concerns operating in interstate commerce. Prince to Prison rn berlin. NIV. 7—(UP)—Prince Friedrich Leopold of Prussia has been sentenced to two years in prison on charges of immorality, the foreign press was informed today. Court Fails to Say All May Assemble In Public, However NEWARK, N. J., NOV. 7.— (AP)—Federal Judge William Clark—putting into effect his decision upholding the right of the CIO and allied organizations to function in Jersey City—signed an injunction today granting them the privilege of holding meetings in the streets as long as others are allowed to do so. The Injunction—finale of a 10-month-old suit against Mayor Frank Hague and fellow officials arising out of Hague's self-styled "war on reds and radicals" and the jailing of 13 CIO organizers In what he called an "invasion"—did not, however, establish the absolute right of any one to use the public streets for meetings. SAME RULE FOR ALL It forbade the state democratic leader and his co-defendants from refusing to grant the plaintiffs permits for meetings in the streets and other public places "unless and until the defendants xxx adopt and enforce the deliberate policy of forbidding meetings of any kind on any of the public streets x x x." The CIO, American Civil Liberties union and co-plaintiffs were granted the right to use the public parks for meetings In Judge Clark's 15,000-word decision of October 27, which also gave them freedom from "deportation" by the police and allowed them the right to distribute leaflets on the streets and carry placards. These rulings were given legal effect in the injunction. Neither In his decision nor in the injunction did Judge Clark upset the city ordinance requiring a police permit for a public meeting. In his "findings of fact" accompanying the injunction, however, he said "The ordinance xxx under which the defendants have purported to act, is in its application void, unconstitutional and of no force or effect." (The plaintiffs, in addition to alleging the ordinance was unconstitutional, complained they were discriminated against in the administration of it.) The injunction restrained Mayor Hague, Publicity Safety Director Daniel Casey, Police Chief Harry Walsh and the city commission "from placing any previous restraint upon or in any other manner what- See CIO WINS Page 9, Col. 6 CHICAGO. Nov. 7—(UP) — Johnny English, 14, the boy who only five weeks ago was given a 1,000 to one chance to live more than a month, is going home. Physicians had believed that neuroma, a swift-spreadtng form of cancer, had doomed him to an early death. As a last resort the Rev. Raymond O'Brien took him to Mercy hospital and a specialist administered supervoltage X-ray. The first treatments appeared to help him. After he had been treated three weeks, he was able to get up and walk around the hospital. Last night his nurse revealed that he will be able to go home some time this week. •In Wintry Weather— MINIMUM VOTE DUE IN COUNTY • (See Page IO for more about general election.) Cold weather, combined with the usual apathy toward a general election in which little or no opposition As expected to the democratic party "lominees, may cut Taylor county balloting to a minimum tomorrow, It was indicated today. Little notice is being given the general election, and banks will be the only business houses or offices to be closed. The court house will conduct business as usual. Absentee balloting, which closed last Friday, resulted in the casting of only 25 votes, County Clerk Vivian Fryar said today. A full slate of republican, socialist and communist party nominees will go on the ballot, but the results are pre-assured. Hungary Hopes For More Gain BUDAPEST. NOV. 7.—(^—Sentiment for further territorial revision rode at high crest in Hungary today. Enthusiasm whipped up by military occupation of a sizeable chunk of Czechoslovakia inspired Hungarian leaders to tell the people this victory was "only partial justice." Hungary, they said, rejoiced that Italian-German arbitration brought the return of 4.875 square miles of territory, about one-fifth of the total lost to Czechoslovakia at the end of the world war. But, speakers added, the nation would not be satisfied with that. The 72-year-old Hapsburg Archduke Joseph, a field marshal in the World war, was one who called for a drive to gain full revision of the World war treaty of Trianon. (The post-war treaty of Trianon transformed Hungary J rom a maritime empire of about 109,000 square miles to a land-locked nation of about 35.000 square