text:
Why frozen?
Brand campaigns
2020 Investor Day
Eating for the Planet – partnering with WWF to help transform how food is grown
One third of food is wasted annually, the food industry accounts for around 30% of global energy consumption and biodiversity, which is crucial for human life, is declining faster than at any time. Consumers, retailers and other stakeholders are increasingly asking for brands that are more sustainable and there is clear evidence that we need to change the way we consume and produce food; and waste less of it, if we are to reduce pressure on resources including land.
As CEO of Nomad Foods, I believe we have a huge opportunity to democratise sustainable eating and play our part in minimising the impact of food production on the planet. We are proud to produce great tasting food that is good for people, good for the planet, affordable and available everywhere. And we are committed to doing our part to support transformation across the food system.
Last year, we commissioned research that confirms a diet rich in vegetables, sustainably sourced fish and plant protein could reduce carbon emissions from food by up to 60%. And when you choose frozen over chilled or fresh, there is even more potential to lower the carbon footprint because frozen food significantly reduces food waste. We have a portfolio that is flexitarian at heart, focused around fish, vegetables and potatoes and our Green Cuisine range is now the fastest growing frozen meat-free brand in Europe. This puts us in a strong position to support a shift towards healthier and more sustainable eating.
To achieve this and ensure the way we source our produce is part of the solution to climate change, not part of the problem, we also need to focus on how we can develop more sustainable and resilient agricultural systems.
We have a target to source 100% of our vegetables and potatoes through sustainable farming practices by the end of 2025, with 77% of our own grown vegetables already verified as such.* We recognise the importance of working closely with our farmers and expert partners to achieve this goal and have introduced the Sustainable Agriculture Initiative Platform (SAI Platform) Farm Sustainability Assessment (FSA) as a benchmark. We are also identifying opportunities to cultivate biodiversity and develop innovative and scaleable solutions to reduce carbon emissions.
In the UK, we have already seen what strong partnerships can achieve through the landmark Sustainable Landscapes Humber Project. Partnering with Yorkshire Water, Hull and Teeside universities and more than 50 farmers, we are looking at ways to improve soil health, reduce flooding and soil erosion and capture carbon from the atmosphere. In just 90 days, the programme has removed enough carbon to make 400 families of four in the UK carbon neutral for a year. While still in pilot phase, this is a fantastic example of how farming can be part of the solution to wider climate change and biodiversity loss.
Today I'm very proud to say we're going a step further, by announcing a new partnership with WWF.
The partnership has two aims. The first is to focus on developing a blueprint to increase food production through "nature positive" farming solutions, while the second will measure the impact of biodiversity at farm level to increase pollinators. This will allow us to build a deeper understanding of how innovation in agriculture can help to reduce carbon emissions and enrich biodiversity – enabling us to make a positive contribution to the planet while serving nutritious, great tasting food that consumers love.
Information on our packs of famous Birds Eye peas and Findus vegetables is just the start of a much broader and deeper awareness-raising programme, to encourage consumers to make great choices for themselves and our planet.
I'm hugely excited to see what we can achieve as our partnership develops and look forward to sharing our learnings.
To find out more, please see our press release or visit the WWF website
Stéfan Descheemaeker, CEO
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text:
SCWA reverses flow in Orient
By Times Review
What a difference eight months make.
Back in September when the Suffolk County Water Authority announced it would receive federal stimulus money to pay for part of its proposed three-mile-long water main from East Marion to Orient's Brown's Hills community, CEO Stephen Jones said the availability of stimulus funds made the controversial project economically feasible.
"This money was offered, which pays half the cost, so it's not prohibitively expensive any longer," he told a reporter for The Suffolk Times.
Fast-forward to the spirited April 6 Town Hall hearing held to consider an amendment to the town's water supply map that would include the proposed main. There, Mr. Jones said in response to a question that the $3.8 million project could proceed with or without stimulus funds.
Why the change? According to a SCWA spokesman, the authority's board of directors decided last month "they were going to go ahead with the project one way or another because of the water situation in Orient." Both the authority and the county's Department of Health Services say water quality there is compromised by agricultural chemicals and other contaminants. Some residents point to the continuing water quality issues in supporting the main extension.
The SCWA board's latest stance on stimulus funds represents an about-face. Excerpts of minutes from the Oct. 1, 2009, directors meeting show that directors voted to approve expenditures for the water main only "after assurances from the chief financial officer and general counsel that the closing [on the project] would not proceed unless the authority was satisfied that the money would be forthcoming from the EFC" — the state's Environmental Facilities Corp., which dispenses stimulus funds for drinking water projects.
Ironically, the SCWA appears to be in no danger of losing the $1.9 million in stimulus funding awarded to the project this winter. Even though the money is unavailable to the authority pending the outcome of a lawsuit demanding a full environmental assessment of the project, "there's no sunset provision that they break ground by a specified date," said Jeffrey Hammond, a spokesman for the state Department of Health, which approved the use of stimulus funds for the project.
Those who filed the lawsuit and many other Orient residents fear that the water main could eventually extend service to a much larger area and perhaps prompt unwanted development.
While saying they don't oppose the introduction of public water, these residents want a complete State Environmental Quality Review Act, or SEQRA, assessment of the project and completion of the town's comprehensive master plan before the project can go forward.
Times Review
Email Times Review Email Created with Sketch. Email Times Review
Historic Orient home receives landmark status
When Robert Hanlon and his wife, Jessica Frankel, bought the old Orient home on the Main Road that belonged...

redpajama_set_name: RedPajamaCommonCrawl


text:
Erwin Pokorny (* 11. März 1920 in Wiener Neustadt; † 4. März 1973 ebenda) war ein österreichischer Politiker (ÖVP) und Gewerkschaftssekretär. Er war von 1969 bis 1973 Abgeordneter zum Landtag von Niederösterreich.

Pokorny absolvierte eine Gärtnerlehre und war als Textilarbeiter beschäftigt. Er engagierte sich als Betriebsrat und wirkte von 1956 bis 1959 als ÖAAB-Hauptbezirksobmann. Zudem war er Bundesobmann der Fraktion Christlicher Gewerkschafter in der Textilarbeitergewerkschaft und vertrat die ÖVP zwischen dem 4. Dezember 1969 und dem 4. März 1973 im Niederösterreichischen Landtag.

Literatur
 NÖ Landtagsdirektion (Hrsg.): Biographisches Handbuch des NÖ Landtages und der NÖ Landesregierung 1921–2000 (= NÖ-Schriften. Band 128). NÖ Landtagsdirektion, St. Pölten 2000, ISBN 3-85006-127-2.

Weblinks

Landtagsabgeordneter (Niederösterreich)
ÖVP-Mitglied
Österreicher
Geboren 1920
Gestorben 1973
Mann

redpajama_set_name: RedPajamaWikipedia


text:
Catalog Home / Warren E. Burger Library
The Warren E. Burger Library supports the research and curricular needs of the students, faculty, and staff of Mitchell Hamline School of Law. The Library also welcomes Mitchell Hamline alumni, the practicing bar, and public patrons to use its resources.
The Library has over 500 seats for patrons including 150 individual study carrels. 17 study rooms can be reserved online by students for group study sessions. Wireless access is available throughout the facility. Laptop computers are available for checkout to students. Five copying, scanning, and printing machines are located in the Library.
The Warren E. Burger Library's collection consists of over 320,000 physical volumes with access to over 700,000 titles in electronic format via the Library's 75 database subscriptions. The Library holds a comprehensive collection of federal and Minnesota primary source materials augmented by extensive periodical, treatise, loose-leaf, and reference work holdings. Special emphasis is placed on collecting intellectual property, taxation, legal research and writing, employment law, and practice skills materials. The Library selectively collects United States federal government publications through the Federal Depository Library Program. Materials that are not available in the collection can be requested though the Library's online interlibrary loan system.
The Library offers regularly scheduled reference service and individualized research assistance by appointment. The reference librarians teach legal research courses and give presentations on research techniques and resources to both doctrinal and skills classes. Technical services staff maintain access to the Library collection, curate the Mitchell Hamline archives, manage the Mitchell Hamline Open Access institutional repository, and collaborate with faculty, students, and staff on digital projects.
Students must follow all library rules as published on the library website or otherwise publicly promulgated. A violation of the Library's Behavior Policy is subject to sanctions under the Student Code of Conduct or other law school policies (see the Student Conduct page in the Policies section of this Catalog). For all library policies and additional information, see the Warren E. Burger Library policies webpage.
For complete information about library services at Mitchell Hamline, see the Warren E. Burger Library website.


text:
T4Templates
===========

T4 templates to use with T4Toolbox

Usage
-----

1. Install [T4Toolbox](http://t4toolbox.codeplex.com/)
2. Add template to a project (You can use NuGet)
3. Set "Custom Tool Template" to desired template

ImplementNotifyPropertyChanged.tt
---------------------------------

Define properties in an interface.

```c#
public interface IClass1Properties
{
    string StringProperty { get; set; }
    int IntProperty { get; set; }
}
```
Define **partial** class with *ImplementNotifyPropertyChanged* attribute

```c#
[ImplementNotifyPropertyChanged(typeof(IClass1Properties))]
public partial class Class1 : IClass1Properties
{
}
```
Properties will be generated with *NotifyPropertyChanging* and *NotifyPropertyChanged* events.

