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LA CROSSE, Wisc. – The eighth-ranked University of Massachusetts Dartmouth men's track and field team wrapped up the 2018 Division III Outdoor National Championships on Saturday, earning the third All-America award of the event to mark the first time since 1986 that the Corsairs had three such recognition at a single championship.
UMass Dartmouth finished the event with 13 points, knotting the team with John Carroll and DePauw for 21st amongst the 72 scored teams at the event.
Senior Jared Louf-Woods (Salem, Mass.) collected the third All-America honor of his career to finish the season strong for the Blue and Gold. The Salem-native registered a throw of 59.30 meters (194-07) to finish sixth overall in the 20-person field. Jared advanced to the finals on his third attempt but fouled on two of his last three attempts in the championship round. With that, he becomes the third Corsair to earn All-America honors in the hammer throw, joining Rich Volkman (1985) and Stephan Baptista (1986, 1987).
Louf-Woods (2) and Jordan Entwistle (Northborough, Mass.) each earned All-America honors at the 2018 Division III Outdoor Championships, marking the first time since 1986 that the Corsairs had three All-America awards at a single championship.


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Once again I find myself somewhat bewildered by a new move in the reclassification of current UK society and in particular a new attempt at putting us into a new "class" structure. This is the BBC having carried out an experiment if you don't click on the link.
So I filled it in the questions. I'm apparently "Established Middle Class". What the hell does that mean? For a start the important thing surely is how you describe yourself. I'm working class. I may have a job that might be defined loosely as a profession and be in a management position but to me I'm working class due to my background. My sister did the test too and came out as "Technical Middle Class" she stated on Facebook that she is "... definitely working class - dockyard born and bred!!" My son insists we are middle class but he takes this from simply from our financial position which is born of the fact that I was incredibly lucky to have a ridiculously overpaid job for a good few years which ended with a ridiculously overblown redundancy package (I'm not frivolous about it but recognise largely that was not of my direct making and purely luck and circumstances). So I get promoted up the class structure on the basis of pure luck? If I'd have won the lottery does that instantly move me to the new "Elite" class? I really never get this, it is like saying I'm no longer a Caucasian male when clearly I am as that is my genetic makeup.
I don't mean to say that people can't move up the wealth ladder through luck or hard work, they can and they can change their circle of friends etc. should they find the opportunities to do so. However I really don't see how that changes their intrinsic class. See I consider class intrinsic to me social mobility is about wealth and where you live and who you live with but doesn't change who you are deep down, your roots. Subsequent generations - maybe. The fact my son has grown up in a household with considerably more wealth than I knew as a child and he has gone onto university (btw the first person ever to do so in my family) possibly mean he has some legitimacy in his feelings that he is middle class. Starting his working life with impressive letters after his name and possibly if he does get a PhD placement for September a change of honorific give him some legitimacy to his argument. However his dear old Dad even in his dotage will still consider himself "dockyard born and bred" along with it seems his Aunt as well.
Finally the real confusing bit for me is in the questionnaire you have to answer questions on your "cultural capital". Now here I am lost. How can listening to jazz or attending art galleries move you from one class to another? This kind of cultural stereotyping I find most disturbing of all in this new class structure - are we saying an appreciation for jazz or art galleries are too good for the working class? Whatever happened to the late 20th century emancipation of the masses through public libraries, galleries, museums and the efforts of the education system to promote cultural interest? Is it now all purely in the name of social ladder climbing? I find that really sad if that is true. One thing, to me, that is the greatest leveller of all is a love of some art form, when I stand in front of a picture or listen to some music and the person next to me is a lord or a tramp if we both appreciate it for what it is in a shared mutual love of the art form that to me is the best demonstration of true equality at work. I feel very sad if today someone is in whatever few HMV shops are still open buying Miles Davis CDs purely to convince their friends, and more worryingly themselves, that their cultural capital is greater than they thought they needed it to be yesterday.

subset: commoncrawl


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This is how we spent a few afternoons on our London flat. So the view was NOT amazing but just being there WAS amazing. With all the walking we did, we NEEDED to put our feet up at the end of the day.
My husband really wanted to get a shot of the wineglass on the windows sill...the very narrow window sill.
As soon as he was done taking the shot, the glass shattered to the ground!
It is known as THE shot of the wine glass.
Here's a close up of the banner. I actually cut it out of a journaling card from one of the cut apart sheets.
I used the Weekend Neutrals stack.


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Lunch Lady Brownies
~1 cup unsalted butter (melted)
~1/2 cup cocoa powder (unsweetened)
~2 cups all-purpose flour
~2 cups sugar
~1/4 cup milk
~4 eggs
~4 teaspoons vanilla
~OPTIONAL: chopped nuts
~1/4 cup softened butter
~1/4 cup milk
~1/4 cup cocoa
~3 cups powdered sugar
~Dash of salt
For the brownies: Melt the butter in the microwave or in a sauce pan over the stove. Pour the butter into a mixing bowl, and add the cocoa. Beat with a hand-held mixer or paddle mixer until combined. Add in the flour and sugar, mix together. Add in the milk while mixing the the flour and sugar in with the butter-cocoa mixture, (the milk gives it more consistency because you might notice that the flour and sugar makes the mixture more powdery. just add in some milk to make it easier). Next, add in the vanilla and eggs, beat together but do not over stir! In a greased and floured 9x13 pan, pour the brownie batter in the pan and spread around with a spatula. Bake at 350 degrees for 25 to 35 minutes.
Collage form:
For the frosting: Combine all the ingredients together in a bowl and mix with a hand held mixer or paddle mixer. Frost the brownies ten minutes after the brownies are taken from the oven. Use a spatula to spread the frosting on the brownies.
And here they are! Beautiful in structure, rich in taste (a wee bit bland), but a really good, frosted, Lunch Lady brownies!
I am going to keep tinkering with this recipe because I want to perfect it! I want equal parts chocolate, I want the brownies to have the perfect chocolaty taste and keep their structure. I am really pleased with this recipe because every time I try to make brownies from scratch, they always end up sinking in the middle due to not being done. I end up burning the edges of the brownies, and having the middle still be gooey, but these brownies were perfect in the baking process.


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Building a Custom Food Truck or Pre-Owned: The Best Choice for Your BusinessLegion Food Trucks | October 16th, 2017 | No Comments »
Your goals are likely in line with most other entrepreneurs: expand your reach, brand your business, create a memorable experience for customers, and drive revenue with a strong ROI. While these are common goals, the food truck business model is entirely different. You don't have a brick and mortar shop where diners can sit toContinue reading →


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In my last entry, I mentioned that we stayed at Superview Lodge in Tadapani. The lodge is aptly named because of its superb views of the Annapurna region like this:
As the sun started rising, a few trekkers had also woken up to capture the sunrise.
After breakfast at around 8.45am we continued our trek back to Nayapul.
When Kapil explained that it would be a couple more hours till we reached Nayapul where a taxi is waiting to take us back to Pokhara, we formulated a plan to take public transportation.
Apparently there's a base in Kimche (near Ghandruk) that has taxis and buses heading to Nayapul. So we sent Siva our porter ahead to Kimche to enquire. The good boy managed to book an entire taxi for the 4 of us for 2,000 Nepalese Rupees. I was a happy trekker :-)
It was about 4.00pm by the time the dhall bhat was served and I whacked my heart out!
The delicious meal was a delightful end to our 4 day trek to Poon Hill.