miles. (In the dismemberment of the former Austro-Hungarian empire, Czechoslovakia got about 24.300 square miles; Rumania, about 38,000 square miles; and Yugoslavia, 8,100 squarae miles. In the separation of Austria and Hungary, Austria got about 1.900 square miles. Italy got the port of Flume.) While the troops continued military occupation of the new Hungary, a special commission met today to adjust a final border with Czechoslovakia. The limitation was to take into consideration military, economic, railway, postal and administrative requirements. Salvation Army's Drive Nears End Final plans for the Salvation Army's annual drive to raise funds for the winter expenditures, launched two weeks ago, were mapped at a meeting of the board of directors this morning. Tom Brownlee, chairman, reported they hoped to conclude the drive tomorrow. Directors at the session were E. M. Overshiner. C. M. Lovelace. Bob Wiley, Jim Shelton, R. M. Means and H. G James. Demos Evade Garner Boom State Committee Expected to Elect Secretary Again MINERAL WELLS, NOV. 7.—(UP) The Garner-for-president movement was sidetracked today, when the state democratic executive committee dropped from its agenda a proposal endorsing his candidacy. The controversial issue, most wide-discussed of any on the committee docket, was dismissed from the agenda at the session's beginning. Chairman E. B. Germany of Dallas announced that the first session of the new committee, following preeednt, would be a "purely social gathering '' HARMONY ON SECRETARY The resolution endorsing Vice-President John Garner for president in 1940 was kept from reaching a vote at the state democratic convention in Beaumont last September. Opponents declared Garners differences with President Roosevelt made any declarations inopportune. The "social gathering" attitude was expected to preserve harmony j within the committee, but to block attempts to settle controversial issues. A threatened committee fight over election of an executive secretary also had a peaceful solution in sight. I An informal survey indicated that a majority of committeemen favored elevation of W. S. Sypert of Halls-1 Ville to vice-chairman, eliminating him as an opponent to Secretary Vann M. Kennedy's reelection. Kennedy, an Austin newspaper- 1 man, said that he had prepared a formal resignation, which he would present if the committee showed that they preferred Sypert as secretary. Kennedy added that he was "ready to serve" if the committee chose him. Baird Election Suit 1 Set for Wednesday ^ BAIRD. Nov. 7—(Spl>—Hearing of a suit brought by a citizens committee against the city of Baird, contesting a September 30 municipal bond election, was set for 9 o'clock Wednesday morning in 42d district court today by Judge Milburn S. Long. Set for last week, the hearing was postponed when plaintiff's counsel requested a jury. Reich Breaks Policy To Mark Armistice BERLIN, Nov. 7—(UP)—A 20-year tradition by which Armistice day has been ignored in Germany was broken today when the semiofficial Deutscer Dienst agency said that this year, because of Its triumphs, Germany could observe the day with honor. Owner to Bury Dog Taken from Mine Tomb In Front Yard, Mount Guard for Ghouls SPELTER, W. Va., Nov. 7.—(UP)—Townsfolk today viewed the body of Sport, five-year-old beagle hound, after a crew of diggers removed the dog from a mine sink where he had been entombed 17 days. Howard Walls. 19, a store clerk who owned the dog. said that Sport would be buried "under six feet of earth in the front yard of my home where I can see that no one digs him up." The dog slipped into the hole while chasing a fox. The crew of miners and WPA workers removed 25 ton* of rock trying to rescue him. INVESTIGATION SHOWS GERMAN SHIP BLAST SABOTEURS' WORK OAKLAND. Cal., Nov. 7.—(UP)—, Dist, Atty. Earl Warren of Alameda county said today there was no doubt "criminal action was involved" in the explosion that blasted a five-foot hole in the hull of the nazi steamer Vancouver at the Oakland estuary last Thursday. Warren said his investigation showed conclusively that the explo- ; sion, which injured four of the Vancouver's seamen in the engine room, came from outside the ship. German Consul-General Baron Manfred von Killinger charged that the explosion was the work of saboteurs. He suspected "anti-nazis." * "There Is no doubt that criminal action Is involved in the explosion of the nazi steamer Vancouver," Warren said. He discounted the theory of an accident by floating explosives, pointing out that the explosion occurred between seven and IO feet below the ship s water line. Warren, who directed six separate agencies in the investigation, said all the investigators, Including the Federal Bureau of Investigation, were agreed that the explosion occurred outside the ship. They sought evidence that the blast might have been caused by a time bomb. Two Anti-Trust Cases Settled WASHINGTON, Nov. 7.