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I have developed a tool that will create bobbin lace tessellation patterns from a template and then allow you to edit the designs using a Scalable Vector Graphic (SVG) image editing tool called InkScape.
Below is a gallery of over 200 lace tessellations which you can use to design lace patterns in InkScape. All of these templates are available for download.
How to Install the Tool
Step 1) Install InkScape.
InkScape is a free, open source drawing tool that runs on Windows, Mac OS X and Linux. It is very similar to Adobe Illustrator. You can download InkScape from the following website: www.inkscape.org
Note: If you are using Mac OS X Mountain Lion (10.8) or higher, you will need to follow the MAC-OS install instructions in order to make InkScape work.
Step 2) Install the lace tool extensions.
Download the zip file extensions.zip. It contains the following six files:
- lace_grid.inx
- lace_grid.py
- lace_ground.inx
- lace_ground.py
- lace_circular.inx
- lace_circular.py
Extract the files from the zip file and place them in the InkScape extensions folder.
- Windows: "C:\Program Files\InkScape\share\extensions"
- Windows 64 bit: "C:\Program Files (x86)\InkScape\share\extensions"
- Linux: "/usr/share/inkscape/extensions"
- Mac OS X: "/Applications/InkScape.app/Contents/Resources/extensions"
For more information, consult the InkScape Extensions wiki page.
How to Use the Tool
When you start InkScape, if the lace tool extensions are installed correctly you should see a menu called "Bobbin Lace" under the main "Extensions" menu. Under the "Bobbin Lace" menu you will see three options: "Circular Ground from Template…", "Ground from Template…" and "Regular Grid…".
The Bobbin Lace "Regular Grid" tool will allow you to draw a grid of dots. In the pop up dialog you can specify the angle of the grid, the distance between the footside pins and the size of rectangle you want to fill with dots. After you have selected the desired values, click on the "Apply" button.
The distance between footside pins is the vertical measurement between two dots on the grid. When designing lace, you can use the handy reference by Brenda Paternoster to determine the size of your grid based on the size of your thread.
The Bobbin Lace "Ground from Template" tool will allow you to draw a lace ground pattern. Note: In the ground pattern, each line represents a pair of threads. In the pop up dialog you can specify the grid angle, distance between footside pins and the size of rectangle you want to fill with the ground pattern. You must also choose what type of ground to draw by giving the location and name of a template file.
The Bobbin Lace "Circular Ground from Template" tool will allow you to draw a lace ground pattern wrapped around a circle. In the pop up dialog you can specify the inner radius of the circle, the number of copies of the pattern around the circle, number of rings and the grid angle. You must also choose what type of ground to draw by giving the location and name of a template file.
In the overview section at the top of this page, you will see a number of example ground patterns that can be drawn with this tool. You can download these template files for your own use.
For general information on how to use the InkScape drawing tool, there is an excellent on line book as well as tutorials. For example, you might like the section on bending images.
Design Your Own Templates
In addition to the templates that I have provided, you can create your own.
Here is a sample template which draws the rose ground:
The templates must have the following format:
The first line contains the word "CHECKER" (all in upper case) followed by a tab followed by a number followed by a tab followed by another number. The word CHECKER indicates that the pattern will be repeated in a checkerboard fashion. In the future I hope to support other ways of tiling the ground but for now only CHECKER is supported. The first number is the number of rows in a single copy of the pattern. The second number is the number of columns.
The next lines of text describe the lines in the pattern. They consist of square brackets separated by tabs. Inside the square brackets, the numbers are separated by commas and the numbers represent the positions of three points (x1,y1), (x2,y2) and (x3,y3) as shown in the following diagram.
The values are written in the order [x1,y1,x2,y2,x3,y3] and the numbers represent the column and row position of the points in the pattern. Counting starts at 0 and increases to the right for columns and increases downward for rows. For example, in the diagram above, we have a pattern that is 5 rows by 5 columns and the lines drawn are represented as [0,1,0,3,3,2]
For the x and y values, you can also you use decimal numbers for lines that end somewhere in between the grid points.
You can put all of your square brackets on one line or break them into several lines to make it easier to read.
NOTE: Do not leave any blank lines at the end of your template.


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Cigarette smoke is a profound proinflammatory stimulus that causes acute lung inflammation and chronic lung disease, including chronic obstructive pulmonary disease (COPD, emphysema, and chronic bronchitis), via a variety of mechanisms, including oxidative stress. Cigarette smoke contains high levels of free radicals, whereas inflammatory cells, including macrophages and neutrophils, express enzymes, including NADPH oxidase, nitric oxide synthase, and myeloperoxidase, that generate reactive oxygen species in situ and contribute to inflammation and tissue damage. Neu-164 and Neu-107 are small-molecule inhibitors of myeloperoxidase, as well as potent antioxidants. We hypothesized that Neu-164 and Neu-107 would inhibit acute cigarette smoke-induced inflammation. Adult C57BL/6J mice were exposed to mainstream cigarette smoke for 3 days to induce acute inflammation and were treated daily by inhalation with Neu-164, Neu-107, or dexamethasone as a control. Inflammatory cells and cytokines were assessed by bronchoalveolar lavage and histology. mRNA levels of endogenous antioxidant genes heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were determined by qPCR. Cigarette smoke exposure induced acute lung inflammation with accumulation of neutrophils and upregulation of proinflammatory cytokines, including IL-6, macrophage inflammatory protein-2, and keratinocyte-derived cytokine. Both Neu-164 and Neu-107 significantly reduced the accumulation of inflammatory cells and the expression of inflammatory cytokines as effectively as dexamethasone. Upregulation of endogenous antioxidant genes was dampened. Neu-164 and Neu-107 inhibit acute cigarette smoke-induced inflammation by scavenging reactive oxygen species in cigarette smoke and by inhibiting further oxidative stress caused by inflammatory cells. These compounds may have promise in preventing or treating lung disease associated with chronic smoke exposure, including COPD.
- chronic obstructive pulmonary disease
- antioxidants
- inflammation
- anti-inflammatory
- cigarette smoke
chronic obstructive pulmonary disease (COPD, chronic bronchitis, and emphysema) is the fourth leading cause of death worldwide and is projected to be the third by the year 2020 (44). In the United States alone, COPD affects 15 million people at an annual direct and indirect cost-of-illness of more than $6.6 billion (7). Cigarette smoking is the leading risk factor for developing COPD. Approximately 22% of Americans smoke. While significant gains have been made in reducing smoking rates among adults, teenage smoking is on the rise, and a disproportionate number of smokers are minorities (7, 44). COPD associated with cigarette smoking and burning of biomass fuels for heating and cooking is an increasing problem in less well-developed countries (63). There are no effective treatments to cure or reverse COPD; the disease can only be symptomatically managed. Thus, there is intense and ongoing interest in the development of novel therapeutic agents for smoking-related lung diseases.