You can define methods with names *On<propName>Changing* and *On<propName>Changed*. They will be called besides firing OnPropertyChanging and OnPropertyChanged events.
```c#
[ImplementNotifyPropertyChanged(typeof(IClass1Properties))]
public partial class Class1 : IClass1Properties
{
    protected void OnStringPropertyChanged(string oldValue, string newValue)
    {
    // do some stuff with oldValue or newValue
    }
}
```

ImplementPropertyChangedCaliburn.tt
---------------------------------
Same as **ImplementNotifyPropertyChanged** template but uses *PropertyChangedBase* from [Caliburn.Micro](https://caliburnmicro.codeplex.com/) framework. *PropertyChangedBase* dispatches all property changed events to UI thread.

Note that *INotifyPropertyChanging* is not implemented in PropertyChangedBase. Everything else is the same as **ImplementNotifyPropertyChanged** template.

AddDataMsTests.tt
-----------------

Add **partial** keyword to a test class

```c#
[TestClass]
public partial class UnitTest1
{
```
Add a method to a test class with *DataTestMethod* attributes

```c#
[DataTestMethod("10", 10)]
[DataTestMethod("20", 20)]
[DataTestMethod("30", 30)]
private void DataTest(string stringParam, int intParam)
{
    Assert.AreEqual(intParam, Int32.Parse(stringParam));
}
```
Test methods will be generated for each *DataTestMethod* attribute.

If you set the *Result* attribute property the result of a method will be asserted.

```c#
[DataTestMethod("10", Result = 10)]
[DataTestMethod("12", Result = 12)]
private int DataTestWithResult3(string stringParam)
{
    return Int32.Parse(stringParam);
}
```
Other properties of *DataTestMethod* attribute are:
* Message
* TestName
* Description
* ExpectedException
* Ignore
* Priority
* Timeout
* WorkItem

They translate to *MsTest* attributes. You can also use original attributes and they will be added to all generated
tests. The attributes will still be overwritten with properties of *DataTestMethod* attribute.
Description attribute will be formatted using test parameters and result.

```c#
[DataTestMethod("10", Result = 10, Priority = 3)]
[DataTestMethod("12", Result = 12)]
[Priority(10)]
[Description("Test for \"{0}\" should return {1}")]
private int DataTest(string stringParam)
{
    return Int32.Parse(stringParam);
}
```
Following test will be generated from this code.

```c#
[TestMethod]
[Priority(3)]
[Description("Test for \"10\" should return 10")]
public void DataTest_10_10()
{
    Assert.AreEqual(10, DataTest("10"));
}

[TestMethod]
[Description("Test for \"12\" should return 12")]
[Priority(10)]
public void DataTest_12_12()
{
    Assert.AreEqual(12, DataTest("12"));
}
```

redpajama_set_name: RedPajamaGithub


text:
Q: Operating with very small numbers I want to do a subtraction 1-x, where x is a very small number(Order of magnitude of -19 or-20).I do not get the number I want: after the operation the number is still 1.
I know that's because Matlab only calculates to 53 bits which allows to operations up to 1E-16, but is there an alternative method to solve this kind of operations?
Thanks.

A: If you have Symbolic Math Toolbox, there is a simple way to increase arithmetics precision.
As pointed on this webpage, take vpa() function from your inputs. You can either change the default precision by changing digits variable or specify the desired precision by the second argument in vpa() function

redpajama_set_name: RedPajamaStackExchange


text:
William Gordon "Bill" Thompson (* 10. August 1921 in Glasgow; † 26. Dezember 1988 in Portsmouth) war ein schottischer Fußballspieler und -trainer. Als Verteidiger war er im erweiterten Kader des FC Portsmouth, der in den Jahren 1949 und 1950 zwei englische Meisterschaften in Serie gewann. Später trainierte er in den Niederlanden Sparta Rotterdam und den HFC Haarlem sowie in Ägypten den Ismaily SC.

Karriere
Thompson spielte zunächst Fußball in seiner schottischen Heimat in der Kleinstadt Carnoustie und nach dem Ende des Zweiten Weltkriegs wechselte er im März 1946 nach England zum Erstligisten FC Portsmouth. Bei "Pompey" wurde Thompson als vielseitig einsetzbarer Ergänzungsspieler betrachtet, wobei seine bevorzugte Position die des linken Außenläufers war. Als Ersatzmann hinter Jimmy Dickinson musste er gut drei Jahre auf die ersten Bewährungschancen in der Profielf warten und als Portsmouth in der Saison 1948/49 die englische Meisterschaft gewann, steuerte Thompson drei Einsätze dazu bei. Dabei vertrat er Dickinson nach der bereits gefallenen Entscheidung im letzten Heimspiel gegen Huddersfield Town (2:0) und war danach linker Verteidiger sowie Mittelläufer in den beiden letzten Ligapartien.

Im Oktober 1949 absolvierte er weitere fünf Pflichtspiele in Serie, wozu auch der Charity Shield (englischer Supercup) gehörte, in dem sich Portsmouth von den Wolverhampton Wanderers mit 1:1 trennte. Hier profitierte er von dem Ausfall von Reg Flewin, der sich von einer Blinddarmoperation erholte. Während der Saison 1949/50, in der Portsmouth den Ligatitel verteidigte, kam Thompson noch zu weiteren Einsätzen, wobei er nach Vertretungen für Jimmy Scoular, Flewin und Dickinson am letzten Spieltag den wohl bedeutendsten Moment seiner Karriere erlebte. Thompson, der während seiner ganzen Karriere als Abwehrspieler unterwegs gewesen war, musste plötzlich als Ersatz für Ike Clarke als Mittelstürmer dienen. Portsmouth benötigte gegen Aston Villa noch einen Sieg und es dauerte gerade einmal 20 Sekunden, bevor er per Weitschuss den Führungstreffer erzielte. Er steuerte noch ein weiteres Tor zum 5:1-Sieg bei und sicherte so dem Verein den Meistertitel aufgrund des besseren Torquotienten gegenüber Wolverhampton. In den folgenden gut zweieinhalb Jahren bestritt Thompson noch weitere insgesamt 28 Ligaspiele und wechselte dann im Januar 1953 zum Drittligisten Bournemouth & Boscombe. Für Bournemouth absolvierte Thompson 45 Pflichtspiele, bevor Verletzungsprobleme für das Ende seiner aktiven Profikarriere sorgten.

In der Spätphase der Saison 1955/56 übernahm Thompson bei Guildford City die Trainerfunktion in der Southern League und gewann dort die Meisterschaft. Mit dieser Empfehlung konnte er sich im Sommer 1957 gegen mehr 30 Mitbewerber als neuer Trainer des Drittligisten Exeter City durchsetzen. Letztlich gestaltete sich seine Amtszeit dort jedoch schwierig und kurz. Neben einer sportlichen Abwärtsentwicklung häuften sich die Meinungsverschiedenheiten mit dem Präsidenten A. S. Line und so musste Thompson Exeter schon im Januar 1958 wieder verlassen. Nur wenige Tage später nahm in mit Worcester City wieder ein Klub aus der Southern League unter Vertrag. Während seiner Zeit in Worcester machte er in der Saison 1958/59 auf sich aufmerksam, als ihm mit seinem Team im FA Cup ein überraschender Sieg gegen den FC Liverpool gelang. In den folgenden beiden Jahren blieben die Erfolge trotz prominenter Verpflichtungen wie die von Billy Reed und Johnny Nicholls aber aus.

Nach der Entlassung von Freddie Cox wurde er interimistisch im Frühjahr 1961 dessen Nachfolger in Portsmouth. Zu seiner Enttäuschung mündete dies nicht in eine permanente Beschäftigung als Cheftrainer, aber er blieb dem Klub zunächst als Assistent von George Smith erhalten. Anschließend betätigte sich Thompson als Trainer jenseits der britischen Inseln. Dabei betreute er in den Niederlanden Sparta Rotterdam zwischen 1963 und 1966 sowie den HFC Haarlem zwischen 1970 und 1971. Größter Erfolg war hier 1966 der Sieg im niederländischen Pokal. Weiteres Highlight war sein Engagement in Ägypten für den Ismaily SC, mit dem er 1967 die heimische Meisterschaft gewann. Später kehrte Thompson nach Portsmouth zurück und kümmerte sich bei seinem Ex-Verein speziell um die Betreuung ausländischer Klubs, die den Weg nach England gefunden hatten. Er starb am 2. Weihnachtstag des Jahres 1988 im Alter von 67 Jahren.