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Areas We Serve
RECENT EXPANSION to parts of Chapel Hill!
Our team currently provides professional pet sitting & dog walking services to homes in Wake County including: Apex, Cary, Morrisville, Holly Springs, Fuquay Varina and all parts of Raleigh including Brier Creek. We've also recently expanded to parts of Chapel Hill. If you are outside of this area we may still be able to provide service.
Please Contact Us to discuss your request.
Expansion area in Chapel Hill, North Carolina


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Use our handy mail in form.
As a further description of the studies, letter codes have been included below each study. The codes are defined as:
A = Line drawing included
B = Instructions and painting suggestions included.
C = Multiple firing sequences shown/discussed
D = Other ideas
E = Complete lesson on a given subject
Credit Union website design and hosting


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As death approaches, he leaves his body behind. Angels usher him out of the only world he's ever known and up into a land filled with beautiful flowers and trees. He arrives at a city whose walls beam with light.
The first person he meets is Jesus, clothed all in white. The Lord's face projects a youthful radiance, and he greets the new arrival with warmth and tenderness. The visitor then encounters a parade of faces from earth. He doesn't know them, but they are all excited to finally meet him.
Eventually, this heavenly expedition ends, and he awakens back on earth. His experience is recorded in a wildly popular book read around the world.
No, this isn't the story of Colton Burpo, the four-year-old boy who supposedly traveled to heaven during an emergency appendectomy. It's the story of Saturus, a third-century Christian martyr. Saturus recorded this ecstatic experience shortly before he was brutalized by wild animals and then killed by gladiators in celebration of Emperor Geta's birthday in A.D. 209. His account is found in The Passion of St. Perpetua, St. Felicitas, and their Companions, one of the oldest Christian texts.
Most 21st-century Christians have never heard of Saturus. But Colton's experience has become something of a phenomenon. Heaven Is for Real, his father's account of the uncanny event, has become a mainstay of contemporary evangelical apologetics. It's sold over eight million copies and has recently been turned into a hit movie.
Yet Colton's story is hardly unique. Eight million people in America claim to have had a "near-death experience" (NDE), a term coined in 1975 by physician Raymond Moody. NDE patients tell eerily similar tales: a dark tunnel, ...1


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The CReader Pro CRP123 is a convenient and handy tool
The CReader Pro CRP123 is a convenient and handy tool that makes collecting and reading diagnostic information easy and most importantly, accessible. This product comes with a one year warranty against faults and includes lifetime access to valuable software updates which are released by Launch over the internet. If the CRP123 does not meet your requirements take a look at the CReader CRP129, which has all the abilities of the Launch Creader Professional CRP123 as well as the CResetter II.
The CRP123 amalgamates the best features of code scanners and professional mid-line scan tools. It opens up a whole world of diagnostics, which is further improved by its enhanced data streams for ABS, SRS, Transmission and Engine; which is available across a wide range of makes and models. With all the operational ability of a traditional ARS/SRS Code Reader the Launch CRP123 boasts a great deal more functionality
The Launch CReader Pro CRP 123 is a handheld diagnostic tool used to detect and report the cause of vehicle faults. It boasts state-of-the-art hardware and software making it one of the most accurate diagnostic tool in today's market. All this along with its compact design and full colour screen, the CRP123 is easy to use and understand while not being in the least bit cumbersome.
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War Service: Henry Edward Grainger (or Granger) served as a Private with the Essex Regiment and his service number was 22774. He previusly served with the Royal West Kent Regiment. He died on 21st October 1918 at the General Hospital, Sheffield.
Location of Memorial: He is buried in Brockley cemetery, where his name is recorded on the screen wall listing those whose graves have no headstone.
Details: His effects were claimed by his brothers William and Charles, his sisters Mrs Amelia Gay, Mrs Ellen White and Mrs Jane Page, and his sister-in-law, Helen French.
Contributed By:
Jackie Sellars
Do you have more information on this person or the memorial they are commemorated on? If so click here to contribute information.
by Local History and Archives Centre, Lewisham and licensed for reuse under this Creative Commons Licence


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Ways to Distribute In the Stage Without the need of Providing In the Stage
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The recipe calls for cake flour, which I have never worked with before. I did some research and found that cake flour is better for fluffier results. I had to try it, especially because that was one of my complaints about the last cupcakes. I was very happy with the results! The only problem with these extra light and tasty cupcakes is that our chocolate chips sank to the bottom! However, it makes for a yummy surprise!
Perfect White Cake
adapted from allrecipes
2 3/4 c. sifted cake flour
4 tsp. baking powder
3/4 tsp. salt
4 egg whites
1 1/2 c. white sugar
3/4 c. butter
1 c. milk
1 tsp. vanilla extract
1 1/2 c. Ghirardelli chocolate chips
1. Sift together cake flour, baking powder and salt. Set aside.
2. In a mixing bowl, beat egg whites until frothy. Add 1/2 cup of sugar gradually and beat until soft peaks form. Set aside.
3. In another bowl, cream butter and the remaining cup of sugar. Alternating between sifted ingredients and milk, gradually add to bowl and mix.
4. Add in vanilla extract and meringue (the egg whites/sugar mixture). Be careful not to over-mix. To help avoid over-mixing, I folded in the meringue instead of using a hand mixer. Fold in chocolate chips, if desired.
5. Spread batter in a large cake pan or scoop into a lined cupcake pan. The recipe makes a few more than 24 cupcakes.
6. Bake at 350 degrees for 30 to 35 minutes for a cake, 20 to 25 minutes for cupcakes. Cool in pan for 5 minutes and then transfer to a wired rack.
7. Frost with your favorite recipe or the one below once completely cooled.
We made chocolate frosting found on the can of Ghirardelli's sweet ground chocolate and cocoa for these cupcakes. I struggled to get the perfect consistency. I actually made the frosting twice! The first time I added too much sugar so I scraped it off and tried again. The second round turned out great! It still had a bit more powdered sugar than the recipe called for so it was a good thickness. So don't be afriad to use a little more than the recipe calls for.
Ghirardelli Chocolate Frosting
1/4 c. butter
3 Tbsp. milk
1/2 c. Ghirardelli sweet ground chocolate and cocoa
2 1/2 c. powdered sugar
1/2 tsp. vanilla extract
dash of salt
1. Melt butter in a saucepan on low heat. Add milk and ground chocolate and cocoa. Remove from heat
2. Add powdered sugar, salt, and vanilla.
3. Beat until smooth
4. Frost onto the cupcakes above or your favorite baking good


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The Perfect All Weather ShoeReviewing: Land's End All Weather Moc | Rating:
Finding a good shoe to carry you through the cold rainy months ahead can be daunting. A good all around shoe should be waterproof, stylish, have good firm soles, and fit like a glove. I found mine at www.landsend.com. More than one million pairs of their All Weather Mocs have sold since they first offered them for sale.
These are very comfortable shoes. They slip on easily, and have a handy tab to help you get it right the first time you put them on. Top quality leather snugs around your feet, giving you support and cushiony comfort. The improved All Weather Moc offers better soles for firmer traction on wet, muddy or slippery ground. You can walk with assurance through rain, snow, slush or sun, without damaging their good looking suede uppers. Yes, these are truly waterproof.
Twin gores assure you of a more custom comfortable fit, and the new sleeker body looks great with just about anything you wear. These mocs come in 8 colors for women and 6 for men. They are lined with a soft breathable knit lining and a padded stretchy collar. At $29.95 these are a real bargain. Of course they are backed by Land's End's 100% anytime anywhere guarantee. If you don't want to order online, you can find them at Sears too.
I'm hard on my shoes, yet these stand up to my muddiest wettest days outdoors. Kids love 'em because there is no more griping from Mom about ruining shoes! I'm on my 5th pair of these nifty mocs, so I feel very confident in recommending them. Give them a try, you'll soon wonder how you ever lived without them.