Cigarette smoke (CS) is a strong inflammatory stimulus that induces production of proinflammatory cytokines such as IL-6, IL-8, and TNF-α and recruits macrophages and neutrophils to lung tissue (13, 37, 47). CS contains high levels of free radicals and other reactive oxygen species (ROS) that contribute to proinflammatory activation of lung cells via NF-κB and other redox-sensitive transcription factors (10, 35, 52, 53). Additional ROS, including superoxide, H2O2, and hypochlorus acid, are released by inflammatory macrophages and neutrophils via the action of enzymes, including xanthine/xanthine oxidase, myeloperoxidase (MPO), and NADPH oxidase (30, 69). Current smokers exhibit multiple indications of chronic oxidative stress, including decreased levels of glutathione peroxidase in the saliva, higher levels of ROS in the blood, decreased circulating endothelial precursor cells, and higher levels of glutathione in epithelial lining fluid (24, 25, 50). Epidemiological studies have suggested a link between higher dietary antioxidant consumption and reduced severity of smoking-associated lung disease, and numerous antioxidants have been tested in animal models of cigarette smoking (12, 48). Significantly, 8-isoprostane, a marker of oxidative stress, was elevated in ex-smokers with COPD relative to both nonsmokers and "healthy" smokers (39), whereas an MPO inhibitor was recently shown to reduce airspace enlargement in mice chronically exposed to CS (14). Taken together, these results suggest that inflammatory cells in COPD contribute significantly to the overall burden of oxidative stress in smoking.
The role of leukotrienes in COPD has also been investigated. Cysteinyl leukotrienes are synthesized from arachidonic acid via the enzyme 5-lipoxygenase (5-LO) and are generally proinflammatory. Cysteinyl leukotrienes are potent bronchoconstrictors and also act to increase vascular permeability to cause edema and enhance mucus secretion (36). Leukotriene B4, a neutrophil chemoattractant and activator, is increased in exhaled breath condensate from COPD patients (21, 27). Inhibitors of the leukotriene pathway were found somewhat effective in several clinical trials in COPD (20, 54).
Caffeic acid is a potent antioxidant and 5-LO inhibitor (26). Several indole-related compounds have been studied as reversible inhibitors of MPO activity (34). We hypothesized that combining these two functional groups in a single compound would have beneficial effects in smoking-related lung disease by attacking multiple pathological pathways, including oxidative stress, MPO, and 5-LO. Neu-164 and Neu-107 are novel small-molecule caffeic acid-indole conjugates with different bridges (Fig. 1, A and B). Here, we report that Neu-164 and Neu-107, delivered by inhalation, strongly inhibited acute CS-induced inflammation in a widely used preclinical mouse model.
Ethics statement.
All animal procedures were approved and supervised by the University of Rochester University Committee on Animal Resources (UCAR permit no. 2007-127). For euthanasia and tissue harvest, mice were anesthetized with an intraperitoneal injection of Avertin (2,2,2-tribromoethanol, 250 mg/kg), followed by exsanguination and tissue harvest once the animals reached a surgical plane of anesthesia. All efforts were made to minimize suffering.
Antioxidant assays.
Inhibition of the oxidation of the fluorescent molecule scopoletin to a nonfluorescent product by horseradish peroxidase (HRP) was determined in the presence of 2 μM H2O2 and varying concentrations of Neu-164 (18) by Cerep (Paris, France). The reduction in fluorescence is reported as a percent of control.
Superoxide scavenging was measured using a commercial superoxide dismutase assay kit (Cayman Chemical, Ann Arbor, MI). Superoxide (generated by xanthine oxidase and hypoxanthine) oxidizes a tetrazolium salt to a colored formazan dye. For this assay, the reactions were run without superoxide dismutase but with increasing concentrations of Neu-164, and the formation of the colored product was measured at 420 nm.
The MPO inhibition assay assessed the ability of the Neu compounds to inhibit the conversion of guiacol to tetraguiacol by purified human MPO (60). A large excess (44 μM) of H2O2 was included in the reaction to exclude H2O2 scavenging as the explanation for the activity decrease. The 5-LO inhibition assay measured the ability of the Neu compounds to inhibit the conversion of arachidonic acid to leukotriene B4 by 5-LO in human peripheral blood mononuclear leukocytes. The MPO and 5-LO assays were performed at MDS Pharma Services (Taiwan).
CS exposure.
Adult female C57BL/6J mice were purchased from The Jackson Laboratory (Bar Harbor, ME) and housed in the Inhalation Core Facility at the University of Rochester. Mainstream CS exposures were as previously described (35, 61, 62). Mice were placed in individual compartments of a wire cage that was placed inside a closed plastic box connected to the smoke source. Research cigarettes (2R4F, University of Kentucky College of Agriculture Reference Cigarette Program) were smoked according to the FTC protocol (1 puff/min of 2-s duration and 35-ml volume) in a Jaeger-Baumgartner CSM2072i cigarette smoking machine (CH Technologies, Westwood, NJ). Mainstream CS was diluted with filtered air and directed into the exposure chamber. The smoke exposure (total particulate matter/cubic meter of air, TPM) was monitored by gravimetric sampling. The smoke concentration was set at a nominal value of 400 mg/m3 TPM by adjusting the flow rate of the dilution air. The average actual exposure for these experiments was 418 ± 31 mg/m3. Mice received two 1-h exposures, 4 h apart, for three consecutive days and were harvested on the 4th day. Control mice were exposed to filtered air in an identical chamber according to the same schedule. All animal procedures were performed under the supervision of the University Committee on Animal Research.
Neu-164 and Neu-107 were provided by Neurim Pharmaceuticals (Tel Aviv, Israel); dexamethasone was from Sigma (St. Louis, MO). The compounds were administered by oropharyngeal aspiration (29) under isoflurane anesthesia. The mice received Neu-164, Neu-107, or dexamethasone at 1 μg/day, or Neu-164 only at 5 μg/day in a 40-μl volume, corresponding to 40 or 200 μg/kg for a 25-g mouse. The mice were treated one time per day, beginning 1 day before the first smoke exposure, and continuing daily 1 h before the first smoke exposure of each day, for the duration of the 3-day exposure protocol. The compounds were prepared as 10 mg/ml stock solutions in DMSO and were diluted on the day of use with sterile PBS; the final dilutions contained 2% DMSO, and 2% DMSO in PBS was used for vehicle controls.
Tissue harvest and analysis.
