Digital manager, Cory Goemble uses the HWC on a daily basis and frequently utilizes the capabilities included with Xante's iQueue Workflow. "We have another machine but this one is so far advanced that we use it a lot more. I can go into my Xante Workflow and within five minutes you can be printing envelopes off the Heavyweight. All of the features help out." Overall, both Lesnar and Goemble would recommend the HWC Heavyweight Champion Digital Print System to other shops in need of a printer with both heavy stock and envelope printing capabilities. "As well as the machine runs, the company makes more money and saves money. Hopefully we have a couple more of these in the near future, " says Lesnar.


text:
Q: @configurable Vaadin app controller not reinjecting after tomcat restart I am using a @configurable annotated Vaadin controller together with my Spring context, and it is working fine - except when I need to restart Tomcat, and the sessions are deserialized. Then I get this for my Vaadin app:
org.springframework.beans.factory.wiring.BeanConfigurerSupport BeanFactory has not been set on BeanConfigurerSupport: Make sure this configurer runs in a Spring container. Unable to configure bean of type [web.vaadin.ui.BackOfficeApplication]. Proceeding without injection.
I am thinking that this can be because the vaadin app is reserializing before the spring bean factory has a chance to?
(I am using CTW - aspectj and Spring 3.1.1.RELEASE)
Note:
It seems in the log that these errors come before the "Root WebApplicationContext: initialization started". How can it be that the beans are being autowired before the context initialization is started?

A: I am not an expert on (de)serialization with Spring and Tomcat, and this is not an answer but might be a workaround.
If BackOfficeApplication is your Vaadin application then there is an alternative to using @Configurable on that class. Instead, create a per-Vaadin Application Spring application context XML file and add this to it to cause your BackOfficeApplication instances to be autowired, etc.:
<bean id="backOfficeApplication"
  class="org.dellroad.stuff.vaadin.ContextApplication"
  factory-method="get"/>

In general, @Configurable can be more troublesome than normal bean wiring because they require the configuration to occur at object construction rather than allowing the bean factory to do the wiring later on, where it may be better able to detect loops, enforce ordering, etc.
Ideally normal bean wiring should be used for singletons that are initialized once at the beginning of the application and @Configurable should be used for "on the fly" beans created randomly during normal operation.

redpajama_set_name: RedPajamaStackExchange


text:
Whisky Auctioneer
Search Auction(s)
January Auction Now LIVE, Ends Monday 6 February from* 7pm GMT. February Auction Bottle Deadline 13 February.
Glenrothes 1979 Adelphi 20 Year Old
Winning Bid: £850
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Important: Currency exchange rates are constantly changing; this feature is to be used as a guide price only. All final transactions occur in British Pounds (£).
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Adelphi has a rich history, operating as a distillery in the Gorbals district of Glasgow from 1825, producing spirit from the waters of Loch Katrine. The distillery ceased production in the early 20th century however and several changes in ownership culminating in a takeover by Distillers Company Ltd in 1902. The Adelphi name was revived in 1993 by Jamie Walker, great-grandson of former distillery owner Archibald. With a lineage of whisky expertise he operated Adelphi as private bottling company, which now in the hands of Keith Falconer and David Houston, continues the fine work he began of bottling top quality expressions from Scotland's finest distilleries. The company is now also distilling their own whisky at Ardnamurchan distillery in Glenbeg.
This 20 year old Glenrothes was distilled in 1979 and bottled in 1999.
Earmarked from an early stage an ideal component in blended Scotch whiskies, Glenrothes has long been a key part of big brands such as Cutty Sark and Famous Grouse. Its relationship with the former, lead to a two decade-long association with London wine-merchants, Berry Brothers & Rudd, when they traded their famous blend for the rights to the Glenrothes single malt brand in 2010. The distillery itself remained with Edrington through, and the two were reunited when the now hugely successful brand was returned in 2017. Releases from independent labels like this have also always been highly regarded.
We would recommend viewing/close inspection prior to placing any bids. If this is not an option and you have questions beyond the offered description and images, please contact us for a more in-depth condition report. Otherwise lots will be sold as seen in the images.
Please note: Due to the various ages of bottles and their seals, condition of liquid is at the buyer's discretion and no claim can be lodged against failure/leakage in transit.
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redpajama_set_name: RedPajamaCommonCrawl


Plaid Cymru Assembly Member Adam Price has welcomed the decision by the Assembly's Presiding Officer to fly the flag of Owain Glyndwr outside of the National Assembly for Wales.
MP Jonathan Edwards has used today's session of Prime Minister's Questions to challenge Theresa May over the future of Wales's agricultural sector and the thousands of jobs it supports.
Local Assembly Member, Adam Price met with members of NFU Wales and the Black Mountain Graziers Association last week to discuss rural crime and the agricultural industry post-Brexit.
Local MP and Plaid Cymru's Transport spokesperson, Jonathan Edwards, writes in today's Western Mail highlighting the injustice of Westminster's infrastructure decisions.
Assembly Member Adam Price has called on the Welsh Government to ensure the recommendations made in the Our Valleys, Our Future report produced by the South Wales Valleys Taskforce are extended to see the Amman and Gwendraeth Valleys included in Welsh Government economic plans.


text:
Johann Stamitz Op. 3 Symphonies
Home > Johann Stamitz Op. 3 Symphonies
Blessed with a gift for musical invention and structural organisation, Johann Stamitz was one of the pioneering figures in symphonic music before the emergence of Haydn.
He drove the development of symphonic form via the assimilation of the new operatic overture style resulting in works of brilliance and skilful orchestration.
Stamitz' Op. 3 symphonies, though not composed as a set, showcase why Stamitz was held in such high regard and was so influential: outer movements fizz with energy, and contain virtuosic string writing with frequent dynamic contrasts, while slow movements are intricate and refined.
A new album released on the Naxos label presents recordings Symphonies 1, 3, 4, 5 and 6 performed by the Music Viva Moscow Chamber Orchestra led by Alexander Rudin.
See our full collection of sheet music by Johann Stamitz.
Stamitz, Johann: Symphony in G major, Op. 3, No. 1 (AE049)
Stamitz, Johann: Symphony in E flat major, Op. 3, No. 4 (AE051)
Stamitz, Johann: Symphony in A major, Op. 3, No. 5 (AE052)
Stamitz, Johann: Symphony in F major, Op. 3, No. 6 (AE053)


We are a family run business established in 1921, whose wealth of experience in the furniture and floor covering business has given us a reputation for high quality furniture and unbeatable prices. We belong to A.I.S., the country's largest independently owned buying group of over 600 stores in total, meaning our prices are as keen as any found in other stores, or on the internet.
Here at Marshalls, we believe that creating a beautiful and comfortable home is important. Home is a place that you love, and that reflects who you are. It's your retreat, a place to catch up, an escape. At Marshalls, we know that furnishing your home can be daunting, and we are committed to making the process easy and fun.
Our brands are carefully chosen to ensure that they meet our customer's expectations. Use our website to research ranges and possibilities from the comfort of your home, then ring or call in and we will listen to your ideas, discuss your needs, and help you to develop the perfect solution for your home, your budget and your lifestyle.
We have 3 floors of furniture and flooring, with easy parking in nearby Gascoigne Way car park, or the new on-street 30-minute parking nearby.
Huge selection of suites and recliners, all British made.
Extensive range of dining sets on display.
Large selection of beds and mattresses.
Hundreds of flooring samples to borrow, including carpet, laminate, vinyl or engineered and solid wood.
Friendly advice and excellent product knowledge, along with a heritage of quality and service.
We guarantee competitive prices to all of our customers giving genuine value for money, excellent customer service and free local delivery. If you find a reputable retailer, including online websites, offering identical new goods for sale at a lower inclusive price, then we would appreciate the opportunity to price match.


text:
package org.jvnet.jaxb2_commons.tests.one;

import java.io.StringWriter;

import javax.xml.bind.JAXBContext;
import javax.xml.bind.JAXBElement;
import javax.xml.bind.JAXBException;
import javax.xml.namespace.QName;

import org.junit.Assert;
import org.junit.Test;

public class JavaTypeExampleTest {

	@Test
	public void rountripsBoolean() throws JAXBException {
		final JAXBContext context = JAXBContext
				.newInstance(JavaTypeExample.class);

		final JavaTypeExample value = new JavaTypeExample();
		value.setCustomBooleanProperty(true);
		final StringWriter sw = new StringWriter();
		context.createMarshaller().marshal(
				new JAXBElement<JavaTypeExample>(new QName("test"),
						JavaTypeExample.class, value), sw);
		Assert.assertTrue(sw.toString().contains(">true<"));
//		System.out.println(sw.toString());
	}
}

redpajama_set_name: RedPajamaGithub


text:
Q: Cannot find class in same jar during SBT build I am trying to build an sbt plugin like swagger2markup, but I face an issue when executing this in sbt:
org.apache.commons.configuration2.ex.ConfigurationRuntimeException: java.lang.ClassNotFoundException: org.apache.commons.configuration2.PropertiesConfiguration
    at org.apache.commons.configuration2.beanutils.BeanHelper.fetchBeanClass(BeanHelper.java:549)
..snip..
Caused by: java.lang.ClassNotFoundException: org.apache.commons.configuration2.PropertiesConfiguration
    at java.net.URLClassLoader.findClass(URLClassLoader.java:381)
    at java.lang.ClassLoader.loadClass(ClassLoader.java:424)
    at java.lang.ClassLoader.loadClass(ClassLoader.java:357)
    at java.lang.Class.forName0(Native Method)
    at java.lang.Class.forName(Class.java:348)
    at org.apache.commons.lang3.ClassUtils.getClass(ClassUtils.java:909)

So, trying to lookup the PropertiesConfiguration from a class within the same jar is failing. It seems that sbt runs tasks in a classloader that does not include dependencies. This happens when I run the task from the sbt console.