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- Research
- Open Access
Hepcidin induces HIV-1 transcription inhibited by ferroportin
© Xu et al; licensee BioMed Central Ltd. 2010
- Received: 22 March 2010
- Accepted: 2 December 2010
- Published: 2 December 2010
Physiological regulation of cellular iron involves iron export by the membrane protein, ferroportin, the expression of which is induced by iron and negatively modulated by hepcidin. We previously showed that iron chelation is associated with decreased HIV-1 transcription. We hypothesized that increased iron export by ferroportin might be associated with decreased HIV-1 transcription, and degradation of ferroportin by hepcidin might in turn induce HIV-1 transcription and replication. Here, we analyzed the effect of ferroportin and hepcidin on HIV-1 transcription.
Expression of ferroportin was associated with reduced HIV-1 transcription in 293T cells and addition of hepcidin to ferroportin-expressing cells counteracted this effect. Furthermore, exposure of promonocytic THP-1 cells to hepcidin was associated with decreased ferroportin expression, increased intracellular iron and induction of reporter luciferase gene expression. Finally, exposure of human primary macrophages and CD4+ T cells to hepcidin and iron was also associated with induction of viral production.
Our results suggest that the interplay between ferroportin-mediated iron export and hepcidin-mediated degradation of ferroportin might play a role in the regulation of HIV-1 transcription and may be important for understanding of HIV-1 pathogenesis.
- Deferiprone
- Ferric Ammonium Citrate
- Hepcidin Expression
- Human Primary Monocyte
- Labile Iron Pool
Movement of dietary iron from absorptive enterocytes to portal plasma and of macrophage iron to systemic plasma is mediated by the iron transport protein, ferroportin, and regulated by the hormone, hepcidin, which is synthesized in hepatocytes [1]. Hepcidin binds to ferroportin, and this leads to ferroportin internalization and degradation by lysosomes [1]. Cellular iron is important for HIV-1 transcription, as its removal by iron chelators is associated with inhibition of HIV-1 transcription in cultured cells [2, 3].
Several studies suggest that iron stores may influence the course of HIV infection in humans. Increased iron stores correlated with faster HIV-1 progression in HIV-1- positive thalassemia major patients, in HIV-positive patients given oral iron and in HIV-positive subjects with the haptoglobin 2-2 polymorphism [4]. Survival of HIV-positive patients correlated inversely with higher iron stores in bone marrow macrophages [4]. Non-anemic HIV-positive women in Zimbabwe with increased serum ferritin concentration had increased viral load, suggesting that high iron stores may adversely affect HIV infection [5]. Elevated iron predicted higher mortality in Gambian adults infected with HIV-1 [6]. A more recent study showed that both higher and lower iron status correlated with increased mortality in Gambian adults [7]. Different SLC1 (NRAMP1) polymorphisms were also shown to be protective or associated with greater mortality [7].
Experiments by other investigators indicated that, in cultured CEM T cells, excess of iron was associated with increased HIV-1 viral replication, whereas iron chelation with desferrioxamine (DFO) correlated with lower viral replication [8]. Also, the iron chelators, deferoxamine and deferiprone inhibited HIV-1 replication in human primary peripheral blood lymphocytes and macrophages, although the inhibition was attributed to decreased cellular proliferation [9]. Recently, the topical fungicide, ciclopirox, and the iron chelator, deferiprone, were shown to inhibit HIV-1 gene expression at the level of transcription initiation [10]. Both drugs interfered with the hydroxylation step in the hypusine modification of eIF5A [10]. In our own recent studies, the iron chelators, 311 and ICL670, inhibited HIV-1 transcription by inhibiting the cellular activity of cell cycle kinase 2 (CDK2) and by inhibiting phosphorylation of HIV-1 transcriptional activator protein Tat by CDK2 [2]; we previously showed CDK2 to be important for HIV-1 transcription [11]. Our most recent study showed that BpT-based iron chelators, Bp4eT and Bp4aT, prevented association of CDK9 with cyclin T1 and inhibited the activity of the CDK9/cyclin T1 complex [3].
Thus, the studies of others and our own investigation suggest that a decrease in cellular iron might have a negative effect on host HIV-1 gene expression and be protective against HIV-1. In this paper we investigate the effect of the iron exporter, ferroportin, and the ferroportin negative regulator, hepcidin, on HIV-1 transcription and replication in cultured and primary cells. We expressed ferroportin in 293T cells that have undetectable levels of ferroportin and analyzed the effect of ferroportin expression on HIV-1 transcription in the absence and the presence of hepcidin. We proceeded to investigate the effect of ferroportin on HIV-1 in cultured T-cells and monocytes and also in human primary monocytes and CD4+ T cells. Cultured and primary human cells provide a biologically relevant system for the analysis of the effect of ferroportin expression on HIV-1 transcription. Our findings suggest that the interplay between ferroportin expression and its degradation by hepcidin may play a regulatory role in HIV-1 transcription.
Expression of ferroportin inhibits HIV-1 transcription
Ferroportin expression is associated with inhibition of basal HIV-1 transcription
The HIV-1 promoter contains several binding sites for host transcription factors, including three Sp1 and two NF-κB binding sites [13]. In the absence of Tat, HIV-1 basal transcription is largely regulated by the Sp1 transcription factor [14, 15]. Efficiency of transfection was verified by co-expression of EGFP (Figure 1D). Basal, non-Tat-induced activity of the WT HIV-1 LTR promoter was inhibited in 293T cells that expressed ferroportin (Figure 1E, panel 1). As a positive control, we used the PP1 inhibitor, cdNIPP1 (Figure 1E, panel 1), which we previously showed to be a potent inhibitor of Tat-induced and basal HIV-1 transcription [16]. To determine whether the expression of ferroportin has an effect on Sp1-driven or NF-κB-driven HIV-1 transcription, we analyzed the activity of HIV-1 promoters with inactivation of Sp1 sites or deletion of NF-κB sites [17]. Expression of ferroportin was associated with inhibition of the activity of HIV-1 LTR in both settings (Figure 1E, panels 2 and 3). These results indicate that ferroportin expression inhibits basal HIV-1 transcription driven either by Sp1 or NF-kB.
Hepcidin mediates degradation of ferroportin and is associated with restoration of HIV-1 transcription
Ferroportin, hepcidin and HIV-1 in cultured monocytes
Exposure to hepcidin is associated with upregulation of HIV-1 production in primary human mononuclear cells
The present study suggests that expression of ferroportin is associated with an inhibitory effect on HIV-1 transcription and that this inhibition can be reversed by hepcidin. Thus the ferroportin/hepcidin interplay may have a role in the regulation of HIV-1 in ferroportin-expressing cells such as monocytes and macrophages as well as, unexpectedly, in T cells.
HIV-1 infection of macrophages has been recognized as an important component of viral pathogenesis [22]. An important function of human macrophages is a recycling of iron to the bone marrow from aged red blood cells, involving iron export by ferroportin [23]. The role of cellular iron in the regulation of HIV-1 replication is not well understood. We recently showed that HIV-1 transcription was inhibited by iron chelators which inhibited cellular activities of the host cell co-activators of HIV-1 transcription, CDK2 and CDK9 [2, 3]. The present study shows that increased expression of the iron exporter, ferroportin, is associated with a significant reduction in both basal and Tat-activated HIV transcription. This finding extends our previous observation and suggests that physiological regulators of cellular iron such as ferroportin and hepcidin might be regulators of HIV-1. It is not clear yet if ferroportin or hepcidin has an effect on HIV-1 disease progression. Hepcidin expression is facilitated by IL-6 and other cytokines elevated during inflammation [24], and underlying inflammation is a risk factor for HIV-1 disease progression and pathogenesis [25].
HIV-1 infection of macrophages prolongs their life-time through the induction of PI3K/Akt cell survival pathway [26]. In non-infected macrophages, the PI3K/Akt pathway is negatively regulated PTEN [27]. The PTEN level is lowered by HIV-1 Tat protein in HIV-1 infected macrophages, inducing cell survival [26]. Interestingly, hexamethylene bisacetamide, a potent inducer of cell differentiation and HIV production in chronically infected cells, transiently activates PI3K/Akt pathway; this leads to the phosphorylation of HEXIM1 and the subsequent release of active CDK9/cyclin T1 from its transcriptionally inactive complex with HEXIM1 and 7SK RNA in chronically infected T cell lines and resting CD4+ T-cells [28]. Alkylphospholipds specifically inhibit the activation of Akt kinase activity in HIV-1 expressing macrophages and induce the death of HIV-1 infected macrophages [29]. Because iron deficiency downregulates Akt pathway [30], it is possible that the increase of iron in the hepcidin-treated cells activates Akt pathway and induces HIV-1 transcription.
Iron might be important for different proliferative steps in the life cycle of HIV-1 including reverse-transcription, activation of NF-κB, regulation of HIV-1 transcription, translation of viral mRNA and viral assembly [31]. Previously, Nef, an HIV-1 accessory protein, was shown to down regulate the expression of HFE protein, a modulator of iron homeostasis that is mutated in the iron-overloading disorder hereditary hemochromatosis [32]. Deregulation of HFE by Nef increases iron levels, which coincides with increased HIV-1 gag expression, suggesting a beneficial effect of increased iron on the production of HIV-1 virions and HIV-1 replication [32]. The analysis of HFE deregulation by Nef was carried out in THP-1 cells and also in ex-vivo macrophages expressing WT or C282Y HFE [32]. In this study, we used VSV G-pseudotyped HIV-1, which expresses luciferase in place of Nef and therefore lacks the effect of Nef on HFE. It would be of interest to analyze replication of HIV-1 with and without Nef in primary macrophages, with WT and C326Y ferroportin.
Our study showed that HIV-1 transcription is induced in the cells transfected with HIV-1 LTR LacZ expression vector and Tat expression vector. Interestingly, higher concentrations of hepcidin are required for the induction as compared to the induction of transcription from HIV-1 proviral DNA. This may reflect the differences in HIV-1 promoters; HIV-1 genomic DNA contains a full promoter, whereas the HIV-1 LTR LacZ includes only nucleotides -138 to +82 of the HIV-1 genomic DNA. It is possible that induction of HIV-1 transcription by hepcidin involves additional transcriptional factors that act in concert with the HIV-1 Tat protein, such as AP-1 and NFAT [33]. We showed that exposure of differentiated monocytes to hepcidin induced HIV-1 production. Recently, differentiated THP-1 cells were shown to express ferroportin [34, 35], and exposure of differentiated THP-1 cells to hepcidin led to a quick degradation of ferroportin [34]. Several ferroportin mutations, including C326Y, that were associated with greater transferrin saturation and more prominent iron deposition in liver in vivo, were also resistant to hepcidin. This suggests that these ferroportin mutations continuously export iron, even in the presence of hepcidin [12, 36]. Our finding that exposure of the ferroportin C326Y mutant to hepcidin is not associated with enhanced HIV transcription, suggests that other factors that upregulate ferroportin might modulate HIV-1 infection as well. Interestingly, treatment of primary CD4+ T cells with iron and hepcidin augmented the expression of an HIV-1 reporter gene. Thus, our results indicate that the level of ferroportin expression might inversely relate to the level of HIV replication, whereas hepcidin might augment HIV-1 replication. Thus, physiological iron depletion by ferroportin as shown here, iron depletion by iron chelators as we previously showed [2], or reduction of hepcidin expression might restrict HIV-1 replication and be thought of as potential avenues for future HIV-1 therapy. Hepcidin expression, on the other hand, may be associated with augmentation of HIV-1 replication in macrophages and T cells and potential acceleration of HIV-1 progression. Future studies on the effect of hepcidin-resistant mutations in ferroportin and the effect of hepcidin on HIV-1 replication in patients might provide further insights on HIV-1 pathogenesis.
We are the first to address the effect of ferroportin expression and hepcidin on HIV-1. Collectively, our results indicate that HIV-1 transcription is lower in the cells that express ferroportin and that inhibition of ferroportin expression with hepcidin is associated with augmentation of HIV-1 transcription and viral production.
Mouse monoclonal anti-ferroportin (MTP-1) antibody was purchased from Alpha Diagnostics. Anti-α-tubulin was purchased from Santa Cruz Biotechnology (Santa Cruz, CA). CEM and 293T cells were purchased from ATCC (Manassas, VA). The Human Promonocytic (THP-1) cells were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH from Drs. Li Wu and Vineet N. KewalRamani [37].
Cell culture
293T cells were cultured in Dulbecco's Modified Eagles Medium (DMEM) containing 10% fetal bovine serum (FBS) (Life Technologies) and 1% glutamine (Life Technologies) at 37°C in the presence of 5% CO2. CEM T cells and human primary monocyte and macrophages (see below) were grown at 37°C in RPMI-1640 medium (Life Technologies) supplemented with 10% fetal bovine serum, 1% glutamine, 1% penicillin and 1% streptomycin. THP-1 cells were grown under the same conditions except that the media was supplemented with 0.05 mM β-mercaptoethanol. The cells were seeded at 0.5 × 106 cells/ml into 6-well plates.
Human WT ferroportin and C326Y mutant ferroportin cloned with c-Myc and histidine tags in pcDNA3.1 expression vector was kindly provided Dr. Hal Drakesmith [12]. To generate GFP-tagged human ferroportin, the ferroportin coding sequences from WT ferroportin and ferroportin C326Y mutant were amplified by PCR with primers (forward primer: GCCTCGAGATGACCAGGGCGGGAGATCAC and reverse primer: GCGGTACCGTAACAACAGATGTATTTGCTTGATTTTC) that included XhoI and Kpn1 restriction sites (shown in italic). The PCR products were digested with XhoI and Kpn1 (BioLabs, Ipswich, MA) and ligated into the pEGFP-N1 vector (Clontech, Mountain View, CA) that was also digested with XhoI and Kpn1 and ligated. The ligation products were transformed into E. coli DH5α cells (Invitrogen, Carlsbad, CA) and kanamycin-resistant colonies were selected. WT ferroportin-EGFP and ferroportin C326Y-GFP-expressing plasmids were purified using Qiagen (Valencia, CA) purification kit and sequenced using Macrogen service (Rockville, MD). The HIV-1 reporter contained HIV-1 LTR (-138 to +82) followed by a nuclear localization signal (NLS) and the LacZ reporter gene (courtesy of Dr. Michael Emerman, Fred Hutchinson Cancer Institute, Seattle, WA) [38]. The pHEF-VSVG expression vector (courtesy of Dr. Lung-Ji Chang) and pNL4-3.Luc.R-E- (Courtesy of Dr. Nathaniel Landau) were obtained from the NIH AIDS Research and Reference Reagent Program. The luciferase reporters under the control of WT HIV-1 LTR (-105 to +77), HIV-1 LTR (-105 to +77) with Sp1-inactivated sites and HIV-1 LTR (-81 to +77) with NF-κB-deleted sites were courtesy of Dr. Manuel López-Cabrera (Unidad de Biología Molecular, Madrid, Spain) [17]. CD4 expression vector was created by cloning CD4 coding sequence under the control of CMV promoter in the Adeno link vector and was a courtesy of Dr. Marina Jerebtsova (Childrens National Medical Center, Washington DC).
293T cells were seeded in 6 well plates to achieve 50% confluence at the day of transfection. The cells were transfected with indicated plasmids using Lipofectamine and Plus reagents (Life Technologies) following manufacturer's protocol. The efficiency of transfection was verified using a plasmid encoding green fluorescent protein. The cells were cultured for 48 hours post-transfection and then analyzed for HIV-1 transcription or ferroportin expression.
Western blotting
To measure the expression of c-myc tagged ferroportin expression in 293T cell or endogenous ferroportin in CEM and THP-1 cells, the cells were lyzed in ferritin lysis buffer (50 mM Tris-HCl pH 7.5, 150 mm NaCl, 0.5% NP-40 and 5 mm EDTA). Equal amount of protein (30 μg) was supplemented with SDS-loading buffer (50 mM Tris-HCl pH 6.8, 2% SDS, 10% glycerol, 1% β-mercaptoethanol, 0.1% bromophenol blue), heated at 70°C 2 min and separated on 8% polyacrylamide gel (293T cells) or 8% Tris-Tricine gel (CEM and THP-1 cells). Proteins were transferred to PVDF membranes (Millipore, Allen, TX). Membranes were blocked with 5% milk and incubated overnight at 4°C with anti-c-Myc Tag (Upstate) antibodies, then washed, incubated with anti-rabbit horseradish peroxidase linked F(ab')2 fragment (GE Healthcare UK Limited) and analyzed using Super Signal West Pico Chemiluminescent Substrate Kit (Pierce). For a loading control, we used mouse anti-α-tubulin antibodies (Santa Cruz, CA).
Measurement of cellular ferritin
The cells were lysed in ferritin lysis buffer (50 mM Tris-HCl pH 7.5, 150 mm NaCl, 0.5% NP-40 and 5 mm EDTA) for 10 min at 4°C. Lysates were spun at 10,000 g for 15 min to precipitate nuclear material and organelles. Protein concentration was measured using Bradford assay (Bio-Rad, Hercules, CA). Ferritin concentration was measured using Spectro Ferritin ELISA kit (Ramco Laboratories,TX). Typically, we used for the ELISA about 50 μg of total protein from 293T cell lysate or lysates of non-iron treated THP-1 or primary monocytes or macrophages. For the iron treated monocytes or macrophages, we used lower amounts of protein (0.5-5 μg).
Preparation of pseudotyped HIV-1 virus expressing Luciferase (VSV G-HIV-1 Luc)
293T cells were grown on 100 mm plates and transfected using Ca-Phosphate method [16] with VSVG-expressing vector (gpHEF-VSVG) and pNL4-3.Luc.R-E- molecular clone that contained two nonsense frame shifts in Env and Vpr genes and Luciferase gene cloned in place of nef [18, 19]. At 72 h posttransfection, the medium was collected, briefly centrifuged at 1,000 g for 10 min; and then the virus was collected by centrifugation at 4°C for 6 h at 14,000 g. The precipitated virus was resuspended in PBS containing 10% glycerol, aliquoted and stored at -70°C.
Luciferase Assays, EGFP fluorescence measurements and β-galactosidase assays