Mice were anesthetized with 2,2,2-tribromoethanol (Avertin, 250 mg/kg ip) and killed by exsanguination. The heart and lungs were removed en bloc, and the lungs were lavaged two times with 0.5 ml PBS. The lavage fluid was centrifuged, and the cell-free supernatants were frozen for later analysis. The lungs were snap-frozen in liquid nitrogen for later analysis. The bronchoalveolar lavage (BAL) cell pellet was resuspended in PBS, and the total cell number was determined by counting on a hemacytometer. Differential cell counts (minimum of 300 cells/slide) were performed on cytospin-prepared slides (Thermo Shandon, Pittsburgh, PA) stained with Diff-Quik (Dade Behring, Newark, DE). Cytokines in BAL fluid were measured by cytokine multiplex analysis (Milliplex MAP; Millipore, Temecula, CA) and read on a Luminex 100 (Luminex, Austin, TX). Total protein in BAL fluid was measured by the bicinchoninic acid colorimetric assay (Thermo Scientific, Rockford, IL).
For histological sections, mouse lungs that had not been lavaged were fixed by inflation with 10% neutral buffered formalin at a pressure of 15 cmH2O. Tissues were embedded in paraffin, sectioned (5 μm), and stained with hematoxylin and eosin. To visualize neutrophils, sections were stained with a rat monoclonal anti-mouse neutrophil antibody (MCA771GA, 1:25 dilution; Serotec, Oxford, UK), developed with NovaRed (Vector Laboratories, Burlingame, CA), and counterstained with hematoxylin. Oxidation of DNA was detected using an antibody to 8-oxoguanine (8-oxoG, ab64548, 1:250 dilution; Abcam, Cambridge, MA) and developed with NovaRed.
Quantitative RT-PCR.
Forty milligrams of lung were excised from total frozen lung, and RNA was extracted using a commercial kit according to the manufacturer's instructions (Qiagen, Valencia, CA). RNA (1 μg) was reverse-transcribed using the iScript cDNA synthesis Kit (Bio-Rad, Hercules, CA), and the cDNA was subjected to quantitative real-time PCR using SYBR GreenER in a Bio-Rad iQ5 cycler. In brief, a 20-μl mixture was used containing 10 μl iQ SYBR Green Supermix, 0.5 μl forward and reverse primer, 7.5 μl sterile water, and 2 μl of the 1:5 diluted cDNA template. The real-time PCR was performed under the following conditions: 1 cycle at 95°C for 3 min, then 40 cycles at 95°C for 10 s, 55°C for 30 s, 95°C for 1 min followed by 55°C for 1 min. The intron-spanning primers were designed using sequence information from the NCBI database. The Ct values were normalized to the endogenous control (18S RNA). Primer sequences are listed: m18s RNA, 5′-GCTTGCTCGCGCTTCCTTACCT-3′; m18s RNA, 5′-TCACTGTACCGGCCGTGCGTA-3′; mHo1 forward, 5′-AGGTACACATCCAAGCCGAGA-3′; mHo1 reverse, 5′-CATCACCAGCTTAAAGCCTTCT-3′; mGlgc forward, 5′-CTACCACGCAGTCAAGGACC-3′; and mGlgc reverse, 5′-CCTCCATTCAGTAACAACTGGAC-3′.
Statistical analysis.
All results are reported as means ± SE. Statistical significance was assessed by ANOVA using GraphPad Prism. A P value <0.05 was considered significant.
Neu-164 and Neu-107 have potent antioxidant and anti-MPO activity.
Oxidative stress plays an important role in the pathology of CS-induced lung inflammation. The experimental anti-inflammatory compounds Neu-164 and Neu-107 were assayed for their antioxidant properties using antioxidant enzyme assays under standard conditions, with increasing amounts of the compounds. HRP catalyzes the conversion of scopoletin to a nonfluorescent product in the presence of H2O2. With the use of fixed amounts of HRP and H2O2 and increasing amounts of Neu-164, it was found that Neu-164 inhibited the reaction with micromolar affinity (Fig. 1C). Similarly, Neu-164 has potent scavenging activity against superoxide radical (generated by xanthine oxidase and hypoxanthine) and inhibited the superoxide-mediated oxidation of a tetrazolium indicator to its colored product (Fig. 1D). Large numbers of neutrophils are recruited to lung tissue following acute CS exposure, and it is believed that MPO released by neutrophils plays a causative role in lung tissue damage seen in emphysema (14, 34). Neu-164 and Neu-107 inhibit MPO activity with low-micromolar affinity (Table 1 and Fig. 1E). Finally, Neu-164 and Neu-107 were also effective 5-LO inhibitors with submicromolar affinity (Fig. 1F).
Neu-164 and Neu-107 inhibit acute CS-induced lung inflammation.
To investigate the anti-inflammatory effect of Neu-164 and Neu-107 in vivo, C57BL/6J mice were exposed to CS for 1 h, two times a day for 3 days. Neu-164 or Neu-107 was given by inhalation 1 h before the first smoke exposure on each day. Dexamethasone was included as a positive control for the inhibition of acute inflammation. The mice were killed on the 4th day, and the acute inflammatory response was determined.
As previously described with this model system, mice exposed to CS for 3 days develop acute lung inflammation, characterized by significant increases in the number of neutrophils recovered by BAL (23, 61). Neu-164 and Neu-107 each inhibited the CS-induced increase in total BAL cell numbers (Fig. 2A). Neu-164 and Neu-107 also significantly inhibited neutrophil accumulation. Dexamethasone had similar effects. There were no significant differences in the number of BAL lymphocytes or eosinophils between drug-treated and vehicle-treated mice (Fig. 2D and data not shown).
Neu-164 and Neu-107 reduce infiltration of lung tissue by neutrophils in CS-exposed mice.
Lungs from mice exposed to air or CS and treated with Neu-164, Neu-107, or dexamethasone were fixed, and sections were stained with hematoxylin and eosin. Exposure to CS induced a significant perivascular inflammation compared with air exposure (Fig. 3, A and E). Neu-164 and Neu-107 at 40 μg/kg both reduced the number and size of these infiltrates (Fig. 3, F and G). Neu-164 at 200 μg/kg had a similar effect (data not shown). Neutrophils were also visualized by immunostaining with Vector Red. Neu-164 and Neu-107 (Fig. 3, N and O) also reduced the number of perivascular and tissue-infiltrating neutrophils in CS-exposed mice compared with CS-exposed vehicle-treated controls (Fig. 3M). The results are comparable to inhaled dexamethasone at the same dose.
Neu-164 and Neu-107 inhibit the production of inflammatory cytokines.