—— The justice department asked the United States district court at South Bend. Ind., today to approve consent decrees settling anti-trust suits in the Ford and Chrysler automobile finance cases. Because General Motors, indictee^ with the other two firms, did not propose an ' acceptable" plan for a consent decree, the department said, the case against it "must be vigorously prosecuted." Should the government lose its General Motors case, officials explained. the department will not attempt to hold Ford and Chrysler to their agreements. Although It said presentation of the decrees for court approval tn the Ford and Chrysler cases "involves no admission of guilt." the department said that on the basis of the evidence it had collected and viewed, it believed the two concerns "guilty of the anti-trust law violations charged in the Indictments." AU three were accused of restraining the competition of about 375 independent finance companies by forcing dealers to finance the C. of C. Directors To Meet Tuesday Board of directors if the Abilene chamber of commerce will meet Tuesday morning at IO o'clock In regular monthly session. Routine business and reports will occupy most of the session. Merle Qguver, manager, said today. Ride on Kitty Car May Not Be Tame POPLAR BLUFF. Mo., Nov. 7.—(UP)—A thief who stole a truck and trailer from the Harwell shows here early today is in for a surprise of his life. The highway patrol was told by managers of the show that the trailer contained wUd animals, Including two vicious tigers. f cars they sold through a manufacturer-affiliated finance company. { With Ford, it was the Universal Credit company and with Chrysler the Commercial Credit company. 'The result was," the department said, "that three-quarters of all automobile financing in the United States has been handled by the three finance companies which have had the favor, respectively, of the three large manufacturers— Ford. Chrysler and General Motors." Asserting the decrees eliminate all the coercive practices complained of, the department said they "go farther in accomplishing the purpose of the anti-trust laws than would be possible through criminal prosecution." British Ambassador And Kai-Shek Confer LONDON. Nov. 7—(UP)—The for-eign office was advised today that Sil A. Clarke Kerr, British ambassador. had conferred with Chlang Kai-Shek after trying for several days to locate the Chinese generalissimo. A foreign office spokesman said he had no knowledge of whether ! they discussed a possible peace effort. To Manege Browns ST. LOUIS, Nov. 7—(/TV—Fred I Haney, pilot of the Toledo Mud-hens of the American association the last two years and a former major league player, was named manager today of the St. Louis Browns for the 1939 season. At Stamford; Fall Is .4 Here Mercury Plunges To 16 at Texline In Cold Onslaught The earliest snow In local weather bureau history peppered Abilene and vicinity last night as the temperature ducked to 28 degrees for the season's first killing frost. When the 4 inch snow was chalked up this morning, a record established in 1889 and equaled twice since was broken by five days. The previous earliest fall was November 12, when .2 inch of snow was reported. Today's fall yielded .06 inch of moisture. TWO RECORDS THIS YEAR All North and West Texas and much of the nation shivered in the unpredictable weather that turned savage Sunday, hanging around 38 degrees all day in Abilene. At midnight the temperature was 31.9 degrees. From that time there was a gradual decline until 7 a. rn., when the low was registered. Yesterday'* misty rain brought .OI inch before turning into sleet, then snow. Thus, history twice has been written in the weatherman's hook for 1938. The hard killing freeze of April 9 had no parallel, just as last night's snow. Texline was the coldest spot in Texas with a new season low of 16 degrees. Snow and sleet amounting to an inch blanketed the Panhandle. Snow that was three-quarters to an inch deep on the South Plains was of great value to fall and winter pastures, especially wheat, according to reports from Lubbock, where below 20-degree weather spent the