A: commons-configuration2 is using commons-lang3 to load the class file for ConfigurationBuilder. And commons-lang is trying to use ClassLoader from the current thread to perform the loading see ClassUtils, but it seems that sbt doesn't give you any guaranties about Thread.currentThread().getContextClassLoader, see discussion for more details.
The workaround is to current thread classLoader manually, like:
Thread.currentThread().setContextClassLoader(
  PluignObject.getClass.getClassLoader
)

But to be honest, I'm not sure how safe is this solution.

A: The workaround I managed in the end, was to invoke the task in a forked jvm process:
val runner: ScalaRun = initScoped(myTask.scopedKey, Defaults.runnerInit).value
val log: Logger = streams.value.log
val arguments = Seq()
runner.run(mainClass, classpath.map(_.data), arguments, log)

This worked for me when there was a main class available in the tool I was using.


Are you a boomer or Gen Xer who wants to start a business? Do you wonder if you have what it takes to make it happen? Could you use some insights and encouragement from others who became successful entrepreneurs later in life?
Late-Blooming Entrepreneurs: Eight Principles for Starting a Business after Age 40 features dozens of 40-and-older entrepreneurs, including some who were first introduced on this blog. They'll tell you, in their own words, about the ups and downs of owning a business and what enabled them to succeed.
Late-Blooming Entrepreneurs: Eight Principles for Starting a Business after Age 40 shows why the second half of life can be the right time to start a business. This easy, conversational read delivers a healthy dose of inspiration — and leaves you with the belief that you're never too old to go after what you want.
Don't wait. Grab your copy today from one of these outlets.
"It's never too late to start your own business. Strang's dozens of interviews with boomer entrepreneurs identified eight common threads"….(read the full review here).
— Len Forkas, Founder and President, Milestone Communications, Inc.


Location in Dubai: Offering a spa centre and a private beach area, Jumeirah Al Naseem-Madinat Jumeirah is located in the Umm Suqeim district in Dubai. Mall of the Emirates is 2.4 km from Jumeirah Al Naseem-Madinat Jumeirah, while Galleria Shopping Mall is 10 km from the property. The nearest airport is Dubai International Airport, 21 km from the hotel.
– Valid ID must be presented upon check-in otherwise Best Available rate will apply.


text:
How Reece Works For You
Discover maX
Previous PDF issues
Talent in full bloom
The biggest event of its kind in Victoria, the Melbourne International Flower and Garden Show took place last month in the Carlton Gardens with a five-day display of gardens, floral arrangements, plant sales, gardening talks and demonstrations.
The show also included an awards component celebrating some of Australia's best landscapers and gardeners, recognised for their outstanding talent in the field.
Taking out second place in the Boutique Garden Competition was Joel Barnett. The 34-year-old from InStyle Gardens in Geelong themed this year's entry around his love of tropical foliage and a desire to create a holiday-type environment at home. He's coined his submission 'Lush'.
"I love plants with interesting foliage all year round," Joel explained. "There is still a big push towards low-maintenance gardens and foliage plants are low-maintenance, much more so than lawns."
Competitors in this category had just nine days to construct their show landscapes in a 5m x 5m zone. As the Carlton Gardens is a World Heritage Site, nothing was allowed to penetrate the ground, and there were several tree protection zones to work around. In addition to these restrictions, Joel said scale is the biggest challenge, as he ran into trouble last year with structures that were too large for the site.
"Another lesson was just being more organised and having as much as possible built beforehand," he said.
His award-winning design incorporated a plunge pool, deck and pergola, and featured vertical gardens and green walls. A dynamic space, Joel's design made use of integrated lighting to add drama for the Gardens by Twilight evening session held on Friday, March 31.
"Using lights is an underrated part of garden design," he said. "You can play with shadows and it looks completely different to during the day."
Also featured in Joel's garden was the Skydrop controller, keeping the vertical plants irrigated with WiFi connectivity for truly smart watering.
"There is not a better looking controller on the market than these!" Joel said.
The controller was supplied by Reece Irrigation in Bell Park and helped keep Joel's garden looking fresh for the duration of the event.
See the other winners in their respective categories at melbflowershow.com.au.
Source: https://www.theweeklyreview.com.au/live/top-10-tips-for-small-gardens/
http://melbflowershow.com.au/show-features/boutique-gardens/
Competitions & Promotions Trade Shows & Expos Product Profile Irrigation
Footy Tipping is back in 2019!
Footy Tipping is back in 2019! This year, you can win just by signing up. Register in February to go...
Rothenberger Romax Axial Rehau Tool Package
Every good plumber knows that REHAU is famous for quality. And right now, it's never been easier to ...
Reece Roadshow Passbook Major Prize Winner!
It's been another big year taking the Reece Roadshow across the country, highlighting some of the ne...


text:
est une chanson du groupe de garage rock américain Question Mark and the Mysterians (ou ? & The Mysterians) écrite et composée par son chanteur, Rudy Martinez. Elle sort en single en août 1966 et figure sur le premier album du groupe également intitulé 96 Tears.

Premier single de ? & The Mysterians, il sort dans un premier temps de façon limitée sur le petit label Pa-Go-Go, avant d'être distribué à plus grande échelle par le label Cameo-Parkway. Il connaît alors un grand succès aux États-Unis et au Canada, se classant en tête des ventes dans les deux pays, et entre dans les hit-parades de plusieurs pays d'Europe.

La chanson, devenue un classique du genre garage rock, avec sa ligne d'orgue qui permet aussitôt de l'identifier, et sa production sans fioritures, est souvent présentée comme un des morceaux à l'origine du mouvement punk rock.

96 Tears figure au  de la liste Les 500 plus grandes chansons de tous les temps selon Rolling Stone.

Classements et certifications

Reprises

La chanson a été reprise par différents artistes tels que : Aretha Franklin, The Residents, Thelma Houston, Garland Jeffreys, Suicide, The Stranglers (dont la version se classe  au Royaume-Uni et  en Irlande en 1990), Iggy Pop, Tom Tom Club et en France par The Dogs.

Notes et références

Liens externes
 Discographie du groupe sur Discogs

Chanson de rock américaine
Chanson interprétée par les Stranglers
Chanson interprétée par Thelma Houston
Premier single
Single certifié or aux États-Unis
Single musical sorti en 1966
Single numéro un dans le Billboard Hot 100
Single numéro un dans le Top Singles de RPM

redpajama_set_name: RedPajamaWikipedia


The puppeteer operates the head with its left hand. The left hand of this doll has a device.
The puppeteer moves the right hand of the doll by the right hand. The left hand of the doll is called "yunde". There is a portion on the elbow where the puppet could be strapped. The puppet master handles it with the restrictions that were lacking in the right wrist and the finger of the left hand with the neck.
The puppeteer controls and handles the foot of the doll by holding the hook sticking to the heel of the doll. By doing this, the foot of the doll can walk the stage directly.
In the box, there are three wheels. The front has two wheels and the back has one wheel. The back wheel is wider than the front. When puppeteer places weight on the wheel, he can change direction freely.


An all i-line 0.22 um T-gate process is demonstrated. A resist structure suitable for metal deposition and lift-off is constructed sequentially with two different resist materials. The lithographic process is described in details in this paper.