Titel
als Spieler
 Charity Shield (1): 1949 (geteilt)
als Trainer
 Ägyptische Meisterschaft (1): 1967
 Niederländischer Pokal (1): 1966
 Southern League (1): 1956

Weblinks

 Statistische Daten der Post War English & Scottish Football League A-Z Player's Database (englisch)

Einzelnachweise

Fußballspieler (FC Portsmouth)
Fußballspieler (AFC Bournemouth)
Fußballtrainer (Exeter City)
Fußballtrainer (Sparta Rotterdam)
Fußballtrainer (Ismaily SC)
Schotte
Brite
Geboren 1921
Gestorben 1988
Mann


text:
Seasons After + Shallow Side Play Parking Lot Jam in San Antonio
Sometimes when the best laid plans go awry, you get something even more memorable. Such was the case in San Antonio this past week when a scheduling snafu left Seasons After and Shallow Side without a venue to play, so they made the best out of the situation and delivered a parking lot jam for fans lucky enough to catch it.
The groups traveled to San Antonio Thursday night (Feb. 23) to play the Korova only to learn that there was a mix-up and that the venue was closed. But rather than pack it in and move on to the next stop, the bands put on an hour-plus jam in the parking lot for fans who had shown up. Seasons After started things off, before members of Shallow Side later joined in on the fun.
As you can see in the fan-shot footage from Yvonne Laughlin, Seasons After pulled up some chairs and played unplugged, working out the track "So Long Goodbye" as seen below. They also performed a number of cover songs, including the Lost Boys soundtrack Gerard McMahon favorite "Cry Little Sister" (seen below). Members of Shallow Side then joined in for covers of Phil Collins' "In the Air Tonight" (seen below), Alice in Chains' "Rooster" (seen above) and the Mark Ronson / Bruno Mars favorite "Uptown Funk" (seen below). The evening also included performances of Shallow Side's "Rebel," covers of Michael Jackson's "Dirty Diana" and Garth Brooks' "Friends in Low Places," and more. Check out Seasons After's Instagram photo from the performance below as well.
Kudos to both bands for leaving the fans who showed up to the show with a memory they won't soon forget. And be sure to catch Seasons After and Shallow Side on the road when they come to your town.
Seasons After are currently touring in support of their 2016 album, Manifesto, which features the single "Fighter." See the dates for their touring with Shallow Side and beyond here. Meanwhile, Shallow Side just released their I (One) album earlier this year featuring the songs "Rebel" and their cover of Styx's "Renegade." The band was voted as Best New Artist in the 6th Annual Loudwire Music Awards and they also have plenty of dates, both with Seasons After and beyond. See their tour schedule here.
Seasons After, "So Long Goodbye" San Antonio Parking Lot Jam
Seasons After, "In the Air Tonight" San Antonio Parking Lot Jam
Seasons After, "Cry Little Sister" San Antonio Parking Lot Jam
Seasons After + Shallow Side, "Uptown Funk" San Antonio Parking Lot Jam
Watch Seasons After's 'Fighter' Video
Watch Shallow Side's 'Renegade' Video
Filed Under: Seasons After, Shallow Side
Categories: Concerts, News, Rock


TOYOPEARL AF-rProtein A HC-650F is a high capacity Protein A resin for monoclonal antibody purification. An enhanced rProtein A ligand is bound to the TOYOPEARL HW-65F base bead via multipoint attachment resulting in excellent base stability for up to 200 CIP cycles with 0.1 mol/L NaOH.
TOYOPEARL AF-rProtein A HC-650F resin maintains 80% of initial dynamic binding capacity after 40 CIP cycles with 0.5 mol/L NaOH. TOYOPEARL AF-rProtein A HC-650F resin exhibits dynamic binding capacities of greater than 65 g/L at residence times of 5 minutes and greater than 50 g/L at 2 minutes residence time with feed stock concentrations from 1.0 g/L to 10.0 g/L.
Achievement of high linear velocities at relatively low pressure enables high throughput at production scale using equipment with moderate pressure limitations. Improved mass transfer characteristics allow it to maintain a larger percent of its capacity at lower residence times relative to agarose base stable resins. Typical leakage for this rProtein A ligand is 0.6 -1.7 ng rProtein A /mg eluted antibody by ELISA testing. Though TOYOPEARL AF-rProtein A-650F resin is shipped in 20% ethanol, it can be stored in 2% benzyl alcohol if necessary.
TOYOPEARL AF-rProtein A HC-650F utilizes an alkaline resistant recombinant Protein A variant. This non-animal derived ligand is bound to the base bead, Toyopearl HW-65F, using multipoint attachment. This contributes to both the resin's alkaline resistance and its low ligand leakages in the range of 5-25ng/mg IgG. Good pressure-flow characteristics and kinetics contribute to maintaining good capacity, particularly at low residence times.
TOYOPEARL AF-rProtein A HC-650F is available in one particle size, 45 µm, which corresponds to the F-grade designation for TOYOPEARL resins.