night. Although some vegetation was nipped October 25, that was the first killing weather at Lubbock, As not much sappy cotton is left on the Plains, a minimum damage will be suffered. Wichita Falls had first real November snow in its weather bureau history and the first freeze of the season early today. The mercury dipped to 29 degrees while snow ranging from a quarter inch to an inch was gauged. Skies were clear this morning and airline travel which was cancelled by Sunday's rain and low ceiling, was back to schedule, An estimated inch of snow was on the ground at Stamford this morning. Amarillo recorded a low of 24 degrees and the thermometer had risen to 27 degrees early in the morning. The season's first killing frost was felt at San Ai^gelo IO days earlier than in 1937. No livestock damage was reported and yesterday there was .08 inch rain. Rains that began shortly after midnight Saturday visited many sections, breaking an unusually hard fall drouth. South Texas received the first precipitation in months, but much more is needed for fall grains. The same holds See WEATHER Page 9, Col. I KIBITZER "Nippy," a Maltese fox terrier,' puffs her pipe and looks on critically while her master, W. S. Budd of Sydney, Australia, scans his racing form in search of a winning horse. The Weather ABI UEKI and vicinity Fair with freezing temperature tonight, Tueeday fair and not quite *o cold Wast Tex** Fair continued cold, heavy to killing froat tonight. Tueadav fair. not quite ao cold. Bait Tex**: Fair. elighUy colder in south portion, frost neariv to coast, freezing in north portion tonight; Tuesday fair, not quite so cold. PRECIPITATION; 24 hrs. ending 6:30 a m. Mon .07 tnch Since first of year ...........31.63 inches Same period last year ........16 23 inches Normal since first of year ...22.80 Inches Highest temperature yesterday ....45 Lowest temperature this morning 28 ONIZ33UJ TEMPERATURES I Sun. Mon. VO FRAIDY CAT Rats may flee from a sinking ship — but not Fluffy. She stayed with the crew of the burning schooner Pioneer until rescued by the American Banker while 400 miles out of Halifax. She is shown here with one of the sailors who remembered her, Gus Anderson. STI'DENT AT BEGGING An old cockatoo learns new tricks as she watches the morej experienced parrot. Joey, beg-j gins from their caretaker. The, newly-acquired cockatoo is of the silver crested variety and is believed to be more than 140 years old. KRIEN!) OK CRIPPLE Once yearly the crippled boys of the Heritage Craft School at Chancy. Sussex. England, round up all their bird and animal friends and take them to church services. This boy soothes his frightened pigeon bcfoic entering the chapel. ~ Sunset 6:30 p.m 6:30 Dry thermometer 37 Wet thermometer 33 Relative humidity SS * 40 ........7:01 ........5:45 rn. 12:39 p m. 29 42 28 34 SI 411 Mitchell Draws Life Sentence BAIRD. Nov 7—(Spl)—Lonnie Mitchell, Merkel negro, was sentenced to life imprisonment in the state penitentiary in a speedy 424 district court trial this morning. He pleaded guilty to the murder of Chester Hutcheson, city marshal pf Merkel. The verdict was returned Just 25 minutes after testimony was started. Only two witnesses were called. The first took the stand at 10:50 a. rn. At ll o'clock the case went to the jury. The verdict was returned 15 minutes later. Mitchell was given the death penalty twice in 42d district court trial* in Abilene, each sentence being appealed, reversed and remanded. The third trial was transferred to Callahan county in October on a change of venue motion offered by defense attorneys. Hutcheson was shot in front of a cafe operated by Mitchell when he went to make an arrest, April ll? 1936. After Mitchell entered the guilty plea Dist. Atty. J. R. (Bob) Black: See MITCHELL Page 9, Cal. I ;
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The Skit Book: 101 Skits for Kids
Viewing skits as an aspect of folklore this is more a general resource than an actual book of scripts. A list of characters, an outline of the action, and suggested dialogue or improvisations for each is given rather than the formal scripts, stage directions, and production notes found in other collections. Props and scenery are kept to a minimum, and in keeping with the oral tradition, flexibility in length and numbers of actors, as well as variations on the action are indicated. The material, submitted by camps, schools, and youth groups, should appeal to the young and the young-at-heart. Pen-and-ink drawings are a delightful accompaniment to the text.