293T cells transfected with pNL4-3.Luc.R-E- plasmid or VSVG-HIV-1 Luc infected THP-1 cells or primary monocytes were washed with PBS, resuspended in 100 μl of PBS/well in 96-well plate. Then 100 μl of reconstituted Luclite buffer (Luclite kit, Perkin Elmer) were added to each well, and after 10 min incubation the lysates were transferred into the white plates (Perkin Elmer) and luminescence was measured on Labsystems Luminoscan RT (Perkin Elmer). Where indicated, the fluorescence was measured after the measurement of luminescence at 480 nm excitation and 510 nm emission using a Luminescence Spectrometer LS50B (Perkin-Elmer) equipped with a robotic 96-well scanner. The β-galactosidase assays were performed as we previously described [16].
Measurement of labile iron
We analyzed labile iron pool (LIP) following the protocol of Cabantchik and colleagues who used calcein-AM followed by iron chelators SIH to detect the amount of chelatable cellular iron [21]. Untreated or iron treated CEM or THP-1 cells were supplemented with 0.2 μM calcein-AM (Molecular Probes, Invitrogen) for 10 min at 37°C. Then the cells were washed with PBS, and fluorescence was measured on Luminescence Spectrometer LS50B (Perkin-Elmer) equipped with a robotic 96-well scanner using 495 nm excitation and 515 nm emission. This fluorescence measurement was designated as time zero. Then 30 μM SIH was added and fluorescence was measured at the indicated time points. We used the following formula to plot the data: F/Fi = 1 + k(Q) , where Fi = fluorescence in the presence of quencher at time 0, and F = fluorescence at given time, and Q- concentration of quencher. Thus, (F-Fi)/Fivalue is proportional to the concentration of chelatable iron when equilibrium is reached, and calcein fluorescence is dequenched.
Infection of human primary monocytes and CD4+ T cells with dual tropic HIV-1
Human primary monocytes and CD4+ T cells were purchased from Astarte Biologics (Redmond, WA). CD4+ T cells were treated with PHA and IL-2 and half a million cells were infected with dual tropic HIV-1 89.6 (AIDS reagent Catalogue, 50 ng of p24 gag antigen). At 24 hrs postinfection, the cells were treated with 0.3 μM hepcidin for 3 hrs and then with 100 μM FAC for 24 hrs. At 48 hours postinfection, medium was collected, and RT was measured. Monocytes were differentiated into Macrophages via incubation in 10 ng/ml M-CSF for 1 week with medium change every 2 days. At day 4, they were infected with 89.6 virus. For RT assays, viral supernatants (10 μl) were incubated in a 96-well plate with RT reaction mixture containing 1× RT buffer (50 mM Tris-HCl, 1 mM DTT, 5 mM MgCl2, 20 mM KCl), 0.1% Triton, poly(A) (10-2 U), poly(dT) (10-2 U) and [3H]TTP. The mixture was incubated overnight at 37°C and 5 μl of the reaction mix was spotted on a DEAE Filter mat paper (PerkinElmer, Shelton, CT, USA) washed four times with 5% Na2HPO4 and three times with water, and then dried completely. RT activity was measured in a Betaplate counter (Wallac, Gaithersburg, MD).
FACS analysis
C-myc linked ferroportin [12] or CD4 were expressed in 293T cells. The cells were treated with 0.4 μM calcein-AM (Invitrogen) for 1 hr to label the cells for detection in the blue fluorescence channel. The cells were scraped, blocked with 5% goat serum (Sigma) and stained with anti-c-Myc antibodies linked to Allophycocyanin (APC) (Cayman Chemical Company) in 1:100 dilution to detect ferroportin or anti-CD4 antibodies linked to APC (BD Bioscience) in 1:100 dilution to detect CD4 at 4°C for 2 hrs. The cells were precipitated by centrifugation and resuspended in the cell suspension buffer (Agilent) and loaded to the cell checkout chip (Agilent). Fluorescence-Activated Cell Sorting (FACS) was performed on the cell checkout chip in 2100 Bioanalyzer (Agilent). For the analysis of EGFP-linked ferroportin, 293T cells were transfected with GFP-tagged human ferroportin, treated where indicated with 0.1 μM hepcidin for 4 hrs and GFP expression was measured by FACS (Becton-Dickinson) and data were analysed by FlowJo software.
This project was supported by NIH Research Grants 2 R25 HL003679-08 (to VRG) funded by the National Heart, Lung, and Blood Institute and The Office of Research on Minority Health; 2MO1 RR10284 (to VRG), 1SC1GM082325-01 (to SN); by Howard University Seed Grant (to SN), RCMI-NIH 2G12RR003048 (to SN as Proteomics Core Director) from the Research Centers in Minority Institutions (RCMI) Program (Division of Research Infrastructure, National Center for Research Resources, NIH) and AI074410 (to FK) and AI078859 (to FK) from NIAID, NIH. We would like to thank Dr. Hal Drakesmith (John Radcliffe Hospital, Oxford, UK) for the ferroportin expression vectors and Dr. Mitchell D. Knutson (University of Florida, Gainesville, FL) for providing anti-ferroportin antibodies and helpful suggestions on the detection of ferroportin by immunoblotting. We thank Prem Ponka (McGill University) for the gift of SIH. The authors also thank Dr. Michael Emerman (Fred Hutchinson Cancer Institute, Seattle, WA) for the HIV-1 LTR LacZ expression vector; Drs. Mathieu Bollen and Monique Beullens (Catholic University, Leuven, Belgium) for mutant NIPP1 pA-RATA-EGFP-expressing vector and Dr. Marina Jerebtsova (Children's National Medical Center) for CD4 expression vector. The following reagent was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: THP-1 cells (courtesy of Drs. Li Wu and Vineet N. KewalRamani), pHEF-VSVG expression vector (courtesy of Dr. Lung-Ji Chang), pNL4-3.Luc.R-E- (courtesy of Dr. Nathaniel Landau) and HIV-1 89.6 (courtesy of Dr. Ronald Collman). We also thank Dr. Manuel López-Cabrera (Unidad de Biología Molecular, Madrid, Spain) for HIV-1 LTR luciferase reporters.
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With SQL Server 2016, as most of us are aware, there are numerous features that bring some amazing functionality to end users and really strive to complete the end-to-end user experience. Microsoft has improved all key areas of the BI stack over the last decade by leaps and bounds up through SQL Server 2014…..with the exception of SSRS. Yes, there have been improvements, but they've been minor. In my humble yet honest opinion, Microsoft has fallen short of meeting customer expectations in this area. Their visualizations were incomplete, the user experience was a bit clunky, and performance was never terribly great.
There were constant hurdles to overcome when using SSRS. Personally, I would snapshot everything, cache as much as possible, automate delivery during off-hours and do my best to have SSRS display reports and do nothing more because performance seemed sub-part. All of my stored procedures would do all of the heavy lifting on the database side, and the majority of my "report development" time would be spent on the data architecture piece. SSRS would simply render and display the data.
Fast forward to February 4, 2014…..the day Satya Nadella was appointed CEO of Microsoft and the exact day that Microsoft began the path toward data and cloud leadership. He has done more for this company than imaginable and brought it from the brink of obscurity to the industry(ies) leader. He has accepted the shortcomings that the product stack has had and began planning to overcome each and every one of them.
Microsoft knew that the user community wasn't terribly fond of SSRS, licensing was clear evidence of this. Tableau was the recognized market leader with their flashy visualizations and that "shiny new object" appeal. Rather than trying to build in-house with personnel that may not have had the creativity nor vision, they went after a company that clearly illustrated visualization leadership, Datazen.
What came next was a combination of the great visualizations of mobile reports (and still including their paginated reports) with the one piece of SSRS that was stable and highly respected, the security layer.
The Business Case for SSRS 2016 and Mobile Reports
So the obvious question here is, "Well I already have SSRS, why do I need this?" Or "I already have Tableau, Cognos, or some other reporting platform. Why would I want to switch to this?"
So for me, the above image makes one, and possibly the most important [particularly among leadership], aspect crystal clear…..consumability….the ability to consume reports on ANY devices ranging from your PC to your tablet to your mobile phone, all of which have a level of control allowing you to maximize your screen real estate.
Business insights through rich visualizations on any device. Native apps for Windows, iOS and Android
- Access your data from anywhere
- Touch optimized data exploration and perfect scaling to any screen form-factor
- Collaborate with colleagues on the go
- Acquisition of Datazen
- Datazen Migration Assistant (for those that currently ues Datazen)
- New Web Portal
- Branding
- Updated Report Builder
- Mobile Report Publisher
- Higher DPI
- Printing (no ActiveX)
- Visual Studio 2015
With all of this stated, it's important to understand…..
Mobile Reports vs Traditional (Paginated) SSRS Reports
SSRS 2016 Overview
Now that we have a decent understanding of the inception of SSRS 2016, as well as what mobile reporting is, let's dive into what SSRS 2016 IS and how Microsoft came to the conclusions they did by looking at the roadmap below. As we can see, the yellow circled items reflect SSRS 2016, but there's an entire ecosystem of business intelligence that includes Power BI, mobile apps, Excel, etc.
SSRS 2016 also includes the following improvements:
- HTML 5 Rendering Engine
- Cross browser compliant (Edge, Explorer, Firefox, Safari, etc.)
- PDF Replaces ActiveX for Remote Printing
- No ActiveX controls required (security hole)
- Modern paginated reports
- New, modern styles for charts, gauges, maps and other visualizations
- File Export
- XML, CSV, PDF, MHTML, Excel, PowerPoint, TIFF and Word *(advanced features)
- Custom Branding
- Customize the web portal logo and colors by using a branding pack
- KPIs
- Create data-driven and contextual KPIs in the web portal, including the ability to drill-through to more detailed reports (mobile, paginated, etc.)
- Favorites
- Save your daily/favorite content, including KPIs, Mobile/Paginated Reports, and PBI Reports
SSRS Web Portal
Web Portal
One of the great improvements is the addition of the "Web Portal". I generally change the URL to reflect this nomenclature as well so it becomes http://localhost/WebPortal/. I don't follow the traditional "reports" nomenclature because it's so much more than that now. It's a "one stop shop" for all of your reporting needs, from data sources to data sets, to KPIs to mobile reports, to paginated reports, to Power BI reports (to be discussed later), to any other file of your choosing (similar to SharePoint repository).
Similar to SharePoint and modifying the cascading style sheets (CSS), users can modify some of the basic items such as the logo, title, title colors, background colors, etc.
A brand package for Reporting Services consists of three items and is packaged as a zip file, which must then be uploaded to SSRS in the Branding section of the Settings page.
Once at the Power BI Web Portal, users have the ability to add their "every day" items to their list of Favorites. This way, every time they log into the portal, their Favorites are displayed only. This helps to overcome the overbearing directory structure that is traditional seen in SSRS. Users don't need to remember which items reside in which path, they simply need to "Star" it and it's now on their home page at their convenience. There is still the ability to search for specific reports, but I would only use that when you are unsure of what you're looking for.
How to Create SSRS 2016 Mobile Reports
Before we discuss how to create SSRS 2016 Mobile Reports, let's quickly review the evolution of the tools from SQL Server inception to current day.
As we can see, some tools have come and gone, while one has remained relatively stable and that's Visual Studio. This tool will still be the primary and recommended development tool for standard (paginated) SSRS reports. Assuming most have used this tool and written SSRS reports, we're going to focus on SSRS 2016 Mobile Reports, and the new tool we use to create them.
SQL Server Mobile Report Publisher
Install the Mobile Report Publisher tool to create mobile reports. Use this SQL Server Mobile Report Publisher link to download the tool.
This application requires .NET Framework 4.5 (or later) and Visual C++ Redistributable for Visual Studio 2012 (x86).
Once installation is complete, fire up the Mobile Report Publisher!
You'll immediately notice a completely different UI compared to both the classic Report Builder and Visual Studio. There are 6 basic settings you need to understand in order to create reports.
- Layout (Navigators, Gauges, Charts)
- Data (Add, Refresh, Export)
- Report Settings
- Preview
- Grid Control
- Layout Control
Before we dig into more detail, let's decide which approach we want to take when creating our mobile report.
Design First
In the design-first approach, create a mobile report layout first without importing any data. This is a good way to create a mobile report when unsure that the data is formatted correctly. Without real data, gallery elements are automatically bound to generated simulated data, which can be exported and used as a template to describe the required data.
Data First
The data-first approach is to import all required data first, then design the mobile report and set data properties on the mobile report elements. This has the advantage of being able to connect each element to real data when added to the layout. When using a data-first approach, be sure that the real data is formatted correctly for use with Mobile Report Publisher.
My personal preference is the Data First approach. I like to understand how each and every role of user is going to interact with the data, at which level of granularity, etc. Then once that's established, I create data sets at the lowest level first, then aggregate up so each and evern layer of reporting can be satisfied (detailed level [paginated], mobile report, KPI, etc.)
I feel that this process is akin to building a house. The foundation is your data architecture, the windows, curtains, doors, etc. are your reporting solution (final and decorative pieces), while your framing and walls are your data strategy which helps combine the two.
Once you've selected your approach, create a data source and a data set with either the standard Report Builder or Visual Studio. This is a pain point I hope they fix soon, because as of now you cannot create a data source or dataset with the SQL Server Mobile Report Publisher.
Proper Chart Types
Once you've created both the data source and data set, select the proper chart type. There is some overlap with the standard SSRS paginated report chart types, so select the one matching the type and granularity of data. The chart below should be helpful.
Mobile Specific Chart Types
For chart types specific to the mobile reporting component of SSRS, reference the following chart to follow best practices and recommendations.
Number of Charts per Layout
Once you've decided which chart type to use, click and drag it to the grid. You can then resize, change the data source, add drill through actions, etc. from there. To maximize the user experience, be sure to configure each report size with a specific layout. Screen real estate is tricky. Too much is overpowering, while too little leaves something to be desired. Consider putting more report parts on the computer layout, with less on the tablet, and the fewest on the mobile. Prioritize according to chart importance and insight value to the anticipated audience.
Once this is all completed and your high level approach is completed, dig into the details with the Layout, Data and Settings tabs to specify the following information:
- Title
- Sub-Title
- Number Format
- Data Structure
- Drill-through (URL and parameter)
- Series
- Aggregations (Sum, Avg, etc.)
- Currency (USD, EU, etc.)
- Date Information
We won't dig into all of this, or specifics around mobile report development, as the intent of this was to demonstrate the overall value and capabilities of SSRS 2016 Mobile Reports.
One final thing to note is that there is an option to Preview the report similar to Report Builder and Visual Studio, so be sure to use that before you deploy (save) to the SSRS 2016 server.
SSRS 2016 and Power BI
Many people mistakenly think that SSRS 2016 and Power BI are the same thing, but in my opinion, they are completely different. The functionality, the licensing, etc. are all different. The only things they have in common are that they're reporting solutions (geared to different audiences), and they play well with one another.
I'll be posting another blog in the coming weeks comparing and contrasting the two, as well as possibly leveraging BOTH!
The current version (as of now is SP1) currently supports uploading Power BI files, but they function similarly to SharePoint and any other website. When the user clicks on the file in the download bar, your browser detects the MIME type and opens the associated thick client (if available), in this case Power BI Desktop. SSRS 2016 currently DOES NOT render Power BI reports. This means that each and every person that would like to use the Power BI files MUST have the Desktop application installed. There is a workaround where you can create a HTML page that has a iFrame embedded that you can get from the Power BI portal, but bear in mind this isn't truly an on-premises solution. The report and data (usually) is still coming FROM the Power BI portal.
However, with all of that said, the crowd has been clamoring for an on-premises solution for Power BI. Previously, Microsoft's answer would be SSRS 2016…..and it looks like it still is.
SSRS 2016 Technical Preview
Currently in technical preview, Microsoft has answered the call and will support Power BI on-premises. SSRS 2016 Technical Preview can currently RENDER Power BI reports, not just store them. Here are a few important points on the current state.
- On-premises solution to Power BI Sites (Cloud)
- Create reports with Power BI Desktop
- Connect "live" to Analysis Services models – both Tabular and Multidimensional (cubes)
- Visually explore data and create an interactive report
- Save reports to SSRS 2016 Technical Preview
- View and interact with the report in your web browser
- Same version of Power BI Desktop
So it looks like this may be released with SQL Server 2016 SP2, which would be a great addition. It's still a mystery as to which features will be supported and which will not. Things like the Natural Language, Quick Insights and dashboards probably will not, while a myriad of additional data sources and drill-throughs probably will. This is all speculation, but time will tell and there are exciting times ahead!
To see/hear the full Allegient webinar, be sure to check it out here!