text:
Browsing publications of the research group of microbial natural substances([HIPS]MINS) by Title
Division of microbial natural substances ([HIPS]MINS)
publications of the research group of microbial natural substances([HIPS]MINS)
All of HZICommunitiesTitleAuthorsIssue DateSubmit DateSubjectsJournalTypesSubject (MeSH)This CollectionTitleAuthorsIssue DateSubmit DateSubjectsJournalTypesSubject (MeSH)
About: PolicyHelmholtz-Zentrum für Infektionsforschung HomepageHZI-Library HomepageContact usOpen AccessPublishing ApproachGetting StartedEditing ProfileBrowsing OptionsUsing SearchSubmitting ContentLicenced Journals & access details here
Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2.
Preisitsch, Michael; Heiden, Stefan E; Beerbaum, Monika; Niedermeyer, Timo H J; Schneefeld, Marie; Herrmann, Jennifer; Kumpfmüller, Jana; Thürmer, Andrea; Neidhardt, Inga; Wiesner, Christoph; et al. (2016)
In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. LC-MS analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. In addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 putative congeners have been detected. Nine compounds, carbamidocyclophanes M-U, were isolated, and their structural elucidation by 1D and 2D NMR experiments in combination with HRMS and ECD analysis revealed that they are brominated analogues of chlorinated carbamidocyclophanes. Quantification of the carbamidocyclophanes showed that chloride is the preferably utilized halide, but incorporation is reduced in the presence of bromide. Evaluation of the antibacterial activity of 30 [7.7]paracyclophanes and related derivatives against selected pathogenic Gram-positive and Gram-negative bacteria exhibited remarkable effects especially against methicillin- and vancomycin-resistant staphylococci and Mycobacterium tuberculosis. For deeper insights into the mechanisms of biosynthesis, the carbamidocyclophane biosynthetic gene cluster in Nostoc sp. CAVN2 was studied. The gene putatively coding for the carbamoyltransferase has been identified. Based on bioinformatic analyses, a possible biosynthetic assembly is discussed.
Elevated free cholesterol in a p62 overexpression model of non-alcoholic steatohepatitis.
Simon, Yvette; Kessler, Sonja M; Gemperlein, Katja; Bohle, Rainer M; Müller, Rolf; Haybaeck, Johannes; Kiemer, Alexandra K; Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbrücken, Germany. (2014-12-21)
To characterize how insulin-like growth factor 2 (IGF2) mRNA binding protein p62/IMP2-2 promotes steatohepatitis in the absence of dietary cholesterol.
An endothelial cell line infected by Kaposi's sarcoma-associated herpes virus (KSHV) allows the investigation of Kaposi's sarcoma and the validation of novel viral inhibitors in vitro and in vivo.
Dubich, Tatyana; Lieske, Anna; Santag, Susann; Beauclair, Guillaume; Rückert, Jessica; Herrmann, Jennifer; Gorges, Jan; Büsche, Guntram; Kazmaier, Uli; Hauser, Hansjörg; et al. (2019-01-04)
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), a tumor of endothelial origin predominantly affecting immunosuppressed individuals. Up to date, vaccines and targeted therapies are not available. Screening and identification of anti-viral compounds are compromised by the lack of scalable cell culture systems reflecting properties of virus-transformed cells in patients. Further, the strict specificity of the virus for humans limits the development of in vivo models. In this study, we exploited a conditionally immortalized human endothelial cell line for establishment of in vitro 2D and 3D KSHV latency models and the generation of KS-like xenograft tumors in mice. Importantly, the invasive properties and tumor formation could be completely reverted by purging KSHV from the cells, confirming that tumor formation is dependent on the continued presence of KSHV, rather than being a consequence of irreversible transformation of the infected cells. Upon testing a library of 260 natural metabolites, we selected the compounds that induced viral loss or reduced the invasiveness of infected cells in 2D and 3D endothelial cell culture systems. The efficacy of selected compounds against KSHV-induced tumor formation was verified in the xenograft model. Together, this study shows that the combined use of anti-viral and anti-tumor assays based on the same cell line is predictive for tumor reduction in vivo and therefore allows faithful selection of novel drug candidates against Kaposi's sarcoma. KEY MESSAGES: Novel 2D, 3D, and xenograft mouse models mimic the consequences of KSHV infection. KSHV-induced tumorigenesis can be reverted upon purging the cells from the virus. A 3D invasiveness assay is predictive for tumor reduction in vivo. Chondramid B, epothilone B, and pretubulysin D diminish KS-like lesions in vivo.
ExoCET: exonuclease in vitro assembly combined with RecET recombination for highly efficient direct DNA cloning from complex genomes.
Wang, Hailong; Li, Zhen; Jia, Ruonan; Yin, Jia; Li, Aiying; Xia, Liqiu; Yin, Yulong; Müller, Rolf; Fu, Jun; Stewart, A Francis; et al. (2017-12-12)
The exponentially increasing volumes of DNA sequence data highlight the need for new DNA cloning methods to explore the new information. Here, we describe 'ExoCET' (Exonuclease Combined with RecET recombination) to directly clone any chosen region from bacterial and mammalian genomes with nucleotide precision into operational plasmids. ExoCET combines in vitro exonuclease and annealing with the remarkable capacity of full length RecET homologous recombination (HR) to retrieve specified regions from genomic DNA preparations. Using T4 polymerase (T4pol) as the in vitro exonuclease for ExoCET, we directly cloned large regions (>50 kb) from bacterial and mammalian genomes, including DNA isolated from blood. Employing RecET HR or Cas9 cleavage in vitro, the directly cloned region can be chosen with nucleotide precision to position, for example, a gene into an expression vector without the need for further subcloning. In addition to its utility for bioprospecting in bacterial genomes, ExoCET presents straightforward access to mammalian genomes for various applications such as region-specific DNA sequencing that retains haplotype phasing, the rapid construction of optimal, haplotypic, isogenic targeting constructs or a new way to genotype that presents advantages over Southern blotting or polymerase chain reaction. The direct cloning capacities of ExoCET present new freedoms in recombinant DNA technology.
ExoCET: exonuclease in vitro assembly combined with RecET recombination for highly efficient direct DNA cloning from complex genomes. (Erratum)
Wang, Hailong; Li, Zhen; Jia, Ruonan; Yin, Jia; Li, Aiying; Xia, Liqiu; Yin, Yulong; Müller, Rolf; Fu, Jun; Stewart, A Francis; et al. (Oxford University Press, 2018-03-16)
The exponentially increasing volumes of DNA sequence data highlight the need for new DNA cloning methods to explore the new information. Here, we describe 'ExoCET' (Exonuclease Combined with RecET recombination) to directly clone any chosen region from bacterial and mammalian genomes with nucleotide precision into operational plasmids. ExoCET combines in vitro exonuclease and annealing with the remarkable capacity of full length RecET homologous recombination (HR) to retrieve specified regions from genomic DNA preparations. Using T4 polymerase (T4pol) as the in vitro exonuclease for ExoCET, we directly cloned large regions (>50 kb) from bacterial and mammalian genomes, including DNA isolated from blood. Employing RecET HR or Cas9 cleavage in vitro, the directly cloned region can be chosen with nucleotide precision to position, for example, a gene into an expression vector without the need for further subcloning. In addition to its utility for bioprospecting in bacterial genomes, ExoCET presents straightforward access to mammalian genomes for various applications such as region-specific DNA sequencing that retains haplotype phasing, the rapid construction of optimal, haplotypic, isogenic targeting constructs or a new way to genotype that presents advantages over Southern blotting or polymerase chain reaction. The direct cloning capacities of ExoCET present new freedoms in recombinant DNA technology.
Extracellular-regulated kinase 2 is activated by the enhancement of hinge flexibility.
Sours, Kevin M; Xiao, Yao; Ahn, Natalie G; Helmholtz Institute for Pharmaceutical Research, Saarland University, Saarbrücken, Germany. (2014-05-01)
Protein motions underlie conformational and entropic contributions to enzyme catalysis; however, relatively little is known about the ways in which this occurs. Studies of the mitogen-activated protein kinase ERK2 (extracellular-regulated protein kinase 2) by hydrogen-exchange mass spectrometry suggest that activation enhances backbone flexibility at the linker between N- and C-terminal domains while altering nucleotide binding mode. Here, we address the hypothesis that enhanced backbone flexibility within the hinge region facilitates kinase activation. We show that hinge mutations enhancing flexibility promote changes in the nucleotide binding mode consistent with domain movement, without requiring phosphorylation. They also lead to the activation of monophosphorylated ERK2, a form that is normally inactive. The hinge mutations bypass the need for pTyr but not pThr, suggesting that Tyr phosphorylation controls hinge motions. In agreement, monophosphorylation of pTyr enhances both hinge flexibility and nucleotide binding mode, measured by hydrogen-exchange mass spectrometry. Our findings demonstrate that regulated protein motions underlie kinase activation. Our working model is that constraints to domain movement in ERK2 are overcome by phosphorylation at pTyr, which increases hinge dynamics to promote the active conformation of the catalytic site.
Fatty acid elongation in non-alcoholic steatohepatitis and hepatocellular carcinoma.
Kessler, Sonja M; Simon, Yvette; Gemperlein, Katja; Gianmoena, Kathrin; Cadenas, Cristina; Zimmer, Vincent; Pokorny, Juliane; Barghash, Ahmad; Helms, Volkhard; van Rooijen, Nico; et al. (2014)
Non-alcoholic steatohepatitis (NASH) represents a risk factor for the development of hepatocellular carcinoma (HCC) and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice). Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD)-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h) increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.
Fatty acid-related phylogeny of myxobacteria as an approach to discover polyunsaturated omega-3/6 Fatty acids.
Garcia, Ronald; Pistorius, Dominik; Stadler, Marc; Müller, Rolf (2011-04)
In an analysis of 47 aerobic myxobacterial strains, representing 19 genera in suborders Cystobacterineae, Nannocystineae, Sorangiineae, and a novel isolate, "Aetherobacter" SBSr008, an enormously diverse array of fatty acids (FAs) was found. The distribution of straight-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) supports the reported clustering of strains in the phylogenetic tree based on 16S rRNA genes. This finding additionally allows the prediction and assignment of the novel isolate SBSr008 into its corresponding taxon. Sorangiineae predominantly contains larger amounts of SCFA (57 to 84%) than BCFA. On the other hand, Cystobacterineae exhibit significant BCFA content (53 to 90%), with the exception of the genus Stigmatella. In Nannocystineae, the ratio of BCFA and SCFA seems dependent on the taxonomic clade. Myxobacteria could also be identified and classified by using their specific and predominant FAs as biomarkers. Nannocystineae is remarkably unique among the suborders for its absence of hydroxy FAs. After the identification of arachidonic (AA) FA in Phaselicystidaceae, eight additional polyunsaturated fatty acids (PUFAs) belonging to the omega-6 and omega-3 families were discovered. Here we present a comprehensive report of FAs found in aerobic myxobacteria. Gliding bacteria belonging to Flexibacter and Herpetosiphon were chosen for comparative analysis to determine their FA profiles in relation to the myxobacteria.
First Bispecific Inhibitors of the Epidermal Growth Factor Receptor Kinase and the NF-κB Activity As Novel Anticancer Agents.
Hamed, Mostafa M; Darwish, Sarah S; Herrmann, Jennifer; Abadi, Ashraf H; Engel, Matthias; HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1,66123 Saarbrücken, Germany. (2017-04-13)
The activation of the NF-κB transcription factor is a major adaptive response induced upon treatment with EGFR kinase inhibitors, leading to the emergence of resistance in nonsmall cell lung cancer and other tumor types. To suppress this survival mechanism, we developed new thiourea quinazoline derivatives that are dual inhibitors of both EGFR kinase and the NF-κB activity. Optimization of the hit compound, identified in a NF-κB reporter gene assay, led to compound 9b, exhibiting a cellular IC50 for NF-κB inhibition of 0.3 μM while retaining a potent EGFR kinase inhibition (IC50 = 60 nM). The dual inhibitors showed a higher potency than gefitinib to inhibit cell growth of EGFR-overexpressing tumor cell lines in vitro and in a xenograft model in vivo, while no signs of toxicity were observed. An investigation of the molecular mechanism of NF-κB suppression revealed that the dual inhibitors depleted the transcriptional coactivator CREB-binding protein from the NF-κB complex in the nucleus.
A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.
Menchon, Grégory; Prota, Andrea E; Lucena-Agell, Daniel; Bucher, Pascal; Jansen, Rolf; Irschik, Herbert; Müller, Rolf; Paterson, Ian; Díaz, J Fernando; Altmann, Karl-Heinz; et al. (2018-05-29)
Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.
Foxp3+ regulatory T cells are required for recovery from severe sepsis.
Kühlhorn, Franziska; Rath, Matthias; Schmoeckel, Katrin; Cziupka, Katharina; Nguyen, Huu Hung; Hildebrandt, Petra; Hünig, Thomas; Sparwasser, Tim; Huehn, Jochen; Pötschke, Christian; et al. (2013)
The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of CD4(+)Foxp3(+) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
Future Directions of Marine Myxobacterial Natural Product Discovery Inferred from Metagenomics.
Garcia, Ronald; La Clair, James J; Müller, Rolf; HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany. (2018-08-29)
Over the last two decades, halophilic (organisms that thrive at high salt concentrations) and halotolerant (organisms that have adapted to high salt concentrations) myxobacteria emerged as an important source of structurally diverse secondary metabolites from the marine environment. This review explores the advance of metagenomics analysis and 16S rRNA gene phylogeny of the cultured and uncultured myxobacteria from marine and other salt-environments up to July 2018. The diversity of novel groups of myxobacteria in these environments appears unprecedented, especially in the
Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering.
Tu, Qiang; Herrmann, Jennifer; Hu, Shengbiao; Raju, Ritesh; Bian, Xiaoying; Zhang, Youming; Müller, Rolf; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany. (2016)