The innate immune system has been implicated in both AKI and CKD. Damaged mitochondria release danger molecules, such as reactive oxygen species, DNA, and cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL-18 and IL-1β. It is not known if mitochondrial damage persists long after ischemia to sustain chronic inflammasome activation. We conducted a 9-month study in Sprague–Dawley rats after 45 minutes of bilateral renal ischemia. We detected glomerular and peritubular capillary rarefaction, macrophage infiltration, and fibrosis at 1 month. Transmission electron microscopy revealed mitochondrial degeneration, mitophagy, and deformed foot processes in podocytes. These changes progressed over the study period, with a persistent increase in renal cortical expression of IL-18, IL-1β, and TGF-β, despite a gradual decline in TNF-α expression and macrophage infiltration. Treatment with a mitoprotective agent (SS-31; elamipretide) for 6 weeks, starting 1 month after ischemia, preserved mitochondrial integrity, ameliorated expression levels of all inflammatory markers, restored glomerular capillaries and podocyte structure, and arrested glomerulosclerosis and interstitial fibrosis. Further, helium ion microscopy vividly demonstrated the restoration of podocyte structure by SS-31. The protection by SS-31 was sustained for ≥6 months after treatment ended, with normalization of IL-18 and IL-1β expression. These results support a role for mitochondrial damage in inflammasome activation and CKD and suggest mitochondrial protection as a novel therapeutic approach that can arrest the progression of CKD. Notably, SS-31 is effective when given long after AKI and provides persistent protection after termination of drug treatment.
Inflammation plays a critical role in the initiation and progression of renal fibrosis.8 Injured epithelial cells secrete proinflammatory cytokines to recruit inflammatory cells to sites of injury to drive tissue repair. Profibrotic cytokines, such as TGF-β, stimulate matrix-producing cells to produce extracellular matrix. Antifibrotic treatments have mostly targeted TGF-β, but TGF-β is a pleiotropic cytokine with vital anti-inflammatory functions, and blocking TGF-β activity may incite immune activation.10 It is thus imperative that novel targets be identified that can arrest the chronic inflammation and progressive fibrosis.
Inflammasome activation in response to a variety of stimuli appears to converge upon mitochondrial reactive oxygen species (ROS).17–19 Mitochondrial DNA and N-formyl peptides represent two other sources of mitochondrial DAMPs.20 Compounds that cause mitochondrial damage enhance NRLP3 activation, whereas compounds that reduce mitochondrial ROS inhibit inflammasome activation.21–23 Further, NLRP3 appears to bind directly to cardiolipin, a phospholipid that is only expressed on the inner mitochondrial membrane, suggesting that mitochondrial damage and the translocation of cardiolipin to the outer mitochondrial membrane (OMM) may provide the docking signal for inflammasome assembly and activation.24 Ischemia causes mitochondrial injury,25 but it is not known if mitochondrial damage persists long after ischemia to account for sustained inflammasome activation.
SS-31 (also known as elamipretide) is a synthetic tetrapeptide (D-Arg-2′6′-dimethylTyr-Lys-Phe-NH2) that selectively targets cardiolipin on the inner mitochondrial membrane to protect cristae curvature, stabilizes mitochondrial structure, facilitates electron transport, and minimizes ROS production.26–28 SS-31 is very effective in minimizing ischemic AKI and preventing the development of interstitial fibrosis and glomerulosclerosis.25,29 It is not known if later administration of SS-31 can stop the progression of CKD. We conducted a 9-month study in rats subjected to bilateral renal ischemia. Significant mitochondrial damage was found in endothelial cells, podocytes, and proximal tubular cells 9 months after ischemia. Treatment with SS-31, starting 1 month after ischemia and maintained for 6 weeks, protected mitochondrial integrity and halted the progression of glomerulosclerosis and tubulointerstitial fibrosis. The protection by SS-31 was sustained for at least 6 months after treatment ended. Upregulation of IL-1β and IL-18 at 9 months after ischemia was normalized by SS-31 treatment, suggesting that SS-31 reduced CKD by protecting mitochondria and preventing inflammasome activation.
Adult rats (n=53) were subjected to bilateral renal ischemia for 45 minutes and then allowed to recover for 4 weeks. Mortality was approximately 30% with 45 minutes ischemia, but normal renal function was fully restored after 4 weeks.29 Surviving animals (n=37) were randomly assigned to treatment with saline or SS-31 (2 mg/kg per day) for 1.5 months via a subcutaneously implanted osmotic pump (see Table 1).
We previously reported that this duration of ischemia results in tubular necrosis and significant increase in serum creatinine, BUN, and fractional excretion of Na+ and K+.25 Although full recovery of renal function is achieved <1 week after ischemia, interstitial fibrosis is seen in the outer medulla 1 month later.29 In this study, we found progressive increase in interstitial fibrosis and glomerulosclerosis through 9 months after ischemia (Figure 1, A–D) that were associated with continuing increase in TGF-β expression in renal cortical tissue (Figure 1E). Six weeks of treatment with SS-31, starting 1 month after ischemia, significantly blunted the upregulation of TGF-β (Figure 1E, Supplemental Figure 1) and halted the progression of interstitial fibrosis and glomerulosclerosis (Figure 1, A–D). This antifibrotic effect of SS-31 was sustained for >6 months after treatment (Figure 1, A–D).
SS-31 halts progression of interstitial fibrosis and glomerulosclerosis after acute renal ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. (A) Representative images of trichrome stain of the renal cortex showing progressive increase in glomerulosclerosis at 1 month (1M), 2.5 months (2.5M), and 9 months (9M) after acute ischemia. Treatment with SS-31 starting at 1M prevented progression of fibrosis at 2.5M, and protection was seen even 6 months after termination of treatment. (B) Representative images of trichrome stain of the inner stripe of the outer medulla (ISOM) showing prevention of fibrosis by SS-31 treatment. (C) Quantification of trichrome stain in glomeruli at various times after ischemia. Data shown as mean±SEM; n=4/group; ***P<0.001. (D) Quantification of trichrome stain in ISOM at various times after ischemia. Data shown as mean±SEM; n=4/group; **P<0.01; ***P<0.001. (E) Representative Western blot and densitometric analysis of TGF-β expression in renal cortical tissue. Data shown as mean±SEM; n=4/group; ***P<0.001. (See Supplemental Figure 1 for all Western blots).
We previously reported >15-fold increase in TNF-α and interstitial infiltration of lymphocytes and macrophages 1 month after acute ischemic injury.29 Here we report further increase in TNF-α expression in renal cortical tissue and glomerular infiltration of CD68+ macrophages 2.5 months after acute ischemia (Figure 2, A and B, Supplemental Figure 1). This inflammatory response remained high but began to decline by 9 months. SS-31 significantly reduced TNF-α expression and macrophage infiltration at 2.5 months, and this effect was sustained for >6 months after termination of treatment.
SS-31 reduces inflammation after acute renal ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. (A) The number of CD68+ macrophages per glomerulus at various times after ischemia. The number shown reflects the average determined from ten glomeruli per sample and averaged. Data shown as mean±SEM; n=4/group; ***P<0.001. (B) Representative Western blot and densitometric analysis of TNF-α expression in renal cortical tissue at various times after acute ischemia. Data shown as mean±SEM; n=4/group; **P<0.01; ***P<0.001. (C) Representative Western blot and densitometric analysis of IL-18 expression in renal cortical tissue at various times after acute ischemia. Data shown as mean±SEM; n=4/group; **P<0.01; ***P<0.001. (D) Representative Western blot and densitometric analysis of IL-1β expression in renal cortical tissue at various times after acute ischemia in saline and SS-31-treated rats, versus age-matched controls. Data shown as mean±SEM; n=4/group; **P<0.01. (See Supplemental Figure 1 for all Western blots).
The eventual decline in TNF-α and macrophage infiltration led us to question if inflammasome activation plays a role in sustaining the continual upregulation of TGF-β. The expression of IL-18 and IL-1β continued to increase at 9 months after ischemia, but they were abolished by 6 weeks of SS-31 treatment (Figure 2, C and D, Supplemental Figure 1).
Renal ischemia causes peritubular microvascular rarefaction that contributes to further tissue damage.29–31 There was significant loss of CD31 immunostaining in the renal cortex 1 month after ischemia, primarily in the glomeruli (Figure 3, A and C). There was also significant loss of CD31 in the inner stripe of the outer medulla (Figure 3, B and D). Despite partial recovery of CD31 expression in the renal cortex by 2.5 months, there was persistent upregulation of vascular endothelial growth factor even 9 months after ischemia (Figure 3E, Supplemental Figure 1), suggesting prolonged tissue hypoxia. The dramatic upregulation of vWF expression in post-ischemic glomeruli (Figure 3, A and F) indicates persistent endothelial injury after acute ischemia. vWF is a glycoprotein that mediates platelet adhesion to the subendothelium at sites of vascular injury, and it is normally not expressed in human glomeruli.32 We found no vWF expression in normal rat glomeruli, but vWF was clearly present in glomeruli at 1 month and progressively increased over 9 months after ischemia (Figure 3, A and F). Treatment with SS-31 did not improve CD31 expression (Figure 3, C and D), but significantly reduced vWF and vascular endothelial growth factor expression at 2.5 and 9 months, and the effect persisted for 6 months after treatment (Figure 3, E and F). Mesangial deposition of vWF is associated with mesangial matrix expansion and fibrin deposition,33 and periodic acid–Schiff staining showed that SS-31 prevented mesangial expansion at 9 months (Figure 3G).
SS-31 reduces endothelial injury after acute ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. (A) Representative microscopic images of glomeruli showing endothelial cell marker CD31 (green) and vWF (red) in saline- and SS-31-treated rats at 1 month (1M), 2.5 months (2.5M), and 9 months (9M) after ischemia. (B) Representative microscopic images of inner stripe of outer medulla (ISOM) showing CD31 (green) in saline and SS-31-treated rats at 1M, 2.5M, and 9M after ischemia. (C) Densitometric analysis of CD31 staining in renal cortex showing significant decrease in endothelial cell marker 1M after ischemia and partial recovery by 2.5M. SS-31 treatment had no effect on CD31 recovery. Data shown as mean±SEM; n=4/group; ***P<0.001. (D) Densitometric analysis of CD31 staining in ISOM showing significant decrease in endothelial cell marker 1M after ischemia and partial recovery by 2.5M. SS-31 treatment had no effect on CD31 recovery. Data shown as mean±SEM; n=4/group; ***P<0.001. (E) Representative Western blot and densitometric analysis of vascular endothelial growth factor (VEGF) expression in renal cortical tissue at various times after acute ischemia. Data shown as mean±SEM; n=4/group; **P<0.01; ***P<0.001. (See Supplemental Figure 1 for all Western blots). (F) Densitometric analysis of vWF stain in renal cortex showing marked increase in endothelial injury marker that was sustained over 9M after ischemia. SS-31 treatment abolished the increase. Data shown as mean±SEM; n=4/group; ***P<0.001. (G) Representative images of periodic acid–Schiff stain of glomeruli at 1M after ischemia, and at 9M in saline versus SS-31-treated rats.
We used helium ion microscopy (HIM) to further investigate damage to glomerular capillaries and endothelial fenestrations after acute ischemia. HIM provides subnanometer resolution images of biologic tissues with greater detail than scanning electron microscopy.34,35 Figure 4A shows a representative cross-section of an age-matched (11 months) normal rat glomerulus with numerous capillary loops. In contrast, mesangial expansion and compressed capillary loops were observed 9 months after ischemia. SS-31 restored majority of capillary loops and reduced mesangial volume. Closer examination of the capillary endothelial surface shows uniform fenestrations in a normal glomerulus (Figure 4B). In contrast, there was loss of fenestrations and extensive adhesive material on the endothelial surface 9 months after ischemia. SS-31 restored normal fenestrations and reduced adhesive material, consistent with reduction of vWF expression.
SS-31 reduces glomerular capillary compression and damage to endothelial fenestrations after acute ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Glomerular capillary structure was examined by HIM. (A) Representative cross-sectional images of glomeruli at 9M after acute ischemia from saline and SS-31-treated rats, compared with age-matched normal rats. Ischemia caused capillary compression because of mesangial expansion (*) in saline-treated rats. Capillary loops are much more apparent in SS-31-treated rats and similar to image from normal rat. (B) Representative HIM images showing endothelial fenestrations from saline versus SS-31 rats compared with age-matched normal rats. Fenestrations are uniform in normal rats, whereas saline-treated rats show distorted fenestrations and adhesive material (white arrow). SS-31 treatment restored normal fenestration pattern. (C) Representative electron micrograph showing glomerular endothelial cell mitochondria from saline versus SS-31 rats at 2.5M after ischemia, compared with normal rat. Saline-treated ischemic cells show degenerative changes in mitochondria with disruption of cristae architecture, reduced matrix density, and some loss of OMM. SS-31 treatment restored normal endothelial mitochondria. (More examples are provided in Supplemental Figure 2). M, mitochondria.
Ischemia causes extensive mitochondria damage in renal endothelial cells.29 Normal glomerular endothelial mitochondria are elongated, with dense cristae membranes and a dark matrix (Figure 4C, Supplemental Figure 2). Significant degenerative changes were still found in endothelial cells 2.5 months after ischemia, with loss of cristae membranes and matrix density, and evidence of rupture of the OMM. These degenerative changes were abolished by 6 weeks of treatment with SS-31.
Podocytes are secretory cells that contain a well developed Golgi system, many mitochondria, prominent lysosomes, and abundant endoplasmic reticulum (ER) responsible for the folding and trafficking of proteins (Figure 5A).36 Transmission electron microscopy showed pronounced dilation of ER lumen, an indication of ER stress, in many podocytes 1 month after ischemia (Figure 5B) compared with sham rats (Figure 5A). By 2.5 months, the podocytes were highly vacuolated and there was a general loss of cytoplasmic density (Figure 5C). Podocyte stress was still apparent 9 months after ischemia (Figure 5D). However, 6 weeks of SS-31 restored normal ER structure (Figure 5E) and this persisted for at least 6 months after treatment (Figure 5F).
SS-31 prevents podocyte stress after acute ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Podocyte structure was examined by transmission electron microscopy. (A) Representative image of a normal podocyte showing dense cytoplasm containing large number of endoplasmic reticulum (ER; arrows) and mitochondria. (B) Representative image obtained 1 month after ischemia showing pronounced dilation of ER (arrows). (C) Representative image obtained 2.5 months after ischemia showing loss of cytoplasmic density and large number of vacuoles. (D) Representative image obtained 9 months after ischemia with numerous dilated ER (arrows). (E) Representative image obtained 2.5 months after ischemia following short-term SS-31 treatment showing normal cytoplasmic structures. (F) Representative image obtained from an SS-31-treated rat 9 months after ischemia showing persistent podocyte protection with normal ER (arrows).
Podocytes have a complex cellular architecture with interdigitating foot processes maintained by a precise organization of actin filaments in the cellular cytoplasm. Podocyte swelling and effacement of foot processes have been reported after 45 minutes of ischemia in rats, but little is known about long-term changes after acute ischemia.37 Transmission electron microscopy revealed swollen podocytes and foot process effacement 9 months after acute ischemia compared with age-matched controls (Figure 6A). Condensation of actin microfilaments can be seen in the flattened foot process. Short-term SS-31 treatment restored normal foot processes. HIM provided a much clearer image of the damage to podocytes (Figure 6B). In normal podocytes, the foot processes are long and tightly interdigitated to provide an effective filtration barrier. Ischemia resulted in shortened and deformed foot processes that did not interdigitate well. Podocyte foot processes were normalized with SS-31 treatment.