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As a result of a number of analytic projects for different intelligence agencies, a major focus of my work during the past several years has involved examining the practice of analysis within the US Intelligence Community.[1] This study was prompted by a growing conviction—shared by others, to be sure—that improving the analytic products delivered by Intelligence Community components had to begin with a critical and thorough appraisal of the way those products are created. A conversation with a physicist friend in 2002 had triggered thoughts on several basic differences between the practice of science and intelligence analysis. Shortly thereafter, an invitation to give a seminar on intelligence analysis at Stanford University led me to prepare a briefing entitled "Intelligence and Warning: Analytic Pathologies," which focused on a diagnosis of the problems highlighted by recent intelligence failures.[2] As Donald Stokes noted in his seminal book on science and technological innovation, Pasteur's Quadrant, "Pathologies have proved to be both a continuing source of insight into the system's normal functioning and a motive for extending basic knowledge."[3]
The Analytic Pathologies framework yields four insights that are crucial both to accurate diagnosis and to developing effective remedies. First, the framework enables analysts to identify individual analytic impediments and determine their sources. Second, it prompts analysts to detect the systemic pathologies that result from closely-coupled networks and to find the linkages among the individual impediments. Third, it demonstrates that each of these networks, and thus each systemic pathology, usually spans multiple levels within the hierarchy of the Intelligence Community. Fourth, the framework highlights the need to treat both the systemic pathologies and the individual impediments by focusing effective remedial measures on the right target and at the appropriate level.
In response to presentations to community audiences, a number of senior intelligence officials subsequently recommended that I use the diagnostic framework of the briefing to develop corrective measures for the dysfunctional analysis practices identified there. I circulated the resulting draft for comment and was delighted to receive many useful suggestions, most of which have been incorporated in this version.
Several knowledgeable readers of the draft also raised the issue of the intended audience, strongly suggesting that this should be the senior decisionmakers, in both the Executive Branch and Congress, who could take action to implement the ideas it presented. They also pointedly recommended that the study be substantially condensed, as it was too long and "too rich" for that readership. That audience is, after all, composed of very busy people.
From the beginning, however, I have intended this study to serve as a vehicle for an in-depth discussion of what I believe to be the real sources of the analytic pathologies identified in the briefing—the ingrained habits and practices of the Intelligence Community's analytic corps—and not the organizational structures and directive authorities that are the focus of most legislative and executive branch reformers. Thus, my intended audience has been the cadre of professional intelligence officers who are the makers and keepers of the analytic culture. Without their agreement on causes and corrective measures, I believe real transformation of intelligence analysis will not occur.
Moreover, during the writing of this study, I was fortunate enough to serve on the selection panel for the inaugural Galileo Awards.[4] One of the winning papers focused on a similar issue—the appropriate audience for intelligence—and this reinforced my original inclination.[5] I have decided, therefore, not to condense this study in an effort to fit the time constraints of very high-level readers. I hope, instead, that the summary that follows this introduction proves sufficiently interesting to tempt them to tackle the remainder of the study, where the logic chains that I believe are necessary to convince intelligence professionals of the correctness of the diagnosis and the appropriateness of the suggested remedies are laid out in detail.
[1]Although this paper will use the common terminology of "Intelligence Community" (IC), it is worth noting that the agencies of which it is composed seldom exhibit the social cohesion or sense of purpose that a real community should. A more appropriate term might be "intelligence enterprise," which is defined in Webster's Third International edition as "a unit of economic or business organization or activity."
[2]The briefing was first presented in early November 2003 to a seminar at Stanford University's Center for International Security and Cooperation (CISAC) and was revised for a Potomac Institute seminar on the "Revolution in Intelligence Affairs" on 17 May 2004. It will be cited hereafter as "Analytic Pathologies Briefing."
[3]Donald E. Stokes, Pasteur's Quadrant: Basic Science and Technological Innovation.
[4]The Galileo Awards were an initiative of DCI George Tenet, who, in June 2004, invited members of the Intelligence Community to submit unclassified papers dealing with all aspects of the future of US intelligence. DCI Porter Goss presented the first awards in February 2005.
[5]David Rozak, et al., "Redefining the First Customer: Transforming Intelligence Through Peer-Reviewed Publications."