We analyzed the levels in BAL fluid of several proinflammatory cytokines that are important to lung inflammation. IL-6, a key regulatory cytokine that is strongly upregulated by CS, was significantly inhibited by Neu-164 (Fig. 4A). Neu-107 reduced IL-6 levels by 33%. Although this reduction was not significant, neither was there significantly more IL-6 than with Neu-164. Interestingly, another key cytokine, TNF-α, which is also upregulated by CS exposure, was not affected by Neu-164 or Neu-107 (Fig. 4B). Macrophage inflammatory protein (MIP)-2 and keratinocyte-derived cytokine (KC) are the mouse homologs of IL-8 and recruit neutrophils by binding to CXCR2 on the neutrophil surface (62, 71). Consistent with the reduction in neutrophilic inflammation, both Neu-164 and Neu-107 inhibited production of KC, whereas Neu-164, but not Neu-107, inhibited MIP-2 (Fig. 4, C and D). Finally, we analyzed the production of macrophage chemotactic protein (MCP)-1 (CCL2), which is produced by fibroblasts and epithelial and endothelial cells and recruits monocytes and macrophages. Although Neu-164 and Neu-107 reduced levels of MCP-1 in BAL fluid to a lesser degree than that of KC, MIP-2, or IL-6, the reduction is statistically significant (Fig. 4E). The anti-inflammatory steroid dexamethasone has approximately the same effectiveness at Neu-164 at the same dose. Acute smoke exposure also increases total protein in BAL fluid, an indicator of edema (61). Here, acute CS exposure results in a significant upregulation of total BAL protein in vehicle-treated mice (Fig. 4F). Treatment with dexamethasone or the Neu compounds somewhat reduces total BAL protein, suggesting a partial protective effect against edema.
Activation of antioxidant genes is reduced in mice treated with Neu-164 and Neu-107.
Because Neu-164 and Neu-107 are potent antioxidants, we examined whether drug treatment altered the expression of two key antioxidant genes known to be upregulated by acute CS exposure. Heme oxygenase-1 (HO-1) catalyzes the conversion of heme to biliverdin and carbon monoxide, both of which have free radical scavenging activity, and has been demonstrated to be critical for maintaining appropriate redox balance in CS exposure (8, 31). Glutamate-cysteine ligase (modifier subunit, GCLm) is the rate-limiting enzyme in the synthesis of glutathione, a key intracellular antioxidant (31). These oxidative stress response genes were shown to be strongly upregulated in mice exposed to CS (51). Here, RNA was extracted from lung tissue from mice exposed to air or CS treated with vehicle, Neu-164, or Neu-107. As shown in Fig. 5, GCLm and HO-1 were both significantly upregulated by CS. Neu-164 significantly inhibited upregulation of both HO-1 and GCLm. Neu-107 also prevented upregulation of both HO-1 and GCLm.
To further examine oxidative stress, we used immunohistochemistry to detect 8-oxoG, an important mutagenic DNA lesion generated under oxidative stress. Because the lungs are constantly exposed to oxygen, the airway epithelium of air-exposed mice exhibited a basal level of 8-oxoG staining (Fig. 5, C and D). Consistent with prior reports (68), acute CS exposure strongly induced 8-oxoG staining (Fig. 5E) in airway epithelial cells and also in parenchymal cells. Interestingly, 8-oxoG staining was reduced by treatment with Neu-164.
CS is a profound proinflammatory stimulus, causing inflammation within minutes of the first cigarette. CS contains numerous chemicals that activate proinflammatory pathways, including nicotine, acrolein, acetaldehyde, benzo[a]pyrene, and others (2, 38, 57, 58). CS also incites inflammation through oxidative stress. There are two principal sources of ROS in smoke. Tobacco smoke itself contains up to 1 × 1017 oxidants and free radicals per puff, and CS tar contains reactive aldehydes, quinones, and other organic molecules that can generate ROS in situ after deposition in the lungs (11, 42). A second significant source of ROS in cigarette smoking are inflammatory cells themselves, including monocytes/macrophages and neutrophils, that produce free oxygen and nitrogen radicals via the action of multiple enzymes, including NAPDH oxidase, xanthine/xanthine oxidase, and MPO (64, 69). ROS contribute to inflammation by activating multiple proinflammatory signaling pathways, including notably the activator protein-1 and NF-κB transcription factors (3, 10, 35, 40, 52, 67, 70). ROS also cause oxidation of proteins, lipids, and DNA, leading to cellular damage and death (via apoptosis or necrosis) and also contributing to inflammation and chronic tissue damage (1, 28, 53, 67, 70). Thus, there is great interest in the use of antioxidants to prevent and treat smoking-related lung disease. Thiol compounds such as N-acetylcysteine and carbocysteine have been extensively studied, as well as mimetics of superoxide dismutase and glutathione peroxidase, and inhibitors of nitric oxide synthase (4, 49).
Caffeic acid derivatives are potent antioxidants and have shown some protective effects in CS-exposed rats and rabbits (19, 46, 55). Caffeic acid is also a potent inhibitor of 5-LO (26), which is upregulated in COPD patients (21, 27). Indole compounds also have antioxidant properties and have been developed as MPO inhibitors (34). Neu-164 and Neu-107 were developed as caffeic acid-indole conjugates and evaluated for their antioxidant and enzyme inhibitory activities. Neu-164 and Neu-107 are potent scavengers of superoxide and inhibit MPO and 5-LO at micromolar or submicromolar concentrations (Fig. 1 and Table 1). We did not specifically study the mechanism of action, but we note that indoles are reversible inhibitors of MPO that act as poor peroxidase substrates and inhibitors of the chlorination reaction (reviewed in Ref. 34). This inhibition can be partially lifted by superoxide, which reduces the heme group in the enzyme back to its native state. In this context, the superoxide scavenging function provided by the caffeic acid functional group (22) may potentiate the efficacy of the Neu compounds by limiting their reversibility by in situ superoxide. We also note that, while the scopoletin assay is generally described as an assay for H2O2 scavenging by antioxidants (6), we cannot determine whether inhibition of the assay by Neu-164 (Fig. 1C) was due to H2O2 scavenging or inhibition of the HRP used in the assay. However, Neu-164 and Neu-107 clearly are potent superoxide scavengers and inhibitors of MPO and 5-LO.