SS-31 preserves podocyte foot processes after acute ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Podocyte structure was examined 9 months after ischemia. (A) Representative images of podocyte foot processes obtained by transmission electron microscope. Podocyte swelling and foot process effacement are common 9 months after acute ischemia compared with age-matched control. Condensation of actin microfilaments can be seen in the flattened foot processes (black arrow). Short-term SS-31 treatment restores normal foot processes. (B) Representative images of podocyte foot processes obtained by helium ion microscope. In normal podocytes, the foot processes are long and tightly interdigitated. Ischemia resulted in shortened and deformed foot processes. Short-term SS-31 treatment restores normal structural organization of foot processes.
Mitochondria play a major role in providing ATP for maintaining the actin cytoskeleton in podocytes.38,39 The collapse of the podocyte actin cytoskeleton at 9 months suggests sustained mitochondrial damage after an acute event. Normal podocyte mitochondria are elongated with cristae membranes and a dark matrix (Figure 7A). One month after ischemia, mitochondria showed degenerative changes with loss of cristae membranes and matrix swelling (Figure 7B). These degenerative changes were extensive and persisted at 2.5 months, with some mitochondria showing destruction of the OMM (Figure 7C). At 9 months, most mitochondria were small with only remnants of cristae membranes and a clear matrix, whereas others underwent extensive proteolysis with just some residual matrix density (Figure 7, D–F). Six weeks of SS-31 treatment restored mitochondria structure (Figure 7G), and mitochondria remained normal even 9 months after ischemia (Figure 7H).
SS-31 reverses ischemia-induced mitochondria damage in podocytes. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Podocyte mitochondria were examined 9 months after ischemia using transmission electron microscopy. (A) Representative image from normal podocyte showing elongated mitochondria with cristae membranes and a dark matrix. (B) Representative image obtained 1 month after ischemia showing mitochondria with degenerative changes including loss of cristae membranes and matrix swelling. (C) Representative image obtained 2.5 months after ischemia showing persistent mitochondrial damage. (D–F) Representative images obtained 9 months after ischemia. Many mitochondria are small with remnants of cristae membranes and a clear matrix, whereas others have undergone extensive proteolysis. (G) Representative image obtained from an SS-31-treated rat 2.5 months after ischemia showing normal mitochondria cristae and matrix density. (H) Representative image from an SS-31-treated rat 9 months after ischemia showing normal podocyte mitochondria. M, mitochondria.
Persistent upregulation of autophagy in podocytes after acute ischemia. Rats were subjected to bilateral renal ischemia for 45 minutes and podocytes examined by transmission electron microscopy. (A) Autophagic vacuoles (arrows) containing organelles and cytoplasmic contents in podocytes 1 month after ischemia. (B) An intact mitochondrion can be seen inside an autophagosome. (C and D) Interaction between lysosomes (arrows) and mitochondria can be seen 9 months after ischemia. (E) Autophagolysosomes containing digested material and myelin bodies 9 months after ischemia. (F) Dilated endoplasmic reticulum wrapping around mitochondria causing mitochondrial fission. M, mitochondria.
Proximal tubules are highly susceptible to ischemic injury, with rapid loss of brush border and cell detachment.25,26 However, tubular cells can regenerate, and brush borders are intact 9 months after acute ischemia (Figure 9A). Unlike the elongated mitochondria found in normal proximal tubules, post-ischemic proximal tubule mitochondria are small and highly disorganized, and there is an abundance of lysosomes (Figure 9B). There is also evidence of mitophagy, with early and complete autophagosomes around mitochondria (Figure 9, C and D). Some autophagolysosomes contain cytoplasmic content or are completely homogenized (Figure 9, E and F). Autophagy was not observed in proximal tubules treated with SS-31.
Mitophagy in proximal tubules after acute ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Proximal tubules were examined by transmission electron microscopy. (A and B) Representative images obtained 9 months after acute ischemia showing normal brush border (BB). Mitochondria are small and highly disorganized, and there is an abundance of lysosomes (L). (C and D) Representative images showing early and complete autophagic vesicles (AV) surrounding mitochondria (M). (E and F) Representative images showing autophagic vacuoles containing mitochondria and other cytoplasmic content.
In addition to mitophagy, some proximal tubule mitochondria appear relatively normal but have membrane vesicles in close apposition to the OMM (Figure 10, A–D). These vesicles may be dilated ER that are in close apposition to the OMM, commonly termed mitochondria-associated membranes. These structures were not seen in rats that received SS-31 treatment (Figure 10, E and F).
Mitochondria-associated membranes in proximal tubules after ischemia. Rats were treated with SS-31 (2 mg/kg per day) or saline for 1.5 months starting 1 month after acute ischemia. Proximal tubules were examined by transmission electron microscopy 9 months after ischemia. (A–D) Representative images showing membrane vesicles in close apposition to the OMM. (E and F) Representative images from SS-31-treated samples did not show these mitochondria-associated membranes.
Our results suggest that persistent mitochondrial damage underlies the progression of CKD, and this was confirmed with the mitoprotective agent SS-31. Treatment with SS-31 before ischemia protected endothelial and epithelial mitochondria, preserved peritubular and glomerular capillaries, and prevented inflammation and fibrosis.29 Here we show that SS-31, started 1 month after ischemia, can repair mitochondria in endothelial cells, podocytes, and tubular cells. This led to restoration of peritubular and glomerular capillaries, preservation of podocyte architecture, suppression of inflammation, and fibrosis. SS-31 abolished the increase in TNF-α and TGF-β over the 6-week treatment interval. Remarkably, renal protection persisted for at least 6 months after termination of SS-31 treatment. No other experimental treatment has been shown to accomplish this when given so late after AKI. Most experimental treatments evaluated in animal studies are given prior to or shortly after acute injury, although the clinical reality is that most patients present with established disease.
SS-31 protects mitochondrial structure by interacting with cardiolipin on the inner mitochondrial membrane and protecting cristae structure.26,47,48 Cardiolipin promotes membrane folding and promotes respiratory complexes to form supercomplexes to facilitate electron transfer, promote ATP synthesis, and reduce electron leak. Dysfunctional mitochondria generate ROS, and cardiolipin is particularly susceptible to lipid peroxidation. In the presence of ROS, cytochrome c acts as a peroxidase and causes cardiolipin peroxidation and cristae degradation. SS-31 acts as a multifunctional antioxidant by minimizing electron leak, scavenging excess electrons, and inhibiting cytochrome c peroxidase activity.28,47,49 SS-31 has been reported to restore cardiolipin content and mitochondrial cristae structure, and improve mitochondrial energetics, in experimental models of chronic kidney and heart failure.50–52 The recovery of podocyte bioenergetics allowed repair of the actin cytoskeleton and podocyte structure.
SS-31 protects mitochondrial integrity and prevents inflammasome activation and upregulation of IL-18 and IL-1β. Ischemia causes mitochondria damage resulting in decreased ATP production, increased ROS production, and cardiolipin peroxidation. Damage to mitochondrial membranes leads to the release of mitochondrial DNA (mt DNA), mitochondrial reactive oxygen species (mt ROS), and cardiolipin that are known to activate the NLRP3 inflammasome. The NLRP3 inflammasome, together with the adaptor protein (ASC), triggers activation of caspase-1 (Casp1), which then processes the proinflammatory cytokines pro–IL-1β and pro–IL-18 into their bioactive mature forms (IL-1β and IL-18). SS-31 (blue dots) targets cardiolipin, inhibits cardiolipin peroxidation, and protects mitochondrial cristae membrane.26 By preserving mitochondrial integrity, SS-31 not only preserves ATP production but also prevents NLRP3 inflammasome activation and normalizes IL-18 and IL-1β expression. ASC, Apoptosis-associated speck-like protein containing a caspase-recruitment domain.
Several inhibitors of IL-1β and IL-18 are in clinical development, as well as inhibitors of the NLRP3 inflammasome and caspase-1.58,59 Targeting upstream of the inflammasome might prove more effective than single anticytokine therapies and carry less risk. SS-31 has been shown to be highly effective in preventing acute and chronic kidney injury, including ischemia-reperfusion injury, UUO, contrast dye, endotoxemia, and streptozotocin-induced diabetic kidney injury.25,29,55,60–62 SS-31 has also been reported to reverse progressive CKD after chronic ischemia caused by renovascular stenosis, and reduce glomerulopathy and tubular injury caused by high-fat diet.63,64 SS-31 (also known as MTP-131, elamipretide, and Bendavia) may represent a novel treatment for CKD in addition to BP control.
The study was performed using male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA) weighing 250–300 g. Animals were housed in 12:12-hour light/dark cycle and allowed free access to water and standard rat chow. Care of the rats before and during the experimental procedures was conducted in accordance with the policies of the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. All protocols had received prior approval from the Weill Cornell Medical College Institutional Animal Care and Use Committee.
SS-31 was supplied by Stealth Peptides Inc., Newton Centre, MA. Unless otherwise specified, reagents and assay kits were purchased from Sigma-Aldrich (St. Louis, MO).
Rats were anesthetized with ketamine/xylazine and bilateral renal ischemia was induced by application of nontraumatic microvascular clamps around both left and right renal pedicles for 45 minutes, as previously described in detail.25 After ischemia, the animals were allowed to recover for 1 month. Surviving rats were randomly assigned to 6 weeks of treatment with SS-31 (2.0 mg/kg per day) or saline by subcutaneously implanted osmotic pump (Alza, Cupertino, CA). Rats were euthanized either immediately after drug treatment or 6 months after termination of drug treatment. Kidneys were harvested for biochemical and histologic analysis. Kidney tissues were frozen at −80°C for Western blotting or embedded in OCT-cryostat sectioning medium containing 30% sucrose for immunohistochemistry. Other samples were fixed in 4% paraformaldehyde for paraffin sections and ultrastructural examination by transmission electron microscopy or HIM.
Paraffin sections (3 μm) were stained with periodic acid–Schiff and examined by light microscopy (Nikon Eclipse TE2000-U). Masson trichrome staining was used to assess interstitial fibrosis and glomerulosclerosis.
Microvascular density and endothelial injury were assessed by immunohistochemical staining of CD31 and vWF, respectively. Frozen OCT blocks were cut into 8 μm sections, fixed in acetone for 4–5 minutes at room temperature, and incubated with anti-mouse CD31 (BD Biosciences, San Jose, CA) and anti-rabbit vWF (Sigma-Aldrich) overnight at 4°C. Sections were then incubated with anti-mouse IgG-conjugated Alexa Fluor-488 (Invitrogen, Carlsbad, CA) or goat anti-rabbit IgG-conjugated with biotin (Vector Laboratories, Burlingame, CA), and then treated with streptavidin-conjugated Alexa Fluor-594 (Invitrogen) for 30 minutes at room temperature, covered with VECTASHIELD Mounting Medium with DAPI (Vector Laboratories), and imaged by fluorescence microscopy (Nikon Eclipse TE2000-U). For each animal, ten representative glomeruli were selected in the renal cortex, and the green fluorescence intensity of the CD31 immunostain was quantified (ImageJ; National Institutes of Health) and averaged. Similarly, ten representative areas of the inner stripe of the outer medullar were quantified and averaged.
Macrophages were assessed by immunohistochemical staining of 4 μm paraffin sections for CD68. The kidney sections were incubated with anti-mouse CD68 (Abcam, Inc., Cambridge, MA) overnight at 4°C and incubated with HRP-conjugated anti-mouse IgG (Dako, Carpinteria, CA) for 30 minutes at room temperature, and color developed by DAB substrate kit (Vector Laboratories). The number of CD68+ cells were counted from five different fields for each sample and averaged.
The cytokines TNF-α, TGF-β1, IL-18 and IL-1β were quantified by Western blotting. Kidney homogenates were prepared according to standard protocol (Santa Cruz Biotechnology, Santa Cruz, CA), suspended in loading buffer, and subjected to 4%–15% SDS-PAGE. The resolved proteins were transferred to an Immuno-Blot polyvinylidene difluoride membrane (Bio-Rad, Hercules, CA). After electroblotting, the membrane was incubated overnight with primary antibodies against TNF-α (αβ1793; Abcam, Inc.), TGB-β (sc-146; Santa Cruz Biotechnology), IL-18 (MAB521; R&D Systems, Minneapolis, MN), and IL-1β (MB5011; R&D Systems). Membranes were further incubated for 1 hour with HRP-conjugated secondary antibodies (Dako). Protein bands were detected with an enhanced chemiluminescence detection system (Bio-Rad) and autoradiography. Bands were evaluated for integrated density values on Image Lab Software (Bio-Rad).
Pieces of renal tissue were fixed in 4% paraformaldehyde, postfixed in 1% osmium tetroxide, dehydrated in graded alcohols, and embedded in Epon. Ultrathin sections (200–400 Å) were cut on nickel grids, stained with uranyl acetate and lead citrate, and examined using a digital electron microscope (JEM-1400; JEOL Ltd.).
Kidney tissues were sectioned at 500 μm on a Leica vibrating microtome. The slices were cut into smaller, wedge-shaped pieces so that they would remain flat during the drying process. Tissues were dehydrated through a graded PBS-MeOH series at 4°C, according to previously published methods.35 Tissues were subjected to critical point drying with CO2. Dried samples were mounted on scanning electron microscope stubs using carbon sticky tabs and stored in a desiccator until imaging. HIM was carried out on the Carl Zeiss Orion Plus helium ion microscope (Carl Zeiss GmbH, Jena, Germany) operating at 30 KeV acceleration voltage, with a beam current of approximately 0.5 pA. A 10 nm layer of Au was evaporated on the samples to minimize local charging effects. For all images taken, an electron flood gun was used for charge neutralization at an accelerating voltage of 900 eV. The vacuum reading in the analysis chamber was 2×10−7 torr.
Results are expressed as means±SEM. Statistical analysis was carried out using Prism software (GraphPad Software Inc., San Diego, CA). Multiple group comparisons were performed using ANOVA followed by a Tukey post hoc test. A P value <0.05 was considered statistically significant.
The SS peptide described in this article has been licensed for commercial research and development to Stealth Peptides Inc. (now Stealth BioTherapeutics, Newton, MA), a clinical stage biopharmaceutical company, in which H.H.S. and the Cornell Research Foundation have financial interests. H.H.S. is the inventor of SS-31 and the Scientific Founder of Stealth BioTherapeutics.
We thank Juan Pablo Jimenez of the Electron Microscopy & Histology Core Facility at Weill Cornell Medical College for his technical assistance.
This work was supported, in part, by the Research Program in Mitochondrial Therapeutics at Weill Cornell Medicine. S.L. and Y.S. acknowledge support from the Social Profit Network. L.C.F., T.G., and V.M. acknowledge support from National Science Foundation grant Division of Materials Research 1126468. V.M. was also supported by a Graduate Assistance in Areas of National Need fellowship.
See related editorial, "Preventing the Progression of AKI to CKD: The Role of Mitochondria," on pages 1327–1329.
This article contains supplemental material online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2016070761/-/DCSupplemental.