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The Grand Canyon is home to some of nature's most striking wonders, many of which you only get to see when you hike up to them. Even experienced hikers sometimes face difficulty in this high desert climate, though. In fact, the National Park Service's website for the Grand Canyon warns (in bold font), "Everyone who hikes in the canyon for the first time reports that it was more difficult than they expected."
Don't worry, though. A little pre-trip conditioning, paired with smart hiking strategies will help make sure you see everything the canyon has to offer, and that you do it safely. Here are 6 tips to hike smart in the Grand Canyon:
These simple tips will help you tackle all the side hikes your guides can throw at you and make sure that you see all the canyon's hidden gems on your Grand Canyon expedition.
6 Tips for Hiking on Your Grand Canyon Expedition was last modified: August 31st, 2015 by


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Congratulations! You've taken the first steps toward losing weight and living a healthier, more vibrant lifestyle. Now that you've lost some pounds and are feeling better than ever, it's time to shift strategies and focus on keeping off that weight for good. Here are some tried-and-true ways to maintain your weight loss and overall health for the long haul.
Eat Often
This may sound counterintuitive, but eating three healthy meals and a few snacks each day will never give your body a chance to feel hungry. You will be far less likely to overeat or overindulge in unhealthy snacks, and your metabolism will work at a steady rate, burning calories and keeping you lean.
Don't Overindulge in High-fat Additions
Salads are a great choice for any meal, but if you pile on the cheese, croutons, and heavy dressing, you are probably adding way more calories than you think. Just a slice of cheddar on your sandwich adds 100 calories to your meal. Instead, opt for healthy, but flavorful additions – sunflower seeds, grainy mustard, onions, pickles, or extra veggies. You don't want to nix your favorite foods altogether, just think of them as rewards and not your day-to-day reality.
Schedule Your Workouts
You are much more likely to stick to a workout routine if you write it down. Just like grocery shopping and doctor appointments, your exercise routine is too important to skip. Sit down each week and pencil in your physical activities. If you know you have a crunch-day at work, try to make up for it by exercising longer on another day. Your body will thank you for making it a priority.
Don't Drink Your Calories
This is such an easy way to consume fewer calories. Instead of drinking coffee each morning, soda in the afternoon, and a cocktail after work … aim to drink lots of water instead. Water will hydrate your body, plump up your skin, keep your cells working more efficiently, and keep your appetite in check. Water is the elixir of life, with zero calories and countless health benefits. Keep your water bottle full and at the ready, and you'll be well on your way to keeping the pounds off for good.
Make Half of Your Meal Fruits and Veggies
Fruits and vegetables pack lots of nutrients into a small package. They contain very few calories, and give you tons of energy. For breakfast, try a bowl of mixed fruit with a dollop of yogurt and granola. Lunch can be a big salad with a side of lean meat or fish. Whole grains and a small protein serving can complement a pile of baked or roasted vegetables in the evening. As an added bonus, when you consume lots of fruits and vegetables, you can eat more and gain less.
Eat Slowly and Mindfully
Multitasking is a common part of modern life, but when it comes to eating, you'll fare better if you take your time and focus on the enjoyment of the food. Wholesome, healthy meals tastes fantastic, but many people hardly register the taste, smell, or feel of their food. The art of eating has been put on autopilot, and people are eating more and enjoying it less. Chew your food slowly, and really focus on the taste, the smell, and the feel of it in your mouth. This will give your body a chance to register when it is feeling full, and it will give you a chance to really savor your meals.
You've worked hard on this weight loss journey, and you've developed important eating and exercise habits that need to be continued to have lasting effects. Once you've achieved your desired weight, you can work with a Medifast diet counselor to develop strategies that will keep the weight off permanently. Yes, this will take time and perseverance, but the results will be well worth the effort. You're working toward a goal that is about more than losing weight; it's more energy, and a long and vibrant life.