Next, we investigated the effects of Neu-164 and Neu-107 in an acute model of CS exposure. Both Neu-164 and Neu-107 inhibited acute neutrophilia in mice exposed to CS for 3 days (Figs. 2 and 3). Neu-107, which was more effective at inhibiting MPO and 5-LO enzyme activity, was also more effective at reducing cellular inflammation. The compounds also inhibited upregulation of proinflammatory cytokines, including IL-6, MIP-2, KC, and MCP-1, and total BAL protein (Fig. 4). The efficacy of Neu-164 and Neu-107 at 40 μg/kg was similar to dexamethasone. Neu-164 did not show an increased dose-response when tested at 200 μg/kg, suggesting that its maximum effect was achieved with the lower dose. Interestingly, Neu-164 and Neu-107 did not affect TNF-α levels upregulated by CS exposure, and only weakly inhibited MCP-1. This may indicate that IL-6 is more closely regulated by oxidative stress while upregulation of TNF-α is less dependent on oxidative stress and more dependent on other proinflammatory components of CS and suggests that, for maximum effect, it might be desirable to combine these compounds with other drugs that target other proinflammatory pathways.
It should be noted that, while dexamethasone (included as a positive control for the inhibition of inflammation) was effective at inhibiting acute CS-induced inflammation, corticosteroids alone are not effective in long-term management of COPD (65). Corticosteroids are used to treat acute exacerbations and to provide symptomatic relief in long-term care, but they do not prevent the long-term decline in lung function and are associated with many detrimental side effects (65). Additionally, COPD patients and animals exposed to chronic CS develop steroid resistance due to epigenetic changes to histone acetylation (4, 9). This is one of the factors that has prompted the search for novel anti-inflammatory compounds in the treatment of CS-induced lung disease.
In rodent models of CS exposure, neutrophilic inflammation predominates the acute phase, whereas both macrophages and neutrophils are important in the chronic phase (15, 17). Macrophages and neutrophils are also both important in human COPD. COPD patients have chronic neutrophilia, and it is believed that neutrophil elastase is one of the key proteases responsible for lung tissue destruction in emphysema (16, 56). Indeed, direct instillation of elastase into the lungs of rodents is a long-recognized experimental model of emphysema. However, recent evidence suggests that MPO, produced by both neutrophils and macrophages, contributes significantly to the pathology of inflammatory diseases and emphysema (34). For example, ex-smokers with COPD exhibit levels of oxidative stress in their lungs twofold higher than healthy current smokers (39), and MPO in human COPD sputum is correlated with poor clinical outcome (45), suggesting that inflammatory cells are a significant contributor to oxidative stress in situ. Recently, an MPO inhibitor successfully prevented emphysema in a guinea pig model of chronic CS exposure (14).
We hypothesize that Neu-164 and Neu-107 inhibit CS-induced acute inflammation by at least two mechanisms (Fig. 6). First, by acting as antioxidants, they scavenge ROS present in smoke and smoke tars, which reduces proinflammatory signaling and recruitment of inflammatory cells, including neutrophils. Second, by inhibiting MPO and scavenging superoxide produced by neutrophils and macrophages, Neu-164 and Neu-107 reduce the burden of oxidative stress produced by inflammatory cells, resulting in reduced tissue damage and dampening the positive feedback loop between ROS, ROS-sensitive proinflammatory transcription factors, and inflammatory cell recruitment. In support of this hypothesis, we demonstrated that Neu-164 reduced the level of DNA oxidation in CS-exposed lung tissue (Fig. 5). We also investigated the upregulation of endogenous antioxidant enzymes HO-1 and GCLm. Acute CS exposure upregulated both HO-1 and GCLm. Treatment with Neu-164 significantly inhibited the upregulation of both antioxidant enzymes. Neu-107 inhibited upregulation of GCLm and partially inhibited HO-1 (Fig. 5). HO-1 and GCLm are regulated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (33). Nrf2 is regulated by its binding partner Kelch like-ECH-associated protein 1 (Keap1), which acts as a sensor for oxidative stress and retains Nrf2 in the cytoplasm until it becomes oxidized, at which point Keap1 dissociates from Nrf2 and is degraded, allowing Nrf2 to translocate to the nucleus (41). However, Keap1 and Nrf2 recycle so quickly (43) that they would not be informative in these experiments in which the mice were harvested 24 h after the last exposure, hence the need to investigate their downstream targets. Overall, these results suggest that Neu-164 and Neu-107 did indeed reduce the oxidative stress burden associated with acute CS exposure, resulting in reduced Nrf2 activity and reduced upregulation of antioxidant response genes.
Neu-164 and Neu-107 also have potent inhibitory activity against 5-LO. Neutrophils express 5-LO, which participates in the synthesis of leukotrienes that cause bronchoconstriction, and have been found to be upregulated in COPD patients (32, 36). Therefore, it is likely that 5-LO inhibition would contribute to the beneficial effects of these compounds in patients. Unfortunately, leukotrienes were not upregulated in our mouse model of acute CS exposure (data not shown), so our study cannot address the possible benefits of 5-LO inhibition by Neu-164 and Neu-107. Studies of other leukotriene pathway inhibitors have shown beneficial effects (20).
The potential therapeutic role of antioxidants in smoking-related lung disease is complex. There are numerous studies suggesting antioxidants such as N-acetylcysteine have some benefit in COPD (reviewed in Ref. 4). However, there is also some evidence that dietary antioxidants may promote cancer (5). In an ex-smoker with COPD, the predominant source of ROS in the lungs is ongoing chronic inflammation (macrophages and neutrophils) that does not resolve for several years after smoking cessation (59, 66). We suggest that treatment with compounds such as Neu-164, which have antioxidant and MPO-inhibitory effect, may act to reduce the overall burden of ROS on the lungs, interrupting the positive feedback loop between ROS and inflammatory cell recruitment. As such, the treatment might be able to be discontinued after downregulating the inflammation, thus mitigating possible procancer effects of antioxidants.
Taken together, our results demonstrate that Neu-164 and Neu-107, novel therapeutic candidates with antioxidant and anti-MPO activity, have potent anti-inflammatory effects in vivo in an acute cigarette smoking model. This is an important first proof-of-principle study on the efficacy of dual MPO inhibitor/antioxidant compounds in smoking-related inflammation. While we believe these compounds could be useful prophylactically (such as in acute smoke inhalation), or in other non-smoking-related lung inflammatory conditions such as asthma, the main goal would be to treat the effects of cigarette smoking that persist after smoking cessation. As such, further experiments in chronic smoke exposure models are needed. We also note that, although the Neu compounds did not appear to have short-term side effects (such as nonspecific inflammation in mice exposed to air and treated with the compounds), long-term toxicological data are also needed. Given the recent report that an orally delivered MPO inhibitor prevents emphysema in a guinea pig model of chronic CS exposure (14), we expect that Neu-164, with strong anti-inflammatory activity and multiple disease-relevant functions (anti-MPO, anti-5-LO, and antioxidant), will have similar results in chronic CS exposures. Importantly, these effects were seen when the compounds were delivered by inhalation, which may result in increased availability at the target organ and decreased systemic side effects. This demonstrates the utility of small molecule inhibitors with multiple targets in treating disease and suggests the potential of these compounds in long-term studies of chronic CS exposure.