My friend Suzanne invited us down for a day to Ocean Grove, where she was renting a shore house.
I loved the idea of a beach day, except that even after dropping pounds, heading to the beach still kind of freaked me out. While I've been up Kilimanjaro three times, putting on a swimsuit requires more bravery than taking on Mount Everest, the world's highest peak.
Still, I do it. I do it because it's important to get out and about with my kids. I bolster up bravery and courage, thanks to Jennifer Weiner, one of my literary heroes, who encouraged people to just wear the swimsuit. [Link here].
But putting on a swimsuit and going in the water are two very different things. This was our first ocean visit of the season. I had been a journalist for a decade and found myself paranoid about all the bad things that could happen.
I reminded myself that I had done everything right. We picked a spot on the beach deemed safe for swimming. It was a safe distance from the rocks along the coast. Lifeguards patrolled it. We went during low tide and we could be waist-high. We had enough adults to supervise the kids.
With Anna and her friend out on the ocean riding the waves, and my husband jumping with Emily and her friend, I found myself with Elliott on the sand.
Maybe I would go calf-deep, with my little guy on my hip. When my friend's mother offered to take the kids to see the crabs on nearby rocks, and Chris took Elliott out in the waves, I was free to join Anna deep in the water.
She begged me to go in with her.
At first, I was terrified. While I love to watch the rhythm of the waves coming to the shore, I don't like the push and pull of the ocean. Plus, the water was shockingly cold but Anna really wanted to go in with me. So I took a deep breath and trudged in against the waves.
We found a spot along the tide line where we could just enjoy the ride of the ocean, bouncing up and down like buoys. From there, I could see the beautiful beach. Anna and I felt the fear of an impending wave. As it enveloped us and pushed us off along the tide, I tried to let go and just experience it. I enjoyed feeling out of control.
In those moments, I could remember the joy of when my mother took me to Maine and I felt the ocean for the first time. Back then, I spent the whole day in the water and went home with a blistering sunburn. But the experience was magical and amazing. The ocean, while powerful, was mysterious and wonderful, not complicated by any issues I'd accumulate later while I grew up and distanced myself from the beach.
Now, as an adult, though I'm much more adamant about reapplying sunscreen, I don't want to put my weight, fear, or body image issues in the way of Anna or any of my kids having that same amazing experience.
From now on, I'll ride the waves.