Disorazol, a macrocyclic polykitide produced by the myxobacterium Sorangium cellulosum So ce12 and it is reported to have potential cytotoxic activity towards several cancer cell lines, including multi-drug resistant cells. The disorazol biosynthetic gene cluster (dis) from Sorangium cellulosum (So ce12) was identified by transposon mutagenesis and cloned in a bacterial artificial chromosome (BAC) library. The 58-kb dis core gene cluster was reconstituted from BACs via Red/ET recombineering and expressed in Myxococcus xanthus DK1622. For the first time ever, a myxobacterial trans-AT polyketide synthase has been expressed heterologously in this study. Expression in M. xanthus allowed us to optimize the yield of several biosynthetic products using promoter engineering. The insertion of an artificial synthetic promoter upstream of the disD gene encoding a discrete acyl transferase (AT), together with an oxidoreductase (Or), resulted in 7-fold increase in disorazol production. The successful reconstitution and expression of the genetic sequences encoding for these promising cytotoxic compounds will allow combinatorial biosynthesis to generate novel disorazol derivatives for further bioactivity evaluation.
Genome Analysis of the Fruiting Body-Forming Myxobacterium Chondromyces crocatus Reveals High Potential for Natural Product Biosynthesis.
Zaburannyi, Nestor; Bunk, Boyke; Maier, Josef; Overmann, Jörg; Müller, Rolf; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany. (2016)
Here, we report the complete genome sequence of the type strain of the myxobacterial genus Chondromyces, Chondromyces crocatus Cm c5. It presents one of the largest prokaryotic genomes featuring a single circular chromosome and no plasmids. Analysis revealed an enlarged set of tRNA genes, along with reduced pressure on preferred codon usage compared to that of other bacterial genomes. The large coding capacity and the plethora of encoded secondary metabolite biosynthetic gene clusters are in line with the capability of Cm c5 to produce an arsenal of antibacterial, antifungal, and cytotoxic compounds. Known pathways of the ajudazol, chondramide, chondrochloren, crocacin, crocapeptin, and thuggacin compound families are complemented by many more natural compound biosynthetic gene clusters in the chromosome. Whole-genome comparison of the fruiting-body-forming type strain (Cm c5, DSM 14714) to an accustomed laboratory strain which has lost this ability (nonfruiting phenotype, Cm c5 fr-) revealed genetic changes in three loci. In addition to the low synteny found with the closest sequenced representative of the same family, Sorangium cellulosum, extensive genetic information duplication and broad application of eukaryotic-type signal transduction systems are hallmarks of this 11.3-Mbp prokaryotic genome.
The glucocorticoid-induced leucine zipper mediates statin-induced muscle damage.
Hoppstädter, Jessica; Valbuena Perez, Jenny Vanessa; Linnenberger, Rebecca; Dahlem, Charlotte; Legroux, Thierry M; Hecksteden, Anne; Tse, William K F; Flamini, Sara; Andreas, Anastasia; Herrmann, Jennifer; et al. (Wiley, 2020-02-06)
Statins, the most prescribed class of drugs for the treatment of hypercholesterolemia, can cause muscle-related adverse effects. It has been shown that the glucocorticoid-induced leucine zipper (GILZ) plays a key role in the anti-myogenic action of dexamethasone. In the present study, we aimed to evaluate the role of GILZ in statin-induced myopathy. Statins induced GILZ expression in C2C12 cells, primary murine myoblasts/myotubes, primary human myoblasts, and in vivo in zebrafish embryos and human quadriceps femoris muscle. Gilz induction was mediated by FOXO3 activation and binding to the Gilz promoter, and could be reversed by the addition of geranylgeranyl, but not farnesyl, pyrophosphate. Atorvastatin decreased Akt phosphorylation and increased cleaved caspase-3 levels in myoblasts. This effect was reversed in myoblasts from GILZ knockout mice. Similarly, myofibers isolated from knockout animals were more resistant toward statin-induced cell death than their wild-type counterparts. Statins also impaired myoblast differentiation, and this effect was accompanied by GILZ induction. The in vivo relevance of our findings was supported by the observation that gilz overexpression in zebrafish embryos led to impaired embryonic muscle development. Taken together, our data point toward GILZ as an essential mediator of the molecular mechanisms leading to statin-induced muscle damage.
Growth Medium-Dependent Glycine Incorporation into the Peptidoglycan of Caulobacter crescentus.
Takacs, Constantin N; Hocking, Jason; Cabeen, Matthew T; Bui, Nhat Khai; Poggio, Sebastian; Vollmer, Waldemar; Jacobs-Wagner, Christine; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, United States of America. (2013)
The peptidoglycan (PG) is a macromolecular component of the bacterial cell wall that maintains the shape and integrity of the cell. The PG of , unlike that of many other Gram-negative bacteria, has repeatedly been shown to contain significant amounts of glycine. This compositional peculiarity has been deemed an intrinsic characteristic of this species. By performing a comprehensive qualitative and quantitative analysis of the PG by high-performance liquid chromatography (HPLC) and mass spectrometry (MS), we show here that glycine incorporation into the PG depends on the presence of exogenous glycine in the growth medium. High levels of glycine were detected at the fifth position of the peptide side chains of PG isolated from cells grown in the complex laboratory medium PYE or in defined medium (M2G) supplemented with casamino acids or glycine alone. In contrast, glycine incorporation was undetectable when cells were grown in M2G medium lacking glycine. Remarkably, glycine incorporation into peptidoglycan occurred even in the presence of low millimolar to sub-millimolar concentrations of free glycine. High glycine content in the PG had no obvious effects on growth rates, mode of PG incorporation or cell morphology. Hence, the PG is able to retain its physiological functions in cell growth and morphogenesis despite significant alterations in its composition, in what we deem to be unprecedented plasticity.
Heterologous expression of the atypical tetracycline chelocardin reveals the full set of genes required for its biosynthesis.
Lukežič, Tadeja; Pikl, Špela; Zaburannyi, Nestor; Remškar, Maja; Petković, Hrvoje; Müller, Rolf; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (BMC (part of Springer), 2020-12-19)
Background: Chelocardin (CHD) exhibits a broad-spectrum antibiotic activity and showed promising results in a small phase II clinical study conducted on patients with urinary tract infections. Importantly, CHD was shown to be active also against tetracycline-resistant Gram-negative pathogens, which is gaining even more importance in today's antibiotic crisis. We have demonstrated that modifications of CHD through genetic engineering of its producer, the actinomycete Amycolatopsis sulphurea, are not only possible but yielded even more potent antibiotics than CHD itself, like 2-carboxamido-2-deacetyl-chelocardin (CD-CHD), which is currently in preclinical evaluation. A. sulphurea is difficult to genetically manipulate and therefore manipulation of the chd biosynthetic gene cluster in a genetically amenable heterologous host would be of high importance for further drug-discovery efforts. Results: We report heterologous expression of the CHD biosynthetic gene cluster in the model organism Streptomyces albus del14 strain. Unexpectedly, we found that the originally defined CHD gene cluster fails to provide all genes required for CHD formation, including an additional cyclase and two regulatory genes. Overexpression of the putative pathway-specific streptomyces antibiotic regulatory protein chdB in A. sulphurea resulted in an increase of both, CHD and CD-CHD production. Applying a metabolic-engineering approach, it was also possible to generate the potent CHD analogue, CD-CHD in S. albus. Finally, an additional yield increase was achieved in S. albus del14 by in-trans overexpression of the chdR exporter gene, which provides resistance to CHD and CDCHD. Conclusions: We identified previously unknown genes in the CHD cluster, which were shown to be essential for chelocardin biosynthesis by expression of the full biosynthetic gene cluster in S. albus as heterologous host. When comparing to oxytetracycline biosynthesis, we observed that the CHD gene cluster contains additional enzymes not found in gene clusters encoding the biosynthesis of typical tetracyclines (such as oxytetracycline). This finding probably explains the different chemistries and modes of action, which make CHD/CD-CHD valuable lead structures for clinical candidates. Even though the CHD genes are derived from a rare actinomycete A. sulphurea, the yield of CHD in the heterologous host was very good. The corrected nucleotide sequence of the CHD gene cluster now contains allgene products required for the production of CHD in a genetically amenable heterologous host, thus opening new possibilities towards production of novel and potent tetracycline analogues with a new mode of action.
A high-affinity fluorescence probe for copper(II) ions and its application in fluorescence lifetime correlation spectroscopy.
Grüter, Andreas; Hoffmann, Michael; Müller, Rolf; Wohland, Thorsten; Jung, Gregor; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Springer, 2019-04-26)
Copper is one of the most important transition metals in many organisms where it catalyzes a manifold of different processes. As a result of copper's redox activity, organisms have to avoid unbound ions, and a dysfunctional copper homeostasis may lead to multifarious pathological processes in cells with very severe ramifications for the affected organisms. In many neurodegenerative diseases, however, the exact role of copper ions is still not completely clarified. In this work, a high-affinity and highly selective copper probe molecule, based on the naturally occurring tetrapeptide DAHK is synthesized. The sensor (log KD = - 12.8 ± 0.1) is tagged with a fluorescent BODIPY dye whose fluorescence lifetime distinctly decreases from 5.8 ns ± 0.2 ns to 0.4 ns ± 0.1 ns on binding to copper(II) cations. It is shown by using fluorescence lifetime correlation spectroscopy that the concentration of both probe and probe-copper complex can be simultaneously measured even at nanomolar concentration levels. This work presents a possible starting point for a new type of probe and method for future in vivo studies to further reveal the exact role of copper ions in organisms. Graphical abstract.
Homologous bd oxidases share the same architecture but differ in mechanism.
Theßeling, Alexander; Rasmussen, Tim; Burschel, Sabrina; Wohlwend, Daniel; Kägi, Jan; Müller, Rolf; Böttcher, Bettina; Friedrich, Thorsten; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Nature Publication group, 2019-11-13)
Cytochrome bd oxidases are terminal reductases of bacterial and archaeal respiratory chains. The enzyme couples the oxidation of ubiquinol or menaquinol with the reduction of dioxygen to water, thus contributing to the generation of the protonmotive force. Here, we determine the structure of the Escherichia coli bd oxidase treated with the specific inhibitor aurachin by cryo-electron microscopy (cryo-EM). The major subunits CydA and CydB are related by a pseudo two fold symmetry. The heme b and d cofactors are found in CydA, while ubiquinone-8 is bound at the homologous positions in CydB to stabilize its structure. The architecture of the E. coli enzyme is highly similar to that of Geobacillus thermodenitrificans, however, the positions of heme b595 and d are interchanged, and a common oxygen channel is blocked by a fourth subunit and substituted by a more narrow, alternative channel. Thus, with the same overall fold, the homologous enzymes exhibit a different mechanism.
How to Study the Metabolism of New Psychoactive Substances for the Purpose of Toxicological Screenings-A Follow-Up Study Comparing Pooled Human Liver S9, HepaRG Cells, and Zebrafish Larvae.
Wagmann, Lea; Frankenfeld, Fabian; Park, Yu Mi; Herrmann, Jennifer; Fischmann, Svenja; Westphal, Folker; Müller, Rolf; Flockerzi, Veit; Meyer, Markus R; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Frontiers, 2020-07-17)
The new psychoactive substances (NPS) market continues to be very dynamic. A large number of compounds belonging to diverse chemical groups continue to emerge. This makes their detection in biological samples challenging for clinical and forensic toxicologists. Knowledge of the metabolic fate of NPS is crucial for developing comprehensive screening procedures. As human studies are not feasible due to ethical concerns, the current study aimed to compare the NPS' metabolic pattern in incubations with pooled human liver S9 fraction (pHLS9), human liver HepaRG cells, and zebrafish larvae. The latter model was recently shown to be a promising preclinical surrogate for human hepatic metabolism of a synthetic cannabinoid. However, studies concerning other NPS classes are still missing and therefore an amphetamine-based N-methoxybenzyl (NBOMe) compound, a synthetic cathinone, a pyrrolidinophenone analog, a lysergamide, as well as another synthetic cannabinoid were included in the current study. Liquid chromatography coupled to Orbitrap-based high-resolution tandem mass spectrometry was used to analyze metabolic data. Zebrafish larvae were found to produce the highest number of phase I but also phase II metabolites (79 metabolites in total), followed by HepaRG cells (66 metabolites). Incubations with pHLS9 produced the least metabolites (57 metabolites). Furthermore, the involvement of monooxygenases and esterases in the metabolic phase I transformations of 4F-MDMB-BINACA was elucidated using single-enzyme incubations. Several cytochrome P450 (CYP) isozymes were shown to contribute, and CYP3A5 was involved in all CYP-catalyzed reactions, while amide and ester hydrolysis were catalyzed by the human carboxylesterase (hCES) isoforms hCES1b and/or hCES1c. Finally, metabolites were compared to those present in human biosamples if data were available. Overall, the metabolic patterns in HepaRG cells provided the worst overlap with that in human biosamples. Zebrafish larvae experiments agreed best with data found in human plasma and urine analysis. The current study underlines the potential of zebrafish larvae as a tool for elucidating the toxicokinetics of NPS in the future.
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text:
Son juntas de estanqueidad compuestas por un cordón de estanqueidad con base elastomérica, que es depositado por impresión serigráfica sobre un soporte plano, en una zona definida técnicamente a priori. La elección de las zonas de estanqueidad y la forma de los contornos son absolutamente libres. El proceso de fabricación desarrollado a este efecto permite realizar el depósito de material elastomérico en tolerancias muy precisas.