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Private accommodation
Enjoy the rural life
Private rooms are rented by residents in the area of climbers in their private houses. Their advantage is the price and that is the reason why many tourists decided to stay in such places.
Choosing this type of accommodation, we often have the opportunity to commune with domestic animals: ride a horse or cow milk.
If you eat meals in such places very often they are prepared with products from the farm.


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Municipal Court is a division of the Circuit Court of Adair County, 2nd Judicial Circuit. Cases in Municipal Court involve alleged violation of City of Kirksville laws. If you received a ticket/summons for a municipal ordinance violation, you have certain rights and responsibilities.
The prosecuting attorney does not provide legal advice to the general public. To obtain an attorney, you may want to refer to the "Attorney" section in the yellow pages "Attorneys" or contact the Missouri Bar Legal Reference Service at 573.636.3635 for legal referrals. There is a charge for the legal referral service.
Until May 31, 2019
201 South Franklin Street
Kirksville, MO 63501
Phone: 660.627.1237
Fax: 660.665.0940
Office Hours:
Monday - Friday, 8:00 am - 5:00 pm
Closed from 11:00am - 12:00pm for lunch.
Linda Sandstrom, Municipal Court Clerk
As of June 1, 2019 the Kirksville Municipal Court will be handled by the Adair County Circuit Court's Office on 3rd floor of the Courthouse. All payments will be taken there.
Honorable Kristie J. Swaim, Judge
Court will be held on Wednesday's at 11:00 am at the Adair County Courthouse, Division 2 Courtroom.