Nigerian artist and lyricist, Tokunbo Fola Gabriel Okunowo prominently known as Tee Kay has no uncertainty come to remain, he's really showing and proving as well that gospel music in Nigeria has come to stay.
The Afrobeat pop gospel artist has never been marked into any records name however he is the Founder of Campus Celebrity Network (Magazine, TV, Web) and achievers/big names Awards (A.C.A) ballerz NG, serving more than 30 colleges in Nigeria and Ghana with astonishing substance.
The Hit tune & raving success melody, "Papa God" which was recorded a couple of years back has got him a few honors, locally and universally. Here comes another successful track that mist be added to your playlist titled "ORE".


A tech startup CEO sat across from me in a D.C. restaurant in 1999 and said, "Who do you know at BusinessWeek?" I wanted to smack him…until the agency CEO sitting with me SUPPORTED him by saying, "Well, one of us (in the agency) has a contact there." (Did I mention it was a new business meeting? And, as it happens, D.C. people really do believe that it IS all about the relationships.) BTW, right before that lovely exchange, the CEO said he wanted us to buy him an ad – for his B2B tech company – in the first quarter of that year's Super Bowl. The conversation took place in October of that year. Ad buyers – feel free to laugh.
– My (ethically challenged?) agency leader did win the client account.
– During the first major media engagement I secured for the company (despite their laughably weak story, I get them a sit-down with InformationWeek), the CEO utterly embarrassed himself and the company by ignoring all my counsel, and antagonized the reporters in the process.
– The client company collapsed within one year.
– The agency I worked for at the time sold itself a few years later.
Mike – Thanks for the comment. If I'm remembering your career path correctly, I know of which agency you speak of (said agency where we enjoyed a nice long bike ride), and this surprises me not.
Here's the deal – – having a contact that you've worked with before IS helpful in that they will recognize your name and – hopefully – know that you'll be pitching a good story. If anyone believes a reporter or producer is going to do a story because you are friends…not the case.


Meeting people in O pazo(caldas de reis) for free on mobifriends is very easy and fun.
Meet new people in O pazo(caldas de reis) for free and free chat. Everything on mobifriends is 100% free, fun and easy to use, on the Internet and mobile phones.
Join a big community of men and women who are seeking love and friendship in O pazo(caldas de reis) for free with people like you! Meet men from O pazo(caldas de reis) for free. Search and meet a man from O pazo(caldas de reis) or woman from O pazo(caldas de reis) with the Chat, messages and mobis.
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text:
package teams.domain;

import org.junit.Test;
import teams.Seed;

import java.util.HashSet;
import java.util.Set;

import static org.junit.Assert.assertFalse;
import static org.junit.Assert.assertTrue;

public class ExternalTeamTest implements Seed{
    @Test
    public void equals() throws Exception {
        Set<ExternalTeam> set = new HashSet<>();

        ExternalTeam externalTeam = externalTeam("identifier_1");
        set.add(externalTeam);
        set.add( externalTeam("identifier_1"));

        assertFalse(externalTeam.equals(null));
        assertFalse(externalTeam.equals("nope"));

        assertTrue(externalTeam.equals(externalTeam));
    }

}


text:
Interview with Environmental Activist and Consumer Advocate Mr. Grinch: On the Christmas Story and the Post-consumer era
by: Tweedy and Sasha
For this interview, journalist Sasha Viasasha traveled three thousand miles up the snowy slope of Mount Crumpit to visit Mr. Grinch in his environmentally-friendly, carbon-neutral eco-dwelling, where Mr. Grinch lives with his dog Max. Mr. Grinch is currently penning his memoir.
SVS: Thank you so much for having me, Mr. Grinch. I must say it is quite an honor to actually be here, after such a long and arduous journey. Thank you for the hot chocolate, it's really quite wonderful. It is so cozy and comfortable in here, not at all what I expected.
Mr. Grinch: Yes, Max and I have made ourselves quite at home over the years.
SVS: You have such a reputation as a recluse, and of living a severely spartan existence, that I did not expect to find it so warm and inviting in here. And what are all these drawing on the wall?
Mr Grinch: Ah, yes, from the children, the children. The children, you know, really do understand. Yes, I have lived a life apart, I've lived in exile, and it has been at times a difficult choice, but the only one for me. Not having children has often pained me, you know. But the choices I have made for myself have been so agonizing that I did not think I could make them for others. Not because I doubted, you know. It was only a question of will. It has taken every ounce of my strength to live as I have. I do not call myself an exceptional man.
SVS: And yet you've lived an exceptional life.
Mr. Grinch: An exceptional life, yes. And only when the exceptional become unexceptional will we have successfully returned to a simpler way of living. You see a lot of young people now trying to return, and their attempts are energized by a sense of novelty, with the thrill of their own exceptionalness. You get this, too, reading Thoreau, who was still quite a young man, I think just twenty-seven years old, when he went to Walden, and you can easily see, reading his writings, how positively exhilarated he was by his own exceptionalness. It has taken all of these many years for my own sense of novelty to fade, for the wonderfulness of it all to diminish, many years of solitude and simple living.
SVS: Do you think, then, that the movement to live simpler, to live in harmony with our environment, to decrease our impact on the planet, is just a fad?
Mr. Grinch: Just a fad? A fad, certainly, but whether just a fad, I couldn't say. I know the market is acutely attuned to any impulse that arises in the public psyche; and it will systematically assimilate any movement that the counter-culture can generate. If we succeed it will be disorganized, spontaneous, private and apolitical.
SVS: If this is true, then what is the future of activism? What kind of activity is useful?
Mr. Grinch: What kind of activity is useful? Any activity that is consciousness-raising. That is all.
SVS: But as far as organizing? You are opposed to it?
Mr. Grinch: Not so much opposed as indifferent.
SVS: And you've also stated many times that you are not opposed to Christmas, but merely indifferent to it. Yet I think many would describe your activities as fervently oppositional. In Dr. Seuss' work, for example—
Mr. Grinch: I tell you that if Ted Geisel had anticipated the popular interpretation of his work that has most recently found expression in a movie by the same name as his poem, he would never have lifted a pen! I do not wish to discuss his work, which relates to my life only incidentally. It is only in contrast to the fanatical fervor of the pro-Christmas lobby that my indifference seems like opposition. That is their genius.
SVS: The pro-Christmas lobby?
Mr. Grinch: The pro-Christmas lobby? (chuckles) A loose coalition of retailers, churches, politicians, entertainers, media outlets and corporations, united only by their self-interest, and entirely reliant on the consumer for their very survival. And you can see why they are so very threatened by indifference! Opposition, active resistance, can be harnessed, but with indifference there is simply nothing for them to get their hooks into! Through the early 50's, Ted and I had many conversations about this: I felt the oppositional tendencies of the character he created would be used to attack the anti-consumerist message of his poem. And that is exactly what happened. The anti-consumerist message, well, on the Grinch '66 all that just went missing – it's not there. That Grinch is merely a crotchety curmudgeon whose tiny heart is filled with spite and revenge. Grinch 2000 took that, bizarrely, as its starting point. I wash my hands of the entire affair. I know Ted felt that indifference did not make for an exciting story. Well, what do I know about telling stories? Enough, with storytelling! Our stories are destroying us!
SVS: And instead of stories?
Mr. Grinch: (picks up a ball of yarn and begins knitting) It truly is a strain on the mind to imagine living in a world where we don't constantly tell ourselves lies in order to explain the world to ourselves. Yet in truth the tales we invent are so poor, so paltry…
SVS: You mean the Christmas story?
Mr. Grinch: Ah, the Christmas story. Always back to the Christmas story. I wonder if I shall ever escape it. The Christmas story is as relevant to our lives today as frankincense and myrrh. Yet here it is again. This December, why not tell your children about Franken-food and M.E.R?
SVS: M.E.R?
Mr. Grinch: Exactly, why do I have to be the one to explain this to you? Middle East Realities—the international think tank that is right now making decisions about the future of your oil dependency. Yes, yes, I know, gas prices have dropped recently—just in time for the shopping season. I can't help but notice this year, in the circulars sent around, and on the few morning shows and such that I caught on television over the Thanksgiving holiday—don't look so surprised, I do have friends—that the products being promoted as holiday gifts are particularly superfluous this year. Self-baking muffin tins, steam-powered trouser presses. Yes, yes, the retailers will have their pound of flesh, and they will cut it right out of the heart this year! The most ridiculous rubbish, you know, nothing that anyone needs, and it will all be in the garbage bins before the year is out, or sent to the Good Will to be puzzled over in the sorting room. What is the morality of using our precious resources to manufacture, promote, and then dispose of such a heap of dung? The problem with capitalism, you see, in a world with dwindling resources, is that it is entirely driven by the production of waste. Of profit, in other words. Well, people do lose their senses, what senses are left to them, around the holidays. Visit any mall or shopping center, and observe, very carefully, and you will see.
It is frightening, any time of year. I know, I know. "Oh Mr. Grinch, we haven't time to discuss renewable energy – we're off to buy more oil-based plastic toys for the Who's down in Whoville!" Where will it all end, can you tell me this, hmmmm?
SVS: Mr. Grinch, please don't be upset, but just now you really did bear the most striking resemblance to Seuss' Grinch! It is absolutely delightful, sir! And as far as the end goes, in the end, if I remember correctly, the Who's are all liberated from consumerism and discover the magic of Christmas in the absence of all the material trappings you so eloquently decry. Do you share Seuss' optimism for humanity?
Mr. Grinch: I truly have nothing else to say about Ted's work, which was in itself merely a piece of pop entertainment, and subject to the narrow restrictions of Christian narrative, that is to say, sacrifice and redemption. In fact, the more you examine western literature, the more you cannot help but see the Christmas story as the subtext for every piece of writing, film, entertainment, and even advertising. But as to the question of optimism, I do have absolute faith in the coming of post-consumer era in the very near future.
SVS: A post-consumer era? You think it's actually possible?
Mr. Grinch: Oh my, yes. A post-consumer era is inevitable. The only question is whether or not there will be any humans around to witness it.
Sasha Viasasha is a writer and editor for: www.scornmonger.blogspot.com
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One option for treating uterine fibroids is noninvasive MR-guided focused ultrasound ablation. The procedure uses MRI as guidance for the radiologist to pinpoint the area in the core of the uterine fibroid where the ultrasound waves will be focused. When many ultrasound waves converge on a single area, it creates enough heat to destroy the tissue. The procedure is repeated over and over until the central core of the fibroid is destroyed.
Haney AF. Leiomyomata. In: Gibb RS, et al. Danforth's Obstetrics and Gynecology. 10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2008:916.
Hudson SBA, et al. Magnetic resonance-guided focused ultrasound surgery. Clinical Obstetrics and Gynecology. 2008;51:159.