This work was supported in part by National Institutes of Health Grants 8UL1-TR-000042, R01-HL-088325, and P30-ES-001247. These funders had no role in study design, data collection; and analysis, decision to publish, or preparation of the manuscript.
This study was funded in part by Neurim Pharmaceuticals. E.P. and M.L. were employed by Neurim Pharmaceuticals and performed the experiments shown in Fig. 1 and Table 1. M.L. is an inventor on patents covering Neu-164 and Neu-107 that are assigned to Neurim Pharmaceuticals. E.P. consulted on the design of the other experiments. While these authors concur in the overall submission of the manuscript, neither these authors nor Neurim Pharmaceuticals had veto power over the manuscript or presentation of the results. R.P.P. has served as a consultant to Neurim. T.H.T., H.H., S.J.P., and P.J.S. have no conflicts to declare.
Author contributions: T.H.T., E.P., P.J.S., and R.P.P. conception and design of research; T.H.T., H.-M.H., E.P., M.L., and S.J.P. performed experiments; T.H.T., H.-M.H., E.P., M.L., S.J.P., P.J.S., and R.P.P. analyzed data; T.H.T., E.P., P.J.S., and R.P.P. interpreted results of experiments; T.H.T. and H.-M.H. prepared figures; T.H.T. drafted manuscript; T.H.T., H.-M.H., P.J.S., and R.P.P. edited and revised manuscript; T.H.T., H.-M.H., E.P., M.L., S.J.P., P.J.S., and R.P.P. approved final version of manuscript.
We thank Kathryn Sewernyiak for expert technical assistance and Tirumalai Rangasamy for advice and comment.
- Copyright © 2013 the American Physiological Society
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subset: commoncrawl


text:
The compromise finances everything from airports to war costs and brims with victories and concessions for both parties.
WASHINGTON — A $1.1 trillion spending bill for operating the government until just before next fall's election steamed through the battle-weary House on Wednesday over tepid protests from tea party conservatives, driven by a bipartisan desire to restore painful cuts in domestic and defense programs and show disaffected voters that Congress can do its job.
The bill swept through the House on a 359-67 vote and was on track for a big Senate vote by week's end. Republicans voted for the bill by a 2 1/2-1 margin, and just three Democrats were opposed.
The measure funds virtually every agency of government and contains compromises on almost every one of its 1,582 pages. It covers the one-third of government spending subject to annual decisions by Congress and the White House, programs that have absorbed the brunt of budget cuts racked up since Republicans reclaimed control of the House three years ago.
Excluded are the giant benefit programs like Social Security, Medicare, Medicaid and food stamps that run on autopilot and are increasingly driving the government deeper into debt.
Tea party Republicans, chastened after sparking a 16-day partial shutdown of the government in October in a kamikaze attempt to derail President Barack Obama's health care law, appeared resigned to the bill.
"I don't think there's going to be a lot of opposition," one tea party leader, Rep. Raul Labrador, R-Idaho, said before the vote. "The die has been cast for the next year on budget fights."
To buy time for the Senate debate, Congress on Wednesday sent President Barack Obama a three-day funding bill in time to avert a scheduled shutdown at midnight. The Senate cleared that measure by an 86-14 vote and Obama quickly signed it into law.
The bill increases core agency spending by $26 billion over the fiscal 2013 year that began Oct. 1, after last year's automatic spending cuts took them to $986 billion. But it's $31 billion less than Congress passed last March before automatic cuts known as sequestration took effect.
The Pentagon faces a tight squeeze even as it avoids what would have been another $20 billion wave of automatic cuts. The Pentagon's core budget is basically frozen at $487 billion after most accounts absorbed an 8 percent automatic cut last year. Adding $6 billion to Obama's war request provides some relief to readiness accounts, however, though active duty troop levels would still be cut by 40,000 to 1.36 million. It includes $85 billion for overseas military operations, a slight cut from last year.
Domestic programs generally fare better and are kept, on average, at levels agreed to last year before the automatic cuts of 5 percent kicked in across the board. Those broadly applied cuts, called sequestration, were triggered by Washington's inability to follow up a 2011 budget deal with additional deficit savings.
NASA, the FBI and the Border Patrol all won spending increases at the expense of cuts to the Transportation Security Administration, Internal Revenue Service and foreign aid. There's money to repair the iconic cast iron dome of the U.S. Capitol, full funding for food aid for low-income pregnant women and their children, and a $150 million increase over 2013 for high-priority transportation infrastructure projects. Army Corps of Engineers construction accounts get a more than $300 million hike over Obama's request for flood control, shoreline protection and environmental restoration and other projects.
The bill fills out the budget agreement sealed last month by Sen. Patty Murray, D-Wash., and Rep. Paul Ryan, R-Wis., the heads of the House and Senate Budget Committees. Murray and Ryan left it to the chairmen of Congress' appropriations committees, Sen. Barbara Mikulski, D-Md., and Rep. Hal Rogers, R-Ky., to work out the details.
The measure changes a Ryan-Murray provision cutting military pension cost-of-living increases for working age retirees to exempt disabled veterans and surviving spouses from the cut. The Veterans Administration gets an almost automatic boost of $2.3 billion, almost 4 percent, driven by increased health care costs.
The lowest-common-denominator bill doesn't contain big-ticket wins for either side, but the simple fact that a deal came together was seen as a win for Congress as an institution and its band of 81 appropriators. House Speaker John Boehner, R-Ohio, strongly pushed for a deal, even though the end product was a six-inch-high "omnibus" compilation of what was supposed to be a dozen separate spending bills. Presidents and lawmakers alike deride such measures.
The alternatives, however, were to allow automatic spending cuts to strike for a second year and risk another politically debilitating government shutdown.
Democrats celebrated winning an addition $1 billion over last year for the Head Start early childhood education program and excluding from the bill a host of conservative policy "riders" advanced by the GOP.
"We were able to strip out nearly all the new, divisive riders relating to abortion, contraception, gun control, immigration, implementation of the Affordable Care Act, Dodd-Frank, environmental protection," said Rep. Nita Lowey of New York, the top Democrat on the House Appropriations Committee. "This is very important to Democrats."
Some Democrats said they would support it but only reluctantly, complaining that despite some increases, spending for education, health and other programs would still be too low.
"With this bill, we are waist deep in manure instead of neck deep in manure. Hooray, I guess," Rep. Jim McGovern, D-Mass., said.