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School pupils could be taught a second language from primary one
The Modern Languages Working Group has recommended that language learning begins at a younger age.
Scots children could start learning a second language from primary one under new recommendations.
A report from the Modern Languages Working Group has recommended that language learning begins when a child starts primary school.
Responding to the recommendations Minister for Learning Alasdair Allan said the Scottish Government will now explore opportunities for all young people to start learning a second language from primary one.
The report's other key recommendations include advice that learning a third language should start no later than primary five and that primary and secondary schools should work more closely together to ensure better progression in language learning.
To increase its support for language learning Scotland's National Centre for Languages (SCILT) is to receive an uplift in funding to over £600,000 in 2012-13.
As part of this, £120,000 is for pilot projects to further explore how language learning could start from primary one rather than primary six, which is when most schools currently introduce it.
Dr Allan said: "The world is changing rapidly and radically and the government has a duty to ensure that Scottish schools prepare young people so they can flourish and succeed in the globalised, multi-lingual world we now live in.
"One indisputable aspect of modern life is that more people travel widely for jobs and leisure and we must respond accordingly; we will not be as successful as a country and economy if we remain essentially a mono-lingual society.
"The Scottish Government is committed to radically improving the provision of modern languages in our schools. We see the Barcelona Agreement to the '1+2' arrangement – learning two languages in addition to the mother tongue – as key to delivering this commitment.
"This is unique within the UK and will bring us more into line with other EU member states.
"The Modern Languages Working Group has endorsed this approach, and set out a strong case that Scotland can and must do more to provide our young people with a better language learning experience.
"We already set aside £4m annually for local authorities to support modern language teaching. I invite local authorities to work with SCILT to lead the way in what I see as a radical change of approach.
"Introducing two additional languages is an ambitious goal, but these recommendations give us an excellent platform to deliver it.
"Today sees our initial response to this report and we will continue to work to raise language learning to higher levels in the years ahead."


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Spain is a land of artistes, known for its cultural heritage. It is one of the best tourist destinations in Europe as music and dance enthusiasts from the world over crowd the destination to catch a glimpse of its artistic heritage. Spanish dance is gaining popularity among the top dance forms of the world. In this context, a brief description of the Spanish various dance forms becomes imperative.
Spanish various dance forms can be broadly classified as:
Flamenco: Flamenco is the most popular dance form of Spanish. Madrid and Andalucia are the major centers of this dance and most Spanish dancers have taken to this genre of Spanish dance. This dance form has singers who sing live for the performers with frequent clapping to aid the rhythm of the dancer. The dance along with the music has a strong Arabic influence on them. The later forms of the Flamenco developed variations according to the province and its traditions. The costumes for Flamenco dance forms are varied, very colorful and elaborate.
Classical Spanish Dance: Classical Spanish dance is also known as Estilización. It has dances choreographed by famous music composers of Spain such as Granado, Falla and Turina. It is a smooth blend of Classical ballet, Flamenco and Folklorica forms
Folklorica: Folklorica is a dance form that is as diverse as Spanish. Each province in Spain has a distinct tradition and culture and these folk art forms have incorporated that into their dance. Hence they are known by different names in different regions – Zorcico of Basque, Sardana of Catalonia, Muneira of Galicia and Verdiales of Malaga.
18th Century Dance: 18th century dance form is known as Escuela Bolera in Spanish. This is a very unique dance form where the dancers sport the ancient outfits of Spain from the time of the famous Spanish painter, Goya. Hence this dance form is also referred to as Goyescas. Not only the outfits, the choreography and the expressions are all typical of the 18th century.
Classical Dance: Classical dance or ballet is a very serious form of dance that includes display of movements that are mastered after years of practice. It is an elegant and classical dance form that is highly technical and difficult to master.
Castanets: Castanet is a simple percussion instrument that Spanish dancers use as an accompaniment. It is a small hand held instrument that has two shells connected on one end by strings. Using these strings, the dancer holds the castanet and plays to the rhythm of the music and dance. Only a few dance forms use castanets, Sevillanas in particular. Only those dance forms are grouped under Castanets.
Dancers who learn and practice Spanish various dance forms are also experimenting and trying to popularize these forms in countries other than Europe.
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I feel like I've been neglecting this site some lately. My time is being stretched incredibly thin between a certain someone and law school finals. As soon as exams are over, I should be back to my normal posting routine and will start replying to the growing mountain of 'non-pressing' e-mail.
As you were.


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New York, New York.
I am a little addicted to the history of New York.
It's been a very interesting week here. Spring has come to New York in all of its glory. I've been reading all of the DC folks commenting on Facebook about their cherry blossoms and chuckling to myself. Ohhh you have cherry blossoms, do you? How about a little of THIS?
That's a picture of City Hall. I took it this weekend when I marched myself over the Brooklyn Bridge and down Broadway and Wall Street to revisit the places I've been reading so much about. I'm only up to the late 17th century in Gotham, so the scope of New York at that time is much more walkable. Bowling Green to Wall Street walkable.
Of course, I did not lug that heavy book on my walk. Instead I caught up on my reading when I discovered this awesome time line in the City Hall park:
I never went through the New Yorker tourist phase because I grew up so close to the city and because, frankly, I wasn't interested. New York wasn't Paris and I was pissed about it. Lately I've been a lot more at peace with that old issue and maybe that's made me more ready to be interested in America at all (see: trip WITHIN the country for Easter).
One final nerdy recommendation. I've been downloading some pretty interesting podcasts. They're called Stuff You Missed in History Class and the girls that do it sound a lot like that old SNL skit where two women have a super-nice radio show. But if you can get past that vibe, you'll learn some cool stuff about the Stamp Act of 1765 and Pocahontas.
Is anyone else into American History? Have any of you been good NY tourists? What kinds of stuff do you recommend?
2 comments:
- cecilbgulpy said...
Hey, I hear you about being a tourist at home! Something I'm really looking forward to when I visit my family this summer is my mom taking me on a tour of different stops on the Underground Railroad in Delaware. There were loads of them, apparently, and we, of course, never visited any on school trips or really studied the UR in any depth at all! Last year, I read this fantastic book about runaway slaves in Maryland (Song Yet Sung) and it made me really interested in the the Underground Railroad, communication codes, etc. It's also kind of the Amer. equiv. to the French Resistance... Bizz, Blythe
- Jen said...
Oh, nice! I'd love to see the Underground Railroad stuff... btw, very cool when I'm reading stuff to notice what was up in the US in 1789 and imagine la Revolution happening across the way!


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old joe
11:37 AM angeleyes: just got an email on some info This is huge!!! Iraq is claiming stocks traded on the ISX (Iraq Stock Exchange) will be traded publicly as of Feb 3, 2013. It also states the initial public offering will take place from January 3rd to February 2, 2013 and that the share must be determined by December 25, 2012. In essence, the ISX cant trade stocks publicly without first having a International Tradeable Currency. Hoping, Iraq gets their act together and add value to their currency before the end of this year. This article is consistent to what other articles are telling us, replacing ration card with smart cards, implementing tariffs before the end of year, removing oil subsidizes and the CBI telling us the new currency with Kurdistan, Arabic and English language will be introduced on or about January 1, 2013.


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Tyre trade folks are seeing a lot of dangerous tyres on vehicles with current Warrants of Fitness. The Campaign for Better Tyres says this is a consequence of 12 month Warrants of Fitness (WOF's) where vehicles tyres decline dramatically in the 12 months between WOF tests. For instance, a vehicle may pass it's WOF with front tyres that are worn below the tread on one side but have road legal tread over the other 75% of the tread.
The big problem with WOF compliant tyres with 75% road legal tread is that the other 25% is highly likely to wear down to the steel belts or explode long before the next WOF test. Of course there are some people crying out for random police road checks and road blocks etc to enforce legal tyre standards but do we really want to end up living in a police state when the issue can quite simply be resolved by reverting to 6 monthly WOF checks where vehicle defects can be identified before they progress too far? And surely it is better for our police force to target illegal drugs and violence etc than chase after consumers with worn out tyres.
We recommend motorists check their tyres every 3 of at least 6 months for cracks, bulges and low tread. Unfortunately the best way of doing this is to jack each wheel up and spin them to look for defects or at least bend down or lay on the ground so you can see the inside edge of the tyre. Alternately you could get your tyres checked at a tyre shop. But the best tyre safety check is for an impartial WOF inspector to raise the vehicle on a hoist and rotate each tyre under a high powered light while searching for defects; no other check comes close in terms of effectiveness.
Many motorists will never check their tyres, some of this may due to laziness but for many drivers the issue is simply outside of their skill set. 6 monthly WOF checks will always be a better option than police enforcement traps that load vehicle owners up with penalties and as an added bonus, 6 monthly WOF checks would save lives!
Tyresales has a huge range of cost effective tyre options to ensure your winter motoring safety and WOF compliance.