Certified Pest Management, LLC is a licensed, fully insured locally owned pest control company established in Chelsea, Maine. Our number one priority is quality services.
Our lead service technician Mike Cote has 18 years' of experience and holds a masters technician's license.
Certified Pest Management specialize in the provision of a large range of pest control and extermination services.
We have products and equipment for the treatment needed to perform the applications. Our licensed technicians rely on the safest available pest control methods. We use natural and organic treatments, which are harmless to children and pets. We also offer chemical treatments that are of special nature and formulations, which are registered for use in houses and public places. These chemicals are in accordance with local and national regulations and EPA standards.
We pride ourselves on providing pricing that is extremely fair and affordable.
Obtains the proper license that qualifies him to use pesticides that the general public cannot. Certification is administered by Board of Pesticide Control a State Government Office. Training provides instruction on proper pesticide use and handling to individuals who want to obtain or retain certification. Training is primarily conducted by University Extension as well as by associations, industry, non-profit organizations, private companies, and federal and state government agencies.
In order for you to ensure the safety and health of your family, your customers and your employees on your residential and commercial property in Maine, it is important that you exercise the right choice for the services of a professional. Call CERTIFIED PEST MANAGEMENT today for your free initial inspection.
We'll help you identify your pest and provide preventative treatment.
Capable of thriving in most climates, silverfish prefer to dwell in dark, damp areas such as basements, attics, kitchens and bathrooms. They are especially attracted to paper and damp clothing. Commonly found in stored boxes in garages and sheds. Silverfish feed on carbohydrates, particularly sugars and starches.
Silverfish enter a house on their own or in a container such as a box that has been stored outside. They are pests and destroy property, but as far as researchers know they don't transmit diseases.
The insects are nocturnal creatures. During the day, they hide unnoticed in cracks and crevices. At night, they become active and search for food. They sometimes leave scales and yellow stains behind as they travel.
Silverfish eat a wide variety of food, especially carbohydrates. They feed on paper, photographs, wallpaper paste, starch in clothes, fabrics such as cotton and linen and any foods rich in carbohydrates that they find in the house. These foods include sugar, flour, bread, rolled oats and other cereals. The insects even feed on starches in the glue found in book bindings.
Silverfish also eat mold, dandruff and body coverings from silverfish molts. In addition, they eat high–protein foods such as meat and dead insects. They can survive for several months without food.
Sure, we all know ticks are nuisance but do really know what they are and what they do. Here are 10 facts you probably didn't know about those pesky ticks.
Ticks are arachnids. Meaning, they are more closely related to spiders and scorpions than insects.
There about 850 tick species, some of which are capable of transmitting diseases such as Lyme disease, Ehrlichia, Powassan virus, and Rocky Mountain Spotted Fever.
Ticks feed on the blood of their host -- humans, birds, reptiles, and wild and domestic mammals.
Ticks may appear as a small dark speck on your pet's fur.
Never remove a tick with your bare hand. Instead, using tweezers, grasp the tick close to the skin and pull gently.
Cockroaches have been around since the time of dinosaurs! A cockroach can live almost a month without food. A cockroach can live about two weeks without water.
A cockroach can live for up to one week without its head! Cockroaches can hold their breath for up to 40 minutes! Cockroaches can run up to 3 miles an hour.
 Cockroaches are commonly found in buildings and homes because they prefer warm environments close to food and water.
Unfortunately, cockroaches can cause allergies and trigger asthma attacks, especially in children. They can also spread nearly 33 different kinds of bacteria.
These annoying insects are widely distributed and known by all. Although there are over 40 species in Maine, less than half are considered biting pests of humans. However, one of the most common complaints from people enjoying the outdoors during the spring and summer months is the annoyance caused by the often enormous populations of these small, slender, long-legged flies, the bites they inflict and, for some, the almost intolerable itching from the bite. Both males and females will use flower nectar for food, but it is only the females that feed on blood to obtain the required protein needed to produce and lay eggs. In this biting process the females can act as vectors of parasites and disease organisms, such as malaria, yellow fever, and various forms of viral encephalitis, and spreading them from one host to another. For example, heartworm, a disease of dogs caused by filarial worms, is transmitted by mosquitoes and is now established throughout most of New England. In the past, mosquito-carried diseases have not usually been considered a problem in Maine. Recently, however, concern has been expressed regarding the increased incidence in the Northeast of arboviruses (viruses carried by insects, ticks, and other closely related organisms) such as Eastern Equine Encephalitis (EEE), which was quite severe in 2009.
In 1999, another form of encephalitis known as the West Nile Virus (WNV) was detected in the eastern US in New York City. This virus, which is deadly to the American crow and its relatives, is also a serious problem for horses and humans. By 2003, the virus had spread across the continental US and caused several hundred human deaths. Most people contracting the disease develop a mild case of "West Nile Fever" that resembles a mild cold or flu. Maine, although having had many dead, WNV-positive birds, has not yet had a human case. As a result of increasing concerns of mosquito-borne viruses, a monitoring system has been developed for Maine mosquito species, which may serve as vectors, especially of WNV and EEE.
Ladybugs, also known as lady beetles or ladybirds, are a small type of beetle, commonly found with reddish orange shells with black antennae, legs, and heads. With an approximate lifespan of 2 to 3 years, ladybugs survive the winter months by overwintering and consuming their body fat for nutrients.
Today, there are over 450 species of ladybugs in North America. Of those 450 types of ladybugs, only three of them feed on plants. You might have noticed these ones in your garden feeding on your vegetables, shrubs and flowers.
Ladybugs are very good at surviving our harsh Canadian winters. They typically do this by overwintering in a warm place away from the elements of the outdoors, and this is how you might end up with ladybugs in the house. In the fall and winter, you will notice them gathering in large numbers on the hunt for a place to spend the winter. They are attracted to buildings and homes with sunny exposures and find any crack, crevice or opening to sneak into to survive the winter.
Ladybugs release pheromones like a perfume to attract other ladybugs, and this scent can be detected up to 0.4 kilometres away. It can also remain year after year on the outside of your house. If you have ladybugs in the house, these pheromones can also stay on the inside of your walls.
Spiders are arachnids, not insects.
Other members of the arachnid family include scorpions, mites, ticks and harvestmen.
Spiders have 8 legs while insects have 6.
Spiders don't have antennae while insects do.
There are around 40000 different species of spider.
Most spiders make silk which they use to create spider webs and capture prey.
Queens dominate hornet hives and are the only females to reproduce. Most other hornets are asexual female workers that perform essential community duties such as building the hive, gathering food, feeding the young, and protecting the colony.
Males are few and they have only one real role—mating with the queen. Males typically die soon after their sexual task is complete. Workers defend their hive with potent stingers.
Though these insects do not sting humans unless provoked, some people are allergic to their venom and can have very dangerous reactions to a sting.
Hornets are often considered pests, particularly when they nest near humans, because they will defend a nest aggressively if they feel it is threatened.
There are more than 10,000 known species of ants living throughout the world. Ants can be identified by the constriction between the abdomen and thorax that looks like a narrow waist. Their bodies are covered with a hard armor called the exoskeleton. Most ants are either red or black in color and length can be anywhere from 1/3" to 1/2". Like other insects, they have six legs; each with three joints. Ants have large heads with compound eyes, elbowed antennae, and powerful jaws.
An estimated 20,000 different species worldwide, ants represent one of the most prevalent and successful types of insects on the planet. The small but highly prolific creatures are found in virtually every possible environment ranging from subarctic regions to tropical rainforests. Many ant species also thrive in temperate climate zones like New England. While most species of ants are harmless, others create problems by nesting in residential areas, invading homes in search of food, and even causing structural damage to buildings. Within the highly developed urban areas of New England, certain kinds of ants commonly build nests in or near homes and become pests that send unsightly trails of workers throughout a structure to take advantage of the various food and moisture sources available in such household settings. Although the different types of ants share many of the same general traits regarding overall appearance and behavior, each species retains unique characteristics affecting identification and management of the pest insects.
Immature bedbugs, called nymphs, shed their skins five times before reaching maturity and require a meal of blood before each shedding.
Because bedbugs live solely on blood, having them in your home is not a sign of dirtiness. The biggest problem with bed bug it that they are etremely hard to remove. Conventional pesticides do not work on them and they will gradually spread to other rooms throughout your home. Because of this professional bed bug control service is recommended.
Whenever you see adult fleas crawling on your pet, it is only a symptom of a much larger problem. Current studies indicate that adult fleas account for only 5% of the total flea population in any given situation. Eggs account for 50%, larvae account for about 35%, and the remaining 10% are the pupa cocoons. That means that for every single adult flea living on your dog or cat, there are ten eggs, seven larvae, and two cocoons.
If an animal needs to be trapped and you are uncomfortable or have no interest in doing the work yourself, contact CERTIFIED PEST MANAGEMENT to do the job for you.
We offer a variety of trapping services for different species of animals.
Experienced trappers know the behavior of each species and the methods required to trap them. They also recognize signs of diseases and nursing females. Often their solution to a conflict will involve setting several cage traps to make sure the entire family of animals is caught—or as many as possible at one time. Multiple traps are not something most homeowners have on hand.