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text: Collegiate Flags > USC Trojans Flag USC 2x3 Flag View All USC Trojans Flag ITEMS Quantity $29.95 Out of Stock Add to Cart IN STOCK Standard & Express Shipping Available Order by 2pm CST (M-F) — Ships Same Day Item ID#: NM-2x3NM-USC Tweet Wish Share Our USC 2x3 Flag is constructed of 100% nylon, measures 2'x3', has quadruple-stitched fly ends, and metal grommets. The Official Southern Cal 2x3 athletic logos are embroidered into our USC 2x3 Flag which results in a durable and quality flag.This flag is viewable on both sides with the opposite side being a reverse image.Use this flag as a large boat flag or fly under your US Flag on our tailgate flagpole. Customers Also Bought... Flag & Pennant Accessories USA 3x5 Ft. Flag $28.95 Out of Stock Add To Cart


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Conley harnesses tools of social science, genomics to answer lifelong questions
Driven by questions that date to his childhood, sociology professor Dalton Conley combines the power of new genetic tools with traditional social science in research that focuses on how genes and environment interact to shape life outcomes.
Princeton launches new main website, more improvements to come
Princeton University has launched a redesigned main website that features improved search capabilities, streamlined navigation and greater emphasis on photos and videos. Its flexible format adjusts to screens of all sizes.
University News
Kleiner, two Princeton alumni, receive 2017 Kimmel Scholar Award for cancer research
Study identifies RNA molecule that shields breast cancer stem cells from immune system
Princeton to honor four outstanding New Jersey secondary school teachers
New model helps predict regional and seasonal sea ice extent
Nitrogen contained in coral provides evidence of human impact on the open ocean
Alumnus Lloyd Cotsen, emeritus trustee and 'transformative' benefactor, dies at 88
Bright future: Unlocking the potential of light
The leader in the emerging field of using light to perform feats of chemistry is David MacMillan, who arrived in Princeton's chemistry department in 2006. He was intrigued by the potential for using light to coax new chemical reactions. Like most chemists, he'd spent years learning the rules that govern the interactions of elements such as carbon, oxygen and hydrogen, and then using those rules to fashion new molecules. Could light help change these rules and catalyze reactions that have resisted previous attempts at manipulation?
Learning through the camera lens: International Eye photo contest captures student perspectives abroad
For the ninth year, the International Eye Photo Contest has provided an opportunity for students to share their experiences studying, working, doing service or conducting research abroad.


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The mission of Business Advisers of
Cleveland (BAC) is to contribute to the success of start-up and small for-profit businesses and
non-profit organizations by providing cost effective business advice and counsel, through its
experienced, professional members.
BAC counsel individuals residing in the greater Cleveland area and Northeast Ohio. Although the majority of our individual clients reside in Cuyahoga County, we also present talks on entrepreneurism, marketing and finance for business at public libraries all over Northeast Ohio.
Through our partnership with Business Volunteers Unlimited in Cleveland and Akron, we assist area non-profits in developing better business/operational practices.
Ms. Nicholi Evans
Free advice to businesses, start-ups and nonprofits
Also Known As
Business Advisors of CLEVELAND﹨BAC
Physical Address
401 Prospect Park Building 4614 Prospect Ave
Cleveland, OH 44103
See more addresses
Main Address
4614 Prospect Ave Suite 401
Cleveland, OH 44103
Physical Address
401 Prospect Park Building 4614 Prospect Ave
Cleveland, OH 44103
Management Services for Small Business/Entrepreneurs (S43)
Single Organization Support (J11)
Management & Technical Assistance (B02)
IRS Filing Requirement
This organization is required to file an IRS Form 990 or 990-EZ.
How does this organization make a difference?
Self-reported by organization
For almost sixty years, Business Advisers of Cleveland (BAC) has given free advice and counsel to individuals interested in starting their own businesses or small business owners who want to expand their businesses. Our members are passionate supporters of economic growth in Cleveland and they recognize the critical role small business plays in this effort.
Over the past year, BAC has continued to offer free seminars to interested individuals at several public libraries. This year, we have formalized an agreement with Cuyahoga County Public Library to offer business seminars in 6 different branches throughout the county. We have also expanded our presentations to include in-depth information on Developing a Business Plan; Understanding Finances for Small Business; and Grow Your Business - Developing a Marketing Plan.
We have also continued our relationship with Business Volunteers Unlimited in offering counseling services to nonprofit organizations. Other partnerships we have developed and continue to maintain include Cuyahoga Community College-Corporate College and Ashland University's Scholarship for Entrepreneurial Engagement for high school students.