Se puede incrementar la presión del cierre en zonas alejadas del apriete aumentando la anchura o altura del cordón.

Descripción de algunos elementos sellantes:

- Sellantes con base epoxi. Asequibles en un rango de dureza amplio, ambos en forma celular y compacta.
La compatibilidad con fluidos es muy buena siendo conveniente para: aceites minerales, querosenos, fuel de aviación, anticongelantes, carbón y gas natural.
La resistencia a la temperatura es de 120 °C como máximo. Estos materiales se consideran sellantes de tipo general, y pueden ir impresos sobre metal, plástico y papel, además de como impresión pura (sin soporte).

- Sellantes basados en poliuretano. Con mayores resistencias y alargamiento que el grupo epoxi, se emplea normalmente para altas presiones.
Se adecua a presiones cíclicas de 340 bares y bajo condiciones de presión estática puede sobrepasarlo. Es compatible con la mayoría de aceites minerales y otros fluidos.
La temperatura de trabajo puede alcanzar 60 °C y puede ir impreso sobre papel, plástico y metal. Allí donde existen condiciones de desgaste debido al movimiento de las partes a unir, este sellante es particularmente conveniente debido a sus propiedades de alta resistencia a la abrasión.

- Sellantes basados en silicona. Disponibles en forma compacta y celular.
Rango de temperaturas entre -60 °C y 200 °C. Con unos valores modestos de resistencia a la tracción, las siliconas son convenientes en aquellas aplicaciones donde las temperaturas de trabajo son condicionantes.

- Sellantes basados en PVC. Disponible en forma expandida y es utilizado básicamente para el sellado contra el polvo y humedad, allí donde las exigencias de rendimiento son básicamente bajas.

Véase Embega, S. Coop.

Junta de estanqueidad por impresion elastomerica


Make Architecture's M House is a small home in Melbourne, Australia, that explores how modern renovations can improve the way we live in our homes. A window-filled addition to the home allows light to fill the space, while the new M-shaped roof (from which the home derives its name) creates expansive ceilings to further the feel of openness.
The residence emphasizes northern sunlight using an window-filled addition so that the home receives plenty of natural light even in the winter. The addition was kept small to maximize the outdoor space. To help minimize summer sun, the home uses deep timber eaves, reducing the amount of heating and cooling necessary.
The new spaces provides an open communal area which encompasses a living area and the kitchen so that the family can share time together. The front of the home was left untouched, allowing it to blend in with the neighborhood.
The front of the home was left untouched, allowing it to blend in with the neighborhood.
The addition was kept small to maximize the outdoor space.
The new spaces provides an open communal area which encompasses a living area and the kitchen so that the family can share time together.
The bathroom was created with a sunken bathtub that includes hand-made tiles.
To help minimize summer sun, the home uses deep timber eaves, reducing the amount of heating and cooling necessary.
The renovation creates a light-filled space for the family to enjoy.
retail of the old and new home.
Cutaway elevation of the home.


Many college, university, and system leaders have significant others, but few studies have examined their campus roles, responsibilities, and perspectives. In spring 2016, researchers at the University of Minnesota surveyed spouses and partners across various institutional types, as a follow-up to a 1983 survey, seeking data to describe these institutional players in a contemporary context. The purpose of the study was to inform practice, governance, and leadership in higher education and to identify avenues for future research. The results of the current study highlight the nature and scope of the roles and respondents' involvement with them. The team also will present research findings on the availability and management of official presidential residences, personal and professional pursuits of spouses and partners, and rewards and challenges of the roles. Members of the research team will discuss how the roles of presidential spouses and partners have changed over the last 30 years.
Gwendolyn H. Freed is chief development officer at the Humphrey School of Public Affairs of the University of Minnesota and a faculty member at the university's Jandris Center for Innovative Higher Education. Previously, she served as vice president for institutional advancement at Cornish College of the Arts in Seattle and vice president for marketing and communication at Gustavus Adolphus College, among other positions. She is an investigator for the 2016 survey of presidential spouses and partners. Freed's writing has appeared in the Wall Street Journal and Chronicle of Higher Education. Her primary research interests include governance and leadership, external relations, and organizational identity in higher education. An alumna of the Harvard Institute for Educational Management, she holds a PhD in educational policy and administration and a master's degree in public affairs from the University of Minnesota, as well as music degrees from the Juilliard School and Oberlin Conservatory.
Darwin D. Hendel is an associate professor in the College of Education and Human Development at the University of Minnesota and is the principal investigator for the 2016 survey of presidential spouses and partners. His research involves addressing student and faculty issues in higher education from the perspective of differential psychology, with a particular interest in institutional planning, performance, and accountability; student performance, retention, and satisfaction; and evaluation of teaching and measurement of learning. Hendel earned a BA from Saint John's University (MN) in mathematics and psychology and a PhD from the University of Minnesota in psychology.
Presidential spouses and partners are invited to gather for a lively social event that will provide an opportunity to talk with other spouses and partners, one at a time, about topics of mutual interest. Come meet new friends and greet dear ones. A short informal reception, with refreshments, will follow the initial introductions.
The role of presidential spouse or partner is full of joys, challenges, and stresses. There are many scheduling demands, events to attend, and family members to look after, as well as jobs and opportunities for travel. Learn from fellow spouses and partners about ways to balance your life, reduce stress, and stay active.
As a follow-up to a 1983 survey, in 2016 researchers at the University of Minnesota surveyed spouses and partners of presidents across various institutional types seeking data to describe these institutional players in their contemporary context. Members of the research team will present an overview of the results and lead a discussion with CIC-member spouses and partners on the significance of the findings.
Although some presidential couples still feel comfortable in the traditional roles of president and spouse, many do not. How do spouses and partners who have demanding careers outside the college or university, live and work in another place, or are in other nontraditional circumstances find their way through the maze of responsibilities of the role of presidential spouse or partner?


text:
Q: Alert User When Changing Navigation or When Going to Specific Screen on React-Native So I'm currently trying to make a trigger event whenever the user is about to go to a specific page. Say for example I'm on a the Cart page and I decide to go back to the Dashboard page, I want to be able to prompt the user that he's about to leave the Cart page and go back to the Dashboard page. How can I do that in react-native?