Republicans successfully "zeroed out" funding for high-speed rail, a slap at California Democrats, and they were able to keep tight limits on the implementation of "Obamacare" and the 2010 Dodd-Frank overhaul of financial regulations.
Civilian federal workers would get their first pay hike in four years, even if it is just 1 percent. The bill contains a familiar provision backed by postal worker unions prohibiting the Postal Service from ending Saturday mail delivery and closing rural post offices even as it hemorrhages money.
Conservatives complained that the bill keeps the money flowing to wasteful programs, but the actual debate was a sleepy affair dominated by the old-school lawmakers who populate the Appropriations Committee.
"What's this money going for?" said Rep. Tom McClintock, R-Calif. "It continues funding for the scandalous Essential Air Service that pays to fly empty and near empty planes across the country. It continues to throw money at all manner of immensely expensive and failed green energy programs and other forms of corporate welfare."
The much-criticized Essential Air Service, which subsidizes airlines serving smaller rural airports and enjoys support from many conservatives whose districts benefit from its largess, would receive a record budget of $249 million. House-proposed reforms to limit per-ticket subsidies to no more than $500 were stripped out of the measure, preserving service to the average three people a day flying out of Great Bend, Kansas, and the two people who fly out of Glendive, Mont., per day.
The bill also blocks the Federal Emergency Management Agency from increasing flood insurance premiums on people whose homes are found to be in flood zones after FEMA remapping, a strike against changes enacted in 2012.
Stuffy oil paintings of Cabinet secretaries are out. Old-style light bulbs win a reprieve. For the health care overhaul, it's a wash.
Policy trades big and small make up the $1.1 trillion spending deal that Republican and Democratic leaders are rushing through Congress this week to avoid a repeat of October's partial government shutdown.
Five things to know about the compromise, and something to watch for next:
So long shutdown, "sequester" and "fiscal cliff." Next to you, a deal to keep the government's lights on for nine more months feels like a masterwork of negotiation.
Lawmakers began backing down from three years of government-by-standoff after watching their approval ratings sink into the single digits. Republicans, especially, were stung by shutdown backlash.
To keep the government running past this week's deadline, negotiators had to agree on 1,582 pages of details, completing a budget approved before Christmas.
They did it without those pet projects often referred to as "pork" that used to be handy for winning over wavering lawmakers, but now are banned.
Budget-making still wasn't the lengthy, open process that civics textbooks say it should be.
The horse-trading was done by only about four dozen of Congress's 533 members, working in private. What's supposed to be 12 separate spending bills was combined into one mammoth stack that finances the government through Sept. 30.
Head Start gets more money for its preschool programs, federal workers and troops see a 1 percent pay raise, and the Pentagon can build new aircraft carriers and fighter jets.
In all, the bill halts $45 billion in automatic spending cuts due to kick in this year. It also restores some of the money chopped last year when a budget device known as the sequester took hold government-wide.
Those across-the-board cuts were never supposed to happen. They were time-released to compel lawmakers and President Barack Obama to set aside their differences and substitute a more logical deficit-reduction plan before it was too late.
Didn't work as intended.
With Washington deadlocked, the cuts took effect last year, nipping programs favored by Democrats and those esteemed by Republicans. In the end, they are belatedly doing their job, giving lawmakers on both sides additional incentive to make nice and make a deal.
Two unloved agencies — the Transportation Security Administration and the Internal Revenue Service — are among those getting less money than last year.
Republicans added restrictions to ensure the IRS never again targets conservative groups seeking tax-exempt status.
Spending for Obama's high-speed rail plan is cut off. Money promised to the International Monetary Fund is withheld.
The deal prohibits spending any more on the portraits of Cabinet secretaries, Congress members and other big shots.
Environmentalists' loss is a boon to fans of incandescent bulbs. Enforcement of a national shift to energy-efficient lighting is banned.
The bill puts the kibosh on the post office's plan to stop delivering mail on Saturdays.
The December budget imposed pension changes that will cost newly hired federal workers and younger military retirees; the new bill exempts disabled veterans from the military cut.
Overall, spending for government operations will drop $79 billion, or 7 percent, from the high-water mark set by Democrats in 2010.
The October shutdown grew out of tea party-backed Republicans' determination to kill Obama's health law before it could take root.
That backfired, leaving GOP leaders with even less muscle to "defund" it this time around.
They did nibble around the edges, refusing to add additional spending that the president sought and shrinking a public health fund created by the Affordable Care Act. The Obama administration says that won't hinder implementation.
The bulk of its spending is on autopilot — think Social Security and Medicare — and separate from annual appropriation bills, anyway.
The compromise lays out day-to-day government spending, decreeing which programs will flourish and which will wither.
That's a humble feat next to the tattered dream that congressional leaders and Obama could come together to overhaul taxes, fix the nation's long-term debt problem, and secure the future of Medicare and Social Security as baby boomers retire.
The Appropriations Committee leaders, Rep. Hal Rogers, R-Ky., and Sen. Barbara Mikulski, D-Md., described their accomplishment as achieving the most basic duty of Congress: financing the government.
You've got to start somewhere.
Does this mean a spending truce, at least through the November election?
Probably. But there is a catch.
If conservative Republicans want to fight another day, they could demand concessions in exchange for raising the nation's borrowing limit. Obama says he won't negotiate that.
The Treasury Department estimates that money to pay the nation's bills will run out in late February or early March if Congress fails to act.
Once the big spending bill is approved, you can expect a return to warnings about the perils of a U.S. default.
-- Associated Press


text:
Workplace Communication
In an era of Casual Fridays and work-from-home colleagues, how can you maintain effective office communication in a changing business climate?
We'll steer you through changes in business etiquette, and help you successfully navigate through the new realities of workplace conflict and office politics.
Did you get passed over for a promotion that you were certain was yours?
Even with workplace environments becoming more casual, you should avoid some conversations.
For the third year in a row, journalism brought up the rear in employment research firm CareerCast.com's annual 10 Job Rated Worst Jobs report.
A good, well-timed handshake to pair with your grin is a sure way to stand out, whether you're at the company picnic or an industry conference. Here's how important it is: The prospective employee with the best handshake is more likely to get the job, research shows.
This month's Best Communicator Award was won for responding appropriately to someone who is arguably the month's Worst Communicator.
Surprisingly, one of the biggest battles you'll face in the workplace involves disagreements over room temperature.
If you spent an hour and a half each day in the office doing something you hated and that stressed you out, you'd think about looking for another job. But day after day, most of us suffer through joyless commutes of aggravating lengths, and merely throw our hands into the air helplessly: What's to be done? Actually, plenty.
To get ahead in business, it doesn't hurt to have an expansive network. But what do you do when you're drowning in contacts' invitations for lunch or after-hour drinks?