So strongly do our members believe in their work that almost one-half of our annual operating support is generated by their membership dues. In 2010, we are actively organizing a new membership campaign to recruit men and women who are interested in giving back to the community and supporting small business endeavors in northeastern Ohio.
Self-reported by organization
What are the organization's current programs, how do they measure success, and who do the programs serve?
Program 1
Counseling Services free-of-charge Seminar Programs offered in public libraries
Program long term success
Counseled approximately 300 clients
Program success monitored by
Not available
Program success examples
Not available
Population(s) Served
BAC counsel individuals residing in the greater Cleveland area and Northeast Ohio. Although the majority of our individual clients reside in Cuyahoga County, we also present talks on entrepreneurism, marketing and finance for business at public libraries all over Northeast Ohio.
Through our partnership with Business Volunteers Unlimited in Cleveland and Akron, we assist area non-profits in developing better business/operational practices.
Funding Needs
Throughout our history, BAC has relied on the fees generated from our members for at least half of our operating support. And like other non-profits, BAC also relies on the support of generous individual, foundation and corporate donors. But over the past few years, we have experienced a significant drop in corporate donations. BAC was founded by retired business people, so it is from there we have tried to secure additional operating support. Unfortunately, many of BAC's corporate supporters have either merged with other organizations, moved out of the city, or have been acquired. Even though the overall economy in Cleveland is extremely difficult, people are still excited about starting their own businesses. So we continue to solicit additional funds that will enable us to carry out our mission.
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The people, governance practices, and partners that make the organization tick.
Ms. Nicholi Evans
Mr. Roger S. Vail
Retired, No Affiliation
Term: Jan 2012 - Dec 2012
GuideStar worked with BoardSource, the national leader in nonprofit board leadership and governance, to create this section, which enables organizations and donors to transparently share information about essential board leadership practices. Self-reported by organization
Does the board conduct a formal orientation for new board members and require all board members to sign a written agreement regarding their roles, responsibilities, and expectations?
Has the board conducted a formal, written assessment of the chief executive within the past year?
Have the board and senior staff reviewed the conflict-of-interest policy and completed and signed disclosure statements in the past year?
Does the board ensure an inclusive board member recruitment process that results in diversity of thought and leadership?
Has the board conducted a formal, written self-assessment of its performance within the past three years?


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Closed streets in downtown Orlando cause big headache for drivers
ORLANDO, Fla. - Rosalind Avenue is closed for a block in front of the new Dr. Phillips Center for the Performing Arts, which forced a lot of drivers coming off the State Road 408 to take a detour.
Despite the fact that only one block of busy Rosalind Avenue is closed, it is expected to cause some traffic problems for many drivers heading into downtown.
The section of the three-lane street will be shut down until Saturday, Feb. 22.
"We know there will be some disruption to people's ordinary routines," said transportation engineer Charles Ramdatt.
City officials posted signs in the area several weeks ahead of time to warn drivers and posted the routes online, but it was still a hectic morning for many drivers.
"The teachers were late getting to their classrooms this morning," said Teresa Manno, who works at a day care on Rosalind Avenue.
Faced with the detour, many drivers went whatever way they wanted, blocking lanes as traffic lights changed. A community patrol officer was on the scene, but that didn't seem to stop drivers from going whichever way they wanted.
The city now has cones out to help guide drivers, and traffic engineers are reprogramming the traffic light.
City officials said construction crews will do their work as quickly as possible to get out of the way of drivers as soon as possible.
The street is being reinforced for a heavier load of traffic, including the weight of tractor-trailers that will use the street to get equipment in and out for shows at the new Dr. Phillips Center for the Performing Arts.
City officials are now trying to complete the work ahead of schedule.
More Information: Map of closure and alternate routes
Plan your route: WFTV.com Traffic Tracker
For up-to-the minute traffic information follow @WFTVTraffic on Twitter
Closed streets in downtown Orlando cause big headache for drivers
Stable gas prices expected to boost Memorial Day road trips
Woman killed in wrong-way crash in Orange County, troopers say
Brush fire briefly shut down portion of SR 408 in Orange County
State Road 44 reopens after being closed due to smoke from Volusia…