A: Use the following code on back button press
onPressBack = () = {
  // Works on both iOS and Android
    Alert.alert(
      'Alert Title',
      'You are about to leave this screen',
      [
        {text: 'Cancel', onPress: () => console.log('Cancel Pressed'), style: 'cancel'},
        {text: 'OK', onPress: () => this.props.navigation.navigate('DashboardScreen') //code to navigate},
      ],
      { cancelable: false }
    )
}


I'm subscribing to the Twitter-feed for vCampus via the RSS option available.
But I have a small problem - if you check out the image I've attached you'll see that my Win7 gadget doesn't display much else than 'OSIsoftvCampus:' because of the width of the gadget. It appears that Twitter adds the username before the tweet, when you watch the rss feed.
Anyone got a solution for removing the username from the beginning of each tweet in the rss?
I find that sometimes the RSS feed is really bad for other uses.
I hadn't really done any research before asking - just tried the rss since there are so many options for rss/feeds these days (I can even set up an rss-feed on my sony tv).
The twadget looked promising - I had to create a Twitter account first (yes, I know - should have done that ages ago, but with so many social networks etc. out there, one has to prioritize), but nothing is displayed in the gadget. When I look at my twitter homepage all the news from OSIsoftvCampus are there (I'm only following OSIsoftvCampus) and that's also what I wanted to see in the gadget.
other than that I do not have windows 7 here to try it out and suggest my personal favorite, but I really think you can actually get on with a free alternative. Just remember that there is a maximum of messages the twitter API will allow you to pick every 45 minutes as a DOS-Attack preventing mechanism.
I personally use Twitter Explorer as a Windows 7 desktop gadget and I like it.
Checked out the Twitter Explorer and that was actually very good, Steve!


text:
The 2007–08 Texas A&M Aggies men's basketball team represented    Texas A&M University in the 2007–08 college basketball season. The team was    led by first-year head coach Mark Turgeon, who replaced Billy Gillispie in April 2007. In 2006–07, the Aggies finished 27–7 (13–3 in the Big 12), advanced to the NCAA Sweet Sixteen, and finished 9th in the final AP Poll — their first top 25 finish since the 1979–80 season.

The 2007–08 team won the NIT Season Tip-Off tournament. The 98–54 home win against Texas Tech matched the Aggies' largest margin of victory set in 1959 against Texas.

Leading into the season

Summer games
Six Aggie players participated in summer games during the summer prior to the start of the season. Junior Josh Carter participated in the Kobe Bryant Skills Academy in late June, and tried out for the Team USA basketball team for the 2007 Pan American Games. Though Carter was one of the 14 finalists to play for the team, he was one of the two who got eliminated. He later joined Athletes in Action to play several games in Australia. Incoming freshmen B.J. Holmes, DeAndre Jordan, and Nathan Walkup participated in the Global Games in Dallas in June. Jordan later joined Team USA for the under-19 world championship game in Serbia, where the team lost in the gold medal game. Sophomore Donald Sloan played for a different Athletes in Action team in the William Jones Cup in July. Sloan's team finished with a 5–4 record and tied for third place. Sophomore Bryan Davis played for the East Coast All-Stars, who went on a 10-day tour in Belgium and the Netherlands in August. Against the Dutch national team, Davis scored 16 points and made 11 rebounds. Davis' team finished with a 3–4 record.

Rankings
The preseason Big 12 Coaches' Poll picked the Aggies to finish third. The preseason Coaches Poll ranked the Aggies 14th, tied with the Gonzaga Bulldogs, and the preseason AP Poll ranked the Aggies 16th. ESPN columnist Andy Katz ranked the Aggies 17th in his "pre-preseason" top 25 rankings.

Preseason honors
Joseph Jones was named to the Wooden Award preseason top 50 list, and the preseason all-Big 12 team. Though Jones declared for the NBA draft in the summer, he withdrew himself prior to the deadline and decided to continue playing for the Aggies his senior season. Josh Carter was the 2007 NCAA leader in 3 point accuracy and currently holds the Big 12 record for career accuracy. Dominique Kirk is a Defensive All-American.

Recruiting

Players

Honors
 Senior Joseph Jones, along with Texas Longhorns player D. J. Augustin, was featured on the front cover of the November 15, 2007 issue of Sports Illustrated.
 After the Ouachita Baptist game, freshman DeAndre Jordan had made 16 consecutive field goals, breaking the Big 12 record of 13, set by Nebraska's Mikki Moore in 1998. Jordan also broke the A&M record, which was set in 1978.
 Senior point guard Dominique Kirk started his 110th consecutive game when the Aggies played Rice, breaking the Big 12 record set by Kansas point guard Aaron Miles from 2001 to 2005. Kirk's 110 consecutive starts is also an A&M record.

Roster

Information from 2007–08 roster and,  subject to change.

Schedule

|-
!colspan=9| Exhibition

|-
!colspan=9| Regular season

|-
!colspan=9| Postseason Big 12 Tournament

|-
!colspan=9| NCAA Tournament

References

External links
 Official website
 2007–08 NCAA Team national rankings
 Texas A&M Aggies basketball at ESPN.com

Texas A&M Aggies men's basketball seasons
Texas AandM
Texas AandM


Definition at line 34 of file baro_hca.c.
Definition at line 51 of file baro_hca.c.
Definition at line 37 of file baro_hca.c.
Definition at line 35 of file baro_hca.c.
Definition at line 38 of file baro_hca.c.
Definition at line 36 of file baro_hca.c.
Definition at line 47 of file baro_hca.c.
Definition at line 42 of file baro_hca.c.
Definition at line 62 of file baro_hca.c.
References baro_hca_i2c_trans, baro_hca_valid, I2CTransDone, pBaroRaw, i2c_transaction::status, and TRUE.
Definition at line 76 of file baro_hca.c.
References baro_hca_i2c_trans, BARO_HCA_MAX_OUT, BARO_HCA_MIN_OUT, BARO_HCA_PRESSURE_OFFSET, BARO_HCA_SCALE, BARO_HCA_SENDER_ID, baro_hca_valid, i2c_transaction::buf, DefaultChannel, DefaultDevice, FALSE, foo, I2CTransDone, pBaroRaw, i2c_transaction::status, and TRUE.
Definition at line 69 of file baro_hca.c.
References BARO_HCA_ADDR, BARO_HCA_I2C_DEV, baro_hca_i2c_trans, i2c_receive(), I2CTransDone, and i2c_transaction::status.
Definition at line 60 of file baro_hca.c.
Referenced by baro_hca_init(), baro_hca_read_event(), and baro_hca_read_periodic().
Definition at line 57 of file baro_hca.c.
Definition at line 56 of file baro_hca.c.
Referenced by baro_hca_init(), and baro_hca_read_event().
Definition at line 55 of file baro_hca.c.


text:
package org.apache.spark.carbondata.iud

import org.apache.spark.sql.Row
import org.apache.spark.sql.test.util.QueryTest
import org.scalatest.BeforeAndAfterAll

class DeleteCarbonTableSubqueryTestCase extends QueryTest with BeforeAndAfterAll {
  override def beforeAll {
    sql("use default")
    sql("drop database  if exists iud_db_sub cascade")
    sql("create database  iud_db_sub")

    sql("""create table iud_db_sub.source2 (c11 string,c22 int,c33 string,c55 string, c66 int) STORED AS carbondata""")
    sql(s"""LOAD DATA LOCAL INPATH '$resourcesPath/IUD/source2.csv' INTO table iud_db_sub.source2""")
    sql("use iud_db_sub")
  }

  test("delete data from  carbon table[where IN (sub query) ]") {
    sql("""drop table if exists iud_db_sub.dest""")
    sql("""create table iud_db_sub.dest (c1 string,c2 int,c3 string,c5 string) STORED AS carbondata""").show()
    sql(s"""LOAD DATA LOCAL INPATH '$resourcesPath/IUD/dest.csv' INTO table iud_db_sub.dest""")
    sql("""delete from  iud_db_sub.dest where c1 IN (select c11 from source2)""").show(truncate = false)
    checkAnswer(
      sql("""select c1 from iud_db_sub.dest"""),
      Seq(Row("c"), Row("d"), Row("e"))
    )
    sql("drop table if exists iud_db_sub.dest")
  }

  test("delete data from  carbon table[where IN (sub query with where clause) ]") {
    sql("""drop table if exists iud_db_sub.dest""")
    sql("""create table iud_db_sub.dest (c1 string,c2 int,c3 string,c5 string) STORED AS carbondata""").show()
    sql(s"""LOAD DATA LOCAL INPATH '$resourcesPath/IUD/dest.csv' INTO table iud_db_sub.dest""")
    sql("""delete from  iud_db_sub.dest where c1 IN (select c11 from source2 where c11 = 'b')""").show()
    checkAnswer(
      sql("""select c1 from iud_db_sub.dest"""),
      Seq(Row("a"), Row("c"), Row("d"), Row("e"))
    )
    sql("drop table if exists iud_db_sub.dest")
  }

  override def afterAll {
    sql("use default")
    sql("drop table if exists iud_db_sub.source2")
    sql("drop database  if exists iud_db_sub cascade")
  }
}