Meetings that are unfocused and long-winded are the bane of many managers' lives.
Business giants Warren Buffett and Richard Branson think its important to invest in your communications skills


text:
Aces Up Solitaire Flash Game
The aim of the Aces Up Solitaire game:
- Remove all of the cards until only the Aces are left
- When the top cards of the two columns have the same suit you can click the lower ranked card and remove it
- Aces are the highest rank cards which is why you want those to be the only ones left at the end of the game.
Find more free online flash games at Fupa.com
3 Comments
I quite enjoyed this Solitaire game
thank you for posting it
I spent some hours on this solitaire! Thanks 🙂
solitaire is not just for seniors and elderly!!! 🙂


text:
- Fuel economy - combined (L/100 km) N/A
- Recommended fuel N/A
- Fuel tank capacity (L) N/A
- Fuel economy - highway (L/100 km) N/A
- Fuel economy - city (L/100 km) N/A
Ruggedly handsome and practically indestructible, our Low Kms 2015 Chevrolet Silverado 1500 LTZ Z71 Crew Cab 4x4 is proudly displayed for your pleasure in brilliant Blue. Under the hood of this stellar truck is a 5.3 Liter V8 powerhouse kicking out 355hp. It offers exceptional fuel economy of 10.2L/100km and a tough 6 Speed Automatic transmission. Muddy rural roads, rugged trails, towing your boat, or hauling lumber are no challenge for our 4x4 Silverado. The off-road suspension eases you down the road in comfort while the rear set up is tough enough to keep up with your demanding life.
Take one look at the formidable appearance of this Silverado LTZ Z71 and you'll know it means business. The upscale interior features an exclusive dash design with wood and metallic accents, running boards, vent visors, sunroof, leather upholstery, heated front bucket seats and driver-seat memory settings that make you feel like the king of the road. MyLink, a huge central display, Bluetooth and a premium audio system with CD, a USB/iPod interface and rear audio controls keeps you connected and entertained along the way.
Well-known GM safety features are in place like StabiliTrak, hill descent control, 4-wheel ABS, daytime running lamps, and plenty of airbags. This no-nonsense truck will make sure it fulfills your needs for work and play. Get the job done right with the security, performance, and comfort that only come from the Chevy Silverado. Print this page and call us Now... We Know You Will Enjoy Your Test Drive Towards Ownership!
* Please note that all the above options, with the exception of 'Installed Options', are drawn from the generic 'base' version of the vehicle. The options listed might not exactly match this specific vehicle.
* Although every attempt is made to ensure the accuracy of the data above, due to the possibility of human error, we cannot guarantee the accuracy of the displayed information, the availability of this vehicle, or the accuracy of its photo or "stock photo." Such information may not reflect exact vehicle colour, trim, options, price or other specifications. Please contact the dealership for verification or if you would like more information on this vehicle.
All prices are in Canadian Dollars unless otherwise stated.
The Payment Calculator is for comparison purposes only and are based on the vehicle price, term of 72 months and a rate of 5.99%. Taxes and License are additional. All financing is OAC. Please contact our dealership for more information.


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NPI - National Provider Identifier
This post deserves a repeat since many practitioners are not giving this the attention it needs. Like it or not, it will be here soon.
By May of 2007 (or sooner) if you submit your claims electronically, you will have to obtain a ten digit NPI from the government.
The application can be made over the web and usually takes only short time to process and receive. Or you can download and commplete a paper form and mail it in,
Data you will need when you apply is any tax ID's you use, state license number, home and practice address.
More information can be obtained by going to the ADA website www.ada.org.
You can apply at http://nppes.cms.hhs.gov or by calling 800-465-3203.
If you would like to post a subject and start a discussion, EMAIL US BY CLICKING HERE
Visit us at The Huskin Group about our dental insurance and practice management services.
If you would like to subscribe to the RSS feed and be notified whenever this Blog is updated, click on the XML icon below for more information.


text:
anskyber 09:27 26 Dec 2007
As a general principle an integrated card uses the installed RAM for it's use leaving less memory for the normal work of the computer.
A card with it's own dedicated graphics memory offers the chance of using faster and more successful graphics intensive programs. Can you link us to the two machines you have in mind so an overall assessment can be given?


text:
Bioprocess Control Specialist Focuses on Single-Use Sensors
Lab Automation through Single-Use Sensors and Monitors
Lonza Upgrades Live-Cell Imaging System
For Obtaining Better Cell-Culture Analyses
Antibody Characterization Balances Rigor and Reason
Emphasizes a Combination of Antibody-Dependent and -Independent Testing Methods
Cancer Immunotherapy Spurs Work on Better Animal Models
GEN Spoke to Several Researchers on Advances in Engineered Animal Models Used to Study Novel Cancer Im-munotherapies
For full access to this article login to GEN Select now.
March 15, 2014 (Vol. 34, No. 6)
With New Tools, Physicians Become Better NGS Customers
- The ability of physicians to tailor treatments according to distinct characteristics of individual patients—an ability also known as personalized medicine—is becoming more of a reality every day. One of the driving forces behind this progress is increasing access of physicians to their patients' genomic information. Personalized medicine could ...
Not registered yet? Please fill out the form below and enjoy complimentary access to this and an exclusive collection of premium content and personalization features as a GEN Select insider. Learn More.
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- Do not put any letters or characters here if you are not a spy program.


text:
Wow day twenty eight of the Blogtember challenge with only two more days left I am happy to say I have loved taking part and think its such a great idea so thanks again Bailey!
Todays prompt: What were your highs and lows for this month?
The biggest highlight of this month was the welcoming of my nephew Joey, I can't believe my little sister is a mummy and I am now an aunt its wonderful!! Other highlights have to be going on holiday to Spain with Dale and his mum and stepdad it was such a lovely time away, I will be recapping next week. My friends wedding just before we went away was a definite highlight, it was a beautiful day filled with laughter and lots of love which just made me warm and fuzzy inside! And of course doing the Blogtember challenge has been a high for me, I have loved blogging about all sorts of different things and it has definitely inspired me to do other stuff on here that takes me out of my comfort zone, like my vlog, I was terrified to do it but actually really enjoyed it and think I will make it a regular feature : )
Thankfully I haven't had many lows this month its been rather good, there have been one or two like my back being a total bitch and not getting better as quick as I want it too but slowly does it and I'm sure its on the road to being fixed now, thank god! If I had to say one more it would be losing a couple of clients but luckily other work has covered that so I can't complain.
Lucky really aren't I? I am glad to be able to write the highs definitely out weigh the lows.
What were your highs and lows for this month?