Honningbrew Meadery is a small meadery owned by Sabjorn. It is located at the crossroad by the bridges to the southeast of Whiterun.
It produces Honningbrew Mead in direct competition with Black-Briar Mead. The site consists of two buildings: Honningbrew Meadery and Honningbrew Boilery, both of which share a basement.
* This person only becomes a fence and is placed in-charge of the meadery after completing Dampened Spirits.
† This person is no longer available after the related quest.
There are two "Honningbrew Meadery" signs, one on either side of the path leading to the entrance to the meadery, which is always unlocked. There is a third sign to the right of the entrance to the boilery, which is kept locked and requires a key. Stacked around the entrance are many barrels, some containing bottles of Honningbrew Mead and other regular foodstuffs. There are numerous flowers and plants in the immediate vicinity as well as monarch butterflies and blue butterflies during the day and luna moths and torchbugs in the evenings and at night.
The meadery is the larger right-hand building. It contains a counter in front of the wall opposite the entrance. Prior to starting the related quest Sabjorn and his employees, Eimar and Mallus Maccius, can be found here. Sabjorn is happy to buy and sell foodstuffs. On your immediate left upon entering is a bookcase holding eleven common books and on your right is an end table with a bowl of red apples on top. The counter has five bottles of Honningbrew Mead, a sweet roll and a honey nut treat on top and a further twenty-one bottles underneath. Behind the bar are two sets of shelves holding nine more bottles and another sweet roll, as well as some cheap crockery. Against the west wall is a long wooden table with several mead barrels set up on top with a bowl containing four honey nut treats beside them. In both the southeastern and southwestern corners are small tables and chairs with a total of four bottles of Honningbrew Mead, an apple pie and two red apples, a honey nut treat and sliced eidar cheese on top. A third small table is against the west wall with a single bottle of Honningbrew Mead and a sweet roll on top. In the northeastern corner is a stack of barrels containing more bottles of Honningbrew Mead. There are double doors in the middle of the east wall leading to the storage area.
After starting the related quest, when you enter you will find Sabjorn standing in front of the counter alone with two dead skeevers on the floor, one at either end of the room. When speaking with Sabjorn and convincing him to let you help, he will hand you a copy of the Honningbrew Meadery key which opens both the door into the basement and also the door to his sleeping quarters in the loft.
The storage area is filled with many stacks of barrels containing bottles of Honningbrew Mead and sacks of foodstuffs. Towards the rear of the room is a set of shelves holding seventeen bottles, a narrow table with five more bottles on top and a bucket containing four more bottles underneath. At the northern end of the room is a flight of stairs leading down to a door to Honningbrew Basement, which is locked and requires the key given by Sabjorn. There are three bear traps at the top of the stairs and another at the bottom by the door.
At the southern end of the room are four more bottles of Honningbrew Mead on top of barrels. In the southwestern corner is a doorway to a flight of stairs leading up to the left. Under the stairs is one more bottle of the mead. The loft is only partially boarded along the east, north and part of the west walls with a railing overlooking the storage area below. Against the east wall is a single owned bed with a wall shelf above it holding a copy of The Lusty Argonian Maid, v2, a red apple and an eidar cheese wedge. Against the north wall is a small square table with a bottle of Honningbrew Mead on top and an owned bed roll beside it. At the end of the boarding on the west wall is an adept-locked door, which is opened using the key given by Sabjorn.
You can leave the loft area until you complete the quest, as you will need to visit his quarters to access the information needed for Maven Black-Briar at this point. His bedroom contains a large owned double bed coming out from the south wall with end tables on either side. On top of the one on the left is a bottle of Honningbrew Mead, a red apple and a goat cheese wedge, while on the one on the right is a common book. Under the bed is a bowl containing a bottle of Black-Briar Mead. Against the west wall is an expert-locked door; to the left is Sabjorn's dresser, which is locked and requires a key. It has a set of clothes and a bowl containing boiled creme treats on top. To the right of the door is a tall wardrobe containing fine clothes. Against the north wall is a long wooden table with a plate of grilled leeks and two salmon steaks, an iron dagger, a bottle of wine, a note entitled Have Need of Cynric from Maven, and an empty display case. To the right is a small cupboard. The east wall has a set of shelves against it holding ten common books, a bottle of alto wine, and a bottle of wine. To the left on the floor is a drum and to the right is a small wooden table and two chairs. On the table is a bottle of alto wine, two honey nut treats, a common book, and a copy of the Alchemy skill book A Game at Dinner.
The expert-locked door leads to a small room with two wall shelves behind the door on the south wall. On these is a medium coin purse and some fine crockery, and next to them is a tall wardrobe containing fine clothes. Opposite, against the north wall is a long end table with three silver ingots, a medium coin purse, a silver necklace, an empty strongbox and Honningbrew Decanter, a unique item prized by Delvin Mallory as part of the quest The Litany of Larceny. To the right of the end table, on the floor, is a large coin purse.
The basement only becomes accessible once you start the related quest and receive the Honningbrew Meadery key from Sabjorn. Upon entering you will see several dead skeevers and a bear trap in front of you. Off to the left is a skeever that has been magically enhanced to be poisonous, similarly to frostbite spiders. The room contains several large vats and large stacks of unusable barrels. In the middle of the south wall is a set of shelves holding five bottles of Honningbrew Mead and on the west wall, at the far end, are two barrels containing more bottles of Honningbrew Mead with a set of shelves that have been knocked over to reveal a tunnel behind. Two bear traps have been set up in front of the hole.
Just inside the tunnel is another dead skeever, near where the tunnel descends to the west. At the bottom it turns to the south and then opens out into a cave containing four more skeever, some of which are venomous. The cave has quite a lot of vegetation that can obscure your view. On the ground are a couple of bottles of Honningbrew Mead and against the south wall a barrel containing more bottles of the mead. To the east is a narrow tunnel leading onwards. Follow the tunnel as it continues to descend and take a couple of turns. Just after turning to the west and passing through a thin cobweb there is a frostbite spider. There is also a web sac containing a skeever tail and high on the wall a glowing mushroom. More spiders converge on you as soon as the first spider sees you. The tunnel opens out into another cave with many more web sacs and glowing mushrooms on the walls. Again to the east is a narrow tunnel and after a couple of turns opens into a cave which contains only a couple of crates, barrels and bear traps. At the far end a tunnel with a tripwire across the entrance that triggers a swinging mace trap descends to the south. Keep following the tunnel as it takes several turns before opening out into another cave. You will be immediately spotted by a skeever unless your Sneak skill is exceptional. There are several other skeevers, some venomous, and also a mad alchemist named Hamelyn.
Once they are all defeated loot Hamelyn to find his journal, which explains how he was exiled from the College of Winterhold, and jailed in Whiterun for being a danger and insane. It explains that he escaped the jail while continuing to revile both the people of Whiterun and also the college. To the southeast you will find the skeever nest to the right of an alchemy lab. Between the nest and lab is a novice-locked chest, a leveled potion of healing, a leveled potion of stamina, and a copy of the Sneak skill book Three Thieves. To the east another narrow tunnel that takes several turns as it rises and eventually leads to the basement under the boilery. At the exit from the tunnel there are two more bear traps and another set of shelves that have been moved forward to reveal the tunnel. The basement contains many large vats and barrels, all except one of which are unusable. The one barrel is on your left as you enter the basement. It contains more bottles of Honningbrew Mead. At the far end, on the east wall, is a door leading up into the boilery itself.
The boilery contains four large boilers, three of which have fires under them. They are on a raised section in the middle of the room. To the right of the vat without the fire is a long wooden table with a bowl containing three bottles of Honningbrew Mead, with two more on the table along with a sweet roll. To the right of the table is a barrel containing more bottles of the mead. Around the outside of the room are several crates, food sacks, barrels containing more bottles of the mead, and a tall wardrobe containing fine clothes. In the middle of the east wall is a door leading outside which is locked and requires a key. To the right of the door, on a hook, is the key that is required. To the left of the door is a flight of wooden stairs leading up to a balcony that runs around the edge of three of the wall to provide access to the lids of the boilers. At the top of the stairs is a small cupboard and on the balcony are several food sacks and a few barrels containing more bottles of the mead. In the middle of the south wall is an apprentice-locked chest containing minor loot. At the far end of the balcony is a dresser containing clothes.
Once you have added the poison the quest will instruct you to return to Sabjorn. When you reenter the meadery you will find the commander of the guard in Whiterun, Commander Caius, with Sabjorn standing behind the counter and Mallus Maccius standing at the other end of the room. The skeevers and blood have been cleaned up and Sabjorn has been delaying the commander awaiting the all-clear from you. Sabjorn will tell you that have to wait for the end of the tasting for your pay. Once Sabjorn has been taken to Dragonsreach by the commander you are free to speak to Mallus who, after a short monologue, will hand you the key to Sabjorn's dresser. It contains a promissory note and a few septims. Once you have returned to Maven, Mallus will be available as a fence.
Honning is Danish and Norwegian for honey.
The main building will respawn after ten days. However, the Honningbrew Basement and Honningbrew Boilery never respawn.
There is a Loot shadowmark to the left of the entrance door.
A Fence shadowmark replaces the Loot shadowmark. Mallus Maccius is the fence.
"Black-Briar Meadery" signs replace the "Honningbrew Meadery" signs.
One clay depositHF can be found just northeast of the meadery on the river bank, beside the stone bridge.
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