In water video at the following link:https://youtu.be/rGUJKQERVZMThis is your chance to own a very nice boat way below market value. Local trade in will be sold for abargain. Don't miss out on this one.
This 2012 Rinker Captiva 216 bow rider is powered by a upgraded 5.0 MPI Mercruiser engine with only 140 hours of use on the engine. Some features include: bow and cockpit covers, Bimini top, dual batteries with switch, AM/FM radio, snap in carpet, and a depth finder. Perfect boat to take 4-6 people out for a day of fun on the water. With the upgraded power package you can still pull a tube or wakeboard fully loaded with ease. Boat comes with a 2019 Aluminum dual axle trailer.Be sure to shop this price because its a smoking deal on a pretty boat for a fraction of the cost of a new one.
We take trades... We finance... We buy boats as well..


Fixed windows are most typically found in business and non-residential settings such as courtrooms and office buildings, as well as religious and educational facilities. They have a long-standing tradition and are designed mainly to offer a superior view. They do not have a movable sash so they are unable to open for ventilation, but they are excellent in assisting with climate control.
They simply consist of glass, screen and a frame to protect the glass. This frame is than transfixed to the window space. Casement windows are the most popular as they are designed with a fix part at the top. However, the fixed part can also be designed at the bottom if that is your preference.
The main concerns of fixed windows are usually ventilation versus aesthetics. While picture windows are aesthetically pleasing and energy efficient, they are not designed for ventilation. However, they do provide superior protection from harsh weather conditions.
The primary advantage of fixed windows is that the frame can be designed for tempered or stained glass in order to minimize sun glare. Often places of worship will opt for fixed windows beautifully designed with scenes depicting various religious passages while offices utilize fixed windows to beautify the interior of their building.
Fixed windows are most typically installed to give an impression of spaciousness. They are extremely easy to clean and low maintenance as well. They are extremely durable and are able to resist cracking and fading. Fixed windows are designed to facilitate internal drainage and may be custom designed upon request with triple glazing to ensure excellent water and air performance.
Fixed windows are extremely affordable and can last for years. They are often installed with combination of other window types for style and efficiency as well. Fixed windows are designed with multi-chamber. They are also made with a unique 100% uPVC powder compound that is 100% lead-free, which makes them more resistant. Fixed windows are virtually maintenance free and will not blister, fade, warp or crack.
Window Mart has the best selection of fixed windows in the Edmonton area. We can custom design windows according to your needs and specifications. Our friendly and helpful is always willing to assist you and answer any questions or concerns you have.


text:
Gwen Ifill
Author Gwen Ifill examines the American political landscape and its relation to race in America in her book, "The Breakthrough."
Politics Society
January 2017 November 2016 November 2016 October 2012 October 2012 January 2011 March 2009 March 2009 May 2008 April 1993
Adam Nagourney; Gwen Ifill; Shirley Tilghman
Politics, Business, Education, Science
The journalist on the bank bailout and AIG bonuses. Author of "The Breakthrough." Princeton's president on the importance of science education. 53:44
Politics, Society
Ta-Nehisi Coates introduces his new book, "We Were Eight Years in Power: An American Tragedy." 31:23
Ta-Nehisi Coates; Laura Ingraham
Ta-Nehisi Coates introduces his new book, "We Were Eight Years in Power; a conversation with conservative radio host Laura Ingraham. 54:15
'Blacks & Jews'
Books, Society, History, Religion
Academics Cornel West and Michael Lerner discuss the tensions between the Black and Jewish communities in America. 16:38
Politics, Media
Columnist for New York Magazine Kurt Andersen talks about Barack Obama and the relationship candidates have with the press. 25:02


PURE brings you the ideal activity holiday experience in Kadikalesi nr. Turgutreis, Bodrum, Turkey.
PURE believe your holiday should be more than just a windsurf and sailing holiday. They hold to the highest values in quality holidays and responsible tourism to ensure that you have everything you need for a real experience of Turkish culture. Have a look around their website and see how they can create your ideal break.
Click here for the puretourism website.
AVTA is situated in Kadikalesi just five minutes from Turgutreis and forty five minutes from Bodrum making it perfect for exploring the Bodrum peninsular.
To get your Windsurfing off to a great start PURE offers group and private lessons and hire for all ages and abilities.


text:
The White House - 1600 Daily: A special message for the holiday season
President Donald J. Trump welcomes Native American Code Talkers to the White House | November 27, 2017 (Official White House Photo by Joyce N. Boghosian)
A few days ago, Americans counted our blessings as we sat down for Thanksgiving dinners with our families and friends across the country. Today, many will choose to go one step further in celebrating their good fortune by honoring #GivingTuesday, a global day of charitable giving.
This year's #GivingTuesday is especially important. "Earlier this year, Hurricanes Harvey, Irma, and Maria devastated communities across the southern United States and in the Caribbean, and vast wildfires ravaged California," said President Donald J. Trump in a statement. "We saw millions of Americans lose everything, from homes to businesses . . . [to] the unbearable loss of loved ones."
The President thanks all those who have contributed to charitable organizations this year, including our houses of worship. If you would like to take part in #GivingTuesday, please consider supporting one of the great organizations partnering with us to help communities rebuild: https://www.nvoad.org.
As the President said, "Together, we can ensure that the blessings of this holiday season are shared around the world."
President Trump meets with members of the Senate Finance Committee
Yesterday, President Trump hosted Vice President Mike Pence and five members of the Senate Finance Committee at the White House for lunch in the Private Dining Room. The topic on everyone's mind? "A tremendous tax cut – the biggest in the history of our country," said President Trump.
The President reiterated his support for the tax bill proposed by Republican leadership and is pleased with the momentum it has inspired for passing crucial legislation well before the year's end. As part of the Administration's continued support, President Trump will join Senate Republicans today for lunch at the U.S. Capitol, where he'll make the case for swift action.
Learn more about President Trump's pro-job, pro-family, and pro-America principles for tax reform here.
Bonus: Read Sen. Rand Paul's (R-KY) op-ed on why he plans to vote for tax reform.
First Lady gives special thanks to Christmas volunteers
Yesterday, First Lady Melania Trump held a special gathering for volunteers who helped turn this year's White House Christmas theme, "Time-Honored Traditions," into reality. A Gold Star Family Tree honoring service members is proudly on display in the White House East Wing, and historic pieces celebrating holiday traditions – including a nod to the first White House Christmas theme, 1961's "Nutcracker Suite" – can be found throughout.
More than 150 volunteers came together from 29 states to assist with decorating and baking. The numbers tell the story best:
• 31,000: Number of cookies baked
• 53: Number of White House Christmas trees decorated
• 1,000: Feet of garland strung
• 12,000: Number of ornaments hung
The First Lady thanked the volunteers, who spent more than 1,600 hours bringing the First Family's first Christmas at the White House to life. She and the President look forward to hosting more than 25,000 visitors during the upcoming holiday season.
Watch First Lady Melania Trump unveil this year's Christmas decorations here.
POTUS TODAY
In the early afternoon, President Trump will be at the U.S. Capitol to have lunch with Senate Republicans as they continue to work toward passing historic tax reform. Later in the day, the President will meet with congressional leadership at the White House.
Vice President Pence will travel to New York as he prepares to keynote an event celebrating the 70th anniversary of the United Nations' vote calling for the establishment of a Jewish state in the Land of Israel. In the evening, the Vice President will deliver keynote remarks and receive the Herman Kahn Award at the Hudson Institute's 2017 Herman Kahn Award Dinner.
Tomorrow, President Trump will travel to St. Charles, Missouri, to discuss the crucial need for tax reform for all Americans.
On Thursday, the First Family will participate in the National Christmas Tree Lighting on the Ellipse at the White House.
By Middletown Insider - November 29, 2017


I have a two person household. Should I use the individual or family plan?
Can I buy a single meal plan?
I'm not sure I can afford $14.99 a month, do you have discounts?
I'm new and can't access the forums?
Would it be possible to see the list of meals before purchasing them?
How can I access my Dashboard?
What day does the meal plan start?
Does the family plan take into account the caloric needs of children?
Will I be automatically charged?
When are the new plans released?
I paid for the plan, but I haven't received it - help!
Can I send a personal check or call with my credit card?
I live in Australia, New Zealand, or elsewhere Southern Hemisphere. Can I buy plans that are more seasonal to my location?
Can I buy a gift membership?
Payment Successful but no meal plan?